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Biomedical subjects

T Midtvedt

Publications and source records attributed to T Midtvedt.

At least 91 records · Page 5Linked to original sources
PubMed1991

Expression of a dietary protein in E. coli renders it strongly antigenic to gut lymphoid tissue.

Bacteria that colonize the intestinal mucosa elicit a strong mucosal immune response, whereas food antigens such as ovalbumin are very weakly immunogenic to the gut-associated lymphoid tissue. This may either be due to special physico-chemical properties of bacterial substances versus proteins from animals and plants, or to stimulating properties of the bacteria on, e.g., antigen presentation, rendering all substances contained within bacteria antigenic. To test these hypotheses, ovalbumin was expressed in wild-type Escherichia coli and germ-free female rats were colonized with this strain. The systemic and mucosal antibody response of these rats was compared with that of rats given large amounts of dietary ovalbumin. Biliary IgA antibodies, which reflect the local IgA antibody production in the intestine, were only found in the rats colonized with ovalbumin-synthesizing E. coli. IgG antibodies in the bile were also only seen in these rats. We conclude that mucosal immunogenicity depends on the context in which a protein is presented to the gut-associated lymphoid tissue, rather than to special antigenic characteristics of the protein in itself.

Animals↗
PubMed1990

Enteral nutrition and the function of the intestinal microflora in healthy adults.

An oral feeding formula was given to 5 healthy volunteers for 8 days. Faecal samples were collected before, during and after the feeding period. The effect of enteral nutrition (EN) on the following seven intestinal microflora-associated characteristics (MACs) was studied: formation of urobilinogen, coprostanol and deoxycholic acid, degradation of mucin and beta-aspartylglycine, faecal tryptic activity, and production of short-chain fatty acids (SCFAs). None of the microbial functions studied were lost during the study. The urobilinogen level increased during EN (P < 0.05) but it seems reasonable to assume that this was a concentration effect due to a decrease in stool mass. The concentration of SCFAs decreased during EN (P < 0.05) and this reflects the absence of dietary fibre in the feed used.

Journal Article↗
PubMed1990

Mutagen excretion and cytochrome P-450-dependent activity in germfree and conventional rats fed a diet containing fried meat.

To evaluate a possible role of the intestinal microflora in the metabolism of the highly mutagenic compounds formed in fried meat, conventional and germfree male AGUS rats were fed a semi-synthetic diet containing fried meat. Changes in mutagen excretion in urine and faeces over time were studied using the Ames Salmonella assay. The faecal and urinary extracts were separated by means of high-performance liquid chromatography (HPLC), and the mutagenicity of the collected fractions was determined. Cytochrome P-450 IA (IA1 and/or IA2) were detected by the use of antibodies with the Western blot technique, and the corresponding enzyme activities were measured in microsomes from the small intestine and the liver. A quantitative as well as qualitative difference in excretion of mutagens between germfree and conventional rats was observed. The total excreted of mutagenicity was significantly higher for the conventional than for the germfree rats, as a result of a higher faecal excretion of mutagens in the conventional animals. The HPLC separations of urinary and faecal extracts showed a different mutagenic metabolite pattern between the germfree and conventional rats. An increased activity of the cytochrome P-450-dependent enzyme ethoxyresorufin-O-deethylase was observed in the small intestine of conventional rats on the fried meat diet, whereas no effect of this diet was observed in the germfree rats. Similar results were obtained in immunoblotting experiments using a P-450 IA antiserum. The present study indicates that the excretion pattern and thus also the metabolism of compounds present in fried meat are affected by the germfree status.

Animals↗
PubMed1990

HPLC separation and quantification of bilirubin and its glucuronide conjugates in faeces and intestinal contents of germ-free rats.

We describe an accurate reverse-phase high-performance liquid chromatography (HPLC) method for the separation and quantification of unconjugated bilirubin (UCB) and its monoglucuronide (BMG) and diglucuronide (BDG) conjugates in faeces and intestinal contents from germ-free (GF) rats. We demonstrated that female GF rats excreted predominantly BMG and that the percentage of this conjugate was at most 71.7% of the total bilirubin excreted with the faeces. The highest percentages for BDG and the UCB were 27.9% and 6.0%, respectively. The bile pigment composition in duodenal contents was 59.8% BDG and 40.2% BMG (median percentage) and was 47.7% BDG, 50.1% BMG and 2.2% UCB in ileal contents. Deconjugation of BDG to BMG was profound in caecal contents with 26.0% BDG, 67.4% BMG and 6.6% UCB. Endogenous (mammalian) beta-glucuronidase activity was present in intestinal contents throughout the entire length of the intestine and in faeces of the GF rats. The results indicated that it is very likely that endogenous beta-glucuronidase plays a role in the deconjugation of bilirubin glucuronides as well as of other glucuronides in the intestine of the GF rat.

Animals↗
PubMed1990

Ecosystems: development, functions and consequences of disturbances, with special reference to the oral cavity.

