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Biomedical subjects

T Midtvedt

Publications and source records attributed to T Midtvedt.

At least 127 records · Page 7Linked to original sources
PubMed1986

Epoxydicarboxylic aciduria resulting from the ingestion of castor oil.

A woman who was investigated because of suspected malabsorption was found to excrete large amounts of 3,6-epoxyoctanedioic, 3,6-epoxydecanedioic and 3,6-epoxydodecanedioic acids. The origin of these compounds could be traced to the factitious ingestion of castor oil. Healthy subjects and conventional as well as germ-free rats also excrete these substances after ingestion of castor oil. The epoxydicarboxylic acids are thus endogenous metabolites from ricinoleic acid. The shortest of the three homologues is present in small amounts in normal urine. It may be formed by cyclization of a hydroxylated beta-oxidation intermediate.

Animals↗
PubMed1986

Glycosphingolipid patterns of the gastrointestinal tract and feces of germ-free and conventional rats.

Acid and non-acid glycosphingolipids of stomach, small and large intestine, and stimulated feces of germ-free and conventional rats of the same stain have been isolated and characterized. The glycosphingolipid patterns of the intestinal organs were chemically and immunologically very similar between the two groups of rats and relatively unaffected by the presence of an intestinal microbial flora. The major exception was the presence of hematoside with N-glycoloylneuraminic acid (NeuGc) (NeuGc alpha 2----3Gal beta 1----4Glc beta 1----1Cer) in the stomach of conventional rats not found in the stomach of germ-free animals. Glycosphingolipids of stimulated feces of germ-free animals were derived from epithelial cells mainly of the small intestine and showed no signs of degradation. Glycosphingolipids of feces of conventional rats completely retained the pattern of blood group A-, B-, and H-active glycolipids as found in sterile feces but contained less of hematoside and more of lactosylceramide. This effect was probably due to degradation by bacteria, as demonstrated in vitro with the production of lactosylceramide after treatment of the isolated acid glycolipids of sterile feces with neuraminidase from Clostridium perfringens. The amount of total non-acid glycosphingolipids per dry weight was similar for stomach, was 50% higher for small intestine, and 300% higher for large intestine of germ-free animals compared to conventional animals. Due to the presence of large amounts of mucins the dry sterile feces contained 12% less non-acid glycolipids than conventional feces. However, calculated per rat per day the germ-free animal excreted more of non-acid glycosphingolipids (1.8 and 1.2 mg, respectively).

Animals↗
PubMed1986

Influence of antibiotics on intestinal mucin in healthy subjects.

To determine the effect on microbial breakdown of intestinal mucin healthy volunteers were treated orally with ten different antibiotics. The most pronounced effects were seen after administration of bacitracin, clindamycin or vancomycin: the electrophoretic mucin pattern in faeces changed from a normal conventional pattern to a specific pattern similar to that found in germ-free rats. Disturbed patterns were also observed in some of the subjects treated with ampicillin, doxycycline, erythromycin, metronidazole or nalidixic acid. In most cases the electrophoretic mucin pattern normalized within five weeks after the end of treatment. There were no effects on the microbial breakdown of intestinal mucin in the groups treated with ofloxacin or trimethoprim/sulfamethoxazole. Thus, administration of antimicrobial drugs in clinically recommended doses may cause long-term disturbances in one microflora-associated characteristic, the breakdown of intestinal mucin.

Administration, Oral↗
PubMed1986

Bacterial growth in the duodenum and in the bile of patients with gallstone disease treated with endoscopic papillotomy (EPT).

Bacterial growth in the duodenum and in the bile was studied in 30 patients treated by endoscopic papillotomy (EPT) for stones in the common bile duct. Duodenal sampling was done endoscopically with a microbiology specimen brush, and bile was collected from the common bile duct using a catheter designed to avoid contamination from other sources. The same type of fecal flora was found in the duodenum and in the bile. The majority of patients had more than one strain in the duodenum as well as in the bile. Strains belonging to the Enterobacteriaceae and fecal streptococci dominated. Anaerobes were found in the duodenum in 27.7% of the patients, and in the bile in 16.7%. The heavy bacterial infestation of the common bile duct in our patients did not give rise to clinical symptoms.

Adult↗
PubMed1986

Short-chain fatty acids in germfree mice and rats.

