Hepatitis C virus core antigen as a possible alternative for evaluation of treatment effectiveness after treatment with direct-acting antivirals.

Background: Chronic hepatitis C is a major public health problem around the world. In monitoring treatment efficacy, although costly and labour-intensive methods of molecular biology are often used, much cheaper and technically easier serological methods evaluating the concentration of HCV core antigen in serum are available. We evaluated HCVcAg quantification as a possible assessment of the treatment efficacy instead of HCV RNA quantification.Methods: We collected 514 serum samples from treated HCV infected patients. Quantitative evaluation of HCV RNA and HCVcAg was carried out before treatment, at the end of treatment, and at least 12 weeks following treatment termination. HCV RNA was determined by automated assay (Roche COBAS) and HCVcAg quantitation with ARCHITECT ci8200 analyser.Results: There was a significant correlation between HCVcAg and HCV RNA concentrations at baseline and follow-up visits, but not at the end of treatment. Among samples collected before the treatment, at the end of treatment and follow-up visit, concordance of HCV RNA and HCVcAg reached level of 98.1%, 98.9% and 98.7%, respectively. Diagnostic sensitivity, specificity, positive and negative predictive values of HCVcAg detection were >97%.Conclusions: HCVcAg measurement could be an alternative for determining HCV treatment efficacy after chemotherapy and could be an option in the diagnosis of HCV infection.

The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in ovarian cancer and ovarian cysts.

PURPOSE: The metabolism of cancerous cells is in many ways different than in healthy cells. In ovarian cancer, cells exhibit activity of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which participate in metabolism of many biological substances. The aim of this study was to compare the metabolism of ovarian cancer cells, ovarian cysts and normal ovarian cells by measurement of ADH isoenzymes and ALDH activities. MATERIAL AND METHODS: The study material consisted of 36 cancerous ovarian tissues. Class III, IV of ADH and total ADH activity was measured by the photometric method and class I, II ADH and ALDH activity by the fluorometric method with class-specific fluorogenic substrates. RESULTS: The activity of the class I ADH isoenzyme and the total ADH was significantly higher in ovarian cancer as compared to ovarian cysts and healthy tissues but there are no significant differences between ovarian cysts and healthy cells. The other classes of ADH tested, did not show significant differences between activity of cancerous cells and healthy ovary. CONCLUSION: The increased activity of total ADH in ovarian cancer, especially the class I isoenzyme and normal activity of ALDH, may be the factor for the disturbances in important biological substances metabolism and could increase the concentration of highly carcinogenic acetaldehyde.

Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the sera of patients with colorectal cancer.

Various isoenzymes of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) exist in human colorectal mucosa. In our last experiments we have shown that ADH and ALDH are present also in colorectal cancer cells. Moreover the activities of total ADH and class I isoenzymes were significantly higher in cancer tissue than healthy mucosa. This may suggest that these changes may be reflected by enzyme activity in the serum. Therefore, we have measured the activity of total ADH, and classes I-IV of this enzyme and ALDH in the sera of patients suffering from this cancer. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline (NDMA) as a substrate and ALDH activity by the fluorometric method with 6-methoxy-2-naphtaldehyde as a substrate. For the measurement of the activity of class I and II isoenzymes we employed fluorometric methods, with class-specific fluorogenic substrates. The activity of class III ADH was measured by the photometric method with formaldehyde and class IV with m-nitrobenzaldehyde as a substrate. Serum samples were taken for routine biochemical investigations from 52 patients with colorectal carcinoma before treatment. A statistically significant increase of class I ADH isoenzymes was found. Therefore the total ADH activity was also significantly increased. The total ALDH and the activity of other tested ADH isoenzymes were unchanged. We also observed the increasing tendency of ADH I activity in accordance with the advance of disease. The activity of class I ADH isoenzymes was elevated in the serum of patients with colorectal cancer. This activity was derived from colorectal cancer cells and probably from severely damaged liver by metastatic disease.

The activity of class I, II, III and IV alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in breast cancer.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) play a significant role in the metabolism of many biological substances. ADH participates in the metabolism of ethanol, retinoic acid, lipid peroxidation products, leukotriene and glutathione metabolism. ALDH is responsible for oxidation of acetaldehyde and other aldehydes and metabolism of histamine and retinoic acid. The aim of this study was to compare the metabolism in breast cancer cells and normal breast parenchyma by measuring ADH isoenzymes and ALDH activities in these tissues. Total ADH activity was measured by a photometric method with p-nitrosodimethylaniline (NDMA) as a substrate. For the measurement of the activity of ALDH and class I and II isoenzymes of ADH we employed the fluorometric methods, with class-specific fluorogenic substrates. The activity of class III alcohol dehydrogenase was detected by the photometric method with n-octanol and class IV with m-nitrobenzaldehyde as substrates. The samples were taken surgically during resection of breast carcinoma from 75 women. The activity of the class I ADH isoenzyme was significantly lower in breast cancer cells than in healthy tissues. The other tested classes of ADH had a tendency for higher levels of activity in cancer cells than in normal mammary tissue. The activity of total ADH and ALDH was also not significantly lower in the cancer cells. The decrease of activity of class I ADH isoenzyme in breast cancer tissues may be a factor of some disorders in metabolic pathways with participation of these isoenzymes that can lead to carcinogenesis.

