Hepat Mon. 2012 Apr;12(4):278-85. doi: 10.5812/hepatmon.846. Epub 2012 Apr 30. Heme oxygenase-1 mRNA expression in egyptian patients with chronic liver disease. Bessa SS, Mohamed Ali EM, Abd El-Wahab Ael-S, Nor El-Din SA. Source Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt. Abstract BACKGROUND: Chronic liver disease (CLD) is a global medical problem. This disease is associated with increased hepatic oxidative stress. One of the antioxidant enzymes that protect cells against this stress is heme oxygenase-1 (HO-1). OBJECTIVES: This study aimed to investigate the mRNA expression of HO-1 in Egyptian patients with CLD and its relation to oxidative stress biomarkers. PATIENTS AND METHODS: Levels of serum ferritin, carboxyhemoglobin, malondialdehyde (MDA), and erythrocytereduced glutathione (GSH) were measured, and HO-1 mRNA expression was detected in 45 CLD patients (15 with nonalcoholic steatohepatitis [NASH], 15 with chronic hepatitis C, and 15 with liver cirrhosis) and 15 healthy controls. RESULTS: HO-1 mRNA expression was increased in patients with NASH, chronic hepatitis C, and liver cirrhosis compared to controls. The expression in cirrhotic patients was significantly higher than that in patients with NASH and chronic hepatitis C. Compared to controls, patients with NASH, chronic hepatitis C, and liver cirrhosis had higher levels of ferritin, carboxyhemoglobin, and MDA and lower levels of GSH. HO-1 mRNA expression was positively correlated with levels of carboxyhemoglobin, serum ferritin, and serum MDA and negatively correlated with levels of erythrocyte GSH in CLD patients. CONCLUSIONS: HO-1 mRNA expression was significantly increased in CLD patients, and the increase reflected the severity of the disease. The significant relationship between the increased HO-1 expression and oxidative stress biomarkers in patients with CLD suggests that HO-1 may play an important role in protecting the liver from oxidative stress-dependent damage. Therefore, induction of HO-1 could be a novel therapeutic option for CLD. Ren Fail. 2012;34(6):670-5. doi: 10.3109/0886022X.2012.674438. Epub 2012 Apr 10. Urinary platelet-derived growth factor-BB as an early marker of nephropathy in patients with type 2 diabetes: an Egyptian study. Bessa SS, Hussein TA, Morad MA, Amer AM. Source Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Al-Gharbia, Egypt. saharbessa@yahoo.com Abstract BACKGROUND: Diabetic nephropathy (DN) is one of the most serious complications of diabetes worldwide. Strong evidence suggests that several growth factors may contribute to the initiation and progressive fibrosis of DN. Recently, there is an overexpression of platelet-derived growth factor (PDGF) in renal biopsies from patients with DN. This study aimed to investigate the clinical significance of urinary PDGF-BB level in type 2 diabetic patients with and without nephropathy and to evaluate its relationship with various clinical and laboratory parameters. METHODS: Urinary levels of PDGF-BB were measured in 60 Egyptian type 2 diabetic patients categorized into three equal groups (normo-, micro-, and macroalbuminuria), according to urinary albumin level. In addition, 20 healthy subjects were selected to serve as controls. RESULTS: The urinary PDGF-BB levels were significantly increased in type 2 diabetic patients as compared to controls (p < 0.001). Moreover, diabetics with micro- and macroalbuminuria had significantly higher levels than in those with normoalbuminuria (p < 0.001). Urinary PDGF-BB correlated positively with disease duration, low-density lipoprotein (LDL)-cholesterol, and urinary albumin and negatively with creatinine clearance in diabetic patients. In a multiple regression model, urinary PDGF-BB was strongly and independently associated with nephropathy in diabetic patients (β = -0.03, p < 0.001). CONCLUSIONS: PDGF-BB may play an important role in the initiation and progression of DN. It is considered as a good predictor for early deterioration of renal function in DN. Thus, measurement of urinary PDGF-BB in type 2 diabetic patients could be used for early detection of diabetic renal disease. Int J Lab Hematol. 