The short-chain fatty acids (SCFAs) have been analyzed in small intestinal and cecal content of 10 germfree and six conventional mice from a Norwegian laboratory, in cecal content and serum of five germfree rats and two germfree mice from a Swedish laboratory and in Norwegian and Swedish autoclaved, nonpurified rodor diets. The mean total SCFA concentration was 1020 mumol/kg in cecum and 1010 mumol/kg in small intestine of Norwegian germfree mice; 124,600 mumol/kg in cecum and 6,250 mumol/kg in small intestine of conventional mice; 490 mumol/kg in cecum and 370 mumol/L in serum of Swedish rats; 360 mumol/kg in cecum and 290 mumol/L in serum of Swedish mice; 31.4 mmol/kg in Norwegian and 19.5 mmol/kg in Swedish nonpurified diets. Acetic acid accounted for more than 90% of the total concentration in all samples from germfree animals and diet, but detectable concentrations of propionic, isobutyric, n-butyric, isovaleric and n-valeric acid were also present. Thus, germfree animals have low, but measurable, concentrations of SCFAs in intestinal content compared to conventional animals. Most probably these acids originate mainly from the diet.

Animals↗
PubMed1986

Influence of peroral antibiotics upon the biotransformatory activity of the intestinal microflora in healthy subjects.

The effects of ampicillin, clindamycin or metronidazole, given perorally for 6 days to eighteen healthy volunteers, upon the following intestinal microflora-associated characteristics (MACs) were evaluated: breakdown of mucin, formation of coprostanol, hydrolysis of bilirubin conjugates, formation of urobilinogen, and of some short chain fatty acids (SCFAs), presence of beta-aspartylglycine and inactivation of trypsin. Clindamycin markedly influenced the expression of all characteristics, but trypsin and beta-aspartylglycine, resulting in a pattern very much alike what has been found in germ-free animals. Ampicillin caused a significant reduction in total amount of SCFAs (P less than 0.05) and urobilinogen (P less than 0.05) present in the faecal samples. Metronidazole caused a significant reduction in the formation of coprostanol and the deconjugation of bilirubin (P less than 0.05). We conclude that orally given antibiotics may cause major alterations in several parameters reflecting the normal biotransformatory activity of the intestinal microflora, probably caused by severe disturbances in the intestinal ecosystem.

Administration, Oral↗
PubMed1986

Isolation and characterization of a mucin-degrading strain of Peptostreptococcus from rat intestinal tract.

A mucin-degrading microorganism was isolated from the intestinal tract by serial sectioning from the serosal side of the caecum wall from a conventional rat. The ability of degrading the intestinal water-soluble mucin was present both in vivo after monocontamination of germ-free rats and in vitro, when adding the microbe to Mucin medium. The morphology, Gram-positive cocci single or in short chains and the very weak biochemical activities allow us to place this strain in the species Peptostreptococcus micros.

Animals↗
PubMed1986

Influence of intestinal microflora on the tryptic activity during lactation in rats.

On comparing germ-free and conventional rats, inactivation of the tryptic activity was found to take place in the caecum of conventional adult rats only. A microbial intestinal inactivation of the tryptic activity was established in suckling conventional rats within 10 days after birth. At 3 weeks of age, suckling germ-free rats were found to have less faecal tryptic activity than their early-weaned littermates.

Animals↗
PubMed1986

Effects of feeding ursocholic acid to germfree rats.

Germfree rats were fed 24-14C-ursocholic acid (UC) mixed into the diets for 10 days. The bile was then drained by cannulation for 6 hours to collect the bile salt pool. No biotransformation of the labelled UC occurred and it constituted approximately equal to 75% of an enlarged bile salt pool. Less phospholipid and cholesterol were secreted into the bile per mumol bile salt compared to normal rats. The critical micellar concentration (CMC) of the bile was determined by equilibrium dialysis and found to be increased. Faecal excretion of labelled triolein added to the diet was unaffected by feeding ursocholic acid. Excretion of 14C-octadecane and 14C-cholesterol increased significantly under the same conditions. Ursocholic acid feeding thus resulted in a selective malabsorption of octadecane and cholesterol.

Animals↗
PubMed1986

Intestinal deconjugation of bilirubin in germfree and conventional rats.

