Background: Indoxyl sulfate (IS) is a non-dialyzable gut-derived uremic toxin that is reported to be cardiotoxic in patients with advanced chronic kidney disease stages. Aim of the Work:The aim of this study was to investigate the role of IS as a risk factor for cardiovascular complications in children with end stage kidney disease (ESKD) on regular HD.Patients and Methods: This is a cross-sectional analytical study that included children with ESKD on regular hemodialysis (HD) for at least 6 months following at Nephrology Unit of Cairo University Pediatric Hospitals.Serum IS level was measured for all patients by the enzymelinked immunosorbent assay (ELISA).Cardiac complications was assessed using the M mode and 2D transthoracic echocardiography. Results:The study comprised 88 children with ESKD on regular HD for a mean ± SD of 31.94 ± 26.05 months, with a mean age ± SD of 9 ± 3.2 years (range 3.3-14 years).Of them 52 (59.1%) were males.Obstructive uropathy (28.4%), and focal segmental glomerulosclerosis (20.5%), were the main causes of ESKD in the study group.Cardiovascular complications were identified in 48 (54.5%) patients in the form of dilated cardiomyopathy in 44 (50%) children with decreased fractional shortening <30% and moderate to severe left ventricular hypertrophy above 95th for age and gender in 10 (11.4%).Cardiovascular affection correlated with duration of HD, hypertension, and IS serum level (p=<0.001for each).Hypertension was reported in 55 (62.5%) of patients, and vascular access related complications were evident in 40 (45.4%)patients with thrombosis being the commonest complication in 16 (18.1%).The mean IS was 29.14 ± 17.43 µg/ml in ESKD patients with normal cardiac function, and 77 ± 15.18 µg/ml among those with cardiac compromise (p < 0.001).The IS level correlated with longer duration of HD (p= 0.002), and older age (p= 0.043).IS level and duration of HD did not predict cardiomyopathy, (p=0.192), and (p=0.760)respectively.Conclusion: Cardiac complications are common among children on HD.Both cardiovascular complications and IS accumulation correlated positively with longer duration of HD, and age of children with ESKD.IS is non-dialysable and there is a need to control its production from the gut. Level of Evidence of Study: IV (1).
Chitosan, a natural product derived from chitin, has attracted much attention as a promising polysaccharide compound, owing to its unique biological activities. This study was designed to explore the possible improving potential of chitosan, as a natural marine product, on liver regeneration in hepatotoxicity induced by thioacetamide in male albino rats. Fifty animals were divided into 5 groups, including the control group; a group which was injected intraperitoneally with a single dose of thioacetamide(300 mg/kg b. wt) for induction of liver toxicity; a group received a diet containing 5% chitosan for 14 days; a group received a diet containing 5% chitosan for 14 days then they were injected with thioacetamide(300 mg/kg b. wt) once, and the last group which was injected with thioacetamide(300 mg/kg b. wt) once then received a diet containing 5% chitosan for 14 days. The biochemical results revealed that the intake of chitosan before or after thioacetamide intoxication improved liver markers (ALAT, ASAT, GGT, ALP, albumin) and kidney functions and also plasma TNF-α. QRT- PCR analysis revealed that chitosan downregulated hepatic TNF-α, survivin, and c-Myc quantitative gene expression. Moreover, chitosan improved the histological picture of the liver. This study indicated the promising action of chitosan in liver regeneration.
Abstract Background Hashimoto's thyroiditis is the most widespread autoimmune illness targeting a specific organ. "Redox homeostasis" is achieved when the production of Reactive Oxygen Species and their elimination are in balance. Advanced glycation end products (AGEs) are formed when glucose and/or α -oxaloaldehydes react non-enzymatically with the amino groups of lipids, proteins, and DNA. Nowadays, many studies are concerned with AGEs, the polymorphisms of their receptors, and their association with increased risk of HT. However, few studies investigated the role of receptors of advanced glycation end product (RAGE) SNP in Egyptian females. Objective The goals of this investigation were to ascertain whether oxidative stress plasma malondialdehyde (MDA) and total antioxidant capacity (TAC) were associated with HT, in addition, to assess the association of RAGE polymorphisms (− 374 T > A and the − 429 T > C and Gly82Ser) with HT. Subject and methods. Our case–control study has 80 patients enrolled who have newly been diagnosed with HT and 80 age and sex-matched healthy female controls. Each participant underwent a thorough medical history, physical examination, and laboratory investigations, which included Genotyping of RAGE Gly82Ser, − 374 T > A and − 429 T > C using polymerase chain reaction-restriction fragment length polymorphisms (PCR–RFLP). Results Chi-square revealed a significant association regarding the distribution of RAGE (− 374 T < C) genotypes TT and CC between patients and control ( P = 0.04). Non-significant associations regarding the distribution of Gly82Ser genotypes Gly/Gly, Gly/Ser, Ser/Ser were found between patients and control ( P = 0.5), and non-significant associations related to − 429 T > C gene polymorphism were revealed. In addition, patients with HT had higher MDA and lower TCA compared with controls. Conclusion The elevated MDA and decreased TAC as an antioxidant may be one of several risk factors associated with the prevalence of HT in individuals with the − 429 T > C RAGE mutation polymorphism that is associated with an increased risk of HT in Egyptian females.
