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PubMed1980

Isolation and characterization of outer and inner membranes of Selenomonas ruminantium: lipid compositions.

The isolation procedure and characterization of the outer and inner membranes from Selenomonas ruminatium cells, a strictly anaerobic bacterium, are described. The metabolic fate of [14C]decanoate incorporated into the outer and inner membranes was examined. The percent distribution of radioactivities in the outer and inner membranes was about 40 and 50% of the total incorporated activity, respectively. Approximately 47% of the radioactivity incorporated into the outer membrane was recovered in the phospholipid fraction, and the remaining radioactivity was found in both aqueous and phenol layers when the outer membrane was treated with phenol-water. In contrast to [14C]decanoate, the percent distribution of [3H]glycerol in the outer and inner membranes was about 25 and 70% of the total incorporated activity, respectively. Most of the assimilated 3H was located in the phospholipid fraction of both membranes. However, no significant label was detected in either the protein or cell wall fraction. The following observations were made concerning lipid compositions in the outer and inner membranes by chemical and isotopic analyses. (i) The outer and inner membranes contained no detectable phosphatidyl glycerol or cardiolipin. (ii) A prominent radioactive compound, designated band III lipid, was found mainly in the outer membrane as a major radioactive spot when cells were grown with [14C]decanoate. This lipid contained phosphorus, 2-keto-3-deoxyoctulosonic acid and 3-OH fatty acid but no detectable glycerol. This lipid was identified tentatively to be 2-keto-3-deoxyoctulosonic acid-lipid A. (iii) Although the ubiquity of phosphatidyl ethanolamine plasmalogen in both outer and inner membranes was confirmed, the occurrence of the molecular species of phosphatidyl ethanolamine plasmalogen was quite different in the outer and inner membranes.

Aldehydes↗
PubMed2006

The beta-oxidation systems of Escherichia coli and Salmonella enterica are not functionally equivalent.

Based on its genome sequence, the pathway of beta-oxidative fatty acid degradation in Salmonella enterica serovar Typhimurium LT2 has been thought to be identical to the well-characterized Escherichia coli K-12 system. We report that wild-type strains of S. enterica grow on decanoic acid, whereas wild-type E. coli strains cannot. Mutant strains (carrying fadR) of both organisms in which the genes of fatty acid degradation (fad) are expressed constitutively are readily isolated. The S. enterica fadR strains grow more rapidly than the wild-type strains on decanoic acid and also grow well on octanoic and hexanoic acids (which do not support growth of wild-type strains). By contrast, E. coli fadR strains grow well on decanoic acid but grow only exceedingly slowly on octanoic acid and fail to grow at all on hexanoic acid. The two wild-type organisms also differed in the ability to grow on oleic acid when FadR was overexpressed. Under these superrepression conditions, E. coli failed to grow, whereas S. enterica grew well. Exchange of the wild-type fadR genes between the two organisms showed this to be a property of S. enterica rather than of the FadR proteins per se. This difference in growth was attributed to S. enterica having higher cytosolic levels of the inducing ligands, long-chain acyl coenzyme As (acyl-CoAs). The most striking results were the differences in the compositions of CoA metabolites of strains grown with octanoic acid or oleic acid. S. enterica cleanly converted all of the acid to acetyl-CoA, whereas E. coli accumulated high levels of intermediate-chain-length products. Exchange of homologous genes between the two organisms showed that the S. enterica FadE and FadBA enzymes were responsible for the greater efficiency of beta-oxidation relative to that of E. coli.

Acetyl Coenzyme A↗
PubMed1995

Evolution of serum erythropoietin after androgen administration to hemodialysis patients: a prospective study.

