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Many animal models that are currently used in appetite and obesity research share at least some main features of human obesity and its comorbidities. Hence, even though no animal model replicates all aspects of "common" human obesity, animal models are imperative in studying the control of energy balance and reasons for its imbalance that may eventually lead to overt obesity. The most frequently used animal models are small rodents that may be based on mutations or manipulations of individual or several genes and on the exposure to obesogenic diets or other manipulations that predispose the animals to gaining or maintaining excessive weight. Characteristics include hyperphagia or changes in energy metabolism and at least in some models the frequent comorbidities of obesity, like hyperglycemia, insulin resistance, or diabetes-like syndromes. Some of the most frequently used animal models of obesity research involve animals with monogenic mutations of the leptin pathway which in fact are useful to study specific mechanistic aspects of eating controls, but typically do not recapitulate "common" obesity in the human population. Hence, this review will mention advantages and disadvantages of respective animal models in order to build a basis for the most appropriate use in biomedical research.

Amylin acts in the area postrema (AP) and arcuate nucleus (ARC) to control food intake. Amylin also increases axonal fiber outgrowth from the AP→nucleus tractus solitarius and from ARC→hypothalamic paraventricular nucleus. More recently, exogenous amylin infusion for 4 wk was shown to increase neurogenesis in adult rats in the AP. Furthermore, amylin has been shown to enhance leptin signaling in the ARC and ventromedial nucleus of the hypothalamus (VMN). Thus, we hypothesized that endogenous amylin could be a critical factor in regulating cell birth in the ARC and AP and that amylin could also be involved in the birth of leptin-sensitive neurons. Amylin+/− dams were injected with BrdU at embryonic day 12 and at postnatal day 2; BrdU+ cells were quantified in wild-type (WT) and amylin knockout (KO) mice. The number of BrdU+HuC/D+ neurons was similar in ARC and AP, but the number of BrdU+Iba1+ microglia was significantly decreased in both nuclei. Five-week-old WT and KO littermates were injected with leptin to test whether amylin is involved in the birth of leptin-sensitive neurons. Although there was no difference in the number of BrdU+c-Fos+ neurons in the ARC and dorsomedial nucleus, an increase in BrdU+c-Fos+ neurons was seen in VMN and lateral hypothalamus (LH) in amylin KO mice. In conclusion, these data suggest that during fetal development, endogenous amylin favors the birth of microglial cells in the ARC and AP and that it decreases the birth of leptin-sensitive neurons in the VMN and LH.

As one of the first Direct Acting Antivirals (DAA), the protease inhibitor Telaprevir (TVR) was available in the European Union from 9/2011 until 9/2016 as a new treatment option for chronic Hepatitis C.Aim. To assess the implementation of therapy stopping rules or shortening of the treatment and their impact on sustained virological response (SVR), as well as the safety and efficacy of the TVR-based therapy during routine daily treatment of patients in Germany.Materials and Methods. 802 patients were assessed (272 treatment naïve, 520 pre-treated) in the noninterventional, multi-center study.Results. 56.6 % of the patients achieved SVR. SVR rate was higher in patients with relapse after previous treatment (68.0 %) than in patients with a previous null-response (31.1 %) and in previously untreated patients (58.1 %). Stopping rule conditions were fulfilled by 3.2 % of patients and it was implemented in 65.4 % of these. 34.3 % of the patients fulfilled the conditions for a therapy shortening. This rule was adhered to in 48.4 % of these, in 34.5 % it was not adhered to. Thus recommendations were not always being followed. Therapy shortening was considered more frequently in previously untreated (54.8 %) than for previously treated patients (24.2 %). Stopping rule application but not shortened treatment reduced therapy costs.Conclusion. The TVR-based therapy represented a breakthrough at that time. Further DAAs have been added as therapeutic options since, increasing the complexity of treatment choice and correct implementation. They represent both an opportunity and a challenge for all those involved.As one of the first Direct Acting Antivirals (DAA), the protease inhibitor Telaprevir (TVR) was available in the European Union from 9/2011 until 9/2016 as a new treatment option for chronic Hepatitis C.Aim. To assess the implementation of therapy stopping rules or shortening of the treatment and their impact on sustained virological response (SVR), as well as the safety and efficacy of the TVR-based therapy during routine daily treatment of patients in Germany.Materials and Methods. 802 patients were assessed (272 treatment naïve, 520 pre-treated) in the noninterventional, multi-center study.Results. 56.6 % of the patients achieved SVR. SVR rate was higher in patients with relapse after previous treatment (68.0 %) than in patients with a previous null-response (31.1 %) and in previously untreated patients (58.1 %). Stopping rule conditions were fulfilled by 3.2 % of patients and it was implemented in 65.4 % of these. 34.3 % of the patients fulfilled the conditions for a therapy shortening. This rule was adhered to in 48.4 % of these, in 34.5 % it was not adhered to. Thus recommendations were not always being followed. Therapy shortening was considered more frequently in previously untreated (54.8 %) than for previously treated patients (24.2 %). Stopping rule application but not shortened treatment reduced therapy costs.Conclusion. The TVR-based therapy represented a breakthrough at that time. Further DAAs have been added as therapeutic options since, increasing the complexity of treatment choice and correct implementation. They represent both an opportunity and a challenge for all those involved. Ингибитор протеазы Телапревир (ТПВ) является одним из первых противовирусных препаратов прямого действия (ПППД) и применялся в странах Евросоюза при лечении хронического гепатита С в качестве нового метода с сентября 2011 года по сентябрь 2016 года. Цель: Оценить применение правил остановки (прекращения) или сокращения периода терапии и их влияние на устойчивый вирусологический ответ (УВО), а также безопасность и эффективность противовирусной терапии на основе ТПВ при рутинном применении в Германии. Материалы и методы. В неинтервенционном мультицентровом исследовании участвовали 802 пациента (272 пациента, ранее не получавшие, и 520 пациентов, ранее получавшие противовирусные препараты). Результаты. Устойчивый вирусологический ответ (УВО) был достигнут у 56,6 % пациентов. Доля пациентов с УВО среди пациентов с рецидивом после предыдущего лечения была выше (68,0 %), чем у пациентов с предыдущим нулевым ответом (31,1 %) и у пациентов, ранее не получавших противовирусные препараты (58,1 %). Критериям прекращения терапии соответствовали 3,2 % пациентов, из них у 65,4 % лечение было остановлено. Критериям сокращения терапии соответствовали 34,3 % пациентов. Это правило было применено в отношении 48,4 % из них, у 34,5 % оно не соблюдалось. Таким образом, не всегда соблюдались рекомендации по прекращению или сокращению терапии. Чаще терапию сокращали в группе пациентов, ранее не получавших лечения (54,8%), чем в группе пациентов, получавших противовирусную терапию в анамнезе (24,2%). Именно применение правил прекращения терапии, а не сокращение ее продолжительности, позволило снизить затраты на лечение. Заключение. Терапия на основе ТПВ в свое время стала прорывом в лечении гепатита С. Позже были предложены новые варианты ПППД для терапии, что усложнило выбор и точность применения препаратов. ПППД привнесли одновременно как новые возможности, так и новые сложности.

