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PubMed1986

Sudden child death and 'healthy' affected family members with medium-chain acyl-coenzyme A dehydrogenase deficiency.

A family is described in which the father and three (and probably all four) of his children had a decreased capacity for the oxidation of medium-chain fatty acids. One of the children suddenly died at the age of 16 months following an episode of a rapidly deteriorating Reye syndrome-like illness with hypoketotic hypoglycemia and dicarboxylic aciduria, but without any previous alarming symptoms. The eldest sibling had died at the age of 19 months under similar conditions. The other family members had always been healthy. On fasting, all affected family members accumulated in their plasma the medium-chain fatty acids octanoic, decanoic, and cis-4-decenoic acids. Their urinary organic acid excretion profile could be characterized as "dicarboxylic aciduria." A deficiency of medium-chain acyl-coenzyme A dehydrogenase was demonstrated in a postmortem liver sample of the index patient. Cultured fibroblasts from the father and the two healthy children had a decreased rate of [14C]octanoate oxidation. It is suggested that a deficiency of medium-chain acyl-coenzyme A dehydrogenase may lead to a life-threatening illness when other complicating factors such as diarrhea and vomiting result in an abnormal depletion of the body's glycogen stores. Careful monitoring of at-risk patients during a minor illness is necessary.

Acyl-CoA Dehydrogenase↗
PubMed1985

Fertility of young mares after long-term anabolic steroid treatment.

The effect of prior treatment with anabolic steroids was studied in 46 three-year-old mares. In the preceding year, these mares had been assigned to 1 of 4 treatment groups and had received the manufacturer's recommended dosage of 1.1 mg of boldenone undecylenate (BU)/kg of body weight, 4.4 mg of boldenone undecylenate (4 BU)/kg, 1.1 mg of nandrolone decanoate (ND)/kg, or 0.04 ml of sesame oil/kg (control, C). Mares had received an injection every 3 weeks for 54 weeks for a total of 19 injections, with the final injection in December. In the following breeding season, fewer (P less than 0.05) mares in all groups previously administered anabolic steroids displayed estrous behavior than did mares in the control group. Duration of estrus was shortened (P less than 0.05) in mares that had received steroids. Abnormal sexual behavior that was observed during steroid treatment continued (P less than 0.05) for up to 6 months after treatment ceased. However, observations of abnormal behavior declined with time (P less than 0.05). All mares in each treatment group ovulated by the end of the trial, and the interval to first ovulation was similar (P greater than 0.05). Ovarian size, follicular development, and conditions of the tubular genitalia was adversely (P less than 0.05) affected in mares in all steroid-treatment groups until approximately the middle of March. After that time, no difference was noted among groups. First-cycle pregnancy rates were 83%, 67%, 50%, and 42% for mares in the untreated, BU, 4 BU, and ND groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Effects of androgen on transient endogenous spleen colonies and other hemopoietic stem cells in mice.

To clarify the effects of androgen on hemopoiesis in mice, we investigated changes in hemopoietic stem cells at various stages of differentiation after injection of 19-nandrolone decanoate (19-ND). 19-ND induced (a) a marked increase in the population of CFUe, especially in the spleen, and (b) a less significant increase in the number of CFUs, GM-CFC, and BFUe. The number of endogenous spleen colonies developed transiently on day 4 after irradiation (TE-CFU) increased significantly, and the initiation and induction of erythropoietic maturation was enhanced. Growth of the pluripotent stem cells (CFUs) assessed by endogenous spleen colony formation was influenced more than was the population size. Production of erythropoietin (Ep) in mice was not affected by the treatment with 19-ND. These results indicate that 19-ND affects mature precursors in erythroid cell lineage rather than pluripotent stem cells and that the effect is unlikely to be induced through an increase in the production of Ep.

Animals↗
PubMed1978

Drug monitoring at an Australia depot phenothiazine clinic.

Three aspects of treatment with injectable neuroleptics, are presented. An individualized approach to the dosage of Fluphenazine decanoate must be practiced in conjunction with, and taking into account the time spent in treatment and the sex and age variables reported. Our flexible approach to the interval between injections, indicated a large group could be maintained at intervals of 5 to 8 weeks. Complex and challenging problems can be found with antiparkinsonian drugs; 30% of nearly 400 outpatients still require these drugs.

Adult↗
PubMed1984

[Effect of anabolic steroid on immune response].

Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin.

