يعرض 1 - 10 نتائج من 17 نتيجة بحث عن '"P Cavallo-Perin"', وقت الاستعلام: 0.87s تنقيح النتائج
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    المصدر: Neuroscience. 227:154-162

    الوصف: Hippocampal abnormalities are believed to increase the risk of cognitive decline in diabetic patients. The underlying mechanism is unknown, but both hyperglycemia and oxidative stress have been implicated. Cellular stresses induce the expression of heat shock protein 25 (HSP25) and this results in cytoprotection. Our aim was to assess hippocampal expression of HSP25 in experimental diabetes. Mice were rendered diabetic by streptozotocin injection. Ten weeks after diabetes onset hippocampal HSP25 expression was studied by immunoblotting and immunohistochemistry (IHC). Expression of glial fibrillary acidic protein, nitrotyrosine, iNOS, HSP72, HSP90, and Cu/Zn superoxide dismutase (SOD) was assessed by either IHC or immunoblotting, Cu/Zn-SOD activity by enzymatic assay, and malondialdehyde (MDA) content by colorimetric assay. Hippocampal HSP25 was significantly increased in diabetic as compared to non-diabetic animals and localized predominantly within the pyramidal neurons layer of the CA1 area. This was paralleled by overexpression of nitrotyrosine, iNOS, SOD expression/activity, and enhanced MDA content. In experimental diabetes, HSP25 is overexpressed in the CA1 pyramidal neurons in parallel with markers of oxidative stress.

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    المصدر: American Journal of Transplantation. 6:2601-2611

    الوصف: Donor intra-islet endothelial cells contribute to neovascularization after transplantation. Several factors may interfere with this process and ultimately influence islet engraftment. Rapamycin, a central immunosuppressant in islet transplantation, is an mTOR inhibitor that has been shown to inhibit cancer angiogenesis. The aim of this study was to evaluate the effects of rapamycin on islet endothelium. Rapamycin inhibited the outgrowth of endothelial cells from freshly purified human islets and the formation of capillary-like structures in vitro and in vivo after subcutaneous injection within Matrigel plugs into SCID mice. Rapamycin decreased migration, proliferation and angiogenic properties of human and mouse islet-derived endothelial cell lines with appearance of apoptosis. The expression of angiogenesis-related factors VEGF, alphaVbeta3 integrin and thrombospondin-1 on islet endothelium was altered in the presence of rapamycin. On the other hand, rapamycin decreased the surface expression of molecules involved in immune processes such as ICAM-1 and CD40 and reduced the adhesion of T cells to islet endothelium. Our results suggest that rapamycin exerts dual effects on islet endothelium inducing a simultaneous inhibition of angiogenesis and a down-regulation of receptors involved in lymphocyte adhesion and activation.

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    المصدر: Diabetic Medicine. 18:59-67

    الوصف: SUMMARY Aims To examine the relationship between increased urinary albumin excretion rate and fasting plasma lipids among male and female respondents to the EURODIAB IDDM Complications Study, and attempt to explain inconsistencies in previous reports. Methods A cross-sectional study of 3250 randomly selected Type 1 diabetic patients from 31 diabetes clinics in 16 European countries was carried out between 1989 and 1990. Plasma lipids and urinary albumin were measured centrally. The present analysis was confined to the subgroup of 2205 patients attending after a 10–12 h overnight fast. Mean age was 33 years (sd 10) and mean duration of Type 1 diabetes mellitus was 15 years (sd 9). Results The prevalence of microalbuminuria (24-h urinary albumin excretion rate 20–200 μg/min) was 21.7% (95% confidence interval 19.9–23.5) and macroalbuminuria (24-h urinary albumin excretion rate > 200 μg/min) 7.8% (6.6–9.0). In comparison to patients with normal urinary albumin excretion rate (

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    المؤلفون: P Cavallo Perin, R. Quadri, S. Maule

