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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Relationship between serum osteoprotegerin and vascular calcifications in hemodialysis patients.

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) (p < 0.005), and negatively with hemoglobin, ejection fraction (p < 0.005) and HDL (p < 0.05). CONCLUSIONS: These findings suggest that osteoprotegerin may be involved in the development of vascular calcification in hemodialysis patients.

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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

Cyclin A and cyclin D1 as significant prognostic markers in colorectal cancer patients.

BACKGROUND: Colorectal cancer is a common cancer all over the world. Aberrations in the cell cycle checkpoints have been shown to be of prognostic significance in colorectal cancer. METHODS: The expression of cyclin D1, cyclin A, histone H3 and Ki-67 was examined in 60 colorectal cancer cases for co-regulation and impact on overall survival using immunohistochemistry, southern blot and in situ hybridization techniques. Immunoreactivity was evaluated semi quantitatively by determining the staining index of the studied proteins. RESULTS: There was a significant correlation between cyclin D1 gene amplification and protein overexpression (concordance = 63.6%) and between Ki-67 and the other studied proteins. The staining index for Ki-67, cyclin A and D1 was higher in large, poorly differentiated tumors. The staining index of cyclin D1 was significantly higher in cases with deeply invasive tumors and nodal metastasis. Overexpression of cyclin A and D1 and amplification of cyclin D1 were associated with reduced overall survival. Multivariate analysis shows that cyclin D1 and A are two independent prognostic factors in colorectal cancer patients. CONCLUSIONS: Loss of cell cycle checkpoints control is common in colorectal cancer. Cyclin A and D1 are superior independent indicators of poor prognosis in colorectal cancer patients. Therefore, they may help in predicting the clinical outcome of those patients on an individual basis and could be considered important therapeutic targets.

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

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.