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Inhibition of Yeast Growth by Octanoic and Decanoic Acids Produced during Ethanolic Fermentation.

The inhibition of growth by octanoic or decanoic acids, two subproducts of ethanolic fermentation, was evaluated in Saccharomyces cerevisiae and Kluyveromyces marxianus in association with ethanol, the main product of fermentation. In both strains, octanoic and decanoic acids, at concentrations up to 16 and 8 mg/liter, respectively, decreased the maximum specific growth rate and the biomass yield at 30 degrees C as an exponential function of the fatty acid concentration and increased the duration of growth latency. These toxic effects increased with a decrease in pH in the range of 5.4 to 3.0, indicating that the undissociated form is the toxic molecule. Decanoic acid was more toxic than octanoic acid. The concentrations of octanoic and decanoic acids were determined during the ethanolic fermentation (30 degrees C) of two laboratory media (mineral and complex) by S. cerevisiae and of Jerusalem artichoke juice by K. marxianus. Based on the concentrations detected (0.7 to 23 mg/liter) and the kinetics of growth inhibition, the presence of octanoic and decanoic acids cannot be ignored in the evaluation of the overall inhibition of ethanolic fermentation.

Journal Article↗

Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis.

Haloperidol decanoate is a depot preparation of haloperidol, a commonly used butyrophenone derivative with antipsychotic activity. Haloperidol decanoate has no intrinsic activity: its pharmacodynamic actions are those of haloperidol--primarily that of central antidopamine activity. The monthly administered depot formulation has several clinical and practical advantages over oral haloperidol: better compliance and more predictable absorption; more controlled plasma concentrations; fewer extrapyramidal side effects; less frequent reminders of condition; and reduced medical workload. In open and controlled studies, haloperidol decanoate has produced adequate maintenance or improvement of the condition of patients with psychoses (mainly schizophrenia) when an abrupt change from orally administered haloperidol or other antipsychotic drugs has been instituted. Limited comparative studies indicate that the depot and oral forms of haloperidol are equally effective, and that haloperidol decanoate is at least as effective as depot forms of fluphenazine, pipothiazine, flupenthixol and perphenazine in controlling the symptoms of psychosis. Extrapyramidal side effects and the need for concomitant anti-Parkinsonian drugs may be a problem, but may be less frequent than with oral haloperidol or other depot antipsychotics. Thus, haloperidol decanoate offers a useful alternative in the treatment of psychoses to orally administered haloperidol or to other depot antipsychotic drugs.

Haloperidol↗

Differential effects of haloperidol decanoate, a long-acting neuroleptic, in behavioral and biochemical tests.

The pharmacological activities of haloperidol decanoate in several behavioral and biochemical tests for neuroleptics were pursued to validate its clinical mode of action. Haloperidol decanoate itself was about 40 times less potent than haloperidol in inhibiting 3H-spiperone binding to rat striatum in vitro and its direct application into the cerebral ventricle of mice showed no effect on brain concentrations of dopamine metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC). When injected intramuscularly, haloperidol decanoate exhibited various behavioral and biochemical effects together with prolonged accumulation of the parent drug haloperidol in dopamine-rich areas of the brain, but there was a clear difference in the time-course patterns of the effects. Conditioned avoidance responses in mice and rats were suppressed for a long period of days in the time-course pattern parallel to the elevation of brain haloperidol levels; the effect reached the peak a couple of days after the treatment and remained there over a week with gradual recovery towards 1 month after the injection. On the other hand, tolerance developed as rapidly as within 7 days to the antagonistic effects on apomorphine-induced stereotyped behaviours in mice and rats and to prolactin-releasing activity in rats. Biochemically, there was a regional difference in the brain in the time-course of effect of haloperidol decanoate. Namely, the initial increase in dopamine metabolites was no longer seen in the striatum on day 21, whereas it still persisted in the frontal cortex. Thus, the present study has confirmed on the one hand the assumption that haloperidol decanoate is a pro-drug which itself has no neuroleptic activity and validated on the other hand the clinical results that it exhibits long-lasting antipsychotic activities with minimum and tolerable extrapyramidal and prolactin-related side effects.

Animals↗

Comparison of the effects of two lipophilic acids, hexachlorophene and decanoate, on Bacillus subtilis.

