High glucose/lysophosphatidylcholine levels stimulate extracellular matrix deposition in diabetic nephropathy via platelet­activating factor receptor.

Platelet-activating factor (PAF), protein kinase C (PKC)ßI, transforming growth factor (TGF)­ß1 and aberrant extracellular matrix (ECM) deposition have been associated with diabetic nephropathy (DN). However, the mechanistic basis underlying this association remains to be elucidated. The present study investigated the association among the aforementioned factors in a DN model consisting of human mesangial cells (HMCs) exposed to high glucose (HG) and lysophosphatidylcholine (LPC) treatments. HMCs were divided into the following treatment groups: Control; PAF; PAF+PKCßI inhibitor LY333531; HG + LPC; PAF + HG + LPC; and PAF + HG + LPC + LY333531. Cells were cultured for 24 h, and PKCßI and TGF­ß1 expression was determined using the reverse transcription­quantitative polymerase chain reaction and western blotting. The expression levels of the ECM­associated molecules collagen IV and fibronectin in the supernatant were detected using ELISA analysis. Subcellular localization of PKCßI was assessed using immunocytochemistry. PKCßI and TGF­ß1 expression was increased in the PAF + HG + LPC group compared with the other groups (P<0.05); however, this effect was abolished in the presence of LY333531 (P<0.05). Supernatant fibronectin and collagen IV levels were increased in the PAF + HG + LPC group compared with the others (P<0.05); this was reversed by treatment with LY333531 (P<0.05). In cells treated with PAF, HG and LPC, PKCßI was translocated from the cytosol to the nucleus, an effect which was blocked when PKCßI expression was inhibited (P<0.05). The findings of the present study demonstrated that PAF stimulated ECM deposition in HMCs via activation of the PKC­TGF­ß1 axis in a DN model.

Benefits and harm of niacin and its analog for renal dialysis patients: a systematic review and meta-analysis.

PURPOSE: Clinical trials have shown that niacin and its analog, niacinamide, significantly reduce serum phosphate in patients undergoing dialysis. This review aimed to assess the benefits and harm of niacin and niacinamide in renal dialysis patients. METHODS: PubMed, EMBASE, and Cochrane Library were searched, without language limitation, randomized controlled trials (RCTs). Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, version 5.2, was used for meta-analysis. RESULTS: Five RCTs with a sample size of 230 patients were included. The meta-analysis showed that niacin and niacinamide significantly decreased serum phosphorus levels [weight mean difference (WMD) -0.88; 95 % confidence interval (CI) -1.19 to -0.57] as well as the calcium × phosphorus product (Ca × P) (WMD -9.15; 95 % CI -13.23 to -5.08), and increased high-density lipoprotein (HDL) levels (WMD 9.30; 95 % CI 5.86-12.74) in renal dialysis patients. Niacin significantly increased the risk of flushing [relative risk (RR) 33; 95 % CI 4.71-232.12] in these patients, while the risk of thrombocytopenia was significantly increased in the niacinamide group (RR 2.82; 95 % CI 1.14-6.94). However, sensitivity analysis showed that our finding regarding thrombocytopenia should be regarded with a low degree of certainty. CONCLUSION: Niacin and its analog effectively improved phosphorus metabolism in renal dialysis patients. However, niacin can cause flushing and niacinamide probably cause thrombocytopenia. Further larger sample size and well-designed RCTs are needed.

Enalapril versus losartan for adults with chronic kidney disease: a systematic review and meta-analysis.

AIM: Both enalapril and losartan are effective and widely used in patients with chronic kidney disease (CKD). This review aimed to evaluate the benefits of enalapril and losartan in adults with CKD. METHODS: PubMed, EMBASE, the Cochrane Library and ClinicalTrials.gov were searched, without language limitations, for randomized controlled trials (RCT), in which enalapril and losartan were compared in adults with CKD. Standard methods, consistent with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, were used. Reviewer Manager software, ver. 5.2, was used for meta-analysis. RESULTS: Of 318 citations retrieved, 17 RCT (14 parallel-group and three cross-over) met our inclusion criteria. The pooled analysis for parallel RCT showed that the effects of enalapril and losartan on blood pressure, renal function and serum uric acid (UA) were similar. Meta-analysis indicated that patients taking enalapril had a higher risk of dry cough (risk ratio, 2.88; 95% CI, 1.11-7.48; P=0.03). Sensitivity analysis showed good robustness of these findings. CONCLUSION: Enalapril has similar effects to losartan on systemic blood pressure, renal function and serum UA in patients with CKD, but carries a higher risk of dry cough. Larger trials are required to evaluate the effects of these medications on clinical outcomes.

Mycophenolate mofetil versus azathioprine as maintenance therapy for lupus nephritis: a meta-analysis.

