Organogold(III)-dithiocarbamate compounds and their coordination analogues as anti-tumor and anti-leishmanial metallodrugs.
The limited chemical stability of gold(III)-based compounds in physiological environment has been a challenge in drug discovery, and organometallic chemistry might provide the solution to overcome this issue. In this work, four novel cationic organogold(III)-dithiocarbamate complexes of general structure [(C^N)AuIIIDTC]PF6 (C1a - C4a, DTC = dithiocarbamate, L1 - L4, C^N = 2-anilinopyridine) are presented, and compared to their coordination gold(III)-dithiocarbamate analogues [AuIIIDTCCl2] (C1b - C4b), as potential anti-cancer and anti-leishmanial drugs. Most of the complexes effectively inhibited cancer cell growth, notably C3a presented anti-proliferative effect in the nanomolar range against breast cancer (MCF-7 and MDA-MB-231 cells with moderate selectivity. Pro-apoptotic studies on treated MCF-7 cells showed a high population of cells in early apoptosis. Reactivity studies of C3a towards model thiols (N-acetyl-L-cysteine) refer to a possible mode of action involving bonding between the organogold(III)-core and the thiolate. In the scope of neglected diseases, gold complexes are emerging as promising therapeutic alternatives against leishmaniasis. In this regard, all gold(III)-dithiocarbamate complexes presented anti-leishmanial activity against at least one Leishmania species. Complexes C1a, C4a, C1b, C4b were active against all tested parasites with IC50 values varying between 0.12 and 42 μM, and, overall, organometallic compounds presented more intriguing inhibition profiles. For C4a selectivity over 500-fold for L. braziliensis; even higher than the reference anti-leishmanial drug amphotericin B. Overall, our findings revealed that the organogold(III) moiety significantly amplified the anti-cancer and anti-leishmanial effects with respect to the coordination analogues; thus, showing the great potential of organometallic chemistry in metallodrug-based chemotherapy for cancer and leishmaniasis.


Microarray analysis of gene expression following the formalin test in the infant rat.
Injury and pain experienced by the infant results in immediate changes in pain sensitivity that last into adulthood. These long-term changes are likely initiated by altered gene expression. Here we measured how injury alters gene expression in the lumbar spinal cord early and late in the preweaning period of the rat. The expression of large numbers of genes was altered significantly at 3 days of age, when injury has long-term consequences. The functional classes of altered genes included transcription factors, cell death related and metal ion genes. The intensity of the stimulus in the 3-day-old pups induced changes in different classes of genes. Fewer changes were noted at 21 days of age. The increased expression of transcription factors and decreased expression of genes whose products are protective against cell death are hypothesized to underlie the long-term changes that are seen after injury in the neonate.


Hypoxia and anaemia in patients with cancer of the uterine cervix.
Hypoxia and/or anaemia have an adverse prognostic impact in locally-advanced cancers of uterine cervix. Moreover, these parameters are independent of other well-known prognostic factors. However, the mechanisms by which treatment efficacy and survival are compromised by anaemia are not fully understood. Although it is clear that erythropoietin can reduce the need for transfusions for cancer patients with anaemia, there is no proof that the use of erythropoietin is in any way superior to transfusions with respect to the impact on clinical outcome, especially for patients receiving radiation therapy. Whether haemoglobin levels at the start of therapy, during therapy, or at the end of therapy are of prognostic value for better disease-free and overall survival, are matters for further studies as is the question of the best option for increasing the level of the patient's haemoglobin.


Post-transplant cutaneous T-cell lymphomas.
Post-transplant cutaneous lymphomas are rare. Cutaneous T-cell lymphomas account for 30% of these lymphomas. The clinical appearance of the skin lesions is identical to cutaneous lymphomas observed in non-immunosuppressed patients, with infiltrated plaques, nodular and ulcerated tumors, but with an increased frequency of erythroderma. Standard histology and immunohistochemistry are also consistent with the features of mycosis fungoides and CD30+ cutaneous lymphomas observed in the general population. However, the pronostic differs from the usually favourable outcome of cutaneous T-cell lymphomas, as 8 out of the 13 patients of our series died, in less than 1 year for 6 of them. This unfavourable course appears to be the same as that observed for systemic T-cell lymphoma in transplant recipients. In contrast to post-transplant B-cell lymphomas (systemic and primary cutaneous), the link to a virus has not been demonstrated. The prognosis is also less favourable for post-transplant cutaneous T-cell lymphomas than for post-transplant cutaneous B-cell lymphomas.


