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Differential effects of nandrolone decanoate in fast and slow rat skeletal muscles.

PURPOSE: We studied the effects of high doses of an anabolic-androgenic steroid, exercise training, and a combination of steroid and training on mammalian fast- and slow-twitch skeletal muscles at the cellular level. METHODS: Thirty-two male rats were divided into sedentary and treadmill-trained groups (increased speed and time: 18 m.min-1, 0.5 h.d-1, 5 d.wk-1). Eight animals of each group were treated with nandrolone decanoate (ND) (15 mg.kg-1.wk-1), and others received the same doses of solvent. The animals were killed after 5 wk, and the contractile parameters for isolated small bundles of soleus and extensor digitorum longus (edl) fibers were estimated. RESULTS: Muscle mass, twitches, and K+ contractures were increased in soleus and edl muscles after the drug treatment and after the exercise training. Caffeine contractures were increased only after the exercise training. The combination of exercise with ND treatment produced greater effects, particularly a significant increase in sensitivity to caffeine and the amplitude of K+ contractures as well as a shortening of the time required to restore contracture. These modifications were more marked in slow than fast muscle. CONCLUSION: These results show that 5 wk of exercise training produced changes in the contractile responses developed by isolated skeletal muscle cells. The combination of exercise training with ND treatment potentiated these effects, suggesting that there was some modification in the excitation-contraction coupling mechanism. ND treatment also produced a more potent effect in soleus than edl sedentary muscle.

Anabolic Agents↗

Virilization of the voice in post-menopausal women due to the anabolic steroid nandrolone decanoate (Decadurabolin). The effects of medication for one year.

In a prospective study the effects on the voice of nandrolone decanoate super-imposed on cyclical hormonal replacement therapy (HRT) given to post-menopausal women suffering from a severe form osteoporosis were compared with the effects of HRT alone. Comparing the experimental group with the control group, after one year of medication in the experimental group a higher percentage of patients had: a lower fundamental frequency during speech, a loss of high frequencies and an increase in voice instability and creakiness. The lowering of the frequencies and the increase of instability can be explained by histological changes in the vocal cords and by problems in the adaptation to these histological changes.

Aged↗

Modulation of human leukocyte histamine release by sn-1,2-isopropylidene-3-decanoyl-glycerol and decanoic acid cyclopentyl methylester in comparison with effects of synthetic diacylglycerols and a phorbol ester.

Previous studies have shown that the glyceride derivative, sn-1,2-isopropylidene-3-decanoyl-glycerol (IpOCOC9), can trigger human leukocyte histamine release. Approximately 25% of the total cellular histamine content is extruded in the presence of 206 microM of IpOCOC9; at 69 microM, however, the secretagogue action of the compound is marginal. The characteristics of the release induced by IpOCOC9 are closely similar to those reportedly recorded at hyperosmolar triggering of basophils with mannitol, and in many respects they also mimic those observed at phorbol ester-induced histamine release. The compound decanoic acid cyclopentyl methylester (DACPME), a structural analogue of IpOCOC9, fails to induce histamine release. IpOCOC9, but not DACPME, stimulates human polymorphonuclear leukocyte cytosolic Ca2+- and phospholipid-dependent histone III-S kinase activity (unpublished observations). The secretagogue action of IpOCOC9 has therefore tentatively, at least partly, been attributed to a direct protein kinase C activation. In the present studies, we examined the influence of IpOCOC9 and DACPME on histamine release triggered by an ensuing exposure to anti-IgE, the calcium ionophore A23187, formyl-methionyl-leucyl-phenylalanine (FMLP), or 4 beta-phorbol 12-myristate 13-acetate (PMA). It is shown that IpOCOC9-treatment of cells results in either enhancement or reduction of the release induced by anti-IgE or by A23187, whereas FMLP-induced release is consistently reduced and PMA-induced release consistently enhanced by such a treatment. Treatment of cells with DACPME enhances but does not reduce anti-IgE-triggered release, whereas FMLP-induced release is not affected. Pretreatment of the cells with other putative protein kinase C activators like PMA, sn-1-oleoyl-2-acetyl-glycerol (OAG), 1,2-dioctanoyl-glycerol (DiC8) or the glycerol derivative sn-1,2-diacetyl-3-decanoyl-glycerol (DiC2OCOC9) affects secretagogue-induced basophil histamine release according to specific patterns similar to but not identical with those recorded for IpOCOC9 and DACPME. Thus, e.g., DiC2OCOC9 consistently reduces but does not enhance anti-IgE-triggered release. These data show that limited structural changes of IpOCOC9 may qualitatively affect its modulating properties in the human basophil histamine release system.

