Enhancement of committed hematopoietic stem cell colony formation by nandrolone decanoate after sublethal whole body irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gallicchio, V.S.; Chen, M.G.; Watts, T.D.

1984-11-01

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,more » 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.« less

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

PubMed

Noorafshan, Ali; Karbalay-Doust, Saied; Ardekani, Fakhrodin Mesbah

2005-02-01

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.

PDE7B is involved in nandrolone decanoate hydrolysis in liver cytosol and its transcription is up-regulated by androgens in HepG2.

PubMed

Strahm, Emmanuel; Rane, Anders; Ekström, Lena

2014-01-01

Most androgenic drugs are available as esters for a prolonged depot action. However, the enzymes involved in the hydrolysis of the esters have not been identified. There is one study indicating that PDE7B may be involved in the activation of testosterone enanthate. The aims are to identify the cellular compartments where the hydrolysis of testosterone enanthate and nandrolone decanoate occurs, and to investigate the involvement of PDE7B in the activation. We also determined if testosterone and nandrolone affect the expression of the PDE7B gene. The hydrolysis studies were performed in isolated human liver cytosolic and microsomal preparations with and without specific PDE7B inhibitor. The gene expression was studied in human hepatoma cells (HepG2) exposed to testosterone and nandrolone. We show that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate and nandrolone decanoate in liver cytosol. The gene expression of PDE7B was significantly induced 3- and 5- fold after 2 h exposure to 1 μM testosterone enanthate and nandrolone decanoate, respectively. These results show that PDE7B is involved in the activation of esterified nandrolone and testosterone and that the gene expression of PDE7B is induced by supra-physiological concentrations of androgenic drugs.

Anabolic androgenic steroid nandrolone decanoate reduces hypothalamic proopiomelanocortin mRNA levels.

PubMed

Lindblom, Jonas; Kindlundh, Anna M S; Nyberg, Fred; Bergström, Lena; Wikberg, Jarl E S

2003-10-03

Supratherapeutical doses of anabolic androgenic steroids (AASs) have dramatic effects on metabolism in humans, and also inhibit feeding and reduce the rate of body weight gain in rats. In order to test the hypothesis that the AAS metabolic syndrome is accompanied by alterations in the central melanocortin system, we evaluated body weight, food intake and hypothalamic agouti-related protein (AgRP) and proopiomelanocortin (POMC) mRNA levels following administration of different doses of the anabolic androgenic steroid nandrolone decanoate. In order to distinguish changes induced by the steroid treatment per se from those resulting from the reduced food intake and growth rate, we also compared the effect of nandrolone decanoate on AgRP and POMC mRNA expression with both normally fed, and food restricted control groups. We here report that administration of nandrolone specifically reduces arcuate nucleus POMC mRNA levels while not affecting the expression level of AgRP. The effect on POMC expression was not observed in the food restricted controls, excluding the possibility that the observed effect was a mere response to the reduced food intake and body weight. These results raise the possibility that some of the metabolic and behavioural consequences of AAS abuse may be the result of alterations in the melanocortin system.

Detection of nandrolone, testosterone, and their esters in rat and human hair samples.

PubMed

Höld, K M; Borges, C R; Wilkins, D G; Rollins, D E; Joseph, R E

1999-10-01

Nandrolone and testosterone are anabolic androgenic steroids occasionally abused by athletes. A sensitive, specific, and reproducible gas chromatography-mass spectrometry method for the quantitative determination of nandrolone, testosterone, and their esters in hair has been developed. The limits of quantitation of this method, based on 20 mg of hair, were 50 pg/mg for nandrolone and testosterone, 100 pg/mg for testosterone acetate, and 200 pg/mg for nandrolone-decanoate. Nandrolone-d3 and testosterone-d3 were used as internal standards. This method has been applied to the analysis of these compounds incorporated into rat and human hair. Male Long-Evans rats were given nandrolone decanoate 60 mg/kg intraperitoneally (i.p.) once daily for 10 days over a time period of 14 days. Two of the three rats contained nandrolone in the pigmented hair collected at day 21 at a concentration of 63 and 76 pg/mg, respectively. No drug was found in the corresponding nonpigmented hair. The rat hair samples that tested positive for nandrolone contained also nandrolone decanoate in concentrations of 0.9 and 1.2 ng/mg, respectively. In a separate experiment rats were given testosterone acetate 10 mg/kg i.p. once daily for five days. No testosterone or testosterone acetate was detected in the rat hair samples. Hair specimens were also obtained from four self-reported steroid users. The hair of two subjects were determined to be positive for testosterone in concentrations of 54 and 81 pg/mg. These data demonstrate that it is possible to detect the steroids nandrolone, testosterone, and nandrolone decanoate in hair after systemic administration.

Administration of the anabolic androgenic steroid nandrolone decanoate affects substance P endopeptidase-like activity in the rat brain.

PubMed

Magnusson, Kristina; Hallberg, Mathias; Högberg, Anna M S Kindlundh; Nyberg, Fred

2006-01-01

The effect of the anabolic androgenic steroid, nandrolone decanoate, on substance P endopeptidase-like activity was examined in adult male Sprague-Dawley rats. Nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) were administered by intramuscular injections during 14 days. Substance P endopeptidase, a predominantly cytosolic enzyme, generates the bioactive N-terminal fragment substance P(1-7) from the enzyme substrate substance P. Nandrolone decanoate significantly reduced the substance P endopeptidase-like activity compared to control animals in hypothalamus (43% reduction), caudate putamen (44%), substantia nigra (32%) and the ventral tegmental area (27%). It was previously reported that both hypothalamus and caudate putamen contained significantly higher levels of substance P after nandrolone administration. The higher concentration of substance P in these regions could to an extent be attributed to the reduction in substance P endopeptidase-like activity. This result elucidates the important role of peptidase activity in the regulation of the substance P transmitter system. The present study provides additional support for the hypothesis that alterations in the substance P system in certain brain areas may contribute to some of the personality changes reported in connection with AAS abuse.

Effects of nandrolone decanoate on the toxicity and anti-tumour action of CCNU and FU in murine tumours.

PubMed Central

Bibby, M. C.; Double, J. A.; Mughal, M. A.

1981-01-01

Pre-treatment with the anabolic steroid nandrolone decanoate (ND) increases the LD50 of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and 5-Fluorouracil (FU) in NMRI mice. Administration of ND did not affect the anti-tumour action of CCNU against a transplantable mouse adenocarcinoma of the colon (MAC 13) or the anti-tumour action of FU against MAC 26. In both tumour lines ND had no significant effect on tumour growth. These data suggest that an increase in the anti-tumour selectivity of these agents may be produced by pre-treatment with ND. PMID:7295514

Chronic administration of the anabolic androgenic steroid nandrolone alters neurosteroid action at the sigma-1 receptor but not at the sigma-2 or NMDA receptors.

PubMed

Elfverson, Martin; Johansson, Tobias; Zhou, Qin; Le Grevès, Pierre; Nyberg, Fred

2011-12-01

Studies have shown that anabolic androgenic steroids (AASs) can induce profound changes to mental health. Commonly reported psychiatric side effects among AAS users include aggression, anxiety, depression, drug abuse and cognitive disabilities. In experimental animals, many of these effects have been associated with alterations in a number of neurotransmitter systems. We have observed that chronic administration of the AAS nandrolone (nandrolone decanoate) can affect excitatory amino acids as well as monoaminergic and peptidergic pathways in a way that is compatible with nandrolone-induced behavioural changes. The aim of the present work was to further explore the mechanisms underlying nandrolone-induced effects, with a particular focus on components known to be involved in aggression and cognitive function. Male rats were given daily injections of nandrolone decanoate for 14 days and the effects on neurosteroid interactions with sites on the N-methyl-D-aspartyl (NMDA) and sigma receptors were examined. These receptors were chosen because of their involvement in aggressive and cognitive behaviors and the hypothesis that nandrolone might affect the brain via interaction with neurosteroids. Radiolabelled [³H]ifenprodil was used in the binding studies because of its significant affinity for the NMDA and sigma receptors. The results indicated that [³H]ifenprodil binds to both sigma-1 and sigma-2 sites and can be displaced to a certain extent from both sites by the neurosteroids pregnenolone sulphate (PS), pregnanolone sulphate (3α5βS) and dehydroepiandrosterone sulphate (DHEAS). The remainder of the [³H]ifenprodil was displaced from the sigma-1 site by the sigma-1 receptor-selective ligand (+)-SKF 10,047. Chronic nandrolone treatment changed the sigma-1 receptor target for the neurosteroids but not for ifenprodil. The sigma-2 receptor site was unaltered by treatment with nandrolone decanoate. The results also indicated that the neurosteroid-induced allosteric modulation of the NMDA receptor subunit NR2B was not affected by nandrolone treatment. We conclude that chronic treatment with nandrolone changes the affinity of the neurosteroids PS, 3α5βS and DHEAS at the sigma-1 site but not at the sites on the sigma-2 receptor or the NMDA receptor subunit NR2B. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cardiotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Vasilaki, Fotini; Tsitsimpikou, Christina; Tsarouhas, Konstantinos; Germanakis, Ioannis; Tzardi, Marias; Kavvalakis, Matthaios; Ozcagli, Eren; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-01-22

Abuse of anabolic androgenic steroids is linked to a variety of cardiovascular complications. The aim of our study was to investigate the possible cardiovascular effects of nandrolone decanoate on young rabbits using echocardiography, histology and monitoring of telomerase activity, oxidative stress and biochemical markers. Fourteen rabbits were divided into three administration groups and the control group. Doses of 4mg/kg and 10mg/kg of nandrolone decanoate, given intramuscularly and subcutaneously, two days per week for six months were applied. A 4-months wash-out period followed. Focal fibrosis and inflammatory infiltrations of cardiac tissue were observed in the high dose groups. Thiobarbituric acid-reactive species (TBARS) levels were significantly increased in the high dose groups, while catalase activity decreased. Myocardial Performance Index (MPI) is the main echocardiographic index primarily affected by nandrolone administration in rabbits. Despite the preserved systolic performance, histological lesions observed associated with distorted MPI values, point to diastolic impairment of the thickened myocardium due to nandrolone treatment. Oxidative stress accumulates and telomerase activity in cardiac tissue rises. Subcutaneous administration seems to be more deleterious to the cardiovascular system, as oxidative stress, telomerase activity and biochemical markers do not appear to return into normal values in the wash-out period. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nandrolone administration with or without strenuous exercise promotes overexpression of nephrin and podocin genes and induces structural and functional alterations in the kidneys of rats.

PubMed

Tofighi, Asghar; Ahmadi, Shima; Seyyedi, Seyyedeh Masoumeh; Shirpoor, Alireza; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini

2018-01-05

Among the various adverse effects of nandrolone administration with or without strenuous exercise, kidney abnormalities, where there are associations between nandrolone decanoate consumption, have not been well defined yet. The aim of this study was to investigate the effect of nandrolone decanoate intake with or without strenuous exercise on nephrin and podocin gene expressions, cystatin C, oxidative DNA damage, and histological changes in the kidneys of rats. Thirty-two male wistar rats were assigned into four groups, namely control, nandrolone, nandrolone with strenuous exercise, and strenuous exercise groups. After six weeks of treatment, the results revealed a significant increase in the nephrin and podocin gene expression, plasma cystatin C, and the amount of 8-OHdG in the kidney tissue; as well as a decrease in creatinine clearance in nandrolone and nandrolone with strenuous exercise groups compared to the control group. Moreover, compared to the control group, the nandrolone and the nandrolone with strenuous exercise groups, showed histological changes such as fibrosis and kidney tissue cells proliferation. These findings indicate that nandrolone induces kidney abnormalities, which may in part be associated with overexpression of nephrin and podocin genes mediated by oxidative stress, which was manifested in increased 8-OHdG in kidney tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Administration of Nandrolone Decanoate upon Aldosterone Concentration and Serum Na+/K+ Levels in Albino Mice.

PubMed

Chowdhury, Parmita; Mahanta, Rita

2017-01-01

This article is a study of adverse effects associated with the abuse of recreational drugs such as anabolic androgenic steroids. Nandrolone decanoate is one such drug often abused by athletes and bodybuilders seeking enhanced physical strength or appearance. The use of such steroids has increased dramatically over the years. The present study was conducted to investigate the impact of nandrolone decanoate when consumed at an abused dose, upon serum aldosterone concentration in albino mice. Sodium and potassium ion concentrations were also monitored with the same experimental dosage. 0.1ml of 25 mg Nandrolone decanoate was administered to the animals twice a week for a period of 90 days. Blood samples for obtaining the serum from both normal and treated group of animals were collected at an interval of 15 days upto the 90th day. The present investigation revealed a significant increase (p<0.01) in the serum aldosterone and sodium ion concentrations in the treated group of animals compared to that in the normal group. Potassium ion concentration in the treated group did not exhibit a significant alteration when compared with the untreated animals. From the above observation, nandrolone decanoate abuse could be suggested as one of the causes of aldosterone and electrolyte imbalance in the body that could possibly be a serious risk factor for cardiovascular related disorders. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enhanced hepatic and kidney cytochrome p-450 activities in nandrolone decanoate treated albino mice.

PubMed

Acharjee, B K; Mahanta, R

2009-04-01

Anabolic androgenic steroids are the xenobiotic substrates that are metabolized in the body by the protective enzyme systems. Mixed function oxygenase enzymes include a group of enzymes which play an essential role in the metabolism of a broad range of xenobiotics including endogenous and exogenous substrates. Cytochrome P-450, a member of mixed function oxygenase enzymes, plays an important role in oxidative metabolism of drugs and xenobiotics entering human body. Various anabolic steroids are found either to increase or decrease the activity of cytochrome P-450. However, effect of nandrolone decanoate, most commonly abused anabolic steroid, on cytochrome P-450 activity is still fragmentary. In the present study, albino mice were administered intramuscular 2.5 mg of nandrolone decanoate injection at 15 days interval. Cytochrome P-450 activity is determined by following the method of Omura and Sato (1964) in liver and kidney tissues of both normal and experimental groups upto 90 days. Investigation shows a significant (p <0.01) increase of cytochrome P-450 (nmol/mg) activity in liver tissue as compared to that of kidney tissues. A tissue specific and dose specific increase of cytochrome P-450 activity is observed. Mean cytochrome P-450 is found highest in liver tissue on 45(th) day whereas the activity in kidney tissue is noticed on 90(th) day of treatment. From the above observation, nandrolone decanoate can be suggested as a potent inducer of cytochrome P-450 activity like other anabolic steroids.

Atypical excretion profile and GC/C/IRMS findings may last for nine months after a single dose of nandrolone decanoate.

PubMed

Palonek, Elzbieta; Ericsson, Magnus; Gårevik, Nina; Rane, Anders; Lehtihet, Mikael; Ekström, Lena

2016-04-01

The use of the anabolic androgenic steroid nandrolone and its prohormones is prohibited in sport. A common route of nandrolone administration is intramuscular injections of a nandrolone ester. Here we have investigated the detection time of nandrolone and 19-norandrosterone and 19-noretiocholanolone metabolites in eleven healthy men after the administration of a 150 mg dose of nandrolone decanoate. The urinary concentrations of nandrolone and the metabolites were monitored by GC-MS/MS for nine months and in some samples the presence of 19-norandrosterone was confirmed by GC/C/IRMS analysis. The participants were genotyped for polymorphisms in PDE7B1 and UGT2B15 genes previously shown to influence the activation and inactivation of nandrolone decanoate. There were large inter-individual variations in the excretion rate of nandrolone and the metabolites, although not related to genetic variations in the UGT2B15 (rs1902023) and PDE7B1 (rs7774640) genes. After the administration, 19-norandrosterone was found at 2-8-fold higher concentrations than 19-noretiocholanolone. We showed that nandrolone doping can be identified 4 and 9 months after the injection of only one single dose in six and three individuals, respectively. We also noted that GC/C/IRMS confirms the presence of exogenous 19-norandrosterone in the urine samples, showing δ13 values around -32 ‰. This was true even in a sample that was not identified as an atypical finding after the GC-MS/MS analysis further showing the power of using GC/C/IRMS in routine anti-doping settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Therapeutic effects of nandrolone decanoate, tibolone, lynestrenol and ethylestrenol on Sjögren's syndrome-like disorder in NZB/W mice.

PubMed Central

Verheul, H A; Schot, L P; Schuurs, H W

1986-01-01

Growth of mononuclear cell infiltration in submandibular glands is significantly inhibited by Org OD14 (tibolone), lynestrenol and ethylestrenol given orally to New Zealand Black/White (NZB/W) mice from 26 weeks of age onwards. In addition, the extent of already established mononuclear cell infiltrations is significantly inhibited and reduced by nandrolone decanoate injected from 43 weeks of age onwards. Tibolone and nandrolone decanoate are the most potent of the four drugs. The therapeutic effect of these four steroids on the Sjögren's syndrome-like disorder in NZB/W mice is not related to their endocrine activities. Images Fig. 1 PMID:3742875

Use of Nandrolone Decanoate in Treatment of Pure Red Cell Aplasia Secondary to Diclofenac Administration: A Case Report.

PubMed

de Marchi, Paula Nassar; Sueur Vieira, André Nanny Le; Antunes Ribeiro, José Francisco; Geraldes, Silvano Salgueiro; Rodrigues Ramos, Paulo Roberto; Melchert, Alessandra; Guimarães-Okamoto, Priscylla Tatiana Chalfun

2017-03-01

Pure red cell aplasia (PRCA) is a disorder that leads to a nonregenerative anemia that results from erythroid precursors failing to reach maturity in the bone marrow, whereas the numbers of mature myeloid and megakaryocytic cells remain normal. PRCA can be induced by autoimmune processes, infections, drugs, toxins, and radiation, and is diagnosed by a bone marrow cytology examination after excluding the most common causes of nonregenerative anemia. Immunosuppressive therapies are used to treat PRCA, and usually involve the use of glucocorticoids, cyclosporin, or azathioprine. Alternatively, although little studied in veterinary medicine, drugs which stimulate bone marrow (e.g., nandrolone decanoate) have been mentioned as possible therapeutic agents. A case of PRCA that presented at the Veterinary Teaching Hospital of the Faculty of Veterinary Medicine and Animal Science (UNESP)-Botucatu, Brazil showed a good therapeutic response to weekly administration of nandrolone decanoate. Therefore, it was concluded that bone marrow stimulants might improve the quality of life of PRCA patients, provided they are used with caution and under close clinical supervision. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

Schot, L P; Verheul, H A; Schuurs, A H

1984-01-01

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. Images Fig. 1 PMID:6467680

The impact of chronic nandrolone decanoate administration on the NK1 receptor density in rat brain as determined by autoradiography.

PubMed

Hallberg, Mathias; Kindlundh, Anna M S; Nyberg, Fred

2005-07-01

Adult male Sprague-Dawley rats were treated with the anabolic androgenic steroid nandrolone decanoate (15 mg/kg day) or oil vehicle (sterile arachidis oleum) during 14 days. The effect on the densities of the neurokinin NK1 receptor in brain was examined with autoradiography. An overall tendency of attenuation of NK1 receptor density was observed after completed treatment with nandrolone decanoate. The density of the NK1 receptor was found to be significantly lower compared to control animals in the nucleus accumbens core (37% density reduction), in dentate gyrus (26%), in basolateral amygdaloid nucleus (23%), in ventromedial hypothalamic nucleus (36%), in dorsomedial hypothalamic nucleus (43%) and finally in the periaqueductal gray (PAG) (24%). In the cortex region, no structures exhibited any significant reduction of NK1 receptor density. This result provides additional support to the hypothesis that substance P and the NK1 receptor may be involved as important components that participate in mediating physiological responses including the adverse behaviors often associated with chronically administrated anabolic androgenic steroids in human.

Nandrolone inhibits MMP-2 in the left ventricle of rats.

PubMed

Marqueti, R C; Micocci, K C; Leite, R D; Selistre-de-Araujo, H S

2012-03-01

The indiscriminate use of anabolic-androgenic steroids has been shown to induce left ventricular dysfunctions. The main objective of the present study was to investigate the effects of nandrolone decanoate on matrix metalloprotease (MMP-2) activity and protein level in the left ventricle (LV) of rats after 7 weeks of mechanical load exercise. Wistar rats were grouped into: sedentary (S); nandrolone decanoate-treated sedentary (AAS); trained without AAS (T) and trained and treated with AAS (AAST). Exercised groups performed a 7-weeks water-jumping program. Training significantly increased the MMP-2 activity by zymography and the protein level by Western blotting analysis. However, the AAS treatment abolished both the increase in MMP activity and protein level induced by exercise. These results suggest that AAS may impair cardiac tissue remodeling which may lead to the heart malfunction. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial.

PubMed

Mulligan, Kathleen; Zackin, Robert; Clark, Rebecca A; Alston-Smith, Beverly; Liu, Tun; Sattler, Fred R; Delvers, Thomas B; Currier, Judith S

2005-03-14

Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.

Ovarian histology and follicular score in female rats treated with nandrolone decanoate and submitted to physical effort.

PubMed

Cherici Camargo, Isabel Cristina; Barreiros de Souza, Roberta; de Fátima Paccola Mesquita, Suzana; Chuffa, L G A; Frei, F

2009-09-01

The study was conducted to analyze the histology of the ovaries of adults rats treated with steroids, and submitted or not to physical effort. The control group consisted of females submitted to physical effort and sedentary females, both of which received a physiological solution of 0.9% saline. Treated females, sedentary or not, received 6 mg/kg of body weight of nandrolone decanoate. The steroid and physiological solution were administered intraperitoneally, with a single injection per week for 4 consecutive weeks. The applied physical effort was swimming (20 minutes daily, 5 days/week, for the 4 weeks of treatment). Serial sections (5 mum) of ovaries were prepared for histological evaluation and follicular score. The weight of ovaries and hypophysis, the number of antral and atretic follicles, and the area of corpus luteum were all affected by the steroids. In the ovaries of the control groups, well-developed corpus luteum was observed. In the treated groups, the cortical stroma was occupied by ovarian interstitial tissue. The females treated with steroids presented estral acyclicity. The use of nandrolone decanoate, whether associated with physical effort or not, affected the morphological pattern of the ovaries.

Effect of nandrolone decanoate on skeletal muscle repair.

PubMed

Piovesan, R F; Fernandes, K P S; Alves, A N; Teixeira, V P; Silva Junior, J A; Martins, M D; Bussadori, S K; Albertini, R; Mesquita-Ferrari, R A

2013-01-01

This study analyzed the effect of nandrolone decanoate (ND) on muscle repair and the expression of myogenic regulatory factors following cryoinjury in rat skeletal muscle. Adult male Wistar rats were randomly divided into 4 groups: control group, sham group, cryoinjured group treated with ND and non-injured group treated with ND. Treatment consisted of subcutaneous injections of ND (5 mg/kg) twice a week. After sacrifice, the tibialis anterior muscle was removed for the isolation of total RNA and analysis of myogenic regulatory factors using real-time PCR as well as morphological analysis using the hematoxylin-eosin assay. There was a significant increase in MyoD mRNA after 7 days and in myogenin mRNA after 21 days in the cryoinjured ND group in comparison to other groups in the same period. The morphological analysis revealed no edema or myonecrosis after 7 days as well as no edema or inflammatory infiltrate after 14 days in the cryoinjured ND group. In conclusion the anabolic steroid nandrolone decanoate can modulate the muscle repair process in rats following cryoinjury by influencing the expression of regulatory myogenic factors and phases of muscle repair. © Georg Thieme Verlag KG Stuttgart · New York.

Chronic nandrolone decanoate exposure during adolescence affects emotional behavior and monoaminergic neurotransmission in adulthood.

PubMed

Rainer, Quentin; Speziali, Simona; Rubino, Tiziana; Dominguez-Lopez, Sergio; Bambico, Francis Rodriguez; Gobbi, Gabriella; Parolaro, Daniela

2014-08-01

Nandrolone decanoate, an anabolic androgen steroid (AAS) illicitly used by adult and adolescent athletes to enhance physical performance and body image, induces psychiatric side effects, such as aggression, depression as well as a spectrum of adverse physiological impairments. Since adolescence represents a neurodevelopmental window that is extremely sensitive to the detrimental effects of drug abuse, we investigated the long-term behavioral and neurophysiological consequences of nandrolone abuse during adolescence. Adolescent rats received daily injections of nandrolone decanoate (15 mg/kg, i.m.) for 14 days (PND 40-53). At early adulthood (PND 68), forced swim, sucrose preference, open field and elevated plus maze tests were performed to assess behavioral changes. In vivo electrophysiological recordings were carried out to monitor changes in electrical activity of serotonergic neurons of the dorsal raphe nucleus (DRN) and noradrenergic neurons of the locus coeruleus (LC). Our results show that after early exposure to nandrolone, rats display depression-related behavior, characterized by increased immobility in the forced swim test and reduced sucrose intake in the sucrose preference test. In addition, adult rats presented anxiety-like behavior characterized by decreased time and number of entries in the central zone of the open field and decreased time spent in the open arms of the elevated plus maze. Nandrolone decreased the firing rate of spontaneously active serotonergic neurons in the DRN while increasing the firing rate of noradrenergic neurons in the LC. These results provide evidence that nandrolone decanoate exposure during adolescence alters the emotional profile of animals in adulthood and significantly modifies both serotonergic and noradrenergic neurotransmission. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cytoarchitecture of steroid dependent target tissues after testosterone administration compared to nandrolone decanoate in castrated rats in the aim of Hershberger bio test.

PubMed

Cristina, Romeo Teodor; Hanganu, Flavia; Brezovan, Diana; Dumitrescu, Eugenia; Muselin, Florin; Chiurciu, Viorica; Stancu, Adrian Constantin; Pentea, Marius Cristian; Motoc, Andrei Gheorghe Marius

2014-01-01

The objective was the cytoarchitecture evaluation of known steroid dependent target tissues after administering of testosterone, compared to action of its more active ester, nortestosterone (nandrolone decanoate) in castrated rat males in the aim of Hershberger bio test. Study was performed on 30 castrated male Wistar rats, aged between 35 and 39 days, in peripubertal period, divided into five groups. Androgen doses administration begun at the rats' age of 49 days. Animals were injected i.m., daily, for 10 consecutive days as follows: Aquatest (Balkan Pharmaceuticals Ltd., Moldova) testosterone aqueous solution: Testosterone I group (0.4 mg/animal); Testosterone II (0.8 mg/animal); (Deca-Durabolin, Balkan Pharmaceuticals); nandrolone decanoate oily solution: Nortestosterone I (1.5 mg/kg body weight); Nortestosterone II (7.5 mg/kg body weight) and Control (White sesame oil, Manicos, Romania, 0.1 mL/animal). Gonadectomy (GDX) induced modifications of target tissues wet weight accompanied by important modifications in cytoarchitecture. Changes following exogenous administration of testosterone and nortestosterone decanoate were found in: liver (granular dystrophy, mega-mitochondria, tubular intumescences), prostate (increasing of the structural elements), seminal vesicles (hyalinosis, thickening of cell walls and the hyaline presence), levator ani-bulbo-cavernosus muscle (muscle fibbers dilacerations), bulbourethral glands (muscular fibbers rarefaction by fluid accumulation) demonstrating the disruptor activity especially for overdosed nandrolone decanoate.

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

PubMed

Bagchus, Wilma M; Smeets, Jean M W; Verheul, Herman A M; De Jager-Van Der Veen, Suzanne M; Port, Andreas; Geurts, T B Paul

2005-05-01

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.

The impact of nandrolone decanoate on the central nervous system.

PubMed

Busardò, Francesco P; Frati, Paola; Sanzo, Mariantonia Di; Napoletano, Simona; Pinchi, Enrica; Zaami, Simona; Fineschi, Vittorio

2015-01-01

Nandrolone is included in the class II of anabolic androgenic steroids (AAS) which is composed of 19-nor-testosterone-derivates. In general, AAS is a broad and rapidly increasing group of synthetic androgens used both clinically and illicitly. AAS in general and nandrolone decanoate (ND) in particular have been associated with several behavioral disorders. The purpose of this review is to summarize the literature concerning studies dealing with ND exposure on animal models, mostly rats that mimic human abuse systems (i.e. supraphysiological doses). We have focused in particular on researches that have investigated how ND alters the function and expression of neuronal signaling molecules that underlie behavior, anxiety, aggression, learning and memory, reproductive behaviors, locomotion and reward.

The effect of local use of nandrolone decanoate on rotator cuff repair in rabbits.

PubMed

Papaspiliopoulos, Athanasios; Papaparaskeva, Kleo; Papadopoulou, Eleni; Feroussis, John; Papalois, Apostolos; Zoubos, Aristedes

2010-08-01

There is still controversy about the effect of anabolic steroid on connective tissue. This study examines the hypothesis that the local use of nandrolone decanoate, an anabolic steroid on rotator cuff, facilitates the healing process when used in combination with surgical repair. Forty-eight male rabbits were divided in four groups with anabolic steroids (Nandrolone Decanoate 10 mg/kg) and immobilization as variables. The groups were the following: first group, nonsteroid use-immobilization (NSI); second group, nonsteroid use-nonimmobilization (NSNI); third group, steroid use-immobilization (SI); fourth group steroid use-nonimmobilization (SNI). Every rabbit underwent a rotator cuff incision and reconstruction. Fifteen days later the tendons were sent for biomechanical and histological evaluation. Groups that did not receive anabolic steroids showed better healing and more tendon strength in comparison to groups that received anabolic steroids. Microscopic examination of specimens from the groups without the use of anabolic steroid showed extensive fibroblastic activity whereas the specimens from those groups with anabolic steroid use showed focal fibroblastic reaction and inflammation. Immobilization provided better results in the groups with anabolic steroid use but it did not influence healing in groups without steroids. The effect of local nandrolone decanoate use on a rotator cuff tear is detrimental, acting as a healing inhibitor.

Chronic nandrolone administration promotes oxidative stress, induction of pro-inflammatory cytokine and TNF-α mediated apoptosis in the kidneys of CD1 treated mice.

PubMed

Riezzo, Irene; Turillazzi, Emanuela; Bello, Stefania; Cantatore, Santina; Cerretani, Daniela; Di Paolo, Marco; Fiaschi, Anna Ida; Frati, Paola; Neri, Margherita; Pedretti, Monica; Fineschi, Vittorio

2014-10-01

Nandrolone decanoate administration and strenuous exercise increase the extent of renal damage in response to renal toxic injury. We studied the role played by oxidative stress in the apoptotic response caused by nandrolone decanoate in the kidneys of strength-trained male CD1 mice. To measure cytosolic enzyme activity, glutathione peroxidase (GPx), glutathione reductase (GR) and malondialdehyde (MDA) were determined after nandrolone treatment. An immunohistochemical study and Western blot analysis were performed to evaluate cell apoptosis and to measure the effects of renal expression of inflammatory mediators (IL-1β, TNF-α) on the induction of apoptosis (HSP90, TUNEL). Dose-related oxidative damage in the kidneys of treated mice is shown by an increase in MDA levels and by a reduction of antioxidant enzyme GR and GPx activities, resulting in the kidney's reduced radical scavenging ability. Renal specimens of the treated group showed relevant glomeruli alterations and increased immunostaining and protein expressions, which manifested significant focal segmental glomerulosclerosis. The induction of proinflammatory cytokine expression levels was confirmed by Western blot analysis. Long-term administration of nandrolone promotes oxidative injury in the mouse kidneys. TNF-α mediated injury due to nandrolone in renal cells appears to play a role in the activation of both the intrinsic and extrinsic apoptosis pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

Nandrolone decanoate and load increase remodeling and strength in human supraspinatus bioartificial tendons.

PubMed

Triantafillopoulos, Ioannis K; Banes, Albert J; Bowman, Karl F; Maloney, Melissa; Garrett, William E; Karas, Spero G

2004-06-01

To date, no studies document the effect of anabolic steroids on rotator cuff tendons. Controlled laboratory study. Anabolic steroids enhance remodeling and improve the biomechanical properties of bioartificially engineered human supraspinatus tendons. Bioartificial tendons were treated with either nandrolone decanoate (nonload, steroid, n = 18), loading (load, nonsteroid, n = 18), or both (load, steroid, n = 18). A control group received no treatment (nonload, nonsteroid [NLNS], n = 18). Bioartificial tendons' remodeling was assessed by daily scanning, cytoskeletal organization by staining, matrix metalloproteinase-3 levels by ELISA assay, and biomechanical properties by load-to-failure testing. The load, steroid group showed the greatest remodeling and the best organized actin cytoskeleton. Matrix metallo-proteinase-3 levels in the load, steroid group were greater than those of the nonload, nonsteroid group (P <.05). Ultimate stress and ultimate strain in the load, steroid group were greater than those of the nonload, nonsteroid and nonload, steroid groups (P <.05). The strain energy density in the load, steroid group was greater when compared to other groups (P <.05). Nandrolone decanoate and load acted synergistically to increase matrix remodeling and biomechanical properties of bioartificial tendons. Data suggest anabolic steroids may enhance production of bioartificial tendons and rotator cuff tendon healing in vitro. More research is necessary before such clinical use is recommended.

Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus.

PubMed

Sattler, F R; Jaque, S V; Schroeder, E T; Olson, C; Dube, M P; Martinez, C; Briggs, W; Horton, R; Azen, S

1999-04-01

This nonplacebo-controlled, open label, randomized study was conducted to test the hypotheses that pharmacological doses of nandrolone decanoate would increase lean body tissue, muscle mass, and strength in immunodeficient human immunodeficiency virus-infected men, and that these effects would be enhanced with progressive resistance training (PRT). Thirty human immunodeficiency virus-positive men with fewer than 400 CD4 lymphocytes/mm3 were randomly assigned to receive weekly injections of nandrolone alone or in combination with supervised PRT at 80% of the one-repetition maximum three times weekly for 12 weeks. Total body weight increased significantly in both groups (3.2 +/- 2.7 and 4.0 +/- 2.0 kg, respectively; P < 0.001), with increases due primarily to augmentation of lean tissue. Lean body mass determined by dual energy x-ray absorptiometry increased significantly more in the PRT group (3.9 +/- 2.3 vs. 5.2 +/- 5.7 kg, respectively; P = 0.03). Body cell mass by bioelectrical impedance analysis increased significantly (P < 0.001) in both groups (2.6 +/- 1.0 vs. 2.9 +/- 0.8 kg), but to a similar magnitude (P = NS). Significant increases in cross-sectional area by magnetic resonance imaging of total thigh muscles (1538 +/- 767 and 1480 +/- 532 mm2), quadriceps (705 +/- 365 and 717 +/- 288 mm2), and hamstrings (842 +/- 409 and 771 +/- 295 mm2) occurred with both treatment strategies (P < 0.001 for the three muscle areas); these increases were similar in both groups (P = NS). By the one-repetition method, strength increased in both upper and lower body exercises, with gains ranging from 10.3-31% in the nandrolone group and from 14.4-53.0% in the PRT group (P < 0.006 with one exception). Gains in strength were of significantly greater magnitude in the PRT group (P < or = 0.005 for all comparisons), even after correction for lean body mass. Thus, pharmacological doses of nandrolone decanoate yielded significant gains in total weight, lean body mass, body cell mass, muscle size, and strength. The increases in lean body mass and muscular strength were significantly augmented with PRT.

The anabolic steroid nandrolone enhances motor and sensory functional recovery in rat median nerve repair with long interpositional nerve grafts.

PubMed

Ghizoni, Marcos Flávio; Bertelli, Jayme Augusto; Grala, Carolina Giesel; da Silva, Rosemeri Maurici

2013-01-01

Recovery from peripheral nerve repair is frequently incomplete. Hence drugs that enhance nerve regeneration are needed clinically. To study the effects of nandrolone decanoate in a model of deficient reinnervation in the rat. In 40 rats, a 40-mm segment of the left median nerve was removed and interposed between the stumps of a sectioned right median nerve. Starting 7 days after nerve grafting and continuing over a 6-month period, we administered nandrolone at a dose of 5 mg/kg/wk to half the rats (n = 20). All rats were assessed behaviorally for grasp function and nociceptive recovery for up to 6 months. At final assessment, reinnervated muscles were tested electrophysiologically and weighed. Results were compared between rats that had received versus not received nandrolone and versus 20 nongrafted controls. Rats in the nandrolone group recovered finger flexion faster. At 90 days postsurgery, they had recovered 42% of normal grasp strength versus just 11% in rats grafted but not treated with nandrolone. At 180 days, the average values for grasp strength recovery in the nandrolone and no-nandrolone groups were 40% and 33% of normal values for controls, respectively. At 180 days, finger flexor muscle twitch strength was 16% higher in treated versus nontreated rats. Thresholds for nociception were not detected in either group 90 days after nerve grafting. At 180 days, nociceptive thresholds were significantly lower in the nandrolone group. Nandrolone decanoate improved functional recovery in a model of deficient reinnervation.

The Effects of Nandrolone Decanoate Along with Prolonged Low-Intensity Exercise on Susceptibility to Ventricular Arrhythmias.

PubMed

Binayi, Fateme; Joukar, Siyavash; Najafipour, Hamid; Karimi, Abdolah; Karimi, Ali; Abdollahi, Farzane; Masumi, Yaser

2016-01-01

We examined the influence of chronic administration of nandrolone decanoate with low-intensity endurance swimming exercise on susceptibility to lethal ventricular arrhythmias in rat. The animal groups included the control group, exercise group (EX), nandrolone group (Nan), vehicle group (Arach), trained vehicle group (Arach + Ex) and trained nandrolone group (Nan + Ex) that treated for 8 weeks. Then, arrhythmia induction was performed by intravenous infusion of aconitine and electrocardiogram recorded. Then, malondialdehyde (MDA), hydroxyproline (HYP) and glutathione peroxidase of heart tissue were measured. Chronic administration of nandrolone with low-intensity endurance swimming exercise had no significant effect on blood pressure, heart rate and basal ECG parameters except RR interval that showed increase (P < 0.05). Low-intensity exercise could prevent the incremental effect of nandrolone on MDA and HYP significantly. It also increased the heart hypertrophy index (P < 0.05) and reduced the abating effect of nandrolone on animal weighting. Nandrolone along with exercise significantly increased the duration of VF (P < 0.05) and reduced the VF latency (P < 0.05). The findings suggest that chronic co-administration of nandrolone with low-intensity endurance swimming exercise to some extent facilitates the occurrence of ventricular fibrillation in rat. Complementary studies are needed to elucidate the involved mechanisms of this abnormality.

Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial.

PubMed

Sardar, Partha; Jha, Ayan; Roy, Deeptarka; Majumdar, Uddalak; Guha, Pradipta; Roy, Sabyasachi; Banerjee, Ramtanu; Banerjee, Amit Kumar; Bandyopadhyay, Dipanjan

2010-01-01

We aimed to compare therapeutic effects of intramuscular (IM) nandrolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome (AWS) with placebo control. In this randomized, double-blind, placebo-controlled, 12-week trial, 104 patients with AWS who satisfied our inclusion criteria were randomly allotted in a 2:2:1 ratio to the 3 intervention groups: nandrolone, testosterone, and placebo. We administered 150 mg nandrolone and 250 mg testosterone (both IM, biweekly). The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the nandrolone decanoate, testosterone, and placebo groups. Intent-to-treat analysis was done. The nandrolone group recorded maximum mean increase in weight (3.20 kg; post hoc P < .01 compared to placebo). Body mass index (BMI) of subjects in the nandrolone group had a significantly greater increase (mean = 1.28) compared to both testosterone (post hoc P < .05) and placebo (post hoc P < .01). Waist circumference and triceps skinfold thickness of patients on nandrolone showed similar results. Nandrolone also ensured a better quality of life. Patients with low testosterone level (<3 ng/mL) benefited immensely from nandrolone therapy, which increased their weight and BMI significantly compared to placebo (P < .05). Our trial demonstrates the superior therapeutic effects of nandrolone in male AWS patients, including the androgen deficient.

Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial.

PubMed

Johansen, Kirsten L; Painter, Patricia L; Sakkas, Giorgos K; Gordon, Patricia; Doyle, Julie; Shubert, Tiffany

2006-08-01

Patients who are on hemodialysis commonly experience muscle wasting and weakness, which have a negative effect on physical functioning and quality of life. The objective of this study was to determine whether anabolic steroid administration and resistance exercise training induce anabolic effects among patients who receive maintenance hemodialysis. A randomized 2 x 2 factorial trial of anabolic steroid administration and resistance exercise training was conducted in 79 patients who were receiving maintenance hemodialysis at University of California, San Francisco-affiliated dialysis units. Interventions included double-blinded weekly nandrolone decanoate (100 mg for women; 200 mg for men) or placebo injections and lower extremity resistance exercise training for 12 wk during hemodialysis sessions three times per week using ankle weights. Primary outcomes included change in lean body mass (LBM) measured by dual-energy x-ray absorptiometry, quadriceps muscle cross-sectional area measured by magnetic resonance imaging, and knee extensor muscle strength. Secondary outcomes included changes in physical performance, self-reported physical functioning, and physical activity. Sixty-eight patients completed the study. Patients who received nandrolone decanoate increased their LBM by 3.1 +/- 2.2 kg (P < 0.0001). Exercise did not result in a significant increase in LBM. Quadriceps muscle cross-sectional area increased in patients who were assigned to exercise (P = 0.01) and to nandrolone (P < 0.0001) in an additive manner. Patients who exercised increased their strength in a training-specific fashion, and exercise was associated with an improvement in self-reported physical functioning (P = 0.04 compared with nonexercising groups). Nandrolone decanoate and resistance exercise produced anabolic effects among patients who were on hemodialysis. Further studies are needed to determine whether these interventions improve survival.

Beneficial effects of nandrolone decanoate in wasting associated with HIV.

PubMed

Saha, Bibhuti; Rajadhyaksha, Girish C; Ray, Subrat K

2009-05-01

Recent studies have demonstrated the role of nandrolone decanoate (ND) in reversal of wasting associated with HIV infection. However, such studies in Indian scenario are lacking. Hence, the present study was planned with an objective to assess the effect of ND in patients of HIV-associated wasting in Indian subjects. The study was a prospective, randomised, multicentric, open labelled and comparative one in male HIV-infected subjects, aged between 18 and 65 years with involuntary weight loss of 10% over 12 months or 7.5% over 6 months or 5% over 3 months. The subjects were on stable antiretroviral therapy including at least 2 agents with CD, count > or =50 cells/microl. In the treatment group, ND (150 mg) intramuscularly every 2 weeks for 12 weeks was administered according to randomisation. Fat-free mass (FFM), body weight, CD4 count, and patient perception of treatment were the main outcomes measures. Of the 73 enrolled subjects, 69 completed study duration of 12 weeks. Compared to baseline, ND treated group demonstrated significant increase in FFM (0.49 +/- 1.26 kg; p < 0.01) and body weight (1.31 +/- 1.87 kg; p < 0.01) and control group demonstrated significant increase in body weight (0.99 +/- 1.48 kg; p < 0.01) at the end of treatment period. Compared to control group, patient perception of benefit and subjective recovery of symptoms was significantly (p < .0001) greater in the ND group. None of the patients had any clinically significant deterioration of biochemical as well as laboratory safety parameters. Nandrolone was well tolerated with few reported adverse events of mild and non-serious in nature. Nandrolone improved patient perception of benefit and subjective recovery of symptoms in wasting associated HIV. Nandrolone therapy may prove to be effective and safe in reversing wasting associated with Indian HIV patients on antiretroviral therapy (ART) and nutritional replacement.

Nephrotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Tsitsimpikou, Christina; Vasilaki, Fotini; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tzardi, Maria; Goutzourelas, Nikolaos; Nepka, Charitini; Kalogeraki, Alexandra; Heretis, Ioannis; Epitropaki, Zoi; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-09-30

Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status. Copyright © 2016. Published by Elsevier Ireland Ltd.

Nandrolone decanoate increases satellite cell numbers in the chicken pectoralis muscle.

PubMed

Allouh, Mohammed Z; Rosser, Benjamin W C

2010-02-01

The anabolic androgenic steroid nandrolone decanoate has minimal androgenic effects and, thus, is widely used to induce muscle hypertrophy in both patients and athletes. Although increases in satellite cell numbers and satellite cells giving rise to new myonuclei are associated with hypertrophy in many experimental models, the relationship between nandrolone and satellite cells is poorly understood. Here we test the hypothesis that nandrolone administration is associated with an increase in satellite cell numbers in muscle. Nandrolone was injected at weekly intervals for four weeks into the right pectoralis muscle of female white leghorn chickens aged 63 days post hatch. Age/size/sex matched control birds received saline injections. The contralateral pectoralis was excised for study from each control and nandrolone treated bird. An antibody against Pax7 and immunocytochemical techniques were used to identify satellite cells. Nandrolone significantly increased mean pectoralis mass by approximately 22%, and mean fiber diameter by about 24%. All satellite cell indices that were quantified increased significantly in chicken pectoralis with administration of nandrolone. Nandrolone injected birds had on average higher satellite cell frequencies (#SC nuclei/all nuclei within basal lamina), number of satellite cells per millimeter of fiber, and satellite cell concentrations (closer together). Myonuclei were further apart (less concentrated) in nandrolone injected muscle. However, an overall increase in myonuclear numbers was revealed by a significantly greater mean number of myonuclei per millimeter of fiber in nandrolone injected muscle. Our results suggest that satellite cells may be key cellular vectors for nandrolone induced muscle fiber hypertrophy.

Combination of running exercise and high dose of anabolic androgenic steroid, nandrolone decanoate, increases protamine deficiency and DNA damage in rat spermatozoa.

PubMed

Shokri, S; Hemadi, M; Bayat, G; Bahmanzadeh, M; Jafari-Anarkooli, I; Mashkani, Beta

2014-03-01

High doses of anabolic-androgenic steroids (AAS) are used by some athletes to increase muscle mass, that is often associated with male infertility. The aim of this study was to investigate the possible cause/s of male infertility using a rat model by analysing sperm quality, including its protamine content and DNA integrity, as well as pregnancy rate. Five groups of male Wistar rats were treated for 10 weeks as follows: nandrolone decanoate (10 mg kg(-1) per week) (ND); running exercise (50 min per day, 5 days a week) (EX); Combination of ND and exercise (ND-EX); nandrolone decanoate solvent (Sham); and control without any injection or exercise (CO). Deterioration in sperm quantity was observed in all test groups (P ≤ 0.01). The frequency of fertile rats was decreased in the ND-EX and ND groups (P ≤ 0.05). Chromomycin-A3 staining showed a protamine deficiency in the epididymal spermatozoa in the ND-EX rats (P ≤ 0.05). Chromatin analysis indicated an abnormal maturation of the sperm nuclei in all test groups compared with the controls (P ≤ 0.05). TUNEL analyses showed a highly significant increase in apoptosis in the EX, ND, and ND-EX groups (P ≤ 0.01). Our data show that a combination of exercise and high doses of nandrolone decanoate negatively influences the DNA integrity and protamine content resulting in lower sperm quality and reduced pregnancy rate. © 2013 Blackwell Verlag GmbH.

The Impact of Nandrolone Decanoate on the Central Nervous System

PubMed Central

Busardò, Francesco P.; Frati, Paola; Sanzo, Mariantonia Di; Napoletano, Simona; Pinchi, Enrica; Zaami, Simona; Fineschi, Vittorio

2015-01-01

Nandrolone is included in the class II of anabolic androgenic steroids (AAS) which is composed of 19-nor-testosterone-derivates. In general, AAS is a broad and rapidly increasing group of synthetic androgens used both clinically and illicitly. AAS in general and nandrolone decanoate (ND) in particular have been associated with several behavioral disorders. The purpose of this review is to summarize the literature concerning studies dealing with ND exposure on animal models, mostly rats that mimic human abuse systems (i.e. supraphysiological doses). We have focused in particular on researches that have investigated how ND alters the function and expression of neuronal signaling molecules that underlie behavior, anxiety, aggression, learning and memory, reproductive behaviors, locomotion and reward. PMID:26074747

Immediate and residual effects of low-dose nandrolone decanoate and treadmill training on adipose and reproductive tissues of male Wistar rats.

PubMed

Rodrigues, Josilene M; Oliveira, Vinicius P P; P Furlan, Julia; Munhoz, Ana Claudia; S Rempel, Marcelo R; Brito, Marcia N; Brito, Nilton A; Pedrosa, Maria M D; M Costa, Cecília E

2017-05-01

Residual effects after nandrolone decanoate (ND) treatment are not reported. Immediate and residual effects of low-dose ND and treadmill training were investigated. Male rats were trained and/or ND-treated for four weeks and the assessments were made after this period or four weeks later. The groups did not differ in final plasma glucose or AUC of the ivGTT, but hyperinsulinemia was noticed in some trained/treated groups. Training with ND increased muscle mass and ND decreased the reproductive structures. Decreased fat with training was reversed by detraining. The anabolic action of ND on skeletal muscle was enhanced by training. Fat and lipid changes were more linked to training/detraining, but the effects of ND on the reproductive structures persisted after treatment. The effects of training on fat and muscle were not maintained after detraining, but low-dose ND had persistent effects on the reproductive structures.

Subchronic steroid administration induces long lasting changes in neurochemical and behavioral response to cocaine in rats.

PubMed

Kailanto, Sanna; Kankaanpää, Aino; Seppälä, Timo

2011-11-01

The abuse of anabolic androgenic steroids (AASs), such as nandrolone, is not only a problem in the world of sports but is associated with the polydrug use of non-athletes. Among other adverse effects, AAS abuse has been associated with long term or even persistent psychiatric problems. We have previously found that nandrolone decanoate treatment could produce prolonged changes in rats' brain reward circuits associated to drug dependence. The aim in this study was to evaluate whether AAS-induced neurochemical and behavioral changes are reversible. The increases in extracellular dopamine (DA) and serotonin (5-HT) concentration, as well as stereotyped behavior and locomotor activity (LMA) evoked by cocaine were attenuated by pretreatment with nandrolone. The recovery period, which was needed for the DA system to return back to the basic level, was fairly long compared to the dosing period of the steroid. In the 5-HT system, the time that system needed to return back to the basal level, was even longer than in the DA system. The attenuation was still seen though there were no detectable traces of nandrolone in the blood samples. Given that accumbal outflow of DA and 5-HT, as well as LMA and stereotyped behavior are all related to reward of stimulant drugs, this study suggests that nandrolone decanoate has significant, long-lasting but reversible effects on the rewarding properties of cocaine. Copyright © 2011 Elsevier Ltd. All rights reserved.

On the association between nandrolone-mediated testosterone reduction during alcohol intoxication and attenuated voluntary alcohol intake in rats.

PubMed

Etelälahti, T J; Eriksson, C J P

2013-11-01

Human studies have indicated that the use of anabolic androgenic steroids may be associated with the abuse of alcohol and other drugs. Also, experimental animal research has indicated that chronic nandrolone administration subsequently increases voluntary alcohol drinking. The aim of our study was to test our hypothesis that alcohol-induced testosterone elevation, especially associated with stress conditions derived by nandrolone treatment, could be the underlying factor in causing increased alcohol drinking. Male alcohol-preferring AA and low drinking Wistar rats were randomly divided into control and nandrolone decanoate treated (15 mg/kg for 14 days) groups. Basal serum testosterone and corticosterone were determined before the first nandrolone treatment, after 7 days of treatment, and after an additional (7-day) washout period, during which also the acute effect of alcohol (1.5 g/kg) on steroid hormones was determined. Hereafter followed a (5-week) voluntary alcohol consumption period, during the last 2 weeks of which the rats were treated again with nandrolone. Both normal and reversed dark- vs. light-cycle experimental designs were used. Contrary to our hypothesis, nandrolone treatment decreased voluntary alcohol consumption in both AA and Wistar rats. Also, instead of stress causation, elevated basal testosterone and lowered basal corticosterone levels were observed after nandrolone treatment in both AA rats and Wistars. During acute alcohol intoxication the frequency of testosterone decreases was higher in the nandrolone-treated groups compared with control AA and Wistar rats. Present data support the hypothesis that nandrolone-treatment mediated attenuation of alcohol intake in both AA and Wistar rats may be the result of negative reinforcement caused by alcohol-mediated testosterone reduction. © 2013.

A comparison of megestrol acetate, nandrolone decanoate and dietary counselling for HIV associated weight loss.

PubMed

Batterham, M J; Garsia, R

2001-08-01

This randomized, prospective study compared three treatments, nandrolone decanoate (ND), megestrol acetate (MA) or dietary counselling, for managing human immunodeficiency syndrome (HIV) associated weight loss. It was centred on a Tertiary referral hospital, Sydney, Australia. Fifteen patients were randomized to receive ND (100 mg/fortnight), or MA (400 mg/day) or dietary counselling for 12 weeks. Those patients randomized to dietary counselling were further randomized to receive nandrolone or megestrol after completing the dietary counselling arm. Weight, fat free mass (FFM), percentage body fat mass (FM), dietary intake and appetite were assessed before commencing and at the completion of each treatment arm. Weight increased significantly in all treatment arms (dietary counselling 1.13 kg +/- 0.36, nandrolone 4.01 kg +/- 1.68, megestrol 10.20 kg +/- 4.51, p < 0.05 paired t-test). FFM increased significantly in patients receiving ND (3.54 +/- 1.98 kg, p=0.001) and those receiving MA (2.76 +/- 0.55 kg, p=0.002), whereas the change in those receiving dietary counselling alone was not significant. Percentage body fat mass increased significantly only in those receiving MA (7.77 +/- 4.85%, p=0.049). The change in weight and percentage body fat mass was significantly greater in those receiving MA than the other two treatment arms. The increase in FFM was significantly greater in both the nandrolone and megestrol arms than the dietary counselling arm. It was concluded that ND and MA both resulted in an increase in FFM greater than dietary counselling alone. Megestrol produced a significantly greater increase in weight, percentage fat mass, intake and appetite than did the other two treatment arms, suggesting it may be the preferred agent, particularly in a palliative care setting in which weight, appetite and intake increase are desirable without regard to the composition of the body. The long-term use of these agents in people with HIV should be reviewed in the context of improved survival on highly active antiretroviral therapy regimens.

Effect of different doses of nandrolone decanoate on lipid peroxidation, DNA fragmentation, sperm abnormality and histopathology of testes of male Wister rats.

PubMed

Mohamed, Hanaa Mahmoud; Mohamed, Manal Abdul-Hamid

2015-01-01

The present study aims of to investigate the effects of low and high doses of nandrolone decanoate (ND) on histopathology and apoptosis of the spermatogenic cells as well as lipid peroxidation, antioxidant enzyme activities, sperm abnormality and DNA fragmentation. Eighteen animals were divided into three groups each group contain six animals. The rats were divided into three groups as following: Group 1 was administered saline (control). Group 2, received nandrolone decanoate (3 mg/kg/weekly) (low dose) with intramuscular injection. Group 3, received intramuscular injection dose of nandrolone decanoate (10 mg/kg/weekly) (high dose). After 8 weeks, caspase-3 assay was used to determine the apoptotic cells. The sperm parameters, lipid peroxidation, antioxidant enzyme activities and testosterone concentration were also investigated in the experimental groups of both low and high dose compared to the control groups. Treated group with high dose showed degenerated germinal epithelial cells sloughed in the lumina of seminiferous tubules, where almost seminiferous tubules were devoid of spermatids and spermatozoa compared to control and group treated with low dose. Also, a significant increase of lipid peroxidation levels and heat shock proteins was observed in two groups administrated with two different doses of ND while, antioxidant enzyme activities, and testosterone concentration was significantly decreased in two treated group when compared with control. Administration of ND at high and low doses leads to deteriorated sperm parameters, DNA fragmentation and testicular apoptosis. In conclusion, the administration ND at high doses more effective on lipid peroxidation, antioxidant enzyme activities, sperm abnormality, histopathology, apoptotic and DNA changes compared to low dose group and to control group. Published by Elsevier GmbH.

Effects of protein-rich supplementation and nandrolone on bone tissue after a hip fracture.

PubMed

Tengstrand, Birgitta; Cederholm, Tommy; Söderqvist, Anita; Tidermark, Jan

2007-08-01

Osteoporosis is a major health problem worldwide. Low weight is a major risk factor for low bone mass and fractures. The aim of this study was to investigate the effects on bone tissue of protein-rich supplementation alone or in combination with nandrolone decanoate in lean elderly women after a hip fracture. Sixty elderly women with BMI <24 kg/m(2) admitted to hospital due to a femoral neck fracture were randomised to a control group, to receive a protein-rich formula or to receive the same formula with an addition of nandrolone decanoate for 6 months. All patients received additional calcium and vitamin D. The effects after 6 and 12 months were measured by means of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DXA), and with biochemical bone markers. Osteocalcin and C-terminal telopeptide of collagen-1 (CTX) were used to estimate bone formation and bone resorption, respectively. The analyses showed an increase in total body BMD at 6 and 12 months in patients who received protein-rich supplementation. Nandrolone decanoate did not appear to have any additional effect on BMD. Osteocalcin increased in all groups while no significant changes were found for CTX. The overall results of the study indicated that protein-rich supplementation given to lean elderly female hip fracture patients increased the total body BMD.

Androgens for the anaemia of chronic kidney disease in adults.

PubMed

Yang, Qianchun; Abudou, Minawaer; Xie, Xi Sheng; Wu, Taixiang

2014-10-09

Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial. The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD. We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014. All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion. Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently. We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.

The risk of life-threatening ventricular arrhythmias in presence of high-intensity endurance exercise along with chronic administration of nandrolone decanoate.

PubMed

Abdollahi, Farzane; Joukar, Siyavash; Najafipour, Hamid; Karimi, Abdolah; Masumi, Yaser; Binayi, Fateme

2016-01-01

Anabolic steroids used to improve muscular strength and performance in athletics. Its long-term consumption may induce cardiovascular adverse effects. We assessed the risk of ventricular arrhythmias in rats which subjected to chronic nandrolone plus high-intensity endurance exercise. Animals were grouped as; control (CTL), exercise (Ex): 8 weeks under exercise, vehicle group (Arach): received arachis oil, and Nan group: received nandrolone decanoate 5 mg/kg twice a week for 8 weeks, Arach+Ex group, and Nan+Ex. Finally, under anesthesia, arrhythmia was induced by infusion of 1.5 μg/0.1 mL/min of aconitine IV and ventricular arrhythmias were recorded for 15 min. Then, animals' hearts were excised and tissue samples were taken. Nandrolone plus exercise had no significant effect on blood pressure but decreased the heart rate (P<0.01) and increased the RR (P<0.01) and JT intervals (P<0.05) of electrocardiogram. Nandrolone+exercise significantly increased the ventricular fibrillation (VF) frequency and also decreased the VF latency (P<0.05 versus CTL group). Combination of exercise and nandrolone could not recover the decreasing effects of nandrolone on animals weight gain but, it enhanced the heart hypertrophy index (P<0.05). In addition, nandrolone increased the level of hydroxyproline (HYP) and malondialdehyde (MDA) but had not significant effect on glutathione peroxidase of heart. Exercise only prevented the effect of nandrolone on HYP. Nandrolone plus severe exercise increases the risk of VF that cannot be explained only by the changes in redox system. The intensification of cardiac hypertrophy and prolongation of JT interval may be a part of involved mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Ameliorative Effects of Endurance Exercise with Two Different Intensities on Nandrolone Decanoate-Induced Neurodegeneration in Rats: Involving Redox and Apoptotic Systems.

PubMed

Joukar, Siyavash; Vahidi, Reza; Farsinejad, Alireza; Asadi-Shekaari, Majid; Shahouzehi, Beydolah

2017-07-01

Despite the importance of this issue, less has been paid to the influence of exercise on the neural side effects of anabolic androgenic steroids and mechanisms. We investigated the effects of two levels of endurance exercise on neurodegeneration side effects of nandrolone. The study period was 8 weeks. Wistar rats were divided into nine groups including the control (CTL) group, mild exercise (mEx) group, and vehicle (Arach) group which received arachis oil intramuscularly, nandrolone (Nan) group which received nandrolone decanoate 5 mg/kg two times weekly, mEx+Arach group which treated with arachis oil along with mild exercise, mEx+Nan group which treated with nandrolone along with mild exercise, severe exercise (sEx) group, sEx+Arach, and sEx+Nan groups. Finally, brain samples were taken for histopathological, biochemical, and western blot analysis. Nandrolone significantly decreased the intact cells of the hippocampus, total antioxidant capacity (TAC) (P < 0.05 versus CTL and Arach groups), TAC to malondialdehyde ratio (TAC/MDA), and Bcl-2. Nandrolone increased the Bax/Bcl-2 ratio of the brain tissue (P < 0.01 versus CTL and Arach groups). Combination of mild exercise and nandrolone rescued the intact cells to some extent, and this effect was associated with the improvement of Bcl-2 level and Bax/Bcl-2 ratio of brain tissue. Combination of severe exercise and nandrolone rescued the intact cells and improved the TAC, TAC/MDA, and Bax/Bcl-2 ratios. The findings suggest that low- and high-intensity endurance exercise decreased the risk of neurodegeneration effect of nandrolone in the hippocampus of rats. This effect can be explained by the regulation of the redox system and cell homeostasis.

Successful treatment of refractory anemia with a combination regimen containing recombinant human erythropoietin, low-dose methylprednisolone and nandrolone.

PubMed

Tsiara, S N; Chaidos, A; Gouva, M; Christou, L; Panteli, K; Kapsali, E; Bourantas, K L

2004-03-01

Myelodysplastic syndromes (MDS) are a heterogenous group of hematological clonal malignancies. Patients belonging to the refractory anemia (RA) subtype are usually treated with recombinant human erythropoietin (EPO). Not all patients respond to EPO administration and they are strictly dependent on supportive therapy with red cell blood (RBC) transfusions. The aim of this study was to investigate the efficacy of an alternative combination regimen containing EPO, low-dose methylprednisolone and nandrolone decanoate, in patients with RA unresponsive to EPO administration alone. Ten patients, 4 women and 6 men, median age: 70 years (range: 55-78 years) with refractory anemia unresponsive to EPO administration and RBC transfusion-dependent were included in the study. Median hematological data at baseline were Hb: 8.7 g/dl, (range 6.2-9.8), WBC: 3.35x10(9)/l (range 2.1-4), PLT: 82.5x10(9)/l (range 59-110). EPO 150 U/Kg three times/week subcutaneously, low-dose methylprednisolone 8 mg/day orally and nandrolone decanoate (Decadurabolin) 50 mg two-times/week intramuscularly were administered. As complete response (CR) to treatment was considered the normalization of the peripheral blood and bone marrow smears and biopsy. As partial response (PR) was considered increase in Hb level > or = 2 g/dl, or up to 10 g/dl and discontinuation of RBC transfusions. The response to therapy was evaluated on the 4th week after the initiation of the combination treatment. Bone marrow smear evaluation was carried out at baseline and every six months afterwards. After a 4-week treatment all patients achieved PR and discontinued RBC transfusions. Median and range hematological values on the 4th week after treatment initiation were Hb: 11.2 g/dl, (range: 9.8-12.8), WBC: 4.4x10(9)/l (3.5-6.6), PLT: 130x10(9)/l (95-160). The increase observed in hematological values was significant (p = 0.0001, 0.0004 and < 0.0001, respectively, for Hb, WBC and PLT counts). Treatment was well tolerated. Furthermore, two women, on treatment with the combination regimen, achieved CR one after six months and the second after 12 months. They are alive after 5 years from initiation of the combination treatment. After a median period of 18 months (range 12 to 20 months) in PR three men developed acute leukemia; they received intensive antileukemic chemotherapy without any response and died during the phase of pancytopenia. Three other men achieved CR, one after 6 and two after 12 months of therapy and they are on regular follow-up. Two women after 10 and 14 months in PR developed acute leukemia and died. In conclusion, combination therapy with EPO, nandrolone decanoate and low-dose methylprednisolone may be effective as an alternative treatment for RBC transfusion-dependent patients with RA unresponsive to EPO administration alone.

Benzyl alcohol increases voluntary ethanol drinking in rats.

PubMed

Etelälahti, T J; Eriksson, C J P

2014-09-01

The anabolic steroid nandrolone decanoate has been reported to increase voluntary ethanol intake in Wistar rats. In recent experiments we received opposite results, with decreased voluntary ethanol intake in both high drinking AA and low drinking Wistar rats after nandrolone treatment. The difference between the two studies was that we used pure nandrolone decanoate in oil, whereas in the previous study the nandrolone product Deca-Durabolin containing benzyl alcohol (BA) was used. The aims of the present study were to clarify whether the BA treatment could promote ethanol drinking and to assess the role of the hypothalamic-pituitary-adrenal-gonadal axes (HPAGA) in the potential BA effect. Male AA and Wistar rats received subcutaneously BA or vehicle oil for 14 days. Hereafter followed a 1-week washout and consecutively a 3-week voluntary alcohol consumption period. The median (± median absolute deviation) voluntary ethanol consumption during the drinking period was higher in BA-treated than in control rats (4.94 ± 1.31 g/kg/day vs. 4.17 ± 0.31 g/kg/day, p = 0.07 and 1.01 ± 0.26 g/kg/day vs. 0.38 ± 0.27 g/kg/day, p = 0.05, for AA and Wistar rats, respectively; combined effect p < 0.01). The present results can explain the previous discrepancy between the two nandrolone studies. No significant BA effects on basal and ethanol-mediated serum testosterone and corticosterone levels were observed in blood samples taken at days 1, 8 and 22. However, 2h after ethanol administration significantly (p = 0.02) higher frequency of testosterone elevations was detected in high drinking AA rats compared to low drinking Wistars, which supports our previous hypotheses of a role of testosterone elevation in promoting ethanol drinking. Skin irritation and dermatitis were shown exclusively in the BA-treated animals. Altogether, the present results indicate that earlier findings obtained with Deca-Durabolin containing BA need to be re-evaluated. Copyright © 2014 Elsevier Inc. All rights reserved.

Sex steroid receptors profiling is influenced by nandrolone decanoate in the ampulla of the fallopian tube: Post-treatment and post-recovery analyses.

PubMed

Andrade, G H B; Simão, V A; Souza, B R; Chuffa, L G A; Camargo, I C C

2018-02-01

Anabolic androgenic steroids (AAS) are recommended for therapeutic clinic, but their use has increased in recent decades for aesthetic reasons. No study has evaluated the impact of AAS in the fallopian tube, after treatment and recovery periods. Herein, the aim of study was to investigate the effects of Nandrolone Decanoate (ND), administered in different doses (1.87; 3.75; 7.5 and 15 mg/kg) on the ampulla of the fallopian tube in rats, following post-treatment (PT; 15 consecutive days) and post-recovery (PR; 30 consecutive days) periods. The control group received mineral oil. Estrous cycle was monitored daily during both periods and in sequence the rats (n = 8/group/period) were killed. All ND-treated animals showed estral acyclicity during the PT and PR periods, but the histomorphometric changes in the fallopian tube varied according to the ND dose level. The expression of AR, ERα and ERβ varied in the nucleus and cytoplasm of epithelial cells. No AR expression was observed in the stroma. The muscle cells exhibited variation in immunostaining. In conclusion, ND promoted histomorphometric and immunohistochemical changes in the ampullary portion of the fallopian tube after treatment and recovery periods in a dose-independent manner. Copyright © 2018 Elsevier Ltd. All rights reserved.

Nandrolone decanoate and resistance exercise training favor the occurrence of lesions and activate the inflammatory response in the ventral prostate.

PubMed

Gomes, F C; Chuffa, L G A; Scarano, W R; Pinheiro, P F F; Fávaro, W J; Domeniconi, R F

2016-05-01

Age is a key factor in the development of prostatic lesions. An increase in reactive oxygen species levels occurs during aging. Furthermore, the indiscriminate use of anabolic androgenic steroids and physical exercise alter the availability of hormones and may promote the appearance of lesions. This study examined whether the use of nandrolone decanoate (ND), associated or not with resistance exercise training, affects the pathways related to the inflammatory response in the ventral prostate of adult and aged rats. Sprague-Dawley rats were distributed into eight experimental groups: sedentary with ND, sedentary without ND, exercise with ND, and exercise without ND. The animals performed resistance exercise training and received ND two times/week (5 mg/kg, i.m.) for 8 weeks. Adult rats were killed immediately following treatment completion, and aged rats remained untreated until reaching 300 days of age. The adult animals that received ND and performed resistance exercise training showed a higher occurrence of lesions with TLR4 activation. Marked IL-6 expression occurred in the group that performed resistance exercise training. The group exposed to ND showed overexpression of TLR2, TLR4, NOX1, Nrf2, TNF-α, and P38MAPK. The animals that received ND and performed training showed increase levels of NFκB, IRF3, IL-6, TNF-α, and NOX1. TLR2 and TLR4 showed no upregulation in the aged animals. The groups exercise + ND showed lesions in the adult stage and after aging, followed by molecular alterations. We concluded that nandrolone decanoate and resistance exercise training can promote the onset of prostatic tumors in the adult stage, and during aging, activating pathways involved in the inflammatory response. © 2016 American Society of Andrology and European Academy of Andrology.

The effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the testis in adult male rats: a transmission electron microscope study.

PubMed

Naraghi, M A; Abolhasani, F; Kashani, I; Anarkooli, I J; Hemadi, M; Azami, A; Barbarestani, M; Aitken, R J; Shokri, S

2010-08-01

Anabolic-androgenic steroids (AAS) are used in high doses by athletes to improve athletic ability, physical appearance, and muscle mass. Unfortunately, the abuse of these agents has significantly increased. It has been established that exercise and high doses of AAS may influence the hypothalamic-pituitary gonadal (H-P-G) axis, which can in turn affect the ultrastructure of the testes. However, the effect of the combination of exercise and high doses of AAS on the ultrastructure of the testes is not known. This study was undertaken in order to examine the combination effects of swimming exercise and supraphysiological doses of nandrolone decanoate on the ultrastructural changes in rat testes. Five groups of male Wistar strain albino rats were treated as follows for 8 weeks: solvent of nandrolone decanoate (peanut oil) as a vehicle (sham); nandrolone decanoate (ND) (10 mg/kg/week) - ND; exercise (1 h/day, 5 days a week) - exercise; ND (10 mg/kg/week) and exercise (1 h/day, 5 days a week) - ND-EX; and sedentary control without any injection or exercise - control. Ultrastructural changes in the rat testes were characterised by transmission electron microscopy. The number and size of Leydig cells were considerably decreased in the interstitial space in the experimental rats. The increased thickness and irregular wavy multilaminar appearance of basement membrane in the treated animals, especially in the ND-EX group, are associated with well developed myoid cells. Cytoplasm vacuolisation, vesicular-like crista of the mitochondria, numerous lipid droplets, and lysosome and phagolysosome in Sertoli cells were significantly observed in the experimental groups. Several apoptotic germ cells were considerably observed in the experimental rats (p ≤ 0.05). Exercise training seems to increase the extent of ultrastructural changes caused by supraphysiological doses of ND in rats, which in turn may affect fertility.

A randomized, placebo-controlled trial of nandrolone decanoate in human immunodeficiency virus-infected men with mild to moderate weight loss with recombinant human growth hormone as active reference treatment.

PubMed

Storer, Thomas W; Woodhouse, Linda J; Sattler, Fred; Singh, Atam B; Schroeder, E Todd; Beck, Keith; Padero, MaClara; Mac, Phong; Yarasheski, Kevin E; Geurts, Paul; Willemsen, Arnold; Harms, Marloes K; Bhasin, Shalender

2005-08-01

We compared the effectiveness of a biweekly regimen of 150 mg nandrolone with placebo in HIV-infected men with mild to moderate weight loss and contrasted its effects against a Food and Drug Administration-approved regimen of recombinant human (rh)GH. In this placebo-controlled, randomized, 12-wk trial, placebo and nandrolone (150 mg im biweekly) were administered double blind, and rhGH (6 mg sc daily) was administered in an open-label manner. Participants were HIV-infected men with 5-15% weight loss over 6 months and on stable antiretroviral therapy for more than 12 wk. Lean body mass (LBM), muscle performance, physical function, endurance, hormone levels, insulin sensitivity, sexual function, quality of life, and appetite were assessed at baseline and after 12 wk. Nandrolone administration was associated with a greater increase in LBM (+1.6 +/- 0.3 kg) by dual-energy x-ray absorptiometry scan than placebo (+0.4 +/- 0.3 kg; P < 0.05); however, the change in LBMs with nandrolone was not significantly different from rhGH (+2.5 +/- 0.3 kg). Nandrolone administration was also associated with significantly greater gains in fat-free mass (+1.6 +/- 0.3 kg), body cell mass (+1.0 +/- 0.2 kg), and intracellular water (+0.9 +/- 0.2 kg) than placebo; these changes in the nandrolone group were not significantly different from the rhGH group. rhGH administration was associated with greater loss of whole body fat mass and higher frequency of drug-related adverse effects and treatment discontinuations than nandrolone and placebo and a greater increase in extracellular water than nandrolone. Nandrolone treatment was associated with greater improvements in perception of health than rhGH and sexual function than placebo. The cachexia/anorexia scores, health care resource use, and insulin sensitivity did not significantly change. We conclude that nandrolone is superior to placebo and not significantly different from a Food and Drug Administration-approved regimen of rhGH in improving lean body mass in HIV-infected men with mild to moderate weight loss.

Fundamental understanding of drug absorption from a parenteral oil depot.

PubMed

Kalicharan, Raween W; Schot, Peter; Vromans, Herman

2016-02-15

Oil depots are parenteral drug formulations meant for sustained release of lipophilic compounds. Until now, a comprehensive understanding of the mechanism of drug absorption from oil depots is lacking. The aim of this paper was to fill this gap. A clinical study with healthy volunteers was conducted. An oil depot with nandrolone decanoate and benzyl alcohol was subcutaneously administered in the upper arm of female volunteers. Pharmacokinetic profiles of both substances were related to each other and to literature data. Benzyl alcohol absorbs much more rapidly than nandrolone. In detail, it appears that benzyl alcohol enters the central compartment directly, while nandrolone decanoate is recovered in serum after a lag time. This lag time is also seen in literature data, although not reported explicitly. The absorption of nandrolone is enhanced by the presence of benzyl alcohol. This is most likely an effect of altered oil viscosity and partition coefficient between the oil and aqueous phase. The absorption rate constant of compounds is found to be related to the logP of the solubilized prodrug. The absorption rate is however not only determined by the physico-chemical properties of the formulation but also by the tissue properties. Here, it is argued that lymphatic flow must be considered as a relevant parameter. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of protein-rich supplementation and nandrolone in lean elderly women with femoral neck fractures.

PubMed

Tidermark, Jan; Ponzer, Sari; Carlsson, Pronoti; Söderqvist, Anita; Brismar, Kerstin; Tengstrand, Birgitta; Cederholm, Tommy

2004-08-01

To evaluate the effects of a protein-rich liquid supplementation, alone or in combination with the anabolic steroid nandrolone decanoate, on body composition, activities of daily living (ADL) status and the health-related quality of life (HRQoL) after a femoral neck fracture. Sixty women, aged 83 +/- 5 years (mean +/- SD), BMI < 24 kg/m2 (20.4 +/- 2 kg/m2 ) and capable of co-operating, with a femoral neck fracture treated with internal fixation, were randomised to open treatment during 6 months with a protein-rich liquid formula alone (PR, Fortimel, 200 ml/day, 20 g protein/day) or in combination with nandrolone decanoate (PR/N, Deca-Durabol 25 mg i.m./3 weeks) or to a control group (C). The patients were re-examined after 6 and 12 months regarding body weight (BW), lean body mass (LBM, DXA), ADL status according to Katz, HRQoL according to EQ 5-D and fracture healing. LBM decreased in the C (-1.2 +/- 2 kg) and PR groups (-1.2 +/- 1 kg) but remained the same in the PR/N group (0.3 +/- 1 kg) (P < 0.05 between groups). ADL remained at a high level in the two intervention groups but declined significantly in the C group (P < 0.005 between groups). The decline in HRQoL was least pronounced in the PR/N group at 6 months (P < 0.05 between groups). Patients with fracture healing complications lost more BW (P < 0.05) and LBM (P < 0.01) than patients with uneventful fracture healing. Protein-rich liquid supplementation in combination with nandrolone given for 6 months to lean elderly women after a femoral neck fracture may positively affect LBM, ADL and HRQoL. Copyright 2003 Elsevier Ltd.

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

PubMed

Cuerda, Cristina; Zugasti, Ana; Bretón, Irene; Camblor, Miguel; Miralles, Pilar; García, Pilar

2005-02-01

Malnutrition, especially loss of lean body mass, is a frequent complication of people living with HIV that may increase their mortality and morbidity. 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. 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. 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.

Effect of nandrolone decanoate administration on recovery from bupivacaine-induced muscle injury

PubMed Central

White, James P.; Baltgalvis, Kristen A.; Sato, Shuichi; Wilson, L. Britt

2009-01-01

Although testosterone administration elicits well-documented anabolic effects on skeletal muscle mass, the enhancement of muscle regeneration after injury has not been widely examined. The purpose of this study was to determine whether anabolic steroid administration improves skeletal muscle regeneration from bupivacaine-induced injury. Male C57BL/6 mice were castrated 2 wk before muscle injury induced by an intramuscular bupivacaine injection into the tibialis anterior (TA) muscle. Control mice received an intramuscular PBS injection. Anabolic steroid [nandrolone decanoate (ND), 6 mg/kg] or sesame seed oil was administered at the time of initial injury and continued every 7 days for the study's duration. Mice were randomly assigned to one of four treatment groups for 5, 14, or 42 days of recovery, as follows: 1) control (uninjured); 2) ND only (uninjured + ND); 3) bupivacaine only (injured); or 4) bupivacaine + ND (injured + ND). TA morphology, protein, and gene expression were analyzed at 14 and 42 days after injury; protein expression was analyzed at 5 days after injury. After 14 days of recovery, the injury and injury + ND treatments induced small-diameter myofiber incidence and also decreased mean myofiber area. The increase in small-myofiber incidence was 65% greater in injury + ND muscle compared with injury alone. At 14 days, injury + ND induced a fivefold increase in muscle IGF-I mRNA expression, which was greater than injury alone. Muscle Akt activity and glycogen synthetase kinase-3β activity were also induced by injury + ND at 14 days of recovery, but not by injury alone. ND had a main effect for increasing muscle MyoD and cyclin D1 mRNA expression at 14 days. After 42 days of recovery, injury + ND increased large-diameter myofiber incidence compared with injury only. Nandrolone decanoate (ND) administration can enhance castrated mouse muscle regeneration during the recovery from bupivacaine-induced injury. PMID:19745189

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

PubMed

Sattler, Fred R; Schroeder, E Todd; Dube, Michael P; Jaque, S Victoria; Martinez, Carmen; Blanche, Patricia J; Azen, Stanley; Krauss, Ronald M

2002-12-01

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.

Nandrolone decanoate for the treatment of erythropoietin refractory anemia: a case series.

PubMed

Chawla, Bobby; Iqbal, Fahad M; Chawla, Manjeet S

2009-01-01

Erythropoietin refractory anemias represent a continuing and increasing burden on the healthcare system. The current practice of providing these patients with rHuEPO does not seem to be working. Fewer than 50% of patients respond in some studies. We demonstrate that androgens have multiple benefits in this population. They control anemia and stop transfusion dependence and improve nutritional parameters. In some patients, they also have a salutary effect on both white blood cell and platelet counts.

Lipoic acid and pentoxifylline mitigate nandrolone decanoate-induced neurobehavioral perturbations in rats via re-balance of brain neurotransmitters, up-regulation of Nrf2/HO-1 pathway, and down-regulation of TNFR1 expression.

PubMed

Ahmed, Maha A E; El-Awdan, Sally A

2015-07-01

Behavioral perturbations associated with nandrolone decanoate abuse by athletes and adolescents may be attributed to oxidative stress and inflammation. However, the underlying mechanisms are not yet fully explored. On the other hand, the natural antioxidant lipoic acid can pass the blood brain barrier and enhance Nrf2/HO-1 (nuclear factor erythroid-2 related factor 2/heme oxygenase-1) pathway. In addition, the phosphodiesterase-IV inhibitor xanthine derivative pentoxifylline has a remarkable inhibitory effect on tumor necrosis factor-alpha (TNF-α). Therefore, this study aimed at investigation of the possible protective effects of lipoic acid and/or pentoxifylline against nandrolone-induced neurobehavioral alterations in rats. Accordingly, male albino rats were randomly distributed into seven groups and treated with either vehicle, nandrolone (15mg/kg, every third day, s.c.), lipoic acid (100mg/kg/day, p.o.), pentoxifylline (200mg/kg/day, i.p.), or nandrolone with lipoic acid and/or pentoxifylline. Rats were challenged in the open field, rewarded T-maze, Morris water maze, and resident-intruder aggression behavioral tests. The present findings showed that nandrolone induced hyperlocomotion, anxiety, memory impairment, and aggression in rats. These behavioral abnormalities were accompanied by several biochemical changes, including altered levels of brain monoamines, GABA, and acetylcholine, enhanced levels of malondialdehyde and TNF-α, elevated activity of acetylcholinesterase, and up-regulated expression of TNF-α receptor-1 (TNFR1). In addition, inhibited catalase activity, down-regulated Nrf2/HO-1 pathway, and suppressed acetylcholine receptor expression were observed. Lipoic acid and pentoxifylline combination significantly mitigated all the previously mentioned deleterious effects mainly via up-regulation of Nrf2/HO-1 pathway, inhibition of TNF-α and down-regulation of TNFR1 expression. In conclusion, the biochemical and histopathological findings of this study revealed the protective mechanisms of lipoic acid and pentoxifylline against nandrolone-induced behavioral changes and neurotoxicity in rats. Copyright © 2015 Elsevier Inc. All rights reserved.