OBJECTIVE: To develop a Childhood Lupus Improvement Index (CHILI) as a tool to measure response to therapy in childhood-onset systemic lupus erythematosus (cSLE), with a focus on clinically relevant improvement (CRIc SLE ). METHODS: Pediatric nephrology and rheumatology subspecialists (n = 213) experienced in cSLE management were invited to define CRIc SLE and rate a total of 433 unique patient profiles for the presence/absence of CRIc SLE . Patient profiles included the following cSLE core response variables (CRVs): global assessment of patient well-being (patient-global), physician assessment of cSLE activity (MD-global), disease activity index score (here, we used the Systemic Lupus Erythematosus Disease Activity Index), urine protein-to-creatinine ratio, and Child Health Questionnaire physical summary score. Percentage and absolute changes in these cSLE- CRVs (baseline versus follow-up) were considered in order to develop candidate algorithms and validate their performance (sensitivity, specificity, area under the receiver operating characteristic curve [AUC] ; range 0-1). RESULTS: During an international consensus conference, unanimous agreement on a definition of CRIc SLE was achieved ; cSLE experts (n = 13) concurred (100%) that the preferred CHILI algorithm considers absolute changes in the cSLE- CRVs. After transformation to a range of 0-100, a CHILI score of ≥54 had outstanding accuracy for identifying CRIc SLE (AUC 0.93, sensitivity 81.1%, and specificity 84.2%). CHILI scores also reflect minor, moderate, and major improvement for values exceeding 15, 68, and 92, respectively (all AUC ≥0.92, sensitivity ≥93.1%, and specificity ≥73.4%). CONCLUSION: The CHILI is a new, seemingly highly accurate index for measuring CRI in cSLE over time. This index is useful to categorize the degree of response to therapy in children and adolescents with cSLE.

Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. This nationwide observational study included treatment-naive chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of

Vorgeschichte: Bei der Patientin K.R. (Jahrgang 2002) wurde 2012 ein Ullrich-Turner-Syndrom nachgewiesen, und bei Kleinwuchs eine Therapie mit Wachstumshormon begonnen. Der Erstkontakt erfolgte 2014 bei akuter Optikusneuritis links mit bulbären Schmerzen, Visusverschlechterung und Skotomen. Die[zum vollständigen Text gelangen Sie über die oben angegebene URL], 47. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 33. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 29. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Background Systemic juvenile idiopathic arthritis (SJIA) is an autoinflammatory disease associated with chronic arthritis. Early diagnosis and effective therapy of SJIA is desirable, so that complications are avoided. The PRO-KIND initiative of the German Society for Pediatric Rheumatology (GKJR) aims to define consensus-based strategies to harmonize diagnostic and therapeutic approaches in Germany. Methods We analyzed data on patients diagnosed with SJIA from 3 national registries in Germany. Subsequently, via online surveys and teleconferences among pediatric rheumatologists with a special expertise in the treatment of SJIA, we identified current diagnostic and treatment approaches in Germany. Those were harmonized via the formulation of statements and, supported by findings from a literature search. Finally, an in-person consensus conference using nominal group technique was held to further modify and consent the statements. Results Up to 50% of patients diagnosed with SJIA in Germany do not fulfill the International League of Associations for Rheumatology (ILAR) classification criteria, mostly due to the absence of chronic arthritis. Our findings suggest that chronic arthritis is not obligatory for the diagnosis and treatment of SJIA, allowing a diagnosis of probable SJIA. Malignant, infectious and hereditary autoinflammatory diseases should be considered before rendering a diagnosis of probable SJIA. There is substantial variability in the initial treatment of SJIA. Based on registry data, most patients initially receive systemic glucocorticoids, however, increasingly substituted or accompanied by biological agents, i.e. interleukin (IL)-1 and IL-6 blockade (up to 27.2% of patients). We identified preferred initial therapies for probable and definitive SJIA, including step-up patterns and treatment targets for the short-term (resolution of fever, decrease in C-reactive protein by 50% within 7 days), the mid-term (improvement in physician global and active joint count by at least 50% or a JADAS-10 score of maximally 5.4 within 4 weeks) and the long-term (glucocorticoid-free clinically inactive disease within 6 to 12 months), and an explicit treat-to-target strategy. Conclusions We developed consensus-based strategies regarding the diagnosis and treatment of probable or definitive SJIA in Germany. Electronic supplementary material The online version of this article (10.1186/s12969-018-0224-2) contains supplementary material, which is available to authorized users.

Amylin is secreted by pancreatic beta-cells and seems to function as a physiological signal of satiation and possibly also as an adiposity signal. Amylin's satiating effect is mediated via a direct action at area postrema (AP) neurons. The central pathways mediating amylin's effects rely on connections from the AP to the nucleus of the solitary tract and lateral parabrachial nucleus. Amylin was shown to interact, probably at the brainstem, with other satiating signals, namely cholecystokinin, glucagon-like peptide 1 and peptide YY, and other adiposity signals, namely leptin and insulin. The interaction with leptin, which is thought to involve the hypothalamus, may have important implications for the development of new and improved hormonal anti-obesity treatments. Steve Woods has contributed to the recent literature on amylin's eating inhibitory effect by some frequently cited publications. Steve's work concentrated more on the central administration of amylin and on amylin's potential role as an adiposity signal. His work will be reviewed here and discussed in the context of other important findings on amylin's role in the control of energy homeostasis.

Einleitung: Untersuchungen weisen auf die Existenz eines mild verlaufenden heterozygoten FMF-Phänotyps hin, bei dem Colchizin erfolgreich abgesetzt werden kann. Die vorliegende Studie untersucht, ob heterozygote FMF-Patienten nach Absetzen der Colchizintherapie klinisch stabil bleiben und inwiefern[zum vollständigen Text gelangen Sie über die oben angegebene URL], 45. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh), 31. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh), 27. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

The pancreatic peptide amylin is best known for its role as a satiation hormone in the control of food intake and as the major component of islet amyloid deposits in the pancreatic islets of patients with type 2 diabetes mellitus (T2DM). Epidemiological studies have established a clear association between metabolic and neurodegenerative disorders in general, and between T2DM and Alzheimer's disease (AD) in particular. Here, we discuss that amylin may be an important player acting at the interface between these metabolic and neurodegenerative disorders. Abnormal amylin production is a hallmark peripheral pathology both in the early (pre-diabetic) and late phases of T2DM, where hyperamylinemic (early phase) and hypoamylinemic (late phase) conditions coincide with hyper- and hypo-insulinemia, respectively. Moreover, there are notable biochemical similarities between amylin and β-amyloids (Aβ), which are both prone to amyloid plaque formation and to cytotoxic effects. Amylin's propensity to form amyloid plaques is not restricted to pancreatic islet cells, but readily extends to the CNS, where it has been found to co-localize with Aβ plaques in at least a subset of AD patients. Hence, amylin may constitute a “second amyloid” in neurodegenerative disorders such as AD. We further argue that hyperamylinemic conditions may be more relevant for the early processes of amyloid formation in the CNS, whereas hypoamylinemic conditions may be more strongly associated with late stages of central amyloid pathologies. Advancing our understanding of these temporal relationships may help to establish amylin-based interventions in the treatment of AD and other neurodegenerative disorders with metabolic comorbidities. ISSN:1662-453X ISSN:1662-4548

