Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model.

Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ∼20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (θ) for FITC-Ficoll (molecular radius 20-90 Å) using size exclusion HPLC. The values of θ for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (θ for 50-69 Å = 0.001 vs. 0.0002, and θ for 70-90 Å = 0.0007 vs. 0.00006, P < 0.001), while θ for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (θ for 36-49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes.

Responses to dehydration in the one-humped camel and effects of blocking the renin-angiotensin system.

Our objectives were to compare the levels of circulating electrolytes, hormones, and renal function during 20 days of dehydration in camels versus the level in non-dehydrated camels and to record the effect of blocking angiotensin II AT1 receptors with losartan during dehydration. Dehydration induced significant increments in serum sodium, creatinine, urea, a substantial fall in body weight, and a doubling in plasma arginine vasopressin (AVP) levels. Plasma aldosterone, however, was unaltered compared with time-matched controls. Losartan significantly enhanced the effect of dehydration to reduce body weight and increase serum levels of creatinine and urea, whilst also impairing the rise in plasma AVP and reducing aldosterone levels. We conclude that dehydration in the camel induces substantial increments in serum sodium, creatinine, urea and AVP levels; that aldosterone levels are altered little by dehydration; that blockade of angiotensin II type 1 receptors enhances the dehydration-induced fall in body weight and increase in serum creatinine and urea levels whilst reducing aldosterone and attenuating the rise in plasma AVP.

Association between homocysteine and endothelial dysfunction markers in stroke disease.

BACKGROUND: Evidence shows that there is an increase in concentrations of markers of endothelial dysfunction immediately following acute ischaemic stroke. Several studies suggest that endothelial dysfunction may be partly caused by oxidation related to the effects of raised total plasma homocysteine. OBJECTIVE: The aim of this study was to measure changes in total plasma homocysteine and markers of endothelial dysfunction in stroke disease within a known period of time post infarct. SUBJECTS AND METHODS: We studied 40 acute ischaemic stroke patients (mean age +/- SD, 50.2 +/- 9.5 years) and 42 hospitalised non-stroke patients (mean age, 44.3 +/- 14.9 years). Fasting venous blood was obtained within 24 h, 3 days and 7 days after the stroke onset and hospitalisation for non-stroke patients for measurements of total plasma homocysteine, markers of endothelial dysfunction including intracellular adhesion molecule (i-CAM), vascular cell adhesion molecule-1 (v-CAM) and leukocyte adhesion molecule-1 (E-selectin) and C-reactive proteins (CRPs). RESULTS: We found no significant differences in baseline total plasma homocysteine, E-selectin, v-CAM, vitamin B(12), and folate concentrations between ischaemic stroke patients and non-stroke controls. i-CAM concentrations were significantly higher and CRPs non-significantly lower at baseline in stroke patients compared with controls. Although all endothelial dysfunction markers increased significantly during the study period, the rise in E-selectin levels was less than that seen in i-CAM, and v-CAM. Total plasma homocysteine concentrations showed positive correlations with creatinine (r = 0.537; P < 0.02), and inverse correlations with both vitamin B(12) (r = -0.560; P < 0.001) and folate (r = -0.469; P < 0.002); however, there were no significant correlations between total plasma homocysteine or B-vitamins and markers of endothelial dysfunction in ischaemic stroke patients or controls. CONCLUSIONS: We found evidence of an increase in markers of endothelial dysfunction following acute ischaemic stroke but this had no relationship with total plasma homocysteine concentrations.

Interrelationships between B-type natriuretic peptides and vitamin D in patients on maintenance peritoneal dialysis.

OBJECTIVE: Experimental evidence suggests that vitamin D deficiency impairs cardiac structure and function. Our objective was to observe relationships between circulating levels of the cardiac natriuretic peptides and vitamin D levels in patients on chronic peritoneal dialysis. METHOD: Measurements were made of circulating levels of 25-hydroxyvitamin D [25(OH)D] and plasma B-type natriuretic peptide (BNP) levels in patients receiving chronic peritoneal dialysis. RESULTS: Both BNP and the 1-76 amino-terminal fragment of pro-BNP correlated inversely with 25(OH)D levels (rs = -0.60, p = 0.007, and rs = -0.64, p = 0.003, respectively) in patients on peritoneal dialysis. CONCLUSIONS: Vitamin D deficiency in chronic renal failure may impair cardiac function, as manifested by elevated levels of B-type cardiac natriuretic peptides.

Under- treatment and under diagnosis of hypertension: a serious problem in the United Arab Emirates.

BACKGROUND: Hypertension, notably untreated or uncontrolled, is a major risk factor for cardiovascular diseases (CVD) morbidity and mortality. In countries in transition, little is known about the epidemiology of hypertension, and its biochemical correlates. This study was carried out in Al Ain, United Arab Emirates, to characterize self-reported (SR) normotensives and hypertensives in terms of actual hypertension status, demographic variables, CVD risk factors, treatment, and sequalae. METHODS: A sample, stratified by SR hypertensive status, of 349 SR hypertensives (Mean age +/- SD; 50.8 +/- 9.2 yrs; Male: 226) and 640 SR normotensives (42.9 +/- 9.3 yrs, Male: 444) among nationals and expatriates was used. Hypertensives and normotensive subjects were recruited from various outpatient clinics and government organizations in Al-Ain city, United Arab Emirates (UAE) respectively. Anthropometric and demographic variables were measured by conventional methods. RESULTS: Both under-diagnosis of hypertension (33%) and under-treatment (76%) were common. Characteristics of undiagnosed hypertensives were intermediate between normotensives and SR hypertensives. Under-diagnosis of hypertension was more common among foreigners than among nationals. Risk factors for CVD were more prevalent among SR hypertensives. Obesity, lack of exercise and smoking were found as major risk factors for CVD among hypertensives in this population. CONCLUSION: Hypertension, even severe, is commonly under-diagnosed and under-treated in the UAE. Preventive strategies, better diagnosis and proper treatment compliance should be emphasized to reduce incidence of CVD in this population.