The influence of industry sponsorship on the acceptance of abstracts and their publication.
The purpose of this study was to determine whether abstracts with industry sponsorship are more likely to be oral presentations, be published, and the effect of nonspecific author disclosure on identification of sponsorship. We reviewed abstracts accepted for the urogynecology scientific meeting from 1998-2006 and subanalyzed publication status of studies from 2002-2004. One hundred twenty-four of 1091 abstracts (11.4%) and 45/376 (11.9%) of oral presentations had industry sponsorship. Industry-sponsored was not significantly more likely than nonindustry sponsored research (RR, 1.06; 95% CI, 0.33-1.36) to be an oral presentation or be published (RR, 0.85; 95% CI, 0.53-1.34). Twelve of 36 studies (34%) were correctly identified as sponsored with the use of a nonspecific author disclosure compared to 22/22 (100%) when sponsorship was disclosed separately. Researchers without sponsorship can be reassured their work is as likely to be accepted for oral presentation and publication. A policy of full author disclosure makes identification of sponsored studies difficult, and specific sponsorship statement is necessary.


Marginal impaction in complex posterior wall acetabular fractures: role of allograft and mid-term results.
To evaluate the functional and radiological outcome of complex posterior wall acetabular fractures with marginal impaction treated with cancellous allograft and internal fixation. A total of 16 patients with marginal impaction on pre-operative CT scan, who underwent internal fixation and allograft were analysed. Mean follow-up was 28 months (range 24-42). The mean age was 46.5 years (range 22-71). Out of 16 patients, 8 were AO A1.2- and 8 were AO A1.3-type fractures. Functional evaluation was performed using modified Merle d'Aubigné and Postel scores and radiological evaluation by Matta's criteria for quality of initial reduction and final outcome. The quality of reduction was anatomical in 12 patients (75%) and imperfect in 4 patients (25%). The radiological outcome at final follow-up was excellent in 9 (56.25%), good in 5 (31.25%) and fair in 2 patients (12.5%). None of the patients had a secondary loss of reduction at final follow-up. Functional outcome was excellent in 2 (12.5%), good in 8 (50%) and fair in 6 patients (37.5%). The use of cancellous allograft to fill the bone void provides good mechanical stability without any secondary loss of reduction. This surgical technique seems to be effective and safe in treating comminuted posterior wall fractures with marginal impaction without any donor site complications and other disadvantages of synthetic bone graft materials.


Chronic rhinitis in adults.
Chronic rhinitis afflicts many American adults; the exact number is unknown because of the difficulty in establishing an exact diagnosis and because of the likely presence of overlap syndromes, including perennial allergic rhinitis, perennial nonallergic rhinitis with eosinophilia, and so-called vasomotor rhinitis. Nasal allergic reactions with release of pharmacologically active chemical mediators can participate in the pathogenesis of chronic rhinitis. In addition, reflex mechanisms probably play an important role in the initiation and maintenance of chronic nasal symptoms. Diagnosis is best achieved by a detailed history, with special attention to home, environmental, and occupation-related exposures and to selective epicutaneous skin tests and repeated smears of nasal secretions for detection of eosinophils. Therapy includes avoidance of all sorts of dust, fumes, sprays, and the like and appropriate attention to minimizing home environmental and occupational exposures. Pharmacotherapy is discussed elsewhere in this supplement.


Inflammatory, proliferative, and neoplastic lesions at the site of metallic identification ear tags in Wistar [Crl:(WI)BR] rats.
During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcomas) was diagnosed in 168 rats. Histologically, almost 90% of the rats in this study (henceforth referred to as Study I) showed some significant lesion at the tag site including various degrees of chronic inflammation, chondrous hyperplasia, and osseous metaplasia of the pinnal cartilage. In marked contrast, only two tumors were detected in 193 animals in a second study (Study II) in the same strain of rats, and only 56% of the rats had lesions at the tag site. A high incidence (greater than 25%) of clinically severe inflammation at the tag site was seen early in Study I and persisted during the first 6 mo of the study, while the incidence of such reactions in Study II was never more than 1%. Elemental analysis of the tags provided no explanation for the differences between the two studies, as tags used in both studies were of the same composition, predominantly nickel and copper. Metallic internal prostheses have induced local malignancies in humans and animals, and the present observations provide further evidence of the hazard posed by such devices at the site of prolonged contact with tissues. These findings suggest that a persistent tissue reaction may be an important factor in tumor development.


[Results of laboratory and clinical tests on the new Soviet heart valve model LIKS-2].
LIKS-2 rotatable disk prostheses were tested in laboratories for wear, atraumatic performance, and hemodynamic efficacy. Accelerated tests on testing units demonstrated their high reliability and lasting performance. The values of drops in, pressure and regurgitation volumes were negligible. The late-term results (of up to 5 years) of using LIKS-2 prostheses for correcting mitral and aortic valvular diseases were studied in the department of heart surgery of the All-Union Scientific Centre of Surgery. The prostheses showed high thrombo-resistance, mechanical reliability, and atraumatic performance in patients in the late-term follow-up periods.