Effect of Helicobacter pylori infection on the activity of class I, III and IV alcohol dehydrogenase in the human stomach.

BACKGROUND/AIMS: In the human stomach various alcohol dehydrogenase (ADH) isoenzymes exist. The gastric ADH activity is affected by a number of factors including also the infection of Helicobacter pylori. The objective was to investigate the activity of alcohol dehydrogenase isoenzymes of class I, III and IV in endoscopic specimens of gastric mucosa from the different parts of the stomach of men and women, considering the H. pylori infection. METHOD: Biopsy samples of gastric mucosa were taken from the corpus and antrum of 68 patients (42 of men and 26 of women) suspected for gastric ulcer. The colonization of H. pylori was present in 22 samples of men and 13 samples of women. The activity of class I isoenzyme was measured by the fluorimetric method with a specific substrate (4-methoxy-1-naphthaldehyde) and the activity of class III and IV by the photometric method with n-octanol and m-nitrobenzaldehyde as a substrates, respectively. RESULTS: In infected samples from the antrum and corpus of men's and women's stomachs the activity of class IV isoenzyme was decreased as compared to non-infected specimens. The activity of class III isoenzyme was decreased in the infected samples from the corpus of male patients, but the activity of class I does not significantly differ between infected and noninfected specimens from both sexes. CONCLUSION: H. pylori infection leads to significant decrease in the activity of class IV ADH in the stomach of men and women.

Alcohol and aldehyde dehydrogenase activity in the stomach and small intestine of rats poisoned with methanol.

The activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were measured with fluorogenic naphthaldehydes in the stomach and small intestine homogenates of rats dosed with 6 g methanol/kg bw after 6, 12, 24 h and 2, 5, 7 days. After intoxication with a sublethal dose, the ADH activity measured with these naphthaldehydes and ALDH activities in the stomach and small intestine were significantly decreased. This inhibition is stronger in the stomach and probably depends on cell damage and protein denaturation. We conclude that the activity measured with 6-methoxy-2-naphthaldehyde (MONAL-62) may be due to the activity of rat ADH-1 isoenzyme, and the activity detected with 4-methoxy-1-naphthaldehyde (MONAL-41) to the activity of rat ADH-2 isoenzyme.

[Human aldehyde dehydrogenase (ALDH)]. / Dehydrogenaza aldehydowa (ALDH) czlowieka.

The paper presents the molecular and kinetics aspects of aldehyde dehydrogenase polymorphism. The role in acetaldehyde metabolism and differences in substrate specificity of isoenzymes are discussed.

Alcohol and aldehyde dehydrogenase activity measured with fluorogenic substrates in the liver of rats poisoned with methanol.

The effect of methanol poisoning of rats on the hepatic activities of enzymes metabolizing alcohols was evaluated. The activities of alcohol (ADH) and aldehyde dehydrogenase (ALDH) in the liver of rats dosed with 1.5 and 3 g of methanol/kg b.w. were measured with new fluorogenic substrates (4-methoxy-1-naphthaldehyde [MONAL-41] for ADH and 6-methoxy-2-naphthaldehyde [MONAL-62] for ADH and ALDH) after 6, 12 and 24 hours and 2, 5 and 7 days. The methanol intoxication led to a dose dependent induction of ADH and ALDH activities. The higher dose of methanol induced the activities measured with both MONAL-41 and MONAL-62 with the peak on day 5; its effect was largest on the activity of ADH measured with MONAL-41. Only ADH activity measured with this substrate was induced by the lower dose of methanol during the whole time of the experiment; the activity of ADH measured with MONAL-62 and that of ALDH were induced only on day 1 of the intoxication. It is evident that sublethal methanol intoxication induces the hepatic activities of ADH and ALDH measured with fluorogenic substrates, and this induction depends on the dose of this alcohol.

[Metabolism of ethyl alcohol in the human body]. / Metabolizm alkoholu etylowego w organizmie ludzkim.

More than 90% of ingested ethanol is metabolized in the body to acetaldehyde and acetate. Ethanol is metabolized in the liver via three distinct enzymatic pathways: alcohol dehydrogenase (ADH), the microsomal ethanol oxidizing system (MEOS) and catalase. It is generally accepted that alcohol dehydrogenase is the predominant pathway for hepatic ethanol oxidation. Acetaldehyde is metabolized to acetate by a group of dehydrogenase enzymes called aldehyde dehydrogenase.