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At least 1,369 records · Page 76Linked to original sources
PubMed1992

Growth hormone and lean tissue catabolism during long-term glucocorticoid treatment.

OBJECTIVES: The aim of the study was to determine whether growth hormone (GH) treatment decreased net protein catabolism of lean tissues in patients receiving chronic glucocorticoid treatment. DESIGN: Whole body leucine kinetics were measured in post-absorptive conditions using a 1-14C-leucine infusion before and during GH administration (0.0125 mg/kg/day; 0.033 U/kg/day) for 7 days. PATIENTS: We studied four patients (age range 31-71 years) who had taken prednisone (mean +/- SEM 0.21 +/- 0.03 mg/kg/day, total dose 10-27.5 mg/day) for longer than 5 months for various lung diseases. RESULTS: During GH treatment leucine oxidation decreased (baseline 0.44 +/- 0.07 vs GH 0.37 +/- 0.05 mumol/kg lean body mass/min, P = 0.01) and non-oxidative leucine disposal increased (1.95 +/- 0.10 vs 2.05 +/- 0.09 mumol/kg lean body mass/min, P = 0.02) but leucine appearance was unaltered. CONCLUSIONS: We conclude that GH decreased amino acid catabolism and improved protein synthesis without altering protein breakdown in patients receiving chronic glucocorticoid treatment. There may be a role for GH in mitigating the protein catabolic side-effects of prolonged glucocorticoid treatment.

Body Composition↗
PubMed1988

Relationships between plasma isotope enrichments of leucine and alpha-ketoisocaproic acid during continuous infusion of labelled leucine.

The ratio at steady-state of alpha-ketoisocaproic acid (KIC) to leucine 13C enrichments in plasma during continuous infusion of [13C]leucine was examined in 58 studies under a variety of conditions. The ratio was lower (P less than 0.001) in 'arterialized' venous plasma (mean +/- SD 0.85 +/- 0.09) than in deep venous plasma (0.95 +/- 0.08), the sampling site enrichment differences being greater for leucine than for KIC. Variation in the ratio between the various conditions studied was largely explained by analytical variation. Three normal subjects were given an intravenous bolus dose of L-[1-13C, 15N]leucine. Both [13C]KIC and [13C]leucine appeared quantitatively in plasma within 10 min, indicating that both transamination of leucine and KIC, and their equilibration between intracellular fluid and plasma, is rapid. This study suggests that changes in sampling site, rather than in study conditions, are more likely to lead to variation in the KIC:leucine enrichment ratio. The lesser variation for KIC, and the rapid equilibration of the [13C]leucine bolus, favour KIC as tracee for [13C]leucine protein turnover studies.

Adult↗
PubMed1990

Effect of excipients on the stability of levothyroxine sodium tablets.

Levothyroxine sodium tablets from two different manufacturers were analysed using the USP-NF method of analysis, a stability-indicating high pressure liquid chromatographic (HPLC) procedure. The results indicate that one particular manufacturer's 0.2-mg pink tablets contain some excipient(s) which act as a catalyst to hasten decomposition after extraction of levothyroxine for analysis. The same tablets from a different batch showed an additional long peak in the chromatogram, which indicated that the excipient(s) may have been changed. The same manufacturer has also used three different types of bottles/lids for the same product during the last year. Good manufacturing practice requires that new compatibilities/stability studies be conducted to assure the quality of the product. Ongoing stability studies are required by the Food and Drugs Administration (FDA). The use-life of 0.2-mg pink tablets of this manufacturer may be short.

17 alpha-Hydroxyprogesterone Caproate↗
PubMed2004

Blockage of methylcitrate cycle inhibits polyketide production in Aspergillus nidulans.

Aspergillus nidulans produces the polyketide toxin sterigmatocystin (ST) of which the biosynthetic and pathway specific regulatory genes compose a stc gene cluster. A previous mutagenesis screen identified 23 mutants defective in production of ST. Five mutants constitute a single locus. Genetic complementation and sequencing analysis revealed the mutant locus to be mcsA encoding methylcitrate synthase that converts propionyl-CoA to methylcitrate. Feeding downstream products of methylcitrate synthase, methylcitrate and pyruvate, did not restore ST production in mcsA mutants, indicating that loss of methylcitrate cycle products is not the cause of the ST defect. However, propionate, a precursor for propionyl-CoA, inhibited ST production and induced transcription of mcsA in the wild type. Furthermore, propionate impaired formation of two polyketide spore pigments whereas overexpression of mcsA relieved inhibition of ST production by propionate. Transcription analyses revealed that disruption of mcsA did not affect expression of the specialized fatty acid synthase genes (stcJ and stcK) or polyketide synthase gene (stcA) required for formation of norsolorinic acid (NOR), the first stable intermediate in the ST biosynthetic pathway. Feeding studies showed that NOR but not hexanoic acid (the fatty acid produced by StcJ/StcK and primer unit of StcA) or malonate (source of the extender unit of StcA) restored ST production in the mcsA mutant. We hypothesize that excess buildup of propionyl-CoA in mcsA mutants interferes with polyketide synthase activity.

Aspergillus nidulans↗
PubMed1977

Heterogeneity in maple syrup urine disease: aspects of cofactor requirement and complementation in cultured fibroblasts.

