Serum matrix metalloproteinase-2 in patients with chronic hepatitis C and hepatocellular carcinoma

The present study aimed to examine the possible involvement of matrix metalloproteinase-2 [MMP-2] in the development of liver diseases caused by HCV infection. The serum activities of MMP-2 enzyme were studied by enzyme immunoassay [EIA] in sera from patients with HCV and HCC on the top of HCV. This study included 46 Egyptian patients presenting with either chronic hepatitis C infection [HCV] or hepatocellular carcinoma [HCC]. Eighteen subjects were included as a control group. The serum levels of MMP-2 were found to be significantly higher in both patient groups as compared with the control group. However, there was no significant difference between HCV and HCC patient groups. There was a significant positive correlation between the serum levels of MMP-2 and the severity of the liver disease as shown in its significant relationship with other liver function tests, but no correlation was found with alpha fetoprotein [ALP] levels

Evaluation of BCL-2 and transforming growth factor alpha oncoproteins in patients with chronic hepatitis C infection: impact on hepatocellular carcinoma

Persistent hepatitis C virus [HCV] infection is associated with the development of human hepatocellular carcinoma [HCC], although the mechanism of HCV-related hepatocarcinogenesis remains unclear. bcl-2 oncoprotein can prolong cell survival by blocking apoptosis without affecting cellular proliferation. Transforming growth factor alpha [TGF-alpha] is alleged to play a role in malignant progression as well as normal cell growth in an autocrine manner. The present study was carried out to investigate the kinetics of bcl-2, TGF-alpha and alpha-fetoprotein [AFP] release in sera, ascetic fluid and liver tissue from chronically infected HCV infected patients and those with HCC. The impact of these biomarkers on the development of HCC was also investigated. The obtained results revealed that serum bcl-2 was significantly higher [p <0.001] in HCV and HCC as compared to the healthy control group. Moreover, serum bcl-2 levels in HCC were significantly higher [p <0.001] than in HCV patients. This may suggest that the antiapoptotic oncoprotein bcl-2 may provide hepatocytes with sufficient time in the inflamed tissue to accumulate the specific gene mutations that culminate cancer. This work showed that serum TGF-alpha. level was significantly higher in HCV and HCC patients [p <0.001] as compared to the healthy control adults. However, there was non-significant difference in serum TGF-alpha level in HCV patients as compared to those with HCC. This finding could suggest that TGF-alpha might be the primary marker to start the process of carcinogenesis, however, higher levels of TGFa may not be needed to the progress of malignancy. Serum TGF-a levels were significantly higher [p<0.05] in HCV patients with liver cirrhosis than HCV without cirrhosis. This might suggest that the hepatocyte regeneration occurring in cirrhosis could contribute to the higher serum TGF-alpha levels in HCV patients with liver cirrhosis. The sensitivity and specificity to detect HCC in HCV patients were 62.5% and 90.9% for serum bcl-2; 37.5% and 68.2% for serum TGF-alpha; 56.3% and 90.1% for AFP. In conclusion, bcl-2 oncoprotein overexpression in hepatocytes in HCV suggests that the available mechanism of apoptosis may be suppressed by bcl-2. The increased expression of bcl-2 oncoprotein in HCC, by its antiapoptotic action, is essential for carcinogenesis to proceed to malignancy. Serum bcl-2 may be helpful for diagnosis of HCC developing in HCV patients. Although the increased expression of bcl-2 oncoprotein in HCC suggests that bcl-2 may be involved in hepatocarcinogenesis, further investigations through molecular techniques is necessary, in order to define the exact role of apoptosis-related genes in this neoplastic process

Alkaline phoshatase, tumor necrosis factor-alpha and matrix metalloproteinase-8 in crevicular fluid from peri-implantitis versus chronic periodontitis patients

