Possible association of interleukin-1beta [-511C/T] and interleukin-6 [-174G/C] gene polymorphisms with atherosclerosis in end stage renal disease Egyptian patients on maintenance haemodialysis

In end stage renal disease, inflammation is considered a critical regulator of atherosclerotic plaque formation and progression, to which many dialysis and non-dialysis-related factors may contribute. Since circulating inflammatory cytokine levels vary inter-individually, one may speculate that genetic factors, such as polymorphisms in genes encoding them, may be involved in determining the individual inflammatory reaction in response to a given insult. The present work aimed to study interleukin-1B [-511C/T], and interleukin-6 [-174G/C] gene polymorphisms and their possible association with atherosclerosis in Egyptian patients with end stage renal disease on maintenance haemodialysis. The present study was conducted on 100 Egyptian subjects, the control group [n = 30] and the patient group [n = 70] with end stage renal disease on maintenance haemodialysis which were further subdivided into two subgroups with [n = 33] and without atherosclerosis [n = 37] as evidenced by CIMT, ECG ischaemic changes, cerebrovascular insufficiency [CVI], and peripheral vascular insufficiency [PVI]. All studied subjects were subjected to detailed history taking, routine laboratory investigations and molecular studies including detection of IL-1B [-511C/T] and IL-6 [-174G/C] gene polymorphisms using the Polymerase chain reaction/Restriction fragment length polymorphism [PCR/RFLP] technique. The genotype distribution and allele frequency of IL-1B [-511C/T] and IL-6 [-174G/C] showed no statistical significant difference among the studied groups. To conclude the development of atherosclerosis among Egyptian patients on maintenance haemodialysis cannot be attributed to these two gene polymorphisms

Serotonin: is it a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients?

Hepatocellular carcinoma [HCC] is the third most frequent cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, ligand of a family of 5-HT receptors that reflect the diversity of serotonergic actions. Majority of serotonin in body [90%] is synthesized by enterochromaffin cells of the gastrointestinal tract and is exported to various sites. Serotonin regulates blood flow and vascular tone at portal and sinusoidal levels, serotonin acts as a mitogen for hepatocytes and promotes liver regeneration. 5HT emerges as a mediator of different pathological conditions [double edged sword]. It contributes to liver fibrosis, mediates oxidative stress in nonalcoholic steatotic hepatitis and aggravates viral hepatitis, these conditions are involved in tumourigenesis of hepatocellular carcinoma [HCC]. Impaired metabolic function in liver cirrhosis and slow uptake and storage of serotonin by the platelets is a sequelae of kinetic change of serotonin transport mechanisms or abnormal serotonin release from dense granules of activated platelets is a condition defined as ''platelet exhaustion'', contributes to elevated plasma serotonin which may facilitate tumour growth of primary liver hepatocellular carcinoma. To determine whether serotonin is a marker for the diagnosis of hepatocellular carcinoma in cirrhotic patients. Patients were classified into two groups; 45 patients with cirrhosis only and 30 patients with cirrhosis and HCC. Ten healthy subjects were taken as controls. Patients underwent; full history taking, clinical examination, and abdominal ultrasonography. Laboratory methods include SGOT, SGPT, GGT, bilirubin, alkaline phosphatase, total proteins, albumin, CBC, prothrombin, INR, APRI score, Child-pugh score, MELD score, AFP and serum serotonin. Plasma serotonin was significantly higher in the patients group with cirrhosis with a median level of 119.4 ng/ml than in the control group which showed a median value of 51.5 ng/ml p< 0.001. A significance difference was also seen between cirrhosis and the HCC group with a median value of 478.35 ng/ml than the control group and a cirrhosis group with p< 0.001was found. Plasma serotonin level was significantly higher in patients with cirrhosis and HCC than in those with cirrhosis only and it was involved in the tumourigenesis of hepatocellular carcinoma

Adiponectin: a differential marker between steatosis and steatohepatitis

Nonalcoholic fatty liver disease [NAFLD] becoming a world-wide public health problem.It represents a spectrum of disease ranging from simple steatosis to steatohepatitis [NASH]. Adipocytokines refer to adipocyte-derived biologically active molecules TNF-alpha, leptin and adiponectin, all been implicated in development of hepatic inflammation and fibrosis in NAFLD patients. This new hormone differ from its predecssors in important feature, production and concentration actually decrease in obesity, and all adipose-derived hormone are increased. It is possible that adiponectin expression is activated during adipogenesis, a feed back inhibition on its production may occur during the development of obesity. Adiponectin may exert a hepatic protective effect. Was to evaluate adiponectin level as a differential marker between steatosis and Steatohepatitis. Twenty NAFLD patients, twenty biopsy proved NASH and twenty control subjects, matched for age, sex and BMI. All the subjects were subjected to an abdominal ultrasonography, routine biochemical evaluation: liver function ALT and AST, lipid profile [cholesterol, triglycerides, HDL-C], CRP and Adipocytokines [TNF-alpha, IL-6, LEPTIN, and Adiponectin]. Plasma adiponectin levels were significantly lower in NAFLD patients than control gp [6.15 +/- 1.39ng/ml vs12.03 +/- 3.46ng/ml]. Adiponctin was significantly lower in NASH than NAFLD [1.80 0 +/- 0.96 ng/ml vs 6.15 +/- 1.39 ng/ml]. leptin level was significantly higher in NAFLD than NASHgp [69.50 +/- 18.70ng/ml vs 43.20 +/- 6.93ng/ml]. adiponectin ROC curve showed an AUROC curve in NAFLD gp [o.945 p=0.049] while inNASH was[0.995 p=0.007].TNF-alpha and IL-6 was significantly higher in NASH than NAFLD gp [79.25 +/- 13.89 pg/ml vs41.25 +/- 17.53 pg/ml]and [110.20 +/- 55.34 pg/ml vs 43.85 +/- 16.13]. Plasma adiponectin level in NAFLD gp was inversely correlated with T.G [r=-0.368 p=0.111]. GOT [r=-0.037 p=0.878] and GPT [r=-0.022 p=0.926] while it was +ve correlated in NASH gp with Cholesterol [r=0.317 p=0.174] and T.G [r=0.042 p=0.861]. This data support a role for low circulating adiponectin in the pathogenisis of NAFLD and hypoadiponectinemia found to be a feature of NASH. ADIPONECTIN found to be a non-invasive differential marker between NAFLD and NASH