text:
Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine.
Haghikia, Aiden; Jörg, Stefanie; Duscha, Alexander; Berg, Johannes; Manzel, Arndt; Waschbisch, Anne; Hammer, Anna; Lee, De-Hyung; May, Caroline; Wilck, Nicola; Balogh, Andras; Ostermann, Annika I; Schebb, Nils Helge; Akkad, Denis A; Grohme, Diana A; Kleinewietfeld, Markus; Kempa, Stefan; Thöne, Jan; Demir, Seray; Müller, Dominik N; Gold, Ralf; Linker, Ralf A
Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis. PMID:26488817
Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms
Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio; Fromm, M; Schulzke, JD
Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on celiac disease (CD), an autoimmune enteropathy, and type I diabetes (TID), a hyperglycosaemia caused by a destructive autoimmune p
The hygiene hypothesis revisited: autoimmune diseases, intestinal microbiota and vitamin D's role
Clark, Allison
The hygiene hypothesis postulates that higher levels of hygiene and improper exposure to microorganisms early in childhood could disturb the intestinal microbiome functions resulting in abnormal immune responses that can later lead to allergies and autoimmune diseases. Additionally, vitamin D deficiency and vitamin D receptor (VDR) polymorphisms and function might also trigger abnormal immune responses that can lead to an autoimmune disease. Therefore, this review explores the role Western li...
Curcumin Attenuates Gamma Radiation Induced Intestinal Damage in Rats
Small Intestine exhibits numerous morphological and functional alterations during radiation exposure. Oxidative stress, a factor implicated in the intestinal injury may contribute towards some of these alterations. The present work was designed to evaluate the efficacy of curcumin, a yellow pigment of turmeric on y-radiation-induced oxidative damage in the small intestine by measuring alterations in the level of thiobarbituric acid reactive substances (TSARS), serotonin metabolism, catecholamine levels, and monoamine oxidase (MAO) activity in parallel to changes in the architecture of intestinal tissues. In addition, monoamine level, MAO activity and TSARS level were determined in the serum. Curcumin was supplemented orally via gavages, to rats at a dose of (45 mg/ Kg body wt/ day) for 2 weeks pre-irradiation and the last supplementation was 30 min pre exposure to 6.5 Gy gamma radiations (applied as one shot dose). Animals were sacrificed on the 7th day after irradiation. The results demonstrated that, whole body exposure of rats to ionizing radiation has induced oxidative damage in small intestine obvious by significant increases of TSARS content, MAO activity and 5-hydroxy indole acetic acid (5-HIAA) and by significant decreases of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) levels. In parallel histopathological studies of the small intestine of irradiated rats through light microscopic showed significant decrease in the number of villi, villus height, mixed sub mucosa layer with more fibres and fibroblasts. Intestinal damage was in parallel to significant alterations of serum MAO activity, TBARS, 5-HT, DA, NE and EPI levels. Administration of curcumin before irradiation has significantly improved the levels of monoamines in small intestine and serum of irradiated rats, which was associated with significant amelioration in MAO activity and TBARS contents
Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with Intestinal Oxidative Stress Injury
Yu, Chao; Wang, Qiang; Zhou, Chunyu; Kang, Xin; Zhao, Shuang; Liu, Shuai; Fu, Huijun; Yu, Zhen; Peng, Ai
Background. To investigate whether intestinal mucosal barrier was damaged or not in chronic kidney disease progression and the status of oxidative stress. Methods. Rats were randomized into two groups: a control group and a uremia group. The uremia rat model was induced by 5/6 kidney resection. In postoperative weeks (POW) 4, 6, 8, and 10, eight rats were randomly selected from each group to prepare samples for assessing systemic inflammation, intestinal mucosal barrier changes, and the status of intestinal oxidative stress. Results. The uremia group presented an increase trend over time in the serum tumor necrosis factor-alpha, interleukin-6 (IL-6) and IL-10, serum D-lactate and diamine oxidase, and intestinal permeability, and these biomarkers were significantly higher than those in control group in POW 8 and/or 10. Chiu's scores in uremia group were also increased over time, especially in POW 8 and 10. Furthermore, the intestinal malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were significantly higher in uremia group when compared with those in control group in POW 8 and/or 10. Conclusions. The advanced chronic kidney disease could induce intestinal mucosal barrier damage and further lead to systemic inflammation. The underlying mechanism may be associated with the intestinal oxidative stress injury. PMID:27493661
Intestinal damage and malabsorption after treatment for cervical carcinoma
Sixty-two patients with cervical carcinoma were treated in 1966 to 1968. Thirty-two patients who were alive in 1982 were reevaluated concerning intestinal function. An initial low folate value associated with the disease did not correlate with prognosis. A late low folate value indicated malabsorption and not recurrence of the carcinoma. Malabsorption was found in 5/23 patients (22%) and 3 of these (13%) had vitamin B12 deficiency. Intestinal damage in tumour free patients occurred in 2/62 (3%) patients. It is suggested that late silent complications such as malabsorption should be looked for in the preventive care of these patients. (Auth.)
Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage
Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)
Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation
Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage
Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation
Intestinal barrier damage caused by trauma and lipopolysaccharide
Lian-An Ding; Jie-Shou Li; You-Sheng Li; Nian-Ting Zhu; Fang-Nan Liu; Li Tan
AIM: To investigate the intestinal barrier function damage induced by trauma and infection in rats.METHODS: Experimental models of surgical trauma and infection were established in rats. Adult Sprague-Dawley rats were divided into 4 groups: control group (n = 8), EN group (n = 10), PN group (n = 9) and Sep group (n = 8).The rats in PN and Sep groups were made into PN models that received isonitrogenous, isocaloric and isovolumic TPN solution during the 7-d period. Rats in EN and Sep groups received laparotomy and cervical catheterization on day 1 and received lipopolysaccharide injection intraperitoneally on d 7. On the 7th day all the animals were gavaged with lactulose and mannitol to test the intestinal permeability.Twenty-four hours later samples were collected and examined.RESULTS: The inflammatory responses became gradually aggravated from EN group to Sep group. The mucosal structure of small intestine was markedly impaired in PN and Sep groups. There was a low response in IgA level in Sep group when compared with that of EN group.Lipopolysaccharide injection also increased the nitric oxide levels in the plasma of the rats. The intestinal permeability and bacterial translocation increased significantly in Sep group compared with that of control group.CONCLUSION: One wk of parenteral nutrition causes an atrophy of the intestinal mucosa and results in a moderate inflammatory reaction in the rats. Endotoxemia aggravats the inflammatory responses that caused by laparotomy plus TPN, increases the production of nitric oxide in the body, and damages the intestinal barrier function.
Protection effect of Emodin pretreatment on intestinal I - RI damage of intestinal mucosa in ratsa
Shu-Jie Zhao; Shi-Ji Wang; Hong-Xiang Li; Li-Hua Dong; Huai-Jiang He; Zhong-Min Liu; Yu-Shan Wang
Objective:To tinvestigate the protective effect and mechanism of emodin pretreatment on intestinal mucosa of rats with intestinal ischemia-reperfusion injury.Methods:A total of50 SD rats were randomly divided into control group, model group, emodin groups of low, medium and high dose, with10 in each group.Ischemia-reperfusion injury(I-RI) mode was established by using noninvasive clamp on superior mesentericartery(SMA).Control group and model group were pretreated with0.5% sodium carboxymethyl cellulose solution lavage2 h before operation, emodin groups of low, medium and high dose were given emodin lavage with20,40,60 mg/kg pretreatment, femoral venous blood before the lavage pretreatment(T0) and1 h ischemia(T1) , and inferior vena venous blood after1 h of reperfusion(T2) were extracted from each group of rats for detection of serum level of intestinal fatty acid binding protein(I-FABP), tumor necrosis factor(TNF-α), endotoxin, interleukin6(IL-6), and the content of diamine oxidase(DAO);After model establishment, the rats were sacrificed, intestine homogenate was prepared by using blind intestinal tissue to detect intestinal tissue myeloperoxidase(MPO), malondialdehyde(MDA) and superoxide dismutase(SOD) levels.And upper small intestine tissue was retrieved, followed by fixation and conventionalHE staining to observe intestinal tissue morphology under light microscopy.Results:In emodin groups of low, medium and high dose atT1 andT2,I -FABP, TNF-α, endotoxin,IL-6 andDAO level were significantly lower than that of model group(P<0.05); in emodin group of low,medium and high dose,MPO andMDA content in intestinal tissue homogenate was significantly lower than that in model group(P<0.05),SOD level was significantly higher than that of model group(P<0.05).Intestinal damage of emodin low, medium and high dose groups were significantly lighter than model group.Conclusions:Emodin pretreatment has certain protective effect on intestinal mucosa in ischemia reperfusion injury.
Role of damage control enterostomy in management of children with peritonitis from acute intestinal disease
Ameh, Emmanuel A; Michael A Ayeni; Stephen A Kache; Philip M Mshelbwala
Background: Intestinal anastomosis in severely ill children with peritonitis from intestinal perforation, intestinal gangrene or anastomotic dehiscence (acute intestinal disease) is associated with high morbidity and mortality. Enterostomy as a damage control measure may be an option to minimize the high morbidity and mortality. This report evaluates the role of damage control enterostomy in the treatment of these patients. Materials and Methods: A retrospective review of 52 children with acu...
Toll-Like Receptor Mediated Modulation of T Cell Response by Commensal Intestinal Microbiota as a Trigger for Autoimmune Arthritis
Rebecca Rogier
Full Text Available In autoimmune diseases, a disturbance of the balance between T helper 17 (Th17 and regulatory T cells (Tregs is often observed. This disturbed balance is also the case in rheumatoid arthritis (RA. Genetic predisposition to RA confers the presence of several polymorphisms mainly regulating activation of T lymphocytes. However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors. Multiple studies have shown that commensal gut microbiota is of great influence on immune homeostasis and can trigger the development of autoimmune diseases by favoring induction of Th17 cells over Tregs. However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood. Here we review the current evidence supporting the involvement of commensal intestinal microbiota in rheumatoid arthritis, along with a potential role of Toll-like receptors (TLRs in modulating the relevant Th cell responses to trigger autoimmunity. A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.
Selective accumulation of pro-inflammatory T cells in the intestine contributes to the resistance to autoimmune demyelinating disease.
Kerstin Berer
Full Text Available Myelin-specific, pro-inflammatory TH17 cells are widely regarded as the drivers of experimental autoimmune encephalomyelitis (EAE, an animal model for Multiple sclerosis (MS. The factors, responsible for the generation and maintenance of TH17 cells as well as their participation in the pathogenic cascade leading to the demyelinating disease, have been studied extensively. However, how these harmful autoreactive cells are controlled in vivo remains unclear. By comparing TCR transgenic mice on a disease susceptible and a disease resistant genetic background, we show here that pathogenic TH17 cells are sequestered within the intestine of spontaneous EAE resistant B10.S mice. Disease resistant B10.S mice harbored higher frequencies of TH17 cells in the intestine compared to EAE susceptible SJL/J mice. Moreover, transferred TH17 cells selectively migrated to intestinal lymphoid organs of B10.S mice. The sequestration of TH17 cells in the gut was partially dependent on the gut homing receptor α4β7-mediated adhesion to the intestine. Administration of α4β7 blocking-antibodies increased the peripheral availability of TH17 cells, resulting in increased EAE severity after immunization in B10.S mice. Together, these results support the concept that the intestine is a check-point for controlling pathogenic, organ-specific T cells.
Trimetazidine effect on burn-induced intestinal mucosal injury and kidney damage in rats
Yalcin, Arzu Didem; Bisgin, Atil; Erbay, Riza Hakan; Oguz, Oguzhan; Demir, Suleyman; Yilmaz, Mustafa; Gumuslu, Saadet
Background: Trimetazidine (TMZ) has been used in cardiology practice for protection from ischemiareperfusion injury. But its effects on intestinal mucosa are not well known. Our aim was to investigate the protective effect of TMZ on intestinal mucosa and on damaged kidney due to thermal injury in rats. Material and methods: Total of 30 male Sprague-Dawley rats were used in the study of intestinal mucosa damage and 24 female Sprague-Dawley rats in renal injury model. Back regions were shaved a...
Differentially expressed genes in repairing irradiation-induced damage in mouse intestinal tract by foreign mouse small intestinal RNA
To study the differentially expressed genes correlative to irradiation-induced damage in mouse intestinal tract and its repair by foreign mouse small intestinal RNA. Divide 90 mice into 4 groups randomly. For the experimental groups, each mouse was given 40μg foreign mouse small intestinal RNA, and for the control groups, 0.4 mL of 0.9% NaCl. The intestinal specimens were collected form each group 6h, 12h, 24h, 4d and 8d after 60Co γ-rays irradiation respectively. The differentially expressed genes in the tested and control groups were checked and cloned by long-distance PCR based on subtractive hybridization. 165 differential gene clones were obtained, of which 75 named as AXCZI-75 maybe were correlated with the irradiation-induced damage in mouse intestinal tract; and 90 named as XCZ1-90 maybe were correlated with repairing of the damaged mouse intestinal tract by foreign mouse small intestinal RNA
Damage to the optic chiasm in myelin oligodendrocyte glycoprotein-experimental autoimmune encephalomyelitis mice.
Herrera, Sheryl L; Palmer, Vanessa L; Whittaker, Heather; Smith, Blair Cardigan; Kim, Annie; Schellenberg, Angela E; Thiessen, Jonathan D; Buist, Richard; Del Bigio, Marc R; Martin, Melanie
Optic chiasm lesions in myelin oligodendrocyte glycoprotein (MOG)-experimental autoimmune encephalomyelitis (EAE) mice were characterized using magnetic resonance imaging (MRI) and validated using electron microscopy (EM). MR images were collected from 3 days after induction to remission, approximately 20 days after induction. Hematoxylin and eosin, solochrome cyanin-stained sections, and EM images were obtained from the optic chiasms of some mice approximately 4 days after disease onset when their scores were thought to be the highest. T2-weighted imaging and apparent diffusion coefficient map hyperintensities corresponded to abnormalities in the optic chiasms of EAE mice. Mixed inflammation was concentrated at the lateral surface. Degeneration of oligodendrocytes, myelin, and early axonal damage were also apparent. A marked increase in chiasm thickness was observed. T2-weighted and diffusion-weighted MRI can detect abnormalities in the optic chiasms of MOG-EAE mice. MRI is an important method in the study of this model toward understanding optic neuritis. PMID:25520558
Tinospora cordifolia inhibits autoimmune arthritis by regulating key immune mediators of inflammation and bone damage.
Sannegowda, K M; Venkatesha, S H; Moudgil, K D
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints leading to tissue damage. Despite the availability of potent drugs including the biologics, many patients fail to respond to them, whereas others suffer adverse effects following long-term use of these drugs. Accordingly, the use of natural herbal products by RA patients has been increasing over the years. However, limited information about the mechanism of action of these natural products is a major shortcoming that prevents the widespread acceptance of herbal therapy by professionals and patients alike. In this study, we demonstrated the anti-arthritic activity of Tinospora cordifolia extract (TCE) using the rat adjuvant-induced arthritis model of human RA and elaborated the immune mechanisms underlying this effect. TCE treatment suppressed arthritic inflammation and bone and cartilage damage. The anti-inflammatory effect of TCE was mediated via reduction of the pro-inflammatory cytokines such as: IL-1β, TNF-α, IL-6, and IL-17; the frequency of IL-17-producing T cells; and the production of chemokines such as RANTES. Furthermore, TCE treatment limited bone damage by shifting the balance of mediators of bone remodeling (e.g., receptor activator of nuclear factor-kB ligand [RANKL] and MMP-9) in favor of anti-osteoclastic activity. Our results suggest that TCE and its bioactive components should be evaluated for their utility as therapeutic adjuncts to conventional drugs against RA. PMID:26467057
Autoimmune gastritis and parietal cell reactivity in two children with abnormal intestinal permeability
Greenwood, Deanne L. V.; Crock, Patricia; Braye, Stephen; Davidson, Patricia; Sentry, John W.
Autoimmune gastritis is characterised by lymphocytic infiltration of the gastric submucosa, with loss of parietal and chief cells and achlorhydria. Often, gastritis is expressed clinically as cobalamin deficiency with megaloblastic anaemia, which is generally described as a disease of the elderly. H
Role of small intestinal bacterial overgrowth in severe small intestinal damage in chronic non-steroidal anti-inflammatory drug users.
Muraki, Motoko; Fujiwara, Yasuhiro; Machida, Hirohisa; Okazaki, Hirotoshi; Sogawa, Mitsue; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Tominaga, Kazunari; Watanabe, Toshio; Arakawa, Tetsuo
OBJECTIVE. Enteric bacteria play a significant role in the pathogenesis of non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal damage. However, the association between small intestinal bacterial overgrowth (SIBO) and NSAID-induced small intestinal damage remains unclear. The aim of the study was to examine the association between SIBO and the presence of NSAID-induced severe small intestinal damage or its symptoms in chronic NSAID users. MATERIALS AND METHODS. Forty-three patients who had been using NSAIDs for over 3 months were enrolled. They were examined by capsule endoscopy and a lactulose hydrogen breath test (LHBT). We defined severe small intestinal damage as the presence of more than four small erosions or large erosions/ulcers. The LHBT result was considered positive if there was an increase in the level of breath hydrogen gas of >20 ppm above baseline. RESULTS. Out of 43 patients, 22 (51%) had severe small intestinal damage. The LHBT was positive in 5 of 21 patients (24%) without severe small intestinal damage and in 13 of 21 patients (59%) with severe small intestinal damage. Multiple logistic regression analysis showed that an LHBT-positive result was significantly associated with increased odds ratio for severe small intestinal damage (OR, 6.54; 95% CI, 1.40-30.50). There was no significant difference in the presence of symptoms between the LHBT-positive and LHBT-negative patients with severe small intestinal damage. CONCLUSION. SIBO might have a role in the development of severe small intestinal damage in chronic NSAID users. PMID:24417613
The relationship between intestinal parasites and some immune-mediated intestinal conditions
Mohammadi, Rasoul; Hosseini-Safa, Ahmad; Ehsani Ardakani, Mohammad Javad; Rostami-Nejad, Mohammad
Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease (CD), inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Celiac disease is a digestive and autoimmune disorder that can damage the small intestin...
Temporal relationship of serum markers and tissue damage during acute intestinal ischemia/reperfusion
Francisco Javier Guzmán-de la Garza
Full Text Available OBJECTIVE: It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage. METHODS: We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student's t-test. RESULTS: The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group. CONCLUSION: For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion.
Proteins derived from neutrophil extracellular traps may serve as self-antigens and mediate organ damage in autoimmune diseases.
Jason S. Knight
Full Text Available Neutrophils are the most abundant leukocytes in circulation and represent one of the first lines of defense against invading pathogens. Neutrophils possess a vast arsenal of antimicrobial proteins, which can be released from the cell by a death program termed NETosis. Neutrophil extracellular traps (NETs are web-like structures consisting of decondensed chromatin decorated with granular and cytosolic proteins. Both exuberant NETosis and impaired clearance of NETs have been implicated in the organ damage of autoimmune diseases, such as systemic lupus erythematosus (SLE, small vessel vasculitis (SVV, and psoriasis. NETs may represent a source of modified autoantigens in SLE and SVV. Here, we review the autoimmune diseases linked to NETosis, with a focus on how modified proteins externalized on the NETs may trigger loss of immune tolerance and promote organ damage.
Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides
J. Tang
Full Text Available Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6 was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS. In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.
Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides
Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries
Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides
Tang, J.; Jiang, Y. [Southern Medical University, Nanfang Hospital, Department of Anesthesia, Guangzhou, China, Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou (China); Tang, Y.; Chen, B. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China); Sun, X. [Laboratory of Traditional Chinese Medicine Syndrome, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou (China); Su, L.; Liu, Z. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China)
Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.
Recombinant Human Epidermal Growth Factor Accelerates Recovery of Mouse Small Intestinal Mucosa After Radiation Damage
Purpose: To determine whether systemically administered recombinant human epidermal growth factor (rhEGF) accelerates the recovery of mouse small intestinal mucosa after irradiation. Methods and Materials: A mouse mucosal damage model was established by administering radiation to male BALB/c mice with a single dose of 15 Gy applied to the abdomen. After irradiation, rhEGF was administered subcutaneously at various doses (0.04, 0.2, 1.0, and 5.0 mg/kg/day) eight times at 2- to 3-day intervals. The evaluation methods included histologic changes of small intestinal mucosa, change in body weight, frequency of diarrhea, and survival rate. Results: The recovery of small intestinal mucosa after irradiation was significantly improved in the mice treated with a high dose of rhEGF. In the mice that underwent irradiation without rhEGF treatment, intestinal mucosal ulceration, mucosal layer damage, and severe inflammation occurred. The regeneration of villi was noticeable in mice treated with more than 0.2 mg/kg rhEGF, and the villi recovered fully in mice given more than 1 mg/kg rhEGF. The frequency of diarrhea persisting for more than 3 days was significantly greater in the radiation control group than in the rhEGF-treated groups. Conclusions: Systemic administration of rhEGF accelerates recovery from mucosal damage induced by irradiation. We suggest that rhEGF treatment shows promise for the reduction of small intestinal damage after irradiation
Role of damage control enterostomy in management of children with peritonitis from acute intestinal disease
Emmanuel A Ameh
Full Text Available Background: Intestinal anastomosis in severely ill children with peritonitis from intestinal perforation, intestinal gangrene or anastomotic dehiscence (acute intestinal disease is associated with high morbidity and mortality. Enterostomy as a damage control measure may be an option to minimize the high morbidity and mortality. This report evaluates the role of damage control enterostomy in the treatment of these patients. Materials and Methods: A retrospective review of 52 children with acute intestinal disease who had enterostomy as a damage control measure in 12 years. Results: There were 34 (65.4% boys and 18 (34.6% girls aged 3 days-13 years (median 9 months, comprising 27 (51.9% neonates and infants and 25 (48.1% older children. The primary indication for enterostomy in neonates and infants was intestinal gangrene 25 (92.6% and perforated typhoid ileitis 22 (88% in older children. Enterostomy was performed as the initial surgery in 33 (63.5% patients and as a salvage procedure following anastomotic dehiscence in 19 (36.5% patients. Enterostomy-related complications occurred in 19 (36.5% patients, including 11 (21.2% patients with skin excoriations and eight (15.4% with hypokalaemia. There were four (7.7% deaths (aged 19 days, 3 months, 3½ years and 10 years, respectively directly related to the enterostomy, from hypokalaemia at 4, 12, 20 and 28 days postoperatively, respectively. Twenty other patients died shortly after surgery from their primary disease. Twenty of 28 surviving patients have had their enterostomy closed without complications, while eight are awaiting enterostomy closure. Conclusion: Damage-control enterostomy is useful in management of severely ill children with intestinal perforation or gangrene. Careful and meticulous attention to fluid and electrolyte balance, and stoma care, especially in the first several days following surgery, are important in preventing morbidity and mortality.
Protective Effect of Wheat Peptides Against Small Intestinal Damage Induced by Non-Steroidal Anti-Inlfammatory Drugs in Rats
YIN Hong; PAN Xing-chang; WANG Shao-kang; YANG Li-gang; SUN Gui-ju
Non-steroidal anti-inlfammatory drugs (NSAIDs) were able to produce tissue damage and oxidative stress in animal models of small intestinal damage. In this study, the putative protective effect of wheat peptides was evaluated in a NSAID-induced small intestinal damage model in rats, different doses of wheat peptides or distilled water were administered daily by intragastric administration for 30 d until small intestinal damage was caused. Before sacriifcing, NSAIDs (aspirin and indomethacin) or physiological saline were infused into the digestive tract twice. Wheat peptides administration reduced edema and small intestinal damage, and signiifcantly decreased the level of tumor necrosis factor (TNF)-α in mucous membrane of small intestine. Oxidative stress was signiifcantly increased after NSAID infusion and was reduced by wheat peptides. Wheat peptides increased glutathione peroxidase(GSH-Px) activity in mucous membrane of small intestine. µ-Opioid receptor mRNA expression decreased more signiifcantly in wheat peptides treated rats than in the model control group. Overall, the results suggest that non-steroidal anti-inlfammatory drugs induced small intestinal damage in rats and wheat peptides administration may be an effective tool for protecting small intestinal tissue against NSAID-induced small intestinal damage and oxidative stress.
Protection of intestinal damage by pretreatment with cytarabine (cytosine arabinoside)
Phelps, T.A.; Blackett, N.M.
The circumstances in which cytarabine (cytosine arabinoside) ''protects'' intestinal epithelial stem cells against radiation have been investigated. Special attention has been given to this protective effect with radiation doses in the clinically used range in order to determine whether the protective effect might be of use in radiotherapy. It has been shown that 12 hours after cytarabine the D/sub 0/ and extrapolation number are increased when large single doses of radiation are used. To determine the effect of cytarabine at lower doses, it is necessary to use a second irradiation as an ''assay'' dose. By this means it is shown that there is more protection than can be accounted for by the change in D/sub 0/ and extrapolation number at the time of the first dose. Evidence is presented indicating that the rate of stem cell regeneration is not increased by cytarabine pretreatment. Finally, the relation between intestinal protection, bone marrow stem cell enhanced recovery and improved animal survival as a result of cytarabine pretreatment is discussed.
High beta-palmitate fat controls the intestinal inflammatory response and limits intestinal damage in mucin Muc2 deficient mice.
Peng Lu
Full Text Available BACKGROUND: Palmitic-acid esterified to the sn-1,3 positions of the glycerol backbone (alpha, alpha'-palmitate, the predominant palmitate conformation in regular infant formula fat, is poorly absorbed and might cause abdominal discomfort. In contrast, palmitic-acid esterified to the sn-2 position (beta-palmitate, the main palmitate conformation in human milk fat, is well absorbed. The aim of the present study was to examine the influence of high alpha, alpha'-palmitate fat (HAPF diet and high beta-palmitate fat (HBPF diet on colitis development in Muc2 deficient (Muc2(-/- mice, a well-described animal model for spontaneous enterocolitis due to the lack of a protective mucus layer. METHODS: Muc2(-/- mice received AIN-93G reference diet, HAPF diet or HBPF diet for 5 weeks after weaning. Clinical symptoms, intestinal morphology and inflammation in the distal colon were analyzed. RESULTS: Both HBPF diet and AIN-93G diet limited the extent of intestinal erosions and morphological damage in Muc2(-/- mice compared with HAPF diet. In addition, the immunosuppressive regulatory T (Treg cell response as demonstrated by the up-regulation of Foxp3, Tgfb1 and Ebi3 gene expression levels was enhanced by HBPF diet compared with AIN-93G and HAPF diets. HBPF diet also increased the gene expression of Pparg and enzymatic antioxidants (Sod1, Sod3 and Gpx1, genes all reported to be involved in promoting an immunosuppressive Treg cell response and to protect against colitis. CONCLUSIONS: This study shows for the first time that HBPF diet limits the intestinal mucosal damage and controls the inflammatory response in Muc2(-/- mice by inducing an immunosuppressive Treg cell response.
Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.
Mehrnaz Nouri
Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE, the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers. These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms and at 14 days (i.e., at the stage of paralysis after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.
Specific responses in rat small intestinal epithelial mRNA expression and protein levels during chemotherapeutic damage and regeneration
M. Verburg (Melissa); I.B. Renes (Ingrid); D.J. van Nispen; S. Ferdinandusse; M. Jorritsma; H.A. Büller (Hans); A.W.C. Einerhand (Sandra); J. Dekker (Jan)
textabstractThe rapidly dividing small intestinal epithelium is very sensitive to the cytostatic drug methotrexate. We investigated the regulation of epithelial gene expression in rat jejunum during methotrexate-induced damage and regeneration. Ten differentiation markers were loca
Milk with and without lactoferrin can influence intestinal damage in a pig model of malnutrition.
Garas, Lydia C; Feltrin, Cristiano; Kristina Hamilton, M; Hagey, Jill V; Murray, James D; Bertolini, Luciana R; Bertolini, Marcelo; Raybould, Helen E; Maga, Elizabeth A
Malnutrition remains a leading contributor to the morbidity and mortality of children under the age of five worldwide. However, the underlying mechanisms are not well understood necessitating an appropriate animal model to answer fundamental questions and conduct translational research into optimal interventions. One potential intervention is milk from livestock that more closely mimics human milk by increased levels of bioactive components that can promote a healthy intestinal epithelium. We tested the ability of cow milk and milk from transgenic cows expressing human lactoferrin at levels found in human milk (hLF milk) to mitigate the effects of malnutrition at the level of the intestine in a pig model of malnutrition. Weaned pigs (3 weeks old) were fed a protein and calorie restricted diet for five weeks, receiving cow, hLF or no milk supplementation daily from weeks 3-5. After three weeks, the restricted diet induced changes in growth, blood chemistry and intestinal structure including villous atrophy, increased ex vivo permeability and decreased expression of tight junction proteins. Addition of both cow and hLF milk to the diet increased growth rate and calcium and glucose levels while promoting growth of the intestinal epithelium. In the jejunum hLF milk restored intestinal morphology, reduced permeability and increased expression of anti-inflammatory IL-10. Overall, this pig model of malnutrition mimics salient aspects of the human condition and demonstrates that cow milk can stimulate the repair of damage to the intestinal epithelium caused by protein and calorie restriction with hLF milk improving this recovery to a greater extent. PMID:26751615
Davydovskaya, M V; Boyko, A N; Beliaeva, I A; Martynov, M Yu; Gusev, E I
The authors consider the issues related to pathogenesis, clinical features, diagnosis and treatment of autoimmune encephalitis. It has been demonstrated that the development of autoimmune encephalitis can be associated with the oncologic process or be of idiopathic character. The pathogenesis of autoimmune encephalitis is caused by the production of antibodies that directly or indirectly (via T-cell mechanism) damage exo-and/or endocellular structures of the nerve cells. The presence of antobodies to endocellular structures of neurons in the cerebrospinal fluid of patients with autoimmune encephalitis in the vast majority of cases (> 95%) indicates the concomitant oncologic process, the presence of antibodies to membranes or neuronal synapses can be not associated with the oncologic process. Along with complex examination, including neuroimaging, EEG, cerebrospinal fluid and antibodies, the diagnostic algorithm in autoimmune encephalitis should include the search for the nidus of cancer. The treatment algorithm in autoimmune encephalitis included the combined immunosupressive therapy, plasmapheresis, immunoglobulines, cytostatics as well as treatment of the oncologic process. PMID:26322363
Axonal damage in myelin oligodendrocyte glycoprotein peptide-induced experimental autoimmune encephalomyelitis in a C57BL/6 mouse model may be not secondary to inflammatory demyelination
Boting Gao; Juan Chen; Qiong Wang; Wei Wang; Zhouping Tang
The present study established a chronic experimental autoimmune encephalomyelitis model in C57BL/6 mice induced by myelin oligodendrocyte glycoprotein peptides and complete Freund's adjuvant. Onset latency was 12 days, with an incidence rate of 100%. Neuropathological characteristics included perivascular inflammatory cell infiltration, demyelination, neuronal degeneration, and axonal damage within cerebral and myelic white matter. Electron microscopy revealed swollen mitochondria, complete organ disappearance, and fused or broken myelin sheath structure, which were accompanied by myelin sheath reconstruction. Moreover, axonal damage was not consistent with demyelination distribution, and severity of axonal damage did not correlate with demyelination. Results suggested that axonal damage in an experimental autoimmune encephalomyelitis model is not secondary to inflammatory demyelination.
The Relationship Between Intestinal Iron Absorption and Hepatic Parenchymal Cell Damage
Since the iron balance is maintained by regulated intestinal absorption rather than regulated excretion, there have been many reports concerning the factors which may influence the intestinal iron absorption. As the liver is the largest iron storage organ of the body, any hepatocellular damage may result in disturbances in iron metabolism, e,g., frequent co-existence of haemochromatosis and liver cirrhosis, or elevated serum iron level and increased iron absorption rate in patients with infectious hepatitis or cirrhosis. In one effort to demonstrate the influence of hepatocellular damage on intestinal iron absorption, the iron absorption rate was measured in the rabbits whose livers were injured by a single subcutaneous injection of carbon tetrachloride (doses ranging from 0.15 to 0.5 cc per kg of body weight) or by a single irradiation of 2, 000 to 16, 000 rads with Co on the liver locally. A single oral dose of 1μCi of Fe-citrate with 0.5 mg of ferrous citrate was fed in the fasting state, 24 hours after hepatic damage had been induced, without any reducing or chelating agents, and stool was collected for one week thereafter. Serum iron levels, together with conventional liver function teats, were measured at 24, 48, 72, 120 and 168 hours after liver damage had been induced. All animals were sacrificed upon the completing of the one week's test period and tissue specimens were prepared for H-E and Gomori's iron stain. Following are the results. 1. Normal iron absorption rate of the rabbit was 41.72±3.61% when 0.5 mg of iron was given in the fasting state, as measured by subtracting the amount recovered in stool collected for 7 days from the amount given. The test period of 7 days is adequate, for only 1% of the iron given was excreted thereafter. 2. The intestinal iron absorption rate and serum iron level were significantly increased when the animal was poisoned by a single subcutaneous injection of 0.15 cc, per kg. of body weight of carbon tetrachloride or
The Relationship Between Intestinal Iron Absorption and Hepatic Parenchymal Cell Damage
Kim, Mok Hyun; Hahn, Shin Suck [Seoul National University College of Medicine, Seoul (Korea, Republic of)
Since the iron balance is maintained by regulated intestinal absorption rather than regulated excretion, there have been many reports concerning the factors which may influence the intestinal iron absorption. As the liver is the largest iron storage organ of the body, any hepatocellular damage may result in disturbances in iron metabolism, e,g., frequent co-existence of haemochromatosis and liver cirrhosis, or elevated serum iron level and increased iron absorption rate in patients with infectious hepatitis or cirrhosis. In one effort to demonstrate the influence of hepatocellular damage on intestinal iron absorption, the iron absorption rate was measured in the rabbits whose livers were injured by a single subcutaneous injection of carbon tetrachloride (doses ranging from 0.15 to 0.5 cc per kg of body weight) or by a single irradiation of 2, 000 to 16, 000 rads with Co on the liver locally. A single oral dose of 1muCi of Fe-citrate with 0.5 mg of ferrous citrate was fed in the fasting state, 24 hours after hepatic damage had been induced, without any reducing or chelating agents, and stool was collected for one week thereafter. Serum iron levels, together with conventional liver function teats, were measured at 24, 48, 72, 120 and 168 hours after liver damage had been induced. All animals were sacrificed upon the completing of the one week's test period and tissue specimens were prepared for H-E and Gomori's iron stain. Following are the results. 1. Normal iron absorption rate of the rabbit was 41.72+-3.61% when 0.5 mg of iron was given in the fasting state, as measured by subtracting the amount recovered in stool collected for 7 days from the amount given. The test period of 7 days is adequate, for only 1% of the iron given was excreted thereafter. 2. The intestinal iron absorption rate and serum iron level were significantly increased when the animal was poisoned by a single subcutaneous injection of 0.15 cc, per kg. of body weight of carbon
Consequences of PAI-1 specific deletion in endothelium on radiation-induced intestinal damage
Radiation-induced injury to healthy tissues is a real public health problem, since they are one of the most limiting factors that restrict efficiency of radiation therapy. This problematic is also part of the French Cancer Plan 2014-2017, and involves clinical research. Concepts surrounding the development of radiation-induced damage have gradually evolved into a contemporary and integrated view of the pathogenesis, involving all compartments of target tissue. Among them, endothelium seems to be central in the sequence of interrelated events that lead to the development of radiation-induced damage, although there are rare concrete elements that support this concept. By using new transgenic mouse models, this PhD project provides a direct demonstration of an endothelium-dependent continuum in evolution of radiation-induced intestinal damage. Indeed, changes in the endothelial phenotype through targeted deletion of the gene SERPINE1, chosen because of its key role in the development of radiation enteritis, influences various parameters of the development of the disease. Thus, lack of PAI-1 secretion by endothelial cells significantly improves survival of the animals, and limits severity of early and late tissue damage after a localized small bowel irradiation. Furthermore, these mice partially KO for PAI-1 showed a decrease in the number of apoptotic intestinal stem cells in the hours following irradiation, a decrease in the macrophages infiltrate density one week after irradiation, and a change in the polarization of macrophages throughout the pathophysiological process. In an effort to protect healthy tissues from radiation therapy side effects, without hindering the cancer treatment, PAI-1 seems to be an obvious therapeutic target. Conceptually, this work represents the direct demonstration of the link between endothelium phenotype and radiation enteritis pathogenesis. (author)
Alterations in the glutathione metabolism could be implicated in the ischemia-induced small intestinal cell damage in horses
de la Muela Mercedes
Full Text Available Abstract Background Colic could be accompanied by changes in the morphology and physiology of organs and tissues, such as the intestine. This process might be, at least in part, due to the accumulation of oxidative damage induced by reactive oxygen (ROS and reactive nitrogen species (RNS, secondary to intestinal ischemia. Glutathione (GSH, being the major intracellular thiol, provides protection against oxidative injury. The aim of this study was to investigate whether ischemia-induced intestinal injury could be related with alterations in GSH metabolism. Results Ischemia induced a significant increase in lipid hydroperoxides, nitric oxide and carbon monoxide, and a reduction in reduced glutathione, and adenosine triphosphate (ATP content, as well as in methionine-adenosyl-transferase and methyl-transferase activities. Conclusion Our results suggest that ischemia induces harmful effects on equine small intestine, probably due to an increase in oxidative damage and proinflammatory molecules. This effect could be mediated, at least in part, by impairment in glutathione metabolism.
Mechanism for radiation-induced damage via TLR3 on the intestinal epithelium
When the small-intestinal epithelium is injured due to high-dose radiation exposure, radiation-induced gastrointestinal syndrome (GIS) such as absorption inhibition and intestinal bacterial infection occurs, and lead to subacute death. The authors immunologically analyzed the disease onset mechanism of GIS. In the small-intestinal mucosal epithelium, the intestinal epithelial stem cells of crypt structure and their daughter cells are renewed through proliferation and differentiation in the cycle of 3 or 4 days. When DNA is damaged by radiation, although p53 gene stops cell cycle and repairs DNA, cell death is induced if the repair is impossible. When stem cells perish, cell supply stops resulting in epithelial breakdown and fatal GIS. The authors analyzed the involvement in GIS of toll-like receptor (TLR) with the function of natural immunity, based on lethal γ-ray irradiation on KO mice and other methods. The authors found the mechanism, in which RNA that was leaked due to cell death caused by p53 gene elicits inflammation by activating TLR3, and leads to GIS through a wide range of cell death induction and stem cell extinction. The administration of a TLR3/RNA binding inhibitor before the irradiation of mice decreased crypt cell death and greatly improved survival rate. The administration one hour after the irradiation also showed improvement. The administration of the TLR3 specific inhibitor within a fixed time after the exposure is hopeful for the prevention of GIS, without affecting the DNA repair function of p53 gene. (A.O.)
Boswellia serrata Preserves Intestinal Epithelial Barrier from Oxidative and Inflammatory Damage.
Daniela Catanzaro
elucidates the pharmacological mechanisms mediated by BSE, in protecting intestinal epithelial barrier from inflammatory damage and supports its use as safe adjuvant in patients affected by IBD.
Increased demyelination and axonal damage in metallothionein I+II-deficient mice during experimental autoimmune encephalomyelitis
Penkowa, M; Espejo, C; Martínez-Cáceres, E M;
, oxidative stress, and apoptotic cell death during EAE were increased by MT-I+II deficiency. We now show for the first time that demyelination and axonal damage are significantly increased in MT-I+II deficient mice during EAE. Furthermore, oligodendroglial regeneration, growth cone formation, and tissue...... repair including expression of trophic factors were significantly reduced in MT-I+II-deficient mice during EAE. Accordingly, MT-I+II have protective and regenerative roles in the brain....
Ricin crosses polarized human intestinal cells and intestines of ricin-gavaged mice without evident damage and then disseminates to mouse kidneys.
Alyssa D Flora
Full Text Available Ricin is a potent toxin found in the beans of Ricinus communis and is often lethal for animals and humans when aerosolized or injected and causes significant morbidity and occasional death when ingested. Ricin has been proposed as a bioweapon because of its lethal properties, environmental stability, and accessibility. In oral intoxication, the process by which the toxin transits across intestinal mucosa is not completely understood. To address this question, we assessed the impact of ricin on the gastrointestinal tract and organs of mice after dissemination of toxin from the gut. We first showed that ricin adhered in a specific pattern to human small bowel intestinal sections, the site within the mouse gut in which a variable degree of damage has been reported by others. We then monitored the movement of ricin across polarized human HCT-8 intestinal monolayers grown in transwell inserts and in HCT-8 cell organoids. We observed that, in both systems, ricin trafficked through the cells without apparent damage until 24 hours post intoxication. We delivered a lethal dose of purified fluorescently-labeled ricin to mice by oral gavage and followed transit of the toxin from the gastrointestinal tracts to the internal organs by in vivo imaging of whole animals over time and ex vivo imaging of organs at various time points. In addition, we harvested organs from unlabeled ricin-gavaged mice and assessed them for the presence of ricin and for histological damage. Finally, we compared serum chemistry values from buffer-treated versus ricin-intoxicated animals. We conclude that ricin transverses human intestinal cells and mouse intestinal cells in situ prior to any indication of enterocyte damage and that ricin rapidly reaches the kidneys of intoxicated mice. We also propose that mice intoxicated orally with ricin likely die from distributive shock.
Bistability in autoimmune diseases
Rapin, Nicolas; Mosekilde, Erik; Lund, Ole
Autoimmune diseases damage host tissue, which, in turn, may trigger a stronger immune response. Systems characterized by such positive feedback loops can display co-existing stable steady states. In a mathematical model of autoimmune disease, one steady state may correspond to the healthy state and...... another to an autoimmune steady state characterized by widespread tissue damage and immune activation. We show how a triggering event may move the system from the healthy to the autoimmune state and how transient immunosuppressive treatment can move the system back to the healthy state....
Methotrexate-induced nitrosative stress may play a critical role in small intestinal damage in the rat
Kolli, Viswa Kalyan; Abraham, Premila [Christian Medical College, Department of Biochemistry, Vellore, Tamil Nadu (India); Rabi, Suganthy [Christian Medical College, Department of Anatomy, Vellore, Tamil Nadu (India)
Methotrexate (MTX), a structural analogue of folic acid, is widely used as a chemotherapeutic agent for leukemia and other malignancies. One of the major toxic effects of MTX is intestinal injury and enterocolitis.The mechanism of gastrointestinal toxicity of methotrexate has not been investigated completely. Therefore cancer chemotherapy has to be accompanied by symptomatic therapy such as antibiotics and anti-diarrheal drugs. It is important to investigate the mechanism by which methotrexate induces intestinal damage in order to perform cancer chemotherapy effectively by preventing the side effects. This study aimed at investigating whether nitrosative stress plays a role in methotrexate induced small intestinal damage using a rat model. Adult male rats were administered methotrexate at the dose of 7 mg/kg body weight intraperitoneally for 3 consecutive days and sacrificed 12 or 24 h after the final dose of methotrexate. Vehicle treated rats served as control. The intestinal tissue was used for light microscopic studies and markers of nitrosative stress including tissue nitrite level and nitrotyrosine. Myeloperoxidase (MPO) activity, a marker of neutrophil infiltration was also measured in intestinal homogenates. The villi were damaged at 12 h and the damage progressed and became severe at 24 h after the final dose of MTX. Biochemically, tissue nitrate was elevated fivefold at 12 h and fourfold at 24 h after the final dose of MTX as compared with control. Nitrotyrosine, measured immunohistochemically was detected in all the parts of the small intestine. Duodenum stained the most for nitrotyrosine, followed by ileum and then jejunum. The staining for nitrotyrosine was more intense at 24 h as compared with 12 h after the final dose of methotrexate. There was marked neutrophil infiltration as evidenced by increase in MPO activity in the small intestines. In conclusion, the results of the present study reveal that nitrosative stress may play a critical role in
Design of endoscopic micro-robotic end effectors: safety and performance evaluation based on physical intestinal tissue damage characteristics.
Kim, Young-Tae; Kim, Dae-Eun; Yang, Sungwook; Yoon, Eui-Sung
During the last several years, legged locomotive mechanism has been considered as one of the main self-propelling mechanisms for future endoscopic microrobots due to its superior propulsion efficiency of an endoscopic microrobot inside the intestinal track. Nevertheless, its clinical application has been largely limited since the legged locomotive mechanism utilizes an end effector which has a sharp tip to generate sufficient traction by physically penetrating and interlocking with the intestinal tissue. This can cause excessive physical tissue damage or even complete perforation of the intestinal wall that can lead to abdominal inflammation. Hence, in this work two types of new end effectors, penetration-limited end effector (PLEE) and bi-material structured end effector (BMEE) were specially designed to acquire high medical safety as well as effective traction generation performance. The microscopic end effector specimens were fabricated with micro-wire electric discharge machining process. Traction generation performance of the end effectors was evaluated by direct measurement of resistance forces during contact-sliding tests using a custom-built contact-sliding tester. The safety of the end effector design was evaluated by examination of microscopic intestinal tissue damage using a scanning electron microscope (SEM). Physical damage characteristics of the intestinal tissue and related contact physics of the end effectors were discussed. From the results, the end effectors were evaluated with respect to their prospects in future medical applications as safe end effectors as well as micro-surgical tools. PMID:24634056
Neuroprotective evaluation of Tilia americana and Annona diversifolia in the neuronal damage induced by intestinal ischemia.
Angeles-López, Guadalupe E; González-Trujano, María Eva; Déciga-Campos, Myrna; Ventura-Martínez, Rosa
Tilia americana and Annona diversifolia are plants widely distributed in Mexico and sold in markets for their medicinal properties on the central nervous system (CNS) including possible neuroprotection. Pharmacological studies have corroborated CNS activities due to flavonoid constituents, but evidence of their neuroprotector effects are lacking. This study was conducted to test aqueous and organic extracts of these two plants for neuroprotective effects in a novel experimental model of intestinal ischemia in situ. T. americana and A. diversifolia aqueous and organic extracts were administrated to guinea pigs at an oral dose of 100 and 300 mg/kg for 15 days. Twenty four hours after the last administration, the animals were anesthetized and intestinal ischemia in situ was induced by clamping for 80 min selected branches of the superior mesenteric artery. Ischemic segments placed in an in vitro organ bath were stimulated electrically (0.3 Hz frequency, 3.0 ms duration, 14 V intensity) and chemically (ACh; 1 × 10(-9) to 1×10(-5) M). Neuroprotection was considered present when the depressed contractile response of the ischemic tissue to electrical stimulation was normalized in the treated animals. Results showed that pretreatment with the T. americana hexane and aqueous extracts, but not with those from A. diversifolia, significantly improved responses of the ischemic tissue. These results suggest that T. americana possesses neuroprotective effects against neuronal damage induced by ischemia, and that flavonoids as well as non-polar constituents are involved. Our study supports the use of this plant in folk medicine and suggests its possible effectiveness for stroke prevention. PMID:23739919
Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage
P. Aparicio-Domingo (Patricia); M. Romera-Hernandez (Monica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)
textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence
Effects of glycine betaine on bone marrow death and intestinal damage by gamma rays and carbon ions
In this study, we investigated the effects of glycine betaine (GB) on bone marrow death and intestinal damage by gamma rays or carbon ions. C3H/He female mice received an i.p.-injection of GB before or after whole-body irradiation with gamma rays or 50 keV μm-1 carbon ions. The irradiated mice were observed to determine the mortality for 30 days after exposure. Mice were also killed at 3.5 days after the exposure to determine the intestinal damage. The numbers of crypts per transverse circumference were counted using a microscope. For the bone marrow death, GB (93 mg GB per mouse) significantly (p < 0.05) increased the percentage survival for both radiations. For the intestinal damage, GB (93 mg GB per mouse) significantly (p < 0.05) increased the crypt survival for gamma rays, but not for carbon ions. GB might be a potential protector against normal tissue damage as a side effect in radiotherapy. (authors)
Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron-and zinc-deficient rats
AIM: To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats,and their consequences on intestinal oxidant-antioxidant balance.METHODS: Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet (< 6.5 mg Fe and 4.0 mg Zn/kg diet) for 4 wk were randomly divided into three groups (n = 8, each) and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron + 3.3 mg zinc for 2wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of 55Fe or 65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein.Duodenal homogenates (mitochondrial and cytosolic fractions), were used to assess aconitase activity,oxidative stress, functional integrity and the response of antioxidant enzymes.RESULTS: Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone;these data provide evidence for antagonistic interactions.This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression,but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION: Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron
The relationship between intestinal parasites and some immune-mediated intestinal conditions.
Mohammadi, Rasoul; Hosseini-Safa, Ahmad; Ehsani Ardakani, Mohammad Javad; Rostami-Nejad, Mohammad
Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease (CD), inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Celiac disease is a digestive and autoimmune disorder that can damage the small intestine and characterized by a multitude gastrointestinal (GI) and extra GI symptoms. IBD (including ulcerative colitis and Crohn's disease) is a group of inflammatory conditions of the small intestine and colon. The etiology of IBD is unknown, but it may be related to instability in the intestinal microflora that leading to an immoderate inflammatory response to commensal microbiota. Irritable bowel syndrome (IBS) is a common, long-term condition of the digestive system. Bloating, diarrhoea and/or constipation are nonspecific symptoms of IBS. Various studies have shown that some intestinal parasites can effect on immune system of infected hosts and in some cases, they are able to modify and change the host's immune responses, particularly in autoimmune disorders like celiac disease and IBD. The main objective of this review is to investigate the relationship between intestinal parasites and different inflammatory bowel disorders. PMID:25926937
DNA damage and reactive nitrogen species are barriers to Vibrio cholerae colonization of the infant mouse intestine.
Bryan W Davies
Full Text Available Ingested Vibrio cholerae pass through the stomach and colonize the small intestines of its host. Here, we show that V. cholerae requires at least two types of DNA repair systems to efficiently compete for colonization of the infant mouse intestine. These results show that V. cholerae experiences increased DNA damage in the murine gastrointestinal tract. Agreeing with this, we show that passage through the murine gut increases the mutation frequency of V. cholerae compared to liquid culture passage. Our genetic analysis identifies known and novel defense enzymes required for detoxifying reactive nitrogen species (but not reactive oxygen species that are also required for V. cholerae to efficiently colonize the infant mouse intestine, pointing to reactive nitrogen species as the potential cause of DNA damage. We demonstrate that potential reactive nitrogen species deleterious for V. cholerae are not generated by host inducible nitric oxide synthase (iNOS activity and instead may be derived from acidified nitrite in the stomach. Agreeing with this hypothesis, we show that strains deficient in DNA repair or reactive nitrogen species defense that are defective in intestinal colonization have decreased growth or increased mutation frequency in acidified nitrite containing media. Moreover, we demonstrate that neutralizing stomach acid rescues the colonization defect of the DNA repair and reactive nitrogen species defense defective mutants suggesting a common defense pathway for these mutants.
Protective effect of ellagic acid and pumpkin seed oil against methotrexate-induced small intestine damage in rats.
El-Boghdady, Noha A
Gastrointestinal toxicity is one of the most serious side effects in the methotrexate (MTX) treatment. This study was designed to investigate whether ellagic acid (EA) and/or pumpkin seed oil (PSO) had a protective effect on MTX-induced small intestine damage. Forty albino rats were randomized into five groups of 8 rats each. Group I served as a normal control group. In Group II, MTX was administered as a single dose (20 mg/kg) intraperitoneally. Groups III, IV and V were pre-treated respectively with either PSO (40 mg/kg), EA (10 mg/kg) or 0.2% DMSO (vehicle control) orally every day by gavage for 5 days and then they received MTX. All animals were sacrificed 5 days after the intraperitoneal injection of MTX for histopathological examination, estimation of serum prostaglandin E2 (PGE2) level, assay of tissue malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) levels and myloperoxidase (MPO), xanthine oxidase (XO) and adenosine deaminase (AD) activities. Administration of EA and/or PSO decreased the intestinal damage, PGE2, MDA and NO levels and MPO, XO and AD activities and increased GSH level. These results suggest that EA and PSO protect the small intestine of rats from MTX-induced damage through their antioxidant and anti-inflammatory effects and thus have potential as a promising drug in the prevention of undesired side effects of MTX. PMID:22329239
Contribution of intestinal barrier damage, microbial translocation and HIV-1 infection status to an inflammaging signature.
Amanda K Steele
Full Text Available Systemic inflammation is a characteristic of both HIV-1 infection and aging ("inflammaging". Intestinal epithelial barrier damage (IEBD and microbial translocation (MT contribute to HIV-associated inflammation, but their impact on inflammaging remains unclear.Plasma biomarkers for IEBD (iFABP, MT (LPS, sCD14, T-cell activation (sCD27, and inflammation (hsCRP, IL-6 were measured in 88 HIV-1 uninfected (HIV(neg and 83 treated, HIV-1-infected (HIV(pos adults from 20-100 years old.Age positively correlated with iFABP (r = 0.284, p = 0.008, sCD14 (r = 0.646, p = <0.0001 and LPS (r = 0.421, p = 0.0002 levels in HIV(neg but not HIV(pos subjects. Age also correlated with sCD27, hsCRP, and IL-6 levels regardless of HIV status. Middle-aged HIV(pos subjects had elevated plasma biomarker levels similar to or greater than those of elderly HIV(neg subjects with the exception of sCD14. Clustering analysis described an inflammaging phenotype (IP based on iFABP, sCD14, sCD27, and hsCRP levels in HIV(neg subjects over 60 years of age. The IP in HIV(neg subjects was used to develop a classification model that was applied to HIV(pos subjects to determine whether HIV(pos subjects under 60 years of age were IP+. HIV(pos IP+ subjects were similar in age to IP- subjects but had a greater risk of cardiovascular disease (CVD based on Framingham risk score (p = 0.01.We describe a novel IP that incorporates biomarkers of IEBD, MT, immune activation as well as inflammation. Application of this novel IP in HIV-infected subjects identified a group at higher risk of CVD.
CXCR4 antagonist AMD3100 ameliorates thyroid damage in autoimmune thyroiditis in NOD.H‑2h4 mice.
Liu, Xin; Mao, Jinyuan; Han, Cheng; Peng, Shiqiao; Li, Chenyan; Jin, Ting; Fan, Chenling; Shan, Zhongyan; Teng, Weiping
CXC chemokine ligand 12 (CXCL12) and its receptor, CXC chemokine receptor 4 (CXCR4), are upregulated in mice with autoimmune thyroid diseases. However, whether this interaction is involved in the pathophysiology of autoimmune thyroiditis (AIT) remains to be elucidated. In the present study, the effects of the CXCR4 antagonist, AMD3100, in an iodine‑induced autoimmune thyroiditis model were investigated. NOD.H‑2h4 mice were randomly separated into a control, AIT and AIT+AMD3100 groups. The mice were fed with 0.05% sodium iodide water for 8 weeks to induce AIT. The AMD3100‑treated mice were administered with the CXCR4 antagonist at a dose of 10 mg/kg intraperitoneally three times a week during the experimental period. The percentages of CD19+interleukin (IL)10+ B cells and CD4+IL10+ T cells, and the mRNA expression levels of IL10 in the splenocytes were reduced in the AIT group, compared with the control group, however, they increased following AMD3100 treatment, compared with the untreated AIT group. The percentages of CD4+ T cells, CD8+ T cells, CD19+ B cells and CD8+ interferon (IFN)γ+ T cells, and the mRNA expression levels of IFNγ increased in the AIT group, compared with the control group, however, these were reduced in the AMD3100 group, compared with the AIT group. The AMD3100‑treated mice also had lower serum thyroglobulin antibody titers and reduced lymphocytic infiltration in the thyroid, compared with the untreated AIT mice. These results suggested that inhibition of this chemokine axis may offer potential as a therapeutic target for the treatment of AIT. PMID:26935473
Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage.
Booth, C; Booth, D; Williamson, S; Demchyshyn, L L; Potten, C S
Glucagon-like peptide-2 and its dipeptidyl peptidase (DP-IV) resistant analogue teduglutide are trophic for the gastrointestinal epithelium. Exposure increases villus height and crypt size and results in increased overall intestinal weight. As these effects may be mediated through stimulation of the stem cell compartment, they may promote intestinal healing and act as potential anti-mucositis agents in patients undergoing cancer chemotherapy. A study was initiated to investigate the protective effects of teduglutide on the murine small intestinal epithelium following gamma-irradiation using the crypt microcolony assay as a measure of stem cell survival and functional competence. Teduglutide demonstrated intestinotrophic effects in both CD1 and BDF1 mouse strains. In BDF1 mice, subcutaneous injection of GLP-2 or teduglutide (0.2 mg/kg/day, b.i.d.) for 14 days increased intestinal weight by 28% and resulted in comparable increases in crypt size, villus height and area. Teduglutide given daily for 6 or 14 days prior to whole body, gamma-irradiation significantly increased crypt stem cell survival when compared with vehicle-treated controls. The mean levels of protection over a range of doses provided protection factors from 1.3 to 1.5. A protective effect was only observed when teduglutide was given before irradiation. These results suggest that teduglutide has the ability to modulate clonogenic stem cell survival in the small intestine and this may have a useful clinical application in the prevention of cancer therapy-induced mucositis. PMID:15548172
Protective effect of vitamin E against ethanol-induced small intestine damage in rats.
Shirpoor, Alireza; Barmaki, Hanieh; Khadem Ansari, Mohamadhasan; Lkhanizadeh, BehrouzI; Barmaki, Haleh
The role of oxidative stress and inflammatory reaction has been reported in various ethanol-induced complications. The purpose of this study was to evaluate the effect of ethanol-induced structural alteration, oxidative stress, and inflammatory reaction on the small intestine of rats, and plausible protective effect of vitamin E to determine whether it inhibits the abnormality induced by ethanol in the small intestine. Twenty-four male wistar rats were divided into three groups, namely: Control(©), ethanol, and vitamin E treated ethanol groups. After six weeks of treatment, the small intestine length, villus height, crypt depth and muscular layer thickness, oxidative stress, and inflammatory parameters showed significant changes in the ethanol treated group compared to the control group. Vitamin E consumption along with ethanol ameliorated structural alteration of the small intestine and reduced the elevated amount of oxidative stress and inflammatory markers such as protein carbonyl, OX-LDL, IL-6, Hcy, and TNF-α. Furthermore, their total antioxidant capacity was increased significantly compared to that of the ethanol group. These findings indicate that ethanol induces the small intestine abnormality by oxidative and inflammatory stress, and that these effects can be alleviated by using vitamin E as an antioxidant and anti-inflammatory molecule. PMID:26898436
... diagnosed? A health care provider will make a diagnosis of autoimmune hepatitis based on symptoms, a physical exam, blood tests, ... 2. A health care provider will make a diagnosis of autoimmune hepatitis based on symptoms, a physical exam, blood tests, ...
Acid fibroblast growth factor reduces rat intestinal mucosal damage caused by ischemia-reperfusion insult
Wei Chen; Xiao-Bing Fu; Shi-Li Ge; Tong-Zhu Sun; Wen-Juan Li; Zhi-Yong Sheng
AIM: To detect the effects of acid fibroblast growth factor (aFGF) on apoptosis and proliferation of intestinal epithelial cells in differentiation or proliferation status to explore the protective mechanisms of aFGF.METHODS: Wistar rats were randomly divided into sham-operated control group (C, n = 6), intestinal ischemia group (I,n = 6), aFGF treatment group (A,n =48) and intestinal ischemia-reperfusion group (R, n = 48). Apoptosis of intestinal mucosal cells was determined with terminal deoxynucleotidyl transferasemediated dUTP-biotin nick-end labeling (TUNEL)technique. Proliferating cell nuclear. antigen (PCNA)protein expression and distribution were detected with immunohistochemical method. Plasma levels of D-lactate were determined with modified Brandts method.RESULTS: In A group, administration of exogenous aFGF could improve intestinal histological structure and decrease plasma D-lactate levels at 2-12 h after the reperfusion compared with R group. The apoptotic rates and PCNA protein expressions were not increased until 2 h after reperfusion and were maximal at 12 h. After reperfusion for 2-12 h, the apoptotic rates were gradually augmented along the length of jejunal crypt-villus units.Administration of aFGF could significantly reduce the apoptotic response at 2-12 h after reperfusion (P<0.05).Apoptosis rates in villus and crypt epithelial cells in A group at 12 h after reperfusion were (62.5±5.5)% and (73.2±18.6)% of those in R group, respectively.Treatment of aFGF could apparently induce protein expression of PCNA in intestinal mucosal cells of A group compared with R group during 2-12 h after reperfusion (P<0.05). There were approximately 1.3- and 1.5-times increments of PCNA expression levels in villus and crypt cells in A group at 12 h after reperfusion compared with R group, respectively.CONCLUSION: Intestinal I/R insult could lead to histological structure change and apoptotic rate increment. The protective effects of aFGF against ischemia
Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage
Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with γ-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal damage
Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage
Nakayama, Fumiaki, E-mail: firstname.lastname@example.com [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yasuda, Takeshi [Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Zakrzewska, Malgorzata [Faculty of Biotechnology, University of Wroclaw (Poland); Imamura, Toru [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)
Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal
Bo-Guang Fan
Full Text Available Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis.
Bo-Guang Fan
Full Text Available Since the autoimmune pancreatitis was introduced in 1995, it has been recognized as a form of chronic pancreatitis, which is always associated with autoimmune manifestations. As the improvement of technical and instrumental made in ultrasonography, computed tomography and magnetic resonance imaging, the diagnoses of autoimmune pancreatitis is no longer such difficult. Even though the treatment of autoimmune pancreatitis is available with a conservative therapy, there are many points that are still unclearly. These have stimulated widespread interest in this disease from gastroenterologists, endoscopists, pathologists, and prevalent research. The present article provides with our better understanding of the diagnosis and treatment of autoimmune pancreatitis.
[Polyglandular autoimmune syndromes : An overview].
Komminoth, P
Polyglandular autoimmune syndromes (PGAS), also known as autoimmune polyendocrinopathy syndromes (APS), are a heterogeneous group of rare, genetically caused diseases of the immune system which lead to inflammatory damage of various endocrine glands resulting in malfunctions. In addition, autoimmune diseases of non-endocrine organs may also be found. Early diagnosis of PGAS is often overlooked because of heterogeneous symptoms and the progressive occurrence of the individual diseases. The two most important forms of PGAS are the juvenile and adult types. The juvenile type (PGAS type 1) is caused by mutations in the autoimmune regulator (AIRE) gene on chromosome 21, exhibits geographic variations in incidence and is defined by the combination of mucocutaneous candidiasis, Addison's disease and hypoparathyroidism. In addition, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome and other autoimmune diseases can also occur. The adult form of PGAS (PGAS type 2) is a multigenetic disorder associated with some HLA haplotypes, is more common than the juvenile type, shows female predominance and exhibits the combination of type 1 diabetes, autoimmune thyroid disease, Addison's disease and other autoimmune disorders. The histological alterations in affected organs of PGAS patients are similar to findings in sporadically occurring autoimmune diseases of these organs but there are no pathognomic fine tissue findings. If patients exhibit autoimmune changes in two different endocrine glands or if there are indications of several autoimmune disorders from the patient history, it is important to consider PGAS and inform the clinicians of this suspicion. PMID:27099223
Serological Markers of Enterocyte Damage and Apoptosis in Patients With Celiac Disease, Autoimmune Diabetes Mellitus and Diabetes Mellitus Type 2
Hoffmanová, I.; Sánchez, Daniel; Hábová, Věra; Anděl, M.; Tučková, Ludmila; Tlaskalová-Hogenová, Helena
Roč. 64, č. 4 (2015), s. 537-546. ISSN 0862-8408 R&D Projects: GA ČR GA13-14608S; GA ČR(CZ) GAP304/11/1252; GA MZd(CZ) NT13483; GA TA ČR TA01010737; GA TA ČR TA04010762 Institutional support: RVO:61388971 Keywords : Cytokeratin 18 caspase-cleaved fragment * Intestinal fatty acid-binding protein * Soluble CD14 Subject RIV: ED - Physiology Impact factor: 1.293, year: 2014
Roles of Treg/Th17 Cell Imbalance and Neuronal Damage in the Visual Dysfunction Observed in Experimental Autoimmune Optic Neuritis Chronologically.
Liu, Yuanyuan; You, Caiyun; Zhang, Zhuhong; Zhang, Jingkai; Yan, Hua
Optic neuritis associated with multiple sclerosis and its animal model, experimental autoimmune optic neuritis (EAON), is characterized by inflammation, T cell activation, demyelination, and neuronal damage, which might induce permanent vision loss. Elucidating the chronological relationship among the features is critical for treatment of demyelinating optic neuritis. EAON was induced in C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein subcutaneously, and visual function was assessed by flash-visual evoked potential (F-VEP) at days 7, 11, 14, 19, 23, 28 post-immunization. Retinal ganglion cell (RGC) apoptosis was measured by terminal-deoxynucleotidyl transferase-mediated nick-end labeling. Demyelination and axonal damage were verified with myelin basic protein (MBP) and β-amyloid precursor protein staining, respectively. Real-time polymerase chain reaction quantified IL-17, IL-1β, TGF-β, FoxP3, IL-6, and IL-10 mRNA expression in the optic nerve, as well as FoxP3 and IL-17 staining. Systemic changes of Th17 and Treg cells were tested by flow cytometry in spleen. F-VEP latency was prolonged at 11 days and peaked at 23 days commensurate with demyelination. However, F-VEP amplitude was reduced at 11 days, preceding axon damage, and was exacerbated at 23 days when a peak in RGC apoptosis was detected. Th17 cells up-regulated as early as 7 days and peaked at 11 days, while Treg cells down-regulated inversely compared to Th17 cells change as verified by IL-17 and FoxP3 expression; spleen cell samples were slightly different, demonstrating marked changed at 14 days. Treg/Th17 cell imbalance in the optic nerve precedes and may initiate neuronal damage of axons and RGCs. These changes are commensurate with the appearances of visual dysfunction reflected in F-VEP and hence may offer a novel therapeutic avenue for vision preservation. PMID:26318182
Effect of certain natural antioxidants in protecting against damage caused by gamma radiation in ischemic rat intestine
Oxidative stress plays an important role in various clinical pathologies one of which is ischemia/reperfusion (I/R)- induced injury. Intestinal I/R enhances production of reactive oxygen species (ROS), inflammatory mediators and induces apoptosis. In other hand. the intestinal tract shows a high sensitivity to ionizing radiation due to a rapid cell turnover and is often implicated in radiation sickness the radiation damage may either be a consequence of a direct effect resulting in disruption of critical molecule (such as an enzyme or DNA) or an indirect effect through ionization of water molecules and formation of ROS. consequently, supplementation of antioxidants may be a beneficial approach to protect against cellular damages associated with oxidative stress. the current study was aimed to evaluate the possible protective effects of vitamin E (100 mg/kg p.o.), tomato extract (67 mg/kg. p.o.) and turmeric (100 mg/kg, p.o) against ileal injury induced in rats by total occlusion of the superior mesenteric artery for 30 min followed by reperfusion for another 30 min. Furthermore, this protective effect of the mentioned drugs was extended into injury that could happened in ileal tissues of rats exposed to (6 Gy) gamma radiation followed by intestinal I/R. Drugs were administered one daily for 14 consecutive days prior to the ischemic insult. Damage induced by I/R was manifested by depletion of ileal content of reduced glutathion (GSH) as well as Lactate dehydrogenas (LDH) activity, associated with elevation of ileal contents of thiobarbituric acid reactive substances (TBARS), nitrite, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Intestinal ischemic insults were exacerbated by radiation injury on comparing different untreated controls; except the ileal content of GSH which has elevated due to the preconditioning effect of irradiation. Vitamin E provided a significant protection against the decrease in LDH activity as well as the increase in TBARS
Immunizing effect of irradiated homogenate of schistosomal cercariae against bilharzial ultrastructural damage in mice intestinal epithelium
The present study is a parasitological and electron microscopical investigation on the immunizing effect of normal and gamma irradiated homogenate cercariae of Schistosoma Mansoni against Bilharzial complications in the fine structure of the intestinal epithelium of mice. A group of mice was exposed, through tail immersion to live wild cercariae and was used as a control, (1st group), whereas the two other groups were injected with either unirradiated (400 Gy) (2nd group) or irradiated homogenate (3rd group) of schistosoma Mansoni cercariae and challenged with wild cercariae. All group were sacrificed 6 weeks post infection and the intestinal tissues were examined by the electron microscope. The Ist group showed considerable alterations in the different organelles of the cells. Abnormalities in epithelial cells appeared in goblet cells being deformed, shorter and adhering to microvilli, with degenerative cytoplasm and nuclei. In 2nd group, the intestinal epithelial cells were injured showing dark goblet cells. swollen mitochondria whereas microvilli and nuclei appeared normal. The 3rd group displayed epithelial cells with a relatively normal ultrastructure
Ethanol in utero induces epithelial cell damage and altered kinetics in the developing rat intestine.
Estrada, G; Del Rio, J A; García-Valero, J; López-Tejero, M D
The effect of prenatal ethanol exposure on the intestinal maturation of rat fetuses was investigated to understand the nutritional alterations found in the offspring of alcoholic mothers. Female Wistar rats were maintained on solid diet and 25% ethanol solution as drinking fluid during pregnancy, and non-alcoholic isocaloric pregnant mothers were used as controls. At birth, intestines from unsuckled pups were removed for study. The weight and length of the intestine decreased significantly when ethanol was present in utero. Ultrastructural evaluation of the epithelium revealed loss of contact between neighboring enterocytes and abnormal dilation of the cisternae of the Golgi apparatus in ethanol-exposed pups. Further, increased lysosome-like vesiculation and enhanced lysosomal beta-galactosidase activity was observed in these neonates. The total number of absorptive enterocytes in the epithelium was reduced by 30% in ethanol-exposed neonates as compared to controls, due to altered cell growth and death during fetal life. Ethanol in utero stimulated epithelial cell migration which compensated cell loss, as demonstrated by 5'-Bromodeoxyuridine labeling. These findings could have important implications for the assimilation of nutrients and failure to thrive in infants with fetal alcohol syndrome. PMID:9035346
Petzold, Axel; Wong, Sui; Plant, Gordon T
There are a number of autoimmune disorders which can affect visual function. There are a very large number of mechanisms in the visual pathway which could potentially be the targets of autoimmune attack. In practice it is the retina and the anterior visual pathway (optic nerve and chiasm) that are recognised as being affected in autoimmune disorders. Multiple Sclerosis is one of the commonest causes of visual loss in young adults because of the frequency of attacks of optic neuritis in that condition, however the basis of the inflammation in Multiple Sclerosis and the confirmation of autoimmunity is lacking. The immune process is known to be highly unusual in that it is not systemic and confined to the CNS compartment. Previously an enigmatic partner to Multiple Sclerosis, Neuromyelitis Optica is now established to be autoimmune and two antibodies - to Aquaporin4 and to Myelin Oligodendrocyte Glycoprotein - have been implicated in the pathogenesis. The term Chronic Relapsing Inflammatory Optic Neuropathy is applied to those cases of optic neuritis which require long term immunosuppression and hence are presumed to be autoimmune but where no autoimmune pathogenesis has been confirmed. Optic neuritis occurring post-infection and post vaccination and conditions such as Systemic Lupus Erythematosus and various vasculitides may cause direct autoimmune attack to visual structures or indirect damage through occlusive vasculopathy. Chronic granulomatous disorders such as Sarcoidosis affect vision commonly by a variety of mechanisms, whether and how these are placed in the autoimmune panoply is unknown. As far as the retina is concerned Cancer Associated Retinopathy and Melanoma Associated Retinopathy are well characterised clinically but a candidate autoantibody (recoverin) is only described in the former disorder. Other, usually monophasic, focal retinal inflammatory disorders (Idiopathic Big Blind Spot Syndrome, Acute Zonal Occult Outer Retinopathy and Acute Macular
Silica, Silicosis, and Autoimmunity.
Pollard, Kenneth Michael
Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response, which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements, suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, and autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However, numerous questions remain unanswered. PMID:27014276
Silica, Silicosis and Autoimmunity.
Kenneth Michael Pollard
Full Text Available Inhalation of dust containing crystalline silica is associated with a number of acute and chronic diseases including systemic autoimmune diseases. Evidence for the link with autoimmune disease comes from epidemiological studies linking occupational exposure to crystalline silica dust with the systemic autoimmune diseases SLE, SSc and RA. Although little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease, there is a voluminous literature on silica exposure and silicosis that may help identify immune processes that precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of silica particles in the alveoli of the lung. Ingestion of these particles by macrophages initiates an inflammatory response which stimulates fibroblasts to proliferate and produce collagen. Silica particles are encased by collagen leading to fibrosis and the nodular lesions characteristic of the disease. The steps in the development of silicosis, including acute and chronic inflammation and fibrosis, have different molecular and cellular requirements suggesting that silica-induced inflammation and fibrosis may be mechanistically separate. Significantly, it is unclear whether silica-induced inflammation and fibrosis contribute similarly to the development of autoimmunity. Nonetheless, the findings from human and animal model studies are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, pulmonary inflammation leading to activation of adaptive immunity, breaking of tolerance, autoantibodies and tissue damage. The variable frequency of these immunological features following silica exposure suggests substantial genetic involvement and gene/environment interaction in silica-induced autoimmunity. However numerous questions remain unanswered.
Effects of garlic oil and two of its major organosulfur compounds, diallyl disulfide and diallyl trisulfide, on intestinal damage in rats injected with endotoxin
Garlic and its active components are known to possess antioxidant and antiinflammatory effects. The present study investigated the effects of garlic oil and its organosulfur compounds on endotoxin-induced intestinal mucosal damage. Wistar rats received by gavage 50 or 200 mg/kg body weight garlic oil (GO), 0.5 mmol/kg body weight diallyl disulfide or diallyl trisulfide, or the vehicle (corn oil; 2 ml/kg body weight) every other day for 2 weeks before being injected with endotoxin (i.p., 5 mg/kg body weight). Control rats were administered with corn oil and were injected with sterile saline. Samples for the measurement of proinflammatory cytokines were collected 3 h after injection, and all other samples were collected 18 h after injection. The low dose of GO suppressed endotoxin-induced inducible nitric oxide synthase (iNOS) activity, ulceration, and apoptosis in the intestinal mucosa (P < 0.05). The high dose of GO significantly lowered the peripheral level of nitrate/nitrite and endotoxin-induced iNOS activity in the intestinal mucosa (P < 0.05) but worsened intestinal mucosal damage accompanied by elevated peripheral proinflammatory cytokines. Diallyl trisulfide but not diallyl disulfide showed similar toxic effect as that of high-dose GO. These results suggest the preventive effect and possible toxicity of garlic oil and its organosulfur compounds in endotoxin-induced systemic inflammation and intestinal damage
A Pilot Study on the Noninvasive Evaluation of Intestinal Damage in Celiac Disease Using I-FABP and L-FABP
Derikx, Joep P. M.; Vreugdenhil, Atita C. E.; Van den Neucker, Anita M.; Grootjans, Joep; van Bijnen, Annemarie A.; Damoiseaux, Jan G. M. C.; van Heurn, L. W. Ernest; Heineman, Erik; Buurman, Wim A.
Background and Goals: In the clinical management of celiac disease, new noninvasive tools for evaluation of intestinal damage are needed for diagnosis and for follow-up of diet effects. Fatty acid binding proteins (FABP) are potentially useful for this purpose as these arc small cytosolic proteins p
Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens.
Shigeta, Mika; Saiki, Minoru; Tsuruta, Daisuke; Ohata, Chika; Ishii, Norito; Ono, Fumitake; Hamada, Takahiro; Dainichi, Teruki; Furumura, Minao; Zone, John J; Karpati, Sarolta; Sitaru, Cassian; Hashimoto, Takashi
Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten-sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme-linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti-endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten-sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten-sensitive enteropathy and no DH-specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH. PMID:22963165
Autophagy Deficiency Diminishes Indomethacin-Induced Intestinal Epithelial Cell Damage through Activation of the ERK/Nrf2/HO-1 Pathway.
Harada, Satoshi; Nakagawa, Takatoshi; Yokoe, Shunichi; Edogawa, Shoko; Takeuchi, Toshihisa; Inoue, Takuya; Higuchi, Kazuhide; Asahi, Michio
Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause epithelial cell damage in the stomach, intestine, and colon. NSAIDs are reported to induce autophagy and apoptosis in intestinal epithelial cells; however, their role in cell damage is poorly understood. To examine the role of autophagy in cell damage, we used autophagy-related gene Atg5-conditional knockout mice, in which the Atg5 gene is only knocked out in intestinal epithelial cells. In an indomethacin (IM)-induced gastrointestinal ulcer mouse model, intestinal epithelium damage was reduced in Atg5-conditional knockout mice compared with wild-type mice. IM-induced damage in IEC6 rat intestinal epithelial cells was reduced when Atg5 was silenced (IEC6shAtg5 cells). Western blot analyses indicated that IM-induced apoptosis decreased, and the potent, oxidative stress-related extracellular signal-regulated kinase (ERK)/nuclear factor-erythroid2-like2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway was upregulated in IEC6shAtg5 cells. An experiment using a reactive oxygen species (ROS)-sensitive fluorescent dye in IEC6shAtg5 cells revealed that the amount of ROS at the baseline and the rate of increase after IM treatment were lower than in intact IEC6 cells. The mitochondrial membrane potential at the baseline and the reduction rate in IM-treated IEC6shAtg5 cells were lower than in intact IEC6 cells, indicating that autophagy deficiency increased ROS production caused by mitochondrial disturbance. Furthermore, MnTMPyP, a manganese-superoxide dismutase mimetic, significantly inhibited IM-induced autophagy and subsequent apoptosis as well as activation of the ERK/Nrf2/HO-1 pathway. These data suggest that autophagy deficiency and subsequent activation of the ERK/Nrf2/HO-1 pathway diminished IM-induced, apoptosis-mediated intestinal epithelial cell damage, and genetic analyses of single nucleotide polymorphisms in autophagy-related genes could predict NSAID-induced intestinal injury. PMID:26404472
Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways
Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: email@example.com [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)
Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.
Sulfated polysaccharide from the marine algae Hypnea musciformis inhibits TNBS-induced intestinal damage in rats.
