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At least 199 records · Page 11Linked to original sources

PubMed1988

N-methyl-D-aspartate receptors in the spinal cord mediate pressor responses to stimulation of the rostral ventrolateral medulla in the rat.

1. Activation of bulbospinal neurons projecting from the C1 area of the rostral ventrolateral medulla evokes a pressor response. The nature of the neurotransmitters involved in mediating this response at spinal cord level has not been established. 2. Amino acid antagonists were introduced into the spinal subarachnoid space to investigate the role of spinal amino acid receptors in mediating this pressor response in the anaesthetized rat. 3. Intrathecal administration of the amino acid receptor antagonists 2-amino-phosphono valeric acid (2APV), gamma-glutamyl glycine, kynurenate or glutamic acid diethylester (GDEE) attenuated the pressor responses to stimulation of the C1 area. These compounds have been shown to antagonize N-methyl-D-aspartate (NMDA) sensitive receptors. 4. Intrathecal administration of 2APV significantly attenuated the increase in blood pressure produced by injection of NMDA into the spinal subarachnoid space. 5. These results suggest that the pressor response produced by stimulation in the area of the C1 neurons in the rostral ventrolateral medulla of the rat is mediated at least in part by NMDA receptors in the spinal cord.

2-Amino-5-phosphonovalerate↗

PubMed1976

Serum concentrations of individual monocarboxylic short-chain fatty acids C2-C6 in underweight children.

The serum concentrations of individual short-chain fatty acids containing 2-6 carbon atoms were studied in 12 underweight children. Mean n-butyric and iso-valeric acid levels were significantly elevated in underweight children, while those of n-valeric and iso-caproic acids were not significantly higher than in the control group. The level of total free fatty acids was also increased in the underweight group. A reduced enzymatic activity in fatty acid synthesis is supposed to be the factor underlying the impaired lipogenesis.

Adolescent↗

PubMed1991

Derivatives of butyric acid as potential anti-neoplastic agents.

A novel derivative of butyric acid, pivalyloxymethyl butyrate (AN-9) has been shown, in vitro, to: (a) induce cytodifferentiation and inhibit the proliferation of leukemic cells; (b) inhibit the growth and formation of Lewis lung carcinoma colonies in semi-solid agar. AN-9 affect cells at about 10-fold lower concentration and at a faster rate than does butyric acid. The pivalyloxymethyl esters of propionic, isobutyric and valeric acids do not elicit effects similar to those of AN-9, while the isobutyryloxymethyl butyrate does, which strongly suggests that the activity of AN-9 stems from intracellular metabolic degradation of the pro-drug to butyric acid. In vivo, AN-9, increased the survival of mice in Lewis lung carcinoma primary cancer model and significantly decreased the number of lung lesions of the animals inoculated with highly metastatic cells, but did not affect their life span. Acute LD50 studies have shown that AN-9 possesses low toxicity. These results suggest that AN-9 is a potential anti-neoplastic agent as well as a tool for investigation of the differentiation induction mechanism.

Animals↗

PubMed1995

Heparan-dependent endothelial antithrombin binding is increased by butyrate.

Heparin biosynthesis involves a critical early step of N-deacetylation which is inhibited by the short chain fatty acid n-butyrate. Such inhibition causes mast cells to produce heparins with high affinity for antithrombin (AT). We have cultured endothelial cells in media supplemented with short chain fatty acids and have found that isobutyric, propionic and valeric acids cause significant increases in endothelial binding of AT measured by flow cytometry, but n-butyric acid was the most effective fatty acid to increase AT binding. Such binding,was heparan sulfate-dependent, for it was decreased significantly by pre-treatment of the cells with heparinase. These findings suggest that inhibition of N-deacetylation in heparan biosynthesis affects sulfation and results in the distribution of negative charges and conformation changes within the heparan domain that binds AT to endothelial plasma membranes. These changes also were associated with up-regulation of the intercellular adhesion molecule-1, which is a marker of endothelial activation.

Anticoagulants↗

PubMed1979

Induction of a microsomal butyrylesterase in rat liver by phenobarbital treatment.

A carboxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1) was induced in the liver of rats after repeated administration of phenobarbital. This enzyme migrated most rapidly towards the anode among Triton X-100-solubilized liver esterases by electrophoresis on the cellulose acetate membrane and it was tentatively designated as L-I. L-I increased in the microsomal fraction and was mainly concentrated in the fraction of smooth endoplasmic reticulum that proliferated after phenobarbital treatment. L-I- was separated from other liver esterases and purified about 800-fold. The purified L-I was homogeneous as judged by polyacrylamide gel electrophoresis and exhibited a molecular weight of about 55 000 as determined by gel filtration. L-I split the 1-naphthyl ester of butyric acid faster than esters of acetic, propionic or valeric acids; it therefore seemed to be a butyrylesterase.

Animals↗

PubMed1987

Microbiological Degradation of Malodorous Substances of Swine Waste under Aerobic Conditions.

Phenol, p-cresol, and volatile fatty acids (VFA; acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids) were used as odor indicators of swine waste. Aeration of the waste allowed the indigenous microorganisms to grow and degrade these malodorous substances. The time required for degradation of these substances varied according to the waste used, and it was not necessarily related to their concentrations. Using a minimal medium which contained one of the malodorous compounds as sole carbon source, we have selected from swine waste microorganisms that can grow in the medium. The majority of these microorganisms were able to degrade the same substrate when inoculated in sterilized swine waste but with an efficiency varying from one strain to the other. None of these strains was able to degrade all malodorous substances studied. Within 6 days of incubation these selected strains degraded the following: Acinetobacter calcoaceticus, phenol and all VFA; Alcaligenes faecalis, p-cresol and all VFA; Corynebacterium glutamicum and Micrococcus sp., phenol, p-cresol, and acetic and propionic acids; Arthrobacter flavescens, all VFA. On a laboratory scale, the massive inoculation of swine waste with C. glutamicum or Micrococcus sp. accelerated degradation of the malodorous substances. However, this effect was not observed with all of the various swine wastes tested. These results suggest that an efficient deodorization process of various swine wastes could be developed at the farm level based on the aerobic indigenous microflora of each waste.

Journal Article↗

PubMed1984

Serum branched-chain amino and keto acid response to a protein-rich meal in man.

In 8 healthy volunteers blood levels of branched-chain amino (BCAA) and keto acids (BCKA) were determined in response to a protein-rich meal. Serum concentrations of leucine, isoleucine, valine, alpha-ketoisocaproic acid and alpha-keto-beta-methyl-n-valeric acid increased within 30 min and continued to rise throughout the observation. Only the keto analog of valine remained unaffected. As the BCAA increased significantly more percentagewise than their keto analogs, the ratios between amino and keto acids became augmented. It is suggested that (1) augmentation of keto acids may reflect transamination of amino acids rather than intestinal uptake; (2) the overall capacity of the organism for decarboxylation of ketovaline is greater than for the other keto acids, and (3) augmentation of the ratio between BCAA and BCKA may favor the storage of amino acids from the protein load into the body's protein stores.

Adult↗

PubMed1999

Which organic acids does hemofiltrate contain in the presence of acute renal failure?

It is not generally possible to measure most organic acids in the serum of critically ill patients, due to rapid metabolism and methodological problems. Only the regular measurement of lactic acid and the arterial ketone body ratio (acetoacetate/beta-hydroxybutyrate, AKBR) have been introduced in clinical practice, but these parameters can represent only a part of the disturbed metabolism. In pediatric patients, a chromatographical urine analysis has been established for detection of inborn errors of metabolism, which allows the determination of more than 50 organic acids simultaneously (gas chromatographic (GC) analysis in combination with mass spectrometry (MS)]. In continuous treatment of acute renal failure, hemofiltrate is always available, but it contains only low protein concentrations and after the filtration process, metabolism is rapidly stopped. The sieving coefficient of lactic acid is nearly one in hemofiltration. The aim of our study was to compare results of the regular and CG/MS methods in blood and hemofiltrate for lactic acid, and to find other organic acids of possible clinical importance. We investigated serum (lactic acid) and hemofiltrate of 40 critically ill patitens, similar to the urine analysis method for infants. All patients suffered from acute renal failure and were treated by continuous veno-venous hemofiltration (CVVH). The conditions of treatment were standardized (spontaneous ultrafiltration in the first hour), and the material (blood/hemofiltrate) was taken one hour after the beginning of extracorporeal circulation. Statistical methods included correlation analysis, nonparametric ANOVA with Wilcoxon scores (ranks of data), and stepwise discriminant analysis. Regular and GC/MS methods in hemofiltrate showed a good correlation for lactic acid. The best correlation with lactic acid was found for 4-hydroxy-phenyllactic acid (n=20, r=0.866), 2-hydroxy-valeric acid (n=22, r=0.7491) and 2-hydroxybutyric acid (n=32, r=0.5148). Age, sex, diagnosis, and APACHE II score play a subordinate role, but the presence of glyceric and citric acid possibly have prognostic importance [nonparimetric ANOVA with Wilcoxon scores (ranks of data)], as does the combination of 3-hydroxypropionic acid, glyceric acid, and threonic-acid-4-lacton (stepwise discriminant analysis). It can be concluded that in acute renal failure, the measurement of lactic acid and AKBR can reflect only a small part of disturbed metabolism. Hemofiltrate can be a useful medium in describing metabolic processes in critically ill patients with acute renal failure. Some inherited metabolic diseases in infants (phenylketonuria, maple syrup disease) and ketoacidosis show similar metabolic modifications.

APACHE↗

PubMed1988

Evidence for a labile intermediate in the butyrate induced reduction of the level of c-myc RNA in SW837 rectal carcinoma cells.

We have found that the differentiation inducer butyric acid causes the synthesis of a cellular protein(s) that mediates a rapid decline in the level of myc RNA in SW837, a cell line derived from a human adenocarcinoma of the rectum. This effect was dose-dependent and was maximal at 1 mM. Among the short chain fatty acids tested, butyric acid was found to be the most potent. Valeric acid was less effective, and acetic, propionic, isobutyric, and caproic acids did not cause a significant change in myc RNA level. Dimethylsulfoxide, another inducer of differentiation, also caused a marked diminution of myc RNA level, but was only tested at a relatively high dose (282 mM). The reduction in myc RNA level caused by butyrate was blocked by inhibitors of protein synthesis, and was rapidly reversed by removing the inducer. This suggests that butyrate causes the induction of a labile activity that has a negative effect on myc RNA abundance.

Adenocarcinoma↗

PubMed1984

Oral administration of alpha-ketoisovaleric acid or valine in humans: blood kinetics and biochemical effects.

alpha-Ketoisovaleric acid levels increase from 10.6 +/- 0.8 to 121 +/- 20 mumol/L, and valine levels increase from 175 +/- 14 to 940 +/- 50 mumol/L after oral administration of an isomolar (62.5 mg/kg) bolus of alpha-ketoisovaleric acid or valine to healthy human subjects. alpha-Ketoisovaleric acid levels have a different time course relative to valine. alpha-Ketoisovaleric acid and valine affect various other amino and keto acids, and some of these effects are qualitatively different. alpha-Ketoisovaleric acid enhances alpha-ketoisocaproic acid and alpha-keto-beta-methyl-n-valeric acid, but diminishes the corresponding amino acids, and causes an early decline of ornithine along with a late augmentation of plasma arginine. Valine does the opposite. The data suggest that in humans, overall capacity for alpha-ketoisovaleric acid decarboxylation appears greater than the capacity for valine transamination, and that all branched-chain amino acids and branched-chain keto acids seem to be interconvertible by reversible transaminations.

Administration, Oral↗

PubMed1983

The relationship between branched-chain amino acids and alpha-keto acids in blood in uremia.

Branched-chain alpha-keto acid (BCKA) supplements are used as a nitrogen-free source of branched-chain amino acids (BCAA) in patients with chronic renal failure. Their use is dependent on the freely reversible interconversion of BCKA and BCAA in muscle tissue. In a group of eight young adults on dialysis compared to 11 normal healthy adults, the ratios of the fasting plasma concentrations of leucine and isoleucine to their corresponding alpha-keto acids, alpha-keto isocaproic acid and alpha-keto-beta-methyl-eta-valeric acid, respectively, were significantly elevated. These ratios appear to be sensitive to changes in intracellular glutamate and pyruvate. The ratios increased in seven insulin-dependent diabetics following insulin withdrawal, a situation where intracellular glutamate is increased. The ratios decreased in six normal healthy adults in response to submaximal treadmill exercise, a situation where intracellular pyruvate is increased. The elevated BCAA/BCKA ratios in uremia could be a reflection of reduced peripheral glucose utilization. A consequence of this will be enhanced conversion of supplemented BCKA to their corresponding BCAA. The close association between muscle BCAA and glucose metabolism suggests that the timing of BCKA administration in relation to energy intake might prove important.