Peri-implantitis is an inflammatory reaction affecting the tissues surrounding osseointegrated dental implants resulting in loss of supporting bone. Recent advances in the understanding of biologic events involved in the pothogenesis of periodontitis indicating that bone mediators e.g. tumor necrosis factor-alpha [TNF-alpha], alkaline phosphatase [ALP] and matrix metalloproteinase-8 [MMP-8] may also be operating in the pathogenesis of peri-implantitis. This study aimed to explore whether pro-inflammatory mediator TNF-alpha and markers of bone loss; ALP and MMP-8 in per-implant crevicular fluid [PICF] provide a diagnostic information as to the status of the implant. The present study evaluated 11 implants in patients having peri-implantitis and 12 without implantitis as compared to 12 patients with chronic periodontitis. The clinical assessment for all patient groups included pocket depth [PD], plaque index [PI] and gingival index [GI]. There were significant differences [p<0.05] in PI, PD and GI in peri-implantitis and periodontitis patient groups as compared to healthy implant group, while there were non significant difference between per-implantitis and periodontitis patient groups. ALP, MMP-8 and TNF-alpha were measured in gingival crevicular fluid [GCF] and PICF 2 years postoperatively. The ALP activity and MMP-8 concentration were significantly higher in periodontitis and peri-implantitis patients than healthy implant group [p<0.01, and p<0.05, respectively]. There were no statistically significant differences TNF-alpha concentration between the three study groups. There were no statistically significant differences in MMP-8 concentration and ALP activity between periodontitis group and patients with per-implantitis. The ALP activity showed a significant positive correlation with GI and PD [p<0.01]. In conclusion, the present results might suggest that ALP and MMP-8 in PICF has a possible role as a markers of peri-implantitis

cardioprotective effect of urea against acute doxorubicin induced cardiotoxicity in rats

Recently, urea is considered one of the endogenous antioxidant substances that have a potential antioxidant cardioprotective effect against ex vivo post-ischemic reperfusion and oxidative stress induced cardiac injury in rats. A single injection of doxorubicin, 15 mg Kg[-1], intrapeirtoneal [i.p] in rats induced cardiac toxicity manifested biochemically by the significant increase [P<0.01] of serum creatine phosphokinase [CPK] and lactate dehydrogenase [LDH] after 48 hours and significant decrease [P<0.01] of heart homogenate superoxide dismutase [SOD] and reduced glutathione [GSH] compared to normal control rats. Administration of urea [500 mg Kg[-1] day[-1] i.p] for 2 successive days improved doxorubicin induced cardiotoxicity in rats represented by the significant decrease [P<0.01] of serum CPK and LDH in comparison to rats injected with doxorubicin only. The cardioprotective effect of urea could be explained by the observed significant reduction [P<0.01] of heart homogenate lipid peroxidation, expressed as thiobarbituric acid reacting substances [TBARS], and significant increase [P<0.01] of SOD and GSH compared to doxorubicin-induced cardiotoxicity rats. In conclusion, urea could have antioxidant cardioprotective effect in vivo against acute doxorubicin-induced cardiotoxicity. This newly observed effect of urea might have broad applications towards many oxidative stress-related pathophysiological situations

possible role for testosterone hormone on lipid peroxidation and some parameters of oxidant-antioxidant balance in rat myocardial tissue

The link between androgens and coronary artery disease remains elusive and the possible mechanisms that may relate testosterone to the development of cardiovascular diseases have not been well established yet. This study was designed to clarify the effect of testosterone hormone on lipid peroxidation and oxidants-antioxidant balance in rat myocardial tissue. Forty male albino rats included in this study were divided into 4 equal groups. Group [1] served as control rats and the other three groups were subjected to castration. One week after castration, group [2] rats were injected with solvent, group [3] rats received i.m. testosterone enanthate 10 mg/kg once weekly and group [4] received i.m.daily injections of vitamin E [alpha-tocopherol] in a dose of 20 mg/kg/day. All injections were continued for 4 weeks then all rats were sacrificed by decapitation and the hearts were obtained and prepared for the estimation of lipid peroxides as thiobarbituric acid reactive substance [TBARS], nitrite concentration, glutathione [GSH], glutathione peroxidase [GSH-PX] activity and vitamin E [alpha tocopherol]. TBARS and nitrites concentrations were significantly higher in the myocardial tissue extract of group [2] than group [1] rats while GSH and GSH-PX were sign lower, indicating that castration put the rat myocardial tissue under oxidative stress. However, in group [3] and group [4], TBARS and nitrites were sign lower and GSH and GSH-PX activity were sign higher than group [2], indicating that testosterone replacement therapy as well as vitamin E therapy protected the castrated rats from the oxidative stress and restored the oxidant- antioxidant balance in rat myocardial tissue. It could be concluded that testosterone may have a role in preserving oxidant- antioxidant balance in myocardial tissue of albino rats and this may be one of the mechanisms that could explain a suggested cardioprotective role of testosterone