V Brito, Tarcisio; Barros, Francisco C N; Silva, Renan O; Dias Júnior, Genilson J; C Júnior, José Simião; Franco, Álvaro X; Soares, Pedro M G; Chaves, Luciano S; Abreu, Clara M W S; de Paula, Regina C M; Souza, Marcellus H L P; Freitas, Ana Lúcia P; R Barbosa, André Luiz
Sulfated polysaccharides extracted from seaweed have important pharmacological properties. Thus, the aim of this study was to characterize the sulfated polysaccharide (PLS) from the algae Hypnea musciformis and evaluate its protective effect in colitis induced by trinitrobenzene sulfonic acid in rats. The sulfated polysaccharide possess a high molecular mass (1.24×10(5)gmol(-1)) and is composed of a κ-carrageenan, as depicted by FT-IR and NMR spectroscopic data. PLS was administered orally (10, 30, and 60mg/kg, p.o.) for three days, starting before TNBS (trinitrobenzene sulfonic acid) instillation (day 1). The rats were killed on day three, the portion of distal colon (5cm) was excised and evaluated macroscopic scores and wet weight. Then, samples of the intestinal were used for histological evaluation and quantification of glutathione, malonyldialdehyde acid, myeloperoxidase, nitrate/nitrite and cytokines. Our results demonstrate that PLS reduced the colitis and all analyzed biochemical parameters. Thus, we concluded that the PLS extracted from the marine algae H. musciformis reduced the colitis in animal model and may have an important promising application in the inflammatory bowel diseases. PMID:27474644
Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling
Nakayama, Fumiaki, E-mail: email@example.com [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Yasuda, Takeshi [Radiation Emergency Medicine Research Program, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Fujita, Mayumi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan); Asada, Masahiro [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Meineke, Viktor [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany); Imamura, Toru [Signaling Molecules Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, Chiba (Japan)
Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the
Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling
Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation with γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the
Alpha1A-adrenergic receptor-directed autoimmunity induces left ventricular damage and diastolic dysfunction in rats.
Katrin Wenzel
Full Text Available BACKGROUND: Agonistic autoantibodies to the alpha(1-adrenergic receptor occur in nearly half of patients with refractory hypertension; however, their relevance is uncertain. METHODS/PRINCIPAL FINDINGS: We immunized Lewis rats with the second extracellular-loop peptides of the human alpha(1A-adrenergic receptor and maintained them for one year. Alpha(1A-adrenergic antibodies (alpha(1A-AR-AB were monitored with a neonatal cardiomyocyte contraction assay by ELISA, and by ERK1/2 phosphorylation in human alpha(1A-adrenergic receptor transfected Chinese hamster ovary cells. The rats were followed with radiotelemetric blood pressure measurements and echocardiography. At 12 months, the left ventricles of immunized rats had greater wall thickness than control rats. The fractional shortening and dp/dt(max demonstrated preserved systolic function. A decreased E/A ratio in immunized rats indicated a diastolic dysfunction. Invasive hemodynamics revealed increased left ventricular end-diastolic pressures and decreased dp/dt(min. Mean diameter of cardiomyocytes showed hypertrophy in immunized rats. Long-term blood pressure values and heart rates were not different. Genes encoding sarcomeric proteins, collagens, extracellular matrix proteins, calcium regulating proteins, and proteins of energy metabolism in immunized rat hearts were upregulated, compared to controls. Furthermore, fibrosis was present in immunized hearts, but not in control hearts. A subset of immunized and control rats was infused with angiotensin (Ang II. The stressor raised blood pressure to a greater degree and led to more cardiac fibrosis in immunized, than in control rats. CONCLUSIONS/SIGNIFICANCE: We show that alpha(1A-AR-AB cause diastolic dysfunction independent of hypertension, and can increase the sensitivity to Ang II. We suggest that alpha(1A-AR-AB could contribute to cardiovascular endorgan damage.
... Some examples of CAM are herbal products, chiropractic , acupuncture , and hypnosis . If you have an autoimmune disease, ... Toll-Free: 877-226-4267 National Institute of Diabetes and Digestive and Kidney Diseases, NIH, HHS Phone: ...
To observe the intensity of the inflammatory reaction caused by neonatal urine and meconium on the intestinal wall of rats in order to understand etiology of intestinal damage in gastroschisis
Devdas S Samala
Full Text Available Objectives: The aim of this experimental study was to observe the intensity of the inflammatory reaction caused by neonatal urine and meconium on the intestinal wall of rats to better understand etiology of intestinal damage in gastroschisis. Materials and Methods: A total of 24 adult Wistar rats were used as experimental models to simulate the effect of exposed bowel in cases of gastroschisis. The peritoneal cavity of the rats was injected with substances which constitute human amniotic fluid to study the effect on the bowel. Sterile urine and meconium were obtained from newborn humans. The rats were divided into four groups according to the material to be injected. In Group I (Control group 3 mL of distilled water was injected, in Group II (Urine group 3 mL of neonatal urine was injected, in Group III (Meconium group 5% meconium suspension was injected, while in Group IV, a combination of 5% meconium suspension and urine was injected. A total of 3mL solution was injected into the right inferior quadrant twice a day for 5 days. The animals were sacrificed on the 6 th day by a high dose of thiopentone sodium. A segment of small bowel specimen was excised, fixed in paraffin, and stained with hematoxylin-eosin for microscopic analysis for determination of the degree of inflammatory reaction in the intestinal wall. All pathology specimens were studied by the same pathologist. Results: The maximum bowel damage was seen in Group II (Urine group in the form of serositis, severe enteritis, parietal necrosis, and peeling. A lesser degree of damage was observed in Group III (Meconium group as mild enteritis (mild lymphoid hyperplasia. The least damage was seen in Group IV (Combination of meconium and urine and Group I (Control group. Conclusion: The intraabdominal injection of neonatal human urine produces significant inflammatory reactions in the intestinal wall of rats.
Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation
Ponemone, Venkatesh; Fayad, Raja; Gove, Melissa E.; Pini, Maria [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States); Fantuzzi, Giamila, E-mail: email@example.com [Department of Kinesiology and Nutrition, University of Illinois at Chicago, Chicago, IL 60612 (United States)
Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4{sup +}, CD8{sup +} and CD4{sup +}CD8{sup +} T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.
Effect of adiponectin deficiency on intestinal damage and hematopoietic responses of mice exposed to gamma radiation
Adiponectin (APN) is an adipose tissue-derived cytokine that regulates insulin sensitivity and inflammation. It is also involved in modulation of cell proliferation by binding to various growth factors. Based on its known effects in modulating cell proliferation and oxidative stress, APN may potentially be involved in regulating tissue damage and repair following irradiation. Adiponectin KO mice and their WT littermates were exposed to a single whole-body dose of 3 or 6 Gy gamma radiation. Radiation-induced alterations were studied in jejunum, blood, bone marrow and thymus at days 1 and 5 post-irradiation and compared with sham-irradiated groups. In WT mice, irradiation did not significantly alter serum APN levels while inducing a significant decrease in serum leptin. Irradiation caused a significant reduction in thymocyte cellularity, with concomitant decrease in CD4+, CD8+ and CD4+CD8+ T cell populations, with no significant differences between WT and APN KO mice. Irradiation resulted in a significantly higher increase in the frequency of micronucleated reticulocytes in the blood of APN KO compared with WT mice, whereas frequency of micronucleated normochromatic erythrocytes in the bone marrow at day 5 was significantly higher in WT compared with APN KO mice. Finally, irradiation induced similar alterations in villus height and crypt cell proliferation in the jejunum of WT and APN KO mice. Jejunum explants from sham-irradiated APN KO mice produced higher levels of IL-6 compared with tissue from WT animals, but the difference was no longer apparent following irradiation. Our data indicate that APN deficiency does not play a significant role in modulating radiation-induced gastrointestinal injury in mice, while it may participate in regulation of damage to the hematopoietic system.
Crisp, Sarah J; Kullmann, Dimitri M; Vincent, Angela
Autoantibodies targeting proteins at the neuromuscular junction are known to cause several distinct myasthenic syndromes. Recently, autoantibodies targeting neurotransmitter receptors and associated proteins have also emerged as a cause of severe, but potentially treatable, diseases of the CNS. Here, we review the clinical evidence as well as in vitro and in vivo experimental evidence that autoantibodies account for myasthenic syndromes and autoimmune disorders of the CNS by disrupting the functional or structural integrity of synapses. Studying neurological and psychiatric diseases of autoimmune origin may provide new insights into the cellular and circuit mechanisms underlying a broad range of CNS disorders. PMID:26806629
Krarup, Therese; Hagen, Claus
Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women...... during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either...
2005164 Optimal cut-point of glutamic acid decar-boxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (LADA). LI Xia(李霞), et al. Dept Endocrinol, 2nd Xiangya Hosp, Central South Univ, Changsha, 410011. Chin J Diabetes, 2005;13(1) :34-38. Objective: To investigate the optimal cut-point of glutamate decarboxylase antibody (GAD-Ab) for differentiating two subtypes of latent autoimmune diabetes in adults (I. ADA). Methods: The frequency
Mouse models of intestinal inflammation and cancer.
Westbrook, Aya M; Szakmary, Akos; Schiestl, Robert H
Chronic inflammation is strongly associated with approximately one-fifth of all human cancers. Arising from combinations of factors such as environmental exposures, diet, inherited gene polymorphisms, infections, or from dysfunctions of the immune response, chronic inflammation begins as an attempt of the body to remove injurious stimuli; however, over time, this results in continuous tissue destruction and promotion and maintenance of carcinogenesis. Here, we focus on intestinal inflammation and its associated cancers, a group of diseases on the rise and affecting millions of people worldwide. Intestinal inflammation can be widely grouped into inflammatory bowel diseases (ulcerative colitis and Crohn's disease) and celiac disease. Long-standing intestinal inflammation is associated with colorectal cancer and small-bowel adenocarcinoma, as well as extraintestinal manifestations, including lymphomas and autoimmune diseases. This article highlights potential mechanisms of pathogenesis in inflammatory bowel diseases and celiac disease, as well as those involved in the progression to associated cancers, most of which have been identified from studies utilizing mouse models of intestinal inflammation. Mouse models of intestinal inflammation can be widely grouped into chemically induced models; genetic models, which make up the bulk of the studied models; adoptive transfer models; and spontaneous models. Studies in these models have lead to the understanding that persistent antigen exposure in the intestinal lumen, in combination with loss of epithelial barrier function, and dysfunction and dysregulation of the innate and adaptive immune responses lead to chronic intestinal inflammation. Transcriptional changes in this environment leading to cell survival, hyperplasia, promotion of angiogenesis, persistent DNA damage, or insufficient repair of DNA damage due to an excess of proinflammatory mediators are then thought to lead to sustained malignant transformation. With
Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad;
Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...
Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand.
Diego J Martinel Lamas
Full Text Available Based on previous data on the histamine radioprotective effect on highly radiosensitive tissues, in the present work we aimed at investigating the radioprotective potential of the H4R ligand, JNJ7777120, on ionizing radiation-induced injury and genotoxic damage in small intestine, salivary glands and hematopoietic tissue. For that purpose, rats were divided into 4 groups. JNJ7777120 and JNJ7777120-irradiated groups received a daily subcutaneous JNJ7777120 injection (10 mg/kg starting 24 h before irradiation. Irradiated groups received a single dose of 5 Gy on whole-body using Cesium-137 source and were sacrificed 3 or 30 days after irradiation. Tissues were removed, fixed, stained with hematoxylin and eosin or PAS staining and histological characteristics were evaluated. Proliferative and apoptotic markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate DNA damage. Submandibular gland (SMG function was evaluated by methacholine-induced salivation. Results indicate that JNJ7777120 treatment diminished mucosal atrophy and preserved villi and the number of crypts after radiation exposure (240±8 vs. 165±10, P<0.01. This effect was associated to a reduced apoptosis and DNA damage in intestinal crypts. JNJ7777120 reduced radiation-induced aplasia, preserving medullar components and reducing formation of micronucleus and also it accelerated bone marrow repopulation. Furthermore, it reduced micronucleus frequency in peripheral blood (27±8 vs. 149±22, in 1,000 erythrocytes, P<0.01. JNJ7777120 completely reversed radiation-induced reduced salivation, conserving glandular mass with normal histological appearance and reducing apoptosis and atrophy of SMG. JNJ7777120 exhibits radioprotective effects against radiation-induced cytotoxic and genotoxic damages in small intestine, SMG and hematopoietic tissues and, thus, could be of clinical value for patients undergoing radiotherapy.
Leypoldt, Frank; Wandinger, Klaus-Peter; Bien, Christian G; Dalmau, Josep
The term autoimmune encephalitis is used to describe a group of disorders characterised by symptoms of limbic and extra-limbic dysfunction occurring in association with antibodies against synaptic antigens and proteins localised on the neuronal cell surface. In recent years there has been a rapidly expanding knowledge of these syndromes resulting in a shift in clinical paradigms and new insights into pathogenic mechanisms. Since many patients respond well to immunosuppressive treatment, the r...
Fjordside, Eva; Novovic, Srdan; Schmidt, Palle Nordblad;
Autoimmune pancreatitis (AIP) is a rare inflammatory disease. AIP has characteristic histology, serology and imaging findings. Two types of AIP exist, type 1, which is a part of the systemic immunoglobulin G4-related disease, and type 2, which is only localized to the pancreas. Patients with type 1...... are predominantly older men, have involvement of other organs and more often experience relapse than patients with type 2. Both types respond well to steroid treatment. The most important differential diagnose is pancreatic cancer....
Histological damage and inflammatory response elicited by Monobothrium wageneri (Cestoda in the intestine of Tinca tinca (Cyprinidae
Sayyaf Dezfuli Bahram
Full Text Available Abstract Background Among the European cyprinids, tench, Tinca tinca (L., and the pathological effects their cestodes may effect, have received very little or no attention. Most literature relating to Monobothrium wageneri Nybelin, 1922, a common intestinal cestode of tench, for example, has focused on aspects of its morphology rather than on aspects of the host-parasite interaction. Results Immunopathological and ultrastructural studies were conducted on the intestines of 28 tench, collected from Lake Piediluco, of which 16 specimens harboured tight clusters of numerous M. wageneri attached to the intestinal wall. The infection was associated with the degeneration of the mucosal layer and the formation of raised inflammatory swelling surrounding the worms. At the site of infection, the number of granulocytes in the intestine of T. tinca was significantly higher than the number determined 1 cm away from the site of infection or the number found in uninfected fish. Using transmission electron microscopy, mast cells and neutrophils were frequently observed in close proximity to, and inside, the intestinal capillaries; often these cells were in contact with the cestode tegument. At the host-parasite interface, no secretion from the parasite's tegument was observed. Intense degranulation of the mast cells was seen within the submucosa and lamina muscularis, most noticeably at sites close to the tegument of the scolex. In some instances, rodlet cells were encountered in the submucosa. In histological sections, hyperplasia of the mucous cells, notably those giving an alcian blue positive reaction, were evident in the intestinal tissues close to the swelling surrounding the worms. Enhanced mucus secretion was recorded in the intestines of infected tench. Conclusions The pathological changes and the inflammatory cellular response induced by the caryophyllidean monozoic tapeworm M. wageneri within the intestinal tract of an Italian population of wild
Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine
Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz
Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the act...
[Diagnostics of autoimmune diseases].
Beleznay, Zsuzsanna; Regenass, Stephan
Autoantibodies play a key role in diagnostic laboratories as markers of autoimmune diseases. In addition to their role as markers they mediate diverse effects in vivo. Autoantibodies with protective effect have been described. Natural protective IgM autoantibodies against tumour-antigens of malignant cells or their precursors may contribute to increased survival rates of carcinoma patients. In a mouse model of systemic lupus erythematosus it has been shown that anti-dsDNA IgM autoantibodies protect from glomerular damage. In contrast, a direct pathogenic role of autoantibodies has been well established e.g. in myasthenia gravis or in Goodpasture syndrome. Similarly autoantibodies against SSA Ro52 are detrimental in neonatal lupus erythematosus with congenital heart block. Moreover, putatively protective autoantibodies may become pathogenic during the course of the disease such as the onconeuronal autoantibodies whose pathogenicity depends on their compartmentalisation. In patients with paraneoplastic syndromes tumour cells express proteins that are also naturally present in the brain. Anti-tumour autoantibodies which temporarily suppress tumour growth can provoke an autoimmune attack on neurons once having crossed the blood-brain barrier and cause specific neurological symptoms. Only a restricted number of autoantibodies are useful follow-up markers for the effectiveness of treatment in autoimmune diseases. Certain autoantibodies hold prognostic value and appear years or even decades before the diagnosis of disease such as the antimitochondrial antibodies in primary biliary cirrhosis or anti-citrullinated protein (CCP)-antibodies in rheumatoid arthritis. It is crucial to know whether the autoantibodies in question recognise linear or conformational epitopes in order to choose the appropriate detection methods. Indirect immunofluorescence microscopy remains a very useful tool for confirmation of results of commercially available immunoassays and for detection of
Autoimmune liver disease panel
Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...
Update in Endocrine Autoimmunity
Anderson, Mark S.
Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases.
Lubiprostone prevents nonsteroidal anti-inflammatory drug-induced small intestinal damage by suppressing the expression of inflammatory mediators via EP4 receptors.
Hayashi, Shusaku; Kurata, Naoto; Yamaguchi, Aya; Amagase, Kikuko; Takeuchi, Koji
Lubiprostone, a bicyclic fatty acid derived from prostaglandin E1, has been used to treat chronic constipation and irritable bowel syndrome, and its mechanism of action has been attributed to the stimulation of intestinal fluid secretion via the activation of the chloride channel protein 2/cystic fibrosis transmembrane regulator (ClC-2/CFTR) chloride channels. We examined the effects of lubiprostone on indomethacin-induced enteropathy and investigated the functional mechanisms involved, including its relationship with the EP4 receptor subtype. Male Sprague-Dawley rats were administered indomethacin (10 mg/kg p.o.) and killed 24 hours later to examine the hemorrhagic lesions that developed in the small intestine. Lubiprostone (0.01-1 mg/kg) was administered orally twice 30 minutes before and 9 h after the indomethacin treatment. Indomethacin markedly damaged the small intestine, accompanied by intestinal hypermotility, a decrease in mucus and fluid secretion, and an increase in enterobacterial invasion as well as the up-regulation of inducible nitric-oxide synthase (iNOS) and tumor necrosis factor α (TNFα) mRNAs. Lubiprostone significantly reduced the severity of these lesions, with the concomitant suppression of the functional changes. The effects of lubiprostone on the intestinal lesions and functional alterations were significantly abrogated by the coadministration of AE3-208 [4-(4-cyano-2-(2-(4-fluoronaphthalen-1-yl)propionylamino)phenyl)butyric acid], a selective EP4 antagonist, but not by CFTR(inh)-172, a CFTR inhibitor. These results suggest that lubiprostone may prevent indomethacin-induced enteropathy via an EP4 receptor-dependent mechanism. This effect may be functionally associated with the inhibition of intestinal hypermotility and increase in mucus/fluid secretion, resulting in the suppression of bacterial invasion and iNOS/TNFα expression, which are major pathogenic events in enteropathy. The direct activation of CFTR/ClC-2 chloride channels is not
The novel porcine Lactobacillus sobrius strain protects intestinal cells from enterotoxigenic Escherichia coli K88 infection and prevents membrane barrier damage.
Roselli, Marianna; Finamore, Alberto; Britti, Maria Serena; Konstantinov, Sergey R; Smidt, Hauke; de Vos, Willem M; Mengheri, Elena
Lactobacilli have a potential to overcome intestinal disorders; however, the exact mode of action is still largely unknown. In this study, we have used the intestinal porcine intestinal IPEC-1 epithelial cells as a model to investigate a possible protective activity of a new Lactobacillus species, the L. sobrius DSM 16698(T), against intestinal injury induced by enterotoxigenic Escherichia coli (ETEC) K88 infection and the underlying mechanisms. Treatment of infected cells with L. sobrius strongly reduced the pathogen adhesion. L. sobrius was also able to prevent the ETEC-induced membrane damage by inhibiting delocalization of zonula occludens (ZO)-1, reduction of occludin amount, rearrangement of F-actin, and dephosphorylation of occludin caused by ETEC. RT-PCR and ELISA experiments showed that L. sobrius counteracted the ETEC-induced increase of IL-8 and upregulated the IL-10 expression. The involvement of IL-8 in the deleterious effects of ETEC was proven by neutralization of IL-8 with a specific antibody. A crucial role of IL-10 was indicated by blockage of IL-10 production with neutralizing anti-IL-10 antibody that fully abrogated the L. sobrius protection. L. sobrius was also able to inhibit the internalization of ETEC, which was likely favored by the leaking barrier. The protective effects were not found with L. amylovorus DSM 20531(T) treatment, a strain derived from cattle waste but phylogenetically closely related to L. sobrius. Together, the data indicate that L. sobrius exerts protection against the harmful effects of ETEC by different mechanisms, including pathogen adhesion inhibition and maintenance of membrane barrier integrity through IL-10 regulation. PMID:18029488
Detlefsen, Sönke; Drewes, Asbjørn M
bile duct. Obstructive jaundice is a common symptom at presentation, and pancreatic cancer represents an important clinical differential diagnosis. In late stages of the disease, the normal pancreatic parenchyma is often replaced by large amounts of fibrosis. Histologically, there seem to be two...... AIP responds to steroid treatment, also a trial with steroids, can help to differentiate AIP from pancreatic cancer. OUTLOOK AND DISCUSSION: This review presents the pathological, radiologic and laboratory findings of AIP. Moreover, the treatment and pathogenesis are discussed.......BACKGROUND: Autoimmune pancreatitis (AIP) is a relatively newly recognized type of pancreatitis that is characterized by diffuse or focal swelling of the pancreas due to lymphoplasmacytic infiltration and fibrosis of the pancreatic parenchyma. MATERIAL AND METHODS: A PubMed literature search was...
Applications of Next-generation Sequencing in Systemic Autoimmune Diseases
Yiyangzi Ma; Na Shi; Mengtao Li; Fei Chen; Haitao Niu
Systemic autoimmune diseases are a group of heterogeneous disorders caused by both genetic and environmental factors. Although numerous causal genes have been identified by genome-wide association studies (GWAS), these susceptibility genes are correlated to a relatively low disease risk, indicating that environmental factors also play an important role in the pathogen-esis of disease. The intestinal microbiome, as the main symbiotic ecosystem between the host and host-associated microorganisms, has been demonstrated to regulate the development of the body's immune system and is likely related to genetic mutations in systemic autoimmune diseases. Next-generation sequencing (NGS) technology, with high-throughput capacity and accuracy, provides a powerful tool to discover genomic mutations, abnormal transcription and intestinal microbiome identification for autoimmune diseases. In this review, we briefly outlined the applications of NGS in systemic autoimmune diseases. This review may provide a reference for future studies in the pathogenesis of systemic autoimmune diseases.
Inhibition of long myosin light-chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury
Zahs, Anita; Bird, Melanie D.; Ramirez, Luis; Turner, Jerrold R; Choudhry, Mashkoor A.; Kovacs, Elizabeth J
Laboratory evidence suggests that intestinal permeability is elevated following either binge ethanol exposure or burn injury alone, and this barrier dysfunction is further perturbed when these insults are combined. We and others have previously reported a rise in both systemic and local proinflammatory cytokine production in mice after the combined insult. Knowing that long myosin light-chain kinase (MLCK) is important for epithelial barrier maintenance and can be activated by proinflammatory...
Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease.
Mathewson, Nathan D; Jenq, Robert; Mathew, Anna V; Koenigsknecht, Mark; Hanash, Alan; Toubai, Tomomi; Oravecz-Wilson, Katherine; Wu, Shin-Rong; Sun, Yaping; Rossi, Corinne; Fujiwara, Hideaki; Byun, Jaeman; Shono, Yusuke; Lindemans, Caroline; Calafiore, Marco; Schmidt, Thomas C; Honda, Kenya; Young, Vincent B; Pennathur, Subramaniam; van den Brink, Marcel; Reddy, Pavan
The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity. PMID:26998764
Anaya, Juan-Manuel
Although autoimmune diseases exhibit contrasting epidemiological features, pathology, and clinical manifestations, three lines of evidence demonstrate that these diseases share similar immunogenetic mechanisms (that is, autoimmune tautology). First, clinical evidence highlights the co-occurrence of distinct autoimmune diseases within an individual (that is, polyautoimmunity) and within members of a nuclear family (that is, familial autoimmunity). Second, physiopathologic evidence indicates th...
Bioprotection by local and whole-body preheating. Bioprotection of damage to mice tongue from burning by local preheating of oral cavity and of radiation damage of small intestine from whole-body preheating
We have reported the cytoprotective effects of heat shock protein (HSP) 70 on various stress damage induced by mild heating. In this study, we examined the cytoprotective effects of HSP 70 induced by the local preheating of the oral cavity of mice at 42 deg C for 30 mm, and the following results were obtained. We also examined the cytoprotective effects against radiation injury by whole-body preheating at 41.3-41.6 deg C for 30 min. The concentration of HSP 70 in lymphocytes was increased 2 days after preheating, but not significantly. The concentration of HSP 70 in masseter muscle was significantly increased 2 days after preheating. Under non-heat stress (control), tongue muscle was strongly stained with immunoblotting of HSP 72 antibody, an antibody of induced-type HSP 70. Tongue damage and weight loss of the mice in the preheating group, whose tongues were burned, were less than in the control group. These results showed that HSP 70 induced by local preheating of the oral cavity protected against tongue damage from burning. Radiation injury of the small intestine on HE stain of whole-body radiated mice was obviously reduced by whole-body preheating. Decrease of the ratio of the villus length to the crypt of whole body-irradiated mice was significantly improved by whole-body preheating. From these results, it was concluded that local and whole-body preheating were useful for cytoprotection from stressful damage. (author)
Radioprotector WR-2721 and mitigating peptidoglycan synergistically promote mouse survival through the amelioration of intestinal and bone marrow damage
The identification of an agent effective for the treatment of intestinal and bone marrow injury following radiation exposure remains a major issue in radiological medicine. In this study, we evaluated the therapeutic impact of single agent or combination treatments with 2-(3-aminopropylamino) ethylsulphanyl phosphonic acid (WR-2721) and peptidoglycan (PGN, a toll-like receptor 2 (TLR-2) agonist) on radiation-induced injury of the intestine and bone marrow in lethally irradiated male C57BL/6 mice. A dose of 3 mg of WR-2721 per mouse (167 mg/kg, intraperitoneally) was given 30 min before irradiation, and 30 μg of PGN per mouse (1.7 mg/kg) was injected intraperitoneally 24 h after 10 Gy irradiation. Bone marrow cluster of differentiation (CD)45+ and CD34+ markers of multiple haematopoietic lineages, number of granulocyte-erythroid-macrophage-megakaryocyte (GEMM) progenitor colonies, bone marrow histopathology, leucine-rich repeat-containing G-protein-coupled receptor 5 (Lgr5) expression in the intestines, xylose absorption and intestinal histopathology were all assessed at various time-points after irradiation. Furthermore, nuclear factor kappa B (NF-κB) p65 protein in the ileum was stained by immunofluorescent labelling. PGN-treated irradiated mice showed an increase in CD45+CD34+ cells compared with untreated mice 1.25 days after 10 Gy ionizing radiation (IR) (P < 0.05). Furthermore, combined PGN and WR-2721 treatment had an obviously synergistic radio-protective effect in nucleated cells in the bone marrow, including GEMM progenitors and CD45+CD34+ cells 4 days after 10 Gy IR. Single agent PGN or WR-2721 treatment after 10 Gy IR clearly increased Lgr5-positive pit cells (P < 0.05) and xylose absorption (P < 0.05). However only PGN and WR-2721 combination treatment markedly increased villus height (P < 0.05), number of crypts (P < 0.05) and whole-body weights after 10 Gy whole-body irradiation (WBI). The NF-κB p65 subunit was translocated to the nucleus, and
Questions and Answers on Autoimmunity and Autoimmune Diseases
... dermatomyositis . What are some of the treatments for autoimmune diseases? Of first importance in treating any autoimmune disease ... being researched. What is the family connection in autoimmune diseases? The ability to develop an autoimmune disease is ...
... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...
Autoimmune Autonomic Ganglionopathy
... Accessed 9/2/2015. Autoimmune Autonomic Ganglionopathy Summary. Dysautonomia International . http://www.dysautonomiainternational.org/page.php?ID= ... page Basic Information In Depth Information Basic Information Dysautonomia International offers an information page on Autoimmune autonomic ...
... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Intestine Transplant Although it is possible for a living donor to donate an intestine segment, most intestine transplants involve a whole organ ...
Transgenic mice that overexpress the human trefoil peptide pS2 have an increased resistance to intestinal damage.
Playford, R J; Marchbank, T; Goodlad, R A; Chinery, R A; Poulsom, R.; Hanby, A M
pS2 is a member of the trefoil peptide family, all of which are overexpressed at sites of gastrointestinal injury. We hypothesized that they are important in stimulating mucosal repair. To test this idea, we have produced a transgenic mice strain that expresses human pS2 (hpS2) specifically within the jejunum and examined the effect of this overexpression on proliferation and susceptibility to indomethacin-induced damage. A transgenic mouse was produced by microinjecting fertilized oocytes wi...
Immunomodulatory effects of dietary non-digestible oligosaccharides in T cell-mediated autoimmune arthritis
Rogier, R.; Ederveen, T.; Hartog, A.; Walgreen, B.; Van Den Bersselaar, L.; Helsen, M.; Vos, P.; Garssen, J.; Willemsen, L.; Van Den Berg, W.; Koenders, M.; Abdollahi-Roodsaz, S.
Background: Accumulating evidence indicates the relevance of intestinal microbiota in shaping the immune response and supports its contribution to the development of autoimmune diseases. Prebiotic non-digestible oligosaccharides are known to selectively support growth of commensal Bifidobacteria and
Sirolimus for Autoimmune Disease of Blood Cells
Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis
Porphyria cutanea tarda associated with autoimmune hypothyroidism, vitiligo and alopecia universalis.
Sabán, J; Rodríguez-García, J L; Gil, J; País, J R; Medina, S
The aetiology of porphyria cutanea tarda (PCT) has not been elucidated, but the possibility of an autoimmune mechanism has been proposed. We report a case of an unknown clinical combination of PCT with autoimmune hypothyroidism, alopecia universalis and vitiligo with thyroid and parietal cell circulating antibodies. This is highly suggestive of underlying autoimmune damage in this patient. PMID:1803247
Environmental Basis of Autoimmunity.
Floreani, Annarosa; Leung, Patrick S C; Gershwin, M Eric
The three common themes that underlie the induction and perpetuation of autoimmunity are genetic predisposition, environmental factors, and immune regulation. Environmental factors have gained much attention for their role in triggering autoimmunity, with increasing evidence of their influence as demonstrated by epidemiological studies, laboratory research, and animal studies. Environmental factors known to trigger and perpetuate autoimmunity include infections, gut microbiota, as well as physical and environmental agents. To address these issues, we will review major potential mechanisms that underlie autoimmunity including molecular mimicry, epitope spreading, bystander activation, polyclonal activation of B and T cells, infections, and autoinflammatory activation of innate immunity. The association of the gut microbiota on autoimmunity will be particularly highlighted by their interaction with pharmaceutical agents that may lead to organ-specific autoimmunity. Nonetheless, and we will emphasize this point, the precise mechanism of environmental influence on disease pathogenesis remains elusive. PMID:25998909
NK cell autoreactivity and autoimmune diseases
Alessandro ePoggi
Full Text Available Increasing evidences have pointed out the relevance of Natural Killer (NK cells in organ specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands upregulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILC, comprising the classical CD56+ NK cells, have a role in maintaining or alterating tissue homeostasis secreting protective and/or proinflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular matrix components and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity.
Sanjuan, Miguel A; Sagar, Divya; Kolbeck, Roland
There is accumulating evidence to suggest that IgE plays a significant role in autoimmunity. The presence of circulating self-reactive IgE in patients with autoimmune disorders has been long known but, at the same time, largely understudied. However, studies have shown that the increased IgE concentration is not associated with higher prevalence for atopy and allergy in patients with autoimmune diseases, such as systemic lupus erythematosus. IgE-mediated mechanisms are conventionally known to facilitate degranulation of mast cells and basophils and promote TH2 immunity, mechanisms that are not only central to mounting an appropriate defense against parasitic worms, noxious substances, toxins, venoms, and environmental irritants but that also trigger exuberant allergic reactions in patients with allergies. More recently, IgE autoantibodies have been recognized to participate in the self-inflicted damaging immune responses that characterize autoimmunity. Such autoimmune responses include direct damage on tissue-containing autoantigens, activation and migration of basophils to lymph nodes, and, as observed most recently, induction of type 1 interferon responses from plasmacytoid dendritic cells. The importance of IgE as a central pathogenic mechanism in autoimmunity has now been clinically validated by the approval of omalizumab, an anti-IgE mAb, for patients with chronic spontaneous urticaria and for the clinical benefit of patients with bullous pemphigoid. In this review we summarize recent reports describing the prevalence of self-reactive IgE and discuss novel findings that incriminate IgE as central in the pathogenesis of inflammatory autoimmune disorders. PMID:27264000
... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...
Autoimmune liver disease, autoimmunity and liver transplantation.
Carbone, Marco; Neuberger, James M
Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) represent the three major autoimmune liver diseases (AILD). PBC, PSC, and AIH are all complex disorders in that they result from the effects of multiple genes in combination with as yet unidentified environmental factors. Recent genome-wide association studies have identified numerous risk loci for PBC and PSC that host genes involved in innate or acquired immune responses. These loci may provide a clue as to the immune-based pathogenesis of AILD. Moreover, many significant risk loci for PBC and PSC are also risk loci for other autoimmune disorders, such type I diabetes, multiple sclerosis and rheumatoid arthritis, suggesting a shared genetic basis and possibly similar molecular pathways for diverse autoimmune conditions. There is no curative treatment for all three disorders, and a significant number of patients eventually progress to end-stage liver disease requiring liver transplantation (LT). LT in this context has a favourable overall outcome with current patient and graft survival exceeding 80% at 5years. Indications are as for other chronic liver disease although recent data suggest that while lethargy improves after transplantation, the effect is modest and variable so lethargy alone is not an indication. In contrast, pruritus rapidly responds. Cholangiocarcinoma, except under rigorous selection criteria, excludes LT because of the high risk of recurrence. All three conditions may recur after transplantation and are associated with a greater risk of both acute cellular and chronic ductopenic rejection. It is possible that a crosstalk between alloimmune and autoimmune response perpetuate each other. An immunological response toward self- or allo-antigens is well recognised after LT in patients transplanted for non-autoimmune indications and sometimes termed "de novo autoimmune hepatitis". Whether this is part of the spectrum of rejection or an autoimmune
American Autoimmune Related Diseases Association
... Its 25th Anniversary With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune ... will benefit AARDA. Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two ...
Juan-Manuel eAnaya
Full Text Available Autoimmune diseases (ADs represent a heterogeneous group of disorders that affect specific target organs or multiple organ systems. These conditions share common immunopathogenic mechanisms (i.e., the autoimmune tautology, which explain the clinical similarities they have among them as well as their familial clustering (i.e., coaggregation. As part of the autoimmune tautology, the influence of environmental exposure on the risk of developing ADs is paramount (i.e., the autoimmune ecology. In fact, environment, more than genetics, shapes immune system. Autoimmune ecology is akin to exposome, that is all the exposures - internal and external - across the lifespan, interacting with hereditary factors (both genetics and epigenetics to favor or protect against autoimmunity and its outcomes. Herein we provide an overview of the autoimmune ecology, focusing on the immune response to environmental agents in general, and microbiota, cigarette smoking, alcohol and coffee consumption, socioeconomic status, gender and sex hormones, vitamin D, organic solvents and vaccines in particular. Inclusion of the autoimmune ecology in disease etiology and health will improve the way personalized medicine is currently conceived and applied.
Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease?
Cornet, Anne; Savidge, Tor C.; Cabarrocas, Julie; Deng, Wen-Lin; Colombel, Jean-Frederic; Lassmann, Hans; Desreumaux, Pierre; Liblau, Roland S.
Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8+ T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.
从肠黏膜免疫系统损害探讨AIDS脾虚病机%Discuss the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage
王春芳; 李真; 徐立然
HIV/AIDS patients with intestinal mucosal immune system damage promoting the immunodeficiency of body and the incidence of opportunistic infections, which is consistent with the evolution of spleen deficiency pathogenesis point of view of TCM. This paper discusses the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage, and proposed strengthening the spleen to improve immune function of intestinal mucosa of AIDS.%HIV/AIDS患者肠黏膜免疫系统损害促进了机体免疫功能的缺失和机会性感染的发生,AIDS以脾虚为主的中医病机演变过程,与HIV感染所致以肠黏膜损伤为重要表现的全身免疫损伤过程相符合.文章从肠黏膜免疫系统损害角度探讨AIDS脾虚病机,提出健脾扶正以改善肠黏膜免疫功能的中医药治疗AIDS思路.
Andrew W. Campbell
Full Text Available Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity.
Autoimmune Pancreatitis: A Succinct Overview
Juan Putra; Xiaoying Liu
Autoimmune pancreatitis is a rare type of chronic pancreatitis with characteristic clinical, radiologic, and histopathologic findings. Diagnosis of autoimmune pancreatitis is often challenging due to its low incidence and nonspecific clinical and radiologic findings. Patients with autoimmune pancreatitis and pancreatic cancer share similar clinical presentations, including obstructive jaundice, abdominal pain and weight loss. Due to these overlapping features, autoimmune pancreatitis patients...
Urticarial Vasculitis-Associated Intestinal Ischemia
Uni Wong
Full Text Available Urticarial vasculitis (UV is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia.
Urticarial Vasculitis-Associated Intestinal Ischemia.
Wong, Uni; Yfantis, Harris; Xie, Guofeng
Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a case of urticarial vasculitis-associated intestinal ischemia. PMID:27190661
Pietro Invernizzi; Ian R Mackay
The liver was one of the earliest recognized sites among autoimmune diseases yet autoimmune hepatitis,primary biliary cirrhosis,primary sclerosing cholangitis,and their overlap forms,are still problematic in diagnosis and causation.The contributions herein comprise 'pairs of articles' on clinical characteristics,and concepts of etiopathogenesis,for each of the above diseases,together with childhood autoimmune liver disease,overlaps,interpretations of diagnostic serology,and liver transplantation.This issue is timely,since we are witnessing an ever increasing applicability of immunology to a wide variety of chronic diseases,hepatic and non-hepatic,in both developed and developing countries.The 11 invited expert review articles capture the changing features over recent years of the autoimmune liver diseases,the underlying immunomolecular mechanisms of development,the potent albeit still unexplained genetic influences,the expanding repertoire of immunoserological diagnostic markers,and the increasingly effective therapeutic possibilities.
Reactive oxygen species in organ-specific autoimmunity.
Di Dalmazi, Giulia; Hirshberg, Jason; Lyle, Daniel; Freij, Joudeh B; Caturegli, Patrizio
Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response. PMID:27491295
Etiopathogenesis of insulin autoimmunity.
Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna
Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...
Intestinal ischemia and infarction
... cases, the condition needs to be treated with surgery. The section of intestine that has died is removed, and the healthy ... outcome. Possible Complications Damage or death of the bowel tissue may require a colostomy or ileostomy. This may be short-term or permanent. Peritonitis is common in these ...
Coeliac disease in endocrine diseases of autoimmune origin.
Miśkiewicz, Piotr; Kępczyńska-Nyk, Anna; Bednarczuk, Tomasz
Abstract Coeliac disease (CD, sometimes called gluten-sensitive enteropathy or nontropical sprue) is an inflammatory disorder of the small intestine of autoimmune origin. It occurs in genetically predisposed people and is induced by a gluten protein, which is a component of wheat. The prevalence of histologically confirmed CD is estimated in screening studies of adults in the United States and Europe to be between 0.2% and 1.0%. The results of previous studies have indicated that the prevalence of CD is increased in patients with other autoimmune disorders such as: autoimmune thyroid diseases, type 1 diabetes mellitus, and Addison's disease. A coincidence of the above diseases constitutes autoimmune polyglandular syndrome (APS). The high prevalence of CD in APS is probably due to the common genetic predisposition to the coexistent autoimmune diseases. The majority of adult patients have the atypical or silent type of the disease. This is the main reason why CD so often goes undiagnosed or the diagnosis is delayed. CD, if undiagnosed and untreated, is associated with many medical disorders including haematological (anaemia), metabolical (osteopenia/osteoporosis), obstetric-gynaecological (infertility, spontaneous abortions, late puberty, early menopause), neurological (migraine, ataxia, epilepsy) as well as with an increased risk of malignancy, especially: enteropathy-associated T-cell lymphoma, small intestine adenocarcinoma, and oesophageal and oropharyngeal carcinomas. Early introduction of a gluten-free diet and lifelong adherence to this treatment decreases the risk of these complications. PMID:22744631
Cardiovascular Involvement in Autoimmune Diseases
Jenny Amaya-Amaya
Full Text Available Autoimmune diseases (AD represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD.
... of the major causes of intestinal obstruction in infants and children. Causes of paralytic ileus may include: Bacteria or viruses that cause intestinal infections ( gastroenteritis ) Chemical, electrolyte, or mineral imbalances (such as decreased ...
Selenium status and over-expression of interleukin-15 in celiac disease and autoimmune thyroid diseases
Anna Velia Stazi
Full Text Available In celiac disease (CD, for its multifactorial nature, the target organs are not limited to the gut, but include thyroid, liver, skin and reproductive and nervous systems. Between the extraintestinal symptoms associated with CD, autoimmune thyroid diseases (AITDs are more evident, underlining as CD-related autoimmune alterations can be modulated not only by gluten but also by various concurrent endogenous (genetic affinity, over-expression of cytokines and exogenous (environment, nutritional deficiency factors. In their pathogenesis a central role for over-expression of interleukin-15 (IL-15 is shown, by inhibiting apoptosis, leading to the perpetuation of inflammation and tissue destruction. Thyroid is particularly sensitive to selenium deficiency because selenoproteins are significant in biosynthesis and activity of thyroid hormones; besides, some selenoproteins as glutathione peroxidase are involved in inhibiting apoptosis. Thus, selenium malabsorption in CD can be thought as a key factor directly leading to thyroid and intestinal damage. Considering the complexity of this interaction and on the basis of available evidence, the aim of this review is to assess as preventive and therapeutic target the role of IL-15 and selenium in the pathogeneses of both CD and AITD.
Autoimmune basal ganglia disorders.
Dale, Russell C; Brilot, Fabienne
The basal ganglia are deep nuclei in the brain that include the caudate, putamen, globus pallidus, and substantia nigra. Pathological processes involving the basal ganglia often result in disorders of movement and behavior. A number of different autoimmune disorders predominantly involve the basal ganglia and can result in movement and psychiatric disorders. The classic basal ganglia autoimmune disorder is Sydenham chorea, a poststreptococcal neuropsychiatric disorder. Resurgence in the interest in Sydenham chorea is the result of the descriptions of other poststreptococcal neuropsychiatric disorders including tics and obsessive-compulsive disorder, broadly termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection. Encephalitic processes affecting the basal ganglia are also described including the syndromes basal ganglia encephalitis, encephalitis lethargica, and bilateral striatal necrosis. Last, systemic autoimmune disorders such as systemic lupus erythematosus and antiphospholipid syndrome can result in chorea or parkinsonism. Using paradigms learned from other autoantibody associated disorders, the authors discuss the autoantibody hypothesis and the role of systemic inflammation in autoimmune basal ganglia disorders. Identification of these entities is important as the clinician has an increasing therapeutic repertoire to modulate or suppress the aberrant immune system. PMID:22832771
Autoimmunity and Asbestos Exposure
Jean C. Pfau
Full Text Available Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA, a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a a lack of statistical power due to relatively small or diffuse exposure cohorts, (b exposure misclassification, (c latency of clinical disease, (d mild or subclinical entities that remain undetected or masked by other pathologies, or (e effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease.
Endometriosis intestinal Intestinal endometriosis
C.I. González; M. Cires; F. J. Jiménez; Rubio, T.
La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada). En la afectación intestinal, el colon es el segmento más frecuen...
Endometriosis intestinal Intestinal endometriosis
C.I. González
Full Text Available La endometriosis es un trastorno ginecológico crónico, benigno y frecuente entre las mujeres en edad fértil, estimándose que existe algún grado de endometriosis hasta en el 15% de las mujeres premenopáusicas, asociándose a historia de infertilidad, antecedente de cesárea, dismenorrea y anormalidad en el sangrado uterino. Se cree que es debida al ascenso por las trompas de Falopio de contenido menstrual (menstruación retrógrada. En la afectación intestinal, el colon es el segmento más frecuentemente afectado, sobre todo a nivel rectosigmodeo. La clínica de presentación es inespecífica, siendo lo más frecuente el dolor abdominal y/o pélvico de tipo cólico que coincide o se exacerba con la menstruación. El diagnóstico diferencial incluye la enfermedad inflamatoria intestinal, diverticulitis, colitis isquémica y procesos neoplásicos, siendo el diagnóstico definitivo anatomopatológico. En cuanto al tratamiento, éste dependerá de la clínica y de la edad de la paciente, así como de sus deseos de embarazo.Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation. In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment
Anesthetic Effects on Damage of Intestinal Mucosal Barrier Function Caused by Cardiopulmonary Bypass%麻醉药物对体外循环致肠道屏障功能损害作用的影响
苏日娜(综述); 于建设; 温再和(审校)
肠道是全身应激反应的重要靶器官,又是全身炎症反应综合征、多器官功能障碍综合征的重要诱因。而临床患者当中手术创伤、应激反应、严重感染、休克、心血管外科手术中体外循环等均可导致肠黏膜屏障功能受损,这些过程最终导致肠屏障通透性增加,继而与脓毒症、全身炎症反应综合征、多器官功能障碍综合征发生有密切关系。在临床实践中证实许多常规麻醉药物预处理对体外循环引起的肠道缺血/再灌注损伤有保护作用,继而减轻肠黏膜损伤。%The gut is an important target organ of the systemic stress response ,and an important cause of the systemic inflammatory response syndrome ( SIRS ) and multiple organ dysfunction syndrome ( MODS ) . Surgical trauma,stress,shock,infection,cardiopulmonary bypass all can lead to impaired intestinal mucosal barrier function.These processes eventually lead to intestinal mucosal permeability increase,which is closely associated with sepsis,SIRS and MODS.In clinical practice it′s confirmed that many conventional anesthetics preconditioning can protect the intestine from ischemia reperfusion injury due to cardiopulmonary bypass and decrease the damage of intestinal mucosa .
Selmi, Carlo
Compared to the clear trend observed in previous years, the number of peer-reviewed articles published during 2015 and retrieved using the "autoimmunity" key word declined by 4 %, while remaining 5 % of immunology articles. On the other hand, a more detailed analysis of the published articles in leading immunology and autoimmunity journals revealed exciting scenarios, with fascinating lines of evidence being supported by convincing data and likely followed by rapid translational or clinical developments. As examples, the study of the microbiome, the development of new serum or other tissue biomarkers, and a more solid understanding of disease pathogenesis and tolerance breakdown mechanisms have been central issues in the past year. Furthermore and similar to the oncology field, progress in the understanding of single autoimmune condition is becoming most specific with psoriatic and rheumatoid arthritis being ideal paradigms with treatment options diverging after decades of common therapies, as illustrated by IL17-targeting approaches. The ultimate result of these advances is towards personalized medicine with an ideal approach being tailored on a single patient, based on a finely tuned definition of the immunogenetics, epigenetics, microbiome, and biomarkers. Finally, experimental reports suggest that cancer-associated immune mechanisms or the role of T and B cell subpopulations should be better understood in autoimmune diseases. While we hailed the 2014 literature in the autoimmunity world as part of an annus mirabilis, we should not be mistaken in the strong stimulus of research in autoimmunity represented by the 2015 articles that will be summarized in this article. PMID:27422713
[Autoimmune hemolytic anemia in children].
Becheur, M; Bouslama, B; Slama, H; Toumi, N E H
Autoimmune hemolytic anemia is a rare condition in children which differs from the adult form. It is defined by immune-mediated destruction of red blood cells caused by autoantibodies. Characteristics of the autoantibodies are responsible for the various clinical entities. Classifications of autoimmune hemolytic anemia include warm autoimmune hemolytic anemia, cold autoimmune hemolytic anemia, and paroxysmal cold hemoglobinuria. For each classification, this review discusses the epidemiology, etiology, clinical presentation, laboratory evaluation, and treatment options. PMID:26575109
Autoimmunity in Addison's disease.
Martín Martorell, P; Roep, B O; Smit, J W A; Martorell, P M
Addison's disease has a low incidence and is most frequently the result of an autoimmune disease in developed countries. Addison's disease can present as an isolated entity or in combination with other autoimmune diseases: Addison's disease can be part of the distinct polyglandular autoimmune syndromes APS I and II. Autoantibodies in patients with isolated Addison's disease are directed against the enzymes involved in steroid synthesis, P45oc21, P45oscc and P45oc17. Addison's disease, both isolated and in the context of APS II, has been associated with the haplotype HLA-A1, -B8 and DR3. The value of the increased expression of these molecules on adrenocortical cells could point towards an infectious pathogenesis. Given the prevalence, up to 80 %, of autoantibodies in Addison's disease as well as the high predictive value for developing the disease when antibodies are present (41% in three years), we advise screening high-risk populations, such as patients with other autoimmune endocrinopathies or their relatives for the presence of these antibodies. The adrenocortical function of patients positive for antibodies should be followed yearly. PMID:12430572
Autoimmunity and Turner's syndrome.
Lleo, Ana; Moroni, Luca; Caliari, Lisa; Invernizzi, Pietro
Turner Syndrome (TS) is a common genetic disorder, affecting female individuals, resulting from the partial or complete absence of one sex chromosome, and occurring in approximately 50 per 100,000 liveborn girls. TS is associated with reduced adult height and with gonadal dysgenesis, leading to insufficient circulating levels of female sex steroids and to infertility. Morbidity and mortality are increased in TS but average intellectual performance is within the normal range. TS is closely associated to the presence of autoantibodies and autoimmune diseases (AID), especially autoimmune thyroiditis and inflammatory bowel disease. Despite the fact that the strong association between TS and AID is well known and has been widely studied, the underlying immunopathogenic mechanism remains partially unexplained. Recent studies have displayed how TS patients do not show an excess of immunogenic risk markers. This is evocative for a higher responsibility of X-chromosome abnormalities in the development of AID, and particularly of X-genes involved in immune response. For instance, the long arm of the X chromosome hosts a MHC-locus, so the loss of that region may lead to a deficiency in immune regulation. Currently no firm guidelines for diagnosis exist. In conclusion, TS is a condition associated with a number of autoimmune manifestations. Individuals with TS need life-long medical attention. As a consequence of these findings, early diagnosis and regular screening for potential associated autoimmune conditions are essential in the medical follow-up of TS patients. PMID:22154619
Autoimmune paediatric liver disease
Giorgina Mieli-Vergani, Diego Vergani
Full Text Available Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH, autoimmune sclerosing cholangitis (ASC, and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 or liver kidney microsomal antibody (LKM1, type 2. There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether
Autoimmune paediatric liver disease
Giorgina Mieli-Vergani; Diego Vergani
Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC),and de novo AIH after liver transplantation.AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA,type 1) or liver kidney microsomal antibody (LKM1,type 2).There is a female predominance in both.LKM1 positive patients tend to present more acutely,at a younger age,and commonly have partial IgA deficiency,while duration of symptoms before diagnosis,clinical signs,family history of autoimmunity, presence of associated autoimmune disorders,response to treatment,and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC.The clinical,biochemical, immunological,and histological presentation of ASC is often indistinguishable from that of AIH type 1.In both,there are high IgG,non-organ specific autoantibodies,and interface hepatitis.Diagnosis is made by cholangiography.Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates,times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However,the cholangiopathy can progress.There may be evolution from AIH to ASC over the years,despite treatment.De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH,including elevated titres of serum antibodies, hypergammaglobulinaemia,and histological findings of interface hepatitis,bridging fibrosis,and collapse.Like classical AIH,it responds to treatment with prednisolone and azathioprine.De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection.Whether this condition is a distinct entity or a form of
A Difficult and Rare Diagnosis of Autoimmune Enteropathy in a Patient Affected by Down Syndrome.
Depince-Berger, Anne; Cremilieux, Clara; Rinaudo-Gaujous, Melanie; Genin, Christian; de Freminville, Benedicte; Lambert, Claude; Bruneau, J; Paul, Stephane
Patients with Down syndrome are more susceptible to autoimmune pathologies, in particular endocrine or digestive diseases such as celiac disease. Autoimmune enteropathy is another form of digestive autoimmune disease, non-gluten-dependant, more often diagnosed in male neonates with immunodysregulation and polyendocrinopathy such as the Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked syndrome. It also exists in the adult, but this pathology is less known and therefore frequently under-diagnosed. Clinical manifestations are similar to celiac disease, but not improved after a gluten-free diet. Autoimmune enteropathy is frequently associated with other autoimmune diseases, such as thyroiditis, myasthenia gravis, lupus or immune deficiencies, as Common Variable Immunodeficiency. Pathological analysis of intestinal biopsies can frequently distinguish autoimmune enteropathy and celiac disease. Autoimmune enteropathy usually has an important lymphoplasmacytic infiltration of the mucosa and a lack of intraepithelial lymphocytes in the gastrointestinal mucosal surface, while celiac disease usually has a polymorph infiltration of the mucosa and an important intraepithelial lymphocytes infiltration. Nevertheless, the two pathological patterns may overlap. Here we report the first case of a patient with Down syndrome associated to autoimmune enteropathy (initially diagnosed as celiac disease), chronic pancreatitis and cutaneous lupus erythematosus. Even if autoimmune pathologies are much more common in patients with Down syndrome, we would like to report on this rare and original association found in our patient. PMID:27072857
Escherichia coli Nissle 1917-derived factors reduce cell death and late apoptosis and increase transepithelial electrical resistance in a model of 5-fluorouracil-induced intestinal epithelial cell damage.
Wang, Hanru; Bastian, Susan E P; Cheah, Ker Y; Lawrence, Andrew; Howarth, Gordon S
We evaluated the capacity for supernatants (SNs) derived from Escherichia coli Nissle 1917 (EcN), cultured under different growth conditions, to prevent 5-fluorouracil (5-FU)-induced intestinal epithelial cell damage. EcN was cultured in: Luria Bertani (LB) broth, tryptone soya broth (TSB), de Man Rogosa Sharpe (MRS) broth, and M17 broth supplemented with 10% (v/v) lactose solution (M17). Intestinal epithelial cells (IEC-6) were treated with the following EcN SNs: LB(+), TSB(+), MRS(+), and M17(+) in the presence and absence of 5-FU (1.5 or 5 μM). Cell viability, apoptotic activity and cell monolayer permeability were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and transepithelial electrical resistance (TER) assays, respectively. 5-FU significantly reduced cell viability (P<0.05) at both 24 and 48 h. However, only EcN SN produced from LB and M17 growth media significantly decreased cell death induced by 5-FU (by approximately 10% after 24 and 48 h; and 10% after 24 h, respectively [P<0.05]). When measured by flow cytometry all EcN SNs in the presence of 5-FU increased the proportion of viable cells (by 3-5% for 24 h, 3-7% for 48 h, P<0.05) and reduced late-apoptotic cells after 24 and 48 h, compared with 5-FU control. Moreover, all EcN SNs significantly reduced the disruption of IEC-6 cell barrier function induced by 5-FU by 7-10% (P<0.05), compared with DMEM control. We conclude that EcN derived factors could potentially reduce the severity of intestinal mucositis. PMID:24556751
The role of autoimmunity in premature ovarian failure
Mahbod Ebrahimi
Full Text Available Premature ovarian failure (POF is a heterogeneous syndrome with several causative factors. Autoimmune mechanisms are involved in pathogenesis of 4-30 % of POF cases. The present review focuses on the role of autoimmunity in the pathophysiology of POF. The evidences for an autoimmune etiology are: demonstration of ovarian autoantibodies, the presence of lymphocytic oophoritis, and association with other autoimmune disorders. Several ovarian antigenic targets have been identified in POF patients. The oocyte seems to be the most often targeted cell. Lymphocytic oophoritis is widely present in POF associated adrenal insufficiency. Addisonۥs disease is one of the most common autoimmune disorders associated with POF. Early detection of this potentially life threatening disease was recommended in several studies. The gold standard for detecting autoimmune POF is ovarian biopsy. This procedure is not recommended due to unknown clinical value, expense, and risks. Several immunoassays have been proposed as substitute diagnostic tools. Nevertheless, there is no clinically proven sensitive and specific serum test to confirm the diagnosis of autoimmune POF or to anticipate the patient's chance of developing POF or associated diseases. Some authors suggested the possible effects of immuno-modulating therapy on the resumption of ovarian function and fertility in a selected group of autoimmune POF patients. However, in most instances, this treatment fails to reverse the course of the disease. Numerous studies illustrated that standard treatment outcome for infertility is less effective in the presence of ovarian autoimmunity. The antibody-induced damage could be a pathogenic factor. Nevertheless, the precise cause remains obscure.
Update on autoimmune hepatitis
Andreas Teufel; Peter R Galle; Stephan Kanzler
Autoimmune hepatitis (AIH) is a necroinflammatory liver disease of unknown etiology that occurs in children and adults of all ages. Characteristics are its autoimmune features, hyperglobulinemia (IgG), and the presence of circulating autoantibodies, as well as a response to immunosuppressant drugs. Current treatment consists of prednisone and azathioprine and in most patients this disease has become very treatable. Over the past 2 years, a couple of new insights into the genetic aspects, clinical course and treatment of AIH have been reported, which will be the focus of this review. In particular, we concentrate on genome-wide microsatellite analysis, a novel mouse model of AIH, the evaluation of a large AIH cohort for overlap syndromes,suggested novel criteria for the diagnosis of AIH, and the latest studies on treatment of AIH with budenoside and mycophenolate mofetil.
Gangliosides and autoimmune diabetes.
Misasi, R; Dionisi, S; Farilla, L; Carabba, B; Lenti, L; Di Mario, U; Dotta, F
Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin
肝性脑病食醋灌肠导致肠黏膜屏障损伤及改进方法*%Damage of Intestinal Mucosal Barrier Caused by Vinegar Enema and Improvement for Hepatic Encephalopathy
张凤; 徐旭娟; 沈美云
目的探讨肝性脑病食醋保留灌肠对肠黏膜屏障的损伤,并比较传统高渗食醋灌肠液与改进的等渗食醋灌肠液对兔肠黏膜屏障的损伤程度。方法选用成年家兔16只,随机分为2组,高渗组灌肠液为生理盐水和白醋混合成的高渗溶液;等渗组灌肠液为双蒸水和白醋混合的同等pH值和体积分数的等渗溶液。在相同灌肠条件下,使用不同渗透压食醋灌肠液给动物保留灌肠。通过肠黏膜病理切片,光镜下观察肠黏膜结构改变,电镜下观察细胞结构及紧密连接情况,比较2组肠黏膜屏障损伤程度。结果光镜下可见等渗组直肠部位与远端结肠肠黏膜损伤程度较高渗组轻。电镜下,等渗组细胞形态正常,微绒毛排列整齐,细胞连接紧密;高渗组微绒毛减少或消失,细胞连接增宽或开放,细胞核固缩,并可见凋亡、坏死细胞。结论等渗性食醋灌肠液对肠黏膜屏障损伤较传统高渗性食醋灌肠液轻。临床上肝性脑病患者可选用等渗性食醋灌肠液以减少渗透压对肠黏膜屏障的损伤。%Objective To explore the damage of intestinal mucosal barrier caused by vinegar retention enema, and compare the degree of injury in intestinal mucosal barrier between isotonic vinegar and traditional hypertonic vinegar treat-ment. Methods Sixteen adult rabbits were randomly divided into two groups. The solution of vinegar mixed with normal so-dium was given to hypertonic group. Isotonic group was administered with isosmotic solution made of vinegar and double dis-tilled water, with the same volume fraction and pH as hypertonic group. Then two different osmosis solutions were given as enema solution to rabbits under the same condition. Finally, damages of intestinal mucosa were observed by light microscope and transmission electron microscope (TEM) in two groups. Results It was observed that injuries of rectum and distal part of colon were
Cripps, James G.; Gorham, James D.
Myeloid derived suppressor cells (MDSC) were first described nearly two decades ago. Until recently, however, descriptions of MDSC populations were found almost exclusively in animal models of cancer or in cancer patients. Over the last few years, an increasing number of reports have been published describing populations of myeloid cells with MDSC-like properties in murine models of autoimmune disease. In contrast to the proposed deleterious role of MDSC in cancer - where these cells likely i...
Autoimmune Progesterone Anaphylaxis
Mohammad Hassan Bemanian
Full Text Available Progesterone induced dermatitis is a rare disorder. It typically occurs in females due to anautoimmune phenomenon to endogenous progesterone production, but can also be caused byexogenous intake of a synthetic progestin. Here in, we present a case of autoimmune progesterone anaphylaxis (AIPA observed in an adolescent female.The patient is an 18-year-old Caucasian female with no significant past medical history and noprior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions with dyspnea, cough and respiratory distress. She noted that her symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cml of progesterone was performed. The patient developed a 15mm wheal after 15 minutes, confirming the diagnosis of AIPA.The patient was started on a continuous regimen of an oral conjugated estrogen (0.625mg. The skin eruptions and respiratory symptoms have not returned since the initiation of this therapy.Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions.Women with the disorder commonly present with dermatologic lesions in the luteal phase of themenstrual cycle, if there are any other organ involvement in addition to skin (e.g. lung, GI thereaction should be called as autoimmune progesterone anaphylaxis. Diagnosis of AIPA is confirmed by performing a skin allergen test using progesterone.
Etiopathogenesis of Insulin Autoimmunity
Norio Kanatsuna
Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.
Autoimmune thyroid disease and other non-endocrine autoimmune diseases
Todorović-Đilas Ljiljana; Ičin Tijana; Novaković-Paro Jovanka; Bajkin Ivana
Introduction, Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a...
Bouguen, Guillaume; Dubuquoy, Laurent; Desreumaux, Pierre; Brunner, Thomas; Bertin, Benjamin
Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of steroidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor-1 (SF-1) but a closely related homolog, namely the liver receptor homolog-1 (LRH-1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel diseases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions. PMID:25560486
慢性放射性肠损伤的营养支持治疗%Nutrition support trerapy in chronic intestinal radiation damage
李宁; 龚剑峰
慢性放射性肠损伤是放疗后常见的胃肠道并发症,其外科治疗是对外科医生手术技能和围手术期处理水平的挑战。合理的手术前期营养支持治疗能够降低围手术期并发症发生率和造口率,而术后的营养支持治疗可避免肠衰竭的发生。应尽可能以肠内营养(EN)作为慢性放射性肠损伤围手术期支持治疗的主要途径。针对肠道共生菌群及其代谢产物的特殊药理营养素在放射性肠损伤的营养支持治疗中可能起到一定作用。%Chronic radiation enteritis (CRE) is a common complication after pelvic radiotherapy, which severely affects patients′ quality of life. Surgical treatment of CRE is challenging both for surgical skills and perioperative treatment strategy. Proper preoperative nutrition support therapy can reduce the morbidity of postoperative complication and the use of stoma, while postoperative nutrition support therapy can avoid the intestinal failure. Enteral nutrition should be the primary route of perioperative nutrition support therapy in CRE as possible. Pharmaconutrients aiming at intestinal commensal microbiota and its metabolites may play a role in the management of radiation enteritis.
Autoimmune Thyroid Diseases in Children
Francesca Crea; Carla Bizzarri; Marco Cappa
The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environment...
Combined treatment with lisofylline and exendin-4 reverses autoimmune diabetes
Type 1 diabetes mellitus (T1DM) is an autoimmune disease leading to near complete pancreatic β-cell destruction. New evidence suggests that β-cell regeneration is possible, but ongoing autoimmune damage prevents restoration of β-cell mass. We tested the hypothesis that simultaneously blocking autoimmune cytokine damage and supplying a growth-promoting stimulus for β-cells would provide a novel approach to reverse T1DM. Therefore, in this study we combined lisofylline to suppress autoimmunity and exendin-4 to enhance β-cell proliferation for treating autoimmune-mediated diabetes in the non-obese diabetic (NOD) mouse model. We found that this combined therapy effectively reversed new-onset diabetes within a week of therapy, and even maintained euglycemia up to 145 days after treatment withdrawal. The therapeutic effect of this regimen was associated with improved β-cell metabolism and insulin secretion, while reducing β-cell apoptosis. It is possible that such combined therapy could become a new strategy to defeat T1DM in humans
... 2 Diabetes, Heart Disease a Dangerous Combo Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... inflammation and infection of the abdominal cavity ( peritonitis ). Causes Causes of intestinal obstruction differ depending on the ...
... to maintain adequate nutrition (a condition known as short bowel syndrome). They may be dependent on intravenous nutrition for a time after surgery (or even permanently if too little intestine remains) ...
MJ Ggaravi
Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycl...
Autoimmune diseases and myelodysplastic syndromes.
Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K
Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. Am. J. Hematol. 91:E280-E283, 2016. © 2016 Wiley Periodicals, Inc. PMID:26875020
Chronic primary intestinal pseudo-obstruction from visceral myopathy Pseudo-osbtrucción intestinal crónica primaria debida a miopatía visceral
M. T. Muñoz-Yagüe; J. C. Marín; Colina, F; C. Ibarrola; G. López-Alonso; Martín, M. A.; J. A. Solís Herruzo
Chronic intestinal pseudo-obstruction is an uncommon syndrome characterized by relapsing episodes suggesting intestinal obstruction during which no mechanical causes are identified to account for symptoms. Etiologic factors may be manifold. Among them a number of neurologic conditions, gastrointestinal smooth muscle myopathies, endocrino-metabolic and autoimmune diseases, and the use of selected drugs stand out. We report a case of chronic intestinal pseudo-obstruction originating in a sporad...
Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease
Deanna L. Gibson
Full Text Available The gastrointestinal (GI microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn's disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.
... disease Crohn's disease Infections Intestinal cancer Intestinal obstruction Irritable bowel syndrome Ulcers, such as peptic ulcer Treatment of disorders of the small intestine depends on the cause.
Infections and autoimmune diseases.
Bach, Jean-François
The high percentage of disease-discordant pairs of monozygotic twins demonstrates the central role of environmental factors in the etiology of autoimmune diseases. Efforts were first focussed on the search for triggering factors. The study of animal models has clearly shown that infections may trigger autoimmune diseases, as in the case of Coxsackie B4 virus in type I diabetes and the encephalomyocarditis virus in autoimmune myositis, two models in which viruses are thought to act by increasing immunogenicity of autoantigens secondary to local inflammation. The induction of a Guillain-Barré syndrome in rabbits after immunization with a peptide derived from Campylobacter jejuni is explained by mimicry between C. jejuni antigens and peripheral nerve axonal antigens. Other models involve chemical modification of autoantigens, as in the case of iodine-induced autoimmune thyroiditis. These mechanisms have so far only limited clinical counterparts (rheumatic fever, Guillain-Barré syndrome and drug-induced lupus or myasthenia gravis) but one may assume that unknown viruses may be at the origin of a number of chronic autoimmune diseases, such as type I diabetes and multiple sclerosis) as illustrated by the convergent data incriminating IFN-alpha in the pathophysiology of type I diabetes and systemic lupus erythematosus. Perhaps the difficulties met in identifying the etiologic viruses are due to the long lag time between the initial causal infection and onset of clinical disease. More surprisingly, infections may also protect from autoimmune diseases. Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases, inflammatory bowel diseases, and some lymphocyte malignancies. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries, posing the question of the causal relationship and more precisely the
Mast Cell and Autoimmune Diseases
Yunzhi Xu; Guangjie Chen
Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases.
Antinuclear antibodies defining autoimmunity pathways
Tan, Eng M.
Immunofluorescent imaging has been a powerful technique in helping to identify intracellular nuclear and cytoplasmic molecules which are target antigens of autoantibodies in systemic autoimmune disorders. Patterns of staining can be correlated with molecules engaged in specific cellular functions and distributed in distinct cellular domains. Different autoimmune disorders have different profiles of autoantibodies, and immunodiagnostics has become an important adjunct in differential diagnosis...
Urticarial Vasculitis-Associated Intestinal Ischemia
Uni Wong; Harris Yfantis; Guofeng Xie
Urticarial vasculitis (UV) is a rare small vessel vasculitis. UV is often idiopathic but can also present in the context of autoimmune disorders such as systemic lupus erythematosus, drug reactions, infections, or a paraneoplastic syndrome. Extracutaneous complications include intestinal ischemic injuries, in UV patients with nonspecific gastrointestinal symptoms such as abdominal pain and nausea. Prompt recognition and treatment can minimize morbidity and mortality. This paper describes a ca...
Gastrointestinal Autoimmunity Associated With Loss of Central Tolerance to Enteric alpha-Defensins
Dobeš, Jan; Neuwirth, Aleš; Dobešová, Martina; Vobořil, Matouš; Balounová, Jana; Ballek, Ondřej; Lebl, J.; Meloni, A.; Krohn, K.; Kluger, N.; Ranki, A.; Filipp, Dominik
Roč. 149, č. 1 (2015), s. 139-150. ISSN 0016-5085 R&D Projects: GA ČR(CZ) GBP302/12/G101 Institutional support: RVO:68378050 Keywords : Enteric defensins * Intestinal autoimmunity * Mouse Model of APECED Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 16.716, year: 2014
Outer Membrane Vesicles from the Probiotic Escherichia coli Nissle 1917 and the Commensal ECOR12 Enter Intestinal Epithelial Cells via Clathrin-Dependent Endocytosis and Elicit Differential Effects on DNA Damage
Cañas, María-Alexandra; Giménez, Rosa; Fábrega, María-José; Toloza, Lorena; Badia, Josefa
Interactions between intestinal microbiota and the human host are complex. The gut mucosal surface is covered by a mucin layer that prevents bacteria from accessing the epithelial cells. Thus, the crosstalk between microbiota and the host mainly rely on secreted factors that can go through the mucus layer and reach the epithelium. In this context, vesicles released by commensal strains are seen as key players in signaling processes in the intestinal mucosa. Studies with Gram-negative pathogens showed that outer membrane vesicles (OMVs) are internalized into the host cell by endocytosis, but the entry mechanism for microbiota-derived vesicles is unknown. Escherichia coli strains are found as part of normal human gut microbiota. In this work, we elucidate the pathway that mediate internalization of OMVs from the probiotic E.coli Nissle 1917 (EcN) and the commensal ECOR12 strains in several human intestinal epithelial cell lines. Time course measurement of fluorescence and microscopy analysis performed with rhodamine B-R18-labeled OMVs in the presence of endocytosis inhibitors showed that OMVs from these strains enter epithelial cells via clathrin-mediated endocytosis. Vesicles use the same endocytosis pathway in polarized epithelial monolayers. Internalized OMVs are sorted to lysosomal compartments as shown by their colocalization with clathrin and specific markers of endosomes and lysosomes. OMVs from both strains did not affect cell viability, but reduce proliferation of HT-29 cells. Labeling of 8-oxo-dG adducts in DNA revealed that neither OMVs from EcN nor from ECOR12 promoted oxidative DNA damage. In contrast, flow cytometry analysis of phosphorylated γH2AX evidenced that OMVs from the probiotic EcN significantly produced more double strand breaks in DNA than ECOR12 OMVs. The EcN genotoxic effects have been attributed to the synthesis of colibactin. However, it is not known how colibactin is exported and delivered into host cells. Whether colibactin is secreted
韩磊; 单信芝; 刘芝军; 王娟娟
Objective To establish a stable animal model that consistent with the requirements for research of radiation damage of intestinal mucosal barrier. Methods SD rats were randomly divided into control group (group A, 10 rats) and radiation groups B, C, D (20 in each group). The rats in groups B, C, and D were given single fraction irradiation on abdomen with linear accelerator, the dosage being 8. 5, 9.0, and 9.5 Gy, respectively, the radiation scope was from the xyphoid to anus. No radiation was given to the rats in group A. At day 4 after radiation, a segment of intestine, 10 cm from Treitz's ligament, was taken for making specimen. The length of crypt-villus axis (CVA) was measured light-microscopically, and intestinal mucous membrane structure observed electron-microscopically. Plasma endotoxin levels were detected by using tachypleus amebocyte lysate. Results At day 4 after radiation, death rates of the rats in groups B, C, and D were 10%, 30%, and 60%, respectively. A comparison of the length of CVA among the four groups showed: the difference between groups A and B was not significant (P>0.05) ; the length of CVA was shorter in group C than that in groups A and B; and that in group D was shorter than that in groups A, B, and C, the differences were all significant (F= 100.48,q=4.617-18.560,P<0.05). Plasma endotoxin concentration of group C was higher that that of groups A and B, that of group D was higher than that of groups A, B and C (F=50.468,q=5.380-15.898,P<0.05). Electron microscopically, intestinal epithelial cell shedding, ulcer formation, no normal cellular structure, exposure of basal lamina, and bacteria penetrating the stratum mucosum could be seen. Conclusion A model of radiation-induced damage of intestinal mucosal structure in the rat is created successfully. The model of radiation enterocolitis caused by total abdominal irradiation of a dose of 9. 0 Gy is applicable to research for radiation damage of mucosa barrier of intestine
Histological, Scanning And Transmission Electron Microscopic Studies On The Possible Protective Role Of Ginger Extract Against AcrylamideInduced Intestinal Damage In Mice
Hala Galal El-Tantawi
Full Text Available Objective: This study was carried out to evaluate the protective effect of ginger Zingeber officinale extract (ZOE against the acrylamide (AC which is an industrial chemical used in water treatment and it is synthesized during cooking of starch food at high temperature. Method: Thirty adult male albino mice, each weighs 20-25 g were divided into three groups (10 mice/group: (Icontrol group. (IIacrylamide treated group. (III acrylamide & ginger group. Acrylamide was given to experimental animals in the drinking water at a non-lethal dose of 200 p.p.m for 10 weeks (3 days/week. Ginger extract was orally administrated at 50 mg/L (~5 ml/day for 10 weeks (3 days/week. The ileum samples were collected for light microscope study and for scanning and transmission electron microscope examination. Results: This study revealed that acrylamide induces pathological changes of the ileum of the treated mice specially the absorptive epithelial cells. The scanning electron microscopic study revealed damage of the ileal villi, some red blood corpuscles appeared at the site of damage. The transmission electron microscopic examination clearly demonstrated degeneration of most cell organelles as mitochondria, deterioration and degranulation of the rough endoplasmic reticulum, dilatation of Golgi apparatus. Conclusion: The administration of ginger extract decreased the histological alterations and ensuring the anti-inflammatory, and antitoxic effects of ZOE at its chosen dosage level
Protective effects of the fermented milk Kefir on X-ray irradiation-induced intestinal damage in B6C3F1 mice
Gastrointestinal damage associated with radiation therapy is currently an inevitable outcome. The protective effect of Kefir was assessed for its usefulness against radiation-induced gastrointestinal damage. A Kefir supernatant was diluted by 2- or 10-fold and administered for 1 week prior to 8 Gray (Gy) X-ray irradiation at a dose rate of 2 Gy/min, with an additional 15d of administration post-irradiation. The survival rate of control mice with normal drinking water dropped to 70% on days 4 through 9 post-irradiation. On the other hand, 100% of mice in the 10- and 2-fold-diluted Kefir groups survived up to day 9 post-irradiation (p<0.05 and p<0.01, respectively). Examinations for crypt regeneration against 8, 10 and 12 Gy irradiation at a dose rate of 4 Gy/min revealed that the crypt number was significantly increased in the mice administered both diluted Kefir solutions (p<0.01 for each). Histological and immunohistochemical examinations revealed that the diluted Kefir solutions protected the crypts from radiation, and promoted crypt regeneration. In addition, lyophilized Kefir powder was found to significantly recover the testis weights (p<0.05), but had no effects on the body and spleen weights, after 8 Gy irradiation. These findings suggest that Kefir could be a promising candidate as a radiation-protective agent. (author)
Sexual dimorphism of miRNA expression: a new perspective in understanding the sex bias of autoimmune diseases
Dai R; Ahmed SA
Rujuan Dai, S Ansar Ahmed Department of Biomedical Sciences and Pathobiology, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, USA Abstract: Autoimmune diseases encompass a diverse group of diseases which emanate from a dysregulated immune system that launches a damaging attack on its own tissues. Autoimmune attacks on self tissues can occur in any organ or body system. A notable feature of autoimmune disease is that a majority of these disorders occu...
Endocrine autoimmunity in Turner syndrome
Background Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and the presence of clinical/pre-clinical autoimmune disorders and of autoantibodies was examined. Results Out of the 66 Turner patients, 26 had thyroid autoimmune disorders (39.4%), 14 patients had Hashimoto's thyroiditis with clinical or subclinical hypothyroidism (21.2%) and 12 patients had circulating anti-thyroid antibodies, echographic pattern of diffuse hypoechogenicity and normal thyroid hormone levels (18.2%). None were affected by Graves' disease. We analyzed the overall incidence of thyroid autoimmunity within the 3 different age groups 0–9.9, 10–19.9 and 20–29.9 years. No statistically significant difference was observed in the incidence of thyroid autoimmunity within the age-groups (χ2-test p > 0.05). Out of the 66 patients, 31 patients had the 45,X karyotype; within this first group 14 out of 31 patients were affected by autoimmune thyroid disease. A second group of 29 patients included 19 patients with mosaicism, 5 patients with deletions and 5 patients with ring chromosome; out of these 29 patients 7 were affected by autoimmune thyroid disease. A third group included 6 patients with X isochromosome; 5 out of 6 were affected by autoimmune thyroid disease. A statistically significant difference in the frequency of thyroid autoimmunity within the different karyotype groups was observed (χ2-test p = 0.0173). When comparing the X isochromosome group with the pooled group of other karyotypes, of note, the frequency of thyroid autoimmunity was
... the large intestine produces no digestive enzymes. Chemical digestion is completed in the small intestine before the chyme reaches the large intestine. Functions of the large intestine include the absorption of water and electrolytes and the elimination of ...