The modern world faces an exploding obesity epidemic, and despite many years of intensive research, the current clinically available nonsurgical treatment strategies are rather unsuccessful and drugs that were expected to alleviate the obesity problem had to be withdrawn from the market. Hence, understanding the physiological controls of eating has never been more important; this understanding may potentially help to develop effective pharmacological tools that reduce eating and eventually body weight without unacceptable side effects. Obesity research has to a large extent been focused on central nervous system neurotransmitters and also on long-term adiposity signals; the controls of individual meals were less in that focus, but it is now recognized that adiposity signals influence eating by modulating the effect of meal size controls (e.g. Refs. 1 and 2). The effects of adiposity signals and meal size controls appear to exhibit sex differences, and at least in females, estradiol appears to be the major factor that is involved in the control of eating, mainly by modulating meal size controls (3–6). Basic research on the estrogenic inhibition of eating is of great health relevance. This research is expected to promote our understanding of disordered control of meal size in human eating disorders; women seem to be disproportionately more vulnerable to these disorders than men (7– 9). These disorders include anorexia nervosa, bulimia nervosa, and binge-eating disorder, which is an important contributor to obesity. Further, morbid obesity is more prevalent in women than men (10). Estradiol has been shown to control eating and body weight mainly via modulating the potency of feedback signals that control meal size (5, 6). The best investigated interaction is that between cholecystokinin (CCK) and estradiol; the data indicate that estradiol increases the satiating potency of exogenous and endogenous CCK (11– 13). Similar mechanisms may be operational for glucagon because the effects of glucagon and of glucagon antibodies to decrease or increase meal size, respectively, were both amplified by estradiol in ovariectomized (OVX) rats (14). Finally, our own unpublished data indicate that estradiol enhanced the acute eating inhibitory effect of exogenous amylin in OVX rats (Asarian L., N. Geary, and T. Lutz, unpublished observations). It is a well-established phenomenon that the absence of estradiol leads to a temporary increase in eating and a sustained increase in body weight (5, 9, 11). This phenomenon is of clinical relevance because estradiol levels decrease in postmenopausal women; importantly, postmenopausal women make up a high percentage of the obese population. Because most nonsurgical treatment options for obese people have been withdrawn from the market due to unacceptable side effects, the amylin-based combination therapy with leptin has raised increased interest as an effective antiobesity treatment. The recent paper by Trevaskis et al. (15) provides new and to a large extent surprising insight into the role of estradiol in the control of eating, in particular in terms of estradiol’s interaction with chronic amylin treatment. Trevaskis et al. used diet-induced obese (DIO) female rats that were OVX; part of the OVX rats received cyclic estradiol replacement that mimics the physiology of an intact female sexual cycle (16). Several key findings reported in this paper are worth mentioning here. Similar to previous studies in intact male DIO rats (17; see also Ref. 18), amylin reduced the body weight gain in sexually intact female sham-operated DIO rats. The effect was similar in OVX rats that received physiological estradiol replacement therapy; interestingly, amy

Vorgeschichte: Ein 11-jähriger Junge wird mit unklarem Fieber, das tägl. undulierend bis 40C° über 3 Wochen besteht und weder mit antibiotischer noch antipyretischer Therapie beherrschbar ist, in reduziertem Allgemeinzustand in die Kinderklinik zur weiteren Abklärung eingewiesen.[zum vollständigen Text gelangen Sie über die oben angegebene URL], 44. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 30. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 26. Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Summary In 2001 two outbreak episodes (January – March and June – July) caused by vancomycin-resistant E. faecium (VRE) of the VanA-type were observed at a neonatal intensive care unit (NICU) of a university hospital in south-west Germany. To identify the initial source and the route of transmission environmental samples were examined as well as stool samples from patients and the staff. VRE was not found in environmental samples. However, stool samples from 24 hospitalised children tested positive and bacterial clonality was assessed by Smal-based macro restriction analysis. Furthermore, esp gene and vancomycin resistance gene carriage were examined as well as bacteriocin production. PCR analysis showed that all 24 isolates carried vanA gene cluster, encoding resistance to vancomycin and teicoplanin. However, five of the vanA-positive isolates were resistant to vancomycin but not to teicoplanin. Only these five isolates produced bacteriocin, but in none of the isolates esp gene was detected. PFGE revealed that both outbreaks were caused by two different clones. The patient initiating the first episode, was identified whereas the origin of the second episode remained unknown. From one of the 40 staff stool samples VRE was isolated. This strain was related to the clone of the summer outbreak. In conclusion there were two independent episodes of self limiting VRE outbreaks and transmission on the ward is highly probable.

Outbreaks of gram-negative bacteria such as Pseudomonas aeruginosa in neonatal intensive care units (NICU) can be life-threatening to pre-term infants, which are highly susceptible to serious infections with bacteria. Forty-two ventilated neonates in the NICU of the University Children's Hospital of Tuebingen were found to be colonized (n = 40) or infected (n = 2) with P. aeruginosa within a sampling period of one year. To investigate the colonization patterns and identify potential outbreak sources, epidemiological investigations, environmental surveillance and typing by serotyping and pulsed-field gel electrophoresis of the recovered isolates were performed. The investigation demonstrated a genetically related cluster of P. aeruginosa isolates during the surveillance period in 39 neonates and a second cluster at the end of the period in two neonates. A third strain representing a genetically distinct group was found in only one patient. Environmental investigations demonstrated the presence of P. aeruginosa in the ventilation equipment of 22 patients: binasal prongs (n = 22), water reservoir (n = 9), and heater (n = 1). In one case, P. aeruginosa was found in breast milk. Other environmental investigations revealed no P. aeruginosa. Although no evidence for a unique source was found, a series of intervention steps were initiated by the NICU personnel, medical microbiologists and infection control experts. The intervention steps included reinforced training of health care staff and a change from chemical to thermal disinfection of binasal prongs. Implementation of these measurements successfully stopped the recurrent occurrence of P. aeruginosa colonization.