The minimal growth-inhibitory amount of either hexachlorophene (HCP) or decanoate stopped growth, respiration, adenosine 5'-triphosphate synthesis, and amino acid transport of Bacillus subtilis in a culture containing amino acids and citrate as carbon sources. The electron transport system was not affected by this dose. Addition of 27.8 mM glucose or 10 mM malate to an inhibited culture did not reverse the binding of HCP or decanoate to the cells, but it allowed resumption of growth, respiration, and adenosine 5'-triphosphate synthesis, as the glucose or malate then supplied the needed carbon. The addition of glucose or malate did not reverse amino acid transport inhibition caused by decanoate, but it did reverse that due to HCP. However, if the dose of HCP was raised in the presence of glucose or malate, only growth and amino acid transport were affected; this indicates that both HCP and decanoate act at their minimal growth inhibitory doses by inhibiting substrate transport. As active transport of amino acids and ketoacids depends on the proton gradient and the membrane potential of the cells, we conclude that the primary effect of these lipophilic acids is the destruction of the proton-motive force.

Adenosine Triphosphate↗

The enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation.

The ability of an anabolic steroid, nandrolone decanoate, to increase committed topoietic stem cell (CFU-gm, CFU-e, and BFU-e) colony formation after sublethal irradiation was evaluated. Immediately after receiving whole body irradiation and on the next two days, each mouse was injected intraperitoneally with nandrolone decanoate (1.25 mg) in propylene glycol. Irradiated control mice received only propylene glycol. Compared to controls, drug-treated mice showed marked peripheral blood leukocytosis and more stable packed red cell volume. Drug-treated mice also demonstrated increased erythropoiesis, as CFU-e/BFU-e concentrations from both marrow (9% to 581%) and spleen (15% to 797%) were elevated. Granulopoiesis was increased similarly, as CFU-gm concentrations from marrow (38% to 685%) and spleen (9% to 373%) were elevated. These results demonstrate that nandrolone decanoate enhances hematopoietic stem cell recovery after sublethal whole body irradiation. This suggests that following hematopoietic suppression, nandrolone decanoate may stimulate the recovery of hematopoiesis at the stem cell level and in peripheral blood.

Animals↗

Nandrolone decanoate treatment affects sarcoplasmic reticulum Ca(2+) ATPase function in skinned rat slow- and fast-twitch fibres.

The effects of anabolic-androgenic steroid administration on the function of the sarcoplasmic reticulum (SR) pump were investigated in chemically skinned fibres from the extensor digitorum longus (EDL) and soleus muscles of sedentary rats. Twenty male rats were divided into two groups, one group received an intramuscular injection of nandrolone decanoate (15 mg x kg(-1)) weekly for 8 weeks, the second received similar weekly doses of vehicle (sterile peanut oil). Compared with control muscles, nandrolone decanoate treatment reduced SR Ca(2+) loading in EDL and soleus fibres by 49% and 29%, respectively. In control and treated muscles, the rate of Ca(2+) leakage depended on the quantity of Ca(2+) loaded. Furthermore, for similar SR Ca(2+) contents, the Ca(2+) leakage rate was not significantly modified by nandrolone decanoate treatment. Nandrolone decanoate treatment thus affects Ca (2+) uptake by the SR in a fibre-type dependent manner.

Anabolic Agents↗

Treatment of postmenopausal osteoporosis: is the anabolic steroid nandrolone decanoate a candidate?

Thirty-nine postmenopausal women (aged 55-75 years) with at least one osteoporotic fracture were allocated to one year of treatment with the anabolic steroid nandrolone decanoate (50 mg i.m. every 3 weeks) or placebo injection. Both groups also received a daily intake of 500 mg calcium. Thirty-six women (92%) completed the study. In the nandrolone decanoate-treated group the fat corrected bone mineral content in the proximal part of the distal forearm (measured by single photon absorptiometry) showed a significant increase of 3% compared with placebo (P less than 0.01), and the same tendency was seen in the bone mineral content of the distal part of the distal forearm and density of the lumbar spine (measured by dual photon absorptiometry). However, this did not reach significance. In the placebo group all bone mineral measurements remained unchanged. The biochemical estimates of bone formation (plasma bone Gla protein (BGP), serum alkaline phosphatase) and whole body retention (WBR) of 99mTc-diphosphonates were not statistically significantly changed by the nandrolone decanoate therapy. We conclude that treatment with nandrolone decanoate does increase the bone mineral content; however, this may not be due to a direct increase in bone formation. The mechanism may theoretically be a combination of decreased bone resorption and increased muscle mass, which both play a beneficial role in conserving bone.

Aged↗

Influence of the diet on the portal and lymph transport of decanoic acid in rats. Simultaneous study of its mucosal catabolism.

The absorption route of decanoic acid, a medium chain fatty acid, infused in the intestinal lumen in the presence and absence of long chain fatty acids, has been analyzed. Ex vivo perfusion of isolated intestinal loop and intestinal lymph fistula was the technique used. Decanoic acid infused alone was essentially transported through the portal system. If infused in association with monopalmitin, oleic or palmitic acid, up to 3% of decanoic acid could be diluted in the lymph. Moreover, decanoic acid oxidation by the mucosa increased significantly with palmitic acid and in contrast decreased with oleic acid. These data show that both intestinal absorption processes and mucosal oxidation of the medium chain fatty acids are modulated by the lipid components of the diet.

Animals↗

Bone mineral content, cortical thickness and fracture rate in osteoporotic women after withdrawal of treatment with nandrolone decanoate, 1-alpha hydroxyvitamin D3, or intermittent calcium infusions.

Twenty-six post-menopausal osteoporosis patients were studied prospectively over a 2-yr period after the cessation of 2 yr of treatment with either nandrolone decanoate (anabolic steroid), 1 alpha hydroxyvitamin D3 or intermittent calcium infusions, the total observation period being 4 yr. Serial evaluations of bone mineral content in the radius, cortical thickness of the metacarpals and spinal roentgenograms were obtained. Nine patients who had been treated with 50 mg nandrolone decanoate every three weeks did not lose bone from the radius or the metacarpals during the 2 yrs following withdrawal of therapy. Eight patients who had received 1 microgram/day of oral 1 alpha hydroxyvitamin D3 retained a positive bone mineral content in the radius but lost cortical thickness from the metacarpals after withdrawal of therapy. Nine patients who had been treated with intermittent calcium infusions over 12 consecutive days annually did not lose further bone mineral content from the radius, but did lose cortical thickness at the expected rate during the 2-yr post-treatment period. The fracture rate at the end of the 4-yr observation period was 40% lower in the nandrolone decanoate group than in the 1-alpha-hydroxyvitamin D3 and calcium infusion groups. The results of this study indicate that, in contrast to oestrogen and calcium therapy, nandrolone decanoate and 1-alpha-hydroxyvitamin D3 have lasting beneficial effects, and that data obtained by photon absorptiometry do not always coincide with those obtained by radiogrammetry. These findings are highly relevant to the design of future therapeutic trials.

Aged↗

Effect of nandrolone decanoate and 1-alpha-hydroxy-calciferol on patients with vertebral osteoporotic collapse. A double-blind clinical trial.

Eighty-eight postmenopausal women with at least one vertebral collapse were randomly assigned to two groups of 44 patients each. All patients were treated for a period of 12 months with 50 mg of nandrolone decanoate every 3 weeks or 1 microgram of 1-alpha-hydroxy-calciferol daily. Both groups received an identical placebo of the inactive drug. Pain intensity was significantly decreased in the nandrolone group and mobility was improved. Patients treated with vitamin D metabolite had also a beneficial but less obvious clinical result. Bone mineral measurements showed an increase of 5% in the nandrolone decanoate group, but a 2.5% decrease in the vitamin D metabolite group. Biochemical results showed a significant hypercalciuric effect of vitamin D metabolite, while nandrolone decanoate caused a reduction in calcium/creatinine excretion. No difference in serum lipids was found during the annual treatment in both groups. It is concluded that nandrolone decanoate has a beneficial effect in clinical symptoms, bone mineral density and biochemical parameters in patients with established osteoporotic vertebral fractures.

Aged↗

Nandrolone decanoate reduces serum lipoprotein(a) concentrations in hemodialysis patients.

We have studied the changes in the lipid profile of 14 chronic hemodialysis patients receiving a 6-month cycle of nandrolone decanoate as treatment for anemia. Nandrolone decanoate was administered in a weekly intramuscular dose of 200 mg and resulted in an increase in the hemoglobin concentration (baseline, 7.9 +/- 0.9 g/dL; month 6, 10.8 +/- 1.7 g/dL; P < 0.001, ANOVA) and also produced relevant modifications in the lipid concentrations. The most significant finding was a decrease in the concentration of lipoprotein(a) [Lp(a)]: baseline, 19.8 mg/dL (median), month 2, 10.6 mg/dL; month 4, 8.7 mg/dL; and month 6, 7.1 mg/dL (P < 0.001, Friedman). Other lipid changes induced by nandrolone decanoate were an increase in the concentrations of apolipoprotein B (P < 0.02, ANOVA) and triglyceride (P = NS, ANOVA) and a decrease of high-density lipoprotein (HDL) cholesterol (P < 0.001, ANOVA) and apolipoprotein A-I (P = NS, ANOVA). The decrease in HDL cholesterol was at the expense of the HDL2 cholesterol subfraction, whereas HDL3 remained unchanged. These lipid modifications were reversible; 4 months after nandrolone decanoate withdrawal, the lipid concentrations were similar to the basal values. The changes in Lp(a) levels did not correlate with those of hemoglobin or the other lipid parameters, suggesting that the underlying mechanisms are unrelated. Our findings could be clinically relevant if confirmed by further studies.