Chronic nandrolone administration induces dysfunction of the reward pathway in rats.

PubMed

Zotti, Margherita; Tucci, Paolo; Colaianna, Marilena; Morgese, Maria Grazia; Mhillaj, Emanuela; Schiavone, Stefania; Scaccianoce, Sergio; Cuomo, Vincenzo; Trabace, Luigia

2013-10-24

Data in animal models and surveys in humans have shown psychiatric complications of long-term anabolic androgenic steroids abuse. However, neurobiochemical mechanisms behind observed behavioral changes are poorly understood. The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats. Behavioral reactivity to elevated plus maze and social interaction test was used to assess anxiety-related symptoms, while sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas. Chronic administration of nandrolone, at 5 mg kg -1 injected for 4 weeks, induced loss of sweet taste preference, as sign of anhedonia and dysfunction of reward pathway. Behavioral outcomes were accompanied by reduction of dopamine, serotonin and noradrenaline contents in nucleus accumbens. Neither alterations in time spent in open arms nor in social interaction test were found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between experimental groups in the amygdala in terms of neurotransmitters measured. Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be underlined that our data could contribute to a better understanding of altered reward induced by nandrolone treatment and to develop appropriate treatment. Copyright © 2013. Published by Elsevier Inc.

Nandrolone decanoate is able to modulate proliferation and adhesion of myoblasts.

PubMed

Oliveira, E N; Fernandes, K P; Silva, C A; Oliveira, T S; Junior, J A; Bussadori, S K; Renno, A C; Mesquita-Ferrari, R A

2014-07-01

The search for a more efficient repair process of muscle injuries has become evident in clinical practice. The aim of the present study was to evaluate the effect of nandrolone decanoate (ND) on the proliferation, adhesion, and expression of myogenic regulatory factors (MRFs) in C2C12 cells.Methods. Cell proliferation and adhesion were assessed using an MTT assay. The expression of MRFs was assessed by real-time PCR.Results. ND applied at 10 or 25 µM concentration induced after 60 min an increase in adhesion, at 5 µM concentration induced after 5 days an increase in cell proliferation, and ND at 50 µM concentration led after 5 days to a decrease in cell proliferation in comparison with other groups. The steroid did not alter the expression of MRFs.Conclusions. The positive effects of ND regarding the proliferation and adhesion of C2C12 cells suggest that this steroid may have positive effects following a muscle injury.

The Anabolic Androgenic Steroid Nandrolone Decanoate Disrupts Redox Homeostasis in Liver, Heart and Kidney of Male Wistar Rats

PubMed Central

Frankenfeld, Stephan P.; Oliveira, Leonardo P.; Ortenzi, Victor H.; Rego-Monteiro, Igor CC.; Chaves, Elen A.; Ferreira, Andrea C.; Leitão, Alvaro C.; Carvalho, Denise P.; Fortunato, Rodrigo S.

2014-01-01

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g−1 body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state. PMID:25225984

The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

PubMed

Frankenfeld, Stephan P; Oliveira, Leonardo P; Ortenzi, Victor H; Rego-Monteiro, Igor C C; Chaves, Elen A; Ferreira, Andrea C; Leitão, Alvaro C; Carvalho, Denise P; Fortunato, Rodrigo S

2014-01-01

The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g(-1) body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.

Long-term treatment with Nandrolone Decanoate impairs mesenteric vascular relaxation in both sedentary and exercised female rats.

PubMed

Caliman, Izabela F; Bernabe, Cristian S; de Melo, Antônio F; Brasil, Girlândia A; do Nascimento, Andrews M; de Lima, Ewelyne M; Figueiredo, Suely G; de Andrade, Tadeu U; Bissoli, Nazaré S

2017-04-01

Nandrolone Decanoate (ND) is an Anabolic Androgenic Steroid (AAS) that under abusive regimen can lead to multiple physiological adverse effects. Studies of AAS-mediated cardiovascular (CV) alterations were mostly taken from male subjects, even though women are also susceptible to the effects of AAS and gender-specific differences in susceptibility to vascular diseases exist. Here we investigate ND-induced vascular reactivity alterations in both sedentary and exercised female rats and whether these alterations depend on endothelium-derived factors. We show that chronic exposure of female Wistar rats to ND (20mg/Kg/week for 4weeks) impaired the vascular mesenteric bed (MVB) reactivity to vasodilator (acetylcholine) agonist. The endothelium-dependent Nitric Oxide (NO) component was reduced in ND-treated rats, whereas neither the endothelium-derived hyperpolarizing factor (EDHF) component nor prostanoids were altered in the MVBs. Endothelial dysfunction observed in ND-treated rats was associated with decreased eNOS (Ser 1177 ) and Akt (Ser 473 ) phosphorylation sites and upregulation of iNOS and NADPH oxidase expression. Exercise training by weight lifting in water did not improve the vascular alterations induced by ND treatment. ND treatment also significantly reduced the serum levels of estradiol in females, overriding its CV protective effect. These results help uncover the role of ND modulating endothelial function in the setting of CV disease caused by the abuse of AAS in females. If this translates to humans, young women abusing AAS can potentially lose the cardio protective effect rendered by estrogen and be more susceptible to CV alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

75 FR 48351 - Determination That DECA-DURABOLIN (Nandrolone Decanoate) Injection, 200 Milligrams/Milliliter, 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-10

... Not Withdrawn From Sale for Reasons of Safety or Effectiveness AGENCY: Food and Drug Administration... withdrawn from sale for reasons of safety or effectiveness. This determination will allow FDA to approve... or effectiveness, or if FDA determines that the listed drug was withdrawn from sale for reasons of...

Cardiopulmonary reflex, cardiac cytokines, and nandrolone decanoate: response to resistance training in rats.

PubMed

Lima, Ewelyne Miranda; Nascimento, Andrews Marques; Brasil, Girlandia Alexandre; Kalil, Ieda Carneiro; Lenz, Dominik; Endringer, Denise Coutinho; Andrade, Tadeu Uggere; Bissoli, Nazaré Souza

2015-11-01

This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

PubMed

Simão, Vinícius Augusto; Berloffa Belardin, Larissa; Araújo Leite, Gabriel Adan; de Almeida Chuffa, Luiz Gustavo; Camargo, Isabel Cristina Cherici

2015-10-01

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.75, 7.5 and 15 mg/kg body weight, or received mineral oil (control group) for 15 days, subcutaneously. All animals were divided into three groups according to the treatment periods: (i) ND treatment for 15 days; (ii) ND treatment followed by a 30-day recovery; and (iii) ND treatment followed by a 60-day recovery. Estrous cycle was monitored daily, and at the end of each period, the animals were euthanized for histopathological analysis. During ND treatment and after 30-day recovery, all animals exhibited persistent diestrus. After a 60-day recovery, persistent diestrus was only maintained in the group that had received the highest dose. Ovarian weight was decreased significantly after the 30-day recovery, regardless of ND doses, compared with the control group. There was a reduction (P < 0.05) in the number of corpora lutea and antral and growing follicles, in contrast to an increase (P < 0.05) in atretic follicles in a dose- and time-dependent manner. Remarkable histopathological changes occurred in the ovaries of all ND-treated groups. In conclusion, the different doses of ND caused changes in the estrous cycle and ovarian tissue of rats, and recovery periods (30 and 60 days) were insufficient to completely restore the damage in the animals treated with the highest dose. © 2015 The Authors. International Journal of Experimental Pathology © 2015 International Journal of Experimental Pathology.

Chronic nandrolone administration induces dysfunction of the reward pathway in rats.

PubMed

Zotti, Margherita; Tucci, Paolo; Colaianna, Marilena; Morgese, Maria Grazia; Mhillaj, Emanuela; Schiavone, Stefania; Scaccianoce, Sergio; Cuomo, Vincenzo; Trabace, Luigia

2014-01-01

Data in animal models and surveys in humans have revealed psychiatric complications of long-term anabolic androgenic steroid abuse. However, the neurobiochemical mechanisms behind the observed behavioral changes are poorly understood. The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats. The behavioral reactivity to the elevated plus maze and the social interaction test was used to assess anxiety-related symptoms, and the sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas. The chronic administration of nandrolone, at 5 mg kg(-1) injected daily for 4 weeks, induced the loss of sweet taste preference, a sign of anhedonia and dysfunction of the reward pathway. The behavioral outcomes were accompanied by reductions in the dopamine, serotonin and noradrenaline contents in the nucleus accumbens. Alterations in the time spent in the open arms and in the social interaction test were not found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between the experimental groups in the amygdala in terms of the neurotransmitters measured. Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be highlighted that our data could contribute to a better understanding of the altered rewards induced by nandrolone treatment and to the development of appropriate treatments.

Nandrolone decanoate and physical activity affect quadriceps in peripubertal rats.

PubMed

Sretenovic, Jasmina; Ajdzanovic, Vladimir; Zivkovic, Vladimir; Srejovic, Ivan; Corbic, Milena; Milosevic, Verica; Jakovljevic, Vladimir; Milosavljevic, Zoran

2018-07-01

Anabolic androgenic steroids (AASs) are synthetic analogs of testosterone often used by athletes to increase the skeletal muscle mass. Our goal was to examine the effects of physical activity and physical activity combined with supraphysiological doses of nandrolone on functional morphology of the quadriceps muscle. The study included 32 peripubertal Wistar rats, divided into 4 groups: control (T-N-), nandrolone (T-N+), physical activity (T+N-) and physical activity plus nandrolone (T+N+) groups. The T+N- and T+N+ group swam for 4 weeks, 1 h/day, 5 days/week. The T-N+ and T+N+ groups received nandolone decanoate (20 mg/kg b.w.) once per week, subcutaneously. Subsequently, the rats were sacrificed and muscle specimens were prepared for the processing. Tissue sections were histochemically and immunohistochemically stained, while the image analysis was used for quantification. Longitudinal diameter of quadriceps muscle cells was increased for 21% in T-N+, for 57% in T+N- and for 64% in T+N+ group while cross section muscle cell area was increased in T-N+ for 19%, in T+N- for 47% and in T+N+ group for 59%, compared to the control. Collagen fibers covered area was increased in T-N+ group for 36%, in T+N- for 109% and in T+N+ group for 159%, compared to the control. Erythrocyte depots were decreased in T-N+ group and increased in T+N- and T+N+ group, in comparison with T-N-. VEGF depots were increased in all treated groups. Chronic administration of supraphysiological doses of AASs alone or in combination with physical activity induces hypertrophy and significant changes in the quadriceps muscle tissue structure. Copyright © 2018 Elsevier GmbH. All rights reserved.

Nandrolone decanoate and physical effort: histological and morphometrical assessment in adult rat uterus.

PubMed

de Almeida Chuffa, Luiz Gustavo; de Souza, Roberta Barreiros; Frei, Fernando; de Fátima Paccola Mesquita, Suzana; Camargo, Isabel Cristina Cherici

2011-02-01

In the past decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit abuse of these drugs by athletes and non-athletes. Since that AAS can affect the reproductive tract, resulting in reproduction and fertilization damages, the purpose of this study was to investigate the nandrolone decanoate (ND) effects, associated or not with physical effort, on the uterine histomorphometric parameters. Female Wistar rats, sedentary or not, were exposed to treatment with ND by intraperitoneal injection (5 mg/kg/day, once a week) during four consecutive weeks. Control animals, sedentary or not, received vehicle alone (propylene glycol) in the same manner. The physical activity was forced swimming (20 min/day). During the experiment, all animals were monitored by daily vaginal smears. After 30 days of treatment, the females were sacrificed and their uteri collected and examined under light microscopy techniques. The ND-treated females showed estrus acyclicity and decreased thickness of both the epithelium and endometrial stroma. A reduction in the number and size of blood vessels was also found in ND-treated rats submitted to physical effort when compared to ND sedentary rats. ND-treated rats, regardless of exercise, exhibited stromal fibrosis and reduced gland ducts that displayed high mitotic activity. A remarkable widespread presence of leukocytes occurred in rats receiving ND and submitted to exercise. These results suggest that ND associated or not with physical effort causes histomorphometric changes to the rat uterus. 2010 Wiley-Liss, Inc.

The effect of nandrolone decanoate on bone mineral density, muscle mass, and hemoglobin levels in elderly women with osteoporosis: a double-blind, randomized, placebo-controlled clinical trial.

PubMed

Frisoli, Alberto; Chaves, Paulo H M; Pinheiro, Marcelo Medeiros; Szejnfeld, Vera Lucia

2005-05-01

In a randomized, double-blind, placebo-controlled clinical trial, we evaluated the effect of a 2-year treatment with nandrolone decanoate (ND) on bone mineral density (BMD) of lumbar spine, femoral neck, and trochanter and on vertebral fracture rate, muscle mass, and hemoglobin levels. Sixty-five osteoporotic women older than 70 years were studied. Thirty-two patients received injections of 50 mg ND, and 33 received placebos every 3 weeks. All patients received 500 mg calcium tablets daily. Compared to baseline, ND increased the BMD of the lumbar spine (3.4% +/- 6.0 and 3.7% +/- 7.4; p < .05) and femoral neck (4.1% +/- 7.3 and 4.7% +/- 8.0; p < .05) after 1 and 2 years, respectively. The BMD of trochanter increased significantly only after the first year (4.8% +/- 9.3, p < .05). Compared to the placebo group, the ND group presented with significantly increased BMD of the trochanter and neck. ND significantly reduced incidence of new vertebral fractures (21% vs 43% in the placebo group; p < .05). ND showed a significant statistical increase in lean body mass after the first (6.2% +/- 5.8; p < .01) and second years (11.9% +/- 29.2; p < .01). In addition, a 2-year treatment with ND significantly increased hemoglobin levels compared to baseline (14.3%; p < .01) and placebo (p < .01). ND increased BMD, hemoglobin levels, and muscle mass, and reduced the vertebral fracture rate of elderly osteoporotic women.

AT1 and aldosterone receptors blockade prevents the chronic effect of nandrolone on the exercise-induced cardioprotection in perfused rat heart subjected to ischemia and reperfusion.

PubMed

Marques-Neto, Silvio Rodrigues; Ferraz, Emanuelle Baptista; Rodrigues, Deivid Carvalho; Njaine, Brian; Rondinelli, Edson; Campos de Carvalho, Antônio Carlos; Nascimento, Jose Hamilton Matheus

2014-04-01

Myocardial tolerance to ischaemia/reperfusion (I/R) injury is improved by exercise training, but this cardioprotection is impaired by the chronic use of anabolic androgenic steroids (AAS). The present study evaluated whether blockade of angiotensin II receptor (AT1-R) with losartan and aldosterone receptor (mineralocorticoid receptor, MR) with spironolactone could prevent the deleterious effect of AAS on the exercise-induced cardioprotection. Male Wistar rats were exercised and treated with either vehicle, nandrolone decanoate (10 mg/kg/week i.m.) or the same dose of nandrolone plus losartan or spironolactone (20 mg/kg/day orally) for 8 weeks. Langendorff-perfused hearts were subjected to I/R and evaluated for the postischaemic recovery of left ventricle (LV) function and infarct size. mRNA and protein expression of angiotensin II type 1 receptor (AT1-R), mineralocorticoid receptor (MR), and KATP channels were determined by reverse-transcriptase polymerase chain reaction and Western blotting. Postischaemic recovery of LV function was better and infarct size was smaller in the exercised rat hearts than in the sedentary rat hearts. Nandrolone impaired the exercise-induced cardioprotection, but this effect was prevented by losartan (AT1-R antagonist) and spironolactone (MR antagonist) treatments. Myocardial AT1-R and MR expression levels were increased, and the expression of the KATP channel subunits SUR2a and Kir6.1 was decreased and Kir6.2 increased in the nandrolone-treated rat hearts. The nandrolone-induced changes of AT1-R, MR, and KATP subunits expression was normalized by the losartan and spironolactone treatments. The chronic nandrolone treatment impairs the exercise-induced cardioprotection against ischaemia/reperfusion injury by activating the cardiac renin-angiotensin-aldosterone system and downregulating KATP channel expression.

Nandrolone decanoate induces cardiac and renal remodeling in female rats, without modification in physiological parameters: The role of ANP system.

PubMed

Brasil, Girlandia Alexandre; Lima, Ewelyne Miranda de; Nascimento, Andrews Marques do; Caliman, Izabela Facco; Medeiros, Ana Raquel Santos de; Silva, Mauro Sérgio Batista; Abreu, Gláucia Rodrigues de; Reis, Adelina Martha dos; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

2015-09-15

Anabolic-androgenic steroids are misused, including women, but little is known about the cardiovascular effects of these drugs on females. Evaluated the effects of nandrolone decanoate (ND), physical exercise and estrogen deficiency on female rats. Female Wistar rats were divided into 8 groups: S and OVX: (SHAM: sham surgery; OVX: ovariectomy, vehicle), SE and OVXE (resistance exercise 5 times a week, vehicle), SD and OVXD (treated with ND, 20 mg/kg/week for 4 weeks); SDE and OVXDE. Treatments were initiated 21 days after surgery. The Bezold–Jarisch reflex was assessed by Phenylbiguanide administration. The right atrium, kidney, and serum were collected for molecular analyses by RT-PCR of atrial natriuretic peptide (ANP), A-type natriuretic peptide receptor (NPR-A) and NPR-C. ELISA assay to estradiol and testosterone concentrations. The gastrocnemius muscle, heart and kidney weights/tibia length were measured.Morphometric analysis of heart was made (H/E) and collagen content of heart and kidney were evaluated using Pirossirius Red. ND treatment increased ANP expression on atrium and decreased NPR-A expression in kidney. Physical exercise and ovariectomy did not alter this parameter. NPR-C level was reduced in the SDE and OVXDE. Renal and cardiac hypertrophy was observed after ND treatment, with collagen deposition. Plasma estrogen concentrations were reduced and serum testosterone concentrations were increased after ND treatment. ANP has an important role in modulating the cardiovascular effects of ND in females. Thismodulating may have occurred by the increasing ANP expression, reducing NPR-A and NPR-C expression levels, and changing sex hormone levels.

Nandrolone Plus Moderate Exercise Increases the Susceptibility to Lethal Arrhythmias

PubMed Central

Ghorbani Baravati, Hamideh; Joukar, Siyavash; Fathpour, Hossein; Kordestani, Zeinab

2015-01-01

Background: Until now, no experimental study has directly assessed the arrhythmogenesis of chronic consumption of anabolic androgenic steroids along with moderate-intensity endurance exercise. Objectives: We evaluated the influence of integration of anabolic androgenic steroids along with moderate-intensity endurance exercise on susceptibility to lethal ventricular arrhythmias in rat. Materials and Methods: The animal groups were as follows: control group (CTL); exercise group (EX) which were under 6 weeks of treadmill exercise; nandrolone group (Nan) which received 5 mg/kg of nandrolone decanoate twice a week; vehicle group (Arach) which received Arachis oil (solvent of nandrolone); trained vehicle group (Arach + Ex); and trained nandrolone group (Nan + Ex). One day after ending of the intervention period, arrhythmia was inducted by intravenous infusion of aconitine and ventricular arrhythmias were recorded. Then malondialdehyde (MDA) and glutathione peroxidase (GPX) of heart tissue were measured. Results: Nandrolone, exercise, and their combination were associated with heart hypertrophy. Exercise could prevent the incremental effect of nandrolone on MDA/GPX ratio. Chronic administration of nandrolone with moderate-intensity endurance exercise had no significant effect on blood pressure, heart rate, and basal electrocardiographic parameters. Combination of nandrolone and exercise significantly increased the incidence of ventricular fibrillation (VF) and reduced the VF latency (P < 0.05). Conclusions: The findings suggest that chronic coadministration of nandrolone with moderate-intensity endurance exercise facilitates the VF occurrence in rat. Complementary studies are needed to elucidate the involved mechanisms of this abnormality. PMID:26396972

Dose-dependent effects and reversibility of the injuries caused by nandrolone decanoate in uterine tissue and fertility of rats.

PubMed

Belardin, Larissa Berloffa; Simão, Vinícius Augusto; Leite, Gabriel Adan Araújo; Chuffa, Luiz Gustavo de Almeida; Camargo, Isabel Cristina Cherici

2014-04-01

This study is the first to investigate the effects of different doses of nandrolone decanoate (ND) upon uterine tissue and fertility, and if the reproductive alterations can be restored after cessation of the treatment. Wistar female rats were treated with ND at doses of 1.87, 3.75, 7.5, and 15 mg/kg body weight, diluted in vehicle (n = 30/group), or received only mineral oil (control group, n = 45). The animals were divided into three periods of study: ND-treated receiving a daily subcutaneous injection for 15 consecutive days (1), and treatment with ND followed by 30-day recovery (2), and 60-day recovery (3). At the end of each period, five females per group were induced to death to histopathological analysis and the others were allowed to fertility evaluation (at 19th gestational day). Animals that received ND followed by 30-day recovery exhibited persistent diestrous and marked suppression of reproductive capacity. Conversely, after 60-day recovery, only lowest doses females (1.87 and 3.75 mg/kg) exhibited restoration of normal estrous cyclicity. Uterine weights were increased after ND treatment similarly to that of the controls after 60-day recovery. The ND-treated groups showed histopathological changes in the endometrium, myometrium, and perimetrium, and an increase in the thickness of both muscular and serous layers. Notably, the recovery of uterine tissue after ND treatment was dose- and period-dependent. We reported that administration of ND promoted damage in uterine tissue and fertility of rats, and the recovery periods were insufficient to restore all of the side effects caused by ND under a dose-dependent response. © 2014 Wiley Periodicals, Inc.

Where does hydrolysis of nandrolone decanoate occur in the human body after release from an oil depot?

PubMed

Kalicharan, R W; Bout, M R; Oussoren, C; Vromans, H

2016-12-30

Long-term therapy of nandrolone (N) is recommended to increase mineral density and muscle strength. Using a parenteral sustained release drug formulation with nandrolone decanoate (ND), therapeutic N levels can be achieved and maintained. Until now, it is unknown if hydrolysis of ND into N occurs in tissue at the injection site or after systemic absorption. Therefore, hydrolysis studies were conducted to investigate the location and rate of ND hydrolysis after its release from the oil depot. ND hydrolysis was studied in porcine tissues, to mimic the human muscular and subcutaneous tissues. Additionally, the ND hydrolysis was studied in human whole blood, plasma and serum at a concentration range of 23.3-233.3μM. ND hydrolysis only occurred in human whole blood. The hydrolysis did not start immediately, but after a lag time. The mean lag time for all studied concentrations was 34.9±2.5min. Because of a slow penetration into tissue, hydrolysis of ND is found to be very low in surrounding tissue. Therefore the local generation of the active compound is clinically irrelevant. It is argued that after injection of the oil depot, ND molecules will be transported via the lymphatic system towards lymph nodes. From here, it will enter the central circulation and within half an hour it will hydrolyse to the active N compound. Copyright © 2016 Elsevier B.V. All rights reserved.

Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

PubMed

Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

2014-01-01

Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

The effects of chronic administration of nandrolone decanoate on redox status in exercised rats.

PubMed

Nikolic, Tamara; Zivkovic, Vladimir; Jevdjevic, Maja; Djuric, Marko; Srejovic, Ivan; Djuric, Dragan; Jeremic, Nevena; Djuric, Dusan; Bolevich, Sergey; Jakovljevic, Vladimir

2016-01-01

For the past 40 years, anabolic-androgenic steroids have been used by a wide variety of athletes with the hope of improving their training, endurance, and performance. The aim of this study was to examine the chronic effects of nandrolone decanoate (20 mg/kg, s.c, Deca-Durabolin DECA(®)) on oxidative stress biomarkers in the hearts of sedentary and exercised rats. The male Wistar albino rats (n = 180, four groups with three subgroups, 15 per subgroup, age 10 weeks, body mass 200-220 g) were sacrificed, and in the collected samples of blood, the following markers of oxidative stress were measured spectrophotometrically: (1) index of lipid peroxidation (measured as TBARS-thiobarbituric acid reactive substances); (2) nitrites (NO2 (-)); (3) hydrogen peroxide (H2O2); (4) superoxide anion radical (O2 (-)), and superoxide dismutase, catalase, and glutathione reductase. The results clearly show that the impact of ND alone, or in combination with physical training in general, is mildly pro-oxidative. The chronic physical training probably induces the protective antioxidant enzyme system , which may be of clinical interest when faced with overdosage of this drug.

Non-classic androgen actions in Sertoli cell membrane in whole seminiferous tubules: effects of nandrolone decanoate and catechin.

PubMed

Cavalari, Fernanda Carvalho; de Castro, Alexandre Luz; Fracasso, Bianca de Moraes; Loss, Eloísa da Silveira

2012-01-01

Studies show a mechanism of action of testosterone, nandrolone and catechin as agonists of the membrane androgen receptor. The aim of this work is to investigate the non-classical effect of androgens and catechin in Sertoli cells from immature rats. The membrane potential of Sertoli cells in whole seminiferous tubules was recorded using a standard single microelectrode technique. It was performed a topical application of testosterone (1 μM), nandrolone (0.1, 0.5 and 1 μM) and the flavonoid catechin (0.1, 0.5 and 1 μM) alone and also after infusion with flutamide (1 μM), diazoxide (100 μM) or U73122 (1 μM). The immature testes were incubated for 5 min in KRb with (45)Ca(2+), with or without nandrolone (1 μM). The results were given as mean±SEM. The data were analyzed using ANOVA for repeated measures with Bonferroni post-test. Testosterone produces a depolarization in the membrane potential at 120 s after application. Catechin (1 μM) and nandrolone (1 μM) have shown a similar response to testosterone: depolarization at 120 s after the application. The same response of catechin and nandrolone was observed at different doses. The effects of testosterone, catechin and nandrolone were not affected after perfusion with flutamide. Perfusion with diazoxide and U73122 nullified the effect of nandrolone (1 μM) and catechin (1 μM). Nandrolone and testosterone increased (45)Ca(2+) uptake with or without flutamide within 5min. These results indicate that nandrolone and catechin act through a receptor on the plasmatic membrane, as well as testosterone, showing a non-classical pathway in Sertoli cells from immature rat testes. Copyright © 2011 Elsevier Inc. All rights reserved.

Effect of anabolic steroids on skeletal muscle mass during hindlimb suspension

NASA Technical Reports Server (NTRS)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass of plantaris and soleus of a rats in hindlimb suspension, and on the isomyosin expression in these muscles, was investigated in young female rats divided into four groups: normal control (NC), normal steroid (NS), normal suspension (N-sus), and suspension steroid (sus-S). Steroid treatment of suspended animals (sus-S vs N-sus) was found to partially spare body weight and muscle weight, as well as myofibril content of plantaris (but not soleus), but did not modify the isomyosin pattern induced by suspension. In normal rats (NS vs NC), steroid treatment did enhance body weight and plantaris muscle weight; the treatment did not alter isomyosin expression in either muscle type.

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone

PubMed Central

Wijnhoven, Hanneke JH; Ennen, Leo; Rodenburg, Richard JT; Dekhuijzen, PN Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model. PMID:18046906

Mitochondrial function in diaphragm of emphysematous hamsters after treatment with nandrolone.

PubMed

Wijnhoven, Hanneke J H; Ennen, Leo; Rodenburg, Richard J T; Dekhuijzen, P N Richard

2006-01-01

Respiratory failure in patients with COPD may be caused by insufficient force production or insufficient endurance capacity of the respiratory muscles. Anabolic steroids may improve respiratory muscle function in COPD. The effect of anabolic steroids on mitochondrial function in the diaphragm in emphysema is unknown. In an emphysematous male hamster model, we investigated whether administration of the anabolic steroid nandrolone decanoate (ND) altered the activity of mitochondrial respiratory chain complexes in the diaphragm. The bodyweight of hamsters treated with ND was decreased after treatment compared with initial values, and serum testosterone levels were significantly lower in hamsters treated with ND than in control hamsters. No difference in the activity of mitochondrial respiratory chain complexes in the diaphragm between normal and emphysematous hamsters was observed. Treatment with ND did not change the activity of mitochondrial respiratory chain complexes in the diaphragm of both normal and emphysematous hamsters. In emphysematous hamsters, administration of ND decreased the activity of succinate:cytochrome c oxidoreductase compared with ND treatment in normal hamsters. We conclude that anabolic steroids have negative effects on the activity of succinate:cytochrome c oxidoreductase and anabolic status in this emphysematous hamster model.

The impact of nandrolone decanoate and growth hormone on biosynthesis of steroids in rats.

PubMed

Grönbladh, Alfhild; Johansson, Jenny; Kushnir, Mark M; Bergquist, Jonas; Hallberg, Mathias

2013-12-11

Growth hormone (GH) and anabolic androgenic steroids (AAS) are commonly used in sports communities. Several studies have suggested an association between GH and AAS. We have investigated the impact of GH in rats treated with nandrolone decanoate (ND). Male Wistar rats received ND (15 mg/kg) every third day during three weeks and were subsequently treated with recombinant human GH (1.0I U/kg) for ten consecutive days. Plasma samples were collected and peripheral organs (i.e. heart, liver, testis and thymus) were dissected and weighed. Concentration of thirteen endogenous steroids was measured in the rat plasma samples using high specificity LC-MS/MS methods. Seven steroids were detected and quantified, and concentrations of estrone, testosterone, and androstenedione were significantly different among the groups, while concentrations of pregnenolone, DHEA, 17-hydroxyprogesterone and corticosterone were not altered. Administration of rhGH alone altered the plasma steroid distribution, and the results demonstrated significantly increased concentrations of plasma estrone as well as decreased concentrations of testosterone and androstenedione in the ND-treated rats. Administration of rhGH to ND-pretreated rats did not reverse the alteration of the steroid distribution induced by ND. Administration of ND decreased the weight of the thymus, and addition of rhGH did not reverse this reduction. However, rhGH administration induced an enlargement of thymus. Taken together, the plasma steroid profile differed in the four groups, i.e. control, AAS, rhGH and the combination of AAS and rhGH treatment. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Adjuvant Androgen on Anemia and Nutritional Parameters in Chronic Hemodialysis Patients Using Low-dose Recombinant Human Erythropoietin

PubMed Central

Lee, Myeung Su; Ahn, Seon Ho; Song, Ju Hung

2002-01-01

Background: Recombinant human erythropoietin (epoetin) has greatly contributed to improvement of the anemia of chronic renal failure patients on hemodialysis. However, the reduced erythropoietic effect to epoetin and its high cost have induced lots of supplementary treatments. Therefore, we performed a prospective study to evaluate the effects of adjuvant low-dose androgen therapy in patients using a lower-dose of epoetin than the commonly recommended dose on anemia and the nutritional parameters. Methods : 17 patients of hemoglobin (Hgb) less than 9 g/dL even after being treated with 1,000 U epoetin subcutaneously (s.c.) 3 times per week on a stable status for more than 6 months, who were on hemodialysis at our institution were examined. They were injected with the same dose of epoetin s.c. and nandrolone decanoate 100 mg intramuscularly (i.m) weekly for another 6 months. Blood test was performed every month before therapy for 6 months and after therapy for 6 months and the mean values were reviewed for comparison. Results: Hgb (7.75±0.9 vs 8.99±1.39 g/dL, p <0.01) and hematocrit (Hct) (23.68±2.85 vs 26.66±3.91%, p <0.01) were apparently changed before and after adjuvant therapy. Hgb and Hct, weekly dose of epoetin were not statistically different in 9 male patients before and after adjuvant therapy. The weekly dose of epoetin was not statistically different in 8 female patients, but Hgb and Hct (8.02±0.6 vs 9.72±1.31 g/dL, 24.54±1.7 vs 28.74±3.06%, p <0.01) were statistically different before and after adjuvant therapy. In comparison between male and female groups, weekly doses of epoetin and nandrolone decanoate were significantly greater in the female group than the male group (epoetin: 50.66±6.23 vs 61.18±8.76 U/kg/week, nandrolone decanoate: 1.69±0.2 vs 2.04±0.29 mg/kg/week, p <0.05). Conclusion : Our data show that the adjuvant androgen therapy is effective for the anemia of hemodialysis patients who did not recover from anemia even after being continuously treated with low-dose epoetin. PMID:12298427

Evaluation of anabolic steroid induced renal damage with sonography in bodybuilders.

PubMed

Kantarci, Umut H; Punduk, Zekine; Senarslan, Omer; Dirik, Alper

2017-11-17

The aim of this study was to investigate the effect of anabolic steroids on kidneys in bodybuilders. Twenty two bodybuilders were included in the study. Participants were divided into three groups according to the scheme of steroid usage: Group 1 (n=8, intramuscular 500 mg testosterone enanthate, intramuscular 400 mg nandrolone decanoate and oral 40 mg methandrostenolone for 12 weeks), Group 2 (n=7, intramuscular 500 mg testosterone enanthate, intramuscular 300 mg nandrolone decanoate and intramuscular 300 mg boldenone undecylenate for 16 weeks) and Group 3 (n=7, no steroid intake). Blood urea nitrogen (BUN), creatinine (Cr), urine microalbumin and electrolyte levels were measured. Renal volume, cortical thickness and echogenicity were obtained in ultrasonographic scans. Renal volume, cortical thickness, echogenicity and protein intake value were significantly higher in group 2 than group 1 and 3. Plasma levels of BUN and Cr in group 2 were significantly higher than other groups (p ˂ 0.001). Urine microalbumin and electrolyte levels were normal in all groups. The results of this study indicate that high protein intake, steroid usage, particularly the schemes, including boldenone undecylenate increases cortical echogenicity, thickness of renal parenchyma and renal volume in bodybuilders.

Anabolic steroid and gender-dependent modulation of cytosolic HSP70s in fast- and slow-twitch skeletal muscle.

PubMed

González, B; Hernando, R; Manso, R

2000-09-01

Besides their clinical uses, anabolic steroids (AASs) are self-administered by athletes to improve muscle mass and sports performance. The biological basis for their presumed effectiveness at suprapharmacological doses, however, remains uncertain. Since the expression of high levels of some stress proteins (HSPs) has been associated with an increased tolerance to stress and chronic exercise up-regulates HSP72 in skeletal muscle, this investigation was aimed at testing whether the administration of suprapharmacological doses of AASs, either alone or in conjunction with chronic exercise, induced changes in HSP72. Nandrolone decanoate (ND), an estrene derivative, but not stanozolol (ST), a derivative of the androstane series, up-regulated the levels of HSP72 and changed the proportions of various charge variants of the cytosolic HSP70s in sedentary and exercise-trained rats, exclusively in fast-twitch fibres. Since the expression of HSP73-levels in skeletal muscle was dependent on gender but not on muscle type, and that of HSP72-levels was muscle type specific but gender-independent, ND effects on cytosolic HSP70s could not be explained solely by a functional relationship with sex steroids. The reported results indicate that, by up-regulating the expression levels of HSP72 in fast-twitch fibres, nandrolone decanoate could contribute to improving the tolerance of skeletal muscle to high-intensity training.

Effects of nandrolone decanoate on time to consolidation of bone defects resulting from osteotomy for tibial tuberosity advancement.

PubMed

Marques, Danilo R C; Marques, Danilo; Ibanez, Jose F; Freitas, Itallo B; Hespanha, Ana C; Monteiro, Juliana F; Eggert, Mayara; Becker, Amanda

2017-09-12

Experimental study. The aim of this study was to evaluate the effect of nandrolone decanoate (ND) on the time taken for bone consolidation in dogs undergoing tibial tuberosity advancement surgery (TTA). Seventeen dogs that underwent TTA surgery were randomly divided into two groups: group C (TTA; 9 stifles), and group TTA+ND (TTA and systemic administration of ND; 8 stifles). Three observers (two radiologists and an orthopaedic surgeon), assessed bone consolidation by visual inspection of serial radiographs at intervals of 21 days following surgery. There were no differences in median weight and age between groups, nor between the medians of the variables right and left stifle. Only weight and age values were normally distributed. The other variables, right and left stifle and time to consolidation, showed non-normal distribution. Meniscal injury was present in all animals in group C and all animals in group TTA+ND. There was a significant difference between time to consolidation in groups C and TTA+ND (p <0.05). One animal in the group TTA+ND showed increased libido. Kappa agreement among observers on radiographs was 0.87. Administration of ND reduces time to bone consolidation in dogs undergoing TTA.

Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study.

PubMed

Chung, T; Kelleher, S; Liu, P Y; Conway, A J; Kritharides, L; Handelsman, D J

2007-02-01

Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5alpha reduction) of testosterone on cardiac muscle been directly studied. To assess the effects of testosterone and nandrolone, a non-amplifiable and non-aromatizable pure androgen, on cardiac muscle function in healthy young men. Double-blind, randomized, placebo-controlled, three-arm parallel group clinical trial. Ambulatory care research centre. Healthy young men randomized into three groups of 10 men. Weekly intramuscular injections of testosterone (200 mg mixed esters), nandrolone (200 mg nandrolone decanoate) or matching (2 ml arachis oil vehicle) placebo for 4 weeks. Comprehensive measures of cardiac muscle function involving transthoracic cardiac echocardiography measuring myocardial tissue velocity, peak systolic strain and strain rates, and bioimpedance measurement of cardiac output and systematic vascular resistance. Left ventricular (LV) function (LV ejection fraction, LV modified TEI index), right ventricular (RV) function (ejection area, tricuspid annular systolic planar motion, RV modified TEI index) as well as cardiac afterload (mean arterial pressure, systemic vascular resistance) and overall cardiac contractility (stroke volume, cardiac output) were within age- and gender-specific reference ranges and were not significantly (P < 0.05) altered by either androgen or placebo over 4 weeks of treatment. Minor changes remaining within normal range were observed solely within the testosterone group for: increased LV end-systolic diameter (30 +/- 7 vs. 33 +/- 5 mm, P = 0.04) and RV end-systolic area (12.8 +/- 1.3 vs. 14.6 +/- 3.3 cm(2), P = 0.04), reduced LV diastolic septal velocity (Em, 9.5 +/- 2.6 vs. 8.7 +/- 2.0 cm/s, P = 0.006), increased LV filling pressure (E/Em ratio, 7.1 +/- 1.6 vs. 8.3 +/- 1.8, P = 0.02) and shortened PR interval on the electrocardiogram (167 +/- 13 vs. 154 +/- 12, P = 0.03). Four weeks of treatment with testosterone or nandrolone had no beneficial or adverse effects compared with placebo on cardiac function in healthy young men.

Detection and quantification of 12 anabolic steroids and analogs in human whole blood and 20 in hair using LC-HRMS/MS: application to real cases.

PubMed

Fabresse, Nicolas; Grassin-Delyle, Stanislas; Etting, Isabelle; Alvarez, Jean-Claude

2017-07-01

We developed and validated a method to detect and quantify 12 anabolic steroids in blood (androstenedione, dihydrotestosterone, boldenone, epitestosterone, mesterolone, methandienone, nandrolone, stanozolol, norandrostenedione, tamoxifene, testosterone, trenbolone) and eight more in hair samples (nandrolone phenylpropionate, nandrolone decanoate, testosterone propionate, testosterone benzoate, testosterone cypionate, testosterone decanoate, testosterone phenylpropionate, testosterone undecanoate) using liquid chromatography coupled to high-resolution mass spectrometry. This method used a benchtop Orbitrap mass spectrometer operating with an APCI probe under positive ionization mode. Analysis was realized in full scan experiment with a nominal resolving power of 140,000. After addition of the internal standard (testosterone-D3) and incubation in phosphate buffer pH = 5 for hair, 200 μL of blood and 30 mg of hair samples were extracted with heptane. LOQ and LOD were determined at 5 and 1 ng mL -1 in whole blood and 10 to 100 pg mg -1 and 2 to 20 pg mg -1 in hair according to the compounds, respectively. The method was linear in the 5-1000 ng mL -1 range in whole blood and between 10 or 100 pg mg -1 and 1000 pg mg -1 in hair with correlation coefficients >0.99, and intra- and inter-day accuracy and precision were <14.8% for all compounds except for some esters in hairs (<19.9%) probably due to an important matrix effect for these compounds. This sensitive and specific method to detect anabolic steroids has been successfully applied to two real cases, for which various anabolic steroids in whole blood, urine, and hair were identified and quantified.

Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein (a)

PubMed Central

Hartgens, F; Rietjens, G; Keizer, H; Kuipers, H; Wolffenbuttel, B

2004-01-01

Objectives: To investigate the effects of two different regimens of androgenic-anabolic steroid (AAS) administration on serum lipid and lipoproteins, and recovery of these variables after drug cessation, as indicators of the risk for cardiovascular disease in healthy male strength athletes. Methods: In a non-blinded study (study 1) serum lipoproteins and lipids were assessed in 19 subjects who self administered AASs for eight or 14 weeks, and in 16 non-using volunteers. In a randomised double blind, placebo controlled design, the effects of intramuscular administration of nandrolone decanoate (200 mg/week) for eight weeks on the same variables in 16 bodybuilders were studied (study 2). Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-C), HDL2-cholesterol (HDL2-C), HDL3-cholesterol (HDL3-C), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and lipoprotein (a) (Lp(a)) were determined. Results: In study 1 AAS administration led to decreases in serum concentrations of HDL-C (from 1.08 (0.30) to 0.43 (0.22) mmol/l), HDL2-C (from 0.21 (0.18) to 0.05 (0.03) mmol/l), HDL3-C (from 0.87 (0.24) to 0.40 (0.20) mmol/l, and Apo-A1 (from 1.41 (0.27) to 0.71 (0.34) g/l), whereas Apo-B increased from 0.96 (0.13) to 1.32 (0.28) g/l. Serum Lp(a) declined from 189 (315) to 32 (63) U/l. Total cholesterol and triglycerides did not change significantly. Alterations after eight and 14 weeks of AAS administration were comparable. No changes occurred in the controls. Six weeks after AAS cessation, serum HDL-C, HDL2-C, Apo-A1, Apo-B, and Lp(a) had still not returned to baseline concentrations. Administration of AAS for 14 weeks was associated with slower recovery to pretreatment concentrations than administration for eight weeks. In study 2, nandrolone decanoate did not influence serum triglycerides, total cholesterol, HDL-C, HDL2-C, HDL3-C, Apo-A1, and Apo-B concentrations after four and eight weeks of intervention, nor six weeks after withdrawal. However, Lp(a) concentrations decreased significantly from 103 (68) to 65 (44) U/l in the nandrolone decanoate group, and in the placebo group a smaller reduction from 245 (245) to 201 (194) U/l was observed. Six weeks after the intervention period, Lp(a) concentrations had returned to baseline values in both groups. Conclusions: Self administration of several AASs simultaneously for eight or 14 weeks produces comparable profound unfavourable effects on lipids and lipoproteins, leading to an increased atherogenic lipid profile, despite a beneficial effect on Lp(a) concentration. The changes persist after AAS withdrawal, and normalisation depends on the duration of the drug abuse. Eight weeks of administration of nandrolone decanoate does not affect lipid and lipoprotein concentrations, although it may selectively reduce Lp(a) concentrations. The effect of this on atherogenesis remains to be established. PMID:15155420

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

PubMed Central

Bruley-Rosset, M; Dardenne, M; Schuurs, A

1985-01-01

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. PMID:3878753

Effect of supraphysiological dose of Nandrolone Decanoate on the testis and testosterone concentration in mature and immature male rats: A time course study.

PubMed

Jannatifar, Rahil; Shokri, Saeed; Farrokhi, Ahmad; Nejatbakhsh, Reza

2015-12-01

Most studies on anabolic-androgenic steroids abuse have been done in adult rats, but few data are available to immature. This study was conducted to assay the effect of Nandrolone Decanoate (ND) on the testis and testosterone concentration in male immature rats compare with mature ones in short and long time. 40 mature rats were divided into 4 groups: group A (short term) and group B (long-term) received 10 mg/kg/day ND interaperitoneally for 35 and 70 days, respectively. Group C (control) without any treatment, and group D (vehicle) received dimethyl sulfoxide (DMSO) solution in two periods 35 and 70 days. 40 immature rats were divided into 4 groups same as mature ones. After surgery body weight, testis size, histomorphometry of testis, and serum testosterone level were evaluated. Our results showed that ND decreased the number of Leydig cells in group B (39.9 ±. 919), group A (43.4 ±. 120), and long term (40.6 ±. 299) immature rats, which could result in a reduction of testosterone concentration significantly in all experimental groups except short term mature group. Number of sertoli cells, testis size, and diameter of seminiferous tubules decreased in the long-term immature group. Eventually, the number of sperm was decreased in mature and immature groups, but a severe depletion of sperm was occurred in both mature and immature in long time in comparison to the control group (p< 0.05). This time course study showed that supraphysiological dose of ND may negatively affect the number of Leydig cells, sperm cell, and testosterone concentration of immature rats in the same matter of mature rats. However, the number of sertoli cell, testis size, and seminferous diameter were decreased only in the long immature rats.

GH improves spatial memory and reverses certain anabolic androgenic steroid-induced effects in intact rats.

PubMed

Grönbladh, Alfhild; Johansson, Jenny; Nöstl, Anatole; Nyberg, Fred; Hallberg, Mathias

2013-01-01

GH has previously been shown to promote cognitive functions in GH-deficient rodents. In this study we report the effects of GH on learning and memory in intact rats pretreated with the anabolic androgenic steroid nandrolone. Male Wistar rats received nandrolone decanoate (15 mg/kg) or peanut oil every third day for 3 weeks and were subsequently treated with recombinant human GH (1.0 IU/kg) or saline for 10 consecutive days. During the GH/saline treatment spatial learning and memory were tested in the Morris water maze (MWM). Also, plasma levels of IGF1 were assessed and the gene expression of the GH receptors (Ghr), Igf1 and Igf2, in hippocampus and frontal cortex was analyzed. The results demonstrated a significant positive effect of GH on memory functions and increased gene expression of Igf1 in the hippocampus was found in the animals treated with GH. In addition, GH was demonstrated to increase the body weight gain and was able to attenuate the reduced body weight seen in nandrolone-treated animals. In general, the rats treated with nandrolone alone did not exhibit any pronounced alteration in memory compared with controls in the MWM, and in many cases GH did not induce any alteration. Regarding target zone crossings, considered to be associated with spatial memory, the difference between GH- and steroid-treated animals was significant and administration of GH improved this parameter in the latter group. In conclusion, GH improves spatial memory in intact rats and can reverse certain effects induced by anabolic androgenic steroid.

Subchronic nandrolone administration reduces cocaine-induced dopamine and 5-hydroxytryptamine outflow in the rat nucleus accumbens.

PubMed

Kurling-Kailanto, Sanna; Kankaanpää, Aino; Seppälä, Timo

2010-04-01

The abuse of anabolic androgenic steroids (AASs) is not only a problem in the world of sports but is associated with the polydrug use of nonathletes. Investigations of the neurochemical effects of AAS have focused in part on the monoaminergic systems, involving, among other things, the development of dependence. We have previously shown that pretreatment with nandrolone decanoate attenuates dose-dependently the increase in extracellular dopamine (DA) concentration evoked by amphetamine and 3,4-methylenedioyxymethamphetamine in the nucleus accumbens (NAc). The aim of this study was to investigate whether the nandrolone pre-exposure modulates the acute neurochemical and behavioral effects of cocaine in rats and whether the effects are long lasting. DA, 5-hydroxytryptamine (5-HT), and their metabolites were measured from samples collected from the NAc by microdialysis. The behavior of the animals was recorded. The present study demonstrates that five injections of nandrolone (5 and 20 mg/kg) inhibited cocaine-evoked DA and 5-HT outflow in the NAc, locomotor activity (LMA), and stereotyped behavior in experimental animals, and that these effects are seen even after elimination of nandrolone from bloodstream. Given that accumbal outflow of DA and 5-HT, as well as LMA and stereotyped behavior, is related to gratification of stimulant drugs, this study suggests that nandrolone, at the doses tested, has a significant effect on the pleasurable properties of cocaine. Furthermore, because neurochemical and behavioral responses were still attenuated after a fairly long recovery period, it seems that nandrolone may induce long-lasting changes in the brains of rat.

Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men.

PubMed

Gårevik, N; Börjesson, A; Choong, E; Ekström, L; Lehtihet, M

2016-06-01

The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long-term consequences on cardiovascular risk that may appear in users remain to be elucidated. © 2015 Blackwell Verlag GmbH.

The effects of high doses of nandrolone decanoate and exercise on prostate microvasculature of adult and older rats.

PubMed

de Melo Neto, João Simão; de Campos Gomes, Fabiana; Pinheiro, Patrícia Fernanda Felipe; Pereira, Sérgio; Scarano, Wellerson Rodrigo; Fávaro, Wagner José; Domeniconi, Raquel Fantin

2015-01-15

The present study aimed to investigate the effects of the interaction between the abusive use of nandrolone decanoate (ND) and physical activity on the prostate structure of adult and older rats. We evaluated whether the use of ND, associated or not with physical exercise during the post-pubertal stage, interferes with the morphophysiology of the prostate. Fifty-six male Sprague-Dawley rats were divided into eight groups. The animals were treated for eight weeks and divided into sedentary and trained groups, with or without ND use. Four groups were sacrificed 48 h after the end of the eight week experiment (adult groups), and four other groups were sacrificed at 300 days of age (older groups). The prostate was collected and processed for stereological and histopathological analysis and for the expression of AQP1 and VEGF by the Western blotting technique. Both ND and physical activity altered the ventral prostate structure of the rats; the AQP1 and VEGF expression increased in young animals subjected to physical exercise. Thus, it was concluded that the use of ND, associated or not with exercise during the post-pubertal stage, interferes with the morphophysiology of the prostate. Copyright © 2014 Elsevier Inc. All rights reserved.

Low-intensity endurance exercise plus nandrolone decanoate modulates cardiac adiponectin and its receptors.

PubMed

Karimi, A; Joukar, S; Najafipour, H; Masoumi-Ardakani, Y; Shahouzehi, B

2017-03-01

Vast adverse effects of anabolic-androgenic steroids (AASs) on athletes' cardiovascular systems have been reported. However, there is still a lack of adequate information regarding the pathways and mechanisms involved. We tested the hypothesis that adiponectin and its receptors in the heart may be affected by long-term use of AASs alongside exercising. Male Wistar rats were randomized into the control (CTL), exercise (EX), nandrolone (Nan), arachis (Arach) group which treated with arachis as vehicle, trained vehicle (EX+Arach) and trained nandrolone (EX+Nan) groups that were treated for 8 weeks. One day after the end of the protocol, animals were sacrificed and their hearts were frozen. TNF-α and adiponectin proteins of hearts were evaluated quantitatively by ELISA kits, and Western blot analysis was used for measuring adiponectin receptor protein expression. TNF-α protein increased significantly in the EX+Nan group (P<.05 vs CTL group). The AdipoR1 protein was significantly higher in the presence of nandrolone alongside exercise (P<.05 vs Nan and EX+Arach groups, P<.01 vs CTL and Arach groups). In addition, AdipoR2 protein enhanced in the EX+Nan group when compared with the other groups (P<.05 vs EX and EX+Arach groups, P<.01 vs CTL, Arach and Nan groups). Chronic nandrolone plus mild endurance exercise may be associated with imbalance in pro-/anti-inflammatory cytokines and may induce a positive modulatory effect on cardiac adiporeceptors in rat. Further studies are required before these findings can be generalized to humans. © 2017 John Wiley & Sons Ltd.

Stereological estimation of ovarian oocyte volume, surface area and number: application on mice treated with nandrolone decanoate.

PubMed

Karbalay-Doust, Saied; Noorafshan, Ali

2012-07-05

Changes in the number and size of oocytes can lead to fertilization problems. The present study aimed to evaluate the number, volume, and surface area of oocytes in healthy as well as nandrolone decanoate-treated (ND) mice using stereological methods. Five control mice received vehicle, and five ND-treated mice received ND. Using the 'isotropic Cavalieri' design', the ovary was sectioned. The volume of the ovary (cortex and medulla) was estimated. The oocytes' volume and surface area were estimated using the invariator. The number of the oocytes was estimated using an optical disector. The volumes of the ovary, cortex, and medulla decreased ~50% in the ND-treated mice. The mean number (coefficient of variation) of preantral, antral, and atretic oocytes in the control ovary were 1,690 (0.29), 2,100 (0.52), and 3,900 (0.2), respectively, which decreased ~54%, ~87%, and ~91%, respectively in the ND-treated animals. The mean volume (coefficient of variation) of the preantral, antral, and atretic oocytes were 86,000 (0.27), 110,000 (0.48), and 27,000 (0.33) μm³, respectively. The mean surface area (coefficient of variation) of the three types of oocytes were 9,000 (0.24), 9,900 (0.28), and 4,700 (0.21) μm², respectively. These parameters remained unchanged in the ND-treated mice. ND induces reduction in the number of oocytes, but not in the volume or the surface area.

Bodybuilders' body composition: effect of nandrolone decanoate.

PubMed

van Marken Lichtenbelt, Wouter D; Hartgens, Fred; Vollaard, Niels B J; Ebbing, Spike; Kuipers, Harm

2004-03-01

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. 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. 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. 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.

Pharmacokinetic-pharmacodynamic study of subcutaneous injection of depot nandrolone decanoate using dried blood spots sampling coupled with ultrapressure liquid chromatography tandem mass spectrometry assays.

PubMed

Singh, Gurmeet K S; Turner, Leo; Desai, Reena; Jimenez, Mark; Handelsman, David J

2014-07-01

Testosterone (T) and nandrolone (N) esters require deep im injections by medical personnel but these often deposit injectate into sc fat so that more convenient sc self-administration may be feasible. To investigate the feasibility and pharmacology of sc injection of N decanoate in healthy men using dried blood spot (DBS) for frequent blood sampling without clinic visits. Healthy male volunteers received 100 mg N decanoate by a single sc injection. Finger-prick capillary blood was spotted onto filter paper before injection daily at home for 21 d and stored at room temperature. Venous whole blood was also spotted onto filter paper before and weekly for 3 wk after injection. DBS were extracted for assay of N and T by liquid chromatography tandem mass spectrometry in a single batch with serum concentrations estimated with adjustment for capillary blood sample volume and hematocrit to define peak (N) or nadir (T) time and concentration from individual daily measurements. Daily serum N peaked 2.50 ± 0.25 (SEM) ng/mL at a median (range) of 6 (4-13) days causing a reduction in serum T from 3.50 ± 0.57 ng/mL at baseline to a nadir of 0.38 ± 0.13 (SEM) ng/mL (89 ± 3% suppression) at a median (range) of 8 (5-16) days. Simultaneously sampled capillary, venous whole blood, and serum gave almost identical results for serum T and N. Finger-pricks and sc injections were well tolerated. This study demonstrates that A) DBS sampling with liquid chromatography mass spectrometry steroid analysis achieves frequent time sampling in the community without requiring clinic visits, venesection, or frozen serum storage, and B) androgen esters in an oil vehicle can be delivered effectively by sc injection, thus avoiding the need for medically supervised deep-im injections.

Nandrolone decanoate as anabolic therapy in chronic kidney disease: a randomized phase II dose-finding study.

PubMed

Macdonald, Jamie H; Marcora, Samuele M; Jibani, Mahdi M; Kumwenda, Mick J; Ahmed, Wasim; Lemmey, Andrew B

2007-01-01

In patients with chronic kidney disease (CKD) receiving adequate erythropoietin therapy, the ideal dose of nandrolone decanoate (ND) to enhance muscle mass is not known. In this phase II dose-finding study, 54 patients with CKD stage 5 were randomized to either low, medium or high doses of ND (50, 100 or 200 mg/week for 24 weeks, respectively, in males; doses halved in females), while 7 patients acted as non-randomized controls. The primary outcome measure was appendicular lean mass (ALM) by dual-energy X-ray absorptiometry. Fluid overload (hydration of the fat-free mass) and indicators of physical functioning were secondary measures. Harms were also recorded. Data were analysed using Quade's (1967) non-parametric analysis of covariance. ND increased ALM in a dose-responsive manner (change scores = 0.3 +/- 0.3 vs. 0.8 +/- 0.3 vs. 1.5 +/- 0.5 vs. 2.1 +/- 0.4 kg, control vs. low vs. medium vs. high dose groups, respectively, p < 0.001) with no increases in fluid overload but no consistent effect on physical functioning. The highest dose of ND (100 mg/week) was intolerable in females because of virilizing effects. If goals of future studies are to improve body composition, dosing of ND up to 200 mg/week in males and 50 mg/week in females should be investigated. However, to realize improvements in physical functioning, future phase III trials of ND may require additional interventions such as exercise training. Copyright 2007 S. Karger AG, Basel.

Nandrolone decanoate negatively reverses the beneficial effects of exercise on cardiac muscle via sarcolemmal, but not mitochondrial K(ATP) channel.

PubMed

Bayat, Gholamreza; Javan, Mohammad; Safari, Fatemeh; Khalili, Azadeh; Shokri, Saeed; Goudarzvand, Mahdi; Salimi, Mehdi; Hajizadeh, Sohrab

2016-03-01

ATP-sensitive potassium channels are supposed to have a substantial role in improvement of cardiac performance. This study was performed to evaluate whether nandrolone decanoate (ND) and (or) exercise training could affect the expression of cardiac K(ATP) channel subunits. Thirty-five male albino Wistar rats were randomly divided into 5 groups, including sedentary control (SC), sedentary vehicle (SV), sedentary ND (SND), exercise control (EC), and exercise and ND (E+ND). Exercise training was performed on a treadmill 5 times per week. ND was injected (10 mg/kg/week, i.m.) to the rats in the SND and E+ND groups. Following cardiac isolation, the expression of both sarcolemmal and mitochondrial subunits of K(ATP) channel was measured using Western blot method. The expression of sarcolemmal, but not mitochondrial, subunits of K(ATP) channel (Kir6.2 and SUR2) of EC group was significantly higher compared with SC group while ND administration (SND group) did not show any change in their expression. In the E+ND group, ND administration led to decrease of the over-expression of sarcolemmal Kir6.2 and SUR2 which was previously induced by exercise. There was no significant association between the mitochondrial expression of either Kir6.2 or SUR2 proteins and administration of ND or exercise. Supra-physiological dosage of ND negatively reverses the effects of exercise on the cardiac muscle expression of sarcolemmal, but not mitochondrial, K(ATP) channel subunits.

Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components.

PubMed

Barone, Rosario; Pitruzzella, Alessandro; Marino Gammazza, Antonella; Rappa, Francesca; Salerno, Monica; Barone, Fulvio; Sangiorgi, Claudia; D'Amico, Daniela; Locorotondo, Nicola; Di Gaudio, Francesca; Cipolloni, Luigi; Di Felice, Valentina; Schiavone, Stefania; Rapisarda, Venerando; Sani, Gabriele; Tambo, Amos; Cappello, Francesco; Turillazzi, Emanuela; Pomara, Cristoforo

2017-08-01

The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography-mass spectrometry. Western blot analysis and quantitative real-time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression levels of the blood-testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein-1 (TJP1). ND stimulation deregulated metalloproteinase-9, metalloproteinase-2 (MMP-2) and the tissue inhibitor of MMP-2. Moreover, ND administration resulted in a mislocalization of mucin-1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP-2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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

PubMed

Sheashaa, Hussein; Abdel-Razek, Waleed; El-Husseini, Amr; Selim, Amal; Hassan, Nabil; Abbas, Tarek; El-Askalani, Hassan; Sobh, Mohamed

2005-01-01

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. 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. 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. 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.

Nandrolone decanoate inhibits gluconeogenesis and decreases fasting glucose in Wistar male rats.

PubMed

Frankenfeld, Stephan Pinheiro; de Oliveira, Leonardo Pires; Ignacio, Daniele Leão; Coelho, Raquel Guimarães; Mattos, Mariana Nigro; Ferreira, Andrea Claudia Freitas; Carvalho, Denise Pires; Fortunato, Rodrigo Soares

2014-02-01

The use of anabolic-androgenic steroids to improve physical performance or appearance has increased notably. The doses used are 10- to 100- fold higher than the therapeutic dose (TD), and this abuse can cause several side effects. Glucose metabolism is significantly affected by anabolic-androgenic steroid abuse, but studies about glycemic regulation during fasting are scarce. There are some evidences showing that testosterone can antagonize glucocorticoids action, which are crucial to glucose production during fasting. Thus, the aim of this study was to determine the impact of supraphysiological doses (SDs) of nandrolone decanoate (DECA) on rat glucose metabolism during fasting. Male Wistar rats were treated with i.m. injections of vehicle, a low TD (0.016 mg/100 g b.w.-TD group) or a high SD (1 mg/100 g b.w.-SD group) of DECA, once a week for 8 weeks. After 12 h fasting, we evaluated glucose and pyruvate tolerance tests, liver glycogen content, serum levels of gluconeogenic substrates, insulin and corticosterone, glucose uptake and hexokinase (HK) activity in skeletal muscle, and the adrenal catecholamine content. SD group had increased serum insulin levels and a blunted response to insulin regarding glucose uptake in skeletal muscle. Fasting serum glucose decreased significantly in SD group, as well as the pyruvate tolerance test and liver glycogen content. Moreover, serum levels of glycerol were increased in SD group. Our data indicate that SDs of DECA exert effects on different regulatory points of glucose metabolism, resulting in defective gluconeogenesis and decreased skeletal muscle glucose uptake in response to insulin.

Melatonin improve the sperm quality in forced swimming test induced oxidative stress in nandrolone treated Wistar rats.

PubMed

Minaii, Bagher; Moayeri, Ardeshir; Shokri, Saeed; Habibi Roudkenar, Mehryar; Golmohammadi, Taghi; Malek, Fatemeh; Barbarestani, Mohammad

2014-01-01

This study investigates the effects of melatonin on the sperm quality and testis weight after the combination of swimming exercise and nandrolone decanoate (DECA). Two groups of male Wistar rats were treated for eight weeks as follows; group A consist of CO (control), Sham, N (DECA), S (swimming) and NS (DECA plus swimming); and group B: Sham M (sham melatonin), M (melatonin), MN (melatonin plus DECA), MS (melatonin plus swimming), MNS (melatonin, DECA plus swimming). The motility of sperm was significantly improved in melatonin groups in comparison to N, S and NS groups (P≤0.05).  The left testes weight was decreased in N, NS and MNS groups, and the right testes weight was decreased in N,S,NS, MS and MNS groups in compare with the control group. This study concluded that melatonin probably could improve the sperm motility and sex organs weight after the combination of DECA and exercise.

Subchronic nandrolone administration reduces cardiac oxidative markers during restraint stress by modulating protein expression patterns.

PubMed

Pergolizzi, Barbara; Carriero, Vitina; Abbadessa, Giuliana; Penna, Claudia; Berchialla, Paola; De Francia, Silvia; Bracco, Enrico; Racca, Silvia

2017-10-01

Nandrolone decanoate (ND), an anabolic-androgenic steroid prohibited in collegiate and professional sports, is associated with detrimental cardiovascular effects through redox-dependent mechanisms. We previously observed that high-dose short-term ND administration (15 mg/kg for 2 weeks) did not induce left heart ventricular hypertrophy and, paradoxically, improved postischemic response, whereas chronic ND treatment (5 mg/kg twice a week for 10 weeks) significantly reduced the cardioprotective effect of postconditioning, with an increase in infarct size and a decrease in cardiac performance. We wanted to determine whether short-term ND administration could affect the oxidative redox status in animals exposed to acute restraint stress. Our hypothesis was that, depending on treatment schedule, ND may have a double-edged sword effect. Measurement of malondialdehyde and 4-hydroxynonenal, two oxidative stress markers, in rat plasma and left heart ventricular tissue, revealed that the levels of both markers were increased in animals exposed to restraint stress, whereas no increase in marker levels was noted in animals pretreated with ND, indicating a possible protective action of ND against stress-induced oxidative damage. Furthermore, isolation and identification of proteins extracted from the left heart ventricular tissue samples of rats pretreated or not with ND and exposed to acute stress showed a prevalent expression of enzymes involved in amino acid synthesis and energy metabolism. Among other proteins, peroxiredoxin 6 and alpha B-crystallin, both involved in the oxidative stress response, were predominantly expressed in the left heart ventricular tissues of the ND-pretreated rats. In conclusion, ND seems to reduce oxidative stress by inducing the expression of antioxidant proteins in the hearts of restraint-stressed animals, thus contributing to amelioration of postischemic heart performance.

The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin-positive interneurons.

PubMed

Selakovic, Dragica; Joksimovic, Jovana; Zaletel, Ivan; Puskas, Nela; Matovic, Milovan; Rosic, Gvozden

2017-01-01

The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.

Administration of growth hormone and nandrolone decanoate alters mRNA expression of the GABAB receptor subunits as well as of the GH receptor, IGF-1, and IGF-2 in rat brain.

PubMed

Grönbladh, Alfhild; Johansson, Jenny; Nyberg, Fred; Hallberg, Mathias

2014-01-01

The illicit use of anabolic androgenic steroids (AAS), especially among young adults, is of major concern. Among AAS users it is common to combine the AAS nandrolone decanoate (ND), with intake of growth hormone (GH) and a connection between gonadal steroids and the GH system has been suggested. Both AAS and GH affect functions in the brain, for example those associated with the hypothalamus and pituitary, and several GH actions are mediated by growth factors such as insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2). The GABAergic system is implicated in actions induced by AAS and previous studies have provided evidence for a link between GH and GABAB receptors in the brain. Our aim was to examine the impact of AAS administration and a subsequent administration of GH, on the expression of GABAB receptors and important GH mediators in rat brain. The aim was to investigate the CNS effects of a high-dose ND, and to study if a low, but physiological relevant, dose of GH could reverse the ND-induced effects. In the present study, male rats were administered a high dose of ND every third day during three weeks, and subsequently the rats were given recombinant human GH (rhGH) during ten days. Quantitative PCR (qPCR) was used to analyze gene expression in hypothalamus, anterior pituitary, caudate putamen, nucleus accumbens, and amygdala. In the pituitary gland, the expression of GABAB receptor subunits was affected differently by the steroid treatment; the GABAB1 mRNA expression was decreased whereas a distinct elevation of the GABAB2 expression was found. Administration of ND also caused a decrease of GHR, IGF-1, and IGF-2 mRNA expression in the pituitary while the corresponding expression in the hypothalamus, caudate putamen, nucleus accumbens, and amygdala was unaffected. The rhGH administration did not alter the GABAB2 expression but increased the GABAB1 gene expression in the hypothalamus as compared to the AAS treated group. These results provide new insights on the impact of ND and GH on the brain and highlight the interaction of these hormones with systems influencing GABAB receptor expression. The physiological significance of the observed effects of these hormones is discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effect of anabolic steroids on overloaded and overloaded suspended skeletal muscle

NASA Technical Reports Server (NTRS)

Tsika, R. W.; Herrick, R. E.; Baldwin, K. M.

1987-01-01

The effect of treatment with an anabolic steroid (nandrolone decanoate) on the muscle mass, the subcellular protein content, and the myosin patterns of normal overloaded and suspended overloaded plantaris muscle in female rat was investigated, dividing rats into six groups: normal control (NC), overload (OV), OV steroid (OV-S), normal suspended (N-sus), OV suspended (OV-sus), and OV suspended steroid (OV-sus-S). Relative to control values, overload produced a sparing effect on the muscle weight of the OV-sus group as well as increases of muscle weight of the OV group; increased protein content; and an increased expression of slow myosin in both OV and OV-sus groups. Steroid treatment of OV animals did not after the response of any parameter analyzed for the OV group, but in the OV-sus group steroid treatment induced increases in muscle weight and in protein content of the OV-sus-S group. The treatment did not alter the pattern of isomyosin expression observed in the OV or the OV-sus groups. These result suggest that the steroid acts synergistically with functional overload only under conditions in which the effect of overload is minimized by suspension.

The effect of nandrolone treatment with and without enforced swimming on histological and biochemical changes in the heart and coronary artery of male rats

PubMed Central

Tofighi, Asghar; Shirpoor, Minoo; Ansari, Mohammad Hasan Khadem; Shirpoor, Alireza; Zerehpoosh, Mitra

2017-01-01

Objective: Chronic anabolic androgenic steroid (AAS) consumption increases incidence of cardiovascular abnormalities in athletes and mechanisms underlying those abnormalities continue to be investigated. This study examines whether nandrolone consumption induced cardiac and coronary artery wall abnormalities via oxidative stress. It was also designed to determine whether enforced swimming augmented possible cardiotoxic effects of nandrolone in rat heart. Methods: Twenty-four male Wistar rats were divided into 3 groups: control, nandrolone, and nandrolone with enforced swimming. Nandrolone group received 10 mg/kg body weight nandrolone 3 times a week for 6 weeks. Nandrolone group with enforced swimming received the same amount of nandrolone and was forced to swim with excess weight of 20% body weight. Results: After 6 weeks of treatment, results indicated proliferation of heart muscle and coronary smooth muscle cells and lipid peroxidation; significant rise in levels of 8-hydroxy-2’-deoxyguanosine (8-OHdG), nicotinamide adenine dinucleotide phosphate oxidase, homocysteine (Hcy), apolipoprotein B, low-density lipoprotein, and cholesterol, as well as severe fibrosis in heart tissue and around coronary arteries of nandrolone and nandrolone with enforced swimming groups compared with control group. Conclusion: These findings strongly support idea that nandrolone intake by sedentary rats and exercised rats induced heart abnormality mediated by oxidative stress, which was manifest in increased lipid peroxidation, Hcy, and 8-OHdG in heart tissue. PMID:27752030

Nandrolone decreases mu opioid receptor expression in SH-SY5Y human neuroblastoma cells.

PubMed

Guarino, Goffredo; Spampinato, Santi

2008-07-16

Nandrolone and other anabolic androgenic steroids alter the expression and function of neurotransmitter systems and contribute to drug dependence. Nandrolone treatment (10-10 M) caused a time-dependent and concentration-dependent downregulation of mu opioid receptor (MOPr) transcripts in SH-SY5Y human neuroblastoma cells. This effect was prevented by the androgen receptor antagonist hydroxyflutamide. Receptor binding assays confirmed a decrease in MOPr of approximately 40% in nandrolone-treated cells. Treatment with actinomycin D (10 (-5)M), a transcription inhibitor, revealed that nandrolone might regulate MOPr mRNA stability. In SH-SY5Y cells transfected with a human MOPr luciferase promoter/reporter construct, nandrolone did not alter the rate of gene transcription. These results suggest that nandrolone may regulate MOPr expression through posttranscriptional mechanisms requiring the androgen receptor.

Androgens affect muscle, motor neuron, and survival in a mouse model of SOD1-related amyotrophic lateral sclerosis.

PubMed

Aggarwal, Tanya; Polanco, Maria J; Scaramuzzino, Chiara; Rocchi, Anna; Milioto, Carmelo; Emionite, Laura; Ognio, Emanuela; Sambataro, Fabio; Galbiati, Mariarita; Poletti, Angelo; Pennuto, Maria

2014-08-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective loss of upper and lower motor neurons and skeletal muscle atrophy. Epidemiologic and experimental evidence suggest the involvement of androgens in ALS pathogenesis, but the mechanism through which androgens modify the ALS phenotype is unknown. Here, we show that androgen ablation by surgical castration extends survival and disease duration of a transgenic mouse model of ALS expressing mutant human SOD1 (hSOD1-G93A). Furthermore, long-term treatment of orchiectomized hSOD1-G93A mice with nandrolone decanoate (ND), an anabolic androgenic steroid, worsened disease manifestations. ND treatment induced muscle fiber hypertrophy but caused motor neuron death. ND negatively affected survival, thereby dissociating skeletal muscle pathology from life span in this ALS mouse model. Interestingly, orchiectomy decreased androgen receptor levels in the spinal cord and muscle, whereas ND treatment had the opposite effect. Notably, stimulation with ND promoted the recruitment of endogenous androgen receptor into biochemical complexes that were insoluble in sodium dodecyl sulfate, a finding consistent with protein aggregation. Overall, our results shed light on the role of androgens as modifiers of ALS pathogenesis via dysregulation of androgen receptor homeostasis. Copyright © 2014 Elsevier Inc. All rights reserved.

The non-preventive effects of human menopausal gonadotropins on ovarian tissues in Nandrolone decanoate-treated female rats: A histochemical and ultra-structural study.

PubMed

Mesbah, Fakhroddin; Bordbar, Hossein; Talaei Khozani, Tahereh; Dehghani, Farzaneh; Mirkhani, Hossein

2018-03-01

The follicular growth and development may be affected by abused drugs. Nandrolone decanoate (ND) as an anabolic androgenic steroid can damage the morphological and functional features of the ovary and may lead to reproductive failure. This study was designed to evaluate the effects of synchronized and non-synchronized administration of Human Menopausal Gonadotropins (hMG) with ND on ovarian tissue and level of sex hormones in the adult female rat. Forty adult female Sprague Dawley rats were divided into eight groups. The five experimental groups received 3 and/or 10 mg/kg of ND synchronized and non-synchronized with 10 IU of hMG and hMG alone. The two shams and control groups received solvents of ND and hMG. The animals' serum levels of Follicle-stimulating hormone, Luteinizing hormone, progesterone and estrogen and the weight, volume and dimensions of the ovaries were measured. The ovaries were prepared for apoptosis assessment and morphological study. The ovarian volume and sex hormones in the experimental groups were decreased, but ovarian weight and dimensions didn't change. The rate of apoptosis was increased in the experimental groups as follows; a low and high dose of ND synchronized with hMG 48.80±18.70 and 65.20±14.20 respectively vs. Sham 1, 33.20±17.80, a low and high dose of ND non-synchronized with hMD 55.80±17.20 and 75.20±14.30 respectively vs. Sham 2, 31.60±32.40 groups, p˂0.01. Follicular and stromal cells were damaged in the experimental groups except for the hMG group. Administration of ND decreased the serum level of Luteinizing hormone, Follicle-stimulating hormone, progesterone and estrogen and damaged ovarian tissue irreversibly and irreparably and hMG cannot prevent the destruction of the follicles in the adult female rats. This can be a serious warning to women who abuse ND.

The opposite effects of nandrolone decanoate and exercise on anxiety levels in rats may involve alterations in hippocampal parvalbumin–positive interneurons

PubMed Central

Selakovic, Dragica; Joksimovic, Jovana; Zaletel, Ivan; Puskas, Nela; Matovic, Milovan

2017-01-01

The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols. PMID:29232412

Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model.

PubMed

Isaacs, Jonathan; Feher, Joseph; Shall, Mary; Vota, Scott; Fox, Michael A; Mallu, Satya; Razavi, Ashkon; Friebe, Ilvy; Shah, Sagar; Spita, Nathalie

2013-10-01

Suboptimal recovery following repair of major peripheral nerves has been partially attributed to denervation atrophy. Administration of anabolic steroids in conjunction with neurotization may improve functional recovery of chronically denervated muscle. The purpose of this study was to evaluate the effect of the administration of nandrolone on muscle recovery following prolonged denervation in a rat model. Eight groups of female Sprague-Dawley rats (15 rats per group, 120 in all) were divided into 3- or 6-month denervated hind limb and sham surgery groups and, then, nandrolone treatment groups and sham treatment groups. Evaluation of treatment effects included nerve conduction, force of contraction, comparative morphology, histology (of muscle fibers), protein electrophoresis (for muscle fiber grouping), and immunohistochemical evaluation. Although a positive trend was noted, neither reinnervated nor normal muscle showed a statistically significant increase in peak muscle force following nandrolone treatment. Indirect measures, including muscle mass (weight and diameter), muscle cell size, muscle fiber type, and satellite cell counts, all failed to support significant anabolic effect. There does not seem to be a functional benefit from nandrolone treatment following reinnervation of either mild or moderately atrophic muscle (related to prolonged denervation) in a rodent model.

Iatrogenic dependence of anabolic-androgenic steroid in an Indian non-athletic woman

PubMed Central

Tripathi, Adarsh; Tekkalaki, Bheemsain; Saxena, Shashwat; Dandu, Himanshu

2014-01-01

Anabolic-androgenic steroids (AAS) are increasingly being used by athletes and youngsters to become masculine and to loose body fat. Long-term consumption of AAS causes multiple physical and psychological morbidities. Research has also concluded that AAS have addictive potential and AAS abuse is commonly found with other substance abuse. Abuse of AAS is rare in eastern countries. Abuse among women is even rarer. Here is a case report of an Indian woman, who was prescribed nandrolone decanoate injections by an unqualified medical practitioner to treat multiple non-specific somatic pains and reported weakness, leading to dependence for nandrolonedecanoate. This case report supports the research finding of abuse potential of AAS, raises concern about the need for spreading the awareness about AAS abuse among medical professionals, regulating medical practice by unqualified practitioners, and strict legal check against AAS availability in developing countries. PMID:24503662

Effects of nandrolone and resistance training on the blood pressure, cardiac electrophysiology, and expression of atrial β-adrenergic receptors.

PubMed

das Neves, Vander José; Tanno, Ana Paula; Cunha, Tatiana Sousa; Fernandes, Tiago; Guzzoni, Vinicius; da Silva, Carlos Alberto; de Oliveira, Edilamar Menezes; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein

2013-05-30

This study was performed to assess isolated and combined effects of nandrolone and resistance training on the blood pressure, cardiac electrophysiology, and expression of the β1- and β2-adrenergic receptors in the heart of rats. Wistar rats were randomly divided into four groups and submitted to a 6-week treatment with nandrolone and/or resistance training. Cardiac hypertrophy was accessed by the ratio of heart weight to the final body weight. Blood pressure was determined by a computerized tail-cuff system. Electrocardiography analyses were performed. Western blotting was used to access the protein levels of the β1- and β2-adrenergic receptors in the right atrium and left ventricle. Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased systolic blood pressure depending on the treatment time. Resistance training decreased systolic, diastolic and mean arterial blood pressure, as well as induced resting bradycardia. Nandrolone prolonged the QTc interval for both trained and non-trained groups when they were compared to their respective vehicle-treated one. Nandrolone increased the expression of β1- and β2-adrenergic receptors in the right atrium for both trained and non-trained groups when they were compared to their respective vehicle-treated one. This study indicated that nandrolone, associated or not with resistance training increases blood pressure depending on the treatment time, induces prolongation of the QTc interval, and increases the expression of β1- and β2-adrenergic receptors in the cardiac right atrium, but not in the left ventricle. Copyright © 2013. Published by Elsevier Inc.

Nandrolone slows hindlimb bone loss in a rat model of bone loss due to denervation.

PubMed

Cardozo, Christopher P; Qin, Weiping; Peng, Yuanzhen; Liu, Xuan; Wu, Yong; Pan, Jiangping; Bauman, William A; Zaidi, Mone; Sun, Li

2010-03-01

Nandrolone is an anabolic steroid that has been demonstrated to reduce the loss of bone and muscle from hindlimb unweighting and to slow muscle atrophy after nerve transection. To determine whether nandrolone has the ability to protect bone against loss due to disuse after denervation, male rats underwent sciatic nerve transaction, followed 28 days later by treatment with nandrolone or vehicle for 28 days. Bone mineral density (BMD) was determined 28 days later or 56 days after nerve transection. Denervation led to reductions in BMD of 7% and 12% for femur and tibia, respectively. Nandrolone preserved 80% and 60% of BMD in femur and tibia, respectively, demonstrating that nandrolone administration significantly reduced loss of BMD from denervation. This study offers a potential novel pharmacological strategy for use of nandrolone to reduce bone loss in severe disuse- and denervation-related bone loss, such as that which occurs after spinal cord injury.

Nandrolone and resistance training induce heart remodeling: role of fetal genes and implications for cardiac pathophysiology.

PubMed

Tanno, Ana Paula; das Neves, Vander José; Rosa, Kaleizu Teodoro; Cunha, Tatiana Sousa; Giordano, Fernanda Cristina Linarello; Calil, Caroline Morini; Guzzoni, Vinicius; Fernandes, Tiago; de Oliveira, Edilamar Menezes; Novaes, Pedro Duarte; Irigoyen, Maria Cláudia; Moura, Maria José Costa Sampaio; Marcondes, Fernanda Klein

2011-10-24

This study was conducted to assess the isolated and combined effects of nandrolone and resistance training on cardiac morphology, function, and mRNA expression of pathological cardiac hypertrophy markers. Wistar rats were randomly divided into four groups and submitted to 6 weeks of treatment with nandrolone and/or resistance training. Cardiac parameters were determined by echocardiography. Heart was analyzed for collagen infiltration. Real-time RT-PCR was used to assess the pathological cardiac hypertrophy markers. Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone increased the cardiac collagen content, and reduced the cardiac index in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the ratio of maximum early to late transmitral flow velocity in non-trained and trained groups, when compared with the respective vehicle-treated groups. Nandrolone reduced the alpha-myosin heavy chain gene expression in both non-trained and trained groups, when compared with the respective vehicle-treated groups. Training reduced the beta-myosin heavy chain gene expression in the groups treated with vehicle and nandrolone. Only the association between training and nandrolone increased the expression of the skeletal alpha-actin gene and atrial natriuretic peptide in the left ventricle. This study indicated that nandrolone, whether associated with resistance training or not, induces cardiac hypertrophy, which is associated with enhanced collagen content, re-expression of fetal genes the in left ventricle, and impaired diastolic and systolic function. Copyright © 2011 Elsevier Inc. All rights reserved.

