Lipid changes in neurogenic muscular atrophies.
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Biomedical subjects
Publications and source records attributed to F Maffei.
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Five patients with multiple sclerosis and four normal subjects have been followed for over two years. Plasma phospholipid levels and phospholipid fatty acid composition have been assayed periodically. The increased amount of plasma lysolecithin already described by us has been confirmed in this longitudinal study. A significant increase in saturated fatty acids of lysolecithin has also been demonstrated. In contrast, the lecithin concentration and fatty acid composition do not show any significant variations. The lysolecithin saturated/unsaturated fatty acid ratio was different in the same patients at different times, but no correlation was established between these variations and the clinical symptoms measured using the Kurtzke scale. The possible significance of saturated fatty acid increase in lysolecithin in the pathogenetic mechanisms of multiple sclerosis is discussed.
Acute intraperitoneal administration of benzo(a)pyrene (80 mg/kg b.wt.) resulted in time-dependent increases in chromosome aberrations, especially of break-type in the bone marrow of treated mice. Pretreatment with murine interferon-alpha/beta (5 x 10(4) IU daily for two days) caused a significative decrease in the cytogenetic response in vivo of benzo(a)pyrene (up to 51%) and a stabilization of aberrant cells up to 48 hr. The administration of murine interferon-alpha/beta gave rise to a marked depression of microsomal monooxygenase system after 24 hr, as exemplified by the significant reduction of cytochrome P450 content as well as deethylation of ethoxyresorufin. Interferon treatment delayed the obtainment of basal levels of oxidative metabolism to approximately 30 hr. After interferon plus benzo(a)pyrene treatment, ethoxyresorufin O-deethylase activity showed a reduction up to 60%; levels comparable to benzo(a)pyrene treated group were restored by 48 hr. Immunoblotting analysis confirmed reduced CYP1A1 level. Results suggest that the inhibition of benzo(a)pyrene hepatic metabolism by interferon was reflected by changes in its clastogenic activity. Persistence of low level of chromosome aberration at 48 hr may be reconducible to other interferon sensitive processes than effects on hepatic mixed-function oxidase system, such as DNA repair activity and cell proliferation.
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BACKGROUND/AIMS: Although a primary carcinogenic role of alcohol is not proven, alcohol abuse is associated with an increased risk of cancer of the upper airways, esophagus and liver. METHODOLOGY: Chromosome aberrations and the presence of micronuclei that reflect two types of genetic damage were analyzed in peripheral blood lymphocytes from 11 alcoholic patients who were heavy smokers and in a fair state of general nutrition and 9 subjects who had abstained from alcohol for at least a year. Ten heavy smokers were studied as healthy controls. RESULTS: Chromosome aberrations and micronuclei in alcoholics showed significantly elevated frequencies compared to the control groups, while in alcohol abstainers the values of all two parameters were similar to the values of the control subjects. CONCLUSIONS: These results show that long-term alcohol intake could induce genetic alterations in synergy with tobacco smoke. Interestingly, this damaging action is reversed by abstinence. Our results call for a further effort to find an eventual diagnostic role for these early genetic damage markers.
The ambient air of urban centres is polluted with potentially toxic chemicals mostly arising from the combustion or fuels used for transport, heating and industrial activities. Alongside the risk to the general public, atmospheric pollution could be considered an occupational health hazard to professional groups, such us traffic police or professional drivers working in urban areas. Molecular epidemiology can facilitate health risk assessment by investigating the relationship between exposure to environmental pollutants and quantification of biomarkers that lie on the pathway of carcinogenesis upstream of clinical disease. In particularly, biomarkers of early effects and susceptibility are playing an increase role in the investigation of the impact of air pollution on human carcinogenesis.
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The primary basis of 5-nitro-3-thiophenecarboxanilides (NTCAs) direct-acting mutagenicity in Salmonella typhimurium appears to be the reduction of the nitro function to the corresponding hydroxylamine via diamagnetic and free radicals intermediates. In Ames test conditions, mutagenicity of NTCAs may be partly attributed to the action of reactive oxygen species and other radicals generated during the bioreductive process. The nitro anion radical seems to be particularly susceptible to react with oxygen and generate superoxide, as shown by the inhibitory effects exerted by superoxide dismutase on genotoxicity by most NTCAs in the study. On the other hand, hydroxyl radical-trapping agents such as mannitol, the enzyme catalase and other scavengers as 3-tert-butyl-4-hydroxyanisole (BHA), and vitamins C, A, and E showed weak inhibitory potency, and rather increased the mutagenic activity of some NTCAs. Our results contribute to the mechanistic understanding of genotoxic activity of NTCAs.