Apoptosis and mitochondrial membrane potential changes of T lymphocytes from children with Down’s syndrome

Background: Down's syndrome (DS) patients present a high risk of developing alterations of the immune system. The increased susceptibility to bacterial and viral infection, hematologic malignancies and autoimmune disease, suggest that immunodeficiency is an integral part of DS. Little is known about the mitochondrial damage and tendency to apoptosis in peripheral T lymphocyte cells in DS individuals. Objective: to evaluate the tendency to apoptosis and mitochondrial membrane potential (ΔΨm) changes in peripheral T lymphocytes of DS children both in the presence and in the absence of acute infection. Patients and methods: The present study included thirty children had DS (all of them trisomy 21 of nondisjunction type), and thirty normal children, fifteen of each group had no evidence of acute infection and fifteen had acute infection. Potential apoptosis was measured by flow cytometry using annexin V. The ΔΨm was assessed by the retention of Rhodamine 123. Results: There was no significant difference in the percentage of CD3+ cells or potential apoptotic T lymphocytes between DS children and controls either in presence or in absence of acute infection. However, there was a significant decrease in ΔΨm in the peripheral T lymohocytes of DS children when compared to the controls. Conclusion: The function of T cells not their number is the main mechanism responsible for the impairment of the immune system in DS children. T lymphocytes in peripheral blood from DS patients do not display an increased tendency to undergo apoptosis although a significant loss of ΔΨm was found.Keywords: Down's syndrome, apoptosis, mitochondrial membrane potentialEgypt J Pediatr Allergy Immunol 2010;8(1):35-4

cardiotoxicity with immune system targeting drugs a meta analysis of anti pd pd l1 immunotherapy randomized clinical trials

n/

Myocardial dysfunction in malnourished children

<b>Background</b> : Malnourished children suffer several alterations in body composition that could produce cardiac abnormalities. <b>Aim</b> : The aim of the present study was to detect the frequency of myocardial damage in malnourished children as shown by echocardiography and cardiac troponin T (cTnT) level. <b>Methods</b> : Forty-five malnourished infants and young children (mean&#177;SD of age was 11.24 &#177;7.88 months) were matched with 25 apparently healthy controls (mean&#177;SD of age was 10.78&#177;6.29 months). Blood sample was taken for complete blood picture, liver and kidney function tests, serum sodium, potassium, calcium levels and cTnT. All the malnourished children were subjected to echocardiographic evaluation. <b>Results</b> : Malnourished children showed a significantly lower left ventricular (LV) mass than the control group. The LV systolic functions were significantly impaired in patients with severe malnutrition. The cTnT level was higher than the upper reference limits in 11 (24.44&#x0025;) of the studied malnourished children and all of them had a severe degree of malnutrition. The cTnT level was significantly higher in patients with anemia, sepsis and electrolyte abnormalities and it correlated negatively with LV ejection fraction (EF). Six of the studied children with high cTnT levels (54.5&#x0025;) died within 21 days of treatment while only one case (2.9&#x0025;) with normal level of cTnT died within the same period. <b>Conclusions</b>: LV mass is reduced in malnourished children. Children with severe malnutrition have a significant decrease in LV systolic functions. Elevated cTnT levels in malnourished children has both diagnostic and prognostic significance for cardiomyocyte damage

Amelioration of the Protein Expression of Cox2, NFB, and STAT-3 by Some Antioxidants in the Liver of Sodium Fluoride–Intoxicated Rats

The present study aimed to explore the efficiency of N-acetyl cysteine (NACC) or thymoquinone (TMQ) alone or in combination in the downregulation of inflammatory molecule expression and decreasing hepatic injury in response to sodium fluoride (SF). Sodium fluoride upregulated serum alanine and aspartate transferases activities, tumor necrosis factor α and hepatic malondialdehyde and nitric oxide levels, and the expression of cyclooxygenase 2, nuclear factor κB cell, and signal transducer and activator of transcription 3. In contrast, hepatic glutathione level, superoxide dismutase activity, and nuclear factor erythroid 2-related factor 2 expression were decreased. However, the concurrent treatment with antioxidants, alone or in combination, modulated the levels of these parameters. Histopathological examination revealed that SF treatment resulted in focal areas of massive hepatic degeneration and many degenerated hepatocytes, whereas the treatment with TMQ or NACC exhibited moderate improvement in cellular degeneration of the liver with many abnormal cells. Rats receiving a combination of TMQ and NACC showed marked improvement in cellular degeneration of liver with apparently normal hepatic architecture with very few degenerated hepatocytes. The results also revealed that the combination of TMQ and NACC is the most effective regimen in ameliorating SF toxicity, suggesting their efficacy against the toxicity of fluoride compounds. Their activities might be mediated via multiple molecular pathways