Anabolic steroids reduce spinal cord injury-related bone loss in rats associated with increased Wnt signaling

PubMed Central

Sun, Li; Pan, Jiangping; Peng, Yuanzhen; Wu, Yong; Li, Jianghua; Liu, Xuan; Qin, Yiwen; Bauman, William A.; Cardozo, Christopher; Zaidi, Mone; Qin, Weiping

2013-01-01

Background Spinal cord injury (SCI) causes severe bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men after SCI and may exacerbate bone loss. The anabolic steroid nandrolone reduces bone loss due to microgravity or nerve transection. Objective To determine whether nandrolone reduced bone loss after SCI and, if so, to explore the mechanisms of nandrolone action. Methods Male rats with complete transection of the spinal cord were administered nandrolone combined with a physiological replacement dose of testosterone, or vehicle, beginning on day 29 after SCI and continued for 28 days. Results SCI reduced distal femoral and proximal tibial bone mineral density (BMD) by 25 and 16%, respectively, at 56 days. This bone loss was attenuated by nandrolone. In ex vivo osteoclasts cultures, SCI increased mRNA levels for tartrate-resistant acid phosphatase (TRAP) and calcitonin receptor; nandrolone-normalized expression levels of these transcripts. In ex vivo osteoblast cultures, SCI increased receptor activator of NF-kB ligand (RANKL) mRNA levels but did not alter osteoprotegerin (OPG) mRNA expression; nandrolone-increased expression of OPG and OPG/RANKL ratio. SCI reduced mRNA levels of Wnt signaling-related genes Wnt3a, low-density lipoprotein receptor-related protein 5 (LRP5), Fzd5, Tcf7, and ectodermal-neural cortex 1 (ENC1) in osteoblasts, whereas nandrolone increased expression of each of these genes. Conclusions The results demonstrate that nandrolone reduces bone loss after SCI. A potential mechanism is suggested by our findings wherein nandrolone modulates genes for differentiation and activity of osteoclasts and osteoblasts, at least in part, through the activation of Wnt signaling. PMID:24090150

A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive.

PubMed

Brady, B M; Amory, J K; Perheentupa, A; Zitzmann, M; Hay, C J; Apter, D; Anderson, R A; Bremner, W J; Pollanen, P; Nieschlag, E; Wu, F C W; Kersemaekers, W M

2006-01-01

The combination of etonogestrel implants with injectable testosterone decanoate was investigated as a potential male contraceptive. One hundred and thirty subjects were randomly assigned to three treatment groups, all receiving two etonogestrel rods (204 mg etonogestrel) and 400 mg testosterone decanoate either every 4 weeks (group I, n = 42), or every 6 weeks (group II, n = 51) or 600 mg testosterone decanoate every 6 weeks (group III, n = 37) for a treatment period of 48 weeks. One hundred and ten men completed 48 weeks of treatment. Sperm concentrations of <1 x 10(6)/ml were achieved in 90% (group I), 82% (group II) and 89% (group III) of subjects by week 24. Suppression was slower in group II, which also demonstrated more frequent escape from gonadotrophin suppression than groups I and III. Peak testosterone concentrations remained in the normal range throughout in all groups. Mean trough testosterone concentrations were initially subphysiological but increased into the normal range during treatment. Mean haemoglobin levels increased in group I, and a non-significant increase in weight and decline in high-density lipoprotein cholesterol was observed in all groups. Fourteen subjects discontinued treatment due to adverse events. Subcutaneous etonogestrel implants in combination with injectable testosterone decanoate resulted in profound suppression of spermatogenesis that could be maintained for up to 1 year. Efficacy of suppression was less in group II, probably due to inadequate testosterone dosage. This combination has potential as a long-acting male hormonal contraceptive.

Highly sensitive avidin-biotin ELISA for detection of nandrolone and testosterone in dietary supplements.

PubMed

Jurášek, Michal; Göselová, Sandra; Mikšátková, Petra; Holubová, Barbora; Vyšatová, Eva; Kuchař, Martin; Fukal, Ladislav; Lapčík, Oldřich; Drašar, Pavel

2017-04-01

Avidin-biotin technology was used for the implementation of an enzyme-linked immunosorbent assay (AB-ELISA) as a sensitive method for the detection of anabolic androgenic steroids (AAS) present in dietary supplements. Using click chemistry, novel haptens (linker-optimized biotinylated nandrolone (NT) and testosterone (T) at positions C-3 and C-17, respectively) were designed and synthesized to be then applied as four different immobilized competitors in a proposed set of four indirect competitive AB-ELISAs. Four rabbit polyclonal antibodies of various specificities were prepared using four different immunogens synthesized from C-3 and C-17 carboxymethyloxime and hemisuccinate derivatives of NT and T, respectively. Assembled AB-ELISAs were characterized to establish method parameters such as a half-maximum inhibition concentration (0.18-12.99 ng/mL), limit of detection (0.004-0.032 ng/mL) and linear working range (the best with 0.02-1.38 ng/mL). The stability of the set simulating storage in different conditions was demonstrated. Cross reactivity (CR) was tested for 59 steroids including both endogenous and synthetic analogues in four assembled AB-systems. The focus was placed on the practical use of the method in detection of various AAS in 49 samples of counterfeit dietary supplements. The concordance between ultra high performance liquid chromatography-mass spectrometry (UHPLC-MS) and the CR corrected data from AB-ELISA indicated the potential of this method even to quantification of T propionate, NT phenyl propionate, and NT decanoate in such a complex matter. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

An acute oral intoxication with haloperidol decanoate.

PubMed

Dekkers, Bart G J; Eck, Ruben J; Ter Maaten, Jan C; Touw, Daniël J

2017-09-01

Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy for schizophrenia and mood disorders formulated as an ester for intramuscular injection. Cases of oral haloperidol decanoate intoxications have not been described in literature. In this report, we present for the first time a case of an oral ingestion of haloperidol decanoate of a young woman who presented to the emergency department following an intentional oral ingestion of 1 ampoule of haloperidol decanoate 100mg. At presentation, she had a bilateral rest tremor of both hands and mild hypothermia. No other obvious signs of an intoxication were observed. She was treated with a single dose of activated charcoal and laxative and was admitted to the intensive care for rhythm monitoring and observation. During the night the QTc interval increased to 453ms, but stayed within the normal range. Haloperidol plasma levels increased as well, but also stayed within therapeutic ranges. These findings indicate that treatment with oral activated charcoal was sufficient to prevent any serious events. Copyright © 2017 Elsevier Inc. All rights reserved.

Lipid peroxidation and apoptotic response in rat brain areas induced by long-term administration of nandrolone: the mutual crosstalk between ROS and NF-kB.

PubMed

Turillazzi, Emanuela; Neri, Margherita; Cerretani, Daniela; Cantatore, Santina; Frati, Paola; Moltoni, Laura; Busardò, Francesco Paolo; Pomara, Cristoforo; Riezzo, Irene; Fineschi, Vittorio

2016-04-01

The aim of this study was to evaluate the played by oxidative stress in the apoptotic response in different brain areas of rats chronically treated with supra-physiological doses of nandrolone decanoate (ND). Immunohistochemical study and Western blot analysis were performed to evaluate cells' apoptosis and to measure the effects of expression of specific mediators, such as NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), Bcl-2 (B-cell lymphoma 2), SMAC/DIABLO (second mitochondria-derived activator of caspases/direct IAP-binding protein with low PI) and VMAT2 (vesicular monoamine transporter 2) on apoptosis. The results of the present study indicate that a long-term administration of ND promotes oxidative injury in rat brain specific areas. A link between oxidative stress and NF-κB signalling pathways is supported by our results. In addition to high levels of oxidative stress, we consistently observed a strong immunopositivity to NF-κB. It has been argued that one of the pathways leading to the activation of NF-κB could be under reactive oxygen species (ROS)-mediated control. In fact, growing evidence suggests that although in limited doses, endogenous ROS may play an activating role in NF-κB signalling, while above a certain threshold, they may negatively impact upon this signalling. However, a mutual crosstalk between ROS and NF-κB exists and recent studies have shown that ROS activity is subject to negative feedback regulation by NF-κB, and that this negative regulation of ROS is the means through which NF-κB counters programmed cells. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

PubMed

Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

2017-01-01

Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB 1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB 1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB 1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of cannabis and other drugs in humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Investigations into the feasibility of routine ultra high performance liquid chromatography-tandem mass spectrometry analysis of equine hair samples for detecting the misuse of anabolic steroids, anabolic steroid esters and related compounds.

PubMed

Gray, Bobby P; Viljanto, Marjaana; Bright, Jane; Pearce, Clive; Maynard, Steve

2013-07-17

The detection of the abuse of anabolic steroids in equine sport is complicated by the endogenous nature of some of the abused steroids, such as testosterone and nandrolone. These steroids are commonly administered as intramuscular injections of esterified forms of the steroid, which prolongs their effects and improves bioavailability over oral dosing. The successful detection of an intact anabolic steroid ester therefore provides unequivocal proof of an illegal administration, as esterified forms are not found endogenously. Detection of intact anabolic steroid esters is possible in plasma samples but not, to date, in the traditional doping control matrix of urine. The analysis of equine mane hair for the detection of anabolic steroid esters has the potential to greatly extend the time period over which detection of abuse can be monitored. Equine mane hair samples were incubated in 0.1M phosphate buffer (pH 9.5) before anabolic steroids (testosterone, nandrolone, boldenone, trenbolone and stanozolol), anabolic steroid esters (esters of testosterone, nandrolone, boldenone and trenbolone) and associated compounds (fluticasone propionate and esters of hydroxyprogesterone) were extracted by liquid-liquid extraction with a mix of hexane and ethyl acetate (7:3, v:v). Further sample clean up by solid phase extraction was followed by derivatisation with methoxylamine HCL and analysis by UHPLC-MS/MS. Initial method development was performed on a representative suite of four testosterone esters (propionate, phenylpropionate, isocaproate and decanoate) and the method was later extended to include a further 18 compounds. The applicability of the method was demonstrated by the analysis of mane hair samples collected following the intramuscular administration of 500 mg of Durateston(®) (mixed testosterone esters) to a Thoroughbred mare (560 kg). The method was subsequently used to successfully detect boldenone undecylenate and stanozolol in hair samples collected following suspicious screening findings from post-race urine samples. The use of segmental analysis to potentially provide additional information on the timing of administration was also investigated. Copyright © 2013 Elsevier B.V. All rights reserved.

ANABOLIC STEROIDS HAVE LONG-LASTING EFFECTS ON MALE SOCIAL BEHAVIORS

PubMed Central

Salas-Ramirez, Kaliris Y.; Montalto, Pamela R.; Sisk, Cheryl L.

2010-01-01

Anabolic androgenic steroids (AAS) use by adolescents is steadily increasing. Adolescence involves remodeling of steroid-sensitive neural circuits that mediate social behaviors, and previous studies using animal models document effects of AAS on male social behaviors. The present experiments tested whether AAS have persistent and more pronounced behavioral consequences when drug exposure occurs during adolescence as compared to exposure in adulthood. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27-41 days of age) or adulthood (63-77 days of age). As adults, subjects were tested two or four weeks after the last injection for either sexual behavior with a receptive female or male-male agonistic behavior in a resident-intruder test. Compared with vehicle-treated males, AAS-treated males, regardless of age of treatment, displayed fewer long intromissions and a significant increase in latency to the first long intromission, indicative of reduced potential to reach sexual satiety. Increased aggression was observed in males exposed to AAS compared with males treated with vehicle, independently of age of AAS treatment. However, unlike hamsters exposed to AAS in adulthood, hamsters exposed to AAS during adolescence did not display any submissive or risk-assessment behaviors up to 4 weeks after discontinuation of AAS treatment. Thus, AAS have long-lasting effects on male sexual and agonistic behaviors, with AAS exposure during adolescence resulting in a more pronounced reduction in submissive behavior compared to AAS exposure in adulthood. PMID:20036695

Serca2a and Na(+)/Ca(2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid.

PubMed

Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco; Silva, Josiane Fernandes da; Lemos, Virgínia Soares; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

2016-06-15

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated). The haemodynamic parameters (+dP/dtmax, -dP/dtmin and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na(+)/Ca(2+) exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. Copyright © 2016 Elsevier Inc. All rights reserved.

Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness.

PubMed

Pan, Michael M; Kovac, Jason R

2016-04-01

Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required.

Beyond testosterone cypionate: evidence behind the use of nandrolone in male health and wellness

PubMed Central

Pan, Michael M.

2016-01-01

Characterized by low serum testosterone levels and diverse symptoms, male hypogonadism is a common condition. Current medical treatment focuses on testosterone supplementation using multiple modalities such as injections, gels and pellets. Interestingly, while testosterone is considered an anabolic androgenic steroid, it has not been saddled with the social stigma that other, similar medications have. The goal of this review is to highlight an anabolic steroid, 19-nortestosterone (i.e., nandrolone, deca-durabolin) and illustrate prospective therapeutic applications for male health. Containing a chemical structure similar to testosterone, nandrolone has a higher myotrophic: androgenic ratio resulting in improved effects on muscle mass. Animal models have suggested application in the improvement of joint healing following rotator cuff repair. Minimal literature exists regarding the use of nandrolone and, as such, further human studies are required. PMID:27141449

Concentrations of nandrolone metabolites in urine after the therapeutic administration of an ophthalmic solution.

PubMed

Avois, Lidia; Mangin, Patrice; Saugy, Martial

2007-05-09

Nandrolone, an anabolic steroid, is used for the treatment of several diseases and is available in various pharmaceutical formulations. The most widely used pharmaceutical formulation is Deca-Durabolin, but other products, such as Keratyl eye drops solution, are also currently administered. Nandrolone is one of the most abused anabolic steroid in sports. Analyses for this anabolic steroid according to the World Anti-Doping Agency (WADA) protocol are based on the identification of the nandrolone two main urinary metabolites which, in humans, are glucuronides of 19-norandrosterone and 19-noretiocholanolone. A positive cut off limit of 2 ng/mL has been set by the anti-doping code for the first metabolite, 19-norandrosterone. In this preliminary study, an eye drops solution (Keratyl) containing a therapeutic dose of a nandrolone sodium sulphate was administered to several male volunteers during 3 days and urines were collected during 3 weeks. Surprisingly, contrary to all expectations, the urinary concentrations measured in urines reached 450 ng/mL and 70 ng/mL for norandrosterone and noretiocholanolone, respectively. Moreover, concentration levels near to 2 ng/mL were found, more than 2 weeks after the last administration, depending on individual metabolism. Inter-variability as well as intra-variability of nandrolone excretion kinetic, regarding this particular administration mode, were also evaluated. Quantification of nandrolone metabolites was performed by GC-MS. The method was previously validated in terms of specificity, precision, linearity, LOD, LOQ, robustness, accuracy and the expanded uncertainty was also evaluated.

Nandrolone-induced aggressive behavior is associated with alterations in extracellular glutamate homeostasis in mice.

PubMed

Kalinine, Eduardo; Zimmer, Eduardo Rigon; Zenki, Kamila Cagliari; Kalinine, Iouri; Kazlauckas, Vanessa; Haas, Clarissa Branco; Hansel, Gisele; Zimmer, Aline Rigon; Souza, Diogo Onofre; Müller, Alexandre Pastoris; Portela, Luis Valmor

2014-07-01

Nandrolone decanoate (ND), an anabolic androgenic steroid (AAS), induces an aggressive phenotype by mechanisms involving glutamate-induced N-methyl-d-aspartate receptor (NMDAr) hyperexcitability. The astrocytic glutamate transporters remove excessive glutamate surrounding the synapse. However, the impact of supraphysiological doses of ND on glutamate transporters activity remains elusive. We investigated whether ND-induced aggressive behavior is interconnected with GLT-1 activity, glutamate levels and abnormal NMDAr responses. Two-month-old untreated male mice (CF1, n=20) were tested for baseline aggressive behavior in the resident-intruder test. Another group of mice (n=188) was injected with ND (15mg/kg) or vehicle for 4, 11 and 19days (short-, mid- and long-term endpoints, respectively) and was evaluated in the resident-intruder test. Each endpoint was assessed for GLT-1 expression and glutamate uptake activity in the frontoparietal cortex and hippocampal tissues. Only the long-term ND endpoint significantly decreased the latency to first attack and increased the number of attacks, which was associated with decreased GLT-1 expression and glutamate uptake activity in both brain areas. These alterations may affect extracellular glutamate levels and receptor excitability. Resident males were assessed for hippocampal glutamate levels via microdialysis both prior to, and following, the introduction of intruders. Long-term ND mice displayed significant increases in the microdialysate glutamate levels only after exposure to intruders. A single intraperitoneal dose of the NMDAr antagonists, memantine or MK-801, shortly before the intruder test decreased aggressive behavior. In summary, long-term ND-induced aggressive behavior is associated with decreased extracellular glutamate clearance and NMDAr hyperexcitability, emphasizing the role of this receptor in mediating aggression mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

Chronic Anabolic Androgenic Steroid Exposure Alters Corticotropin Releasing Factor Expression and Anxiety-Like Behaviors in the Female Mouse

PubMed Central

Costine, Beth A; Oberlander, Joseph G; Davis, Matthew C; Penatti, Carlos A A; Porter, Donna M; Leaton, Robert N; Henderson, Leslie P

2010-01-01

Summary In the past several decades, the therapeutic use of anabolic androgenic steroids (AAS) has been overshadowed by illicit use of these drugs by elite athletes and a growing number of adolescents to enhance performance and body image. As with adults, AAS use by adolescents is associated with a range of behavioral effects, including increased anxiety and altered responses to stress. It has been suggested that adolescents, especially adolescent females, may be particularly susceptible to the effects of these steroids, but few experiments in animal models have been performed to test this assertion. Here we show that chronic exposure of adolescent female mice to a mixture of three commonly abused AAS (testosterone cypionate, nandrolone decanoate and methandrostenolone; 7.5 mg/kg/day for 5 days) significantly enhanced anxiety-like behavior as assessed by the acoustic startle response (ASR), but did not augment the fear-potentiated startle response (FPS) or alter sensorimotor gating as assessed by prepulse inhibition of the acoustic startle response (PPI). AAS treatment also significantly increased the levels of corticotropin releasing factor (CRF) mRNA and somal-associated CRF immunoreactivity in the central amygdala (CeA), as well as neuropil-associated immunoreactivity in the dorsal aspect of the anterolateral division of the bed nucleus of the stria terminalis (dBnST). AAS treatment did not alter CRF receptor 1 or 2 mRNA in either the CeA or the dBnST; CRF immunoreactivity in the ventral BNST, the paraventricular nucleus (PVN) or the median eminence (ME); or peripheral levels of corticosterone. These results suggest that chronic AAS treatment of adolescent female mice may enhance generalized anxiety, but not sensorimotor gating or learned fear, via a mechanism that involves increased CRF-mediated signaling from CeA neurons projecting to the dBnST. PMID:20537804

Anabolic androgenic steroids reverse the beneficial effect of exercise on tendon biomechanics: an experimental study.

PubMed

Tsitsilonis, Serafim; Chatzistergos, Panayiotis E; Panayiotis, Chatzistergos E; Mitousoudis, Athanasios S; Athanasios, Mitousoudis S; Kourkoulis, Stavros K; Stavros, Kourkoulis K; Vlachos, Ioannis S; Ioannis, Vlachos S; Agrogiannis, George; George, Agrogiannis; Fasseas, Konstantinos; Konstantinos, Fasseas; Perrea, Despina N; Despina, Perrea N; Zoubos, Aristides B; Aristides, Zoubos B

2014-06-01

The effect of anabolic androgenic steroids on tendons has not yet been fully elucidated. Aim of the present study was the evaluation of the impact of anabolic androgenic steroids on the biomechanical and histological characteristics of Achilles tendons. Twenty-four male Wistar rats were randomized into four groups with exercise and anabolic steroids (nandrolone decanoate) serving as variables. Protocol duration was 12 weeks. Following euthanasia, tendons' biomechanical properties were tested with the use of a modified clamping configuration. Histological examination with light and electron microscopy were also performed. In the group of anabolic steroids and exercise the lowest fracture stress values were observed, while in the exercise group the highest ones. Histological examination by light and electron microscopy revealed areas of collagen dysplasia and an increased epitendon in the groups receiving anabolic steroids and exercise. These findings suggest that anabolic androgenic steroids reverse the beneficial effect of exercise, thus resulting in inferior maximal stress values. Copyright © 2013 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Serca2a and Na{sup +}/Ca{sup 2+} exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nascimento, Andrews Marques do; Lima, Ewelyne Mira

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt{sub max}, − dP/dt{sub min} and Tau) were assessed in the leftmore » ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na{sup +}/Ca{sup 2+} exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.« less

Confirmation of the progesterone receptor as an efficient marker of treatment with 17β-estradiol in veal calves.

PubMed

Pezzolato, Marzia; Botta, Mario; Baioni, Elisa; Richelmi, Guia Benedetta; Pitardi, Danilo; Varello, Katia; Caramelli, Maria; Bozzetta, Elena

2016-01-01

Under current European Union legislation the use of anabolic steroids in food-producing livestock is banned because of their long-term adverse effects on human health. We examined the expression profile of the immunohistochemical marker progesterone receptor in veal calves' sex accessory glands following experimental administration of anabolic compounds. The aim was to confirm the accuracy of the immunohistochemical approach in the detection of the over-expression of the progesterone receptor induced by the administration of sexual steroids at low levels (17β-estradiol and nandrolone alone or in combination). A total of 217 male veal calves were randomly divided into four groups: group A (104 calves) treated with 17β-estradiol (5 mg/head; 4 weekly injections); group B (20 calves) treated with nandrolone (50 mg/head; 4 weekly injections); group C (20 calves) treated with the association of the two steroids (5 mg estradiol + 50 mg nandrolone; 4 weekly injections); and group K (73 calves) kept as a control. All the sexual accessory glands were collected at the slaughterhouse (15 days after the last administration) and subjected to immunohistochemical staining with anti-progesterone receptor antibody. All the calves treated with 17β-estradiol alone or in association with nandrolone (groups A and C) showed strong positivity, while nandrolone-treated calves and controls (groups B and K) gave negative results to the immunohistochemical investigation. The statistical analysis showed that the progesterone receptor is a significant predictor of 17β-estradiol treatment alone or in association with nandrolone (p < 0.001): the immunohistochemical study resulted in 100% sensitivity (CI = 95%: 97.1-100%) and specificity (CI = 95%: 95.1-100%) for prostate and 99% sensitivity (CI = 95%: 95.6-100%) and 100% specificity (CI = 95%: 95.1-100%) for bulbo-urethral glands. The data confirm that this innovative biological approach offers a reliable tool to enhance the efficacy of the histological test to detect illegal treatments with estrogens alone or in association with androgens.

Intramuscular preparations of antipsychotics: uses and relevance in clinical practice.

PubMed

Altamura, A Cario; Sassella, Francesca; Santini, Annalisa; Montresor, Clauno; Fumagalli, Sara; Mundo, Emanuela

2003-01-01

Intramuscular formulations of antipsychotics can be sub-divided into two groups on the basis of their pharmacokinetic features: short-acting preparations and long-acting or depot preparations. Short-acting intramuscular formulations are used to manage acute psychotic episodes. On the other hand, long-acting compounds, also called "depot", are administered as antipsychotic maintenance treatment to ensure compliance and to eliminate bioavailability problems related to absorption and first pass metabolism. Adverse effects of antipsychotics have been studied with particular respect to oral versus short- and long-acting intramuscular formulations of the different compounds. For short-term intramuscular preparations the main risk with classical compounds are hypotension and extrapyramidal side effects (EPS). Data on the incidence of EPS with depot formulations are controversial: some studies point out that the incidence of EPS is significantly higher in patients receiving depot preparations, whereas others show no difference between oral and depot antipsychotics. Studies on the strategies for switching patients from oral to depot treatment suggest that this procedure is reasonably well tolerated, so that in clinical practice depot antipsychotic therapy is usually begun while the oral treatment is still being administered, with gradual tapering of the oral dose. Efficacy, pharmacodynamics and clinical pharmacokinetics of haloperidol decanoate, fluphenazine enanthate and decanoate, clopenthixol decanoate, zuclopenthixol decanoate and acutard, flupenthixol decanoate, perphenazine enanthate, pipothiazine palmitate and undecylenate, and fluspirilene are reviewed. In addition, the intramuscular preparations of atypical antipsychotics and clinical uses are reviewed. Olanzapine and ziprasidone are available only as short-acting preparations, while risperidone is to date the only novel antipsychotic available as depot formulation. To date, acutely ill, agitated psychotic patients have been treated with high parenteral doses of typical antipsychotics, which often cause serious EPS, especially dystonic reactions. Intramuscular formulations of novel antipsychotics (olanzapine and ziprasidone), which appear to have a better tolerability profile than typical compounds, showed an equivalent efficacy to parenteral typical agents in the acute treatment of psychoses. However, parenteral or depot formulations of atypical antipsychotics are not yet widely available.

The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice

PubMed Central

Martínez-Rivera, Freddyson J.; Natal-Albelo, Eduardo J.; Martínez, Namyr A.; Orozco-Vega, Roberto A.; Muñiz-Seda, Oscar A.; Barreto-Estrada, Jennifer L.

2015-01-01

Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking their anabolic effects, even though later on, many could develop neuropsychological dependence. Previously, we have shown that nandrolone induces conditioned place preference (CPP) in adult male mice. However, whether nandrolone induces CPP during adolescence remains unknown. In this study, the CPP test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for reward-related processes, the effect of nandrolone on the expression of D1DR in the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to our previous results, nandrolone induced CPP in adults. However, in adolescents, nandrolone failed to produce place preference. At the molecular level, nandrolone decreased D1DR expression in the NAc only in adult mice. Our data suggest that nandrolone may not be rewarding in adolescents at least during short-term use. The lack of nandrolone rewarding effects in adolescents may be due, in part to differences in D1DR expression during development. PMID:25612844

Nandrolone decanoate determines cardiac remodelling and injury by an imbalance in cardiac inflammatory cytokines and ACE activity, blunting of the Bezold-Jarisch reflex, resulting in the development of hypertension.

PubMed

Franquni, João Vicente Maggioni; do Nascimento, Andrews Marques; de Lima, Eweliny Miranda; Brasil, Girlândia Alexandre; Heringer, Otávio Arruda; Cassaro, Karla Oliveira Dos Santos; da Cunha, Thony Vinicius Pita; Musso, Carlos; Silva Santos, Maria Carmen L F; Kalil, Ieda Carneiro; Endringer, Denise Coutinho; Boëchat, Giovanna Assis Pereirra; Bissoli, Nazaré Souza; de Andrade, Tadeu Uggere

2013-03-01

The aims of this study were to evaluate the effects of nandrolone (ND) on cardiac inflammatory cytokines, ACE activity, troponin I, and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were administered either ND (20 mg/kg; DECA) or vehicle (control animals; CONT) for 4 weeks. BJR was analyzed by measuring the bradycardia and hypotension responses elicited by serotonin administration (2-32 μg/kg). Mean arterial pressure (MAP) was assessed and myocyte hypertrophy was determined by the heart weight/body weight ratio and by morphometric analysis. Matrix collagen deposition was assessed by histological analysis of the picrosirius red-stained samples. Mesenteric vascular reactivity was performed and central venous pressure (CVP) evaluated. Cardiac inflammatory cytokine levels and angiotensin-converting enzyme (ACE) activity were studied as well the biomarker of cardiac lesion, troponin I. DECA group showed enhancement of matrix type I collagen deposition (p < 0.01) and cardiac ACE activity (p < 0.01) compared with the CONT. Interleukin (IL)-10 was reduced (p < 0.01) and pro-inflammatory cytokines (TNF-α and IL-6; p < 0.01) were increased in the DECA group compared with CONT. Cardiac injury was observed in the DECA group shown by the reduction in cardiac troponin I (p < 0.01) compared with the CONT group. Animals in the DECA group also developed myocyte hypertrophy and reduction of BJR sensitivity. The MAP of animals treated with ND reached hypertensive levels (p < 0.01; compared with CONT). No changes in CVP and vascular reactivity were observed in both experimental groups. We conclude that high doses of ND elicit cardiotoxic effects with cardiac remodelling and injury. Cardiac changes reduce the BJR sensitivity. Together, these abnormalities contributed to the development of hypertension in animals in the DECA group. Copyright © 2012 Elsevier Inc. All rights reserved.

The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice.

PubMed

Martínez-Rivera, Freddyson J; Natal-Albelo, Eduardo J; Martínez, Namyr A; Orozco-Vega, Roberto A; Muñiz-Seda, Oscar A; Barreto-Estrada, Jennifer L

2015-04-01

Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking their anabolic effects, even though later on, many could develop neuropsychological dependence. Previously, we have shown that nandrolone induces conditioned place preference (CPP) in adult male mice. However, whether nandrolone induces CPP during adolescence remains unknown. In this study, the CPP test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for reward-related processes, the effect of nandrolone on the expression of D1DR in the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to our previous results, nandrolone induced CPP in adults. However, in adolescents, nandrolone failed to produce place preference. At the molecular level, nandrolone decreased D1DR expression in the NAc only in adult mice. Our data suggest that nandrolone may not be rewarding in adolescents at least during short-term use. The lack of nandrolone rewarding effects in adolescents may be due, in part to differences in D1DR expression during development. Copyright © 2015 Elsevier B.V. All rights reserved.

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xin-Hua; Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029; Yao, Shen

2011-10-14

Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signalingmore » in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.« less

Determination of nandrolone and metabolites in urine samples from sedentary persons and sportsmen.

PubMed

Galán Martín, A M; Mariño, J I; García de Tiedra, M P; Marabé, J J; Caballero Loscos, M J; Mariño, M M

2001-09-25

Metabolites of nandrolone were determined in the urine of several sportsmen, sedentary and post-menopausal women by capillary gas chromatography-mass spectrometry quadrupole (GC-MS) and capillary gas chromatography mass-mass spectrometry ion trap (GC-MS-MS) methods. The method employed was GC-EI-MS with 17alpha-methyltestosterone as internal standard with ethyl ether extraction prior to selected ion monitoring of the bis(trimethylsilyl) ethers at ion masses m/z 405 and 420 for the nandrolone metabolites, and 418 and 403 for nandrolone derivative. Recovery for nandrolone, 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) was 97.20, 94.17 and 95.54%, respectively. Detection limits for nandrolone, 19-NA and 19-NE were 0.03, 0.01 and 0.06 ng/ml. Metabolites of nandrolone (19-NA and 19-NE) were found in 12.5% (n = 40) of sportsmen and 40% (n = 10) of post-menopausal women.

Nandrolone: a multi-faceted doping agent.

PubMed

Hemmersbach, Peter; Grosse, Joachim

2010-01-01

Nandrolone or nortestosterone, an anabolic-androgenic steroid, has been prohibited by doping control regulations for more than 30 years. Although its main metabolism in the human body was already known at that time, and detection of its misuse by gas or liquid chromatographic separation with mass spectrometric detection is straightforward, many interesting aspects regarding this doping agent have appeared since.Over the years, nandrolone preparations have kept their position among the prohibited substances that are most frequently detected in WADA-accredited laboratories. Their forms of application range from injectable fatty acid esters to orally administered nandrolone prohormones. The long detection window for nandrolone ester preparations and the appearance of orally available nandrolone precursors have changed the pattern of misuse.At the same time, more refined analytical methods with lowered detection limits led to new insights into the pharmacology of nandrolone and revelation of its natural production in the body.Possible contamination of nutritional supplements with nandrolone precursors, interference of nandrolone metabolism by other drugs and rarely occurring critical changes during storage of urine samples have to be taken into consideration when interpreting an analytical finding.A set of strict identification criteria, including a threshold limit, is applied to judge correctly an analytical finding of nandrolone metabolites. The possible influence of interfering drugs, urine storage or natural production is taken into account by applying appropriate rules and regulations.

[13C]Nandrolone excretion in trained athletes: interindividual variability in metabolism.

PubMed

Baume, Norbert; Avois, Lidia; Schweizer, Carine; Cardis, Christine; Dvorak, Jiri; Cauderay, Michel; Mangin, Patrice; Saugy, Martial

2004-02-01

Nandrolone is one of the most abused anabolic steroids, and its use in doping is increasing, as revealed by numerous positive cases during recent years in various sports. Different authors have reported the possible natural production of nandrolone metabolites in humans, and some of these authors argued that exhaustive exercise could increase nandrolone production in the body or induce dehydration and consequently lead to an increase of nandrolone metabolites in urine. Volunteers (n = 22) ingested two 25-mg doses of [(13)C]nandrolone at 24-h intervals and collected urine specimens for 5 days. The labeled nandrolone metabolites 19-norandrosterone and 19-noretiocholanolone were identified and quantified by gas chromatography-mass spectrometry. Interindividual variability was observed in nandrolone excretion patterns and kinetics, as well as for the noretiocholanolone:norandrosterone ratio. The amounts of nandrolone metabolites measured at the excretion peak varied between 1180 and 38 661 microg/L for norandrosterone and 576 and 12 328 microg/L for noretiocholanolone. At the end of the excretion period, the noretiocholanolone:norandrosterone ratio was sometimes >1. The analysis of numerous spot-urine samples allowed the determination of an acceptable correlation between urinary creatinine and specific gravity for placebo- and steroid-treated individuals: y = 0.0052ln(x) + 1.0178 (r(2) = 0.8142) and y = 0.0068ln(x) + 1.0172 (r(2) = 0.7730), respectively. The excretion kinetics and patterns of labeled nandrolone show interindividual variability. More investigations are currently underway to estimate the influence of exhaustive exercises on excretion of labeled nandrolone metabolites in urine.

Treatment continuation of four long-acting antipsychotic medications in the Netherlands and Belgium: A retrospective database study

PubMed Central

Sermon, Jan; Geerts, Paul; Denee, Tom R.; De Vos, Cedric; Malfait, Bart; Lamotte, Mark; Mulder, Cornelis L.

2017-01-01

Achieving greater continuation of treatment is a key element to improve treatment outcomes in schizophrenia patients. However, reported treatment continuation can differ markedly depending on the study design. In a retrospective setting, treatment continuation remains overall poor among patients using antipsychotics. This study aimed to document the difference in treatment continuation between four long-acting injectable antipsychotics based on the QuintilesIMS LRx databases, national, longitudinal, panel based prescription databases of retail pharmacies, in the Netherlands and Belgium. Paliperidone palmitate once monthly, risperidone microspheres, haloperidol decanoate, and olanzapine pamoate were studied. This study demonstrated significantly higher treatment continuation of paliperidone palmitate once monthly compared to risperidone microspheres (p-value<0,01) and haloperidol decanoate (p-value<0,01) in both countries, a significantly higher treatment continuation of paliperidone palmitate once monthly compared to olanzapine pamoate in the Netherlands (p-value<0,01), and a general trend towards better treatment continuation versus olanzapine pamoate in Belgium. Analysing the subgroup of patients without previous exposure to long-acting antipsychotic treatment revealed the positive impact of previous exposure on treatment continuation with a subsequent long acting treatment. Additionally, the probability of restarting the index therapy was higher among patients treated with paliperidone palmitate once monthly compared to patients treated with risperidone microspheres and haloperidol decanoate. The data source used and the methodology defined ensured for the first time a comparison of treatment continuation in a non-interventional study design for the four long-acting injectable antipsychotics studied. PMID:28614404

Differential alterations in gene expression profiles contribute to time-dependent effects of nandrolone to prevent denervation atrophy

PubMed Central

2010-01-01

Background Anabolic steroids, such as nandrolone, slow muscle atrophy, but the mechanisms responsible for this effect are largely unknown. Their effects on muscle size and gene expression depend upon time, and the cause of muscle atrophy. Administration of nandrolone for 7 days beginning either concomitantly with sciatic nerve transection (7 days) or 29 days later (35 days) attenuated denervation atrophy at 35 but not 7 days. We reasoned that this model could be used to identify genes that are regulated by nandrolone and slow denervation atrophy, as well as genes that might explain the time-dependence of nandrolone effects on such atrophy. Affymetrix microarrays were used to profile gene expression changes due to nandrolone at 7 and 35 days and to identify major gene expression changes in denervated muscle between 7 and 35 days. Results Nandrolone selectively altered expression of 124 genes at 7 days and 122 genes at 35 days, with only 20 genes being regulated at both time points. Marked differences in biological function of genes regulated by nandrolone at 7 and 35 days were observed. At 35, but not 7 days, nandrolone reduced mRNA and protein levels for FOXO1, the mTOR inhibitor REDD2, and the calcineurin inhibitor RCAN2 and increased those for ApoD. At 35 days, correlations between mRNA levels and the size of denervated muscle were negative for RCAN2, and positive for ApoD. Nandrolone also regulated genes for Wnt signaling molecules. Comparison of gene expression at 7 and 35 days after denervation revealed marked alterations in the expression of 9 transcriptional coregulators, including Ankrd1 and 2, and many transcription factors and kinases. Conclusions Genes regulated in denervated muscle after 7 days administration of nandrolone are almost entirely different at 7 versus 35 days. Alterations in levels of FOXO1, and of genes involved in signaling through calcineurin, mTOR and Wnt may be linked to the favorable action of nandrolone on denervated muscle. Marked changes in the expression of genes regulating transcription and intracellular signaling may contribute to the time-dependent effects of nandrolone on gene expression. PMID:20969782

Anabolic Steroid Reversal of Denervation Atrophy

DTIC Science & Technology

2012-03-01

rabbit model treated with nandrolone decanoate12 and Zhao et al. found that nandrolone significantly reduced chronic denervation atrophy (but not acute...surprising results, the most important question is whether the concept of augmenting reinnervated muscle is flawed or whether nandrolone (at the dosage...administration of supraphysiological doses of anabolic or natural steroids to normal rats22, 23. Egginton administered nandrolone to sedentary female

Use of high-dose nandrolone aggravates septic shock in a mouse model.

PubMed

Lin, Che; Chen, Shou-Tung; Chien, Su-Yu; Kuo, Shou-Jen; Chen, Dar-Ren

2011-06-01

Nandrolone, an anabolic-androgenic steroid, is widely misused by athletes who wish to rapidly increase muscle mass and performance. An increasing number of reports have indicated that nandrolone may affect and modulate the immune system. This study aimed to investigate the effects of nandrolone on septic shock-caused immune responses and the cellular mechanism of action using a sepsis murine model. Before septic shock induction, BALB/c mice were given a high dose of nandrolone or peanut oil only. After septic shock induction, mice were sacrificed at different time points. Their blood and tissue specimens were analyzed. It was found that the high-dose nandrolone group had significantly increased mortality compared with the control group (p<0.001). The serum malondialdehyde level was significantly increased in the high-dose group compared with the control group. Animals administered a high dose of nandrolone had significantly increased hepatic tumor necrosis factor-α or splenic interferon-γ at 0 and 6 hours. In lung tissue, insulin-like growth factor-1, insulin-like growth factor binding proteins (IGFBPs) and insulin-like growth factor-1 receptor, and IGFBP1 and IGFBP2 mRNA expression were increased in the high-dose nandrolone group at 6 hours. Nandrolone abuse may hasten the death of patients with septic shock and may aggravate septic shock in mice. Copyright © 2011. Published by Elsevier B.V.

Anorexia in end-stage renal disease: pathophysiology and treatment.

PubMed

Aguilera, A; Selgas, R; Diéz, J J; Bajo, M A; Codoceo, R; Alvarez, V

2001-11-01

Anorexia is a frequent complication of uraemic syndrome, which contributes to malnutrition in dialysis patients. Uraemic anorexia has been associated with many factors. This paper reviews the current knowledge about mechanisms responsible for uraemic anorexia, the treatments and new drugs used to control the loss of appetite. Traditionally, anorexia in dialysis patients has been considered as a sign of uraemic toxicity, therefore, two hypotheses have been proposed, the 'middle molecule' and 'peak-concentration' hypotheses, both of which are still unproved. Recently, our group proposed the tryptophan-serotonin hypothesis, which is based on a disorder in the amino acid profile acquired in the uraemic status. This is characterised by low concentrations of large neutral and branched chain amino acids (LNAA/BCAA) in the cerebrospinal fluid. This situation permits a high level of tryptophan transport across the blood-brain barrier, causing an increase in the synthesis of serotonin (responsible for appetite inhibition). There are two main treatment targets for anorexia in dialysis patients. The first is to decrease the free plasma tryptophan concentration and transport across the blood brain barrier to the cerebrospinal fluid, thus decreasing the intracerebral serotonin levels. Nutritional formulae enriched with LNAA and BCAA have this effect. Secondly, plasma levels of cytokines with cachectin effect (TNF-alpha), should be decreased. This also induces a decrease in LNAA and BCAA levels. In this group are megestrol acetate, anti-TNF-alpha antibodies, thalidomide, pentoxifyilline, n-3 fatty acids and possibly nandrolone decanoate. Additionally, other targets should be explored including antagonists of cholecystokinin (a potent anorexigen retained by renal failure), analogues of neuropeptide Y (the most potent orexigen), cannabinoids, cyproheptadine, hydrazine sulfate. In conclusion, uraemic anorexia is a complex complication associated with malnutrition, high morbidity and mortality. The pharmacological treatment should address key points in the pathogenesis of uraemic anorexia, reducing intra-cerebral concentration of serotonin with LNAA/BCAA oral diet formulae and the plasma levels of pro-inflammatory molecules. Others forms of treatment should also be explored.

Differential alterations in gene expression profiles contribute to time-dependent effects of nandrolone to prevent denervation atrophy.

PubMed

Qin, Weiping; Pan, Jiangping; Bauman, William A; Cardozo, Christopher P

2010-10-22

Anabolic steroids, such as nandrolone, slow muscle atrophy, but the mechanisms responsible for this effect are largely unknown. Their effects on muscle size and gene expression depend upon time, and the cause of muscle atrophy. Administration of nandrolone for 7 days beginning either concomitantly with sciatic nerve transection (7 days) or 29 days later (35 days) attenuated denervation atrophy at 35 but not 7 days. We reasoned that this model could be used to identify genes that are regulated by nandrolone and slow denervation atrophy, as well as genes that might explain the time-dependence of nandrolone effects on such atrophy. Affymetrix microarrays were used to profile gene expression changes due to nandrolone at 7 and 35 days and to identify major gene expression changes in denervated muscle between 7 and 35 days. Nandrolone selectively altered expression of 124 genes at 7 days and 122 genes at 35 days, with only 20 genes being regulated at both time points. Marked differences in biological function of genes regulated by nandrolone at 7 and 35 days were observed. At 35, but not 7 days, nandrolone reduced mRNA and protein levels for FOXO1, the mTOR inhibitor REDD2, and the calcineurin inhibitor RCAN2 and increased those for ApoD. At 35 days, correlations between mRNA levels and the size of denervated muscle were negative for RCAN2, and positive for ApoD. Nandrolone also regulated genes for Wnt signaling molecules. Comparison of gene expression at 7 and 35 days after denervation revealed marked alterations in the expression of 9 transcriptional coregulators, including Ankrd1 and 2, and many transcription factors and kinases. Genes regulated in denervated muscle after 7 days administration of nandrolone are almost entirely different at 7 versus 35 days. Alterations in levels of FOXO1, and of genes involved in signaling through calcineurin, mTOR and Wnt may be linked to the favorable action of nandrolone on denervated muscle. Marked changes in the expression of genes regulating transcription and intracellular signaling may contribute to the time-dependent effects of nandrolone on gene expression.

Vascular adaptive responses to physical exercise and to stress are affected differently by nandrolone administration.

PubMed

Bruder-Nascimento, T; Cordellini, S

2011-04-01

Androgenic anabolic steroid, physical exercise and stress induce cardiovascular adaptations including increased endothelial function. The present study investigated the effects of these conditions alone and in combination on the vascular responses of male Wistar rats. Exercise was started at 8 weeks of life (60-min swimming sessions 5 days per week for 8 weeks, while carrying a 5% body-weight load). One group received nandrolone (5 mg/kg, twice per week for 8 weeks, im). Acute immobilization stress (2 h) was induced immediately before the experimental protocol. Curves for noradrenaline were obtained for thoracic aorta, with and without endothelium from sedentary and trained rats, submitted or not to stress, treated or not with nandrolone. None of the procedures altered the vascular reactivity to noradrenaline in denuded aorta. In intact aorta, stress and exercise produced vascular adaptive responses characterized by endothelium-dependent hyporeactivity to noradrenaline. These conditions in combination did not potentiate the vascular adaptive response. Exercise-induced vascular adaptive response was abolished by nandrolone. In contrast, the aortal reactivity to noradrenaline of sedentary rats and the vascular adaptive response to stress of sedentary and trained rats were not affected by nandrolone. Maximum response for 7-10 rats/group (g): sedentary 3.8 ± 0.2 vs trained 3.0 ± 0.2*; sedentary/stress 2.7 ± 0.2 vs trained/stress 3.1 ± 0.1*; sedentary/nandrolone 3.6 ± 0.1 vs trained/nandrolone 3.8 ± 0.1; sedentary/stress/nandrolone 3.2 ± 0.1 vs trained/stress/nandrolone 2.5 ± 0.1*; *P < 0.05 compared to its respective control. Stress and physical exercise determine similar vascular adaptive response involving distinct mechanisms as indicated by the observation that only the physical exercise-induced adaptive response was abolished by nandrolone.

Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression.

PubMed

Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A; Cardozo, Christopher P

2011-10-14

Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy. Copyright © 2011. Published by Elsevier Inc.

Evaluation of nandrolone and ractopamine in the urine of veal calves: liquid chromatography-tandem mass spectrometry approach.

PubMed

Chiesa, L; Panseri, S; Cannizzo, F T; Biolatti, B; Divari, S; Benevelli, R; Arioli, F; Pavlovic, R

2017-04-01

Under European legislation, the use of growth promoters is forbidden in food-producing livestock. The application of unofficial protocols with diverse combinations of veterinary drugs, administered in very low concentrations, hinders reliable detection and subsequent operative prevention. It was observed that nandrolone (anabolic steroid) and ractopamine (β-adrenergic agonist) are occasionally administered to animals, but little is known about their synergic action when they are administered together. Two specific analytical methods based on liquid chromatography-tandem mass spectrometry have been developed, both of which include hydrolysis of the corresponding conjugates. For the nandrolone method, solid-phase extraction was necessary for the complete elimination of the interferences, while employment of the Quantitation Enhanced Data-Dependent scan mode during MS acquisition of ractopamine enabled the utilization of simple liquid-liquid extraction. The nandrolone method was linear in the range of 0.5-25 ng/mL, while the ractopamine calibration curve was constructed from 0.5 to 1000 ng/mL. The corresponding coefficients of correlations were >0.9907. The lower limit of quantification for both methods was 0.5 ng/mL, followed by overall recoveries >81%. Precisions expressed as relative standard deviations were <17%, while matrix effects were minimal. Urine samples taken at the slaughterhouse from veal calves enrolled in an experimental treatment consisting of intramuscular administration of β-nandrolone-phenylpropionate accompanied with a ractopamine-enriched diet were analysed. Those methods might be useful for studying the elimination patterns of the administered compounds along with characterization of the main metabolic pathways. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Histopathologycal findings in the ovaries and uterus of albino female rats promoted by co-administration of synthetic steroids and nicotine.

PubMed

Camargo, Isabel Cristina Cherici; Leite, Gabriel Adan Araújo; Pinto, Tiago; Ribeiro-Paes, João Tadeu

2014-07-01

The use of anabolic androgenic steroids is often associated with the use of other substances, licit or not, such as nicotine present in the tobacco. The present study investigated for the first time the effects of co-administration of synthetic steroids and nicotine on the ovarian and uterine tissue and fertility of adult female rats. Animals were submitted to treatment groups (n=16/group): nandrolone decanoate (ND; 7.5mg/kg BW/week); testosterone mixture (T; 7.5mg/kg BW/week); nicotine (N; 2.0mg/kg BW/day), and co-administration of ND/N, T/N and ND/T/N. The control group received saline solution daily. The injections were administered subcutaneously for 30 consecutive days. Results demonstrated that all androgenized rats exhibited estral acyclicity and there was suppression of reproductive capacity due to notable ovarian and uterine histological changes. Treatments promoted decrease (p<0.05) in the ovarian weight. Uterine weight increased (p<0.05) in the T and T/N groups, in comparison to control group. ND or T co-administered or not to nicotine promoted intense follicular degeneration, with formation of cysts in the ovaries. High levels of circulating androgens in the ND/T/N group induced the presence of ovarian sex cord-stromal tumors of Sertoli cell pattern. Androgenized females presented endometrial changes characterized by papilliferous or pleated luminal epithelium, oedematous and hemorrhagic stroma and presence of gland cysts. In conclusion, the co-administration of three drugs promoted atypical morphological pattern on the ovaries and uterus of female rats. Copyright © 2014 Elsevier GmbH. All rights reserved.

Mitigative Effects of a Combination of Multiple Pharmaceutical Drugs on the Survival of Mice Exposed to Lethal Ionizing Radiation.

PubMed

Hirouchi, Tokuhisa; Ito, Koichi; Nakano, Manabu; Monzen, Satoru; Yoshino, Hironori; Chiba, Mitsuru; Hazawa, Masaharu; Nakano, Akira; Ishikawa, Junya; Yamaguchi, Masaru; Tanaka, Kimio; Kashiwakura, Ikuo

2015-01-01

It is important to establish an easy-to-use therapeutic protocol for the emergency medical care of patients involved in radiation accidents to reduce the radiation-related casualties. The present study aimed to establish an optimum therapeutic protocol using currently approved pharmaceutical drugs to increase the survival of victims exposed to lethal radiation. Different combinations of four drugs-recombinant human erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), c-mpl receptor agonist romiplostim (RP) and nandrolone decanoate (ND)-were administered to mice within 2 h after exposure to a lethal 7 Gy dose of γ-irradiation. On day 30 after irradiation, the condition of the mice was analyzed using various hematological parameters, such as the number of peripheral blood cells, bone marrow cells, hematopoietic progenitor cells and the expression of cell surface antigens. Approximately 10% of the untreated irradiated control mice survived for 21 days, but all of the control mice died by day 30. The combined administration of G-CSF, EPO and RP for five days immediately after irradiation led to a complete survival of the irradiated mice until day 30. However, the treatment with G-CSF, EPO and RP with ND led to only 75% survival at day 30. The hematological analyses showed that the numbers of almost all of hematopoietic cells in the surviving mice treated with effective medications recovered to the levels of non-irradiated mice. The present findings show that the combination of G-CSF, EPO and RP may be a useful countermeasure for victims exposed to accidental lethal irradiation.

Effects of high-intensity exercises on 13C-nandrolone excretion in trained athletes.

PubMed

Baume, Norbert; Avois, Lidia; Sottas, Pierre-Edouard; Dvorak, Jiri; Cauderay, Michel; Mangin, Patrice; Saugy, Martial

2005-05-01

Nandrolone is an anabolic steroid widely used in several sports. The numerous nandrolone positive cases in the recent years (International Olympic Committee statistics) led to several studies in the antidoping field. Nevertheless, essential questions pertaining to nandrolone endogenous production, the effects of physical exercise on the excretion of nandrolone metabolites, and contamination from nutritional supplements must still be addressed. The purpose of this study was to evaluate the influence of exhaustive exercises on 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) urinary excretion rates after administration of labeled nandrolone. A total of 34 healthy male Caucasian volunteers from the Institute of Sports Sciences and Physical Education (University of Lausanne) applied to participate in the study. All subjects were free from any physical drug addiction and were instructed strictly to avoid any nutritional supplement or steroid before and during the study. The participants were randomly dispatched in 2 groups in a double-blind way: a placebo group and a group treated with C-labeled nandrolone. The urinary concentrations of the 2 main nandrolone metabolites, 19-NA and 19-NE, were measured using gas chromatography coupled with mass spectrometry. In addition, clinical parameters such as creatinine, total protein, and beta2-microglobuline levels were determined using immunologic assays. After an oral ingestion of a 25 mg 3,4-C2-nandrolone dose, followed by a second identical dose 24 hours later, 19-NA and 19-NE could be detected in the urine for a period of 6 days after the initial intake. Despite several interesting observations, the measurements were very scattered and did not appear to be significantly influenced by exercise sessions in the athlete population. The results of this study suggest that physical exercise cannot be considered as a reliable parameter that systematically affects nandrolone metabolite concentrations in the urine.

Nandrolone, an anabolic steroid, stabilizes Numb protein through inhibition of mdm2 in C2C12 myoblasts.

PubMed

Liu, Xin-Hua; Yao, Shen; Levine, Alice C; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Collier, Lauren; Bauman, William A; Cardozo, Christopher P

2012-01-01

Nandrolone, an anabolic steroid, slows denervation atrophy of rat muscle, prevents denervation-induced nuclear accumulation of intracellular domain of the Notch receptor, and elevates expression of Numb. Numb acts as an inhibitor of Notch signaling and promotes myogenic differentiation of satellite cells. Turnover of Numb is regulated by mdm2, an E3 ubiquitin ligase. With these considerations in mind, we investigated the effects of nandrolone on the expression of Numb and mdm2 proteins and determined the effect of mdm2 on nandrolone-induced alterations in Numb protein in C2C12 myoblasts. When C2C12 cells were cultured in a medium favoring differentiation (Dulbecco modified Eagle medium containing 2% horse serum), nandrolone up-regulated Numb protein levels in a time-dependent manner and prolonged Numb protein half-life from 10 to 18 hours. In contrast, nandrolone reduced the expression of mdm2 protein. To determine whether the decreased mdm2 expression induced by nandrolone was responsible for the increased levels and prolonged half-life of Numb protein in this cell line, mdm2-small interfering RNA (siRNA) was employed to inhibit mdm2 expression. Compared to cells transfected with scrambled siRNA (negative control), transfection with mdm2-siRNA increased basal Numb protein expression but abolished the further increase in Numb protein levels by nandrolone. In addition, transfection of mdm2-siRNA mimicked the effect of nandrolone to prolong the half-life of Numb protein. Moreover, when C2C12 cells were forced to overexpress mdm2, there was a significant decline in the expression of both basal and inducible Numb protein. Our data suggest that nandrolone, by a novel mechanism for this agent in a muscle cell type, increases Numb protein levels in C2C12 myoblasts by stabilizing Numb protein against degradation, at least in part, via suppression of mdm2 expression.

Ex vivo spontaneous generation of 19-norandrostenedione and nandrolone detected in equine plasma and urine.

PubMed

Guan, Fuyu; Uboh, Cornelius E; Soma, Lawrence R; You, Youwen; Li, Xiaoqing; McDonnell, Sue

2012-01-01

19-Norandrostenedione (NAED) and nandrolone are anabolic-androgenic steroids (AASs). Nandrolone was regarded solely as a synthetic AAS until the 1980s when trace concentrations of apparently endogenous nandrolone were detected in urine samples obtained from intact male horses (stallions). Since then, its endogenous origin has been reported in boars and bulls; endogenous NAED and nandrolone have been identified in plasma and urine samples collected from stallions. More recently, however, it was suggested that NAED and nandrolone detected in urine samples from stallions are primarily artifacts due to the analytical procedure. The present study was undertaken to determine whether NAED and nandrolone detected in plasma and urine samples collected from stallions are truly endogenous or artifacts from sample processing. To answer this question, fresh plasma and urine samples from ≥8 stallions were analyzed for the two AASs, soon after collection, by liquid chromatography hyphenated to tandem mass spectrometry (LC-MS/MS). NAED and nandrolone were not detected in fresh plasma samples but detected in the same samples post storage. Concentrations of both AASs increased with storage time, and the increases were greater at a higher storage temperature (37°C versus 4°C, and ambient temperature versus 4°C). Although NAED was detected in some fresh stallion urine samples, its concentration (<407 pg/mL) was far lower (<0.4%) than that in the same samples post storage (at ambient temperature for 15 days). Nandrolone was not detected in most of fresh urine samples but detected in the same samples post storage. Based on these results, it is concluded that all NAED and nandrolone detected in stored plasma samples of stallions and most of them in the stored urine samples are not from endogenous origins but spontaneously generated during sample storage, most likely from spontaneous decarboxylation of androstenedione-19-oic acid and testosterone-19-oic acid. To our knowledge, it is the first time that all NAED and nandrolone detected in plasma of stallions and most of them detected in the urine have been shown to be spontaneously generated in vitro during sample storage. This finding would have significant implications with regard to the regulation of the two steroids in horse racing. Copyright © 2011 Elsevier Ltd. All rights reserved.

The effect of nandrolone, an anabolic steroid on putrescine metabolism in the mouse.

PubMed Central

Henningsson, S; Rosengren, E

1976-01-01

1 The catabolism of injected 14 C-putrescine was studied in mice treated with nandrolone phenpropionate, an anabolic steroid. 2 The putrescine was rapidly metabolized; almost 50% of the injected radioactivity was recovered within 2 h as 14 CO2 in the expired air. 3 Considerable amounts of radioactive gamma-aminobutyric acid (GABA) and an unidentified compound were found in the kidney and in the urine in addition to radioactive putrescine, spermidine and spermine both in controls and nandrolone-treated mice. 4 Nandrolone elevated the concentration of endogenous putrescine in the kidney and urine, eightfold and twentyfold, respectively, and the concentrations of spermidine and spermine were also increased 5 after the injection of 14C-putrescine the incorporation of 14C into spermidine was significantly increased in the kidney of mice receiving nandrolone. PMID:990594

An intra-hippocampal injection of nandrolone induces learning and memory impairments in rat.

PubMed

Karamian, A; Pakdel, F G; Ilkhanipoor, M; Farokhi, F; Ahmadi, A

2015-01-01

This study was investigated to evaluate the effect of intra-hippocampal injection of the nandrolone on spatial learning task in rats. The drug or vehicle was manually injected into the hippocampus with a 10-µl Hamilton syringe attached via polyethylene tubing to 27-gauge stainless-steel injection cannula. After 6 days of recovery, learning behaviors were evaluated using an 8-arm radial maze. The results showed that intra-hippocampal injection of nandrolone can impair trained spatial learning at a dose of 5 µl. We also observed a dense cytoplasm and nucleus in CA1 neurons as well as signs of necrosis. Nandrolone can impair the time required to reach the baited arm as well as the frequency of successful arm entries. At the 10 µl dose of nandrolone, neural hypertrophy and increased dentate gyrus volume were also observed. © Georg Thieme Verlag KG Stuttgart · New York.

Androgens Up-regulate Transcription of the Notch Inhibitor Numb in C2C12 Myoblasts via Wnt/β-Catenin Signaling to T Cell Factor Elements in the Numb Promoter*

PubMed Central

Liu, Xin-Hua; Wu, Yong; Yao, Shen; Levine, Alice C.; Kirschenbaum, Alexander; Collier, Lauren; Bauman, William A.; Cardozo, Christopher P.

2013-01-01

Androgen signaling via the androgen receptor is a key pathway that contributes to development, cell fate decisions, and differentiation, including that of myogenic progenitors. Androgens and synthetic steroids have well established anabolic actions on skeletal muscle. Wnt and Notch signaling pathways are also essential to myogenic cell fate decisions during development and tissue repair. However, the interactions among these pathways are largely unknown. Androgenic regulation of Wnt signaling has been reported. Nandrolone, an anabolic steroid, has been shown to inhibit Notch signaling and up-regulate Numb, a Notch inhibitor. To elucidate the mechanisms of interaction between nandrolone and Wnt/Notch signaling, we investigated the effects of nandrolone on Numb expression and Wnt signaling and determined the roles of Wnt signaling in nandrolone-induced Numb expression in C2C12 myoblasts. Nandrolone increased Numb mRNA and protein levels and T cell factor (Tcf) transcriptional activity via inhibition of glycogen synthase kinase 3β. Up-regulation of Numb expression by nandrolone was blocked by the Wnt inhibitors, sFRP1 and DKK1, whereas Wnt3a increased Numb mRNA and protein expression. In addition, we observed that the proximal promoter of the Numb gene had functional Tcf binding elements to which β-catenin was recruited in a manner enhanced by both nandrolone and Wnt3a. Moreover, site-directed mutagenesis indicated that the Tcf binding sites in the Numb promoter are required for the nandrolone-induced Numb transcriptional activation in this cell line. These results reveal a novel molecular mechanism underlying up-regulation of Numb transcription with a critical role for increased canonical Wnt signaling. In addition, the data identify Numb as a novel target gene of the Wnt signaling pathway by which Wnts would be able to inhibit Notch signaling. PMID:23649620

Synthesis and biological evaluation of nandrolone-bodipy conjugates.

PubMed

Jurášek, Michal; Rimpelová, Silvie; Pavlíčková, Vladimíra; Ruml, Tomáš; Lapčík, Oldřich; Drašar, Pavel B

2015-05-01

Here, we report synthesis and biological evaluation of fluorescent nandrolone-3-carboxymethyloxime derivatives conjugated with green-emitting bodipy dye via PEG linkers. All the newly-synthesized compounds were evaluated for their effect on cell proliferation in vitro in MCF-7, LNCaP, PC-3 and HEK 293T model cell lines using WST-1 assay. By means of live-cell fluorescence microscopy, the intracellular localization of nandrolone-bodipy conjugates was revealed in endoplasmic reticulum. Moreover, we performed competitive localization study with nonfluorescent nandrolone, metandrolone, boldenone, trenbolone, and testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells.

PubMed

Pomara, Cristoforo; Barone, Rosario; Marino Gammazza, Antonella; Sangiorgi, Claudia; Barone, Fulvio; Pitruzzella, Alessandro; Locorotondo, Nicola; Di Gaudio, Francesca; Salerno, Monica; Maglietta, Francesca; Sarni, Antonio Luciano; Di Felice, Valentina; Cappello, Francesco; Turillazzi, Emanuela

2016-06-01

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin-releasing hormone, luteinizing hormone, and follicle-stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real-time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the basal level a 15.6 μM dose of nandrolone. Nandrolone-induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a-hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down-regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Novel Uses for the Anabolic Androgenic Steroids Nandrolone and Oxandrolone in the Management of Male Health.

PubMed

Wu, Christopher; Kovac, Jason R

2016-10-01

There has recently been renewed interest in novel clinical applications of the anabolic-androgenic steroid (AAS) testosterone and its synthetic derivatives, particularly given with the rising popularity of testosterone supplementation therapy (TST) for the treatment of male hypogonadism. In this manuscript, we provide a brief review of the history of AAS and discuss clinical applications of two of the more well-known AAS: nandrolone and oxandrolone. Both agents exhibit favorable myotrophic/androgenic ratios and have been investigated for effectiveness in numerous disease states. We also provide a brief synopsis of selective androgen receptor modulators (SARMs) and postulate how these orally active, non-aromatizing, tissue-selective agents might be used in contemporary andrology. Currently, the applications of testosterone alternatives in hypogonadism are limited. However, it is tempting to speculate that these agents may one day become accepted as alternatives, or adjuncts, to the treatment of male hypogonadism.

Cost-effectiveness model of long-acting risperidone in schizophrenia in the US.

PubMed

Edwards, Natalie C; Rupnow, Marcia F T; Pashos, Chris L; Botteman, Marc F; Diamond, Ronald J

2005-01-01

Schizophrenia is a devastating and costly illness that affects 1% of the population in the US. Effective pharmacological therapies are available but suboptimal patient adherence to either acute or long-term therapeutic regimens reduces their effectiveness. The availability of a long-acting injection (LAI) formulation of risperidone may increase adherence and improve clinical and economic outcomes for people with schizophrenia. To assess the cost effectiveness of risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI over a 1-year time period in outpatients with schizophrenia who had previously suffered a relapse requiring hospitalisation. US healthcare system. Published medical literature, unpublished data from clinical trials and a consumer health database, and a clinical expert panel were used to populate a decision-analysis model comparing the four treatment alternatives. The model captured: rates of patient compliance; rates, frequency and duration of relapse; incidence of adverse events (bodyweight gain and extrapyramidal effects); and healthcare resource utilisation and associated costs. Primary outcomes were: the proportion of patients with relapse; the frequency of relapse per patient; the number of relapse days per patient; and total direct medical cost per patient per year. Costs are in year 2002 US dollars. Based on model projections, the proportions of patients experiencing a relapse requiring hospitalisation after 1 year of treatment were 66% for haloperidol decanoate LAI, 41% for oral risperidone and oral olanzapine and 26% for risperidone LAI, while the proportion of patients with a relapse not requiring hospitalisation were 60%, 37%, 37% and 24%, respectively. The mean number of days of relapse requiring hospitalisation per patient per year was 28 for haloperidol decanoate LAI, 18 for oral risperidone and oral olanzapine and 11 for risperidone LAI, while the mean number of days of relapse not requiring hospitalisation was 8, 5, 5 and 3, respectively. This would translate into direct medical cost savings with risperidone LAI compared with oral risperidone, oral olanzapine and haloperidol decanoate LAI of USD 397, USD 1742, and USD 8328, respectively. These findings were supported by sensitivity analyses. The use of risperidone LAI for treatment of outpatients with schizophrenia is predicted in this model to result in better clinical outcomes and lower total healthcare costs over 1 year than its comparators, oral risperidone, oral olanzapine and haloperidol decanoate LAI. Risperidone LAI may therefore be a cost saving therapeutic option for outpatients with schizophrenia in the US healthcare setting.

An Experimental and Kinetic Modeling Study of Methyl Decanoate Combustion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarathy, S M; Thomson, M J; Pitz, W J

2009-12-04

Biodiesel is a mixture of long chain fatty acid methyl esters derived from fats and oils. This research study presents opposed-flow diffusion flame data for one large fatty acid methyl ester, methyl decanoate, and uses the experiments to validate an improved skeletal mechanism consisting of 648 species and 2998 reactions. The results indicate that methyl decanoate is consumed via abstraction of hydrogen atoms to produce fuel radicals, which lead to the production of alkenes. The ester moiety in methyl decanoate leads to the formation of low molecular weight oxygenated compounds such as carbon monoxide, formaldehyde, and ketene.

Chronic administration of nandrolone increases susceptibility to morphine dependence without correlation with LVV-hemorphin 7 in rats.

PubMed

Huang, Eagle Yi-Kung; Chen, Yuan-Hao; Huang, Tzu-Ying; Chen, Ying-Jie; Chow, Lok-Hi

2016-10-01

LVV-hemorphin 7 (LVVYPWTQRF; LVV-H7), an N-terminal fragment of the β-chain of hemoglobin cleaved by cathepsin D/pepsin, is an atypical endogenous opioid peptide that is found in high concentration in blood. LVV-H7 acts as a μ-opioid agonist and an inhibitor of insulin-regulated aminopeptidase. Subchronic administration of anabolic androgenic steroids (AAS) has been clinically proven to induce the synthesis of erythrocytes and increase hemoglobin concentrations. Patients with a history of AAS abuse are more susceptible to opioid abuse. We hypothesized that this association could be at least partially attributed to the sensitization of the mesocorticolimbic dopaminergic pathway by LVV-H7. Using the conditioned place preference test and neurochemical analysis, we investigated the possible mechanism underlying the effect of chronic nandrolone administration on morphine-induced reward and its correlation with LVV-H7 in rats. Either LVV-H7 may not sensitize the rewarding neural circuits or its inhibition on locomotor activity could mask reward-related behaviors. Chronic nandrolone pretreatment indeed caused a significant reward by low dose morphine, which did not cause any reward in control rats. However, coadministration of anti-LVV-H7 antiserum with nandrolone did not block this effect. This may rule out the possibility of the involvement of LVV-H7 in the action of nandrolone to intensify morphine-induced reward. Moreover, the serum level of LVV-H7 was mildly increased in response to chronic nandrolone administration in our animal model. According to the current clinical observations, we may conclude that the chronic administration of nandrolone can increase susceptibility to morphine dependence, but that this effect is not related to elevated LVV-H7. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genomic and lipidomic actions of nandrolone on detached rotator cuff muscle in sheep.

PubMed

Flück, Martin; Ruoss, Severin; Möhl, Christoph B; Valdivieso, Paola; Benn, Mario C; von Rechenberg, Brigitte; Laczko, Endre; Hu, Junmin; Wieser, Karl; Meyer, Dominik C; Gerber, Christian

2017-01-01

Reversal of fatty infiltration of pennate rotator cuff muscle after tendon release is hitherto impossible. The administration of nandrolone starting at the time of tendon release prevents the increase in fat content, but does not revert established fatty infiltration. We hypothesised that tendon release and myotendinous retraction cause alterations in lipid related gene expression leading to fatty muscle infiltration, which can be suppressed by nandrolone through its genomic actions if applied immediately after tendon release. The effects of infraspinatus tendon release and subsequent tendon repair at 16 weeks were studied in six Swiss Alpine sheep. In the interventional groups, 150mg nandrolone was administered weekly after tendon release until sacrifice (N22W, n=6) or starting at the time of repair (N6W, n=6). Infraspinatus volume, composition, expressed transcripts, lipids, and selected proteins were analyzed at baseline, 16 and 22 weeks. Tendon release reduced infraspinatus volume by 22% and increased fat content from 11% to 38%. These changes were not affected by repair. Fatty infiltration was associated with up-regulation of 227 lipid species, and increased levels of the adipocyte differentiation marker PPARG2 (peroxisome proliferator-activated receptor gamma 2). Nandrolone abrogated lipid accumulation, halved the loss in fiber area percentage, and up-regulated androgen receptor levels and transcript expression in the N22W but not the N6W group. The results document that nandrolone mitigates muscle-to-fat transformation after tendon release via a general down-regulation of lipid accumulation concomitantly with up-regulated expression of its nuclear receptor and downstream transcripts in skeletal muscle. Reduced responsiveness of retracted muscle to nandrolone as observed in the N6W group is reflected by a down-regulated transcript response. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

PubMed Central

Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

2015-01-01

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. PMID:19463691

Monitoring the endogenous steroid profile disruption in urine and blood upon nandrolone administration: An efficient and innovative strategy to screen for nandrolone abuse in entire male horses.

PubMed

Kaabia, Z; Dervilly-Pinel, G; Popot, M A; Bailly-Chouriberry, L; Plou, P; Bonnaire, Y; Le Bizec, B

2014-04-01

Nandrolone (17β-hydroxy-4-estren-3-one) is amongst the most misused endogenous steroid hormones in entire male horses. The detection of such a substance is challenging with regard to its endogenous presence. The current international threshold level for nandrolone misuse is based on the urinary concentration ratio of 5α-estrane-3β,17α-diol (EAD) to 5(10)-estrene-3β,17α-diol (EED). This ratio, however, can be influenced by a number of factors due to existing intra- and inter-variability standing, respectively, for the variation occurring in endogenous steroids concentration levels in a single subject and the variation in those same concentration levels observed between different subjects. Targeting an efficient detection of nandrolone misuse in entire male horses, an analytical strategy was set up in order to profile a group of endogenous steroids in nandrolone-treated and non-treated equines. Experiment plasma and urine samples were steadily collected over more than three months from a stallion administered with nandrolone laurate (1 mg/kg). Control plasma and urine samples were collected monthly from seven non-treated stallions over a one-year period. A large panel of steroids of interest (n = 23) were extracted from equine urine and plasma samples using a C18 cartridge. Following a methanolysis step, liquid-liquid and solid-phase extractions purifications were performed before derivatization and analysis on gas chromatography-tandem mass spectrometry (GC-MS/MS) for quantification. Statistical processing of the collected data permitted to establish statistical models capable of discriminating control samples from those collected during the three months following administration. Furthermore, these statistical models succeeded in predicting the compliance status of additional samples collected from racing horses. Copyright © 2013 John Wiley & Sons, Ltd.

Testing for nandrolone metabolites in urine samples of professional athletes and sedentary subjects by GC/MS/MS analysis.

PubMed

Gambelunghe, Cristiana; Sommavilla, Marco; Rossi, Ruggero

2002-12-01

The concentrations of nandrolone metabolites, 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) were analysed in urine samples of professional athletes doing intense physical activity and sedentary subjects to verify if there was endogenous production of nandrolone and if there was any link between physical effort and the urinary metabolites of the steroid. We collected 18 urine samples from professional footballers age range 20-30 years, all from the same team, and 18 urine samples from males not doing any physical activity, age range 20-30 years. Neither group used nandrolone. Qualitative and quantitative analyses of urinary nandrolone metabolites were carried out by GC/MS followed by GC/MS/MS to confirm positive samples. This technique has been demonstrated to be an excellent analytical approach for the determination of anabolic steroids at very low detection limits in complex matrices such as urine. In five urine samples from professional footballers traces of 19-NA were detected. No trace of 19-NA was found in the group of sedentary subjects and no trace of 19-NE was found in any urine sample. The absence of nandrolone metabolites in sedentary subjects supports the hypothesis that the presence of 19-NA and 19-NE could be linked to physical effort even though the origin is not yet clear. Copyright 2002 John Wiley & Sons, Ltd.

Endogenous nandrolone metabolites in human urine: preliminary results to discriminate between endogenous and exogenous origin.

PubMed

Le Bizec, Bruno; Bryand, Fabrice; Gaudin, Isabelle; Monteau, Fabrice; Poulain, Frédéric; Andre, François

2002-02-01

When administered to human subjects, nandrolone is metabolized into two main products, 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE). Recent studies demonstrated the endogenous production of these compounds in man at concentrations very close to the threshold of the International Olympic Committee (IOC), i.e. 2 ng/ml. Because the possibility of reaching or exceeding this fateful limit is difficult to exclude, a complementary biochemical parameter is necessary for the differentiation of endogenous 19-NA and 19-NE production from residues resulting from nandrolone consumption. We measured the endogenous concentrations of 19-NA and 19-NE in 385 urine samples from professional football players, and we studied the phase II metabolite composition in individuals excreting the highest concentrations. The results showed that around 30% of endogenous 19-norandrosterone was sulfo-conjugated, whereas 100% of 19-norandrosterone was excreted conjugated to a glucuronic acid when nandrolone was administered. This significant qualitative difference appears to be a promising complementary criterion to more definitively conclude about an athlete's culpability, especially when nandrolone metabolites are found in the low ng/ml range.

Illegal treatment of barrows with nandrolone ester: effect on growth, histology and residue levels in urine and hair.

PubMed

Groot, M J; Lasaroms, J J P; van Bennekom, E O; Meijer, T; Vinyeta, E; van der Klis, J D; Nielen, M W F

2012-01-01

The effect of 17β-19-nortestosterone (17βNT) treatment of barrows on residue levels and growth was evaluated. Five barrows were treated three times during the fattening period with 17βNT phenylpropionate (Nandrosol, nandrolone phenylpropionate 50 mg/ml,1 mg/kg body weight). Another five barrows were untreated and five boars (untreated) were kept as positive control. Boars and treated barrows showed a 13 and 9% improvement in growth compared to untreated barrows, with mean final body weights of 121.6, 117.8 and 109.0 kg, respectively. The bulbourethral glands of the treated barrows were three times heavier than untreated barrows. The histology of the prostate and bulbourethral gland of the treated barrows was comparable to the boars, whereas the control barrows showed atrophic glands. Levels of 17βNT ester in hair from treated barrows were high, whereas boars and untreated barrows did not show levels above LLQ. It is concluded that analysis of hair can detect illegal treatment with 17βNT ester in barrows. The size of the bulbourethral gland can also be used for screening in the slaughterhouse.

Detection of nandrolone metabolites in urine after a football game in professional and amateur players: a Bayesian comparison.

PubMed

Robinson, N; Taroni, F; Saugy, M; Ayotte, C; Mangin, P; Dvorak, J

2001-11-01

Nandrolone (19-nortestosterone) is a widely used anabolic steroid in sports where strength plays an essential role. Once nandrolone has been metabolised, two major metabolites are excreted in urine, 19-norandrosterone (NA) and 19-noretiocholanolone (NE). In 1997, in France, quite a few sportsmen had concentrations of 19-norandrosterone very close to the IOC cut off limit (2ng/ml). At that time, a debate took place about the capability of the human male body to produce by itself these metabolites without any intake of nandrolone or related compounds. The International Football Federation (FIFA) was very concerned with this problematic, especially because the World Cup was about to start in France. In this respect, a statistical study was held with all football players from the first and second divisions of the Swiss Football National League. All players gave a urine sample after effort and around 6% of them showed traces of 19-norandrosterone. These results were compared with amateur football players (control group) and around 6% of them had very small amounts of 19-norandrosterone and/or 19-noretiocholanolone in urine after effort, whereas none of them had detectable traces of one or the other metabolite before effort. The origin of these compounds in urine after a strenuous physical activity is still unknown, but three hypotheses can be put forward. First, an endogenous production of nandrolone metabolites takes place. Second, nandrolone metabolites are released from the fatty tissues after an intake of nandrolone, some related compounds or some contaminated nutritive supplements. Finally, the sportsmen may have taken something during or just before the football game.

Neurotoxic properties of the anabolic androgenic steroids nandrolone and methandrostenolone in primary neuronal cultures.

PubMed

Caraci, Filippo; Pistarà, V; Corsaro, A; Tomasello, Flora; Giuffrida, Maria Laura; Sortino, Maria Angela; Nicoletti, Ferdinando; Copani, Agata

2011-04-01

Anabolic-androgenic steroid (AAS) abuse is associated with multiple neurobehavioral disturbances. The sites of action and the neurobiological sequels of AAS abuse are unclear at present. We investigated whether two different AASs, nandrolone and methandrostenolone, could affect neuronal survival in culture. The endogenous androgenic steroid testosterone was used for comparison. Both testosterone and nandrolone were neurotoxic at micromolar concentrations, and their effects were prevented by blockade of androgen receptors (ARs) with flutamide. Neuronal toxicity developed only over a 48-hr exposure to the steroids. The cell-impermeable analogues testosterone-BSA and nandrolone-BSA, which preferentially target membrane-associated ARs, were also neurotoxic in a time-dependent and flutamide-sensitive manner. Testosterone-BSA and nandrolone-BSA were more potent than their parent compounds, suggesting that membrane-associated ARs were the relevant sites for the neurotoxic actions of the steroids. Unlike testosterone and nandrolone, toxicity by methandrostenolone and methandrostenolone-BSA was insensitive to flutamide, but it was prevented by the glucocorticoid receptor (GR) antagonist RU-486. Methandrostenolone-BSA was more potent than the parent compound, suggesting that its toxicity relied on the preferential activation of putative membrane-associated GRs. Consistently with the evidence that membrane-associated GRs can mediate rapid effects, a brief challenge with methandrostenolone-BSA was able to promote neuronal toxicity. Activation of putative membrane steroid receptors by nontoxic (nanomolar) concentrations of either nandrolone-BSA or methandrostenolone-BSA became sufficient to increase neuronal susceptibility to the apoptotic stimulus provided by β-amyloid (the main culprit of AD). We speculate that AAS abuse might facilitate the onset or progression of neurodegenerative diseases not usually linked to drug abuse. Copyright © 2011 Wiley-Liss, Inc.

Fullerene-C60-modified electrode as a sensitive voltammetric sensor for detection of nandrolone--an anabolic steroid used in doping.

PubMed

Goyal, Rajendra N; Gupta, Vinod K; Bachheti, Neeta

2007-07-30

The electrochemical behaviour of nandrolone is investigated by cyclic, differential pulse and square-wave voltammetry in phosphate buffer system at fullerene-C60-modified electrode. The modified electrode shows an excellent electrocatalytic activity towards the oxidation of nandrolone resulting in a marked lowering in the peak potential and considerable improvement of the peak current as compared to the electrochemical activity at the bare glassy carbon electrode. The oxidation process is shown to be irreversible and diffusion-controlled. A linear range of 50 microM to 0.1 nM is obtained along with a detection limit and sensitivity of 0.42 nM and 0.358 nA nM(-1), respectively, in square-wave voltammetric technique. A diffusion coefficient of 4.13x10(-8) cm2 s(-1) was found for nandrolone using chronoamperometry. The effect of interferents, stability and reproducibility of the proposed method were also studied. The described method was successfully employed for the determination of nandrolone in human serum and urine samples. A cross-validation of observed results by GC-MS indicates that the results are in good agreement with each other.