Patient-reported outcomes in Gaucher's disease: a systematic review.
Gaucher's disease (GD), a rare condition, represents the most common lysosomal storage disorder. The cardinal manifestations of GD are fatigue, hepatosplenomegaly, anemia, thrombocytopenia, bone pain, and bone infarction, thereby culminating in a marked deterioration of patients' quality of life (QoL). Patient-reported outcomes (PROs) offer valuable insights into the impact of GD on patients' QoL and symptoms. This systematic review aimed to identify and analyze PROs and outcome measures in GD patients. We systematically searched PubMed, Web of Science Core Collections, EMBASE, SCOPUS, Cochrane Library, PsycINFO, Wan Fang Data, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CBM). The methodological quality of the included studies was assessed using a mixed methods assessment tool. A total of 33 studies were identified, encompassing 24 distinct patient-reported outcome instruments, with the most frequently employed instrument being the SF-36. The study designs included eighteen cross-sectional studies, seven pre- and post-intervention investigations, three randomized controlled trials, two cohort studies, two qualitative inquiries, and one validation study. These studies explored diverse domains such as the QoL and cardinal symptoms (e.g., fatigue, pain, bleeding, cognition, social relationships, and psychological functioning) in patients with GD. Furthermore, significant attention was directed towards the appraisal of the therapeutic benefits of various interventions in patients with GD. A novel GD-specific instrument has also been developed, which has two applied versions: a 24-item variant for routine clinical monitoring and a 17-item form for use in clinical trials. PROs have garnered increased attention and concern in the realm of GD. Despite this progress, it is noteworthy that the instruments used to measure PROs in GD are still predominantly generic instruments. While researchers have endeavored to develop and validate a disease-specific instrument, currently the use of this instrument is limited. Owing to several challenges, including the small number of patients, heterogeneity of the disease, and cross-regional discrepancies in study findings, GD poses substantial difficulties in the measurement of QoL and development of instruments. Consequently, patients with GD require more dependable measurement instruments that accurately reflect their QoL, efficacy of treatment, and facilitate healthcare decision-making.


[Distribution of bone tissue renewal processes in the skeleton of rats on a hypocaloric diet].
The present study was undertaken to confirm if the mechanical forces can control the pattern of bone turnover as previously demonstrated in our researches on the skeleton of dog. The bone turnover pattern in spongy and compact long bones of lactating female rats submitted to a Calcium deficient diet has been investigated. One group of female rats was maintained on a Ca++ deficient diet for 10 days and a second group for 30 days. Both groups were submitted after this period to a normal diet for 10 days. A third group of female rats of the same age maintained to a normal diet was used as control. The results obtained are in agreement with our previous researches and indicate that mechanical stresses appreciably control the bone turnover pattern. In fact the diminished assumption of Ca++ with diet has caused bone loss at first in the metaphyseal deeply located spongiosa, region less essential to mechanical resistance; only if the ipocalcic diet is protracted, the epiphyseal spongiosa and compact bone of the metaphysis and diaphysis -more heavily mechanical loaded portions of the long bones- were removed.


Synthesis of 5-substituted quinazolinone derivatives and their inhibitory activity in vitro.
Quinazolinone derivatives I and their methyl esters were synthesized and evaluated as nonclassical lipophilic inhibitors of thymidylate synthase. Compounds Ib and Ic containing OH and CO2H as R substituents, respectively, were most effective, indicating that hydrogen bonding may contribute to the increased inhibitory activity. These compounds further showed high cytotoxic activity against tumor cells in culture.


Wideband SSFP: alternating repetition time balanced steady state free precession with increased band spacing.
Balanced steady-state free precession (SSFP) imaging is limited by off-resonance banding artifacts, which occur with periodicity 1/TR in the frequency spectrum. A novel balanced SSFP technique for widening the band spacing in the frequency response is described. This method, called wideband SSFP, utilizes two alternating repetition times with alternating RF phase, and maintains high SNR and T(2)/T(1) contrast. For a fixed band spacing, this method can enable improvements in spatial resolution compared to conventional SSFP. Alternatively, for a fixed readout duration this method can widen the band spacing, and potentially avoid the banding artifacts in conventional SSFP. The method is analyzed using simulations and phantom experiments, and is applied to the reduction of banding artifacts in cine cardiac imaging and high-resolution knee imaging at 3T.


Release of norepinephrine from rat hypothalamic slices: effects of desipramine and tyrosine.
We studied the release of endogenous norepinephrine (NE) from rat hypothalamic slices. The slices were superfused with Krebs-bicarbonate buffer and field-stimulated with 960 or 1800 pulses applied 40 min apart. The spontaneous and stimulation-evoked overflow of NE into the medium were both enhanced by addition of a NE reuptake inhibitor, desipramine (10 microM). Repeated stimulations in the presence of desipramine decreased the evoked release of NE during the second and third stimulation periods (S2 and S3). The attenuation of NE release during S2 was not reversed by the addition of tyrosine (50 microM) to the medium.


