Effects of chronic treatment with a nitric oxide donor on nerve conduction abnormalities and endoneurial blood flow in streptozotocin-diabetic rats

Abstract. This study examined the ability of nitrova-sodilator treatment with isosorbide dinitrate to prevent the development of reduced nerve conduction velocity and nutritive blood flow in streptozotocin-induced diabetes mellitus in rats. Two month untreated diabetes caused approximately 23% and 13% reductions in sciatic motor and saphenous nerve sensory conduction velocity ( P < 0.001). Isosorbide dinitrate treatment provided 64.6 and 67.6% protection for motor and sensory nerves, respectively ( P < 0.01). Sciatic endoneurial nutritive blood flow was measured by microelectrode polarography and a hydrogen clearance technique. After 1 month untreated diabetes, flow was reduced by 41.9% ( P < 0.001). Isosorbide dinitrate treatment for 1 month in non-diabetic and diabetic rats significantly increased blood flow ( P < 0.01). When between-group variations in blood pressure were taken into account, vascular conductance increased by 29% and 31% in non-diabetic and diabetic rats, respectively ( P < 0.01). Thus, nitrovasodilator treatment improves nerve perfusion and function in experimental diabetes, probably by compensating for reduced endothelium-derived nitric oxide release or action.     

Idiopathic membranous glomerulonephritis in Brazil

Summary: A survey of the medical records and renal biopsy reports of 41 patients with a diagnosis of membranous glomerulonephritis seen at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo was undertaken between 1961 and April 1992. Twenty-three of these patients were found to have idiopathic membranous glomerulonephritis (IMG) and 22 of them were treated with corticosteroids and/or immunosuppressants. Data for these 22 patients showed that the age at clinical presentation was 36.3± 17.5 years, white skin colour predominated (14 patients), and 15 were males; nephrotic syndrome was the clinical presentation in 20 patients and proteinuria was accidentally discovered in two patients. On the first hospital visit 11 patients presented proteinuria of up to 3 g/24 h and 16 presented serum creatinine below 1.5 mg/dL, and 14 developed renal hypertension during follow up. Clinicalmorphological correlation permitted us to conclude (in agreement with the literature) that advanced patient age, intensity of proteinuria, serum creatinine levels above 1.5 mg/dL on the occasion of the first hospital visit, and arterial hypertension are clinical-laboratory factors indicating a poor prognosis for IMG. More advanced staging of glomerular damage, presence of segmental mesangial sclerosis and tubulointerstitial involvement are microscopic factors indicating a poor prognosis for IMG.     

Determination of functional kidney volume by single-photon emission computed tomography in patients with insulin-dependent diabetes mellitus.

Functional parenchymal kidney volume was determined by single-photon emission computed tomography (SPECT) for 99mTc-dimercaptosuccinic acid (DMSA) using a rotating gamma camera in phantom experiments and in patients with insulin-dependent diabetes mellitus (IDDM). The results from the patient examinations were corrected according to the phantom studies and were thereafter set in relation to renal haemodynamics, blood pressure, and urinary albumin excretion. Functional parenchymal kidney volume was significantly greater in diabetic patients compared to that of 11 healthy controls (P < 0.003). Urinary albumin excretion was increased and glomerular filtration rate (GFR) per renal parenchymal volume significantly less in patients with a duration of diabetic disease of more than 15 years compared to patients with shorter duration of disease (P < 0.03 and P < 0.05 respectively). Diabetic patients with a GFR of more than 120 ml/min had greater renal parenchymal volume than patients with lower GFR (P < 0.02). Patients with increased GFR, renal plasma flow (RPF), renal blood flow, or filtration fraction had significantly greater functional parenchymal volume than the healthy subjects (P < 0.01 for all comparisons). We conclude that by application of SPECT for DMSA we were able to show that IDDM patients have greater renal parenchymal volumes than healthy subjects. GFR/kidney volume was increased in IDDM patients with a duration of disease of < 15 years compared to patients with long-standing diabetes. The SPECT technique seems suitable for prospective long-term follow-up studies of functional kidney volume in IDDM patients.     