Effects of Nandrolone Stimulation on Testosterone Biosynthesis in Leydig Cells

PubMed Central

Barone, Rosario; Marino Gammazza, Antonella; Sangiorgi, Claudia; Barone, Fulvio; Pitruzzella, Alessandro; Locorotondo, Nicola; Di Gaudio, Francesca; Salerno, Monica; Maglietta, Francesca; Sarni, Antonio Luciano; Di Felice, Valentina; Cappello, Francesco; Turillazzi, Emanuela

2015-01-01

Anabolic androgenic steroids (AAS) are among the drugs most used by athletes for improving physical performance, as well as for aesthetic purposes. A number of papers have showed the side effects of AAS in different organs and tissues. For example, AAS are known to suppress gonadotropin‐releasing hormone, luteinizing hormone, and follicle‐stimulating hormone. This study investigates the effects of nandrolone on testosterone biosynthesis in Leydig cells using various methods, including mass spectrometry, western blotting, confocal microscopy and quantitative real‐time PCR. The results obtained show that testosterone levels increase at a 3.9 μM concentration of nandrolone and return to the basal level a 15.6 μM dose of nandrolone. Nandrolone‐induced testosterone increment was associated with upregulation of the steroidogenic acute regulatory protein (StAR) and downregulation of 17a‐hydroxylase/17, 20 lyase (CYP17A1). Instead, a 15.6 µM dose of nandrolone induced a down‐regulation of CYP17A1. Further in vivo studies based on these data are needed to better understand the relationship between disturbed testosterone homeostasis and reproductive system impairment in male subjects. J. Cell. Physiol. 231: 1385–1391, 2016. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. PMID:26626779

Antinociceptive effects of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; Braun, Jana M; Steagall, Paulo V M; Keuler, Nicholas S; Heath, Timothy D; Krugner-Higby, Lisa A; Brown, Carolyn S; Paul-Murphy, Joanne R

2013-02-01

To evaluate the thermal antinociceptive effects and duration of action of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 10 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (33.7 mg/kg) or saline (0.9% NaCl) solution was administered IM in a randomized complete crossover experimental design (periods 1 and 2). Foot withdrawal threshold to a noxious thermal stimulus was used to evaluate responses. Baseline thermal withdrawal threshold was recorded 1 hour before drug or saline solution administration, and thermal foot withdrawal threshold measurements were repeated 1, 2, 3, 6, 12, 24, 48, and 72 hours after drug administration. Nalbuphine decanoate administered IM at a dose of 33.7 mg/kg significantly increased thermal foot withdrawal threshold, compared with results after administration of saline solution during period 2, and also caused a significant change in withdrawal threshold for up to 12 hours, compared with baseline values. Nalbuphine decanoate increased the foot withdrawal threshold to a noxious thermal stimulus in Hispaniolan Amazon parrots for up to 12 hours and provided a longer duration of action than has been reported for other nalbuphine formulations. Further studies with other types of nociceptive stimulation, dosages, and dosing intervals as well as clinical trials are needed to fully evaluate the analgesic effects of nalbuphine decanoate in psittacine birds.

Effect of nandrolone decanonate on paraoxonase activity in hemodialysis patients.

PubMed

Ghorbanihaghjo, Amir; Argani, Hassan; Rahbaninoubar, Mohammad; Rashtchizadeh, Nadereh

2005-12-01

This study was designed to determine the effect of nandrolone decanonate (ND) on HDL-C, apolipoproteins and paraoxonase (PON) activity in stable hemodialysis patients. 64 hemodialysis patients were treated with ND at a dose of 100 mg/I.M./week for 4 months. HDL-C, Apo-AI, Apo B, concentrations and PON activity were measured before and after 2 and 4 months of treatment as well as 2 months after withdrawing the treatment. After 4 months of treatment, an elevation in the serum levels of Apo B (P<0.0001) and a marked decrease in the concentration of HDL-C (P<0.0001), Apo-AI (P<0.0001) and PON activity (P<0.0001) were found. A significant correlation between PON and both Apo-AI (r=0.270, P<0.04) and HDL-C (r=0.455, P<0.0001) and also between HDL-C and Apo-AI (r=0.305, P<0.02) were found. Results revealed the adverse effects of ND on apolipoprotein levels in our study population. It is possible that ND reduces PON activity mostly by reducing both the HDL-C and Apo-AI levels.

Urinary nandrolone metabolites of endogenous origin in man: a confirmation by output regulation under human chorionic gonadotropin stimulation.

PubMed

Reznik, Y; Dehennin, L; Coffin, C; Mahoudeau, J; Leymarie, P

2001-01-01

19-Nortestosterone (nandrolone) is an anabolic steroid compound widely used as a doping agent by athletes. The analysis of its urinary metabolites, 19-norandrosterone (NA) and 19-noretiocholanolone (NE) glucuronides, allows the detection of surreptitious administration of nandrolone in sport. A threshold concentration at 2 microgram/L urinary nandrolone metabolites is advocated by the International Olympic Committee for the detection of doping, but some controversy concerning the validity of this threshold arose from the demonstration of endogenous production of nandrolone in mammals, including humans. The regulation of human nandrolone production and its contribution in vivo to the process of aromatization remain unknown. In the present study 10 healthy men were successively submitted to insulinic stress and gonadal stimulation by hCG administration. Urinary NA and NE concentrations were quantified by gas chromatography-mass spectrometry. NA was detected in basal urine samples from all subjects, with a mean urinary excretion rate (UER) of 3.17 +/- 0.35 ng/h, whereas NE was detected in 4 of 10 (UER range, 0.8-4.7 ng/h). Insulinic hypoglycemia did not significantly modify mean NA UER despite random intraindividual variations between timed urine collections. After hCG administration, NA UER increased by 250% (P < 0.01) and estradiol (E(2)) UER by 260% (P < 0.001). The maximum NA concentration obtained after stimulation was 0.43 microgram/L. NA UER, plasma E(2), and E(2)/T ratio peaked on day 1 after hCG administration, whereas plasma T peaked later on day 3. NA UER correlated with plasma E(2) (r = 0.61; P < 0.001) and E(2)/T (r = 0.51; P < 0.001), but not with plasma T. In conclusion, insulinic stress did not significantly alter nandrolone metabolism, whereas the effect of hCG was a stimulation of NA excretion in all subjects, which constitutes strong support for the endogenous origin of low basal NA excretion. The comparative kinetics of NA UER, plasma E(2), and E(2)/T ratio suggest a contribution of the aromatase process to nandrolone biosynthesis in man.

Nandrolone androgenic hormone presents genotoxic effects in different cells of mice.

PubMed

do Carmo, Carolina Almeida; Gonçalves, Álvaro Luiz Martini; Salvadori, Daisy Maria Fávero; Maistro, Edson Luis

2012-10-01

Nandrolone is an androgenic-anabolic steroid (AAS) with diverse medical applications but taken indiscriminately by some to rapidly increase muscle mass. The aim of this study was to evaluate the genotoxic and clastogenic potential of nandrolone (deca-durabolin®) in vivo in different cells of mice, using the comet assay and micronucleus test, respectively. The animals received subcutaneous injection of the three doses of the steroid (1.0, 2.5 and 5.0 mg kg⁻¹ body weight). Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE-NCE ratio). The results showed a significant dose-related increase in the frequency of DNA damage in leukocytes, liver, bone marrow, brain and testicle cells at the three tested doses and a significant increase of the micronucleated polychromatic erythrocytes at all tested doses. Under our experimental conditions, the nandrolone steroid hormone showed genotoxic and clastogenic effects when administered subcutaneously to mice. Copyright © 2011 John Wiley & Sons, Ltd.

Evidence of boldenone, nandrolone, 5(10)-estrene-3β-17α-diol and 4-estrene-3,17-dione as minor metabolites of testosterone in equine.

PubMed

Wong, Jenny K Y; Leung, David K K; Curl, Peter; Schiff, Peter J; Lam, Kenneth K H; Wan, Terence S M

2017-09-01

The detection of boldenone, nandrolone, 5(10)-estrene-3β,17α-diol, and 4-estrene-3,17-dione in a urine sample collected from a gelding having been treated with testosterone (500 mg 'Testosterone Suspension 100', single dose, injected intramuscularly) in 2009 led the authors' laboratory to suspect that these 'testicular' steroids could be minor metabolites of testosterone in geldings. Administration trials on six castrated horses with Testosterone Suspension 100 confirmed that low levels of boldenone, nandrolone, 5(10)-estrene-3β,17α-diol, and 4-estrene-3,17-dione could indeed be detected and confirmed in the early post-administration urine samples from all six geldings. Although boldenone has been reported to be present in urine after testosterone administration, there has been no direct evidence reported that boldenone, nandrolone, 5(10)-estrene-3β,17α-diol, and 4-estrene-3,17-dione are metabolites of testosterone in geldings. Subsequent in vitro experiments involving the incubation of testosterone with horse liver microsomes, liver, adipose and muscle tissues, and adrenal cortex homogenates failed to provide evidence that these four substances are minor metabolites of testosterone. An administration trial using 'Testosterone Suspension 100' supplemented with 13 C-labelled testosterone (500 mg, 1:1 ratio, injected intramuscularly) was performed. The similarities of the excretion curves of 12 C-testosterone and 13 C-testosterone in urine suggest that there was minimal kinetic isotope effect. 13 C-Labelled boldenone, nandrolone and 4-estrene-3,17-dione were detected but not 5(10)-estrene-3β,17α-diol and its 13 C-counterpart. This is the first unequivocal evidence of boldenone, nandrolone and 4-estrene-3,17-dione being metabolites of testosterone in geldings. In view of these results, caution should be exercised when interpreting findings of boldenone, nandrolone and/or 4-estrene-3,17-dione together with a relatively high level of testosterone in gelding urine. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of chronic administration of anabolic androgenic steroids and taurine on blood pressure in rats

PubMed Central

Roşca, A.E.; Stoian, I.; Badiu, C.; Gaman, L.; Popescu, B.O.; Iosif, L.; Mirica, R.; Tivig, I.C.; Stancu, C.S.; Căruntu, C.; Voiculescu, S.E.; Zăgrean, L.

2016-01-01

Supraphysiological administration of anabolic androgenic steroids has been linked to increased blood pressure. The widely distributed amino acid taurine seems to be an effective depressor agent in drug-induced hypertension. The purpose of this study was to assess the impact of chronic high dose administration of nandrolone decanoate (DECA) and taurine on blood pressure in rats and to verify the potentially involved mechanisms. The study was conducted in 4 groups of 8 adult male Wistar rats, aged 14 weeks, treated for 12 weeks with: DECA (A group); vehicle (C group); taurine (T group), or with both drugs (AT group). Systolic blood pressure (SBP) was measured at the beginning of the study (SBP1), 2 (SBP2) and 3 months (SBP3) later. Plasma angiotensin-converting enzyme (ACE) activity and plasma end products of nitric oxide metabolism (NOx) were also determined. SBP3 and SBP2 were significantly increased compared to SBP1 only in the A group (P<0.002 for both). SBP2, SBP3 and ACE activity showed a statistically significant increase in the A vs C (P<0.005), andvs AT groups (P<0.05), while NOx was significantly decreased in the A and AT groups vs controls (P=0.01). ACE activity was strongly correlated with SBP3 in the A group (r=0.71, P=0.04). These findings suggest that oral supplementation of taurine may prevent the increase in SBP induced by DECA, an effect potentially mediated by angiotensin-converting enzyme. PMID:27254659

Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemic colon anastomosis in rats.

PubMed

Yarimkaya, Ali; Apaydin, Berat; Unal, Ethem; Karabicak, Ilhan; Aydogan, Fatih; Uslu, Ezel; Erginoz, Ethem; Artis, Tarik; Eyuboglu, Erhun

2003-12-01

Recombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the healing of ischemic colon anastomosis in rats. Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemic colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic healing. Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemic colonic anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonic anastomosis.

Tridecanoin is anticonvulsant, antioxidant, and improves mitochondrial function

PubMed Central

Tan, Kah Ni; Carrasco-Pozo, Catalina; McDonald, Tanya S; Puchowicz, Michelle

2016-01-01

The hypothesis that chronic feeding of the triglycerides of octanoate (trioctanoin) and decanoate (tridecanoin) in “a regular non-ketogenic diet” is anticonvulsant was tested and possible mechanisms of actions were subsequently investigated. Chronic feeding of 35E% of calories from tridecanoin, but not trioctanoin, was reproducibly anticonvulsant in two acute CD1 mouse seizure models. The levels of beta-hydroxybutyrate in plasma and brain were not significantly increased by either treatment relative to control diet. The respective decanoate and octanoate levels are 76 µM and 33 µM in plasma and 1.17 and 2.88 nmol/g in brain. Tridecanoin treatment did not alter the maximal activities of several glycolytic enzymes, suggesting that there is no reduction in glycolysis contributing to anticonvulsant effects. In cultured astrocytes, 200 µM of octanoic and decanoic acids increased basal respiration and ATP turnover, suggesting that both medium chain fatty acids are used as fuel. Only decanoic acid increased mitochondrial proton leak which may reduce oxidative stress. In mitochondria isolated from hippocampal formations, tridecanoin increased respiration linked to ATP synthesis, indicating that mitochondrial metabolic functions are improved. In addition, tridecanoin increased the plasma antioxidant capacity and hippocampal mRNA levels of heme oxygenase 1, and FoxO1. PMID:27418037

Pharmacokinetics of long-acting nalbuphine decanoate after intramuscular administration to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Sanchez-Migallon Guzman, David; KuKanich, Butch; Heath, Timothy D; Krugner-Higby, Lisa A; Barker, Steven A; Brown, Carolyn S; Paul-Murphy, Joanne R

2013-02-01

To evaluate the pharmacokinetics of nalbuphine decanoate after IM administration to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots of unknown sex. Nalbuphine decanoate (37.5 mg/kg) was administered IM to all birds. Plasma samples were obtained from blood collected before (time 0) and 0.25, 1, 2, 3, 6, 12, 24, 48, and 96 hours after drug administration. Plasma samples were used for measurement of nalbuphine concentrations via liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated with computer software. Plasma concentrations of nalbuphine increased rapidly after IM administration, with a mean concentration of 46.1 ng/mL at 0.25 hours after administration. Plasma concentrations of nalbuphine remained > 20 ng/mL for at least 24 hours in all birds. The maximum plasma concentration was 109.4 ng/mL at 2.15 hours. The mean terminal half-life was 20.4 hours. In Hispaniolan Amazon parrots, plasma concentrations of nalbuphine were prolonged after IM administration of nalbuphine decanoate, compared with previously reported results after administration of nalbuphine hydrochloride. Plasma concentrations that could be associated with antinociception were maintained for 24 hours after IM administration of 37.5 mg of nalbuphine decanoate/kg. Safety and analgesic efficacy of nalbuphine treatments in this species require further investigation to determine the potential for clinical use in pain management in psittacine species.

Nandrolone excretion is not increased by exhaustive exercise in trained athletes.

PubMed

Schmitt, Nelly; Flament, Marie-Madeleine; Goubault, Claude; Legros, Patrick; Grenier-Loustalot, Marie France; Denjean, André

2002-09-01

The anabolic steroid nandrolone is widely used as a performance enhancer. Traces of its naturally occurring metabolite 19-norandrosterone (19-NA) have been found in human urine (below 0.6 ng.mL(-1)), and it has been suggested that strenuous exercise may increase urinary 19-NA. The aim of our study was to assess the effect of exhaustive exercise on the nandrolone excretion under controlled conditions in two groups of trained male athletes, one composed of judoka and the other of long-distance runners. A Wingate test and a treadmill limited-time test (running at 85% (.)VO(2max)) were carried out on 14 judoka and 15 athletes. Hydration was controlled during each session. Urine samples were obtained before each test and 30 min, 60 min, and 24 h after each test. Urinary 19-NA concentrations were determined using gas chromatography coupled with mass spectrometry. Baseline urinary 19-NA concentrations varied widely across individuals, from undetectable levels to 0.250 ng.mL (-1)(mean, 0.048 +/- 0.050 ng.mL(-1)). The both exercise tests did not significantly modified urinary 19-NA levels in the two groups of subjects. Our study provides compelling evidence that endogenous nandrolone production in male athletes, during two very different types of exercise, produces urine levels far below the IOC threshold of 2 ng.mL(-1) urine. Thus, exercise does not induce endogenous nandrolone secretion.

Analysis of anabolic steroids in human hair using LC-MS/MS.

PubMed

Deshmukh, Nawed; Hussain, Iltaf; Barker, James; Petroczi, Andrea; Naughton, Declan P

2010-10-01

New highly sensitive, specific, reliable, reproducible and robust LC-MS/MS methods were developed to detect the anabolic steroids, nandrolone and stanozolol, in human hair for the first time. Hair samples from 180 participants (108 males, 72 females, 62% athletes) were screened using ELISA which revealed 16 athletes as positive for stanozolol and 3 for nandrolone. Positive samples were confirmed on LC-MS/MS in selective reaction monitoring (SRM) mode. The assays for stanozolol and nandrolone showed good linearity in the range 1-400pg/mg and 5-400pg/mg, respectively. The methods were validated for LLOD, interday precision, intraday precision, specificity, extraction recovery and accuracy. The assays were capable of detecting 0.5pg stanozolol and 3.0pg nandrolone per mg of hair, when approximately 20mg of hair were processed. Analysis using LC-MS/MS confirmed 11 athletes' positive for stanozolol (5.0pg/mg to 86.3pg/mg) and 1 for nandrolone (14.0pg/mg) thus avoiding false results from ELISA screening. The results obtained demonstrate the application of these hair analysis methods to detect both steroids at low concentrations, hence reducing the amount of hair required significantly. The new methods complement urinalysis or blood testing and facilitate improved doping testing regimes. Hair analysis benefits from non-invasiveness, negligible risk of infection and facile sample storage and collection, whilst reducing risks of tampering and cross-contamination. Owing to the wide detection window, this approach may also offer an alternative approach for out-of-competition testing.

Afebrile Neuroleptic Malignant Syndrome associated with Fluphenazine decanoate: A case report

PubMed Central

Assareh, Marzieh

2010-01-01

Neuroleptic Malignant Syndrome (NMS) is unusual but could be a lethal reaction associated with neuroleptic drugs. It occurs in almost 0.07-2.2% of patients under treatment with neuroleptics. There are some medical treatments that may also be helpful for its treatment, including dopamine agonists, muscle relaxants, and electroconvulsive therapy (ECT). We present this case to alert the clinicians to the potential for inducing afebrile NMS. Our case is a 41-year-old man with a history of schizophrenia showing signs and symptoms in accordance with NMS, 2 weeks after receiving one dose of 12.5 mg fluphenazine decanoate, abruptly following the 3rdsession of ECT. The patient presented with decreased level of consciousness, muscular rigidity, waxy flexibility, mutism, generalized tremor, sever diaphoresis and tachycardia which progressed during the previous 24 h. Laboratory data indicated primarily leukocytosis, an increasing level of creatinine phosphokinase and hypokalemia during the next 72h. In patients receiving antipsychotics, any feature of NMS should carefully be evaluated whether it is usual or unusual particularly in patients receiving long acting neuroleptics. PMID:22952496

Simultaneous determination of nandrolone, testosterone, and methyltestosterone by multi-immunoaffinity column and capillary electrophoresis.

PubMed

Qi, Xiao-Hua; Zhang, Li-Wei; Zhang, Xin-Xiang

2008-08-01

A multitarget antibody immunoaffinity column was proposed for the purification and enrichment of nandrolone, testosterone, and methyltestosterone from urine. Nandrolone-3-site substituted antigen was designed and synthesized and the polyclonal antibody was prepared with immunizing rabbits. The stationary phase of the immunoaffinity column was synthesized by covalently bonding the antibodies specific to nandrolone, testosterone, and methyltestosterone onto CNBr-actived Sepharose 4B. The analytes of interest were extracted with a methanol/water mixture in one step. The immunoaffinity column showed high affinity and high selectivity to a class of structurally related compounds. The elution was then transferred to a micellar electrokinetic CE system with a running buffer of sodium borate and sodium cholate for separation and determination. Recoveries of the three steroids from complex matrix were 88-94% with RSD values less than 5.2%. Optimization of the immunoaffinity column purification was achieved and the feasibility of the technique for the analysis of steroid hormone was discussed. The results indicated that the combination of multi-immunoaffinity column and CE was an effective technique, which was rapid, simple, and sensitive for the assay of steroids.

Anabolic androgenic steroids differentially affect social behaviors in adolescent and adult male Syrian hamsters

PubMed Central

Salas-Ramirez, Kaliris Y.; Montalto, Pamela R.; Sisk, Cheryl L.

2010-01-01

Anabolic androgenic steroids (AAS) are synthetic derivatives of testosterone used by over half a million adolescents in the United States for their tissue-building potency and performance-enhancing effects. AAS also affect behavior, including reports of heightened aggression and changes in sexual libido. The expression of sexual and aggressive behaviors is a function of complex interactions among hormones, social context, and the brain, which is extensively remodeled during adolescence. Thus, AAS may have different consequences on behavior during adolescence and adulthood. Using a rodent model, these studies directly compared the effects of AAS on the expression of male sexual and aggressive behaviors in adolescents and adults. Male Syrian hamsters were injected daily for 14 days with either vehicle or an AAS cocktail containing testosterone cypionate (2 mg/kg), nandrolone decanoate (2 mg/kg), and boldenone undecylenate (1 mg/kg), either during adolescence (27–41 days of age) or in adulthood (63–77 days of age). The day after the last injection, males were tested for either sexual behavior with a receptive female or agonistic behavior with a male intruder. Adolescent males treated with AAS showed significant increases in sexual and aggressive behaviors relative to vehicle-treated adolescents. In contrast, AAS-treated adults showed significantly lower levels of sexual behavior compared with vehicle-treated adults and did not show heightened aggression. Thus, adolescents, but not adults, displayed significantly higher behavioral responses to AAS, suggesting that the still-developing adolescent brain is more vulnerable than the adult brain to the adverse consequences of AAS on the nervous system and behavior. PMID:18201704

Nandrolone normalizes determinants of muscle mass and fiber type after spinal cord injury.

PubMed

Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A; Cardozo, Christopher P

2012-05-20

Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation.

Nandrolone attenuates aortic adaptation to exercise in rats.

PubMed

Sun, Mengwei; Shen, Weili; Zhong, Meifang; Wu, Pingping; Chen, Hong; Lu, Aiyun

2013-03-15

In this study, we investigated the interaction between exercise-induced mitochondrial adaptation of large vessels and the effects of chronic anabolic androgenic steroids (AASs). Four groups of Sprague-Dawley rats were studied: (i) sedentary, (ii) sedentary + nandrolone-treated, (iii) aerobic exercise trained, and (iv) trained + nandrolone-treated. Aerobic training increased the levels of aortic endothelial nitric oxide synthase (eNOS) and heme oxygenase-1 (HO-1) in accordance with improved acetylcholine-induced vascular relaxation. These beneficial effects were associated with induction of mitochondrial complexes I and V, increased mitochondrial DNA copy number, and greater expression of transcription factors involved in mitochondrial biogenesis/fusion. We also observed enhanced mitochondrial autophagy pathway activity, including increased conversion of LC3-I to LC3-II and greater expression of beclin1 and autophagy-related protein-7 (ATG7). The levels of thiobarbituric acid-reactive substances and protein carbonyls remained unchanged, whereas significant increases in catalase and mitochondrial manganese superoxide dismutase (MnSOD) levels were observed in the aortas of trained animals, when compared with sedentary controls. Nandrolone increased oxidative stress biomarkers and inhibited exercise-induced increases of eNOS, HO-1, catalase, and MnSOD expression. In addition, it also attenuated elevated peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and mitofusin-2 expression, and further up-regulated LC3II conversion, beclin1, ATG7, and dynamin-related protein-1 expression. These results demonstrate that nandrolone attenuates aortic adaptations to exercise by regulating mitochondrial dynamic remodelling, including down-regulation of mitochondrial biogenesis and intensive autophagy.

Pharmacokinetics of testosterone cream applied to scrotal skin.

PubMed

Iyer, R; Mok, S F; Savkovic, S; Turner, L; Fraser, G; Desai, R; Jayadev, V; Conway, A J; Handelsman, D J

2017-07-01

Scrotal skin is thin and has high steroid permeability, but the pharmacokinetics of testosterone via the scrotal skin route has not been studied in detail. The aim of this study was to define the pharmacokinetics of testosterone delivered via the scrotal skin route. The study was a single-center, three-phase cross-over pharmacokinetic study of three single doses (12.5, 25, 50 mg) of testosterone cream administered in random sequence on different days with at least 2 days between doses to healthy eugonadal volunteers with endogenous testosterone suppressed by administration of nandrolone decanoate. Serum testosterone, DHT and estradiol concentrations were measured by liquid chromatograpy, mass spectrometry in extracts of serum taken before and for 16 h after administration of each of the three doses of testosterone cream to the scrotal skin. Testosterone administration onto the scrotal skin produced a swift (peak 1.9-2.8 h), dose-dependent (p < 0.0001) increase in serum testosterone with the 25 mg dose maintaining physiological levels for 16 h. Serum DHT displayed a time- (p < 0.0001), but not dose-dependent, increase in concentration reaching a peak concentration of 1.2 ng/mL (4.1 nm) at 4.9 h which was delayed by 2 h after peak serum testosterone. There were no significant changes in serum estradiol over time after testosterone administration. We conclude that testosterone administration to scrotal skin is well tolerated and produces dose-dependent peak serum testosterone concentration with a much lower dose relative to the non-scrotal transdermal route. © 2017 American Society of Andrology and European Academy of Andrology.

Body mass reduction markedly improves muscle performance and body composition in obese females aged 61-75 years: comparison between the effects exerted by energy-restricted diet plus moderate aerobic-strength training alone or associated with rGH or nandrolone undecanoate.

PubMed

Sartorio, Alessandro; Maffiuletti, Nicola A; Agosti, Fiorenza; Marinone, Pier Giulio; Ottolini, Saverio; Lafortuna, Claudio L

2004-04-01

To investigate the effectiveness of a body mass reduction programme entailing diet caloric restriction and moderate physical activity with or without supplementary treatment with recombinant (r) GH or steroids to improve body composition and muscle performance in severely obese women aged 61-75 years. Twenty women were randomly assigned to one of three groups: body mass reduction alone; body mass reduction plus rGH; body mass reduction plus nandrolone undecanoate. Body composition, isotonic muscle strength and anaerobic power output during jumping were determined before and after the 3-week period. Whatever the experimental group considered, body mass (P<0.01), body mass index (P<0.05) and fat mass (P<0.05) decreased significantly, whereas muscle strength and power increased significantly (P<0.05) after the intervention. Small body mass reductions after 3 weeks of energy-restricted diet combined with moderate aerobic and strength exercise are associated with significant improvements in upper and lower limb muscle strength and power and reduction of fat mass in severely obese women aged 61-75 years. Although the association of rGH or nandrolone undecanoate does not appear to exert additional effects on body composition and muscle performance attained by body mass reduction alone, further additional studies with larger study groups, different dosages and more prolonged periods are required for definitive conclusions to be drawn.

Nandrolone and stanozolol upregulate aromatase expression and further increase IGF-I-dependent effects on MCF-7 breast cancer cell proliferation.

PubMed

Sirianni, Rosa; Capparelli, Claudia; Chimento, Adele; Panza, Salvatore; Catalano, Stefania; Lanzino, Marilena; Pezzi, Vincenzo; Andò, Sebastiano

2012-11-05

Several doping agents, such as anabolic androgenic steroids (AAS) and peptide hormones like insulin-like growth factor-I (IGF-I), are employed without considering the potential deleterious effects that they can cause. In addition, androgens are used in postmenopausal women as replacement therapy. However, there are no clear guidelines regarding the optimal therapeutic doses of androgens or long-term safety data. In this study we aimed to determine if two commonly used AAS, nandrolone and stanozolol, alone or in combination with IGF-I, could activate signaling involved in breast cancer cell proliferation. Using a human breast cancer cell line, MCF-7, as an experimental model we found that both nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and, consequently, estradiol production. Moreover, when nandrolone and stanozolol were combined with IGF-I, higher induction in aromatase expression was observed. This increase involved phosphatidylinositol 3-kinase (PI3K)/AKT and phospholipase C (PLC)/protein kinase C (PKC), which are part of IGF-I transductional pathways. Specifically, both AAS were able to activate membrane rapid signaling involving IGF-I receptor, extracellular regulated protein kinases 1/2 (ERK1/2) and AKT, after binding to estrogen receptor (ER), as confirmed by the ability of the ER antagonist ICI182, 780 to block such activation. The estrogenic activity of nandrolone and stanozolol was further confirmed by their capacity to induce the expression of the ER-regulated gene, CCND1 encoding for the cell cycle regulator cyclin D1, which represents a key protein for the control of breast cancer cell proliferation. In fact, when nandrolone and stanozolol were combined with IGF-I, they increased cell proliferation to levels higher than those elicited by the single factors. Taken together these data clearly indicate that the use of high doses of AAS, as occurs in doping practice, may increase the risk of breast cancer. This potential risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS with this type of cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Anabolic Steroids as a Novel Therapeutic Strategy for the Prevention of Bone Loss after Spinal Cord Injury: Animal Model and Molecular Mechanism

DTIC Science & Technology

2012-10-01

bone loss. At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common...TERMS- Spinal cord injuries, Nandrolone, Androgens, Hypogonadism , Bone loss, Wnt signaling 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...At present, there is no practical treatment to delay or prevent bone loss in individuals with motor-complete SCI. Hypogonadism is common in men

Microbial transformation of nandrolone with Cunninghamella echinulata and Cunninghamella blakesleeana and evaluation of leishmaniacidal activity of transformed products.

PubMed

Baydoun, Elias; Karam, Martin; Atia-tul-Wahab; Khan, Mahwish Shafi Ahmed; Ahmad, Malik Shoaib; Samreen; Smith, Colin; Abdel-Massih, Roula; Choudhary, M Iqbal

2014-10-01

Therapeutic potential of nandrolone and its derivatives against leishmaniasis has been studied. A number of derivatives of nandrolone (1) were synthesized through biotransformation. Microbial transformation of nandrolone (1) with Cunninghamella echinulata and Cunninghamella blakesleeana yielded three new metabolites, 10β,12β,17β-trihydroxy-19-nor-4-androsten-3-one (2), 10β,16α,17β-trihydroxy-19-nor-4-androsten-3-one (3), and 6β,10β,17β-trihydroxy-19-nor-4-androsten-3-one (4), along with four known metabolites, 10β,17β-dihydroxy-19-nor-4-androsten-3-one (5), 6β,17β-dihydroxy-19-nor-4-androsten-3-one (6) 10β-hydroxy-19-nor-4-androsten-3,17-dione (7) and 16β,17β-dihydroxy-19-nor-4-androsten-3-one (8). Compounds 1-8 were evaluated for their anti-leishmanial activity. Compounds 1 and 8 showed a significant activity in vitro against Leishmania major. The leishmanicidal potential of compounds 1-8 (IC50=32.0±0.5, >100, 77.39±5.52, 70.90±1.16, 54.94±1.01, 80.23±3.39, 61.12±1.39 and 29.55±1.14 μM, respectively) can form the basis for the development of effective therapies against the protozoal tropical disease leishmaniasis. Copyright © 2014 Elsevier Inc. All rights reserved.

Nandrolone excretion in sedentary vs physically trained young women.

PubMed

Enea, C; Boisseau, N; Bayle, M L; Flament, M M; Grenier-Loustalot, M F; Denjean, A; Diaz, V; Dugué, B

2010-02-01

We investigated the effects of the menstrual cycle, oral contraception and physical training on exhaustive exercise-induced changes in the excretion of nandrolone metabolites [19-norandrosterone (19-NA), and 19-noretiocholanolone (19-NE)] in young women. Twenty-eight women were allocated to an untrained group (n=16) or a trained group (n=12), depending on their physical training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-), while the trained group was entirely composed of OC+ subjects. Three laboratory sessions were conducted in a randomized order: a prolonged exercise test, a short-term exercise test and a control session. Urine specimens were collected before and 30, 60 and 90 min after the exercise test and at the same times of the day during the control session. Urinary concentrations of nandrolone metabolites were determined by gas chromatography coupled to mass spectrometry. Urinary concentrations of 19-NA and 19-NE ranged from undetectable levels to 1.14 and 0.47 ng/mL, respectively. Nandrolone excretion was not affected by the menstrual cycle phase (early follicular vs mid-luteal), prior physical training, oral contraception or acute physical exercise. Therefore, a urinary concentration of 2 ng/mL of 19-NA appears to be fair as the upper acceptable limit in doping control tests for female athletes.

Effectiveness of long-acting antipsychotics in clinical practice : 1. A retrospective, 18-month follow up and comparison between paliperidone palmitate, risperidone long-acting injection and zuclopenthixol decanoate

PubMed Central

Cordiner, Matthew; Shajahan, Polash; McAvoy, Sarah; Bashir, Muhammad; Taylor, Mark

2016-01-01

Objectives: In the UK, nine different compounds are available as long-acting antipsychotic injections (LAIs). There are few clinical guidelines for determining which LAIs are most effective in specific patient groups. To measure the clinical effectiveness of LAIs we aimed to determine the now-established concept of antipsychotic discontinuation rates and measure Clinical Global Impression (CGI) outcomes. Method: The population (n was approximately 560,000) was a secondary care NHS adult mental health service in Lanarkshire, Scotland, UK. This was a retrospective, electronic case note search of LAI-naïve patients commenced on paliperidone palmitate (n = 31), risperidone long-acting injection (RLAI) (n = 102) or zuclopenthixol decanoate (n = 105), with an 18-month follow up. Kaplan–Meier survival statistics for discontinuation rates and hospital admission were calculated. CGI severity and improvement scores were retrospectively assigned by the investigating team. Results: Paliperidone palmitate performed less favourably than risperidone long-acting injection (RLAI) or zuclopenthixol decanoate. Paliperidone palmitate had higher discontinuation rates due to any cause, inefficacy and increased hospitalization risk. Paliperidone palmitate had the smallest proportion of patients assigned a clinically desirable CGI-I score of 1 (very much improved) or 2 (much improved). Conclusions: Paliperidone palmitate had less favourable discontinuation and CGI outcomes compared with RLAI and zuclopenthixol decanoate. This could not be adequately explained by patients in the paliperidone group being more chronically or severely unwell, nor by the presence of comorbidities such as alcohol or substance misuse, or by the use of lower mean dosages compared with RLAI or zuclopenthixol decanoate. We considered that prescribers are familiarizing themselves with paliperidone and outcomes may improve over time. PMID:26913175

Hexyl decanoate, the first trail pheromone compound identified in a stingless bee, Trigona recursa.

PubMed

Jarau, Stefan; Schulz, Claudia M; Hrncir, Michael; Francke, Wittko; Zucchi, Ronaldo; Barth, Friedrich G; Ayasse, Manfred

2006-07-01

Foragers of many species of stingless bees guide their nestmates to food sources by means of scent trails deposited on solid substrates between the food and the nest. The corresponding trail pheromones are generally believed to be produced in the mandibular glands, although definitive experimental proof has never been provided. We tested the trail following behavior of recruits of Trigona recursa in field experiments with artificial scent trails branching off from natural scent trails of this stingless bee. First-time recruits (newcomers) did not follow these trails when they were laid with pure solvent or mandibular gland extract. However, they did follow trails made with labial gland extract. Chemical analyses of labial gland secretions revealed that hexyl decanoate was the dominant component (72.4 +/- 1.9% of all volatiles). Newcomers were significantly attracted to artificial trails made with synthetic hexyl decanoate, demonstrating its key function in eliciting scent-following behavior. According to our experiments with T. recursa, the trail pheromone is produced in the labial glands and not in the mandibular glands. Hexyl decanoate is the first component of a trail pheromone identified and proved to be behaviorally active in stingless bees.

Carbon isotope ratios of nandrolone, boldenone, and testosterone preparations seized in Norway compared to those of endogenously produced steroids in a Nordic reference population.

PubMed

Hullstein, Ingunn; Sagredo, Carlos; Hemmersbach, Peter

2014-01-01

Determining the origin of anabolic androgenic steroids (AAS) that also are produced endogenously in the human body is a major issue in doping control. In some cases, the presence of nandrolone and boldenone metabolites might result from endogenous production. The GC-C-IRMS technique (gas chromatography-combustion-isotope ratio mass spectrometry) enables the carbon isotopic ratio (CIR) to be measured to determine the origin of these metabolites. The aim of this study was to use GC-C-IRMS to determine the δ(13) CVPDB values of seized boldenone and nandrolone preparations to decide if the steroids themselves were depleted in (13) C, compared to what is normally seen in endogenously produced steroids. In addition, several testosterone preparations were analyzed. A total of 69 seized preparations were analyzed. The nandrolone preparations showed δ(13) CVPDB values in the range of -31.5 ‰ to -26.7 ‰. The boldenone preparations showed δ(13) CVPDB values in the range of -32.0 ‰ to -27.8 ‰, and for comparison the testosterone preparations showed δ(13) CVPDB values of -31.0 ‰ to -24.2 ‰. The results showed that the values measured in the nandrolone and boldenone preparations were in the same range as those measured in the testosterone preparations. The study also included measurements of CIR of endogenously produced steroids in a Norwegian/Danish reference population. The δ(13) CVPDB values measured for the endogenous steroids in this population were in the range of -21.7 to -26.8. In general, most of the preparations investigated in this study show (13) C-depleted delta values compared to endogenously produced steroids reflecting a northern European diet. Copyright © 2014 John Wiley & Sons, Ltd.

Nandrolone Normalizes Determinants of Muscle Mass and Fiber Type after Spinal Cord Injury

PubMed Central

Wu, Yong; Zhao, Jingbo; Zhao, Weidong; Pan, Jiangping; Bauman, William A.

2012-01-01

Abstract Spinal cord injury (SCI) results in atrophy of skeletal muscle and changes from slow oxidative to fast glycolytic fibers, which may reflect reduced levels of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), increased myostatin signaling, or both. In animals, testosterone reduces loss of muscle fiber cross-sectional area and activity of enzymes of energy metabolism. To identify the molecular mechanisms behind the benefits of androgens on paralyzed muscle, male rats were spinal cord transected and treated for 8 weeks with vehicle, testosterone at a physiological replacement dose, or testosterone plus nandrolone, an anabolic steroid. Treatments were initiated immediately after SCI and continued until the day animals were euthanized. In the SCI animals, gastrocnemius muscle mass was significantly increased by testosterone plus nandrolone, but not by testosterone alone. Both treatments significantly reduced nuclear content of Smad2/3 and mRNA levels of activin receptor IIB and follistatin-like 3. Testosterone alone or with nandrolone reversed SCI-induced declines in cellular and nuclear levels of PGC-1α protein and PGC-1α mRNA levels. For PGC-1α target genes, testosterone plus nandrolone partially reversed SCI-induced decreases in levels of proteins without corresponding increases in their mRNA levels. Thus, the findings demonstrate that following SCI, signaling through activin receptors and Smad2/3 is increased, and that androgens suppress activation of this signaling pathway. The findings also indicate that androgens upregulate PGC-1α in paralyzed muscle and promote its nuclear localization, but that these effects are insufficient to fully activate transcription of PGC-1α target genes. Furthermore, the transcription of these genes is not tightly coupled with their translation. PMID:22208735

Lactate dehydrogenase regulation in aged skeletal muscle: Regulation by anabolic steroids and functional overload.

PubMed

Washington, Tyrone A; Healey, Julie M; Thompson, Raymond W; Lowe, Larry L; Carson, James A

2014-09-01

Aging alters the skeletal muscle response to overload-induced growth. The onset of functional overload is characterized by increased myoblast proliferation and an altered muscle metabolic profile. The onset of functional overload is associated with increased energy demands that are met through the interconversion of lactate and pyruvate via the activity of lactate dehydrogenase (LDH). Testosterone targets many of the processes activated at the onset of functional overload. However, the effect of aging on this metabolic plasticity at the onset of functional overload and how anabolic steroid administration modulates this response is not well understood. The purpose of this study was to determine if aging would alter overload-induced LDH activity and expression at the onset of functional overload and whether anabolic steroid administration would modulate this response. Five-month and 25-month male Fischer 344xF1 BRN were given nandrolone decanoate (ND) or sham injections for 14days and then the plantaris was functionally overloaded (OV) for 3days by synergist ablation. Aging reduced muscle LDH-A & LDH-B activity 70% (p<0.05). Aging also reduced LDH-A mRNA abundance, however there was no age effect on LDH-B mRNA abundance. In 5-month muscle, both ND and OV decreased LDH-A and LDH-B activity. However, there was no synergistic or additive effect. In 5-month muscle, ND and OV decreased LDH-A mRNA expression with no change in LDH-B expression. In 25-month muscle, ND and OV increased LDH-A and LDH-B activity. LDH-A mRNA expression was not altered by ND or OV in aged muscle. However, there was a main effect of OV to decrease LDH-B mRNA expression. There was also an age-induced LDH isoform shift. ND and OV treatment increased the "fast" LDH isoforms in aged muscle, whereas ND and OV increased the "slow" isoforms in young muscle. Our study provides evidence that aging alters aspects of skeletal muscle metabolic plasticity normally induced by overload and anabolic steroid administration. Copyright © 2014 Elsevier Inc. All rights reserved.

The anabolic steroids testosterone propionate and nandrolone, but not 17alpha-methyltestosterone, induce conditioned place preference in adult mice.

PubMed

Parrilla-Carrero, Jeffrey; Figueroa, Orialis; Lugo, Alejandro; García-Sosa, Rebecca; Brito-Vargas, Paul; Cruz, Beatriz; Rivera, Mélanis; Barreto-Estrada, Jennifer L

2009-02-01

Anabolic androgenic steroids (AAS) are often misused by adolescents and athletes. Their effects vary according to chemical structure and metabolism, route of administration, and AAS regimen. In this study, adult C57Bl/6 male mice were systemically exposed to testosterone propionate (TP), nandrolone or 17alpha-methyltestosterone (17alpha-meT), type I, type II and type III AAS, respectively, in order to determine the hedonic or aversive properties of each drug. For this purpose, the conditioned place preference (CPP) test was employed at three different AAS doses (0.075, 0.75 and 7.5 mg/kg). Other behavioral domains monitored were light-dark transitions (side changes) and general activity. TP shifted place preference at all doses tested, and nandrolone shifted place preference at 0.75 and 7.5 mg/kg, but not at 0.075 mg/kg, the lower dose tested. Conversely, mice receiving 17alpha-meT did not show alteration in the preference score. The lower dose of nandrolone did modify exploratory-based anxiety showing a decrease in light-dark transitions if compared to vehicle-treated animals, while mice treated with TP or 17alpha-meT were not affected. Our data suggest that when studying hedonic and rewarding properties of synthetic androgens, distinction has to be made based on type of AAS and metabolism.

THE ANABOLIC STEROIDS TESTOSTERONE PROPIONATE AND NANDROLONE, BUT NOT 17α-METHYLTESTOSTERONE, INDUCE CONDITIONED PLACE PREFERENCE IN ADULT MICE

PubMed Central

Parrilla-Carrero, Jeffrey; Figueroa, Orialis; Lugo, Alejandro; García-Sosa, Rebecca; Brito-Vargas, Paul; Cruz, Beatriz; Rivera, Melanis; Barreto-Estrada, Jennifer L.

2009-01-01

Anabolic androgenic steroids (AAS) are often misused by adolescents and athletes. Their effects vary according to chemical structure and metabolism, route of administration, and AAS regimen. In this study, adult C57Bl/6 male mice were systemically exposed to testosterone propionate (TP), nandrolone or 17α-methyltestosterone (17α-meT), type I, type II and type III AAS, respectively, in order to determine the hedonic or aversive properties of each drug. For this purpose, the conditioned place preference (CPP) test was employed at three different AAS doses (0.075, 0.75 and 7.5 mg/kg). Other behavioral domains monitored were light-dark transitions (side changes) and general activity. TP shifted place preference at all doses tested, and nandrolone shifted place preference at 0.75 and 7.5mg/kg, but not at 0.075 mg/kg, the lower dose tested. Conversely, mice receiving 17α-meT did not show alteration in the preference score. The lower dose of nandrolone did modify exploratory based-anxiety showing a decrease in light-dark transitions if compared to vehicle-treated animals, while mice treated with TP or 17α-meT were not affected. Our data suggest that when studying hedonic and rewarding properties of synthetic androgens, distinction has to be made based on type of AAS and metabolism. PMID:19028026

Muscle protein turnover in rats treated with corticosterone (CC) or/and nandrolone decanoate (ND) and fed an adequate or a low-protein diet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santidrian, S.; Cuevillas, F.; Goena, M.

1986-03-01

In order to investigate the possible antagonistic effect between glucocorticoids and androgens on muscle protein turnover, the authors have measured the fractional rates of gastrocnemius muscle protein synthesis (k/sub s/) and degradation (k/sub d/) by the constant-intravenous-infusion method using L-//sup 14/C/-tyrosine in rats receiving via s.c. per 100 g b.wt. 10 mg of CC, or 2 mg of ND or CC+ND at the indicated doses, and fed either an 18% or 5% protein diets over a period of 5 days. As an additional index of protein synthesis, RNA activity (g of synthesized protein/day/g RNA) was determined as well. Results showedmore » that as compared to vehicle-injected animals fed the adequate diet, CC-treated rats exhibited a reduction of muscle k/sub d/, while ND-treated rats had an outstanding increase of muscle k/sub s/. However, rats receiving CC+ND showed k/sub s/ and k/sub d/ values similar to those displayed by control animals. Nevertheless, when the steroids were injected to rats fed the low-protein diet, CC has a catabolic effect on muscle protein but by reducing k/sub s/, while the anabolic action of ND is still displayed but by a significant reduction of muscle k/sub d/. CC+ND given to these protein-deficient rats caused an increase in muscle k/sub s/ and a reduction in k/sub d/. These results might indicate that, at least in part, ND antagonizes the catabolic action of high doses of CC on muscle protein metabolism.« less

Understanding the Chemical Reactivity of Phosphonium-Based Ionic Liquids with Tellurium.

PubMed

Zhang, Tao; Schwedtmann, Kai; Weigand, Jan J; Doert, Thomas; Ruck, Michael

2018-05-15

The chemical reactivity of phosphonium based ionic liquids (ILs) towards tellurium at temperatures above 220 °C was systematically investigated by a series of dissolution experiments, tracking the solute tellurium species by nuclear magnetic resonance, and characterizing the reaction products by X-ray diffraction and scanning electron microscopy. The initial step is the thermal elimination of an alkyl group of the phosphonium cation of the ILs, most probably via an S N 2 mechanism. The addition of tellurium follows to form trialkylphosphane tellurides as evidenced by 31 P and 125 Te NMR spectroscopic experiments. The trialkylphosphane tellurides can serve as a tellurium reservoir for the formation of metal tellurides, like Bi 2 Te 3 and Ag 2 Te. It was observed that trihexyltetradecylphosphonium chloride ([P 6 6 6 14 ]Cl) shows a very weak reactivity that is reflected by a low solubility of tellurium, while trihexyltetradecylphosphonium dicyanamide/decanoate ([P 6 6 6 14 ][N(CN) 2 ]/[P 6 6 6 14 ][decanoate]) and tetrabutylphosphonium decanoate ([P 4 4 4 4 ][decanoate]) dissolve tellurium to a much higher extent. We attribute these observations to the different Lewis basicity of the anions of the ILs as main influencing factor. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

The anti-doping hot-line, a means to capture the abuse of doping agents in the Swedish society and a new service function in clinical pharmacology.

PubMed

Eklöf, Ann-Charlotte; Thurelius, Ann-Mari; Garle, Mats; Rane, Anders; Sjöqvist, Folke

2003-11-01

With the support of the Swedish National Institute of Health a national information service was started in 1993 aiming to capture the abuse of doping agents in the general public. It was organized as a telephone service, called the Anti-Doping Hot-Line, from our department and managed by trained nurses co-operating with clinical pharmacologists. Important information collected about all callers (anonymous) was: date of call, its origin, category of caller, doping experience and main question being asked. Abusers were asked about their age, sex, affiliation, abused drug(s), duration of abuse, habit of administration and adverse reactions (ADRs). Between October 1993 and December 2000 25,835 calls were received with a peak during spring and autumn. Most calls (12,400) came from non-abusers, 60% being males. Callers connected with gyms represented the largest group (30%). Most calls about specific drugs concerned anabolic androgenic steroids (AAS). Other drugs or products included ephedrine, clenbuterol and creatine. The most commonly abused anabolic steroids were testosterone, nandrolone-decanoate, methandienone and stanozolol. The ten most commonly reported ADRs of AAS were aggressiveness (835), depression (829), acne (770), gynecomastia (637), anxiousness (637), potency problems (413), testicular atrophy (404), sleep disorders (328), fluid retention (318) and mood disturbances (302). Female side effects included menstruation disturbances, hair growth in the face, lower voice and enlarged clitoris. During the period 1996-200, totally 4339 persons reported about 10,800 side effects. This figure should be compared with the very low number of ADRs (27) reported by prescribers to the Swedish ADR committee during the same period. Abuse of doping agents appears to be a new public health problem that needs detection, medical care and prevention.

Bovine teeth as a novel matrix for the control of the food chain: liquid chromatography-tandem mass spectrometry detection of treatments with prednisolone, dexamethasone, estradiol, nandrolone and seven β2-agonists.

PubMed

Chiesa, Luca Maria; Nobile, Maria; Panseri, Sara; Biolatti, Bartolomeo; Cannizzo, Francesca Tiziana; Pavlovic, Radmila; Arioli, Francesco

2017-01-01

Veterinary drugs usually have rapid clearance rates in the liver and kidney, hampering their detection in conventional matrices such as the liver or urine. Pharmacological principles such as esterification may be applied to facilitate the administration of veterinary drugs and increase drug half-life. Prednisolone, whose therapeutic administration is regulated for food producing animals in the EU, is available in its acetate form as well as nandrolone, a banned anabolic steroid, which may be obtained as nandrolone phenylpropionate and estradiol as a benzoyl ester. While the distribution and accumulation of lipophilic and hydrophilic substances in human teeth have been well documented, studies on residues in bovine teeth are lacking. We hypothesised that analysis of bovine teeth could be used to detect both regulated and banned veterinary drugs. Steroids may be illegally used as growth promoters in food producing animals, alone or combined with β2-agonists; therefore, we developed, and validated, in accordance with the Commission Decision 2002/657/EC, two analytical confirmatory LC-MS/MS methods to detect these classes of compounds following a unique liquid extraction procedure. Finally, we analysed teeth from three male Friesian veal calves treated with intramuscular estradiol benzoate, oral prednisolone acetate or intramuscular nandrolone phenylpropionate in combination with oral ractopamine, respectively, and from seven bovines from the food chain. Teeth from treated animals were positive for their respective drugs, with the exception of nandrolone phenylpropionate. One sample from a food chain bovine was positive for isoxsuprine, one of the seven β2-agonists studied. Non-esterified forms of the steroids were not found. These results demonstrate that bovine teeth are a suitable matrix for the determination of pseudoendogenous substances or illicit administration of veterinary drugs.

A multicenter phase IIb study of a novel combination of intramuscular androgen (testosterone decanoate) and oral progestogen (etonogestrel) for male hormonal contraception.

PubMed

Hay, Cathy J; Brady, Brian M; Zitzmann, Michael; Osmanagaoglu, Kaan; Pollanen, Pasi; Apter, Dan; Wu, Frederick C W; Anderson, Richard A; Nieschlag, Eberhard; Devroey, Paul; Huhtaniemi, Ilpo; Kersemaekers, Wendy M

2005-04-01

The effect of a novel combination of oral etonogestrel (ENG) and im testosterone decanoate (TD) on suppression of gonadotropins and spermatogenesis as a potential lead for male contraception was investigated. Healthy male volunteers were randomized into two groups receiving 300 microg ENG daily and 400 mg TD every 4 (n = 55) or 6 (n = 57) wk for 48 wk. At wk 48, all men except one in the 6-wk group suppressed sperm concentration to less than 1 million/ml. Faster suppression occurred in the 4-wk group. Gonadotropins were suppressed in both groups and most consistently in the 4-wk group. During treatment, trough testosterone levels increased into the normal range in the 4-wk group but remained just below normal in the 6-wk group. All peak levels were within the normal range. After treatment cessation, recovery of sperm counts and gonadotropins to normal levels occurred in both groups. Minor effects on weight and cholesterol were noted. Fourteen subjects withdrew because of an adverse event with those possibly related to the study medication reported more frequently in the 6-wk group (nine vs. one). In conclusion, the combination of 300 microg ENG with 400 mg TD every 4 wk was superior in terms of efficacy, hormone profiles, and safety. This represents a promising approach to male hormonal contraception.

Development and validation of RP HPLC method to determine nandrolone phenylpropionate in different pharmaceutical formulations.

PubMed

Mukherjee, Jayanti; Das, Ayan; Chakrabarty, Uday Sankar; Sahoo, Bijay Kumar; Dey, Goutam; Choudhury, Hira; Pal, Tapan Kumar

2011-01-01

This study describes development and subsequent validation of a reversed phase high performance liquid chromatographic (RP-HPLC) method for the estimation of nandrolone phenylpropionate, an anabolic steroid, in bulk drug, in conventional parenteral dosage formulation and in prepared nanoparticle dosage form. The chromatographic system consisted of a Luna Phenomenex, CN (250 mm x 4.6 mm, 5 microm) column, an isocratic mobile phase comprising 10 mM phosphate buffer and acetonitrile (50:50, v/v) and UV detection at 240 nm. Nandrolone phenylpropionate was eluted about 6.3 min with no interfering peaks of excipients used for the preparation of dosage forms. The method was linear over the range from 0.050 to 25 microg/mL in raw drug (r2 = 0.9994). The intra-day and inter-day precision values were in the range of 0.219-0.609% and 0.441-0.875%, respectively. Limits of detection and quantitation were 0.010 microg/mL and 0.050 microg/mL, respectively. The results were validated according to International Conference on Harmonization (ICH) guidelines in parenteral and prepared nanoparticle formulation. The validated HPLC method is simple, sensitive, precise, accurate and reproducible.

Determination of nandrolone metabolites in human urine: comparison between liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry.

PubMed

Buiarelli, Francesca; Giannetti, Luigi; Jasionowska, Renata; Cruciani, Claudia; Neri, Bruno

2010-07-15

Nandrolone (19-nortestosterone) is an androgenic anabolic steroid illegally used as a growth-promoting agent in animal breeding and as a performance enhancer in athletics. Therefore, its use was officially banned in 1974 by the Medical Commission of the International Olympic Committee (IOC). Following nandrolone administration, the main metabolites in humans are 19-norandrosterone, 19-norethiocolanolone and 19-norepiandrosterone, and their presence in urine is the basis of detecting its abuse. The present work was undertaken to determine, in human urine, nandrolone metabolites (phase I and phase II) by developing and comparing multiresidue liquid chromatography/tandem mass spectrometry (LC/MS/MS) and gas chromatography/mass spectrometry (GC/MS) methods. A double extraction by solid-phase extraction (SPE) was necessary for the complete elimination of the interfering compounds. The proposed methods were also tested on a real positive sample, and they allow us to determine the conjugated/free fractions ratio reducing the risk of false positive or misleading results and they should allow laboratories involved in doping control analysis to monitor the illegal use of steroids. The advantages of LC/MS/MS over GC/MS (which is the technique mainly used) include the elimination of the hydrolysis and derivatization steps: it is known that during enzymatic hydrolysis several steroids can be converted into related compounds and deconjugation is not always 100% effective. The validation parameters for the two methods were similar (limit of quantification (LOQ) <1 ng/mL and percentage coefficient of variance (CV%) <16.4), and both were able to confirm unambiguously all the analytes, thus confirming the validity of both techniques. Copyright 2010 John Wiley & Sons, Ltd.

[Identification of candidate genes and expression profiles, as doping biomarkers].

PubMed

Paparini, A; Impagnatiello, F; Pistilli, A; Rinaldi, M; Gianfranceschi, G; Signori, E; Stabile, A M; Fazio, V; Rende, M; Romano Spica, V

2007-01-01

Administration of prohibited substances to enhance athletic performance represents an emerging medical, social, ethical and legal issue. Traditional controls are based on direct detection of substances or their catabolites. However out-of-competition doping may not be easily revealed by standard analytical methods. Alternative indirect control strategies are based on the evaluation of mid- and long-term effects of doping in tissues. Drug-induced long-lasting changes of gene expression may be taken as effective indicators of doping exposure. To validate this approach, we used real-time PCR to monitor the expression pattern of selected genes in human haematopoietic cells exposed to nandrolone, insulin-like growth factor I (IGF-I) or growth hormone (GH). Some candidate genes were found significantly and consistently modulated by treatments. Nandrolone up-regulated AR, ESR2 and PGR in K562 cells, and SRD5A1, PPARA and JAK2 in Jurkat cells; IGF-I up-regulated EPOR and PGR in HL60 cells, and SRD5A1 in Jurkat; GH up-regulated SRD5A1 and GHR in K562. GATA1 expression was down-regulated in IGF-1-treated HL60, ESR2 was down-regulated in nandrolone-treated Jurkat, and AR and PGR were down-regulated in GH-treated Jurkat. This pilot study shows the potential of molecular biology-based strategies in anti-doping controls.

Effect of ethylene and 1-methylcyclopropene on the postharvest behavior of cape gooseberry fruits (Physalis peruviana L.).

PubMed

Balaguera-López, Helber E; Espinal-Ruiz, Mauricio; Zacarías, Lorenzo; Herrera, Aníbal O

2017-01-01

Cape gooseberry (Physalis peruviana L.) fruits are highly perishable berries that exhibit a climacteric respiratory behavior. The objective of this study was to evaluate the effect of ethylene and the ethylene action inhibitor 1-methylcyclopropene on the postharvest behavior of cape gooseberry fruits (ecotype Colombia). Fruits were treated with ethylene, in an ethephon application (1000 µL L -1 ), and pretreated with 1-methylcyclopropene (1 µL L -1 ), 1-methylcyclopropene+ethylene, and results compared with a control without application. Subsequently, the fruits were maintained at room temperature (20 ℃, 75% RH) for up to 11 days. The pretreatment of the cape gooseberry fruits with 1-methylcyclopropene delayed most of the ripening-associated parameters, with a reduction in the respiration rate and ethylene production, skin color development, total soluble solids, total carotenoid content, loss of firmness, loss of total titratable acidity and emission of volatile compounds such as ethyl octanoate, ethyl butanoate, ethyl decanoate, and hexyl decanoate. Conversely, application of ethephon accelerated most of these physiological changes and also overcame most of the effects prevented by the ethylene action inhibitor. Altogether, the results supported the idea of a climacteric-like behavior for cape gooseberry fruits and pointing out that the pretreatment with 1-methylcyclopropene may be a promising and efficient postharvest treatment to delay maturity and extend the postharvest period. © The Author(s) 2016.

Experimental and modeling study of the thermal decomposition of methyl decanoate

PubMed Central

Herbinet, Olivier; Glaude, Pierre-Alexandre; Warth, Valérie; Battin-Leclerc, Frédérique

2013-01-01

The experimental study of the thermal decomposition of methyl decanoate was performed in a jet-stirred reactor at temperatures ranging from 773 to 1123 K, at residence times between 1 and 4 s, at a pressure of 800 Torr (106.6 kPa) and at high dilution in helium (fuel inlet mole fraction of 0.0218). Species leaving the reactor were analyzed by gas chromatography. Main reaction products were hydrogen, carbon oxides, small hydrocarbons from C1 to C3, large 1-olefins from 1-butene to 1-nonene, and unsaturated esters with one double bond at the end of the alkyl chain from methyl-2-propenoate to methyl-8-nonenoate. At the highest temperatures, the formation of polyunsaturated species was observed: 1,3-butadiene, 1,3-cyclopentadiene, benzene, toluene, indene, and naphthalene. These results were compared with previous ones about the pyrolysis of n-dodecane, an n-alkane of similar size. The reactivity of both molecules was found to be very close. The alkane produces more olefins while the ester yields unsaturated oxygenated compounds. A detailed kinetic model for the thermal decomposition of methyl decanoate has been generated using the version of software EXGAS which was updated to take into account the specific chemistry involved in the oxidation of methyl esters. This model contains 324 species and 3231 reactions. It provided a very good prediction of the experimental data obtained in jet-stirred reactor. The formation of the major products was analyzed. The kinetic analysis showed that the retro-ene reactions of intermediate unsaturated methyl esters are of importance in low reactivity systems. PMID:23710078

Update on nandrolone and norsteroids: how endogenous or xenobiotic are these substances?

PubMed

Bricout, V; Wright, F

2004-06-01

Norsteroids are xenobiotics with androgenic and anabolic properties known since as far back as the 1930s. In doping controls, the use of the banned xenobiotic norsteroids is detected in the competitor's urines by the measurement of norandrosterone (19-NA) and noretiocholanolone (19-NE), which are the main metabolites for nandrolone (NT) and most norsteroids with anabolic properties. In 1996, the IOC subcommission "Doping and Biochemistry of Sport" informed the Heads of the "IOC Accredited Laboratories" that the recommended cut-off limit for reporting an offence was to be 1-2 ng ml(-1) urine for either 19-NA or 19-NE. We will discuss how technical progress in gas chromatography coupled to high-resolution mass spectrometry permitted a dramatic increase in sensitivity with a detection limit of 1 pg ml(-1) urine, or less, and an assay limit of 20-50 pg ml(-1) urine, for either 19-NA or 19-NE. As a paradox, norsteroids have been known for decades as not only xenobiotics but also obligatory endogenous intermediates in the biosynthesis of estrogens from androgens in all species, man included. It is this biochemical observation which fed the active scientific and medical controversy initiated in 1998 over the possibly endogenous production of nandrolone and metabolites well over the new IOC's recommended cut-off limit of 2 ng ml(-1) urine. Notwithstanding the particular technical difficulties attached, we will provide data and discuss the minute endogenous levels detected and measured in man either at rest, after performance or training and compare them to the relatively high levels reported in male athlete's doping controls today. We will also discuss data on the pharmacological effects of some contraceptive therapies containing norsteroids in women. In view of the well-documented noxious effects repeatedly observed after anabolic steroid misuse, the confirmation and implementation of technically proven procedures for reporting norsteroid abuse in sports seems an important enough goal to protect athlete's health against such abuses and justifies up dating the review of the patent scientific and medical experience and knowledge gained over the last 50 years on nandrolone and its minor production in man and woman.

Investigation of methyl decanoate combustion in an optical direct-injection diesel engine

DOE PAGES

Cheng, A. S.; Dumitrescu, Cosmin E.; Mueller, Charles J.

2014-11-24

In this study, an optically accessible heavy-duty diesel engine was used to investigate the impact of methyl decanoate (MD) on combustion and emissions. A specific goal of the study was to determine if MD could enable soot-free leaner-lifted flame combustion (LLFC) – a mode of mixing-controlled combustion associated with fuel-air equivalence ratios below approximately two. An ultra-low sulfur diesel certification fuel (CF) was used as the baseline fuel, and experiments were conducted at two fuel-injection pressures with three levels of charge-gas dilution. In addition to conventional pressure-based and engine-out emissions measurements, exhaust laser-induced incandescence, in-cylinder natural luminosity (NL), and in-cylindermore » chemiluminescence (CL) diagnostics were used to provide detailed insight into combustion processes.« less

Investigation of methyl decanoate combustion in an optical direct-injection diesel engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, A. S.; Dumitrescu, Cosmin E.; Mueller, Charles J.

In this study, an optically accessible heavy-duty diesel engine was used to investigate the impact of methyl decanoate (MD) on combustion and emissions. A specific goal of the study was to determine if MD could enable soot-free leaner-lifted flame combustion (LLFC) – a mode of mixing-controlled combustion associated with fuel-air equivalence ratios below approximately two. An ultra-low sulfur diesel certification fuel (CF) was used as the baseline fuel, and experiments were conducted at two fuel-injection pressures with three levels of charge-gas dilution. In addition to conventional pressure-based and engine-out emissions measurements, exhaust laser-induced incandescence, in-cylinder natural luminosity (NL), and in-cylindermore » chemiluminescence (CL) diagnostics were used to provide detailed insight into combustion processes.« less

The effect of age on the pharmacological management of ambulatory patients treated with depot neuroleptic medications for schizophrenia and related psychotic disorders.

PubMed

Mamo, David C; Sweet, Robert A; Chengappa, K N Roy; Reddy, Ravinder R; Jeste, Dilip V

2002-11-01

Cross-sectional studies indicate that, in comparison to younger patients, older schizophrenic patients have a higher risk for neuroleptic-induced Parkinsonism and tardive dyskinesia (TD). It has been suggested, therefore, that older patients with schizophrenia could be maintained on reduced doses of conventional neuroleptics. We examined the effect of age on psychopharmacological management in a naturalistic study of a group of 165 patients with a clinical diagnosis of schizophrenia or a related psychotic disorder (age range = 21-84 years; subjects > or = 1;45 years n = 86) treated with either haloperidol decanoate or fluphenazine decanoate. Increasing age was not correlated with total daily dose of neuroleptics or anticholinergic medication. However, a modest negative correlation of age with daily neuroleptic dose was found in patients aged 45 years and older. The results of this study highlight the need for prospective assessments of depot neuroleptic dose requirements in older patients suffering from primary psychotic disorders. Copyright 2002 John Wiley & Sons, Ltd.

An insight into the molecular mechanism of the temporary enhancement effect of isopulegol decanoate on the skin.

PubMed

Liu, Xiaochang; Liu, Meiying; Liu, Chao; Quan, Peng; Zhao, Yongshan; Fang, Liang

2017-08-30

Chemical enhancers are widely used to facilitate drug permeation in transdermal drug delivery system (TDDS) and the effect of chemical enhancers is desired to be temporary. Though temporary enhancement effect of chemical enhancers has been widely discussed, there is still a lack of knowledge about the molecular mechanism of temporary enhancement effect. Using the skin permeation of flurbiprofen as a probe, the temporary enhancement effect of isopulegol decanoate (ISO-10) was evaluated with in vitro permeation experiment and confocal laser scanning microscopy (CLSM). In addition, molecular mechanism of skin recovery was explored with skin retention of ISO-10, attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), molecular dynamic (MD) simulation and transepidermal water loss (TEWL). Temporary enhancement effect of ISO-10 was observed by the permeation of flurbiprofen after the treatment of 180min. Furthermore, temporary enhancement effect of ISO-10 on the diffusion of intercellular lipid in the stratum cornuem (SC) was observed by ATR-FTIR, molecular dynamic (MD) simulation. The SC barrier function recovered with the existence of ISO-10 in the lipid bilayer as indicated by the retention study and TEWL. In conclusion, the lipid bilayer accepted the enhancer as a new component to form a new stable arrangement, resulted the recovery of the skin barrier function. This work processed a novel mechanism of the recovery of skin barrier function after the addition of chemical enhancers. Copyright © 2017 Elsevier B.V. All rights reserved.

Testosterone regulation of Akt/mTORC1/FoxO3a Signaling in Skeletal Muscle

PubMed Central

White, James P.; Gao, Song; Puppa, Melissa J.; Sato, Shuichi; Welle, Stephen L.; Carson, James A.

2012-01-01

Low endogenous testosterone production, known as hypogonadism is commonly associated with conditions inducing muscle wasting. Akt signaling can control skeletal muscle mass through mTOR regulation of protein synthesis and FoxO regulation of protein degradation, and this pathway has been previously identified as a target of androgen signaling. However, the testosterone sensitivity of Akt/mTOR signaling requires further understanding in order to grasp the significance of varied testosterone levels seen with wasting disease on muscle protein turnover regulation. Therefore, the purpose of this study is to determine the effect of androgen availability on muscle Akt/mTORC1/FoxO3a regulation in skeletal muscle and cultured C2C12 myotubes. C57BL/6 mice were either castrated for 42 days or castrated and treated with the nandrolone decanoate (ND) (6 mg/kg bw/wk). Testosterone loss (TL) significantly decreased volitional grip strength, body weight, and gastrocnemius (GAS) muscle mass, and ND reversed these changes. Related to muscle mass regulation, TL decreased muscle IGF-1 mRNA, the rate of myofibrillar protein synthesis, Akt phosphorylation, and the phosphorylation of Akt targets, GSK3β, PRAS40 and FoxO3a. TL induced expression of FoxO transcriptional targets, MuRF1, atrogin1 and REDD1. Muscle AMPK and raptor phosphorylation, mTOR inhibitors, were not altered by low testosterone. ND restored IGF-1 expression and Akt/mTORC1 signaling while repressing expression of FoxO transcriptional targets. Testosterone (T) sensitivity of Akt/mTORC1 signaling was examined in C2C12 myotubes, and mTOR phosphorylation was induced independent of Akt activation at low T concentrations, while a higher T concentration was required to activate Akt signaling. Interestingly, low concentration T was sufficient to amplify myotube mTOR and Akt signaling after 24h of T withdrawal, demonstrating the potential in cultured myotubes for a T initiated positive feedback mechanism to amplify Akt/mTOR signaling. In summary, androgen withdrawal decreases muscle myofibrillar protein synthesis through Akt/mTORC1 signaling, which is independent of AMPK activation, and readily reversible by anabolic steroid administration. Acute Akt activation in C2C12 myotubes is sensitive to a high concentration of testosterone, and low concentrations of testosterone can activate mTOR signaling independent of Akt. PMID:23116773

77 FR 16039 - Abbott Laboratories et al.; Withdrawal of Approval of 35 New Drug Applications and 64 Abbreviated...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-19

... Do. nitroprusside for Injection USP), 50 mg. ANDA 071015 Haloperidol Oral Teva Pharmaceuticals... 075065 Acyclovir Sodium for Do. Injection. ANDA 075176 Haloperidol Do. Decanoate Injection, 50 mg/mL and...

Nandrolone and stanozolol induce Leydig cell tumor proliferation through an estrogen-dependent mechanism involving IGF-I system.

PubMed

Chimento, Adele; Sirianni, Rosa; Zolea, Fabiana; De Luca, Arianna; Lanzino, Marilena; Catalano, Stefania; Andò, Sebastiano; Pezzi, Vincenzo

2012-05-01

Several substances such as anabolic androgenic steroids (AAS), peptide hormones like insulin-like growth factor-I (IGF-I), aromatase inhibitors and estrogen antagonists are offered via the Internet, and are assumed without considering the potential deleterious effects that can be caused by their administration. In this study we aimed to determine if nandrolone and stanozolol, two commonly used AAS, could have an effect on Leydig cell tumor proliferation and if their effects could be potentiated by the concomitant use of IGF-I. Using a rat Leydig tumor cell line, R2C cells, as experimental model we found that nandrolone and stanozolol caused a dose-dependent induction of aromatase expression and estradiol (E2) production. When used in combination with IGF-I they were more effective than single molecules in inducing aromatase expression. AAS exhibited estrogenic activity and induced rapid estrogen receptor (ER)-dependent pathways involving IGF1R, AKT, and ERK1/2 phosphorylation. Inhibitors for these kinases decreased AAS-dependent aromatase expression. Up-regulated aromatase levels and related E2 production increased cell proliferation as a consequence of increased cyclin E expression. The observation that ER antagonist ICI182,780 was also able to significantly reduce ASS- and AAS + IGF-induced cell proliferation, confirmed a role for estrogens in AAS-dependent proliferative effects. Taken together these data clearly indicate that the use of high doses of AAS, as it occurs in doping practice, enhances Leydig cell proliferation, increasing the risk of tumor development. This risk is higher when AAS are used in association with IGF-I. To our knowledge this is the first report directly associating AAS and testicular cancer. Copyright © 2011 Wiley Periodicals, Inc.

Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation

PubMed Central

Camerino, Giulia Maria; Desaphy, Jean-François; De Bellis, Michela; Capogrosso, Roberta Francesca; Cozzoli, Anna; Dinardo, Maria Maddalena; Caloiero, Roberta; Musaraj, Kejla; Fonzino, Adriano; Conte, Elena; Jagerschmidt, Catherine; Namour, Florence; Liantonio, Antonella; De Luca, Annamaria; Conte Camerino, Diana; Pierno, Sabata

2015-01-01

Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol) muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND), an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU). Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery. PMID:26066046

Effects of Nandrolone in the Counteraction of Skeletal Muscle Atrophy in a Mouse Model of Muscle Disuse: Molecular Biology and Functional Evaluation.

PubMed

Camerino, Giulia Maria; Desaphy, Jean-François; De Bellis, Michela; Capogrosso, Roberta Francesca; Cozzoli, Anna; Dinardo, Maria Maddalena; Caloiero, Roberta; Musaraj, Kejla; Fonzino, Adriano; Conte, Elena; Jagerschmidt, Catherine; Namour, Florence; Liantonio, Antonella; De Luca, Annamaria; Conte Camerino, Diana; Pierno, Sabata

2015-01-01

Muscle disuse produces severe atrophy and a slow-to-fast phenotype transition in the postural Soleus (Sol) muscle of rodents. Antioxidants, amino-acids and growth factors were ineffective to ameliorate muscle atrophy. Here we evaluate the effects of nandrolone (ND), an anabolic steroid, on mouse skeletal muscle atrophy induced by hindlimb unloading (HU). Mice were pre-treated for 2-weeks before HU and during the 2-weeks of HU. Muscle weight and total protein content were reduced in HU mice and a restoration of these parameters was found in ND-treated HU mice. The analysis of gene expression by real-time PCR demonstrates an increase of MuRF-1 during HU but minor involvement of other catabolic pathways. However, ND did not affect MuRF-1 expression. The evaluation of anabolic pathways showed no change in mTOR and eIF2-kinase mRNA expression, but the protein expression of the eukaryotic initiation factor eIF2 was reduced during HU and restored by ND. Moreover we found an involvement of regenerative pathways, since the increase of MyoD observed after HU suggests the promotion of myogenic stem cell differentiation in response to atrophy. At the same time, Notch-1 expression was down-regulated. Interestingly, the ND treatment prevented changes in MyoD and Notch-1 expression. On the contrary, there was no evidence for an effect of ND on the change of muscle phenotype induced by HU, since no effect of treatment was observed on the resting gCl, restCa and contractile properties in Sol muscle. Accordingly, PGC1α and myosin heavy chain expression, indexes of the phenotype transition, were not restored in ND-treated HU mice. We hypothesize that ND is unable to directly affect the phenotype transition when the specialized motor unit firing pattern of stimulation is lacking. Nevertheless, through stimulation of protein synthesis, ND preserves protein content and muscle weight, which may result advantageous to the affected skeletal muscle for functional recovery.

Concurrent Oral Antipsychotic Drug Use Among Schizophrenia Patients Initiated on Long-Acting Injectable Antipsychotics Post-Hospital Discharge.

PubMed

Doshi, Jalpa A; Pettit, Amy R; Stoddard, Jeffrey J; Zummo, Jacqueline; Marcus, Steven C

2015-08-01

Pharmacological treatment is central to effective management of schizophrenia. Prescribing clinicians have an increasing array of options from which to choose, and oral antipsychotic polypharmacy is common in routine clinical practice. Practice guidelines recommend long-acting injectable (LAI) formulations, typically viewed as monotherapeutic alternatives, for patients with established nonadherence. Yet there are limited data on the prevalence and nature of concurrent oral antipsychotic prescriptions in patients receiving LAIs. Our observational, claims-based study examined the frequency and duration of concurrent oral prescriptions in 340 Medicaid patients receiving LAI therapy. Specifically, we examined patients with a recent history of nonadherence and hospitalization for schizophrenia and included both first-generation antipsychotic depot medications (fluphenazine decanoate, haloperidol decanoate) and more recently available second-generation injectables (LAI risperidone, paliperidone palmitate). Of all patients initiated on LAIs, 75.9% had a concurrent oral antipsychotic prescription in the 6 months post-hospital discharge. Patients receiving concurrent prescriptions were frequently prescribed an oral formulation of their LAI agent, but many first-generation LAI users received a concurrent second-generation oral medication. The lowest rate of concurrent prescribing (58.8%) was found with paliperidone palmitate, whereas the highest rate was with LAI risperidone (88.9%). Overlap in oral and LAI prescriptions typically occurred for a substantial period of time (ie, >30 days) and for a notable percentage of the days covered by LAIs (often 50% or more). Our findings highlight the need to further examine such prescribing patterns, to probe the reasons for them, and to clarify the optimal roles of different antipsychotic treatments in clinical practice.

Cost-Effectiveness of Long-Acting Injectable Paliperidone Palmitate Versus Haloperidol Decanoate in Maintenance Treatment of Schizophrenia.

PubMed

Rosenheck, Robert A; Leslie, Douglas L; Sint, Kyaw J; Lin, Haiqun; Li, Yue; McEvoy, Joseph P; Byerly, Matthew J; Hamer, Robert M; Swartz, Marvin S; Stroup, T Scott

2016-10-01

This study assessed the relative cost-effectiveness of haloperidol decanoate (HD), a first-generation long-acting injectable (LAI) antipsychotic, and paliperidone palmitate (PP), a second-generation LAI antipsychotic. A double-blind, randomized 18-month clinical trial conducted at 22 clinical research sites in the United States compared the cost-effectiveness of HD and PP among 311 adults with schizophrenia or schizoaffective disorder who had been clinically assessed as likely to benefit from an LAI antipsychotic. Patients were randomly assigned to monthly intramuscular injections of HD (25-200 mg) or PP (39-234 mg) for up to 24 months. Quality-adjusted life years (QALYs) were measured by a schizophrenia-specific algorithm based on the Positive and Negative Syndrome Scale and side-effect assessments; total health care costs were assessed from the perspective of the health system. Mixed-model analysis showed that PP was associated with .0297 greater QALYs over 18 months (p=.03) and with $2,100 more in average costs per quarter for inpatient and outpatient services and medication compared with HD (p<.001). Bootstrap analysis with 5,000 replications showed an incremental cost-effectiveness ratio for PP of $508,241 per QALY (95% confidence interval=$122,390-$1,582,711). Net health benefits analysis showed a .98 probability of greater cost-effectiveness for HD compared with PP at an estimated value of $150,000 per QALY and a .50 probability of greater cost-effectiveness at $500,000 per QALY. HD was more cost-effective than PP, suggesting that PP's slightly greater benefits did not justify its markedly higher costs, which are likely to fall once the medication's patent expires.

The anabolic/androgenic steroid nandrolone exacerbates gene expression modifications induced by mutant SOD1 in muscles of mice models of amyotrophic lateral sclerosis.

PubMed

Galbiati, Mariarita; Onesto, Elisa; Zito, Arianna; Crippa, Valeria; Rusmini, Paola; Mariotti, Raffaella; Bentivoglio, Marina; Bendotti, Caterina; Poletti, Angelo

2012-02-01

Anabolic/androgenic steroids (AAS) are drugs that enhance muscle mass, and are often illegally utilized in athletes to improve their performances. Recent data suggest that the increased risk for amyotrophic lateral sclerosis (ALS) in male soccer and football players could be linked to AAS abuse. ALS is a motor neuron disease mainly occurring in sporadic (sALS) forms, but some familial forms (fALS) exist and have been linked to mutations in different genes. Some of these, in their wild type (wt) form, have been proposed as risk factors for sALS, i.e. superoxide dismutase 1 (SOD1) gene, whose mutations are causative of about 20% of fALS. Notably, SOD1 toxicity might occur both in motor neurons and in muscle cells. Using gastrocnemius muscles of mice overexpressing human mutant SOD1 (mutSOD1) at different disease stages, we found that the expression of a selected set of genes associated to muscle atrophy, MyoD, myogenin, atrogin-1, and transforming growth factor (TGF)β1, is up-regulated already at the presymptomatic stage. Atrogin-1 gene expression was increased also in mice overexpressing human wtSOD1. Similar alterations were found in axotomized mouse muscles and in cultured ALS myoblast models. In these ALS models, we then evaluated the pharmacological effects of the synthetic AAS nandrolone on the expression of the genes modified in ALS muscle. Nandrolone administration had no effects on MyoD, myogenin, and atrogin-1 expression, but it significantly increased TGFβ1 expression at disease onset. Altogether, these data suggest that, in fALS, muscle gene expression is altered at early stages, and AAS may exacerbate some of the alterations induced by SOD1 possibly acting as a contributing factor also in sALS. Copyright © 2011 Elsevier Ltd. All rights reserved.

The anabolic/androgenic steroid nandrolone exacerbates gene expression modifications induced by mutant SOD1 in muscles of mice models of amyotrophic lateral sclerosis

PubMed Central

Galbiati, Mariarita; Onesto, Elisa; Zito, Arianna; Crippa, Valeria; Rusmini, Paola; Mariotti, Raffaella; Bentivoglio, Marina; Bendotti, Caterina; Poletti, Angelo

2012-01-01

Anabolic/androgenic steroids (AAS) are drugs that enhance muscle mass, and are often illegally utilized in athletes to improve their performances. Recent data suggest that the increased risk for amyotrophic lateral sclerosis (ALS) in male soccer and football players could be linked to AAS abuse. ALS is a motor neuron disease mainly occurring in sporadic (sALS) forms, but some familial forms (fALS) exist and have been linked to mutations in different genes. Some of these, in their wild type (wt) form, have been proposed as risk factors for sALS, i.e. superoxide dismutase 1 (SOD1) gene, whose mutations are causative of about 20% of fALS. Notably, SOD1 toxicity might occur both in motor neurons and in muscle cells. Using gastrocnemius muscles of mice overexpressing human mutant SOD1 (mutSOD1) at different disease stages, we found that the expression of a selected set of genes associated to muscle atrophy, MyoD, myogenin, atrogin-1, and transforming growth factor (TGF)β1, is up-regulated already at the presymptomatic stage. Atrogin-1 gene expression was increased also in mice overexpressing human wtSOD1. Similar alterations were found in axotomized mouse muscles and in cultured ALS myoblast models. In these ALS models, we then evaluated the pharmacological effects of the synthetic AAS nandrolone on the expression of the genes modified in ALS muscle. Nandrolone administration had no effects on MyoD, myogenin, and atrogin-1 expression, but it significantly increased TGFβ1 expression at disease onset. Altogether, these data suggest that, in fALS, muscle gene expression is altered at early stages, and AAS may exacerbate some of the alterations induced by SOD1 possibly acting as a contributing factor also in sALS. PMID:22178654

Research of stimulants and anabolic steroids in dietary supplements.