Aged↗

Effects of nandrolone decanoate compared with placebo or testosterone on HIV-associated wasting.

Objectives Current research is unclear about the most effective pharmacological agents for managing the loss of weight and fat-free mass common in HIV/AIDS. The aim of this study was to compare nandrolone decanoate with placebo and testosterone. Methods The study was a multicentre randomized double-blind placebo-controlled trial. Three hundred and three adult HIV-positive male patients with a weight loss of 5-15% in the last 12 months, or a body mass index of 17-19 kg/m(2), or a body cell mass/height ratio lower than 13.5 kg/m, were randomly assigned to receive nandrolone decanoate (150 mg), testosterone (250 mg) or placebo intramuscularly every 2 weeks for 12 weeks. Fat-free mass, weight, immune markers and perception of treatment were the main outcome measures. Results Treatment with nandrolone resulted in significantly greater increases in fat-free mass [mean increase 1.34 kg; 95% confidence interval (CI) 0.60; 2.08 kg] and in weight (mean increase 1.48 kg; 95% CI 0.82; 2.14 kg) compared with placebo. The mean increase in weight with nandrolone of 1.00 kg (95% CI 0.27; 1.74 kg) when compared with testosterone was significant, although the difference in fat free mass did not reach significance (mean increase 0.69 kg; 95% CI-0.13; 1.51 kg). Patient perception of benefit was significantly greater in the nandrolone group when compared with both the placebo and the testosterone groups. Conclusions Treatment with nandrolone decanoate increased body weight when compared with placebo and testosterone. Nandrolone decanoate treatment resulted in greater increases in fat-free mass than placebo and demonstrated a trend for a significant increase when compared with testosterone.

Adult↗

High doses of nandrolone decanoate reduce volume of testis and length of seminiferous tubules in rats.

Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely abused with the goal of improving athletic ability, appearance, or muscle mass. It has been shown that these compounds have adverse effects on human and animal physiology and sperm quality, but quantitative structural changes of the testis have received less attention. The present study was conducted to evaluate the effects of nandrolone decanoate, which is one of the AAS compounds, on testis weight and volume, diameter and length of seminiferous tubules in rats by unbiased stereological methods. Adult rats were divided into three groups. The first comprised control rats; the second and third groups received low and high doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for 14 weeks. After removal of the testis, stereological study of these tissues showed that the mean volume of testis and length of the seminiferous tubules in the animals that received high doses of nandrolone decanoate were reduced approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in comparison with the control group. It can be concluded that the high doses of nandrolone decanoate produce structural changes in the rat testis that remain 14 weeks after stopping injection of the drug.

Anabolic Agents↗

Nandrolone decanoate modulates cell cycle regulation in functionally overloaded rat soleus muscle.

Functionally overloading rat soleus muscle by synergist ablation induces a rapid increase in mass. Muscle remodeling during the first week of overload is critical for the overload-induced growth. Anabolic steroid modulation of this overload-induced remodeling response is not well understood. The purpose of this study was to determine whether pretreatment with nandrolone decanoate, a clinically administered anabolic steroid, alters muscle morphology and gene expression related to muscle growth during the initiation of functional overload in the rat soleus muscle. Adult (5 mo) male Fisher 344 x Brown Norway rats were randomly assigned to control (Sham), 3-day functional overload (OV), nandrolone decanoate administration (ND), or 3-day functional overload with nandrolone decanoate administration (OV+ND) treatment groups. Morphologically, OV increased the percentage of small (361%) and large (150%) fibers and expanded the ECM 50%. ND administration decreased the 3-day OV induction of small fibers 51% and nuclei associated with the ECM 20%. ND administration also attenuated the induction of cell cycle regulator p21 (64%) and myogenin (37%) mRNAs after 3 days of overload. These data demonstrate that nandrolone decanoate pretreatment can alter morphological and cell cycle regulator expression related to muscle growth at the onset of functional overload.

Anabolic Agents↗

Low neuroleptic serum levels in patients receiving fluphenazine decanoate.