Some general rules for the development and maintenance of microbial ecosystems are outlined. Studies on germ-free animals have given valuable baselines concerning structures and functions in the host per se. The oral cavity represents several consortia of micro-organisms, governed by factors deriving from the host, the diet and/or the micro-organisms. Alterations in these factors, as well as intake of antibiotics, etc., may give disturbances, which can be analyzed according to general guidelines.

Animals↗
PubMed1990

Intestinal microbial conversion of cholesterol to coprostanol in man. Influence of antibiotics.

The intestinal microbial conversion of cholesterol to coprostanol has been measured in groups of healthy subjects before, during and after they received the antibiotics ampicillin, bacitracin, clindamycin, co-trimoxazole, doxycycline, erythromycin, metronidazole, nalidixic acid, ofloxacin or vancomycin orally for 6 days. Before they received antibiotics, the subjects demonstrated two distinct patterns of cholesterol conversion. One pattern was characterised by extensive conversion of cholesterol, the other by little or no conversion. Intake of bacitracin, clindamycin, erythromycin, metronidazole and vancomycin significantly reduced the conversion to coprostanol. In the groups receiving ampicillin or doxycycline, marked reductions were found in most of the subjects. No alterations were found in the groups receiving co-trimoxazole, nalidixic acid or ofloxacin. In 6 subjects no conversion of cholesterol to coprostanol was found up to 5 weeks after the end of the antibiotic intake. We conclude that orally given antibiotics may cause alterations in the intestinal conversion of cholesterol, reflecting changes in the anaerobic, Gram-positive component of the gut flora.

Adult↗
PubMed1990

The function of the intestinal microflora in patients with ulcerative colitis before and after colectomy.

The function of the intestinal microflora was studied in patients with ulcerative colitis before and after colectomy. The following six microflora-associated characteristics (MACs) were investigated: formation of coprostanol and urobilinogen; degradation of mucin, water-soluble protein, and beta-aspartylglycine; and presence of faecal tryptic activity. In 12 unoperated patients without sulphasalazine as maintenance therapy the six MACs were similar to those in normal subjects. In 12 unoperated patients receiving sulphasalazine the formation of coprostanol and urobilinogen was significantly lower (p less than 0.01 and p less than 0.001, respectively) and the level of faecal tryptic activity was significantly higher (p less than 0.01) than in normal subjects. The functional capacity of the microflora in operated patients treated by colectomy combined with one of four surgical procedures (ileorectal anastomosis, ileoanal anastomosis with pelvic pouch, Kock's continent ileostomy, or conventional ileostomy) was disturbed with regard to all six MACs. The disturbance was most pronounced in patients with conventional ileostomy.

Adult↗
PubMed1990

The secretory antibody response in milk and bile against fimbriae and LPS in rats monocolonized or immunized in the Peyer's patches with Escherichia coli.

The homing of lymphoid cells to mucosa-associated lymphoid tissue is, amongst other factors, influenced by the nature of the antigen used to induce an immune response. To study this phenomenon we have monocolonized rats with a type 1 fimbriated Escherichia coli O6K13H1 strain and compared the secretory antibody response to colonization with the primary and secondary response obtained in rats immunized in the Peyer's patches (PP). Samples were tested with respect to the titres of antibodies against two antigens present on the E. coli strain: O6 lipopolysaccharide (LPS) and type 1 fimbrial antigen. In the primary immunized animals, IgA anti-fimbrial antibodies were mainly seen in milk and IgA anti-LPS antibodies mostly found in bile. In the booster immunized, and in the monocolonized, animals there was a shift of the antibody response towards the bile. Thus anti-fimbrial antibodies appeared in milk at approximately the same or at a lower level than in bile and the IgA anti-LPS antibodies were almost completely absent in the milk. The IgG antibody response of the animals immunized in the PP was primarily confined to milk for both anti-LPS and anti-fimbrial antibodies, while the colonized animals responded with higher levels in bile than in milk. IgM antibodies were only seen in the milk, except in primary immunized animals in which biliary IgM antibodies also were found. The data illustrate that: (i) primary stimulated cells predestined to produce IgA anti-LPS antibodies home mainly to the intestine, while cells predestined to anti-fimbrial antibody production have a greater tendency to populate the mammary gland; (ii) after repeated antigen stimulation and maturation of the immune response the cells are directed from the mammary gland to the intestine. We thus conclude that the nature of the antigen and the stage of lymphocyte maturation influences the homing of the cells and the appearance of various antibodies in different secretions.

Animals↗
PubMed1990

The influence of quinolones on the faecal flora.

Ingestion of antimicrobial agents may in several ways influence the indigenous flora of the human digestive tract. The influence can be evaluated by following qualitative and/or quantitative alterations in the composition of the flora and of its antibiotic resistance profile (ARP). Another approach is to follow alterations in physiological and/or biochemical intestinal characteristics which depend on the intestinal flora. In a Norwegian-Swedish collaborative study, the influence of 10 orally given antimicrobial drugs on seven to nine various biochemical microflora-associated characteristics in groups of healthy volunteers was followed. In contrast to most of the other drugs given, ofloxacin exerted almost no influence upon the characteristics investigated. The result of this study are reviewed, as well as the results of other studies dealing with the influence of the quinolones on the faecal flora.