PubMed

Baume, N; Mahler, N; Kamber, M; Mangin, P; Saugy, M

2006-02-01

The purpose of this study was to analyze the composition of 103 dietary supplements bought on the internet. The supplements were dispatched in four different categories according to their announced contents [creatine, prohormones, "mental enhancers" and branched chain amino acids (BCAA)]. All the supplements were screened for the presence of stimulants and main anabolic steroids parent compounds. At the same time, the research was focused on the precursors and metabolites of testosterone and nandrolone. The study pointed out three products containing an anabolic steroid, metandienone, in a very high amount. The ingestion of such products induced a high quantity of metandienone metabolites in urines that would be considered as a positive antidoping test. The results have also shown that one creatine product and three "mental enhancers" contained traces of hormones or prohormones not claimed on the labels and 14 prohormone products contained substances other than those indicated by the manufacturer. The oral intake of the creatine product revealed the presence of the two main nandrolone metabolites (19-norandrosterone and 19-noretiocholanolone) in urine.

Modeling of the oxidation of methyl esters—Validation for methyl hexanoate, methyl heptanoate, and methyl decanoate in a jet-stirred reactor

PubMed Central

Glaude, Pierre Alexandre; Herbinet, Olivier; Bax, Sarah; Biet, Joffrey; Warth, Valérie; Battin-Leclerc, Frédérique

2013-01-01

The modeling of the oxidation of methyl esters was investigated and the specific chemistry, which is due to the presence of the ester group in this class of molecules, is described. New reactions and rate parameters were defined and included in the software EXGAS for the automatic generation of kinetic mechanisms. Models generated with EXGAS were successfully validated against data from the literature (oxidation of methyl hexanoate and methyl heptanoate in a jet-stirred reactor) and a new set of experimental results for methyl decanoate. The oxidation of this last species was investigated in a jet-stirred reactor at temperatures from 500 to 1100 K, including the negative temperature coefficient region, under stoichiometric conditions, at a pressure of 1.06 bar and for a residence time of 1.5 s: more than 30 reaction products, including olefins, unsaturated esters, and cyclic ethers, were quantified and successfully simulated. Flow rate analysis showed that reactions pathways for the oxidation of methyl esters in the low-temperature range are similar to that of alkanes. PMID:23710076

Impact of flavouring substances on the aggregation behaviour of dissolved barley β-glucans in a model beer.

PubMed

Kupetz, M; Sacher, B; Becker, T

2016-06-05

Structural polymers such as cereal β-glucan may cause various processing problems in beverage industry depending on concentration, molar size distribution and agglomeration behaviour. In this context, influences of the beer volatiles dodecanoic acid, octyl butanoate, ethyl decanoate and decyl acetate on molar mass and radii of barley β-glucan were investigated in ethanolic (4% w/w) model solution. After addition of 100mg/l ethyl decanoate and decyl acetate to the β-glucan solution, a wider-ranging molar mass distribution could be observed by means of asymmetric field-flow-fractionation. Due to agglomeration, average molar mass of β-glucan standard (MW=6.8×10(6)g/mol) increased by 2×10(6)g/mol (P<0.05) in solution containing decyl acetate. Furthermore, a significant growth (P<0.05) from 86 to 102 nm in gyration radius was measured. The obtained results elucidate the importance of fatty acid derived flavouring substance composition in beer regarding the aggregation behaviour of β-glucan. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Development and Single-Laboratory Validation of a Method for the Determination of Steroid Residues in Fish and Fish Products.

PubMed

Watson, Lynn; Potter, Ross; Murphy, Cory; Gibbs, Ryan

2015-01-01

Due to potential use in aquacultured fish products, the Canadian Food Inspection Agency has identified residue testing for steroids as a priority. These compounds are used in aquaculture primarily to direct sexual differentiation with both androgens and estrogens applied depending on the desired outcome. Published research is lacking with respect to steroid residue testing in fish; however, recent studies in other matrixes provided transferable cleanup techniques. A simple, rapid, and sensitive method was developed and validated for use in monitoring aquacultured fish products for the presence of methyltestosterone, nandrolone, epi-nandrolone, boldenone, and epi-boldenone residues. The developed method consists of solvent extraction followed by cleanup using hexane and dual cartridge SPE with analysis by ultra-HPLC-MS/MS. The method is capable of detecting and confirming steroid residue levels ranging from 0.05 to 25 ng/g in salmon and tilapia, depending on the analyte. Recoveries ranged from 88 to 130% for the analytes. Instrument repeatability was less than 13% for all compounds, while intermediate precision ranged from 5 to 25% RSD. HorRat values were within acceptable ranges.

Anabolic androgenic steroid-induced Takotsubo cardiomyopathy

PubMed Central

Sella, Gianluigi; Bellanti, Giancarlo; Margheri, Massimo

2015-01-01

Anabolic steroid abuse, aimed at increasing muscle mass, has been growing in recent years. We describe a case of a 25-year-old bodybuilder who, after taking nandrolone and stanozolol, presented with Takotsubo syndrome. The angiography showed a normal coronary anatomy with the absence of stenosis. The left ventricular function was completely normalised after 1 week. PMID:25804946

Cuphea Oil as Source of Biodiesel with Improved Fuel Properties Caused by High Content of Methyl Decanoate

USDA-ARS?s Scientific Manuscript database

Biodiesel, defined as the mono-alkyl esters of vegetable oils and animal fats, is an alternative to conventional petroleum-based diesel fuel. Biodiesel has been prepared from numerous common vegetable oils or fats as well as new or less common feedstocks. Major issues facing biodiesel include seve...

Modification of the association between antipsychotic treatment response and childhood adversity by MMP9 gene variants in a first-episode schizophrenia cohort.

PubMed

McGregor, Nathaniel; Thompson, Nicole; O'Connell, Kevin Sean; Emsley, Robin; van der Merwe, Lize; Warnich, Louise

2018-04-01

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies. Copyright © 2018 Elsevier B.V. All rights reserved.

Signals and cues in the recruitment behavior of stingless bees (Meliponini).

PubMed

Barth, Friedrich G; Hrncir, Michael; Jarau, Stefan

2008-04-01

Since the seminal work of Lindauer and Kerr (1958), many stingless bees have been known to effectively recruit nestmates to food sources. Recent research clarified properties of several signals and cues used by stingless bees when exploiting food sources. Thus, the main source of the trail pheromone in Trigona are the labial, not however the mandibular glands. In T. recursa and T. spinipes, the first stingless bee trail pheromones were identified as hexyl decanoate and octyl decanoate, respectively. The attractant footprints left by foragers at the food source are secreted by glandular epithelia of the claw retractor tendon, not however by the tarsal gland. Regarding intranidal communication, the correlation between a forager's jostling rate and recruitment success stresses the importance of agitated running and jostling. There is no evidence for a "dance" indicating food source location, however, whereas the jostling rate depends on food quality. Thoracic vibrations, another intranidal signal well known in Melipona, were analyzed using modern technology and distinguishing substrate vibrations from airborne sound. Quantitative data now permit estimates of signal and potential communication ranges. Airflow jets as described for the honeybee were not found, and thoracic vibrations do not "symbolically" encode visually measured distance in M. seminigra.

The Impact of Exogenic Testosterone and Nortestosterone-Decanoate Toxicological Evaluation Using a Rat Model

PubMed Central

Cristina, Romeo Teodor; Hanganu, Flavia; Dumitrescu, Eugenia; Muselin, Florin; Butnariu, Monica; Constantin, Adriana; Chiurciu, Viorica

2014-01-01

The impact of exogenic testosterone (T): 1.5 and 3.0 mg/kg.bw) and 19-nortestosterone 17-decanoate (ND): 1.5 and 7.5 mg/kg.bw) in castrated male rats was evaluated based on: (a) weight increase of the androgen target tissues, respecting the Hershberger methodology; (b) the 17α and β-testosterone, 17 α and β-estradiol and 17 α and β-nortestosterone levels using the GC-MS/MS technique; and (c) observation of the serum free thyroxine levels (T4). Results revealed that T and ND significantly increased the weight of androgen target tissues as follows: ND was more influential on seminal vesicles, levator ani-bulbocavernosus muscle (LABC) and Cowper's glands and T (at a dose of 3.0 mg/kg.bw) influenced the weight of the ventral prostate and glans penis. Serum samples analyzed for steroid hormone levels showed the presence of 17β-testosterone, 17β-estradiol and 17β-nor-testosterone, in castrated male rats injected with testosterone and nortestosterone, but no significant differences were found between thyroid responses and thyroid hormone levels. The results of this research proved the disrupting activity of T and ND when administered in high doses and the useful application of the Hershberger bioassay in the case of ND. PMID:25302584

Optimization of lipase-catalyzed synthesis of ginsenoside Rb1 esters using response surface methodology.

PubMed

Hu, Jiang-Ning; Lee, Jeung-Hee; Zhu, Xue-Mei; Shin, Jung-Ah; Adhikari, Prakash; Kim, Jae-Kyung; Lee, Ki-Teak

2008-11-26

In the lipase (Novozyme 435)-catalyzed synthesis of ginsenoside Rb1 esters, different acyl donors were found to affect not only the degree of conversion but also the regioselectivity. The reaction of acyl donors with short carbon chain was more effective, showing higher conversion than those with long carbon chain. Among the three solvent systems, the reaction in tert-amyl alcohol showed the highest conversion rate, while the reaction in the mixed solvent of t-BuOH and pyridine (1:1) had the lowest conversion rate. To allow the increase of GRb1 lipophilicity, we decided to further study the optimal condition of synthesis of GRb1 with vinyl decanoate with 10 carbon chain fatty acids in tert-amyl alcohol. Response surface methodology (RSM) was employed to optimize the synthesis condition. From the ridge analysis with maximum responses, the maximum GRb1 conversion was predicted to be 61.51% in a combination of factors (40.2 h, 52.95 degrees C, substrate mole ratio 275.57, and enzyme amount 39.81 mg/mL). Further, the adequacy of the predicted model was examined by additional independent experiments at the predicted maximum synthesis conditions. Results showed that the RSM was effective to optimize a combination of factors for lipase-catalyzed synthesis of ginsenoside Rb1 with vinyl decanoate.

Androgen-induced cerebral venous sinus thrombosis in a young body builder: case report

PubMed Central

Sahraian, Mohammad Ali; Mottamedi, Mahmood; Azimi, Amir Reza; Moghimi, Babak

2004-01-01

Background Cerebral venous sinus thrombosis is an infrequent disease with a variety of causes. Pregnancy, puerperium, contraceptive pills and intracranial infections are the most common causes. The patient may present with headache, focal neurological deficits and seizures. The clinical outcome is highly variable and treatment with heparin is advised. Case presentation The patient is a 22 year old male who presented with headache, repeated vomiting and papilledema. He was a bodybuilder doing exercise since 5 years ago, who had used nandrolone decaonoate 25 milligrams intramuscularly during the previous 5 months. Brain MRI and MRV showed superior sagital and transverse sinus thrombosis and extensive investigations did not reveal any known cause. Conclusions We suggested that androgen was the predisposing factor in our patient. Androgens may increase coagulation factors or platelet activity and cause arterial or venous thrombosis. As athletes may hide using androgens it should be considered as a predisposing factor for thrombotic events in such patients. PMID:15579201

Treatment of Experimentally Induced Caval Thrombosis With Oral Low Molecular Weight Heparin and Delivery Agent in a Porcine Model of Deep Venous Thrombosis

PubMed Central

Salartash, Khashayar; Lepore, Michael; Gonze, Mark D.; Leone-Bay, Andrea; Baughman, Robert; Charles Sternbergh, W.; Bowen, John C.; Money, Samuel R.

2000-01-01

Objective This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. Summary Background Data SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. Methods Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. Results The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. Conclusion The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa. PMID:10816621

Brain volume changes over the first year of treatment in schizophrenia: relationships to antipsychotic treatment.

PubMed

Emsley, R; Asmal, L; du Plessis, S; Chiliza, B; Phahladira, L; Kilian, S

2017-09-01

Progressive brain volume reductions have been described in schizophrenia, and an association with antipsychotic exposure has been reported. We compared percentage changes in grey and white matter volume from baseline to month 12 in 23 previously antipsychotic-naïve patients with a first episode of schizophrenia or schizophreniform disorder who were treated with the lowest effective dose of flupenthixol decanoate depot formulation, with 53 matched healthy individuals. Total antipsychotic dose was precisely calculated and its relationship with brain volume changes investigated. Relationships between volumetric changes and treatment were further investigated in terms of treatment response (changes in psychopathology and functionality) and treatment-related adverse-events (extrapyramidal symptoms and weight gain). Excessive cortical volume reductions were observed in patients [-4.6 (6.6)%] v. controls [-1.12 (4.0)%] (p = 0.009), with no significant group differences for changes in subcortical grey matter and white matter volumes. In a multiple regression model, the only significant predictor of cortical volume change was total antipsychotic dose received (p = 0.04). Cortical volume change was not significantly associated with the changes in psychopathology, functionality, extrapyramidal symptoms and body mass index or age, gender and duration of untreated psychosis. Brain volume reductions associated with antipsychotic treatment are not restricted to poor outcome patients and occur even with the lowest effective dose of antipsychotic. The lack of an association with poor treatment response or treatment-related adverse effects counts against cortical volume reductions reflecting neurotoxicity, at least in the short term. On the other hand, the volume reductions were not linked to the therapeutic benefits of antipsychotics.

A reduced mechanism for biodiesel surrogates with low temperature chemistry for compression ignition engine applications

NASA Astrophysics Data System (ADS)

Luo, Zhaoyu; Plomer, Max; Lu, Tianfeng; Som, Sibendu; Longman, Douglas E.

2012-04-01

Biodiesel is a promising alternative fuel for compression ignition (CI) engines. It is a renewable energy source that can be used in these engines without significant alteration in design. The detailed chemical kinetics of biodiesel is however highly complex. In the present study, a skeletal mechanism with 123 species and 394 reactions for a tri-component biodiesel surrogate, which consists of methyl decanoate, methyl 9-decanoate and n-heptane was developed for simulations of 3-D turbulent spray combustion under engine-like conditions. The reduction was based on an improved directed relation graph (DRG) method that is particularly suitable for mechanisms with many isomers, followed by isomer lumping and DRG-aided sensitivity analysis (DRGASA). The reduction was performed for pressures from 1 to 100 atm and equivalence ratios from 0.5 to 2 for both extinction and ignition applications. The initial temperatures for ignition were from 700 to 1800 K. The wide parameter range ensures the applicability of the skeletal mechanism under engine-like conditions. As such the skeletal mechanism is applicable for ignition at both low and high temperatures. Compared with the detailed mechanism that consists of 3299 species and 10806 reactions, the skeletal mechanism features a significant reduction in size while still retaining good accuracy and comprehensiveness. The validations of ignition delay time, flame lift-off length and important species profiles were also performed in 3-D engine simulations and compared with the experimental data from Sandia National Laboratories under CI engine conditions.

Valeriana officinalis does not alter the orofacial dyskinesia induced by haloperidol in rats: role of dopamine transporter.

PubMed

Fachinetto, Roselei; Villarinho, Jardel G; Wagner, Caroline; Pereira, Romaiana P; Avila, Daiana Silva; Burger, Marilise E; Calixto, João Batista; Rocha, João B T; Ferreira, Juliano

2007-10-01

Chronic treatment with classical neuroleptics in humans can produce a serious side effect, known as tardive dyskinesia (TD). Here, we examined the effects of V. officinalis, a medicinal herb widely used as calming and sleep-promoting, in an animal model of orofacial dyskinesia (OD) induced by long-term treatment with haloperidol. Adult male rats were treated during 12 weeks with haloperidol decanoate (38 mg/kg, i.m., each 28 days) and with V. officinalis (in the drinking water). Vacuous chewing movements (VCMs), locomotor activity and plus maze performance were evaluated. Haloperidol treatment produced VCM in 40% of the treated rats and the concomitant treatment with V. officinalis did not alter either prevalence or intensity of VCMs. The treatment with V. officinalis increased the percentage of the time spent on open arm and the number of entries into open arm in the plus maze test. Furthermore, the treatment with haloperidol and/or V. officinalis decreased the locomotor activity in the open field test. We did not find any difference among the groups when oxidative stress parameters were evaluated. Haloperidol treatment significantly decreased [(3)H]-dopamine uptake in striatal slices and V. officinalis was not able to prevent this effect. Taken together, our data suggest a mechanism involving the reduction of dopamine transport in the maintenance of chronic VCMs in rats. Furthermore, chronic treatment with V. officinalis seems not produce any oxidative damage to central nervous system (CNS), but it also seems to be devoid of action to prevent VCM, at least in the dose used in this study.

The prostate after administration of anabolic androgenic steroids: a morphometrical study in rats.

PubMed

Vargas, Rafael Arêas; Oliveira, Leonardo Pires; Frankenfeld, Stephan; Souza, Diogo Benchimol de; Costa, Waldemar Silva; Favorito, Luciano Alves; Sampaio, Francisco José Barcellos

2013-01-01

Many adverse effects have been associated with abuse of anabolic-androgenic steroids (AAS), including disorders of the urogenital tract. The objective of this study is to analyze the morphological modifications in the prostate ventral lobe of pubertal and adult rats chronically treated with AAS, using morphometric methods. We studied 39 male Wistar rats weighing between 400 g and 550 g. The rats were divided into four groups: (a) control rats, with 105 days of age (C105) (n = 7); (b) control rats with 65 days of age (C65) (n = 9), injected only with the vehicle (peanut oil); (c) treated rats, with 105 days of age (T105) (n = 10) and (d) treated rats with 65 days of age (T65) (n = 13). The treated rats were injected with nandrolone decanoate at a dose of 10 mg.Kg-1 body weight. The steroid hormone and the vehicle were administered by intramuscular injection once a week for eight weeks. The rats were killed at 161 days of age (C105 and T105) and 121 days of age (C65 and T65) and the ventral prostate lobe was dissected and processed for histology. The height of the acinar epithelium, the surface densities of the lumen, epithelium and stroma were observed with X400 magnification using an Olympus light microscope coupled to a Sony CCD video camera, and the images transferred to a Sony monitor KX14-CP1. The selected histological areas were then quantified using the M42 test-grid system on the digitized fields. The data were analyzed with the Graphpad software. To compare the quantitative data in both groups (controls and treated) and the outcomes, Student's t-test was used (p < 0.05 was considered significant). The weight (p < 0.001) and volume (p = 0.004) of the prostate ventral lobe showed differences between C65 and T65 groups and between C105 and T105 groups. The epithelium height showed no difference between groups C65 and T65 (p = 0.8509), but the T105 group showed an increase of 32% compared to C105 (p = 0.0089). Concerning the lumen, surface density presented no difference between C65 and T65 (p = 0.9031) and a decrease of 19% for T105 compared to C105 (p = 0.0061). There was no difference in epithelium surface density between C65 and T65 (p = 0.7375), but it was 51% higher (p = 0.0065) in T105 compared with C105. Regarding stroma surface density, there were no differences between C65 and T65 or between C105 and T105. Finally, there was no difference in collagen pattern between C105 and T105, but T65 showed a predominance of collagen fibers compared to C65. The use of anabolic androgenic steroids in rats promotes structural changes in the prostate. We observed structural changes in the weight, volume and epithelium height of the prostate ventral lobe and a predominance of collagen fibers.

Adherence to depot versus oral antipsychotic medication in schizophrenic patients during the long-term therapy.

PubMed

Stanković, Zana; Ille, Tatjana

2013-03-01

There is a high rate of schizophrenic patients who do not adhere to their prescribed therapy, despite the implementation of antipsychotic long-acting injections and the introduction of atypical antipsychotics. The aim of this study was to investigate the differences in sociodemographic, clinical and medication adherence variables between the two groups of schizophrenic patients on maintenance therapy with depot antipsychotic fluphenazine decanoate and oral antipsychotics only as well as a correlation between the medication adherence and other examined variables. A total of 56 patients of both genders, aged < 60 years, with the diagnosis of schizophrenia (F20) (ICD-10, 1992) clinically stable for at least 6 months were introduced in this cross-sectional study. The patients from the depot group (n = 19) were on classical depot antipsychotic fluphenazine decanoate administering intramuscularly every 4 weeks (with or without oral antipsychotic augmentation) and the patients from the oral group (n = 37) were on oral therapy alone with classical or atypical antipsychotics, either as monotherapy or combined. The Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Item G12 of the PANSS was used to assess insight into the illness. The patients completed the Medical Adherence Rating Scale (MARS) was used to assess adherence to the therapy. A higher MARS score indicates behavior [Medical Adherence Questionnaire (MAQ subscale)] and attitudes toward medication [Drug Attitude Inventory (DAI subscale)] that are more consistent with treatment adherence. The exclusion criteria were determined. The Pearson's chi2 test was used to compare categorical variables, Student's t-test to compare continuous variables and Pearson's correlation to test the correlation significance; p = 0.05. Significant between-group differences in age, illness duration, chlorpromazine equivalents, PANSS score and DAI subscore were found. Item G12 of the PANSS subscore and MARS score correlated significantly negatively. A significant positive correlation between receiving depot antipsychotic and DAI subscore as well as between illness duration and both DAI subscore and MARS score were also found. Schizophrenic patients on classical depot antipsychotic maintenance therapy might present subpopulation of patients with significantly longer illness duration, more favorable medication attitude and outcome in relation to those on oral antipsychotics alone.

Cost-effectiveness of antipsychotics for outpatients with chronic schizophrenia.

PubMed

Obradovic, M; Mrhar, A; Kos, M

2007-12-01

The aim of the present analysis was to evaluate the cost-effectiveness of alternative treatments for outpatients with chronic schizophrenia from the healthcare payer's perspective. Decision analysis was used to evaluate the cost-effectiveness of the following antipsychotic drugs: amisulpride, aripiprazole, haloperidol (oral formulation), haloperidol (depot formulation), olanzapine, quetiapine, risperidone (oral formulation), risperidone (depot formulation) and ziprazidone. Clinical and economic outcomes were modelled over 1-year time horizon. Effectiveness was measured as a percentage of patients in remission. Clinical parameters used in the model included compliance rates, rehospitalisation rates for compliant and non-compliant patients, duration and frequency of hospitalisation, and adverse event rates. One-way sensitivity analysis was performed to test the robustness of the model. The most effective treatment was treatment with olanzapine where 64.1% of patients remained in remission. The least effective treatment was treatment with quetiapine where 32.7% of patients remained in remission. Overall costs ranged from 3,726.78 Euro for haloperidol to 8,157.03 Euro for risperidone in depot formulation. Inpatient costs represented the major part of costs for most of antipsychotic drugs. Typical antipsychotic drugs had substantially smaller outpatient costs (6.5%) compared with atypical antipsychotics (37.9%). In the base case scenario the non-dominated treatment strategies were haloperidol, haloperidol decanoate and olanzapine. Additionally, risperidone can also be considered to be part of the efficient frontier based on the sensitivity analysis results. Among second-generation antipsychotics, which have a better safety profile than first-generation antipsychotics, olanzapine and risperidone showed to be the most cost-effective treatment strategies for outpatient treatment of chronic schizophrenia.

Enhancement of skin permeation of flurbiprofen via its transdermal patches using isopulegol decanoate (ISO-C10) as an absorption enhancer: pharmacokinetic and pharmacodynamic evaluation.

PubMed

Chen, Yang; Quan, Peng; Liu, Xiaochang; Guo, Wenjia; Song, Wenting; Cun, Dongmei; Wang, Zhongyan; Fang, Liang

2015-09-01

The study aimed to prepare a transdermal patch for flurbiprofen using isopulegol decanoate (ISO-C10) as a permeation enhancer, and to evaluate the in-vitro and in-vivo percutaneous permeation of the drug, as well as the pharmacodynamic efficacy of the formulation. The permeation experiments were conducted on rabbit skin, and the pharmacokinetic profiles and synovial fluid drug concentration were measured after in-vivo transdermal administration. A deconvolution approach was employed to analyse the correlation between the in-vitro and in-vivo drug permeation. The anti-inflammatory and analgesic effects were, respectively, assessed using the adjuvant arthritis model and the acetic acid induced pain model. ISO-C10 could increase the in-vitro permeation of flurbiprofen from 46.22 ± 5.65 μg/cm(2) to 101.07 ± 10.85 μg/cm(2) . The in-vivo absorption of the drug was also improved by the enhancer, and a good linear correlation was observed between the in-vitro and in-vivo drug permeation. Meanwhile, the ISO-C10 contained patches increased the drug disposition in synovial fluid and enhanced the pharmacodynamic efficacy of the formulation. ISO-C10 would be a promising permeation enhancer for improving the in-vitro and in-vivo delivery of flurbiprofen from its transdermal patches. © 2015 Royal Pharmaceutical Society.

Endogenous nandrolone metabolites in human urine. Two-year monitoring of male professional soccer players.

PubMed

Le, Bizec Bruno; Bryand, Fabrice; Gaudin, Isabelle; Monteau, Fabrice; Poulain, Frédéric; Andre, François

2002-01-01

19-Norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are the two main indicators used to prove the illegal use of nandrolone by humans. Recent studies showed that 19-NA and 19-NE can be endogenously produced in some individuals. The mediated cases observed over the last three years generated some questions about the appropriateness of the official International Olympic Committee cutoff level, which is 2 ng/mL of 19-NA in male urine samples. In the present study, professional soccer players belonging to the French First League were studied over a period of 19 months. In total, 385 urine samples were taken immediately before and after soccer competitions and were coupled with 200 blood samples for testosterone and LH determination. Results of the study showed that the mean values for 19-NA and 19-NE were 0.097 ng/mL and 0.033 ng/mL, respectively. For 19-NA, 70% of the samples proved to be below 0.1 ng/mL, whereas less than 20% were found to be between 0.1 and 0.2 ng/mL, and 7% were between 0.2 and 0.3 ng/mL. Only four urine samples were above 1.0 ng/mL; the maximal value was 1.79 ng/mL. For 19-NE, only one sample was above 1.0 ng/mL; the value was 1.42 ng/mL. Concentrations of these compounds after games were generally significantly higher than those before games.

Anabolic steroid abuse and tooth size-arch dimensions in the rat.

PubMed

Barrett, R L; Harris, E F; Tolley, E A; Nutting, D F

1993-01-01

Anabolic steroids are misused by adolescents and adults to increase muscle mass and improve appearance and athletic performance. Since anabolics strongly enhance protein synthesis, it was speculated that alterations in tooth size and arch length could occur. This study quantified the effects of the anabolic steroid nandrolone phenpropionate on these parameters in a rat model. The steroid significantly increased mandibular arch length. No difference in mesiodistal dimensions of the molars occurred. In consequence, the increased arch dimensions combined with unaltered tooth size may result in dental spacing and/or other malocclusions.

The role of sex differences in the effect of anabolics on the liver.

PubMed

Kulcsár-Gergely, J; Kulcsár, A; Kiss, A

1975-03-01

The effect of two anabolic steroids, norandrostenolone-phenylpropionate (Nerobolil) and norandrostenolone-decanoate (Retabolil) on the liver was studied in rats. Body weight, wet liver weight and the protein content of the liver homogenisates were found to increase under the effect of anabolic treatment, the most explicitely in females treated with Nerobolil. The function of the liver to metabolize hexobarbital, measured in vivo, is increased by a single dose of anabolic. The prolongation of treatment keeps on shortening hexobarbital anaesthesia only in females. Even 8 weeks after the end of treatment the effect is invariably lasting in females, in males it is not. Studies of the vaginal cycle cannot prove a decline of ovarial function. In females the hepatotropic effect of anabolic treatment, performed simultaneously with the chronic carbon tetrachloride lesion can be demonstrated. The liver weight and protein content are maintained on the control level. Under the effect of anabolic treatment the function to metabolize the effect of anabolic treatment the function to metabolize hexobarbital, which has been impaired by the lesion, remains near the level of the untreated animals. Our experiments support the observations of the inductive property of the steroids being parallel to their anabolic characteristics. Their catatoxic effect is pronounced in females. Nerobolil was found to be more advantageous from the point of view of both anabolic and hepatotropic effect. Our experiments do not suggest the possibility of liver damage during the administration of these two anabolics. The effect of the anabolics on the enzymatic induction may be of therapeutic value when adequate preparations are selected and sex differences as well as the character of the liver damage are taken into consideration.

Drug-induced parkinsonism following chronic methamphetamine use by a patient on haloperidol decanoate.

PubMed

Matthew, Binoj J; Gedzior, Joanna S

2015-01-01

This report attempts to highlight that use of an antipsychotic and concurrent chronic use of methamphetamine can cause drug-induced parkinsonism. Methamphetamine is usually not encountered in the list of agents that induce drug-induced parkinsonism and so its consideration particularly during chronic use by a patient who is also on an antipsychotic is worthwhile because of its popularity as an illegal narcotic. This case report describes just such a case of drug-induced parkinsonism which is a subacute syndrome that mimics Parkinson's disease. Although less alarming than dystonia, it is more common, more difficult to treat and can be the cause of significant disability during maintenance treatment especially in the elderly. In most cases, symptoms are reversible in days or weeks, but occasionally, especially in the elderly, or if long-acting injectable antipsychotics are used-as in this case-symptoms may last for weeks or months. The report also illustrates the neuronal workings due to chronic methamphetamine-use and the additive effects of dopamine blockade by antipsychotics such as haloperidol. © The Author(s) 2015.

The scaffold protein RACK1 is a target of endocrine disrupting chemicals (EDCs) with important implication in immunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buoso, Erica; Galasso, Marilisa; Ronfani, Melania

We recently demonstrated the existence of a complex hormonal balance between steroid hormones in the control of RACK1 (Receptor for Activated C Kinase 1) expression and immune activation, suggesting that this scaffold protein may also be targeted by endocrine disrupting chemicals (EDCs). As a proof of concept, we investigated the effect of the doping agent nandrolone, an androgen receptor (AR) agonist, and of p,p′DDT (dichlorodiphenyltrichloroethane) and its main metabolite p,p′DDE (dichlorodiphenyldichloroethylene), a weak and strong AR antagonist, respectively, on RACK1 expression and innate immune response. In analogy to endogenous androgens, nandrolone induced a dose-related increase in RACK1 transcriptional activity andmore » protein expression, resulting in increased LPS-induced IL-8 and TNF-α production and proliferation in THP-1 cells. Conversely, p,p′DDT and p,p′DDE significantly decrease RACK1 expression, LPS-induced cytokine production and CD86 expression; with p,p′DDE exerting a stronger repressor effect than p,p′DDT, consistent with its stronger AR antagonistic effect. These results indicate that RACK1 could be a relevant target of EDCs, responding in opposite ways to agonist or antagonist of AR, representing a bridge between the endocrine system and the innate immune system. - Highlights: • RACK1 expression can be induced by AR agonists with a consequent enhancement of the response to LPS. • RACK1 can be negatively modulated by the AR antagonists DDT and its main metabolite p,p′DDE. • RACK1 can be a relevant target of EDCs, representing a bridge between the endocrine system and the immune system.« less

Identification and analysis of putative polyhydroxyalkanoate synthase (PhaC) in Pseudomonas fluorescens.

PubMed

Lim, Ju Hyoung; Rhie, Ho-Gun; Kim, Jeong Nam

2018-05-11

Pseudomonas fluorescens KLR101 was found to be capable of producing polyhydroxyalkanoate (PHA) using various sugars and fatty acids with carbon numbers ranging from 2 to 6. PHA granules mainly consisted of poly(3-hydroxybutyrate) homopolymer and/or poly(3-hydroxybutyrate- co -3-hydroxyvalerate) copolymer. Genomic DNA of P. fluorescens was fractionated and cloned into a lambda library, in which a 5.8-kb fragment hybridized to a heterologous phaC probe from Ralstonia eutropha was identified. In vivo expression in Klebsiella aerogenes KC2671 (pUMS), restriction mapping, Southern hybridization experiments, and sequencing data revealed that PHA biosynthesis by P. fluorescens relied upon a polypeptide encoded by a 1,683-bp non-operonal ORF, which was preceded by a possible -24/-12 promoter and highly similar to DNA sequences of a gene encoding PHA synthase in the genus Pseudomonas . In vivo expression of the putative PHA synthase gene ( phaC Pf ) in a recombinant Escherichia coli strain was investigated by using glucose and decanoate as substrates. E. coli ( phaC Pf + , pUMS) grown in medium containing glucose accumulated PHA granules mainly consisting of 3-hydroxybutyrate, whereas only a trace amount of 3-hydroxydecanoate was detected from E. coli fadR mutant ( phaC Pf + ) grown in medium containing decanoate. In vitro enzymatic assessment experiments showed that 3-hydroxybutyryl-CoA was efficiently used as a substrate of purified PhaC Pf , suggesting that the putative PHA synthase of P. fluorescens mainly utilizes short-chain-length PHA precursors as a substrate.

Kinetic studies of Chromobacterium viscosum lipase in AOT water in oil microemulsions and gelatin microemulsion-based organogels.

PubMed

Jenta, T R; Batts, G; Rees, G D; Robinson, B H

1997-06-05

Kinetic studies have shown that octyl decanoate synthesis by Chromobacterium viscosum (CV) lipase in sodium bis-2-(ethylhexyl) sulfosuccinate (AOT) water in oil (w/o) microemulsions occurs via the nonsequential (ping-pong) bi bi mechanism. There was evidence of single substrate inhibition by decanoic acid at high concentrations. Initial rate data yielded estimates for acid and alcohol Michaelis constants of ca. 10(-1) mol dm(-3) and a maximum rate under saturation conditions of ca. 10(-3) mol dm(-3) s(-1) for a lipase concentration of 0.36 mg cm(-3). CV lipase immobilized in AOT microemulsion-based organogels (MBGs) was also found to catalyze the synthesis of octyl decanoate according to the ping-pong bi bi mechanism. Reaction rates were similar in the free and immobilized systems under comparable conditions. Initial rates at saturating (but noninhibiting) substrate concentrations were first order with respect to CV lipase concentration in both w/o microemulsions and the MBG/oil systems. Gradients yielded an apparent k(cat) = 4.4 x 10(-4) mol g(-1) s(-1) in the case of w/o microemulsions, and 6.1 x 10(-4) mol g(-1) s(-1) for CV lipase immobilized in the MBGs. A third system comprising w/o microemulsions containing substrates and gelatin at concentrations comparable to those employed in the MBG formulations, provided a useful link between the conventional liquid microemulsion medium and the solid organogels. The nongelation of these intermediate systems stems from the early inclusion of substrate during a modified preparative protocol. The presence of substrate appears to prevent the development of a percolated microstructure that is thought to be a prerequisite for MBG formation. FT-NMR was employed as a semicontinuous in situ assay procedure. The apparent activity expressed by CV lipase in compositionally equivalent liquid and solid phase gelatin-containing systems was similar. An apparent activation energy of 24 +/- 2 kJ mol(-1) was determined by (1)H-NMR for esterification in gelatin-containing w/o microemulsions. This value agrees with previous determinations for CV lipase-catalyzed synthesis of octyl decanoate in "conventional" w/o microemulsions and MBG/oil systems. The similarities in lipase behavior are consistent with the claim, based largely on structural measurements, that the physico-chemical properties of the lipase-containing w/o microemulsion are to a large extent preserved on transformation to the daughter organogel. The close agreement of apparrent activation energies suggests that substrate mass transfer is not rate determining in the three studied systems.

Investigation of transport mechanism of exendin-4 across Madin Darby canine kidney cell monolayers.

PubMed

Wang, Mengshu; Sun, Bingxue; Feng, Jiao; Zhang, Haihong; Liu, Bin; Li, Chun; Chen, Yan; Zhang, Yong; Kong, Wei

2012-01-01

The purpose of this study was to investigate the transport mechanism of exendin-4 using Madin Darby canine kidney (MDCK) cell monolayer as an in vitro model of the human intestinal barrier. The roles of active and passive mechanisms of exendin-4 in the cell models were well studied and the corresponding contributions of the transcelluar and paracellular pathway to exendin-4 transport were also evaluated. Moreover, the apparent permeability coefficient (P(app)) values of exendin-4 were determined in the presence of chitosan, sodium decanoate and ethylenediaminetetraacetic acid (EDTA) to further confirm the relative transport mechanism and to evaluate their potential utility in future formulation design. The results revealed the low transport capacity of exendin-4 (P(app), 0.10±0.06×10(-6) cm/s). And exendin-4 transport across the cell models was time and concentration-dependence, direction and energy-independence, and similar to the passive transport marker. Drug efflux and active transport were not observed. In the presence of absorption enhancers, the P(app) value significantly increased up to 2.2-11.9 folds without apparent cytotoxicity, which is comparable to that of the paracellular transport marker. And the order of enhancement was to the effect of chitosan>EDTA>sodium decanoate, and the order of safety was sodium decanoate≈chitosan>EDTA. These findings demonstrated that exendin-4 transport across MDCK cell monolayer mainly by passive paracellular pathway, which agrees with the result of confocal laser scanning microscopy. And these absorption enhancers can be used as potential safe ingredients to improve oral efficacy of exendin-4.

Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion.

PubMed

Namjoshi, Dhananjay R; Cheng, Wai Hang; Carr, Michael; Martens, Kris M; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A; Cripton, Peter A; Wellington, Cheryl L

2016-01-01

Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8-16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI.

Determination of testosterone esters in the hair of male greyhound dogs using liquid chromatography-high resolution mass spectrometry.

PubMed

Devi, Jayasree Leela; Zahra, Paul; Vine, John H; Whittem, Ted

2018-03-01

The doping of greyhound dogs with testosterone is done in an attempt to improve their athletic performance, but such doping cannot easily be confirmed, especially in male dogs owing to the natural presence of endogenous testosterone. As testosterone is usually administered as its esters, their direct detection in hair would provide confirmatory evidence of the administration of a pharmaceutical product. This article demonstrates that the use of a liquid chromatography-high resolution mass spectrometry method with heated electrospray ionisation (HESI) combined with the use of amino solid-phase extraction (SPE) cartridges for sample clean-up, is suitable for the sensitive determination of propionate, phenyl propionate, isocaproate, decanoate, and enanthate esters of testosterone in greyhound hair. The method is linear over the range, 0.1 μg/kg-10 μg/kg, for all the testosterone esters analysed. The limits of detection (LOD) are 0.05 μg/kg for testosterone phenyl propionate, isocaproate, and decanoate, 0.025 μg/kg for testosterone propionate, and 0.25 μg/kg for testosterone enanthate. This method was applied to hair samples collected from male greyhounds before and after a single administration of a product containing several testosterone esters, each of which could be detected up to 100 days post-administration. The study also demonstrates that tail hair is the specimen of choice for the analysis of testosterone in dog hair and that washing of dogs does not impact the analysis of testosterone esters in hair. This method may be useful in racing regulation for the detection of illegitimate use of testosterone in all species. Copyright © 2017 John Wiley & Sons, Ltd.

Urinary nandrolone metabolite detection after ingestion of a nandrolone precursor.

PubMed

Watson, Phillip; Judkins, Catherine; Houghton, Ed; Russell, Caroline; Maughan, Ronald J

2009-04-01

Quantities of various anabolic/androgenic steroids have been found in dietary supplements without their presence being disclosed on the label. The aim of this study was to quantify the excretion patterns of the diagnostic metabolites, 19-norandrosterone (19-NA), and 19-noretiocholanolone (19-NE) after ingestion of small doses of 19-nor-4-androstene-3,17-dione (19-norandrostenedione). Eleven males and nine females entered the laboratory in the morning after an overnight fast. An initial urine sample was collected, and volunteers then ingested 500 mL of water containing 5 g of creatine monohydrate and 1.0, 2.5, or 5.0 microg of 19-norandrostenedione. The volume of each urine void was measured, and an aliquot was taken. Samples were analyzed for the metabolites 19-NA and 19-NE by GCMS. Baseline urinary 19-NA concentrations were 0.19 +/- 0.14 ng x mL. Ingestion of the supplement resulted in peak mean urinary 19-NA concentrations of 0.68 +/- 0.36, 1.56 +/- 0.86, and 3.89 +/- 3.11 ng.mL in the 1.0-, 2.5-, or 5.0-microg trials, respectively. Under current WADA regulations, ingestion of the 1.0-microg dose produced 0 positive doping tests, 5 subjects (20%) tested positive in the 2.5-microg trial, and 15 subjects (75%) had urinary 19-NA concentrations exceeding 2 ng x mL after ingesting creatine containing 5.0 microg of the steroid. The recovery of the ingested dose was highly variable between individuals, with values ranging from 11% to 84% (mean +/- SD = 47% +/- 18%). Ingestion of trace amounts of 19-norandrostenedione can result in transient elevations of urinary 19-NA and 19-NE concentrations. The addition of as little as 2.5 microg of 19-norandrostenedione to a supplement (0.00005% contamination) appears sufficient to result in a doping violation in some individuals.

Influence of chain length and double bond on the aqueous behavior of choline carboxylate soaps.

PubMed

Rengstl, Doris; Diat, Olivier; Klein, Regina; Kunz, Werner

2013-02-26

In preceding studies, we demonstrated that choline carboxylates ChC(m) with alkyl chain lengths of m = 12 - 18 are highly water-soluble (for m = 12, soluble up to 93 wt % soap and 0 °C). In addition, choline soaps are featured by an extraordinary lyotropic phase behavior. With decreasing water concentration, the following phases were found: micellar phase (L(1)), discontinuous cubic phase (I(1)' and I(1)"), hexagonal phase (H(1)), bicontinuous cubic phase (V(1)), and lamellar phase (L(α)). The present work is also focused on the lyotropic phase behavior of choline soaps but with shorter alkyl chains or different alkyl chain properties. We have investigated the aqueous phase behavior of choline soaps with C(8) and C(10) chain-lengths (choline octanoate and choline decanoate) and with a C(18) chain-length with a cis-double bond (choline oleate). We found that choline decanoate follows the lyotropic phase behavior of the longer-chain homologues mentioned above. Choline octanoate in water shows no discontinuous cubic phases, but an extended, isotropic micellar solution phase. In addition, choline octanoate is at the limit between a surfactant and a hydrotrope. The double bond in choline oleate leads also to a better solubility in water and a decrease of the solubilization temperature. It also influences the Gaussian curvature of the aggregates which results in a loss of discontinuous cubic phases in the binary phase diagram. The different lyotropic mesophases were identified by the penetration scan technique with polarizing light microscope and visual observations. To clarify the structural behavior small (SAXS) and wide (WAXS) angle X-ray scattering were performed. To further characterize the extended, isotropic micellar solution phase in the binary phase diagram of choline octanoate viscosity and conductivity measurements were also carried out.

Aroma-active ester profile of ale beer produced under different fermentation and nutritional conditions.

PubMed

Hiralal, Lettisha; Olaniran, Ademola O; Pillay, Balakrishna

2014-01-01

A broad range of aroma-active esters produced during fermentation are vital for the complex flavour of beer. This study assessed the influence of fermentation temperature, pH, and wort nutritional supplements on the production of yeast-derived ester compounds and the overall fermentation performance. The best fermentation performance was achieved when wort was supplemented with 0.75 g/l l-leucine resulting in highest reducing sugar and FAN (free amino nitrogen) utilization and ethanol production. At optimum fermentation pH of 5, 38.27% reducing sugars and 35.28% FAN was utilized resulting in 4.07% (v/v) ethanol. Wort supplemented with zinc sulphate (0.12 g/l) resulted in 5.01% ethanol (v/v) production and 54.32% reducing sugar utilization. Increase in fermentation temperature from 18°C to room temperature (± 22.5°C) resulted in 17.03% increased ethanol production and 14.42% and 62.82% increase in total acetate ester concentration and total ethyl ester concentration, respectively. Supplementation of worth with 0.12 g/l ZnSO4 resulted in 2.46-fold increase in both isoamyl acetate and ethyl decanoate concentration, while a 7.05-fold and 1.96-fold increase in the concentration of isoamyl acetate and ethyl decanoate, respectively was obtained upon 0.75 g/l l-leucine supplementation. Wort supplemented with l-leucine (0.75 g/l) yielded the highest beer foam head stability with a rating of 2.67, while highest yeast viability was achieved when wort was supplemented with 0.12 g/l zinc sulphate. Results from this study suggest that supplementing wort with essential nutrients required for yeast growth and optimizing the fermentation conditions could be an effective way of improving fermentation performance and controlling aroma-active esters in beer. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Analysis of Volatile Components of Cape Gooseberry (Physalis peruviana L.) Grown in Turkey by HS-SPME and GC-MS

PubMed Central

2014-01-01

Volatile components in cape gooseberry fruit at ripe stage were collected using headspace-solid phase microextraction, and analyzed by gas chromatography-mass spectrometry. Three solid phase microextraction fiber coatings (DVB/CAR/PDMS, CAR/PDMS, and PDMS/DVB) were tested for evaluation of volatile compounds. DVB/CAR/PDMS fiber showed a strong extraction capacity for volatile compounds and produced the best result in case of total peak areas. A total of 133 volatile compounds were identified in fruit pulp; among them 1-hexanol (6.86%), eucalyptol (6.66%), ethyl butanoate (6.47%), ethyl octanoate (4.01%), ethyl decanoate (3.39%), 4-terpineol (3.27%), and 2-methyl-1-butanol (3.10%) were the major components in the sample extracts. PMID:24741358

Analysis of methyloxime derivatives of intact esters of testosterone and boldenone in equine plasma using ultra high performance liquid chromatography tandem mass spectrometry.

PubMed

Gray, Bobby P; Teale, Phil; Pearce, Clive M

2011-04-01

Analysis of equine plasma samples to detect the abuse of anabolic steroids can be complicated when the parent steroid is endogenous to the animal. Anabolic steroids are usually administered intramuscularly as synthetic esters and therefore detection of the exogenous esters provides unequivocal proof of illegal administration. An ultra high performance liquid chromatography tandem mass spectrometric (UPLC-MSMS) method for the analysis of esters of testosterone (propionate, phenylpropionate, isocaproate, and decanoate) and boldenone (undecylenate) in equine plasma has been developed. Esters were extracted from equine plasma using a mixture of hexane and ethyl acetate and treated with methoxyamine hydrochloride to form methyloxime derivatives. Metenolone enanthate was used as an internal standard. After chromatographic separation, the derivatized steroid esters were quantified using selected reaction monitoring (SRM). The limit of detection for all of the steroid esters, based on a signal to noise ratio (S/N) of 3:1, was 1-3 pg/mL. The lower limit of quantification (LLOQ) for the all of the steroid esters was 5 pg/mL when 2 mL of plasma was extracted. Recovery of the steroid esters was 85-97% for all esters except for testosterone decanoate which was recovered at 62%. The intra-day coefficient of variation (CV) for the analysis of plasma quality control (QC) samples was less than 9.2% at 40 pg/mL and less than 6.0% at 400 pg/mL. The developed assay was used to successfully confirm the presence of intact testosterone esters in equine plasma samples following intramuscular injection of Durateston® (mixed testosterone esters). Copyright © 2011 John Wiley & Sons, Ltd.

[Determination of doping in human urine by gas chromatography-high resolution mass spectrometry].

PubMed

Xing, Yan-Yi; Liu, Xin; Zhang, Yu-Mei; Wang, Xiao-Bing; Xu, You-Xuan

2012-12-01

A method was evaluated for determination of twenty-one doping (including nandrolone, boldenone and methandienone) in human urine by gas chromatography-high resolution mass spectrometry. Samples were prepared by liquid-liquid extraction, concentrated, TMS derivatization and limit of detection at ng x mL(-1) by MID/GC/HRMS. According to the code of the World Anti-Doping Agency (WADA), precision and recoveries of the procedure were evaluated by replicate analysis (n = 6), the recoveries in the range of 66%-103%, with the RSD below 10.0%. The precision within the day of the method with three different concentrations was also determined RSD were less than 9.5%, 10.0% and 9.7%.

[New drugs for small animals in 2017].

PubMed

Emmerich, Ilka Ute

2018-04-01

In 2017 the active pharmaceutical ingredient Lokivetmab (Cytopoint®), a caninized anti-canine Interleukin 31 monoclonal antibody, was released on the German market for small animals. One substance was authorized for an additional species. Sarolaner, an ectoparasiticide of the isoxazoline group, is now authorized for use in combination with Selamectin (Stronghold® Plus) additionally for cats. The testosterone derivate Nandrolone (Nandrosol®) and the combination of the benzodiazepine Zolazepam with the "dissociative anesthetic" Tiletamine (Zoletil®) were once again authorized. Furthermore, two veterinary drugs with a new combination of active ingredients, one drug with a new active ingredient and two veterinary drugs with a new pharmaceutical form have been launched on the market for small animals. Schattauer GmbH.

Chronic Exposure to Androgenic-Anabolic Steroids Exacerbates Axonal Injury and Microgliosis in the CHIMERA Mouse Model of Repetitive Concussion

PubMed Central

Namjoshi, Dhananjay R.; Cheng, Wai Hang; Carr, Michael; Martens, Kris M.; Zareyan, Shahab; Wilkinson, Anna; McInnes, Kurt A.; Cripton, Peter A.; Wellington, Cheryl L.

2016-01-01

Concussion is a serious health concern. Concussion in athletes is of particular interest with respect to the relationship of concussion exposure to risk of chronic traumatic encephalopathy (CTE), a neurodegenerative condition associated with altered cognitive and psychiatric functions and profound tauopathy. However, much remains to be learned about factors other than cumulative exposure that could influence concussion pathogenesis. Approximately 20% of CTE cases report a history of substance use including androgenic-anabolic steroids (AAS). How acute, chronic, or historical AAS use may affect the vulnerability of the brain to concussion is unknown. We therefore tested whether antecedent AAS exposure in young, male C57Bl/6 mice affects acute behavioral and neuropathological responses to mild traumatic brain injury (TBI) induced with the CHIMERA (Closed Head Impact Model of Engineered Rotational Acceleration) platform. Male C57Bl/6 mice received either vehicle or a cocktail of three AAS (testosterone, nandrolone and 17α-methyltestosterone) from 8–16 weeks of age. At the end of the 7th week of treatment, mice underwent two closed-head TBI or sham procedures spaced 24 h apart using CHIMERA. Post-repetitive TBI (rTBI) behavior was assessed for 7 d followed by tissue collection. AAS treatment induced the expected physiological changes including increased body weight, testicular atrophy, aggression and downregulation of brain 5-HT1B receptor expression. rTBI induced behavioral deficits, widespread axonal injury and white matter microgliosis. While AAS treatment did not worsen post-rTBI behavioral changes, AAS-treated mice exhibited significantly exacerbated axonal injury and microgliosis, indicating that AAS exposure can alter neuronal and innate immune responses to concussive TBI. PMID:26784694

Influence of delivery mode on the urinary excretion of nandrolone metabolites.

PubMed

Watson, Phillip; Houghton, Ed; Grace, Philip B; Judkins, Catherine; Dunster, Paula M; Maughan, Ronald J

2010-04-01

This study examined the influence of a supplement matrix on the excretion pattern of nandrolone metabolites in response to ingestion of a trace amount of 19-norandrostenedione. Ten male and nine female volunteers (mean ± SD: age = 26 ± 3 yr, height = 1.71 ± 0.09 m, body mass = 70.9 ± 13.2 kg) were recruited. On two occasions, subjects entered the laboratory in the morning after an overnight fast. After an initial urine collection, subjects ingested either 500 mL of plain water or a commercially available energy bar; 10 µg of 19-norandrostenedione was added to each. The volume of each urine sample passed during the next 24 h was measured, and an aliquot was retained for analysis. All samples were analyzed for the metabolites 19-norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) by gas chromatography-mass spectrometry. The total volume of urine passed was higher in the water trial (2.10 ± 0.52 L) than in the bar trial (1.85 ± 0.55 L; P = 0.040). Baseline urinary 19-NA concentrations were all below the limit of quantification for the assay. Peak urinary 19-NA was lower (P = 0.002) in the water trial (4.80 ± 2.84 ng·mL(-1)) than in the bar trial (8.46 ± 4.44 ng·mL(-1)). The time elapsed between ingestion of the supplement and the peak urinary 19-NA concentration was longer (P = 0.023) on the bar trial (4.6 ± 2.4 h) than on the water trial (2.8 ± 1.9 h). There was no difference in the total recovery of 19-NA + 19-NE between the liquid and solid supplements (water 30 ± 10%; bar 28 ± 12%; P < 0.140). Peak 19-NA concentrations were higher, and occurred later, when the 19-norandrostenedione was added to a solid supplement. This may be due to a slower rate of absorption and/or a reduced diuresis, resulting in a longer period for the metabolites to accumulate in the urine.

Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease.

PubMed

Cunnane, Stephen C; Courchesne-Loyer, Alexandre; St-Pierre, Valérie; Vandenberghe, Camille; Pierotti, Tyler; Fortier, Mélanie; Croteau, Etienne; Castellano, Christian-Alexandre

2016-03-01

Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed. © 2016 New York Academy of Sciences.

Norandrosterone and noretiocholanolone concentration before and after submaximal standardized exercise.

PubMed

de Geus, B; Delbeke, F; Meeusen, R; Van Eenoo, P; De Meirleir, K; Busschaert, B

2004-10-01

19-Norandrosterone (19-NA) and 19-noretiocholanolone (19-NE) are the two main urinary indicators used to detect illegal use of nandrolone. Recent studies showed that 19-NA and 19-NE can be endogenously produced in non-treated humans. The concentrations were close to the threshold of the International Olympic Committee (IOC), i.e. 2 ng/ml for men and seem to increase after prolonged intense effort. Androgens are involved in the biosynthesis of estrogens and estrogen has a protective effect against skeletal muscle damage following eccentric exercise. Furthermore, the testicular tissue can synthesize 19-norandrogens from androgens, we hypothetisize that the 19-norandrogen production might be influenced by muscle damage following eccentric exercise. Therefore the purpose of this study is to examine if three different exercise methods will influence the urinary concentration of 19-NA and 19-NE in healthy young subjects. Fifteen amateur hockey players undertook a 30 min submaximal standardized exercise protocol. They were randomised for three different types of exercise, namely a cycle ergometer test (cyclic muscle activity), a treadmill test (concentric muscle activity), or a bench-steptest (eccentric muscle activity) at a target heart rate corresponding to 65 % (+/- 5 %) of Karvonen heart rate. Urine samples were obtained before the test and 60 min and 120 min after the end of exercise. Subjects completed a Likert scale of muscle soreness before and 12 h after exercise. 19-NA and 19-NE were determined by gas chromatography-tandem mass spectrometry (GC-MS-MS). Baseline urinary 19-NA and 19-NE concentrations were under limit of detection of 0.05 ng/ml, except for one sample (0.13 ng/ml). No 19-NA or 19-NE could be detected post exercise. In our experimental conditions, the exercise mode (eccentric or concentric) had no impact on 19-NA or 19-NE excretion. Our findings confirm that the current International Olympic Committee threshold level for nandrolone metabolites is sufficiently high to avoid false positive cases.

Carcinostatic effects of diverse ascorbate derivatives in comparison with aliphatic chain moiety structures: Promotion by combined hyperthermia and reduced cytotoxicity to normal cells.

PubMed

Asada, Ryoko; Kageyama, Katsuhiro; Tanaka, Hiroshi; Kimura, Masatugu; Saitoh, Yasukazu; Miwa, Nobuhiko

2012-05-01

In this study, using human tongue squamous carcinoma cells (HSC-4) carcinostatic activity was compared for diverse L-ascorbic acid (Asc) derivatives, including the 'straight-C(16)-chain types', 6-O-palmitoyl-Asc (A6-P) and Asc-2-phosphate-6-O-palmitate sodium salt (APPS), as well as the 'branched-C(16)-chain types', Asc-2-phosphate-6-O-(2'-hexyl)decanoate (APHD), an isomer of APPS, and Asc-2,3,5,6-O-tetra-(2'-hexyl)decanoate (VCIP). The order of magnitude of the carcinostatic effects at 37°C was: APPS>A6-P = APHD>VCIP and at 42°C was APPS = A6-P>APHD>VCIP. Therefore, the two straight-C(16)-chain derivatives, APPS and A6-P, had a greater effect compared to the two branched-C(16)-chain Asc derivatives, which are considered to have more difficulty with 'orientation along cell-membrane-glycerolipid direction'. APPS-treated HCS-4 cells were observed for a decrease in cell number, cell shrinkage, pycnosis indicative of apoptosis and cell deformation. The order of cytotoxicity for the normal human dermal fibroblasts (OUMS-36) at 37°C was: A6-P (50% inhibitory concentration: 150-300 μM)>APHD (450-600 μM)>Asc = APPS (800-1000 μM). Accordingly, APHD was more cytotoxic than APPS, since the straight-C(16)-chain type, which was eliminated after the enzymatic esterolysis of APPS, is metabolized via the 'fatty acid β-oxidation cycle' more efficiently in normal cells. Thus, APPS had a greater advantage over APHD, A6-P and VCIP in terms of carcinostatic effects at 37°C, carcinostasis promotion at 42°C and a decrease of cytotoxicity to normal cells. This observation suggests a marked potential for aliphatic chain-moiety structures as anticancer agents, due to their cancer-selective carcinostasis and combined efficacy with hyperthermia, without causing side effects.

Analysis of volatile components of cape gooseberry (Physalis peruviana L.) grown in Turkey by HS-SPME and GC-MS.

PubMed

Yilmaztekin, Murat

2014-01-01

Volatile components in cape gooseberry fruit at ripe stage were collected using headspace-solid phase microextraction, and analyzed by gas chromatography-mass spectrometry. Three solid phase microextraction fiber coatings (DVB/CAR/PDMS, CAR/PDMS, and PDMS/DVB) were tested for evaluation of volatile compounds. DVB/CAR/PDMS fiber showed a strong extraction capacity for volatile compounds and produced the best result in case of total peak areas. A total of 133 volatile compounds were identified in fruit pulp; among them 1-hexanol (6.86%), eucalyptol (6.66%), ethyl butanoate (6.47%), ethyl octanoate (4.01%), ethyl decanoate (3.39%), 4-terpineol (3.27%), and 2-methyl-1-butanol (3.10%) were the major components in the sample extracts.

A complementary set of electrochemical and X-ray synchrotron techniques to determine the passivation mechanism of iron treated in a new corrosion inhibitor solution specifically developed for the preservation of metallic artefacts

NASA Astrophysics Data System (ADS)

Mirambet, F.; Reguer, S.; Rocca, E.; Hollner, S.; Testemale, D.

2010-05-01

Metallic artefacts of the cultural heritage are often stored in uncontrolled environmental conditions. They are very sensitive to atmospheric corrosion caused by a succession of wet and dry periods due to variations of relative humidity and temperature. To avoid the complete degradation of the metallic artefacts, new preventive strategies must be developed. In this context, we have studied new compounds based on sodium carboxylates solutions CH3(CH2) n-2COO-, Na+ hereafter called NaC n . They allow the formation of a passive layer at the metallic surface composed of a metal-carboxylate complex. To understand the action of those inhibitors in the passivation process of iron we have performed electrochemical measurements and surface characterisation. Moreover, to monitor in real time the growth of the coating, in situ X-ray absorption spectroscopy (XAS) experiments at iron K-edge were carried out in an electrochemical cell. These analyses have shown that in the case of NaC10 solution, the protection of iron surface is correlated to the precipitation of a well-organised layer of FeC10. These experiments confirmed that this compound is a fully oxidised trinuclear Fe(III) complex containing decanoate anions as ligands. Such information concerning the passive layer is a key factor to evaluate its stability and finally the long-term efficiency of the protection treatment.

Preparation and electrical properties of oil-based magnetic fluids

NASA Astrophysics Data System (ADS)

Sartoratto, P. P. C.; Neto, A. V. S.; Lima, E. C. D.; Rodrigues de Sá, A. L. C.; Morais, P. C.

2005-05-01

This paper describes an improvement in the preparation of magnetic fluids for electrical transformers. The samples are based on surface-coated maghemite nanoparticles dispersed in transformer insulating oil. Colloidal stability at 90°C was higher for oleate-grafted maghemite-based magnetic fluid, whereas decanoate and dodecanoate-grafted samples were very unstable. Electrical properties were evaluated for samples containing 0.80%-0.0040% maghemite volume fractions. Relative permittivity varied from 8.8 to 2.1 and the minimum value of the loss factor was 12% for the most diluted sample. The resistivity falls in the range of 0.7-2.5×1010Ωm, whereas the ac dielectric strength varied from 70to79kV. These physical characteristics reveal remarkable step forward in the properties of the magnetic fluid samples and may result in better operation of electrical transformers.

Synthesis of medium-chain length capsinoids from coconut oil catalyzed by Candida rugosa lipases.

PubMed

Trbojević Ivić, Jovana; Milosavić, Nenad; Dimitrijević, Aleksandra; Gavrović Jankulović, Marija; Bezbradica, Dejan; Kolarski, Dušan; Veličković, Dušan

2017-03-01

A commercial preparation of Candida rugosa lipases (CRL) was tested for the production of capsinoids by esterification of vanillyl alcohol (VA) with free fatty acids (FA) and coconut oil (CO) as acyl donors. Screening of FA chain length indicated that C8-C12 FA (the most common FA found in CO triglycerides) are the best acyl-donors, yielding 80-85% of their specific capsinoids. Hence, when CO, which is rich in these FA, was used as the substrate, a mixture of capsinoids (vanillyl caprylate, vanillyl decanoate and vanillyl laurate) was obtained. The findings presented here suggest that our experimental method can be applied for the enrichment of CO with capsinoids, thus giving it additional health promoting properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

The metabolism of anabolic-androgenic steroids in the greyhound.

PubMed

McKinney, Andrew R; Cawley, Adam T; Young, E Bruce; Kerwick, Carmel M; Cunnington, Karen; Stewart, Rhiannon T; Ambrus, Joseph I; Willis, Anthony C; McLeod, Malcolm D

2013-04-01

Effective control of the use of anabolic-androgenic steroids (AASs) in animal sports is essential in order to ensure both animal welfare and integrity. In order to better police their use in Australian and New Zealand greyhound racing, thorough metabolic studies have been carried out on a range of registered human and veterinary AASs available in the region. Canine metabolic data are presented for the AASs boldenone, danazol, ethylestrenol, mesterolone, methandriol, nandrolone and norethandrolone. The principal Phase I metabolic processes observed were the reduction of A-ring unsaturations and/or 3-ketones with either 3α,5β- or 3β,5α-stereochemistry, the oxidation of secondary 17β-hydroxyl groups and 16α-hydroxylation. The Phase II β-glucuronylation of sterol metabolites was extensive. The presented data have enabled the effective analysis of AASs and their metabolites in competition greyhound urine samples.

Analysis of 19-nortestosterone residue in animal tissues by ion-trap gas chromatography-tandem mass spectrometry*

PubMed Central

Jiang, Jin-qing; Zhang, Lei; Li, Guang-ling; Zhang, Hai-tang; Yang, Xue-feng; Liu, Jun-wei; Li, Ren-feng; Wang, Zi-liang; Wang, Jian-hua

2011-01-01

A rapid sample treatment procedure for the gas chromatography-tandem mass spectrometry (GC-MS) determination of 19-nortestosterone (19-NT) in animal tissues has been developed. In our optimized procedures, enzymatic hydrolysis with β-glucuronidase from Escherichia coli was performed in an acetate buffer (pH 5.2, 0.2 mol/L). Next, the homogenate was mixed with methanol and heated at 60 °C for 15 min, then placed in an ice-bath at −18 °C for 2 h. After liquid-liquid extraction with n-hexane, the analytes were subjected to a normal-phase solid phase extraction (SPE) C18 cartridge for clean-up. The dried organic extracts were derivatized with heptafluorobutyric anhydride (HFBA), and then the products were injected into GC-MS. Using electron impact mass spectrometry (EI-MS) with positive chemical ionization (PCI), four diagnostic ions (m/z 666, 453, 318, and 306) were determined. A standard calibration curve over the concentration range of 1–20 ng/g was reached, with Y=467 084X−68 354 (R 2=0.999 7) for 19-NT, and the detection limit was 0.3 ng. When applied to spiked samples collected from bovine and ovine, the recoveries ranged from 63% to 101% with relative standard deviation (RSD) between 2.7% and 8.9%. The procedure is a highly efficient, sensitive, and more economical method which offers considerable potential to resolve cases of suspected nandrolone doping in husbandry animals. PMID:21634039

A report on alterations to the speaking and singing voices of four women following hormonal therapy with virilizing agents.

PubMed

Baker, J

1999-12-01

Four women aged between 27 and 58 years sought otolaryngological examination due to significant alterations to their voices, the primary concerns being hoarseness in vocal quality, lowering of habitual pitch, difficulty projecting their speaking voices, and loss of control over their singing voices. Otolaryngological examination with a mirror or flexible laryngoscope revealed no apparent abnormality of vocal fold structure or function, and the women were referred for speech pathology with diagnoses of functional dysphonia. Objective acoustic measures using the Kay Visipitch indicated significant lowering of the mean fundamental frequency for each woman, and perceptual analysis of the patients' voices during quiet speaking, projected voice use, and comprehensive singing activities revealed a constellation of features typically noted in the pubescent male. The original diagnoses of a functional dysphonia were queried, prompting further exploration of each woman's medical history, revealing in each case onset of vocal symptoms shortly after commencing treatment for conditions with medications containing virilizing agents (eg, Danocrine (danazol), Deca-Durabolin (nandrolene decanoate), and testosterone). Although some of the vocal symptoms decreased in severity with the influences from 6 months voice therapy and after withdrawal from the drugs, a number of symptoms remained permanent, suggesting each subject had suffered significant alterations in vocal physiology, including muscle tissue changes, muscle coordination dysfunction, and propioceptive dysfunction. This retrospective study is presented in order to illustrate that it was both the projected speaking voice and the singing voice that proved so highly sensitive to the virilization effects. The implications for future prospective research studies and responsible clinical practice are discussed.

Rapid Determination of Surfactant Critical Micelle Concentrations Using Pressure-Driven Flow with Capillary Electrophoresis Instrumentation

PubMed Central

Stanley, F. E.; Warner, A. M.; Schneiderman, E.; Stalcup, A. M.

2009-01-01

This work demonstrates a novel, convenient utilization of capillary electrophoresis (CE) instrumentation for the determination of critical micelle concentrations (CMCs). Solution viscosity differences across a range of surfactant concentrations were monitored by hydrodynamically forcing an analyte towards the detector. Upon reaching the surfactant's CMC value, migration times were observed to change drastically. CMC values for four commonly employed anionic surfactants were determined - sodium dodecyl sulfate: 8.1 mM; sodium caprylate- 300 mM; sodium decanoate- 86 mM; sodium laurate- 30 mM; and found to be in excellent agreement with values previously reported in the literature. The technique was then applied to the less well-characterized nonionic surfactants poly(oxyethylene) 8 myristyl ether (CMC ~ 9 μM), poly(oxyethylene) 8 decyl ether (CMC ~ 0.95 mM) and poly(oxyethylene) 4 lauryl ether. PMID:19836753

Characterization of Aronia melanocarpa volatiles by headspace-solid-phase microextraction (HS-SPME), simultaneous distillation/extraction (SDE), and gas chromatography-olfactometry (GC-O) methods.

PubMed

Kraujalytė, Vilma; Leitner, Erich; Venskutonis, Petras Rimantas

2013-05-22

The profiles of volatile constituents of berry fruit of two Aronia melanocarpa genotypes were evaluated by headspace-solid-phase microextraction (HS-SPME), simultaneous distillation and extraction (SDE), and gas chromatography-olfactometry (GC-O). In total, 74 volatile compounds were identified in chokeberry juice, 3-penten-2-one, 3,9-epoxy-p-menth-1-ene, and benzaldehyde being the most abundant constituents; however, their percentage concentrations were remarkably different in the HS-SPME and SDE profiles. Twenty two aroma-active compounds were detected and characterized by the trained panelists in HS-SPME using GC-O detection frequency analysis. Olfactometry revealed that ethyl-2-methyl butanoate, ethyl-3-methyl butanoate, ethyl decanoate ("fruity" aroma notes), nonanal ("green" notes), unidentified compound possessing "moldy" odor, and some other volatiles may be very important constituents in formation of chokeberry aroma of both analyzed plant cultivars.

[Cost-effectiveness analysis of schizophrenic patient care settings: impact of an atypical antipsychotic under long-acting injection formulation].

PubMed

Llorca, P M; Miadi-Fargier, H; Lançon, C; Jasso Mosqueda, G; Casadebaig, F; Philippe, A; Guillon, P; Mehnert, A; Omnès, L F; Chicoye, A; Durand-Zaleski, I

2005-01-01

Schizophrenia is a disease affecting the young adults and amounts to approximately 300,000 people in France. The French public psychiatric sector takes care of approximately 150,000 adults schizophrenics: 50% benefit from ambulatory care, 50% are in partial or full-time hospitalization care. Schizophrenia represents the first diagnosis that psychiatric sectors take in charge. The costs associated with schizophrenia, mainly hospital costs, are important and were estimated at 2% of the total medical costs in France. In the French social welfare system, the social costs (pensions, allowances, managements of custody or guardianship by social workers) are also to be taken into account: it amounts to a third of the global direct cost. Schizophrenia also generates indirect costs (losses of productivity and premature deaths) which would be at least equal, or even more important, than direct medical costs. The non-compliance to the antipsychotic treatment is a major problem with people suffering from schizophrenia. Indeed the lack of compliance to the treatment, estimated at 20 to 40%, is a major handicap for schizophrenic patient stabilization. The poor level of compliance is due to many various causes: adverse effects that are considered unbearable, medicine viewed as persecutory, negation of the disease, nostalgia for the productive phases of the disease, lack of social support, complexity of the prescription, relapse itself. Compliance is thus influenced by the patient's clinical features, local provision of health care and the specific nature of the drug (adverse effects, pharmaceutical formulation). The atypical antipsychotics present fewer extrapyramidal side effects and reduce the cognitive deficits associated with the disease, which results in improved compliance. Long-acting injectable antipsychotics allow a better therapeutic compliance and thus better efficacy of the treatment. Several studies have shown a significant improvement in compliance related to the pharmaceutical formulation of antipsychotics. Hospitalization and relapse risks are lower in compliant than in non-compliant patients. The main objective of this pharmacoeconomic analysis is to evaluate the impact in terms of medical benefits and costs of the following strategies: 1. Risperidone long-acting injection: first long-acting injectable atypical antipsychotic; 2. Haloperidol depot: long-acting injectable conventional neuroleptic; 3. Olanzapine: atypical antipsychotic available commercially in oral formulation. The target population defined for the study are young schizophrenic patients treated for at least 1 year and whose disorder has not been diagnosed for longer than 5 years. The time horizon is 2 years. A cost-effectiveness analysis is performed. The perspective adopted is the French Health System. The main hypothesis of the model is that an increase in compliance linked to the use of long-acting injectable formulation could lead to an increased efficacy and a modification of the cost-effectiveness ratio. A decision tree was built. Six periods of follow-up are identified with a duration of 4-months per period. The tree contains 3 principal arms, each one corresponding to a specific treatment: risperidone LA injection, haloperidol decanoate and olanzapine. For each arm, at the chance node, two health states are identified: either the patient responds favourably to the treatment or does not respond favourably and requires a switch to another drug treatment. After a period of response, the patient can either remain in the same state or experiences a clinical deterioration. If the patient presents a clinical deterioration, he can either go back to a positive response state after a period of intensive follow-up or remain in an insufficient response state; in this case, a change of antipsychotic treatment is necessary. In the model, a patient should receive four different treatments before a long-term hospitalization takes put in place. According to the market authorization labelling, clozapine is proposed only as a 2nd or 3rd line therapeutic option, so when at least one or two successive neuroleptics have failed. The efficacy data used in the model are provided by clinical research recently published. These studies estimate the efficacy of oral risperidone, LA risperidone, olanzapine, and treatment by haloperidol. When available data in the literature were insufficient, the opinion of experts was sought. The effectiveness criteria is the rate of patients treated successfully: patients responding to the initial treatment with the possibility of experiencing one or two episodes of clinical deterioration but without requiring a switch to another drug during 2 years of follow-up. The base case is as follows: efficacy for oral risperidone is used for the LA risperidone strategy, increased by 10% within the first 4 months of follow-up; efficacy for oral haloperidol is used for haloperidol depot, increased by 5% within the first 4 months of follow-up; for olanzapine, observed data in clinical trials were applied. The hypotheses for long acting forms are rather conservative because the increase of efficacy which can be expected for the long-acting injectable formulations varies between 5% to more than 30% according to the literature data. The analysis of sensibility includes three scenarios: scenario 1: for LA risperidone, 5% of patients treated successfully improvement in regard to oral risperidone instead of 10% in the base case; scenario 2: for haloperidol depot, 10% of patients treated successfully improvement in regard of oral haloperidol instead of 5% in the base case; scenario 3: the results of an open trial conducted within the framework of the LA risperidone license are used, leading to an increase of up to 13,3% of the rate of successfully treated patients, compared to oral risperidone literature data. As for the side effects, only extrapyramidal symptoms were considered. Other side effects are described in the literature such as the obesity or the occurrence of a diabetes; these effects were not taken into account in the model, their impact on the cove-rage of schizophrenic patients and on resources utilisation being poorly known. Only direct medical costs were considered in the pharmaco-economic analysis. Two types of costs were identified: hospital costs and community care costs. The stays in overnight hospitalisation and day hospitalisation were derived from the Disease Related Groups (DRG) and valued from the data of the National Cost Study (Etude Nationale de Coûts; 1999). The DRGs corresponding to the diagnosis of schizophrenia are the DRG 627 (complete hospitalization) and DRG 819 (day hospitalisation). Ambulatory care: procedures and visits, were valued in euros in reference with the tariffs for reimbursement issued in the Naming General of the Professional Acts (NGAP) and published by the French National Health Insurance (Year 2001). Medication consumption was quantified by using the daily dosage specified in the the MAA and the French prescription database IMS-Dorema. The cost of medicines was valued from tariffs 2001 (SEMPEX). LA risperidone price being not fixed to date, the reserved hypothesis is a 141,62 Euro retail price. As schizophrenia is listed among the diseases reimbursed at a 100% rate by the Health insurance, out of pocket expenses by patient are not considered in the analysis. The cost for the extrapyramidal effects was attributed to all the strategies. This cost was calculated according to the rates of extrapyramidal effects occurrence collected in the literature. Globally, in the published studies, the incidence of the side effects for the patients treated by olanzapine or risperidone is similar. It was thus decided by the experts to use the same rate of occurrence for extrapyramidal effects for olanzapine and risperidone (20%). This rate is 40% for haloperidol decanoate, 10% for oral clozapine. For the cost estimation, the expenses for treating a schizophrenic patient for two years were taken into account. The results show that in two years, LA risperidone is more effective than the two other antipsychotics. After 2 years, the rate of patients treated successfully is 82,7% for LA risperidone, 74,8% for olanzapine and 57,3% for haloperidol depot. The 2 year-cost per patient treated by LA risperidone is 14,055 Euro. This cost is 14,351 Euro and 17,203 Euro respectively for the strategies olanzapine and haloperidol depot. The cost-efficacy ratios per patient successfully treated are 16,995 Euro for the strategy LA risperidone, 19,186 Euro for olanzapine and 30,023 Euro for haloperidol depot. LA risperidone is a dominant strategy compared with both olanzapine and haloperidol depot. Scenario 1 shows that LA risperidone strategy remains the most effective. Indeed, this strategy allows a response increase of 3,5% regarding olanzapine strategy and of 21% regarding haloperidol depot strategy. Under the hypothesis tested in scenario 1, LA risperidone is a partial dominant strategy against olanzapine and a total dominant strategy against haloperidol depot. In scenario 2, as efficacy is improved for haloperidol decanoate (61,10%), a decrease of 1,763 Euro in the cost per patient treated is observed for this strategy. Cost per patient treated successfully and efficacy for LA risperidone and olanzapine are the same than in the base case. LA risperidone is a total dominant strategy against olanzapine and haloperidol decanoate. In scenario 3, the rate of patients treated successfully at 2 years is 88,6% for LA risperidone with a cost per patient of 12,347 Euro. LA risperidone is dominant against olanzapine and haloperidol depot. The schizophrenia is a relatively frequent disease. (ABSTRACT TRUNCATED)

Monitoring the evolution of volatile compounds using gas chromatography during the stages of production of Moscatel sparkling wine.

PubMed

Soares, Rafael Dutra; Welke, Juliane Elisa; Nicolli, Karine Primieri; Zanus, Mauro; Caramão, Elina Bastos; Manfroi, Vitor; Zini, Cláudia Alcaraz

2015-09-15

This study reports, for the first time, the main changes that occur with some important aroma compounds of Moscatel sparkling wines during winemaking, measured using headspace solid-phase microextraction, one-dimensional and comprehensive two-dimensional gas chromatography (GC×GC) with mass spectrometry detection (MS). The best conditions of volatile extraction included the use of PDMS/DVB fibre, 2mL of wine, 30% of NaCl, 40°C for 30min. The chromatographic profile of sparkling wines showed decreasing amounts of monoterpenes (limonene, 4-terpineol, terpinolene, citronellol, α-terpineol, linalool, hotrienol, and nerol oxide), increasing amounts of esters (terpenyl esters, ethyl octanoate, ethyl decanoate and hexyl acetate) and alcohols (1-nonanol and 2-phenylethanol). Sixty-nine compounds co-eluted in the first dimension; only six co-eluted in the second dimension. GC×GC/TOFMS allows more detailed study of the volatile profile of sparkling wines. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

PubMed Central

Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

2015-01-01

This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

Contamination of supplements: an interview with professor Ron Maughan by Louise M. Burke.

PubMed

Maughan, Ron

2004-08-01

This issue of IJSNEM features two articles related to supplement use by athletes. In one (Morrison et al. 2004), people who undertake regular exercise in a gym were found to report the use of a wide variety of supplements. The other paper (Goel et al. 2004) dealt with one of the issues that a sub-group of athletes need to consider before deciding to take supplements - the risk of a positive drug test if the product contains substances banned by the anti-doping codes under which their sport is conducted. This issue received much publicity earlier in the year when top tennis player Greg Rusedski tested positive for the steroid nandrolone as the result of inadvertent intake via a contaminated supplement. In this article, Professor Ron Maughan, Chair of Sports Nutrition at Loughborough University in the United Kingdom, advisor to the British Olympic team, and co-editor of IJSNEM, provides his insight on this important topic.

Sudden or unnatural deaths involving anabolic-androgenic steroids.

PubMed

Darke, Shane; Torok, Michelle; Duflou, Johan

2014-07-01

Anabolic-androgenic steroids (AASs) are frequently misused. To determine causes of death, characteristics, toxicology, and pathology of AAS positive cases, all cases (n = 24) presenting to the New South Wales Department of Forensic Medicine (1995-2012) were retrieved. All were male, and the mean age was 31.7 years. Deaths were mainly due to accidental drug toxicity (62.5%), then suicide (16.7%) and homicide (12.5%). Abnormal testosterone/epitestosterone ratios were reported in 62.5%, followed by metabolites of nandrolone (58.3%), stanozolol (33.3%), and methandienone (20.8%). In 23 of 24 cases, substances other than steroids were detected, most commonly psychostimulants (66.7%). In nearly half, testicular atrophy was noted, as was testicular fibrosis and arrested spermatogenesis. Left ventricular hypertrophy was noted in 30.4%, and moderate to severe narrowing of the coronary arteries in 26.1%. To summarize, the typical case was a male polydrug user aged in their thirties, with death due to drug toxicity. Extensive cardiovascular disease was particularly notable. © 2014 American Academy of Forensic Sciences.

Spectroscopy reveals that ethyl esters interact with proteins in wine.