A prospective study of the evolution of serum erythropoietin level after androgen therapy was carried out in a group of 25 male patients on chronic hemodialysis treatment with nonferropenic anemia (serum ferritin > 50 ng/ml). The androgen used was nandrolone decanoate (200 mg/week intramuscularly, for 6 months). There was an increase of serum erythropoietin, that reached statistical significance in the 2nd week of treatment (8.6 +/- 6.4 vs. 14.2 +/- 9.8 mIU/ml, p < 0.05), and a stabilization after 1 month (1 month: 17.8 +/- 11.2 mIU/ml, 6 months: 19.6 +/- 14.9 mIU/ml). The hemoglobin also experienced a parallel increase to that observed in serum erythropoietin (basal value: 8 +/- 0.9 g/dl; at 1 month postandrogen: 9.2 +/- 1.3 g/dl, p < 0.001; at 6 months: 10.7 +/- 1.8 g/dl, p < 0.001). According to their response of serum erythropoietin the patients were divided into responders (15 patients) and nonresponders (10 patients). There were no differences between them concerning age, basal levels of serum erythropoietin and hemoglobin, and dose of nandrolone decanoate in relation to body weight. The evolution of hemoglobin was similar in both groups, and a correlation between serum erythropoietin and hemoglobin was not observed in the responder group. Fourteen patients were studied after androgen was discontinued. The serum erythropoietin returned to basal levels 6 weeks after the last dose of nandrolone decanoate (7.7 +/- 5.4 mIU/ml). However, hemoglobin was above the basal levels 16 weeks after discontinuing androgen (9.5 +/- 1.1 g/dl, p < 0.05), with no differences between the responder and nonresponder group.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Population screening for medium-chain acyl-CoA dehydrogenase deficiency: analysis of medium-chain fatty acids and acylglycines in blood spots.

We have developed methods for the measurement of the medium-chain fatty acids octanoate, decanoate and cis-4-decenoate and the acylglycines n-hexanoylglycine (HG) and 3-phenylpropionylglycine (PPG) in blood spots using gas chromatography and mass spectrometry. Normal ranges were obtained for octanoate and decanoate. HG, PPG and cis-4-decenoic acid were not detected in control blood spots. In blood spots from nine patients (including two newborn) with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, all metabolites were present in elevated concentrations although PPG was close to the detection limits and there was overlap for octanoate and decanoate. The lack of detection of cis-4-decenoic acid and HG in controls suggests that these are the metabolites of choice for blood spot identification of infants with MCAD deficiency.

Acyl-CoA Dehydrogenase↗
PubMedDate not supplied

Anabolic steroids in polytrauma patients. Influence on renal nitrogen and amino acid losses: a double-blind study.

Severe trauma leads to considerable losses of nitrogen in the first days after the accident. As nutritional efforts cannot reduce these losses sufficiently, an adjunctive therapy using the anabolic steroid nandrolone decanoate (Nd) was applied. In a double-blind study 10 male multiple-traumatized patients each received 50 mg of Nd on day 3 and 25 mg of Nd on day 6 after the trauma, an additional 10 patients received placebo only. Both groups had identical nutritional support. Nitrogen balance, total nitrogen excretion as well as plasma amino acid concentration, and urine amino acid excretion were measured daily. The anabolic agent improved the nitrogen balance mainly by reducing nitrogen excretion. 3-Methylhistidine excretion and renal amino acid losses were decreased. Nandrolone decanoate increased the concentration of total plasma amino acids. The underlying principle seems to be an amino acid-saving mechanism with a renal site of action. It is shown that in the early posttraumatic period nandrolone decanoate improves nitrogen metabolism. Further studies are required to determine whether this offers a clinical benefit to trauma patients.

Adolescent↗
PubMed1990

Vitamin D metabolism in osteoporotic women during treatment with estrogen, an anabolic steroid, or calcitonin.