2012 Aug;34(4):369-76. doi: 10.1111/j.1751-553X.2012.01404.x. Epub 2012 Feb 9. Role of DNA methyltransferase 3A mRNA expression in Egyptian patients with idiopathic thrombocytopenic purpura. El-Shiekh EH, Bessa SS, Abdou SM, El-Refaey WA. Source Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Abstract INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is an organ-specific autoimmune hemorrhagic disease characterized by breakdown of self-tolerance and triggering autoreactive lymphocytes' response against platelets. The underlying etiology of ITP remains largely unknown. DNA methylation plays an essential role in maintaining T-cell function, and impaired methylation can lead to inappropriate gene expression and contribute to T-cell autoreactivity and autoimmunity. The aim of this study was to evaluate the role of DNA methyltransferase 3A gene expression in the pathogenesis of ITP. METHODS: This study included 60 subjects: 20 healthy volunteers as a control group, 20 patients with acute ITP, and 20 patients with chronic ITP. DNA methyltransferase 3A (DNMT3A) mRNA expression in peripheral blood mononuclear cells was measured by real-time quantitative polymerase chain reaction. Plasma S-adenosylhomocysteine (SAH) levels were assayed with reversed-phase high-performance liquid chromatography. Results: DNMT3A mRNA expression was significantly decreased in patients with ITP as compared with that of the control group. Plasma SAH level was significantly elevated in patients with ITP than in healthy controls. However, no significant difference was found in DNMT3A mRNA expression or plasma SAH level between patients with acute and chronic ITP. Conclusions: Aberrant DNA methylation status reflected by decreased mRNA expression of DNMT3A and increased plasma SAH level may play an important role in the pathogenesis of ITP, although the precise underlying mechanisms still await further investigations, and extensive work in this field is clearly needed to provide novel therapeutic targets for ITP. Eur J Intern Med. 2010 Dec;21(6):530-5. doi: 10.1016/j.ejim.2010.09.011. Epub 2010 Oct 20. Serum visfatin as a non-traditional biomarker of endothelial dysfunction in chronic kidney disease: an Egyptian study. Bessa SS, Hamdy SM, El-Sheikh RG. Source Department of Internal Medicine, Faculty of Medicine, Tanta University, Al-Geish Street, 31527 Tanta, Egypt. saharbessa@yahoo.com Abstract BACKGROUND: Endothelial dysfunction (ED) is closely linked to cardiovascular disease and outcome in patients with chronic kidney disease (CKD). Visfatin is an adipocytokine that recently generated much interest; however, its role in CKD remains to be clarified. This study aimed to assess visfatin in correlation with markers of ED and inflammation in Egyptian patients with CKD. METHODS: The study included 40 non-diabetic, clinically stable CKD patients and 20 healthy volunteers. Serum levels of visfatin, markers of ED (intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) and markers of inflammation (interleukin-6 (IL6), and C-reactive protein (CRP)) were measured. Endothelial function was evaluated using brachial artery flow-mediated dilatation (FMD). RESULTS: Serum visfatin, ICAM-1, VCAM-1, CRP, and IL-6 levels were significantly elevated and FMD% was decreased in CKD patients as compared to controls. Visfatin correlated positively with ICAM-1, VCAM-1, CRP, and IL-6 and negatively with FMD% in CKD patients. In a multiple regression model, visfatin was strongly and independently associated with FMD (Beta=-0.02, P<0.001) in CKD patients. CONCLUSIONS: Serum visfatin is strongly associated with endothelial adhesion molecules and FMD%, suggesting that visfatin is an important promising biomarker for prediction of ED and future cardiovascular risk in CKD patients. Moreover, the relationship between visfatin and IL-6 indicates that circulating visfatin may reflect the sub-clinical inflammatory status. Thus, visfatin might be involved in the complex interactions between ED, inflammation, and atherosclerosis and their major clinical consequences; however, further prospective studies are required to prove this hypothesis. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved. Hepatol Res. 2010 May;40(5):486-93. doi: 10.1111/j.1872-034X.2010.00628.x. Epub 2010 Mar 30. Portal vein thrombosis in Egyptian patients with liver cirrhosis: Role of methylenetetrahydrofolate reductase C677T gene mutation. Gabr MA, Bessa SS, El-Zamarani EA. Source Department of Internal Medicine, Faculty of Medicine, Tanta University, Tanta, Egypt. Abstract Aim: The pathogenesis of non-malignant portal vein thrombosis (PVT) in cirrhotic patients is not clearly defined. This case-control study aimed to investigate the role of methylenetetrahydrofolate reductase (MTHFR) C677T gene mutation in the pathogenesis of PVT in Egyptian cirrhotic patients. Methods: Plasma homocysteine was measured and MTHFR C677T gene mutation was detected in 76 cirrhotic patients (21 with PVT, 55 without PVT) and 20 healthy controls. Results: The frequency of CC genotype (wide type) in cirrhotic patients with PVT was lower than controls and cirrhotics without PVT. However, the frequency of TT genotype (homozygous mutation) was elevated in cirrhotic patients with PVT as compared to controls and those without PVT. Cirrhotic patients with PVT had significantly higher homocysteine than those without PVT. Cirrhotic patients with TT genotype are at a significant risk for PVT (odds ratio = 7.7, 95% confidence interval, 1.50-42.81) when compared with CC genotype. Moreover, subjects carrying TT genotype had a higher homocysteine than those carrying CC genotype. Conclusions: The TT genotype of MTHFR is associated with an increased risk of PVT in Egyptian cirrhotic patients. Hyperhomocysteinemia could be considered as a relatively new risk factor for PVT in cirrhotic patients and plasma homocysteine should be investigated particularly in patients with PVT of unexplained etiology. The important clinical implication is that the readily available therapy of folate, vitamin B6 and B12 supplementation may reduce homocysteine and prevent further thrombotic complications in cirrhotic patients carrying the TT genotype. Eur J Intern Med. 2009 Oct;20(6):625-30. doi: 10.1016/j.ejim.2009.06.003. Epub 2009 Jul 12. The role of glutathione S- transferase M1 and T1 gene polymorphisms and oxidative stress-related parameters in Egyptian patients with essential hypertension. Bessa SS, Ali EM, Hamdy SM. Source Internal Medicine Department, Faculty of Medicine, Tanta University, Tanta, Egypt. Abstract BACKGROUND: Essential hypertension is a complex, multifactorial, polygenic disease in which the underlying genetic components remain unknown. Glutathione S-transferase (GST) enzyme is involved in detoxification of reactive oxygen species. This study aimed to investigate GSTM1 and GSTT1 gene polymorphisms in Egyptian essential hypertensive patients and their relationship with oxidative stress-related parameters. METHODS: The study included 40 newly-diagnosed, untreated, essential hypertensive patients and 40 normotensive subjects. Plasma levels of malondialdehyde (MDA), and nitrate/nitrite and erythrocyte reduced glutathione (GSH), activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione S-transferase (GST) were measured. Genotyping for GSTM1 and GSTT1 was performed. RESULTS: The frequency of GSTM1+ve/GSTT1+ve in hypertensives (5%) was lower than in normotensives (37.5%).The frequency of GSTM1-ve/GSTT1-ve was elevated in hypertensives (35%) as compared to normotensives (7.5%). Plasma MDA was higher and nitrate/nitrite was lower in hypertensives than in normotensives. Erythrocyte GSH, activities of CAT, SOD, GSH-Px, and GST of hypertensives were lower than normotensives. Moreover, GST activity was lower in subjects with GSTM1-ve/GSTT1-ve than in those with GSTM1+ve/GSTT1+ve. In hypertensives, both systolic and diastolic blood pressures were negatively correlated with activities of CAT, GSH-Px, and GST. CONCLUSIONS: GSTM1-ve/GSTT1-ve is a potential genetic factor to predict development of essential hypertension and permit early therapeutic intervention. The significant association between blood pressure and oxidative stress-related parameters indicates the pathogenic role of oxidative stress in hypertension. Antioxidants could be useful in the management of essential hypertension to prevent progressive deterioration and target organ damage however, further studies involving long-term clinical trials may help to assess the efficacy of these therapeutic agents.