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Leung, Po Sing; Cheng, Qianni
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Pancreatic islets secrete multiple factors that act as endocrine, paracrine, and/or autocrine pathways in regulating pancreatic endocrine function. As such, the islets perform critical biological activities in synthesizing metabolic peptide hormones, notably insulin and regulating body glucose homeostasis. These functions are controlled by various conditions and signaling molecules, particularly nutrients like glucose levels. However, more and more clinically relevant regulators, including molecules which stimulate islet β-cell metabolism, regulate β-cell [Ca2+] homeostasis and related channels or adjust β-cell membrane, and nuclear receptors activity continue to be discovered and characterized. Of great interest in this context, glucagon-like peptide-1 can improve glycemic control by regulating insulin secretion and islet cell mass; vitamin D can regulate islet physiology directly by binding its receptors; in addition, the peptide hormone angiotensin II has been implicated in islet function and exhibits effects on islet cell secretion as well as cell mass. In this chapter, these three novel regulators in islet function and thus its clinical relevance to type 2 diabetes mellitus will undergo critical appraisal. Since all of these molecules have biological interactions with pancreatic islets, potential relationships may exist among them and they will also be discussed.
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Wajchenberg, Bernardo Léo
In type 2 diabetes (DM2) there is progressive deterioration in β-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and reduction in β-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the β-cells, those to lead to short-term improvement of β-cell secretion are weight loss, metformin, sulfonylureas, and insulin. The long-term improvement was demonstrated with short-term intensive insulin therapy of newly diagnosed DM2, the use of antiapoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase 4 and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. From the two major incretins, GLP-1 and GIP (glucose-dependent insulinotropic polypeptide), only the first one or its mimetics or enhancers can be used for treatment. The GLP-1 mimetics exenatide and liraglutide as well as the DPP 4 inhibitors (sitagliptin and vildagliptin) were approved for treatment of DM2.
Hiort, Olaf; Danne, Thomas; Wabitsch, Martin
Hermann, Martin; Margreiter, Raimund; Hengster, Paul
Human islet transplantation is one of the three treatment modalities besides the daily administration of exogenous insulin and pancreas transplantation, which can be applied for the treatment of type 1 diabetic patients.
Although the metabolic control achieved after islet transplantation is superior compared to exogenous insulin administration, many hurdles remain to be overcome before islet transplantation can be called a routine therapy for type 1 diabetic patients. In contrast to many other therapeutic approaches, proof of principle has been obtained for islet transplantation: As demonstrated in islet autotransplantation, the transplanted islets are not only able to survive in another organ, namely the liver, but also able to retain their functional role, in some patients even for decades. The main challenge for islet allotransplantation is, therefore, to imitate this success, thereby providing type 1 diabetic patients with a cellular therapy lasting for decades and thus circumventing the daily injections of insulin.
Wabitsch, Martin; Reinehr, Thomas
Es gibt eine Reihe seltener endokriner Ursachen für eine Adipositas einschließlich definierter genetischer Syndrome (▸ Kap. 18). Jedoch gibt es häufige Veränderungen endokriner Funktionen bei Adipositas, die charakteristisch für die Adipositas sind, wie z. B. Störungen der
Insulinsekretion und Wirkung,
Wachstumshormon-IGF-I-Achse und
Fonseca, Vivian A.; Pendergrass, Merri; McDuffie, Roberta Harrison
Microvascular complications are specific for diabetes and are almost certainly related to hyperglycemia (see Figure 5.1). Hyperglycemia leads to multiple biochemical changes, some of which are listed in Figure 5.2, that cause tissue damage [1, 2]. These lead to changes in various organs as summarized in Figure 5.1. Most of these changes can be prevented by good glycemic control which prevents the development of the complications and slows their progression [3].
Badylak, Stephen F.; Ogilvie, Jennifer B.; Gilbert, Thomas W.
Biologic scaffold materials derived from the extracellular matrix (ECM) of intact mammalian tissues are recognized as possessing constructive remodeling properties and have been used successfully in a variety of tissue engineering and regenerative medicine applications in both preclinical studies and clinical practice. This chapter provides an overview of the composition and structure of selected ECM scaffold materials, the effects of manufacturing methods upon the structural properties and resulting mechanical behavior of the scaffold materials, and the in-vivo degradation and remodeling of ECM scaffolds. Finally, the potential application of ECM scaffold materials to regeneration of endocrine tissues is discussed.
Vlassara, Helen; Striker, Gary E.
Diabetes is a very common cause of hospitalization and is listed as a diagnosis in 12% of hospital discharges. This diagnosis has a substantial impact on medical costs since hospital stay for diabetic patients is 1–3 days longer than non-diabetics. Cardiovascular complications are a common cause of hospitalizations for diabetic patients, and diabetes is a listed diagnosis in 29% of cardiac surgery patients.
Leung, Po Sing
Cell culture system studies complement animal studies, providing an indispensable tool for examining the underlying signalling mechanisms by which certain physiological responses are evoked and, at the same time, allowing observation to be attributed to distinct individual treatment factor. They are often applied as primary screenings of the potential effects of certain drug treatment prior to further animal studies. Experiments utilizing pancreatic cell lines or primary pancreatic cell cultures have been widely reported. The term cell line generally refers to an immortalized group of cells originally derived from a single clone which can be, in principle, maintained permanently and proliferated upon exposure to appropriate medium in vitro. Many cell lines are derived from abnormal tissues, such as cancer specimens or tumour cells.
Zweig, Susan B.; Tolentino, Marsha C.; Strizhevsky, Marina; Poretsky, Leonid
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Polycystic ovary syndrome (PCOS) is a common disorder affecting (depending on the population studied and the definition of the syndrome) between 5 and 20% of reproductive age women.1 If the middle of this range is considered as a realistic prevalence, then PCOS may be the most prevalent endocrine disorder in women. In spite of the widespread presence of PCOS, its precise definition still eludes both investigators and practitioners. Most consensus definitions describe PCOS as a disorder characterized by chronic anovulation and the presence of some degree of hyperandrogenism, with the exclusion of specific disorders that may lead to similar phenotypes, particularly, 21-hydroxylase deficiency and other forms of congenital adrenal hyperplasia.
Dieterle, C.; Landgraf, R.
Die Pankreastransplantation wird meistens in Kombination mit einer Nierentransplantation bei Typ-1-Diabetes-Patienten durchgeführt. Die Einjahres-/Zehnjahresüberlebensraten für die Simultantransplantation von Niere und Pankreas betragen laut internationaler Statistik und großen Studien für Patienten 94–100/79%, für die Nieren 89–92/63% und für die Pankreas 85–87/53%. Die hohe Erfolgsrate mit langfristiger Normalisierung des Glukosestoffwechsels führt nicht nur zu einer Stabilisierung oder Verbesserung der Sekundärkomplikationen, sondern auch zu einer signifikanten Senkung der Mortalität, die deutlich höher ist als bei alleiniger Nierentransplantation bei vergleichbaren Patienten. Die alleinige Pankreasverpflanzung bei noch guter Nierenfunktion bleibt einer strengen Indikationsliste vorbehalten. Die Inseltransplantation ist zwar weniger invasiv und zeigt geringere perioperative Risiken, weist aber schlechtere Ergebnisse in Bezug auf die langfristige Insulinunabhängigkeit auf. So zeigt sich eine Insulinunabhängigkeit nach einem Jahr bei nur 44% und nach 2 Jahren bei nur 13% der Patienten. Ein Teilerfolg mit Nachweis einer C-Peptid-Sekretion, Reduktion von HbA1c und Hypoglykämien ließ sich jedoch deutlich häufiger nachweisen.
Tsatsoulis, Agathocles
Polycystic ovary syndrome (PCOS) is a common endocrine/metabolic disorder in women, characterized by hyperandrogenism, chronic anovulation, and/or polycystic ovaries in association with android fat distribution and insulin resistance/hyperinsulinism. The etiology of PCOS remains elusive but there is increasing evidence that the phenotypic traits of the syndrome may be programmed in utero by androgen excess.
Thus, female primates, exposed to androgen excess during fetal life, exhibit the reproductive and metabolic features of PCOS in adulthood. Women with congenital 21-hydroxylase deficiency and congenital adrenal virilizing tumors develop features characteristic of PCOS during adult life, despite the normalization of androgen excess after birth. Rare cases of women with congenital sex hormone-binding globulin (SHBG) and P450 aromatase deficiency may also develop some of the features of PCOS in adulthood.
The potential sources of gestational hyperandrogenism to account for the developmental programming of PCOS in humans are not clearly understood. However, maternal and/or fetal hyperandrogenism, in association with reduced placental SHBG and/or aromatase activity, can provide a plausible mechanism and this, in part, may be genetically determined. Indeed, genetic association studies have indicated that common variants of genes determining androgen activity or genes that influence the availability of androgens to target tissues are associated with PCOS and increased androgen levels. These genetic variants may provide the genetic link to prenatal androgenization in human PCOS.
It appears, therefore, that prenatal androgenization of the female fetus, induced by genetic factors and environmental signals, or by the interaction of both, may program the differentiating target tissues toward the development of PCOS in adult life.
Kraker, Jennifer L.; Ferrando, Stephen J.
Diabetes mellitus (DM) is an increasingly prevalent and complex chronic illness with significant psychosocial and psychiatric ramifications. Stress and psychiatric illness can contribute to the development of the disease itself,1 via neurohormonal pathways and the side effects of psychiatric medication treatment, and psychiatric symptoms and disorders are prevalent and can have profound effects on the disease course of diabetes.2 Thus, there is a pressing need for integration of general medical care and psychiatric care for the diabetic patient in order to improve quality of life and illness outcomes.
Johansson, Bengt
Cardiovascular magnetic resonance (CMR) is an increasingly used imaging tool in cardiology. Initially, technical resources and access to trained staff were limited to a few centers. As scanners become more available and thanks to widespread training of cardiologists and technicians, CMR can now be performed in most cardiology centers. Without exposing the patient to ionizing radiation, a comprehensive cardiac study can be performed in 30–45 min, depending on clinical problem and scanner capabilities. A typical cardiac exam consists of anatomical images for gross anatomy and cine images for the evaluation of ventricular function. Depending on the clinical problem, a number of additional techniques can be added. Using chelated gadolinium contrast agents, first pass myocardial perfusion can be analyzed during pharmacological stress for the diagnosis of coronary artery disease. After injection of contrast in a peripheral vein, high resolution angiography can be performed. Phase contrast velocity maps (which despite the terminology it does not include contrast agents) can also be used to analyze intrathoracic vascular blood flow and flow velocity.
