Assessment of plasma and urinary transforming growth factor beta 1 (TGF-β1) in children with lupus nephritis

Background: Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE). Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Transforming growth factor- β1 (TGF-β1) is an immunosuppressive cytokine, as it inhibits T and B cell proliferation and NK cell cytotoxic activity . Objective: The aim of this study was to assess serum and urinary TGF- β1 levels in children with SLE and their possible role in the renal involvement and activity of the disease. Study design: This cross sectional study was conducted in Nephrology Unit of Pediatric Department, plus Outpatient Clinic of Rheumatology Department, Zagazig University Hospital during the year of 2010. Methods: Twenty-five pediatric patients with SLE were randomly selected and classified according to into 2 groups: Group (Ι): included 13 patients presented with urinary abnormalities and/or disturbed renal function(active nephritis): 5 males, 8 females. Their mean age was 9.7±2.53 years and the mean disease duration was 2.46±1.4 years. Group (ΙΙ): included 12 patients presented by lupus without nephritis : 5 males,7 females. Their mean age was 9.9±2.1 years and the mean disease duration was 2.41±0.9 years. Control group(group ΙΙΙ): Twenty healthy children of matched age and sex served as a control group included 8 males ,12 females. Their mean age was 10.0±2.3 years. Results: There was no significant difference among studied patients groups regarding age, sex , disease duration and lupus therapy (p>0.05). There was a significant difference between both groups regarding urinary albumin and serum creatinine (2.76±0.97 and 1.96±0.84 mg/dl respectively), while there was a high significant difference between them regarding C3 (47.3±12.5 and 76.6±6.6 mg/ml respectively) and anti double stranded DNA (anti-dsDNA) (80.7±32.8 and 26.8±4.5 IU/ml respectively). Plasma TGF- β1 showed significantly lower levels in patients with active nephritis relative to other groups, while urinary TGF- β1 levels were significantly high in SLE patients either with active or silent nephritis when compared with the control group. Plasma TGF- β1 showed a highly significant positive correlation with C3 and a highly significant negative correlation with serum creatinine, urinary albumin, anti dsDNA and SLE disease activity index (SLEDAI) score. While, urinary TGF- β1 had a significant negative correlation with C3 and a high significant positive correlation with anti-dsDNA and SLEDAI score. Conclusion: Low plasma TGF β1 level and increased urinary TGF β1 excretion denotes active renal affection in children with SLE.Keywords: SLE , nephritis , TGF- β1Egypt J Pediatr Allergy Immunol 2011;9(1):21-2

Anti-C1q and anti-dsDNA antibodies in systemic lupus erythematosus: Relationship with disease activity and renal involvement in Sharkia governorate, Egypt

AbstractIntroductionRenal involvement is one of the main determinants of poor prognosis of systemic lupus erythematosus (SLE). Kidney biopsy is an invasive procedure and accompanied by potential risks. Thus defining a reliable biomarker of kidney involvement in SLE is highly desirable.Aim of the workTo assess the role of anti-C1q Ab in combination with anti-dsDNA Ab in detection of SLE disease activity and renal involvement (lupus nephritis).Patients and methodsAnti-C1q Ab and anti-dsDNA antibodies were determined in 60 randomly selected adult SLE patients one of them refused the biopsy and those who completed the study were 59. The control group included 25 age and sex matched volunteers. According to lupus nephritis (LN) and SLEDAI score, patients were divided into four groups: group 1, 11 patients had active disease with LN; group 2, 20 patients had inactive disease with LN; Group3, six patients had active disease without LN; group 4, 22 patients had inactive disease without LN.ResultsA significant association of active lupus nephritis detection and the presence of either one or both of the studied antibodies (anti-C1q Ab or anti-dsDNA). None of the patients of group 1 had anti-C1q Ab only, and none was negative for anti-C1q Ab and anti-dsDNA Ab together. Levels of anti-C1q Ab and anti-dsDNA Ab were significantly higher in more active LN than less active LN. Anti-dsDNA and anti-C1q antibodies sensitivity and specificity for detection of more active LN was 85.0% and 64.0% and 70.0% and 55.0%, respectively, and 75.0% and 91.0% for both. Both antibodies had a positive correlation with SLEDAI score and proteinuria and a negative correlation with C3 reduction. A high significant positive correlation was detected between anti-C1q Ab and anti-dsDNA Ab.ConclusionAnti-C1q Ab, in combination with anti-dsDNA Ab may serve as potential reliable and none invasive markers of SLE disease activity and renal involvement to avoid unnecessary renal biopsies

Protective Effects of Naringin–Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation

Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin–dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites