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Biomedical subjects

D J Tuma

Publications and source records attributed to D J Tuma.

At least 127 records · Page 7Linked to original sources
PubMed1982

Effect of antibiotics in the prevention of jejunoileal bypass-induced liver dysfunction.

Administration of antibiotics has been reported to prevent or minimize liver dysfunction in experimental animals having been subjected to jejunoileal bypass, suggesting that jejunoileal bypass-induced liver dysfunction results from production of toxic substances by bacteria in the defunctionalized bowel. However, improved absorption will also prevent bypass-induced liver injury. We studied the effects of tetracycline on the development of bypass-induced liver dysfunction and compared it to the mucosal adaptation of the intact bowel after bypass. After 6 weeks, rats subjected to bypass but not given antibiotics had decreased levels of serum triglycerides, hepatic cytochrome P-450, and hepatic pentobarbital hydroxylase. Evaluation of intestinal mucosal hyperplasia after bypass indicated that animals given antibiotics after bypass developed greater increases in mucosal DNA content, mucosal protein, and mucosal weight than bypassed animals not receiving antibiotics. We speculate that the beneficial effects of antibiotic administration on liver function after bypass may be a result of improved absorption.

Animals↗
PubMed1982

The effect of methotrexate on homocysteine methylating agents in rat liver.

Methotrexate (MTX) was administered to rats in a time course study throughout a 4-month period. Despite an inhibition of the hepatic dihydrofolate reductase by 88 to 90% in these animals, the body weights and liver weights of the treated animals did not vary from those of the pair-fed controls during this time course, and the livers showed no fatty infiltration as demonstrated by triglyceride analyses. The prime methylating agent of homocysteine, N5 methyltetrahydrofolate, progressively increased in control livers throughout the experimental period; however, MTX impaired the increases at the 2- and 4-month periods in the treated animals. Hepatic betaine, the secondary methylator of homocysteine in the liver, also increased in the controls during the experimental period. These increases were also impaired in the MTX-treated animals. These data suggest that betaine may compensate for N5 methyltetrahydrofolate as a methylating substance when folate metabolism is antagonized in rat liver.

Animals↗
PubMed1981

Etiology of jejunoileal bypass-induced liver dysfunction in rats.

Several recent studies suggest that jejunoileal bypass-induced liver disease results from malabsorption of essential nutrients. However, in experimental animals, resection of the defunctionalized bowel substantially reduces bypass-induced liver injury. Such models are often used to support the theory that bacteria in the defunctionalized bowel produce toxic substances which result in liver damage. We used a rat model to first explore the effects of intestinal bypass vs resection on various parameters of liver injury, and subsequently compared these findings to the effect of both bypass and resection on mucosal adaptation in the remaining intact bowel after each procedure. Bypassed animals had lower levels of hepatic cytochrome P-450, glucose-6-phosphatase, pentobarbital hydroxylase, and serum triglycerides than did animals undergoing resection of defunctionalized bowel. Concurrently, resected animals had much greater increases in mucosal weight, DNA content, and protein content in the intact bowel than did bypassed animals. We speculate that the beneficial effects of resection of bypassed bowel on liver function may be a result of increased mucosal hyperplasia in resected animals, rather than elimination of production of toxic substances in the defunctionalized bowel.

Animals↗
PubMed1980

Effect of improved absorption on development of jejunoileal bypass-induced liver dysfunction in rats.

Jejunoileal bypasses were performed in rats to determine the effect of improved absorption on the development of liver dysfunction occurring after this procedure. Several parameters of liver function were measured in rats 7 weeks after both the standard 85% small-bowel bypass and an 80% bypass in which an extra 5 cm of intact bowel was retained. Animals having undergone 80% bypass had a lesser degree of lowering of serum protein and triglyceride levels, hepatic cytochrome P-450 content, and hepatic glucose-6-phosphatase activity than did the animals undergoing 85% bypass. Abnormalities found in 85% bypass animals were only partially reproduced by reducing food intake in another group of 80% bypassed animals. These findings emphasize the importance of nutritional factors in the etiology of bypass-induced liver disease and militate against toxin production in the defunctionalized bowel as the sole cause of liver dysfunction following bypass.

Animals↗
PubMed1980

Effect of ethanol and its metabolites on microtubule formation.

Ethanol, acetaldehyde, and acetate were investigated for their effects on bovine neurotubulin polymerization. Ethanol at concentrations as high as 50 mM did not affect the rate or extent of tubulin polymerization. Acetyldehyde inhibited tubulin polymerization in a concentration-dependent manner, with complete inhibition at 10 mM and slight inhibition at 1 mM. Sodium acetate caused a concentration-dependent increase in tubulin polymerization, however sodium chloride showed a similar effect. These data indicate that ethanol and acetate were not inhibitors of microtubule formation while acetaldehyde exhibited weak inhibitory activity.

Acetaldehyde↗
PubMed1979

Role of defunctionalized bowel in jejunoileal bypass-induced liver disease in rats.

The pathogenesis of jejunoileal bypass-induced liver disease was investigated in the rat model. Male Sprague-Dawley rats were subjected to 90% jejunoileal bypass and compared to rats having undergone 90% jejunoileal resection, to ad libitum and pair-fed controls and to weight-matched (underfed) controls. After 8 weeks the animals were killed and selected analyses performed. Several indications of liver dysfunction were observed in the bypass rats including hepatomegaly, hypotriglyceridemia, hypoproteinemia, elevated SGOT levels, and markedly decreased levels of cytochrome P-450. All of these abnormalities with the exception of elevated SGOT levels and decreased serum proteins were not observed to the same degree in animals in which the defunctionalized bowel was resected. Rats which were underfed (weight matched) did not develop any of the abnormalities of liver injury demonstrated in the bypass rats. Multiple factors appear to be responsible for the production of bypass-induced liver disease, but the defunctionalized bowel plays an important role.