Plasma alpha glutathione S - transferase in chronic hepatitis C infection in Egypt

Chronic hepatitis C [CHC] infection is a progressive disease whose activity must be regularly assessed. alpha -Glutathione S-transferase [alpha -GST] has been suggested as a better marker of hepatocellular damage than aminotransferases in toxic and autoimmune hepatitis. The present study assessed alpha -GST as a biochemical marker of hepatocellular damage in 50 Egyptian patients with CHC [seropositive for anti-hepatitis C virus [HCV] and HCV-RNA]. They were evaluated for conventional liver biochemistry, plasma alpha -GST, serum HCV-RNA levels and liver biopsy. Plasma alpha -GST was significantly higher in CHC patients than the reference values [p < 0.01] Sixteen patients [32%] had normal values for alanine aminotransferase [ALT], plasma alpha -GST was elevated in 11 of them [3 with minimal hepatitis; 6 mild and 2 moderate hepatitis]. Elevated plasma alpha -GST levels may indicate a hepatocellular damage even when ALT level is normal in CHC infection. Plasma alpha -GST was significantly higher in cirrhotic than non-cirrhotic patients [p < 0.01] suggesting that alpha -GST measurement is probably a sensitive test detecting liver damage occurring in association with cirrhosis. Plasma alpha -GST was significantly correlated with ALT [r = 0.67, p < 0,01] and aspartate aminotransferase [AST] [r = 0.62, p < 0.01] suggesting that alpha -GST may be a potential indicator of chronic hepatocellular damage due to HCV. Furthermore, plasma alpha -GST was significantly correlated with histologic grading score of hepatitis activity [r = 0.94, p < 0.01] and staging score of architectural alterations [r = 0.65, p < 0.01] indicating that plasma alpha -GST may be a sensitive and non invasive marker for detecting hepatitis activity and hepatocellular damage in CHC patients. There was a non-significant correlation between alpha -GST and serum HCV-RNA level indicating that plasma alpha -GST could not reflect the degree of viremia in these patients. The present data showed that alpha-GST has the highest sensitivity, specificity and accuracy [84%, 90% and 90%, respectively] for the diagnosis of parenchymal disintegrity and hepatocellular damage associated with chronic HCV infection followed by ALT [68%, 85% and 80%, respectively] then AST [62%, 75% and 68%, respectively]. This may indicate that alpha -GST gives better results than ALT and AST and may be preferred to them for monitoring hepatocellular damage associated with HCV infection. In conclusion, plasma alpha-GST determination appeared to be a sensitive, specific and non-invasive biochemical marker for detecting hepatocellular damage and may have a role in the follow up of CHC patients

comparative study of different procedures for the diagnosis of tuberculous ascites

To determine the diagnostic features of tuberculous peritonitis that distinguish it from other causes of ascites, 50 ascitic patients were examined prospectively. The biochemical, bacteriological and immunological properties of ascitic fluid from 11 patients with tuberculosis, 24 patients with hepatic cirrhosis and 15 patients with malignant ascites were compared. High values of adenosine deaminase activity [ADA] and gamma interferon [IFN - gamma] were detected in ascitic fluid of tuberculous patients. The sensitivity, tests of IFN. gamma ADA and PCR in the diagnosis of tuberculous ascites were 90.9%, 81.8%, and 36.3%, respectively while the specificity tests of all were 100%. A significant positive correlation was present between ADA activity and IFN - gamma level in ascitic fluid. The same correlation was detected between ADA activity and total protein concentration. However IFN - gamma was considered superior to ADA in diagnosis of tuberculous peritonitis in cases with decreased ascitic fluid total protein. Laparoscopic peritoneal biopsies in the seven tuberculous patients, revealed histopathologic granuloma and gave positive culture for T.B. It is concluded that, increased ascitic IFN - gamma and ADA arc useful, rapid non invasive screening tests in diagnosis of tuberculous peritonitis, whereas PCR has a limited utility. The best confirmation is by laparoscopic peritoneal biopsy followed by histopathologic and culture studies