Publications by authors named "Amal El-Shehaby"

31 Publications

Chemerin level and the relation to insulin resistance in chronic kidney disease.

Saudi J Kidney Dis Transpl 2019 Nov-Dec;30(6):1381-1388

Department of Radiology, Kasr Al-Ainy Cairo University, Cairo, Egypt.

Chemerin has been associated with different components of the metabolic syndrome, including hypertension, hyperlipidemia, and insulin resistance (IR). The aim of this study was to evaluate serum chemerin level in chronic kidney disease (CKD) patients and its relation to IR. This study was conducted on 80 participants who were classified into three groups: Group I (30 CKD patients with mean age 53 ± 12 years), Group II (30 patients with end-stage renal disease on regular hemodialysis with mean age 48 ± 14.8 years) and Group III having 20 healthy age-and sex-matched controls. Serum chemerin level, fasting blood sugar, fasting insulin, HOMA-IR index calculation, urea, creatinine, estimated glomerular filtration rate, total cholesterol, and triglyceride were measured. Body composition was assessed by dual-energy X-ray absorptiometry. In Groups I and II, we found a significantly higher mean chemerin level compared to healthy controls (P <0.001), a highly significant positive correlation between mean chemerin level and the HOMA-IR index [r = 0.56, P <0.001/(r = 0.53, P <0.001)], and a highly significant negative correlation between mean chemerin level and GFR (r = -0.51, P <0.001/r = -0.46, P <0.001). In Group I, there was also a highly significant positive correlation between mean chemerin and systolic blood pressure (r = 0.31, P <0.05), diastolic blood pressure (r = 0.39, P <0.05 and creatinine (r = 0.34, P <0.05). Chemerin might be considered a uremic IR adipokine marker in CKD Stages 3, 4, and 5.
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http://dx.doi.org/10.4103/1319-2442.275482DOI Listing
August 2020

Relationship between serum osteoprotegerin and vascular calcifications in hemodialysis patients.

Egypt Heart J 2017 Jun 9;69(2):149-155. Epub 2017 Mar 9.

Department Cardiology, Faculties of Medicine, Al-Azhar University, Cairo, Egypt.

Background: Uremia is a vasculopathic process, and both cardiac calcification and vascular calcification seen from the early stages of chronic kidney disease. Osteoprotegerin could play a crucial role in atherosclerotic plaque formation, maturation and calcification. The goal of this study was to determine the relationship of serum osteoprotegerin with vascular calcification in patients with end stage kidney disease who were maintained on regular hemodialysis.

Methods: Sixty clinically stable chronic renal failure patients undergoing regular hemodialysis were enrolled in this cross sectional study. Thirty patients (mean age 56.7 ± 10.5 years) with abdominal aortic calcification were selected by basal abdominal X-ray who underwent multi-slice computerized tomography scan to measure coronary artery calcification score; and thirty patients (mean age 56.5 ± 8.4 years) without abdominal aortic calcification. All patients were evaluated by serum calcium, phosphorus, albumin, lipid profile, intact parathyroid hormone (iPTH), serum creatinine, serum urea, serum uric acid, serum C-reactive protein, and hemoglobin. Serum osteoprotegerin samples were collected before dialysis and estimated by the ELISA kit.

Results: Serum osteoprotegerin level was significantly higher in patients with vascular calcification than in those without calcifications. Serum osteoprotegerin correlated positively with serum phosphorus, calcium phosphorus product, alkaline phosphatase, iPTH, C-reactive protein, serum uric acid, low-density lipoprotein (LDL) and left ventricular mass index (LVMI) ( < 0.005), and negatively with hemoglobin, ejection fraction ( < 0.005) and HDL ( < 0.05).

Conclusions: These findings suggest that osteoprotegerin may be involved in the development of vascular calcification in hemodialysis patients.
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http://dx.doi.org/10.1016/j.ehj.2017.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839346PMC
June 2017

Cardiac Affection in Type 1 Diabetic Patients in Relation to Omentin.

Open Access Maced J Med Sci 2015 Dec 13;3(4):699-704. Epub 2015 Dec 13.

Cairo University, Medical Biochemistry, Cairo, Egypt.

Aim: To evaluate cardiac affection in type 1 diabetes in relation to Omentin.

Patients And Methods: Sixty two diabetics and 30 volunteer of the same age and sex were included as a control group. Blood sample was taken for assessment of omentin and oxidized low density lipoprotein (OxLDL), glycosylated hemoglobin (HbA1) and lipid profile. Urine sample was taken for assessment of albumin/creatinine ratio. 24 hour holter was also done. T-test, simple correlation followed by stepwise multiple regression analysis was used for analysis of data.

Results: Parameters of 24 hour holter were significantly lower in diabetics. Omentin was significantly lower, while OxLDL were significantly higher than controls. RMSSD, ST deviation and OxLDL were the parameters related to omentin by stepwise multiple regression analysis in diabetics.

Conclusion: Diabetic patients had a cardiac autonomic neuropathy. A significant reduction of omentin and elevation OxLDL imply that they influence glucose metabolism in type 1 diabetes. Omentin had a significant relation to 24 hr holter which may reflect its role in cardiac affection. Omentin and OxLDL had a role in renal affection.
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http://dx.doi.org/10.3889/oamjms.2015.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4877911PMC
December 2015

Value of the intrarenal arterial resistivity indices and different renal biomarkers for early identification of diabetic nephropathy in type 1 diabetic patients.

J Pediatr Endocrinol Metab 2016 Mar;29(3):273-9

Background: The aim of this study was to compare resistivity index (RI) in type 1 diabetic patients and normal controls and to evaluate whether high RI is associated with different biomarkers of diabetic nephropathy (DN) as early detection of DN offers the best chance of delaying or possibly preventing progression to end-stage renal disease.

Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of glycosylated hemoglobin, lipid profile and urine samples were taken for assessment of albumin/creatinine ratio, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP) and kidney injury molecule-1 (Kim-1). Forty-five diabetic patients and 30 controls had a renal Doppler ultrasonography. t-Test or Mann Whitney U-test for independent variables, Pearson's or Spearman correlation analysis were used.

Results: The mean age of diabetic patients was 16.3±1.5 years, and mean duration of diabetes was 9.4±2.9 years. RI, albumin/creatinine ratio, NGAL, Kim-1 and L-FABP were significantly higher in diabetics than in controls. RI, NGAL, Kim-1, and L-FABP were significantly higher in microalbuminuric compared to normoalbuminuric diabetics. In normoalbuminuric diabetics, RI, NGAL, Kim-1 and L-FABP were significantly higher compared to controls. The study revealed significant positive correlation between the RI in diabetics and both KIM-1 and albumin/creatinine ratio.

Conclusions: Increased RI and renal biomarkers in diabetics are early sensitive specific markers of DN, even preceded the development of microalbuminuria, denoting that they can be used as an early and sensitive markers for early detection of DN.
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http://dx.doi.org/10.1515/jpem-2014-0397DOI Listing
March 2016

Evaluation of fetuin-A and carotid intima-media thickness in adolescent type 1 diabetic patients.

J Pediatr Endocrinol Metab 2015 Mar;28(3-4):287-92

Objective: To evaluate fetuin-A level and carotid intima-media thickness (CIMT) in adolescent type 1 diabetics.

Patients And Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood sample was taken for assessment of glycosylated hemoglobin (HbA1), lipid profile, and fetuin-A. Urine sample was also taken for assessment of albumin/creatinine ratio. Anthropometric measurements were taken, including weight, height, and waist and hip circumference. CIMT was assessed for all patients and controls.

Results: Serum fetuin-A, Rt., Lt. and both CIMT were significantly higher in diabetics. Fetuin-A had a significant positive correlation with duration of disease, waist and hip circumference, BMI, BMI SDS, waist/height ratio, Rt., Lt. and both CIMT. Stepwise multiple regression analysis revealed that the duration of disease, waist/height ratio, and HDL-c were the factors related to fetuin-A.

Conclusion: Adolescent type 1 diabetic patients have high fetuin-A levels and increased CIMT, with the latter representing the development of early atherosclerosis. In this light, adolescents with type 1 diabetes require frequent follow up for early detection of atherosclerosis.
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http://dx.doi.org/10.1515/jpem-2014-0290DOI Listing
March 2015

Assessment of human cartilage glycoprotein 39 (YKL-40), preptin, and nitric oxide in adolescent patients with type 1 diabetes and its relation to cardiorenal affection.

J Pediatr Endocrinol Metab 2015 Mar;28(3-4):309-14

Aim: To evaluate new biomarkers such as YKL-40, preptin, and nitric oxide (NO) in patients with diabetes and to assess its relation to cardiorenal injury.

Patients And Methods: The study included 62 patients with type 1 diabetes and 30 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile, YKL-40, preptin, and NO. Also, urine sample was taken for analysis of albumin/creatinine ratio. Echocardiography was also done.

Results: NO was lower, whereas YKL-40, preptin, and albumin/creatinine ratio were significantly higher in patients with diabetes. NO had a significant negative correlation with LVEDD, LVESD, PWT, LV mass, YKL-40, preptin, and albumin/creatinine ratio. YKL-40 had a significant positive correlation with waist/height ratio, preptin and negative correlation with E/A ratio. Stepwise multiple regression revealed that E/A ratio is the only parameter related to YKL-40. On the contrary, NO and systolic blood pressure are related to preptin.

Conclusion: A significant reduction of NO and elevation of YKL-40 and preptin was found in patients with diabetes. A decrease in NO is associated with diastolic dysfunction, LV hypertrophy, and renal impairment, whereas YKL-40 is associated with diastolic dysfunction. An increase in preptin level was associated with hypertension.
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http://dx.doi.org/10.1515/jpem-2014-0359DOI Listing
March 2015

Relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy in adolescent type 1 diabetic patients.

J Pediatr Endocrinol Metab 2015 Mar;28(3-4):265-73

Objective: Our objective was to evaluate the relationship of plasma level of chemerin and vaspin to early atherosclerotic changes and cardiac autonomic neuropathy (CAN) in adolescent type 1 diabetic patients.

Patients And Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of chemerin, vaspin, asymmetric dimenthylarginine (ADMA), and oxidized low-density lipoprotein (OxLDL) by enzyme-linked immunosorbent assay (ELISA) technique. Also, blood samples were taken for analysis of glycosylated hemoglobin; lipid profiles and urine samples were taken for assessment of albumin/creatinine ratio. Twenty-four-hour holter [for assessment of time domain heart rate variability (HRV)] and carotid intima-media thickness (CIMT) were also done. The t-test or Mann-Whitney U-test for independent variables, Pearson's or Spearman's correlation, and stepwise multiple regression analysis were used.

Results: The mean age of diabetic patients was 16.3±1.5 years, and mean duration of diabetes was 9.4±2.9 years. Chemerin, vaspin, OxLDL, and albumin/creatinine ratio were significantly higher, whereas ADMA was significantly lower than the controls. By stepwise multiple regression analysis, vaspin had a relation with a standard deviation difference RR (SDARR) and waist/height ratio. Conversely, chemerin had a relation with OxLDL. Albumin/creatinine ratio had a significant positive correlation with chemerin and OxLDL, and a negative correlation with ADMA.

Conclusions: Type 1 diabetic patients had impaired time domain HRV associated with increased CIMT. Vaspin had a significant relation to CAN, whereas chemerin, ADMA, and OxLDL had a significant correlation with albumin/creatinine ratio that reflects their role in renal affection.
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http://dx.doi.org/10.1515/jpem-2014-0215DOI Listing
March 2015

Asymmetric dimethyl L-arginine, nitric oxide and cardiovascular disease in adolescent type 1 diabetics.

J Pediatr Endocrinol Metab 2014 May;27(5-6):437-44

Objective: To evaluate asymmetric dimethyl L-arginine (ADMA), nitric oxide (NO) and cardiovascular disease in adolescent type 1 diabetics.

Methods: The study included 62 type 1 diabetic patients and 30 healthy volunteers of the same age and sex. Blood samples were taken for assessment of ADMA, NO, oxidized low density lipoprotein (OxLDL), glycosylated hemoglobin, and lipid profile. Urine samples were taken for assessment of albumin/creatinine ratio. M mode echocardiography and flow mediated dilatation (FMD) via ultrasound were completed; t-test for independent variables, Pearson's correlation, and stepwise multiple regression analysis were used.