Adolescent↗

PubMed1981

Carcinogen bioassay and mutagenicity studies with the hypolipidemic agent gemfibrozil.

Gemfibrozil, a novel hypolipidemic agent identified chemically as 2,2-dimethyl-5-(2,5-xylyoxy) valeric acid, was evaluated for mutagenic potential in in vitro assays with Salmonella typhimurium. For evaluation of tumorigenic potential, gemfibrozil was administered in the diet (0.30, and 300 mg gemfibrozil/kg) to groups of noninbred CD-1 mice (72/sex) and noninbred CD rats (50/sex) for 78 and 104 weeks, respectively. In the bacterial mutagenesis assays, between 100 and 2,500 microgram gemfibrozil/plate failed to induce a significant increase in revertant bacterial colonies. Neither was a mutagenic response in bacterial assays induced at concentrations up to 300 microgram of five in vivo metabolites of gemifibrozil isolated from rat urine/plate. In mice, gemfibrozil did not significantly increase the frequency or the mean latency period of tumors. In rats, the statistically significant increases in hepatocellular tumors and interstitial cell tumors of the testes were dose related. Adrenal medullary and pancreatic acinar tumors were increased in male rats but were inversely dose related. Under the conditions of this assay, gemfibrozil did not elicit a tumorigenic potential in mice and female rats. In male rats and related to the hepatocellular tumor response, the peroxisome proliferation seen did not occur in humans chronically administered hypolipidemics.

Animals↗

PubMed1987

Relationship of branched-chain alpha-keto-acids and lipids in sera of hypertriglyceridemic subjects.

According to the present study, in hyperlipidemias where triglyceride values in serum are raised, the triglyceride values are associated with increased amounts of branched-chain alpha-keto-acids (BCKA) in the serum. In particular, the concentration of alpha-ketoisocaproic acid (KICA), which in the control sera was 34.4 mumol/l, was in type IIB hyperlipidemia 40.4% and in type IV 49.4% higher than in controls with normal serum lipid values. In type IV hyperlipidemia, values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methyl-n-valeric acid (KMVA) were also high when compared to the corresponding mean values of the controls, 7.1 and 18.8 mumol/l. The respective differences were 57.7 and 44.1 per cent. In type IIB hyperlipidemia, KIVA was significantly and KMVA insignificantly increased compared to the control group. In type IIA hyperlipidemia with normal triglyceride values, none of the three BCKA differed significantly from the controls. These results also indicate that the increased amounts of individual BCKA somehow depend on the concentration of triglycerides in serum, while no relationship was found between BCKA values and cholesterol concentration.

Cholesterol↗

PubMed1980

Effect of nicotinic acid on rumen fermentation in vitro and in vivo.

A series of in vitro studies tested effects of nicotinic acid on rumen fermentation. Urea was the nitrogen supplement for all substances. As expected, a substrate of corn produced the most gas and microbial protein followed by a substrate of corn plus brome hay (1:1). A substrate of brome hay produced the least amount of gas and microbial protein. Niacin had no effect on gas production but significantly increased synthesis of microbial protein. The most protein was synthesized with the corn substrate, but the greatest percentage increase due to niacin was with the substance of corn plus hay. Six rumen-fistulated cows were fed a ration of grain and grass hay (1:1) with 2.3% urea. The rations were supplemented with 0 or 200 ppm niacin. Niacin had no important effect on the concentration of rumen dry matter or lactic acid, or the molar proportions of acetic, butyric, or valeric acids. Niacin increased the concentration of rumen bacterial protein, ammonia, and propionic acid. Niacin reduced the rumen concentration of urea nitrogen. There were no differences in the amino acid composition of rumen bacteria due to niacin.

Amino Acids↗

PubMed1985

Pharmacokinetic and metabolic interrelationships among branched-chain keto and amino acids in humans.