In vitro sensitivity of 30 anaerobic bacterial strains of the human intestinal core microbiota to antibiotics: Culture and LC-MS/MS approaches.
We have a vast knowledge on human intestinal microbiota but it can still be regarded incomplete. One of the objectives of scientists using so-called "omics" techniques is to be interested in the consequences that drugs can have on the composition of the intestinal microbiota and inversely. To date, few publications have reported the effects of drugs on the growth of bacteria composing this microbiota using a "culturomics" approach. We focused on antibiotics commonly prescribed for which the only published are the susceptibility of the pathogenic strains and not that of the commensal strains. The aim of our study was to determine the sensitivity of 30 strains considered to represent the intestinal core microbiota to 8 antibiotics and to study the possible modification of these molecules by bacteria. The 30 bacterial strains were cultured under anaerobic conditions in order to determine their sensitivity to the antibiotics. After 48 h of culture, the supernatants were also analyzed via UHPLC-MS/MS in order to determine if the antibiotics have been chemically modified. Under the current experimental conditions, cefpodoxime, metronidazole, erythromycin, sulfamethozaxole, trimethoprim and the trimethoprim/sulfamethozaxole combination have little impact on the core microbiota strain growth. On the contrary, moxifloxacin and amoxicillin inhibit the growth of numerous strains of our panel. Using UHPLC-MS/MS analyses, we have shown that some antibiotics can be modifed by the bacteria composing the intestinal core microbiome. The bacteria that make up the intestinal microbiota core are impacted by the antibiotics most commonly prescribed in clinics today and inversely.


The alteration and significance of surfactant protein A in rats chronically exposed to cigarette smoke.
In order to confirm the alteration and significance of cigarette smoke exposure on SP-A in rats, 20 Wistar rats were assigned randomly to two groups: an N group (n=10), and an S group (n=10). The ultra-structural change was observed by electron microscopy. The number of cells positive for SPA was by immunohistochemically measured. The mRNA expression in the lung tissues was determined by reverse transcription polymerase chain reaction (RT-PCR). The number of cells positive for SPA of the S group (0.52 +/- 0.05) was lower than that of the N group (0.72+/-0.06) (P<0.05). The levels of mRNA of SPA in the lung tissues of the S group (0.3522+/-0.0512) was significantly lower than that of the N group (0.4432+/-0.05628) (P<0.05). It is concluded that cigarette smoke alone decreased the level of SP-A and that might have an important effect on surfactant metabolism and the host defense functions of surfactant in the peripheral airways, which might play a crucial role in the development of chronic obstructive lung disease.


Bias in Whole Genome Amplification: Causes and Considerations.
Whole genome amplification (WGA) is a widely used molecular technique that is becoming increasingly necessary in genetic research on a range of sample types including individual cells, fossilized remains and entire ecosystems. Multiple methods of WGA have been developed, each with specific strengths and weaknesses, but with a common defect in that each method distorts the initial template DNA during the course of amplification. The type, extent, and circumstance of the bias vary with the WGA method and particulars of the template DNA. In this review, we endeavor to discuss the types of bias introduced, the susceptibility of common WGA techniques to these bias types, and the interdependence between bias and characteristics of the template DNA. Finally, we attempt to illustrate some of the criteria specific to the analytical platform and research application that should be considered to enable combination of the appropriate WGA method, template DNA, sequencing platform, and intended use for optimal results.


Potential pre-activation strategies for improving therapeutic efficacy of mesenchymal stem cells: current status and future prospects.
Mesenchymal stem cell (MSC)-based therapy has been considered as a promising approach targeting a variety of intractable diseases due to remarkable multiple effect of MSCs, such as multilineage differentiation, immunomodulatory property, and pro-regenerative capacity. However, poor engraftment, low survival rate of transplanted MSC, and impaired donor-MSC potency under host age/disease result in unsatisfactory therapeutic outcomes. Enhancement strategies, including genetic manipulation, pre-activation, and modification of culture method, have been investigated to generate highly functional MSC, and approaches for MSC pre-activation are highlighted. In this review, we summarized the current approaches of MSC pre-activation and further classified, analysed the scientific principles and main characteristics of these manipulations, and described the pros and cons of individual pre-activation strategies. We also discuss the specialized tactics to solve the challenges in this promising field so that it improves MSC therapeutic functions to serve patients better.