Calcimycin↗

The reversibility of sperm quality after discontinuing nandrolone decanoate in adult male rats.

AIM: To investigate the reversibility of the effect of nandrolone decanoate (ND) on sperm parameters after discontinuing the drug. METHODS: Three groups of rats received peanut oil (control), low and high doses of ND for 14 weeks, respectively. Each group was divided into subgroups A and B, in which rats were killed 14 and 28 weeks after initiating the injection, respectively. RESULTS: Sperm count and motile sperm fraction were decreased in the subgroups A and B that received low and high doses of ND in comparison with the controls A and B, respectively. The sperm count and motile sperm fraction increased in the subgroups B that received low and high doses of ND in comparison with their corresponding subgroups A. The number of normal morphology sperm was decreased significantly in subgroups A receiving low and high doses of ND in comparison with the control subgroup A. However, this parameter was not decreased in subgroups B receiving low and high doses in comparison with the control subgroup B. The normal sperm morphology did not show any significant differences in the subgroups B in comparison with their corresponding subgroups A. CONCLUSION: The 14-week injection of low and high doses of ND decreases sperm quality and quantity in rats. These parameters were improved after discontinuing ND, but not recovered completely even when they are left untreated for 14 weeks.

Anabolic Agents↗

Cytotoxic and cytolytic activity of nonadecafluoro-n-decanoic acid on Acholeplasma laidlawii.

We studied the interactions between the perfluorinated fatty acid nonadecafluoro-n-decanoic acid (NDFDA) and the cell wall-less procaryote Acholeplasma laidlawii, which were cultured in an identical medium base but with different serum supplements. When grown in mycoplasma media supplemented with PPLO serum fraction (Difco Laboratories, Detroit, Mich.), A. laidlawii was rapidly killed by low concentrations of toxicant (less than 1.0 mM). At higher concentrations (greater than 10 mM), NDFDA treatment appeared to lyse cells. A. laidlawii cells grown in horse serum-supplemented mycoplasma media were both killed and lysed at the same NDFDA concentration (greater than 10 mM). These data suggest that this perfluorinated fatty acid can be cytotoxic and cytolytic to mycoplasmas. Changes in active concentrations occurred in parallel with changes in growth medium serum supplementation, which is known to alter mycoplasma membrane composition. We propose that NDFDA interacts with the membranes of A. laidlawii cells, resulting in cell death or cell lysis or both.

Acholeplasma laidlawii↗

Metabolic effects of nandrolone decanoate and resistance training in men with HIV.

Thirty human immunodeficiency virus (HIV)-infected men were randomized to a high dose of nandrolone decanoate weekly (group 1) or nandrolone plus resistance training (group 2) for 12 wk. For the two groups, nandrolone had no significant effects on total cholesterol, LDL cholesterol, LDL phenotype, or fasting triglycerides, although triglycerides decreased by 66 +/- 124 mg/dl for the entire population (P = 0.01). Group 2 subjects had a favorable increase of 5.2 +/- 7.7A in LDL particle size (P = 0.03), whereas there was no change in group 1. Lipoprotein(a) decreased by 7.3 +/- 6.8 mg/dl for group 1 (P = 0.002) and by 6.9 +/- 8.1 for group 2 (P = 0.013). However, HDL cholesterol decreased by 8.7 +/- 7.4 mg/dl for group 1 (P < 0.001) and by 10.6 +/- 5.9 for group 2 (P < 0.001). Percentages of HDL(2b) (9.7-12 nm) and HDL(2a) (8.8-9.7 nm) subfractions decreased similarly for the two groups, whereas HDL(3a) (8.2-8.8 nm) and HDL(3b) (7.8-8.2 nm) increased in the groups during study therapy (P < or = 0.02 for all comparisons). There was no evidence of a decreased insulin sensitivity in either group, whereas fasting glucose, fasting insulin, and homeostasis model assessment improved in group 2 (P < 0.05). These metabolic effects were favorable (other than for HDL), but changes were generally transient (except for HDL in group 2), with measurements returning to baseline 2 mo after the interventions were completed.

