Nitric oxide—mediated renal epithelial cell injury during hypoxia and reoxygenation

The potent endothelial-derived vasodilator nitric oxide (NO) has been identified as a protective agent in acute renal failure. However, some recent studies have suggested a detrimental effect of NO on rat proximal tubules exposed to hypoxia and reoxygenation. We determined whether NO metabolites cause intracellular oxidation during hypoxia and reoxygenation and whether this oxidative stress is linked to irreversible cell injury. Primary cultures of rat proximal tubular epithelial cells were studied in a subconfluent stage and subjected to 60 min hypoxia and 30 min reoxygenation. Intracellular oxidation was assessed by monitoring the conversion of nonfluorescent dihydrorhodamine 123 (DHR) to fluorescent rhodamine 123 as a probe for the long-lived oxidant peroxvnitrite. Hypoxia and reoxygenation produced a marked increase in cellular generation of oxidant species. Intracellular oxidation of DHR was reduced by approsimately 40% when cells were also exposed to the NO svnthase inhibitor L-NAME. Oxidation of DHR following hypoxia and reoxygenation was not affected by SOD or DATTU. A combination of SOD and L-NAME was no more effective than L-NAME alone. Hypoxia and reoxygenation produced substantial injury (as LDH release). There was a 40% reduction in LDH release when cells were pretreated with a NO synthase inhibitor. In summary, increased generation of NO capable of inducing intracellular oxidizing reactions and cell death occurred during renal hypoxia and reoxygenation.     

A single dose of rasburicase in elderly patients with hyperuricaemia reduces serum uric acid levels and improves renal function

Aim: Given the relevance of hyperuricaemia in the development of several diseases, we evaluated rasburicase, generally used in tumor lysis syndrome for uric acid treatment. Our purpose was to evaluate the reduction of serum uric acid and the improvement in renal function. Methods: This is a pilot randomized clinical trial. The study was performed as an 8-week, placebo-controlled group comparison of rasburicase and placebo. Thirty-eight patients were randomly assigned to administration of a single dose of rasburicase (4.5 mg in 100-cc physiological solution versus only physiological solution in 15 min). Results: We observed in the first week a fast decrease in uric acid value. Two months after rasburicase administration we saw a significant reduction of urate (p < 0.05) and creatinine (p < 0.001) and an increase in creatinine clearance (p < 0.001) and urate clearance (p < 0.001). Conclusion: In hyperuricaemic elderly patients, a single dose of rasburicase is very effective in lowering serum uric acid levels. Moreover, in patients treated with rasburicase we noted an improvement of renal function. We conclude that rasburicase is an alternative resource for treating those patients who are allopurinol intolerant, have renal dysfunction or have multiple polypharmacy problems in which drug–drug interaction may be of concern.     

Treatment of Acute Rejection

Abstract

Background: Cardiovascular disease (CVD) is the most important cause of morbidity and mortality in patients with end stage renal disease (ESRD). Apelin expressed in endothelial and other tissues including brain and kidney is an adipocytokine defined recently and is emerging an important mediator of cardiovascular homeostasis. The aim of this study was to test whether apelin levels might be associated with carotid artery atherosclerosis and left ventricular mass index (LVMI) in peritoneal dialysis patients. Patients and methods: Fifty peritoneal dialysis patients (25 female, mean age 41.4?±?11.9 years, mean dialysis vintage 65.0?±?35.4 months) and 18 healthy individuals (9 female, mean age 41.7?±?6.8 years) were included in this cross-sectional study. Serum apelin 12 levels, echocardiographic findings and carotid intima media thickness (CIMT) were recorded as well as clinical and laboratory data. Results: There were no differences between the patient and the control groups with regard to demographic characteristics. In patient group, LVMI, CIMT, CRP and apelin levels were elevated compared to control group. However there was no association between apelin, LVMI and CIMT. There was a positive correlation between apelin and CRP, which was not statistically significant. When patients were divided into two groups according to the mean serum apelin levels, LVMI, CIMT and CRP were higher in the high apelin group but this difference did not reach statistical significance. Conclusion: We observed an increased inflammation and CVD risk in peritoneal dialysis patients. However, serum apelin levels seem not to be associated with cardiovascular risk in this group of patients.     