    المصدر: Clinical and Experimental Hypertension. 23:45-55

    الوصف: Hypertension is twice as frequent in diabetic patients than in the general population. Its prevalence is higher in Type 2 than in Type 1 diabetes: in the former, the onset of hypertension often precedes the diagnosis of diabetes, whereas, in the latter it is strictly related to the presence of nephropathy. Sympathetic nerve overactivity is crucial in the pathogenesis of hypertension in diabetes. It can be related to the activation of the renin-angiotensin-aldosterone (RAA) system in Type 1 diabetic patients with chronic renal failure, or to a condition of insulin resistance/hyperinsulinemia in Type 2 patients with the metabolic syndrome. In patients with early autonomic neuropathy, vagal impairment can lead to a relative predominance of sympathetic activity in the sympatho-vagal balance. In these patients, the onset of hypertension is frequently preceded by reduced nocturnal dipping. Sympathetic overactivity stimulates RAA activity, promotes sodium reabsorption, and increases heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension and increasing cardiovascular risk. A number of drugs acting either directly or indirectly on sympathetic activity are available for the treatment of hypertension in diabetic subjects. Opinions on the potential advantages of the metabolic profile of some of these drugs are as yet conflicting.

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    المصدر: Diabetes/Metabolism Research and Reviews. 15:247-253

    الوصف: Background Genetic factors are involved in the development of diabetic nephropathy in Type 1 diabetes. We have examined the association of four candidate genes, angiotensin converting enzyme (ACE): insertion/deletion (I/D) polymorphism, plasminogen activator inhibitor-1 (PAI-1): 4G/5G polymorphism, decorin: 179/183/185 polymorphism and Werner syndrome helicase: C/R polymorphism, with the presence of diabetic nephropathy in Type 1 diabetic patients. Methods 175 Type 1 diabetic patients with albuminuria (59 with microalbuminuria and 116 with macroalbuminuria) were compared with 136 Type 1 diabetic patients with normoalbuminuria and duration of disease longer than 15 years (meantSD: 25t8 years). 200 non-diabetic subjects were also studied as background population. Results We found no association in the polymorphism of the four genes examined between patients with and without diabetic nephropathy and the control subjects. Conclusions The genes studied are unlikely to be involved in the susceptibility to nephropathy in Type 1 diabetic patients. Copyright # 1999 John Wiley & Sons, Ltd.

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    المصدر: Diabetic Medicine. 12:302-306

    الوصف: The question as to whether the QTc interval correlates with five cardiovascular tests (deep breathing test, 30/15 ratio test, lying to standing test, cough test, and postural blood pressure test) for the diagnosis of diabetic autonomic neuropathy (DAN) was investigated in 168 (38 Type 1, 130 Type 2) consecutive outpatients (mean age 54.9 +/- 11.2 years). QT interval was measured on an ECG recorded at rest and QTc calculated according to Bazett's formula. The percentage of patients with a QTc greater than 0.440 s was: absent DAN = 11% (n = 7), probable DAN = 7% (n = 4), definite DAN = 23% (n = 12) (p < 0.05), and the mean (+/- SD) QTc values were 0.403 +/- 0.028 s, 0.405 +/- 0.023 s, and 0.421 +/- 0.026 s, respectively. A significant correlation between QTc duration and DAN score of autonomic cardiovascular test results (r = 0.34, p < 0.0001) was observed. The calculated specificity, sensitivity, positive and negative predictive values were 89%, 15%, 70% and 37%, respectively. In conclusion, QTc can be considered as an additional specific test in the assessment of diabetic autonomic neuropathy, but cannot replace the standard battery of cardiovascular tests.

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    المصدر: Scopus-Elsevier

    الوصف: To investigate the role of plasma lipid abnormalities in ischemic cerebrovascular disease related to primary vessel disease, the authors assess lipid profiles in a hospital-based cohort of 202 consecutive patients with atherothrombotic or lacunar stroke subtypes. Lipoprotein (a) was the unique lipid parameter that differs between these two subtypes being its value twofold higher in patients with atherothrombotic than in lacunar stroke. This suggests that lipoprotein (a) promotes large vessel atheromatosis rather than small vessel arteriolosclerosis and favors thrombosis on atheromatous plaques by suppressing local fibrinolysis.