PubMed

Di Gaspero, Mattia; Ruzza, Paolo; Hussain, Rohanah; Vincenzi, Simone; Biondi, Barbara; Gazzola, Diana; Siligardi, Giuliano; Curioni, Andrea

2017-02-15

Impairment of wine aroma after vinification is frequently associated to bentonite treatments and this can be the result of protein removal, as recently demonstrated for ethyl esters. To evaluate the existence of an interaction between wine proteins and ethyl esters, the effects induced by these fermentative aroma compounds on the secondary structure and stability of VVTL1, a Thaumatin-like protein purified from wine, was analyzed by Synchrotron Radiation Circular Dichroism (SRCD) spectroscopy. The secondary structure of wine VVTL1 was not strongly affected by the presence of selected ethyl esters. In contrast, VVTL1 stability was slightly increased by the addition of ethyl-octanoate, -decanoate and -dodecanoate, but decreased by ethyl-hexanoate. This indicates the existence of an interaction between VVTL1 and at least some aroma compounds produced during fermentation. The data suggest that proteins removal from wine by bentonite can result in indirect removal of at least some aroma compounds associated with them. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis of a Novel Series of 2-Methylsulfanyl Fatty Acids and their Toxicity on the Human K-562 and U-937 Leukemia Cell Lines

PubMed Central

Carballeira, Néstor M.; Miranda, Carlos; Orellano, Elsie A.; González, Fernando A.

2006-01-01

The hitherto unknown 2-methylsulfanyldecanoic acid and 2-methylsulfanyldodecanoic acid were synthesized from methyl decanoate and methyl dodecanoate, respectively, through the reaction of lithium diisopropylamide and dimethyldisulfide in THF followed by saponification with potassium hydroxide in ethanol. Both α-methylsulfanylated FA were cytotoxic to the human chronic myelogenous leukemia K-562 and the human histiocytic lymphoma U-937 cell lines with EC50 values in the 200-300 μM range, which makes them more cytotoxic to these cell lines than either decanoic acid or dodecanoic acid. The cytotoxicity of the studied FA towards K-562 followed the order: 2-SCH3-12:0 > 2-SCH3-10:0 > 10:0 > 12:0 > 2-OCH3-12:0, while towards U-937 the cytotoxicity was found to be: 2-SCH3-10:0 > 2-SCH3-12:0 > 12:0 > 10:0 > 2-OCH3-12:0. These results indicate that the α-methylsulfanyl substitution increases the cytotoxicity of the C10 and C12 fatty acids towards the studied leukemia cell lines. PMID:16382579

Analysis of confiscated black market drugs using chromatographic and mass spectrometric approaches.

PubMed

Thevis, Mario; Schrader, Yvonne; Thomas, Andreas; Sigmund, Gerd; Geyer, Hans; Schänzer, Wilhelm

2008-04-01

In the context of house searches in Germany, numerous drugs were confiscated and subjected to chemical analysis, including anabolic agents such as various anabolic-androgenic steroids (stanozolol, testosterone derivatives, trenbolone esters, etc.) and clenbuterol, as well as agents with anti-estrogenic activity (tamoxifen, clomiphene), drugs stimulating virility (sildenafil, tadalafil), and unlabeled plastic bags. Liquid chromatography-tandem mass spectrometry, gas chromatography-mass spectrometry with nitrogen-phosphorus specific detection, gel electrophoresis, and immunological tests were employed to test for the effective content of 70 products. In 18 cases (25.7%), the declared ingredients differed from the actual content, in particular concerning anabolic-androgenic steroids. Nandrolone and trenbolone esters, for instance, were frequently substituted or complemented by various testosterone derivatives, and several testosterone depot formulations originally composed of four different esters were found to contain fewer or wrong components. Except for those drugs supposedly originating from so-called underground labs, fake packings were hardly or not distinguishable from original boxes by visual inspection.

GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-mdx mouse model of muscular dystrophy.

PubMed

Cozzoli, Anna; Capogrosso, Roberta Francesca; Sblendorio, Valeriana Teresa; Dinardo, Maria Maddalena; Jagerschmidt, Catherine; Namour, Florence; Camerino, Giulia Maria; De Luca, Annamaria

2013-06-01

Anabolic drugs may counteract muscle wasting and dysfunction in Duchenne muscular dystrophy (DMD); however, steroids have unwanted side effects. We focused on GLPG0492, a new non-steroidal selective androgen receptor modulator that is currently under development for musculo-skeletal diseases such as sarcopenia and cachexia. GLPG0492 was tested in the exercised mdx mouse model of DMD in a 4-week trial at a single high dose (30 mg/kg, 6 day/week s.c.), and the results were compared with those from the administration of α-methylprednisolone (PDN; 1 mg/kg, i.p.) and nandrolone (NAND, 5 mg/kg, s.c.). This assessment was followed by a 12-week dose-dependence study (0.3-30 mg/kg s.c.). The outcomes were evaluated in vivo and ex vivo on functional, histological and biochemical parameters. Similar to PDN and NAND, GLPG0492 significantly increased mouse strength. In acute exhaustion tests, a surrogate of the 6-min walking test used in DMD patients, GLPG0492 preserved running performance, whereas vehicle- or comparator-treated animals showed a significant increase in fatigue (30-50%). Ex vivo, all drugs resulted in a modest but significant increase of diaphragm force. In parallel, a decrease in the non-muscle area and markers of fibrosis was observed in GLPG0492- and NAND-treated mice. The drugs exerted minor effects on limb muscles; however, electrophysiological biomarkers were ameliorated in extensor digitorum longus muscle. The longer dose-dependence study confirmed the effect on mdx mouse strength and resistance to fatigue and demonstrated the efficacy of lower drug doses on in vivo and ex vivo functional parameters. These results support the interest of further studies of GLPG0492 as a potential treatment for DMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

A prospective trial of customized adherence enhancement plus long-acting injectable antipsychotic medication in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder

PubMed Central

Sajatovic, Martha; Levin, Jennifer; Ramirez, Luis F.; Hahn, David Y.; Tatsuoka, Curtis; Bialko, Christopher S.; Cassidy, Kristin A.; Fuentes-Casiano, Edna; Williams, Tiffany D.

2014-01-01

Background Treatment non-adherence in people with schizophrenia is associated with relapse and homelessness. Building upon the usefulness of long-acting medication, and our work in psychosocial interventions to enhance adherence, we conducted a prospective uncontrolled trial of customized adherence enhancement (CAE) plus long-acting injectable antipsychotic (LAI) using haloperidol decanoate in 30 homeless or recently homeless individuals with schizophrenia and schizoaffective disorder. Methods Participants received monthly CAE and LAI (CAE-L) for 6 months. Primary outcomes were adherence as measured by the Tablets Routine Questionnaire (TRQ) and housing status. Secondary outcomes included psychiatric symptoms, functioning, side effects, and hospitalizations. Results Mean age of participants was 41.8 years (SD 8.6), mainly minorities (90% African-American) and mainly single/never married (70%). Most (97%) had past or current substance abuse, and had been incarcerated (97%). Ten individuals (33%) terminated the study prematurely. CAE-L was associated with good adherence to LAI (76% at 6 months) and dramatic improvement in oral medication adherence, which changed from missing 46% of medication at study enrollment to missing only 10% at study end (p = 0.03). There were significant improvements in psychiatric symptoms (p<.001) and functioning (p<.001). Akathisia was a major side effect with LAI. Conclusion While interpretation of findings must be tempered by the methodological limitations, CAE-L appears to be associated with improved adherence, symptoms, and functioning in homeless or recently homeless individuals with schizophrenia or schizoaffective disorder. Additional research is needed on effective and practical approaches to improving health outcomes for homeless people with serious mental illness. PMID:24434094

Evaluation of chemical immersion treatments to reduce microbial populations in fresh beef.

PubMed

Kassem, Ahmed; Meade, Joseph; Gibbons, James; McGill, Kevina; Walsh, Ciara; Lyng, James; Whyte, Paul

2017-11-16

The aim of the current study was to assess the ability of a number of chemicals (acetic Acid (AA), citric acid (CA) lactic acid (LA), sodium decanoate (SD) and trisodium phosphate (TSP)) to reduce microbial populations (total viable count, Campylobacter jejuni, Escherichia coli, Salmonella typhimurium and Listeria monocytogenes) on raw beef using an immersion system. The following concentrations of each chemical were used: 3 & 5% for AA, CA, LA, SD and 10 &12% for TSP. Possible synergistic effects of using combinations of two chemicals sequentially (LA+CA and LA+AA) were also investigated. L*, a* and b* values were measured before and after treatments and ΔE* values were calculated in order to determine any changes in the color of meat due to the use of these chemicals. In general, all chemical treatments resulted in significantly (p<0.05) reduced bacterial counts when compared to untreated controls. The greatest reductions were obtained by using LA3%, SD5%, AA5%, LA5% and SD3% for TVC, C. jejuni, E. coli, S. typhimurium and L. monocytogenes, respectively. However, no significant difference in microbial load was observed between the different concentrations of each chemical used (p>0.05). The application of combinations of chemical immersion treatments (LA3%+AA3% and LA3%+CA3%) did not result in further significant reductions in microbial populations when compared to single chemical treatments (P<0.05). Assessment of color changes in meat following the application of chemical immersion treatments indicated that using AA or CA at either concentration and LA at 5% led to an increase in the ΔE* value of >3 immediately after treatment and after 24h storage. The remaining treatments did not result in significant changes to the color of raw beef. Copyright © 2017 Elsevier B.V. All rights reserved.

The metabotropic glutamate receptor 8 agonist (S)-3,4-DCPG reverses motor deficits in prolonged but not acute models of Parkinson’s disease

PubMed Central

Johnson, Kari A.; Jones, Carrie K.; Tantawy, Mohammed N.; Bubser, Michael; Marvanova, Marketa; Ansari, M. Sib; Baldwin, Ronald M.; Conn, P. Jeffrey; Niswender, Colleen M.

2012-01-01

Metabotropic glutamate receptors (mGlus) are 7 Transmembrane Spanning Receptors (7TMs) that are differentially expressed throughout the brain and modulate synaptic transmission at both excitatory and inhibitory synapses. Recently, mGlus have been implicated as therapeutic targets for many disorders of the central nervous system, including Parkinson’s disease (PD). Previous studies have shown that nonselective agonists of group III mGlus have antiparkinsonian effects in several animal models of PD, suggesting that these receptors represent promising targets for treating the motor symptoms of PD. However, the relative contributions of different group III mGlu subtypes to these effects have not been fully elucidated. Here we report that intracerebroventricular (icv) administration of the mGlu8-selective agonist (S)-3,4-dicarboxyphenylglycine (DCPG [2.5, 10, or 30 nmol]) does not alleviate motor deficits caused by acute (two hour) treatment with haloperidol or reserpine. However, following prolonged pretreatment with haloperidol (three doses evenly spaced over 18–20 hours) or reserpine (18–20 hours), DCPG robustly reverses haloperidol-induced catalepsy and reserpine-induced akinesia. Furthermore, DCPG (10 nmol, icv) reverses the long-lasting catalepsy induced by 20 hour pretreatment with the decanoate salt of haloperidol. Finally, icv administration of DCPG ameliorates forelimb use asymmetry caused by unilateral 6-hydroxydopamine lesion of substantia nigra dopamine neurons. These findings suggest that mGlu8 may partially mediate the antiparkinsonian effects of group III mGlu agonists in animal models of PD in which dopamine depletion or blockade of D2-like dopamine receptors is prolonged and indicate that selective activation of mGlu8 may represent a novel therapeutic strategy for alleviating the motor symptoms of PD. PMID:22546615

Emulsification Increases the Acute Ketogenic Effect and Bioavailability of Medium-Chain Triglycerides in Humans

PubMed Central

Courchesne-Loyer, Alexandre; Lowry, Carolyn-Mary; St-Pierre, Valérie; Vandenberghe, Camille; Fortier, Mélanie; Castellano, Christian-Alexandre; Wagner, J Richard; Cunnane, Stephen C

2017-01-01

Abstract Background: Lower-brain glucose uptake is commonly present before the onset of cognitive deterioration associated with aging and may increase the risk of Alzheimer disease. Ketones are the brain's main alternative energy substrate to glucose. Medium-chain triglycerides (MCTs) are rapidly β-oxidized and are ketogenic but also have gastrointestinal side effects. We assessed whether MCT emulsification into a lactose-free skim-milk matrix [emulsified MCTs (MCT-Es)] would improve ketogenesis, reduce side effects, or both compared with the same oral dose of MCTs consumed without emulsification [nonemulsified MCTs (MCT-NEs)]. Objectives: Our aims were to show that, in healthy adults, MCT-Es will induce higher ketonemia and have fewer side effects than MCT-NEs and the effects of MCT-NEs and MCT-Es on ketogenesis and plasma medium-chain fatty acids (MCFAs) will be dose-dependent. Methods: Using a metabolic study day protocol, 10 healthy adults were each given 3 separate doses (10, 20, or 30 g) of MCT-NEs or MCT-Es with a standard breakfast or no treatment [control (CTL)]. Blood samples were taken every 30 min for 4 h to measure plasma ketones (β-hydroxybutyrate and acetoacetate), octanoate, decanoate, and other metabolites. Participants completed a side-effects questionnaire at the end of each study day. Results: Compared with CTL, MCT-NEs increased ketogenesis by 2-fold with no significant differences between doses. MCT-Es increased total plasma ketones by 2- to 4-fold in a dose-dependent manner. Compared with MCT-NEs, MCT-Es increased plasma MCFA bioavailability (F) by 2- to 3-fold and decreased the number of side effects by ∼50%. Conclusions: Emulsification increased the ketogenic effect and decreased side effects in a dose-dependent manner for single doses of MCTs ≤30 g under matching conditions. Further investigation is needed to establish whether emulsification could sustain ketogenesis and minimize side effects and therefore be used as a treatment to change brain ketone availability over a prolonged period of time. This trial was registered at clinicaltrials.gov as NCT02409927.

Cross-sectional comparison of first-generation antipsychotic long-acting injections vs risperidone long-acting injection: patient-rated attitudes, satisfaction and tolerability

PubMed Central

Singh, Sourabh Moti; Haddad, Peter M.; Husain, Nusrat; Heaney, Eamonn; Tomenson, Barbara; Chaudhry, Imran B.

2016-01-01

Objectives: The objective of this study was to compare patients’ attitudes and satisfaction with medication and patient-rated tolerability between those prescribed a first-generation antipsychotic long-acting injection (FGA-LAI) and those prescribed risperidone long-acting injection (RLAI). Method: A cross-sectional study of a representative sample of outpatients prescribed an FGA-LAI or RLAI for a minimum of 6 months and attending a depot clinic. Attitudes to medication were assessed by the Drug Attitude Inventory (DAI-30), tolerability was measured by the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and satisfaction with antipsychotic medication was assessed by the Satisfaction with Antipsychotic Medication (SWAM) scale. Results: The RLAI (n = 28) and FGA-LAI (n = 39) groups did not differ in terms of mean age, sex, diagnosis and ethnicity. All individual LAIs were prescribed within British National Formulary limits. The most commonly prescribed FGA-LAI was flupentixol decanoate (n = 22). There was no significant difference between the RLAI and FGA-LAI groups in terms of mean total scores on the DAI-30, LUNSERS and SWAM or the tolerability subscales of the LUNSERS or the two subscales (treatment acceptability and medication insight) of the SWAM. In both LAI groups there was a low level of side effects (LUNSERS) and a generally positive attitude (DAI-30) and reasonable satisfaction (SWAM) with medication. Conclusions: Patients treated with FGA-LAI and RLAI for at least 6 months did not differ in terms of patient-rated tolerability, attitudes and satisfaction with medication. The current design cannot determine whether differences would have been evident earlier on during treatment. These results should be regarded as preliminary and are subject to prescribing bias. Randomized studies avoid prescribing bias and are a superior way to compare specific LAIs. Ideally randomized studies should include patient-rated outcome measures including medication tolerability; assessment of side effects, efficacy and quality of life made by blinded raters; and additional objective side-effect data including changes in weight and key blood parameters. PMID:27354904

Carboxylate and amino group coated silver nanoparticles as joining materials for copper-to-copper silver joints.

PubMed

Oestreicher, A; Röhrich, T; Lerch, M

2012-12-01

Organic silver complexes are introduced where silver is linked either with a carboxyl group or with an amino group. Upon heating, nanoparticles are generated if the respective ligands are long enough to act as stabilizing agents in the nanoparticulate regime. With decomposition and volatilization of the organic material, the sintering of silver occurs. The thermal characteristics of the carboxylates silver-n-octanoate, silver-n-decanoate, and AgOOC(CH2OCH2)2CH2OCH3 are compared with silver-n-alkylamines (n = 8, 9, and 12), and their thermal behavior is discussed based on thermogravimetry (TG) measurements. The consecutive stages of a metallization process are addressed based on the properties of AgOOC(CH2OCH2)2CH2OCH3, and the usable effects of the individual phases of this metal organic compound are analyzed by cross-sectional scanning electron microscope (SEM) images of silver joints. Selection criteria are addressed based on the thermal behavior. A mechanism for the joining process is proposed, considering formation and sintering of the nanoparticles. It was found that the bulk material can be used for low-temperature joining processes. Strong adherence to copper as a basic material can be achieved.

Optimization of a Solid-Phase Microextraction method for the Gas Chromatography-Mass Spectrometry analysis of blackberry (Rubus ulmifolius Schott) fruit volatiles.

PubMed

D'Agostino, M F; Sanz, J; Sanz, M L; Giuffrè, A M; Sicari, V; Soria, A C

2015-07-01

A Solid-Phase Microextraction method for the Gas Chromatography-Mass Spectrometry analysis of blackberry (Rubus sp.) volatiles has been fully optimized by means of a Box-Behnken experimental design. The optimized operating conditions (Carboxen/Polydimethylsiloxane fiber coating, 66°C, 20 min equilibrium time and 16 min extraction time) have been applied to the characterization for the first time of the volatile composition of Rubus ulmifolius Schott blackberries collected in Italy and Spain. A total of 74 volatiles of different functionality were identified; esters and aliphatic alcohols were the predominant classes in both sample types. Methylbutanal (2.02-25.70%), ethanol (9.84-68.21%), 2,3-butanedione (2.31-14.71%), trans-2-hexenal (0.49-17.49%), 3-hydroxy-2-butanone (0.08-7.39%), 1-hexanol (0.56-16.39%), 1-octanol (0.49-10.86%) and methylbutanoic acid (0.53-21.48%) were the major compounds in most blackberries analyzed. Stepwise multiple regression analysis of semiquantitative data showed that only two variables (ethyl decanoate and ethyl acetate) were necessary for a successful differentiation of blackberries according to their harvest location. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inorganic selenium speciation analysis in Allium and Brassica vegetables by ionic liquid assisted liquid-liquid microextraction with multivariate optimization.

PubMed

Castro Grijalba, Alexander; Martinis, Estefanía M; Wuilloud, Rodolfo G

2017-03-15

A highly sensitive vortex assisted liquid-liquid microextraction (VA-LLME) method was developed for inorganic Se [Se(IV) and Se(VI)] speciation analysis in Allium and Brassica vegetables. Trihexyl(tetradecyl)phosphonium decanoate phosphonium ionic liquid (IL) was applied for the extraction of Se(IV)-ammonium pyrrolidine dithiocarbamate (APDC) complex followed by Se determination with electrothermal atomic absorption spectrometry. A complete optimization of the graphite furnace temperature program was developed for accurate determination of Se in the IL-enriched extracts and multivariate statistical optimization was performed to define the conditions for the highest extraction efficiency. Significant factors of IL-VA-LLME method were sample volume, extraction pH, extraction time and APDC concentration. High extraction efficiency (90%), a 100-fold preconcentration factor and a detection limit of 5.0ng/L were achieved. The high sensitivity obtained with preconcentration and the non-chromatographic separation of inorganic Se species in complex matrix samples such as garlic, onion, leek, broccoli and cauliflower, are the main advantages of IL-VA-LLME. Copyright © 2016 Elsevier Ltd. All rights reserved.

Combustion of Biofuel as a Renewable Energy Source in Sandia Flame Geometry

NASA Astrophysics Data System (ADS)

Rassoulinejad-Mousavi, Seyed Moein; Mao, Yijin; Zhang, Yuwen

Energy security and climate change are two important key causes of wide spread employment of biofuel notwithstanding of problems associated with its usage. In this research, combustion of biofuel as a renewable energy source was numerically investigated in the well-known and practical Sandia flame geometry. Combustion performance of the flame has been simulated by burning biodiesel (methyl decanoate, methyl 9-decenoate, and n-heptane) oxidation with 118 species reduced/skeletal mechanism. The open-source code OpenFoam was used for simulating turbulent biodiesel-air combustion in the cylindrical chamber using the standard k-epsilon model. To check the accuracy of numerical results, the system was initially validated with methane-air Sandia national laboratories flame D experimental results. Excellent agreements between numerical and experimental results were observed at different cross sections. After ignition, temperature distributions at different distances of axial and radial directions as well as species mass fraction were investigated. It is concluded that biofuel has the capability of implementation in the turbulent jet flame that is a step forward in promotion of sustainable energy technologies and applications.

Cost Effectiveness of Paliperidone Long-Acting Injectable Versus Other Antipsychotics for the Maintenance Treatment of Schizophrenia in France.

PubMed

Druais, Sylvain; Doutriaux, Agathe; Cognet, Magali; Godet, Annabelle; Lançon, Christophe; Levy, Pierre; Samalin, Ludovic; Guillon, Pascal

2016-04-01

French clinical recommendations suggest prescribing long-acting injectable (LAI) antipsychotics to patients with a maintenance treatment indication in schizophrenia. Despite this, and due to their relatively high acquisition and administration costs, LAIs are still underused in clinical practice in France, thus highlighting the need for pharmacoeconomic evaluations. Our objective was to estimate the cost effectiveness of paliperidone LAI (or paliperidone palmitate), a once-monthly second-generation LAI antipsychotic, compared with the most common antipsychotic medications for the maintenance treatment of schizophrenia in France. A Markov model was developed to simulate the progression of a cohort of schizophrenic patients through four health states (stable treated, stable non-treated, relapse and death) and to consider up to three lines of treatment to account for changes in treatment management. Paliperidone LAI was compared with risperidone LAI, aripiprazole LAI, olanzapine LAI, haloperidol LAI (or haloperidol decanoate) and oral olanzapine. Costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over 5 years based on 3-month cycles with a discount rate of 4% and from a French health insurance perspective. Patients were considered to be stabilised after a schizophrenic episode and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on real-life French data to capture adherence effects. Safety and utility data were derived from international publications. Additionally, costs were retrieved from French health insurance databases and publications. Finally, expert opinion was used for validation purposes or in case of gaps in data. The robustness of results was assessed through deterministic and probabilistic sensitivity analyses. All LAI antipsychotics were found to have similar costs over 5 years: approximatively €55,000, except for paliperidone LAI which had a discounted cost of €50,880. Oral olanzapine was less costly than LAIs (i.e. €50,379 after 5 years) but was associated with fewer QALYs gained and relapses avoided. Paliperidone LAI dominated aripiprazole LAI, olanzapine LAI and haloperidol LAI in terms of costs per QALY, and it was associated with slightly fewer QALYs when compared with risperidone LAI (i.e. 3.763 vs 3.764). This resulted in a high incremental cost-effectiveness ratio (ICER) (i.e. €4,770,018 per QALY gained) for risperidone LAI compared with paliperidone LAI. Paliperidone LAI was more costly than olanzapine oral but associated with more QALYs (i.e. ICER of €2411 per QALY gained for paliperidone LAI compared with oral olanzapine). Paliperidone LAI had a probability of being the optimal strategy in more than 50% of cases for a willingness-to-pay threshold of €8000 per QALY gained. This analysis, to the best of our knowledge, is the first of its kind to assess the cost effectiveness of antipsychotics based on French observational data. Paliperidone LAI appeared to be a cost-effective option in the treatment of schizophrenia from the French health insurance perspective.

Analysis of Androgenic Steroids in Environmental Waters by Large-volume Injection Liquid Chromatography Tandem Mass Spectrometry

PubMed Central

Backe, Will J.; Ort, Christoph; Brewer, Alex J.; Field, Jennifer A.

2014-01-01

A new method was developed for the analysis of natural and synthetic androgenic steroids and their selected metabolites in aquatic environmental matrices using direct large-volume injection (LVI) high performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). Method accuracy ranged from 88 to 108% for analytes with well-matched internal standards. Precision, quantified by relative standard deviation (RSD), was less than 12%. Detection limits for the method ranged from 1.2 to 360 ng/L. The method was demonstrated on a series of 1-hr composite wastewater influent samples collected over a day with the purpose of assessing temporal profiles of androgen loads in wastewater. Testosterone, androstenedione, boldenone, and nandrolone were detected in the sample series at concentrations up to 290 ng/L and loads up to 535 mg. Boldenone, a synthetic androgen, had a temporal profile that was strongly correlated to testosterone, a natural human androgen, suggesting its source may be endogenous. An analysis of the sample particulate fraction revealed detectable amounts of sorbed testosterone and androstenedione. Androstenedione sorbed to the particulate fraction accounted for an estimated five to seven percent of the total androstenedione mass. PMID:21391574

Analysis of anabolic steroids in hair: time courses in guinea pigs.

PubMed

Shen, Min; Xiang, Ping; Yan, Hui; Shen, Baohua; Wang, Mengye

2009-09-01

Sensitive, specific, and reproducible methods for the quantitative determination of eight anabolic steroids in guinea pig hair have been developed using LC/MS/MS and GC/MS/MS. Methyltestosterone, stanozolol, methandienone, nandrolone, trenbolone, boldenone, methenolone and DHEA were administered intraperitoneally in guinea pigs. After the first injection, black hair segments were collected on shaved areas of skin. The analysis of these segments revealed the distribution of anabolic steroids in the guinea pig hair. The major components in hair are the parent anabolic steroids. The time courses of the concentrations of the steroids in hair (except methenolone, which does not deposit in hair) demonstrated that the peak concentrations were reached on days 2-4, except stanozolol, which peaked on day 10 after administration. The concentrations in hair appeared to be related to the physicochemical properties of the drug compound and to the dosage. These studies on the distribution of drugs in the hair shaft and on the time course of their concentration changes provide information relevant to the optimal time and method of collecting hair samples. Such studies also provide basic data that will be useful in the application of hair analysis in the control of doping and in the interpretation of results.

One-pot synthesized functionalized mesoporous silica as a reversed-phase sorbent for solid-phase extraction of endocrine disrupting compounds in milks.

PubMed

Gañán, Judith; Morante-Zarcero, Sonia; Pérez-Quintanilla, Damián; Marina, María Luisa; Sierra, Isabel

2016-01-08

A new procedure for the determination of 12 naturally occurring hormones and some related synthetic chemicals in milk, commonly used as growth promoters in cattle, is reported. The method is based on liquid-liquid extraction followed by solid-phase extraction (SPE) using a new one-pot synthesized ordered mesoporous silica (of the SBA-15 type) functionalized with octadecyl groups (denoted as SBA-15-C18-CO) as reversed-phase sorbent. The analytes were eluted with methanol and then submitted to HPLC with diode array detection. Under optimal conditions, the method quantification limit for the analytes ranged from 0.023 to 1.36μg/mL. The sorbent affored the extraction of estrone, 17β-estradiol, estriol, progesterone, hexestrol, diethylstilbestrol, 4-androstene-3,17-dione, ethinylestradiol, 17α-methyltestosterone, nandrolone, prednisolone and testosterone with mean recoveries ranging from 72% to 105% (except for diethylstilbestrol) with RSD<11%. These results were comparable and, in some cases, even better than those obtained with other extraction methods, therefore SBA-15-C18-CO mesoporous silica possess a high potential as a reversed-phase sorbent for SPE of the 12 mentioned endocrine disrupting compounds in milk samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Autoignition Studies of Diesel Alternative Biofuels

NASA Astrophysics Data System (ADS)

Wang, Weijing

The autoignition of biofuel compounds that offer potential as diesel fuel alternatives was studied under high-pressure engine-like conditions using the shock tube technique. Ignition delay times were determined in reflected shock experiments using measured pressure and electronically-excited OH emission. Measurements were made at conditions ranging from 650 to 1350 K, pressures from 6 to 50 atm, and for fuel/air/diluent mixtures at equivalence ratios from 0.5 to 2. The wide range of temperatures examined provides observation of autoignition in three reactivity regimes, including the negative temperature coefficient (NTC) regime which is characteristic of fuels containing alkyl functionalities. Compounds studied include biodiesel-related compounds and real biodiesel fuels, dimethyl ether, and 3-methylheptane which is representative of compounds found in synthetic diesel fuels produced using the Fischer-Tropsch and hydrotreatment processes. Biodiesel compounds studied include biodiesel surrogates, methyl decanoate, methyl-5-decenoate, and methyl-9-decenoate; compounds found in large quantities in biodiesels, methyl palmitate, methyl stearate, methyl oleate, and methyl linoleate; and soy-based and animal fat based methyl ester biodiesels. Comparison of biodiesel compounds illustrates the influence of molecular structure (e.g., chain length, double bonds, and ester functionality) on reactivity. For methyl decanoate, the effect of high pressure exhaust gas recirculation (EGR) conditions relevant to internal combustion engines was also determined. Results showed that the first-order influence of EGR by displacing fuel and O2 to decrease radical branching. Measurements were compared to kinetic modeling results from models available in the literature providing varying degrees of model validation. Reaction flux analyses were also carried out to further examine the kinetic differences in different temperature regimes for fuel compounds. For example, reaction flux analyses illustrates the importance of the long alkyl chain in controlling the overall reactivity of methyl ester biodiesel compounds and the subtle role the ester group has on inhibiting low-temperature reactivity as well as the influence of branching on reactivity for lightly branched alkanes. This thesis work provides a rich database of kinetic information for biofuel-related compounds at conditions relevant to real engine operations, offering quantitative kinetic targets for the development and evaluation of future kinetic models for important alternative fuel compounds. The results quantify the reactivity variability of biodiesel alternatives and illustrate that at temperature greater than 900 to 1000 K fuel structure has little influence on reactivity, as fuel fragmentation results in an intermediate pool that is largely the same for the fuels studied. On the other hand at temperature lower than 900 K, where fuel-specific low-temperature chemistry plays a role, different fuel structures can result in vast differences in reactivity, up to factors of three or more in ignition delay.

Prediction of NOx emissions from a simplified biodiesel surrogate by applying stochastic simulation algorithms (SSA)

NASA Astrophysics Data System (ADS)

Omidvarborna, Hamid; Kumar, Ashok; Kim, Dong-Shik

2017-03-01

A stochastic simulation algorithm (SSA) approach is implemented with the components of a simplified biodiesel surrogate to predict NOx (NO and NO2) emission concentrations from the combustion of biodiesel. The main reaction pathways were obtained by simplifying the previously derived skeletal mechanisms, including saturated methyl decenoate (MD), unsaturated methyl 5-decanoate (MD5D), and n-decane (ND). ND was added to match the energy content and the C/H/O ratio of actual biodiesel fuel. The MD/MD5D/ND surrogate model was also equipped with H2/CO/C1 formation mechanisms and a simplified NOx formation mechanism. The predicted model results are in good agreement with a limited number of experimental data at low-temperature combustion (LTC) conditions for three different biodiesel fuels consisting of various ratios of unsaturated and saturated methyl esters. The root mean square errors (RMSEs) of predicted values are 0.0020, 0.0018, and 0.0025 for soybean methyl ester (SME), waste cooking oil (WCO), and tallow oil (TO), respectively. The SSA model showed the potential to predict NOx emission concentrations, when the peak combustion temperature increased through the addition of ultra-low sulphur diesel (ULSD) to biodiesel. The SSA method used in this study demonstrates the possibility of reducing the computational complexity in biodiesel emissions modelling.

Dibasic Ammonium Phosphate Application Enhances Aromatic Compound Concentration in Bog Bilberry Syrup Wine.

PubMed

Wang, Shao-Yang; Li, Yi-Qing; Li, Teng; Yang, Hang-Yu; Ren, Jie; Zhang, Bo-Lin; Zhu, Bao-Qing

2016-12-29

A nitrogen deficiency always causes bog bilberry syrup wine to have a poor sensory feature. This study investigated the effect of nitrogen source addition on volatile compounds during bog bilberry syrup wine fermentation. The syrup was supplemented with 60, 90, 120 or 150 mg/L dibasic ammonium phosphate (DAP) before fermentation. Results showed that an increase of DAP amounts accelerated fermentation rate, increased alcohol content, and decreased sugar level. Total phenol and total flavonoid content were also enhanced with the increase of DAP amounts. A total of 91 volatile compounds were detected in the wine and their concentrations were significantly enhanced with the increase of DAP. Ethyl acetate, isoamyl acetate, phenethyl acetate, ethyl butanoate, ethyl hexanoate, ethyl octanoate, ethyl decanoate, isobutanol, isoamyl alcohol, levo -2,3-butanediol, 2-phenylethanol, meso -2,3-butanediol, isobutyric acid, hexanoic acid, and octanoic acid exhibited a significant increase of their odor activity value (OAV) with the increase of DAP amounts. Bog bilberry syrup wine possessed fruity, fatty, and caramel flavors as its major aroma, whereas a balsamic note was the least present. The increase of DAP amounts significantly improved the global aroma attributes, thereby indicating that DAP supplementation could promote wine fermentation performance and enhance the sensory quality of bog bilberry syrup wine.

Analysis of androgenic steroids in environmental waters by large-volume injection liquid chromatography tandem mass spectrometry.

PubMed

Backe, Will J; Ort, Christoph; Brewer, Alex J; Field, Jennifer A

2011-04-01

A new method was developed for the analysis of natural and synthetic androgenic steroids and their selected metabolites in aquatic environmental matrixes using direct large-volume injection (LVI) high-performance liquid chromatography (HPLC) tandem mass spectrometry (MS/MS). Method accuracy ranged from 87.6 to 108% for analytes with well-matched internal standards. Precision, quantified by relative standard deviation (RSD), was less than 12%. Detection limits for the method ranged from 1.2 to 360 ng/L. The method was demonstrated on a series of 1 h composite wastewater influent samples collected over a day with the purpose of assessing temporal profiles of androgen loads in wastewater. Testosterone, androstenedione, boldenone, and nandrolone were detected in the sample series at concentrations up to 290 ng/L and loads up to 535 mg/h. Boldenone, a synthetic androgen, had a temporal profile that was strongly correlated to testosterone, a natural human androgen, suggesting its source may be endogenous. An analysis of the sample particulate fraction revealed detectable amounts of sorbed testosterone and androstenedione. Androstenedione sorbed to the particulate fraction accounted for an estimated 5 to 7% of the total androstenedione mass.

Rapid test by liquid chromatography/tandem mass spectrometry to evaluate equine urine reactivity towards 17beta-OH steroids.

PubMed

Fidani, Marco; Casagni, Eleonora; Montana, Marco; Pasello, Emanuela; Pecoraro, Chiara; Gambaro, Veniero

2006-01-01

Bacteria frequently found in equine urine samples may cause degradation of 17beta-OH steroids. A simple liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed to evaluate the microbiological contamination of equine urine as a marker of poor storage conditions. Norethandrolone was used as the internal standard, and the linearity, sensitivity, precision and accuracy of the method were evaluated. 17beta-OH oxidation was demonstrated for testosterone, nandrolone, trenbolone and boldenone, but did not occur in alpha-epimers such as alpha-boldenone and epitestosterone, demonstrating the stereoselectivity of the reaction. A rapid test was performed by spiking one of the four 17beta-OH steroids in samples of diluted equine urine. The steroids were transformed into their respective ketones in the presence of bacterial activity. The test allows direct injection of diluted samples into the LC/MS system, without the need for prior extraction. Results show that the best method of storage is freezing at -18 degrees C. Urine specimens should be analyzed as soon as possible after thawing. This allows bacterial degradation of equine urine to be arrested temporarily, so that the urine can be used for qualitative or quantitative analysis of 17beta-OH steroids.

19. Randomized Controlled Trial of a Neurosteroid Intervention in Schizophrenia

PubMed Central

Marx, Chris; Naylor, Jennifer; Kilts, Jason; Allan, Trina; Smith, Karen; Szabo, Steven; Wagner, Ryan; Buchanan, Robert; Keefe, Richard; Shampine, Lawrence

2017-01-01

Abstract Background: Neurosteroids are endogenous molecules synthesized de novo in brain, adrenals, and other tissues. They demonstrate pleiotropic actions that are highly relevant to the neurobiology of schizophrenia. Clozapine markedly elevates neurosteroids in rodent hippocampus, potentially contributing to its superior therapeutic efficacy. Clinical evidence from a randomized controlled trial (RCT) conducted in Singapore suggests that pregnenolone significantly enhances functional capacity (as demonstrated by improvements in the UPSA Total Score and UPSA Communication Subscale Score) and that neurosteroid changes posttreatment predict therapeutic response (Marx et al 2014; Psychopharmacology). We thus conducted an RCT investigating adjunctive pregnenolone in schizophrenia. Methods: After a 2-week placebo lead-in, 88 participants with schizophrenia were randomized to pregnenolone (n = 42) or placebo (n = 46) for 8 weeks. Neurosteroids were quantified at baseline and posttreatment by mass spectrometry. Functional end points included the UPSA Total Score and UPSA Communication Subscale. Cognitive end points included the MCCB Composite Score and MCCB Subscales. Modified intent-to-treat analyses were conducted. Results: Participants randomized to the pregnenolone group did not outperform placebo on the UPSA Total Score or MCCB Composite Score. However, the pregnenolone group demonstrated significantly greater improvement in the UPSA Communication Subscale compared to participants randomized to placebo (P = .034), replicating prior RCT findings from Singapore. Elevations in pregnenolone post-treatment also predicted improvements in UPSA Total Score (r = .373; P = .039), again replicating prior efforts. In addition, the pregnenolone group demonstrated significantly greater improvement in the MCCB Verbal Learning Subscale compared to placebo (P = .023). Pregnenolone did not outperform placebo in the BACS Composite Score, SANS Total Score, or PANSS Total Score. Pregnenolone was well tolerated. Conclusion: Treatment with pregnenolone appears to improve functional capacity in a US population with schizophrenia, as assessed by the UPSA Communication Subscale and also supported by a significant positive correlation between pregnenolone changes and UPSA Total Score improvements—thus replicating findings from a prior RCT conducted in Singapore. Pregnenolone may also improve verbal memory. Given the positive correlation between pregnenolone increases posttreatment and UPSA Total Score improvements, it is possible that higher doses of pregnenolone may be clinically efficacious, and that neurosteroid quantification has biomarker potential for the predication of therapeutic response. Additional dose-finding investigations will be required to test these hypotheses. A pregnenolone decanoate formulation is currently in preclinical development.

Scaling relation for high-temperature biodiesel surrogate ignition delay times

DOE PAGES

Campbell, Matthew F.; Davidson, David F.; Hanson, Ronald K.

2015-10-11

High-temperature Arrhenius ignition delay time correlations are useful for revealing the underlying parameter dependencies of combustion models, for simplifying and optimizing combustion mechanisms for use in engine simulations, for scaling experimental data to new conditions for comparison purposes, and for guiding in experimental design. Here, we have developed a scaling relationship for Fatty Acid Methyl Ester (FAME) ignition time data taken at high temperatures in 4%O 2/Ar mixtures behind reflected shocks using an aerosol shock tube: τ ign [ms] = 2.24 x 10 -6 [ms] (P [atm]) -.41 (more » $$\\phi$$) 0.30(C n) -.61 x exp $$ \\left(\\frac{37.1 [kcal/mol]}{\\hat{R}_u [kcal / mol K] T [K]}\\right) $$ In addition, we have combined our ignition delay time data for methyl decanoate, methyl palmitate, methyl oleate, and methyl linoleate with other experimental results in the literature in order to derive fuel-specific oxygen-mole-fraction scaling parameters for these surrogates. In conclusion, in this article, we discuss the significance of the parameter values, compare our correlation to others found in the literature for different classes of fuels, and contrast the above expression’s performance with correlations obtained using leading FAME kinetic models in 4%O 2/Ar mixtures.« less

Modeling Study of the Low-Temperature Oxidation of Large Methyl Esters from C11 to C19

PubMed Central

Herbinet, Olivier; Biet, Joffrey; Hakka, Mohammed Hichem; Warth, Valérie; Glaude, Pierre Alexandre; Nicolle, André; Battin-Leclerc, Frédérique

2013-01-01

The modeling of the low temperature oxidation of large saturated methyl esters really representative of those found in biodiesel fuels has been investigated. Models have been developed for these species and then detailed kinetic mechanisms have been automatically generated using a new extended version of software EXGAS, which includes reactions specific to the chemistry of esters. A model generated for a binary mixture of n-decane and methyl palmitate was used to simulate experimental results obtained in a jet-stirred reactor for this fuel. This model predicts very well the reactivity of the fuel and the mole fraction profiles of most reaction products. This work also shows that a model for a middle size methyl ester such as methyl decanoate predicts fairly well the reactivity and the mole fractions of most species with a substantial decrease in computational time. Large n-alkanes such as n-hexadecane are also good surrogates for reproducing the reactivity of methyl esters, with an important gain in computational time, but they cannot account for the formation of specific products such as unsaturated esters or cyclic ethers with an ester function. PMID:23814504

Progress and prospects in male hormonal contraception

PubMed Central

Amory, John K.

2009-01-01

Purpose of review Testosterone functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary. Low concentrations of these hormones deprive the testes of the signals required for spermatogenesis and results in markedly decreased sperm concentrations and effective contraception in a majority of men. Male hormonal contraception is well tolerated and acceptable to most men. Unfortunately, testosterone-alone regimens fail to completely suppress spermatogenesis in all men, meaning that in some the potential for fertility remains. Recent findings Because of this, novel combinations of testosterone and progestins, which synergistically suppress gonadotropins, have been studied. Two recently published testosterone/progestin trials are particularly noteworthy. In the first, a long-acting injectable testosterone ester, testosterone decanoate, was combined with etonogestrel implants and resulted in 80–90% of subjects achieving a fewer than 1 million sperm per milliliter. In the second, a daily testosterone gel was combined with 3-monthly injections of depot medroxyprogesterone acetate producing similar results. Summary Testosterone-based hormone combinations are able to reversibly suppress human spermatogenesis; however, a uniformly effective regimen has remained elusive. Nevertheless, improvements, such as the use of injectable testosterone undecanoate, may lead to a safe, reversible and effective male contraceptive. PMID:18438174

Effects of sustanon on the distribution of satellite cells and the morphology of skeletal muscle fibers during maturation.

PubMed

Allouh, Mohammed Z; Aldirawi, Mohammed H

2012-03-01

Sustanon is one of the most commonly used anabolic androgenic drugs to increase skeletal muscle mass and strength. This drug is a blend of four esterized testosterone derivatives: Testosterone propionate, testosterone phenylpropionate, testosterone isocaproate and testosterone decanoate. Little is known about the effects of this drug on skeletal muscle at the cellular level. This study aimed to investigate the influence of Sustanon on the morphology of skeletal muscle fibers and the distribution of myogenic stem cells known as Satellite Cells (SCs) during postnatal growth. We hypothesized that Sustanon-induced skeletal muscle hypertrophy is associated with an increase in the number of SCs. Robust immunocytochemical techniques and morphometric analyses were used to calculate the numbers of SCs and myonuclei within the pectoralis muscle of chickens. Also, DNA concentration and Pax7 protein levels were measured to confirm immunocytochemical findings. Sustanon significantly increased pectoralis mass and fiber size. All SC indices and the number of myonuclei increased significantly by Sustanon administration. In addition, greater DNA concentration and Pax7 protein expression were found in Sustanon-treated birds. This study indicates that Sustanon can induce avian skeletal muscle hypertrophy and that this is correlated with increased numbers of SCs and myonuclei.

Effect of oxygen on volatile and sensory characteristics of Cabernet Sauvignon during secondary shelf life.

PubMed

Lee, Dong-Hyun; Kang, Bo-Sik; Park, Hyun-Jin

2011-11-09

The oxidation of Cabernet Sauvignon wines during secondary shelf life was studied by headspace solid-phase microextraction (HS-SPME) coupled to gas chromatography-quadrupole mass spectrometry (GC-qMS) and sensory tests, with the support of multivariate statistical analyses such as OPLS-DA loading plot and PCA score plot. Four different oxidation conditions were established during a 1-week secondary shelf life. Samples collected on a regular basis were analyzed to determine the changes of volatile chemicals, with sensory characteristics evaluated through pattern recognition models. During secondary shelf life the separation among collected samples depended on the degree of oxidation in wine. Isoamyl acetate, ethyl decanoate, nonanoic acid, n-decanoic acid, undecanoic acid, 2-furancarboxylic acid, dodecanoic acid, and phenylacetaldehyde were determined to be associated with the oxidation of the wine. PCA sensory evaluation revealed that least oxidized wine and fresh wine was well-separated from more oxidized wines, demonstrating that sensory characteristics of less oxidized wines tend toward "fruity", "citrous", and "sweetness", while those of more oxidized wines are positively correlated with "animal", "bitterness", and "dairy". The study also demonstrates that OPLS-DA and PCA are very useful statistical tools for the understanding of wine oxidation.

Comparative analysis of the volatile composition of honeys from Brazilian stingless bees by static headspace GC-MS.

PubMed

de Lima Morais da Silva, Patricia; de Lima, Liliane Schier; Caetano, Ísis Kaminski; Torres, Yohandra Reyes

2017-12-01

The volatile composition of honeys produced by eight species of stingless bees collected in three municipalities in the state of Paraná (Brazil) was compared by combining static headspace GC-MS and chemometrics methods. Forty-four compounds were identified using NIST library and linear retention index relative to n-alkanes (C 8 -C 40 ). Linalool derivatives were the most abundant peaks in most honeys regardless geographical or entomological origin. However, Principal Component Analysis discriminated honeys from different geographical origins considering their distinctive minor volatile components. Honey samples from Guaraqueçaba were characterized by the presence of hotrienol while those from Cambará showed epoxylinalol, benzaldehyde and TDN as minor discriminating compounds. Punctual species such as Borá showed similar fingerprints regardless geographical origin, with ethyl octanoate and ethyl decanoate as characteristic intense chromatographic peaks, which may suggest a specialized behavior for nectar collection. Discriminant Analysis allowed correct geographic discrimination of most honeys produced in the three spots tested. We concluded that volatile profile of stingless bee honeys can be used to attest authenticity related to regional origin of honeys. Copyright © 2017. Published by Elsevier Ltd.

Analysis of anabolic androgenic steroids as sulfate conjugates using high performance liquid chromatography coupled to tandem mass spectrometry.

PubMed

Rzeppa, S; Heinrich, G; Hemmersbach, P

2015-01-01

Improvements in doping analysis can be effected by speeding up analysis time and extending the detection time. Therefore, direct detection of phase II conjugates of doping agents, especially anabolic androgenic steroids (AAS), is proposed. Besides direct detection of conjugates with glucuronic acid, the analysis of sulfate conjugates, which are usually not part of the routine doping control analysis, can be of high interest. Sulfate conjugates of methandienone and methyltestosterone metabolites have already been identified as long-term metabolites. This study presents the synthesis of sulfate conjugates of six commonly used AAS and their metabolites: trenbolone, nandrolone, boldenone, methenolone, mesterolone, and drostanolone. In the following these sulfate conjugates were used for development of a fast and easy analysis method based on sample preparation using solid phase extraction with a mixed-mode sorbent and detection by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS). Validation demonstrated the suitability of the method with regard to the criteria given by the technical documents of the World Anti-Doping Agency (WADA). In addition, suitability has been proven by successful detection of the synthesized sulfate conjugates in excretion urines and routine doping control samples. Copyright © 2015 John Wiley & Sons, Ltd.

Metabolism of norethisterone in the greyhound.

PubMed

Biddle, S T B; O'Donnell, A; Houghton, E; Creaser, C S

2013-10-30

Norethisterone has been used as a successful oral contraceptive in humans for many years. It was recently permitted for use as an oestrus suppressant in racing greyhounds. To monitor the use of norethisterone as part of a routine drug surveillance programme, knowledge of its metabolism was required to enable detection. Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of norethisterone following oral administration to the greyhound. Metabolites were extracted using solid-phase and liquid-liquid extraction techniques. Several metabolites were identified, including reduced, mono-, di- and trihydroxylated steroids. The major metabolites observed were 17α-ethynyl-5β-estrane-3α,17β-diol, 17α-ethynyl-5α-estrane-3β,17β-diol, three 17α-ethynylestranetriol stereoisomers and two 17α-ethynylestranetetrol stereoisomers. The major metabolites were predominantly excreted as glucuronic acid conjugates and detection of the administration of norethisterone was possible for up to 8 days post-dose using the methods described. The nandrolone metabolites, 19-norepiandrosterone, estranediol and 19-noretiocholanolone, were also identified in the post-administration samples collected up to 8 h after dosing the treated animals. The urinary metabolites identified in this study have further increased the knowledge of steroid metabolism in the greyhound, providing information to support routine drug testing programmes for greyhound racing. Copyright © 2013 John Wiley & Sons, Ltd.

Hyperbranched-dendrimer architectural copolymer gene delivery using hyperbranched PEI conjugated to poly(propyleneimine) dendrimers: synthesis, characterization, and evaluation of transfection efficiency

NASA Astrophysics Data System (ADS)

Alavi, Seyyed Jamal; Gholami, Leila; Askarian, Saeedeh; Darroudi, Majid; Massoudi, Abdolhossein; Rezaee, Mehdi; Kazemi Oskuee, Reza

2017-02-01

The applications of dendrimer-based vectors seem to be promising in non-viral gene delivery because of their potential for addressing the problems with viral vectors. In this study, generation 3 poly(propyleneimine) (G3-PPI) dendrimers with 1, 4-diaminobutane as a core initiator was synthesized using a divergent growth approach. To increase the hydrophobicity and reduce toxicity, 10% of primary amines of G3-PPI dendrimers were replaced with bromoalkylcarboxylates with different chain lengths (6-bromohexanoic and 10-bromodecanoic). Then, to retain the overall buffering capacity and enhance transfection, the alkylcarboxylate-PPIs were conjugated to 10 kDa branched polyethylenimine (PEI). The results showed that the modified PPI was able to form complexes with the diameter of less than 60 nm with net-positive surface charge around 20 mV. No significant toxicity was observed in modified PPIs; however, the hexanoate conjugated PPI-PEI (PPI-HEX-10% PEI) and the decanoate conjugated PPI-PEI (PPI-DEC-10%-PEI) showed the best transfection efficiency in murine neuroblastoma (Neuro-2a) cell line, even PPI-HEX-10%-PEI showed transfection efficiency equal to standard PEI 25 kDa with reduced toxicity. This study suggested a new series of hyperbranched (PEI)-dendrimer (PPI) architectural copolymers as non-viral gene delivery vectors with high transfection efficiency and low toxicity.

Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84.

PubMed

Mahmud, Zobaer Al; Jenkins, Laura; Ulven, Trond; Labéguère, Frédéric; Gosmini, Romain; De Vos, Steve; Hudson, Brian D; Tikhonova, Irina G; Milligan, Graeme

2017-12-20

Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3'-diindolylmethane. 3,3'-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3'-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine 172 , located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3'-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3'-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [ 3 H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3'-diindolylmethane and was not affected adversely by mutation of arginine 172 . These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings.

Pharmacological interventions for borderline personality disorder

PubMed Central

Stoffers, Jutta; Völlm, Birgit A; Rücker, Gerta; Timmer, Antje; Huband, Nick; Lieb, Klaus

2014-01-01

Background Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders (“off-label use”), mostly targeting affective or impulsive symptom clusters. Objectives To assess the effects of drug treatment in BPD patients. Search methods We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. Selection criteria Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM-IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. Data collection and analysis Two authors selected trials, assessed quality and extracted data, independently. Main results Twenty-eight trials involving a total of 1742 trial participants were included. First-generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second-generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega-3 fatty acid) were tested. First-generation antipsychotics were subject to older trials, whereas recent studies focussed on second-generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first-generation antipsychotics and antidepressants. The findings were suggestive in supporting the use of second-generation antipsychotics, mood stabilisers, and omega-3 fatty acids, but require replication, since most effect estimates were based on single studies. The long-term use of these drugs has not been assessed. Adverse event data were scarce, except for olanzapine. There was a possible increase in self-harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition. Direct drug comparisons comprised two first-generation antipsychotics (loxapine versus chlorpromazine), first-generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second-generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes. Authors’ conclusions The available evidence indicates some beneficial effects with second-generation antipsychotics, mood stabilisers, and dietary supplementation by omega-3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients’ characteristics and duration of interventions and observation periods). PMID:20556762

High-performance liquid chromatographic determination of certain salicylates and their major metabolites in plasma following topical administration of a liniment to healthy subjects.

PubMed

Dadgar, D; Climax, J; Lambe, R; Darragh, A

1985-08-09

The liniment used is a topical analgesic and anti-inflammatory preparation containing two active constituents, 3-phenylpropylsalicylate and ethyl-5-methoxysalicylate, in solution in isobutyl decanoate. It is known that 3-phenylpropylsalicylate is metabolised to salicylic acid and salicyluric acid and ethyl-5-methoxysalicylate is metabolised to 5-methoxysalicylic acid and gentisic acid. In the present study the separation of the salicylates and their metabolites was carried out on a Waters mu Bondapak C18 column using two different mobile phases, methanol-water (80:20) for the parent drugs and methanol-5% aqueous acetic acid (27:73) for their metabolites. The salicylates and their metabolites were detected by absorption at 310 nm. The limits of detection for parent drugs and metabolites were respectively 0.2 and 0.1 microgram/ml in plasma, using a 1-ml plasma sample and a 20-microliter injection from a reconstituted volume of 250 microliter. Mean percentage coefficients of variation for intra-assay and inter-assay precision were between 3.3 +/- 1.9% to 9.1 +/- 3.7% and 6.8 +/- 2.2% to 15.7 +/- 10.1%, respectively. Linearity, as measured by the correlation coefficient of intra-assay linear regression curves, was better than 0.998 in all cases.

Lead(ii) soaps: crystal structures, polymorphism, and solid and liquid mesophases.

PubMed

Martínez-Casado, F J; Ramos-Riesco, M; Rodríguez-Cheda, J A; Redondo-Yélamos, M I; Garrido, L; Fernández-Martínez, A; García-Barriocanal, J; da Silva, I; Durán-Olivencia, M; Poulain, A

2017-07-05

The long-chain members of the lead(ii) alkanoate series or soaps, from octanoate to octadecanoate, have been thoroughly characterized by means of XRD, PDF analysis, DSC, FTIR, ssNMR and other techniques, in all their phases and mesophases. The crystal structures at room temperature of all of the members of the series are now solved, showing the existence of two polymorphic forms in the room temperature crystal phase, different to short and long-chain members. Only nonanoate and decanoate present both forms, and this polymorphism is proven to be monotropic. At higher temperature, these compounds present a solid mesophase, defined as rotator, a liquid crystal phase and a liquid phase, all of which have a similar local arrangement. Since some lead(ii) soaps appear as degradation compounds in oil paintings, the solved crystal structures of lead(ii) soaps can now be used as fingerprints for their detection using X-ray diffraction. Pair distribution function analysis on these compounds is very similar in the same phases and mesophases for the different members, showing the same short range order. This observation suggests that this technique could also be used in the detection of these compounds in disordered phases or in the initial stages of formation in paintings.

Physical and monolayer film properties of potential fatty ester biolubricants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yao, Linxing; Hammond, Earl G; Wang, Tong

2014-04-03

The desire to replace petroleum-based lubricants with alternatives that are environmentally friendly and made from sustainable sources has encouraged the development of biolubricants based on vegetable oils. To be good lubricants, the materials should have low melting points, appropriate viscosity and oxidative stability. In this paper, we report the melting point and viscosity of oleate esters of ethylene glycol, 1,2-propanediol, 2,3-butanediol, and pentaerythritol as well as the decanoate esters of 2,3-butanediol and the 12-methyltetradecanoate esters of 1,2-propanediol. Polyol esters that have a free hydroxy group had lower melting points than the completely esterified polyols, but the completely esterified polyol estersmore » exhibited less change in viscosity with temperature than those having a free hydroxy group. 2, 3-Butanediol monooleate, which melted at -48.6°C shows promise as a biolubricant, but its viscosity index was estimated to be 100. Pentaerythritol oleate esters, with melting points below -10°C and viscosity indices in the range of 170–197, may be suitable candidates as biolubricants. The behavior of esters spread as a monomolecular film at air/water interface may provide insight into the way they behave when spread on metal or polar surfaces, so the pressure-area isotherms of 2,3-butanediol monoleate and selected esters are also reported.« less

Targeted analysis and determination of β-agonists, hormones, glucocorticoid and psychiatric drugs in feed by liquid chromatography with electrospray ionization tandem mass spectrometry.

PubMed

Zhu, Yufei; Xie, Shuyu; Chen, Dongmei; Pan, Yuanhu; Qu, Wei; Wang, Xu; Liu, Zhenli; Peng, Dapeng; Huang, Lingli; Tao, Yanfei; Yuan, Zonghui

2016-07-01

A comprehensive strategy combining a quantitative method was developed for 30 banned drugs including β-agonists, hormones, glucocorticoid and psychiatric drugs in swine and chicken feeds. This rapid, simple and effective extraction method was based on matrix solid-phase dispersion and electrospray ionization tandem mass spectrometry. The quantitative method was validated after previous statistical optimization of the main parameters of matrix solid-phase dispersion. The limit of quantification of dopamine hydrochloride, chlormadinone acetate, melengestrol acetate, testosterone propionate, nandrolone and midazolam was 2 μg/kg and that of the other 24 drugs was 1 μg/kg. The recoveries of β-agonists, hormones, glucocorticoid and psychiatric drugs spiked in swine and chicken feeds at a concentration range of 1-8 μg/kg were above 70.1% with inter-day relative standard deviations less than 15.8%. The analytical strategy was applied to 100 feed samples collected from a local market in Wuhan (China). Clenbuterol, ractopamine and melengestrol acetate were identified and quantified at the level 0.2∼3.5 μg/kg. The rapid and reliable method can be used to efficiently separate, characterize and quantify the residues of 30 banned drugs in swine and chicken feeds with advantages of simple pretreatment and environmental friendly nature. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microbial species diversity, community dynamics, and metabolite kinetics of water kefir fermentation.

PubMed

Laureys, David; De Vuyst, Luc

2014-04-01

Water kefir is a sour, alcoholic, and fruity fermented beverage of which the fermentation is started with water kefir grains. These water kefir grains consist of polysaccharide and contain the microorganisms responsible for the water kefir fermentation. In this work, a water kefir fermentation process was followed as a function of time during 192 h to unravel the community dynamics, the species diversity, and the kinetics of substrate consumption and metabolite production. The majority of the water kefir ecosystem was found to be present on the water kefir grains. The most important microbial species present were Lactobacillus casei/paracasei, Lactobacillus harbinensis, Lactobacillus hilgardii, Bifidobacterium psychraerophilum/crudilactis, Saccharomyces cerevisiae, and Dekkera bruxellensis. The microbial species diversities in the water kefir liquor and on the water kefir grains were similar and remained stable during the whole fermentation process. The major substrate, sucrose, was completely converted after 24 h of fermentation, which coincided with the production of the major part of the water kefir grain polysaccharide. The main metabolites of the fermentation were ethanol and lactic acid. Glycerol, acetic acid, and mannitol were produced in low concentrations. The major part of these metabolites was produced during the first 72 h of fermentation, during which the pH decreased from 4.26 to 3.45. The most prevalent volatile aroma compounds were ethyl acetate, isoamyl acetate, ethyl hexanoate, ethyl octanoate, and ethyl decanoate, which might be of significance with respect to the aroma of the end product.

Trail pheromone of ponerine ant Gnamptogenys striatula: 4-methylgeranyl esters from Dufour's gland.

PubMed

Blatrix, Rumsaïs; Schulz, Claudia; Jaisson, Pierre; Francke, Wittko; Hefetz, Abraham

2002-12-01

Dufour's gland is the origin of the trail pheromone of Gnamptogenys striatula. Chemical analysis of the glandular extracts revealed a series of new natural products, especially esters of (2E)-3,4,7-trimethyl-2,6-octadien-1-ol (4-methylgeraniol), and (2E)-3,4,7-trimethyl-2,6-nonadien-1-ol (a bishomogeraniol isomer) with medium-chain fatty acids. Bioassays with synthetic racemates of the esters revealed that the 4-methylgeranyl esters are highly active as trail pheromones, while the bishomogeranyl esters are either marginally active or not active at all. Assays with the individual 4-methylgeranyl esters showed each of them to be inferior to the glandular secretion in eliciting trail following. However, the mixture of racemic 4-methylgeranyl octanoate and the corresponding decanoate and dodecanoate, the main Dufour's volatile constituents, is as active as the natural secretion at similar concentration. We conclude that the trail pheromone constitutes a mixture of at least the 4-methylgeranyl esters identified in the gland. Since G. striatula generally preys on small arthropods rather than monopolizing large resources, we assume that trails are rarely used during foraging, but more often during nest migration. Production of new societies in this species is generally performed by budding, a period of considerable predation risk. Utilizing trails for efficient displacement in this context is, therefore, highly adaptive. This behavioral repertoire may also provide the ants with additional means of food resource exploitation.

Proteins involved in wine aroma compounds metabolism by a Saccharomyces cerevisiae flor-velum yeast strain grown in two conditions.

PubMed

Moreno-García, Jaime; García-Martínez, Teresa; Millán, M Carmen; Mauricio, Juan Carlos; Moreno, Juan

2015-10-01

A proteomic and exometabolomic study was conducted on Saccharomyces cerevisiae flor yeast strain growing under biofilm formation condition (BFC) with ethanol and glycerol as carbon sources and results were compared with those obtained under no biofilm formation condition (NBFC) containing glucose as carbon source. By using modern techniques, OFFGEL fractionator and LTQ-Orbitrap for proteome and SBSE-TD-GC-MS for metabolite analysis, we quantified 84 proteins including 33 directly involved in the metabolism of glycerol, ethanol and 17 aroma compounds. Contents in acetaldehyde, acetic acid, decanoic acid, 1,1-diethoxyethane, benzaldehyde and 2-phenethyl acetate, changed above their odor thresholds under BFC, and those of decanoic acid, ethyl octanoate, ethyl decanoate and isoamyl acetate under NBFC. Of the twenty proteins involved in the metabolism of ethanol, acetaldehyde, acetoin, 2,3-butanediol, 1,1-diethoxyethane, benzaldehyde, organic acids and ethyl esters, only Adh2p, Ald4p, Cys4p, Fas3p, Met2p and Plb1p were detected under BFC and as many Acs2p, Ald3p, Cem1p, Ilv2p, Ilv6p and Pox1p, only under NBFC. Of the eight proteins involved in glycerol metabolism, Gut2p was detected only under BFC while Pgs1p and Rhr2p were under NBFC. Finally, of the five proteins involved in the metabolism of higher alcohols, Thi3p was present under BFC, and Aro8p and Bat2p were under NBFC. Copyright © 2015 Elsevier Ltd. All rights reserved.

Pharmacokinetics of boldenone and stanozolol and the results of quantification of anabolic and androgenic steroids in race horses and nonrace horses.

PubMed

Soma, L R; Uboh, C E; Guan, F; McDonnell, S; Pack, J

2007-04-01

Anabolic steroids (ABS) boldenone (BL; 1.1 mg/kg) and stanozolol (ST; 0.55 mg/kg) were administered i.m. to horses and the plasma samples collected up to 64 days. Anabolic steroids and androgenic steroids (ANS) in plasma were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limit of detection of all analytes was 25 pg/mL. The median absorption (t1/2 partial differential) and elimination (t1/2e) half-lives for BL were 8.5 h and 123.0 h, respectively, and the area under the plasma concentration-time curve (AUCho) was 274.8 ng.h/mL. The median t1/2e for ST was 82.1 h and the was 700.1 ng.h/mL. Peak mean (X+/-SD) plasma concentrations (Cmax) for BL and ST were 1127.8 and 4118.2 pg/mL, respectively. Quantifiable concentrations of ABS and ANS were found in 61.7% of the 988 plasma samples tested from race tracks. In 17.3% of the plasma samples two or more ABS or ANS were quantifiable. Testosterone (TES) concentrations mean (X+/-SE) in racing and nonracing intact males were 241.3+/-61.3 and 490.4+/-35.1 pg/mL, respectively. TES was not quantified in nonracing geldings and female horses, but was in racing females and geldings. Plasma concentrations of endogenous 19-nortestosterone (nandrolone; NA) from racing and nonracing males were 50.2+/-5.5 and 71.8+/-4.6 pg/mL, respectively.

[Comparison of medical and economic benefits of antipsychotics in the treatment of schizophrenia in France].

PubMed

Druais, S; Doutriaux, A; Cognet, M; Godet, A; Lançon, C; Levy, P; Samalin, L; Guillon, P

2017-08-01

The course of schizophrenia can vary widely, and patients experience remission phases alternating with relapse episodes, which generally lead to hospitalisation and have a significant impact on the burden of disease. The prevalence of schizophrenia in France is estimated to be approximately 600,000 people, with an incidence of 10,000 new patients per year. Patients with schizophrenia represent the largest group of hospitalised patients in French public institutions and specialised centres, and the French authorities recognise that the management of schizophrenia is a major public health concern. The Haute Autorité de Santé (HAS) and most of the evidence-based guidelines for the maintenance treatment of schizophrenia recommend long-acting injectable (LAI) antipsychotics to be used predominantly in the prevention of relapse for non-compliant patients; however, in clinical practice, the use of LAIs remains low. This analysis aimed to estimate and to compare the cost-effectiveness of the most common antipsychotic strategies in France in the management of schizophrenia. A Markov model was developed to simulate the progression of a cohort of patients with schizophrenia through four health states (stable treated, stable non-treated, relapse and death) and considered up to three lines of treatment to account for changes in treatment management. Antipsychotics including aripiprazole LAI (ALAI), olanzapine LAI (OLAI), paliperidone LAI (PLAI), risperidone LAI (RLAI), haloperidol decanoate (HD) and oral olanzapine (OO) were compared in terms of costs and clinical outcomes. Thus, costs, quality-adjusted life-years (QALYs) and number of relapses were assessed over five years based on three-month cycles from a French health insurance perspective with a discount rate of 4 %. Patients were considered to be stabilised after clinical decompensation and would enter the model at an initiation phase, followed by a prevention of relapse phase if successful. Data (e.g. relapse or discontinuation rates) for the initiation phase came from randomised clinical trials, whereas relapse rates in the prevention phase were derived from hospitalisation risks based on French real-life data in order to capture adherence effects. Safety and utility data were derived from international publications. Additionally costs were retrieved from French health insurance databases and publications. Robustness of results was assessed through deterministic and probabilistic sensitivity analyses. First and second generations of LAIs were found to have similar costs over five years; i.e. approximately € 55,000, except for PLAI which was associated with a discounted cost of € 50,880. Oral antipsychotics were found to be less costly (i.e. OO cost € 50,379 after five years) but associated with a lower number of QALYs gained and relapse avoided. PLAI and RLAI were associated with the greatest number of QALYs gained; i.e. PLAI dominated ALAI, OLAI and HD and was associated with an incremental costs-effectiveness ratio (ICER) of € 2411 per QALY gained versus OO. Finally, PLAI and OLAI were associated with the lowest number of relapses; i.e. PLAI dominated RLAI, ALAI and HLAI and was associated with an ICER of € 1782 per avoided relapse compared to OO. OO and HD were found to have led to the highest number of relapses. This analysis, to the best of our knowledge, is the first of its kind to assess the cost-effectiveness of antipsychotics based on French observational data. PLAI was associated with the highest probability of being the optimal treatment from the French health insurance perspective. Copyright © 2016. Published by Elsevier Masson SAS.

Gateways to clinical trials.

PubMed

Bayés, M; Rabasseda, X; Prous, J R

2005-12-01

Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data in the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity. prous.com. This issue focuses on the following selection of drugs: 131I-chTNT; Abatacept, adalimumab, alemtuzumab, APC-8015, aprepitant, atazanavir sulfate, atomoxetine hydrochloride, azimilide hydrochloride; Bevacizumab, bortezomib, bosentan, buserelin; Caspofungin acetate, CC-4047, ChAGCD3, ciclesonide, clopidogrel, curcumin, Cypher; Dabigatran etexilate, dapoxetine hydrochloride, darbepoetin alfa, darusentan, denosumab, DMXB-Anabaseine, drospirenone, drospirenone/estradiol, duloxetine hydrochloride, dutasteride; Edodekin alfa, efaproxiral sodium, elaidic acid-cytarabine, erlotinib hydrochloride, ertapenem sodium, escitalopram oxalate, eszopiclone, etonogestrel/testosterone decanoate, exenatide; Fulvestrant; Gefitinib, glycine, GVS-111; Homoharringtonine; ICC-1132, imatinib mesylate, iodine (I131) tositumomab, i.v. gamma-globulin; Levetiracetam, levocetirizine, lintuzumab, liposomal nystatin, lumiracoxib, lurtotecan; Manitimus, mapatumumab, melatonin, micafungin sodium, mycophenolic acid sodium salt; Oblimersen sodium, OGX-011, olmesartan medoxomil, omalizumab, omapatrilat, oral insulin; Parathyroid hormone (human recombinant), pasireotide, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, phVEGF-A165, pimecrolimus, pitavastatin calcium, plerixafor hydrochloride, posaconazole, pramlintide acetate, prasterone, pregabalin, PT-141; Quercetin; Ranolazine, rosuvastatin calcium, rubitecan, rupatadine fumarate; Sardomozide, sunitinib malate; Tadalafil, talactoferrin alfa, tegaserod maleate, telithromycin, testosterone transdermal patch, TH-9507, tigecycline, tiotropium bromide, tipifarnib, tocilizumab, treprostinil sodium; Valdecoxib, vandetanib, vardenafil hydrochloride hydrate, voriconazole. Copyright 2005 Prous Science. All rights reserved.

Combined effects of fermentation temperature and pH on kinetic changes of chemical constituents of durian wine fermented with Saccharomyces cerevisiae.

PubMed

Lu, Yuyun; Voon, Marilyn Kai Wen; Huang, Dejian; Lee, Pin-Rou; Liu, Shao-Quan

2017-04-01

This study investigated the effects of temperature (20 and 30 °C) and pH (pH 3.1, 3.9) on kinetic changes of chemical constituents of the durian wine fermented with Saccharomyces cerevisiae. Temperature significantly affected growth of S. cerevisiae EC-1118 regardless of pH with a higher temperature leading to a faster cell death. The pH had a more significant effect on ethanol production than temperature with higher production at 20 °C (5.95%, v/v) and 30 °C (5.56%, v/v) at pH 3.9, relative to that at pH 3.1 (5.25 and 5.01%, v/v). However, relatively higher levels of isobutyl alcohol and isoamyl alcohol up to 64.52 ± 6.39 and 56.27 ± 3.00 mg/L, respectively, were produced at pH 3.1 than at pH 3.9 regardless of temperature. In contrast, production of esters was more affected by temperature than pH, where levels of ethyl esters (ethyl esters of octanoate, nonanoate, and decanoate) and acetate esters (ethyl acetate and isoamyl acetate) were significantly higher up to 2.13 ± 0.23 and 4.61 ± 0.22 mg/L, respectively, at 20 °C than at 30 °C. On the other hand, higher temperature improved the reduction of volatile sulfur compounds. This study illustrated that temperature control would be a more effective tool than pH in modulating the resulting aroma compound profile of durian wine.

AraC/XylS Family Stress Response Regulators Rob, SoxS, PliA, and OpiA in the Fire Blight Pathogen Erwinia amylovora

PubMed Central

Pletzer, Daniel; Schweizer, Gabriel

2014-01-01

Transcriptional regulators of the AraC/XylS family have been associated with multidrug resistance, organic solvent tolerance, oxidative stress, and virulence in clinically relevant enterobacteria. In the present study, we identified four homologous AraC/XylS regulators, Rob, SoxS, PliA, and OpiA, from the fire blight pathogen Erwinia amylovora Ea1189. Previous studies have shown that the regulators MarA, Rob, and SoxS from Escherichia coli mediate multiple-antibiotic resistance, primarily by upregulating the AcrAB-TolC efflux system. However, none of the four AraC/XylS regulators from E. amylovora was able to induce a multidrug resistance phenotype in the plant pathogen. Overexpression of rob led to a 2-fold increased expression of the acrA gene. However, the rob-overexpressing strain showed increased resistance to only a limited number of antibiotics. Furthermore, Rob was able to induce tolerance to organic solvents in E. amylovora by mechanisms other than efflux. We demonstrated that SoxS from E. amylovora is involved in superoxide resistance. A soxS-deficient mutant of Ea1189 was not able to grow on agar plates supplemented with the superoxide-generating agent paraquat. Furthermore, expression of soxS was induced by redox cycling agents. We identified two novel members of the AraC/XylS family in E. amylovora. PliA was highly upregulated during the early infection phase in apple rootstock and immature pear fruits. Multiple compounds were able to induce the expression of pliA, including apple leaf extracts, phenolic compounds, redox cycling agents, heavy metals, and decanoate. OpiA was shown to play a role in the regulation of osmotic and alkaline pH stress responses. PMID:24936054

Chemical Composition and Allelopathic, Antibacterial, Antifungal, and Antiacetylcholinesterase Activity of Fish-mint (Houttuynia cordataThunb.) from India.

PubMed

Verma, Ram S; Joshi, Neeta; Padalia, Rajendra C; Singh, Ved R; Goswami, Prakash; Kumar, Ajay; Iqbal, Hina; Verma, Rajesh K; Chanda, Debabrata; Chauhan, Amit; Saikia, Dharmendra

2017-10-01

Fish-mint (Houttuynia cordataThunb.), belonging to family Saururaceae, has long been used as food and traditional herbal medicine. The present study was framed to assess the changes occurring in the essential-oil composition of H. cordata during annual growth and to evaluate allelopathic, antibacterial, antifungal, and antiacetylcholinesterase activities. The essential-oil content ranged from 0.06 - 0.14% and 0.08 - 0.16% in aerial parts and underground stem, respectively. The essential oils were analysed by GC-FID, GC/MS, and NMR ( 1 H and 13 C). Major constituents of aerial-parts oil was 2-undecanone (19.4 - 56.3%), myrcene (2.6 - 44.3%), ethyl decanoate (0.0 - 10.6%), ethyl dodecanoate (1.1 - 8.6%), 2-tridecanone (0.5 - 8.3%), and decanal (1.1 - 6.9%). However, major constituents of underground-stem oil were 2-undecanone (29.5 - 42.3%), myrcene (14.4 - 20.8%), sabinene (6.0 - 11.1%), 2-tridecanone (1.8 - 10.5%), β-pinene (5.3 - 10.0%), and ethyl dodecanoate (0.8 - 7.3%). Cluster analysis revealed that essential-oil composition varied substantially due to the plant parts and season of collection. The oils exhibited significant allelopathic (inhibition: 77.8 - 88.8%; LD 50 : 2.45 - 3.05 μl/plate), antibacterial (MIC: 0.52 - 2.08 μl/ml; MBC: bacteriostatic) and antifungal (MIC: 2.08 - 33.33 μl/ml; MFC: 4.16 - 33.33 μl/ml) activities. The results indicate that the essential oil from H. cordata has a significant potential to allow future exploration and exploitation as a natural antimicrobial and allelopathic agent. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

A computational investigation of diesel and biodiesel combustion and NOx formation in a light-duty compression ignition engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zihan; Srinivasan, Kalyan K.; Krishnan, Sundar R.

Diesel and biodiesel combustion in a multi-cylinder light duty diesel engine were simulated during a closed cycle (from IVC to EVO), using a commercial computational fluid dynamics (CFD) code, CONVERGE, coupled with detailed chemical kinetics. The computational domain was constructed based on engine geometry and compression ratio measurements. A skeletal n-heptane-based diesel mechanism developed by researchers at Chalmers University of Technology and a reduced biodiesel mechanism derived and validated by Luo and co-workers were applied to model the combustion chemistry. The biodiesel mechanism contains 89 species and 364 reactions and uses methyl decanoate, methyl-9- decenoate, and n-heptane as the surrogatemore » fuel mixture. The Kelvin-Helmholtz and Rayleigh-Taylor (KH-RT) spray breakup model for diesel and biodiesel was calibrated to account for the differences in physical properties of the fuels which result in variations in atomization and spray development characteristics. The simulations were able to capture the experimentally observed pressure and apparent heat release rate trends for both the fuels over a range of engine loads (BMEPs from 2.5 to 10 bar) and fuel injection timings (from 0° BTDC to 10° BTDC), thus validating the overall modeling approach as well as the chemical kinetic models of diesel and biodiesel surrogates. Moreover, quantitative NOx predictions for diesel combustion and qualitative NOx predictions for biodiesel combustion were obtained with the CFD simulations and the in-cylinder temperature trends were correlated to the NOx trends.« less

Microbial Species Diversity, Community Dynamics, and Metabolite Kinetics of Water Kefir Fermentation

PubMed Central

Laureys, David

2014-01-01

Water kefir is a sour, alcoholic, and fruity fermented beverage of which the fermentation is started with water kefir grains. These water kefir grains consist of polysaccharide and contain the microorganisms responsible for the water kefir fermentation. In this work, a water kefir fermentation process was followed as a function of time during 192 h to unravel the community dynamics, the species diversity, and the kinetics of substrate consumption and metabolite production. The majority of the water kefir ecosystem was found to be present on the water kefir grains. The most important microbial species present were Lactobacillus casei/paracasei, Lactobacillus harbinensis, Lactobacillus hilgardii, Bifidobacterium psychraerophilum/crudilactis, Saccharomyces cerevisiae, and Dekkera bruxellensis. The microbial species diversities in the water kefir liquor and on the water kefir grains were similar and remained stable during the whole fermentation process. The major substrate, sucrose, was completely converted after 24 h of fermentation, which coincided with the production of the major part of the water kefir grain polysaccharide. The main metabolites of the fermentation were ethanol and lactic acid. Glycerol, acetic acid, and mannitol were produced in low concentrations. The major part of these metabolites was produced during the first 72 h of fermentation, during which the pH decreased from 4.26 to 3.45. The most prevalent volatile aroma compounds were ethyl acetate, isoamyl acetate, ethyl hexanoate, ethyl octanoate, and ethyl decanoate, which might be of significance with respect to the aroma of the end product. PMID:24532061

Numerical variation of dark cells in normal and chemically induced hyperplastic epidermis with age of animal and efficiency of tumor promoter. [Mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein-Szanto, A.J.P.; Slaga, T.J.

1981-11-01

The percentage of dark basal keratinocytes was quantitatively assessed in normal epidermis of Sencar mice before and after birth and in adult epidermis after topical application of several compounds of varying promoting efficiency. The percentage of dark keratinocytes reached a maximum at the 19th day of gestation (approx.40%) and fell abruptly after birth (approx.3%). Old animals exhibited a very low number of dark basal cells (0.2%). After topical application of the weak promoters resiniferotoxin, anthralin, ethylphenylpropiolate, and 12-deoxyphorbol-13-2,4,6-decatrienoate, the percentage of dark cells in young adult epidermis did not differ markedly from that in control (acetone-treated) specimens. The strong first-stagemore » promoters 4-O-methyl-12-O-tetradecanoylphorbol-13-acetate and calcium ionophore A 23187, as well as the strong complete promoter 12-deoxyphorbol-13-deoxyphorbol-13-decanoate, induced the appearance of large numbers of dark keratinocytes, in a percentage similar to that seen after 12-O-tetra-decanoylphorbol-13-acetate application (approx.20%). The similarities between the dark keratinocytes seen after topical application of 12-O-tetradecanoylphorbol-13-acetate or other strong promoters and the dark cells observed in the fetal epidermis before the onset of the adult type of epidermal keratinization indicate that potent and/or first stage tumor promoters can be identified by their ability to induce cells resembling fetal-type dedifferentiated keratinocytes.« less

Studies of drug delivery systems for a therapeutic agent used in osteoporosis. I. Pharmacodynamics (hypocalcemic effect) of elcatonin in rabbits following rectal administration of hollow-type suppositories containing elcatonin.

PubMed

Watanabe, Y; Mizufune, Y; Kubomura, A; Kiriyama, M; Utoguchi, N; Matsumoto, M

1998-11-01

In this study, we developed a new hollow-type suppository containing elcatonin ((Asu1,7)-eel calcitonin, ECT), a synthetic derivative of eel calcitonin, which produces hypocalcemia, as a pharmaceutical preparation for self administration, to be used instead of parenteral injections for patients with osteoporosis. The absorption of ECT from the rectal mucous membrane was evaluated by observation of the decrease in serum calcium (Ca) concentrations following rectal administration in rabbits. ECT was efficiently absorbed from the rectum and effectively decreased serum Ca concentrations. The data of the area under the percent decrease in serum Ca concentration (deltaCa%)-time curve (deltaCa%-AUC), assumed to be an index of the pharmacodynamics (pharmacological effect) of ECT, indicated that similar hypocalcemic effects were obtained following rectal and intravenous administrations of ECT. In regard to the effect of coadministration of other compounds on rectal absorption of ECT, no significant difference in the deltaCa%-AUC between rectal ECT administration with or without nafamostat mesilate (a protease inhibitor) was observed. However, the coadministration of ECT with cytochalasin B or monensin (endocytosis inhibitors) significantly decreased the deltaCa%-AUC, indicating that rectal ECT absorption is probably inhibited by endocytosis inhibitors. On the other hand, it was found that sodium decanoate, a medium-chain fatty acid (sodium salt), significantly enhanced the rectal absorption of ECT. We conclude that this ECT hollow-type suppository offers promise as a new method for the administration of ECT.