阿利吉仑与氨氯地平对肾动脉狭窄性大鼠斑块部位MMP9表达的比较研究

目的 选择一肾一夹（1K1C）、二肾一夹（2K1C）肾动脉狭窄性大鼠主动脉弓作为研究对象,比较阿利吉仑与苯磺酸氨氯地平对斑块部位基质金属蛋白酶9（MMP9）表达的影响.方法 将健康雄性SD大鼠随机分为对照组、1K1C组及2K1C组,行平行针灸针缩窄法造模及高脂饲养10周,生理盐水组：0.9% NS 2 ml/d、阿利吉仑组：50 mg/（kg·d）、苯磺酸氨氯地平组：6 mg/（kg·d）,4周后游离并切取SD大鼠主动脉弓,采用免疫组织化学法检测斑块部位MMP9的表达,Western-blot检测MMP9的表达.结果 1K1C及2K1C苯磺酸氨氯地平组与生理盐水组比较,其斑块部位MMP9的表达差异无统计学意义（P﹥0.05）;但阿利吉仑各组差异有统计学意义（P﹤0.05）.结论 苯磺酸氨氯地平对2K1C和1K1C大鼠斑块部位MMP9的表达无明显抑制作用,而阿利吉仑均可抑制各组斑块部位MMP9的表达,提示阿利吉仑稳定动脉粥样硬化斑块的作用可能优于苯磺酸氨氯地平.     

Review of Foot Tumors Seen in a University Tumor Institute

Most tumors of the foot and ankle will be benign, and it has been easy for clinicians to underestimate the malignant potential of a given tumor. The purpose of our study was to gain insight into the incidence of different tumor types diagnosed in patients with tumors of the foot and/or ankle treated at the Rizzoli Institute from September 1990 to December 2007. Our series included 1170 patients and 1170 lesions, with an overall mean age at diagnosis of 43 (range 5 to 81) years. Overall, 870 lesions (74.36%) were nonmalignant and 300 (25.65%) were malignant. Soft tissue lesions were diagnosed in 189 patients (16.15%), of which 91 (48.15%) were nonmalignant (pseudotumors or benign). Bone lesions were diagnosed in 981 patients (83.85%), of which 779 (79.41%) were nonmalignant. Epidemiologic knowledge of foot abnormalities and clinical suspicion, an organized diagnostic method, and evidence-based treatment of musculoskeletal tumors are essential elements to obtaining optimal results in the treatment of malignant foot tumors.     

Vulvar Lichen Sclerosus: Diagnosis and Management

Vulvar lichen sclerosus (VLS) is a chronic, inflammatory skin condition of the vulva that most commonly affects postmenopausal women. Although there is currently no cure, modern treatments can effectively manage VLS once diagnosed. Unfortunately, vulvar conditions are routinely underdiagnosed and undertreated. Untreated VLS can cause significant physical, emotional, and sexual discomfort, which may result in irreversible destruction of the genitalia and can progress to squamous cell carcinoma. Nurse practitioners must be aware of the key features and complications of this condition and must have a good understanding of the diagnostic criteria and treatment strategies for VLS.     

Principles in the management of chronic kidney disease

Chronic kidney disease (CKD) is the term used to describe renal disease or impairment which has persisted for three months. This paper presents a brief overview of CKD, including classification, epidemiology, aetiology, clinical presentation, investigations and a discussion regarding the principles of management. The aims of management include: preservation of remaining renal function, avoiding further injury, correction of electrolyte disturbances, anaemia and fluid imbalance and also maintenance of good nutrition, bone health and growth. Some children will progress to end-stage disease and there is a brief discussion of renal replacement therapy. Prognosis depends largely on the cause of CKD. Where children should be followed-up is dictated primarily by their renal function and the likely clinical course.     

Renal Transplantation: Relationship between Hospital/Surgeon Volume and Postoperative Severe Sepsis/Graft-Failure. A Nationwide Population-Based Study

Background and objects: We explored the relationship between hospital/surgeon volume and postoperative severe sepsis/graft-failure (including death).Methods: The Taiwan National Health Insurance Research Database claims data for all patients with end-stage renal disease patients who underwent kidney transplantation between January 1, 1999, and December 31, 2007, were reviewed. Surgeons and hospitals were categorized into two groups based on their patient volume. The two primary outcomes were severe sepsis and graft failure (including death). The logistical regressions were done to compute the Odds ratios (OR) of outcomes after adjusting for possible confounding factors. Kaplan-Meier analysis was used to calculate the cumulative survival rates of graft failure after kidney transplantation during follow-up (1999-2008).Results: The risk of developing severe sepsis in a hospital in which surgeons do little renal transplantation was significant (odds ratio [OR]; p = 0.0115): 1.65 times (95% CI: 1.12-2.42) higher than for a hospital in which surgeons do many. The same trend was true for hospitals with a low volume of renal transplantations (OR = 2.39; 95% CI: 1.62-3.52; p < 0.0001). The likelihood of a graft failure (including death) within one year for the low-volume surgeon group was 3.1 times higher than for the high-volume surgeon group (p < 0.0001); the trend was similar for hospital volume. Female patients had a lower risk than did male patients, and patients ≥ 55 years old and those with a higher Charlson comorbidity index score, had a higher risk of severe sepsis.Conclusions: We conclude that the risk of severe sepsis and graft failure (including death) is higher for patients treated in hospitals and by surgeons with a low volume of renal transplantations. Therefore, the health authorities should consider exporting best practices through educational outreach and regulation and then providing transparent information for public best interest.