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Biomedical subjects

T Midtvedt

Publications and source records attributed to T Midtvedt.

286 records · Page 16Linked to original sources

Isolated fecal microorganisms capable of 7-alpha-dehydroxylating bile acids.

Strains of microorganisms capable of 7alpha-dehydroxylation of chenodeoxycholate were isolated from rat and human feces. All the strains were strictly anaerobic, non-motile, moderately themioresistant Gram-positive rods. They showed some saccharolytic properties with the production of both acid and gas. They were H(2)S-positive but indole-, skatole-, citrate-, catalase-, and oxidase-negative. The isolated strains capable of 7alpha-dehydroxylation of chenodeoxycholate were also able to oxidize the hydroxyl groups at C-3 and C-7 to keto groups. The following metabolites were isolated: 3-keto-7alpha-hydroxy-5beta-cholanoic acid, 3alpha-hydroxy-7-keto-5beta-cholanoic acid, 3alpha-hydroxy-5beta-cholanoic acid, and 3-keto-5beta-cholanoic acid. The isolated strains did not have the enzymes necessary for hydrolyzing conjugated bile acids. In mixed anaerobic cultures of fecal microorganisms, extensive reduction of the 3-keto group to the 3beta-hydroxyl group occurred. The microorganism(s) responsible for this reaction have as yet not been isolated.

Bacteriological Techniques↗

Lack of differences in blood and tissue concentrations of endogenous ethanol in conventional and germfree rats.

Headspace gas chromatography was used to determine the concentrations of endogenous ethanol in blood and tissue of conventional and germfree rats. In all biological specimens analysed, the four principal volatile endogenous substances were identified as methanol, acetaldehyde, ethanol and acetone. No statistically significant differences in the concentrations of endogenous ethanol were noted between conventional and germfree animals. In whole blood, liver, kidney, and brain of germfree rats the concentrations of endogenous ethanol were 4.2 +/- 0.19 microM, 5.1 +/- 0.55 microM, 8.2 +/- 0.59 microM and 4.4 +/- 0.17 microM (means +/- SE), respectively. The higher concentration in kidney was also observed in conventional rats. Our results suggest that ethanol is a normal metabolic intermediate in rats and does not exclusively arise from microbial fermentation reactions in the gastrointestinal tract.

Acetaldehyde↗

Vitamin A deficiency impairs colonic healing but not adhesion formation in germ-free and conventional rats.

Vitamin A is well recognized as a factor of major importance in epithelial and connective tissue repair mechanisms. Recently it was shown that vitamin A deficiency caused overgrowth and translocation of intestinal bacteria in rats. The aim of this study was to investigate the healing of colonic anastomoses and formation of postsurgical adhesions in vitamin A-deficient germ-free and conventional rats. Fourteen germ-free and 10 conventional rats were allocated to four groups: germ-free rats not given vitamin A, germ-free rats given vitamin A, conventional rats not given vitamin A, and conventional rats given vitamin A. All rats underwent surgery for colonic anastomosis. Seven days afterward, they were euthanized, and the bursting pressure of colonic anastomosis and formation of peritoneal adhesions were evaluated. The bursting pressures in groups not given vitamin A were lower than in groups given vitamin A. The adhesion scores in germ-free groups were lower than in conventional groups. These findings demonstrated that vitamin A had an important role in healing of colonic anastomoses whether in the presence or absence of intestinal flora, and that intestinal bacteria had a greater effect than vitamin A on formation of postsurgical adhesions. This may suggest that the mechanism of healing of colonic anastomoses differs from that of postsurgical adhesion formation.

Animals↗

Postsurgical adhesion formation in germfree and ex-germfree rats--a study using three scoring scales.

Postsurgical adhesions occur commonly after surgical procedures and are the source of substantial postoperative morbidity. No preventive or prophylactic regimen against adhesions has proven successful in all circumstances. The reasons for this are not clear. The basic mechanisms causing adhesion formation have not been elucidated fully, and furthermore, lack of accurate methods of measuring adhesions may be a contributing factor. Postoperative adhesions may occur in all kinds of surgery but are especially prominent in the abdomen, where the bowel flora may be a compromising factor. This study was undertaken to study the influence of the gastrointestinal microflora on adhesion formation. Germfree and ex-germfree DA rats were subjected to a cecal crush model, and adhesions were evaluated after 7 days using 3 different scoring scales. Germfree rats formed significantly fewer adhesions than their ex-germfree (conventionalized) counterparts. The differences were so great that all three scoring scales achieved significance (p < .005). This study corroborates that the endogenous bowel flora per se is involved in adhesion formation without causing frank infection.

Animals↗

Development of five metabolic activities associated with the intestinal microflora of healthy infants.

The establishment of a functionally active intestinal flora was followed in 17 healthy Swedish children from birth up to 6 months of age. Utilizing gas chromatography, spectrophotometry, and gel electrophoresis, feces were analyzed on certain biochemical markers that reflect the action of the intestinal flora in vivo. The establishment of the following five flora-related functions was investigated: production of short chain fatty acids (SCFAs), degradation of mucin, conversion of bilirubin to urobilinogen and of cholesterol to coprostanol, and inactivation of fecal tryptic activity (FTA). Production of SCFAs was the first function to be established, followed by bilirubin conversion and mucin degradation. No child showed conversion of cholesterol. The values of FTA were lower than in adults. This study indicates that the establishment of a functionally active flora is a slow process and that some functions are almost fully established before other functions have started to develop. Environmental factors, such as the diet, seem to be of importance. In general, the functions seem to develop slower in those children receiving breast milk exclusively than in those receiving formula supplements.

Bilirubin↗

Limited role of the intestinal microflora in the nephrotoxicity of hexachloro-1,3-butadiene in rats.

The nephrotoxicity of hexachlorobutadiene has been investigated in germ-free rats and compared to conventional rats that have a normal intestinal microflora. Presynthesized mercapturate intermediates of hexachlorobutadiene, the glutathione and the cysteine S-conjugate, were also administered. Germ-free rats appeared to be slightly more susceptible to hexachlorobutadiene by judging the extent of morphological changes compared to conventional ones. A similar response was also observed after treatment with the glutathione and cysteine S-conjugates. However, no significant difference between germ-free and conventional animals was monitored in the extent of elevation of blood urea nitrogen and plasma creatinine after treatment with hexachlorobutadiene or the glutathione and the cysteine S-conjugates. The urinary excretion of marker enzymes was monitored and showed that gamma-glutamyl transferase was significantly more increased in the germ-free rats when treated with the cysteine S-conjugate. In addition, no difference in the rate of glutathione conjugation of hexachlorobutadiene was measured between the two groups. Although a tendency toward a protective effect by the presence of an intestinal microflora was observed, the role of the intestinal microflora in detoxifying hexachlorobutadiene seems to be of limited importance in rats.

Animals↗

Ontogeny of lymphocyte activating factors in conventional and germfree rats.

Immune regulatory cytokines have previously been demonstrated outside the immune system in, e.g., the skin, testis, and brain, and suggested to serve as barrier site defence mediators. We have recently demonstrated constitutive production of an interleukin-1 (IL-1)-like factor(s) in the proximal gastrointestinal tract, liver, and placenta of adult rats. In the present study we have investigated the developmental production of IL-1-like factors in these tissues in conventional rats and in rats raised under germfree conditions. Slight IL-1 bioactivity was detected at a gestational age of 18 days in the skin and esophagus, and on day 19 significant amounts were detected in the skin, tongue, esophagus, and stomach. The activity was maximal at gestational day 20-21, and stationary at all later time-points. The placenta and liver contained high amounts of IL-1 activity throughout fetal life. The brain showed a transient appearance of IL-1 bioactivity at a gestational age of 19-21 days, but no activity at later time-points. Germfree rats showed no significant difference in the ontogeny or amounts of IL-1 bioactivity compared to conventional rats. It can be concluded that the IL-1 bioactivity appears at a definite time point in all measured tissues in fetal life and that exposure to microbial antigens does not seem to influence its production. As the investigated tissues show a high proliferation rate, it is tempting to suggest that the detected IL-1 (-like factors) might have an alternate function in these tissues, e.g., to serve as growth factors.

Animals↗