Solute carrier (SLC) transporters mediate the uptake of biologically active compounds in the intestine. Reduced oxygenation (hypoxia) is an important factor influencing intestinal homeostasis. The aim of this study was to investigate the pathophysiological consequences of hypoxia on the expression and function of SLCs in human intestine. Hypoxia was induced in human intestinal epithelial cells (IECs) in vitro (0.2; 1% O2or CoCl2). For human in vivo studies, duodenal biopsies and serum samples were obtained from individuals ( n = 16) acutely exposed to 4,554 meters above sea levels. Expression of relevant targets was analyzed by quantitative PCR, Western blotting, or immunofluorescence. Serum levels of inflammatory mediators and nucleosides were determined by ELISA and LC/MS-MS, respectively. In the duodenum of volunteers exposed to high altitude we observed decreased mRNA levels of apical sodium-dependent bile acid transporter (ASBT), concentrative nucleoside transporters 1/2 (CNT1/2), organic anion transporting polypeptide 2B1 (OATP2B1), organic cation transporter 2 (OCTN2), peptide transporter 1 (PEPT1), serotonin transporter (SERT), and higher levels of IFN-γ, IL-6, and IL-17A. Serum levels of IL-10, IFN-γ, matrix metalloproteinase-2 (MMP-2), and serotonin were elevated, whereas the levels of uridine decreased upon exposure to hypoxia. Hypoxic IECs showed reduced levels of equilibrative nucleoside transporter 2 (ENT2), OCTN2, and SERT mRNAs in vitro, which was confirmed on the protein level and was accompanied by activation of ERK1/2, increase of hypoxia-inducible factor (HIF) proteins, and production of IL-8 mRNA. Costimulation with IFN-γ and IL-6 during hypoxia further decreased the expression of SERT, ENT2, and CNT2 in vitro. Reduced oxygen supply affects the expression pattern of duodenal SLCs that is accompanied by changes in serum levels of proinflammatory cytokines and biologically active compounds demonstrating that intestinal transport is affected during systemic exposure to hypoxia in humans.

Einleitung: Wir berichten von einer Patientin mit einer Juvenile Idiopathischen Arthritis (JIA) und einer anterioren Uveitis (AU), die gut auf Tocilizumab, einen relativ neuen humanisierten monoklonalen Antikörper gegen den IL-6 Rezeptor angesprochen hat. Davor war sie therapierefraktär sowohl[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Einleitung: Systemischer Lupus Erythematodes (SLE) ist eine seltene Erkrankung bei Kindern und Jugendlichen. Nur 20% der Patienten erkranken vor dem 16. Lebensjahr, und von diesen die meisten zw. dem 11.-16. Lebensjahr. Als Sonderformen gibt es den in der Regel passageren neonatalen SLE, der nur[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Einleitung: Das PFAPA–Syndrom gehört zu den autoinflammatorischen Erkrankungen, die Diagnosestellung erfolgt anhand klinischer Kriterien. Methoden: Deskriptive Auswertung der PFAPA-Patientendaten aus dem AID-Net ([link:http://www.aid-register.de*http://www.aid-register.de])[for full text, please go to the a.m. URL], 42. Kongress der Deutschen Gesellschaft für Rheumatologie (DGRh); 28. Jahrestagung der Deutschen Gesellschaft für Orthopädische Rheumatologie (DGORh); 24. wissenschaftliche Jahrestagung der Gesellschaft für Kinder- und Jugendrheumatologie (GKJR)

Objective: A mycotic aneurysm of the aorta and adjacent arteries is a dreadful condition, threatening life, organs, and limbs. With regard to the aortic segment involved, repair by either in situ replacement or extra-anatomic reconstruction can be quite challenging. Even when surgery has been successful, the prognosis is described as very poor because of the weakened health status of the patient who has developed this type of aneurysm. The aim of our study was to find out whether any progress could be achieved in a single center over a long time period (18 years) through use of surgical techniques and antiseptic adjuncts. Material and Methods: From January 1983 to December 1999, a total of 2520 patients with aneurysms of the thoracic and abdominal aorta and iliac arteries underwent surgery for aortic or iliac replacement at our institution. During that period, 33 (1.31%) of these patients (mean age, 64.3 years) were treated for mycotic aneurysms of the lower descending and thoracoabdominal (n = 13), suprarenal (n = 4), and infrarenal (n = 10) aorta and iliac arteries (n = 6). Twenty (61%) of these 33 patients had histories of various septic diseases; in the other 13 (39%), the etiology remained uncertain. Preoperative signs of infection, such as leukocytosis and elevated C-reactive protein, were found in 79% of the patients, and fever was apparent in 48%; 76% of the patients complained of pain. At the time of surgery, eight (24%) mycotic aneurysms were already ruptured, and 20 (61%) had penetrated into the periaortic tissues, forming a contained rupture. Five (15%) aneurysms were completely intact. The predominant microorganisms found in the aneurysm sac were Staphylococcus aureus and Salmonella species. Careful debridement of all infected tissue was essential. In the infrarenal aortic and iliac vascular bed, in situ reconstruction was performed only in cases of anticipated "low-grade" infection. Alternative revascularization with extra-anatomic procedures (axillobifemoral or femorofemoral crossover bypass graft) was carried out in eight of 16 cases. All four suprarenal and all 13 mycotic aneurysms of the thoracoabdominal aortic segment were repaired in situ. Antibiotics were administered perioperatively, and all patients were subsequently treated with long-term antibiotics. Results: In-hospital mortality was 36% (n = 12). Because of the smallness and heterogeneity of the sample, we could not demonstrate significant evidence for any influence of aneurysm location or type of reconstruction on patients' outcome. However, survival was clearly influenced by the status of rupture. During long-term follow-up (mean, 30 months; range, 1-139 months), 10 patients (48%) died—one (4.8%) probably as a consequence of the mycotic aneurysm, the others for unrelated reasons. Eleven patients (52%) are alive and well today, with no signs of persistent or recurrent infection. Conclusions: A mycotic aneurysm of the aortic iliac region remains a life-threatening condition, especially if the aneurysm has already ruptured by the time of surgery. Although the content of the aneurysm sac is considered septic, as was proved by positive cultures in 85% of our patients, in situ reconstruction is feasible and, surprisingly, was not more closely related to higher morbidity and mortality in our series than ligation and extra-anatomic reconstruction, although most of the aneurysms repaired in situ were located at the suprarenal and thoracoabdominal aorta. We assume that our operative mortality rate of 36%, which relates to a rupture rate of 85%, could be substantially lowered if the diagnosis of mycotic aneurysm were established before rupture. (J Vasc Surg 2001;33:106-13.)