Background: Rhabdomyolysis is a primary skeletal muscle disruption syndrome with circulatory leakage of its intracellular contents and is seriously complicated by acute kidney injury (AKI).Asprosin is a novel glucogenic adipokine expressed in several tissues, including the kidneys, and has been implicated in some renal disorders via many pathogenic mechanisms.Methods: 32 rats were divided equally into the control group, the calcitriol-treated group, the glycerol-treated group, and the glycerol+calcitriol-treated group.Blood, urine, and renal tissue samples were collected for biochemical, histological, immunohistochemical, and gene investigations.Results: Rats given glycerol had elevated levels of asprosin, creatine kinase, creatinine, BUN, renal MDA, IL-6, caspase-3, and caspase-9, as well as PKA mRNA, TGF-β1, and SMAD-3.While creatinine clearance, renal SOD, and catalase were decreased.Marked histopathological changes imply sever renal injury, faint PAS-positive reaction, strong positive immunoreaction for iNOS and TGF-β were found.These changes were reversed in glycerol+calcitriol-treated rats.Asprosin positively correlated with MDA, IL-6, caspase-3, caspase-9, mRNA levels of PKA, TGF-β1and SMAD-3, while it negatively correlated with SOD, and catalase.Conclusion: Serum asprosin levels are increased in rhabdomyolysis-induced AKI and calcitriol protect against AKI via suppressing asprosin and its dependent PKA-TGF-β1-SMAD-3 signaling pathway.
Abstract Background: The fluorinated substance perfluorooctane sulfonate (PFOS) is a man-made fluorinated compound. It is employed in a variety of industrial and civilian applications. Due to its long elimination half-life and promotion of oxidative stress and inflammation, it is one of the most abundant organic contaminants. The effect of PFOS exposure on the heart, on the other hand, is still quite limited. Aim of work: This study was designed to determine the cytotoxic effect of PFOS on adult male albino rat cardiac tissue and to assess the cardioprotective role of the flavonoid Quercetin (Que), which possesses antioxidant, anti-inflammatory, and anti-apoptotic characteristics. Material and methods: Twenty-four adult male Sprague Dawley rats were randomly divided into four equal groups; Group I (Control). Group II (Que). Group III (PFOS group): supplemented orally with PFOS (20 mg/kg for 4 weeks) and Group IV (PF OS/Que). The rat heart was processed for histological, immunohistochemical and gene expression studies Results: Compared with the control and Que groups, the PFOS group displayed histopathological changes in the myocardium involving disrupted cardiac muscle fibers, congested blood capillaries, inflammatory cellular infiltration and increased the mean area % of the intervening collagen fibers. In addition, this group displayed a weak immunoexpression of connexin 43 (CX43) with a strong immunoexpression of heat shock protein 70 (HSP70). PFOS increased the serum cardiac enzymes (LDH and CK-MB), lipid profile, TSH, MDA, and the inflammatory biomarkers (TNF-α, IL-6, IL-1β). Also, PFOS induced over expression of apoptotic and SERCA2a genes. On the other hand, PFOS decreased total T3, T4 and the antioxidant enzymes; CAT and SOD. Administration of Que with PFOS partially attenuated the PFOS-induced histological and bimolecular changes. Conclusion: PFOS had adverse effects on the cardiac muscle structure and these effects were alleviated by Que which is a promising cardioprotective flavenoid.
Several genetic and non-genetic risk factors are implicated in the etiology and pathogenesis of primary immune thrombocytopenia (ITP). Protein tyrosine phosphatase non-receptor 22 gene (PTPN22) plays an important role in regulation of signal transduction through the T-cell receptors. PTPN22 1858 C > T single nucleotide polymorphism was reported to be associated with increased risk of autoimmune diseases. There are very few studies investigating the role of PTPN22(SNP) 1858 C > T in childhood ITP.This case-control study was designed for assessing the contribution of PTPN22 1858 C > T polymorphism to the risk of ITP in Egyptian children. Eighty children with newly diagnosed ITP were recruited from pediatric hematology out-patient clinic. Also, eighty age and sex-matched healthy children were enrolled as a control group. PTPN22 1858 C/T SNP gene polymorphism was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).Frequency of PTPN22 1858 C/T genotypes CT, CC, and TT were 32.5,55, and 12.5% in patients versus 10, 90, and 0% in controls (p < 0.05).TT genotype was significantly associated with higher risk of ITP (OR = 17.8(0.94-333.35), 95% CI, and P = 0.02).PTPN22 gene polymorphism may play a pivotal role in genetic predisposition to ITP and disease progress in Egyptian children.