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

PubMed

KaplanskiI, A S; Il'ina-Kakueva, E I; Durnova, G N; Alekseev, E A; Loginov, V I

1999-01-01

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.

[Determination of 11 anabolic hormones in fish tissue by multi-function impurity adsorption solid-phase extraction-ultrafast liquid chromatography-tandem mass spectrometry].

PubMed

Yao, Shanshan; Zhao, Yonggang; Li, Xiaoping; Chen, Xiaohong; Jin, Micong

2012-06-01

A method was developed for the determination of 11 anabolic hormones (boldenone, androstenedione, nandrolone, methandrostenolone, methyltestosterone, testosterone, testosterone acetate, trenbolone, testosterone propionate, stanozolol, fluoxymesterone) in fish by multi-function impurity adsorption solid-phase extraction-ultrafast liquid chromatography-tandem mass spectrometry. After the sample was extracted by methanol, the extract was cleaned-up quickly by C18 adsorbent, neutral alumina adsorbent and amino-functionalized nano-adsorbent. The separation was performed on a Shim-Pack XR-ODS II column (100 mm x 2.0 mm, 2.2 microm) using the mobile phases of 0.1% (v/v) formic acid in acetonitrile and 0.1% (v/v) formic acid solution in a gradient elution mode. The identification and quantification were achieved by using electrospray ionization in positive ion mode (ESI+) in multiple reaction monitoring (MRM) mode. The matrix-matched external standard calibration curves were used for quantitative determination. The results showed that the calibration curves were in good linearity for the eleven analytes with the correlation coefficients (r) more than 0.999. The limits of detection (LODs, S/N > 3) for the 11 anabolic hormones were from 0.03 microg/kg to 0.4 microg/kg and the limits of quantification (LOQs, S/N > 10) were from 0.1 microg/kg to 1.5 microg/kg. The average recoveries ranged from 80.9% to 98.1% with the relative standard deviations between 5.2% and 11.5%. The method is simple, rapid, sensitive, accurate and suitable for the quantitative determination and confirmation of the 11 anabolic hormones in fish.

Activation of Two Different Resistance Mechanisms in Saccharomyces cerevisiae upon Exposure to Octanoic and Decanoic Acids▿ †

PubMed Central

Legras, J. L.; Erny, C.; Le Jeune, C.; Lollier, M.; Adolphe, Y.; Demuyter, C.; Delobel, P.; Blondin, B.; Karst, F.

2010-01-01

Medium-chain fatty acids (octanoic and decanoic acids) are well known as fermentation inhibitors. During must fermentation, the toxicity of these fatty acids is enhanced by ethanol and low pH, which favors their entrance in the cell, resulting in a decrease of internal pH. We present here the characterization of the mechanisms involved in the establishment of the resistance to these fatty acids. The analysis of the transcriptome response to the exposure to octanoic and decanoic acids revealed that two partially overlapping mechanisms are activated; both responses share many genes with an oxidative stress response, but some key genes were activated differentially. The transcriptome response to octanoic acid stress can be described mainly as a weak acid response, and it involves Pdr12p as the main transporter. The phenotypic analysis of knocked-out strains confirmed the role of the Pdr12p transporter under the control of WAR1 but also revealed the involvement of the Tpo1p major facilitator superfamily proteins (MFS) transporter in octanoic acid expulsion. In contrast, the resistance to decanoic acid is composite. It also involves the transporter Tpo1p and includes the activation of several genes of the beta-oxidation pathway and ethyl ester synthesis. Indeed, the induction of FAA1 and EEB1, coding for a long-chain fatty acyl coenzyme A synthetase and an alcohol acyltransferase, respectively, suggests a detoxification pathway through the production of decanoate ethyl ester. These results are confirmed by the sensitivity of strains bearing deletions for the transcription factors encoded by PDR1, STB5, OAF1, and PIP2 genes. PMID:20851956

Inhibitors for magnesium corrosion: Metal organic frameworks

NASA Astrophysics Data System (ADS)

Mesbah, Adel; Juers, Caroline; Lacouture, Françoise; Mathieu, Stéphane; Rocca, Emmanuel; François, Michel; Steinmetz, Jean

2007-03-01

Electrochemical measurements demonstrate that magnesium surfaces can be protected by alkyl carboxylate. In a nearly neutral pH solution of sodium decanoate, the reduced corrosion rate and a passivation behaviour are attributed to the formation of Mg(C 10H 19O 2) 2(H 2O) 3 (Mg(C10) 2) at the magnesium surface whereas heptanoate Mg(C 7H 13O 2) 2(H 2O) 3 (Mg(C7) 2) is not efficient in such media. The crystal structures of the two metal carboxylates Mg(C7) 2 and Mg(C10) 2 are determined by X-ray diffraction. Single crystal data: Mg(C7) 2, P2 1/ a, a = 9.130(5) Å, b = 8.152(5) Å, c = 24.195(5) Å, β = 91.476(5)°, V = 1800.3(15) Å 3, Dx = 1.242 g cm -3, Z = 4. Synchrotron powder data: Mg(C10) 2, P2 1/ a, a = 9.070(3) Å, b = 8.165(1) Å, c = 32.124(1) Å, β = 98.39(1)°, V = 2353.85(8) Å 3, Dx = 1.188 g cm -3, Z = 4. Their layered structures are quite similar and differ mainly by the length of the hydrophobic chains. They consist of two planes of O-octahedra centred by Mg atoms, parallel to (001). The distorted octahedra are constituted by three oxygen atoms from carboxylate groups and by three oxygen atoms coming from water molecules. The layers are connected by hydrogen bonds. The carboxylate chains are located perpendicularly and on both sides of these planes. One carboxylate chain is bridging the Mg atom along [010] while the other is monodendate. The presence of structural water is confirmed by thermal analyses.

The use of stable isotopes and gas chromatography/mass spectrometry in the identification of steroid metabolites in the equine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Houghton, E.; Dumasia, M.C.; Teale, P.

1990-10-01

Stable isotope gas chromatography/mass spectrometry has been used successfully in the elucidation of structures of urinary steroid metabolites in the horse and in the identification of metabolites isolated from in vivo perfusion and in vitro incubation studies using equine tissue preparations. Deuterium-labeled steroids, testosterone, dehydroepiandrosterone, and 5-androstene-3 beta,17 beta-diol have been synthesized by base-catalyzed isotope exchange methods and the products characterized by gas chromatography/mass spectrometry. (16,16(-2)H2)Dehydroepiandrosterone (plus radiolabeled dehydroepiandrosterone) was perfused into a testicular artery of a pony stallion and was shown to be metabolized into 2H2-labeled testosterone, 4-androstenedione, isomers of 5-androstene-3,17-diol, 19-hydroxytestosterone, and 19-hydroxy-4-androstenedione. In further studies, equine testicularmore » minces have been incubated with 2H2-labeled and radiolabeled dehydroepiandrosterone and 5-androstene-3 beta, 17 beta-diol. The metabolites, whose identity was confirmed by stable isotope gas chromatography/mass spectrometry, proved the interconversion of the two substrates, as well as formation of testosterone and 4-androstenedione. The aromatization of dehydroepiandrosterone was also confirmed, together with the formation of an isomer of 5(10)-estrene-3,17-diol from both substrates showing 19-demethylation without concomitant aromatization. In studies of the feto-placental unit, the allantochorion was shown to aromatize (2H5)testosterone to (2H4)estradiol, the loss of one 2H from the substrate being consistent with aromatization of the A ring. The formation of 6-hydroxyestradiol was also confirmed in this study. The same technique has been valuable in determining the structure of two metabolites of nandrolone isolated from horse urine.« less

AraC/XylS family stress response regulators Rob, SoxS, PliA, and OpiA in the fire blight pathogen Erwinia amylovora.

PubMed

Pletzer, Daniel; Schweizer, Gabriel; Weingart, Helge

2014-09-01

Transcriptional regulators of the AraC/XylS family have been associated with multidrug resistance, organic solvent tolerance, oxidative stress, and virulence in clinically relevant enterobacteria. In the present study, we identified four homologous AraC/XylS regulators, Rob, SoxS, PliA, and OpiA, from the fire blight pathogen Erwinia amylovora Ea1189. Previous studies have shown that the regulators MarA, Rob, and SoxS from Escherichia coli mediate multiple-antibiotic resistance, primarily by upregulating the AcrAB-TolC efflux system. However, none of the four AraC/XylS regulators from E. amylovora was able to induce a multidrug resistance phenotype in the plant pathogen. Overexpression of rob led to a 2-fold increased expression of the acrA gene. However, the rob-overexpressing strain showed increased resistance to only a limited number of antibiotics. Furthermore, Rob was able to induce tolerance to organic solvents in E. amylovora by mechanisms other than efflux. We demonstrated that SoxS from E. amylovora is involved in superoxide resistance. A soxS-deficient mutant of Ea1189 was not able to grow on agar plates supplemented with the superoxide-generating agent paraquat. Furthermore, expression of soxS was induced by redox cycling agents. We identified two novel members of the AraC/XylS family in E. amylovora. PliA was highly upregulated during the early infection phase in apple rootstock and immature pear fruits. Multiple compounds were able to induce the expression of pliA, including apple leaf extracts, phenolic compounds, redox cycling agents, heavy metals, and decanoate. OpiA was shown to play a role in the regulation of osmotic and alkaline pH stress responses. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Tuning Chocolate Flavor through Development of Thermotolerant Saccharomyces cerevisiae Starter Cultures with Increased Acetate Ester Production.

PubMed

Meersman, Esther; Steensels, Jan; Struyf, Nore; Paulus, Tinneke; Saels, Veerle; Mathawan, Melissa; Allegaert, Leen; Vrancken, Gino; Verstrepen, Kevin J

2016-01-15

Microbial starter cultures have extensively been used to enhance the consistency and efficiency of industrial fermentations. Despite the advantages of such controlled fermentations, the fermentation involved in the production of chocolate is still a spontaneous process that relies on the natural microbiota at cocoa farms. However, recent studies indicate that certain thermotolerant Saccharomyces cerevisiae cultures can be used as starter cultures for cocoa pulp fermentation. In this study, we investigate the potential of specifically developed starter cultures to modulate chocolate aroma. Specifically, we developed several new S. cerevisiae hybrids that combine thermotolerance and efficient cocoa pulp fermentation with a high production of volatile flavor-active esters. In addition, we investigated the potential of two strains of two non-Saccharomyces species that produce very large amounts of fruity esters (Pichia kluyveri and Cyberlindnera fabianii) to modulate chocolate aroma. Gas chromatography-mass spectrometry (GC-MS) analysis of the cocoa liquor revealed an increased concentration of various flavor-active esters and a decrease in spoilage-related off-flavors in batches inoculated with S. cerevisiae starter cultures and, to a lesser extent, in batches inoculated with P. kluyveri and Cyb. fabianii. Additionally, GC-MS analysis of chocolate samples revealed that while most short-chain esters evaporated during conching, longer and more-fat-soluble ethyl and acetate esters, such as ethyl octanoate, phenylethyl acetate, ethyl phenylacetate, ethyl decanoate, and ethyl dodecanoate, remained almost unaffected. Sensory analysis by an expert panel confirmed significant differences in the aromas of chocolates produced with different starter cultures. Together, these results show that the selection of different yeast cultures opens novel avenues for modulating chocolate flavor. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy.

PubMed

Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

2013-01-01

[Corrected] Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion - like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation.

A simplified procedure for GC/C/IRMS analysis of underivatized 19-norandrosterone in urine following HPLC purification.

PubMed

de la Torre, Xavier; Colamonici, Cristiana; Curcio, Davide; Molaioni, Francesco; Pizzardi, Marta; Botrè, Francesco

2011-04-01

Nandrolone and/or its precursors are included in the World Anti-doping Agency (WADA) list of forbidden substances and methods and as such their use is banned in sport. 19-Norandrosterone (19-NA) the main metabolite of these compounds can also be produced endogenously. The need to establish the origin of 19-NA in human urine samples obliges the antidoping laboratories to use isotope ratio mass spectrometry (IRMS) coupled to gas chromatography (GC/C/IRMS). In this work a simple liquid chromatographic method without any additional derivatization step is proposed, allowing to drastically simplify the urine pretreatment procedure, leading to extracts free of interferences permitting precise and accurate IRMS analysis. The purity of the extracts was verified by parallel analysis by gas chromatography coupled to mass spectrometry with GC conditions identical to those of the GC/C/IRMS assay. The method has been validated according to ISO17025 requirements (within assay precision of ±0.3‰ and between assay precision of ±0.4‰). The method has been tested with samples obtained after the administration of synthetic 19-norandrostenediol and samples collected during pregnancy where 19-NA is known to be produced endogenously. Twelve drugs and synthetic standards able to produce through metabolism 19-NA have shown to present δ(13)C values around -29‰ being quite homogeneous (-28.8±1.5; mean±standard deviation) while endogenously produced 19-NA has shown values comparable to other endogenous produced steroids in the range -21 to -24‰ as already reported. The efficacy of the method was tested on real samples from routine antidoping analyses. Copyright © 2011 Elsevier Inc. All rights reserved.

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy

PubMed Central

Afzal, Ehsan; Zakeri, Saba; Keyhanvar, Peyman; Bagheri, Meisam; Mahjoubi, Parvin; Asadian, Mahtab; Omoomi, Nogol; Dehqanian, Mohammad; Ghalandarlaki, Negar; Darvishmohammadi, Tahmineh; Farjadian, Fatemeh; Golvajoee, Mohammad Sadegh; Afzal, Shadi; Ghaffari, Maryam; Cohan, Reza Ahangari; Gravand, Amin; Ardestani, Mehdi Shafiee

2013-01-01

Backgrond Muscular dystrophies consist of a number of juvenile and adult forms of complex disorders which generally cause weakness or efficiency defects affecting skeletal muscles or, in some kinds, other types of tissues in all parts of the body are vastly affected. In previous studies, it was observed that along with muscular dystrophy, immune inflammation was caused by inflammatory cells invasion – like T lymphocyte markers (CD8+/CD4+). Inflammatory processes play a major part in muscular fibrosis in muscular dystrophy patients. Additionally, a significant decrease in amounts of two myogenic recovery factors (myogenic differentation 1 [MyoD] and myogenin) in animal models was observed. The drug glatiramer acetate causes anti-inflammatory cytokines to increase and T helper (Th) cells to induce, in an as yet unknown mechanism. MyoD recovery activity in muscular cells justifies using it alongside this drug. Methods In this study, a nanolipodendrosome carrier as a drug delivery system was designed. The purpose of the system was to maximize the delivery and efficiency of the two drug factors, MyoD and myogenin, and introduce them as novel therapeutic agents in muscular dystrophy phenotypic mice. The generation of new muscular cells was analyzed in SW1 mice. Then, immune system changes and probable side effects after injecting the nanodrug formulations were investigated. Results The loaded lipodendrimer nanocarrier with the candidate drug, in comparison with the nandrolone control drug, caused a significant increase in muscular mass, a reduction in CD4+/CD8+ inflammation markers, and no significant toxicity was observed. The results support the hypothesis that the nanolipodendrimer containing the two candidate drugs will probably be an efficient means to ameliorate muscular degeneration, and warrants further investigation. PMID:23966782

Simulating flame lift-off characteristics of diesel and biodiesel fuels using detailed chemical-kinetic mechanisms and LES turbulence model.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Som, S; Longman, D. E.; Luo, Z

2012-01-01

Combustion in direct-injection diesel engines occurs in a lifted, turbulent diffusion flame mode. Numerous studies indicate that the combustion and emissions in such engines are strongly influenced by the lifted flame characteristics, which are in turn determined by fuel and air mixing in the upstream region of the lifted flame, and consequently by the liquid breakup and spray development processes. From a numerical standpoint, these spray combustion processes depend heavily on the choice of underlying spray, combustion, and turbulence models. The present numerical study investigates the influence of different chemical kinetic mechanisms for diesel and biodiesel fuels, as well asmore » Reynolds-averaged Navier-Stokes (RANS) and large eddy simulation (LES) turbulence models on predicting flame lift-off lengths (LOLs) and ignition delays. Specifically, two chemical kinetic mechanisms for n-heptane (NHPT) and three for biodiesel surrogates are investigated. In addition, the RNG k-{epsilon} (RANS) model is compared to the Smagorinsky based LES turbulence model. Using adaptive grid resolution, minimum grid sizes of 250 {micro}m and 125 {micro}m were obtained for the RANS and LES cases respectively. Validations of these models were performed against experimental data from Sandia National Laboratories in a constant volume combustion chamber. Ignition delay and flame lift-off validations were performed at different ambient temperature conditions. The LES model predicts lower ignition delays and qualitatively better flame structures compared to the RNG k-{epsilon} model. The use of realistic chemistry and a ternary surrogate mixture, which consists of methyl decanoate, methyl 9-decenoate, and NHPT, results in better predicted LOLs and ignition delays. For diesel fuel though, only marginal improvements are observed by using larger size mechanisms. However, these improved predictions come at a significant increase in computational cost.« less

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

PubMed

Lin, C L; Chiang, S H; Lee, H F

1995-07-01

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)

Tuning Chocolate Flavor through Development of Thermotolerant Saccharomyces cerevisiae Starter Cultures with Increased Acetate Ester Production

PubMed Central

Meersman, Esther; Steensels, Jan; Struyf, Nore; Paulus, Tinneke; Saels, Veerle; Mathawan, Melissa; Allegaert, Leen; Vrancken, Gino

2015-01-01

Microbial starter cultures have extensively been used to enhance the consistency and efficiency of industrial fermentations. Despite the advantages of such controlled fermentations, the fermentation involved in the production of chocolate is still a spontaneous process that relies on the natural microbiota at cocoa farms. However, recent studies indicate that certain thermotolerant Saccharomyces cerevisiae cultures can be used as starter cultures for cocoa pulp fermentation. In this study, we investigate the potential of specifically developed starter cultures to modulate chocolate aroma. Specifically, we developed several new S. cerevisiae hybrids that combine thermotolerance and efficient cocoa pulp fermentation with a high production of volatile flavor-active esters. In addition, we investigated the potential of two strains of two non-Saccharomyces species that produce very large amounts of fruity esters (Pichia kluyveri and Cyberlindnera fabianii) to modulate chocolate aroma. Gas chromatography-mass spectrometry (GC-MS) analysis of the cocoa liquor revealed an increased concentration of various flavor-active esters and a decrease in spoilage-related off-flavors in batches inoculated with S. cerevisiae starter cultures and, to a lesser extent, in batches inoculated with P. kluyveri and Cyb. fabianii. Additionally, GC-MS analysis of chocolate samples revealed that while most short-chain esters evaporated during conching, longer and more-fat-soluble ethyl and acetate esters, such as ethyl octanoate, phenylethyl acetate, ethyl phenylacetate, ethyl decanoate, and ethyl dodecanoate, remained almost unaffected. Sensory analysis by an expert panel confirmed significant differences in the aromas of chocolates produced with different starter cultures. Together, these results show that the selection of different yeast cultures opens novel avenues for modulating chocolate flavor. PMID:26590272

Microbial Quality of and Biochemical Changes in Fresh Soft, Acid-Curd Xinotyri Cheese Made from Raw or Pasteurized Goat’s Milk

PubMed Central

Tasioula-Margari, Maria

2017-01-01

Summary The microbiological quality of and changes in the main physicochemical parameters, together with the evolution of proteolysis, lipolysis and volatile profiles of soft Xinotyri, a traditional Greek acid-curd cheese (pH≈4.4, moisture 65%, salt 1%) made from raw (RMC) or pasteurized (PMC) goat’s milk without starters, were evaluated during aerobic storage at 4 oC for 60 days. No statistically significant differences between the total nitrogen (TN) and nitrogen fraction (% of TN) contents, the degradation of intact αs- or β-caseins, total free amino acid (FAA) contents, and the ratio of hydrophilic and hydrophobic peptides in the water-soluble fraction of RMC and PMC were found. Threonine, alanine and lysine were the principal FAAs. Oleic, palmitic, capric and caprylic acids, and ethyl hexonate, ethyl octanoate, ethyl decanoate, ethanol, 3-methyl butanol, phenyl ethyl alcohol and acetone were the most abundant free fatty acids and volatile compounds, respectively. Cheese lipolysis evolved slowly at 4 oC, and milk pasteurization had no significant effect on it. Mesophilic lactic acid bacteria (LAB) were predominant in fresh cheese samples. PMC samples had significantly lower levels of enterococci and enterobacteria than RMC samples, while yeasts grew at similar levels during storage at 4 oC. All cheese samples (25 g) were free of Salmonella and Listeria monocytogenes. Coagulase-
-positive staphylococci exceeded the 5-log safety threshold in fresh RMC samples, whereas they were suppressed (<100 CFU/g) in all PMC samples. Consequently, pasteurization of raw goat milk’s and utilization of commercially defined or natural mesophilic LAB starters are recommended for standardizing the biochemical, microbial and safety qualities of fresh soft Xinotyri cheese. PMID:29540984

Use of Torulaspora delbrueckii Co-fermentation With Two Saccharomyces cerevisiae Strains With Different Aromatic Characteristic to Improve the Diversity of Red Wine Aroma Profile

PubMed Central

Zhang, Bo-Qin; Luan, Yu; Duan, Chang-Qing; Yan, Guo-Liang

2018-01-01

The use of selected Saccharomyces and non-Saccharomyces strains as mixed starters has advantages over pure fermentation due to achieving wine products with distinctive and diversified aroma expected by consumers. To obtain a way to improve the aroma diversity and increase the differentiation of wine product, in this study, the aromatic effect of multi-culture of indigenous Torulaspora delbrueckii (TD12), simultaneous and sequential inoculation with two Saccharomyces strains (indigenous icewine yeast SC45 and commercial yeast BDX) with different enological characteristics were investigated in laboratory-scale 20 L fermenter, respectively. The results showed that T. delbrueckii co-fermented with different S. cerevisiae strain could generate diversified physicochemical and aromatic quality of wine as evidenced by PCA. Mixed fermentation of SC45/TD12 produced higher contents of higher alcohol (3-methyl-1-pentanol and phenylethyl alcohol), ethyl esters (ethyl decanoate and ethyl butanoate), terpenes and phenylacetaldehyde with less fatty acids (hexanoic acid, octanoic acid) and acetic acid, while BDX/TD12 generated more C6 alcohol (1-hexanol) and acetate esters (ethyl acetate and isoamyl acetate). Compared to simultaneous inoculation, sequential inoculation could achieve higher aroma diversity, and generate higher intensity of fruity, flowery and sweet attributes of wine as assessed by calculating the odor activity values. The different S. cerevisiae strain and inoculation method in alcoholic fermentation could further influence the formations of aromatic compounds in malolactic fermentation. Our results highlighted the importance of S. cerevisiae strain in shaping the aromatic quality of wine in mixed fermentation, and also suggested that using different S. cerevisiae strains with distinct aromatic characteristics co-fermentation with specific non-Saccharomyces strain is a potential way to increase the aromatic diversity and quality of wine product, which could provide an alternative way to meet the requirement of wine consumers for diversified aromatic quality. PMID:29674999

Oral self-nanoemulsifying peptide drug delivery systems: impact of lipase on drug release.

PubMed

Mahjub, Reza; Dorkoosh, Farid Abedin; Rafiee-Tehrani, Morteza; Bernkop Schnürch, Andreas

2015-01-01

It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1 ± 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232 ± 53 nm and 235 ± 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p < 0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.

Effects of Fuel Components and Combustion Particle Physicochemical Properties on Toxicological Responses of Lung Cells

PubMed Central

Jaramillo, Isabel C.; Sturrock, Anne; Ghiassi, Hossein; Woller, Diana J.; Deering-Rice, Cassandra E.; Lighty, JoAnn S.; Paine, Robert; Reilly, Christopher; Kelly, Kerry E.

2017-01-01

The physicochemical properties of combustion particles that promote lung toxicity are not fully understood, hindered by the fact that combustion particles vary based on the fuel and combustion conditions. Real-world combustion-particle properties also continually change as new fuels are implemented, engines age, and engine technologies evolve. This work used laboratory-generated particles produced under controlled combustion conditions in an effort to understand the relationship between different particle properties and the activation of established toxicological outcomes in human lung cells (H441 and THP-1). Particles were generated from controlled combustion of two simple biofuel/diesel surrogates (methyl decanoate and dodecane/BD, and butanol and dodecane/AD) and compared to a widely studied reference diesel particle (NIST SRM2975/RD). BD, AD, and RD particles exhibited differences in size, surface area, extractable chemical mass, and the content of individual polycyclic aromatic hydrocarbons (PAHs). Some of these differences were directly associated with different effects on biological responses. BD particles had the greatest surface area, amount of extractable material and oxidizing potential. These particles and extracts induced cytochrome P450 1A1 and 1B1 enzyme mRNA in lung cells. AD particles and extracts had the greatest total PAH content and also caused CYP1A1 and 1B1 mRNA induction. The RD extract contained the highest relative concentration of 2-ring PAHs and stimulated the greatest level of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFα) cytokine secretion. Finally, AD and RD were more potent activators of TRPA1 than BD, and while neither the TRPA1 antagonist HC-030031 nor the antioxidant N-acetylcysteine (NAC) affected CYP1A1 or 1B1 mRNA induction, both inhibitors reduced IL-8 secretion and mRNA induction. These results highlight that differences in fuel and combustion conditions affect the physicochemical properties of particles, and these differences, in turn, affect commonly studied biological/toxicological responses. PMID:29227181

Effects of fuel components and combustion particle physicochemical properties on toxicological responses of lung cells.

PubMed

Jaramillo, Isabel C; Sturrock, Anne; Ghiassi, Hossein; Woller, Diana J; Deering-Rice, Cassandra E; Lighty, JoAnn S; Paine, Robert; Reilly, Christopher; Kelly, Kerry E

2018-03-21

The physicochemical properties of combustion particles that promote lung toxicity are not fully understood, hindered by the fact that combustion particles vary based on the fuel and combustion conditions. Real-world combustion-particle properties also continually change as new fuels are implemented, engines age, and engine technologies evolve. This work used laboratory-generated particles produced under controlled combustion conditions in an effort to understand the relationship between different particle properties and the activation of established toxicological outcomes in human lung cells (H441 and THP-1). Particles were generated from controlled combustion of two simple biofuel/diesel surrogates (methyl decanoate and dodecane/biofuel-blended diesel (BD), and butanol and dodecane/alcohol-blended diesel (AD)) and compared to a widely studied reference diesel (RD) particle (NIST SRM2975/RD). BD, AD, and RD particles exhibited differences in size, surface area, extractable chemical mass, and the content of individual polycyclic aromatic hydrocarbons (PAHs). Some of these differences were directly associated with different effects on biological responses. BD particles had the greatest surface area, amount of extractable material, and oxidizing potential. These particles and extracts induced cytochrome P450 1A1 and 1B1 enzyme mRNA in lung cells. AD particles and extracts had the greatest total PAH content and also caused CYP1A1 and 1B1 mRNA induction. The RD extract contained the highest relative concentration of 2-ring PAHs and stimulated the greatest level of interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFα) cytokine secretion. Finally, AD and RD were more potent activators of TRPA1 than BD, and while neither the TRPA1 antagonist HC-030031 nor the antioxidant N-acetylcysteine (NAC) affected CYP1A1 or 1B1 mRNA induction, both inhibitors reduced IL-8 secretion and mRNA induction. These results highlight that differences in fuel and combustion conditions affect the physicochemical properties of particles, and these differences, in turn, affect commonly studied biological/toxicological responses.

A comprehensive combustion model for biodiesel-fueled engine simulations

NASA Astrophysics Data System (ADS)

Brakora, Jessica L.

Engine models for alternative fuels are available, but few are comprehensive, well-validated models that include accurate physical property data as well as a detailed description of the fuel chemistry. In this work, a comprehensive biodiesel combustion model was created for use in multi-dimensional engine simulations, specifically the KIVA3v R2 code. The model incorporates realistic physical properties in a vaporization model developed for multi-component fuel sprays and applies an improved mechanism for biodiesel combustion chemistry. A reduced mechanism was generated from the methyl decanoate (MD) and methyl-9-decenoate (MD9D) mechanism developed at Lawrence Livermore National Laboratory. It was combined with a multi-component mechanism to include n-heptane in the fuel chemistry. The biodiesel chemistry was represented using a combination of MD, MD9D and n-heptane, which varied for a given fuel source. The reduced mechanism, which contained 63 species, accurately predicted ignition delay times of the detailed mechanism over a range of engine-specific operating conditions. Physical property data for the five methyl ester components of biodiesel were added to the KIVA library. Spray simulations were performed to ensure that the models adequately reproduce liquid penetration observed in biodiesel spray experiments. Fuel composition impacted liquid length as expected, with saturated species vaporizing more and penetrating less. Distillation curves were created to ensure the fuel vaporization process was comparable to available data. Engine validation was performed against a low-speed, high-load, conventional combustion experiments and the model was able to predict the performance and NOx formation seen in the experiment. High-speed, low-load, low-temperature combustion conditions were also modeled, and the emissions (HC, CO, NOx) and fuel consumption were well-predicted for a sweep of injection timings. Finally, comparisons were made between the results of biodiesel composition (palm vs. soy) and fuel blends (neat vs. B20). The model effectively reproduced the trends observed in the experiments.

Lipophilic nalmefene prodrugs to achieve a one-month sustained release.

PubMed

Gaekens, Tim; Guillaume, Michel; Borghys, Herman; De Zwart, Loeckie L; de Vries, Ronald; Embrechts, Roger C A; Vermeulen, An; Megens, Anton A H P; Leysen, Josée E; Herdewijn, Piet; Annaert, Pieter P; Atack, John R

2016-06-28

Nalmefene is an opioid antagonist which as a once-a-day tablet formulation has recently been approved for reducing ethanol intake in alcoholic subjects. In order to address the compliance issue in this patient population, a number of potential nalmefene prodrugs were synthesized with the aim of providing a formulation that could provide plasma drug concentrations in the region of 0.5-1.0ng/mL for a one-month period when dosed intramuscular to dogs or minipigs. In an initial series of studies, three different lipophilic nalmefene derivatives were evaluated: the palmitate (C16), the octadecyl glutarate diester (C18-C5) and the decyl carbamate (CB10). They were administered intramuscularly to dogs in a sesame oil solution at a dose of 1mg-eq. nalmefene/kg. The decyl carbamate was released relatively quickly from the oil depot and its carbamate bond was too stable to be used as a prodrug. The other two derivatives delivered a fairly constant level of 0.2-0.3ng nalmefene/mL plasma for one month and since there was no significant difference between these two, the less complex palmitate monoester was chosen to demonstrate that dog plasma nalmefene concentrations were dose-dependent at 1, 5 and 20mg-eq. nalmefene/kg. In a second set of experiments, the effect of the chain length of the fatty acid monoester promoieties was examined. The increasingly lipophilic octanoate (C8), decanoate (C10) and dodecanoate (C12) derivatives were evaluated in dogs and in minipigs, at a dose of 5mg-eq. nalmefene/kg and plasma nalmefene concentrations were measured over a four-week period. The pharmacokinetic profiles were very similar in both species with Cmax decreasing and Tmax increasing with increasing fatty acid chain length and the target plasma concentrations (0.5-1.0ng/mL over a month-long period) were achieved with the dodecanoate (C12) prodrug. These data therefore demonstrate that sustained plasma nalmefene concentrations can be achieved in both dog and minipig using nalmefene prodrugs and that the pharmacokinetic profile of nalmefene can be tuned by varying the length of the alkyl group. Copyright © 2016 Elsevier B.V. All rights reserved.

Identification of black market products and potential doping agents in Germany 2010-2013.

PubMed

Krug, Oliver; Thomas, Andreas; Walpurgis, Katja; Piper, Thomas; Sigmund, Gerd; Schänzer, Wilhelm; Laussmann, Tim; Thevis, Mario

2014-11-01

The desire to increase the athletic performance, to 'optimize' an individual's appearance, and to complement but also to arguably substitute exercise by means of drugs and drug candidates has generated a considerable (illicit) market for compounds such as anabolic-androgenic steroids, stimulants, growth promoting peptide hormones, and so on. Genuinely developed for therapeutic use, their abuse/misuse generates enormous health risks, which has necessitated comprehensive controls of compound trafficking by customs and anti-doping authorities. From 2012 to 2013, the Bureau of Customs Investigation confiscated products containing anabolic-androgenic steroids (AAS; 259 kg), stimulants (13 kg), selective estrogen receptor modulators (SERMs; 24 kg), and human growth hormone (hGH; 3500 ampules). In cooperation with the Bureau and under the umbrella of the European Monitoring Center for Emerging Doping Agents (EuMoCEDA), the Cologne Anti-Doping Laboratory analyzed an additional 337 (black market) products between 2010 and 2013, allowing to monitor developments in drug use and, hence, the anticipation of new challenges in sports drug testing. Main tools utilized in characterizing confiscated materials were liquid chromatography-high resolution mass spectrometry (LC-HRMS), gas chromatography-high resolution mass spectrometry (GC-HRMS), and polyacrylamide gel electrophoresis (PAGE) with subsequent bottom-up identification of peptidic compounds using nano liquid chromatography-tandem mass spectrometry (nanoLC-MS/MS). Among the 337 substances analyzed in the doping control laboratory in Cologne, 67 active ingredients were found, 49 of which being categorized as doping agents by the World Anti-Doping Agency (WADA). A total of 83.7 % accounted for steroidal substances (predominantly testosterone, trenbolone, and nandrolone and corresponding esters), 12.8 % accounted for peptide hormones and growth factors (predominantly hGH and growth hormone releasing peptides (GHRPs)), 3.2 % of the products contained hormones and metabolic modulators, and 0.3 % accounted for diuretic agents. Outstanding findings were the detection of the selective androgen receptor modulator (SARM) LGD-4033, the thymic hormone thymosin β4, and a fusion protein of unknown biological activity. Trafficking of considerable amounts of arguably performance and/or body-enhancing compounds has been observed during the past 4 years, the majority of which is categorized as relevant to sports drug testing. Several substances are of fake/non-approved nature and represent enormous health risks to the 'customer'.

Regulation of triacylglycerol biosynthesis in embryos and microsomal preparations from the developing seeds of Cuphea lanceolata.

PubMed

Bafor, M; Jonsson, L; Stobart, A K; Stymne, S

1990-11-15

Embryos of Cuphea lanceolata have more than 80 mol% of decanoic acid ('capric acid') in their triacylglycerols, while this fatty acid is virtually absent in phosphatidylcholine (PtdCho). Seed development was complete 25-27 days after pollination, with rapid triacylglycerol deposition occurring between 9 and 24 days. PtdCho amounts increased until day 15 after pollination. Analysis of embryo lipids showed that the diacylglycerol (DAG) pool consisted of mainly long-chain molecular species, with a very small amount of mixed medium-chain/long-chain glycerols. Almost 100% of the fatty acid at position sn-2 in triacylglycerols (TAG) was decanoic acid. When equimolar mixtures of [14C]decanoic and [14C]oleic acid were fed to whole detached embryos, over half of the radioactivity in the DAG resided in [14C]oleate, whereas [14C]decanoic acid accounted for 93% of the label in the TAG. Microsomal preparations from developing embryos at the mid-stage of TAG accumulation catalysed the acylation of [14C]glycerol 3-phosphate with either decanoyl-CoA or oleoyl-CoA, resulting in the formation of phosphatidic acid (PtdOH), DAG and TAG. Very little [14C]glycerol entered PtdCho. In combined incubations, with an equimolar supply of [14C]oleoyl-CoA and [14C]decanoyl-CoA in the presence of glycerol 3-phosphate, the synthesized PtdCho species consisted to 95% of didecanoic and dioleic species. The didecanoyl-glycerols were very selectively utilized over the dioleoylglycerols in the production of TAG. Substantial amounts of [14C]oleate, but not [14C]decanoate, entered PtdCho. The microsomal preparations of developing embryos were used to assess the acyl specificities of the acyl-CoA:sn-glycerol-3-phosphate acyltransferase (GPAT, EC 2.3.1.15) and the acyl-CoA:sn-1-acyl-glycerol-3-phosphate acyltransferase (LPAAT, EC 2.3.1.51) in Cuphea lanceolata embryos. The efficiency of acyl-CoA utilization by the GPAT was in the order decanoyl = dodecanoyl greater than linoleoyl greater than myristoyl = oleoyl greater than palmitoyl. Decanoyl-CoA was the only acyl donor to be utilized to any extent by the LPAAT when sn-decanoylglycerol 3-phosphate was the acyl acceptor. sn-1-Acylglycerol 3-phosphates with acyl groups shorter than 16 carbon atoms did not serve as acyl acceptors for long-chain (greater than or equal to 16 carbon atoms) acyl-CoA species. On the basis of the results obtained, we propose a schematic model for triacylglycerol assembly and PtdCho synthesis in a tissue specialized in the synthesis of high amounts of medium-chain fatty acids.

Regulation of triacylglycerol biosynthesis in embryos and microsomal preparations from the developing seeds of Cuphea lanceolata.

PubMed Central

Bafor, M; Jonsson, L; Stobart, A K; Stymne, S

1990-01-01

Embryos of Cuphea lanceolata have more than 80 mol% of decanoic acid ('capric acid') in their triacylglycerols, while this fatty acid is virtually absent in phosphatidylcholine (PtdCho). Seed development was complete 25-27 days after pollination, with rapid triacylglycerol deposition occurring between 9 and 24 days. PtdCho amounts increased until day 15 after pollination. Analysis of embryo lipids showed that the diacylglycerol (DAG) pool consisted of mainly long-chain molecular species, with a very small amount of mixed medium-chain/long-chain glycerols. Almost 100% of the fatty acid at position sn-2 in triacylglycerols (TAG) was decanoic acid. When equimolar mixtures of [14C]decanoic and [14C]oleic acid were fed to whole detached embryos, over half of the radioactivity in the DAG resided in [14C]oleate, whereas [14C]decanoic acid accounted for 93% of the label in the TAG. Microsomal preparations from developing embryos at the mid-stage of TAG accumulation catalysed the acylation of [14C]glycerol 3-phosphate with either decanoyl-CoA or oleoyl-CoA, resulting in the formation of phosphatidic acid (PtdOH), DAG and TAG. Very little [14C]glycerol entered PtdCho. In combined incubations, with an equimolar supply of [14C]oleoyl-CoA and [14C]decanoyl-CoA in the presence of glycerol 3-phosphate, the synthesized PtdCho species consisted to 95% of didecanoic and dioleic species. The didecanoyl-glycerols were very selectively utilized over the dioleoylglycerols in the production of TAG. Substantial amounts of [14C]oleate, but not [14C]decanoate, entered PtdCho. The microsomal preparations of developing embryos were used to assess the acyl specificities of the acyl-CoA:sn-glycerol-3-phosphate acyltransferase (GPAT, EC 2.3.1.15) and the acyl-CoA:sn-1-acyl-glycerol-3-phosphate acyltransferase (LPAAT, EC 2.3.1.51) in Cuphea lanceolata embryos. The efficiency of acyl-CoA utilization by the GPAT was in the order decanoyl = dodecanoyl greater than linoleoyl greater than myristoyl = oleoyl greater than palmitoyl. Decanoyl-CoA was the only acyl donor to be utilized to any extent by the LPAAT when sn-decanoylglycerol 3-phosphate was the acyl acceptor. sn-1-Acylglycerol 3-phosphates with acyl groups shorter than 16 carbon atoms did not serve as acyl acceptors for long-chain (greater than or equal to 16 carbon atoms) acyl-CoA species. On the basis of the results obtained, we propose a schematic model for triacylglycerol assembly and PtdCho synthesis in a tissue specialized in the synthesis of high amounts of medium-chain fatty acids. PMID:2264835

Combustion Chemistry of Biodiesel for the Use in Urban Transport Buses: Experiment and Modeling

NASA Astrophysics Data System (ADS)

Omidvarborna, Hamid

Biofuels, such as biodiesel, offer benefits as a possible alternative to conventional fuels due to their fuel source sustainability and their reduced environmental impact. Before they can be used, it is essential to understand their combustion chemistry and emission characterizations due to a number of issues associated with them (e.g., high emission of nitrogen oxides (NOx), lower heating value than diesel, etc.). During this study, emission characterizations of different biodiesel blends (B0, B20, B50, and B100) were measured on three different feedstocks (soybean methyl ester (SME), tallow oil (TO), and waste cooking oil (WCO)) with various characteristics, while an ultra-low sulfur diesel (ULSD) was used as base fuel at low-temperature combustion (LTC). A laboratory combustion chamber was used to analyze soot formation, NOx emissions, while real engine emissions were measured for further investigation on PM and NOx emissions. For further study, carbon emissions (CO, CO 2, and CH4) were also measured to understand their relations with feedstocks' type. The emissions were correlated with fuel's characteristics, especially unsaturation degree (number of double bonds in methyl esters) and chain length (oxygen-to-carbon ratio). The experimental results obtained from laboratory experiments were confirmed by field experiments (real engines) collected from Toledo area regional transit authority (TARTA) buses. Combustion analysis results showed that the neat biodiesel fuels had longer ignition delays and lower ignition temperatures compared to ULSD at the tested condition. The results showed that biodiesel containing more unsaturated fatty acids emitted higher levels of NOx compared to biodiesel with more saturated fatty acids. A paired t-test on fuels showed that neat biodiesel fuels had significant reduction in the formation of NOx compared with ULSD. In another part of this study, biodiesel fuel with a high degree of unsaturation and high portion of long chains of methyl esters (SME) produced more CO and less CO2 emissions than those with low degrees of unsaturation and short chain lengths (WCO and TO, respectively). In addition, biodiesel fuels with long and unsaturated chains released more CH4 than the ones with shorter and less unsaturated chains. Experimental results on soot particles showed a significant reduction in soot emissions when using biodiesel compared to ULSD. For neat biodiesel, no soot particles were observed from the combustion regardless of their feedstock origins. The overall morphology of soot particles showed that the average diameter of ULSD soot particles was greater than the average soot particle from biodiesel blends. Eight elements were detected as the marker metals in biodiesel soot particles. The conclusion suggests that selected characterization methods are valuable for studying the structure and distribution of particulates. Experiments on both PM and NOx emissions were conducted on real engines in parallel with laboratory study. Field experiments using TARTA buses were performed on buses equipped with/without post-treatment technologies. The performance of the bus that ran on blended biodiesel was found to be very similar to ULSD. As a part of this study, the toxic nature of engine exhausts under different idling conditions was studied. The results of the PM emission analysis showed that the PM mean value of emission is dependent on the engine operation conditions and fuel type. Besides, different idling modes were investigated with respect to organic carbon (OC), elemental carbon (EC), and elemental analysis of the PMs collected from public transit buses in Toledo, Ohio. In the modeling portion of this work, a simplified model was developed by using artificial neural network (ANN) to predict NOx emissions from TARTA buses via engine parameters. ANN results showed that the developed ANN model was capable of predicting the NOx emissions of the tested engines with excellent correlation coefficients, while root mean square errors (RMSEs) were in acceptable ranges. The ANN study confirmed that ANN can provide an accurate and simple approach in the analysis of complex and multivariate problems, especially for idle engine NOx emissions. Finally, in the last part of the modeling study, a biodiesel surrogate has been proposed and main pathways have been derived to present a simple model for NOx formation in biodiesel combustion via stochastic simulation algorithm (SSA). The main reaction pathways are obtained by simplifying the previously derived skeletal mechanisms, including saturated methyl decenoate (MD), unsaturated methyl 5-decanoate (MD5D), and n-decane (ND). ND is added to match the energy content and the C/H/O ratio of actual biodiesel fuel. The predicted results are in good agreement with a limited number of experimental data at LTC conditions for three different biodiesel fuels consisting of various ratios of unsaturated and saturated methyl esters. The SSA model shows the potential to predict NOx emission concentrations, when the peak combustion temperature increases through the addition of ULSD to biodiesel. The SSA method demonstrates the possibility of reducing the computational complexity in biodiesel emissions modeling. Based on these findings, it can be concluded that both alternative renewable fuels (biodiesel blends) as well as the LTC condition are suitable choices for existing diesel engines to improve the sustainability of fuel and to reduce environmental emissions.

The Impact of Early Substance Use Disorder Treatment Response on Treatment Outcomes Among Pregnant Women With Primary Opioid Use.

PubMed

Tuten, Michelle; Fitzsimons, Heather; Hochheimer, Martin; Jones, Hendree E; Chisolm, Margaret S

2018-03-13

This study examined the impact of early patient response on treatment utilization and substance use among pregnant participants enrolled in substance use disorder (SUD) treatment. Treatment responders (TRs) and treatment nonresponders (TNRs) were compared on pretreatment and treatment measures. Regression models predicted treatment utilization and substance use. TR participants attended more treatment and had lower rates of substance use relative to TNR participants. Regression models for treatment utilization and substance use were significant. Maternal estimated gestational age (EGA) and baseline cocaine use were negatively associated with treatment attendance. Medication-assisted treatment, early treatment response, and baseline SUD treatment were positively associated with treatment attendance. Maternal EGA was negatively associated with counseling attendance; early treatment response was positively associated with counseling attendance. Predictors of any substance use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline cocaine use. The single predictor of any substance use at 2 months was early treatment nonresponse. Predictors of opioid use at 1 month were maternal education, EGA, early treatment nonresponse, and baseline SUD treatment. Predictors of opioid use at 2 months were early treatment nonresponse, and baseline cocaine and marijuana use. Predictors of cocaine use at 1 month were early treatment nonresponse, baseline cocaine use, and baseline SUD treatment. Predictors of cocaine use at 2 months were early treatment nonresponse and baseline cocaine use. Early treatment response predicts more favorable maternal treatment utilization and substance use outcomes. Treatment providers should implement interventions to maximize patient early response to treatment.

Predicting in-treatment performance and post-treatment outcomes in methamphetamine users.

PubMed

Hillhouse, Maureen P; Marinelli-Casey, Patricia; Gonzales, Rachel; Ang, Alfonso; Rawson, Richard A

2007-04-01

This study examines the utility of individual drug use and treatment characteristics for predicting in-treatment performance and post-treatment outcomes over a 1-year period. Data were collected from 420 adults who participated in the Methamphetamine Treatment Project (MTP), a multi-site study of randomly assigned treatment for methamphetamine dependence. Interviews were conducted at baseline, during treatment and during three follow-up time-points: treatment discharge and at 6 and 12 months following admission. The Addiction Severity Index (ASI); the Craving, Frequency, Intensity and Duration Estimate (CFIDE); and laboratory urinalysis results were used in the current study. Analyses addressed both in-treatment performance and post-treatment outcomes. The most consistent finding is that pre-treatment methamphetamine use predicts in-treatment performance and post-treatment outcomes. No one variable predicted all in-treatment performance measures; however, gender, route of administration and pre-treatment methamphetamine use were significant predictors. Similarly, post-treatment outcomes were predicted by a range of variables, although pre-treatment methamphetamine use was significantly associated with each post-treatment outcome. These findings provide useful empirical information about treatment outcomes for methamphetamine abusers, and highlight the utility of assessing individual and in-treatment characteristics in the development of appropriate treatment plans.

Substance abuse treatment engagement, completion and short-term outcomes in the Western Cape province, South Africa: Findings from the Service Quality Measures Initiative.

PubMed

Myers, Bronwyn; Williams, Petal Petersen; Govender, Rajen; Manderscheid, Ron; Koch, J Randy

2018-04-01

Optimizing the effectiveness of substance use disorder (SUD) treatment is critical in low-and middle-income countries (LMICs) with limited opportunities for SUD treatment. This is the first study to identify targets for interventions to improve the quality of SUD treatment in a LMIC. We explored correlates of three indicators of treatment quality (treatment engagement, completion and abstinence at treatment exit) using data from a SUD performance measurement system implemented in the Western Cape Province of South Africa. The sample included data from 1094 adult treatment episodes representing 53% of the treatment episodes in 2016. Using multivariate logistic regression analyses, we modeled socio-demographic, substance use and program correlates of treatment engagement, completion, and abstinence at treatment exit. Overall, 59% of patients completed treatment (48% of patients from outpatient services). Treatment completion was associated with greater likelihood of abstinence at treatment exit. Patients were more likely to complete treatment if they engaged in treatment, were older, and had more severe drug problems (characterized by daily drug use and heroin problems) and attended programs of shorter duration. Residential treatment was associated with greater likelihood of treatment engagement, completion, and abstinence at treatment exit. Improving rates of outpatient treatment completion will enhance the effectiveness of South Africa's SUD treatment system. Interventions that promote engagement in treatment, particularly among younger patients; reduce program length through referral to step-down continuing care; and ensure better matching of drug problem to treatment level and type could improve rates of treatment completion. Copyright © 2018 Elsevier B.V. All rights reserved.

Treatment outcomes of using inhalation sedation for comprehensive dental care.

PubMed

Madouh, M; BaniHani, A; Tahmassebi, J F

2018-02-01

To assess the outcomes of dental treatment under inhalation sedation within a UK specialist hospital setting. This was a retrospective cohort study of the case notes of patients under 17 years of age who received dental treatment using inhalation sedation at a UK specialist setting during the period 2006-2011. Treatment outcomes were categorised into five groups: (1) treatment completed as planned, (2) modified treatment completed, (3) treatment abandoned in sedation unit and patient referred for treatment under general analgesia (GA), (4) treatment abandoned in sedation unit and patient referred for treatment under local analgesia (LA), (5) child failed to return to complete treatment. In total, the case notes of 453 patients were evaluated. The mean age of the patients was 10.3 ± 2.9 years. Treatment was completed successfully in 63.6% of the cases, 15.9% were referred for treatment under GA, 11.2% failed to return to complete the treatment, 7.1% received modified treatment completed, and only 2.2% were referred for treatment under LA. Treatment outcomes were significantly associated with patient`s age (p = 0.002). The treatment outcome "treatment abandoned and child referred to be treated under GA" had significantly lower mean patient ages than the other outcomes. The majority of children referred for inhalation sedation, completed their course of treatment. A significantly higher proportion of those in the younger age group required GA to complete their treatment.

Treatment Expectations for Cognitive-Behavioral Therapy and Light Therapy for Seasonal Affective Disorder: Change Across Treatment and Relation to Outcome

PubMed Central

Meyerhoff, Jonah; Rohan, Kelly J.

2016-01-01

Objective To examine the dynamic relationship between treatment expectations and treatment outcome over the course of a clinical trial for winter seasonal affective disorder (SAD). Method Currently depressed adults with Major Depression, Recurrent with Seasonal Pattern (N = 177) were randomized to 6-weeks of group-delivered cognitive-behavioral therapy for SAD (CBT-SAD) or light therapy (LT). The majority was female (83.6%) and white (92.1%), with a mean age of 45.6 years. Treatment expectations for CBT-SAD and LT were assessed using a modification of the Treatment Expectancy and Credibility Survey (Borkovec & Nau, 1972). Depression severity was assessed using the Beck Depression Inventory-Second Edition (Beck, Steer, & Brown, 1996). All measures were administered at pre-treatment, mid-treatment, and post-treatment. Results As treatment progressed, expectations for the treatment received increased across time steeply in CBT-SAD patients and moderately in LT patients. Collapsing across time, patients with higher treatment expectations had lower depression severity than those with lower treatment expectations. In a cross-lagged panel path analysis, there was a significant effect of treatment expectations at mid-treatment on depression severity at post-treatment among CBT-SAD patients. Conclusions Treatment expectations changed across treatment, affected outcome, and should be assessed and monitored repeatedly throughout treatment. Findings suggest that treatment expectations at mid-treatment are a mechanism by which CBT-SAD reduces depression, which should be replicated in SAD samples and examined for generalizability to non-seasonal depression. These findings underscore the importance of further research examining treatment expectations in mediating CBT’s effects in depression and other types of psychopathology. Public Health Significance This study highlights the importance of monitoring treatment expectations repeatedly during treatment regardless of treatment type. Moreover, therapists administering cognitive-based therapy for depression should actively attend to the degree of patient “buy-in” early in treatment as it has clear indications for depression severity at treatment endpoint. PMID:27281373

Exploring mortality among drug treatment clients: The relationship between treatment type and mortality.

PubMed

Lloyd, Belinda; Zahnow, Renee; Barratt, Monica J; Best, David; Lubman, Dan I; Ferris, Jason

2017-11-01

Studies consistently identify substance treatment populations as more likely to die prematurely compared with age-matched general population, with mortality risk higher out-of-treatment than in-treatment. While opioid-using pharmacotherapy cohorts have been studied extensively, less evidence exists regarding effects of other treatment types, and clients in treatment for other drugs. This paper examines mortality during and following treatment across treatment modalities. A retrospective seven-year cohort was utilised to examine mortality during and in the two years following treatment among clients from Victoria, Australia, recorded on the Alcohol and Drug Information Service database by linking with National Death Index. 18,686 clients over a 12-month period were included. Crude (CMRs) and standardised mortality rates (SMRs) were analysed in terms of treatment modality, and time in or out of treatment. Higher risk of premature death was associated with residential withdrawal as the last type of treatment engagement, while mortality following counselling was significantly lower than all other treatment types in the year post-treatment. Both CMRs and SMRs were significantly higher in-treatment than post-treatment. Better understanding of factors contributing to elevated mortality risk for clients engaged in, and following treatment, is needed to ensure that treatment systems provide optimal outcomes during and after treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Implementation of Cognitive-Behavioral Substance Abuse Treatment in Sub-Saharan Africa: Treatment Engagement and Abstinence at Treatment Exit.

PubMed

Gouse, Hetta; Magidson, Jessica F; Burnhams, Warren; Remmert, Jocelyn E; Myers, Bronwyn; Joska, John A; Carrico, Adam W

2016-01-01

This study documented the treatment cascade for engagement in care and abstinence at treatment exit as well as examined correlates of these outcomes for the first certified Matrix Model® substance abuse treatment site in Sub-Saharan Africa. This retrospective chart review conducted at a resource-limited community clinic in Cape Town, South Africa, assessed treatment readiness and substance use severity at treatment entry as correlates of the number of sessions attended and biologically confirmed abstinence at treatment exit among 986 clients who initiated treatment from 2009-2014. Sociodemographic and clinical correlates of treatment outcomes were examined using logistic regression, modeling treatment completion and abstinence at treatment exit separately. Of the 2,233 clients who completed screening, approximately 44% (n = 986) initiated treatment. Among those who initiated treatment, 45% completed at least four group sessions, 30% completed early recovery skills training (i.e., at least eight group sessions), and 13% completed the full 16-week program. Approximately half (54%) of clients who provided a urine sample had negative urine toxicology results for any substance at treatment exit. Higher motivation at treatment entry was independently associated with greater odds of treatment completion and negative urine toxicology results at treatment exit. Findings provide initial support for the successful implementation the Matrix Model in a resource-limited setting. Motivational enhancement interventions could support treatment initiation, promote sustained engagement in treatment, and achieve better treatment outcomes.

Factors influencing non-adherence to tuberculosis treatment in Jepara, central Java, Indonesia.

PubMed

Rondags, Angelique; Himawan, Ari Budi; Metsemakers, Job Fm; Kristina, Tri Nur

2014-07-01

One of the most serious problems for tuberculosis (TB) control is non-adherence to TB treatment. We studied the factors influencing non-adherence to TB treatment in Indonesia to inform TB treatment adherence strategies. We con- ducted semi-structured interviews with non-adherent patients and key informants in Jepara, Central Java, Indonesia. Three major themes were found in reasons for non-adherence to TB treatment: 1) knowledge about TB, 2) knowledge about TB treatment and 3) choosing and changing a health care treatment facility. Respondents had an inadequate knowledge about TB and its treatment. Feeling healthy and having financial problems were the most common reasons for TB treatment non-adherence. Respondents sought treatment from many different health care providers, and often changed the treatment facility location. TB treatment adherence might improve by providing better education about the disease and its treatment to those undergoing treatment. Providing information about where to receive treatment and that treatment is free could also improve compliance.

[Treatment of Persistent Somatoform Pain Disorder by Floating Needle Therapy and Duloxetine].

PubMed

Ren, Wan-wen; Zhou, Zhi-ying; Xu, Mi-mi; Long, Sen; Tang, Guang-zheng; Mao, Hong-jing; Chen, Shu-lin

2016-02-01

To evaluate clinical effect and safety of floating needle therapy and duloxetine in treating patients with persistent somatoform pain disorder (PSPD). Totally 108 PSPD patients were randomly assigned to the floating needle treatment group, the duloxetine treatment group, and the placebo treatment group, 36 in each group. Patients in the floating needle treatment group received floating needle therapy and placebo. Those in the duloxetine treatment group received duloxetine and simulated floating needle therapy. Those in the placebo treatment group received the placebo and simulated floating needle therapy. All treatment lasted for six weeks. Efficacy and adverse reactions were evaluated using Simple McGill pain scale (SF-MPQ) and Treatment Emergent Symptom Scale (TESS) before treatment and immediately after treatment, as well as at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Hamilton Depression Scale (HAMD, 17 items), Hamilton Anxiety Scale (HAMA) were assessed before treatment and at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Patients in the floating needle treatment group and the duloxetine treatment group with the total reducing score rate of SF-MPQ in Pain Rating index (PRI) ≥ 50% after 6 weeks' treatment were involved in the follow-up study. (1) Compared with the same group before treatment, SF-MPQ score, HAMD score and HAMA total scores all decreased in all the three groups at the end of 1st, 2nd, 4th, and 6th week of treatment (P < 0.05, P < 0.01). Besides , each item of SF-MPQ significantly decreased immediately after treatment in the floating needle treatment group (P < 0.01). Compared with the placebo treatment group, SF-MPQ, HAMD, and HAMA total score in the floating needle treatment group significantly decreased after 1, 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). SF-MPQ score, HAMD score and HAMA total score in the duloxetine treatment group also significantly decreased after 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). (2) There were 3 patients (8.3%) who had adverse reactions in the floating needle treatment group, 17 (50.0%) in the duloxetine treatment group, and 7 (21.2%) in the placebo treatment group. Compared with the placebo treatment group, the incidence of adverse reaction increased in the duloxetine treatment group (χ² = 6.04, P < 0.05). Besides, it was higher in the duloxetine treatment group than in the floating needle treatment group (χ² = 14.9, P < 0.05). (3) There were 19 patients in the floating needle treatment group and 17 patients in the duloxetine treatment group involved in the follow-up study. Compared with 6 weeks after treatment, no significant difference was observed at 3 and 6 months after treatment in the score of SF-MPQ, HAMD, and HAMA in the floating needle treatment group and the duloxetine treatment group. No significant difference was observed between the two groups (P > 0.05). There were 5 patients (29.4%) who had adverse reactions in the duloxetine treatment group, and no adverse reactions were observed in the floating needle treatment group. The adverse reaction rate was significantly different between the two groups (χ² = 4.26, P < 0.05). Floating needle therapy and duloxetine were effective in treatment of patients with PSPD. However, floating needle therapy could relieve pain more rapidly than duloxetine, with obviously less adverse reactions.

Gambling Disorder: Exploring Pre-treatment and In-treatment Dropout Predictors. A UK Study.

PubMed

Ronzitti, Silvia; Soldini, Emiliano; Smith, Neil; Clerici, Massimo; Bowden-Jones, Henrietta

2017-12-01

The aim of this study was to identify predictors of treatment dropout in a sample of gamblers attending a specialist clinic for gambling disorder. We analysed data on 846 treatment-seeking pathological gamblers. Firstly, we investigated differences in socio-demographic and clinical variables between treatment completers and pre-treatment dropouts, as well as between treatment completers and during-treatment dropouts. Subsequently, variables were entered into a multinomial logistic regression model to identify significant predictors of pre-treatment and in-treatment dropout. Overall, 44.8% of clients did not complete the treatment: 27.4% dropped out before starting it, while 17.4% dropped out during the treatment. Younger age and use of drugs were associated with pre-treatment dropout, while family history of gambling disorder, a lower PGSI score, and being a smoker were related with in-treatment dropout. Our findings suggest that pre-treatment dropouts differ from in-treatment dropouts, and, thus, further research will benefit from considering these groups separately. In addition, this newly gained knowledge will also be helpful in increasing treatment retention in specific subgroups of problem gamblers.

75 FR 67963 - Availability of Draft NPDES General Permits MAG580000 and NHG580000 for Discharges From Publicly...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-04

... and NHG580000 for Discharges From Publicly Owned Treatment Works Treatment Plants (POTW Treatment Plants) and Other Treatment Works Treating Domestic Sewage in the Commonwealth of Massachusetts and the... certain Publicly Owned Treatment Works Treatment Plants (POTW treatment plants) and Other Treatment Works...

76 FR 39396 - Availability of Final NPDES General Permits MAG580000 and NHG580000 for Discharges From Publicly...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

... and NHG580000 for Discharges From Publicly Owned Treatment Works Treatment Plants (POTW Treatment Plants) and Other Treatment Works Treating Domestic Sewage in the Commonwealth of Massachusetts and the... Treatment Works Treatment Plants (POTW treatment plants) and Other Treatment Works Treating Domestic Sewage...

40 CFR 133.105 - Treatment equivalent to secondary treatment.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 23 2012-07-01 2012-07-01 false Treatment equivalent to secondary treatment. 133.105 Section 133.105 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS SECONDARY TREATMENT REGULATION § 133.105 Treatment equivalent to secondary treatment...

[Treatment motivation of patients admitted for substance abuse treatment according to the section 64 StGB regulation].

PubMed

Schalast, N

2000-09-01

Describe treatment motivation in offenders with addiction problems, who enter treatment in forensic hospital departments according to section 64 of the German penal code. Consider relevance of treatment motivation with regard to course and outcome of treatment. 83 patients were interviewed within the first days of psychiatric detention and after six month of treatment. They also filled in questionnaires on treatment motivation. Hospital staff reported another six month later about course of treatment. Most patients express awareness of drug/alcohol related problems and an intention to participate in treatment. But only a minority of patients shows a very strong motivation to stay abstinent from alcohol/drugs. More than half of the patients relapse during the first year of treatment. In more than one third of the cases, psychiatric detentions are cancelled due to a negative assessment of prognosis of further treatment. Most of these patients are returned to prison. Initial treatment motivation shows some relevance with regard to course of treatment. But negative outcomes of treatment shouldn't be explained simply as effects of insufficient motivation. A conception of treatment fostering hope and social competence seems to be most effective in strengthening treatment motivation.

Who seeks care where? Utilization of mental health and substance use disorder treatment in two national samples of individuals with alcohol use disorders.

PubMed

Edlund, Mark J; Booth, Brenda M; Han, Xiaotong

2012-07-01

Only a fraction of individuals with alcohol use disorders (AUDs) receive any AUD treatment during a given year. If a substantial proportion of individuals with unmet need for AUD treatment are receiving mental health treatment, accessibility of AUD treatment could potentially be improved by implementing strategies to ensure that individuals receiving mental health care are referred to the AUD sector or by increasing rates of AUD treatment in individuals receiving mental health treatment. We assessed patterns and predictors of mental health treatment and AUD treatment among individuals with 12-month AUDs, using secondary data analyses from two national surveys, the National Survey on Drug Use and Health (NSDUH; n = 4,545 individuals with AUDs) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; n = 3,327 individuals with AUDs). In both NSDUH and NESARC, 8% of individuals with AUDs reported past-year AUD treatment. Among individuals with AUDs, mental health treatment was more common than AUD treatment, with 20% of NSDUH respondents and 11% of NESARC respondents reporting receiving mental health treatment. Greater mental health morbidity increased the odds of mental health treatment, and AUD severity increased the odds of AUD treatment. Mental health morbidity also increased the odds of AUD treatment, mainly by increasing the odds of receiving the category of both AUD and mental health treatment. Because individuals with AUDs are more likely to receive mental health treatment than AUD treatment, a key opportunity to improve the overall accessibility of treatment for AUDs may be to focus on improving AUD treatment among individuals receiving mental health treatment.

A randomized trial of concurrent smoking-cessation and substance use disorder treatment in stimulant-dependent smokers.

PubMed

Winhusen, Theresa M; Brigham, Gregory S; Kropp, Frankie; Lindblad, Robert; Gardin, John G; Penn, Pat; Hodgkins, Candace; Kelly, Thomas M; Douaihy, Antoine; McCann, Michael; Love, Lee D; DeGravelles, Eliot; Bachrach, Ken; Sonne, Susan C; Hiott, Bob; Haynes, Louise; Sharma, Gaurav; Lewis, Daniel F; VanVeldhuisen, Paul; Theobald, Jeff; Ghitza, Udi

2014-04-01

To evaluate the impact of concurrent treatments for substance use disorder and nicotine-dependence for stimulant-dependent patients. A randomized, 10-week trial with follow-up at 3 and 6 months after smoking quit date conducted at 12 substance use disorder treatment programs between February 2010 and July 2012. Adults meeting DSM-IV-TR criteria for cocaine and/or methamphetamine dependence and interested in quitting smoking were randomized to treatment as usual (n = 271) or treatment as usual with smoking-cessation treatment (n = 267). All participants received treatment as usual for substance use disorder treatment. Participants assigned to treatment as usual with concurrent smoking-cessation treatment received weekly individual smoking cessation counseling and extended-release bupropion (300 mg/d) during weeks 1-10. During post-quit treatment (weeks 4-10), participants assigned to treatment as usual with smoking-cessation treatment received a nicotine inhaler and contingency management for smoking abstinence. Weekly proportion of stimulant-abstinent participants during the treatment phase, as assessed by urine drug screens and self-report, was the primary outcome. Secondary measures included other substance/nicotine use outcomes and treatment attendance. There were no significant treatment effects on stimulant-use outcomes, as measured by the primary outcome and stimulant-free days, on drug-abstinence, or on attendance. Participants assigned to treatment as usual with smoking-cessation treatment, relative to those assigned to treatment as usual, had significantly better outcomes for drug-free days at 6-month follow-up (χ(2)(1) = 4.09, P <.05), with a decrease in drug-free days from baseline of -1.3% in treatment as usual with smoking-cessation treatment and of -7.6% in treatment as usual. Participants receiving treatment as usual with smoking-cessation treatment, relative to those receiving treatment as usual, had significantly better outcomes on smoking point-prevalence abstinence (25.5% vs 2.2%; χ(2)(1) = 44.69, P < .001; OR =18.2). These results suggest that providing smoking-cessation treatment to illicit stimulant-dependent patients in outpatient substance use disorder treatment will not worsen, and may enhance, abstinence from nonnicotine substance use. ClinicalTrials.gov identifier: NCT01077024. © Copyright 2013 Physicians Postgraduate Press, Inc.

[Strategies of treatment for febrile neutropenia].

PubMed

Terui, Yasuhito

2013-06-01

The guideline on febrile neutropenia(FN)was published by the Japanese Society of Medical Oncology(JSMO)in 2012. Based on this guideline, the treatment strategy for febrile neutropenia that is discussed in this paper includes empiric treatment strategies, methicillin-resistant Staphylococcus aureus antibiotics in the initial treatment, treatment for severe FN, treatment for outpatients, duration of FN treatment, treatment after recovery from fever associated with neutropenia, and empiric treatment with anti-fungal drugs in patients with prolonged FN.

Willingness to trade-off: An intermediate factor in patient decision-making regarding escalating care

PubMed Central

Seng, Elizabeth K; Grinberg, Amy S; Fraenkel, Liana

2018-01-01

This study aimed to evaluate treatment necessity, treatment concern, and willingness to engage in decisional trade-offs in the context of treatment escalation decision-making. Participants (n = 147) recruited online were randomized to read a vignette about escalating care in psoriasis in a 2 (high treatment concern vs moderate treatment concern) × 2 (high perceived treatment necessity vs moderate perceived treatment necessity) design. High treatment concern was associated with choosing to defer treatment escalation and being unwilling to engage in decisional trade-offs if disease risk changed. Results highlight the importance of treatment concern and willingness trade-off in treatment escalation decision-making. PMID:29662681

Barriers to and Reasons for Treatment Initiation Among Gambling Help-line Callers.

PubMed

Khayyat-Abuaita, Ula; Ostojic, Dragana; Wiedemann, Ashley; Arfken, Cynthia L; Ledgerwood, David M

2015-08-01

Identifying barriers to seeking treatment is essential for increasing problem gambler treatment initiation in the community, given that as few as 1 in 10 problem gamblers ever seek treatment. Further, many problem gamblers who take the initial step of contacting problem gambling help-lines do not subsequently go on to attend face-to-face treatment. There is limited research examining reasons for attending treatment among this population. This study addressed these gaps in the literature by examining barriers and attractions to treatment among callers to the State of Michigan Problem Gambling Help-line. In total, 143 callers (n = 86 women) completed the Barriers to Treatment for Problem Gambling (BTPG) questionnaire and responded to open-ended questions regarding barriers to and reasons for treatment initiation, as part of a telephone interview. Greater endorsement of barriers to treatment was associated with a lower likelihood of initiating treatment, especially perceived absence of problem and treatment unavailability. Correspondingly, problem gamblers who identified more reasons to attend treatment were more likely to attend, with positive treatment perceptions being the most influential. These findings can help get people into treatment by addressing barriers and fostering reasons for attending treatment, as well as reminding clinicians of the importance of identifying and addressing individual treatment barriers among patients with problem gambling.

Predicting sex offender treatment entry among individuals convicted of sexual offense crimes.

PubMed

Jones, Nicole; Pelissier, Bernadette; Klein-Saffran, Jody

2006-01-01

This study examined what factors were predictive of who volunteers for sex offender treatment (self-selection) as well as who enters treatment after volunteering (administration selection). Research participants included 404 treatment volunteers and 387 nonvolunteers to treatment who were convicted of a sexual offense involving minors within the federal prison system. Maximum likelihood probit estimation procedures indicated that when compared with nonvolunteers, treatment volunteers were more likely to be recommended by a judge to receive treatment at the time of sentencing, had received prior treatment for sexually deviant behavior, reported higher levels of motivation to change their sexually deviant behavior, and had lower rates of a substance use disorder in the year prior to incarceration. Of those persons who initially volunteered, 62% were accepted and entered treatment, 16% were denied entry to treatment by program staff, and 22% refused treatment after being accepted to the waiting list. When compared with those who were accepted and entered treatment, motivation was the only predictor of being denied admission into treatment by program staff and for refusal of treatment once accepted. The findings emphasize the need to control for selection bias in treatment outcome studies and the importance of examining the role of motivation in treatment volunteerism and treatment entry for sexual offenders.

Drinking Patterns of Pathological Gamblers Before, During, and After Gambling Treatment

PubMed Central

Rash, Carla J.; Weinstock, Jeremiah; Petry, Nancy M.

2011-01-01

Despite the high co-occurrence of alcohol consumption and gambling, few studies have investigated alcohol use changes during gambling treatment. Using latent growth modeling, we examined weekly alcohol use trajectories of treatment-seeking pathological gamblers across 36 weeks, allowing rates of change to differ across the 12-week pre-treatment, during treatment, and post-treatment periods. For these secondary data analyses, we retained drinking gamblers (N = 163) from a combined sample of two randomized clinical trials for the treatment of pathological gambling. Results indicated a decrease in alcohol use corresponding with treatment entry and maintenance of less drinking during treatment and post-treatment. Despite these decreases in alcohol use overall, 31% (50 of 163) of participants exhibited risky drinking during the treatment or post-treatment periods. Gender, age, at-risk drinking (at any point in the 36-week interval), baseline gambling severity, treatment condition, and gambling during treatment predicted latent alcohol use growth factors. Although entry into gambling treatment was temporally associated with reductions in alcohol use in this retrospective analysis, a substantial portion of the sample exhibited at-risk drinking after treatment entry, suggesting that interventions targeting reductions in alcohol use may be useful for this population. PMID:21928867

The Effects of Positive Patient Testimonials on PTSD Treatment Choice

PubMed Central

Pruitt, Larry D.; Zoellner, Lori A.; Feeny, Norah C.; Caldwell, Daniel; Hanson, Robert

2012-01-01

Despite the existence of effective treatment options for PTSD, these treatments are failing to reach those that stand to benefit from PTSD treatment. Understanding the processes underlying an individual’s treatment seeking behavior holds the potential for reducing treatment-seeking barriers. The current study investigates the effects that positive treatment testimonials have on decisions regarding PTSD treatment. An undergraduate (N = 439) and a trauma-exposed community (N = 203) sample were provided with videotaped treatment rationales for prolonged exposure (PE) and sertraline treatments of PTSD. Half of each sample also viewed testimonials, detailing a fictional patient’s treatment experience. All participants then chose among treatment options and rated the credibility of- and personal reactions toward- those options. Among treatment naïve undergraduates, testimonials increased the proportion choosing PE alone; and among treatment naïve members of the trauma-exposed community sample, testimonials increased the proportion choosing a combined PE plus sertraline treatment. These effects were not observed for those with prior history of either psychotherapeutic or pharmacological treatment. Major barriers exist that prevent individuals with PTSD from seeking treatment. For a critical unreached treatment sample, those who are treatment naïve, positive patient testimonials offer a mechanism in which to make effective treatments more appealing and accessible. PMID:23103234

Algorithms for optimizing the treatment of depression: making the right decision at the right time.

PubMed

Adli, M; Rush, A J; Möller, H-J; Bauer, M

2003-11-01

Medication algorithms for the treatment of depression are designed to optimize both treatment implementation and the appropriateness of treatment strategies. Thus, they are essential tools for treating and avoiding refractory depression. Treatment algorithms are explicit treatment protocols that provide specific therapeutic pathways and decision-making tools at critical decision points throughout the treatment process. The present article provides an overview of major projects of algorithm research in the field of antidepressant therapy. The Berlin Algorithm Project and the Texas Medication Algorithm Project (TMAP) compare algorithm-guided treatments with treatment as usual. The Sequenced Treatment Alternatives to Relieve Depression Project (STAR*D) compares different treatment strategies in treatment-resistant patients.

Willingness to trade-off: An intermediate factor in patient decision-making regarding escalating care.

PubMed

Seng, Elizabeth K; Grinberg, Amy S; Fraenkel, Liana

2018-01-01

This study aimed to evaluate treatment necessity, treatment concern, and willingness to engage in decisional trade-offs in the context of treatment escalation decision-making. Participants ( n  = 147) recruited online were randomized to read a vignette about escalating care in psoriasis in a 2 (high treatment concern vs moderate treatment concern) × 2 (high perceived treatment necessity vs moderate perceived treatment necessity) design. High treatment concern was associated with choosing to defer treatment escalation and being unwilling to engage in decisional trade-offs if disease risk changed. Results highlight the importance of treatment concern and willingness trade-off in treatment escalation decision-making.

Effluent treatment for nuclear thermal propulsion ground testing

NASA Technical Reports Server (NTRS)

Shipers, Larry R.

1993-01-01

The objectives are to define treatment functions, review concept options, discuss PIPET effluent treatment system (ETS), and outline future activities. The topics covered include the following: reactor exhaust; effluent treatment functions; effluent treatment categories; effluent treatment options; concept evaluation; PIPETS ETS envelope; PIPET effluent treatment concept; and future activities.

[Application of digital design of orthodontic-prosthodontic multidisciplinary treatment plan in esthetic rehabilitation of anterior teeth].

PubMed

Liu, Y S; Li, Z; Zhao, Y J; Ye, H Q; Zhou, Y Q; Hu, W J; Liu, Y S; Xun, C L; Zhou, Y S

2018-02-18

To develop a digital workflow of orthodontic-prosthodontic multidisciplinary treatment plan which can be applied in complicated anterior teeth esthetic rehabilitation, in order to enhance the efficiency of communication between dentists and patients, and improve the predictability of treatment outcome. Twenty patients with the potential needs of orthodontic-prosthodontic multidisciplinary treatment to solve their complicated esthetic problems in anterior teeth were recruited in this study. Digital models of patients' both dental arches and soft tissues were captured using intra oral scanner. Direct prosthodontic (DP) treatment plan and orthodontic-prosthodontic (OP) treatment plan were carried out for each patient. For DP treatment plans, digital wax-up models were directly designed on original digital models using prosthodontic design system. For OP treatment plans, virtual-setups were performed using orthodontic analyze system according to orthodontic and esthetic criteria and imported to prosthodontic design system to finalize the digital wax-up models. These two treatment plans were shown to the patients and demonstrated elaborately. Each patient rated two treatment plans using visual analogue scales and the medians of scores of two treatment plans were analyzed using signed Wilcoxon test. Having taken into consideration various related factors, including time, costs of treatment, each patient chose a specific treatment plan. For the patients chose DP treatment plans, digital wax-up models were exported and printed into resin diagnostic models which would be utilized in the prosthodontic treatment process. For the patients chose OP treatment plans, virtual-setups were used to fabricate aligners or indirect bonding templates and digital wax-up models were also exported and printed into resin diagnostic models for prosthodontic treatment after orthodontic treatment completed. The medians of scores of DP treatment plan and OP treatment plan were calculated and analyzed by IBM SPSS 20. The median of scores of DP treatment plan was 8.4, the minimum value was 6.9 and the maximum value was 9.3. The median of scores of OP treatment plan was 9.0, the minimum value was 7.9 and the maximum value was 9.6. The median of scores of OP was significantly higher than that of DP (Z=-3.23, P<0.01). Finally, 12 patients chose OP treatment plans and 8 patients chose DP treatment plans. For cases with complex esthetic problems in anterior teeth, a digital workflow can demonstrate final treatment outcome and help patients make suitable treatment decisions. In our study, the orthodontic-prosthodontic multidisciplinary treatment plan is feasible which can provide predictions of treatment outcome and improve esthetic outcome with patients' satisfaction.

Understanding Treatment Effect Estimates When Treatment Effects Are Heterogeneous for More Than One Outcome.

PubMed

Brooks, John M; Chapman, Cole G; Schroeder, Mary C

2018-06-01

Patient-centred care requires evidence of treatment effects across many outcomes. Outcomes can be beneficial (e.g. increased survival or cure rates) or detrimental (e.g. adverse events, pain associated with treatment, treatment costs, time required for treatment). Treatment effects may also be heterogeneous across outcomes and across patients. Randomized controlled trials are usually insufficient to supply evidence across outcomes. Observational data analysis is an alternative, with the caveat that the treatments observed are choices. Real-world treatment choice often involves complex assessment of expected effects across the array of outcomes. Failure to account for this complexity when interpreting treatment effect estimates could lead to clinical and policy mistakes. Our objective was to assess the properties of treatment effect estimates based on choice when treatments have heterogeneous effects on both beneficial and detrimental outcomes across patients. Simulation methods were used to highlight the sensitivity of treatment effect estimates to the distributions of treatment effects across patients across outcomes. Scenarios with alternative correlations between benefit and detriment treatment effects across patients were used. Regression and instrumental variable estimators were applied to the simulated data for both outcomes. True treatment effect parameters are sensitive to the relationships of treatment effectiveness across outcomes in each study population. In each simulation scenario, treatment effect estimate interpretations for each outcome are aligned with results shown previously in single outcome models, but these estimates vary across simulated populations with the correlations of treatment effects across patients across outcomes. If estimator assumptions are valid, estimates across outcomes can be used to assess the optimality of treatment rates in a study population. However, because true treatment effect parameters are sensitive to correlations of treatment effects across outcomes, decision makers should be cautious about generalizing estimates to other populations.

A Meta-Analysis of Cognitive Behavior Therapy and Medication for Child Obsessive Compulsive Disorder: Moderators of Treatment Efficacy, Response, and Remission

PubMed Central

McGuire, Joseph F.; Piacentini, John; Lewin, Adam B.; Brennan, Erin A; Murphy, Tanya K.; Storch, Eric A.

2015-01-01

Background Individual randomized controlled trials (RCTs) have demonstrated the efficacy of cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) for the treatment of youth with obsessive-compulsive disorder (OCD). While meta-analyses have confirmed these results, there has been minimal examination of treatment moderators or an examination of treatment response and symptom/diagnostic remission for these two treatment types. The present report examined the treatment efficacy, treatment response, and symptom/diagnostic remission for youth with OCD receiving either CBT or SRIs relative to comparison conditions, and examined treatment moderators. Method A comprehensive literature search identified 20 RCTs that met inclusion criteria, and produced a sample size of 507 CBT participants and 789 SRI participants. Results Random effects meta-analyses of CBT trials found large treatment effects for treatment efficacy (g=1.21), treatment response [relative risk (RR)=3.93], and symptom/diagnostic remission (RR=5.40). Greater co-occurring anxiety disorders, therapeutic contact, and lower treatment attrition were associated with greater CBT effects. The number needed to treat (NNT) was three for treatment response and symptom/diagnostic remission. Random effects meta-analyses of SRI trials found a moderate treatment effect for treatment efficacy (g=0.50), treatment response (RR=1.80), and symptom/diagnostic remission (RR=2.06). Greater methodological quality was associated with a lower treatment response for SRI trials. The NNT was five for treatment response and symptom/diagnostic remission. Conclusions Findings demonstrate the treatment effects for CBT and SRIs across three important outcome metrics, and provide evidence for moderators of CBT across trials. PMID:26130211

Facilitators and barriers in treatment seeking for cannabis dependence.