We assessed the effects of a continuous oral combination of estradiol and norethisterone acetate, nandrolone decanoate, or salmon calcitonin on the vitamin D endocrine system. One hundred and nineteen postmenopausal women, aged 55-75 years, with at least one osteoporotic fracture, were randomly allocated to one year of treatment with estradiol and norethisterone acetate, nandrolone decanoate, or calcitonin, all drugs with a beneficial effect on bone. All three trials were double-blind and placebo-controlled; 104 women (87%) completed the study. We measured the total serum concentration of 1,25-dihydroxyvitamin D (1,25(OH)2D) and vitamin D-binding protein, and estimated the free 1,25(OH)2D index and the "24-hydroxylase activity" initially, and at 6 and 12 months. Furthermore, the 24-h urinary excretions of calcium, phosphate, and adenosine 3'-5'-cyclic monophosphate were assessed initially and at 12 months. The serum concentration of vitamin D-binding protein and 1,25(OH)2D increased transiently during estradiol and norethisterone acetate treatment and vitamin D-binding protein decreased transiently during nandrolone decanoate treatment. None of the other parameters were significantly affected by any of the three treatments. The risk of type II errors was below 10 per cent for all vitamin D measurements. We conclude that the vitamin D metabolites are unlikely to be of major importance for the mechanism by which these drugs exert their positive skeletal effects.

Aged↗
PubMed1988

Soleus muscle atrophy in rats induced by cast immobilization: lack of effect by anabolic steroids.

To test the hypothesis that an anabolic steroid such as nandrolone decanoate (ND) will ameliorate or abolish disuse-mediated alterations resulting from five weeks of hindlimb immobilization, female Sprague-Dawley rats were divided into six groups: control, control + ND, shortened-immobilized, shortened-immobilized + ND, stretched-immobilized, and stretched-immobilized + ND. Immobilization was accomplished by wrapping hindlimbs with plaster of Paris. Nandrolone decanoate in sesame oil was administered via weekly intraperitoneal injection (7 mg/kg) while nontreated rats received equivalent volumes of the vehicle. After five weeks selected morphometric, biochemical, and mechanical parameters were examined in the slow-twitch soleus muscle (SOL). Muscle wet weight fell from a control value of 145 +/- 19 mg to 70 +/- 8 mg (p less than .05) in the immobilized-shortened group where ND had no effect (81 +/- 11 mg). Muscle stretch alone prevented weight loss (159 +/- 31 mg). The addition of ND resulted in significant SOL hypertrophy (200 +/- 42 mg), p less than .05. Immobilization resulted in a significant shift in muscle protein distribution toward sarcoplasmic protein, a change unaltered by ND but abolished by stretch. Muscle strength, as indicated by peak tetanic tension, fell 45% (p less than .05) as a result of shortened immobilization. Nandrolone decanoate had no effect on this condition, although the ameliorating effect of stretch was abolished when in combination with ND treatment. The elevation observed in maximal shortening velocity (shortened-immobilized) was unaffected by ND alone, but abolished by stretch with or without ND treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cis-4-decenoic acid in plasma: a characteristic metabolite in medium-chain acyl-CoA dehydrogenase deficiency.

The profile of organic acids in plasma of patients with a deficiency of medium-chain acyl-CoA dehydrogenase (EC 1.3.99.3) was determined by gas-liquid chromatography of trimethylsilylated derivatives of the acids isolated by ethyl acetate extraction. All 13 patients had increased concentrations of free octanoate, cis-4-decenoate, and decanoate in their plasma. Cis-4-decenoate, an intermediary metabolite of linoleic acid, is pathognomonic of medium-chain acyl-CoA dehydrogenase deficiency. This metabolite does not accumulate in plasma after oral loading with medium-chain triglycerides, in contrast to octanoate and decanoate. Two postmortem plasma samples from victims of infant sudden-death syndrome had detectable octanoate and decanoate, but cis-4-decenoate could not be detected. The identification of cis-4-decenoate in plasma may be an aid in the diagnosis of an inherited defect in oxidation of medium-chain fatty acids.

Acyl-CoA Dehydrogenase↗
PubMed1993

Anabolic steroids in corticosteroid-induced osteoporosis.

Severe osteoporosis represents a major complication of corticosteroid (CST) excess. Steroid-induced osteoporosis is characterized by both increased bone resorption and inhibition of bone formation. Excessive bone resorption is attributed to hyperparathyroidism which is secondary to calcium malabsorption. Calcium and vitamin D supplementation or treatment with inhibitors of bone resorption are of benefit but they usually lead to further inhibition of bone formation. The inhibition of bone formation in CST treated patients is due in part to suppression of adrenal androgen secretion. Thus the suppressed circulating levels of osteocalcin, a biochemical marker of osteoblast activity, in patients on CST can be reverted to normal by administration of anabolic steroids. In a prospective controlled trial in patients on long-term CST therapy we have observed that nandrolone decanoate therapy, 50 mg intramuscularly every 3 weeks for 18 months, induces a transient increase in bone mass within the first 6 months of treatment and prevent further losses thereafter. The sequential biochemical changes indicate that nandrolone decanoate in patients on CST inhibits bone resorption without affecting or even increasing bone formation. Furthermore in patients on CST treatment the virilizing activity of nandrolone decanoate was virtually negligible at least within the 18 months of treatment. These results indicate that anabolic steroid administration may represent a rational and convenient strategy for preventing and treating CST-induced osteoporosis.

Adrenal Cortex Hormones↗
PubMed1993

The effect of anabolic steroids on ameliorating the adverse effects of chronic corticosteroids on intestinal anastomotic healing in rabbits.

The ability of anabolic steroids to reverse the deleterious effects of chronic corticosteroids on intestinal anastomotic healing was studied in 32 rabbits. Rabbits received once daily intramuscular injections of saline solution (controls), 0.1 milligram per kilogram of dexamethasone, dexamethasone plus low-dose anabolic steroids (2 milligrams per kilogram of nandrolone decanoate) or dexamethasone plus high-dose anabolic steroid (10 milligrams per kilogram of nandrolone decanoate). Two weeks later, the rabbits underwent small intestinal (SI) or large intestinal (LI) anastomoses. Postoperatively, injections were continued as before with the addition of high-dose anabolic steroids (20 milligrams per kilogram of nandrolone decanoate) to one-half of the dexamethasone only group. Seven days postoperatively, the rabbits had in situ assessment of anastomotic bursting pressure (ABP) and histologic examination using a modified Ehrlich/Hunt scale. Results demonstrated that dexamethasone severely impaired the healing of SI and LI anastomoses, with decreases in ABP to almost 50 percent of normal values and with similar reduction in histologic parameters. High-dose anabolic steroids reversed this inhibitory effect when initiated preoperatively or post-operatively, with increase in ABP to 72 percent of normal for SI anastomoses and 83 percent of normal for LI. No adverse effect of anabolic steroid administration was evident.

Anabolic Agents↗
PubMed1984

Costs and benefits of two doses of fluphenazine.

The relative costs and benefits of low- and conventional-dose neuroleptic maintenance therapy were evaluated in a double-blind comparison of 5 and 25 mg of fluphenazine decanoate administered every two weeks. Subjects were 50 patients fulfilling DSM-III criteria for schizophrenic disorder who had been successfully maintained with 25 mg or less of fluphenazine decanoate. A one-year survival analysis disclosed that there were no statistically significant differences between the two doses insofar as preventing relapse. Patients receiving the higher dose appeared to feel more uncomfortable, as indicated by higher scores on subscales of the Hopkins Symptom Checklist-90. In addition, patients receiving the higher dose had higher side-effect scores. These findings suggest that a substantial proportion of patients who are presently maintained with 25 mg or less of fluphenazine decanoate every two weeks will do just as well with as little as 5 mg.

Adult↗
PubMed2000

Monovalent cation effects on the activity of the xenobiotic/medium-chain fatty acid:CoA ligases are substrate specific.