AIM: The options for long-term maintenance therapy in lupus nephritis (LN) remain controversial. This meta-analysis of randomized controlled trials (RCTs) assessed the prognosis and safety of mycophenolate mofetil (MMF) versus azathioprine (AZA) used as maintenance therapy for lupus nephritis. METHODS: The data of Cochrane Library, PubMed, EMBASE were retrieved to search the studies about the RCT studies that compared MMF with AZA used as maintenance therapy for lupus nephritis. We extracted the data reflecting prognosis, which included mortality, end-stage renal failure (ESRF), renal relapse, doubling serum creatinine, and adverse effects, then further analyzed the combined results of data and calculated the relative risk (RR). RESULTS: Four RCT studies including 328 patients were enrolled into our meta-analysis. There was no difference between the patients receiving either MMF or AZA for maintenance therapy in preventing relapse, progression to end-stage renal failure, death and doubling of serum creatinine. MMF is not superior to AZA in terms of the risks of infection and gastrointestinal upset, but fewer patients receiving MMF developed leukopenia (RR 0.12; 95% confidence interval (CI), 0.04-0.39; P = 0.0004) and amenorrhoea (RR 0.17; 95% CI, 0.04-0.72; P = 0.02) than those receiving AZA. CONCLUSION: The current limited evidence suggests that MMF offers similar prognosis as AZA for maintenance therapy, while MMF appears safer than AZA in the treatment of lupus nephritis.

Differentiation of mesenchymal stem cell in the microenviroment of retinitis pigmentosa.

UNLABELLED: CORRESPONDENCE TO: Fang-Tian Dong. Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China. d_fangtian@sina.com AIM: To access the differentiation of rat mesenchymal stem cell (MSC) in the microenvironment of retinal degeneration induced by the administration of sodium iodate. METHODS: In-vitro cultured Lewis rat MSC were injected into the sub-retinal space of NaIO(3) induced retinal degeneration rat eyes (30g/L NaIO(3) 100mg/kg). To observe the trace and differentiation of MSC by immuno-fluorescent method successively in 5 weeks after the surgery. RESULTS: The majority of the transplanted cells stay in retinal pigment epithelium layer and cones & rods layer. From the 2(nd) week after transplantation, the engrafted MSC express PCK and rhodopsin under fluorescent microscope. CONCLUSION: MSC can survive mainly in the outer layer of retina in the microenvironment of retinal degeneration and differentiate forward the RPE cell and photoreceptor.

[Differentiation of rat mesenchymal stem cells in the microenvironment of choroidal neovascularization].

OBJECTIVE: To assay the differentiation of rat mesenchymal stem cells (MSCs) in the microenvironment of choroidal neovascularization (CNV). METHOD: Cultured BN rat MSCs were injected into the subretinal space in 25 Argon laser-induced CNV rat. The differentiation of MSCs was traced by immunofluorescent labeling successively in 5 weeks after the surgery. RESULTS: MSCs distributed on the surface of CNV in the 1st week after injection. From the 2nd week, CD31 positive MSCs were found in CNV until 5 weeks after cell injection, while rhodopsin positive MSCs in the photoreceptor layer were revealed until the 5th week after the injection. CONCLUSION: Injected MSCs in the microenvironment of CNV can differentiate into endothelium and photoreceptor.

[Prevalence and risk factors of retinopathy of prematurity].

OBJECTIVE: To investigate the prevalence and the risk factors of retinopathy of prematurity (ROP). METHODS: Totally 172 premature infants who were less than 37 weeks postconceptional age, or more than 37 weeks but weighing < 2 500 g at birth, and born at PUMC hospital from May 1, 2003 to November 30, 2004, were enrolled in this study. Their fundus were routinely checked. Diagnosis and staging of ROP were performed according to the international guidelines. Another 20 mature infants were selected as the control group. RESULTS: Twelve infants quitted the treatment or died. The remaining 160 infants completed the follow up. The prevalence of ROP in the premature group was 19.4%, while no ROP was found in the control group. The prevalence of ROP in subgroup with body weight < or = 2 000 g (28.4%) was significantly higher than in subgroup with body weight > 2 000 g (8.3%, chi2 = 10.217, P = 0.001) at birth. The prevalence of ROP in subgroup with postconceptional age < or = 32 weeks (42.5%) was significantly higher than in subgroup with postconceptional age > 32 weeks (11.7%, chi2 = 18.258, P = 0.000). The postconceptional age (OR = 0.959, P = 0.036) and body weight (OR = 0.999, P = 0.026) were the most important risk factors of ROP. Furthermore, blood transfusion ( OR = 0.076, P = 0.029) and Apgar score ( OR = 23.62, P = 0.012) were inversely correlated with ROP. Correlation was not found between ROP prevalence and oxygen inhalation mode, surface active substance, administration of dopamine and dexamethasone, and mother conditions. CONCLUSIONS: The prevalence of ROP is higher in premature infants than in mature infants. Shorter postconceptional age and lower body weight may result in higher ROP incidence. Routine screening of fundus in premature infants may be helpful for the early detection of ROP.

[Recent advances in retinopathy of prematurity].

Retinopathy of prematurity (ROP) is a vasoproliferative retinopathy. Worldwide, ROP is a major cause of blindness in children. This chapter describes its risk factors, etiology, diagnosis, treatment and recent advances.