Design of Epitope-Based Peptide Vaccine against Pseudomonas aeruginosa Fructose Bisphosphate Aldolase Protein Using Immunoinformatics

Pseudomonas aeruginosa is a common pathogen that is responsible for serious hospital-acquired infections, ventilator-associated pneumonia, and various sepsis syndromes. Also, it is a multidrug-resistant pathogen recognized for its ubiquity and its intrinsically advanced antibiotic-resistant mechanisms. It usually affects immunocompromised individuals but can also infect immunocompetent individuals. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against fructose bisphosphate aldolase (FBA) of Pseudomonas aeruginosa using immunoinformatics tools. The protein sequences were obtained from NCBI, and prediction tests were undertaken to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility, and hydrophilicity tests. Six MHC I epitopes were found to be promising, while four MHC II epitopes were found promising from the result set. Nineteen epitopes were shared between MHC I and II results. For the population coverage, the epitopes covered 95.62% worldwide excluding certain MHC II alleles. We recommend in vivo and in vitro studies to prove its effectiveness

Direct conversion of an agricultural solid waste to hydrocarbon gases via the pyrolysis technique

The increased awareness toward the global warming and the environmental pollution problems has stimulated the utilization of the alternative energy sources since they can positively take part in minimizing such problems. Among these sources, biomass based solid wastes is counted as one of the most promising in the field of energy production. Thus, the current research work focuses on the conversion of rice straw (a biomass-based solid waste) into hydrocarbon gases in general and methane (main constituent of natural gas) in particular. The reduction of the operational temperature and the elevated rate of solid-to-gas conversion are newly presented approaches in this research. Specifically, the used operating temperature, in this study, had been 250 °C while the well-known temperature range for slow pyrolysis is 380–550 °C. Another approach is represented in this work via the orientation of the obtained biogas to become mainly hydrocarbon gases instead of CO, CO2 and CH4 mixture, as the common for such pyrolysis processes. The attained high rate of solid-to-gas conversion (80%) while at low temperature is also a new approach of this study since such high rate is just possible in the flash pyrolysis (750–900 °C). The increased conversion rate was achieved via reducing the particles size of the used solid-biomass to a nano-sized range. Keywords: Environmental biomass pollutant, Slow pyrolysis, Bio-fuels, Green energy, Waste managemen

Antimicrobial Resistance and Comparative Genome Analysis of Klebsiella pneumoniae Strains Isolated in Egypt

Klebsiella pneumoniae is an important human pathogen in both developing and industrialised countries that can causes a variety of human infections, such as pneumonia, urinary tract infections and bacteremia. Like many Gram-negative bacteria, it is becoming resistant to many frontline antibiotics, such as carbapenem and cephalosporin antibiotics. In Egypt, K. pneumoniae is increasingly recognised as an emerging pathogen, with high levels of antibiotic resistance. However, few Egyptian K. pneumoniae strains have been sequenced and characterised. Hence, here, we present the genome sequence of a multidrug resistant K. pneumoniae strain, KPE16, which was isolated from a child in Assiut, Egypt. We report that it carries multiple antimicrobial resistance genes, including a blaNDM-1 carbapenemase and extended spectrum β-lactamase genes (i.e., blaSHV-40, blaTEM-1B, blaOXA-9 and blaCTX-M-15). By comparing this strain with other Egyptian isolates, we identified common plasmids, resistance genes and virulence determinants. Our analysis suggests that some of the resistance plasmids that we have identified are circulating in K. pneumoniae strains in Egypt, and are likely a source of antibiotic resistance throughout the world

Impact of tricyclic antidepressants, selective serotonin reuptake inhibitors, and other antidepressants on overall survival of patients with advanced lung cancer from 2004 to 2014: University of Cincinnati experience

OBJECTIVES: To evaluate and categorize the survival benefit of tricyclic antidepressants (TCAs) in lung cancer patients based on systematic computational drug repositioning data. METHODS: Data were retrospectively extracted from the medical records of non-small cell lung cancer (NSCLC) patients from the University of Cincinnati Cancer Medical Center database. Patients receiving antidepressants during their course of anti-cancer treatment were compared with those without antidepressants. Data were analyzed using Kaplan–Meier survival curves with the log-rank test, and overall survival (OS) was calculated from the date of diagnosis until last follow-up or death. RESULTS: The median OS at 2 and 5 years for patients on antidepressants was 20.3 months (54.7% and 42%) vs 44.3 months (47.6% and 43.2%), which was not significant. The median OS for patients receiving TCAs, selective serotonin reuptake inhibitors, and other antidepressants was 3.17 months, 31.33 months, and 18.50 months, respectively. CONCLUSION: We found no significant survival benefit for TCA use in combination with anti-cancer agents in NSCLC patients