Results: The mean age of patients was 16.3±1.5 years and mean duration of diabetes was 9.4±2.9 years. Nitric oxide, ADMA and FMD were significantly lower, while OxLDL and the albumin/creatinine ratio were significantly higher in diabetics. Nitric oxide had a significant negative correlation with left ventricular end-diastolic dimension, left ventricular end-systolic dimension, posterior wall thickness, left ventricular mass, albumin/creatinine ratio, and OxLDL, as well as a positive correlation with ADMA. Albumin/creatinine ratio had a significant positive correlation with OxLDL and negative correlation with ADMA. Stepwise multiple regression analysis revealed that ADMA is the only parameter related to NO, however, albumin/creatinine ratio and OxLDL are related to ADMA.

Conclusions: Type 1 diabetic patients had endothelial and diastolic dysfunction. The reduction in NO, ADMA, and elevation of OxLDL, and its relation to echocardiographic data and albumin/creatinine ratio, may reflect their role in cardiac and renal affection.
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http://dx.doi.org/10.1515/jpem-2013-0280DOI Listing
May 2014

The Association between Fibroblast Growth Factor-23 and Vascular Calcification Is Mitigated by Inflammation Markers.

Nephron Extra 2013 6;3(1):106-112. Epub 2013 Nov 6.

Department of Nephrology, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt.

Background: Fibroblast growth factor-23 (FGF-23) has been linked to vascular calcification, ventricular hypertrophy and mortality in chronic kidney disease (CKD), although these links may not be direct and independent. Similar grave outcomes are associated with inflammation and oxidative stress in CKD. Recently, accumulating evidence has linked components of phosphate homeostasis to inflammation and oxidative stress. The interaction between the triad of inflammation, FGF-23 and cardiovascular outcomes is underinvestigated.

Methods: We studied 65 patients with stage 5 CKD on hemodialysis. Serum levels of FGF-23, high-sensitivity C-reactive protein (hsCRP), endogenous soluble receptor of advanced glycation end products (esRAGE), advanced oxidation protein products (AOPP), parathormone, lipids, calcium and phosphorous were measured. The aortic calcification index (ACI) was determined using non-contrast CT scans of the abdominal aorta.

Results: FGF-23 was elevated (mean: 4,681 pg/ml, SD: 3,906) and correlated with hsCRP, esRAGE, AOPP, dialysis vintage and phosphorus in univariate analysis. In multiple regression analysis, hsCRP, AOPP and phosphorus but not esRAGE were all significantly correlated to FGF-23 (R = 0.7, p < 0.001). In univariate analysis, ACI correlated with hsCRP, esRAGE, FGF-23, dialysis vintage, systolic blood pressure (BP) and serum cholesterol. In multiple regression analysis not including inflammation markers, ACI was associated with FGF-23. However, inclusion of inflammation markers in another multiple regression analyses showed that ACI correlated with hsCRP, BP, dialysis vintage and esRAGE but not with FGF-23 (R = 0.65, p < 0.001).

Conclusion: FGF-23 is strongly correlated to various markers of inflammation and oxidative stress in hemodialysis patients. The association between FGF-23 and vascular calcification was mitigated when corrected for inflammation markers.
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http://dx.doi.org/10.1159/000356118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843931PMC
November 2013

Osteopontin gene polymorphisms as predictors for the efficacy of interferon therapy in chronic hepatitis C Egyptian patients with genotype 4.

Cell Biochem Funct 2013 Oct 11;31(7):620-5. Epub 2013 Feb 11.

Departments of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt.

This study aimed to determine the relationship between osteopontin gene polymorphisms and its protein level and the efficacy of interferon-based therapies in Hepatitis C virus (HCV) patients. Hundreds HCV patients genotype 4, treated with pegylated interferon alfa-2b plus ribavirin and 60 healthy subjects were enrolled. All individuals were subjected to clinical and laboratory parameters, including hepatitis markers and HCV quantitation by real-time polymerase chain reaction. Single nucleotide polymorphisms (SNPs) of osteopontin (OPN) gene (nucleotide -155, -443 and -1748) were analysed by direct sequencing in addition to estimation of serum level of OPN. SNP at -443 (C/C versus C/T, T/T) was found to represent predictors for treatment response by univariate logistic regression analysis. OPN serum level was independent predictors for treatment response by both univariate and multivariate logistic regression analysis. SNP at nucleotide -443 and serum OPN protein levels could be used as useful markers to predict the efficacy of treatment.
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http://dx.doi.org/10.1002/cbf.2954DOI Listing
October 2013

Relationship of BsmI polymorphism of vitamin D receptor gene with left ventricular hypertrophy and atherosclerosis in hemodialysis patients.

Scand J Clin Lab Invest 2013 Feb 3;73(1):75-81. Epub 2012 Dec 3.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Egypt.

Background: Left ventricular hypertrophy (LVH) is a common manifestation of cardiovascular disease and has an important prognostic value in patients with end-stage renal disease (ESRD). Vitamin D receptor (VDR) has been intensively investigated, and one of these (BsmI) already has been associated with survival in the dialysis population.

Objective: The aim of this study was to investigate the role of VDR polymorphism (BsmI) on the development of ventricular hypertrophy and atherosclerosis in hemodialysis patients. Subject and methods. The subjects were 80 patients with end-stage renal disease on maintenance hemodialysis, and 40 healthy controls. Clinical and laboratory parameters, including genetic variation in VDR gene (BsmI), were assessed. In addition, echocardiography and intima-media thickness were performed for all subjects.

Results: There was no significant difference in the distribution of BsmI genotypes either in patients or in the control group. The frequency of the B allele of BsmI polymorphism (41.6%) in dialysis patients was similar to that of healthy control subjects (39.2%). Patients with BB genotype had significantly lower serum concentrations of 25-hydroxy vitamin D compared to both Bb and bb genotypes. The number of B alleles was positively correlated with left ventricular mass index (LVMI), but not with intima-media thickness.

Conclusion: These results suggest that the B alleles of the BsmI polymorphism could be considered as novel markers of altered vitamin D signaling in ESRD patients, and this alteration in BB genotype produces an increase in left ventricle mass.
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http://dx.doi.org/10.3109/00365513.2012.743163DOI Listing
February 2013

CRP and acute renal rejection: a marker to the point.

Int Urol Nephrol 2012 Aug 3;44(4):1251-5. Epub 2012 Jan 3.

Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt.