Schwab, Karl Otfried
Komplikationen in der Behandlung eines Typ-1-Diabetes entstehen entweder durch zu viel oder zu wenig Insulin im Blut. Wird relativ zu der körperlichen Bewegung und der Kohlenhydratzufuhr zu viel Insulin gespritzt, entstehen Unterzuckerungen (▸ Abschn. 11.1). Wurde abhängig vom Bedarf längerfristig zu wenig oder gar kein Insulin injiziert, dann droht eine ketoazidotische Entgleisung ▸ Kap. 12).
Fonseca, Vivian; Pendergrass, Merri; Harrison McDuffie, Roberta
Ludwig, B.; Ludwig, S.; Reichel, A.; Saeger, H.-D.; Solimena, M.; Bornstein, S.R.
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Die Entwicklung eines Diabetes mellitus stellt eine häufige Komplikation von Erkrankungen des Pankreas dar. Wenngleich die Therapie der Primärerkrankung im Vordergrund steht, ist die Behandlung des sekundären Diabetes häufig eine große Herausforderung in der täglichen Praxis und hat entscheidende Bedeutung für die Lebensqualität der Betroffenen. Im vorliegenden Beitrag werden die relevanten Krankheitsbilder der Bauchspeicheldrüse besprochen, die mit der Entwicklung eines Diabetes assoziiert sind und entscheidende Therapiestrategien erläutert. Darüber hinaus soll die Bedeutung eines neu manifestierten Diabetes als richtungweisendes Symptom für die Diagnose von Pankreaserkrankungen dargestellt werden.
Wong, Keye
The fundus abnormalities seen in diabetic retinopathy can conceptually be split into three categories – those findings resulting from leaking microvasculature (hemorrhages, lipid exudates, retinal edema); those findings resulting from structural damage to the microvasculature wall (microaneurysms); and those findings resulting from ischemia with a subsequent overproduction of vascular growth factors (cottonwool patches, intraretinal microvascular abnormalities [IRMA], preretinal neovascularization, fibrous proliferation, and vitreous hemorrhage). The severity of each of these findings can be classified and quantified based on the degree of retina involvement, e.g., the number of microaneurysms and hemorrhages in each quadrant or photographic field, the area of retina affected by neovascular tissue or IRMA, the area of macula involved with retinal thickening. Classification schemes are a means to categorize the varying degrees of such findings to facilitate communication.As with all specialized languages, the value of these languages depends upon who is speaking to whom. The ultimate goal of classification schemes is to provide a system to improve patient care. This may be achieved initially by precise communication among researchers to define categories by which the natural history and subsequent response to intervention(s) can be identified. Once these research goals have been achieved these classification schemes should be understandable and reproducible by practicing clinicians. If not, then modification of these classification schemes is desirable to allow clinicians to communicate among themselves and with their patients the expected results of therapies demonstrated to be beneficial in clinical trials. One should realize that the goals of communication between researchers may be different from the goals of communication between clinicians and may likewise be different from the goals of communication between clinician and patient. Evolution of classification schemes is desirable dependent upon who is communicating with whom.
Lange, Karin
Bei chronischen Krankheiten und endokrinologischen Störungen ist der Erfolg der Langzeitbehandlung vor allem davon abhängig, wie es den Familien auf Dauer gelingt, die Therapie und weitere Belastungen durch körperliche Besonderheiten in den Alltag zu integrieren und mit den allgemeinen Erziehungsaufgaben zu vereinbaren. Deshalb ist die umfassende und praxisorientierte Information der Eltern und altersadäquat auch der Kinder und Jugendlichen unverzichtbar. Dabei sollten neben der somatischen Therapie auch die krankheitsbedingten psychosozialen Belastungen und der kognitive und soziale Entwicklungsstand der betroffenen Kinder und Jugendlichen berücksichtigt werden (Dimatteo 2004; Scheidt-Nave et al. 2008; Taylor et al. 2008)
Roden, M.
Holtrop, R.
Diabetes mellitus is in essentie een stoornis van het glucosemetabolisme. Onder deze algemene omschrijving zijn diverse vormen van diabetes mellitus te onderscheiden. Gemeenschappelijk kenmerk is een verhoogde glucoseconcentratie in het bloed. Glucose is de voorkeursbron voor energie voor alle lichaamscellen. Hersencellen zijn voor de toelevering van energie geheel afhankelijk van glucose en vereisen voor hun functioneren 25% van de glucose die dagelijks in het lichaam wordt verbrand. Andere cellen, zoals spiercellen, kunnen voor hun energievoorziening ook terugvallen op de verbranding van vetten. Bij gezonde mensen wordt de bloedglucosespiegel binnen nauwe grenzen gereguleerd. Na de maaltijd vangt een piek in insuline- uitscheiding de glucose van de maaltijd op. De glucose wordt onder invloed van insuline opgenomen in de perifere cellen van spier- en vetweefsel, terwijl de overmaat aan glucose in de lever als reservevoorraad wordt opgeslagen als glycogeen. Bij patiënten met diabetes mellitus stijgt de bloedglucosespiegel. Dit wordt hyperglykemie genoemd. Verhoogde bloedsuikerwaarden gaan gepaard met klachten zoals dorst (polydypsie), veel plassen (polyurie) en in samenhang met vermoeidheid.
Historically, patient treatment has been reactive, guided by the assessment of patients' symptoms. However, elevated blood glucose, elevated blood pressure and elevated cholesterol often have no symptoms. Yet, research has demonstrated that early and successful treatment of these problems can prevent or delay complications of diabetes [1].
In the long-term, treatment goals of diabetes are intended to prevent microvascular complications, including blindness, kidney failure and amputations, and, to whatever extent possible, prevent macrovascular complications as well. The healthcare provider's goal for the diabetes patient must be proactive, working to extend life while maximizing wellness for the individual patient, based on the patient's informed choice of treatment goals. In the short term, the healthcare provider can be guided by treatment goals established by a variety of experts. Experts recommend that the primary focus of the providers' attention be on controlling the ABCs of diabetes: A1C, blood pressure and cholesterol [2] (see Figure 2.1).
Ahmed, Meftun
The complementary disciplines of genomics and proteomics offer better insights into the molecular mechanisms of diseases. While genomics hunts for defining our static genetic substrate, proteomics explores the structure and function of proteins expressed by a cell or tissue type under specified conditions. In the past decade, proteomics has been revolutionized by the application of techniques such as two-dimensional gel electrophoresis (2DGE), mass spectrometry (MS), and protein arrays. These techniques have tremendous potential for biomarker development, target validation, diagnosis, prognosis, and optimization of treatment in medical care, especially in the field of islet and diabetes research. This chapter will highlight the contributions of proteomic technologies toward the dissection of complex network of signaling molecules regulating islet function, the identification of potential biomarkers, and the understanding of mechanisms involved in the pathogenesis of diabetes.
Torre, Daria; Lernmark, Åke
The pancreatic islet β-cells are the target for an autoimmune process that eventually results in an inability to control blood glucose due to the lack of insulin. The different steps that eventually lead to the complete loss of the β-cells are reviewed to include the very first step of a triggering event that initiates the development of β-cell autoimmunity to the last step of appearance of islet-cell autoantibodies, which may mark that insulitis is about to form. The observations that the initial β-cell destruction by virus or other environmental factors triggers islet autoimmunity not in the islets but in the draining pancreatic lymph nodes are reviewed along with possible basic mechanisms of loss of tolerance to islet autoantigens. Once islet autoimmunity is established the question is how β-cells are progressively killed by autoreactive lymphocytes which eventually results in chronic insulitis. Many of these series of events have been dissected in spontaneously diabetic mice or rats, but controlled clinical trials have shown that rodent observations are not always translated into mechanisms in humans. Attempts are therefore needed to clarify the step 1 triggering mechanisms and the step to chronic autoimmune insulitis to develop evidence-based treatment approaches to prevent type 1 diabetes.
Piemonti, Lorenzo; Guidotti, Luca G.; Battaglia, Manuela
We acknowledge that successful long-term islet survival in the liver and immune tolerance to intrahepatic islet antigens are highly dependent upon the initial inflammatory and priming events that occur at this site. Thromboembolic and necroinflammatory events occurring in the liver early after portal vein islet transplantation are thought to reduce the total islet mass by up to 75%. The magnitude of such loss represents a major factor necessitating the extremely large number of islets needed to achieve normoglycemia. A better understanding and control of these events – including their likely support to effector immune responses – are required if we are to develop ways to prevent them, improve intrahepatic islet engraftment, and achieve long-term tolerance.
Hiort, Olaf
Kalzium und Phosphor sind die hauptsächlichen mineralischen Elemente des Knochens. Dadurch sind diese beiden Metabolite — bezogen auf die im KÖrper vorhandene Gesamtmenge — fast gänzlich (zu 99%) dem Knochen zuzuordnen, obwohl sie zudem in vielen anderen Kompartimenten eine gewichtige Rolle spielen. Kalzium wird sowohl extrazellulär als auch intrazellulär als Kofaktor für verschiedene enzymatische Reaktionen verwendet und stellt einen bedeutsamen intrazellulären Botenstoff zur Signalvermittlung dar. Dies gilt insbesondere für die neuromuskuläre Signalübertragung. Im Serum liegt Kalzium etwa zur Hälfte an spezifische Trägerproteine oder Albumin gebunden vor; nur die ionisierte Fraktion ist als biologisch aktiv anzusehen. Phosphor liegt meist als Phosphat vor, davon ist wiederum der überwiegende Teil im Skelett verankert, während etwa 15% des Phosphats als organische oder anorganische Fraktionen intrazellulär oder extrazellulär zu finden sind. Das organische Phosphat spielt eine wesentliche Rolle im Aufbau von vielen Molekülen, so z. B. in Phosphoproteinen, bei Energieträgern wie Adenosintriphosphat (ATP) und anderen Molekülen der intrazellulären Signalübertragung.