SOCS, inflammation and autoimmunity
Akihiko eYoshimura
Full Text Available Cytokines play essential roles in innate and adaptive immunity. However, excess cytokines or dysregulation of cytokine signaling can cause a variety of diseases, including allergies, autoimmune diseases, inflammation, and cancer. Most cytokines utilize the so-called Janus kinase-signal transducers and activators of transcription (JAK-STAT pathway. This pathway is negatively regulated by various mechanisms including suppressors of cytokine signaling (SOCS proteins. SOCS proteins bind to JAK or cytokine receptors, thereby suppressing further signaling events. Especially, SOCS1 and SOCS3 are strong inhibitors of JAK, because these two contain kinase inhibitory region (KIR at the N-terminus. Studies using conditional knockout mice have shown that SOCS proteins are key physiological as well as pathological regulators of immune homeostasis. Recent studies have also demonstrated that SOCS1 and SOCS3 are important regulators of helper T cell differentiation and functions.
Recent reports have suggested that autoimmune enteropathy involving the small bowel may occur in adults as well as in children. Apparently, the endoscopic and histological changes are similar to celiac disease before treatment, but these are not altered by any form of dietary restriction, including a gluten-free diet. As in celiac disease, histologic changes in gastric and colonic biopsies have also been recorded. Anti enterocyte antibodies detected with immunofluorescent methods have been reported by a few laboratories, but these antibodies appear not to be specific and may simply represent epiphenomena. A widely available, reproducible and quantitative anti-enterocyte antibody assay is needed that could be applied in small bowel disorders that have the histological appearance of celiac disease, but fail to respond to a gluten-free diet.
Restoration of impaired intestinal barrier function by the hydrolysed casein diet contributes to the prevention of type 1 diabetes in the diabetes-prone BioBreeding rat
Visser, J. T. J.; Lammers, K.; Hoogendijk, A.; Boer, M. W.; Brugman, S.; Beijer-Liefers, S.; Zandvoort, A.; Harmsen, H.; Welling, G.; Stellaard, F.; Bos, N. A.; Fasano, A.; Rozing, J.
Aims/hypothesis Impaired intestinal barrier function is observed in type I diabetes patients and animal models of the disease. Exposure to diabetogenic antigens from the intestinal milieu due to a compromised intestinal barrier is considered essential for induction of the autoimmune process leading
DRESS syndrome with autoimmune hepatitis from strontium ranelate.
di Meo, Nicola; Gubertini, Nicoletta; Crocè, Lory; Tiribelli, Claudio; Trevisan, Giusto
Strontium ranelate, which is used for postmenopausal osteoporosis, has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome, a severe, acute, potentially fatal, multisystem adverse drug reaction characterized by skin rash, fever, hematological abnormalities, and lymphadenopathy with involvement of several internal organs. We report the case of a woman who developed DRESS syndrome with a generalized maculopapular rash, eosinophilia, dyspnea, bilateral cervical lymphadenopathy, and reactivation of Epstein-Barr virus (EBV) with liver damage 3 weeks after administration of strontium ranelate for postmenopausal osteoporosis. Approximately 6 months after total remission of cutaneous symptoms, the patient developed autoimmune hepatitis. This case confirms that strontium ranelate should be considered as a possible factor in the etiopathology of DRESS syndrome as well as in the subsequent development of autoimmune hepatitis. The possibility of developing autoimmune hepatitis as a part of DRESS syndrome related to strontium ranelate use can occur months after the acute episode. PMID:27274555
Cancer and autoimmunity: Harnessing longitudinal cohorts to probe the link.
Egiziano, Giordano; Bernatsky, Sasha; Shah, Ami A
In many autoimmune rheumatic diseases, there is an increased risk of cancer compared to the general population. While reasons for this increased risk have not been elucidated, it has been hypothesized that the link between cancer and autoimmunity may be bidirectional. For instance, chronic inflammation and damage from the rheumatic disease or its therapies may trigger malignant transformation; conversely, antitumor immune responses targeting cancers may become cross-reactive resulting in autoimmunity. In rare rheumatic diseases, longitudinal observational studies can play a critical role in studying these complex relationships, thereby enabling investigators to quantify the extent of cancer risk, identify unique clinical phenotypes associated with cancer, investigate the biological link between these conditions, and define optimal strategies for screening and treatment of the underlying cancer. In this review, we discuss recent data on cancer in the rheumatic diseases and suggest a research agenda to address several gaps in our current knowledge base. PMID:27421216
Type 1 diabetes associated autoimmunity.
Kahaly, George J; Hansen, Martin P
Diabetes mellitus is increasing in prevalence worldwide. The economic costs are considerable given the cardiovascular complications and co-morbidities that it may entail. Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the loss of insulin-producing pancreatic β-cells. The pathogenesis of T1D is complex and multifactorial and involves a genetic susceptibility that predisposes to abnormal immune responses in the presence of ill-defined environmental insults to the pancreatic islets. Genetic background may affect the risk for autoimmune disease and patients with T1D exhibit an increased risk of other autoimmune disorders such as autoimmune thyroid disease, Addison's disease, autoimmune gastritis, coeliac disease and vitiligo. Approximately 20%-25% of patients with T1D have thyroid antibodies, and up to 50% of such patients progress to clinical autoimmune thyroid disease. Approximately 0.5% of diabetic patients have concomitant Addison's disease and 4% have coeliac disease. The prevalence of autoimmune gastritis and pernicious anemia is 5% to 10% and 2.6% to 4%, respectively. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Patients and family members should be educated to be able to recognize signs and symptoms of underlying disease. PMID:26903475
Intestinal failure:Pathophysiological elements and clinical diseases
Lian-An Ding; Jie-Shou Li
There are two main functions of gastrointestinal tract,digestion and absorption, and barrier function. The latter has an important defensive effect, which keeps the body away from the invading and damaging of bacteria and endotoxin. It maintains the systemic homeostasis. Intestinal dysfunction would happen when body suffers from diseases or harmful stimulations. The lesser dysfunction of GI tract manifests only disorder of digestion and absorption,whereas the more serious intestinal disorders would harm the intestinal protective mechanism, or intestinal barrier function, and bacterial/endotoxin translocation, of intestinal failure (IF) would ensue. This review disscussed the theory of the intestinal failure, aiming at attracting recognition and valuable comments by clinicians.
Effect of intestinal resection on hydrogen sulfide biosynthesis and the damage of Cajal interstitial cells%肠道手术对肠道硫化氢生成及Cajal间质细胞破坏的影响
黄颖; 邵宇; 叶道雄; 黄胜辉; 徐宗斌; 池畔
the expression of c-kit in order to calculate the area of ICC. Results The mRNA expression of CSE was detected in the small intestine tissue of mice , while no CBS mRNA was found. The mRNA expression of CSE in proximal anastomotic stoma increased in time-dependent manner in the model group. CSE mRNA expression began to increase 1 hour after operation , reached the peak at 6th hour, then decreased gradually, and was similar to the control group at postoperative 24th hour. Compared to the model group, in the intestinal tissues of proximal 3 cm to anastomotic stoma, the mRNA expression of CSE (1.16 ± 0.18 vs. 1.63±0.13, P<0.05), the activity of MPO [(0.54 ± 0.07) U/g vs. (0.83 ± 0.09) U/g, P<0.05], the H2S level [(36.1±6.1) nmol/mg vs. (5.3±5.6) nmol/mg, P<0.05] were significantly reduced in the PPG group. Meanwhile, average percentage of positive ICC area in the PPG groups was significantly higher[(2.26±0.19)%vs. (1.65±0.24)%, P<0.05]. Conclusions Inflammatory reaction in muscular layer induced by intestinal resection up-regulates the mRNA expression of CSE proximal to anastomotic stoma, generates excess H2S to damage ICC leading to intestinal motor dysfunction. Preoperative inhibition of endogenous H2S generation may protect the ICC.
Sensitivity of a hyperosmolar or "low"-osmolar test solution for sugar absorption in recognizing small intestinal mucosal damage in coeliac disease.
Uil, J J; van Elburg, R M; Janssens, P M; Mulder, C J; Heymans, H S
Reliability of differential sugar absorption tests is hampered by a lack of standardization of the content and osmolarity of the test solutions. We evaluated the effect of osmolarity of the test solution of the sugar absorption test on the 5 hour urine excretion of orally administered lactulose and mannitol. A group of 28 controls and 14 coeliacs, with villous atrophy grade II to IV, ingested a hyperosmolar sugar absorption test solution and a "low"-osmolar solution, respectively. After an overnight fast, each subject ingested hyperosmolar sugar absorption test solution (2 g mannitol, 5 g lactulose and 40 g sucrose/100 ml (around 1,560 mmol/l)). After two days, this procedure was repeated with low-osmolar solution (2 g mannitol and 5 g lactulose/100 ml (around 375 mmol/l). The influence of the sequence of the tests on the results had previously been excluded. All urine from the 5 h-period following ingestion of the test solution was collected. To calculate the low-osmolar solution ratio, samples were analysed for lactulose and mannitol concentrations by gas chromatography The sensitivity of hyperosmolar SAT solution and low-osmolar solution for the detection of mucosal abnormalities in coeliacs was 64% and 43%, respectively. In conclusion, a hyperosmolar solution discriminates better between normal and damaged mucosa of the small bowel such as villous atrophy due to a relative increase in permeability for lactulose. PMID:10975768
[Autoimmune pancreatitis as an element of autoimmune polyglandular syndrome].
Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek
Autoimmune pancreatitis constantly belongs to diseases which often causes significant diagnostic problem and often runs out with surgical intervention as considered to be a pancreatic cancer. Important although usually underestimated problems are polyglandular syndromes, which may consist of autoimmune pancreatitis (AIP) problem as well. This case report is an example of autoimmune polyglandular syndrome (APS), which was connected with the surgical treatment with biliary bypass anastomosis because of the unresectable lesion in the head of pancreas. The definite remission of the pancreatic lesion finally came after a steroid therapy. Differentiation between neoplastic and inflammatory pancreatic tumors very often remains a serious clinical problem. On grounds of imaging and cytopathology exams it is often difficult to decide about the nature of a lesion. The negative result of cytopathological biopsy examination does not finally settle straightforward diagnosis. Diagnostic problems affect also autoimmune pancreatitis. It is worth to undertake attempts to differentiate pancreatic lesions especially in cases of concomitance with other autoimmune polyglandular syndromes. That is because it is connected with completely different treatment and outcome. We should remember about diagnostic criteria of autoimmune pancreatitis. Appropriate diagnosis for patients with AIP gives them a chance to avoid serious surgical resection and possible complications. PMID:27234865
Autoimmune Inner Ear Disease (AIED)
... to order. Mention "VEDA" to receive a 15% discount. Paid Advertisement Disclaimer Information on this website is ... treatment of autoimmune inner ear disease. Although drug companies are not directly studying treatments for inner ear ...
Sex differences in autoimmune diseases
Voskuhl Rhonda
Full Text Available Abstract Women are more susceptible to a variety of autoimmune diseases including systemic lupus erythematosus (SLE, multiple sclerosis (MS, primary biliary cirrhosis, rheumatoid arthritis and Hashimoto's thyroiditis. This increased susceptibility in females compared to males is also present in animal models of autoimmune diseases such as spontaneous SLE in (NZBxNZWF1 and NZM.2328 mice, experimental autoimmune encephalomyelitis (EAE in SJL mice, thyroiditis, Sjogren's syndrome in MRL/Mp-lpr/lpr mice and diabetes in non-obese diabetic mice. Indeed, being female confers a greater risk of developing these diseases than any single genetic or environmental risk factor discovered to date. Understanding how the state of being female so profoundly affects autoimmune disease susceptibility would accomplish two major goals. First, it would lead to an insight into the major pathways of disease pathogenesis and, secondly, it would likely lead to novel treatments which would disrupt such pathways.
Epigenetic alterations underlying autoimmune diseases.
Aslani, Saeed; Mahmoudi, Mahdi; Karami, Jafar; Jamshidi, Ahmad Reza; Malekshahi, Zahra; Nicknam, Mohammad Hossein
Recent breakthroughs in genetic explorations have extended our understanding through discovery of genetic patterns subjected to autoimmune diseases (AID). Genetics, on the contrary, has not answered all the conundrums to describe a comprehensive explanation of causal mechanisms of disease etiopathology with regard to the function of environment, sex, or aging. The other side of the coin, epigenetics which is defined by gene manifestation modification without DNA sequence alteration, reportedly has come in to provide new insights towards disease apprehension through bridging the genetics and environmental factors. New investigations in genetic and environmental contributing factors for autoimmunity provide new explanation whereby the interactions between genetic elements and epigenetic modifications signed by environmental agents may be responsible for autoimmune disease initiation and perpetuation. It is aimed through this article to review recent progress attempting to reveal how epigenetics associates with the pathogenesis of autoimmune diseases. PMID:26761426
Endocrine autoimmunity in Turner syndrome
Grossi, Armando; Crinò, Antonino; Luciano, Rosa; Lombardo, Antonietta; Cappa, Marco; Fierabracci, Alessandra
Background Turner syndrome is caused by numeric and structural abnormalities of the X chromosome. An increased frequency of autoimmunity as well as an elevated incidence of autoantibodies was observed in Turner patients. The aim of this study was to conduct a retrospective analysis of the incidence of autoimmunity in 66 Italian patients affected by Turner syndrome. Methods Sixty-six unselected and consecutive Italian Turner patients were recruited. The association between age, karyotype and t...
Gestational Diabetes and Thyroid Autoimmunity
Fabrizio Monaco; Giorgio Napolitano; Cesidio Giuliani; Ester Vitacolonna; Ines Bucci; Barbara Di Nenno; Annalisa Passante; Annunziata Lapolla; Dominique Cerrone; Fabio Capani
Background. About 10% of pregnancies are complicated by previously unknown impairment of glucose metabolism, which is defined as gestational diabetes. There are little data available on prevalence of thyroid disorders in patients affected by gestational diabetes, and about their postgestational thyroid function and autoimmunity. We therefore investigated pancreatic and thyroid autoimmunity in gestational diabetic patients and in women who had had a previous gestational diabetic pregnancy. Met...
Ulcerative Colitis associated with Sclerosing Cholangitis and Autoimmune Hepatitis
Hoduț Andrei
Full Text Available Introduction: Ulcerative colitis is a chronic intestinal inflammation, part of inflammatory bowel disease, which also includes Crohn's disease. Both have extraintestinal manifestations, but those that tend to occur more commonly with ulcerative colitis include chronic active hepatitis, pyoderma gangrenosum and ankylosing spondylitis. Many individuals present with overlapping non-diagnostic features of more than one of these conditions that is referred to in the literature as autoimmune overlap syndrome. Sclerosing cholangitis associated with IBD is often referred to as overlap syndrome.
Silber, Michael H
A number of autoantibodies, some paraneoplastic, are associated with sleep disorders. Morvan syndrome and limbic encephalitis, associated with voltage-gated potassium channel-complex antibodies, principally against CASPR2 and LGI1, can result in profound insomnia and rapid eye movement sleep behavior disorder (RBD). Patients with aquaporin-4 antibodies and neuromyelitis optica may develop narcolepsy in association with other evidence of hypothalamic dysfunction, sometimes as the initial presentation. Central sleep apnea and central neurogenic hypoventilation are found in patients with anti-N-methyl-d-aspartate receptor antibody encephalitis, and obstructive sleep apnea, stridor, and hypoventilation are prominent features of a novel tauopathy associated with IgLON5 antibodies. In addition, paraneoplastic diseases may involve the hypothalamus and cause sleep disorders, particularly narcolepsy and RBD in those with Ma1 and Ma2 antibodies. Patients with antineuronal nuclear autoantibodies type 2 may develop stridor. Several lines of evidence suggest that narcolepsy is an autoimmune disorder. There is a strong relationship with the human leukocyte antigen (HLA) DQB1*06:02 haplotype and polymorphisms in the T-cell receptor alpha locus and purinergic receptor P2Y11 genes. Patients with recent-onset narcolepsy may have high titers of antistreptococcal or other antibodies, although none has yet been shown to be disease-specific but, supporting an immune basis, recent evidence indicates that narcolepsy in children can be precipitated by one type of vaccination against the 2009-2010 H1N1 influenza pandemic. PMID:27112685
González Rodríguez, C I; Cires, M; Jiménez, F J; Rubio, T
Endometriosis is a chronic, benign gynaecological disorder that is frequent in women of a child-bearing age. It is estimated that there is some degree of endometriosis in as many as 15% of pre-menopausal women, associated with a history of infertility, caesarean antecedents, dysmenorrhoea and abnormality in uterine bleeding. It is believed to be due to the rise of menstrual contents through the Fallopian tubes (retrograde menstruation). In the intestinal affectation, the colon is the segment most frequently affected, above all at the rectosigmoidal level. The clinical features are unspecific, with abdominal pain the most frequent and/or pelvic pain of a cholic type that coincides with, or is exacerbated by, menstruation. Differential diagnosis includes intestinal inflammatory disease, diverticulitis, ischemic colitis and neoplastic processes, with the definitive diagnosis being anatomopathological. With respect to treatment, this will depend on the clinical features and the age of the patient, as well as her wishes with regard to pregnancy. PMID:18953367
Bouguen, Guillaume; Dubuquoy, Laurent; Desreumaux, Pierre; Brunner, Thomas; Bertin, Benjamin
Steroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucoc...
A rare presentation of hypopituitarism in hepatic overlap syndrome of autoimmune hepatitis and autoimmune cholangitis
Gupta V; Singh H.; Talapatra P; Ray S
Autoimmune cholangitis is the antimitochondrial antibody-negative autoimmune hepatopathy with clinical and histological features similar to that of primary biliary cirrhosis. Autoimmune cholangitis has a predominant cholestatic phase. However, transaminasemia might be dominant in certain patients, indicating associated autoimmune hepatitis. Such an autoimmune hepatopathy has been termed as hepatic overlap syndrome. Due to the autoimmune nature of the disease, associated diseases of other orga...
Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis
Jun Gao
Full Text Available Primary biliary cirrhosis (PBC is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice.
Severe autoimmune hepatitis triggered by varicella zoster infection
Waleed K Al-Hamoudi
Autoimmune hepatitis (AIH) is a chronic disease of unknown etiology that is characterized by the presence of circulatory autoantibodies and inflammatory histological changes in the liver. Although the pathogenesis of AIH is not known, it is thought that,in a genetically predisposed individual, environmental factors such as viruses can trigger the autoimmune process. Herpes simplex virus, Epstein-Barr virus,measles virus, and hepatitis viruses are thought to play a role in the etiology of AIH. Proteins belonging to these viruses may be similar to the amino acid chains of different autoantigens in the liver, this causes immune cross reactions and liver tissue damage. We report a case of severe AIH following varicella zoster infection in a 23-year-old man, and speculate that,based on the molecular mimicry hypothesis, the liver damage was caused by an immune cross reaction to the viral proteins. Varicella-zoster-induced AIH has not been reported previously.
Primary Biliary Cirrhosis Is a Generalized Autoimmune Epithelitis
Gao, Jun; Qiao, Liang; Wang, Bingyuan
Primary biliary cirrhosis (PBC) is a chronic progressive autoimmune cholestatic liver disease characterized by highly specific antimitochondrial antibodies (AMAs) and the specific immune-mediated injury of small intrahepatic bile ducts. Unique apoptotic feature of biliary epithelial cells (BECs) may contribute to apotope presentation to the immune system, causing unique tissue damage in PBC. Perpetuation of inflammation may result in senescence of BECs, contributing to irreversible loss of bile duct. In addition to the classic liver manifestations, focal inflammation and tissue damage are also seen in salivary glands and urinary tract in a significant proportion of PBC patients. These findings provide potent support to the idea that molecular mimicry may be involved in the breakdown of autoimmune tolerance and mucosal immunity may lead to a systematic epithelitis in PBC patients. Thus, PBC is considered a generalized epithelitis in clinical practice. PMID:25803105
Characterizing intestinal strictures with acoustic resolution photoacoustic microscopy
Lei, Hao; Xu, Guan; Liu, Shengchun; Johnson, Laura A.; Moons, David S.; Higgins, Peter D. R.; Rice, Michael D.; Ni, Jun; Wang, Xueding
Crohn's disease (CD) is an autoimmune disease, which may cause obstructing intestinal strictures due to inflammation, fibrosis (deposition of collagen), or a combination of both. Identifying the different stages of the disease progression is still challenging. In this work, we indicated the feasibility of non-invasively characterizing intestinal strictures using photoacoustic imaging (PAI), utilizing the uniquely optical absorption of hemoglobin and collagen. Surgically removed human intestinal stricture specimens were investigated with a prototype PAI system. 2D PA images with acoustic resolution at wavelength 532, 1210 and 1310 nm were formulated, and furthermore, the PA histochemical components images which show the microscopic distributions of histochemical components were solved. Imaging experiments on surgically removed human intestinal specimens has demonstrated the solved PA images were significantly different associated with the presence of fibrosis, which could be applied to characterize the intestinal strictures for given specimens.
Ana Maria Abreu Velez
Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a "cluster of jewels"-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of
Estrogens and autoimmune diseases.
Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H
Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796
Defective removal of ribonucleotides from DNA promotes systemic autoimmunity
Günther, Claudia; Kind, Barbara; Reijns, Martin A.M.; Berndt, Nicole; Martinez-Bueno, Manuel; Wolf, Christine; Tüngler, Victoria; Chara, Osvaldo; Lee, Young Ae; Hübner, Norbert; Bicknell, Louise; Blum, Sophia; Krug, Claudia; Schmidt, Franziska; Kretschmer, Stefanie; Koss, Sarah; Astell, Katy R.; Ramantani, Georgia; Bauerfeind, Anja; Morris, David L.; Cunninghame Graham, Deborah S.; Bubeck, Doryen; Leitch, Andrea; Ralston, Stuart H.; Blackburn, Elizabeth A.; Gahr, Manfred; Witte, Torsten; Vyse, Timothy J.; Melchers, Inga; Mangold, Elisabeth; Nöthen, Markus M.; Aringer, Martin; Kuhn, Annegret; Lüthke, Kirsten; Unger, Leonore; Bley, Annette; Lorenzi, Alice; Isaacs, John D.; Alexopoulou, Dimitra; Conrad, Karsten; Dahl, Andreas; Roers, Axel; Alarcon-Riquelme, Marta E.; Jackson, Andrew P.; Lee-Kirsch, Min Ae
Genome integrity is continuously challenged by the DNA damage that arises during normal cell metabolism. Biallelic mutations in the genes encoding the genome surveillance enzyme ribonuclease H2 (RNase H2) cause Aicardi-Goutières syndrome (AGS), a pediatric disorder that shares features with the autoimmune disease systemic lupus erythematosus (SLE). Here we determined that heterozygous parents of AGS patients exhibit an intermediate autoimmune phenotype and demonstrated a genetic association between rare RNASEH2 sequence variants and SLE. Evaluation of patient cells revealed that SLE- and AGS-associated mutations impair RNase H2 function and result in accumulation of ribonucleotides in genomic DNA. The ensuing chronic low level of DNA damage triggered a DNA damage response characterized by constitutive p53 phosphorylation and senescence. Patient fibroblasts exhibited constitutive upregulation of IFN-stimulated genes and an enhanced type I IFN response to the immunostimulatory nucleic acid polyinosinic:polycytidylic acid and UV light irradiation, linking RNase H2 deficiency to potentiation of innate immune signaling. Moreover, UV-induced cyclobutane pyrimidine dimer formation was markedly enhanced in ribonucleotide-containing DNA, providing a mechanism for photosensitivity in RNase H2–associated SLE. Collectively, our findings implicate RNase H2 in the pathogenesis of SLE and suggest a role of DNA damage–associated pathways in the initiation of autoimmunity. PMID:25500883
Autoimmune hepatitis in association with lymphocytic colitis.
Cronin, Edmond M
Autoimmune hepatitis is a rare, chronic inflammatory disorder which has been associated with a number of other auto-immune conditions. However, there are no reports in the medical literature of an association with microscopic (lymphocytic) colitis. We report the case of a 53-year-old woman with several autoimmune conditions, including lymphocytic colitis, who presented with an acute hepatitis. On the basis of the clinical features, serology, and histopathology, we diagnosed autoimmune hepatitis. To our knowledge, this is the first report of autoimmune hepatitis in association with lymphocytic colitis, and lends support to the theory of an autoimmune etiology for lymphocytic colitis.