Phospholipid acyl chain rotational dynamics are independent of headgroup structure in unilamellar vesicles containing binary mixtures of dioleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine.
We have examined relationships between phospholipid headgroup structure and acyl chain dynamics, and their respective roles in modulating the physical properties of biological membranes. Fluorescence lifetime and anisotropy measurements were used to assess structural changes involving the lipid acyl chains in homogeneous populations of small and large unilamellar vesicles containing binary mixtures of dioleoyl-phosphatidylcholine (PC) and dioleoyl-phosphatidylethanolamine (PE) in the liquid-crystalline (Lalpha) phase. These measurements involve three different fluorescent lipid analogs containing diphenylhexatriene (DPH) linked to either a trimethylamine moiety (i.e., TMA-DPH) or the sn-1 position of monostearoyl-phospholipids containing PC or PE headgroups (i.e., DPH-PC and DPH-PE). The average lifetimes, rotational correlation times, and order parameters associated with DPH-PC and DPH-PE are virtually identical, and are not affected by alterations in the PE content of the membrane. These results suggest that the average cross-sectional areas of the phospholipid acyl chains of DOPE and DOPC relative to the membrane normal are similar in these unilamellar vesicles. Since PC headgroups are larger than those of PE, differences in the relative orientation of the phosphocholine and phosphoethanolamine moieties relative to the membrane surface probably function to maintain optimal van der Waals contact interactions between acyl chains. On the other hand, the average lifetime associated with TMA-DPH, whose chromophoric group is near the membrane surface, increases with increasing PE content. The position of TMA-DPH relative to the membrane surface does not change, since the rotational dynamics of TMA-DPH are independent of the PE concentration. Therefore, alterations in the average lifetime of TMA-DPH results from polarity differences near the membrane surface at the level of the glycerol backbone. These results are discussed in terms of how differences in the average conformation of the glycerol backbones or phospholipid headgroups of PE and PC have the potential to regulate membrane function.


The myocutaneous platysma flap for the reconstruction of intraoral defects after radical tumour resection.
After performing 54 myocutaneous platysma flaps for reconstruction of intraoral defects following tumour surgery, the results, with reference to the postoperative outcome, are presented. Interest is focused on the anatomical basis of the flap's pedicle and its relevance for the indication of this method.


Three cDNAs encoding vitellogenin homologs from Antarctic copepod, Tigriopus kingsejongensis: Cloning and transcriptional analysis in different maturation stages, temperatures, and putative reproductive hormones.
Three full-length cDNAs encoding lipoprotein homologs were identified in Tigriopus kingsejongensis, a newly identified copepod from Antarctica. Structural and transcriptional analyses revealed homology with two vitellogenin-like proteins, Tik-Vg1 and Tik-Vg2, which were 1855 and 1795 amino acids in length, respectively, along with a third protein, Tik-MEP, which produced a 1517-residue protein with similarity to a melanin engaging protein (MEP) in insects Phylogenetic analysis showed that Vgs in Maxillopods including two Tik-Vgs belong to the arthropod vitellogenin-like clade, which includes clottable proteins (CPs) in decapod crustaceans and vitellogenins in insects. Tik-MEP clustered together with insect MEPs, which appear to have evolved before the apoB-like and arthropod Vg-like clades. Interestingly, no genes orthologous to those found in the apoB clade were identified in Maxillopoda, suggesting that functions of large lipid transfer proteins (LLTPs) in reproduction and lipid metabolism may be different from those in insect and decapod crustaceans. As suggested by phylogenetic analyses, the two Tik-Vgs belonging to the arthropod Vg-like clade appear to play major roles in oocyte maturation, while Vgs belonging to the apoB clade function primarily in the reproduction of decapod crustaceans. Transcriptional analysis of Tik-Vg expression revealed a 24-fold increase in mature and ovigerous females compared with immature female, whereas expression of Tik-MEP remained low through all reproductive stages. Acute temperature changes did not affect the transcription of Tik-Vg genes, whereas Tik-MEP appeared to be affected by temperature change. Among the three hormones thought to be involved in molting and reproduction in arthropods, only farnesoic acid (FA) induced transcription of the two Tik-Vg genes. Regardless of developmental stage and hormone treatment, Tik-Vg1 and Tik-Vg2 exhibited a strong positive correlation in expression, suggesting that expression of these genes may be regulated by the same transcriptional machinery.