Introduction: Bariatric surgery is currently the most effective therapeutic option to treat type 2 diabetes mellitus (T2DM) associated with morbid obesity, but the underlying mechanisms remain unclear. Roux-en-Y Gastric Bypass (RYGB) and Duodenal-Jejunal Bypass (DJB) bypass the proximal small intestine,[for full text, please go to the a.m. URL], 130. Kongress der Deutschen Gesellschaft für Chirurgie

Introduction: Changes in fecal microbiota may be responsible for the metabolic changes observed after Roux-en-Y gastric bypass (RYGB) surgery. Altered nutrient flux after surgery might have different effects on the gut microbiota profile along the intestine. Here we assessed the bacterial composition[for full text, please go to the a.m. URL], 130. Kongress der Deutschen Gesellschaft für Chirurgie

Introduction: Handlebar injuries in children may lead to severe organ lesions despite minimal initial signs and without visible skin bruise. We present our experiences applying a diagnostic and therapeutic algorithm for blunt abdominal trauma, and present the history of two selected cases. Materials and methods: We retrospectively assessed the charts of children below 16 years of age, only who were observed for 24 h or more in our institution due to a handlebar injury between 2004 and 2011. All children were treated according to an institutional algorithm. Results: 40 patients with a median age of 9.5 years were included. Diagnosed lesions were: ruptures of the liver (n = 6), spleen (n = 5), kidney (n = 1), and pancreas (n = 2), small bowel perforation (n = 3), and hernias of the abdominal (n = 2) or thoracic wall (n = 1). Surgical interventions were performed in 8 patients. The outcome was favorable in all the cases. Overall median hospitalization duration was 4.5 days (range 1-19 days). The overall duration between the accident and arrival at our emergency unit was 2.75 h (median, range 1-19 h). 20 children presented directly at our emergency unit after a median of 1.7 h (range 1-19.5 h). 20 children were referred by a family physician or a primary hospital after a median of 4.0 h (range 1-46 h). Conclusion: Handlebar injuries in children resulted in serious trunk lesions in half of the present patient series. The spectrum of injuries in handlebar accidents varies widely, especially injuries to the abdomen can unmask often only in the course. We advocate close observation of patients with thoracic and abdominal handlebar injuries which may be regarded as blunt stab wounds. An institutional algorithm for blunt abdominal trauma management is supportive for emergency care in patients with handlebar injuries. © 2012 Springer-Verlag Berlin Heidelberg. 29 3 269 273

The present study evaluated the effects of prophylactic administration of cefotaxime in patients undergoing therapeutic or complicated diagnostic ERCP. One hundred patients were randomized to two groups of 50 patients each. Patients in group 1 received an intravenous infusion of 2 g cefotaxime 15 minutes before endoscopy; patients in group 2 did not receive an intravenous antibiotic before ERCP (control group). Blood samples were drawn for bacteriologic cultures before endoscopy and 5, 15, 30, and 120 minutes after beginning the procedure. Bacteremia was detected by blood cultures (15- and 30-minute samples) in 4 patients who did not receive prophylactic antibiotics (Escherichia coli in 2 cases, Peptostreptococcus in 1, and Staphylococcus aureus in 1). Cholangitis or sepsis did not occur after the bacteremic episodes in any of these patients. In 4 other patients who did not receive cefotaxime-all of whom had biliary obstruction-clinical cholangitis or sepsis developed during the 3-day follow-up; ERCP had failed to decompress the biliary system completely in these 4 cases. Blood cultures identified bacteria in 3 of these 4 patients (Pseudomonas aeruginosa in 1, E. coli in 2). Thus, bacteremia or clinical sepsis developed in 8/50 patients (16%) in the control group without antibiotic prophylaxis, whereas no such episode was observed in patients who had received prophylactic treatment (chi 2 = 8.7; p < 0.01). The present results indicate that prophylactic administration of an antibiotic such as cefotaxime can reduce the incidence of bacteremia and sepsis in patients who undergo therapeutic or complicated diagnostic ERCP.(ABSTRACT TRUNCATED AT 250 WORDS)

Einleitung: Die Rolle der mechanischen Restriktion für den Erfolg der Magenbypass-Operation ist umstritten. Ziel der Studie war es, die Auswirkungen der Magenbypass-Operation auf die Mahlzeitengröße und -häufigkeit sowie die Essgeschwindigkeit zu untersuchen. Ein etabliertes Rattenmodel[for full text, please go to the a.m. URL], 128. Kongress der Deutschen Gesellschaft für Chirurgie

Background: The extent to which the prognosis for AIDS and death of patients initiating highly active antiretroviral therapy (HAART) continues to be affected by their characteristics at the time of initiation (baseline) is unclear. Methods: We analyzed data on 20,379 treatment-naive HIV-1- infected adults who started HAART in 1 of 12 cohort studies in Europe and North America (61,798 person-years of follow-up, 1844 AIDS events, and 1005 deaths). Results: Although baseline CD4 cell count became less prognostic with time, individuals with a baseline CD4 count 350 cells/μL (hazard ratio for AIDS = 2.3, 95% confidence interval [CI]: 1.0 to 2.3; mortality hazard ratio = 2.5, 95% CI: 1.2 to 5.5, 4 to 6 years after starting HAART). Rates of AIDS were persistently higher in individuals who had experienced an AIDS event before starting HAART. Individuals with presumed transmission by means of injection drug use experienced substantially higher rates of AIDS and death than other individuals throughout follow-up (AIDS hazard ratio = 1.6, 95% CI: 0.8 to 3.0; mortality hazard ratio = 3.5, 95% CI: 2.2 to 5.5, 4 to 6 years after starting HAART). Conclusions: Compared with other patient groups, injection drug users and patients with advanced immunodeficiency at baseline experience substantially increased rates of AIDS and death up to 6 years after starting HAART.

The matrix protein, fibronectin, which is detectable in various tissues, when present in the vaginal fluid of women in labour, indicates the rupture of membranes. It is known that many bacteria adhere to fibronectin, thus establishing a first step of infection. In women in labour, group B streptococci are common agents of chorioamnionitis. For group B streptococci, unspecific adherence mechanisms like negative net charge and hydrophobic interactions have already been discussed in literature. In the present study, group B streptococci isolates from 57 patients with premature rupture of membranes were studied for fibronectin binding activities, using a particle agglutination assay and for cell surface hydrophobicity, by testing adhesion to hydrocarbons. Particle agglutination assays and adhesion assays were done with strains grown on blood-containing media and media without blood. Fibronectin binding was shown to be present in 14 and 11 out of 57 isolates grown on Mueller-Hinton and Tryptic Soy agar, respectively. When the strains were grown on blood-containing media, fibronectin-binding was found to be concomitant with decreased hydrophobicity. According to the results obtained in a total of 57 strains, cell surface hydrophobicity is an unspecific adhesion factor in group B streptococci. Fibronectin binding seems to be an additional adherence factor in some of the strains and may be assumed to play a major role in establishing infectious processes.

Since the description of regional enteritis by Crohn, Ginzburg and Oppenheimer (1) in 1932 only the report of Burnham et al. (2) drew attention to a mycobacterial etiology in Crohn’s disease. In 1978 he isolated Mycobacterium kansasii from one mesenteric lymph node and cell-wall-deficient organisms from 81 % of mesenteric lymph nodes obtained from patients with Crohn’s disease. A mycobacterial etiology in Crohn’s disease was revived by the detection of Mycobacterium paratuberculosis in Crohn’s disease in 1984 (3). Chiodini found Mycobacterium paratuberculosis in the mucosa of patients with Crohn’s disease in 15.4 % and in addition cell-wall-deficient organisms in 46.2 % (4) whereas all controls remained negative. These data are the basis for the connection of Crohn’s disease with Johne’s disease (5) in veterinary medicine. Johne’s disease is a chronic granulomatous and wasting disease of ruminants caused by Mycobacterium paratuberculosis. Both Crohn’s disease and Johne’s disease show remarkable similarities which make them indistinguishable in clinic, epidemiology and pathology (6).