Adult↗

Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis.

BACKGROUND/AIMS: Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. METHODS: This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. RESULTS: A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. CONCLUSION: Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.

Adult↗

Treatment with nandrolone decanoate and megestrol acetate in HIV-infected men.

BACKGROUND: Malnutrition, especially loss of lean body mass, is a frequent complication of people living with HIV that may increase their mortality and morbidity. METHODS: Nine HIV-infected men with unexplained loss of >10% of their usual weight were selected. They received megestrol acetate (MA) (400 mg/day by mouth) and nandrolone decanoate (ND) (100 mg/15 days intermuscular injection) over 16 weeks. Anthropometric evaluations, bioelectrical impedance, grip strength dynamometry, hematologic, biochemical, immunological and hormonal analysis before, during, and after the treatment were performed. Quality of life was evaluated by the Karnofsky index. RESULTS: In the 7 men that finished the treatment, there were significant increases in weight (11.9 +/- 9.1 kg, p < .05), 4-site skinfold measurements (p < .05), midarm circumference (p < .005), and fat-free mass (FFM) (5.1 +/- 4.1 kg, p < .05). The increase in fat mass was not statistically significant (6.9 +/- 6.4 kg, NS). Muscle strength increased significantly (p < .005). The Karnofsky index values increased from 59% to 73% (p < .05). One patient developed mild hyperglycemia and another one had an increase in aspartate transaminase and gamma-glutamyl transpeptidase that reversed after the treatment. Four patients developed asymptomatic adrenal suppression. Testosterone serum levels decreased significantly during the study (p < .05), and 4 patients had serum values below the normal range at week 16. One patient developed gynecomastia. CONCLUSIONS: The combined treatment with MA and ND led to a significant increase in body weight and FFM. Muscle strength and quality of life improved during the study. The treatment was well tolerated with mild side effects.

Adult↗

Pharmacokinetic evaluation of three different intramuscular doses of nandrolone decanoate: analysis of serum and urine samples in healthy men.

The pharmacokinetics of nandrolone in serum and urine were investigated in healthy young men after a single im injection of 50 mg (n = 20), 100 mg (n = 17), or 150 mg (n = 17) nandrolone decanoate. Blood samples were collected before treatment and for up to 32 d after dosing. In addition, in the 50- and 150-mg groups, 24-h urine samples were collected before treatment and on d 1, 7, and 33 after treatment; in the 150-mg group, additional samples were collected after 3 and 6 months. Serum concentrations and the area under the curve of nandrolone increased proportionally with the dose administered. The peak serum concentration ranged from 2.14 ng/ml in the 50-mg group to 4.26 ng/ml in the 100-mg group and 5.16 ng/ml in the 150-mg group. The peak serum concentration was reached after 30 h (50 and 100 mg) and 72 h (150 mg), whereas the terminal half-life was 7-12 d. In urine, pretreatment concentrations of 19-norandrosterone (19-NA) and/or 19-noretiocholanolone (19-NE) were detected in five of 37 subjects (14%). In the 50-mg group, 19-NA and/or 19-NE could be detected at least until 33 d after injection in 16 of 17 subjects (94%). In the 150-mg group, who were presumed to have not previously used nandrolone, nandrolone metabolites could be detected for up to 6 months in eight of 12 subjects (67%) for 19-NE and in 10 of 12 subjects (83%) for 19-NA.

Adult↗

12-O-acetylphorbol-13-decanoate potently inhibits cytopathic effects of human immunodeficiency virus type 1 (HIV-1), without activation of protein kinase C.

Through bioactivity-guided fractionation, eight phorbol diesters, including five new ones (1-5), were isolated from the seeds of Croton tiglium collected in Egypt. 12-O-Acetylphorbol-13-decanoate (6) and 12-O-decanoylphorbol-13-(2-methylbutyrate) (4) potently inhibited the HIV-1-induced cytopathic effect on MT-4 cells (IC100 values of 7.6 ng/ml and 7.81 micrograms/ml, and CC0 values of 62.5 micrograms/ml and 31.3 micrograms/ml, respectively) without activating protein kinase C.