Female↗
PubMed1978

On the quantitative importance of omega-oxidation of fatty acids.

The relative importance of omega-oxidation of fatty acids in livers of starved rats was studied by determination of the ratio between 14C at C1 and at C2, C3, C4 in acetoacetate formed from [16-14C]palmitic acid in vivo and in vitro and from [10(-14)C]decanoic acid in vitro. The results are consistent with the possibility that at least a small fraction of the fatty acids may be subject to primary omega-oxidation prior to beta-oxidation in the ketotic state. The maximal figure for this pathway was calculated to be of the magnitude 5--10%. The metabolic consequences of a pathway involving primary omega-oxidation of fatty acids are discussed.

Acetoacetates↗
PubMed1980

Reversal of cyclophosphamide induced neutropenia by hypertransfusion and androgen therapy.

We injected 300 mg/kg Cyclophosphamide i.p. into female AKR mice and rendered them reversably neutropenic. Group A was hypertransfused; Group B received 5 mg Nandrolone decanoate i.m. q.d X 2; and Group C received both. Group D served as a control. White blood cell counts were followed every other day for 10 days. The nadirs seen on all groups appeared on day 5. At day 10 counts in Groups A, B, and D had returned to normal, while the pattern of granulocyte decline and recovery in Group C was significantly faster than that seen in other groups, returning to normal at day 8. Hypertransfusion and androgen administration together significantly ameliorated drug-induced leukopenia, suggesting synergism. Thus manipulation of the stem-cell compartment may be clinically feasible.

Agranulocytosis↗
PubMed1981

Beneficial effects of an anabolic steroid during cytotoxic chemotherapy for metastatic cancer.

To investigate the effects of concurrent administration of an anabolic steroid upon hematopoiesis and metabolism in patients with cancer who were receiving cytotoxic chemotherapy, a randomized trial was conducted. Thirty-three evaluable patients received intensive multiple-agent chemotherapy: 17 received in addition nandrolone decanoate ("Deca-Durabolin"), 200 mg intramuscularly each week. The nandrolone-treated patients showed significantly better maintenance of hemoglobin concentrations and body weight, and a highly significant reduction in number of blood transfusions. Improved survival in the androgen-treated patients did not achieve significance. There were no differences in neutrophil or platelet counts or in tolerance of cytotoxic drugs. Toxicity from nandrolone therapy was minimal.

Anabolic Agents↗
PubMed1980

Location of the medium chain fatty acid site on human serum albumin. Residues involved and relationship to the indole site.

Human serum albumin (HSA) is found to contain one primary binding site for medium chain fatty acids which is competitive with the binding of N-acetyl-L-tryptophan. The association constant is higher with nondefatted HSA than with HSA defatted by either heptane-acetic acid or charcoal extraction. Affinity labeling of HSA by N-bromoacetyl-n-decylamine (1:1 molar ratio) blocks the primary binding site of hexanoate and decanoate at an equivalency of the molar ratio of label incorporated. CNBr fragmentation reveals that the primary medium chain fatty acid binding site is positioned between Fragment C (residues 124 to 297) and A (residues 298 to 585). With nondefatted HSA, 60% of the label is associated with Fragment C and 35% with Fragment A, whereas upon defatting, this labeling pattern is reversed. The labeled residue in Fragment C is Lys 199, the same residue as acetylated by acetylsalicylate (Hawkins, D., Pinckard, R.N., Crawford, I.P., and Farr, R.S. (1969) J. Clin. Invest. 48, 536). Forty per cent of the label in Fragment A from nondefatted albumin is located in the A-Pro II subfragment (residues 447 to 548) and 60% in the A-Phe subfragment (residues 330 to 446). With defatted HSA, the A-Pro II subfragment contains 25% and the A-Phe subfragment contains 75% of the label. In all cases, labeling in the subfragments of Fragment A occurred at several different residues, indicating that this part of the binding site has considerable flexibility. The secondary binding sites for medium chain fatty acid are found to be the same general region as the primary binding site. N-Bromoacetyl-n-tetradecylamine (a long chain fatty acid-labeling agent) labeled only the A fragment of HSA.

Amines↗
PubMed1980

[Effect of homologous n-alkanoic acids on the function of isolated skeletal muscles. V. Relations between twitch, tetanus and contracture].

Twitch, tetanus, and contractures induced by potassium ions (K+) or caffeine were investigated on isolated bundles of frog muscles. Using supramaximal stimuli the twitch amplitude amounts to about 50% of the tetanic tension (22 degrees C). Usually the contracture in 190 mM K+ is smaller than the tetanic tension, in 20 mM caffeine the contracture maximum corresponds to the tetanus amplitude. All of the mechanical answers are diminished if the fibres were bathed in solutions containing 2.5 to 10 mM Na-octanoate or 0.5 mM decanoic acid. Twitch and tetanic tensions decrease nearly in the same degree. A sequence of tetanic stimulations in a distance of 2 s induces a depression of the amplitudes. Fatty acids increase this depression and delay restoration between the series. Contractures in 190 mM K+ are diminished by a preceding bath in 10 mM Na-octanoate. Contractures with submaximum concentrations of K+ were decreased by lower concentrations of octanoate. The caffeine induced contractures are delayed by fatty acids, but the maximum tension is not reduced. It is supposed that the mobilisation of calcium ions is alterated by fatty acids. The decreasing effect of fatty acids on the mechanical activity, induced by different ways of the muscles' stimulation suggests that the main action may take place in the process of mechanical coupling, probably during the activation of calcium ions.

Animals↗
PubMed1995

Identification and quantification of intermediates of unsaturated fatty acid metabolism in plasma of patients with fatty acid oxidation disorders.

The free fatty acid and total fatty acid profiles in plasma of nine patients with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, two with very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency and two with mild-type multiple acyl-CoA dehydrogenase (MAD-m) deficiency, were analyzed by gas chromatography-mass spectrometry. In the plasma of patients with MCAD deficiency we found increases of octanoic acid (8:0), decanoic acid (10:0), 4-decenoic acid (10:1 omega 6), and 4,7-decadienoic acid (10:2 omega 3), all present almost exclusively in free form. The patients with VLCAD deficiency showed increases of mainly 5-tetradecenoic acid (14:1 omega 9) and to a minor extent 5-dodecenoic acid (12:1 omega 7), 5,8-tetradecadienoic acid (14:2 omega 6), and 7,10-hexadecadienoic acid (16:2 omega 6), in both the free and esterified fatty acid fraction. The MAD-m patients showed variable increases of all the unusual fatty acids present in MCAD- and VLCAD-deficient plasma. The 14:1 omega 9, 14:2 omega 6, and 16:2 omega 6 fatty acids were present mainly in the esterified form. Measurement of these fatty acids in plasma by the relatively simple method presented here provides a sensitive and specific aid in the diagnosis of acyl-CoA dehydrogenase deficiency disorders.

Acyl-CoA Dehydrogenase↗
PubMed1994

Charge modification in rodent hepatic Grp78/BiP following exposure to structurally diverse peroxisome proliferators.

This investigation was conducted to determine the comparative effect of structurally diverse peroxisome proliferators (PP) on the two-dimensional protein pattern of rat liver whole homogenates. Perfluoro-n-decanoic acid (PFDA), perfluoro-n-octanoic acid (PFOA), clofibrate, and di(2-ethylhexyl)phthalate(DEHP) are all known to cause the proliferation of hepatic peroxisomes and the induction of peroxisomal beta-oxidative and microsomal omega-oxidative enzymes. To detect potential differences between these compounds with regard to the liver, we examined the unique patterns of protein alteration produced by in vivo exposure to them. Following exposure to various doses, whole liver homogenates were prepared and separated by two-dimensional gel electrophoresis (2DE) using the ISO-DALT System. Stained gels were digitized and protein patterns analyzed using the Kepler 2D Gel Analysis System. Immunoglobulin heavy-chain binding protein (BiP), also known as 78 kD glucose regulated protein (Grp78), was identified immunologically and by comigration of recombinant Grp78. BiP is a luminal endoplasmic reticular (ER) protein that functions in the assembly and folding of nascent proteins as they enter the ER. The present results suggest a selective posttranslational modification of BiP following PFDA exposure. Single-dose exposure to PFDA was associated with a notable charge-modification of BiP that persists up to 30 days. PFOA, clofibrate, and DEHP had less effect in this regard. Our data suggest the likely nature of this PFDA-associated protein modification is associated with protein-phosphorylation. These results document the unique nature of PFDA's hepatotoxicity with respect to classic peroxisome proliferators and support the utility of 2D gel analysis in toxicity testing.

Animals↗
PubMed1994

13C NMR studies of the binding of medium-chain fatty acids to human serum albumin.

