Zinc Oxide Nanoparticles Induced Testicular Toxicity Through Inflammation and Reducing Testosterone and Cell Viability in Adult Male Rats.

Zinc oxide nanoparticles (ZnO NPs) have wide applications in daily life. Therefore, there is growing interest in the potential harmful impacts of these particles on human health. The present study was conducted to investigate the potential toxic effects of ZnO NPs (40 and 70 nm) compared to ZnO on the testes of rats. ZnO NPs were synthesized and characterized by transmission electron microscopy (TEM) and X-ray diffraction (XRD). Adult male rats were randomly divided into four groups (n = 8): Group I (control), Group II (ZnO) received daily oral administration of ZnO (50 mg/kg), and Groups III and IV received daily oral administration of ZnO NPs of 40 nm or 70 nm at 50 mg/kg, respectively. All treatments continued for 50 consecutive days. ZnO and ZnO NPs reduced body and testis weights, sperm count and motility, serum luteinizing hormone (LH) and testosterone levels, testicular cytochrome p450 17A1 (CYP17A1) and cytochrome p450 1B1 (CYP1B1) concentrations, and the expression of p53 and cdk1. These treatments elevated testicular myeloperoxidase and serum acid phosphatase activities as well as sperm abnormalities. ZnO NPs reduced LH levels, which decreased CYP17A1 and CYP1B1, resulting in reduced synthesis of testosterone. ZnO NPs enhanced testicular inflammation and reduced cell viability. All these effects were manifested as reduced sperm motility and increased sperm deformities. Compared to macromolecules, nanoparticles exhibited significantly higher toxicity. The larger diameter ZnO NPs had more profound toxicity than the smaller-sized particles.

The role of matrix metalloproteinases 2 in atherosclerosis of patients with chronic kidney disease in type 2 diabetes.

Matrix metalloproteinase-2 (MMP2) has been implicated in chronic disease and cardiovascular disease. However, there is no knowledge about the correlations between serum levels of MMP-2, proteinuria and atherosclerosis in patients with diabetic nephropathy (DN). We investigated whether serum MMP-2 levels were associated with proteinuria, intima-media thickness (IMT) in DN patients. Diabetic patients not on hemodialysis (n = 50) were enrolled for the study. MMP-2 levels were measured using an ELISA system. IMT was evaluated by highresolution ultrasonography. Univariate analyses revealed that MMP-2 (P = 0.013) were independent correlates of proteinuria. Further, multivariate analyses revealed that MMP-2 levels (P = 0.001) were independent correlates of IMT. MMP-2 levels were significantly (P = 0.001) higher in patients with atherosclerosis than those without it. The present study demonstrates that serum levels of MMP-2 were one of the independent correlates of proteinuria and IMT in patients with DN. Our results suggest that serum MMP-2 levels may be one of the risk factors for renal damage and atherosclerosis in DN patients.

Serum Soluble Interleukin 2 Receptor Level as a Marker of Acute Rejection in Pediatric Kidney Transplant Recipients.

BACKGROUND: Despite advances in immunosuppression, acute allograft rejection remains one of the key factors affecting patient and graft survival in pediatric kidney transplantation. The aim of the study is to evaluate the role of serum soluble IL2 receptor (sIL2R) level as a noninvasive assessment parameter of acute rejection (AR). METHOD: Serum sIL2R level was measured (using enzyme-linked immune-sorbent assay technique) in 60 pediatric kidney transplant recipients (30 recipients with AR and 30 transplant recipients with stable graft function). RESULTS: The mean values of sIL2R level in patients experiencing AR (14.8 ± 6.54) ng/mL were significantly higher than that in patients with stable graft functions (6.44 ±1.95) ng/mL (p = 0.0001). In addition; patients with AR proved by graft biopsy had their mean values of sIL2R level (16.19 ± 7.48) ng/mL significantly higher than that of other recipients in the study population (p = 0.032). CONCLUSION: Serum sIL2R level may serve as a noninvasive diagnostic indicator in pediatric kidney transplant recipients experiencing AR.

The effect of on-line hemodiafiltration on improving the cardiovascular function parameters in children on regular dialysis.

The cardiovascular disease is an important cause of morbidity and accounts for almost 50% of deaths in patients undergoing maintenance dialysis. Many harmful molecules of the uremic milieu, such as the middle molecules, are difficult to remove by conventional hemodialysis (HD). On-line hemodiafiltration (OL-HDF) can achieve a considerable clearance of middle molecules and, together with its sterile ultrapure infusate, may have favorable effects on inflammation and cardiovascular complications. We aimed in this study to assess the effect of OL-HDF on improving the chronic inflammatory state associated with chronic kidney disease and the possible impact of these changes on myocardial function in chronic HD children. Thirty pediatric patients [12 (40%) males and 18 (60%) females with a mean age of 11.3 ± 3.2 years] on conventional HD for at least six months were switched to OL-HDF for six months. Variables for comparison at the end of each period included the levels of serum C-reactive protein and Kt/V as well as electrocardiography and echocardiographic measurements, including left ventricular mass index (LVMI). On changing from HD to OL-HDF, there was a significant decrease in hs-CRP (from 7.9 ± 8.9 to 3.4 ± 3 µ g/mL) (P = 0.01) and frequency of diastolic dysfunction (P = 0.04), while systolic function (FS and EF) improved significantly (P = 0.007 and 0.05, respectively), while LVMI did not change. We conclude that OL-HDF was well tolerated in children with improvement of the systolic function of the myocardium and the overall frequency of diastolic dysfunction.

Study of serum hepcidin in hereditary hemolytic anemias.

The aim of this study was to assess the level of hepcidin in hereditary chronic hemolytic anemias and to correlate the serum hepcidin levels to the need for blood transfusions (frequency of blood transfusions and the serum ferritin level). Seventy pediatric patients with hereditary chronic hemolytic anemias, attending to hematology clinics of Cairo University and Misr University for Science and Technology (MUST) hospitals were the subjects of this study [53 patients with ß-thalassemia major (ß-TM), 10 patients with ß-thalassemia intermedia (ß-TI), four patients with congenital spherocytosis and three patients with sickle cell disease) (38 males and 32 females)]; their ages ranged from 1-14 years. Seventy normal children, age- and sex-matched, served as the control group. The results of this study revealed decreased hepcidin levels in patients (all types of congenital chronic hemolytic anemias) [mean ± SD (standard deviation) = 22.9 ± 6.0] compared to controls (mean ± SD = 132.4 ± 16.7) with highly significant statistical difference in between. Hepcidin levels were higher in ß-TM patients (mean ± SD = 23.7 ± 6.2) than in ß-TI patients (mean ± SD = 21.8 ± 4.0), the hepcidin to ferritin ratio was significantly less than one. In ß-TM patients, the mean ± SD was 0.03 ± 0.004, and in ß-TI patients the mean ± SD = 0.025 ± 0.002, with highly significant statistical difference with hepcidin-to-ferritin ratios in controls being mean ± SD = 2.3 ± 0.7. Hepcidin and hepcidin/ferritin ratios can be used as good markers of hemolytic anemia and iron overload as they have very high sensitivity (99.0 and 99.0%, respectively) and very high specificity (98.0 and 97.0%, respectively). Our findings highlight the potential usefulness of hepcidin measurement as a diagnostic tool. The use of hepcidin as an adjuvant therapy with iron chelators is important as it has a vital role in combating hemosidrosis.