Anti-HIV Agents↗

[Effect of inclusion complexation of decanoic acid with alpha-cyclodextrin on rectal absorption of cefmetazole sodium suppository in rabbits].

Inclusion complex of decanoic acid (DA) with alpha-cyclodextrin (alpha-CyD) was prepared as an additive of cefmetazole sodium (CMZ) suppository and rectally administered to rabbits. The resulting complexation was examined by the phase solubility method, differential scanning calorimetry (DSC) and X-ray diffractometry. Plasma concentration and AUC of CMZ after rectal administration of a suppository containing DA/alpha-CyD complex to rabbits increased more significantly than those with none additive.

Adjuvants, Pharmaceutic↗

Bodybuilders' body composition: effect of nandrolone decanoate.

INTRODUCTION: The use of androgenic-anabolic steroids (AAS) among bodybuilders to increase muscle mass is widespread. Nandrolone decanoate (ND) is one of the most popular misused AAS, although the effects on body composition are equivocal. Therefore, the purpose of this study was to determine the effect of ND on body composition in male bodybuilders, with special reference to muscle mass alterations. METHODS: Using a randomized "double-blind" "placebo-controlled" design, 16 experienced male bodybuilders (age: 19-44 yr) either received ND (200 mg.wk(-1), intramuscularly) or placebo for 8 wk. Body composition was assessed using the four-component model, combining results from underwater weighing, dual-energy x-ray absorptiometry (DXA), and deuterium dilution. Total bone mineral content and density were measured using DXA. Water compartments (extracellular water [ECW] and intracellular water [ICW]) were determined using deuterium dilution and bromide dilution. RESULTS: ND administration resulted in significant increments of body mass (+2.2 kg), fat-free mass (FFM: +2.6 kg), and total body water (+1.4 kg). No significant changes in fat mass, percentage fat, ECW, ICW, ECW/ICW ratio, hydration of the FFM, and on bone mineral measurements were observed. CONCLUSIONS: The results show that the administration of 200 mg.wk(-1) of ND (intramuscularly) for 8 wk significantly increased body mass and FFM, whereas fat mass, bone mineral content, bone mineral density, and the hydration of the FFM remained unaffected. These data indicate that the changes can be attributed to an increase of muscle mass.

Adult↗

Exuberant local tissue reaction to intramuscular injection of nandrolone decanoate (Deca-Durabolin)--a steroid compound in a sesame seed oil base--mimicking soft tissue malignant tumors: a case report and review of the literature.

We present an unusual pseudotumor that formed in reaction to self-administered intramuscular injections of an anabolic steroid, nandrolone decanoate (Deca-Durabolin) in a young soldier. The histopathologic features which closely mimicked several malignant neoplasms could have led to an incorrect diagnosis of malignancy and unnecessary extensive surgery. To our knowledge, this phenomenon has not been previously reported.

Adult↗

Pathological and hepatic ultrastructural effects of a single dose of perfluoro-n-decanoic acid in the rat, hamster, mouse, and guinea pig.

In rats, the liver is the primary target organ of perfluoro-n-decanoic acid (PFDA) toxicity. Therefore, the effects of PFDA on hepatic ultrastructure were studied in rats. Pathological changes induced by PFDA in hamsters, mice, and guinea pigs were also examined. PFDA caused a severe reduction in body weight in all four species studied. A reduction in food intake was observed in rats and hamsters. However, hamsters continued to consume food at a reduced level, while rats stopped eating for a 5- to 6-day period about 6 days after dosing. The PFDA-induced pathological changes in the hamsters, mice, and guinea pigs resembled those seen in rats to varying degrees. As in the rat, PFDA caused a marked liver enlargement in mice and hamsters and a moderate swelling in guinea pigs. This hepatomegaly was ascribed primarily to individual cell swelling. Thymic atrophy was noted in PFDA-treated hamsters, mice, and guinea pigs. Seminiferous tubular degeneration observed in hamsters and guinea pigs, but not in mice, was not as severe as in the rat, where in some cases frank necrosis has been seen. Ultrastructural changes in the livers of all PFDA-treated animals, regardless of species, included disruption of the rough endoplasmic reticulum, rounding and swelling of the mitochondria with related structural alterations, and mild to extensive proliferation of peroxisomes. This peroxisome proliferative response was greatest in mice and almost absent in guinea pigs. Accumulation of lipid droplets in liver cells due to PFDA treatment was more pronounced in hamsters and guinea pigs than in rats and mice. PFDA-induced hepatomegaly with a concomitant increase in peroxisomes in several rodent species may be associated with an impairment of normal lipid metabolism in the liver by PFDA.