Binding of the medium-chain fatty acids (MCFA), octanoic (OCT) and decanoic (DEC) acid, to human serum albumin (HSA) has been studied by 13C NMR spectroscopy. NMR spectra at 35 degrees C showed an apparently homogeneous binding environment (a single, narrow resonance for the 13C-enriched carboxyl carbon) at different mole ratios and pH values. Changes in the chemical shift of this peak with mole ratio and protein concentration demonstrated rapid equilibration (< or = msec) of bound and unbound MCFA and permitted a direct quantitation of bound/unbound MCFA. Spectra of OCT/HSA mixtures at 6 degrees C revealed at least three distinct binding sites that fill sequentially. The observed heterogeneity of binding at low temperature, compared to 35 degrees C, is attributed to a slower exchange rate of OCT between binding sites. The highest affinity sites for both OCT and DEC have properties similar to those of binding sites for longer-chain fatty acids, such as the close proximity of the fatty acid carboxylate to basic amino acid residue(s). Interestingly, chemical shift data showed that the first mole of OCT and DEC either bind differently to the same site or bind to different sites on HSA. The rapid desorption of MCFA from HSA binding sites has implications for dietary regimens with medium chain triglycerols.

Binding Sites↗
PubMed1994

An acute myocardial infarction occurring in an anabolic steroid user.

Anabolic-androgenic steroid abuse is prevalent and has been associated with numerous adverse effects. The case being presented is of an amateur weight trainer, who suffered an acute myocardial infarction; his only significant risk factor was his nonmedical use of an anabolic steroid, nandrolone decanoate. This case presentation discusses the hematologic effects of this class of drugs and the subsequent impact on ischemic heart disease.

Adult↗
PubMed1995

Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese, older men.

OBJECTIVE: To compare the effects of testosterone enanthate (TE), anabolic steroid (AS) or placebo (PL) on regional fat distribution and health risk factors in obese middle-aged men undergoing weight loss by dietary means. DESIGN: Randomized, double-blind, placebo-controlled clinical trial, carried out for 9 months with primary assessments at 3 month intervals. Due to adverse blood lipid changes, the AS group was switched from oral oxandrolone (ASOX) to parenteral nandrolone decaoate (ASND) after the 3 month assessment point. SUBJECTS: Thirty healthy, obese men, aged 40-60 years, with serum testosterone (T) levels in the low-normal range (2-5 ng/mL). MAIN OUTCOME MEASURES: Abdominal fat distribution and thigh muscle volume by CT scan, body composition by dual energy X-ray absorptiometry (DEXA), insulin sensitivity by the Minimal Model method, blood lipids, blood chemistry, blood pressure, thyroid hormones and urological parameters. RESULTS: After 3 months, there was a significantly greater decrease in subcutaneous (SQ) abdominal fat in the ASOX group compared to the TE and PL groups although body weight changes did not differ by treatment group. There was also a tendency for the ASOX group to exhibit greater losses in visceral fat, and the absolute level of visceral fat in this group was significantly lower at 3 months than in the TE and PL groups. There were significant main effects of treatment at 3 months on serum T and free T (increased in the TE group and decreased in the ASOX group) and on thyroid hormone parameters (T4 and T3 resin uptake significantly decreased in the ASOX group compared with the other two groups). There was a significant decrease in HDL-C, and increase in LDL-C in the ASOX group, which led to their being switched to the parenteral nandrolone decanoate (ASND) after 3 months. ASND had opposite effects on visceral fat from ASOX, producing a significant increase from 3 to 9 months while continuing to decrease SQ abdominal fat. ASND treatment also decreased thigh muscle area, while ASOX treatment increased high muscle. ASND reversed the effects of ASOX on lipoproteins and thyroid hormones. The previously reported effect of T to decrease visceral fat was not observed, in fact, visceral fat in the TE group increased slightly from 3 to 9 months, although SQ fat continued to decrease. Neither TE nor AS treatment resulted in any change in urologic parameters. CONCLUSIONS: Oral oxandrolone decreased SQ abdominal fat more than TE or weight loss alone and also tended to produce favorable changes in visceral fat. TE and ASND injections given every 2 weeks had similar effects to weight loss alone on regional body fat. Most of the beneficial effects observed on metabolic and cardiovascular risk factors were due to weight loss per se. These results suggest that SQ and visceral abdominal fat can be independently modulated by androgens and that at least some anabolic steroids are capable of influencing abdominal fat.