The content of conjugated bilirubin (CB) was about the same in small intestinal contents from germfree (GF) and conventional (CONV) rats. Caecal contents from GF rats contained considerably more CB than from CONV rats. The results indicated that the caecum is the major site of microbial deconjugation of CB in the CONV rat. Separation of azopigments prepared from small intestinal contents of GF and CONV rats revealed similar patterns. Similar separation patterns were also observed with azopigments prepared from caecal contents and faeces of GF rats. Some chemical properties of CB prepared from GF rat faeces were studied.

Animals↗
PubMed1986

Influence of antibiotics on the faecal excretion of bile pigments in healthy subjects.

We have evaluated the effects of 10 antibiotics, given orally for 6 days to healthy subjects, on faecal excretion of urobilinogen. Intake of bacitracin, vancomycin, clindamycin, erythromycin, and ampicillin resulted in a pronounced suppression of the faecal excretion of urobilinogen (p less than 0.05). Intake of doxycycline, metronidazole, nalidixic acid, ofloxacin, and trimethoprim/sulphamethoxazole had no significant effect. The effects of three antibiotics-ampicillin, clindamycin, and metronidazole--on faecal excretion of conjugated bilirubin were similarly evaluated. Intake of clindamycin led to a marked increase of conjugated bilirubin (p less than 0.05) in the faeces, and the pattern of separated azopigment derivatives of the bilirubin conjugates became altered. Intake of ampicillin and metronidazole resulted in far less alterations in faecal conjugated bilirubin, although a significant change was observed in the subjects receiving metronidazole (p less than 0.05). The differences between the antibiotics with regard to altered intestinal bile pigment metabolism may be due to differences in antimicrobial spectra and/or intestinal concentrations of the drugs. Our findings indicate that orally taken antibiotics may cause a suppression of the microbial deconjugation of conjugated bilirubin and urobilinogen formation, respectively. This may reflect a pronounced disturbance of the intestinal microflora.

Adult↗
PubMed1986

Influence of oral intake of seven different antibiotics on faecal short-chain fatty acid excretion in healthy subjects.

Faecal excretion of short-chain fatty acids (SCFAs) has been measured by gas chromatography in groups of six or seven healthy subjects before, during, and after they received the antibiotics bacitracin, co-trimoxazol, doxycycline, erythromycin, nalidixic acid, ofloxazin, or vancomycin orally for 6 days. Intake of bacitracin and vancomycin had pronounced effects on faecal SCFAs excretion and reduced median total concentration of SCFAs from 105.4 mmol/kg to 21.8 mmol/kg and from 69.3 mmol/kg to 19.4 mmol/kg, respectively (p less than 0.05). Erythromycin had moderate effects on the faecal SCFAs excretion, whereas small or no changes were seen during intake of co-trimoxazol, doxycycline, nalidixic acid, and ofloxacin. 2-Methylbutyric acid, a SCFA not previously seen in human faeces, was found in the faeces of all subjects (median concentration before intake of antibiotic, 1.3 mmol/kg). Bacitracin, erythromycin, nalidixic acid, and vancomycin were detected in high concentrations in faeces during therapy, whereas trimethoprim, doxycycline, and ofloxacin were found in relatively low concentrations. In conclusion, some, but not all, peroral antimicrobials induce changes in faecal SCFAs, most likely reflecting changes in the colonic ecosystem.

Administration, Oral↗
PubMed1986

Influence of ampicillin, clindamycin, and metronidazole on faecal excretion of short-chain fatty acids in healthy subjects.

The faecal excretion of short-chain fatty acids (SCFAs) has been measured in groups of six healthy subjects before, during, and after they received the antibiotics clindamycin, ampicillin, or metronidazole perorally for 6 days. Intake of clindamycin reduced the median total concentration of SCFAs from 62.9 mmol/kg faeces (wet weight) to 7.3 mmol/kg (p less than 0.05). During therapy the relative amounts of acetic acid increased from 50% to 90% of the total concentration (p less than 0.05). Ampicillin reduced the median SCFAs concentration from 62.4 mmol/kg to 47.8 mmol/kg (p less than 0.05), whereas metronidazole did not change the SCFAs concentrations significantly. The SCFAs concentrations returned to normal within 5 weeks after the treatment in all subjects. Clindamycin was detected in high concentrations in faeces during therapy. Ampicillin was detected in only one faecal sample, which was from the only subject in the ampicillin group without detectable beta-lactamase activity in faeces. Metronidazole could not be detected in faeces from any subjects receiving this drug. Clindamycin and ampicillin, but not metronidazole, induce pronounced changes in faecal SCFAs, most likely reflecting severe changes in the colonic ecosystem. An antibiotic's influence on the colonic microflora may in part depend on its antimicrobial spectrum and the concentration of antimicrobially active drug in the gut.