Animals↗
PubMed1979

Effect of serum lipoproteins of bile obstructed rats on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in perfused rat liver.

Total lipoproteins as well as fractionated VLDL + LDL and HDL from fasted control rats and bile-ligated rats were tested in liver perfusion for their effect on 3-hydroxy-3-methylglutaryl CoA reductase activity in normal rat livers. The total lipoproteins of bile-obstructed rats had 3 times greater capacity to increase 3-hydroxy-3-methylglutaryl CoA reductase activity than that of the control total lipoproteins. When the fractionated lipoproteins were tested from fasted control rats, it was found that the major stimulating activity was in the HDL fraction with minor activity in the VLDL + LDL fraction. When these plasma components isolated from fasted bile-ligated rats were tested, it was found that the major activity had shifted to the VLDL + LDL fraction with the HDL having only a minor stimulatory role. The possible mechanism of action of the abnormal lipoproteins associated with bile obstruction in regulating 3-hydroxy-3-methylglutaryl CoA reductase activity is discussed.

Animals↗
PubMed1979

Determination of free choline and phosphorylcholine in rat liver.

A simple procedure for determination of levels of free choline and phosphorylcholine in hepatic tissue is outlined. The method makes use of the enzyme acid phosphatase to liberate choline from phosphorylcholine and incorporates the ability of choline to react with potassium triiodide to yield choline periodide for the measurement of choline and phosphorylcholine in liver. The method is accurate for both entities (recovery of 97-100% for choline and 92-98% for phosphorylcholine). For phosphorylcholine, the method is markedly simpler than other methods previously described and the results for normally fed rats are of the same order of magnitude. The applicability of the method was shown when it was demonstrated that diets containing different amounts of choline influenced the level of choline and phosphorylcholine in liver.

Animals↗
PubMed1979

A simplified procedure for the determination of betaine in liver.

A convenient procedure for the determination of hepatic betaine levels is described. The method takes advantage of ethanol precipitation to rid acidified tissue extracts of interfering substances. Betaine is reacted with potassium triiodide to form betaine periodide, which is selectively precipitated via pH adjustment. The precipitate of betaine periodide is dissolved in ethylene dichloride and measured spectrophotometrically. The method is specific, accurate, and simple and showed recoveries of from 97 to 103% at two different levels of added betaine. The applicability of the method was shown when it was demonstrated that diets containing different amounts of choline influenced levels of hepatic betaine.

Animals↗
PubMed1978

Impairment of glycoprotein secretion by phenobarbital in rat liver slices.

The effects of phenobarbital on protein and glycoprotein synthesis and secretion were studied in rat liver slices. Phenobarbital (2 mM) decreased [14C]glucosamine and [14C]leucine incorporation into liver proteins and markedly inhibited their incorporation into medium (secretory) proteins. The inhibitory effect of phenobarbital was dose dependent and not reversible under the conditions of this study. In the presence of cycloheximide, an inhibitor of peptide synthesis, phenobarbital still inhibited the release of glycoproteins into the medium; however, the specific activity of liver glycoproteins was increased. The effects of phenobarbital on hepatic macromolecular secretion, independent of its effects on synthesis, were determined by prelabeling proteins in a liver slice system with either [14C]leucine or [14C]glucosamine. When phenobarbital was present, the secretion of these prelabeled proteins into the medium was inpaired. 12 h after intraperitoneal injections of phenobarbital, glycoprotein secretion was inhibited from liver slices prepared from the pretreated rats. This inhibition of secretion occurred even though protein synthesis was stimulated and intracellular glycosylations unaffected. The results of this study indicate that phenobarbital impairs the secretion of glycoproteins by the liver.

Animals↗
PubMed1978

Assay for free and total choline activity in biological fluids and tissues of rats and man with Torulopsis pintolopessi.

The sensitive, specific growth response to choline activity of the thermophilic enteric yeast Torulopsis pintolopessi enables estimation of free and bound choline activity in rat and human fluids and tissues- as little as 10 ng/ml of choline is measurable. Unlike other microbial assays, estimation of unbound (free) choline activity is not influenced by methionine or phospholipids. The method also distinguishes differences in choline activity of fluids and tissues from choline-deficient and choline-replete rats. Free and bound choline activity in blood, red blood cells, plasma, and liver from choline-deficient rats were almost 2-fold lower than from choline-supplemented animals. Free and bound choline activity in whole brain from choline-deficient rats were signifigantly higher (more than 2-fold). The application of the T. pintolopessi method in studying choline status in man and reasons for high choline activity in brain of choline-deficient rats are suggested.

Adult↗
PubMed1978

Effects of phenobarbital administration on levels of physiological antioxidants in rat liver.

Administration of phenobarbital to rats over a period of 5 days was shown to increase hepatic lipid peroxidation concomitant with induction of cytochrome P-450 and cytochrome c reductase. The purpose of this study was to determine whether the increase in lipid peroxidation was due to a lowering in hepatic antioxidants. The results show that increased lipid peroxidation was not due to a decreased level of antioxidants since the fat-soluble antioxidants were unchanged and ascorbate, a water-soluble antioxidant, was elevated. The relationship of the increase in hepatic ascorbate to enhanced lipid peroxidation is discussed.

Animals↗