Objectives: C-reactive protein (CRP) is increased in end-stage renal disease patients. Recent studies have shown positive associations between inflammatory markers and cardiovascular mortality in kidney transplant recipients. The aim of the present study was to examine the correlation between CRP and early detection of renal allograft rejection. Furthermore, investigate the association between pretransplant levels of CRP with the development of acute renal allograft rejection as a possible predictive marker.

Methods: Ninety-one renal transplant recipients were sequentially analyzed. The median follow up of patients was 8 weeks. Basal and 8 weeks post transplant CRP levels were assessed.

Results: CRP levels were significantly higher in allograft rejection both in the pretransplant (n = 25, P = 0.001) and postransplant (n = 33, P = 0.001) phases when compared to those without rejection. By stepwise multiple regression analysis, rejection in transplanted patients was independently correlated to albumin/creatinine ratio and CRP 8 weeks after transplantation.

Conclusion: Elevated pretransplant serum CRP level is a risk predictor for acute rejection episodes and may be a useful predictive marker in the follow-up of post-transplantation patients.
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http://dx.doi.org/10.1007/s11255-011-0098-4DOI Listing
August 2012

Plasma visfatin and retinol binding protein-4 levels in patients with type 2 diabetes mellitus and their relationship to adiposity and fatty liver.

Clin Biochem 2011 Dec 12;44(17-18):1457-63. Epub 2011 Sep 12.

Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Cairo University, Egypt.

Objectives: We investigated whether plasma visfatin and binding protein-4 (RBP-4) levels correlate with obesity and type 2 diabetes mellitus (T2DM).

Design And Methods: Two groups were enrolled: Group 1: 40 patients with T2DM and Group 2: 40 age- and gender-matched healthy controls. Both groups were subdivided according to body mass index (BMI) into non-obese (BMI < 25 kg/m(2)) and obese subjects (BMI ≥ 30 kg/m(2)) (20 each).

Results: Plasma visfatin and RBP-4 levels were significantly increased in T2DM patients compared with controls with similar BMI values (for both p<0.001). Plasma visfatin and RBP-4 concentrations correlated with BMI, waist/hip ratio, insulin and homeostatic model assessment insulin resistance (HOMA(IR)). Visfatin and RBP-4 correlated with visceral fat and liver fat in diabetic patients (for both p<0.001).

Conclusion: Visfatin level was increased in T2DM, possibly related to hyperglycemia. Plasma RBP-4 correlated positively with liver fat and HOMA(IR) which may reflect its effects on hepatic insulin sensitivity.
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http://dx.doi.org/10.1016/j.clinbiochem.2011.08.1148DOI Listing
December 2011

Correlations of urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and IL-8 with lupus nephritis.

J Clin Immunol 2011 Oct 21;31(5):848-56. Epub 2011 Jun 21.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.

Objective: This case-controlled study was designed to correlate urinary biomarkers, TNF-like weak inducer of apoptosis (TWEAK), osteoprotegerin (OPG), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) levels, with renal involvement in a cohort of systemic lupus erythematosus (SLE) patients to examine their diagnostic performance.

Patients And Methods: In 73 SLE patients, and in 23 healthy volunteers, urinary levels of TWEAK, OPG, MCP-1, and IL-8 levels were measured. Disease activity was assessed by total SLE disease activity index, and renal activity by renal activity index (rSLEDAI), and both were correlated with urinary biomarkers. Sensitivity, specificity, and predictive values of individual biomarkers to predict lupus nephritis were also calculated.

Results: Significantly higher levels of urinary biomarkers were observed in SLE patients with lupus nephritis (LN) compared with those without LN (TWEAK, p < 0.001; MCP-1, p < 0.001; OPG, p < 0.001; IL-8, p < 0.032). Other significantly higher levels were observed in SLE patients with LN compared with control subjects (TWEAK, MCP-1, OPG, and IL-8 p < 0.001). Positive correlations were observed between rSLEDAI and TWEAK (r = 0.612 and p < 0.001), MCP-1 (r = 0.635 and p < 0.001), and OPG (r = 0.505 and p < 0.001).

Conclusions: Urinary levels of TWEAK, OPG, and MCP-1 positively correlate with renal involvement as assessed by rSLEDAI with reasonable sensitivity, specificity, and predictive values to detect lupus nephritis while IL-8 was not significantly associated with global or rSLEDAI.
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http://dx.doi.org/10.1007/s10875-011-9555-1DOI Listing
October 2011

Endogenous soluble receptor of advanced glycation end-products (esRAGE) is negatively associated with vascular calcification in non-diabetic hemodialysis patients.

Int Urol Nephrol 2012 Aug 4;44(4):1193-9. Epub 2011 Jun 4.

Department of Nephrology, Kasr El-Aini School of Medicine, Cairo University, Cairo, Egypt.

Background: Advanced glycation end-products (AGE) accumulate in CKD and may predispose to cardiovascular disease by inducing inflammatory and oxidant stress in the vascular endothelium. Soluble forms of the receptor for AGE (RAGE) may be protective against these effects by binding AGE in the soluble phase. Accumulating evidence suggests a protective role of soluble RAGE against vascular calcification. This study investigates the association between endogenous soluble RAGE (esRAGE) and vascular calcification in hemodialysis patients.

Methods: We studied 65 non-diabetic hemodialysis patients, on 3 × 4 h dialysis schedule, and 19 controls. Serum levels of esRAGE, hsCRP, parathormone, lipids, calcium, and phosphorus were measured. Aortic calcification index (ACI) was measured using non-contrast CT of the abdominal aorta.

Results: Aortic calcification was detected in 64 out of 65 hemodialysis patients. Levels of esRAGE were lower in hemodialysis patients (278 pg/ml, SD 101.1) than in controls (443 ± 109 pg/ml; P = 0.001). ACI correlated negatively in stepwise multivariate analysis with esRAGE (P = 0.002) and positively with hsCRP (<0.0001), systolic blood pressure (P < 0.0001) and dialysis vintage (P = 0.05); R (2) = 0.65.

Conclusion: Levels of esRAGE were low among hemodialysis patients and correlated negatively with ACI.
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http://dx.doi.org/10.1007/s11255-011-0007-xDOI Listing
August 2012

Bone density, body composition, and markers of bone remodeling in type 1 diabetic patients.

Scand J Clin Lab Invest 2011 Sep 8;71(5):387-93. Epub 2011 Apr 8.