Fibroblast strains derived from six patients with maple syrup urine disease have been investigated for their requirements of the cofactors NAD, CoASH, Mg++ and TPP in comparison with 10 normal control strains. The reconstitution of the decarboxylase function of branched chain alpha-keto acid (BCKA) dehydrogenase complex in lysed cells was studied with respect to the substrates alpha-keto-isocaproic acid, alpha-keto-isovaleric acid, and alpha-keto-beta-methylvaleric acid (KIC, KIVA, MEVA). The enzyme activity of all normal control strains for the substrates KIC and KIVA was not reconstituted by TPP + Mg++ alone, but CoASH + NAD could reconstitute the enzyme activity with KIC and KIVA in different degrees. Only two control strains were tested with MEVA as substrate, and these showed in contrast that TPP + Mg++ could partly reconstitute the enzyme activity. In contrast to the relative homogeneity in the reconstitution profiles of normal strains, the five classical and one intermittent MSUD strains showed heterogeneity in cofactor requirements. Complementation analysis using heterokaryons prepared from fibroblasts of four patients with classical MSUD and one patient with intermittent MSUD showed, in contrast to experiments with normal controls, a partial amelioration of the defect in two combinations; it is suggested that the defect in these strains is located at different functional subunits of the multienzyme complex.

Caproates↗
PubMed1987

Examination of the structural requirements for proliferation of peroxisomes and mitochondria in mouse liver by hypolipidemic agents, with special emphasis on structural analogues of 2-ethylhexanoic acid.

We have found here that there are clear structural requirements for peroxisome proliferation (monitored as increases in carnitine acetyltransferase activity, cyanide-insensitive palmitoyl-CoA oxidation, catalase and increases in the protein designated PPA 80) in mouse liver. From the investigation of ten structural analogues of 2-ethylhexanoic acid, it could be concluded that the most effective proliferators all have an ethyl group as the substituent on carbon 2 of the main chain, which consists of six carbons. The further observation from this group of compounds that a charged group is required for effective proliferation leads us to speculate that such a group is involved in the molecular mechanism as well. Many, but not all, of the effective peroxisome proliferators in a second group of compounds contain a phenoxy group, often with a substituted alpha carbon. Interestingly, the 2,4-dichlorophenoxyacetic and 2,4,5-trichlorophenoxyacetic acids are both effective peroxisome proliferators, but the closely related p-chlorophenoxyacetic acid is inactive in this respect, indicating that the chlorine atom at position 2 must be essential to the process in these cases. The results presented here also indicate that the structural requirements for proliferation of mitochondria are similar to those for proliferation of peroxisomes. Certainly, the most effective peroxisome proliferators also cause large increases in 'mitochondrial' protein and cytochrome oxidase activity, i.e. there is an obvious qualitative correlation.

Animals↗
PubMed1992

Short-chain and medium-chain aliphatic-ester synthesis in Saccharomyces cerevisiae.

In the yeast Saccharomyces cerevisiae, the enzymes which catalyse the synthesis of ethyl acetate, ethyl n-hexanoate and isoamyl acetate were partly resolved from a fraction containing slowly sedimenting lipoproteins released during cell disruption with glass beads. Solubilization with detergents and fractionation by affinity chromatography have demonstrated the presence of at least three, and probably four, ester synthases which differ in their catalytic properties. Isoamyl-acetate synthase was solubilized and extensively purified to apparent homogeneity by successive chromatographies on various columns. On the basis of its specific activity in cell-free extracts, the enzyme was purified 19,000-fold with a 5% activity yield. As judged by SDS/PAGE, it consists of a single polypeptide chain with a molecular mass of 57 +/- 3 kDa and its apparent pI is 5.5. The enzyme acetylates isoamyl alcohol, ethanol and 12-DL-hydroxystearic acid from acetyl-CoA but is unable to use n-hexanoyl-CoA as a cosubstrate. This enzyme, defined as an acetyl-CoA: O-alcohol acetyltransferase, could be the product of one of the anaerobically induced genes in S. cerevisiae.

Acetates↗
PubMed2006

Occupational allergic contact dermatitis to cobalt octoate included as an accelerator in a polyester resin.

A 46-year-old woman, who worked as a laminator of spa baths, presented with hand dermatitis, which was suspected to be related to her occupation. Patch testing revealed strong reactions to both cobalt chloride and a polyester resin that the patient had been using at her workplace. She also reacted to latex and had been wearing cotton gloves underneath rubber gloves at work. It was later discovered that cobalt octoate (synonym: cobalt-2-ethylhexanoate), a compound not listed on the manufacturer's material safety data sheet, was included as an accelerator in the polyester resin. She was then tested to cobalt octoate, which was also strongly positive. Her successful treatment included protection of her hands at work with cotton lined PVC gloves. This case highlights the role of cobalt salts as sensitizers and their presence as accelerators used in polyester resins, and the importance of recognizing concomitant latex allergy that may complicate occupational dermatitis. It also illustrates the difficulties in relying on material safety data sheets to identify all possible allergens.

Allergens↗
PubMed1978

The effect of sex steroids on the in vitro synthesis of DNA by malignant ovarian tumours.

The deoxyribonucleic acid (DNA) synthesis of 12 ovarian tumours was studied by means of short term organ tissue culture, exposure to tritiated thymidine and subsequent autoradiography and visual grain counting. The DNA synthesis in each tumour was studied before and after exposure to 12 separate hormone combinations. It was found that any combination of 17 beta-oestradiol with either of the two progestogens used had greater inhibitory potential than when any of three hormones tested was used alone.

Aged↗