Equimolar loads (0.55 mmol/kg) of alpha-ketoisocaproic acid (KICA) or alpha-keto-beta-methyl-n-valeric acid (KMVA), leucine, or isoleucine were given to healthy human subjects. Branched-chain keto acid (BCKA) and amino acid (BCAA) blood levels increased severalfold within minutes for greater than 3 hours. Time course and magnitude of the increments were different for each substance. Keto acids augmented the concentrations of their corresponding amino acids, and amino acids those of the respective keto acids. Each individual keto or amino acid affected all other constituents of the BCKA-BCAA pool. KICA and leucine greatly diminished KMVA, isoleucine, alpha-ketoisovaleric acid, and valine concentrations in blood. Leucine and isoleucine increased significantly more in response to leucine or isoleucine than to administration of equimolar loads of KICA or KMVA. The data suggest that an inappropriate increase in KICA or leucine in BCKA- or BCAA-containing supplements may stimulate the catabolism of BCKAs and BCAAs. Furthermore, if keto acid-containing supplements are given to increase low leucine, isoleucine, or valine concentrations, the dose must be significantly higher than for amino acid-containing supplements.

Adult↗

PubMed1980

Fermentation of 1,2-O-iso-propylidene-D-glucofuranose ("monoacetone glucose") by anaerobic bacteria.

Various species of Clostridium, Bacteroides, Propionibacterium and Eubacterium were incubated in a 1% solution of 1,2-O-iso-propylidene-D-glucofuranose in a peptone-yeast-extract (PY) medium according to the VPI-technique. The volatile and non volatile acids were investigated by gas-liquid chromatography. All microorganisms showed a pattern of VFA different from that one produced by the glucose containing medium. In most microorganisms the formation of acetic acid was suppressed while the production of propionic, butyric, valeric and iso-valeric acids was stimulated. The production of succinic acid was not affected. Simultaneous determination of monoacetone glucose and glucose in the culture medium showed that the glucose analogue is used to a lesser extent than glucose.

Anaerobiosis↗

PubMedDate not supplied

Production of two phase polyhydroxyalkanoic acid granules in Ralstonia eutropha.

To synthesize layered granules consisting of selected phases of polyhydroxybutyrate (PHB) homopolymer and PH(B-co-V) copolymer, Ralstonia eutropha was grown on fructose and limited quantities (1 g/l) of valeric acid. Exhaustion of the valerate resulted in a carbon source shift and a shift in the composition of polyhydroxyalkanoate (PHA) being synthesized within the cell. The synthesis rates were 0.030 g PH(B-co-V)/l per h and 0.033 g PHB/l per h, giving a copolymer composition of 48% HV. The valerate was exhausted at approximately 12 h at a rate of 0.0894 g/l per h after which only PHB was produced through the remaining 12 h at 0.033 g PHB/l per h from the remaining fructose, which was utilized at a constant rate of 0.0861 g/l per h throughout all 24 h of the experiment. Differential scanning calorimetry (DSC) of isolated granules showed two glass transitions, confirming the presence of two distinct polymer phases within the layered granules. Transmission electron microscopic images stained with RuO4 revealed a heavily stained copolymer core within a lighter stained PHB shell, confirming the expected morphology of granule composition. Thus, biosynthesis can be exploited for the control of domain sizes in layered granules, potentially providing metabolic control over the physical properties of the resultant polymer.

Alcaligenes↗

PubMed1981

High-performance liquid chromatographic assay for fenoprofen in human plasma.

A high-performance liquid chromatographic method is described for the quantitation of fenoprofen, dl-2-(3-phenoxyphenyl)-propionic acid, in human plasma. The proteins in plasma were precipitated by the addition of hydrochloric acid. Fenoprofen and the internal standard, dl-2-(4-phenoxyphenyl)valeric acid, were extracted into butyl chloride and then back-extracted into sodium hydroxide. The aqueous solution was injected onto a reversed-phase alkylphenyl column, and the compounds were eluted using a mobile phase of acetonitrile-water-acetic acid (50:50:2 v/v/v). At a flow rate of 1 ml/min, the retention times of fenoprofen and the internal standard were 8 and 12 min, respectively. The absorbance was monitored at 272 nm. The method requires 1.0 ml of plasma and is sensitive to 0.5 microgram/ml. This procedure has been used for routine assay of multiple samples from bioavailability and compliance studies.

Biological Availability↗