Increasing communication ability in aphasic/dysarthric patients.
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Biomedical subjects
Publications and source records attributed to M Beaver.
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Primary BA's secreted into the duodenum are extensively altered by bacteria in the large intestine. Such changes are not found in GF animals. As a result, GF rats reabsorb BA much more efficiently than do CV controls, and BA and cholesterol pools are higher in GF than CV rats. This indicates the importance of the intestinal flora in the homeostasis of cholesterol metabolism. Antibiotics can affect the extent to which BA's are altered by bacteria. In some cases, the antibiotic treatment also affects cholesterol levels in serum or liver. We have found that treatment of CV rats for only 5 days with low levels of Aureomycin (0.85 micron) led to a predominance of omega-MC over HDC in the feces at 10 days after withdrawal of the antibiotic. This reduced the usual HDC/omega-MC ratio from approximately 2.0 to 0.9 or less. These rats were also found to have liver cholesterol levels modestly elevated over those of controls. In other experiments the decrease in hyodeoxycholate/omega-muricholate ratio was found to persist for at least 90 days after discontinuation of treatment. Later experiments carried out with Aureomycin and with penicillin revealed the possible existence of a resistance factor to Aureomycin. A significant lowering of the hyodeoxycholate/omega-muricholate ratio was now found only with antibiotic concentrations 10 to 100 times greater than those used previously. Possible implications of the persistence of antibiotic effects, as measured by changes in fecal BA's, include effects on vitamin metabolism, colon cancer, and cholesterol metabolism.
Feeding of lactose in amounts comparable to the adult human intake in developed countries (6% of diet, and in later studies 10%) had no major effect on cholesterol and bile acid metabolism of germ-free and conventional rats. However, when lactose-containing casein-starch diets were sterilized by autoclaving, changes in intestinal and/or fecal bile acids were found. Both germ-free and conventional rats demonstrated some increase in intestinal beta-muricholic acid concentrations ascribable to the mere presence of lactose in the diet. Autoclaving of the diet produced additional changes, especially in the fecal bile acid pattern of conventional rats. Here the ratio between the beta-muricholic-derived secondary bile acids hyodeoxycholic and omega-muricholic acids changed from the usual 5:3 to approximately 1:10, with omega-muricholic acid becoming the major fecal bile acid. These changes point to a notable effect of lactose-derived products, formed during steam-sterilization, on the microbial modification of intestinal bile acids in the lower gut. Similar changes have been observed after oral administration of aureomycin and other, unrelated antibiotics that inhibit growth of gram positive organisms.
In recent years, the use of milk products and the concomitant intake of lactose have been tentatively linked to the etiology of cardiovascular disease. An effect of lactose on the microbial modification of acid and neutral sterols has been suggested. In the present study lactose intake, ranging up to 30% of total diet increased beta-muricholic (beta-MC) but not cholic acid concentrations in conventional (CV) rat small intestine to the extent that at the 20% and 30% intake level, the intestinal cholic: beta-MC ratio approached that in germ-free (GF) rats. Total intestinal bile acid (BA) content increased by approximately 1/3, but remained at less than half the value found in GF rats. At lactose intake levels within a range corresponding to the consumption of dairy products often recommended for adult man (5% to 10%) only moderate changes in intestinal, and little change in fecal BA were found during and after the 3 months experimental period. Intestinal beta-MC was increased in the presence and in the absence of an intestinal microflora. Experiments with GF rats fed 10% lactose or 10% maltose indicated that this increase is evoked similarly by both carbohydrates. The slight increase in serum cholesterol levels seen with disaccharide feeding, which became evident only in the GF rats, was again not specific for lactose. No influence was found of lactose feeding on liver cholesterol values. Comparison of CV rats fed nonsterile and radiation-sterilized lactose-containing diets suggested that this mode of sterilization has only a minor influence on the resulting data. When GF experiments are to be incorporated, sterilazation of diet by irradiation with 3.5 to 4.0 X 10(6) Rad is preferable to autoclaving. The present data indicate that no major effect specifically related to a normal dietary intake of lactose on cholesterol and BA metabolism of the adult rat could be demonstrated for the duration of these experiments.
The well-known bile acid analysis technique used by us and others (Grundy, Ahrens, and Miettinen. 1965. J. Lipid Res. 6:397-410) does not allow for the detection of hyodeoxycholic acid, a product of quantitative importance in rodent feces. Using updated methodology, it was established that hyodeoxycholic acid and omega-muricholic acid, both apparent conversion products of beta-muricholic acid, occur in apppreciable amounts in intestinal contents and feces of conventional Wistar type Lobund rats. In conventional rats, these bile acids comprise about 50% of fecal bile acids; they are not found in intestinal contents or feces of germfree rats. Others have demonstrated that hyodeoxycholic acid if formed by combined action of gut flora and liver. A new method for the separation of conjugated and free bile acids in biological samples was developed. Results with this method confirmed the total conjugation of bile acids in the germfree rat, and the almost total deconjugation that takes place in the cecum of the conventional rat.