The effect of monovalent cation on the activity of the XL-I and XL-III forms of xenobiotic/medium-chain fatty acid:CoA ligase (XM-ligase) was investigated using a variety of different carboxylic acid substrates. With benzoate or p-hydroxybenzoate as substrate, the XL-I ligase was essentially inactive in the absence of monovalent cation. However, with phenylacetic acid and medium-chain fatty acids as substrate, the enzyme retained 3 to 10% activity upon removal of monovalent cation. Further, while Na+ was ineffective with benzoate and p-hydroxybenzoate as substrates, it was effective with other substrates, although still less effective than K+. For XL-III, activity toward benzoate, hydroxybenzoate, and salicylate was insignificant in the absence of monovalent cation, but this rate was 10% of the K(+)-supported rate for hexanoate and 20% for decanoate. Also, with decanoate as substrate, XL-III was activated more by Na+ than by K+. Thus, the nature of the dependence on monovalent cation for activity is substrate-selective. Kinetic analysis of the effect of K+ on the activity of XL-I and XL-III revealed that activation by K+ was not the result of alteration of the affinity of the enzymes for either ATP or the carboxylic acid. For both forms of XM-ligase, K+ was found to enhance the affinity of the enzyme for CoA, regardless of the substrate, although the extent of the enhancement was substrate-specific. In almost all cases there was further activation, even at saturating concentrations of CoA, which indicates an additional effect of monovalent cation on the catalytic rate constant for the reaction. The exception was activation of XL-III activity toward decanoate, which was solely the result of enhanced binding affinity for CoA.

Animals↗
PubMed1983

Beta-oxidation of C-6-C-10 fatty acids in rat liver homogenates measured by selected ion monitoring: effects of cyanide and clofibrate.

The beta-oxidation of C-6-C-10-fatty acids/acyl CoA/acylcarnitines in whole rat liver homogenates was determined by specific and simultaneous measurements of the C-6-C-10-fatty acids, i.e. hexanoic, octanoic and decanoic acids, in hydrolysed homogenates in relation to time in assays incubated with the above-mentioned substrates. Measurements were performed by a combined gas chromatographic mass spectrometric technique, i.e. selected ion monitoring. The rate of beta-oxidation of the C-6-C-10-fatty acids/acyl CoA/acylcarnitines were registered as the consumption rate of the added substrate. The conversion to the C-2-shortened beta-oxidation products was illustrated simultaneously. The rate of beta-oxidation of C-6-C-10-fatty acids was several times higher in homogenates from clofibrate-treated rats than in control rats, both in the presence and absence of 2.0 mmol l-1 cyanide. Cyanide caused a minor but significant decrease in the beta-oxidation rate in both control and clofibrate-treated rats. No differences were found between the beta-oxidation of decanoic acid and decanoyl CoA in homogenates from clofibrate-treated rats, whereas the degree of beta-oxidation of DL-decanoylcarnitine was halved compared with decanoic acid and decanoyl CoA.

Animals↗
PubMed1987

PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride.

Tracer doses of 11C-SCH 23390 and 11C-raclopride, selective D1-dopamine and D2-dopamine receptor antagonists, respectively, were injected intravenously into three healthy male volunteers and two drug-treated schizophrenic patients. Regional radioactivity in brain and plasma was followed during 1 h by positron emission tomography (PET). After injection of both ligands a high accumulation of radioactivity was observed in the dopamine-rich caudate putamen. Experiments with 11C-SCH 23390, but not 11C-raclopride, showed a conspicuous accumulation of radioactivity also in the neocortex. None of the ligands accumulated in the dopamine-poor cerebellum. Specific binding of 11C-raclopride in the putamen was reduced by more than 80% in schizophrenic patients treated with antipsychotic doses of sulpiride or cis(Z)-flupentixol decanoate. 11C-SCH 23390 binding was slightly reduced in both the cortex and the putamen after treatment with cis(Z)-flupentixol decanoate but not after sulpiride. The results indicate that clinical antipsychotic drug treatment with sulpiride and cis(Z)-flupentixol decanoate causes a substantial blockade of D2-dopamine receptors in the basal ganglia but has only a minor effect on D1-dopamine receptors.

