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Insulin-like growth factors I and II in healthy women with and without established osteoporosis.

We measured serum concentrations of insulin-like growth factors I and II (IGF-I and IGF-II) by radioimmunoassay in 107 healthy women aged 28-78 years and in 116 women with established osteoporosis. The women with established osteoporosis were randomized to a 1-year double-blind, placebo-controlled treatment with continuous estrogen/progestogen, anabolic steroids, salmon calcitonin or placebo and the IGFs were measured every 6 months. Women less than 35 years of age had 29% higher levels of IGF-I (p < 0.001) as compared to women above that age. For women more than 35 years of age, we found no correlation between IGF-I and age (r = 0.02). Correspondingly, we found no significant changes in serum IGF-I in 10 women, who were followed with serial measurements of IGFs every 3 months from 2 years before to 1 year after menopause; IGF-II revealed no correlation with age (r = 0.04). In the group of 116 women with established osteoporosis, IGF-I was 30% lower (p < 0.01) as compared to a group of 19 height-, weight- and age-matched nonfractured women (mean age 64 years). The IGF-II levels were equal in the two groups. Over the 1-year therapeutic intervention period, an increase in IGF-I of 13-15% (p < 0.05) was seen in the nandrolone decanoate-treated group. The same tendency was seen for hormone replacement therapy, although it was not significant. In conclusion, the serum level of IGF-I is high in young women, when peak bone mass is attained, and low in postmenopausal women with established osteoporosis.

Adult↗

[Nandrolone administration does not promote hypertrophy of soleus muscle in rats].

Anabolic androgenic steroids (AAS) are compounds formed from testosterone or one of its derivatives, which are largely used by amateur e professional athletes to improve the athletic performance. However, the scientific information about the relation between the use of AAS and muscle hypertrophy is controversial. The aim of this study was to evaluate the effects of testosterone and physical training on muscle hypertrophy. Male Wistar rats received i.m. injections of Deca-Durabolin or vehicle during 6 weeks. Trained rats were submitted to a resistance physical training, by jumping up and down in water carrying an overload. Sedentary and trained animals were anesthetized and sacrificed. Soleus muscle was removed for the quantification of total protein and DNA concentration. In the end of the treatment, body weight of trained animals treated with vehicle or AAS was lower than the body weight of respective sedentary. Total protein concentration and the ratio muscle weight/body weight of all experimental groups were not altered. Trained group treated with AAS presented lower DNA concentration than trained group treated with vehicle. The administration of nandrolone decanoate did not promote hypertrophy on soleus muscle, not even when the use of AAS was associated to resistance physical training.

Anabolic Agents↗

Anabolic steroid- and exercise-induced cardiac stress protein (HSP72) in the rat.

The present study investigated the effects of exercise and anabolic-androgenic steroids on cardiac HSP72 expression. Male Wistar rats were divided into experimental groups: nandrolone exercise (NE, N = 6), control exercise (CE, N = 6), nandrolone sedentary (NS, N = 6), and control sedentary (CS, N = 6). Animals in the NE and NS groups received a weekly intramuscular injection (6.5 mg/kg of body weight) of nandrolone decanoate, while those in the CS and CE groups received mineral oil as vehicle. Animals in the NE and CE groups were submitted to a progressive running program on a treadmill, for 8 weeks. Fragments of the left ventricle were collected at sacrifice and the relative immunoblot contents of HSP72 were determined. Heart weight to body weight ratio was higher in exercised than in sedentary animals (P < 0.05, 4.65 +/- 0.38 vs 4.20 +/- 0.47 mg/g, respectively), independently of nandrolone, and in nandrolone-treated than untreated animals (P < 0.05, 4.68 +/- 0.47 vs 4.18 +/- 0.32 mg/g, respectively), independently of exercise. Cardiac HSP72 accumulation was higher in exercised than in sedentary animals (P < 0.05, 677.16 +/- 129.14 vs 246.24 +/- 46.30 relative unit, respectively), independently of nandrolone, but not different between nandrolone-treated and untreated animals (P > 0.05, 560.88 +/- 127.53 vs 362.52 +/- 95.97 relative unit, respectively) independently of exercise. Exercise-induced HSP72 expression was not affected by nandrolone. These levels of HSP72 expression in response to nandrolone administration suggest either a low intracellular stress or a possible less protection to the myocardium.

Anabolic Agents↗

Androgen versus erythropoietin for the treatment of anemia in hemodialyzed patients: a prospective study.

According to this facility's protocol for the treatment of anemia in hemodialyzed patients, androgens were administered to male patients aged over 50 yr and recombinant human erythropoietin was administered to male patients below 50 yr of age and to female patients. In the study presented here, both therapeutic approaches have been prospectively analyzed. Patients were divided into two groups. Group A was composed of 18 patients, aged 62 +/- 12 yr, treated with nandrolone decanoate (200 mg/wk im) for 6 months; Group B was composed of 22 patients (6 men, 16 women) aged 47 +/- 15 yr, treated with subcutaneous recombinant human erythropoietin (initial dose, 6000 IU/wk) for 6 months. The increases of hemoglobin were similar in both groups; Group A, from 7.3 +/- 0.8 to 10.8 +/- 1.7 g/dL (P < 0.001), and Group B, from 7 +/- 0.6 to 10.4 +/- 1 g/dL (P < 0.001). In Group A, increases of triglycerides (159 +/- 71 versus 267 +/- 153 mg/dL, P < 0.001), serum albumin (3.9 +/- 0.3 versus 4.2 +/- 0.3 g/dL, P < 0.05), and dry weight (62.1 +/- 9.8 versus 64.9 +/- 10.1 kg, P < 0.001) were observed, which remained unmodified in Group B. Blood pressure control worsened in one patient (6%) from Group A, and in ten patients (45%) from Group B (P < 0.05). In conclusion, androgens produced an improvement in anemia in selected patients, similar to that achieved by use of recombinant human erythropoietin but at a lower cost. Androgens also have an appreciable anabolic effect and did not increase the blood pressure.

Aged↗

Lack of effects of anabolic-androgenic steroids on locomotor activity in intact male mice.

Anabolic-androgenic steroid abusers have reported hyperactivity, euphoria, and decreased fatigue, among other behavioral effects. It has been suggested that the effects of these substances on the central nervous system are similar to those of psychostimulants; however, the influence of steroids on general locomotor activity in laboratory animals is not well understood, especially how noncastrated male rodents are affected. In this study, spontaneous locomotor activity displayed by gonadally intact male mice submitted to several experimental conditions was analyzed. Different housing conditions (individual or cohabiting with a female), diverse steroids (testosterone propionate, nandrolone decanoate, and a mixture of both steroids) and single or repeated injections were employed. At 24 hours after the injection (after the three last injections in the case of chronic treatment) spontaneous locomotor activity was registered on an activity recorder for one 15-min. period. No effects due to the treatment were found in almost every experimental condition. These results contrast with the dramatic decreases in activity described for female mice after treatment with such steroids. It seems that in intact males the steroids' influence on spontaneous locomotor activity may be more subtle than expected. These effects seem very complex depending on duration of treatment and specific situations (spontaneous or forced activity) as well as the interaction with endogenous androgen levels.

Anabolic Agents↗

Utilization of medium-chain triglycerides by neonatal pigs: effects of emulsification and dose delivered.