A large number of animal models are currently used in appetite and obesity research. Because the worldwide incidence of obesity continues to climb, it is imperative that animal models sharing characteristics of human obesity and its co-morbidities be used appropriately in the quest for novel preventions or treatments. There is probably no animal model, at least in rodents, that recapitulates all aspects of "common" human obesity and its comorbidities, but rodent models allow insight into specific mechanisms of disease or its consequences. Frequently used obesity models can be partitioned into different categories, the major ones being a) based on mutations or manipulations of one or a few individual genes or b) those in genetically intact animals exposed to obesogenic environments such as, e.g., being maintained on high-fat diets or being raised in small litters. Characteristics of these models include distinct phenotypes of obesity, hyperphagia or changes in energy metabolism, and frequent comorbidities of obesity, like hyperglycemia, insulin resistance or diabetes-like syndromes. This review which is based on a presentation given during the Annual Meeting of the Society for the Study of Ingestive Behavior in July 2017 points out some observations and characteristics of rodent models in obesity and diabetes research. The choice of rodent models discussed here is subjective and based on the author's own experience or on fruitful discussions with colleagues about the pros and cons of specific models. Hence, this review, by no means, is meant to give a complete picture of rodent models used in this type of research, but the review tries to bring up some issues which, in the author's mind, may also be relevant for models not discussed here. For example, by discussing specific mouse and rat models, similarities and differences between mice and rats will be discussed that need to be considered to interpret experimental findings cautiously and in the context of the respective animal model. Knowing which animal model to use means, knowing its limitations.

Background: Amylin is a pancreatic β-cell hormone that produces effects in several different organ systems. One of its best-characterized effects is the reduction in eating and body weight seen in preclinical and clinical studies. Amylin activates specific receptors, a portion of which it shares with calcitonin gene-related peptide (CGRP). Amylin's role in the control of energy metabolism relates to its satiating effect, but recent data indicate that amylin may also affect hedonic aspects in the control of eating, including a reduction of the rewarding value of food. Recently, several amylin-based peptides have been characterized. Pramlintide (Symlin®) is currently the only one being used clinically to treat type 1 and type 2 diabetes. However other amylin analogs with improved pharmacokinetic properties are being considered as anti-obesity treatment strategies. Several other studies in obesity have shown that amylin agonists could also be useful for weight loss, especially in combination with other agents. Scope of review: This review will briefly summarize amylin physiology and pharmacology and then focus on amylin's role in food reward and the effects of amylin analogs in pre-clinical testing for anti-obesity drugs. Conclusion: We propose here that the effects of amylin may be homeostatic and hedonic in nature. Keywords: Amylin, CGRP, Homeostatic, Hedonic, Reward, Analog

The pancreatic hormone amylin and its agonist salmon calcitonin (sCT) act via the area postrema (AP) and the lateral parabrachial nucleus (PBN) to reduce food intake. Investigations of amylin and sCT signaling in the ventral tegmental area (VTA) and nucleus accumbens (NAc) suggest that the eating inhibitory effect of amylin is, in part, mediated through the mesolimbic 'reward' pathway. Indeed, administration of the sCT directly to the VTA decreased phasic dopamine release (DA) in the NAc. However, it is not known if peripheral amylin modulates the mesolimbic system directly or whether this occurs via the AP and PBN. To determine whether and how peripheral amylin or sCT affect mesolimbic reward circuitry we utilized fast scan cyclic voltammetry under anesthesia to measure phasic DA release in the NAc evoked by electrical stimulation of the VTA in intact, AP lesioned and bilaterally PBN lesioned rats. Amylin (50μg/kg i.p.) did not change phasic DA responses compared to saline control rats. However, sCT (50μg/kg i.p.) decreased evoked DA release to VTA-stimulation over 1h compared to saline treated control rats. Further investigations determined that AP and bilateral PBN lesions abolished the ability of sCT to suppress evoked phasic DA responses to VTA-stimulation. These findings implicate the AP and the PBN as important sites for peripheral sCT to decrease evoked DA release in the NAc and suggest that these nuclei may influence hedonic and motivational processes to modulate food intake.

Reduced insulin sensitivity might increase the susceptibility to acute mountain sickness (AMS). The diabetogenic side effects of dexamethasone should therefore be considered for AMS treatment. To examine whether reduced insulin sensitivity is predictive of AMS and how it is affected by dexamethasone at high altitude, we analyzed endocrine and metabolic parameters obtained from healthy mountaineers in Zurich (LA; 490 m), and 2 and 4 days after fast ascent to the Capanna Regina Margherita (HA2, HA4; 4559 m). 14 of 25 participants developed AMS and were treated with dexamethasone starting in the evening of HA2. Before and after ingestion of an 1800 kJ meal, plasma was analyzed for erythropoietin (EPO) and cholecystokinin (CCK). Insulin sensitivity (HOMA-S) and beta cell activity were calculated. HOMA-S (p0.01) and EPO levels (p0.05) were lower in Zurich in the group developing AMS and given dexamethasone, i.e., before treatment and exposure to hypoxia. CCK was lower (p0.01) and glucose and insulin were higher on HA4 in the dexamethasone group compared to the untreated group. Individuals with low baseline insulin sensitivity and low baseline EPO levels were more susceptible to AMS. Reduced CCK may contribute to the beneficial effect of dexamethasone on high altitude anorexia. However, reduced insulin sensitivity questions the widespread use of dexamethasone to prevent/treat AMS.

The control of meal size is the best studied aspect of the control of energy balance, and manipulation of this system constitutes a promising target to treat obesity. A major part of this control system is based on gastrointestinal hormones such as glucagon-like peptide-1 (GLP-1) or amylin, which are released in response to a meal and which limit the size of an ongoing meal. Both amylin and GLP-1 have also been shown to increase energy expenditure in experimental rodents, but mechanistically we know much less how this effect may be mediated, which brain sites may be involved, and what the physiological relevance of these findings may be. Most studies indicate that the effect of peripheral amylin is centrally mediated via the area postrema, but other brain areas, such as the ventral tegmental area, may also be involved. GLP-1’s effect on eating seems to be mainly mediated by vagal afferents projecting to the caudal hindbrain. Chronic exposure to amylin, GLP-1 or their analogs decrease food intake and body weight gain. Next to the induction of satiation, amylin may also constitute an adiposity signal and in fact interact with the adiposity signal leptin. Amylin analogs are under clinical consideration for their effect to reduce food intake and body weight in humans, and similar to rodents, amylin analogs seem to be particularly active when combined with leptin analogs.

The pancreatic B-cell hormone amylin has been proposed to be both a satiation signal and an adiposity signal. The effects of peripheral amylin on energy balance are well investigated, but the effects of central amylin are less clear. We determined the effects of low doses of amylin administered into the 3rd cerebral ventricle (i3vt) on food intake, body weight and other indices of energy balance. Amylin (2 pmol/h) significantly lowered body weight compared to saline after 2 weeks of infusion, independent of whether prior body weight was decreased by fasting, increased by voluntary overfeeding or unmanipulated. A bolus injection of amylin (10 pmol, i3vt) increased energy expenditure and body temperature, whereas chronic i3vt amylin infusion had no effect on energy expenditure above that of control rats even though body temperature was increased. Chronic amylin also reduced RQ, implying a preferential oxidation of fat. Overall, the data provide new evidence that amylin is an adiposity signal that acts within the brain, and informing the brain about the status of peripheral energy stores.

