Dm Vasudevan

Isolation and identification of a tumour reducing component from mistletoe extract (Iscador)

Using a combination of gel filtration and paper chromatography, a tumour reducing component from mistletoe extract (Iscador) was isolated and identified to be a peptide of approximate molecular weight 5000. The isolated peptide reduced the solid tumour induced by Daltons lymphoma ascites tumour cells (DLA cells) in mice. The isolated component was very cytotoxic to the DLA cells but was not cytotoxic to normal lymphocytes, indicating a cell dependent specificity.

Biochemical diagnosis of alcoholism

Medically diagnosed alcoholics can be differentiated reliably from non-alcoholics using clinically laboratory tests. In the present study, patients with liver diseases either due to alcohol or without alcohol compared with a group of normal healthy persons. Heavy drinkers showed significantly lower body weight and percent body fat, and low BMI compared with other groups. The percentage of hemoglobin and total number of RBC were found to be significantly decreased, whereas mean corpuscular volume (MCV) significantly increased in alcoholic liver disease (ALD). Hyperbilirubinemia, hyperuricemia and hypoalbuminemia correlate with alcohol intake. Albumin/globulin ratio significantly decreased in ALD. In acute liver injury AST/ALT ratio is ≤1.0, whereas in alcoholic hepatitis it is always >1.0. Moderately elevated level of ALP and high GGT values are good discriminator of alcoholic patients. Alcohol-induced liver injury is linked to oxidative stress as observed by decreased level of reduced glutathione and ascorbic acid, and increased level of thiobarbituric acid reactive substances.

Effect of a preparation from Viscum album on tumor development in vitro and in mice

The effect of Iscador, a commercial preparation made from Viscum album was studied on several cell lines using in vitro tissue culture as well as tumor-bearing animals. Iscador was found to be cytotoxic to animal tumor cells such as Daltons lymphoma ascites cells (DLA cells) and Ehrlich ascites cells in vitro and inhibited the growth of lung fibroblasts (LB cells), Chinese hamster ovary cells (CHO cells) and human nasopharyngeal carcinoma cells (KB cells) at very low concentrations. Moreover, administration of Iscador was found to reduce ascites tumours and solid tumours produced by DLA cells and Ehrlich ascites cells. The effect of the drug could be seen when the drug was given either simultaneously, after tumour development or when given prophylactically, indicating a mechanism of action very different from other chemotherapeutic drugs. Iscador was not found to be cytotoxic to lymphocytes.

Biomarkers of alcoholism: an updated review

Alcoholic beverages, and the problems they engender, have been familiar in human societies since the beginning of recorded history. Among a variety of blood tests used to aid the diagnosis of alcohol consumption and related disorders, laboratory tests are particularly useful in settings where cooperativeness is suspected or when a history is not available. Biochemical and haematological tests, such as gamma-glutamyltransferase activity, aspartate aminotransferase activity and erythrocyte mean corpuscular volume, are established markers of alcohol intake. Carbohydrate-deficient transferrin is the only test approved by the FDA for the identification of heavy alcohol use. Total serum sialic acid and sialic acid index of Apolipoprotein J have the potential to be included in a combination of measurements providing an accurate, more exact, assessment of alcohol consumption in a variety of clinical and research settings. Several other markers with considerable potential for measuring recent alcohol intake include beta-hexosaminidase, acetaldehyde adducts and the urinary ratio of serotonin metabolites, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid. These markers provide hope for more sensitive and specific aids to diagnosis and improved monitoring of alcohol intake.Review Article Biomarkers of alcoholism: an updated review S. K. Das , L. Dhanya & D. M. Vasudevan Department of Biochemistry, Amrita Institute of Medical Sciences, Kerala, India The Publisher of the above referenced article, published in Journal of Scandinavian Journal of Clinical and Laboratory Investigation, 2008; 68(2): 81 – 92 (DOI: 10.1080/00365510701532662), retracts this manuscript. A substantial portions of the text and data in this paper were not original and had been previously published in a paper by Martin A. Javors & Bankole A. Johnson, Current status of carbohydrate defi cient transferrin,total serum sialic acid, sialic acid index of apolipoprotein J and serum b-hexosaminidase as markers for alcohol consumption. Addiction, 2003:98;(Suppl. 2), 45 – 50 Scandinavian Journal of Clinical and Laboratory Investigation published this article in good faith, and on the basis of warranties made by the corresponding author regarding the originality of the work. The article is retracted from all editions. The author accepts this action. We thank the author for his cooperation in this matter. Jens Petter Berg Editor-in-Chief Scandinavian Journal of Clinical & Laboratory Investigation, 2012; 72: 343

Consequences of Alcohol Consumption on Neurotransmitters -An Overview

Alcohol one of the important products of the global addiction alters brain function by interacting with multiple neurotransmitter systems, thereby disrupting the delicate balance between inhibitory and excitatory neurotransmitters. Alcohol positively reinforces drinking by producing a mild euphoria. The reinforcing effects of alcohol are mediated by several neurochemical systems and are associated with some of the behavioral manifestations of intoxication. Alcohol consumption is initially accompanied by decreased attention, alterations in memory, mood changes and drowsiness. Generally all vital functions of brain depend on a delicate balance between excitatory and inhibitory neurotransmission,which in turn dependent on short and long term alcohol consumption. Detailed understanding of alcohols mechanism of action on the neurotransmitters of brain is a prerequisite in discovering effective treatments for both alcohol abuse and alcoholism. This review covers the elaborate literature on the subject and highlights the functions and interactions of neurotransmitters and alcoholism.