Calafiore, Riccardo; Basta, Giuseppe
Cell therapy represents an increasingly promising approach for the cure of many chronic and degenerative disorders, such as type 1 (insulin-dependent) diabetes mellitus and Parkinson's disease. Replacement of diseased cells with healthy and functional cells could allow repair and restoration of organ function. This is particularly relevant for organs that execute highly-complex physiological tasks, such as the endocrine pancreas, which maintains glucose homeostasis. However, cell therapy based on the use of allogeneic primary adult cells or progenitor/stem cells faces several fundamental problems. In addition to the need to overcome allograft rejection, optimal function of the transplanted cells may be achieved only if they are embedded in a surrogate extracellular matrix that creates a three-dimensional tissue structure mimicking that of the normal tissue. Cell microencapsulation in artificial membranes made of highly-purified and biocompatible biopolymers can provide immunoprotection and preserve cell viability by allowing passage of oxygen and nutrients across the membrane and blocking humoral or cellular components of the host immune system. The microencapsulated cells are embedded in a three-dimensional configuration that mimics their original site and enhances their function. This chapter reviews the latest advances and applications of this technology, as well as its future prospects.
Laud, Ketan; Shabto, Uri
Diabetes mellitus is a major medical problem in the United States and worldwide. The disease has tremendous social and economic impact as it affects individuals in their economic productive years. It is estimated that societal costs related to the disease exceed a 100 billion dollars per year.1 Diabetes remains a leading cause of newly diagnosed blindness in the United States and worldwide today.
Banerji, Mary Ann; Chaiken, Rochelle L.
This chapter focuses on insulin resistance and its role in diabetes, obesity, and cardiovascular (CV) disease. There is significant evidence that both CV disease and diabetes have common metabolic antecedents. The metabolic syndrome and its relation to insulin resistance, cardiovascular disease, and diabetes will be critically reviewed with a focus on current clinical controversies.
Szmuilowicz, Emily D.; Seely, Ellen W.
Around the time of menopause, there are important changes in body composition and insulin sensitivity, which may impact both the risk for diabetes mellitus as well as glycemic control in individuals with established diabetes. Furthermore, these parameters may be affected by the use of hormone replacement therapy, a common treatment for menopausal vasomotor symptoms. Changes in body composition, beyond changes in weight, occur around the time of menopause, and these alterations in body composition have been correlated with changes in insulin resistance and glucose tolerance. Several studies have suggested that hormone therapy use reduces diabetes risk in postmenopausal women. Clinicians must keep these metabolic changes in mind when caring for postmenopausal women with and without diabetes.
Brillon, David J.
Both type 1 and type 2 diabetes are accompanied by microvascular and macrovascular complications. For decades the association between chronic hyperglycemia and the development of long-term eye, kidney, and nerve disease was suspected based on animal models of diabetes 1–3 and the long-term observations of clinicians.
DeMauro-Jablonski, Samantha; Inzucchi, Silvio E.
Diabetes mellitus and hyperglycemia are frequently encountered in hospitalized patients and present complex management problems. This issue will continue to stress the health-care system in the United States as an increase in the overall diabetes prevalence is anticipated over the coming decades.1 Since diabetic patients are hospitalized more often than their non-diabetic peers, hyperglycemia in the hospital will become an increasingly common scenario. Hospitalizations can relate directly to uncontrolled diabetes, such as diabetic ketoacidosis (DKA), hyperosmotic hyperglycemic syndrome (HHS), or severe hypoglycemia; or to the complications of diabetes including cardiac disease, stroke, foot infections, amputations, and kidney disease; or to the variety of general medical conditions to which the diabetic patient is predisposed (community acquired pneumonia, influenza, etc.). National hospital discharge data from 2004 estimate that 609,000 admissions to the hospital involved a primary diagnosis of diabetes, while 5.2 million admissions carried a non-diabetic principal diagnostic code (i.e., diabetes as a "secondary diagnosis").2 Trends toward monitoring patients more closely in an outpatient setting, with adherence to new practice guidelines concerning glucose management, may potentially decrease hospitalization rates related to metabolic control.
Telander, David G.; Small, Kent W.; Browning, David J.
Diabetic retinopathy (DR) is the leading cause of new cases of blindness for people between 20 and 64 years of age in the United States. While glycemic control is the chief risk factor for development and progression of diabetic retinopathy, there is increasing evidence for heritable risk factors. An increasing number of genetic linkage studies have uncovered the role that several genes have in the development and progression of DR.
Tan, Lip-Bun; Patwala, Ashish Y.; Henein, Michael Y.
Within the medical career covering the past 3–4 decades, heart failure (HF) management has been transformed from that of resignation and mainly palliative treatments to options of proactive prophylactic pharmacological, device and interventional treatments. The prognosis and quality of life of HF patients have also significantly improved over the same period, although they are generally still far below that of normal healthy subjects. A most gratifying of triumphs is that of observing occasionally reversals of severe failure towards normality in cardiac function. However, we are far from being able to ensure such a process in every patient, perhaps until cardiac or myocardial replacement therapy can in practice be as standard a procedure as valve or pacemaker replacement therapies.
Gill, Anne; Hoogwerf, Byron J; Burger, Jude; Bruce, Simon; MacConell, Leigh; Yan, Ping; Braun, Daniel; Giaconia, Joseph; Malone, James
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Cardiovascular effects of glucose-lowering agents are of increasing interest. Our aim was to assess the effects of the glucagon-like peptide-1 receptor agonist exenatide on heart rate (HR) and blood pressure (BP) in subjects with type 2 diabetes mellitus (T2DM).
In this double-blind, placebo-controlled trial, subjects with T2DM on metformin and/or a thiazolidinedione were randomized to receive exenatide (5 μg for 4 weeks followed by 10 μg) or placebo BID for 12 weeks. Heart rate and BP were assessed with 24-hour ambulatory BP monitoring. The primary measure was change from baseline in mean 24-hour HR.
Fifty-four subjects (28 exenatide, 26 placebo) were randomized and comprised the intent-to-treat population. Baseline values (exenatide and placebo) were (mean ± SE) 74.4 ± 2.1 and 74.5 ± 1.9 beats/minute for HR, 126.4 ± 3.2 and 119.9 ± 2.8 mm Hg for systolic BP (SBP), and 75.2 ± 2.1 and 70.5 ± 2.0 mm Hg for diastolic BP (DBP). At 12 weeks, no significant change from baseline in 24-hour HR was observed with exenatide or placebo (LS mean ± SE, 2.1 ± 1.4 versus -0.7 ± 1.4 beats/minute, respectively; between treatments, p = 0.16). Exenatide therapy was associated with trends toward lower 24-hour, daytime, and nighttime SBP; changes in DBP were similar between groups. No changes in daytime or nighttime rate pressure product were observed. With exenatide, body weight decreased from baseline by -1.8 ± 0.4 kg (p < 0.0001; treatment difference -1.5 ± 0.6 kg, p < 0.05). The most frequently reported adverse event with exenatide was mild to moderate nausea.
Exenatide demonstrated no clinically meaningful effects on HR over 12 weeks of treatment in subjects with T2DM. The observed trends toward lower SBP with exenatide warrant future investigation.
Richter-Unruh, Annette
Das Ovulationsalter bezeichnet die Dauer der menschlichen Entwicklung von der Befruchtung bis zur Geburt. Dies sind in der Regel 264–268 Tage (38 Wochen). In der Klinik berechnet man die Schwangerschaftsdauer vom 1. Tag der letzten Menstruation bis zur Geburt entsprechend 280 Tage (40 Wochen) und verwendet den Begriff Gestationsalter.
Partsch, Carl-Joachim; Dörr, Helmuth-Günther
Endokrinologische Testverfahren dienen der Sicherung einer klinischen Verdachtsdiagnose oder dem Ausschluss einer Diagnose. Sie sind damit aus dem klinischen Alltag der Kinderendokrinologie und -diabetologie nicht mehr wegzudenken. Im Laufe der letzten Jahrzehnte wurden eine ganze Reihe neuer Testverfahren und neuer Testsubstanzen entwickelt und für die klinische Routinediagnostik verfügbar gemacht. Ferner haben sich neue Indikationen für den Einsatz von dynamischen Testverfahren ergeben. Die Fülle der verfügbaren Tests und die für die Durchführung, Indikationsstellung und Interpretation notwendigen Detailinformationen sind in diesem Kapitel nicht erschöpfend darstellbar. Daher wurde eine Auswahl der gängigsten Tests ausgewählt. Für weitere Tests und weiterführende Informationen der dargestellten Tests ist das Studium der Originalliteratur unverzichtbar.
Drews, Gisela; Krippeit-Drews, Peter; Düfer, Martina
Stimulus-Secretion Coupling (SSC) of pancreatic islet cells comprises electrical activity. Changes of the membrane potential (Vm) are regulated by metabolism-dependent alterations in ion channel activity.
This coupling is best explored in β-cells. The effect of glucose is directly linked to mitochondrial metabolism as the ATP/ADP ratio determines the open probability of ATP-sensitive K+ channels (KATP channels). Nucleotide sensitivity and concentration in the direct vicinity of the channels are controlled by several factors including phospholipids, fatty acids, and kinases, e.g., creatine and adenylate kinase. Closure of KATP channels leads to depolarization of β-cells via a yet unknown depolarizing current. Ca2+ influx during action potentials (APs) results in an increase of the cytosolic Ca2+ concentration ([Ca2+]c) that triggers exocytosis. APs are elicited by the opening of voltage-dependent Na+ and/or Ca2+ channels and repolarized by voltage- and/or Ca2+-dependent K+ channels. At a constant stimulatory glucose concentration APs are clustered in bursts that are interrupted by hyperpolarized interburst phases. Bursting electrical activity induces parallel fluctuations in [Ca2+]c and insulin secretion. Bursts are terminated by IKslow consisting of currents through Ca2+-dependent K+ channels and KATP channels. This review focuses on structure, characteristics, physiological function, and regulation of ion channels in β-cells. Information about pharmacological drugs acting on KATP channels, KATP channelopathies, and influence of oxidative stress on KATP channel function is provided. One focus is the outstanding significance of L-type Ca2+ channels for insulin secretion. The role of less well characterized β-cell channels including voltage-dependent Na+ channels, volume sensitive anion channels (VSACs), transient receptor potential (TRP)-related channels, and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is discussed. A model of β-cell oscillations provides insight in the interplay of the different channels to induce and maintain electrical activity. Regulation of β-cell electrical activity by hormones and the autonomous nervous system is discussed.
α- and δ-cells are also equipped with KATP channels, voltage-dependent Na+, K+, and Ca2+ channels. Yet the SSC of these cells is less clear and is not necessarily dependent on KATP channel closure. Different ion channels of α- and δ-cells are introduced and SSC in α-cells is described in special respect of paracrine effects of insulin and GABA secreted from β-cells.
Liu, Zhengyu; Habener, Joel F.
