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

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

Fundamental Role of Neurochemicals Aberration in the Pathogenesis of Autism Spectrum Disorders

AIM: The aim of this research was to establish the perturbation of reliable biomarkers implicated in the pathophysiology of autism to help in the early diagnosis and to be as targets in the treatment of autism spectrum disorders (ASDs) in children and to spotlight into the complex crosstalk between these biomarkers. PATIENS AND METHODS: This study included 90 autistic children aged from 2 to 7 years old, who were classified into two groups, the atypical autism of 30 children and the childhood autism. The childhood autism group was further divided into mild-moderate autism group and severe autism group each of 30 children. The control group included 30 matched healthy children. All the participants were subjected to full psychiatric examinations, psychological investigations, and biochemical measurements, including gamma-aminobutaric acid (GABA), serotonin, dopamine (DA) in plasma, and brain-derived neurotrophic factor (BDNF) in serum. RESULTS: The autistic groups showed a highly significant increase in GABA, serotonin, DA, and BDNF levels compared to the control. Of note, the levels of GABA, DA, and BDNF were significantly increased with the increased disease severity. Furthermore, a significant positive correlation between BDNF levels and both GABA and DA levels in the childhood autism group has been recorded. CONCLUSION: The present clinical setting provides new insight into the fundamental role of BDNF in the brain of autistic children as any alterations of its level due to GABA increment cause change in serotonin and DA levels which have empirical evidence in the pathophysiology of ASD. The results received in this research, create a fertile base for the setup of particular targets in the intervention of this ailment