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Eliete Dalla Corte Frantz Camila Crespo-Mascarenhas Andre Rodrigues C. Barreto-Vianna Marcia Barbosa Aguila Carlos Alberto Mandarim-de-Lacerda 《PloS one》2013,8(7)
Background
The associations between obesity, hypertension and diabetes are well established, and the renin-angiotensin system (RAS) may provide a link among them. The effect of RAS inhibition on type 2 diabetes is still unclear; however, RAS seems to play an important role in the regulation of the pancreas and glucose intolerance of mice fed high-fat (HF) diet.Methods
C57BL/6 mice fed a HF diet (8 weeks) were treated with aliskiren (50 mg/kg/day), enalapril (30 mg/kg/day) or losartan (10 mg/kg/day) for 6 weeks, and the protective effects were extensively compared among groups by morphometry, stereological tools, immunostaining, Western blotting and hormonal analysis.Results
All RAS inhibitors significantly attenuated the increased blood pressure in mice fed a HF diet. Treatment with enalapril, but not aliskiren or losartan, significantly attenuated body mass (BM) gain, glucose intolerance and insulin resistance, improved the alpha and beta cell mass and prevented the reduction of plasma adiponectin. Furthermore, enalapril treatment improved the protein expression of the pancreatic islet Pdx1, GLUT2, ACE2 and Mas receptors. Losartan treatment showed the greatest AT2R expression.Conclusion
Our findings indicate that ACE inhibition with enalapril attenuated several of the deleterious effects of the HF diet. In summary, enalapril appears to be responsible for the normalization of islet morphology and function, of alpha and beta cell mass and of Pdx1 and GLUT2 expression. These protective effects of enalapril were attributed, primarily, to the reduction in body mass gain and food intake and the enhancement of the ACE2/Ang (1-7) /Mas receptor axis and adiponectin levels. 相似文献83.
Background
Adhesion dependent mechanisms are increasingly recognized to be important for a wide range of biological processes, diseases and therapeutics. This has led to a rising demand of pharmaceutical modulators. However, most currently available adhesion assays are time consuming and/or lack sensitivity and reproducibility or depend on specialized and expensive equipment often only available at screening facilities. Thus, rapid and economical high-content screening approaches are urgently needed.Results
We established a fully open source high-content screening method for identifying modulators of adhesion. We successfully used this method to detect small molecules that are able to influence cell adhesion and cell spreading of Swiss-3T3 fibroblasts in general and/or specifically counteract Nogo-A-Δ20-induced inhibition of adhesion and cell spreading. The tricyclic anti-depressant clomipramine hydrochloride was shown to not only inhibit Nogo-A-Δ20-induced cell spreading inhibition in 3T3 fibroblasts but also to promote growth and counteract neurite outgrowth inhibition in highly purified primary neurons isolated from rat cerebellum.Conclusions
We have developed and validated a high content screening approach that can be used in any ordinarily equipped cell biology laboratory employing exclusively freely available open-source software in order to find novel modulators of adhesion and cell spreading. The versatility and adjustability of the whole screening method will enable not only centers specialized in high-throughput screens but most importantly also labs not routinely employing screens in their daily work routine to investigate the effects of a wide range of different compounds or siRNAs on adhesion and adhesion-modulating molecules. 相似文献84.
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Judith Brouwers Rintis Noviyanti Rob Fijnheer Philip G. de Groot Leily Trianty Siti Mudaliana Mark Roest Din Syafruddin Andre van der Ven Quirijn de Mast 《PloS one》2013,8(6)
Introduction
The angiogenic proteins angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor (VEGF) are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platelet number, in vivo platelet activation and inadvertent platelet activation during blood processing. We studied plasma Ang-1, Ang-2 and VEGF levels in malaria patients, taking the necessary precautions to avoid ex vivo platelet activation, and related plasma levels to platelet count and the soluble platelet activation markers P-selectin and CXCL7.Methods
Plasma levels of Ang-1, Ang-2, VEGF, P-selectin and CXCL7 were measured in CTAD plasma, minimizing ex vivo platelet activation, in 27 patients with febrile Plasmodium falciparum malaria at presentation and day 2 and 5 of treatment and in 25 healthy controls.Results
Levels of Ang-1, Ang-2 and VEGF were higher at day 0 in malaria patients compared to healthy controls. Ang-2 levels, which is a marker of endothelial activation, decreased after start of antimalarial treatment. In contrast, Ang-1 and VEGF plasma levels increased and this corresponded with the increase in platelet number. Soluble P-selectin and CXCL7 levels followed the same trend as Ang-1 and VEGF levels. Plasma levels of these four proteins correlated strongly in malaria patients, but only moderately in controls.Conclusion
In contrast to previous studies, we found elevated plasma levels of Ang-1 and VEGF in patients with malaria resulting from in vivo platelet activation. Ang-1 release from platelets may be important to dampen the disturbing effects of Ang-2 on the endothelium. Evaluation of plasma levels of these angiogenic proteins requires close adherence to a stringent protocol to minimize ex vivo platelet activation. 相似文献87.
Tiffany N. Eady Larissa Khoutorova Daniela V. Anzola Sung-Ha Hong Andre Obenaus Alena Mohd-Yusof Nicolas G. Bazan Ludmila Belayev 《PloS one》2013,8(10)
Docosahexaenoic acid complexed to albumin (DHA-Alb) is highly neuroprotective after temporary middle cerebral artery occlusion (MCAo), but whether a similar effect occurs in permanent MCAo is unknown. Male Sprague-Dawley rats (270–330 g) underwent permanent MCAo. Neurological function was evaluated on days 1, 2 and 3 after MCAo. We studied six groups: DHA (5 mg/kg), Alb (0.63 or 1.25 g/kg), DHA-Alb (5 mg/kg+0.63 g/kg or 5 mg/kg+1.25 g/kg) or saline. Treatment was administered i.v. at 3 h after onset of stroke (n = 7–10 per group). Ex vivo imaging of brains and histopathology were conducted on day 3. Saline- and Alb-treated rats developed severe neurological deficits but were not significantly different from one another. In contrast, rats treated with low and moderate doses of DHA-Alb showed improved neurological score compared to corresponding Alb groups on days 2 and 3. Total, cortical and subcortical lesion volumes computed from T2 weighted images were reduced following a moderate dose of DHA-Alb (1.25 g/kg) by 25%, 22%, 34%, respectively, compared to the Alb group. The total corrected, cortical and subcortical infarct volumes were reduced by low (by 36–40%) and moderate doses (by 34–42%) of DHA-Alb treatment compared to the Alb groups. In conclusion, DHA-Alb therapy is highly neuroprotective in permanent MCAo in rats. This treatment can provide the basis for future therapeutics for patients suffering from ischemic stroke. 相似文献
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