Adipose Tissue↗
PubMed1996

[Polymer microparticles for right and left heart echocardiography and imaging myocardial perfusion after peripheral vein injection].

It is conceivable that a stable ultrasound contrast agent could be used for reproducible right and left heart echocardiography and myocardial visualization after intravenous injection. Microparticles from different polymers and preparation procedures were screened in six dogs leading to one superior agent with reproducible high quality echo contrast in doses of 1 mg/kg. This special agent is based on condensates of aspartic acid, ethanolamine and decanoic acid. Out of this material particles were formed with an average diameter of 2 micrometers. The easily suspendable particles were used for the following studies in a dose of 1 mg/kg intravenously in eight pigs. Maximal video intensity averaged 116 +/- 42 relative intensity units (IU) in the right, 137 +/- 42 IU in the left ventricle, 42 +/- 7 in the normally perfused and 11 +/- 2 in the hypoperfused myocardium after circumflex ligature. The area under the intensity curve was 1942 +/- 100 IUxs in the right, 2452 +/- 1291 IUxs in the left ventricle, 518 +/- 124 in the normally perfused and 202 +/- 94 in the hypoperfused myocardium after circumflex ligature. There was no change of heart rate, central arterial or pulmonary artery pressure during and after the injections. There was also no loss of echo intensity during the passage of contrast material through the heart due to systolic pressure. The described agent can be used for the opacification and ultrasonic visualization of the right and left heart as well as normally and hypoperfused myocardium without visible side-effects in animal studies.

Animals↗
PubMed1997

Use of filter paper for sample collection and transport in steroid pharmacology.

Field studies of androgen pharmacology are complicated by the necessity to collect, process, and store blood samples in a central facility. We have assessed the feasibility of using capillary blood spots collected by fingerprick and dried on filter paper for pharmacokinetics and pharmacodynamic measurements with nandrolone and testosterone RIAs modified for extracts from capillary blood spots. Assays on punched spots of 7.9-mm diameter (14.9 microL of dried blood) permitted accurate quantification of testosterone down to 0.4 nmol/L from a single spot and nandrolone down to 0.9 nmol/L from two spots. Stability of the steroids in dried blood spots to adverse environmental conditions, notably increased temperatures, was investigated both in the laboratory and in field studies of dried spots sent through the postal system. Storage or postal transport under moderate conditions appeared to have no deleterious effects on apparent androgen concentrations. However, under extreme conditions of storage at 50 degrees C for a week or more, or transport to a very hot tropical location, a rise in the final concentration of nandrolone, and, to a lesser extent, testosterone when corrected for tracer recovery, was noticed. These effects were largely due to apparent susceptibility of tritiated tracer, but not unlabeled androgen, to thermal degradation. In a pilot pharmacological study involving intramuscular injection of 100 mg of nandrolone decanoate in 1 mL of arachis oil, nandrolone concentrations in concurrently collected plasma as well as venous and capillary blood spots showed good agreement. Testosterone concentrations in contemporaneously collected plasma and venous blood spots also showed very good agreement. We propose that these methods may allow patients and experimental subjects to self-collect samples at remote or field locations for convenient mailing to a central laboratory for androgen assay. Applications of this methodology are now under way.

Blood Chemical Analysis↗
PubMed1998

Clinical trials update in human immunodeficiency virus wasting.

The major acquired immunodeficiency syndrome (AIDS) clinical trials groups in the Division of AIDS of the National Institutes of Health have been investigating weight loss and wasting in persons with the human immunodeficiency virus (HIV) and AIDS. Both the AIDS Clinical Trials Group (ACTG) and the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) have developed research projects to study the pathogenesis, diagnosis, prevention, and treatment of HIV-related malnutrition and wasting. This article reviews multicenter trials concerning HIV-related malnutrition and wasting conducted by the AIDS clinical trials groups. CPCRA trials will examine the effects of caloric supplements and triglycerides, or the use of megestrol acetate, oxandrolone, and progressive resistance training, on weight loss in patients with HIV-associated wasting. Planned ACTG trials will study the effects of the combination of megestrol acetate and testosterone, the testosterone derivative nandrolone decanoate, or highly active antiretroviral therapy on weight loss. Results from these studies may also have relevance to clinical oncologists who are treating patients with cancer-related cachexia.

Anabolic Agents↗