Animals↗

Functional and quantitative changes of immune cells of ageing NZB mice treated with nandrolone decanoate. I. Effect on survival and autoantibody development.

We analysed the effect of nandrolone decanoate (ND) on functional and quantitative changes in immune cell populations, on survival, and on autoantibody production of female New Zealand Black (NZB) mice. Our results confirmed that, with increasing age, untreated NZB mice display a lower natural killer (NK) cell activity, an impaired T-cell function as evidenced by a reduced mitogen lymphoproliferative response, IL-2 production and generation of cytotoxic lymphocytes, a lower level of thymic serum factor (TSF), a reduced percentage of Thy-1+ cells; we also observed an increased incidence of mice with abnormally high levels of anti-DNA in the serum. In addition, we demonstrated an important defect in the IL-1 production by LPS-stimulated macrophages. ND administered to female NZB mice increased the survival time of the animals and reduced the anti-DNA titres. This favourable effect was associated with improved immune responses, especially those mediated by T cells; these included increased IL-2 production, complete recovery of cytotoxic T lymphocytes (CTL), a significant augmentation of the percentage of Lyt-2+ cells and enhanced TSF level. Moreover IL-1 production by macrophages returned to normal. These results suggest that ND acts on T-cell differentiation, either by a direct effect on thymic epithelial cells resulting in an increased TSF release, and/or via macrophage regulatory activity. The protective effect of ND may also be attributed in part to the higher number of Lyt-2+ (suppressor) T cells present in the spleen after treatment.

Aging↗

Effect of nandrolone decanoate on Sjögren's syndrome like disorders in NZB/NZW mice.

The effects of 2.5-40 mg/kg nandrolone decanoate (ND) on the development and growth of mononuclear cell infiltrations in the submandibular glands of NZB/W (B/W) mice have been studied using a quantitative histological method. Injections with ND for 9 months, once every 3 weeks, starting at 4 weeks of age, reduced the number and total area of infiltrations in submandibular glands of female and castrated male B/W mice. Since ND has relatively weak virilizing properties, this substance may be useful for the treatment of Sjögren's syndrome in humans.

Animals↗

Nandrolone decanoate reduces the premature mortality of cardiomyopathic hamsters.

Male hamsters of an inbred strain carrying a genetic trait for cardiomyopathy were dosed by sc injection weekly with an anabolic-androgenic steroid, nandrolone decanoate, beginning when 3 months old. Two groups (N = 17) received doses of 2 and 4 mg per animal, while a vehicle control group received an equal volume of sesame oil. Rather than a hypothesized shortening of longevity, the steroid treatment significantly prolonged survival of the hamsters, which ordinarily die of congestive heart failure. At the median time to death for controls (355 days of age, 257 days of treatment), the steroid groups had mortality of only 2/17 and 4/17 (vs. 9/17, p < 0.01).

Anabolic Agents↗

[Bis-(hydroxy-2-ethylthyo)-1,10-decano in hyperlipaemic therapy (author's transl)].

The authors studied the effectiveness and biological tolerability of Tiadenol [Bis-(hydroxy-2-ethylthyo)-1,10-decano] against clofibrate, in a group of 38 hyperlipaemic (volunteers) subjects, with or without atherosclerotic disease. The results showed that the new hypolipidaemic drug has a great effect on cholesterolemia and trigliceridaemia, as does clofibrate. The statistic examination confirmed the results. This research didn't show any side-effects of the drug, which has a very good biological tolerability.

Adult↗