The authors monitored serum levels of fluphenazine in nine patients following injections of fluphenazine decanoate ranging from 10 to 75 mg. Levels were detected by a radioreceptor assay based on the ability of the drug to complete with 3H-spiroperidol for binding to dopamine receptors in rat caudate membranes. Serum levels of fluphenazine were quite stable over a 2- to 3-week period following single intramuscular injections of the decanoate and correlated with injected dose. Following decanoate treatment serum levels of fluphenazine are substantially lower than levels observed for most other neuroleptics administered orally. This raises questions as to how fluphenazine decanoate can exert therapeutic actions.

Administration, Oral↗

[Effects on the bones of nandrolone decanoate therapy in postmenopausal osteoporosis].

In many patients with involutional osteoporosis, anabolic steroids may produce a rapid subjective improvement and pronounced reduction of complaints. In animal experiments it has been demonstrated that anabolic steroids can also have objective effect on bone tissue. Twenty postmenopausal osteoporotic patients have been randomly assigned to two different treatments: 10 patients were treated with 50 mg i.m. of nandrolone decanoate every 3 weeks for 12 months; 10 patients were treated with placebo. Both groups received an oral calcium supplement (1 g/day). Bone mineral content (BMC) was measured by dual photon absorptiometry before and after 1, 3, 6 and 12 months. Plasma alkaline phosphatase (A.Ph.) and urinary hydroxyproline/creatinine ratio (HOP) were measured at the same times. Intestinal calcium absorption was measured by the 47Ca oral test before and after treatment. In 4 patients of both groups a transiliac bone biopsy was performed before and after treatment. After 1 year there was a significant increase in the BMC of the lumbar spine in the group receiving calcium plus nandrolone decanoate. A progressive but not significant increase of A.Ph. was observed in the group treated with nandrolone decanoate. Radiocalcium absorption significantly increased in nandrolone treated patients. The histomorphometric study of bone demonstrated a significant increases in trabecular bone volume and in active osteoid surfaces in patients treated with nandrolone decanoate. Because the plasma A.Ph. tendes to increase with no change in bone resorption (as measured by urinary HOP) and the active osteoid surfaces significantly augment, we conclude that nandrolone therapy increases the bone formation rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Anabolic Agents↗

Long-term effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 or intermittent calcium infusion therapy on bone mineral content, bone remodeling and fracture rate in symptomatic osteoporosis: a double-blind controlled study.

A double-blind controlled study was performed in 60 patients with symptomatic osteoporosis with at least one vertebral crush fracture, comparing the effect of nandrolone decanoate, 1 alpha-hydroxyvitamin D3 and intermittent calcium infusions. Thirty-four out of 60 patients completed the 2 year observation period. Nandrolone decanoate statistically significantly increased the bone mineral content at the radius, reduced the endosteal bone loss at the metacarpals and statistically significantly reduced urinary calcium and hydroxyproline excretion. Calcium infusions and 1 alpha-hydroxyvitamin D3 inhibited further loss of bone mineral content, but endosteal bone loss continued. In the second year fracture rate was reduced in the nandrolone decanoate groups compared to the two other groups. We conclude that nandrolone decanoate is an active drug for increasing bone mineral content and reducing endosteal bone loss, while 1 alpha-hydroxyvitamin D3 and calcium infusions only stop further bone mineral loss at the radius but do not inhibit endosteal bone loss as measured at the metacarpals and that single photon absorptiometry and radiography are complementary in interpreting cortical bone mineral changes.

Aged↗

Monitoring octanoic and decanoic acids in plasma from children with intractable epilepsy treated with medium-chain triglyceride diet.

We describe a procedure for gas-chromatographic determination of n-octanoic and n-decanoic acids in 100 microL of plasma from children with intractable epilepsy treated with medium-chain triglyceride (MCT) diet. With n-nonanoic acid as the internal standard, the extraction efficiencies for octanoic and decanoic acids were 98 and 105%, respectively. Within-run CVs for octanoic acid at 0.5, 1.0, 2.5, 5.0, 7.5, and 10.0 micrograms/0.1 mL were 8.8, 7.9, 8.5, 6.5, 4.3, and 5.7%, respectively. For decanoic acid at identical concentrations, the CVs were 10.0, 7.4, 4.9, 4.0, 2.6, and 3.5%, respectively. For 10 children on MCT diet (45.9% of calories supplied as MCT) the mean concentrations of octanoic and decanoic acids were 44.2 and 27.0 mg/L, respectively. Presence of relatively "high" quantities of these acids in plasma may contribute to seizure control when MCT diet is prescribed for intractable childhood epilepsy.

Caprylates↗