The Wnt signaling pathway is critically important not only for stem cell amplification, differentiation, and migration, but also is important for organogenesis and the development of the body plan. Beta-catenin/TCF7L2-dependent Wnt signaling (the canonical pathway) is involved in pancreas development, islet function, and insulin production and secretion. The glucoincretin hormone glucagon-like peptide-1 and the chemokine stromal cell-derived factor-1 modulate canonical Wnt signaling in β-cells which is obligatory for their mitogenic and cytoprotective actions. Genome-wide association studies have uncovered 19 gene loci that confer susceptibility for the development of type 2 diabetes. At least 14 of these diabetes risk alleles encode proteins that are implicated in islet growth and functioning. Seven of them are either components of, or known target genes for, Wnt signaling. The transcription factor TCF7L2 is particularly strongly associated with risk for diabetes and appears to be fundamentally important in both canonical Wnt signaling and β-cell functioning. Experimental loss of TCF7L2 function in islets and polymorphisms in TCF7L2 alleles in humans impair glucose-stimulated insulin secretion, suggesting that perturbations in the Wnt signaling pathway may contribute substantially to the susceptibility for, and pathogenesis of, type 2 diabetes. This review focuses on considerations of the hormonal regulation of Wnt signaling in islets and implications for mutations in components of the Wnt signaling pathway as a source for risk-associated alleles for type 2 diabetes.
Zipris, Danny
Type 1 diabetes (T1D) is an autoimmune disease that results in the progressive loss of insulin producing cells. Studies performed in humans with T1D and animal models of the disease over the past two decades have suggested a key role for the adaptive immune system in disease mechanisms. The role of the innate immune system in triggering T1D was shown only recently. Research in this area was greatly facilitated by the discovery of toll-like receptors (TLRs) that were found to be a key component of the innate immune system that detect microbial infections and initiate antimicrobial host defense responses. New data indicate that in some situations, the innate immune system is associated with mechanisms triggering autoimmune diabetes. In fact, studies preformed in the BioBreeding Diabetes Resistant (BBDR) and LEW1.WR1 rat models of T1D demonstrate that virus infection leads to islet destruction via mechanisms that may involve TLR9-induced innate immune system activation. Data from these studies also show that TLR upregulation can synergize with virus infection to dramatically increase disease penetrance. Reports from murine models of T1D implicate both MyD88-dependent and MyD88-independent pathways in the course of disease. The new knowledge about the role of innate immune pathways in triggering islet destruction could lead to the discovery of new molecules that may be targeted for disease prevention.
Cravedi, Paolo; Meer, Irene M.; Cattaneo, Sara; Ruggenenti, Piero; Remuzzi, Giuseppe
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Transplantation of pancreatic islets is considered a therapeutic option for patients with type 1 diabetes mellitus who have life-threatening hypoglycaemic episodes. After the procedure, a decrease in the frequency and severity of hypoglycaemic episodes and sustained graft function as indicated by detectable levels of C-peptide can be seen in the majority of patients. However, true insulin independence, if achieved, usually lasts for at most a few years. Apart from the low insulin independence rates, reasons for concern regarding this procedure are the side effects of the immunosuppressive therapy, allo-immunization, and the high costs. Moreover, whether islet transplantation prevents the progression of diabetic micro- and macrovascular complications is largely unknown. Areas of current research include the development of less toxic immunosuppressive regimens, the control of the inflammatory reaction immediately after transplantation, the identification of the optimal anatomical site for islet infusion, and the possibility to encapsulate transplanted islets to protect them from the allo-immune response. At present, pancreatic islet transplantation is still an experimental procedure, which is only indicated for a highly selected group of type 1 diabetic patients with life-threatening hypoglycaemic episodes.
Hypoglykemie is voor patiënten een bedreigende situatie die, zeker bij herhaald optreden, een inperking van de kwaliteit van leven betekent. Het intensiveren van bloedglucoseverlagende behandeling bij type-2-diabetes brengt vaak een toename van het risico op het optreden van hypoglykemie met zich mee. Voor zowel patiënt als zorgverlener betekent dit dan ook een beperking voor het opvoeren van bloedglucoseverlagende therapie.
Adviezen over leefstijl vormen een essentiële eerste stap in de begeleiding van patiënten met type-2-diabetes. De praktijkondersteuner zal direct na het stellen van de diagnose diabetes mellitus aandacht besteden aan advies over leefstijl. Ook later in de begeleiding, wanneer de bloedglucoseverlagende behandeling verder geïntensiveerd moet worden, dient opnieuw aandacht aan leefstijl geschonken te worden. Bij leefstijladviezen wordt vooral uitleg gegeven over de volgende vier onderwerpen:
gezonde voeding;
voldoende lichaamsbeweging;
gewichtsreductie bij overgewicht;
stoppen met roken.
Akirav, Eitan M.; Herold, Kevan C.
Type 1 diabetes is thought to be caused by an immune-mediated destruction of β cells that occurs over years and continues even after presentation with hyperglycemia. Adaptive immune mechanisms are believed to be primary mediators of this process. Immune memory for the initial process that resulted in β-cell failure, the high frequency of alloreactive T cells, and the nonphysiologic environment into which islets have been transplanted all create obstacles for successful reversal of diabetes with islet replacement. In this chapter we review the immune mechanisms that are thought to be responsible for β-cell destruction and discuss the obstacles that stand in the way of the successful achievement of β-cell replacement.
Winchester, James F.; Feinfeld*, Donald A.; Harbord, Nikolas B.; Dubrow, Alan
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Diabetes mellitus (DM) remains the most common primary cause of incident and prevalent chronic kidney disease (CKD) requiring renal replacement therapy in the United States1 and the emerging world.2 In the United States, more than 43% of the new CKD diagnoses in 2004 were attributable to diabetes: a total of 45,871 patients, a rate of 149 per million/population. Although the absolute number of new CKD patients each year is increasing due to population growth, the rate of incident CKD from diabetes has decreased since the year 2000. This trend is reassuring, although CKD attributable to DM remains unacceptably high among blacks, Hispanics, and Native Americans; and continues to increase in the elderly and younger (age 30–39) black adults. The economic impact of advanced kidney disease from diabetes is enormous – total CKD expenditure in 2004 was $32.5 billion, and diabetic patients incur the highest per-person per-year cost. Patients with diabetes have the highest hospitalization rates and mortality (cardiovascular, infectious, and all-cause) among all dialysis patients. They are also less likely to be wait listed for or to receive a kidney transplant. Diabetic individuals fare worse than nondiabetic patients after transplantation, with higher mortality and morbidity from infection.
Ogbera, Anthonia O
The Metabolic syndrome (MetS) is a cardiovascular risk factor of public health significance and of recent has become a topical issue. The prevalence of diabetes mellitus (DM) is on the increase and with this scenario, a possible increase in burden of DM which may be largely attributed to cardiovascular complications is expected. The objective of this report is to determine the prevalence of the MetS and compare gender characteristics in subjects with type 2 DM.
Subjects with type 2 DM were recruited from an urban hospital for the study. Clinical data was obtained by interviewing the patients and referring to their Case folders. The anthropometric indices and blood pressure measurements were documented. Laboratory parameters analysed for included total cholesterol, high density and low density cholesterol, triglyceride and glycosylated haemoglobin. Statistical analysis included usage of Student's t test and chi square.
963 patients with type 2 DM aged between 35-85 years were recruited for the study. The main outcome measures included the prevalence of the metabolic syndrome and the gender differences of its components. The prevalence of the metabolic syndrome was 86%. The frequency of occurrence of the MetS was similar for men (83%) and women (86%) and increased with age in both sexes. The prevalence of MetS increased from 11% among participants aged 20 through 29 years to 89% in participants aged 70 through 79. In our patients with DM, the commonest occurring and least detected MetS defining parameters are central obesity and elevated triglyceride levels respectively. The components of the MetS that differed significantly in both sexes was HDL-C. The combination of the components of the MetS were comparable in both genders and 5.8% of the subjects with the MetS had all components of the MetS.
The prevalence of the MetS in type 2DM is high in both genders and increases with age thus posing a potential high cardiovascular risk in this group of patients. The modifiable risk factors for the MetS should be a focus point in the management of subjects with type 2 DM,
Fischer-Posovszky, Pamela
Adipositas ist durch eine Größenzunahme des Fettgewebes charakterisiert. Diese beruht entweder auf einer Hypertrophie der vorhandenen Fettzellen oder einer Kombination aus Fettzellhypertrophie und -plasie. Jede Gewichtszunahme führt zunächst zu einer Volumenzunahme der Adipozyten. Bei einer kritischen Zellgröße kommt es durch bislang noch unbekannte Signale, die wahrscheinlich von den vergrößerten Fettzellen abgegeben werden, zur Rekrutierung von spezifischen Vorläuferzellen und damit zur Neubildung von Fettzellen.
Meyer*, Douglas F.; Bodenheimer, Henry C., Jr
The prevalence of type 2 diabetes, in the United States, has increased in association with the increase in the mean weight of Americans indicative of the epidemic of obesity in this country. Complications of type 2 diabetes can be expected to rise in the near future. These complications include vascular, renal, ophthalmologic, and importantly liver disease. Hepatic complications include nonalcoholic fatty liver disease (NAFLD), cirrhosis, hepatocellular carcinoma (HCC), acute liver failure, and post-liver transplantation diabetes. There is, additionally, a relationship between type 2 diabetes and chronic hepatitis C infection with type 2 diabetes being considered an extrahepatic manifestation of chronic hepatitis C infection. The association of diabetes and liver disease is being increasingly recognized. The morbidity and mortality of acute and chronic liver disease in patients with diabetes, particularly type 2 diabetes, will continue to rise in Americans in the immediate and near future.
Tibiriça, Eduardo
Cannabis sativa (also known as marijuana) has been cultivated by man for more than 5,000 years. However, there was a rise in its use in the 20th century for recreational, religious or spiritual, and medicinal purposes. The main psychoactive constituent of cannabis, whose structure was identified in the 1960's, is Δ9-tetrahydrocannabinol. On the other hand, the discovery of cannabinoid receptors and their endogenous agonists took place only very recently. In fact, the first cannabinoid receptor (CB1) was cloned in 1990, followed 3 years later by the characterization of a second cannabinoid receptor (CB2). Since the 19th century, the use of cannabis has been reported to stimulate appetite and increase the consumption of sweet and tasty food, sometimes resulting in significant weight gain. The recent description of the endocannabinoid system, not only in the central nervous system but also in peripheral tissues, points to its involvement in the regulation of appetite, food intake and energy metabolism. Consequently, the pharmacological modulation of the over-activity of this system could be useful in the treatment of the metabolic syndrome.
The endocannabinoid system has important physiological functions not only in the central nervous system but also in peripheral tissues. The activation of central CB1 receptors, particularly in hypothalamic nuclei and in the limbic system, is involved in the regulation of feeding behavior, and especially in the control of the intake of palatable food. In the periphery, cannabinoid receptors are present in adipocytes, skeletal muscle, gastrointestinal tract and liver, modulating energy metabolism.
McMahon, Graham T.
The epidemic of diabetes shows no signs of abating.1 Diabetes is already having an enormous impact on the health and well-being of more than 150 million people, a number that is predicted to grow in the United States and throughout the globe, creating substantial strain on health-care systems. 1 Diabetes mellitus causes resource-intensive complications,2 and while preventive care is effective in reducing overall utilization and improving outcome,3 it too is expensive and requires teams of care providers at a time when the United States is facing a shortage of endocrinologists.4 The future of diabetes therapy must include preventive efforts and improvements in therapeutics incorporating oral and injectable therapies, and will also need to embrace improvements in technology and care efficiency if targets are to be met (Table 48.1). This chapter examines some of the ongoing work in preventing and treating diabetes and outlines some of the approaches that will form part of future armamentaria.
Coats, Andrew J. S.
Chronic heart failure is both common and disabling. It predominantly affects older people and there is convincing evidence that it is increasing in prevalence with the aging population of developed societies. Heart failure is associated with a poor prognosis. What, as little as 30 years ago, was a condition of despair with no proven treatments that affected survival has changed with the advent of effective therapies. For a patient with a new diagnosis of heart failure the expectation of surviving 1 year has probably improved from about 60 to 80–90% with the advances in therapy that have become established over this period. These include ACE inhibitors, beta-blockers, aldosterone antagonists, cardiac resynchronization pacemakers and implantable defibrillators. Heart failure is, however, also associated with many debilitating symptoms for the sufferer. These can induce depression, withdrawal from society, an inability to work and even severe limitations on the ability to fulfill the needs of self-care and daily living. Exercise tolerance is particularly limited by a combination of dyspnoea, fatigue and a weakness of the peripheral musculature.
Zajac, Jacek; Shrestha, Anil; Patel, Parini; Poretsky, Leonid
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A medical condition producing excessive thirst, continuous urination, and severe weight loss has interested medical authors for over three millennia. Unfortunately, until the early part of twentieth century the prognosis for a patient with this condition was no better than it was over 3000 years ago. Since the ancient physicians described almost exclusively cases of what is today known as type 1 diabetes mellitus, the outcome was invariably fatal.
In 2003 bracht de Raad voor de Volksgezondheid en Zorg (RVZ) een advies uit over taakherschikking. Onder taakherschikking verstond de RVZ het structureel herverdelen van taken tussen verschillende beroepsgroepen. Een belangrijk motief achter het initiatief van de RVZ vormde het inzicht dat de traditionele zorgverlening, met de dokter voor de 'cure' en de verpleegkundige voor de 'care', voor chronische aandoeningen niet de optimale zorgvorm was gebleken. Het traditionele systeem kwam onvoldoende tegemoet aan de specifieke behoeften en problemen van mensen met een chronische ziekte. Andere argumenten van de RVZ voor het initiatief tot taakherschikking waren de sterke groei van het aantal chronisch zieken en de hieruit voortvloeiende kostentoename en de verzwaarde werkdruk onder artsen.
Rojas, Anabel; Khoo, Adrian; Tejedo, Juan R.; Bedoya, Francisco J.; Soria, Bernat; Martín, Franz
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Over the last years, there has been great success in driving stem cells toward insulin-expressing cells. However, the protocols developed to date have some limitations, such as low reliability and low insulin production. The most successful protocols used for generation of insulin-producing cells from stem cells mimic in vitro pancreatic organogenesis by directing the stem cells through stages that resemble several pancreatic developmental stages. Islet cell fate is coordinated by a complex network of inductive signals and regulatory transcription factors that, in a combinatorial way, determine pancreatic organ specification, differentiation, growth, and lineage. Together, these signals and factors direct the progression from multipotent progenitor cells to mature pancreatic cells. Later in development and adult life, several of these factors also contribute to maintain the differentiated phenotype of islet cells. A detailed understanding of the processes that operate in the pancreas during embryogenesis will help us to develop a suitable source of cells for diabetes therapy. In this chapter, we will discuss the main transcription factors involved in pancreas specification and β-cell formation.
Mezzasalma, Marco André Urbach
Major depression is a disorder that significantly worsens a patient's morbidity and mortality. The association of depression and diabetes is well documented and has clinical impact in diabetes treatment's outcome. Patients usually aren't evaluated initially by a psychiatrist, so it is important that non-psychiatrists learn to evaluate major depression and its impact.
Major depression can and should be evaluated on a routine clinical assessment. Depression's impact on the patients' quality of life, productivity and social interactions is well documented. The initial diagnosis of depression should lead to its prompt treatment, and it has to be emphasized that the incorrect treatment can lead to worsening of the condition, relapses, recurrences or even chronification of major depression.
Hien, Peter; Böhm, Bernhard
Mejhert, Niklas; Laurencikiene, Jurga; Pettersson, Amanda T; Kaaman, Maria; Stenson, Britta M; Rydén, Mikael; Dahlman, Ingrid
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Mice lacking Receptor-interacting protein 140 (RIP140) have reduced body fat which at least partly is mediated through increased lipid and glucose metabolism in adipose tissue. In humans, RIP140 is lower expressed in visceral white adipose tissue (WAT) of obese versus lean subjects. We investigated the role of RIP140 in human subcutaneous WAT, which is the major fat depot of the body.
Messenger RNA levels of RIP140 were measured in samples of subcutaneous WAT from women with a wide variation in BMI and in different human WAT preparations. RIP140 mRNA was knocked down with siRNA in in vitro differentiated adipocytes and the impact on glucose transport and mRNA levels of target genes determined.
RIP140 mRNA levels in subcutaneous WAT were decreased among obese compared to lean women and increased by weight-loss, but did not associate with mitochondrial DNA copy number. RIP140 expression increased during adipocyte differentiation in vitro and was higher in isolated adipocytes compared to corresponding pieces of WAT. Knock down of RIP140 increased basal glucose transport and mRNA levels of glucose transporter 4 and uncoupling protein-1.
Human RIP140 inhibits glucose uptake and the expression of genes promoting energy expenditure in the same fashion as the murine orthologue. Increased levels of human RIP140 in subcutaneous WAT of lean subjects may contribute to economize on energy stores. By contrast, the function and expression pattern does not support that RIP140 regulate human obesity.
Neu, Andreas
Elliot Proctor Joslin (1869–1962) war der Üerzeugung, dass mit der Entdeckung des Insulins der Diabetes mellitus seinen Schrecken verloren habe und formulierte sinngemäß in den 1920er Jahren "today it is not allowed to die of diabetic coma". Dass sich diese Hoffnung nicht erfüllte, kann man in den ISPAD-(International-Society-for-Pediatric- and -Adolescent-Diabetes-)Guidelines des Jahres 2000 nachlesen.
Meivar-Levy, Irit; Aviv, Vered; Ferber, Sarah
Regenerative medicine is designed to produce new cells for repair or replacement of diseased and damaged tissues. Embryonic and adult stem cells have been suggested as attractive sources for generation of new differentiated cells. The leading dogma has maintained that once animal cells are committed to a specific lineage, they become "terminally differentiated" and can no longer change their fate. However, in recent years increasing evidence has demonstrated the remarkable ability of some differentiated cells to convert into a different cell type via a process termed developmental redirection or nuclear reprogramming. For example, abundant human cell types, such as dermal fibroblasts and adipocytes, could potentially be harvested and converted into other, medically important cell types, such as neurons, cardiomyocytes, or pancreatic β cells. In this chapter we review the potential use of adult tissue, specifically liver and bone marrow, to provide a source of tissue for generating functional insulin-producing cells. This approach might generate custom-made autologous surrogate β cells for treatment of diabetes and possibly circumvent both the shortage of cadaveric human donor tissue and the need for life-long immunosuppression.
Nieuwendijk, Lydia
Kawamori, Dan; Welters, Hannah J.; Kulkarni, Rohit N.
Glucagon plays a critical role in glucose homeostasis by counteracting insulin action, especially during hypoglycemia. Glucagon secretion from pancreatic α-cells is regulated by various mechanisms including glycemia, neural input, and secretion from neighboring β-cells. However, glucagon secretion is dysregulated in diabetic states, causing exacerbation of glycemic disorders. Recently, new therapeutic approaches targeting excess glucagon secretion are being explored for use in diabetes treatment. Therefore, understanding the molecular mechanism of how glucagon secretion is regulated is critical for treating the α-cell dysfunction observed in diabetes.
Sedimbi, Saikiran K.; Sanjeevi, Carani B.
Type 1 diabetes (T1D) is an autoimmune disease resulting from the destruction of pancreatic β-cells. The main aim of treatment should be to prevent β-cell destruction and preserve existing β-cells in individuals with progressive autoimmunity. This can be achieved in several ways and in this chapter the authors have reviewed recent approaches that are currently being tested in animal models and human T1D patients under the following categories: i) antigen based therapy, ii) antibody-based therapy iii) other forms of therapy and iv) failed therapies.
Ekeblad, Sara
Pancreatic endocrine tumours can cause hormonal symptoms by over-secretion of hormones. They are less aggressive than exocrine pancreatic cancer, but carry a variable prognosis. The tumours are either sporadic or hereditary, as part of the multiple endocrine neoplasia type 1 syndrome. Despite the rarity of these tumours, they evoke significant interest in the research community and important advances have been made over the past years. This chapter provides an overview of the tumours and recent advances in the field.
Hereditary forms of pancreatic endocrine tumours are caused by mutations in the MEN1 gene. Menin, the protein encoded by this gene, has been shown to interact with numerous transcription factors and proteins involved in cell-cycle control, shedding some light on the importance of the protein. Several genes have been shown to be up- or down-regulated, suggesting candidates to be further evaluated for a role in tumourigenesis.
Several advances have been made in prognostication; a tumour-node-metastasis system has been evaluated and seems to have prognostic value, and several new molecular prognostic markers are under evaluation. It is hoped that the tumour-node-metastasis system and other prognostic markers will be adopted in clinical routine and improve prognostication and treatment choices.