The pancreatic hormone glucagon hyperpolarizes the liver cell membrane. In the present study, we investigated the cellular signalling pathway of glucagon-induced hyperpolarization of liver cells by using the conventional microelectrode method. The membrane potential was recorded in superficial liver cells of superfused mouse liver slices. In the presence of the K+ channel blockers tetraethylammonium (TEA, 1 mmol/l) and Ba2+ (BaCl2, 5 mmol/l) and the blocker of the Na+/K+ ATPase, ouabain (1 mmol/l), no glucagon-induced hyperpolarization was observed confirming previous findings. The hyperpolarizing effect of glucagon was abolished by the leukotriene B4 receptor antagonist CP 195543 (0.1 mmol/l) and the purinergic receptor antagonist PPADS (5 micromol/l). ATPgammaS (10 micromol/l), a non-hydrolyzable ATP analogue, induced a hyperpolarization of the liver cell membrane similar to glucagon. U 73122 (1 micromol/l), a blocker of phospholipase C, prevented both the glucagon- and ATPgammaS-induced hyperpolarization. These findings suggest that glucagon affects the hepatic membrane potential partly by inducing the formation and release of leukotrienes and release of ATP acting on purinergic receptors of the liver cell membrane.

Obesity and its related comorbidities can be detrimental for the affected individual and challenge public health systems worldwide. Currently, the only available treatment options leading to clinically significant and maintained body weight loss and reduction in obesity-related morbidity and mortality are based on surgical interventions. This review will focus on two main clinical effects of Roux-en-Y gastric bypass (RYGB), namely body weight loss and change in eating behavior. Animal experiments designed to understand the underlying physiological mechanisms of these post-gastric bypass effects will be discussed. Where appropriate, reference will also be made to vertical sleeve gastrectomy. While caloric malabsorption and mechanical restriction seem not to be major factors in this respect, alterations in gut hormone levels are invariably found after RYGB. However, their causal role in RYGB effects on eating and body weight has recently been challenged. Other potential factors contributing to the RYGB effects include increased bile acid concentrations and an altered composition of gut microbiota. RYGB is further associated with remarkable changes in preference for different dietary components, such as a decrease in the preference for high fat or sugar. It needs to be noted, however, that in many cases, the question about the necessity of these alterations for the success of bariatric surgery procedures remains unanswered.

Obesity and its related comorbidities can be detrimental for the affected individual and challenge public health systems worldwide. Currently, the only available treatment options leading to clinically significant and maintained body weight loss and reduction in obesity-related morbidity and mortality are based on surgical interventions. Apart from the ‘gold standard' Roux-en-Y gastric bypass (RYGB), the vertical sleeve gastrectomy and gastric banding are two frequently performed procedures. This review will discuss animal experiments designed to understand the underlying mechanisms of body weight loss after bariatric surgery. While caloric malabsorption and mechanical restriction are no major factors in this respect, alterations in gut hormone levels are invariably found after RYGB. However, their causal role in RYGB effects on eating and body weight has recently been challenged. Other potential factors contributing to the RYGB effects include increased bile acid concentrations and an altered composition of gut microbiota. RYGB is further associated with remarkable changes in the preference for different dietary components such as a decrease in the preference for high fat or sugar; it is important to note that the contribution of altered food preferences to the RYGB effects on body weight is not clear.

Compared to traditional weight loss strategies the compensatory decrease in energy expenditure in response to body weight loss is markedly attenuated after Roux en Y gastric bypass surgery (RYGB). Because basal and postprandial levels of glucagon like peptide 1 (GLP 1) are increased after RYGB surgery and because GLP 1 has been shown to increase energy expenditure we investigated if increased GLP 1 levels are involved in the alterations in energy expenditure after RYGB. Adult male Wistar rats were randomized for RYGB (n = 8) or sham surgery (n = 17). Part of the sham operated rats were food restricted and body weight matched (n = 8) to the RYGB animals. The effects of acute subcutaneous administration of the GLP 1 antagonist Exendin (9 39) (Ex 9 30. µg/kg) or the GLP 1 agonist Exendin 4 (Ex 4 5. µg/kg) respectively on energy expenditure were tested using indirect calorimetry. We found that Ex 9 increased food intake in RYGB but not in sham operated rats.Energy expenditure was lower in RYGB and sham operated body weight matched rats compared to sham operated ad libitum fed rats but significantly higher in RYGB rats compared to sham operated body weight matched rats. There was no effect of Ex 9 treatment on energy expenditure in either group of animals. Similarly Ex 4 decreased food intake more in RYGB than in sham operated rats but Ex 4 did not modulate energy expenditure in any surgical group. We conclude that acute modulation of GLP 1 signaling is not directly involved in altered energy expenditure after RYGB surgery in rats. © 2013 Elsevier Inc.

Diabetes mellitus is a common endocrinopathy in humans and in cats. The general prevalence of diabetes mellitus, and in particular of type 2 diabetes, has risen dramatically in recent years. This increase has often been linked to the rise in the obesity pandemic because obesity and the ensuing metabolic consequences constitute major risk factors for human type 2 and for feline diabetes. Feline diabetes shares many features of human type 2 diabetes in respect to its pathophysiology, underlying risk factors and treatment strategies. This review will briefly summarize major characteristics in the human and the feline disease and where available, point out the current knowledge on similarities and differences.

The focus of this overview is on the animal models of obesity most commonly utilized in research. The models include monogenic models in the leptin pathway polygenic diet dependent models and in particular for their historical perspective surgical and chemical models of obesity. However there are far too many models to consider all of them comprehensively especially those caused by selective molecular genetic approaches modifying one or more genes in specific populations of cells. Further the generation and use of inducible transgenic animals (induced knock out or knock in) is not covered even though they often carry significant advantages compared to traditional transgenic animals e.g. influences of the genetic modification during the development of the animals can be minimized. The number of these animal models is simply too large to be covered in this unit. © 2012 by John Wiley Sons Inc.

Amylin is an important player in the control of nutrient fluxes. Amylin reduces eating via a meal size effect by promoting meal-ending satiation. This effect seems to depend on a direct action in the area postrema (AP), which is an area rich in amylin receptors. Subsequent to the activation of AP neurons, the neural signal is conveyed to the forebrain via relays involving the nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (lPBN) to the lateral hypothalamic area (LHA) and other hypothalamic nuclei. While the NTS and lPBN seem to be necessary for amylin's eating inhibitory effect, the role of the LHA has not yet been fully investigated. Amylin may also act as an adiposity signal. Plasma levels of amylin are higher in obese individuals, and chronic infusion of amylin into the brain reduces body weight gain and adiposity; chronic infusion of an amylin receptor antagonist into the brain increases body adiposity. Amylin increases energy expenditure in rats; this effect occurs under various experimental conditions after peripheral and central administration. Together, these animal data, but also clinical data in humans, indicate that amylin is a promising candidate for the treatment of obesity; effects are most pronounced when amylin is combined with leptin. Finally, recent findings indicate that amylin acts as a neurotrophic factor in specific brain stem areas. Whether this effect may be relevant under physiological conditions requires further studies.