Four trials were conducted using 86, 24-h-old pigs to evaluate the utilization of medium-chain triglycerides (MCT). Effects of emulsification and amount of MCT fed were examined. After a 4-h period during which feed was withheld, pigs were force-fed MCT (containing 75% octanoate and 25% decanoate), marking time 0 of the experiment. Blood samples were obtained at 1 and 2 h for subsequent medium-chain fatty acid (MCFA) analysis. In Trials 1 (six pigs/treatment) and 2 (four pigs/treatment) the response to three emulsifying agents was compared to a nonemulsified (NE) control. Twenty milliliters of a 30% (vol/vol) emulsion of MCT or 6 mL of NE MCT was administered. Concentrations of MCFA at 1 h in pigs receiving a Tween 80 (polyoxy-ethylene [20] sorbitan monooleate) emulsion were 3- to 19-fold higher than concentrations in animals administered a gum arabic/gum tragacanth emulsion, a lecithin emulsion, or NE MCT. Trials 3 (eight pigs/treatment) and 4 (six pigs/treatment) were conducted to determine the plasma MCFA concentrations resulting from feeding increasing levels of NE (3, 6, 9, or 12 mL of MCT) or emulsified MCT oil (2, 4, 6, or 8 mL in a 30% Tween 80 emulsion). Plasma octanoate concentrations measured at 1 h increased linearly (P < .05) with increasing MCT dosage through 9 mL of NE and 6 mL of emulsified MCT. A transient narcosis was observed in 8 of 12 animals that received 6 or 8 mL of emulsified MCT and was most pronounced 1 to 2 h after feeding, which roughly corresponded to peak plasma MCFA concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Causes of reduced survival of neonatal pigs by medium-chain triglycerides: blood metabolite and behavioral activity approaches.

Two experiments were conducted to investigate the causes of the failure of orally dosed medium-chain triglycerides (MCT) in improving the survival of neonatal pigs. In Exp. 1, four litters consisting of 24 unsuckled neonatal pigs were either dosed with 6 mL/kg BW.75 of MCT or the dosing process was mimicked by inserting and withdrawing the feeding tube at 10 and 18 h after birth. Blood beta-hydroxybutyrate concentration was increased (P < .06) and the depletion of liver glycogen was reduced (P < .05) by MCT. Plasma octanoate (C8) concentration peaked at 1 h and was minimized at 4 to 8 h after each MCT dosage; decanoate (C10) concentration increased (P < .001) gradually after each dosage. Activity of pigs was decreased (P < .01) by MCT. In Exp. 2, 94 litters consisting of 887 neonatal pigs were dosed with either 6 mL/kg BW.75 of MCT, coconut oil (CO), or saline at 10 to 14 and 20 to 28 h after birth. Milk intake (P < .05) and weight gain were reduced (P < .01) in 1- to 2-d-old pigs dosed with MCT compared with intake and gain of pigs dosed with saline. Mortality of large pigs (> 1 kg) was increased (P < .05) but mortality of small pigs (< 1 kg) was not affected by MCT. Mortality of small pigs was reduced (P < .05) but mortality of large pigs (> 1 kg) was not affected by CO. Standing, walking, and suckling behaviors of pigs were not affected by MCT or CO. Coma was evident in 9.7% of pigs dosed with MCT.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

[Effect of gravitation loading and retabolil on development of atrophy in muscles and bones of rats due to suspension].

In a 3-wk experiment with tail-suspended rats histological and histomorphometric methods were used to determine the effects of graded gravitational loading (GGL) and anabolic steroid retabolil (nortestosterone decanoate) on the course of atrophy in soleus m. (SM), gastrocnemius m. (GM), tibia and humerus, and functioning of somatotrophic hormones (STH) of the pituitary and thyrocytes of the thyroid. Suspension was found to produce atrophy in SM and, to a less degree, in GM, partial transformation of SM slow fibers into the fast ones, suppression of the tibial longitudinal growth, demineralization of the tibial and humeral spongious metaphyses; besides, functional activities of STH-cells and thyrocytes were inhibited. Graded gravitational loading of rats by intermittence of suspension for 2 hrs slowed down atrophy in both muscles and osteopenia in tibia, stimulated the synthetic and secretory functions of STH-cells without any marked effect on thyrocytes or humeral osteopenia. GGL failed to influence the slow-to-fast transformation of SM fibers. Two injections of retabolil at the total dose of 3 mg/kg of the body mass somewhat interfered with the SM atrophy and humoral osteopenia, and were favorable to the synthetic but not secretory activity of STH-cells. Neither SM and tibial atrophies nor thyroid activity of the gland were improved. The prophylactic action of GGL upon the SM and humeral atrophies was significantly higher when combined with retabolil, whereas GM and tibia were not noticeably cured by retabolil. Inhibition of the SM atrophy and humeral osteopenia in rats treated with GGL and retabolil concurred with elevated activities of STH-cells and thyrocytes indirectly suggesting their more intensive production of the growth hormone and thyroid hormones, respectively.