MJ Ggaravi
Full Text Available Intestinal Coccidia are a subclass of Apicomplexa phylum. Eucoccidida are facultative heteroxenous, but some of them are monoxenous. They have sexual and asexual life cycle. Some coccidia are human pathogens, for example: Cryptosporidium: Cryptosporidiums has many species that are mammalian intestinal parasites.C. Parvum specie is a human pathogenic protozoa. Cryptosporidum has circle or ellipse shapes and nearly 4-6 mm. It is transmitted in warm seasons. Oocyst is obtained insexual life cycle that has 20% thin layer and 80% thick layer. Oocyst with thick layer is able to live a long time in nature. They are the third or forth of gastroentritis disease that have digestive disorder like anorexia, nausea, persistent diarrhoea, malabsorption and leanness. The disease forms choronic and acute stages and it is able to kill the immunodeficiency cases. Sometimes it has HIV symptoms similar to pneumonia and respiratory track infection. Laboratory diagnosis is based on Oocyst finding in stool exam and that shitter floatation and Cr (KOH2 are the best methods. Modified zyh-lnelson and fleocroum are the best staining methods too. This parasite is transmitted by zoonotic and Antroponotic origin. Molecular studies have shown two Genotypes (I&II. Genotype I is aquatic and II is zoonotic. The prevalence rate is 3% in infants and 10% in calves. Cyclospora: This parasite is novel and is bigger than cryptosporidium.It isn't known a clear life cycle but is transmitted by water, vegetables and fruits as raspberries. and mulberries. Human is a specific host. When a parasite is in the intestine it causes inflammatory reaction in Entrocyte.The patient shows watery diarrhoea with nausea, vomitting, pain, Stomach cramp, anorexia, malabsorption and cachexia. The disease period is 3 monthes in immunodeficiency cases but it is selflimited in normal cases. Autofluorescence characteristic is differential diagnosis, prevalence rate of disease is unknown. Isospora: This
Type 1 autoimmune pancreatitis
Zen Yoh
Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of
Autoimmune pancreatitis. An update
Autoimmune pancreatitis (AIP) is a rare disease, the pathophysiological understanding of which has been greatly improved over the last years. The most common form, type 1 AIP belongs to the IgG4-related diseases and must be distinguished from type 2 AIP, which is a much rarer entity associated with chronic inflammatory bowel disease. Clinically, there is an overlap with pancreatic cancer. Imaging and further criteria, such as serological and histological parameters are utilized for a differentiation between both entities in order to select the appropriate therapy and to avoid the small but ultimately unnecessary number of pancreatectomies. The diagnostics of AIP are complex, whereby the consensus criteria of the International Association of Pancreatology have become accepted as the parameters for discrimination. These encompass five cardinal criteria and one therapeutic criterion. By applying these criteria AIP can be diagnosed with a sensitivity of 84.9 %, a specificity of 100 % and an accuracy of 93.8 %. The diagnosis of AIP is accomplished by applying several parameters of which two relate to imaging. As for the routine diagnostics of the pancreas these are ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI). Important for the differential diagnosis is the exclusion of signs of local and remote tumor spread for which CT and MRI are established. The essential diagnostic parameter of histology necessitates sufficient sample material, which cannot usually be acquired by a fine needle biopsy. CT or MRI are the reference standard methods for identification of the optimal puncture site and imaging-assisted (TruCut) biopsy. In patients presenting with unspecific upper abdominal pain, painless jaundice combined with the suspicion of a pancreatic malignancy in imaging but a mismatch of secondary signs of malignancy, AIP should also be considered as a differential diagnosis. As the diagnosis of AIP only partially relies on imaging radiologists also
Focal Adhesion Kinase Is Required for Intestinal Regeneration and Tumorigenesis Downstream of Wnt/c-Myc Signaling
Ashton, Gabrielle H.; Morton, Jennifer P; Myant, Kevin; Phesse, Toby J.; Ridgway, Rachel A.; Marsh, Victoria; Wilkins, Julie A.; Athineos, Dimitris; Muncan, Vanesa; Kemp, Richard; Neufeld, Kristi; Clevers, Hans; Brunton, Valerie; Winton, Douglas J.; Wang, Xiaoyan
The intestinal epithelium has a remarkable capacity to regenerate after injury and DNA damage. Here, we show that the integrin effector protein Focal Adhesion Kinase (FAK) is dispensable for normal intestinal homeostasis and DNA damage signaling, but is essential for intestinal regeneration following DNA damage. Given Wnt/c-Myc signaling is activated following intestinal regeneration, we investigated the functional importance of FAK following deletion of the Apc tumor suppressor protein withi...
Large intestine (colon) (image)
The large intestine is the portion of the digestive system most responsible for absorption of water from the indigestible ... the ileum (small intestine) passes material into the large intestine at the cecum. Material passes through the ...
[Bullous autoimmune disorders in children].
Sárdy, M; Kasperkiewicz, M
We review the pathogenesis, clinical features, diagnosis, differential diagnosis, and therapy of autoimmune bullous skin diseases of childhood, especially of the most common linear IgA dermatosis. In autoimmune bullous diseases, autoantibodies are formed against different adhesion molecules of the skin. These are not only pathophysiologically relevant, but also serve as basis for diagnosis and follow-up of these diseases. In case an autoimmune bullous disease is suspected, histopathology and immunohistopathology (direct immunofluorescence microscopy) as well as serological tests (indirect immunofluorescence microscopy, ELISA, immunoblot) should be performed. Therapy depends on the diagnosis. In IgA-mediated pathogenesis, dapsone can be successfully used. In IgG-mediated diseases, immunosuppression with corticosteroids and steroid-sparing agents should be initiated, although only local therapy is sufficient to control a self-limiting pemphigus neonatorum. In dermatitis herpetiformis, a life-long gluten-free diet is recommended. PMID:23677541
Thyroid dysfunction: an autoimmune aspect.
Khan, Farah Aziz; Al-Jameil, Noura; Khan, Mohammad Fareed; Al-Rashid, May; Tabassum, Hajera
Auto immune thyroid disease (AITD) is the common organ specific autoimmune disorder, Hashimoto thyroiditis (HT) and Grave's disease (GD) are its well-known sequelae. It occurs due to loss of tolerance to autoantigens thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid stimulating hormone receptor (TSH-R) which leads to the infiltration of the gland. T cells in chronic autoimmune thyroiditis (cAIT) induce apoptosis in thyroid follicular cells and cause destruction of the gland. Presences of TPO antibodies are common in HT and GD, while Tg has been reported as an independent predictor of thyroid malignancy. Cytokines are small proteins play an important role in autoimmunity, by stimulating B and T cells. Various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-14, TNF-α and IFN-γ are found in thyroid follicular cells which enhance inflammatory response with nitric oxide (NO) and prostaglandins. PMID:26221205
[Infectious agents and autoimmune diseases].
Riebeling-Navarro, C; Madrid-Marina, V; Camarena-Medellín, B E; Peralta-Zaragoza, O; Barrera, R
In this paper the molecular aspects of the relationships between infectious agents and autoimmune diseases, the mechanisms of immune response to infectious agents, and the more recent hypotheses regarding the cause of autoimmune diseases are discussed. The antigens are processed and selected by their immunogenicity, and presented by HLA molecules to the T cell receptor. These events initiate the immune response with the activation and proliferation of T-lymphocytes. Although there are several hypotheses regarding the cause of autoimmune diseases and too many findings against and in favor of them, there is still no conclusive data. All these hypothesis and findings are discussed in the context of the more recent advances. PMID:1615352
Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?
Zhonghui Wen
Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.
Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells
Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4+ T cells mediated the autoimmune prevention but CD8+ T cells did not. CD4+ T cells also appeared to mediate the TLI-induced autoimmune disease because CD4+ T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs
Intestinal failure: Pathophysiological elements and clinical diseases
Ding, Lian-An; Li, Jie-Shou
There are two main functions of gastrointestinal tract, digestion and absorption, and barrier function. The latter has an important defensive effect, which keeps the body away from the invading and damaging of bacteria and endotoxin. It maintains the systemic homeostasis. Intestinal dysfunction would happen when body suffers from diseases or harmful stimulations. The lesser dysfunction of GI tract manifests only disorder of digestion and absorption, whereas the more serious intestinal disorde...
Coeliac disease with autoimmune haemolytic anaemia.
Miller, D. G.
Two patients are described who have developed autoimmune haemolytic anaemia in association with their coeliac disease. Autoimmune haemolytic anaemia may represent an extension of immunological disorders linked with coeliac disease, centred on the histocompatibility antigen B8.
Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases
Huey-Kang Sytwu
Full Text Available Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease.
Radiosensitivity of peripheral blood lymphocytes in autoimmune disease
The proliferation of peripheral blood lymphocytes, cultured with Con A, can be inhibited by ionizing radiation. Lymphocytes from patients with conditions associated with autoimmunity, such as rheumatoid arthritis, systemic lupus erythematosus and polymyositis, are more radiosensitive than those from healthy volunteers or patients with conditions not associated with autoimmunity. Nuclear material isolated from the lymphocytes of patients with autoimmune diseases is, on average, lighter in density than the nuclear material from most healthy controls. This difference in density is not related to increased sensitivity to ionizing radiation but the degree of post-irradiation change in density (lightening) is proportional to the initial density, i.e. more dense nuclear material always shows a greater upward shift after radiation. The recovery of pre-irradiation density of nuclear material, 1 h after radiation exposure, taken as an indication of DNA repair, correlates with the radiosensitivity of lymphocyte proliferation (Con A response); failure to return to pre-irradiation density being associated with increased sensitivity of proliferative response. These results require extension but, taken with previously reported studied of the effects of DNA methylating agents, support the idea that DNA damage and its defective repair could be important in the aetio-pathogenesis of autoimmune disease. (author)
Autoimmune thyroid disorders—An update
Swain, Manorama; Swain, Truptirekha; Mohanty, Binoy Kumar
Background: Autoimmune thyroid disease (AITD), a common organ specific autoimmune disorder is seen mostly in women between 30–50 yrs of age. Thyroid autoimmunity can cause several forms of thyroiditis ranging from hypothyroidism (Hashimoto's thyroiditis) to hyperthyroidism (Graves'Disease). Prevalence rate of autoimmune mediated hypothyroidism is about 0.8 per 100 and 95% among them are women. Graves' disease is about one tenth as common as hypothyroidism and tends to occur more in younger in...
Autoimmune Skin Diseases in the Dog
Parker, W M
Diagnoses of autoimmune skin diseases require very careful observation of the skin lesions, and selection of an intact vesicle for histopathological examination. If available, immunofluorescent studies can be very useful in confirming the diagnosis of autoimmune skin disease. Seven autoimmune skin diseases are briefly reviewed. Therapy must be aggressive and owner warned of the guarded prognosis.
Multiparametric autoimmune diagnostics: recent advances
Damoiseaux J
Jan Damoiseaux Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands Abstract: Autoimmune diagnostics in a routine clinical laboratory is constantly challenged by the discovery of new autoantibodies and technical innovations in the immunoassays applied. These challenges are, in particular, combined in the multiparametric immunoassays. Appropriate positioning of multiparametric immunoassays within the laboratory requires integrated knowledge of the c...
Pancreatic Tuberculosis or Autoimmune Pancreatitis
Ayesha Salahuddin; Muhammad Wasif Saif
Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 relate...
An autosomal locus causing autoimmune disease: Autoimmune polyglandular disease type I assigned to chromosome 21
Aaltonen, Johanna; Björses, Petra; Sandkuijl, Lodewijk; Perheentupa, Jaakko; Peltonen, Leena Johanna
textabstractAutoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease characterized by a variable combination of the failure of the endocrine glands. The pathogenesis of this unique autoimmune disease is unknown; unlike many other autoimmune diseases, APECED does not show association to specific HLA haplotypes. Unravelling the APECED locus will identify a novel gene outside the HLA loci influencing the outcome of autoimmune diseases. We have assigned the di...
Autoimmune congenital heart block: complex and unusual situations.
Brito-Zerón, P; Izmirly, P M; Ramos-Casals, M; Buyon, J P; Khamashta, M A
Autoimmune congenital heart block (ACHB) is an immune-mediated cardiac disease included among the manifestations collectively referred to as neonatal lupus. The placental transference of maternal Ro/La autoantibodies may damage the conduction tissues during fetal development leading to blocking of signal conduction at the atrioventricular (AV) node in an otherwise structurally normal heart. Irreversible complete AV block is the main cardiac manifestation of ACHB, but some babies may develop endocardial fibroelastosis, valvular insufficiency, and/or frank cardiomyopathies with significantly reduced cardiac function requiring transplant. The severity of ACHB is illustrated by a global mortality rate of 20% and pacemaker rates of at least 64%, often within the first year of life. This review analyses the main complex and/or unusual clinical situations associated with ACHB, including unusual maternal immunological profiles, infrequent maternal autoimmune diseases, cardiac damage unrelated to AV block, fetal invasive management, late complications after birth, risk of congenital heart block (CHB) in ovodonation and in vitro fertilization techniques, the role of maternal features other than autoimmunity, the influence of the birth order or the risk of CHB in twins and triplets. PMID:26762645
Thyroid autoimmunity in pregnant Nigerians
Oluwatosin O Kayode
Full Text Available Context: Thyroid autoimmunity is a recognized disorder in pregnancy and is associated with a number of adverse pregnancy outcomes. Aim: This study set out to determine the relationship between pregnancy and thyroid autoimmunity in Nigerian women. Settings and Design: This was an analytical cross-sectional study carried out in a tertiary hospital in South Western Nigeria with a total study population of 108 pregnant and 52 nonpregnant women. Subjects and Methods: Serum thyroid stimulating hormone, free thyroxine and thyroid peroxidase antibodies (TPO-Ab were quantitatively determined using enzyme linked immuno-assays. Pregnant women were grouped into three categories ( 28 weeks. The relationship between pregnancy and thyroid autoimmunity was determined using Spearman correlation. Analysis of variance was used in comparison of means, Chi-square test used in analyzing proportions while P ≤ 0.05 was considered as significant. Results: The mean age of the pregnant women was 30.4 ± 6.0 years while the mean gestational age of all pregnant women was 20.6 ± 9.6 weeks. The mean TPO-Ab of 11.58 IU/ml in the pregnant was significantly higher than that of the controls of 7.23 IU/ml (P < 0.001. Out of 108 pregnant women, 27 (25% had elevated TPO-Ab as against about 2% of the nonpregnant women levels P < 0.001. The number of pregnant women with elevated TPO-Ab levels decreased from 33.3% in the first group to 25.6% and 15.2% in the second and third groups. Conclusion: Thyroid autoimmunity expressed by the presence of TPO-Ab is high among pregnant Nigerian women and the frequency of autoimmunity appears to decline with advancing gestational age.
Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis
Peggy P. Ho; Steinman, Lawrence
Bile acids bind to the nuclear hormone receptor, farnesoid X receptor (FXR). This bile acid–FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, drugs targeting FXR activation have been reported to treat both liver and intestinal inflammatory diseases in both animal models and human clinical trials. Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease of the central nervous system and serves as an animal model for ...
Juvenile autoimmune hepatitis: Spectrum of the disease
Giuseppe; Maggiore; Silvia; Nastasio; Marco; Sciveres
Juvenile autoimmune hepatitis(JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific andorgan-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoan-tibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature.
A Nonsecosteroidal Vitamin D Receptor Modulator Ameliorates Experimental Autoimmune Encephalomyelitis without Causing Hypercalcemia
Songqing Na
Full Text Available Vitamin D receptor (VDR agonists are currently the agents of choice for the treatment of psoriasis, a skin inflammatory indication that is believed to involve an autoimmune component. 1,25-dihydroxyvitamin D3 [1,25-(OH2D3], the biologically active metabolite of vitamin D, has shown efficacy in animal autoimmune disease models of multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, and type I diabetes. However, the side effect of 1,25-(OH2D3 and its synthetic secosteroidal analogs is hypercalcemia, which is a major impediment in their clinical development for autoimmune diseases. Hypercalcemia develops as a result of the action of VDR agonists on the intestine. Here, we describe the identification of a VDR modulator (VDRM compound A that was transcriptionally less active in intestinal cells and as a result exhibited less calcemic activity in vivo than 1,25-(OH2D3. Cytokine analysis indicated that the VDRM not only modulated the T-helper cell balance from Th1 to Th2 effector function but also inhibited Th17 differentiation. Finally, we demonstrate that the oral administration of compound A inhibited the induction and progress of experimental autoimmune encephalomyelitis in mice without causing hypercalcemia.
Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection.
Cunningham, Madeleine W
The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and
Small Intestinal Bacterial Overgrowth: A Case-Based Review
Kristen H. Reynolds
Small intestinal bacterial overgrowth (SIBO) is a condition of increased microbial load in the small intestine. The microbes feed on dietary carbohydrates and starches via fermentation, leading to gas production, inflammation and damage to the lining of the small intestine. Clinical presentation is varied, including abdominal pain, bloating, malabsorption and systemic symptoms. SIBO is associated with many challenging and chronic conditions such as fibromyalgia, chronic fatigue and chronic pa...
Establishment of Intestinal Bacteriology
Mitsuoka, Tomotari
Research on intestinal bacteria began around the end of the 19th century. During the last 5 decades of the 20th century, research on the intestinal microbiota made rapid progress. At first, in my work, I first developed a method of comprehensive analysis of the intestinal microbiota, and then I established classification and identification methods for intestinal anaerobes. Using these methods I discovered a number of ecological rules governing the intestinal microbiota and the role of the int...
Long-term observations of autoimmune-prone mice treated for autoimmune disease by allogeneic bone marrow transplantation
Long-term effects of allogeneic bone marrow transplantation (ABMT) across major histocompatibility complex barriers were studied in (NZB x NZW)F1 (B/W), BXSB, and MRL/Mr-lpr-lpr (MRL/lpr) mice with established autoimmune disease at the time of ABMT. In the BXSB or B/W mice, ABMT cured all aspects of autoimmune disease. Glomerular damage, revealed by histological study was dramatically improved. Serological abnormalities and immunologic functions also were normalized. Correction of autoimmune disease and advanced renal disease in BXSB and B/W mice regularly lasted greater than 5-6 mo and even 1 yr after ABMT. In the MRL/lpr mice, however, autoimmune and renal disease at first improved but then recurred after ABMT, apparently because of intolerance of mice for high doses of irradiation and a high degree of resistance of recipient stem cells to irradiation. In this model, H-2 typing revealed that by the time of relapse, immunocompetent cells of the chimeric mice had been replaced by host (MRL/lpr; H-2k) cells. B220+ Ly-1+ cells, present in increased numbers in untreated MRL/lpr mice, initially returned to normal levels after ABMT but then reappeared in the MRL/lpr mice that had received marrow from donors having few such lymphocytes. Thus, our results show that MRL/lpr mice possess abnormal radioresistant stem cells and provide impressive evidence that the origin of autoimmune diseases in this strain, as in the several other strains studied, resids in abnormalities present in stem cells
Animal Models of Autoimmune Neuropathy
Soliven, Betty
The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy h...
Progranulin antibodies in autoimmune diseases.
Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael
Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338
Immunotherapeutic strategies in autoimmune uveitis
Papotto, Pedro Henrique; Marengo, Eliana Blini; Sardinha, Luiz Roberto; Goldberg, Anna Carla; Rizzo, Luiz Vicente
Autoimmune uveitis is an organ-specific disorder characterized by irreversible lesions to the eye that predominantly affect people in their most productive years and is among the leading causes of visual deficit and blindness. Currently available therapies are effective in the treatment of a wide spectrum of uveitis, but are often associated with severe side effects. Here, we review ongoing research with promising immunomodulatory therapeutic strategies, describing their specific features, in...
Cystic Lesions in Autoimmune Pancreatitis
Gompertz, Macarena; Morales, Claudia; Aldana, Hernán; Castillo, Jaime; Berger, Zoltán
Autoimmune pancreatitis (AIP) can be chronic or recurrent, but frequently completely reversible after steroid treatment. A cystic lesion in AIP is a rare finding, and it can mimic a pancreatic cystic neoplasm. Difficulties in an exact diagnosis interfere with treatment, and surgery cannot be avoided in some cases. We report the history of a 63-year-old male presenting with jaundice and pruritus. AIP was confirmed by imaging and elevated IgG4 blood levels, and the patient completely recovered ...
Autoimmune hypophysitis or lymphocytic hypophysitis
Paiva, I; Gomes, L.; C. Ribeiro; Carvalheiro, M; Ruas, A
This entity, due to the pituitary lymphoplasmacytic infiltrate, was described for the first time in 1962. The clinical suspicion relies on a rapidly progressing hypopituitarism, particularly with adrenal involvement, affecting women in the peripartum period or patients with previously recognized autoimmune disease. Diabetes insipidus is also often reported. A sellar mass is found in 80% of cases. The diagnosis is confirmed by histology, due to the absence of a specific serological test. The e...
Historical reflections on autoimmune hepatitis
Ian R Mackay
Autoimmune hepatitis (AIH),initially known as chronic active or active chronic hepatitis (and by various other names),first came under clinical notice in the late 1940s.However,quite likely,chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver.An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E.cell test positivity and emphasized accompanying multisystem features and immunological aberrations.Young women featured prominently in early descriptions of CAH.AIH was first applied in 1965 as a descriptive term.Disease-characteristic autoantibodies were defined from the early 1960s,notably antinuclear antibody (ANA),smooth muscle antibody (SMA) and liver-kidney microsomal (LKM) antibody.These are still widely used diagnostically but their relationship to pathogenesis is still not evident.A liver and disease specific autoantigen has long been searched for but unsuccessfully.Prolonged immunosuppressive therapy with predisolone and azathioprine in the 1960s proved beneficial and remains standard therapy today.AIH like many other autoimmune diseases is associated with particular HLA alleles especially with the "ancestral" B8,DR3 haplotype,and also with DR4.Looking forwards,AIH is one of the several enigmatic autoimmune diseases that,despite being (relatively) organ specific,are marked by autoimmune reactivities with non-organ-specific autoantigens.New paradigms are needed to explain the occurrence,expressions and pathogenesis of such diseases.
Historical reflections on autoimmune hepatitis
Mackay, Ian R.
Autoimmune hepatitis (AIH), initially known as chronic active or active chronic hepatitis (and by various other names), first came under clinical notice in the late 1940s. However, quite likely, chronic active hepatitis (CAH) had been observed prior to this and was attributed to a persistently destructive virus infection of the liver. An earlier (and controversial) designation in 1956 as lupoid hepatitis was derived from associated L.E. cell test positivity and emphasized accompanying multisy...
[Autoimmune hepatitis induced by isotretionine].
Guzman Rojas, Patricia; Gallegos Lopez, Roxana; Ciliotta Chehade, Alessandra; Scavino, Yolanda; Morales, Alejandro; Tagle, Martín
We describe a case of a teenage patient with the diagnosis of drug induced autoimmune hepatitis. The patient is a 16 years old female, with the past medical history of Hashimoto's hypothyroidism controlled with levothyroxine, who started treatment with Isotretionin (®Accutane) 20 mg q/12 hours for a total of 3 months for the treatment of severe acne. The physical examination was within normal limits and the results of the laboratory exams are: Baseline values of ALT 28 U/L, AST 28 U/L. Three months later: AST 756 U/L, ALT 1199U/L, alkaline phosphatase 114 U/L, with normal bilirrubin levels throughout the process. The serology studies were negative for all viral hepatitis; ANA titers were positive (1/160) and igG levels were also elevated. A liver biopsy was performed, and was compatible with the diagnosis of autoimmune hepatitis. Corticosteroid therapy was started with Prednisone 40 mg per day one week after stopping the treatment with isotretionin, observing an improvement in the laboratory values. We describe this case and review the world literature since there are no reported cases of Isotretinoin-induced autoimmune hepatitis. PMID:27131947
Pancreatic Tuberculosis or Autoimmune Pancreatitis
Ayesha Salahuddin
Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.
Intestinal Iron Homeostasis and Colon Tumorigenesis
Yatrik M. Shah
Full Text Available Colorectal cancer (CRC is the third most common cause of cancer-related deaths in industrialized countries. Understanding the mechanisms of growth and progression of CRC is essential to improve treatment. Iron is an essential nutrient for cell growth. Iron overload caused by hereditary mutations or excess dietary iron uptake has been identified as a risk factor for CRC. Intestinal iron is tightly controlled by iron transporters that are responsible for iron uptake, distribution, and export. Dysregulation of intestinal iron transporters are observed in CRC and lead to iron accumulation in tumors. Intratumoral iron results in oxidative stress, lipid peroxidation, protein modification and DNA damage with consequent promotion of oncogene activation. In addition, excess iron in intestinal tumors may lead to increase in tumor-elicited inflammation and tumor growth. Limiting intratumoral iron through specifically chelating excess intestinal iron or modulating activities of iron transporter may be an attractive therapeutic target for CRC.
Pathogenesis of Autoimmune Diseases: A Short Review
Jithin Jose
Full Text Available Autoimmunity is characterized by the reaction of cells (auto reactive T-lymphocytes or products (autoantibodies of the immune system against the organism's own antigens (autoantigen. It may be part of the physiological immune response (natural autoimmunity or pathologically induced, which may eventually lead to development of clinical abnormalities (autoimmune disease. Different mechanisms are involved in the induction and progression of autoimmunity. These include genetic or acquired defects in immune tolerance or immune regulatory pathways, molecular mimicry to viral or bacterial protein, an impaired clearance of apoptotic cell material. A A number of diseases have been identified in which there is autoimmunity, due to copious production of autoantibodies and autoreactive cells. The aim of the present article is to review on the pathogenesis of autoimmune diseases.
Restoring the balance: immunotherapeutic combinations for autoimmune disease
Smilek, Dawn E.; Ehlers, Mario R.; Nepom, Gerald T.
Autoimmunity occurs when T cells, B cells or both are inappropriately activated, resulting in damage to one or more organ systems. Normally, high-affinity self-reactive T and B cells are eliminated in the thymus and bone marrow through a process known as central immune tolerance. However, low-affinity self-reactive T and B cells escape central tolerance and enter the blood and tissues, where they are kept in check by complex and non-redundant peripheral tolerance mechanisms. Dysfunction or im...
The use of stem cells for the treatment of autoimmune diseases
S.B. Rosa
Full Text Available Autoimmune diseases constitute a heterogeneous group of conditions commonly treated with anti-inflammatory, immunosuppressant and immunomodulating drugs, with satisfactory results in most cases. Nevertheless, some patients become resistant to conventional therapy. The use of high doses of drugs in such cases results in the need for bone marrow reconstitution, a situation which has stimulated research into the use of hematopoietic stem cells in autoimmune disease therapy. Stem cell transplantation in such diseases aims to destroy the self-reacting immune cells and produce a new functional immune system, as well as substitute cells for tissue damaged in the course of the disease. Significant results, such as the reestablishment of tolerance and a decrease in the recurrence of autoimmune disease, have been reported following stem cell transplantation in patients with autoimmune disease in Brazil and throughout the world. These results suggest that stem cell transplantation has the potential to become an important therapeutic approach to the treatment of various autoimmune diseases including rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, multiple sclerosis, systemic sclerosis, Crohn's disease, autoimmune blood cytopenias, and type I diabetes mellitus.
Bushen Yisui Capsule ameliorates axonal injury in experimental autoimmune encephalomyelitis
Ling Fang; Lei Wang; Qi Zheng; Tao Yang; Hui Zhao; Qiuxia Zhang; Kangning Li; Li Zhou; Haiyang Gong; Yongping Fan
A preliminary clinical study by our group demonstrated Bushen Yisui Capsule (formerly cal ed Er-huang Formula) in combination with conventional therapy is an effective prescription for the treat-ment of multiple sclerosis. However, its effect on axonal injury during early multiple sclerosis re-mains unclear. In this study, a MOG 35-55-immunized C57BL/6 mouse model of experimental au-toimmune encephalomyelitis was intragastrical y administered Bushen Yisui Capsule. The results showed that Bushen Yisui Capsule effectively improved clinical symptoms and neurological function of experimental autoimmune encephalomyelitis. In addition, amyloid precursor protein expression was down-regulated and microtubule-associated protein 2 was up-regulated. Experimental findings indicate that the disease-preventive mechanism of Bushen Yisui Capsule in experimental autoim-mune encephalomyelitis was mediated by amelioration of axonal damage and promotion of rege-neration. But the effects of the high-dose Bushen Yisui Capsule group was not better than that of the medium-dose and low-dose Bushen Yisui Capsule group in preventing neurological dysfunction.