Evaluation of blood oxidative stress‐related parameters in alcoholic liver disease and non‐alcoholic fatty liver disease

Oxidative stress is implicated in the pathogenesis of liver disease. We investigated oxidative stress‐related parameters and correlated with clinical findings in 35 non‐alcoholic fatty liver disease (NAFLD) patients, 38 alcoholic liver disease (ALD) patients and 38 normal subjects. NAFLD patients showed significantly higher body mass index, cholesterol, LDL‐cholesterol, VLDL‐cholesterol levels and transaminase activities compared to the other two groups. Haematological parameters were significantly altered in ALD patients and were reported only in male subjects. Glutathione content, catalase activity, glutathione reductase activity and glutathione peroxidase activity in NAFLD patients were reduced by 10.7 %, 18.5 %, 8.1 % and 16.8 %, respectively, and in ALD patients by 21.8 %, 29.6 %, 24.3 % and 45.3 %, respectively, compared to the normal group. However, thiobarbituric acid reactive substance content, superoxide dismutase activity and glutathione s‐transferase activity were increased by 35.2 %, 31.6 % and 5.4 %, respectively, in NAFLD patients, and in ALD patients by 75.2 %, 72.7 % and 32.4 %, respectively, compared to the normal group. Oxidative stress is associated with collagen production and leads to fibrosis. Type IV collagen level in NAFLD patients (190.6±83 ng/mL) was significantly higher than in the normal group (124.5±14.5 ng/mL) and lower than in ALD patients (373.4±170 ng/mL). While type IV collagen level of >124 ng/mL was a predictor of NAFLD patients from normal subjects, elevated ALT (>40 IU/L) activity could discriminate either of the liver disease patients from normal subjects.

Effect of ethanol on liver antioxidant defense systems: Adose dependent study

Alcohol induced oxidative stress is linked to the metabolism of ethanol. In this study it has been observed that administration of ethanol in lower concentration caused gain in body and liver weight. while higher concentration of ethanol caused lesser gain in body and liver weight. Ethanol treatment enhanced lipid peroxidation significantly, depletion in levels of hepatic glutathione and ascorbate, accompanied by a decline in the activities of glutathione peroxidase and glutathione reductase, and increased in hepatic glutathione s-transferase activity. Interestingly catalase activity increases in lower concentration of ethanol exposure, and decreased in higher concentration. Superoxide dismutase activity was also increased on ethanol exposure. But, ethanol feeding did not show any effect on glucose-6-phosphate dehydrogenase activity. Ethanol ingestion perturbs the antioxidant system in a dose and time dependent manner.

BIOCHEMICAL MARKERS FOR ALCOHOL CONSUMPTION

A variety of laboratory tests are available to assist in the diagnosis of alcohol consumption and related disorders. The levels of intake at which laboratory results become abnormal vary from person to person. Laboratory tests are particularly useful in settings where cooperativeness is suspected or when a history is not available. Several biochemical and hematological tests, such as γ-glutamyltransferase (GGT) activity, aspartate aminotransferase (AST) activity, high-density lipoprotein cholesterol (HDL-C) content of serum, and erythrocyte mean corpuscular volume (MCV) are established markers of alcohol intake. Their validity as markers is based largely on correlations with recent intake at a single time point and on decreases in elevated values when heavy drinkers abstain from alcohol. These readily available laboratory tests provide important prognostic information and should be integral part of the assessment of persons with hazardous alcohol consumption. There are several other markers with considerable potential for more accurate reflection of recent alcohol intake. These include carbohydrate deficient transferrin, β-hexosaminidase, acetaldehyde adducts and the urinary ratio of serotonin metabolites, 5-hydroxytryptophol and 5-hydroxyindoleacetic acid. These markers provide hope for more sensitive and specific aids to diagnosis and improved monitoring for intake.

Oxidative stress is the primary event: Effects of ethanol consumption in brain.

Damaging effects of reactive oxygen species on living systems are well documented. They include oxidative attack on vital cell constituents. Chronic ethanol administration is able to induce an oxidative stress in the central nervous system. In the present study, 16–18 week-old male albino rats of Wistar strain were exposed to different concentration of ethanol for 4 weeks. This exposure showed profound effect on body weight. Ascorbic acid level; and activities of alkaline phosphatase and aspartate transaminase in the brain are dependent on the concentration of ethanol exposure. Chronic ethanol ingestion elicits statistically significant increase in thiobarbituric acid reactive substances level and decrease in gluatathione level in the brain. It reduces superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities in a dose dependent manner. However, histological examination could not reveal any pathophysiological changes. Therefore, we conclude that biochemical alterations and oxidative stress related parameters respond early in alcoholism than the histopathological changes in brain.

Monitoring oxidative stress in patients with non-alcoholic and alcoholic liver diseases

Ethanol-induced liver injury may be linked, at least partly, to an oxidative stress resulting from increased free radical production and/or decreased antioxidant defence. Distinguishing alcoholic and non-alcoholic liver disease has important implications. This study looked at the possible changes between alcoholic and non-alcoholic liver diseases by examining the presence of oxidative damage, as monitored by several parameters relating to oxidative stress. Lipid peroxides concentration, superoxide dismutase activity and glutathione S-transferase activity increased, where as glutathione content, glutathione peroxidase activity and glutathione reductase activity decreased among the tested subjects in comparison to normal healthy group. Determination of these parameters may be valuable in the evaluation of liver disease. However, oxidative stress related enzymes and non-enzymes can not be utilized as a marker for alcoholic liver diseases, as these parameters responded in the same way after liver is damaged irrespective of their cause. Their level may help in determining the degree of liver damage. Degree of oxidative injury was similar in patients with non-alcoholic liver disease and in moderate drinkers; while significantly higher in heavy drinkers. The differences between the groups might be based on the type of liver pathological condition rather than its etiology (i.e. alcohol and non alcohol related causes).