Administration, Oral↗
PubMed1986

Beta-glucuronidase-producing bacteria in bile from the common bile duct in patients treated with endoscopic papillotomy for gallstone disease.

This paper reports the occurrence of beta-glucuronidase-producing bacteria in the bile in gallstone patients treated with endoscopic papillotomy (EPT). The study included 36 patients--18 women and 18 men, aged 43-87 years, with a median of 72.5 years. Bile sampling was done with an endoscopic technique. All bacterial strains were tested for beta-glucuronidase activity with a rapid chromogenic tablet test, using 4-nitrophenyl-beta-D-glucuronic acid as substrate. Bacterial growth was found in the bile in 35 patients. Of 103 strains isolated, 30 produced beta-glucuronidase. Twenty-five of the patients had at least one beta-glucuronidase-producing strain in the bile. All 26 strains of Escherichia coli were producing the enzyme. Both strains in the Bacteroides fragilis group and one out of two strains of Clostridium perfringens were producing beta-glucuronidase. The activity of the bacterial beta-glucuronidase was found within the pH range of the bile in these patients. A relationship between the presence of beta-glucuronidase-producing bacteria in the bile and pigment gallstone is suggested.

Adult↗
PubMed1986

Effects of antimicrobial agents upon the functional part of the intestinal flora.

For functional studies of the complex intestinal ecosystem, two recently introduced terms have been shown to be of value. A Microflora-Associated Characteristic--MAC--is defined as the recording of any anatomical structure, physiological or biochemical function in a macroorganism which has been influenced by the microflora. When functionally active microbes are absent, as in germfree animals, the recording of a MAC can be defined as a Germfree Animal Characteristic--GAC. In our ongoing, long-term ecological studies we have investigated the influence of a long list of antimicrobial agents upon various biochemical MACs in man and rats. Parameters such as conversion of cholesterol to coprostanol, 7-dehydroxylation of bile acids, transformation of bilirubin, degradation of mucin, production of short chain fatty acids and inactivation of tryptic activity have been the MACs most often studied. Each antibiotic may create its own MAC/GAC profile, partly reflecting its antibacterial spectrum and concentration in the intestinal tract and partly the characteristics of the microbial species actually involved in the reaction. MACs influenced mainly by species dominated by a K-selection are generally more disturbed than MACs influenced by species dominated by a r-selection.

Animals↗
PubMed1985

Biosynthesis of cholestanol from bile acid intermediates in the rabbit and the rat.

Biliary 7 alpha-hydroxy-4-cholesten-3-one (an intermediate in bile acid biosynthesis) may be 7 alpha-dehydroxylated in the gut and further metabolized to cholestanol (Skrede, S., and Björkhem, I. (1982) J. Biol. Chem. 257, 8363-8367). We have now evaluated the quantitative importance of pathway(s) to cholestanol with 7 alpha-hydroxylated C27 steroids as intermediates. After feeding conventionally fed rabbits or rats or germ-free rats with [7 alpha-3H]cholesterol and [4-14C]cholesterol, tissue cholestanol could be isolated with about a 20% lower 3H/14C ratio than present in cholesterol. We conclude that there is a pathway to cholestanol involving 7 alpha-hydroxylated intermediates. Intestinal microorganisms are not essential for this pathway, which accounts for at most 20% of the cholestanol formed in these species. In bile fistula rats, there was also a significant conversion of intraperitoneally injected [7 beta-3H]7 alpha-hydroxycholesterol and [4-14C]7 alpha-hydroxy-4-cholesten-3-one into cholestanol. The enzymes involved in the 7 alpha-hydroxylation/dehydroxylation pathway for the biosynthesis of cholestanol are probably located in the liver. Both 7 alpha-hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one may be intermediates.

Animals↗