Bacterial superantigen enhances cytokine production by T-helper lymphocyte subset-2 cells and modifies glomerular lesions in experimental immunoglobulin a nephropathy

Background The purpose of this study was to examine the effects of bacterial suporantigens, which can derange the immune response and contribute to the renal lesions of immunoglobulin A (lgA) nephropathy. Methods Twenty-five micrograms of a bacterial superantigen, staphylococcal enterotoxin B (SEB), was injected into IgA nephropathy-prone ddY mice intrathymically when they reached 6 weeks of age. Evaluation included measurement of albumin excretion in urine, immunoglobulin concentration, and lymphokine production in vitro, as well as analysis of T-cell receptor expression in splenic T-cell subsets and examination of renal histology by light and fluorescence microscopy. Results At 40 weeks of age, the serum level of IgA in these mice was substantially increased and the number of Vβ8⁺ CD4⁺splenic T-cells was significantly decreased compared with measurements in untreated controls. Both control and SEB-treated mice excreted less than 30 μg/mL of urinary albumin. In mice given SEB, the amount of interleukin 2 (IL-2) and tumor necrosis factor-α (T helper 1 [Th1]-type cytokines) produced by the in vitro-stimulated lymphocytes significantly decreased. whereas that of interleukin 4 (IL-4) and interleukin 6 (IL-6) (Th2-type cytokines) markedly increased compared with measurements in control mice. At 40 weeks of age, mice given SEB showed marked glomerular hypercellularity and enhanced glomerular C3 deposition by renal histology, compared with control mice. Conclusion These results suggest that bacterial superantigen SEB may modify glomerular lesions through activating Th2 cells, while inducing deletion of Th1 cells in this experimental model.     

血浆中高级糖化终产物的水平与糖尿病并发症的关系研究

目的 探讨高级糖化终产物与糖尿病并发症的关系。方法 采用本实验室自行研制的竞争性酶联免疫吸附分析方法，测定了糖尿病有并发症组病人血浆95例，糖尿病无并发症组人血浆65例，正常对照65例。结果：在糖尿病有并发症组中，高级糖化终产物（AGEs）浓度[（6．625（1．691）U／mL，n=95]明显高于糖尿病无并发症组[（5．904（2．071）U／mL，n=65，P=0．017]，也明显高于正常人组[（5．337（1．138，n=65，p〈0．005]。以有无并发症为应变量进行多元logistic回归分析显示，血浆AGEs浓度〉6．085U／ml者，糖尿病并发症发生的危险性增加（OR值为2．989，95％可信限为1．407—6．350）。多元逐步线性回归显示：糖尿病病程、冠心病史与血浆AGEs浓度之间有线性关系。结论血浆AGEs浓度是糖尿病发生并发症的独立危险因素。     

Non-immune therapy of IgA glomerulonephritis

Summary: The involvement of the IgA immune system and complement components in IgA glomerulonephritis (IgAGN) has prompted the use of immunosuppressive drugs in therapy, but none has so far been shown to alter the natural course of the disease. Because most patients with IgAGN present during the chronic phase of their illness, at the time when the initiating immune events may no longer be active, nonimmune therapy which targets the common pathway of progressive renal injury is likely to be more useful. There is increasing evidence that angiotensin-converting enzyme inhibitors (ACEI) reduce proteinuria and renal injury in patients with IgAGN, and this effect may be observed in both normotensive and hypertensive patients. Yet to be determined is whether this effect is specific for ACEI and whatever other effective antihypertensive drugs may achieve a similar result. Fish oil has recently been shown to retard the progression of renal failure in patients with aggressive IgAGN, but a narrow therapeutic window appears to exist for this form of treatment. Antiplatelet agents on their own appear to be ineffective but in combination with anticoagulation (low dose warfarin) have been shown to have an antiproteinuric effect and may preserve renal function in patients with progressive disease. Future directions of non-immune therapy of IgAGN include evaluation of the renoprotective effect of angiotensin II receptor antagonists, free-radical scavengers and antilipid drugs. More work should also be done to identify factors which put the patients at risk of developing progressive disease and which predict therapeutic response, as has been done recently with the identification of the deletion polymorphism of the angiotensin-converting enzyme gene as a marker of progressive disease and therapeutic response to ACEI in patients with IgAGN.     

