Assessment of immune function in Down syndrome patients

In Down syndrome (DS), trisomy 21 leads to overexpression of gene coding for specific enzymes. This overexpression translates directly into biochemical aberrations that affect multiple interacting metabolic pathways which culminates in cellular dysfunction and contributes to the unique pathogenesis of DS. The aim of this study is to evaluate parameters of immune response in terms of cytokines [tumor necrosis factor-a (TNF-a) and interlukin-2 (IL-2)] together with the quantitative expression of cystathionine beta synthase (CBS), whose transsulfuration pathway generates cysteine and hydrogen sulfide (H2S). H2S is known to boost host defense at physiological concentrations and to display cytotoxic activity at higher concentrations. Calcineurin activity (CAN) was also measured as its dysregulation has been shown to cause immune  suppression. Subjects were 60 DS patients vs. 30 age and socioeconomic matching healthy controls. In their blood, the cytokines: TNF-a and IL-2, together with CBS and its by product H2S as well as CAN activity, were measured. Results showed that CBSmRNA relative expression (0.56± .06 vs. 0.32 ± .02), plasma H2S (72 ±8.5 vs. 50.8 ± 4.1) and TNF-a (8.11 ± .01 vs. 3.6± 0.9) were significantly higher among DS patients compared to controls, while CAN (0.27 ± 0.1 vs. 0.45 ±0.2 units), was significantly decreased in blood of DS patients compared to controls. IL-2 (36.4 ± 2.6 vs. 37.4 ±0.9) showed no significant difference between DS patients and controls. Accordingly it can be concluded that excessive synthesis of multiple gene products derived from overexpression of the genes present on chromosome 21 may be the cause for decreased immunity in DS patients compared to controls

Caveolin 3 gene and mitochondrial tRNA methionin gene in Duchenne muscular dystrophy

Background: It was recently reported that Duchene muscular dystrophy(DMD) patients and mdx mice have elevated levels of caveolin-3 expression in their skeletal muscles. However, it remains unknown whether this increased caveolin-3 levels contribute to the pathogenesis of DMD. Also mitochondrial DNA mutation in the tRNA methionin (tRNA Met) gene has been shown to be associated with muscle weakness, severe exercise intolerance, lactic acidosis and growth retardation. Since DMD is X-linked maternally inherited disease, mitochondrial mutation in tRNA (Met) gene can be suspected to be the cause for the inefficient splicing of dystrophin gene during its expression and can be implicated as the cause of dystrophin inactive protein. Aim of the Work: The aim of the present study is to investigate whether mutations in caveolin gene leads to its increased expression and/or mutation in the tRNA (Met) gene can be associated with DMD pathogenesis. Patients and Methods: Expression of caveolin mRNA by RT-PCR and mutations in caveolin gene and tRNA (Met) gene were measured in 28 patients presented with DMD symptoms using the single strand conformation polymorphism assay (SSCP). Results: Results gave further proof to decreased expression of inducible nitric oxide synthase (iNOS) mRNA, which leads to increased expression in caveolin3 mRNA in lymphocytes of DMD patients compared to controls. However using SSCP, there was no evidence for tRNA (Met) gene mutation among DMD patients and only one patient presented a mutation in the caveolin gene compared to controls. Conclusion: There is an inverse relation between iNOS and Caveolin 3 in lymphocytes of DMD patients compared to controls. However, Caveolin 3 gene mutation is excluded as the main cause of increased caveolin gene expression. Also, there was no evidence for tRNA (Met) gene mutation among DMD patients.Keywords: mRNA, duchene muscular dystrophy (DMD), inducible nitric oxide synthase (iNOS) mRNA, mitochondrial DNA

Indicators of Apoptosis in Duchenne Muscular Dystrophy Patients

Background: Tissue sections of dystrophic muscle demonstrate apoptotic myonuclei in degenerating muscle fibers of Duchene muscle dystrophy (DMD) patients. The apoptosis cascade can be triggered by 2 main pathways, via an intrinsic, endogenous system such as the mitochondrial Bax/Bcl-2 or via an extrinsic system involving transmembrane receptors of the death receptor family Fas and Fas Ligand (FasL). Aim of the Work: The present study is an attempt to demonstrate the levels of Fas and FasL and Bax/Bcl-2 in DMD pathogenesis. Patient and Methods: Subjects were 16 boys with DMD diagnosed clinically and at the molecular level versus 20 age and socioeconomic matching healthy boys. Results: Plasma DNA fragmentation (0.38%±0.12 vs. 0.2%±.0.1.5) and Fas (9.9±2.8 vs. 2±0.1,