Surgery is still the only cure, but several new palliative drugs and interventions are in use or under investigation. Radiofrequency ablation is increasingly used for liver metastases, and a number of new chemotherapy drugs are being tested. Despite improvements in treatment, no clear improvement in survival has been demonstrated.
Schroeder, Brock E.; Kolterman, Orville
The maintenance of the plasma glucose concentration is a critical bodily function. Hyperglycemia is associated with long-term micro- and macrovascular complications, while hypoglycemia can lead to serious injury to the brain, which is dependent on plasma glucose as a fuel source. At any given time the body's plasma glucose concentration is a balance between the relative rates of glucose appearance and disappearance. These rates are regulated by several key organs through the actions of multiple hormonal signals. A brief introduction follows; however, for more detailed information, see Chapter 2.
Chin, Russell L.; Rubin, Michael
Diabetes mellitus (DM) is estimated to affect approximately 20 million Americans (90% with type 2 and 10% with type 1 DM) and is the most common cause of peripheral neuropathy in the United States. There is evidence to suggest that the incidence of neuropathy increases with the duration and severity of disease, and that strict glycemic control delays its development and progression, particularly in patients with type 1 diabetes.
Fiaschi-Taesch, Nathalie; Harb, George; Karsiloglu, Esra; Takane, Karen K.; Stewart, Andrew F.
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For decades, it had been assumed that pancreatic β cells were terminally differentiated and thus unable to replicate, and that β-cell replication did not exist in any quantitatively meaningful way. This view has changed dramatically in the past decade, with abundant data demonstrating that fetal, neonatal, and adult rodent β cells replicate at physiologically important rates. These new data have resulted in a plethora of new reports exploring the nutrient, growth factor, and signaling cascades that lie upstream and regulate the cell cycle machinery that controls rodent β-cell replication. Moreover, myriad reports of murine genetic models of cell cycle molecule knockout or overexpression have appeared and have documented unequivocally the importance and therapeutic relevance of cell cycle regulatory mechanisms in murine β cells. These events contrast with the pace of development of new knowledge regarding human β-cell replication. It seems clear that unlike in rodents, spontaneous replication of adult human β cells is uncommon. Further, standard manipulations, nutrients, and growth factors that induce rodent β-cell replication fail to do so in human β cells. In this chapter we focus on the molecular control of cell cycle progression in human β cells, illustrate the differences between human and rodent β-cell cycle regulatory control, and provide examples of approaches to inducing human β-cell replication.
Nijjar, Aman PK; Wang, Hong; Dasgupta, Kaberi; Rabi, Doreen M; Quan, Hude; Khan, Nadia A
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The aim of this study was to determine whether South Asian patients with diabetes have a worse prognosis following hospitalization for acute myocardial infarction (AMI) compared with their White counterparts. We measured the risk of developing a composite cardiovascular outcome of recurrent AMI, congestive heart failure (CHF) requiring hospitalization, or death, in these two groups.
Using hospital administrative data, we performed a retrospective cohort study of 41,615 patients with an incident AMI in British Columbia and the Calgary Health Region between April 1, 1995, and March 31, 2002. South Asian ethnicity was determined using validated surname analysis. Baseline demographic characteristics and co-morbidities were included in Cox proportional hazard models to compare time to reaching the composite outcome and its individual components.
Among the AMI cohort, 29.7% of South Asian patients and 17.6% of White patients were identified as having diabetes (n = 7416). There was no significant difference in risk of developing the composite cardiovascular outcome (Hazard Ratio = 0.90, 95% CI = 0.80-1.01). However, South Asian patients had significantly lower mortality at long term follow-up (HR = 0.62, 95% CI = 0.51-0.74) compared to their White counterparts.
Following hospitalization for AMI, South Asian patients with diabetes do not have a significantly different long term risk of a composite cardiovascular outcome compared to White patients with diabetes. While previous research has suggested worse cardiovascular outcomes in the South Asian population, we found lower long-term mortality among South Asians with diabetes following AMI.
Gallagher, Emily Jane; Novosyadlyy, Ruslan; Yakar, Shoshana; LeRoith, Derek
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Theories on a connection between diabetes, obesity, and cancer have existed for over a century. In 1910, despite their elusive etiologies, Maynard hypothesized that a correlation between diabetes and cancer could exist, as both conditions were increasing in prevalence and had similar age distributions.
Riepe, Felix G.
Die Nebenniere besteht embryologisch und anatomisch aus zwei Anteilen: der Nebennierenrinde und dem Nebennierenmark. Die Nebennierenrinde ist mesodermalen Ursprungs. Hingegen ist das Nebennierenmark neuroektodermaler Herkunft. Die ersten Vorläufer der Rindenzellen kann man als Verdickung des Zölomepithels neben der primitiven Nierenanlage ungefähr in der 4. Woche post conceptionem identifizieren. Diese Zellen sind der Ursprung der steroidbildenden Zellen der Nebenniere und der Gonaden. Nach der Teilung der Nebennieren- und Gonadenanlage wandern die primitiven adrenalen Zellen zum Oberpol des Mesonephros, bevor es in der 8. Woche zur Einwanderung neuroektodermaler Zellen in die unreife Nebenniere kommt, die später das Mark bilden werden. Die fetale Nebennierenrinde besteht aus einer äußeren definitiven Zone und einer inneren fetalen Zone. Die letztere ist um ein Vielfaches größer und stellt die Synthese von Dehydroepiandrosteron und Dehydroepiandrosteronsulfat sicher, das für die plazentare Synthese von Östriol genutzt wird.
Doehner, Wolfram; Anker, Stefan D.
Our understanding of the pathophysiology of chronic heart failure (CHF) has significantly advanced over the last 15 years from the historic haemodynamic model of mere pumping failure to a much more complex approach including multiple body systems. The concept of neuroendocrine activation is the cornerstone of the current pathophysiological understanding as well as of the therapeutic approaches that are available today. On this basis, the treatment of CHF has made significant advances over the last two decades. Moreover, treatments for acute cardiac events have improved considerably. As a consequence of effective acute and chronic therapy and a steadily growing population of the aged, a growing number of patients live for prolonged periods in a state of compensated cardiac failure. As a result not only a significant increase in prevalence numbers of CHF can be observed giving rise to the word of an epidemic proportion in the development on heart failure. Also clinical features and complications of a long-term disease progression are increasingly coming to the fore in the clinical presentation of patients. With growing understanding of the complexity of CHF pathophysiology and modern therapy starting to adopt to tailored treatment strategies of specific aspects in patients subgroups a broader and more differentiated perspective on the patients might be required with.
Der Typ 1-Diabetes mellitus wird durch einen chronischen Autoimmunprozess bedingt. Der klinischen Manifestation mit Hyperglykämie geht eine längere, zum Teil viele Jahre bestehende prädiabetische Phase voraus, die durch das Auftreten zahlreicher Autoimmunphänomene gekennzeichnet ist.
In't Veld, Peter; Marichal, Miriam
Human islets of Langerhans are complex micro-organs responsible for maintaining glucose homeostasis. Islets contain five different endocrine cell types, which react to changes in plasma nutrient levels with the release of a carefully balanced mixture of islet hormones into the portal vein. Each endocrine cell type is characterized by its own typical secretory granule morphology, different peptide hormone content, and specific endocrine, paracrine, and neuronal interactions. During development, a cascade of transcription factors determines the formation of the endocrine pancreas and its constituting islet cell types. Differences in ontogeny between the ventrally derived head section and the dorsally derived head, body, and tail section are responsible for differences in innervation, blood supply, and endocrine composition. Islet cells show a close topographical relationship to the islet vasculature, and are supplied with a five to tenfold higher blood flow than the exocrine compartment. Islet microanatomy is disturbed in patients with type 1 diabetes, with a marked reduction in β-cell content and the presence of inflammatory infiltrates. Histopathological lesions in type 2 diabetes are less pathognomonic with a more limited reduction in β-cell content and occasional deposition of amyloid in the islet interstitial space.
Leu, James P.; Zonszein, Joel
Diabetes mellitus is a group of diverse metabolic disorders characterized by hyperglycemia and distinctive complications that include premature atherosclerotic cardiovascular disease and small vessel disease manifested as retinopathy with potential loss of vision; nephropathy leading to renal failure; and peripheral neuropathy with a high risk of foot ulcers and amputations. In the past, the classification of diabetes mellitus was based on clinical findings such as age of onset, so-called juvenile- or adult-onset diabetes, or treatment modalities, such as insulin-dependent versus non-insulin-dependent diabetes. In 1979 the National Diabetes Data Group (NDDG) in conjunction with World Health Organization (WHO) revised and published new and unified criteria for the classification and diagnosis of diabetes mellitus.
Williams, Lynne; Lip, Gregory Y. H.; MacFadyen, Robert J.
Heart failure syndromes are characterized by acute and chronic symptomatic clinical presentations of variable etiology. Definitions of heart failure in many studies and surveys vary enormously. Most heart failures involve failure of cardiac mechanics resulting in reduced stroke volume or cardiac work, which in turn occur as a consequence of several processes. Heart failure syndromes are frequently characterized as primarily linked to either systolic or diastolic ventricular dysfunction but most often involve combinations of both to result in elevated pulmonary pressure and pulmonary edema causing breathlessness and exercise limitation.
A local RAS exists in several cell types of the pancreas, which exhibits both exocrine and endocrine activities, and this functional local RAS is responsive to various physiological and pathophysiological stimuli (see Chapter 6). Of particular interest in this context are the expression and localization of key RAS components in the acinar and endothelial cells of the exocrine pancreas; these RAS components are subject to upregulation in response to chronic hypoxia and acute pancreatitis (AP). In this regard, an enhanced sensitivity of angiotensin II-mediated vasoconstriction in pancreatic microcirculation could trigger severe ischemia and/or hypoxia conditions, which result in oxidative stress-induced expression of proinflammatory factors, ultimately leading to pancreatic cell inflammation and injury. Indeed, recent investigations have demonstrated that inhibition of RAS activation supports amelioration of pancreatic oxidative stress and tissue injury in experimentally induced AP.
Weir, Gordon C.; Bonner-Weir, Susan
As diabetes with its devastating complications results from β-cell deficiency, there is a compelling need to know more about the culprit. Whereas type 1 diabetes has a near complete loss of β cells owing to autoimmune destruction, type 2 diabetes is associated with a 40–60% reduction in β-cell mass. Insulin resistance, brought on by our Western lifestyle coupled with genetic factors, is clearly of major importance, but diabetes only develops when β-cell deficiency with its associated dysfunctional insulin secretion occurs. Replenishment of β cells by transplantation or by stimulating regeneration of endogenous islets would eliminate the diabetic state. Improving the dysfunctional insulin secretion of diabetes could also provide help. This chapter is written with an eye toward how β cells, or some kind of β-cell surrogate, might function when transplanted. It is important to understand β cells in their normal pancreatic environment to fully appreciate the compromises that will necessarily accompany β-cell replacement therapy.
