A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Ethnic minorities in British diabetic clinics: a questionnaire survey

A questionnaire was sent by the British Diabetic Association to hospital consultant physicians caring for diabetic patients in the UK to estimate the number of ethnic minority patients attending British Diabetic clinics, and the availability of special facilities for their care. Sixty-two clinics were estimated to have at least 50 Asian patients, and 25 had at least 200 Asian patients. For Afro-Caribbeans the corresponding figures were 33 and 14 clinics, respectively. Clinics serving a relatively high proportion of these patient groups were situated primarily in Greater London, the Midlands and the North West. Approximately 40% of clinics with over 50 Asians had no specifically adapted diet sheets, and 34% had no hospital interpreter service. Tapes, slides or video presentations were available in only eight clinics. There is an urgent need to improve the provision of special facilities to clinics with substantial numbers of ethnic minority patients.     

实验性糖尿病大鼠肾脏损害和脂质过氧化物水平的动态研究

动态观察实验性糖尿病大鼠于发病后２、４、６、１２、和１６周肾脏损害指标和肾脏脂质过氧化物（ＬＰＯ）水平的变化。结果表明，发病后各观察时间．或糖尿病大鼠２４ｈ尿Ａｌｂ、β２──ＭＧ排泄量和尿ＮＡＧ活性均明显增高，而２４ｈ尿ＴＨＰ排泄量显著降低，肾脏ＬＰＯ水平明显升高。其中尿ＮＡＧ活性、ＴＨＰ排泄量和肾脏ＬＰＯ水平均随病程延长而更趋明显。这些结果提示，在糖尿病早期除有肾小球功能损害外，肾小管也明显受损，过氧化损伤在糖尿病肾病发病中可能是重要因素之一。尿Ａｌｂ、β２──ＭＧ、ＴＨＰ含量和ＮＡＧ活性可作为糖尿病肾病早期肾损害的敏感指标。     

Simultaneous noninvasive evaluation of gastric emptying and orocaecal transit times

Summary The aim of the study was to use a novel combination of two methods for the simultaneous evaluation of two effects of oral cisapride in 10 diabetic patients with autonomic neuropathy; gastric emptying time was measured by following radio-opaque markers and orocaecal transit time by the sulphasalazine-sulphapridine method. The study was of double-blind, randomized, placebo-controlled, cross-over design.It was possible to evaluate the effect of a prokinetic drug on gastric emptying and orocaecal transit times using these two noninvasive techniques at the same time. Cisapride significantly reduced both the gastric emptying (1.2 h versus 2.1 h) and orocaecal tansit (5.9 h versus 7.7 h) times.     

Acute Oxalate Nephropathy: A New Etiology for Acute Renal Failure Following Nonrenal Solid Organ Transplantation

Acute renal insufficiency (ARI) is a frequent complication of nonrenal solid organ transplantation and may be responsible for an unfavorable outcome, particularly if dialysis is required. The etiology of post-transplantation ARI is poorly understood, with only isolated clinical cases being reported, most imputed to drug toxicity. We report here, the first three observations of irreversible ARI associated with acute oxalate nephropathy (AON) in the course of nonrenal organ transplants: a lung transplant and a lung-liver transplant in two patients with mucoviscidosis, and a cardiac transplant. The diagnosis of AON was made histologically. In all three cases, the ARI supervened after prolonged consumption of antibiotics capable of interfering with the colonic flora, and leading to enteric hyperoxaluria. The recognition of AON as a cause of post-transplantation, ARI underlines hyperoxaluria and digestive hyperabsorption of oxalate as specific risk factors for AON and should permit better posttransplant care of these patients.     

2型糖尿病肾病患者血清中TNF-α、NO与ET的水平变化及其临床意义

目的：探讨2型糖尿病肾病患者血清肿瘤坏死因子仅（TNF-α）、一氧化氮（NO）和内皮素（ET）的水平变化及其临床意义。方法：用ELISA法检测91例2型糖尿病患者血清TNF-α水平，NO与ET的水平分别用硝酸还原酶法和放射免疫法测定。结果：2型糖尿病肾病各组患者TNF-α和ET水平较对照组明显升高，其中ODN组最高（P〈0．01）。而2型糖尿病肾病各组患者血清NO水平较对照组明显减少（P〈0．01）。显性糖尿病肾病患者血清TNF-α和ET呈正相关；血清TNF-α和NO、ET和NO均成负相关。结论：TNF-α、NO与ET可能参与2型糖尿病肾病的发病及病程变化过程，检测患者TNF-α、NO与ET水平可作为判断预后、指导治疗的指标。     

糖尿病大鼠肾组织中单核细胞趋化蛋白-1的表达及意义

目的：探讨单核细胞趋化蛋白-1(MCP—1)在糖尿病大鼠肾组织中的表达及其意义。方法：用链脲佐菌素制备糖尿病大鼠模型。采用免疫组化及多媒体彩色病理图文分析系统观察肾小球及肾小管中MCP-1的表达。结果：糖尿病大鼠肾小球及肾小管中MCP—1的表达显著上调。结论：MCP-1在糖尿病肾病发病机制中发挥重要作用。     

氧化反应对糖尿病大鼠造影剂肾病发生的影响

目的 :探讨氧化反应对糖尿病大鼠造影剂肾病发生的影响。方法 :建立SD大鼠糖尿病动物模型 ,8w后分 3组 :正常对照组 (SD组 )、糖尿病对照组 (DM组 )和糖尿病 +造影剂组 (CM组 )。其中CM组大鼠经尾静脉一次性注入 76%泛影葡胺 ( 10ml/kg体重 ,3gI(iodine) /10ml) ,DM组注射等量生理盐水。 3d后收集血标本检测血肌酐、血尿素氮 ;取肾脏组织 ,测定肾组织丙二醛 (MDA)与超氧化物歧化酶 (SOD)的含量。结果 :与正常对照组相比 ,糖尿病组 (DM组 )的MDA含量与SOD活性均明显升高 (P <0 .0 5 ) ;糖尿病大鼠注射造影剂 (CM组 ) 3d后MDA含量明显增加 ,SOD活性明显降低 ,与DM组差异有显著性 (P <0 .0 5 )。结论 :糖尿病大鼠造影剂肾病发生时 ,肾脏组织产生过氧化物增多、清除能力下降 ,提示氧化反应对糖尿病造影剂肾病的发生起一定作用     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.