Anabolic Agents↗

Androgens for the treatment of anemia in peritoneal dialysis patients.

Before the advent of recombinant human erythropoietin (EPO), androgens were used for treatment of anemia in dialysis patients. However, after the availability of recombinant EPO in the 1980s, the use of these substances was abondoned. We have previously reported that androgens have beneficial actions on anemia in selected hemodialysis patients. In the present study we have analyzed the effects of androgen administration on hematologic parameters in peritoneal dialysis patients. We evaluated 9 patients treated for 6 months with nandrolone decanoate (200 mg/week intramuscularly). Hemoglobin and hematocrit values experienced a significant increment with respect to basal values during the study (9.2 +/- 0.7 g/dL and 27.7% +/- 2.3% at basal vs. 11.9 +/- 0.5 g/dL and 35.3% +/- 1.6% at month 6, respectively; P < 0.001). In addition to the effects on the hematologic parameters, androgen administration also had beneficial anabolic actions with a significant increment in the serum concentration of total proteins and albumin (basal, 6.1 +/- 0.3 g/dL and 3.1 +/- 0.4 g/dL vs. 6.7 +/- 0.4 g/dL and 3.8 +/- 0.4 g/dL at month 6, respectively, P < 0.01). The only adverse effect was a rise in the serum concentration of triglycerides (176 +/- 54 mg/dL vs. 144 +/- 53 mg/dL, P < 0.01). In conclusion, androgen administration has beneficial effects on erythropoiesis as well as positive anabolic actions in patients under peritoneal dialysis.

Aged↗

The effect of anabolic steroid on the distribution of muscle fiber in rat hind limb.

This study evaluates the effect of anabolic steroid hormone (nandrolone decanoate, 19-Nortestosterone; ND) on histomorphometry and distribution of muscle fiber in the rat tibialis anterior (TA) muscle compared with the control rats. Three male Wistar rats aged of 5 weeks were daily received subcutaneous injection of 0.3 cc vehicle oil included 1mg ND for 6 weeks. Two control (C) rats were done only vehicle oil by the same manner as the experimental (E) group. The TA muscle was stained for myofibrillar adenosine triphosphatease with preincubation at pH 4.35, after cryosectioning at the thickness of 10 microm. Muscle fibers were classified into type I, IIA, IIX, and IIB. The E group showed significantly smaller than the C group in body weight. In histomorphometry, the cross-sectional area of type IIB fibers in the E group showed narrow range, and shifted smaller than those in the C groups. The distribution of type I fibers was restricted to the deep region in the E group. The anabolic steroid facilitated toward the older rat type on distribution and proportion of muscular tissue.

Aging↗

Effects of submaximal training and anabolic androgenic steroids administration on steroidogenic enzyme activity in rat Leydig cells.

The purpose of the present study was to investigate the single and combined effects of submaximal training and anabolic androgenic steroids (AAS) treatment on the activity of 3beta hydroxysteroid dehydrogenase (3betaHSD) in rat Leydig cells (LC). Forty male Wistar rats were distributed into 4 groups. Half of them exercised on treadmill. After 2 weeks half of the trained and sedentary rats received weekly either 10 mg x kg(-1) Nandrolone Decanoate (ND) or Placebo (Pl) i.m. for 6 weeks. The day after the last exercises all the groups: 1) sedentary + Pl (SP); 2) sedentary + ND (SND); 3) trained + Pl (TP) and 4) trained + ND (TND) were decapitated. On fresh cryostat sections of the testes of each animal enzymehistochemical reaction for the activity of 3betaHSD was carried out. Our results demonstrate that in sedentary rats ND treatment decreased the activity of 3betaHSD in the LC in comparison to SP. Endurance training also decreased the activity of 3betaHSD in TP group compared to SP. On sections of the testes of group TND a pronounced reduction in the enzyme activities of 3betaHSD in the LC was found in comparison with the other groups. In conclusion we suggest that submaximal endurance training and/or administration of AAS downregulate the steroidogenic enzyme activity of rat Leydig cells.

