Amani M. Ismail

Effect of Angiotensin II Receptor Blocker on Plasma Levels of TGF-β1 and Interstitial Fibrosis in Hypertensive Kidney Transplant Patients

Background/Aim: Transforming growth factor-β1 (TGF-β1) is involved in the pathogenesis of chronic allograft nephropathy after kidney transplantation. The aim of the study was to evaluate the effect of the angiotensin receptor blocker losartan on TGF-β1 plasma levels and proteinuria in hypertensive transplant recipients. Methods: A total of 162 transplant recipients were included in the study. The patients were randomized into 3 groups: group 1 received losartan; group II received an angiotensin-converting enzyme inhibitor (captopril), and group III received a calcium channel blocker (amlodipine). All the parameters were recorded at the time of therapy initiation and at 1, 4 and 12 weeks and 12 months thereafter. Graft biopsy before the start and at the end of the study was done to evaluate histopathological progression. Results: Blood pressure was controlled in the 3 groups; however, the need for other antihypertensive agents was significant in groups I and II. Treatment with losartan significantly decreased the plasma level of TGF-β1, 24-hour urinary protein and serum uric acid (p < 0.05). No significant changes were seen in the hemoglobin or serum potassium levels. The rate of histopathological progression was significantly lower in the losartan group. No patient was discharged from the study due to side effects. Conclusions: After transplantation all drugs were able to control blood pressure with good safety and tolerability. The study demonstrates that ARB significantly decreases the plasma levels of TGF-β1, proteinuria and uric acid. These results could play an important and decisive role in the treatment and prevention of chronic allograft nephropathy.

Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice.

Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ~5–10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months. Optimization of the culture conditions are required to improve the yield of IPCs and their functional performance.

Long-term follow-up of living kidney donors: a longitudinal study

To analyse retrospectively the general health status and renal and cardiovascular consequences of living‐related kidney donation, as the long‐term effects of unilateral nephrectomy for kidney donation are of particular interest with the currently increasing practice of living‐donor transplantation.

Decline of viral hepatitis prevalence among asymptomatic Egyptian blood donors: A glimmer of hope

BACKGROUND Viral hepatitis is an important etiological agent of chronic hepatitis and liver disease and is a major cause of morbidity and mortality especially in Egypt since it has the highest prevalence of hepatitis C virus (HCV) infection. We aimed to assess if there is any change in the annual seroprevalence of both HCV and hepatitis B virus (HBV) infection in Egypt in the current era. METHODS Our study included 55,922 potentially healthy asymptomatic blood donors; 52,280 males and 3642 females with mean age of 30.98+/-8.6 years. All of them were volunteers for the first time and 70% were from rural areas. We applied our own questionnaire that included past medical history, surgical history, and history of blood donation. We screened their sera for the presence or absence of anti-HCV antibodies with the 3rd generation enzyme-linked immunosorbent assay (ELISA) and the presence or absence of hepatitis B surface antigen (HBsAg) with ELISA. RESULTS The cumulative seroprevalence of HCV and HBV infection was 11.95% and 1.3% respectively. The annual seroprevalence of both viruses showed a declining pattern throughout the study period from 17.7% to 7.4% regarding HCV and HBV infection from 2.3% to 0.9%. The decline trends for both viral infections were observed for both genders. CONCLUSION This study carries a glimmer of hope because of a decline in seroprevalence of viral hepatitis in Egypt. However stringent implementation of infection control programs in Egypt is mandatory to face this furious health problem.

Prediction of graft survival of living-donor kidney transplantation: nomograms or artificial neural networks?

Background. An artificial neural networks (ANNs) model was developed to predict 5-year graft survival of living-donor kidney transplants. Predictions from the validated ANNs were compared with Cox regression-based nomogram. Methods. Out of 1900 patients with living-donor kidney transplant; 1581 patients were used for training of the ANNs (training group), the remainder 319 patients were used for its validation (testing group). Many variables were correlated with the graft survival by univariate analysis. Significant ones were used for ANNs construction of a predictive model. The same variables were subjected to a multivariate statistics using Cox regression model; their result was the basis of a nomogram construction. The ANNs predictive model and the nomogram were used to predict the graft survival of the testing group. The predicted probability(s) was compared with the actual survival estimates. Results. The ANNs sensitivity was 88.43% (95% confidence interval [CI] 86.4-90.3), specificity was 73.26% (95% CI 70-76.3), and predictive accuracy was 88% (95% CI 87-90) in the testing group, whereas nomogram sensitivity was 61.84% (95% CI 50-72.8) with 74.9% (95% CI 69-80.2) specificity and predictive accuracy was 72% (95% CI 67-77). The positive predictive value of graft survival was 82.1% and 43.5% for the ANNs and Cox regression-based nomogram, respectively, and the negative predictive value was 82% and 86.3% for the ANNs and Cox regression-based nomogram, respectively. Predictions by both models fitted well with the observed findings. Conclusions. These results suggest that ANNs was more accurate and sensitive than Cox regression-based nomogram in predicting 5-year graft survival.