Anti-Infective Agents↗
PubMed1990

Resistance situation of oral antibiotics in the Scandinavian countries with special reference to the fluoro-quinolones.

In general, the Scandinavian countries have a rather conservative attitude towards new antimicrobial agents. Our antibiotic policies are based upon many years of clinical and laboratory experiences. It is generally believed, although not always satisfactorily proven, that our relatively restrictive attitude to the use of new as well as of older antimicrobial drugs by one mechanism or another, is a matter of some importance when explaining the relatively low antibiotic resistance profile (ARP) existing in most places in Scandinavia. When a new group of drugs, such as the quinolones, is going to be introduced in the therapeutic armamentarium, the existing ARPs of the microbes actually involved have to be taken into consideration.

4-Quinolones↗
PubMed1989

Glycosphingolipids in feces of germ-free rats as a source for studies of developmental changes of intestinal epithelial cell surface carbohydrates.

Non-acid and acid glycosphingolipids were isolated from feces of one litter of germ-free rats from day 17 to day 51. Quantitative and qualitative changes described for small intestine of conventional rats [Bouhours D, Bouhours J-F (1981) Biochem Biophys Res Commun 99:1384-89] were also found in the feces of these germ-free rats. A decrease in lactosylceramide and sialyllactosylceramide excretion and a change from N-acetylneuraminic acid to N-glycoloylneuraminic acid, as well as an appearance of type 1 chain blood group H-active penta- and decaglycosylceramides were observed during the weaning period. Thus the dramatic changes seen in rat intestinal glycosphingolipids postnatally seem to be primarily regulated by non-microbial factors.

ABO Blood-Group System↗
PubMed1989

The metabolism of 4,8-DiMeIQx in conventional and germ-free rats.

The aromatic amine mutagen, [14C]2-amino-3,4-8-trimethyl-imidazo[4,5-f]quinoxaline (4,8-DiMeIQx), which is derived from cooked food, was administered to conventional and germ-free AGUS rats previously fed either a semi-synthetic diet containing the cytochrome P-450 inducer beta-naphthoflavone (BNF) or a control diet without BNF. The germ-free animals had longer fecal transit times and lower induction of 7-ethoxyresorufin-O-deethylase activity than conventional rats. Induction with BNF caused a greater percentage of the radioactivity to be excreted in the feces of both germ-free and conventional rats. Feeding BNF also caused a 4-fold induction in germ-free and a 24-fold induction in conventional rat intestinal enzyme levels. Analysis of the urinary and fecal metabolites showed no consistent differences between conventional and germ-free rats in the metabolite profile. Major metabolites were identified as 8-hydroxymethyl-DiMeIQx, N-acetyl-8-hydroxymethyl-DiMeIQx, and 3-N-dimethyl-4-hydroxy-methyl-DiMeIQx. The data from this study indicate that intestinal microflora do not play a major role in the metabolism of 4,8-DiMeIQx, but the induction of intestinal enzymes does not affect the route and rate of excretion.

Animals↗
PubMed1989

The influence of cefoperazone, cefotaxime, ceftazidime and aztreonam on phagocytosis by human neutrophils in vitro.

The uptake and intracellular breakdown of Escherichia coli by human neutrophils was studied under the influence of cefoperazone, cefotaxime, ceftazidime and aztreonam. Non-opsonized as well as serum- and IgG-opsonized bacteria were used, and bacteria and neutrophils were exposed both separately before phagocytosis and together during uptake and in the postingestion phase. Preincubation of the neutrophils with the drugs stimulated their subsequent uptake of untreated serum-opsonized and non-opsonized E. coli in an antibiotic-free medium. With serum-opsonized bacteria this stimulating effect was reversed when the drugs were also present during phagocytosis. The uptake of IgG-opsonized bacteria was largely unaffected both after preincubation of the neutrophils and when the antibiotics were present during phagocytosis. With all four drugs, pre-exposure of bacteria before IgG-opsonization gave a much higher uptake than exposure after IgG-opsonization. Contrary to this, preincubation of the bacteria followed by serum-opsonization inhibited (cefotaxime, ceftazidime) or did not influence (cefoperazone, aztreonam) subsequent uptake in the absence of the drugs. The release of bacterial breakdown products from the cells in the postingestion phase was also inhibited by cefotaxime and ceftazidime after serum-opsonization. With non-opsonized and IgG-opsonized bacteria, however, a stimulation of intracellular breakdown was induced by the presence of these drugs during phagocytosis. Aztreonam and cefoperazone did not significantly influence this phase of phagocytosis. These observations suggest that the drugs bind to both neutrophils and bacteria in an individual manner and modify the binding and function of opsonins.

Anti-Bacterial Agents↗