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Herbach N.,Institute of Veterinary Pathology | Bergmayr M.,Institute of Veterinary Pathology | Goke B.,Ludwig Maximilians University of Munich | Wolf E.,Gene Center | Wanke R.,Institute of Veterinary Pathology
PLoS ONE | Year: 2011

The aim of this study was to examine postnatal islet and beta-cell expansion in healthy female control mice and its disturbances in diabetic GIPR dn transgenic mice, which exhibit an early reduction of beta-cell mass. Pancreata of female control and GIPR dn transgenic mice, aged 10, 45, 90 and 180 days were examined, using state-of-the-art quantitative-stereological methods. Total islet and beta-cell volumes, as well as their absolute numbers increased significantly until 90 days in control mice, and remained stable thereafter. The mean islet volumes of controls also increased slightly but significantly between 10 and 45 days of age, and then remained stable until 180 days. The total volume of isolated beta-cells, an indicator of islet neogenesis, and the number of proliferating (BrdU-positive) islet cells were highest in 10-day-old controls and declined significantly between 10 and 45 days. In GIPR dn transgenic mice, the numbers of islets and beta-cells were significantly reduced from 10 days of age onwards vs. controls, and no postnatal expansion of total islet and beta-cell volumes occurred due to a reduction in islet neogenesis whereas early islet-cell proliferation and apoptosis were unchanged as compared to control mice. Insulin secretion in response to pharmacological doses of GIP was preserved in GIPR dn transgenic mice, and serum insulin to pancreatic insulin content in response to GLP-1 and arginine was significantly higher in GIPR dn transgenic mice vs. controls. We could show that the increase in islet number is mainly responsible for expansion of islet and beta-cell mass in healthy control mice. GIPR dn transgenic mice show a disturbed expansion of the endocrine pancreas, due to perturbed islet neogenesis. © 2011 Herbach et al. Source


Schwenteit J.M.,University of Iceland | Schwenteit J.M.,University of Greifswald | Schwenteit J.M.,Friedrich Loeffler Institute | Breithaupt A.,Institute of Veterinary Pathology | And 5 more authors.
Fish and Shellfish Immunology | Year: 2013

Aeromonas salmonicida subsp. achromogenes, the causative agent of atypical furunculosis in many fish species, secretes the toxic metalloendopeptidase AsaP1. This study aimed to analyze innate and adaptive immune parameters induced in Arctic charr. (Salvelinus alpinus, L.) infected with wild type (wt) A.salmonicida subsp. achromogenes and its isogenic asaP1 deletion mutant (AsaP1-deficient).Head-kidney, liver and spleen were obtained from i.p. infected charr (wt, AsaP1-deficient), during a time schedule of 7d post infection. Reverse transcription quantitative real-time PCR (RT-qPCR) was applied to study the expression of immune parameters: pro-inflammatory cytokines IL-1β and TNF-α; anti-inflammatory cytokine IL-10; chemokines CXCL-8 (IL-8) and CC-chemokine; the cytokines IFN-γ and IL-4/13A as tracers for Th1 and Th2 immune responses, respectively; and the cell markers CD8α and CD83. In addition, lymphoid organs were histopathologically examined at days 3 and 7 post infection, including B (IgM) and T (CD3ε) cell staining.The detected immune responses were initially driven by innate mechanisms represented by the up-regulation of pro-inflammatory cytokines and chemokines and later on by adaptive Th2 related responses cumulating in B-cell recruitment as shown by regulation of immune parameters in spleen and head-kidney, with significant differences between mutant and wt infected fish. Histological sections revealed IgM-positive cells around ellipsoid arterioles in spleen, while CD3ε positive cells were found inclusters scattered all over the section. However, histopathological differences were only detected between infected and non-infected fish, but not between AsaP1-deficient mutant and wt infected fish.This work represents the first study on innate and adaptive immune responses of Arctic charr induced by a bacterial infection. © 2013 Elsevier Ltd. Source


Zengin A.,Ludwig Maximilians University of Munich | Kropp B.,Ludwig Maximilians University of Munich | Chevalier Y.,Ludwig Maximilians University of Munich | Junnila R.,Ludwig Maximilians University of Munich | And 8 more authors.
European Journal of Nutrition | Year: 2015