3-Hydroxysteroid Dehydrogenases↗

Cardiomyocyte mitochondrial KATP channels participate in the antiarrhythmic and antiinfarct effects of KATP activators during ischemia and reperfusion in an intact anesthetized rabbit model.

Recent evidence suggests that the mitochondrial K(ATP) channels may be involved as a subcellular mediator in cardioprotection afforded by ischemic and pharmacological preconditioning by K(ATP) activators. The present study investigated the effects of administration of non-hypotensive doses of ATP-sensitive K(+) channel (K(ATP)) openers, nicorandil (NIC) and pinacidil (PIN), and specific blockers of mitochondrial (5-hydroxydecanoate) and sarcolemmal (1-[5-[2-(5-chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl-3-methyl-thiourea, HMR 1883) K(ATP) channels prior to and during coronary occlusion and post-ischemic reperfusion on survival rate, ischemia- and reperfusion-induced arrhythmias and myocardial infarct size in anesthetized rabbits. In Group I, myocardial ischemia-induced arrhythmias were provoked by tightening a ligature over the left main coronary artery for 30 min. In Group II, arrhythmias were induced by reperfusion following a 20 min ligation of the same artery. Both in Group I and Group II, early iv administration of NIC (0.47 mg/kg), PIN (0.1 mg/kg), HMR 1883 (3 mg/kg)/NIC and HMR 1883/PIN just prior to and during ischemia increased survival rate (75%, 86%, 75% and 75%, respectively, vs. 55% in the control in Group I; 75%, 75%, 75% and 67%, respectively, vs. 50% in the control in Group II), significantly decreased the incidence and severity of life-threatening arrhythmias and significantly decreased myocardial infarct size. However, late iv administration of NIC or PIN just prior to reperfusion did not increase survival rate nor confer any antiarrhythmic or cardioprotective effects. The antiarrhythmic and cardioprotective effects were abolished by pretreating rabbits with 5-hydroxy-decanoate (5 mg/kg, iv bolus). In the present study, higher levels of malondialdehyde and lower levels of reduced glutathione and superoxide dismutase in necrotic zone of myocardium in all subgroups in Group II suggest little anti-free radical property of NIC and PIN. Therefore, it may be assumed that mitochondrial K(ATP) channel opening leads to mitochondrial generation and release of ROS providing for IPC and antiarrhythmic activity. The mitochondrial rather than sarcolemmal K(ATP) channel may represent a potential site of cardioprotection and antiarrhythmic activity.

Animals↗

Effect of intravenous calcium load on the serum calcium level in postmenopausal osteoporosis (a study of the pathogenesis, and diagnostic use of the test).

Analysis of calcium tolerance in suggested to represent a valuable diagnostic aid in osteoporosis, particulary in the menopause. The serum calcium level was found to exceed 11.0 mg/dl 60 min after the intravenous injection of 3.6 mg per kg body weight of Ca++ in all patients with osteoporosis, while the level was normal at that point of time in every subject without osteoporosis, including patients with bone disease other than osteoporosis. Administration of norandrosterone decanoate or dehydroepinandrosterone to patients with menopausal osteoporosis resulted in normalization of the post-load hypercalcaemia. Calcium tolerance of menopausal patients without osteoporosis was not affected by dehydroepiandrosterone.

Calcium↗

Combined tamoxifen and anabolic steroid as primary treatment for breast carcinoma in the elderly.

Fifty-one consecutive patients aged over 70 years with localized breast carcinoma received primary treatment with tamoxifen and nandrolone decanoate. Results were compared to a control group of 51 age, tumour volume and nodal status-matched patients selected from a cohort who had primary treatment with tamoxifen alone. One year after commencement of treatment 31 (60%) patients treated with tamoxifen and nandrolone showed regression of their tumour, compared to 24 (47%) in the control group. Twenty-two (44%) patients had side effects attributable to nandrolone. Only four (8%) patients continued nandrolone for more than 12 months, and at 3 years after commencement of treatment 21 (40%) patients from each group had tumour regression. We argue that nandrolone should not be used as primary treatment in breast carcinoma, but may have a role to play in patients who fail to respond to tamoxifen.