Comparison of fundus changes following silicone oil and sterilized air tamponade for macular-on retinal detachment patients.
To investigate different tamponade effects of intravitreal silicone oil (SO) and sterilized air on macular vasculature and structure after successful retinal repair for macular-on rhegmatogenous retinal detachment (RRD) patients. 21 eyes (21 patients) with macular-on RRD underwent single pars plana vitrectomy following intravitreal SO or sterilized air (Gas) tamponade. Optical Coherence Tomography (OCT) and angiography were used to evaluate retinal layer thickness and flow density (FD) changes throughout the observation period of 12 weeks. Retinal layers were segmented into 7 sets: NFL, GCL + IPL, INL, OPL, ONL + IS, OS+RPE and BRM. Macular perfusion system was segmented into superficial and deep capillary plexus flow density (SCPFD, DCPFD), and choriocapillaries plexus flow density (CCPFD). Compared to Gas tamponade, SO tamponade led to more decrease in both superficial and deep retinal blood flow during observation. NFL thickness was found to decrease in both Gas tamponade and SO tamponade eyes. SO tamponade resulted in more pronounced decrease which led to significant intergroup difference. Opposite changing trends were found in GCL + IPL and ONL + IS thicknesses due to different means of tamponade. SO tamponade caused thicknesses of these two segmented layers to decrease, which led to significant intergroup differences. SO tamponade also led to more decrease in INL, OPL thicknesses. No significant intergroup difference of choroidal thickness was observed. Compared to gas, silicone oil could have more negative tamponade effects on both fundus vasculature and structure.


Is increased constitutive skin and hair pigmentation an early sign of puberty?
The paper analyzes data concerning the constitutive skin and hair pigmentation of 7-10-year-old Polish children to examine whether the hormonal activity of the gonads, which increases in this period, causes changes in pigmentation levels that may be considered an early sign of puberty. The study involved 289 children (151 girls and 138 boys). Skin pigmentation was examined on the medial side of the arm, while hair pigmentation on strands of hair close to the scalp in the occipital area. Additionally, body height (B-v) was measured and compared with population norms. On this basis, it was ascertained that the studied sample was representative of the population from which it was taken and that it represented the prepubertal and early pubertal stages of ontogeny (prior to the pubertal growth spurt or the first menstruation in the studied girls). It was found that in 7-10-year-old Polish children there is a statistically significant (p=0.001) increase in skin and hair pigmentation levels, while the degree of pigmentation of both structures at this stage of ontogeny is sexually dimorphic: girls are characterized by stronger pigmentation than boys. At the age of 10 years, the dimorphic differences in skin pigmentation intensify due to a rapid rise in pigmentation in girls. This change may be deemed an early morphological sign of puberty, as it precedes the pubertal growth spurt and menarche. This fast increase in skin pigmentation is not paralleled by an analogous change in hair pigmentation.


Tissue- and species-specific expression patterns of class I, III, and IV Adh and Aldh 1 mRNAs in rodent embryos.
Alcohol and aldehyde dehydrogenases (ADHs and ALDHs) may be of interest in the pathology of Parkinson's disease (PD) because of their role in protection against toxins and in retinoid metabolism, which is required for growth and development of the mesencephalic dopamine system. In the present study, the spatial and temporal expression patterns of Adh 1, Adh 3, Adh 4, and Aldh 1 mRNAs in embryonic C57BL/6 mice (E 9.5-E19.5) and Sprague-Dawley rats (E12.5-P0) have been investigated by using radioactive oligonucleotide in situ hybridization. High expression of Aldh 1 mRNA was found in the developing mesencephalic dopamine neurons of both mice and rats. Expression of Adh 1 and Adh 4 mRNAs was observed in adrenal cortex and olfactory epithelium in mice. Additionally, Adh 1 was expressed in epidermis, liver, conjunctival, and intestinal epithelium. In rat embryos, expression was less extensive, with Adh 1 mRNA being found in liver and intestines. Adh 3 expression was ubiquitous in both mouse and rat embryos, suggesting a housekeeping function of the gene. Consistent with previous studies in adult rats and mice, our data suggest that Adh 3 is the only ADH class present in rodent brain. Adh and Aldh gene activity in mouse and rat embryos indicate the possible involvement of the respective enzymes in retinoid metabolism and participation in defense against toxic insults, including those that may be involved in the pathogenesis of PD.


Structural biology of SARS-CoV-2 Mpro and drug discovery.
Since its outbreak in late 2019, the COVID-19 pandemic has drawn enormous attention worldwide as a consequence of being the most disastrous infectious disease in the past century. As one of the most immediately druggable targets of SARS-CoV-2, the main protease (Mpro) has been studied thoroughly. In this review, we provide a comprehensive summary of recent advances in structural studies of Mpro, which provide new knowledge about Mpro in terms of its biological function, structural characteristics, substrate specificity, and autocleavage process. We examine the remarkable strides made in targeting Mpro for drug discovery during the pandemic. We summarize insights into the current understanding of the structural features of Mpro and the discovery of existing Mpro-targeting drugs, illuminating pathways for the future development of anti-SARS-CoV-2 therapeutics.