Purpose: Studies in humans suggest that consumption of low-carbohydrate, high-fat diets (LC–HF) could be detrimental for growth and bone health. In young male rats, LC–HF diets negatively affect bone health by impairing the growth hormone/insulin-like growth factor axis (GH/IGF axis), while the effects in female rats remain unknown. Therefore, we investigated whether sex-specific effects of LC–HF diets on bone health exist.Methods: Twelve-week-old male and female Wistar rats were isoenergetically pair-fed either a control diet (CD), “Atkins-style” protein-matched diet (LC–HF-1), or ketogenic low-protein diet (LC–HF-2) for 4 weeks. In females, microcomputed tomography and histomorphometry analyses were performed on the distal femur. Sex hormones were analysed with liquid chromatography–tandem mass spectrometry, and endocrine parameters including GH and IGF-I were measured by immunoassay. Results: Trabecular bone volume, serum IGF-I and the bone formation marker P1NP were lower in male rats fed both LC–HF diets versus CD. LC–HF diets did not impair bone health in female rats, with no change in trabecular or cortical bone volume nor in serum markers of bone turnover between CD versus both LC–HF diet groups. Pituitary GH secretion was lower in female rats fed LC–HF diet, with no difference in circulating IGF-I. Circulating sex hormone concentrations remained unchanged in male and female rats fed LC–HF diets. Conclusion: A 4-week consumption of LC–HF diets has sex-specific effects on bone health—with no effects in adult female rats yet negative effects in adult male rats. This response seems to be driven by a sex-specific effect of LC–HF diets on the GH/IGF system. © 2015 Springer-Verlag Berlin Heidelberg Source


Buck F.M.,University of Zurich | Grehn H.,University of Zurich | Hilbe M.,Institute of Veterinary Pathology | Pfirrmann C.W.A.,University of Zurich | And 2 more authors.
Journal of Magnetic Resonance Imaging | Year: 2010

Purpose: To relate histologic changes in rotator cuff tendons to the appearance on T1-weighted as well as fatsuppressed T2-weighted and proton density-weighted magnetic resonance imaging (MRI) sequences. Materials and Methods: T1-weighted, fat-suppressed T2-weighted and fat-suppressed proton density-weighted sequences of 18 cadaveric shoulders were acquired. The supraspinatus, infraspinatus, and subscapularis tendons were evaluated histologically. Twenty-six abnormalities were found in 23 of 37 tendons. In addition, histologically normal tendon parts (n = 32), including three segments with normal histology but abnormal MR signal, considered to represent magic angle effects, were defined. All regions of interest (ROIs) were evaluated by two musculoskeletal radiologists independently and blinded to histology. Results: In the 26 areas with anatomically intact tendons but abnormal histological findings mucoid degeneration (n = 13), chondroid metaplasia (n = 11), fatty infiltration (n = 1), and foreign-body granuloma (n = 1) after tendon suture were found. Compared to normal tendon, mucoid degeneration was hyperintense on T2-weighted fat-suppressed (P = 0.007) and on proton density-weighted fatsuppressed images (P = 0.006). Chondroid metaplasia was hyperintense compared to normal tendon in all sequences (P < 0.05). Mucoid degeneration was hypointense compared to chondroid metaplasia on T2-weighted fat-suppressed images (P = 0.038) and hypointense compared to magic angle artifacts on T1-weighted images (P = 0.046). Conclusion: Chondroid metaplasia of rotator cuff tendons appears to be more common than expected. Both mucoid degeneration and chondroid metaplasia may explain increased tendon signal on MR images of the rotator cuff. © 2010 Wiley-Liss, Inc. Source


Dragert K.,University of Zurich | Dragert K.,University Research Priority Program Dynamics of Healthy Aging | Bhattacharya I.,University of Zurich | Bhattacharya I.,University Research Priority Program Dynamics of Healthy Aging | And 16 more authors.
Hypertension | Year: 2015

The mammalian target of rapamycin complex 2 (mTORC2) contains the essential protein RICTOR and is activated by growth factors. mTORC2 in adipose tissue contributes to the regulation of glucose and lipid metabolism. In the perivascular adipose tissue, mTORC2 ensures normal vascular reactivity by controlling expression of inflammatory molecules. To assess whether RICTOR/mTORC2 contributes to blood pressure regulation, we applied a radiotelemetry approach in control and Rictor knockout (RictoraP2KO) mice generated using adipocyte protein-2 gene promoter-driven CRE recombinase expression to delete Rictor. The 24-hour mean arterial pressure was increased in RictoraP2KO mice, and the physiological decline in mean arterial pressure during the dark period was impaired. In parallel, heart rate and locomotor activity were elevated during the dark period with a pattern similar to blood pressure changes. This phenotype was associated with mild cardiomyocyte hypertrophy, decreased cardiac natriuretic peptides, and their receptor expression in adipocytes. Moreover, clock gene expression was reduced or phase-shifted in perivascular adipose tissue. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus, although Rictor gene expression was also lower in brain of RictoraP2KO mice. Thus, this study highlights the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes, and brain to tune physiological outcomes, such as blood pressure and locomotor activity. © 2015 American Heart Association, Inc. Source

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