Pancreatic amylin plays an important role in the control of nutrient fluxes and is an established therapy in human diabetes as it reduces post-prandial glucagon secretion and slows gastric emptying. Given the similar pathophysiology of human type-2 and feline diabetes mellitus, we investigated whether amylin reduces plasma glucagon levels in cats. Healthy cats were tested using an intravenous arginine stimulation test (IVAST), a meal response test with the test meal comprising 50% of average daily food intake, and an IV glucose tolerance test (IVGTT). Non-amyloidogenic rat amylin injected 5 min before the respective stimulus significantly reduced plasma glucagon levels under all test situations. In the IVAST and IVGTT, cats treated with amylin also had lower plasma insulin concentrations. It was concluded that amylin does reduce plasma glucagon levels in cats, a feature that has treatment potential in diabetic animals as co-administration of amylin would reduce the insulin requirement to control glycaemia.

Amylin is a pancreatic B-cell hormone that plays an important role in the regulation of nutrient fluxes. As such, amylin reduces food intake in laboratory animals and man, slows gastric emptying and it reduces postprandial glucagon secretion. Amylin deficiency which occurs concomitantly to insulin deficiency in diabetes mellitus, may therefore contribute to some of the major derangements associated with this disorder (hyperphagia, excessive glucagon secretion, accelerated rate of gastric emptying). The described actions of amylin all seem to depend on a direct effect of amylin on the area postrema (AP). As to amylin's satiating effect, the physiological relevance of this action is underlined by studies involving specific amylin antagonists and amylin-deficient mice. In the AP, amylin seems to modulate the anorectic signal elicited by CCK. Subsequent to AP activation, the amylin signal is conveyed to the forebrain via distinct relay stations. Within the lateral hypothalamic area, amylin diminishes the expression of orexigenic neuropeptides such as orexin and MCH. Whether these effects contribute to amylin's short term satiating action remains to be determined. Recent studies suggest that amylin may also play a role as a long-term, lipostatic signal, especially when other feedback systems to the brain are deficient. Obese, leptin-resistant Zucker rats which are hyperinsulinemic and hyperamylinemic, were chronically infused with the amylin antagonist AC 187. AC 187 significantly elevated food intake in obese Zucker rats while having no effect in lean controls. This indicates that at least under certain conditions, chronic blockade of endogenous amylin action may lead to an increase in food intake and/or body weight. As mentioned, the site and mechanism of action for peripheral amylin to reduce food intake seems to be well established. It is less clear how centrally administered amylin reduces food intake although it is well known that 3rd ventricular administration of amylin produces a very strong and long-lasting anorectic action. Amylin receptors have been described in various hypothalamic nuclei but the endogenous ligand of these receptors remains to be investigated. The same holds true as to the physiological relevance of the anorectic effect seen after central amylin administration.

Amylin is a pancreatic hormone that is considered to be a satiating signal acting on neurons of the area postrema (AP) in the hindbrain. The adiposity signals leptin and insulin act in the hypothalamus to influence feeding. They also enhance the hindbrain's responsivity to satiating signals, e.g. cholecystokinin (CCK). The orexigenic hormone ghrelin is thought to use the same hypothalamic pathways as leptin and insulin, with opposite actions on feeding behaviour. In fact, CCK and ghrelin also seem to interact in the control of feeding. Because CCK's anorectic effect depends on endogenous amylin, the aim of this study was therefore to evaluate a possible functional interaction between amylin and these hormones on short-term food intake in rats. The experiments were performed with male Wistar rats. Intracerebroventricular injection (i3vt) of an orexigenic dose of ghrelin (5 ng/5 microl) reduced but did not completely reverse the intraperitoneal amylin (5 microg/kg)-induced inhibition of food intake. In comparison, administration of a sub-threshold dose of ghrelin (3 ng/5 microl) did not affect the anorexigenic action of peripheral amylin. Leptin administered into the third ventricle (i3vt; 3.5 microg/5 microl) and intraperitoneal amylin (5 microg/kg) synergistically reduced food intake in chow-fed rats. I3vt insulin, administered at a sub-threshold dose (0.5 mU/5 microl), significantly enhanced the response to peripheral amylin. These results indicate that the lipostatic signals leptin and insulin may synergize with amylin to reduce food intake. In contrast, under the conditions tested, the orexigenic hormone ghrelin does not seem to influence the feeding response to peripheral amylin.

Ghrelin is mainly secreted during fasting. While an orexigenic effect of peripherally injected ghrelin has been reported, reproducing this effect has often proven difficult. Here, we hypothesized that ghrelin's effect to increase food intake may depend on the experimental conditions (e.g., age of animals). We therefore investigated the effect of an IP ghrelin injection (100 microg/kg) on food intake in rats of different age and at different times during the light-dark cycle, i.e. with different levels of baseline food intake. Ghrelin injected at dark onset in ad libitum fed young rats (body weight [BW] 92 g) slightly increased feeding while no such effect was observed in 12 h food deprived rats (BW 150 g). In the middle of the light phase, ghrelin significantly increased feeding up to 2 h after injection in ad libitum fed rats (BW 130 g; food intake 1 h after injection: NaCl 0.4 +/- 0.2 g versus ghrelin 1.2 +/- 0.3 g [p < 0.05]). In various subsequent experiments, older rats (BW 300-490 g) tested under the same conditions did not respond to a single ghrelin injection. However repeated ghrelin injection (15 microg/kg/day once daily at light onset) over 10 days significantly increased food intake in rats (BW 400-460 g) starting from day 4 of the experiment (24 h food intake: NaCl approx. 19.5 g, ghrelin 22.5 g). Interestingly, the latter effect was completely abolished in rats lesioned in the area postrema (AP). Cumulative food intake was also increased in SHAM but not in AP-X animals (e.g., after 7 days: SHAM/NaCl 135.1 +/- 5.3 g versus SHAM/ghrelin 149.7 +/- 3.5 g [p < 0.05], AP-X/NaCl 127.2 +/- 16.4 versus AP-X/ghrelin 127.9 +/- 5.3). We conclude that ghrelin's effect to increase food intake can best be demonstrated when basal food intake is low. Ghrelin increases feeding mainly in young, fast growing animals. Ghrelin may therefore link the high energy needs to body growth in young individuals. In older animals, peripheral ghrelin increased feeding when injected repeatedly over several days. At least under these conditions, ghrelin's effect was mediated by the AP/NTS region. Using repeated administration, ghrelin might be an interesting tool to increase feeding in patients suffering from wasting diseases such as cancer anorexia.