[Sterile inflammatory response to ischemia-reperfusion injury: immediate and long term consequences on graft function].
Solid organs used for transplantation are subjected to ischemia-reperfusion, which induces cellular stress and tissue necrosis. Ischemia-reperfusion injury activates the complement cascade and triggers the release of danger-associated molecular signals. The latter bind to pattern-recognition receptors on innate immune cells, thereby eliciting a sterile inflammatory response that, together with complement activation, increases tissue damage. This sterile inflammatory response also triggers maturation of antigen-presenting cells (macrophages and dendritic cells), enabling them to present donor antigens efficiently to recipient lymphocytes. By initiating adaptive alloimmune responses in the recipient, innate immunity plays a central role in the rejection process, which remains a major cause of late graft failure. Strategies capable of dampening the sterile inflammatory response induced by ischemia-reperfusion could therefore be beneficial, both for immediate post-transplantation graft function and for long-term outcome.


Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer.
The aromatase and quinone reductase-2 inhibition of synthesized heterocyclic pyrazole derivatives fused with steroidal structure for chemoprevention of cancer is reported herein. All compounds were interestingly less toxic than the reference drug (Cyproterone(®)). The aromatase inhibitory activities of these compounds were much more potent than the lead compound resveratrol, which has an IC(50) of 80 μM. In addition, all the compounds displayed potent quinone reductase-2 inhibition. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). The aromatase and quinone reductase-2 inhibitors resulting from this study have potential value in the treatment and prevention of cancer.


Anomalous mitral arcade: echocardiographic and angiographic recognition.
A patient with sudden onset of hemiplegia was noted to have an anomalous mitral arcade at cardiac surgery. Echocardiographic and angiographic data are correlated with the anatomic findings. The clinical significance of this anomaly is discussed.


Indeno[1,2-b]indole derivatives as a novel class of potent human protein kinase CK2 inhibitors.
Herein we describe the synthesis and properties of indeno[1,2-b]indole derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 19 compounds was obtained using a convenient and straightforward synthesis protocol. The compounds were tested for inhibition of human protein kinase CK2, which was recombinantly expressed in Escherichia coli. New inhibitors with IC(50) in the micro- and sub-micromolar range were identified. Compound 4b (5-isopropyl-7,8-dihydroindeno[1,2-b]indole-9,10(5H,6H)-dione) inhibited human CK2 with an IC(50) of 0.11 μM and did not significantly inhibit 22 other human protein kinases, suggesting selectivity towards CK2. ATP-competitive inhibition by compound 4b was shown and a K(i) of 0.06 μM was determined. Our findings indicate that indeno[1,2-b]indoles are a promising starting point for further development and optimization of human protein kinase CK2 inhibitors.


mRNA sequences define an unusually restricted IgG response to 2-phenyloxazolone and its early diversification.
Light and heavy chain mRNAs of 15 anti-oxazolone antibodies were sequenced directly using synthetic primers. Hybridomas obtained 7 days after primary immunization show that they are of restricted heterogeneity. The majority expressed a single sequence with minor differences concentrated in the D region and joining boundaries D--JH and V kappa--J kappa.


Meningitis and septicemia due to Haemophilus influenzae serotype e, biotype IV.
Haemophilus influenzae, serotype e, biotype IV, is a rare cause of infection. We studied a 22-year-old white male who developed septicemia and meningitis due to this pathogen. It is most probable that cerebrospinal fluid (CSF) rhinorrhea caused by a defect in the medial sphenoid region provided the portal of entry.


The effect of Astragalus as an adjuvant treatment in type 2 diabetes mellitus: A (preliminary) meta-analysis.
Astragalus is a traditional Chinese medicine that is widely used for tonifying Qi (Qi mainly means life energy) to treat diabetes mellitus and its complications. We performed a meta-analysis to evaluate the effect of Astragalus in adjuvant treatment of type 2 diabetes mellitus (T2DM), and to provide novel information to improve clinical decision-making. We conducted an exhaustive database search (PubMed, EMbase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI), Wanfang data and SinoMed) of studies associated with "Astragalus" and "type 2 diabetes mellitus" until December 2015. Following quality assessment of study eligibility, the extracted data were statistically analyzed using STATA, ver. 12.0 (Stata Corp.). A total of 13 studies with 1054 participants were included in this meta-analysis. Two subgroups were identified, based on Astragalus dosing regimens: control group vs. Astragalus injection (AI); control group vs. Astragalus aqueous decoction (AAD). The pooled results showed that, in comparison with control group, Astragalus administration significantly reduced fasting plasma glucose (FPG) in both the AI group (WMD=-0.28, 95% CI=-0.46 to -0.10, P=0.002, I(2)=18.5%) and the AAD group (WMD=-0.83, 95% CI=-1.07 to -0.58, P=0.000, I(2)=0.0%); postprandial plasma glucose (PPG) was also significantly reduced in the AI group (WMD=-0.47, 95% CI=-0.77 to -0.17, P=0.002, I(2)=46.8%) and the AAD group (WMD=-1.19, 95% CI=-1.63 to -0.75, P=0.000, I(2)=49.3%). Fasting insulin (Fins) was significantly reduced only in the AAD treatment group (SMD=-0.33, 95% CI=-0.55 to -0.10, P=0.005, I(2)=1.0%) as was the homeostasis model assessment insulin resistance index (HOMA-IRI) levels (SMD=-1.66, 95% CI=-3.24 to -0.09, P=0.038, I(2)=94.0%). Although AAD treatment significantly reduced levels of glycated hemoglobin A1c (HbA1c) (WMD=-1.77, 95% CI=-3.06 to -0.47, P=0.007, I(2)=90.8%), AI treatment failed to show significant efficacy (WMD=-0.28, 95% CI=-0.63 to 0.06, P=0.102, I(2)=83.8%). Sensitivity analysis failed to detect outliers in all studies while Egger's linear regression test revealed a lack of publication bias in this meta-analysis (P=0.771, 95%CI =-3.51 to 4.56). Astragalus may be beneficial as an adjuvant therapy in the treatment of type 2 diabetes. However, due to the limited quality of existing studies, further high-quality studies are warranted before definitive conclusions may be reached.