Schwegler, Guido
Neue, hochpotente Medikamente haben das therapeutische Spektrum bei multipler Sklerose erweitert. Doch auch die Standardtherapie mit Interferon beta und Glatirameracetat behält in der Verlaufsmodifikation ihren Stellenwert. Generell geht der Trend hin zu einer frühen Therapie, um ein bleibendes neurologisches Defizit zu verhindern.
Johnson, James D.; Luciani, Dan S.
Diabetes occurs when β-cells no longer function properly or have been destroyed. Pancreatic β-cell death by apoptosis contributes significantly in both autoimmune type 1 diabetes and type 2 diabetes. Pancreatic β-cell death can be induced by multiple stresses in both major types of diabetes. There are also several rare forms of diabetes, including Wolcott-Rallison syndrome, Wolfram syndrome, as well as some forms of maturity onset diabetes of the young that are caused by mutations in genes that may play important roles in β-cell survival. The use of islet transplantation as a treatment for diabetes is also limited by excessive β-cell apoptosis. Mechanistic insights into the control of pancreatic β-cell apoptosis are therefore important for the prevention and treatment of diabetes. Indeed, a substantial quantity of research has been dedicated to this area over the past decade. In this chapter, we review the factors that influence the propensity of β-cells to undergo apoptosis and the mechanisms of this programmed cell death in the initiation and progression of diabetes.
Jun, Hee-Sook
Type 1 and type 2 diabetes mellitus are considered to be caused by defective control of blood glucose resulting from a reduced β-cell mass. Thus, the restoration of a functional β-cell mass by replacing the damaged β-cells or stimulating β-cell regeneration is a logical approach for the treatment of diabetes. Strategies for increasing the β-cell mass include stimulating β-cell replication and differentiation and inhibiting β-cell death. Treatment with various growth factors such as GLP-1, BTC, HGF, and EGF and forced expression of β-cell transcription factors such as Pdx-1, NeuroD, and MafA resulted in the regeneration of β-cells in vivo. Another approach is the administration of stem/progenitor cells, which can differentiate into insulin-producing cells. However, there are no satisfactory methods yet for clinical application. Understanding the mechanisms of the regenerative process of pancreatic β-cells will pave the way for the development of regenerative medicine for treatment of diabetes.
Bukys, Michael A.; Jensen, Jan
Beta-cell replacement is an effective treatment for type 1 diabetes, but its applicability is limited by the lack of sufficient donor tissue, raising the need for alternative tissue sources. Deriving β cells from stem cell precursors offers an unlimited renewable source of tissue for transplantation and in recent years has become the focus of research in many laboratories. The unique state of embryonic stem (ES) cells is characterized by continuous proliferation through a cell cycle consisting of an abbreviated G1 phase. Although this cell cycle exposes ES cells to potential mutations, it also allows continuous culture of undifferentiated cells. Current protocols directing the differentiation of ES cells mimic the normal embryonic development of β cells through definitive endoderm, foregut endoderm, pancreatic precursors, and endocrine progenitor cells. At present all of these steps are suboptimal, since only some of the cells follow this pathway to the intended product. Moral concerns surrounding the use of embryonic stem cells has led to development of alternative sources of pluripotent cells. Current advances in cellular reprogramming are discussed.
Pancreatitis is an inflammatory disease of the pancreas characterized by acute and chronic condition as well as varying duration and severity. Acute pancreatitis (AP) is a severe abdominal inflammation, characterized by parenchymal edema, necrosis with occasional presence of pseudocysts, abscess, hemorrhage, and inflammatory cell infiltration. Its disease spectrum varies from mild edematous to severe disease with fatal complications. Pancreatic acinar cells are very susceptible to inflammation during an episode of AP attack. It is believed that some initiating factors can lead to the premature transformation of inactive pro-proteases into active proteases within the pancreas. The active proteases degrade a number of cellular proteins such as the structural protein F-actin, thus leading to the collapse and malfunction of acinar and pancreatic damage, a process known as autodigestion of the pancreas.
Svahn, Jennifer K.; Kirk, Jeffrey S.; Llaguna, Omar H.; Habib, Nancy
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Diabetes mellitus is a ubiquitous disease which affects millions of Americans (7% of the US population),1 incurs significant comorbidities, and costs billions annually in health-care dollars. The morbidities associated with diabetes mellitus include a substantial increase in both small vessel (microvascular) and large vessel (macrovascular) diseases. The macrovascular effects of diabetes, causing serious morbidity and mortality, are found in the coronary, cerebral (extra- and intracranial), and peripheral vascular circulation. The focus of this chapter's discussion will be on the lower extremity peripheral vascular complications of diabetes.
Sanderson, John E.; Tan, Yu Ting
It has been increasingly recognized that there are many patients, mainly elderly women, who have symptoms of heart failure but their hearts are not enlarged and echocardiography shows a relatively normal left ventricular ejection fraction. The label "Diastolic heart failure" was coined for this group of patients because it was considered that systolic function was normal in view of the ejection fraction and hence the problem must lie in diastole. However, it has become clear that systolic function is not entirely normal and recent work has demonstrated that in these patients abnormalities exist in left ventricular systolic properties, ventricular-arterial coupling, LV diastolic function, torsion, ventricular−ventricular interaction and pericardial constraint, and other factors such as pulmonary hypertension, impaired chronotropic, vasodilator, and contractile reserves may contribute to the pathophysiology. Thus, the more simple label "heart failure with a normal ejection fraction" or HFNEF is the preferred term to diastolic heart failure (DHF), which implies that the primary or dominant abnormality is in diastole, and as it appears that the problem is not due to diastolic dysfunction only, the label HFNEF is more appropriate, which makes no assumptions about the causation of the condition.
Der Typ 1-Diabetes mellitus ist Folge einer chronisch verlaufenden immunmediierten Erkrankung und wird heute als Autoimmunerkrankung verstanden, bei der es zu einer unwiederbringlichen Zerstörung der Insulin produzierenden β-Zellen kommt.
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Estée Lauder Take It Away - total make up remover 200ml
Item No.1230100085
Item No.1230100085
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THE DEBATE takes place in coaches' offices and front offices all over the National Football League, and on "Monday Night Football" as well. It is now headed here, though, this debate about the so-called Wildcat offense. As Michael Vick prepares to return this weekend, Philadelphia is about to become ground zero.
On ESPN, analysts Ron Jaworski and Jon Gruden have set themselves up for a seasonlong argument - one highlighted on Monday night, when the Miami Dolphins (who brought the Wildcat to the NFL in a significant way last season) played the Indianapolis Colts. The Wildcat - a spread offense that usually features a direct snap to a running back - worked great for the Dolphins, and they ran for a million yards, but Peyton Manning still carved them up in the end. Yes, the passing game is still king.


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5-8, Sophomore, Forward
Stats: Hampton missed all of last season with a broken leg. However she moved into the Lady Eagles' starting lineup to average nine points and five rebounds a game. Hampton was named to the all-state tournament team after scoring 15 points with four assists and four steals in the state title game.
Quote: "She takes a lot from her mom (Sharon Gerber Hampton) and her dad (Johnny Hampton). She's very smart on the court and she's unflappable. She makes very good decisions and it really helped us immensely for her to develop the way she did and give us a complimentary scorer," said Canyon coach Joe Lombard.
LeBron James Drives a $50,000 Hummer. What Do You Drive? "I've just turned 16 and I've got my mom's red Volkswagen Beetle. It's sporty and it's small and I can get around in it. It's big enough to take people around but it's small enough so I can get around in it."
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Knowledge Advancing Social Justice
The Heller School's MPP program at Brandeis University is an interdisciplinary two-year graduate program focusing exclusively on social policy. Located in a top ten school of social policy in the U.S., the Heller MPP empowers future social policy leaders to analyze and solve complex problems in diverse work environments at the national, state and local level.
Heller students develop:
- Critical thinking and communication skills through academic and hands-on experiences.
- Expertise in critical policy areas (concentrations), including health, behavioral health, poverty alleviation, children, youth, and families, and aging.
Specialization Aligns with Heller Research Institutes
Each social policy concentration is aligned with one of Heller's research institutes. This is a unique advantage as students access connections to networks and leaders in the field that lead to internship and research opportunities as well as career opportunities.
The flexibility exists to create your own concentration to provide a better fit with your career goals. With nine research institutes and centers, Heller offers great resources with which to do so.
The opportunity to work directly with faculty and senior researchers on a policy analysis capstone in the final semester is another great benefit of being a student in a policy research environment.
Social Change
The Heller MPP program draws students who are committed to social change, are open, bright and often experienced. The MPP program helps prepare graduates for advanced careers within government and non-governmental settings involving advocacy, philanthropy, policy research and analysis, policy implementation and community work.
With the Heller School's rich tradition of being in the vanguard of critical public and social policy research, analysis and practice, the Heller MPP is specifically designed to help students maximize their career impact.
Working as senior policy analysts, executive directors, program managers, vice presidents, COOs, evaluation coordinators, advocates and researchers, Heller MPP graduates make a policy difference in the areas of children, youth and families, health, poverty alleviation and aging. With the help of a dedicated Career Development Center and an alumni network of 3,000+ professionals working around the world, Heller MPP graduates are able to launch careers in the public, private and nonprofit sectors.
See where some of our graduates are making a difference.
Lifelong Network
The Heller alumni network has more than three thousand members who often help each other with career moves and professional advice. Heller faculty members are deeply engaged in policy fields and share their connections and networks liberally with students and alumni.
The Heller School has helped launch countless careers dedicated to improving the lives of vulnerable populations. We invite you to learn more about the Heller MPP to see if advancing social justice through social policy aligns with your career goals.
Engaged Students
MPP students are fully engaged with the program and in the life of the Heller School. Students are active through the MPP Student Association (MPPSA), which creates opportunities for current and former students to connect while building upon our shared knowledge of current policy issues. The MPPSA is committed to the academic and professional development of all Heller students interested in public policy and values the unique perspectives offered by the diverse backgrounds of the student body. Through publications, networking opportunities, community partnerships, guest lectures and social events, the MPPSA helps students enhance their in-class experiences in the spirit of the Heller mission: knowledge advancing social justice.