Department of Pediatrics, National Research Center, Cairo, Egypt.

Objective: To assess bone mineral density (BMD), body composition by dual X-ray absorptiometry (DXA), and various biochemical markers of bone growth and resorption in a group of children with type 1 diabetes mellitus (T1DM).

Patients And Methods: The study included 47 patients with T1DM and 30 age- and sex-matched controls. Anthropometric measurements, biochemical markers for bone formation, bone resorption and DXA were done for all patients and controls.

Results: Of our diabetes patients, seven (16.7 %), three (7.3 %), and 17 (41.5%) met diagnostic criteria for osteopenia at the right femur, lumbar spine and total body, respectively. On the other hand, osteoporosis as defined by the WHO criteria was diagnosed in 21 patients (51.2%) at the total body by DXA. Lean body mass and lean fat ratio were lower, while, total fat mass, abdominal fat%, soft tissue fat mass%, and fat/lean ratio were higher in diabetics compared to controls. Also, our patients showed lower serum osteocalcin, osteoprotegerin, procollagen type 1, and higher urinary deoxypyridinoline. Pubertal (diabetics and controls) have higher BMD and BMC than prepubertal.

Conclusion: Diabetic patients had a low BMD after adjustment (Z score), low bone formation and high bone resorption markers. Diabetes control and increase in BMI leads to a decrease in the incidence of low bone mineral density. Diabetes causes an increase in body fat especially abdominal fat which leads to an increase in insulin resistance and decrease in lean mass.
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http://dx.doi.org/10.3109/00365513.2011.573574DOI Listing
September 2011

Relationship of increased circulating adrenomedullin with cardiac dysfunction, inflammation, oxidative stress and volume overload in hemodialysis patients.

Scand J Clin Lab Invest 2011 May 24;71(3):208-15. Epub 2011 Jan 24.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Egypt.

Adrenomedullin (AM) is a peptide involved in cardiovascular homeostasis. The aim of our study was to investigate whether circulating AM might be related to cardiac function, volume overload, oxidative stress and inflammation in hemodialysis patients. Plasma adrenomedullin, C-reactive protein (CRP), oxidized LDL (ox-LDL), lipoprotein (a), systolic and diastolic cardiac functions were assessed before hemodialysis in 80 patients as well as in 40 healthy control subjects. Plasma adrenomedullin levels were significantly higher in the hemodialysis group compared to the control group. Plasma adrenomedullin levels were negatively correlated with systolic and diastolic blood pressure, S/D ratio, deceleration time, left ventricular ejection fraction, ox-LDL and lipoprotein (a). However, it was positively correlated with CRP, delta body weight, mitral E/A wave, and inferior vena cava diameter. Higher plasma adrenomedullin levels may provide a possible index of cardiac dysfunction, systemic inflammation, and volume overload conditions in haemodialysis patients with concomitant cardiovascular disease. In addition, the negative correlation between ox-LDL, lipoprotein (a) and adrenomedullin may suggest that endogenous AM is an important protective factor in anti-atherosclerosis and might be useful as a new target for prevention and therapy for the disease.
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http://dx.doi.org/10.3109/00365513.2011.553967DOI Listing
May 2011

Association of fetuin-A and cardiac calcification and inflammation levels in hemodialysis patients.

Scand J Clin Lab Invest 2010 Dec 21;70(8):575-82. Epub 2010 Oct 21.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: Vascular calcification is commonly found in chronic kidney disease (CKD) patients and it is one of the predictors of cardiovascular death. Recently, several studies have demonstrated that low fetuin-A levels are associated with mortality in uremic patients. Objectives. To investigate the importance of non-traditional risk factors of calcification including fetuin-A, IL-6 and high sensitivity CRP (hsCRP) in hemodialysis patients and their relationship to the extent of cardiac calcification by means of multislice computed tomography (MSCT), and echocardiography.

Patients And Methods: The study was conducted on 70 hemodialysis patients as well as 20 healthy control subjects. All patients were subjected to MSCT for evaluation of calcium score in the coronary arteries as well as echocardiography for detecting valvular calcification. In addition, the patients were sampled for evaluation of inflammatory markers such as hsCRP and IL-6 and also fetuin-A.

Results: Mean serum fetuin-A was significantly lower in hemodialysis patients than controls subjects. By dividing the patients into tertiles of serum fetuin-A, a significant association between low levels of fetuin-A and high calcium score and valvular calcification were found. Multiple regression analysis showed that calcium scoring and IL-6 were the most independent risk factors for serum fetuin-A levels.

Conclusion: Serum fetuin-A showed important association with coronary, valvular calcification and inflammation in hemodialysis patients. Assessment of both cardiac calcification and serum levels of fetuin-A may be of value to identify those subjects at higher risk of development and progression of vascular lesion and may be a novel therapeutic approach.
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http://dx.doi.org/10.3109/00365513.2010.528445DOI Listing
December 2010

Apelin: a potential link between inflammation and cardiovascular disease in end stage renal disease patients.

Scand J Clin Lab Invest 2010 Oct;70(6):421-7

Department of Medical Biochemistry, Kasr El-Aini School of Medicine, Cairo University, Egypt.

Background And Objectives: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. In the present study, the plasma level of apelin was studied in patients with hemodialysis to assess the effect of renal transplantation and dialysis session on plasma apelin and whether circulating apelin levels reflect cardiovascular homeostasis and inflammation in these patients.

Patients And Methods: Plasma apelin, high sensitive CRP (hsCRP) and IL-6 levels were investigated in 30 end stage renal disease (ESRD) patients on maintenance hemodialysis (HD), a group of 15 HD patients scheduled for renal transplantation and a group of 15 HD patients on maintenance HD, as well as ten healthy volunteer subjects who served as controls. An echocardiography was performed for all subjects.

Results: Plasma apelin levels were significantly lower in hemodialyzed patients compared to controls. Plasma apelin was also found to be positively correlated with left ventricular end systolic dimension (LVESD), left ventricular end diastolic dimension (LVEDD), interventricular septum (IVS), right ventricle (RV), left atrium (LA), Aorta (Ao), while, it was negatively correlated with hsCRP and IL-6 in ESRD patients. Regarding the effect of hemodialysis on plasma apelin levels, no significant effect was found after a single hemodialysis session, while levels increased significantly in the early post-transplant period.

Conclusions: Apelin is related to echocardiographic features and inflammatory markers in hemodialyzed patients. Apelin may provide a mechanism for systemic inflammatory monitoring and adaptive regulation of cardiovascular function.
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http://dx.doi.org/10.3109/00365513.2010.504281DOI Listing
October 2010

Early diagnostic markers for contrast nephropathy in patients undergoing coronary angiography.

Angiology 2010 Nov 7;61(8):731-6. Epub 2010 Jun 7.

Department of Medical Biochemistry, Faculty of Medicine, Cairo University, Egypt.

Unlabelled: The present work aimed to prove the usage of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker for kidney injury and to assess the relationship between NGAL and serum creatinine and cystatin C in patients with normal serum creatinine undergoing percutaneous coronary angiography. Thirty patients with normal serum creatinine undergoing coronary angiography were enrolled. Estimation of blood glucose, glycosylated hemoglobin, lipid profile, creatinine, NGAL, and cystatin C were done before coronary angiography for all patients. Serum creatinine, NGAL and cystatin C were evaluated again at 4 and 24 hours after coronary angiography. There was a significant increase in serum NGAL level 4 hours and 24 hours after coronary interventions compared to the baseline value before coronary angiography. Before coronary angiography, serum NGAL was positively correlated with serum creatinine, and cystatin C.

Conclusion: Serum NGAL and cystatin C could be valuable in the detection of early renal impairment after coronary angiography.
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http://dx.doi.org/10.1177/0003319710373093DOI Listing
November 2010

Possible role of osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand as markers of plaque instability in coronary artery disease.

Angiology 2010 Nov 24;61(8):756-62. Epub 2010 May 24.

Department of Medical Biochemistry, Cairo University, Maadi, Cairo, Egypt.

Unlabelled: Osteoprotegerin (OPG) produced by cardiovascular system raising the possibility that alterations of OPG serum levels may be associated with coronary artery disease (CAD). Our aim is to assess the possible role of serum OPG and soluble tumor necrosis factor-related apoptosis-inducing ligand (s-TRAIL) in the pathology of CAD and their uses as markers of plaque stability. A total of 80 male participants were categorized into 3 groups: 28 patients with acute myocardial infarction (AMI), 32 established stable CAD, and 20 healthy controls were enrolled in this study. Acute myocardial infarction and CAD groups exhibited significantly higher OPG levels and lower s-TRAIL levels compared to the stable CAD and control participants. These results are aggravated as the number of affected coronary vessels increase in AMI and stable CAD groups.

Conclusion: There is an association between raised serum OPG and reduced s-TRAIL in patients with CAD. Elevation of circulating OPG levels may represent a crucial compensatory mechanism to limit further vascular damage.
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http://dx.doi.org/10.1177/0003319710370961DOI Listing
November 2010

Total and acylated ghrelin in liver cirrhosis: correlation with clinical and nutritional status.

Scand J Clin Lab Invest 2010 Jul;70(4):252-8

Department of Medical Biochemistry, Cairo University, Cairo 11562, Egypt.

Objectives: The pathogenesis of anorexia in cirrhotic patients is complex and the appetite-modulating hormone ghrelin could be involved. Acylated ghrelin is the biologically active form that modifies insulin sensitivity and body composition. The aim of the present study was to compare acylated and total ghrelin concentration in patients with liver cirrhosis and to investigate the possible relationship between ghrelin and clinical and nutritional parameters.

Design And Methods: Sixty patients with viral liver cirrhosis who did not have hepatocellular carcinoma or acute infections were studied. Twenty healthy volunteers were recruited after matching for age, gender, and body mass index with the patients and served as controls. Fasting levels of total, acylated ghrelin, leptin, TNF-alpha and insulin were measured in all subjects, in addition, clinical and nutrition parameters were assessed.

Results: In cirrhotic patients, plasma levels of both acylated and total ghrelin were significantly higher than those in the controls. The mean plasma acylated ghrelin levels were significantly higher in Child C cirrhosis compared to Child A and B. Ghrelin (total and acylated) were negatively correlated with leptin in cirrhotic patients confirming the fact that leptin acts as a physiological counterpart of ghrelin.

Conclusions: Nutritional and metabolic abnormalities in cirrhotic patients may be dependent on the changes in the ghrelin/leptin systems, mainly the acylated form of ghrelin.
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http://dx.doi.org/10.3109/00365511003763349DOI Listing
July 2010

Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients.

Nephrol Dial Transplant 2010 Aug 22;25(8):2679-85. Epub 2010 Feb 22.

Department of Nephrology, School of Medicine, Kasr El-Aini School of Medicine, Cairo University, Cairo, Egypt.

Background: Vascular calcification has detrimental consequences on chronic kidney disease (CKD) patients, yet its pathogenesis is not fully understood. Fibroblast growth factor-23 (FGF-23) is involved in the regulation of mineral metabolism which may in turn affect vascular calcification. Data on the relationship between FGF-23 and peripheral vascular calcification, using conventional radiographs, are conflicting, and less is known about its relation to aortic calcification. We conducted this study to investigate the relationship between FGF-23 and aortic calcification in a standard haemodialysis setting.

Methods: The study included 65 haemodialysis patients (46 prevalent and 19 incident) on a three times 4-h dialysis schedule as well as 15 controls. Those with diabetes, oral anticoagulation or parathyroidectomy were excluded. Intact FGF-23, parathormone, lipids, calcium and phosphorus were measured. Aortic calcification index (ACI) was assessed by a non-contrast computerized tomography (CT) of the abdominal aorta.

Results: FGF-23 levels were higher among haemodialysis patients (4681.3 +/- 3906.1 pg/mL) compared to controls (98.2 +/- 51.9 pg/mL), P = 0.005. ACI was higher in haemodialysis patients (14.1 +/- 12) than controls (3.2 +/- 3.6), P = 0.009. FGF-23 (P < 0.0001) and systolic blood pressure (BP) (P < 0.0001) were independently related to ACI in stepwise multiple regression analysis of pooled analysis of haemodialysis patients, R(2) = 0.476; in subgroup analysis, the independent factors relating to ACI among prevalent dialysis patients were systolic BP (P < 0.0001), FGF-23 (P = 0.002) and age (P = 0.012), R(2)=0.48; whereas in incident patients, only FGF-23 was associated with ACI (P = 0.007), R(2) = 0.37.

Conclusions: In haemodialysis patients, FGF-23 and ACI were significantly increased, and FGF-23 was independently associated with aortic calcification.
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http://dx.doi.org/10.1093/ndt/gfq089DOI Listing
August 2010

The relation between dual energy x-ray absorptiometry measurement of body fat composition and plasma ghrelin in patients with end-stage renal disease.

Saudi Med J 2009 Jan;30(1):109-15

Department of Radiology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Objective: To clarify the role of ghrelin in malnutrition in uremia and its relationship to fat composition using dual x-ray absorptiometry (DXA).

Methods: This is a cohort study including Group I: 60 patients with end stage renal disease 30 on hemodialysis [group IA] and 30 pre-dialysis [group IB] and Group II: 20 controls. This study was carried out in Cairo University Hospital, Kasr Al-Aini, Cairo, Egypt in 2007. Body fat composition (total, differential, and lean body mass) was assessed using DXA, and plasma ghrelin was measured.

Results: Ghrelin was significantly higher in hemodialysis and pre-dialysis groups compared to the control group, and higher in hemodialysis group compared to the pre-dialysis group. In hemodialysis, ghrelin was negatively correlated with weight, body mass index (BMI), and truncal fat mass, and positively correlated with serum creatinine. In pre-dialysis, ghrelin inversely correlated with weight, BMI, and truncal fat mass, and positively correlated with serum creatinine, lean body mass. In control, plasma ghrelin showed negative correlation with weight, BMI, truncal fat mass, and body fat mass, and positive correlation with lean body mass.

Conclusion: Ghrelin was markedly elevated in renal failure due to its decrease in excretion. Negative correlation between ghrelin and fat composition was detected in dialysis patients. Serial evaluation of body fat composition using DXA is recommended for assessment of nutritional status of those patients.
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January 2009

The role of PDE5 inhibitors in heme oxygenase-cGMP relationship in rat cavernous tissues.

J Sex Med 2008 Jul;5(7):1636-45

Molecular Biology Unit, Medical Biochemistry Department, Faculty of Medicine, Cairo University, Cairo 11562, Egypt.

Introduction: Heme oxygenase (HO) enzyme catalyzes oxidative degradation of heme to biliverdin and carbon monoxide (CO). CO shares many properties with nitric oxide (NO) including the activation of soluble guanyl cyclase.

Aim: To assess cavernous tissue HO activity and cyclic guanosine monophosphate (cGMP) levels in response to oral phosphodiesterase type 5 (PDE5) inhibitors.

Methods: Seven hundred twenty male Sprague-Dawley rats, divided into six groups, were investigated. Group 1, controls; group 2 received sildenafil citrate orally; group 3 received vardenafil hydrochloride; and group 4 received tadalafil. Group 5 was subdivided into three equal subgroups, received the same dose of each drug added to the HO inhibitor, Zn protoporphyrin. Group 6 was subdivided into three equal subgroups, received the same dose of each drug added to the NO inhibitor, L-nitroarginine methylester. Eight rats from each group/subgroup were sacrificed at 0.5, 1, 2, 3, 4, 6, 18, 24, and 36 hours, respectively.

Main Outcome Measures: HO enzyme activity assay and cGMP tissue levels in dissected rat cavernous tissues.

Results: Both cavernous tissue HO enzyme activity and cGMP levels were increased significantly in sildenafil-, vardenafil-, and tadalafil-treated rats compared with the controls, with significant decreases after either HO or NO inhibition. Cavernous tissue HO enzyme activity and cGMP showed a positive significant correlation (r = 0.854, P < 0.001).

Conclusion: The effects of PDE5 inhibitors in cavernous tissue are partly mediated through HO enzyme activity.
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http://dx.doi.org/10.1111/j.1743-6109.2007.00729.xDOI Listing
July 2008

p53 mutation in HCV-genotype-4 associated hepatocellular carcinoma in Egyptian patients.

J Egypt Natl Canc Inst 2006 Mar;18(1):17-29

The Department of Virology & Immunology Unit, National Cancer Institute, El-Menoufia School of Medicine, El-Menoufia University, Egypt.

HCV-associated hepatocellular carcinoma (HCC) is a common neoplasm in Egypt where genotype-4 is prevalent. In the present study the incidence and pattern of p53 mutations was assessed in relation to HCV-genotype- 4 in Egyptian HCC patients. We investigated 25 HCV positive HCCs for p53 mutations/overexpression in relation to HCV-NS3 by immunohistochemistry, SSCP and sequencing. Genotyping was done using LiPA-II and TRUGENE 5' NC' sequencing kit. Results were correlated to standard clinicopathologic prognostic factors for HCC. Thirteen cases showed p53 overexpression, and 10 showed p53 mutation (13 mutations) by sequencing (72% concordance). The highest mutation rate was in exons 6 and 7 (30%) followed by exons 5 and 8 (20%). Mutations included 3 transitions, 5 transversions, 3 deletions, and 2 insertions. All exon 7 mutations were at codon 249 specific for AFB1 (AGG-->AGT, Arg-->Ser) and codon 248 specific for vinyl chloride contamination (CGG-->TGG, Arg-->Trp). Other mutations reported are novel. Immunostaining for HCV NS3 was detected in 19 cases independent of p53 mutation. p53 aberrations were significantly associated with poor prognostic factors for HCC. However, no specific pattern for p53 mutations was observed in HCV genotype 4-associated HCC and no significant relation between p53 mutations, HCV-NS3 expressions or any HCV sub-genotype-4 sequence.
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March 2006

Cytokine profile in Egyptian hepatitis C virus genotype-4 in relation to liver disease progression.

World J Gastroenterol 2005 Nov;11(42):6624-30

Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Fom El-Khalig, Cairo 11796, Egypt.

Aim: To observe the imbalance between T helper cell Th1 and Th2 cytokines in several chronic hepatitis disease at different stages of disease progression.

Methods: We measured the cytokine levels of Th1 (IL-2 and IL-2R), Th2 (IL-10) and the pro-inflammatory cytokines (IL-6 and IL-6R and TNF and TNF-RI and II) by the ELISA technique in the sera of 33 hepatocellular carcinoma (HCC) patients and 20 chronic liver disease (CLD) patients. In addition, 20 asymptomatic hepatitis C virus carriers and 20 healthy subjects negative for hepatitis C virus(HCV) markers served as controls.

Results: Anti-HCV antibodies were found to be positive in 94% of HCC cases and 75% of CLD cases. On the other hand, HCV viremia was detected using RT-PCR in 67% of HCC cases and 65% of CLD cases. HBsAg was positive in 9% of HCC cases and 30% of CLD cases. Also bilharzial-Ab was positive in 55% of HCC cases, 65% of CLD cases and in 70% of asymptomatic carriers (ASC). HCC patients had significantly higher values of IL-2R, TNF-RII (P<0.001), and TNF-RI (P>0.05), but lower TNFalpha (P<0.001) and IL-6 (P = 0.032) in comparison to ASC. But, in comparison to non-cancer controls, HCC patients had higher values of IL-2R, IL-6R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). CLD patients had higher IL-2R, TNF-RI, and TNF-RII (P<0.001) than ASC. But, in comparison to non-cancer controls, CLD patients had higher values of IL-2R, TNF-RI and TNF-RII, but lower TNF-alpha (P<0.001). IL-10 was higher (though not significantly) in HCC and CLD patients than in symptomatic carriers and non-cancer controls.

Conclusion: Liver disease progression from CLD to HCC due to HCV genotype-4 infection is associated with an imbalance between Th1 and Th2 cytokines. IL-2R, TNF-RI, and TNF-RII could be used as potential markers.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355755PMC
http://dx.doi.org/10.3748/wjg.v11.i42.6624DOI Listing
November 2005

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival.

Pathol Int 2005 Feb;55(2):53-62

Department of Pathology, National Cancer Institute, Kaser El-Aini School of Medicine, Cairo University, Fom El-Khalig, Cairo 11796, Egypt.

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.
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http://dx.doi.org/10.1111/j.1440-1827.2005.01804.xDOI Listing
February 2005

Alterations of the fragile histidine triad gene in hepatitis C virus-associated hepatocellular carcinoma.

J Gastroenterol Hepatol 2005 Jan;20(1):87-94

Virology and Immunology Unit, Cairo University, Cairo, Egypt.

Background And Aim: The present study was conducted to address whether homozygous deletion (HZD) or transcriptional alterations of the fragile histidine triad (FHIT) gene play a role in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCC).

Methods: Homozygous deletion of the FHIT gene at exons 3-9 was assessed as well as mRNA FHIT expression using reverse transcription polymerase chain reaction. The study included 23 samples of HCC, 11 on top of cirrhosis and 12 non-cirrhotic, in addition to five cases with chronic active hepatitis (CAH), as well as seven morphologically normal tissues distant to the tumor (NDT) and 10 normal liver samples from liver transplantation donors.

Results: Homozygous deletion was found in 18 of 23 HCC cases. The highest incidence of deletion was detected in exon 9 (52.0%) and the lowest in exon 7 (4.3%). Ten of the 18 cases (55.5%) showed deletion in more than one exon, eight in two exons, one in three exons and one in five exons. There was a significant association between HZD of exons 5 and 9 and HCC arising on top of cirrhosis (P = 0.041 and 0.006, respectively) as well as between exons 8 and 9 and the presence of CAH (P = 0.029 and 0.034, respectively). Aberrant FHIT transcripts were detected in 15 HCC cases (65.2%), 13 of them showed complete reduction of the mRNA transcripts and two showed abnormal bands. Sequence analysis of abnormal-sized transcripts revealed that they were generated by the fusion of exons 5 and 7 as well as exons 7 and 9. In contrast, six of the seven NDT samples tested (85.6%) showed HZD in one or more exons. None of the normal liver samples from liver transplantation donors showed any changes. The highest incidence of HZD was detected in exon 9 (five of six cases representing 83.3%) and the lowest was in exon 4 (one of six cases representing 16.7%). Four cases showed the same aberrant FHIT HZD in both NDT and matched HCC.

Conclusions: The results of the present study indicate that the FHIT gene is a frequent target in hepatitis C virus-associated HCC and that alterations affecting this gene could be an early event in this type of neoplasm as they were detected in cirrhotic and CAH patients. However, this should be confirmed by a larger, extended study including more cases of cirrhotic and CAH patients as well as matched tumor and normal samples.
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http://dx.doi.org/10.1111/j.1440-1746.2004.03611.xDOI Listing
January 2005

Risk factors for cytomegalovirus, hepatitis B and C virus reactivation after bone marrow transplantation.

Transpl Immunol 2004 Dec;13(4):305-11

Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Fom El-Khalig, Cairo 11796, Egypt.

To derive guidelines for a safer bone marrow transplantation (BMT) policy, we have to study pre-BMT risk factors that may be associated with an increased post-BMT death. Among those factors, the importance of pre-BMT viral hepatitis markers in BMT donors and recipients remains unsettled. In the present study, we have determined the effect of prior donor and recipient cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV) exposure on the incidence of those viral infections after bone marrow transplantation (BMT). The study included 63 patients presented to the BMT unit; 28 of them underwent transplantation and 35 were not transplanted. All serum markers of CMV, HBV, and HCV infections were monitored using ELISA technique, as well as PCR-DNA for CMV, HBV and HCV RT-PCR techniques for HCV. The incidence of active CMV and HCV was 11/28 (39%) and 6/28 (21%) in post-BMT recipients compared to 2/35 (6%) and 2/35 (6%) in the 35 untransplanted patients (P=0.00003 and P=0.05). Whereas active HBV infection was non significantly (P=0.13) higher 3/28 (11%) in the BMT patients in comparison to 1/35 (3%) in untransplanted patients. Ten out of the 19 (53%) of the CMV-seropositive recipients developed CMV reactivation compared to 1/9 (11%) of the CMV-seronegative recipients who developed CMV seroconversion. In addition, 3/8 (38%) of the HBV-seropositive recipients developed HBV reactivation in comparison to 0/20 of the HBV-seronegative recipients. Moreover, 5/13 (39%) of the HCV-seropositive recipients developed HCV reactivation in comparison to 1/16 (6%) of the HCV-seronegative recipients who developed HCV seroconversion. In conclusion, previous exposure to CMV, HBV, and HCV infections in the recipients of BMT patients were found to influence the risk of developing those viral infections.
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http://dx.doi.org/10.1016/j.trim.2004.10.001DOI Listing
December 2004