Mechanisms of proteinuria in nephrotic humans

The glomerular capillary wall imposes a remarkably efficient barrier to the passage of proteins the size of albumin and larger. The development of heavy proteinuria signifies impairment of the function of this barrier. Because endogenous proteins of graded size are heterogeneous with respect to their molecular charge and undergo extensive tubular reabsorption, they are not useful for quantifying the extent of barrier dysfunction. An alternative approach is to determine the fractional clearance of uncharged and non-reabsorbable polymers of graded size. When combined with a hydrodynamic theory of solute transport through a heteroporous membrane, the intrinsic properties of healthy and diseased glomerular capillary walls can be inferred. This approach reveals the nephrotic range proteinuria that attends minimal change nephropathy to be associated with impairment of both the size- and charge-selective properties of glomerular capillary walls.     

伊那普利治疗糖尿病肾病的临床研究

目的评估伊那普利治疗糖尿病肾病(DN)的临床疗效 ,并探讨其作用机制。方法40例持续微量蛋白尿的非胰岛素依赖型糖尿病(NIDDM)患者随机分为常规治疗组(n=19)和伊那普利治疗组(n=21)。利用 131I -邻碘马尿酸钠测定有效肾血浆流量(ERPF) ;肾小球滤过率(GFR)以内生肌酐清除率表示 ;通过ELISA法测定尿微量蛋白 ,包括白蛋白(ALB)、转铁蛋白(TF)、视黄醇结合蛋白(RBP)和N -乙酰 - β氨基葡萄糖苷酶(NAG)。结果伊那普利治疗组增高的尿ALB、TF、RBP和NAG均显著下降 ;ERPF显著增加 ;增加的滤过分数(FF)显著减低。而常规治疗组这些参数无显著变化。结论伊那普利具有改善DN患者的肾小球血流动力学 ,保护肾小球和肾小管功能的作用     

Measuring oscillatory potentials: Fourier analysis

Studying the oscillatory potentials in diabetic retinopathy, the authors experienced several problems interpreting results of digital filtering. The main problem was the separation of the first potential from the a-wave, since their frequencies are within the same range. To improve the procedure of measuring implicit times and of calculating amplitudes, the filtering was started with a finite impulse response filter and followed by a fast Fourier transform. The power of the oscillatory potential was calculated by determining the dominant frequency in the Fourier transformed response and expressed in microwatts. A group of normal subjects was compared with a group of early diabetic retinopathy patients. It appears that even in pathological circumstances a quantitative expression of the oscillatory potential is possible.     

N-acetylcysteine prophylaxis significantly reduces the risk of radiocontrast-induced nephropathy: comprehensive meta-analysis.

The objectives of this study was to assess the overall effect of N-acetylcysteine (NAC) in preventing radiocontrast-induced nephropathy (RCIN) using all available data in the literature. RCIN is associated with increased morbidity and mortality. Existing randomized trials of NAC are small and show inconsistent results. Prior meta-analyses do not include data from the most current studies. We used standard search protocols to identify all published articles and abstracts of prospective trials using NAC with fluid hydration compared to hydration alone in patients with chronic renal insufficiency undergoing contrast procedures. A rise in serum creatinine by 0.5 mg/dl or 25% above baseline at 48-72 hr after contrast exposure was used as the primary outcome. We identified 14 trials of NAC with 1,584 patients published as full-text articles. Using a random-effects model, the use of oral NAC resulted in a significant reduction in the risk for developing RCIN (RR = 0.57; 95% CI = 0.37-0.84; P = 0.01). This finding did not significantly change in a fixed-effect model (RR = 0.55; 95% CI = 0.42-0.73) or when the data were reanalyzed using only randomized trials in all forms (i.e., articles and abstracts; RR = 0.67; 95% CI = 0.47-0.95). We identified only one important difference between the positive and the negative studies: the cumulative exposure to contrast media (174 vs. 152 ml). Metaregression did not show a significant relationship between contrast volume and the RR of developing RCIN (P > 0.10). In the trials showing benefit for NAC, the treated patients' postprocedure creatinine unexpectedly decreased by 0.21 mg/dl (95% CI = 0.33-0.08). Prophylaxis with NAC significantly reduces the risk for RCIN. The reasons for improvement in serum creatinine in patients treated with NAC are unclear, but may include improved renal blood flow due to NAC and/or vigorous hydration.