Aged↗

Interaction between enteroviruses and human endothelial cells in vitro. Alterations in the physical properties of endothelial cell plasma membrane and adhesion of human granulocytes.

Fluorescent molecular probes were used for study of the interaction between enteroviruses (Echo 9, Echo 12, and Coxsackie B3 virus) and human endothelial cells in monolayer culture. With the use of the monomer-excimer method with pyrene decanoic acid it was shown that a marked dose-dependent restructuring of the plasma membrane occurred following addition of virus to the endothelial cells. This took the form of an increase in the lipid surface available to the lipophil reporter molecules, probably due to an alteration in the domain structure of the plasma membrane caused by insertion of virus capsid proteins. Experiments with diphenylhexatriene indicated that the enteroviruses had only a slight tendency to make the plasma membrane of the endothelial cell more fluid. Concomitant with these alterations in the biophysical properties of the membrane, a virus-induced increase in granulocyte adherence to the endothelial cells was observed for all three enteroviruses studied. Possible mechanisms for this elevated adherence are discussed, as well as the significance of the results for the phenomenon of virus-induced granulocytopenia.

Cell Adhesion↗

A multicenter trial of antithymocyte globulin in aplastic anemia and related diseases.

One hundred fifty patients with bone marrow failure were treated in three groups with antithymocyte globulin (ATG; Upjohn, Kalamazoo, MI) in a multicenter trial. Patients were assessed at 3, 6, and 12 months after initiation of treatment by three criteria: transfusion independence, clinical improvement, and blood counts. Group I consisted of 77 patients with acute severe aplastic anemia, randomized to receive either ten or 28 days of ATG. There was no significant difference between the two arms of this protocol: 47% of all patients were clinically improved and 31% were transfusion independent at 3 months. Of the severely affected patients, 27% died before 3 months; most deaths occurred early in treatment. Factors associated with survival in severely affected patients included male sex, age less than 40 years, absolute neutrophil count greater than 200/microL, and idiopathic etiology. Neutrophil counts generally increased by 8 weeks after treatment, but patients continued to show improvement to 1 year posttreatment. In Group II, 44 patients with moderate or chronic severe aplastic anemia were randomized to receive either ten days of ATG or 3 months of high-dose nandrolone decanoate. No patient initially treated with androgens recovered, but 28% of ATG-treated cases achieved transfusion independence at 3 months. Group III consisted of patients with a variety of bone marrow failure syndromes. Patients with pancytopenia and cellular bone marrow showed response rates similar to those of patients with chronic or moderate aplastic anemia.

Anemia, Aplastic↗

Responsive estrogen-induced aplastic anemia in a dog.

A 4-year-old Airedale Terrier that had developed estrogen-induced aplastic anemia had a complete recovery after supportive treatment and weekly administrations of nandrolone decanoate. The anemia was induced iatrogenically by administration of estradiol cypionate (2 mg, IM each time) at 48- to 72-hour intervals. Clinical signs included lethargy, anorexia, and weakness; hemoglobin was 6.8 g/dl, PCV was 21%, and WBC was 1,500/dl. Supportive treatment included blood transfusions and administration of antibiotics, corticosteroids, and vitamins. Hematologic values returned to normal by day 81, and the dog has remained healthy for one year after treatment.

Anabolic Agents↗

Effects of nandrolone therapy on forearm bone mineral content in osteoporosis.

Forearm bone mineral content (BMC) was measured sequentially on and off anabolic steroid therapy in 52 postmenopausal women with osteoporosis. The steroid used was nandrolone decanoate in a dose of 50 mg every two weeks by intramuscular injection. In 16 of the patients nandrolone was given first (for 6.2 +/- 0.6 months) followed by a control period (6.1 +/- 1.0 months) and in 36 there was an initial control period (9.5 +/- 1.1 months) followed by nandrolone (for 5.8 +/- 0.4 months). Any other therapy was continued unchanged during both treatment and control periods. There was a significant rise in BMC on nandrolone (p less than 0.001) and a nonsignificant fall in BMC off nandrolone. The difference between the rates of change on and off nandrolone was highly significant (+53 vs. -7 mg/cm/year; p less than 0.001).

Aged↗