Markers of neural degeneration and regeneration in Down syndrome patients

On the trisomy Down syndrome Critical Region (DSCR1) is located the APP gene, which accelerates amyloid peptide protein (APP) expression leading to cerebral accumulation of APP-derived amyloid-beta peptides (Ab) and age-dependent cognitive sequelae. Also DSCR1 attenuates endothelial cell proliferation and angiogenesis required for tissue repair. The aim of the present work is to determine markers of neural degeneration and regeneration in the blood of young and adolescent Down syndrome (DS) patients as well as controls. Markers of regeneration were measured in terms of circulating mononuclear cells expressing Nestin and CD34, while markers of degeneration were measured in terms of plasma Ab42 and advanced glycation end products receptors (RAGES). Results showed a significant increase in plasma Ab42 (20 ± 5.1 vs. 11.9 ± 3.4) and RAGES leucocytes mRNA relative expression (1.9 ±0.2 vs. 1.1 ±0.6) in adolescentDS patients compared to young DS. Both parameters were also significantly increased in DS compared to controls: Ab42 (15.4 ± 5.9 vs. 12. 3± 4.5); RAGES (1.4 ± 0.5 vs. 0.7± 0.2). Nestin (5.2 ± 1.4 vs. 6.3± 0.6) and CD34 (52 ± 2.5 vs. 53± 4.7) were non-significantly lower in adolescent DS patients compared to young DS, but significantly lower in DS patients compared to controls: Nestin (6.3 ± 1.5 vs. 9±4.4); CD34 (54 ± 3.4 vs. 60± 4.8). The significant decrease in the number of mononuclear cells bearing Nestin and CD34 markers accompanied by a significantincrease in Ab42 and RAGES indicate that degeneration in DS is an ongoing process, which is not counterbalanced by the regenerative mechanism

PREVALENCE OF CONSANGUINEOUS MARRIAGES IN SOUTH SINAI, EGYPT

A total of 3961 married couples from six major geographical areas representing the South Sinai governorates in Egypt were studied to assess the rate of consanguineous marriage. The population of six selected areas (St Catherines, Nuweiba, Abu Rudeis, Ras Sudr, El Tor and Abu Zenima) were subdivided into Bedouin, urban and mixed populations. A questionnaire-based interview was conducted showing that the consanguinity rate in this region is 37.5%, with the highest rate recorded in Abu Rudeis (52.3%) and lowest rate in Nuweiba (24.1%). Consanguinity was significantly higher among the Bedouin population compared with the urban population in Abu Rudeis, Ras Sudr, El Tor and Abu Zenima, while in St Catherines and Nuweiba there was no statistically significant difference. Among consanguineous couples, 5%, 60% and 35% were double first cousins, first cousins and second cousins respectively. The mean inbreeding coefficient α of the studied population was 0.0184

Serum Interleukin-5 Changes in Partly Controlled Atopic Asthmatic Children

BACKGROUND: Cytokines including Interleukin-5 play a key role in orchestrating the chronic inflammation of asthma. We aimed to determine the level of serum IL-5 in partly controlled atopic asthma in children and to assess the effect of different therapies on their levels.METHODS: The study included 40 children aged 6-12 years with partly controlled asthma. Cases were randomly divided into two groups; group ‘A’ receiving Leukotriene modifiers and group ‘B’ receiving inhaled corticosteroids; each for two months. They were compared to 20 healthy non-asthmatic, matched controls. Serum IL-5 was measured for cases on the first visit and two months after therapy. Absolute eosinophilic count and serum Ig-E were determined. Pulmonary function testing was performed using spirometer at the beginning and two months after regular therapy.RESULTS: Serum Interleukin-5 was significantly increased in asthmatic children during exacerbation and was significantly decreased after treatment. ROC curve analysis showed significant difference of IgE and PEFR after treatment with leukotriene modifier only.CONCLUSION: Serum IL-5 seems to have a role in asthma pathogenesis. Efficiency of the two therapies (ICs & LTA) was similar in this group of patients. Both treatments led to significant decline in serum IL-5, IgE levels and eosinophilic count

Antisperm Antibody Testing: A Comprehensive Review of Its Role in the Management of Immunological Male Infertility and Results of a Global Survey of Clinical Practices

Antisperm antibodies (ASA), as a cause of male infertility, have been detected in infertile males as early as 1954. Multiple causes of ASA production have been identified, and they are due to an abnormal exposure of mature germ cells to the immune system. ASA testing (with mixed anti-globulin reaction, and immunobead binding test) was described in the WHO manual 5th edition and is most recently listed among the extended semen tests in the WHO manual 6th edition. The relationship between ASA and infertility is somewhat complex. The presence of sperm agglutination, while insufficient to diagnose immunological infertility, may indicate the presence of ASA. However, ASA can also be present in the absence of any sperm agglutination. The andrological management of ASA depends on the etiology and individual practices of clinicians. In this article, we provide a comprehensive review of the causes of ASA production, its role in immunological male infertility, clinical indications of ASA testing, and the available therapeutic options. We also provide the details of laboratory procedures for assessment of ASA together with important measures for quality control. Additionally, laboratory and clinical scenarios are presented to guide the reader in the management of ASA and immunological male infertility. Furthermore, we report the results of a recent worldwide survey, conducted to gather information about clinical practices in the management of immunological male infertility

Controversy and consensus on indications for sperm DNA fragmentation testing in male infertility: a global survey, current guidelines, and expert recommendations.

PURPOSE: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. MATERIALS AND METHODS: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. RESULTS: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. CONCLUSIONS: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians