Significance of plasma osteopontin in diagnosis of hepatitis C virus-related hepatocellular carcinoma

Alfa fetoprotein [AFP] is widely used as a surveillance test for hepatocellular carcinoma [HCC] among patients with liver cirrhosis [LC]. However, the clinical use of AFP has been shown to present some important limitations in sensitivity and specificity. Osteopontin [OPN] is a secreted matrix glycoprotein that is emerging as a significant protein in the biology of HCC. The aim of this study was to assess the diagnostic value of plasma OPN compared with that of AFP in the diagnosis of HCC among hepatitis C virus [HCV]-related LC. Plasma levels of OPN and AFP were measured in 69 Egyptian patients with HCV-related LC [35 with HCC and 34 without HCC] and 20 healthy controls. Both median AFP and OPN levels were significantly higher in the HCC group compared to LC and healthy control groups [p < 0.001 in each] and in LC compared to the control group [p < 0.001]. In the HCC group, both OPN and AFP levels were significantly higher in patients with Child-Pugh class C and B compared to class A [p < 0.05 in each]. There was no correlation between OPN and AFP levels. The OPN level was significantly higher in patients with multiple focal lesions than in those with single lesions [p < 0.05] and in patients with portal vein invasion compared to patients without portal vein invasion [p < 0.05]. Receiver operator characteristic [ROC] curves showed that the area under the curve [AUC] for OPN and AFP was 0.824 and 0.730, respectively. OPN is a promising tumour marker which could be used as a screening test for the diagnosis of HCC in patients with LC and, hence, improves the prognosis and survival rate of these patients. The association of OPN with the multiplicity of focal lesions and portal vein invasion suggests an additional prognostic value

Combined blood and pleural levels of mesothelin and osteopontin for the diagnosis of malignant pleural mesothelioma

Malignant pleural mesothelioma [MPM] is a highly aggressive tumor with poor survival rate. It is difficult to diagnose MPM at an early stage. Soluble mesothelin remains the best available biomarker for MPM, however the lack of sensitivity for early stage disease provides a motivation for the search of an additional marker that could be combined with mesothelin for early malignancy detection. The aim was to evaluate the diagnostic value of soluble mesothelin and osteopontin both in blood and pleural fluid of MPM patients and to assess whether combination of these markers could improve the diagnostic accuracy of mesothelin. In this study mesothelin and osteopontin were measured by ELISA method in 197 samples [123 blood and 74 pleural] obtained from 123 participants, divided into 4 groups: 38 MPM patients, 24 patients with metastatic pleural effusion [Mets] of various carcinomas, 29 patients with hydrothorax and 32 healthy asbestos exposed subjects. Receiver operating characteristic [ROC] curves were generated to compare the diagnostic capability of these biomarkers. Combination of markers was done through logistic regression analysis. The median blood and pleural levels of the two markers were significantly higher in MPM patients than in hydrothorax or asbestos exposure groups [P < 0.0001], however the difference between MPM and Mets group was not significant. Combining the data from blood mesothelin and osteopontin using logistic regression model raised the area under the ROC curve [AUC] from 0.774 for serum mesothelin and 0.828 for plasma osteopontin to 0.867 to differentiate MPM from hydrothorax and asbestos exposed subjects. Combining the diagnostic capability of both pleural markers raised the AUC from 0.871 for pleural mesothelin and 0.847 for pleural osteopontin to 0.905 to differentiate MPM from hydrothorax patients. The performance of serum and pleural mesothelin in diagnosing MPM was improved when combined with plasma and pleural osteopontin [respectively] through logistic regression analysis model. This will be a great advance in screening and management of MPM

Assessment of the role of paraoxonase gene polymorphism [Q192R] and paraoxonase activity in the susceptibility to atherosclerosis among lead-exposed workers

Lead exposure is a well known cause of cardiovascular damage, including atherosclerosis. Paraoxonase 1 [PON1], a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus it protects against atherosclerosis. The mechanism by which heavy metals inhibit serum PON1 activity is still not clear. Our aim was to detect the association between lead exposure and serum PON1 activity and lipid profile and also to study the polymorphism of the PON1 gene. A case-control, cross-sectional study conducted from June 2008 until May 2009. Male workers [n=100] in a lead battery manufactory were recruited for this study. They were compared with 100 male age-matched workers not exposed to lead [control group]. Serum lipid profile, paraoxonase activity and lead were measured in blood samples. The DMA was extracted for detecting the Q192R polymorphism of the PON1 gene by polymerase chain reaction followed by restriction fragment length polymorphism. There was significant difference in triglycerides, total cholesterol and high-density lipoprotein cholesterol [HDL-C] [P=.01,.05 and.04, respectively] between cases and controls. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum paraoxonase activity [P=.03] in lead workers. The paraoxonase genotype QR was the most prevalent in 34/53 subjects [64%] among the leadexposed groups, while the genotype QQ was more prevalent in the control group, in 1 5/25 subjects [60%], with a significant difference between the control and other groups [P<.05]. Lead exposure is associated with increased triglycerides, total cholesterol and low-density lipoprotein cholesterol and decreased HDL-C. Because of the protective role of PON1 in the development of atherosclerosis, a decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis

Effect of obesity on lipolytic activity of adipose tissue in male rats

Obesity has become a major problem in the modern world; it is affected genetically and by lifestyle. Since obesity is associated with multi co-morbidities like dyslipidemia, hypertension, and metabolic syndrome, this work studied the effect of induced obesity on body weight, blood pressure, lipid profile, glycemic state and lipolytic activity of adipose tissue in male rats. Twenty male rats of a body weight ranging from 178 to 200 g were divided equally into two groups, one fed commercial rat chow as a control group [Cgp] and the other fed 10% saturated fat to induce obesity as experimental group [SFgp]. After 3 months the body weight, blood pressure, fasting blood glucose, insulin level, and lipid profile of both groups were measured and the lipolytic activity of adipose tissue was assessed by the amount of free glycerol released. Rats fed saturated fat for 3 months showed significant increase in birth weight, systolic blood pressure, TG, Cholesterol, LDL, fasting blood glucose and insulin levels by 55.3%, 15.86% 24%, 7.92%, 19.58% 20.5% and 26.25% respectively with a significant decline in HDL by 12.9%. Lipolytic activity of SC tissue in the presence of adrenaline decreased significantly by 15%, while in the presence of insulin it increased significantly by 33.33%. It showed a significant increase by 18% and 25.84% in the presence of adrenaline and insulin respectively in visceral adipose tissue. A p value less than 0.05 was considered statistically significant. obesity induced in male rats by high saturated fat diet showed a significant rise in BW and is associated with hypertension, dyslipidemia, hyperglycemia and insulin resistance. The adipose tissue of obese male rats showed a significant decrease in lipolytic activity of SC with a significant rise in the corresponding value in visceral adipose tissue

Effect of insulin resistance on lipolytic activity of adipose tissue in male rats

The excess usage of fructose as a sweetener that we all consume everyday in one way or another has raised the incidence of insulin resistance among the population which is associated with dyslipedemia, hypertension and obesity. This work studied the effect of induced insulin resistance on body weight, blood pressure, lipid profile, glycemic state and lipolytic activity of adipose tissue in male rats. 20 male rats of 129.4 g average body weight were divided equally into two groups. Both had free access to water. The control [Cgp] had pure water, the experimental group [Fgp] had water mixed with 25% of fructose to induce insulin resistance. After 3 months the body weight, blood pressure, fasting blood glucose, insulin levels, lipid profile of both groups were measured and lipolytic activity of adipose tissue was assessed by the amount of free glycerol released. Rats given fructose for 3 months showed significant increase in BW, systolic blood pressure, TG, Cholesterol, LDL, fasting blood glucose and insulin levels by 28.7%, 13.9% 23.9%, 3%, 5.61% 115.49% and 232.8% respectively with a significant decline in HDL by 5.98%. Lipolytic activity of SC and visceral adipose tissue in presence of adrenaline increased significantly by 55.25%, and 78.63% respectively, which runs in parallel with the results obtained in presence of insulin as it showed a significant rise in both SC and visceral adipose tissue by 109.3% and 167.12 respectively. data were statistically significant at p<0.05. Insulin resistance induced in male rat by high fructose consumption showed a significant rise in BW and is associated with hypertension and dyslipidemia with significant rise in lipolytic activity of both SC and visceral adipose tissue

Altered serum lipids and paraoxonase activity: a step toward at herosclerosis among lead exposed Egyptian workers

A vast amount of evidence during the past decade, has confirmed that lead is associated with lipid and lipoprotein abnormalities which play a major role in the pathogenesis and progression of atherosclerosis and cardiovascular diseases. This study aimed: to investigate the relationship between chronic occupational lead exposure, lipid profile, and serum PON1 activity as one of the mechanisms of atherosclerosis. Male workers [n=100] in lead battery manufactory were recruited for this study. They were compared with 100 male age matched non-lead workers. Serum lipid profile and paraoxonase activity were done to their samples. Serum Lead was determined vsing atomic absorption spectroscopy. There was significant differences regarding triglycerides, total cholesterol, and HDL- c [p=0.01, 0.05 and 0.04, respectively] between both groups. A cumulative effect of blood lead on lipid profile was significantly detected. Multiple linear regression analysis showed that blood lead level was the only negative significant predictors to serum paraoxonase activity [p=0.03] in lead workers. lead exposure is associated with increased triglycerides, total cholesterol and LDL-c and decrease HDL-c. Because of the protective role of PON1 in the development of atherosclerosis, decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis