ABSTRACT
BACKGROUND: In mice, fibrates induce mdr2 gene expression, and its encoded P-glycoprotein in the canalicular domain of hepatocytes, as well as increasing biliary phospholipid output. It is not known whether this effect is restricted to fibrates or is a common property of peroxisome proliferators. AIMS: To test the effect of structurally unrelated peroxisome proliferators on mdr2 gene expression and biliary phospholipid output, and to explore the molecular mechanism(s) of mdr2 gene induction. METHODS: Male CFI mice were fed on a diet supplemented with several peroxisome proliferators: phenoxyacetic acid herbicides, plasticizers, acetylsalicylic acid and partially hydrogenated fish oil. RESULTS: Increased levels of mdr2 mRNAs, assessed by Northern blot analysis, were observed in the liver of mice treated with phenoxyacetic acid herbicides: 2,4,5-trichlorophenoxyacetic acid 570+/-133%, 2,4-dichlorophenoxyacetic acid 233+/-54% (p<0.005); plasticizers: di-(2-ethylhexyl)phthalate 282+/-78%, di-(isoheptyl)phthalate 163+/-40%, phthalic acid dinonyl ester 225+/-48% (p<0.01); and partially hydrogenated fish oil 372+/-138% (p<0.005). P-glycoprotein traffic ATPase content increased in the canalicular domain of hepatocyte of mice treated with the herbicide 2,4,5-trichlorophenoxyacetic acid and with partially hydrogenated fish oil (108% and 87%, respectively, p<0.05) as well as biliary phospholipid output (106% and 74%, respectively, p<0.05). In 2,4,5-trichlorophenoxyacetic acid-fed mice we found five-fold increase on mdr2 transcription rate, assessed by nuclear run-off assay. CONCLUSIONS: Peroxisome proliferators induce mdr2 gene, its encoded P-gp in the canalicular domain of hepatocytes and increase biliary phospholipid output. The modulation of mdr2 gene might be part of the pleiotrophic response of peroxisome proliferation in mice liver and seems to be regulated mainly at a transcriptional level.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/biosynthesis , ATP Binding Cassette Transporter, Subfamily B , ATP-Binding Cassette Transporters/biosynthesis , Drug Resistance, Multiple/genetics , Fish Oils/pharmacology , Herbicides/pharmacology , Liver/physiology , Microbodies/drug effects , Plasticizers/pharmacology , Transcription, Genetic/drug effects , 2,4,5-Trichlorophenoxyacetic Acid/pharmacology , 2,4-Dichlorophenoxyacetic Acid/pharmacology , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adenosine Triphosphatases/metabolism , Animals , Bile/chemistry , Bile/metabolism , Bile Acids and Salts/metabolism , Cholesterol/metabolism , Hydrogenation , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred Strains , Phospholipids/metabolism , Phthalic Acids/pharmacology , RNA, Messenger/biosynthesisABSTRACT
Parallel to the National Health Survey-II, in 1994 a qualitative study was conducted on the patterns and microsocial determinants of health services utilization. The study was conducted in eight urban areas from all over the country among middle class and middle-low class sectors. A total of 192 individual open-ended interviews and eight focus groups were completed among users of health services; 61 service providers both from public and private services were also interviewed. This paper reports the main findings regarding the users' perspective. The first part summarizes the conceptual and methodological design. The second part presents the results from the users' point of view. Individuals distinguish between "becoming sick" and "falling sick"; preventive measures are adopted when becoming sick, in order to avoid falling sick. Another finding refers to the population tendency to add up different and even contradictory curative paradigms, as opposed to the modern medical paradigm which tends to exclude any competing alternative knowledge. A third series of findings refers to the dilemmas that utilizing health services poses for the population, given the high costs, and the low quality that characterize these services, according to the users' point of view. This paper concludes with a series of recommendations for policies, aimed at improving the quality of the health services provided to the population.
Subject(s)
Health Services/statistics & numerical data , Health Behavior , Health Surveys , Humans , Interviews as Topic/methods , Mexico , Patient Satisfaction , Sick Role , Socioeconomic Factors , Urban PopulationABSTRACT
Garlic has been proposed as a natural hypolipidemic substance. Most hypolipidemic compounds induce peroxisomal proliferation and increase enzyme activities associated with peroxisomal beta-oxidation in rat liver. Here we report that garlic methanol-extracts behave as hypolipidemic drugs, increasing the activity of peroxisomal fatty acyl-coenzyme A oxidase and of total carnitine acetyl-coenzyme A transferase in primary cultures of rat hepatocytes. Both enzymes are considered markers associated with increased peroxisomal beta-oxidation. As in the case of hypolipidemic peroxisome proliferators, garlic extracts partially prevented the decrease in fatty acyl-coenzyme A oxidase as the culture aged. No changes were observed in the activity of microsomal NADPH cytochrome c reductase or of mitochondrial glutamate dehydrogenase.