Chromosomal abnormalities and congenital heart disease.
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Biomedical subjects
Publications and source records attributed to I Emerit.
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The authors evaluated the possible association between dietary history and plasma clastogenic factors in children who immigrated to Israel between 1989 and 1993 from regions contaminated by the Chernobyl accident. The authors compared questionnaire data about demographic variables, dietary histories before and after immigration occurred, and health status with clastogenic factor scores for 162 immigrants. Logistic regression analysis revealed a negative association between clastogenic factor scores and frequency of consumption of fresh vegetables and fruit among children < or = 7 yr of age during the postimmigration period. Intake of eggs and fish by boys who were < or = 7 yr of age prior to immigration was associated positively with clastogenic factor scores. Consumption of fresh vegetables and fruits afforded protection to the immune systems of children who were < or = 7 yr of age.
Oxygen free radicals play a role in the aging process, and the protective effect of various antioxidants has been intensively studied, in particular for cutaneous aging. Besides hereditary factors, free radical-mediated damage to melanocytes of the hair follicle has been considered as a mechanism for aging of the hair. It was the aim of this study to evaluate the role of photosensitization reactions for hair graying and to demonstrate potential protective effects of superoxide dismutase (SOD). Mice with black hair were depilated with the fingertips on a surface of 6 x 2.5 cm on both sides of the dorsum. The right side received five applications of a SOD-containing gel before exposure to psoralen (concentration 0.5 mg/mL) plus UV-A (365 nm, 4 J/cm2). The left side was pretreated in the same way with a gel free of SOD. When the hair started growing again, the SOD-protected side was covered with black hair, whereas the hair on the vehicle-treated side was gray or white in 27 of the 30 animals studied. The 0.01% SOD concentration was as protective as the 0.1% concentration. Heat-inactivated SOD, applied in another five animals, was not protective. Using fluorescent labeling of the SOD with fluorescein isothiocyanate, epifluorescence microscopy and digital imaging processing, we show that SOD applied to the skin surface penetrates through the follicular appendages, as well as through the unbroken stratum corneum. Our findings suggest that superoxide radicals, generated by interaction of UV-A light with the sensitizer, initiated the formation of secondary products with well-known DNA-damaging effects, such as lipid peroxidation products and tumor necrosis factor alpha. SOD prevented the damage to melanocyte DNA by dismutating superoxide. Photosensitization may be another mechanism for hair graying, which can be influenced by antioxidants. Given the large number of exogenous and endogenous sensitizers, this mechanism deserves further study for human hair graying.
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Reperfusion injury remains the most uncontrolled phenomenon during cardiac surgery. Potential myocardial protection by trimetazidine was tested in a double blind placebo controlled study on 19 patients undergoing aorto-coronary bypass surgery. The trimetazidine group was composed of 10 patients and the placebo group of 9 patients. Pretreatment was started three weeks before surgery with 1 tablet (trimetazidine 20 mg) t.i.d. and the same drug was added to the cardioplegic solutions (trimetazidine: 10(-6) M). The cross clamping time was 41.1 +/- 3.8 minutes in the trimetazidine group and 39.8 +/- 2.3 minutes in the placebo group. Metabolic measurements showed that the increase of malondialdehyde measured in the coronary sinus 20 minutes after reperfusion was significantly (p = 0.014) less in the trimetazidine group (from 1.60 +/- 0.11 to 1.79 +/- 0.2 mumol/L-1) than in the placebo group (from 1.17 +/- 0.11 to 2.84 +/- 0.58 mumol/L-1). Myosin was present 4 hours after surgery in all patients in the placebo group and in 5 of the 10 of the trimetazidine group (p = 0.036). Haemodynamic measurements showed that patients pretreated with trimetazidine had a better ventricular function, as assessed by the stroke work index (SWI) significantly (p = 0.01) higher in the trimetazidine group (0.0391 +/- 0.0029 g/min/m2/beta) than in the placebo group (0.0282 +/- 0.0026 g/min/m2/beat), the evolution of SWI during surgery was not significantly different between the two groups. Thus trimetazidine seems to reduce ischaemia-reperfusion damage during cardiac surgery; moreover pretreatment with trimetazidine allows the patient to face the operation with better ventricular function.
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From chromosome breaks observed in lymphocyte culture of patients with auto-immune diseases, the authors study the factors favouring the onset of these breaks, (clastogenic factor and superoxide radicle) and those which appear able to reduce them (D-penicillamine and dismutase superoxide). The therapeutic implications of these findings will be the object of later publications.
The authors present a short series (6 cases) of serum positive rheumatoid arthritis, treated by I.M. injections (5 cases) or intra-articular injections (one case) of dismutase superoxide of bovine origin. The treatment was stopped in one case for local intolerance. Four cases treated for four months by the intramuscular route, were uninfluenced by the treatment, nor was the patient treated by the intra-articular route. The laboratory parameters (E.S.E., Rose Waaler reaction) were not modified. On the other hand, the lymphocyte fragility in culture was improved. The good tolerance of this compound in the laboratory will permit further trials in higher dosage.
Chromosome instability is observed in patients with collagen disease. It is due to the presence of a chromosome-breaking agent in the serum which also induces chromosome breaks and rearrangements in blood cultures from healthy subjects. It is not possible to say at present whether this breakage factor is identical to that in patients with progressive systemic sclerosis, lupus erythematosus or rheumatoid arthritis. In all three diseases the agent is a substance with a low molecular weight between 1000 and 10,000 daltons. Since the enzyme superoxide dismutase has an anticlastogenic protective effect, the action of the agent on chromosomes is probably an indirect one, namely by generation of oxygen-dependent free radicals such as O2- x and OH.