Evaluation of a synchronous twin-pulse technique for shock wave lithotripsy: the first prospective clinical study.

To present the results of the first clinical study of a synchronous twin‐pulse technique for extracorporeal shock‐wave lithotripsy (ESWL), which is effective for in vitro stone fragmentation and safe when assessed in vivo on animal tissue.

Living-donor kidney retransplantation: risk factors and outcome

Authors from Mansoura in Egypt present a study of risk factors and outcome from living‐donor renal re‐transplantation. This is sometimes avoided as being unlikely to have a good outcome, but it is shown here to be the treatment of choice in patients who have lost the primary graft.

Levamisole: adjunctive therapy in steroid dependent minimal change nephrotic children

Abstract In children with minimal change nephrotic syndrome (MCNS), the steroid dependent group constitutes an especially difficult case for management. Patients in this group are prone to serious steroid side effects. Additionally, alkylating agents commonly fail to maintain remission and expose patients to more side effects. Therapy with the immunostimulant drug levamisole may therefore be another option in the attempt to maintain remission with minimal side effects. We prospectively treated 20 of our steroid dependent primary MCNS patients with levamisole. All patients were children, with an age range of 3–15 years; 16 were boys and 4 were girls. Remission was firstly induced by steroids, then levamisole was added in a dose of 2.5 mg/kg body weight on alternate days for 6 months. During this period we attempted to withdraw steroids completely and maintain patients on levamisole alone. We followed up our patients for the occurrence of relapse and side effects during this period and for a further 6 months after stopping levamisole. In 11 out of 20 children (55%), we successfully stopped steroids for more than 2 weeks. At the end of the 6-month treatment period (i.e. after 4 months of steroid discontinuation), ten patients (50%) were maintaining remission on levamisole alone. At the end of the 12-month study period (i.e. after 6 months of levamisole discontinuation), five patients (25%) were still in remission without any treatment for the previous 6 months. No significant side effects were reported during levamisole therapy. None of the patients developed neutropenia, but the leukocyte count showed a significant reduction in those who responded to levamisole treatment. We concluded that levamisole therapy for 6 months is a safe and perhaps effective therapy in a subset of children with steroid dependent MCNS to enable an otherwise infeasible withdrawal of steroids. This may be worth a trial before other types of more hazardous adjunctive therapies are considered.

Determination of Cu2 +, Zn2 + and Pb2 + in biological and food samples by FAAS after preconcentration with hydroxyapatite nanorods originated from eggshell

Hydroxyapatite nanorods (HAPNRs) were prepared from recycled eggshell by using precipitation method. The structure of the HAPNRs was physicochemically and morphologically characterized by X-ray diffraction, transmission electron microscopy and Fourier transform infrared spectroscopy. The resulting HAPNRs were used for solid phase extractive preconcentration of Cu(2+), Zn(2+) and Pb(2+) prior to its determination by flame atomic absorption spectrometry. Experimental variables that influence the quantitative extraction of metal ions were optimized by both batch and column methods. The analytes were quantitatively sorbed on the matrix between pHs6 and 9. The maximum sorption capacity of the HAPNRs has been found to be 2.43, 2.37 and 2.53 mmol g(-1) for Cu(2+), Zn(2+) and Pb(2+), respectively, with the preconcentration factor of 250. The 3σ detection limit and 10σ quantification limit for Cu(2+), Zn(2+) and Pb(2+) were found to be 0.72, 0.55 and 5.12 μg L(-1) and 2.40, 1.83 and 17.06 μg L(-1), respectively. The calibration curves were linear up to 250 μg L(-1) for Cu(2+), 300 μg L(-1) for Zn(2+) and 400 μg L(-1) for Pb(2+). Accuracy of the proposed method was verified using certified reference materials (NCS ZC85006 Tomato, Seronorm Trace Elements Whole Blood L-1, Seronorm Trace Elements Whole Blood L-3 and Seronorm Trace Elements Urine). The present method was successfully applied to the analysis of these metal ions in sea water, biological and food samples.

Generation of Insulin-Producing Cells from Human Bone Marrow-Derived Mesenchymal Stem Cells: Comparison of Three Differentiation Protocols

Introduction. Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs) to form insulin-producing cells (IPCs). We compared the relative efficiency of three differentiation protocols. Methods. Human bone marrow-derived MSCs (HBM-MSCs) were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), and β-mercaptoethanol-based (three-step protocol). At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. Results. By immunolabeling, the proportion of generated IPCs was modest (≃3%) in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. Conclusion. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.