Inflammatory pseudotumor of the abdomen: report of a case.
We report herein the case of a 38-year-old woman in whom a large tumor, 15 cm in diameter, was detected in the right lower quadrant of the abdomen. The tumor was removed and histological examination indicated that it was an inflammatory pseudotumor (IPT). IPT is not completely understood, but according to the few documented cases of IPT of the abdomen, its clinical behavior is benign and no recurrence has ever been reported. Thus, local resection is the most effective treatment.


An anti-B reagent prepared from the alpha-D-galactopyranosyl-binding isolectins from Bandeiraea simplicifolia seeds.
A method for the large scale preparation of the alpha-D-galactosyl binding isolectins from Bandeiraea simplicifolia seeds using an absorbent prepared by linking D-galactosamine to CH-Sepharose is described. The addition of N-acetyl-D-galactosamine (GalNAc) to these isolectins produced an anti-B reagent (BS I + GalNAc anti-B). Although BS I + GalNAc anti-B readily agglutinated red blood cells from the majority of group B and AB donor and patient blood samples tested, it reacted weakly with group B and AB cord red blood cells and failed to agglutinate five of 100 group AB donor blood samples when tested by an automated technique. The reagent did not agglutinate the red blood cells from seven acquired-B red blood cell samples and was strongly reactive with Tn-polyagglutinable red blood cells. These findings indicate that this lectin anti-B preparation may be of more value in investigative immunohematology, rather than as an alternative to human group A serum as a source of anti-B for blood-typing purposes. The results of tests on Tn-polyagglutinable red blood cells with BS I + GalNAc anti-B and the purified isolectins BS I(A4) and BS I(B4) are also presented, and discussed in relation to current concepts on the structure of the Tn receptor.


Clinical outcomes and second-look arthroscopic findings of anterior cruciate ligament reconstruction with autograft, hybrid graft, and allograft.
There is no consensus as to the choice of grafts for primary anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the clinical and second-look arthroscopic outcomes after ACL reconstruction by use of autograft, hybrid graft, and γ-irradiated allograft. Ninety-seven patients who underwent second-look arthroscopy after ACL reconstruction with autografts (28 patients, hamstring autograft), hybrid grafts (32 patients, hamstring autograft augmented with γ-irradiated tibialis anterior tendon allograft), or γ-irradiated allografts (37 patients, tibialis anterior tendons) were included in this study. The clinical outcomes were compared by using Lysholm score, International Knee Documentation Committee (IKDC) score, and Tegner activity score, and the side-to-side differences of KT-1000 measurement. Second-look arthroscopic findings were compared in terms of synovial coverage and graft tension. There were no statistical significances among the three groups in Lysholm score, IKDC score, or Tegner activity score (P > 0.05). The KT-1000 examination showed more anterior laxity in the γ-irradiated allograft group than in the autograft or hybrid graft groups (P = 0.006, and P = 0.013, respectively). Two patients in the autograft group, 2 patients in the hybrid graft group and 4 patients in the allograft group were evaluated as graft failure on second-look arthroscopy. The synovial coverage was superior in the autograft group than that in the hybrid graft group or the allograft group (P = 0.013 and P = 0.010, respectively), and was comparable between the hybrid graft group and allograft group (P = 0.876). With regard to graft tension, the autograft group and hybrid group were comparable (P = 0.883) but showed better results than the allograft group (P = 0.011 and P = 0.007, respectively). The hamstring autografts and hybrid grafts used for ACL reconstruction produced equal efficacy but provided better knee stability than allografts. In addition, the hamstring autografts showed better synovial coverage than the other two graft types.