Adult↗
PubMed1980

Comparative enzyme-inducing effects of chlorpromazine and fluphenazine therapies in psychotic patients.

Antipyrine elimination kinetics were measured in psychotic patients receiving either long-term chlorpromazine or fluphenazine decanoate therapy and in non-medicated control subjects. Patients receiving chlorpromazine metabolised antipyrine faster than the controls while, in patients receiving fluphenazine decanoate, there was not change. The results suggest that long-term chlorpromazine therapy induced the activity of drug-metabolising enzymes, whereas fluphenazine decanoate therapy had no effect.

Adult↗
PubMed1983

A depot neuroleptic withdrawal study neurological effects.

A double-blind withdrawal trial in 41 chronic schizophrenic outpatients was carried out over 6 months. Depot neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were compared with placebo to evaluate neurological side effects during continued therapy and during withdrawal. The drugs were significantly more effective than placebo in preventing relapse and rehospitalization. In the placebo group 62% relapsed compared to 27% in the drug group. A difference was observed in the occurrence of extrapyramidal symptoms (EPS) between the neuroleptics in the study. Akathasia was observed in 9/38 (23.7%) cases, significantly more frequent in the fluphenazine decanoate group. Tardive dyskinesia (TD) was observed in six cases (15.8%); four cases existed at the start of the study and two others were observed after 3-6 weeks of withdrawal. There was no relation between TD symptoms and relapse. There was a significant decrease in the EPS scores during the placebo treatment and also a significant weight decrease.

Adult↗
PubMed1988

Use of a fluorescent radiolabeled triacylglycerol as a substrate for lipoprotein lipase and hepatic triglyceride lipase.

A fluorescent radiolabeled triacylglycerol has been synthesized by using a fluorescent fatty acid (pyrene decanoic acid) and a radiolabeled oleic acid. This analog of the natural substrate, 1(3)pyrene decanoic-2,3 (1,2)-dioleoyl-sn-glycerol, has been tested as substrate for determining lipoprotein lipase and hepatic triacylglycerol lipase activities in post-heparin plasma. Optimal conditions for the determination of the two post-heparin plasma lipases were similar to those using radiolabeled triolein. Using this substrate, both post-heparin lipases exhibited their characteristic properties (pH optimum and effect of inhibitors) and attacked external ester bonds (1 or 3) containing pyrene decanoic and oleic acids at a similar rate.

Animals↗
PubMed1991

Omega-oxidation of fatty acids studied in isolated liver cells.

The omega- and beta-oxidation of medium- and long-chain fatty acids (C10-C18) were studied in hepatocytes from fasted, fed and clofibrate-fed rats. The omega-oxidation systems were most active with lauric acid (12:0) and decanoic acid (10:0) as substrates and there was decreasing activity with chain lengths from 14 to 18 carbon atoms. In fed rats no omega-oxidation of fatty acids was detected unless the mitochondrial beta-oxidation was inhibited. In fasted rats the omega-oxidation was less than 2% and preincubation with (+)-decanoylcarnitine increased the omega-oxidation to 15% of the total fatty acid oxidation. Clofibrate feeding did not increase the omega-oxidation in isolated hepatocytes. Inhibition of the alcohol dehydrogenase with 4-methylpyrazole inhibited both the oxidation of omega-hydroxylated fatty acid and the initial hydroxylation of lauric acid to dicarboxylic acid, suggesting the importance of the alcohol dehydrogenase in the omega-oxidation of fatty acids. 95% of the dicarboxylic acids and 80% of the hydroxy-fatty acids were excreted from the cells in the incubations with decanoic acid (10:0). No chain-shortened dicarboxylic acids were detected with [1-14C]decanoic- or [1-14C]lauric acid as substrate, while small amounts C10 and C12 dicarboxylic acids were observed in incubations with [1-14C]myristic acid (14:0).

Alcohol Dehydrogenase↗