E. Castelli

Biomarkers to assess the genetic damage induced by alcohol abuse in human lymphocytes

Alcohol abuse is a major risk factor for cancer of the upper alimentary tract, the upper respiratory tract, and liver. Chromosome damage is used as early effect biomarker in the surveillance of human exposure to genotoxic carcinogens. In the present study, two genetic markers, namely chromosome aberrations (CAs) and micronuclei (MN), were used to evaluate genetic damage in peripheral lymphocytes from 20 alcoholics, 20 abstinent alcoholics, and 20 controls. Composition of the three groups was fairly similar as regards sex, age and smoking habits. A highly significant increase was observed in the frequencies of CA and MN in lymphocytes of alcoholics as compared both with controls and abstinent alcoholics. However, no correlation was found between the length of alcohol abuse and the frequencies of either biomarkers in alcoholics. CA and MN frequencies in abstinent alcoholics were similar than those in controls. Our data indicate that CA and MN can be two useful biomarkers to assess genetic damage associated with alcohol abuse. They could be included in programs for cancer prevention in alcoholics. Abstinence appears to normalize the frequency of both MN and CA. This could offer therapists another tool to help alcoholics change their lifestyle.

Influence of chronic ethanol consumption on the inositol phospholipid fatty acid composition of human peripheral blood lymphocytes

The breakdown of inositol phospholipids is an important event after the binding of antigens to the T-cell antigen receptor. In alcoholics, changes either in early or in late steps of lymphocyte activation have been documented, however no study on the role of phosphoinositide fatty acid composition in signal transduction has been reported. We have analyzed the fatty acid pattern of phosphatidylinositol, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate from peripheral blood lymphocytes of alcoholic patients and healthy controls, in order to point out the possible compositional differences which could interfere with the signal transmission responsible for the early events in lymphocyte activation. In alcoholics, the arachidonic acid relative molar content in all the inositol phospholipid (PtdIns) fractions derived from lymphocytes was lower than in controls; all PtdIns classes appeared much more saturated than the corresponding fractions from control lymphocytes. The different fatty acid pattern of PtdIns in alcoholic patients could be responsible for an altered second messenger production, above all the production of a modified diacylglycerol which, in turn, could cause a different activation pattern of protein kinase C, with a consequent alteration in cell proliferation. The decrease in arachidonic acid molar content in the phosphoinositides and particularly in the phosphatidylinositol-4,5-bisphosphate fraction of PBL of alcoholic patients could lead to a reduced synthesis of prostanoids of the (n-6) series, and, as a consequence, to an alteration in the mitogenic response of the cells.

Oxatomide in Food Allergies. Comparative Study versus Disodium Chromoglycate

A randomized, controlled, single blind study was carried out to compare the efficacy and safety of oxatomide and disodium chromoglycate in the treatment of adverse reactions to food. Twenty-three patients (16F and 7M) with urticaria (16 patients), respiratory (5 patients), intestinal (15 patients) and/or neurological symptoms (3 patients) were treated for 60 days: 14 (9F and 5M; mean ± SD age 36.3 ± 13.8 years) with oxatomide, 60 mg every evening and 9 (7F and 2M; 31.5 ± 15.1 years) with disodium chromoglycate, 500 mg three times a day. Both therapies lasted two months. On admission and after 15,30 and 60 days skin (wheals, itching, vesicular blisters, scratching lesions), respiratory (rhinorrhea, sneezing, coughing, wheezing), intestinal (constipation, diarrhea, bloating, abdominal pain and/or cramps) and neurological (headache, irritability) symptoms were assessed. Wheals decreased in number and size in both groups (p<0.005). Itching became less severe in the two groups (p<0.05), although the improvement in the oxatomide group was faster. Vesicular blisters, present in one patient in the oxatomide group at baseline, disappeared by days 15 and 30, reappearing in a mild form at the end of the study. The frequency of scratching lesions decreased. Sneezing and wheezing disappeared in both groups. Digestive system symptoms also improved. Both treatments were effective as regards cutaneous, intestinal and respiratory symptoms, with a significant reduction of itching, wheals and vesicular blisters and the complete relies of intestinal disorders. The drugs were well tolerated.

Normalization of immune response and phosphoinositide fatty acid composition of peripheral blood lymphocytes in an alcoholic patient after alcohol abstinence

After 10 months of alcohol abstinence a malnourished alcoholic patient improved his nutritional status. The analysis of peripheral blood lymphocyte response to mitogenic stimulation with the antibody anti‐CD3 and of the fatty acid composition of the (poly)‐phosphoinositide fraction derived from lymphocytes revealed: 1) a similar [3H]‐thymidine uptake as in control (non‐drinker) subjects; 2) a similar relative molar content of the main fatty acids in the (poly)‐phosphoinositides as in control subjects. Alcohol abstinence can normalize both the parameters, which are greatly altered during alcohol abuse. This suggests a link between nutritional status and lymphocyte responsiveness via phosphoinositide fatty acid composition.