Cytokines and growth factors in Duchene muscular dystrophy patients

Introduction: Dystrophin deficiency associated with Duchene muscular dystrophy (DMD) results in chronic inflammation and severe skeletal muscle degeneration, where the extent of muscle fibrosis contributes to disease severity. The microenvironment of dystrophic muscles is associated with variation in levels of cytokine and growth factors. Most of the current researches test for such cytokines and growth factors in tissue biopsies, which is an invasive technique. The Aim: Of the present study is to investigate whether cytokines and growth factors, as indicators of inflammatory response, can be detected in blood of DMD patients as non-invasive technique. Patient and Methods: Accordingly the cytokine tumor necrosis factor alfa (TNF TNF-α), as well as the growth factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were measured in blood of 24 boys with DMD diagnosed clinically and at the molecular level versus 20 age matching healthy boys. Results: Showed a significant increases in TNF-ά (30.2 ± 9.5 vs. 3.6 ± 0.9 pg/ ml) and bFGF (21.7 ± 10.3 vs. 4.75 ± 2.2 pg/ml.), while VEGF was significantly decreased (190 ± 115 vs. 210 ± 142 pg/ml) in blood of DMD patients compared to controls. Conclusion: Results provide further proof that inflammatory response is associated with DMD pathogenesis and favours the use of biomarkers in blood of such patients as a non invasive technique. Keywords:(basic fibroblast growth factor (bFGF), duchene muscular dystrophy, necrosis factor alfa (TNF TNF-α), vascular endothelial growth factor (VEGF)).Egyptian Journal of Medical Human Genetics Vol. 9 (2) 2008: pp. 181-18

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

Assessment of plasma and urinary transforming growth factor beta 1 (TGF-β1) in children with lupus nephritis

Background: Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE). Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Transforming growth factor- β1 (TGF-β1) is an immunosuppressive cytokine, as it inhibits T and B cell proliferation and NK cell cytotoxic activity . Objective: The aim of this study was to assess serum and urinary TGF- β1 levels in children with SLE and their possible role in the renal involvement and activity of the disease. Study design: This cross sectional study was conducted in Nephrology Unit of Pediatric Department, plus Outpatient Clinic of Rheumatology Department, Zagazig University Hospital during the year of 2010. Methods: Twenty-five pediatric patients with SLE were randomly selected and classified according to into 2 groups: Group (Ι): included 13 patients presented with urinary abnormalities and/or disturbed renal function(active nephritis): 5 males, 8 females. Their mean age was 9.7±2.53 years and the mean disease duration was 2.46±1.4 years. Group (ΙΙ): included 12 patients presented by lupus without nephritis : 5 males,7 females. Their mean age was 9.9±2.1 years and the mean disease duration was 2.41±0.9 years. Control group(group ΙΙΙ): Twenty healthy children of matched age and sex served as a control group included 8 males ,12 females. Their mean age was 10.0±2.3 years. Results: There was no significant difference among studied patients groups regarding age, sex , disease duration and lupus therapy (p>0.05). There was a significant difference between both groups regarding urinary albumin and serum creatinine (2.76±0.97 and 1.96±0.84 mg/dl respectively), while there was a high significant difference between them regarding C3 (47.3±12.5 and 76.6±6.6 mg/ml respectively) and anti double stranded DNA (anti-dsDNA) (80.7±32.8 and 26.8±4.5 IU/ml respectively). Plasma TGF- β1 showed significantly lower levels in patients with active nephritis relative to other groups, while urinary TGF- β1 levels were significantly high in SLE patients either with active or silent nephritis when compared with the control group. Plasma TGF- β1 showed a highly significant positive correlation with C3 and a highly significant negative correlation with serum creatinine, urinary albumin, anti dsDNA and SLE disease activity index (SLEDAI) score. While, urinary TGF- β1 had a significant negative correlation with C3 and a high significant positive correlation with anti-dsDNA and SLEDAI score. Conclusion: Low plasma TGF β1 level and increased urinary TGF β1 excretion denotes active renal affection in children with SLE.Keywords: SLE , nephritis , TGF- β1Egypt J Pediatr Allergy Immunol 2011;9(1):21-2

Efficacy of fetal echocardiography in prenatal diagnosis of congenital heart diseases

Background: Congenital heart diseases are the commonest fetal congenital defects and until nowadays most of them are bypassed without prenatal diagnosis to be still considered as unexplained stillbirths or perinatal deaths. In this study, we tried to prove the importance of routine fetal cardiac screening in the ANC visits and also confirming its high accuracy.Methods: This study was prospective longitudinal one, including doing ISUOG extended fetal cardiac screening for one hundred foetuses  scheduled at certain gestational age visits, whom their half were at risks for CHDs and the other were not, with comparing the results to antenatal and postnatal detailed fetal echocardiography.Results: The best gestational age for the fetal cardiac screening was at 18-22 weeks gestation. The accuracy of the screening to the antenatal echocardiogram was 96%-100% and to the postnatal one was 96%-98%.Conclusions: CHDs are still the commonest congenital fetal defects and the antenatal fetal cardiac screening by extended basic views has high accuracy. Making this screening a routine in ANC visits will be of great help in improving the fetal outcome