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    المصدر: Diabetologia. 48(9)

    الوصف: The islet microcirculation has morphological characteristics resembling those of renal glomeruli. Transcription of the nephrin gene, a highly specific barrier protein of the slit diaphragm of podocyte foot processes, has been reported in the pancreas, although its cellular localisation and function remain to be defined. In this study, we purified and characterised microvascular endothelial cells (MECs) isolated from human islets and investigated the expression and distribution of nephrin on these cells.Human islet MECs were extracted and purified using anti-CD105-coated immunomagnetic beads and their endothelial characteristics were confirmed by expression of classical endothelial markers and basal high-level expression of intercellular adhesion molecule-1 and TNF-alpha-inducible vascular cell adhesion molecule-1. Nephrin expression was assessed by immunofluorescence, flow cytometric analysis and western blotting on cell lysates, as well as by RT-PCR.Immunofluorescence studies detected nephrin in a fine, punctate, diffuse pattern on cultured islet MECs, and also in human pancreatic islet sections. In both cases nephrin colocalised with endothelial markers. TNF-alpha treatment induced a marked reduction and redistribution of the protein in one or multiple aggregates. Nephrin expression was confirmed by flow cytometry, western blotting and RT-PCR studies. In contrast, nephrin could not be detected at the protein or mRNA level in human macro- and microvascular cells from other sites.Nephrin is expressed at protein and mRNA levels in islet microendothelium, supporting the hypothesis that islet MECs exhibit distinctive morphological characteristics that indicate functional specialisation of potential pathophysiological importance.

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    المساهمون: De Cosmo, S, Tassi, V, Thomas, S, Piras, G, Trevisan, R, Perin, P, Bacci, S, Zucaro, L, Cisternino, C, Trischitta, V, Viberti, G

    الوصف: Background genetic factors may influence the variability in the rate of progression of kidney disease in type 1 diabetes. In diabetes, progressive mesangial matrix expansion and glomerular sclerosis are, to a large extent, mediated by TGF-β1. Decorin, a proteoglycan which is a component of the extracellular matrix, regulates TGF-β1 activity and expression. We have examined the relationship between the 179/183/185 polymorphism of the Decorin gene and the progression of diabetic nephropathy. Methods: From a cohort of 175 European patients with diabetic nephropathy, we studied 79 patients who were selected because they had a follow-up of at least 2 years (average 6.5 years; range: 2.5–15 years), and regular measurements of serum creatinine on 5 or more occasions. Creatinine clearance (CrCl) calculated from serum creatinine concentration was used as a measure of derived glomerular filtration rate (dGFR). All patients were on antihypertensive therapy. Results: The rate of dGFR decline in the whole cohort was [median (range)] 4.6 (–3.8 to 18) ml/min/year. No patient with 185 allele was found. Patients with 179/183 and 179/179 genotype (n = 14), who were considered together and named 179 carriers, had a slower rate of GFR decline [2.1 (0.06–11.7) ml/min/year] as compared to patients with Decorin 183/183 genotype (n = 65) [5.6 (–3.8 to 18) ml/min/year; p < 0.001]. In addition, when considering individual data, patients carrying the 179 allele had a 3.0 (95%CI: 1.8–4.2)-fold higher probability to be slow progressors (i.e. GFR decline below the median). This difference could not be accounted for by differences in duration of disease, type and duration of antihypertensive therapy, albumin excretion rate, blood glucose or blood pressure control. In a multivariate logistic analysis albumin excretion rate (p < 0.001), mean arterial pressure (p = 0.07) and Decorin gene polymorphism (p = 0.036), but not HbA1c, were independently correlated with the rate of dGFR fall. Conclusion: The 179 allele variant of the Decorin gene is related to a slower progression of DN in type 1 diabetic patients with albuminuria and receiving antihypertensive therapy.

    وصف الملف: STAMPA