The aim of the MPPSA is four-fold:
- Professional and career development, with an emphasis on outside speakers and networking with alumni
- Socialization among and between the two MPP classes in residence at Heller, and among all the graduate students in residence at Heller
- Foster a culture of reflective, critical engagement with community problems and opportunities
- Production of a student-run Journal
Visit Heller
Visit Heller
We offer a variety of opportunities to connect with us, including Visit Days, Virtual Events, and our annual Fall Open House, all of which enable you to learn about our program offerings and the admissions process. You can also meet us on the road, both in the US and at select international locations. Learn more and register online.
Jeanne Mansfield, MPP/MBA'15, at work with Boston Public Market
Jeanne Mansfield, MPP/MBA'15, at work with Boston Public Market
Pioneering HIV prevention strategies for transgender women
Pioneering HIV prevention strategies for transgender women
See the Latest Alumni Employment Data
See the Latest Alumni Employment Data
Knowledge Advancing Social Justice


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water treatment Companies in Costa Rica
Current filtering criteriaYou can remove a filter by clicking on the x
Atec Automatisierungstechnik GmbH
Office in San José, COSTA RICA
In both of its buisiness areas, control engineering and environmental engineering, Atec Neu-Ulm provides high quality products and services. Design and manufacturing of our plants are made by our experienced team and take place in our headquartes in Neu-Ulm, Germany. For installations, commissioning and after sales services Atec has its own experienced engineers and ...
Global Water Solutions Ltd. - member of The Swan Group
Office in San Pedro Montes de Oca, COSTA RICA
Global Water Solutions Ltd. (GWS), a member of the Swan Group, offers a full line of pre-pressurized diaphragm tanks for water well, pressure booster, pressure management, reverse osmosis, hydronic heating and thermal applications. GWS is positioned to serve global markets with strategically located production in Randolph, Massachusetts, USA and Taichung, Taiwan with ...
Office in San José, COSTA RICA
Endress Hauser is leading supplier of products, solutions and services for industrial process measurement and automation. We offer comprehensive process solutions for flow, level, pressure, analysis, temperature, recording and digital communications across a wide range of industries, optimizing processes with regards to economic efficiency, safety and environmental ...
Eijkelkamp Soil & Water
Distributor in COSTA RICA
As part of Royal Eijkelkamp, Eijkelkamp Soil & Water contributes to the following mission and vision. Mission: Royal Eijkelkamp is able to make a continuous contribution to a safe and healthy living environment thanks to more than 100 years' experience and expertise in soil and water research. Vision: Royal Eijkelkamp wants to become the world's preferred supplier of ...
Myron L Company
Distributor in COSTA RICA
Myron L Company manufactures cost-effective high performance tools for solution control and water quality analysis, as well as calibration solutions, accessories and kits that keep instrumentation operating at peak performance in diverse applications. Our current product line includes handheld instruments, inline monitor/controllers and field test kits that measure ...
Office in Escazú, COSTA RICA
Bionest is a family business specialized in wastewater treatment.As a technology company, Bionest designs, manufactures and markets advanced wastewater treatment solutions that have proven themselves by increasing water purification to a level significantly above world standards. The exceptional quality of the water treated by the BIONEST system allows it to be reused, ...
Distributor in -, COSTA RICA
Casella is an ISO 9001-2000 and ISO 14001 certified company with a focus on the development and manufacture of state-of-the-art environmental and workplace monitoring instrumentation. Products include personal air sampling, real-time dust and particulate measurement, personal noise dosimetry, environmental noise measurement and real-time frequency analysis, BOUNDARY ...
Metrohm AG
Distributor in San Jose, COSTA RICA
Metrohm is a worldwide leading manufacturer of precision instruments for chemical analysis. In the field of electrochemical ion analysis Metrohm has been the unchallenged world number one for many years. This is reflected in the company's comprehensive product range: pH meters, ion meters, conductometers, potentiometric, thermometric and Karl Fischer titration, ...
based in San Jose, COSTA RICA
IMRES is operated by a trained engineer familiar with landfills and the landfill industry. IMRES is a distributor of New Waste Concepts products and equipment
Electronic Engineering
based in -, COSTA RICA
Instrumentation Northwest Inc. (INW)
Distributor in COSTA RICA
Our environment requires constant monitoring. Threats can develop rapidly—and every second of response time counts. To stay ahead of environmental risks, you need a system that brings you accurate recordings as quickly as possible.We believe that our world can be better protected with quality information. That's why we take it as our mission to develop systems and ...
New Waste Concepts, Inc.
Distributor in COSTA RICA
New Waste Concepts, Inc. was founded in 1987 in Toledo, Ohio as Newastecon Inc. It is the mission of New Waste Concepts to work closely with our clients to develop products, equipment and operational services that solve the unique problems they face on a daily basis in a simple, reliable and cost effective manner. We develop and supply diversified remedial systems for ...
based in San Jose, COSTA RICA
Metrohm is exclusively represented in more than 80 countries, in more than 40 of which we have our own subsidiaries. This guarantees a tight network for sales and service.
EnviroLogek Technologies
Office in San Jose, COSTA RICA
Envirologek Technologies offers site investigation and remediation technologies for soil and groundwater cleanup. Products include bioremediation, surfactants, vapor extraction equipment, vapor condensation equipment, metals immobilization, soil gas sampling, non-purge groundwater sampling equipment, 3D Modeling, pumps and remediation equipment, aquifer with geophysics, ...


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Waste Management Companies serving Sierra Leone
Current filtering criteriaYou can remove a filter by clicking on the x
Category: Waste & Recycling ×
Subcategory: Waste Management ×
Employees number: 11-100 ×
Industry: Shipbuilding & Water Transport ×
Serving: Africa ×
Serving: Sierra Leone ×
Harmony Enterprises, Inc.
based in Harmony, MINNESOTA (USA)
Harmony Enterprises, Inc. is a leader in the design and manufacture of vertical balers, horizontal balers, and compactors. From our small, highly efficient, and portable M42BC to our System Ten Sixty, our recycling balers can process a wide range of materials and fit almost any baling application. From restaurants, to grocery stores, to large recycling centers, Harmony ...
ifu Hamburg GmbH
based in Hamburg, GERMANY
ifu Hamburg GmbH (Institute for Environmental Informatics Hamburg Ltd.) is a software development and consulting company helping companies to achieve sustainable production and strengthen their competitiveness. We deliver software solutions that support corporate environmental tasks and activities such as Material Flow Management, Resource Efficiency, Life Cycle ...
Delitek AS
based in Alsvaag, NORWAY
Delitek AS is a market leading manufacturer and supplier of stainless steel waste handling equipment for the maritime industry. Our headquarters is located in Norway and our products are distributed via a global network of highly experienced agents and distributors. You can find our patented waste handling products on all kinds and sizes of vessels & rigs stationed around ...
Orwak AB
based in Sävsjö, SWEDEN
Orwak has been a pioneer in developing high-performance waste handling systems based on a market-driven strategy since it was founded in 1971. This is why we can now offer a comprehensive range of compaction and baling solutions for recycling and disposal that improves business efficiency, contributes to a cleaner working and natural environmental, and provides the best ...
International Products Corporation
based in Burlington, NEW JERSEY (USA)
International Products Corporation manufactures a line of free-rinsing concentrated cleaners and P-80 temporary rubber assembly lubricants at their ISO:9001 Certified facility in Burlington, NJ. They are equipped with state-of-the-art manufacturing, packaging, and warehousing equipment, and their on-site laboratory is equipped for analytical work and continued development ...
atg UV Technology
based in Wigan, UNITED KINGDOM
atg UV Technology are leaders in the design and manufacture of UV (ultraviolet) disinfection / treatment systems for municipal drinking water and waste water, oil and gas applications, industrial process water and aquatics. Our applications include: Municipal: Drinking water (validated), waste water, storm water, advanced oxidation, waste water re-use. Oil & Gas: Drinking ...
Terragon Environmental Technologies Inc.
based in Montréal, QUEBEC (CANADA)
Terragon develops and commercializes innovative technologies and practices needed to enable habitats to treat their waste locally and safely in order to recover valuable resources to be reused at the site where waste is generated. Terragon researches and engineers highly innovative waste treatment systems which anyone can operate safely, economically and without special ...
EarthSoft, Inc
based in Concord, MASSACHUSETTS (USA)
EarthSoft`s EQuIS software manages environmental and geotechnical data and is the world`s most widely used environmental data management system. The EQuIS Data Processor (EDP) and Enterprise EDP are the world`s most widely used EDD tools. Many governments, industrials, and especially consultants and labs use EQuIS and EDP. EQuIS Professional and EQuIS for ArcGIS and ...
Tecam Group
based in Llinars del Vallès, SPAIN
Tecam Group offers advanced environmental technology for Emissions Treatment and for Industrial Waste Incineration. Tecam Group designs, manufactures and installs several technology solutions, such as Thermal Oxidizers (TO), Regenerative Thermal Oxidizers (RTO), Regenerative Catalytic Oxidizers (RCO), Zeolite Rotor-Concentrator + Regenerative Thermal Oxidizers (RTO), ...
BELLMER KUFFERATH Machinery GmbH
based in Düren, GERMANY
BELLMER KUFFERATH Machinery GmbH has become a 100%-subsidiary of Gebr. Bellmer GmbH, originated during the transfer of business operations from the Solid/Liquid Separation division of former Andreas Kufferath GmbH & Co. KG. Andreas Kufferath has been dealing with Solid/Liquid Separation issues for many years and consistently introduced new and innovative products to the ...
Tech Oil Products
based in New Iberia, LOUISIANA (USA)
Founded in 1980, Tech Oil Products, Inc. is known for the Enviro-Pak® line of compactors, balers, galley grinders, and other waste management solutions for the offshore and maritime industries. The company is also known for SafeSub®, an innovative solution for the handling and transporting of drilling subs, and its Recycle The Gulf® program for the Gulf of Mexico, a ...


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3 Inch Liza Seersucker Short
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3 Inch Liza Seersucker Short Description
Breaking news - cute shorts for summer are a must. Ok, this isn't rocket science but we think little lace detail shorts really are winners for summer. The Liza Shorts are blue and white striped seersucker with lace on the front. When you break out the seersucker, you know summer is really here.
3" Inseam Short With Forward Seams And Lilly Lace Trim. Seersucker Y/D Stripe (100% Cotton). Machine Wash Cold. Imported.
Style #: 88047