Effect of Everolimus versus Bone Marrow-Derived Stem Cells on Glomerular Injury in a Rat Model of Glomerulonephritis: A Preventive, Predictive and Personalized Implication.

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6-8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

Prevalence of iron deficiency anemia and beta thalassemia carriers among relatives of beta thalassemia patients in Nile Delta region, Egypt: a multicenter study.

BACKGROUND: Screening of ß thalassemia among close relatives is more feasible in highly prevalent countries with limited resources. The purpose of this study is to determine the prevalence of ß thalassemia carriers and iron deficiency anemia among relatives of ß thalassemia patients in Mid Delta, Egypt. METHODS: This is a cross-sectional multi-center study conducted on 2118 relatives of patients with ß thalassemia from different Egyptian governorates in the Mid Delta region. They were subjected to history taking with precise determination of geographic location, general examination, and the following investigations: complete blood counts, serum ferritin for those who showed microcytic hypochromic anemia, and high-performance liquid chromatography for those who were not diagnosed as iron deficiency anemia. RESULTS: The total prevalence of iron deficiency anemia among close relatives of confirmed ß thalassemia patients in the Nile Delta region was 17.19%. The highest prevalence of iron deficiency anemia (45.05%) was reported in Al-Gharbia Governorate, followed by Al-Menoufia Governorate (21.67%), and the lowest prevalence was that of Al-Sharkia Governorate (4.91%). The differences were highly statistically significant (p < 0.001). ß thalassemia carrier prevalence rate in the studied relatives was 35.84%, with the highest prevalence detected in Al-Sharkia Governorate (51.32%), followed by Kafr-Alsheikh and Al-Dakahilia Governorates (41.78%, 37.13%) respectively, while Al-Menoufia Governorate had the lowest prevalence rate (25.00%). These differences were also highly statistically significant (p < 0.001). CONCLUSION: More than one-third of relatives of patients with ß thalassemia are carriers of the disease, while 17.19% suffer from iron deficiency anemia. This study demonstrates the importance of tracing the high number of beta thalassemia carriers among relatives of patients with ß thalassemia in Egypt.

Cell Death Markers in Children with Immune Thrombocytopenic Purpura: A Preliminary Study.

Immune thrombocytopenic purpura (ITP) is an autoimmune disease with possible dysregulation of the apoptotic pathways. We aimed to evaluate the possible role of some apoptotic markers (caspase 3, caspase 8 and BCL2) in the pathogenesis and course of ITP. We investigated some apoptotic markers (caspase 3, caspase 8 and BCL2) using the flow cytometry in 60 children with newly diagnosed ITP, 20 children with chemotherapy-related thrombocytopenia (CRT) and 20 healthy children. We also assessed the effects of intravenous immunoglobulin (IVIG) and methyl prednisolone therapies on the platelet apoptosis in children with newly diagnosed ITP. We demonstrated significantly higher values of caspase 3 in the newly diagnosed ITP group than control and CRT groups, and non-significantly higher values of caspase 8 in the ITP group than the healthy group. After IVIG treatment, the platelet count increased in all patients, and there was a significant decrease in caspase 3 and caspase 8 levels while BCL2 level increased. Regarding methylprednisolone treatment, there was a significant decrease in BCL2 and caspase 8 levels while caspase 3 levels did not significantly decrease. There is a possible role of the caspase dependent cell death pathway of the platelets in the occurrence of newly diagnosed ITP. There is heterogeneity in the apoptotic changes of newly diagnosed ITP children who received IVIG versus those who received methylprednisolone.

Beta Thalassemia Carrier Rate: Problem Burden among High School Children.

Background & Aim of the Work: ß-Thalassemia (ßT) is highly prevalent in some countries like Egypt. Accurate data about actual disease prevalence and heavily prevalent geographic locations are essential to help in early detection and in setting up effective preventive programs. We aim for screening ßT carriers among Egyptian high school students in the Delta region. SUBJECTS AND METHODS: A cross-sectional multicenter study was carried out on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for ßT carrier status using high-performance liquid chromatography. RESULTS: The total prevalence of ßT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al- Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. CONCLUSION: Despite the premarital national screening program for ßT in Egypt, the carrier rate is still high. More effort should be done into the proper implementation of national prevention programs.

Psychiatric Disorders and Quality of Life in Egyptian Patients with Chronic Immune Thrombocytopenic Purpura: A Single Center Study.

The impact of chronic immune thrombocytopenic purpura (ITP) on the psychological health and quality of life is evident among children and adolescents. We aimed to describe psychological disorders and assess quality of life in children with chronic ITP and compared their results with their healthy peers. A cross-sectional comparative study was carried out in a tertiary care university-affiliated hospital during a period from November, 2015 till April, 2018. We enrolled 119 children with chronic ITP and compared with 220 healthy peers. Relevant demographic and clinical data were collected and statistically analyzed. Quality of life for both patients and control groups was measured using pediatric quality of life inventory version 4 (Arabic one). Also psychiatric evaluation of both groups was done using Arabic version of Mini-International Neuropsychiatric Interview for Children (Mini-KID). Majority of patients (90.7%) exhibited mucocutaneous bleeding. Most of patients (61.3%) did not need any definitive treatment for chronic ITP while 38.6% received second line therapy. About one-third of the patients needed rescue medications to control active bleeding. The scores of all sub-scales of Peds QL 4.0 were significantly decreased among patients group when compared to their healthy peers (P < 0.001). General anxiety disorder and oppositional defiant disorders were the commonest psychiatric disorders among children with chronic ITP. Quality of life in children with chronic ITP is markedly impaired with occurrence of a variable spectrum of psychiatric disorders among the studied patients.

Histiocytosis disorders in Northeast Egypt: epidemiology and survival studies (a 5-year study).

Histiocytosis disorders include a wide group of disorders characterized by monocytes, macrophages and dendritic cell infiltration of different tissues. There are few clinico-epidemiologic studies of such disease. Our study was designed to look at the clinico-epidemiological features and outcome of patients with histiocytosis disorders in Northeast Egypt. Twenty-seven cases with histiocytosis disorders accrued over a 5-year period were analyzed and classified as having unifocal, multifocal, or multisystem disease. They were 14 males and 13 females. Twenty-two patients representing 81.5% of cases were more than two years of age while 5 patients (18.5%) were less than 2 years. Lymphadenopathy was the commonest presentation (55.55%) followed by bone lesions (44.44%). Involvement was unifocal in 12, multifocal in 10, and multisystem in 5 cases. The histological features were relatively uniform regardless of the clinical severity, and consisted of Langerhans cells, eosinophils, histiocytes, plasma cells, giant cells and fibrosis. The treatment consisted of a combination of surgery, chemotherapy, and/or radiotherapy. Lymphadenopathy was the most common clinical presentation in our locality. Response to treatment was poor in patients with multisystem disease. Patients with age less than 2 years were more likely to have increased risk of morbidity and mortality, due to widespread disease.