PubMed

van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

2013-12-01

Relatively few cannabis dependent people seek treatment and little is known about determinants of treatment seeking. Treatment determinants were compared among 70 DSM-IV cannabis dependent patients and 241 non-treatment seeking DSM-IV cannabis dependent community subjects. In addition, perceived facilitators for treatment seeking were assessed in patients, whereas perceived barriers were assessed in 160/241 cannabis dependent community subjects not prepared to seek treatment (precluders), of whom 63/160 showed an objective treatment need, and 30/241 showed a subjective treatment need. Compared to non-treatment seekers, patients reported more cannabis use (176.9 versus 82.8 joints monthly), more symptoms of dependence (5.6 versus 4.5), higher perceived lack of social support (70.0% versus 41.1%), more pressure to seek treatment (58.6% versus 21.6%), a more positive attitude to treatment, and more previous treatments. In addition, patients reported more mental health problems (internalising disorders 57.1% versus 24.5%; externalising disorders 52.9% versus 35.3%) and more functional impairments (8.4 versus 4.8 monthly days out of role). Cannabis dependent 'precluders' reported desire for self-reliance (50.0%), preference for informal help (22.5%), and absent treatment need (16.9%) as their main reasons not to seek treatment, whereas cannabis dependent community subjects with a subjective treatment need mainly expressed desire for self-reliance (36.7%), treatment ineffectiveness (16.7%), and avoiding stigma (13.3%). Functional impairment, mental health problems and social pressure are important reasons to seek treatment in people with cannabis dependence. Treatment participation might improve if desire for self-reliance and the preference for informal help are considered, and perceived ineffectiveness of treatment and stigmatisation are publicly addressed. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Predictors of affect following treatment decision-making for prostate cancer: conversations, cognitive processing, and coping.

PubMed

Christie, Kysa M; Meyerowitz, Beth E; Giedzinska-Simons, Antoinette; Gross, Mitchell; Agus, David B

2009-05-01

Research suggests that cancer patients who are more involved in treatment decision-making (TDM) report better quality of life following treatment. This study examines the association and possible mechanisms between prostate cancer patient's discussions about TDM and affect following treatment. We predicted that the length of time patients spent discussing treatment options with social networks and physicians prior to treatment would predict emotional adjustment after treatment. We further predicted that cognitive processing, coping, and patient understanding of treatment options would mediate this association. Fifty-seven patients completed questionnaires prior to treatment and at 1 and 6 months following treatment completion. Findings from the present study suggest that discussing treatment options with others, prior to beginning treatment for prostate cancer, significantly contributed to improvements in affect 1 and 6 months following treatment. Residualized regression analyses indicated that discussing treatment options with patient's social networks predicted a decrease in negative affect 1 and 6 months following treatment, while discussions with physicians predicted an increase in positive affect 1 month following treatment. Patients who spent more time discussing treatment options with family and friends also reported greater pre-treatment social support and emotional expression. Mediation analyses indicated that these coping strategies facilitated cognitive processing (as measured by a decrease in intrusive thoughts) and that cognitive processing predicted improvement in affect. Greater time spent talking with family and friends about treatment options may provide opportunities for patients to cope with their cancer diagnosis and facilitate cognitive processing, which may improve patient distress over time. Copyright (c) 2008 John Wiley & Sons Ltd.

The role of different stigma perceptions in treatment seeking and dropout among active duty military personnel.

PubMed

Britt, Thomas W; Jennings, Kristen S; Cheung, Janelle H; Pury, Cynthia L S; Zinzow, Heidi M

2015-06-01

Many military personnel with mental health problems do not seek treatment from mental health professionals, and if they do seek treatment, they drop out of treatment before receiving the recommended number of sessions. The present study examined the role of 4 different stigma perceptions on these outcomes: perceived stigma to career, perceived stigma of differential treatment, self-stigma from seeking treatment, and stigmatizing perceptions of soldiers who seek treatment. One thousand three hundred twenty-four active duty soldiers completed a self-report survey assessment that included measures of the 4 different stigma perceptions, indices of mental health symptoms, receipt of mental health treatment, and whether they had dropped out of treatment before it was completed. Participants screening positive for a mental health problem reported higher scores on all 4 stigma perceptions. All 4 stigma perceptions were each associated with a reduced likelihood of treatment seeking when considered individually, but only stigmatizing beliefs about those who seek treatment were uniquely associated with treatment seeking. Perceived stigma for one's career and differential treatment from others, along with self-stigma from treatment seeking, were associated with an increased probability of dropping out of mental health treatment. Self-stigma from treatment seeking was the only unique predictor of dropout. Different stigma perceptions were associated with treatment seeking and dropout. Further longitudinal research is needed to examine how stigma perceptions influence these important outcomes. Practitioners need to be aware of how different stigma perceptions can influence treatment seeking and potentially target stigma perceptions during treatment to prevent dropout. (c) 2015 APA, all rights reserved).

Risk factors for treatment default among re-treatment tuberculosis patients in India, 2006.

PubMed

Jha, Ugra Mohan; Satyanarayana, Srinath; Dewan, Puneet K; Chadha, Sarabjit; Wares, Fraser; Sahu, Suvanand; Gupta, Devesh; Chauhan, L S

2010-01-25

Under India's Revised National Tuberculosis Control Programme (RNTCP), >15% of previously-treated patients in the reported 2006 patient cohort defaulted from anti-tuberculosis treatment. To assess the timing, characteristics, and risk factors for default amongst re-treatment TB patients. For this case-control study, in 90 randomly-selected programme units treatment records were abstracted from all 2006 defaulters from the RNTCP re-treatment regimen (cases), with one consecutively-selected non-defaulter per case. Patients who interrupted anti-tuberculosis treatment for >2 months were classified as defaulters. 1,141 defaulters and 1,189 non-defaulters were included. The median duration of treatment prior to default was 81 days (25%-75% interquartile range 44-117 days) and documented retrieval efforts after treatment interruption were inadequate. Defaulters were more likely to have been male (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI] 1.2-1.7), have previously defaulted anti-tuberculosis treatment (aOR 1.3 95%CI 1.1-1.6], have previous treatment from non-RNTCP providers (AOR 1.3, 95%CI 1.0-1.6], or have public health facility-based treatment observation (aOR 1.3, 95%CI 1.1-1.6). Amongst the large number of re-treatment patients in India, default occurs early and often. Improved pre-treatment counseling and community-based treatment provision may reduce default rates. Efforts to retrieve treatment interrupters prior to default require strengthening.

Characteristics and Treatment Preferences of People with Symptoms of Posttraumatic Stress Disorder: An Internet Survey

PubMed Central

Spence, Jay; Titov, Nickolai; Solley, Karen; Dear, Blake F.; Johnston, Luke; Wootton, Bethany; Kemp, Alice; Andrews, Gavin; Zou, Judy; Lorian, Carolyn; Choi, Isabella

2011-01-01

Background Although Posttraumatic Stress Disorder (PTSD) is a severe and disabling anxiety disorder, relatively few people with this condition access evidence-based care. Barriers to treatment are multiple and complex, but the emerging field of Internet therapy for PTSD may improve access to evidence-based treatment. However, little is known about the characteristics of people with PTSD who seek online treatment, or whether they perceive internet treatment as an acceptable treatment option. Methodology An online survey was used to collect information about the demographic and symptom characteristics of individuals with elevated levels of PTSD symptoms, and this was compared to data from corresponding sample from a national survey. Previous treatment experiences, perceived barriers to treatment and treatment preferences for Internet therapy and face-to-face treatment were also compared. Principal Findings High levels of PTSD symptoms were reported by survey respondents. Psychological distress and disability was greater than reported by individuals with PTSD from a national survey. Half of the sample reported not having received treatment for PTSD; however, 88% of those who reported receiving treatment stated they received an evidence-based treatment. Primary barriers to treatment included cost, poor awareness of service availability, lack of prior treatment response and not perceiving personal distress as severe enough to warrant treatment. Most survey respondents indicated they were willing to try Internet treatment for PTSD. Conclusions The Internet sample was symptomatically severe and multiple barriers existed to treatment. Internet therapy is an acceptable option for the treatment of PTSD in an internet sample. PMID:21818274

Facilitating treatment entry among out-of-treatment injection drug users.

PubMed Central

Booth, R E; Kwiatkowski, C; Iguchi, M Y; Pinto, F; John, D

1998-01-01

OBJECTIVE: High risk injection practices are common among injecting drug users (IDUs), even following intervention efforts. Moreover, relapse to risk behaviors has been reported among those who initiate risk reduction. Substance abuse treatment offers the potential to reduce or eliminate injecting risk behaviors through drug cessation. We report on the effectiveness of two intervention strategies in facilitating treatment entry among out-of-treatment IDUs: motivational interviewing (MI), and intervention developed to help individuals resolve their ambivalence about behavior change, and free treatment for 90 days. These conditions were compared with an intervention focusing on a hierarchy of safer injecting practice, referred to here as risk reduction (RR), and no free treatment. METHODS: Nearly 200 out-of-treatment IDUs were randomly assigned to one of four experimental conditions: MI/free treatment, MI/no free treatment, RR/free treatment, and RR/no free treatment. Regardless of assignment, we assisted anyone desiring treatment by calling to schedule the appointment, providing transportation, and waiving the intake fee. RESULTS: Overall, 42% of study participants entered treatment. No significant differences were found between MI and RR; however, 52% of those assigned free treatment entered compare with 32% for those who had to pay. Other predictors of treatment entry included prior treatment experiences, perceived chance of contracting acquired immunodeficiency syndrome (AIDS) greater than 50%, "determination" stage of change, greater frequency of heroin injecting, and fewer drug-using friends. CONCLUSIONS: These findings support the importance of removing barriers to treatment entry. PMID:9722817

Continuation of Weight Loss Treatment Is Associated with the Number of Self-Selected Treatment Modalities

ERIC Educational Resources Information Center

Martin, Corby K.; Drab-Hudson, Danae L.; York-Crowe, Emily; Mayville, Stephen B.; Yu, Ying; Greenway, Frank L.

2007-01-01

Behavior therapy is a cornerstone of weight loss treatment and behaviorists help direct patients' treatment. A novel design was used that allowed participants to choose different treatment modalities during behavioral weight loss treatment. The association between the selection of different treatment modalities and program completion was examined…

[Osteonecrosis of the jaws (ONJ) associated to antiresorptive treatment].

PubMed

Larsson Wexell, Cecilia; Kjellman, Anders; Akre, Olof

2018-05-25

Osteonecrosis of the jaws (ONJ) has been associated to antiresorptive treatment and is an increasing problem all over the world. ONJ is a severe adverse effect of antiresorptive treatment with bisphosphonate and denosumab used for treatment of osteoporosis, metastases from certain malignant conditions and as an adjuvant treatment in postmenopausal women with breast cancer, and of treatment with certain chemotherapeutic drugs. In this paper the epidemiology, symptoms, diagnostic features, clinical findings, and treatment are reviewed. Guidelines are presented for dental treatment, surgery and referral of patients on antiresorptive treatment.

Atypical and Typical Winter Depressive Symptoms and Responsiveness to Light Therapy, Cognitive-Behavioral Therapy, or Combination Treatment

DTIC Science & Technology

2005-01-01

064 -.053 Anxiety Somatic (H13) .248 .148 .246 .370 Hypochondriasis (H14) .179 .432 -.016 .156 Retardation (H16) .157...TREATMENT BDI-II SCORE, POST-TREATMENT SOMATIC SUBSCALE SCORE, AND POST-TREATMENT COGNITIVE-AFFECTIVE SUBSCALE SCORE ……………………………76...Post-Treatment, Percent BDI-II Improvement From Pre- to Post-Treatment, Post-Treatment BDI-II Score, Post-Treatment Somatic

Pricing Mechanism Design for Centralized Pollutant Treatment with SME Alliances

PubMed Central

Li, Yuyu; Huang, Bo; Tao, Fengming

2016-01-01

In this paper, we assume that a professional pollutant treatment enterprise treats all of the pollutants emitted by multiple small and medium-sized enterprises (SMEs). In order to determine the treatment price, SMEs can bargain with the pollutant treatment enterprise individually, or through forming alliances. We propose a bargaining game model of centralized pollutant treatment to study how the pollutant treatment price is determined through negotiation. Then, we consider that there is a moral hazard from SMEs in centralized pollutant treatment; in other words, they may break their agreement concerning their quantities of production and pollutant emissions with the pollutant treatment enterprise. We study how the pollutant treatment enterprise can prevent this by pricing mechanism design. It is found that the pollutant treatment enterprise can prevent SMEs’ moral hazard through tiered pricing. If the marginal treatment cost of the pollutant treatment enterprise is a constant, SMEs could bargain with the pollutant treatment enterprise individually, otherwise, they should form a grand alliance to bargain with it as a whole. PMID:27338440

Methamphetamine dependence: a closer look at treatment response and clinical characteristics associated with route of administration in outpatient treatment.

PubMed

Rawson, Richard A; Gonzales, Rachel; Marinelli-Casey, Patricia; Ang, Alfonso

2007-01-01

Relatively little is known about the clinical treatment response characteristics associated with route of methamphetamine (MA) administration. We examined sociodemographic, drug use, treatment response, as well as psychiatric and medical characteristics associated with route of administration among 974 methamphetamine abusers in outpatient treatment during 1999-2001. Injectors had the poorest treatment prognosis: poorer treatment engagement, greater drug use during treatment, lower treatment completion rates, and more MA use at 12 months post-admission than did smokers and intranasal users. On many treatment response measures, MA smokers were almost as severely impaired as injectors, and in general, intranasal users were least impaired. Psychological and medical impairment, before and after treatment, was also highest among injectors. This study contributes new insights about clinical treatment response and outcomes associated with route of administration among MA-dependent users.

Pricing Mechanism Design for Centralized Pollutant Treatment with SME Alliances.

PubMed

Li, Yuyu; Huang, Bo; Tao, Fengming

2016-06-22

In this paper, we assume that a professional pollutant treatment enterprise treats all of the pollutants emitted by multiple small and medium-sized enterprises (SMEs). In order to determine the treatment price, SMEs can bargain with the pollutant treatment enterprise individually, or through forming alliances. We propose a bargaining game model of centralized pollutant treatment to study how the pollutant treatment price is determined through negotiation. Then, we consider that there is a moral hazard from SMEs in centralized pollutant treatment; in other words, they may break their agreement concerning their quantities of production and pollutant emissions with the pollutant treatment enterprise. We study how the pollutant treatment enterprise can prevent this by pricing mechanism design. It is found that the pollutant treatment enterprise can prevent SMEs' moral hazard through tiered pricing. If the marginal treatment cost of the pollutant treatment enterprise is a constant, SMEs could bargain with the pollutant treatment enterprise individually, otherwise, they should form a grand alliance to bargain with it as a whole.

Smartphone and Mobile Application Utilization Prior to and Following Treatment Among Individuals Enrolled in Residential Substance Use Treatment.

PubMed

Dahne, Jennifer; Lejuez, Carl W

2015-11-01

Following completion of substance use treatment, it is crucial for patients to continue to utilize skills learned in treatment for optimal treatment outcomes. Mobile applications (apps) on smartphones offer a unique platform to promote utilization of evidence-based skills following completion of substance use treatment. Despite the promise of mobile apps and smartphones for treatment delivery, it remains unknown whether patients in substance use treatment in the United States have access to smartphones and utilize mobile apps on smartphones. The present study sought to determine smartphone utilization among individuals enrolled in one residential substance use treatment center in the U.S. catering specifically to low-income adults. Participants included 251 individuals at a residential substance use treatment center in Washington DC admitted to the center between March, 2014 and January, 2015. During the intake process, participants completed interviewer-administered demographics and psychiatric questionnaires as well as a self-report of technology utilization. Results indicated that the majority of patients in this residential substance use treatment center owned mobile phones prior to treatment entry (86.9%) and expected to own mobile phones after leaving treatment (92.6%). Moreover, the majority of these phones were (68.5%) or will be smartphones (72.4%) on which patients reported utilizing mobile applications (prior to treatment: 61.3%; post treatment: 64.3%) and accessing the Internet (prior to treatment: 61.3%; post treatment: 65.9%). Mobile phone and smartphone ownership among this sample were comparable to ownership among U.S. adults broadly. Findings suggest that smartphones and mobile apps may hold clinical utility for fostering continued use of treatment skills following substance use treatment completion. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluating treatment outcomes and durations among cases of smear-positive pulmonary tuberculosis in Yemen: a prospective follow-up study.

PubMed

Jaber, Ammar Ali Saleh; Khan, Amer Hayat; Sulaiman, Syed Azhar Syed

2017-01-01

Evaluating outcomes after tuberculosis (TB) treatment can help identify the primary reasons for treatment success or failure. However, Yemen has a treatment success rate that remains below the World Health Organization's target. This study aimed to identify factors that were associated with unsuccessful treatment and prolonged treatment (>1 year). Newly diagnosed cases of smear-positive pulmonary TB were prospectively followed at two centers (Taiz and Alhodidah, Yemen) between April 2014 and March 2015. Standardized forms were used to obtain information from the patients regarding their socio-demographic and clinical characteristics, treatment duration, and TB-related information. Multivariate logistic regression analyses were performed to identify factors that were associated with unsuccessful treatment and prolonged treatment (>1 year). The study included data from 273 cases of newly diagnosed TB, with treatment being successful in 227 cases (83.1%) and unsuccessful in 46 cases (16.9%). Among the 46 patients with unsuccessful treatment, 29 patients (10.6%) stopped treatment, 6 patients (2.2%) transferred to another facility, 6 patients (2.2%) experienced treatment failure, and 5 patients (1.8%) died. The multivariate logistic regression analyses revealed that unsuccessful treatment was associated with female sex, illiterate status, and the presence of comorbidities. Prolonged treatment durations were associated with living in a rural area, smoking, chewing khat, a cough that lasted for >3 weeks at the beginning of treatment, and bilateral cavities during radiography. These results confirm that the treatment success rate in Yemen is lower than the World Health Organization's target for smear-positive pulmonary tuberculosis. Targeting the risk factors that we identified may help improve treatment outcomes. Furthermore, it may not be prudent to re-treat patients using first-line TB drugs after an initial treatment failure.

Smartphone and Mobile Application Utilization Prior to and Following Treatment Among Individuals Enrolled in Residential Substance Use Treatment

PubMed Central

Dahne, Jennifer; Lejuez, C. W.

2015-01-01

Background Following completion of substance use treatment, it is crucial for patients to continue to utilize skills learned in treatment for optimal treatment outcomes. Mobile applications (apps) on smartphones offer a unique platform to promote utilization of evidence-based skills following completion of substance use treatment. Despite the promise of mobile apps and smartphones for treatment delivery, it remains unknown whether patients in substance use treatment in the United States have access to smartphones and utilize mobile apps on smartphones. The present study sought to determine smartphone utilization among individuals enrolled in one residential substance use treatment center in the U.S catering specifically to low-income adults. Methods Participants included 251 individuals at a residential substance use treatment center in Washington DC admitted to the center between March, 2014 and January, 2015. During the intake process, participants completed interviewer-administered demographics and psychiatric questionnaires as well as a self-report of technology utilization. Results Results indicated that the majority of patients in this residential substance use treatment center owned mobile phones prior to treatment entry (86.9%) and expected to own mobile phones after leaving treatment (92.6%). Moreover, the majority of these phones were (68.5%) or will be smartphones (72.4%) on which patients reported utilizing mobile applications (Prior to treatment: 61.3%; Post treatment: 64.3%) and accessing the internet (Prior to treatment: 61.3%; Post treatment: 65.9%). Conclusions Mobile phone and smartphone ownership among this sample were comparable to ownership among U.S. adults broadly. Findings suggest that smartphones and mobile apps may hold clinical utility for fostering continued use of treatment skills following substance use treatment completion. PMID:26231698

Expectations and effectiveness of medical treatment and classical homeopathic treatment for patients with hypersensitivity illnesses--one year prospective study.

PubMed

Launsø, Laila; Henningsen, Inge; Rieper, Jonas; Brender, Henriette; Sandø, Finn; Hvenegaard, Anne

2007-10-01

To describe and compare characteristics of adult patients who received treatment for hypersensitivity illnesses by general practitioners (GPs) and classical homeopaths (CHs) over a period of 1 year and examine the statistical predictors of self-reported treatment outcomes. We conducted a survey on 151 Danish adult patients with hypersensitivity illnesses, who chose treatment from one of 13 GPs or one of 10 CHs who participated in the project. The treatments were given as individual packages in the naturalistic clinical setting. Patients completed questionnaires at start of treatment, after 6 months and a year after start of treatment. Response rates for the first, second and third questionnaire were respectively 68%, 98%, 95% for the GP patients and 82%, 98%, 94% for the CH patients. Patients seeking CH treatment in this study are significantly different in gender and education from patients seeking GP treatment. We did not find significant differences in terms of occupational training, occupation, sickness absence due to hypersensitivity illnesses, diseases other than hypersensitivity illnesses, symptoms severity due to hypersensitivity illnesses before treatment and expectation of the ability of the treatment to alleviate symptoms. Eighty-eight percent of GP and 21% of CH patients were continuing treatment after 1 year. Regression analysis showed that the only significant independent variables to explain the probability of obtaining very positive effect or cure for GPs and CHs were that the patients were in 'maintenance treatment', and had high expectation before treatment of the ability of the treatment to relieve their symptoms. In this study self-reported very positive effect of GP treatment and very positive effect and cure of CH treatment are associated with the patients' high expectation of the treatment and continuation of maintenance treatment.

Risk factors for unsuccessful tuberculosis treatment outcome (failure, default and death) in public health institutions, Eastern Ethiopia.

PubMed

Amante, Tariku Dingeta; Ahemed, Tekabe Abdosh

2015-01-01

Unsuccessful TB treatment outcome is a serious public health concern. It is compelling to identify, and deal with factors determining unsuccessful treatment outcome. Therefore, study was aimed to determine pattern of unsuccessful TB treatment outcome and associated factors in eastern Ethiopia. A case control study was used. Cases were records of TB patients registered as defaulter, dead and/or treatment failure where as controls were those cured or treatment complete. Multivariate logistic regression models were used to derive adjusted odds ratios (OR) at 95% CI to examine the relationship between the unsuccessful TB treatment outcome and patients' characteristics. A total of 990 sample size (330 cases and 660 controls) were included. Among cases (n = 330), majority 212(64.2%) were because of death, 100(30.3%) defaulters and 18(5.5%) were treatment failure. Lack of contact person(OR = 1.37; 95% CI 1.14-2.9, P, .024), sputum smear negative treatment category at initiation of treatment (OR = 1.8; 95% CI 1.3-5.5,P, .028), smear positive sputum test result at 2(nd) month after initiation treatment (OR = 14; 95% CI 5.5-36, P,0.001) and HIV positive status (OR = 2.5; 95% CI 1.34-5.7, P, 0.01) were independently associated with increased risk of unsuccessful TB treatment outcome. Death was the major cause of unsuccessful TB treatment outcome. TB patients do not have contact person, sputum smear negative treatment category at initiation of treatment, smear positive on 2(nd) month after treatment initiation and HIV positive were factors significantly associated unsuccessful treatment outcome. TB patients with sputum smear negative treatment category, HIV positive and smear positive on 2(nd) nd month of treatment initiation need strict follow up throughout DOTs period.

THE EFFECTIVENESS OF COMPULSORY DRUG TREATMENT: A SYSTEMATIC REVIEW

PubMed Central

Werb, D; Kamarulzaman, A; Meacham, MC; Rafful, C; Fisher, B; Strathdee, SA; Wood, E

2016-01-01

Background Despite widespread implementation of compulsory treatment modalities for drug dependence, there has been no systematic evaluation of the scientific evidence on the effectiveness of compulsory drug treatment. Methods We conducted a systematic review of studies assessing the outcomes of compulsory treatment. We conducted a search in duplicate of all relevant peer-reviewed scientific literature evaluating compulsory treatment modalities. The following academic databases were searched: PubMed, PAIS International, Proquest, PsycINFO, Web of Science, Soc Abstracts, JSTOR, EBSCO/Academic Search Complete, REDALYC, SciELO Brazil. We also searched the Internet, and article reference lists, from database inception to July 15th, 2015. Eligibility criteria are as follows: peer-reviewed scientific studies presenting original data. Primary outcome of interest was post-treatment drug use. Secondary outcome of interest was post-treatment criminal recidivism. Results Of an initial 430 potential studies identified, nine quantitative studies met the inclusion criteria. Studies evaluated compulsory treatment options including drug detention facilities, short (i.e. 21-day) and long-term (i.e., 6 months) inpatient treatment, community-based treatment, group-based outpatient treatment, and prison-based treatment. Three studies (33%) reported no significant impacts of compulsory treatment compared with control interventions. Two studies (22%) found equivocal results but did not compare against a control condition. Two studies (22%) observed negative impacts of compulsory treatment on criminal recidivism. Two studies (22%) observed positive impacts of compulsory inpatient treatment on criminal recidivism and drug use. Conclusion There is limited scientific literature evaluating compulsory drug treatment. Evidence does not, on the whole, suggest improved outcomes related to compulsory treatment approaches, with some studies suggesting potential harms. Given the potential for human rights abuses within compulsory treatment settings, non-compulsory treatment modalities should be prioritized by policymakers seeking to reduce drug-related harms. PMID:26790691

Risk Factors for Treatment Default among Re-Treatment Tuberculosis Patients in India, 2006

PubMed Central

Jha, Ugra Mohan; Satyanarayana, Srinath; Dewan, Puneet K.; Chadha, Sarabjit; Wares, Fraser; Sahu, Suvanand; Gupta, Devesh; Chauhan, L. S.

2010-01-01

Setting Under India's Revised National Tuberculosis Control Programme (RNTCP), >15% of previously-treated patients in the reported 2006 patient cohort defaulted from anti-tuberculosis treatment. Objective To assess the timing, characteristics, and risk factors for default amongst re-treatment TB patients. Methodology For this case-control study, in 90 randomly-selected programme units treatment records were abstracted from all 2006 defaulters from the RNTCP re-treatment regimen (cases), with one consecutively-selected non-defaulter per case. Patients who interrupted anti-tuberculosis treatment for >2 months were classified as defaulters. Results 1,141 defaulters and 1,189 non-defaulters were included. The median duration of treatment prior to default was 81 days (25%–75% interquartile range 44–117 days) and documented retrieval efforts after treatment interruption were inadequate. Defaulters were more likely to have been male (adjusted odds ratio [aOR] 1.4, 95% confidence interval [CI] 1.2–1.7), have previously defaulted anti-tuberculosis treatment (aOR 1.3 95%CI 1.1–1.6], have previous treatment from non-RNTCP providers (AOR 1.3, 95%CI 1.0–1.6], or have public health facility-based treatment observation (aOR 1.3, 95%CI 1.1–1.6). Conclusions Amongst the large number of re-treatment patients in India, default occurs early and often. Improved pre-treatment counseling and community-based treatment provision may reduce default rates. Efforts to retrieve treatment interrupters prior to default require strengthening. PMID:20111727

Inactivation of Geobacillus stearothermophilus Spores by High-Pressure Carbon Dioxide Treatment

PubMed Central

Watanabe, Taisuke; Furukawa, Soichi; Hirata, Junichi; Koyama, Tetsuya; Ogihara, Hirokazu; Yamasaki, Makari

2003-01-01

High-pressure CO2 treatment has been studied as a promising method for inactivating bacterial spores. In the present study, we compared this method with other sterilization techniques, including heat and pressure treatment. Spores of Bacillus coagulans, Bacillus subtilis, Bacillus cereus, Bacillus licheniformis, and Geobacillus stearothermophilus were subjected to CO2 treatment at 30 MPa and 35°C, to high-hydrostatic-pressure treatment at 200 MPa and 65°C, or to heat treatment at 0.1 MPa and 85°C. All of the bacterial spores except the G. stearothermophilus spores were easily inactivated by the heat treatment. The highly heat- and pressure-resistant spores of G. stearothermophilus were not the most resistant to CO2 treatment. We also investigated the influence of temperature on CO2 inactivation of G. stearothermophilus. Treatment with CO2 and 30 MPa of pressure at 95°C for 120 min resulted in 5-log-order spore inactivation, whereas heat treatment at 95°C for 120 min and high-hydrostatic-pressure treatment at 30 MPa and 95°C for 120 min had little effect. The activation energy required for CO2 treatment of G. stearothermophilus spores was lower than the activation energy for heat or pressure treatment. Although heat was not necessary for inactivationby CO2 treatment of G. stearothermophilus spores, CO2 treatment at 95°C was more effective than treatment at 95°C alone. PMID:14660357

Inactivation of Geobacillus stearothermophilus spores by high-pressure carbon dioxide treatment.

PubMed

Watanabe, Taisuke; Furukawa, Soichi; Hirata, Junichi; Koyama, Tetsuya; Ogihara, Hirokazu; Yamasaki, Makari

2003-12-01

High-pressure CO2 treatment has been studied as a promising method for inactivating bacterial spores. In the present study, we compared this method with other sterilization techniques, including heat and pressure treatment. Spores of Bacillus coagulans, Bacillus subtilis, Bacillus cereus, Bacillus licheniformis, and Geobacillus stearothermophilus were subjected to CO2 treatment at 30 MPa and 35 degrees C, to high-hydrostatic-pressure treatment at 200 MPa and 65 degrees C, or to heat treatment at 0.1 MPa and 85 degrees C. All of the bacterial spores except the G. stearothermophilus spores were easily inactivated by the heat treatment. The highly heat- and pressure-resistant spores of G. stearothermophilus were not the most resistant to CO2 treatment. We also investigated the influence of temperature on CO2 inactivation of G. stearothermophilus. Treatment with CO2 and 30 MPa of pressure at 95 degrees C for 120 min resulted in 5-log-order spore inactivation, whereas heat treatment at 95 degrees C for 120 min and high-hydrostatic-pressure treatment at 30 MPa and 95 degrees C for 120 min had little effect. The activation energy required for CO2 treatment of G. stearothermophilus spores was lower than the activation energy for heat or pressure treatment. Although heat was not necessary for inactivationby CO2 treatment of G. stearothermophilus spores, CO2 treatment at 95 degrees C was more effective than treatment at 95 degrees C alone.

Patient- and provider-level risk factors associated with default from tuberculosis treatment, South Africa, 2002: a case-control study.

PubMed

Finlay, Alyssa; Lancaster, Joey; Holtz, Timothy H; Weyer, Karin; Miranda, Abe; van der Walt, Martie

2012-01-20

Persons who default from tuberculosis treatment are at risk for clinical deterioration and complications including worsening drug resistance and death. Our objective was to identify risk factors associated with tuberculosis (TB) treatment default in South Africa. We conducted a national retrospective case control study to identify factors associated with treatment default using program data from 2002 and a standardized patient questionnaire. We defined default as interrupting TB treatment for two or more consecutive months during treatment. Cases were a sample of registered TB patients receiving treatment under DOTS that defaulted from treatment. Controls were those who began therapy and were cured, completed or failed treatment. Two respective multivariable models were constructed, stratified by history of TB treatment (new and re-treatment patients), to identify independent risk factors associated with default. The sample included 3165 TB patients from 8 provinces; 1164 were traceable and interviewed (232 cases and 932 controls). Significant risk factors associated with default among both groups included poor health care worker attitude (new: AOR 2.1, 95% CI 1.1-4.4; re-treatment: AOR 12, 95% CI 2.2-66.0) and changing residence during TB treatment (new: AOR 2.0, 95% CI 1.1-3.7; re-treatment: AOR 3.4, 95% CI 1.1-9.9). Among new patients, cases were more likely than controls to report having no formal education (AOR 2.3, 95% CI 1.2-4.2), feeling ashamed to have TB (AOR 2.0, 95% CI 1.3-3.0), not receiving adequate counseling about their treatment (AOR 1.9, 95% CI 1.2-2.8), drinking any alcohol during TB treatment (AOR 1.9, 95% CI 1.2-3.0), and seeing a traditional healer during TB treatment (AOR 1.9, 95% CI 1.1-3.4). Among re-treatment patients, risk factors included stopping TB treatment because they felt better (AOR 21, 95% CI 5.2-84), having a previous history of TB treatment default (AOR 6.4, 95% CI 2.9-14), and feeling that food provisions might have helped them finish treatment (AOR 5.0, 95% CI 1.3-19). Risk factors for default differ between new and re-treatment TB patients in South Africa. Addressing default in both populations with targeted interventions is critical to overall program success.

20 CFR 404.1537 - What we mean by appropriate treatment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment is...

[Success of treatment, experience of treatment, and satisfaction with treatment from the perspective of patients, parents, and therapists--results of an evaluative study on inpatient treatment in child and adolescent psychiatry].

PubMed

Bredel, Susanne; Brunner, Romuald; Haffner, Johann; Resch, Franz

2004-04-01

In spite of the high importance of subjective opinions as essential evaluation criteria there are hardly any studies available, dealing with the research of subjective judgements made by children and adolescent patients in relation to their inpatient treatment, and comparison with the evaluation of their parents. The evaluative study on an age-group random sample survey (n=95) of patients and parents at the Department of Child and Adolescent Psychiatry at the University of Heidelberg includes success of treatment, experience of treatment and satisfaction with treatment by means of specially constructed and parallelized questionnaires for patients, parents and therapists. Apart from the extent of subjectively experienced changes in precisely defined success variables, not only agreements and differences were studied, but also connections between success of treatment, experience of treatment and satisfaction with treatment as well as influences of success variables and experience variables on treatment satisfaction. Parents', patients' and therapists' evaluations of the treatment in regard of most success variables were all positive. At the end of treatment a perspective convergence was noticeable in some variables. The pressure on the parents requires special therapeutic attention. In the sense of therapy evaluation the change in the way the problem was viewed proved to be a worthwile success criterium. From the patients' and parents' point of view the change in the problem "as a whole" is mainly characterized by a positive change in emotional disposition. The therapeutic atmosphere and organisation of therapeutic relationships were highly appreciated by patients and parents. All in all patients, parents and therapists were highly satisfied with inpatient treatment. The correlations found between the grade of success, experience of treatment and satisfaction with treatment were clearly positive. On the patients' side treatment satisfaction was dictated more by their experiences during the treatment, whereas on the parents' side the success of treatment proved to be the stronger factor.

18 CFR 388.112 - Requests for privileged treatment and Critical Energy Infrastructure Information (CEII) treatment...

Code of Federal Regulations, 2013 CFR

2013-04-01

... treatment and Critical Energy Infrastructure Information (CEII) treatment for documents submitted to the... treatment and Critical Energy Infrastructure Information (CEII) treatment for documents submitted to the... of exemption from disclosure under FOIA, including critical energy infrastructure information (CEII...

20 CFR 404.1537 - What we mean by appropriate treatment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment is...

20 CFR 404.1537 - What we mean by appropriate treatment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment is...

Condition-specific Quality of Life Assessment at Each Stage of Class III Surgical Orthodontic Treatment -A Prospective Study.

PubMed

Tachiki, Chie; Nishii, Yasushi; Takaki, Takashi; Sueishi, Kenji

2018-01-01

Surgical orthodontic treatment has been reported to improve oral health-related quality of life (OHRQL). Such treatment comprises three stages: pre-surgical orthodontic treatment; orthognathic surgery; and post-surgical orthodontic treatment. Most studies have focused on change in OHRQL between before and after surgery. However, it is also necessary to evaluate OHRQL at the pre-surgical orthodontic treatment stage, as it may be negatively affected by dental decompensation compared with at pre-treatment. The purpose of this prospective study was to investigate the influence of surgical orthodontic treatment on QOL by assessing change in condition-specific QOL at each stage of treatment in skeletal class III cases. Twenty skeletal class III patients requiring surgical orthodontic treatment were enrolled in the study. Each patient completed the Orthognathic Quality of Life Questionnaire (OQLQ), which was developed for patients with dentofacial deformity. Its items are grouped into 4 domains: "social aspects of dentofacial deformity"; "facial esthetics"; "oral function"; and "awareness of dentofacial esthetics". The questionnaire was completed at the pre-treatment, pre-surgical orthodontic treatment, and post-surgical orthodontic treatment stages. The results revealed a significant worsening in scores between at pre-treatment and pre-surgical orthodontic treatment in the domains of facial esthetics and oral function (p<0.01), and between at pre-surgical orthodontic and post-surgical orthodontic treatment in all domains except awareness of dentofacial esthetics (p<0.05, p<0.01). A significant correlation was observed between a negative change in overjet and worsening OQLQ scores at the pre-surgical orthodontic treatment stage. Significant correlations were also observed between improvement in upper and lower lip difference, soft tissue pogonion protrusion, and ANB angle and improvement in OQLQ scores at the post-surgical orthodontic treatment stage. These results indicate that morphologic change influences OHRQL in patients undergoing surgical orthodontic treatment not only after surgery, but also during pre-surgical orthodontic treatment.

Tuberculosis treatment discontinuation and symptom persistence: an observational study of Bihar, India’s public care system covering >100,000,000 inhabitants

PubMed Central

2014-01-01

Background The effectiveness of India’s TB control programs depend critically on patients completing appropriate treatment. Discontinuing treatment prior to completion can leave patients infectious and symptomatic. Developing strategies to reduce early discontinuation requires characterizing its patterns and their link to symptom persistence. Methods The 2011 BEST-TB survey (360 clusters, 11 districts) sampled patients (n = 1007) from Bihar’s public healthcare system who had initiated treatment >6 months prior to being interviewed, administering questionnaires to patients about TB treatment duration and symptoms, prior treatment, and sociodemographic characteristics. Multivariate logistic regression models estimated the risk of treatment discontinuation for these characteristics. Similar models estimated probabilities of symptom persistence to 25 weeks post-treatment initiation adjusting for the same predictors and treatment duration. All models included district fixed effects, robust standard errors, and adjustments for the survey sampling design. Treatment default timing and symptom persistence relied solely on self-report. Results 24% of patients discontinued treatment prior to 25 weeks. Higher likelihood of discontinuation occurred in those who had failed to complete previous TB treatment episodes (aOR: 4.77 [95% CI: 1.98 – 11.53]) and those seeing multiple providers (3.67 per provider [1.94 – 6.95]). Symptoms persisted in 42% of patients discontinuing treatment within 5 weeks versus 28% for completing 25 weeks of treatment. Symptom persistence was more likely for those with prior TB treatment (aOR: 5.05 [1.90 – 13.38]); poorer patients (2.94 [1.51 – 5.72]); and women (1.79 [1.07 – 2.99]). Predictors for treatment discontinuation prior to 16 weeks were similar. Conclusions Premature TB treatment discontinuation and symptom persistence is particularly high among individuals who have failed to complete treatment for a prior episode. Strategies to identify and promote treatment completion in this group appear promising. Likewise, effective TB regimens of shortened duration currently in trials may eventually help to achieve higher treatment completion rates. PMID:24886314

20 CFR 416.937 - What we mean by appropriate treatment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... variety of residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment...

20 CFR 404.1537 - What we mean by appropriate treatment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment is...

18 CFR 388.112 - Requests for privileged treatment and Critical Energy Infrastructure Information (CEII) treatment...

Code of Federal Regulations, 2014 CFR

2014-04-01

... treatment and Critical Energy Infrastructure Information (CEII) treatment for documents submitted to the... treatment and Critical Energy Infrastructure Information (CEII) treatment for documents submitted to the... of exemption from disclosure under FOIA, including critical energy infrastructure information (CEII...

Telemedicine of family-based treatment for adolescent anorexia nervosa: A protocol of a treatment development study.

PubMed

Anderson, Kristen E; Byrne, Catherine; Goodyear, Alexandria; Reichel, Ryan; Le Grange, Daniel

2015-01-01

Family-based treatment is an efficacious treatment available for adolescents with anorexia nervosa. Yet the implementation of this treatment, at least in the United States, is challenging due to a limited number of trained family-based treatment therapists and the concentration of these therapists in a limited number of urban centers. The use of telemedicine in the delivery of family-based treatment can increase access to this therapy for this patient population. This two-year treatment development study (December 2013-November 2015) follows a two-wave iterative case series design. The study is ongoing and addresses the treatment needs of families in remote, rural, or underrepresented parts of the United States by delivering family-based treatment via telemedicine (video chat). The first six months of the study was dedicated to selecting a cloud-based secure telemedicine portal for use with participants. Recruitment for the first of two consecutive case series (N = 5) began during month seven. After these five patients completed treatment, a systematic review of treatment via feedback from participants and therapists related to the delivery of this model and use of technology was completed. A second wave of recruitment is underway (N = 5). At the end of both waves (N = 10), and after a second review of treatment, we should be able to establish the feasibility and acceptability of family-based treatment delivered via telemedicine for this patient population. This study is the first attempt to deliver family-based treatment for adolescents with anorexia nervosa via telemedicine. If delivering family-based treatment in this format is feasible, it will provide access to an evidence-based treatment for families heretofore unable to participate in specialist treatment for their child's eating disorder.

The Effects of Cryogenic Treatment on Cutting Tools

NASA Astrophysics Data System (ADS)

Kumar, Satish; Khedkar, Nitin K.; Jagtap, Bhushan; Singh, T. P.

2017-08-01

Enhancing the cutting tool life is important and economic factor to reduce the tooling as well as manufacturing cost. The tool life is improved considerably by 92 % after cryogenic treatment. The cryogenic treatment is a one-time permanent, sub-zero heat treatment that entirely changes cross-section of cutting tool. The cryogenic treatment is carried out with deep freezing of cutting tool materials to enhance physical and mechanical properties. The cryogenic treatment improves mechanical such as hardness, toughness and tribological properties such as wear resistance, coefficient of friction, surface finish, dimensional stability and stress relief. The deep cryogenic treatment is the most beneficial treatment applied on cutting tools. The cryogenic treatment is the most advanced heat treatment and popular to improve performance of the cutting tool. The optimization of cryogenic treatment variables is necessary to improve tool life. This study reviews the effects of cryogenic treatment on microstructure, tribological properties of tool steels and machining applications of cutting tool by investigating the surface and performing the surface characterization test like SEM. The economy of cutting tool can be achieved by deep cryogenic treatment.

20 CFR 416.937 - What we mean by appropriate treatment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... variety of residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment...

Residential treatment following outpatient treatment for children with mild to borderline intellectual disabilities: a study of child and family characteristics.

PubMed

Embregts, Petri J C M

2009-01-01

In this study, the question was explored whether children with a mild intellectual disability (MID) who were placed in residential treatment following outpatient treatment differ significantly on child and family characteristics from children with MID and not placed in residential treatment following outpatient treatment. The records of the children were examined with respect to various child and family characteristics. Retrospective case analyses were thus undertaken. The results showed those children placed in residential treatment to have experienced significantly more often a traumatic event than the other children. Those children placed in residential treatment had received significantly fewer months of outpatient treatment than those not placed in residential treatment. Finally, there were significantly more children placed in residential treatment having educationally incapable parents or parents with alcohol/drug problems and/or psychiatric problems than in the other group. The findings are discussed in light of a disturbed balance between the support needs and means of the family which can lead to placement of a child in a residential treatment. The possibilities of a multisystemic model for outpatient treatment are discussed.

20 CFR 416.937 - What we mean by appropriate treatment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... variety of residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment...

20 CFR 416.937 - What we mean by appropriate treatment.

Code of Federal Regulations, 2014 CFR

2014-04-01

... variety of residential treatment settings including acute detoxification, short-term intensive residential treatment, long-term therapeutic residential treatment, and long-term recovery houses. Appropriate treatment...

Barriers to Implementing Treatment Integrity Procedures: Survey of Treatment Outcome Researchers

ERIC Educational Resources Information Center

Perepletchikova, Francheska; Hilt, Lori M.; Chereji, Elizabeth; Kazdin, Alan E.

2009-01-01

Treatment integrity refers to implementing interventions as intended. Treatment integrity is critically important for experimental validity and for drawing valid inferences regarding the relationship between treatment and outcome. Yet, it is rarely adequately addressed in psychotherapy research. The authors examined barriers to treatment integrity…

Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats.

PubMed

Karimipour, Mojtaba; Shojaei Zarghani, Sara; Mohajer Milani, Majid; Soraya, Hamid

2018-04-01

To explore the effects of pre versus post ischemic treatment with metformin after global cerebral ischemia in rats. Male Wister rats underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Metformin (200 mg/kg) or vehicle was given orally by gavage for 7-14 days. Rats were divided into: control, metformin pre-treatment, metformin post-treatment and metformin pre and post continuous treatment groups. Cerebral infarct size, histopathology, myeloperoxidase and serum malondialdehyde were measured 7 days after ischemia. Histopathological analysis showed that metformin pre-treatment significantly decreased leukocyte infiltration, myeloperoxidase activity and also malondialdehyde level. Metformin pre-treatment and metformin post-treatment reduced infarct size compared with the control group, but it was not significant in the pre and post continuous treatment group. Our findings suggest that pre-treatment with metformin in comparison with post-treatment in experimental stroke can reduce the extent of brain damage and is more neuroprotective at least in part by inhibiting oxidative stress and inflammation.

Radiation treatment in older patients: a framework for clinical decision making.

PubMed

Smith, Grace L; Smith, Benjamin D

2014-08-20

In older patients, radiation treatment plays a vital role in curative and palliative cancer therapy. Radiation treatment recommendations should be informed by a comprehensive, personalized risk-benefit assessment that evaluates treatment efficacy and toxicity. We review several clinical factors that distinctly affect efficacy and toxicity of radiation treatment in older patients. First, locoregional tumor behavior may be more indolent in older patients for some disease sites but more aggressive for other sites. Assessment of expected locoregional relapse risk informs the magnitude and timeframe of expected radiation treatment benefits. Second, assessment of the competing cancer versus noncancer mortality and morbidity risks contextualizes cancer treatment priorities holistically within patients' entire spectrum and time course of health needs. Third, assessment of functional reserve helps predict patients' acute treatment tolerance, differentiating those patients who are unlikely to benefit from treatment or who are at high risk for treatment complications. Potential radiation treatment options include immediate curative treatment, delayed curative treatment, and no treatment, with additional consideration given to altered radiation target, dose, or sequencing with chemotherapy and/or surgery. Finally, when cure is not feasible, palliative radiation therapy remains valuable for managing symptoms and achieving meaningful quality-of-life improvements. Our proposed decision-making framework integrates these factors to help radiation oncologists formulate strategic treatment recommendations within a multidisciplinary context. Future research is still needed to identify how advanced technologies can be judiciously applied in curative and palliative settings to enhance risk-benefit profiles of radiation treatment in older patients and more accurately quantify treatment efficacy in this group. © 2014 by American Society of Clinical Oncology.

Human rights and access to hepatitis C treatment for people who inject drugs.

PubMed

Wolfe, D; Luhmann, N; Harris, M; Momenghalibaf, A; Albers, E; Byrne, J; Swan, T

2015-11-01

People who inject drugs (PWID) achieve adherence to and outcomes from hepatitis C virus (HCV) treatment comparable to other patients. Nonetheless, this population has been excluded from treatment by regulation or practice. Approval of safer and more effective oral HCV medicines should offer greater treatment options for PWID, although high medicine prices have led to continued treatment rationing and exclusion in developed countries. In middle-income countries (MICS), treatment is largely unavailable and unaffordable for most PWID. Human rights analysis, with its emphasis on the universal and interconnected nature of the economic, social and political spheres, offers a useful framework for HCV treatment reform. Using peer-reviewed and grey literature, as well as community case reports, we discuss barriers to treatment, correlate these barriers to rights violations, and highlight examples of community advocacy to increase treatment for PWID. Structural drivers of lack of treatment access for PWID include stigma in health settings; drug use status as a criterion for treatment exclusion; requirements for fees or registration by name as a drug user prior to treatment initiation; and incarceration/detention in prisons and rehabilitation centers where treatment is unavailable. High medicine prices force further exclusion of PWID, with cost containment masked as concern about treatment adherence. These barriers correlate to multiple rights violations, including of the rights to privacy; non-discrimination; health; freedom of information; fair trial; and freedom from cruel, inhuman and degrading treatment. Needed reforms include decriminalization of drug use, possession of drugs and drug injecting equipment; removal of exclusionary or discriminatory treatment protocols; approaches to strengthen links between health providers and increase participation of PWID in treatment design and implementation; and measures to increase transparency in government/pharmaceutical company negotiations and reduce treatment price. Copyright © 2015. Published by Elsevier B.V.

Organizational Predictors and Use of Evidence-Based Practices in Adolescent Substance Abuse Treatment.

PubMed

Paino, Maria; Aletraris, Lydia; Roman, Paul M

2015-01-01

Adolescent substance abuse remains a significant problem in the United States, yet treatment centers do not always admit adolescent clients. In this paper, we first determine the extent to which treatment is available for adolescents in general and whether or not adolescent-specific (segregated) tracks are offered. Second, we examine the organizational characteristics associated with adolescent treatment. Third, we illuminate how the adolescent caseload in a treatment center is related to offering evidence-based practices (EBPs). Drawing upon a nationally representative sample of US treatment programs, we use logistic regression to assess how organizational characteristics are associated with the provision of adolescent treatment. Using ordinal logistic regression, we analyze how the treatment center's adolescent caseload and organizational characteristics affect the extent to which a treatment center offers medication-assisted treatment (MAT) and psychosocial treatment. Half (49.5%) of treatment programs admitted adolescents, and 41.8% offered an adolescent-specific track. Findings from the logistic regression suggested several organizational characteristics that were significantly associated with treating adolescents and/or having an adolescent-only track. Our findings from the ordinal models indicated a negative relationship between the percent of adolescents in a treatment center and the extent of MAT, and a positive relationship between the percent of adolescent clients and the extent of psychosocial treatment offered. This paper highlights organizational barriers to treatment entry for adolescents, who remain a small proportion of clients in treatment centers. When treatment centers serve adolescents, however, those adolescents are likely to receive care in adolescent-only tracks and/or services and in programs that offer several psychosocial EBPs. Finally, adolescents are less likely to receive treatment in centers that offer a variety of MAT.

Economic comparison of common treatment protocols and J5 vaccination for clinical mastitis in dairy herds using optimized culling decisions.

PubMed

Kessels, J A; Cha, E; Johnson, S K; Welcome, F L; Kristensen, A R; Gröhn, Y T

2016-05-01

This study used an existing dynamic optimization model to compare costs of common treatment protocols and J5 vaccination for clinical mastitis in US dairy herds. Clinical mastitis is an infection of the mammary gland causing major economic losses in dairy herds due to reduced milk production, reduced conception, and increased risk of mortality and culling for infected cows. Treatment protocols were developed to reflect common practices in dairy herds. These included targeted therapy following pathogen identification, and therapy without pathogen identification using a broad-spectrum antimicrobial or treating with the cheapest treatment option. The cost-benefit of J5 vaccination was also estimated. Effects of treatment were accounted for as changes in treatment costs, milk loss due to mastitis, milk discarded due to treatment, and mortality. Following ineffective treatments, secondary decisions included extending the current treatment, alternative treatment, discontinuing treatment, and pathogen identification followed by recommended treatment. Average net returns for treatment protocols and vaccination were generated using an existing dynamic programming model. This model incorporates cow and pathogen characteristics to optimize management decisions to treat, inseminate, or cull cows. Of the treatment protocols where 100% of cows received recommended treatment, pathogen-specific identification followed by recommended therapy yielded the highest average net returns per cow per year. Out of all treatment scenarios, the highest net returns were achieved with selecting the cheapest treatment option and discontinuing treatment, or alternate treatment with a similar spectrum therapy; however, this may not account for the full consequences of giving nonrecommended therapies to cows with clinical mastitis. Vaccination increased average net returns in all scenarios. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Organizational Predictors and Use of Evidence-Based Practices in Adolescent Substance Abuse Treatment

PubMed Central

Paino, Maria; Aletraris, Lydia; Roman, Paul M.

2014-01-01

Background Adolescent substance abuse remains a significant problem in the United States, yet treatment centers do not always admit adolescent clients. In this article, we first determine the extent to which treatment is available for adolescents in general and whether or not adolescent-specific (segregated) tracks are offered. Second, we examine the organizational characteristics associated with adolescent treatment. Third, we illuminate how the adolescent caseload in a treatment center is related to offering evidence-based practices (EBPs). Methods Drawing upon a nationally representative sample of U.S. treatment programs, we use logistic regression to assess how organizational characteristics are associated with the provision of adolescent treatment. Using ordinal logistic regression, we analyze how the treatment center’s adolescent caseload and organizational characteristics affect the extent to which a treatment center offers medication-assisted treatment (MAT) and psychosocial treatment. Results Half (49.5%) of treatment programs admitted adolescents and 41.8% offered an adolescent-specific track. Findings from the logistic regression suggested several organizational characteristics that were significantly associated with treating adolescents and/or having an adolescent-only track. Our findings from the ordinal models indicated a negative relationship between the percent of adolescents in a treatment center and the extent of MAT, and a positive relationship between the percent of adolescent clients and the extent of psychosocial treatment offered. Conclusions This paper highlights organizational barriers to treatment entry for adolescents, who remain a small proportion of clients in treatment centers. When treatment centers serve adolescents, however, those adolescents are likely to receive care in adolescent-only tracks and/or services and in programs that offer several psychosocial EBPs. Finally, adolescents are less likely to receive treatment in centers that offer a variety of MAT. PMID:25257691

Treatment of Selective Mutism: A Best-Evidence Synthesis.

ERIC Educational Resources Information Center

Stone, Beth Pionek; Kratochwill, Thomas R.; Sladezcek, Ingrid; Serlin, Ronald C.

2002-01-01

Presents systematic analysis of the major treatment approaches used for selective mutism. Based on nonparametric statistical tests of effect sizes, major findings include the following: treatment of selective mutism is more effective than no treatment; behaviorally oriented treatment approaches are more effective than no treatment; and no…

The influence of location of local anesthesia and complexity/duration of restorative treatment on children's behavior during dental treatment.

PubMed

Davidovich, Esti; Wated, Alham; Shapira, Joseph; Ram, Diana

2013-01-01

The purpose of this study was to investigate whether the region of local anesthetic injection and the complexity and duration of restorative treatment were associated with children's behavior during and immediately after dental treatment. This study examined 90 children, divided into two age groups (2-3.5 years old and >3.5-5.5 years old), who underwent dental treatment while lightly sedated. The region of local anesthesia (maxillary infiltration or mandibular block), complexity and duration of treatment, and behavior during and after treatment were assessed. Children's behavior during and after dental treatment, within and between age groups, was not found to be associated with the region of local anesthesia or complexity of treatment. For both age groups, more children exhibited negative behaviors during treatment when procedures exceeded 30 minutes. For younger children, more negative behaviors were also observed after longer vs shorter procedures. Treatment duration, not the region of local anesthesia or complexity of treatment, was associated with children's behavior during and after dental procedures.

“How Will It Help Me?”: Reasons Underlying Treatment Preferences Between Sertraline and Prolonged Exposure in PTSD

PubMed Central

Chen, Jessica A.; Keller, Stephanie M.; Zoellner, Lori A.; Feeny, Norah C.

2014-01-01

Individuals with posttraumatic stress disorder (PTSD) often wait years before seeking treatment. Improving treatment initiation and adherence requires a better understanding patient beliefs that lead to treatment preferences. Using a treatment-seeking sample (N = 200) with chronic PTSD, qualitative reasons underlying treatment preferences for either prolonged exposure (PE) or sertraline (SER) were examined. Reasons for treatment preference primarily focused on how the treatment was perceived to reduce PTSD symptoms rather than practical ones. Patients were more positive about PE than SER. Individual differences did not reliably predict underlying preference reasons, suggesting that what makes a treatment desirable is not strongly determined by current functioning, treatment, or trauma history. Taken together, this information is critical for treatment providers, arguing for enhancing psychoeducation about how treatment works and acknowledging pre-existing biases against pharmacotherapy for PTSD that should be addressed. This knowledge has the potential to optimize and better personalize PTSD patient care. PMID:23896851

Alone on the Inside: The Impact of Social Isolation and Helping Others on AOD Use and Criminal Activity

PubMed Central

Johnson, Byron R.; Pagano, Maria E.; Lee, Matthew T.; Post, Stephen G.

2015-01-01

Because addiction is a socially isolating disease, social support for recovery is an important element of treatment planning. This study examines the relationship between social isolation, giving and receiving social support in Alcoholics Anonymous during treatment, and post-treatment outcomes among juvenile offenders court-referred to addiction treatment. Adolescents (N = 195) aged 14 to 18 years were prospectively assessed at treatment admission, treatment discharge, 6 months, and 12 months after treatment discharge. The influence of social isolation variables on relapse and severe criminal activity in the 12-months post-treatment was examined using negative binomial logistic regressions and event history methods. Juveniles entering treatment with social estrangement were significantly more likely to relapse, be incarcerated, and commit a violent crime in the 12-months post-treatment. Giving help to others in Alcoholics Anonymous during treatment significantly reduced the risk of relapse, incarceration, and violent crime in the 12-months post-treatment whereas receiving help did not. PMID:29628533

Treatment Intensity and Childhood Apraxia of Speech

ERIC Educational Resources Information Center

Namasivayam, Aravind K.; Pukonen, Margit; Goshulak, Debra; Hard, Jennifer; Rudzicz, Frank; Rietveld, Toni; Maassen, Ben; Kroll, Robert; van Lieshout, Pascal

2015-01-01

Background: Intensive treatment has been repeatedly recommended for the treatment of speech deficits in childhood apraxia of speech (CAS). However, differences in treatment outcomes as a function of treatment intensity have not been systematically studied in this population. Aim: To investigate the effects of treatment intensity on outcome…

Treatment of urban river contaminated sediment with ex situ advanced oxidation processes: technical feasibility, environmental discharges and cost-performance analysis.

PubMed

Yan, Dickson Y S; Liu, Tongzhou; Lo, Irene M C

2015-01-01

The technical feasibility, environmental discharges and cost-performance of urban river contaminated sediment treatment with ex situ advanced oxidation processes were evaluated for the purpose of achieving an ideal treatment goal (for marine disposal) and a cost-performance treatment goal (for beneficially reusing as a filling material). Sediment samples were collected from a river located in southern China. To achieve the ideal treatment goal, sequential treatments (Fenton's reaction+activated persulphate oxidation) were carried out. One-step Fenton's reaction was applied to achieve the cost-performance treatment goal. The resulting effluent was treated and discharged, and sludge generated in wastewater treatment was characterized. The resources input throughout the treatment processes were recorded for cost estimation. After the treatment designed for achieving the ideal treatment goal, most pollutants fulfilled the treatment goal except Pb, Cd, Hg and Ag, probably because these four metals were present mainly in stable fractions of the sediment. The cost-performance treatment goal was achieved in view of low pollutant contents in the toxicity characteristic leaching procedure leachate of treated sediment. The cost for achieving the cost-performance treatment goal is much less than that for achieving the ideal treatment goal. The major cost difference is attributed to chemical cost. Stringent sediment treatment goals based on existing standards would lead to massive chemical use, complex treatment and hence huge cost. A simpler treatment with fewer chemicals is adequate for sediment beneficially reused as a filling material, and is economically more advantageous than handling sediment for marine disposal.

Dental treatment and caries prevention preceding treatment under general anaesthesia in healthy children and adolescents: a retrospective cohort study.

PubMed

Grindefjord, M; Persson, J; Jansson, L; Tsilingaridis, G

2018-04-01

This was to examine healthy children and adolescents treated under general anaesthesia (GA) and a matched control group not receiving GA to compare treatment and preventive care received prior to GA treatment. This retrospective cohort study included 71 healthy subjects and 213 age- and gender-matched control subjects. The treatment group had been consecutively referred from the Public Dental Health Service (PDS) in Stockholm to the Department of Paediatric Dentistry, Eastman Institute, Stockholm during 2006-2007. Data was extracted from the patient records at the PDS, including variables such as number of dental visits, treatment/prophylaxis prior to GA, number of missed and cancelled appointments, and number of decayed teeth. On average, the treatment group had significantly more decayed teeth (p < 0.001) than the control group. Furthermore, the treatment group had significantly more restorations (p < 0.01), had visited the dentist significantly more often (p < 0.001), and had undergone significantly more behaviour management treatment and preventive treatment (p < 0.001). In the treatment group 65% of the children and adolescents, had received no behaviour management treatment and 48%, no preventive treatment. In the Stockholm PDS, over half of the children and adolescents referred by general dentists to paediatric specialists had no behaviour management treatment and nearly half, no preventive treatment, despite receiving significantly more operative treatment compared with matched controls. General dentists should target high caries-risk patients for additional behaviour management and preventive care to reduce the need for treatment under GA.

Understanding Treatment Readiness in Recently Assessed, Pre-Treatment Substance Abusers

PubMed Central

Rapp, Richard C.; Xu, Jiangmin; Carr, Carey A.; Timothy Lane, D.; Redko, Cristina; Wang, Jichuan; Carlson, Robert G.

2007-01-01

The goal of this study was to more fully understand readiness for treatment in a pre-treatment sample of 446 substance abusers. Structural Equation Modeling (SEM) was used to: (1) examine the relationships between readiness factors identified in the Pre-Treatment Readiness Scale; and (2) identify the effects of predisposing, illness, and inhibiting determinants on the factors. As with in-treatment samples, Problem Recognition was found to influence Treatment Readiness, although through a different intervening factor, Desire for Change rather than Desire for Help. A fourth factor, Treatment Reluctance, was also influenced by the Desire for Change factor. Fixed characteristics such as age and gender had minimal influences on readiness factors, as did inhibiting characteristics that reflected recent functioning. Illness characteristics including drug severity and perceived treatment barriers had a more robust influence on readiness factors. This study provides an increased understanding of readiness for treatment among pre-treatment substance abusers and also supported the construct validity of the Pre-Treatment Readiness Scale. PMID:19274847

Patient learning of treatment contents in cognitive therapy.

PubMed

Gumport, Nicole B; Dong, Lu; Lee, Jason Y; Harvey, Allison G

2018-03-01

Research has demonstrated that both memory and learning for treatment contents are poor, and that both are associated with worse treatment outcome. The Memory Support Intervention has been shown to improve memory for treatment, but it has not yet been established if this intervention can also improve learning of treatment contents. This study was designed to document the number of times participants exhibited each of the indices of learning, to examine the indices of learning and their relationship to recall of treatment points, and to investigate the association between the indices of learning and depression outcome. Adults diagnosed with major depressive disorder (N = 48) were randomly assigned to 14 sessions of cognitive therapy-as-usual (CT-as-usual) or cognitive therapy plus the Memory Support Intervention (CT + Memory Support). Measures of learning, memory, and depressive symptomatology were taken at mid-treatment, post-treatment, and at 6-month follow-up. Relative to the CT-as-usual group, participants in the CT + Memory Support group reported more accurate thoughts and applications of treatment points at mid-treatment, post-treatment, and 6-month follow-up. Patient recall was significantly correlated with application and cognitive generalization. Thoughts and application at mid-treatment were associated with increased odds of treatment response at post-treatment. The learning measure for this study has not yet been psychometrically validated. The results are based on a small sample. Learning during treatment is poor, but modifiable via the Memory Support Intervention. These results provide encouraging data that improving learning of treatment contents can reduce symptoms during and following treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reasons for HCV non-treatment in underserved African Americans: implications for treatment with new therapeutics.

PubMed

Schaeffer, Sarah; Khalili, Mandana

2015-01-01

African Americans are disproportionately affected by hepatitis C (HCV) and are less likely to undergo HCV treatment. Underserved populations are especially at risk for experiencing health disparity. Aim. To identify reasons for HCV non-treatment among underserved African Americans in a large safetynet system. Medical records of HCV-infected African Americans evaluated at San Francisco General Hospital liver specialty clinic from 2006-2011 who did not receive HCV treatment were reviewed. Treatment eligibility and reasons for non-treatment were assessed. Factors associated with treatment ineligibility were assessed using logistic regression modeling. Among 118 patients, 42% were treatment ineligible, 18% treatment eligible, and 40% were undergoing work-up to determine eligibility. Reasons for treatment ineligibility were medical (54%), non-medical (14%), psychiatric (4%), or combined (28%). When controlling for age and sex, active/recent substance abuse (OR 6.65, p = 0.001) and having two or more medical comorbidities (OR 3.39, p = 0.005) predicted treatment ineligibility. Excluding those ineligible for treatment, 72% of all other patients were lost to follow-up; they were older (55 vs. 48 years, p = 0.01) and more likely to be undergoing work up to determine treatment eligibility (86 vs. 21%, p < 0.0001) than those not lost to follow-up. Medical comorbidities and substance abuse predicted HCV treatment ineligibility in underserved African Americans. Importantly, the majority of those undergoing work-up to determine HCV treatment eligibility were lost to follow-up. While newer anti-HCV agents may increase treatment eligibility, culturally appropriate interventions to increase compliance with evaluation and care remain critical to HCV management in underserved African Americans.

Women-focused treatment agencies and process improvement: Strategies to increase client engagement

PubMed Central

Wisdom, Jennifer P.; Hoffman, Kim; Rechberger, Elke; Seim, Kay; Owens, Betta

2009-01-01

Behavioral health treatment agencies often struggle to keep clients engaged in treatment. Women clients often have additional factors such as family responsibilities, financial difficulties, or abuse histories that provide extra challenges to remaining in care. As part of a national initiative, four women-focused drug treatment agencies used process improvement to address treatment engagement. Interviews and focus groups with staff assessed the nature and extent of interventions. Women-focused drug treatment agencies selected relational-based interventions to engage clients in treatment and improved four-week treatment retention from 66% to 76%. Process improvement interventions in women-focused treatment may be useful to improve engagement. PMID:20046914

Atmospheric pressure plasma processing of polymeric materials utilizing close proximity indirect exposure

DOEpatents

Paulauskas, Felix L.; Bonds, Truman

2016-09-20

A plasma treatment method that includes providing treatment chamber including an intermediate heating volume and an interior treatment volume. The interior treatment volume contains an electrode assembly for generating a plasma and the intermediate heating volume heats the interior treatment volume. A work piece is traversed through the treatment chamber. A process gas is introduced to the interior treatment volume of the treatment chamber. A plasma is formed with the electrode assembly from the process gas, wherein a reactive species of the plasma is accelerated towards the fiber tow by flow vortices produced in the interior treatment volume by the electrode assembly.

Quitting smoking during substance use disorders treatment: Patient and treatment-related variables.

PubMed

Campbell, Barbara K; Le, Thao; Tajima, Barbara; Guydish, Joseph

2017-02-01

Although individuals in substance use disorders (SUD) treatment continue to smoke at high rates, regulatory, policy and programming changes promoting tobacco cessation are being implemented and some patients quit successfully. We examined associations of smoking patterns, tobacco advertising receptivity, anti-tobacco message awareness, health risk perception, attitudes towards addressing smoking and availability of smoking cessation services with quitting smoking during SUD treatment. Surveys were completed by 1127 patients in 24 programs chosen randomly, stratified by program type (residential, methadone maintenance, outpatient), from among publicly funded, adult treatment programs within the National Drug Abuse Treatment Clinical Trials Network. Among respondents who had been in SUD treatment for at least one month, there were 631 current smokers and 52 former smokers who reported quitting smoking during treatment for at least one month prior to survey completion; these respondents comprised our sample (N=683). Results showed that participants who reported health concerns as a reason for quitting were 1.27 times more likely to have quit during treatment (p=0.015) than those reporting health concerns affected quitting a little or not at all. Additionally, participants who reported that smoking cessation was part of their personal treatment plan during SUD treatment were 1.08 times more likely to have quit during treatment (p<0.001). Participants in methadone treatment were 49% less likely to report successfully quitting during treatment than those in outpatient treatment (95%CI: 0. 35-0.75, p<0.001). Leveraging health concerns about smoking and including smoking cessation in an individualized treatment plan may help increase smoking cessation during SUD treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

Patients' willingness to trade off between the duration and frequency of rheumatoid arthritis treatments.

PubMed

Poulos, Christine; Hauber, A Brett; González, Juan Marcos; Turpcu, Adam

2014-07-01

Biologic treatments for rheumatoid arthritis (RA) vary widely in both the time required to administer treatment and treatment frequency. This study aimed to quantify the rate at which RA patients are willing to trade off between the time required to administer treatment (duration) and treatment frequency. Respondents with a self-reported physician diagnosis of moderate to severe RA completed an online discrete choice experiment survey (also known as conjoint analysis). Respondents were presented with a series of treatment-choice questions. Each hypothetical treatment included 6 attributes: response rate, mode of administration, treatment duration, treatment frequency, and the risks of immediate mild and serious treatment reactions. Preference weights, also called marginal utilities or relative importances, were estimated using mixed-logit methods and then used to calculate the marginal rates of substitution between attributes, including treatment duration and treatment frequency. Among the 901 respondents, 505 were in the RA Information, Service, and Education group (www.risesupport.com) and 396 were members of an online panel. The marginal utility of changes in treatment features was largest for a 1-hour change in treatment duration, while a 1-unit change in the annual frequency of treatment was the second least important change. The marginal utility of changes in annual treatment frequency depends on the treatment duration and vice versa. Respondents would accept treatments with lower efficacy and greater risk to achieve lower duration and frequency. Previous studies have linked patient preferences to treatment adherence, suggesting that reductions in duration or frequency could improve adherence and health outcomes. Copyright © 2014 by the American College of Rheumatology.

Quitting Smoking During Substance Use Disorders Treatment: Patient and Treatment-related Variables

PubMed Central

Campbell, Barbara K.; Le, Thao; Tajima, Barbara; Guydish, Joseph

2016-01-01

Although individuals in substance use disorders (SUD) treatment continue to smoke at high rates, regulatory, policy and programming changes promoting tobacco cessation are being implemented and some patients quit successfully. We examined associations of smoking patterns, tobacco advertising receptivity, anti-tobacco message awareness, health risk perception, attitudes towards addressing smoking and availability of smoking cessation services with quitting smoking during SUD treatment. Surveys were completed by 1127 patients in 24 programs chosen randomly, stratified by program type (residential, methadone maintenance, outpatient), from among publicly funded, adult treatment programs within the National Drug Abuse Treatment Clinical Trials Network. Among respondents who had been in SUD treatment for at least one month, there were 631 current smokers and 52 former smokers who reported quitting smoking during treatment for at least one month prior to survey completion; these respondents comprised our sample (N=683). Results showed that participants who reported health concerns as a reason for quitting were 1.27 times more likely to have quit during treatment (p=.015) than those reporting health concerns affected quitting a little or not at all. Additionally, participants who reported that smoking cessation was part of their personal treatment plan during SUD treatment were 1.08 times more likely to have quit during treatment (p<.001). Participants in methadone treatment were 49% less likely to report successfully quitting during treatment than those in outpatient treatment (95%CI: 0. 35-0.75, p<.001). Leveraging health concerns about smoking and including smoking cessation in an individualized treatment plan may help increase smoking cessation during SUD treatment. PMID:28017183

Treatment Components and Their Relationships with Drug and Alcohol Abstinence.

ERIC Educational Resources Information Center

Orwin, Rob; Ellis, Bruce

This study evaluates the effect of treatment components through a secondary analysis of data from the National Treatment Improvement Evaluation Study (NTIES). The study examines the relationship between treatment components, client-level factors, and treatment outcomes, and how these relationships vary by treatment modality. It seeks to understand…

42 CFR 485.916 - Condition of participation: Treatment team, person-centered active treatment plan, and...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 false Condition of participation: Treatment team, person... Health Centers (CMHCs) § 485.916 Condition of participation: Treatment team, person-centered active treatment plan, and coordination of services. The CMHC must designate an interdisciplinary treatment team...

Treatment Utilization and Unmet Treatment Need among Hispanics Following Brief Intervention

PubMed Central

Cochran, Gerald; Caetano, Raul

2012-01-01

Background In a large randomized trial examining ethnic differences in response to a brief alcohol intervention following an alcohol related injury, we showed that Hispanics, but not non-Hispanics, were more likely to reduce alcohol intake in comparison to treatment as usual (Field et al, 2010). The current study evaluates whether the observed improvements in drinking outcomes previously reported among Hispanics following brief intervention might be related to prior or subsequent treatment utilization. . Methods The present study is a secondary analysis of data collected in a randomized clinical trial that evaluated ethnic differences in the effect of a brief motivational intervention (BMI) on alcohol use among medical inpatients admitted for alcohol related injury. For the current study, statistical analyses were carried out to compare alcohol use, alcohol problems, treatment utilization and unmet treatment need between Hispanic (n=539) and White, non-Hispanic (n=667). In addition, we examined the relationship between prior treatment utilization and unmet treatment need and alcohol use outcomes following brief intervention and the impact of brief intervention on subsequent treatment utilization and unmet treatment need. Results In comparison to White, non-Hispanics, Hispanics at baseline reported heavier drinking, more alcohol problems, greater unmet treatment need and lower rates of treatment utilization. Among Hispanics, multilevel analyses showed that prior treatment utilization or unmet treatment need did not moderate the effect of BMI on alcohol outcomes. Furthermore, BMI did not significantly impact subsequent treatment utilization or unmet treatment need among Hispanics. Finally, treatment utilization and unmet treatment need at six-months were not significant mediators between BMI and alcohol use outcomes at follow up. Conclusion The benefits of brief intervention among Hispanics do not appear to be better explained by subsequent engagement in mutual help groups or formal substance abuse treatment. Prior history of treatment, regardless of the severity of alcohol problems, does not appear to influence the impact of brief intervention on alcohol use among Hispanics. These findings support prior results reporting the benefits of brief intervention among Hispanics and demonstrate that these improvements are not related to prior or subsequent treatment utilization. PMID:22823528

Treatment Utilization Among Adolescent Substance Users: Findings from the 2002 to 2013 National Survey on Drug Use and Health.

PubMed

Haughwout, Sarah P; Harford, Thomas C; Castle, I-Jen P; Grant, Bridget F

2016-08-01

Adolescent substance users face serious health and social consequences and benefit from early diagnosis and treatment. The objectives of this study were to observe trends in treatment utilization; examine correlates of treatment utilization and treatment types/settings among adolescent substance users with and without substance use disorder (SUD); and assess gender differences. National Survey on Drug Use and Health data were pooled across 2002 to 2013, with a combined sample of 79,885 past-year substance users ages 12 to 17 (17,510 with SUD and 62,375 without SUD). Treatment was defined as receiving treatment or counseling for use of alcohol or any drug, not counting cigarettes. Trends were assessed by joinpoint linear regression, and multivariable logistic regression assessed odds ratios of treatment utilization. Percentages of past-year treatment use did not change in 2002 to 2013. Treatment utilization was more prevalent among adolescents with SUD than without (11.4% vs. 1.4%) and among males than females. Among adolescents with and without SUD, criminal justice involvement and perceiving a need for treatment increased adolescent treatment utilization, while SUDs other than alcohol abuse, older age, and talking to parents increased treatment use among adolescents with SUD, and polysubstance use and male gender increased treatment among those without SUD. Treatment gaps persisted among non-Hispanic Blacks for both groups with and without SUD, male Hispanics with SUD, female non-Hispanic Asians without SUD, and private insurance coverages. Gender differences were observed in SUD, race/ethnicity, and insurance coverage. Most adolescents received treatment for both alcohol and drug use, and self-help group and outpatient rehabilitation facility were the most used treatment settings. Treatment utilization among adolescents with past-year substance use remained low and unimproved in 2002 to 2013. Treatment gaps among minority populations, insurance coverage, and in educating adolescents on seeking relevant treatment must be addressed. Using screening processes such as Screening, Brief Intervention, and Referral to Treatment, health professionals can help prevent lifelong SUD by recognizing and addressing substance misuse early. Copyright © 2016 by the Research Society on Alcoholism.

Prompted to treatment by the criminal justice system: Relationships with treatment retention and outcome among cocaine users.

PubMed

Kiluk, Brian D; Serafini, Kelly; Malin-Mayor, Bo; Babuscio, Theresa A; Nich, Charla; Carroll, Kathleen M

2015-04-01

A substantial portion of individuals entering treatment for substance use have been referred by the criminal justice system, yet there are conflicting reports regarding treatment engagement and outcome differences compared to those not referred. This study examined baseline characteristic and treatment outcome differences among cocaine-dependent individuals participating in cocaine treatment randomized trials. This secondary analysis pooled samples across five completed randomized controlled trials, resulting in 434 participants. Of these, 67 (15%) were prompted to treatment by the criminal justice system. This subsample of criminal justice prompted (CJP) individuals did not differ from those not prompted by the criminal justice system in terms of gender, race/ethnicity, marital status, or age. However, the CJP group reported more years of regular cocaine use, more severe employment and legal problems, as well as less readiness to change prior to treatment. Treatment outcomes did not differ significantly from those without a criminal justice prompt, and on some measures the outcomes for CJP group were better (e.g., percentage of days cocaine abstinent, number of therapy sessions attended). These findings suggest that being prompted to treatment by the criminal justice system may not lead to poorer treatment engagement or substance use outcomes for individuals participating in randomized controlled treatment trials. Despite some baseline indicators of poorer treatment prognosis, individuals who have been prompted to treatment by the criminal justice system have similar treatment outcomes as those presenting to treatment voluntarily. © American Academy of Addiction Psychiatry.

Examining Treatment Climate Across Prison-Based Substance Abuse Treatment Groups.

PubMed

Kelly, Christopher E; Welsh, Wayne N

2016-06-06

With notable exceptions, few studies have looked critically at the role and effects of factors other than individual or programmatic differences that contribute to the climate within substance abuse treatment programs. De Leon's work on the therapeutic community, however, indicates that factors beyond the individual and program can contribute to the overall functioning of similarly situated communities. In this study, we introduce and examine the concept of the "treatment group," the level of aggregation between the individual who participates in treatment and the organization that provides it. The treatment group refers to the social context and dynamics that operate among treatment participants, and we sought to study differences in treatment climate across 12 prison-based treatment groups within a single prison. Using data from 604 participants who were assigned at random to one of the 12 groups, we analyzed differences on seven treatment climate indicators from one month and six months into the program across the treatment groups. No differences were found among the treatment groups at after one month; however, after 6 months, significant differences emerged across the groups on three treatment climate variables: program structure, counselor rapport, and counselor competence. This study is among the first of its kind to conceptualize and examine treatment climate across otherwise similar groups and find that differences emerge on several indicators of climate. As such, we argue that the treatment group may be important to consider in both the delivery and evaluation of substance abuse treatment.

Gender differences in prison-based drug treatment participation.

PubMed

Belenko, Steven; Houser, Kimberly A

2012-08-01

Prisons inmates have high rates of substance abuse and associated social and health problems, and a concomitant high need for drug treatment while incarcerated. Female inmates have an even greater treatment need, yet most inmates do not participate in treatment while incarcerated. Using data from a nationally representative sample of prison inmates, this article examines the impact of gender on prison treatment participation and gender differences in the factors associated with clinical treatment participation. Females were significantly more likely to participate in prison drug treatment than males, controlling for other factors. For both males and females, severity of drug problems predicted participation in treatment. For males but not females, race was associated with prison treatment participation, and among those with drug abuse or dependence, females with co-occurring mental health problems were more likely to participate in treatment. Implications for prison assessment and treatment policies, and future research, are discussed.

Are Treatment Outcomes Determined by Type of Gambling? A UK Study.

PubMed

Ronzitti, Silvia; Soldini, Emiliano; Smith, Neil; Bayston, Andrew; Clerici, Massimo; Bowden-Jones, Henrietta

2018-01-30

One of the main difficulties faced in treating gambling disorder is compliance with psychological treatment. Gambling takes many forms and can differ greatly in its features such as speed of play and skill requirements. The type of gambling a pathological gambler opts for may play a key role in treatment compliance. The aim of the present study was to determine whether within treatment seeking sample of gambling disorder clients, gambling activity has any correlation with their resultant treatment outcomes. The study incorporated 524 treatment-seeking individuals who are clients of the National Problem Gambling Clinic in London. All of the clients were assessed prior to treatment and fulfilled the Problem Gambling Severity Index criteria for problem gambling. Data concerning clients' gambling behavior over the previous year was gathered using self-reports. Subsequently, the data was fitted to a multinomial logistic regression model, with the treatment outcome (i.e. pre-treatment dropouts, during treatment dropouts, and completed treatment) as the dependent variable and gambling behavior as the independent variable, whilst controlling for socio-demographic factors. The use of gaming machines was a significant predictor of dropping out pre-treatment (p < 0.05, RRR 1.616), whilst betting on sports events was a significant predictor of dropping out during treatment (p < 0.01, RRR 2.435). Treatment outcomes have been found to significantly differ based on participation in certain gambling activities. Further research into the salient features of these gambling activities may help to further explain pre-treatment and during treatment dropouts within this population.

Depressed patients’ perceptions of depression treatment decision‐making

PubMed Central

Simon, Daniela; Loh, Andreas; Wills, Celia E.; Härter, Martin

2006-01-01

Abstract Objective  Little is known about the feasibility and effects of patient‐clinician shared decision‐making (SDM) for depression treatment. Within a goal of informing the design of a SDM intervention, the objective of this study was to investigate depressed patients’ perceptions of the treatment decision‐making process with general practitioners (GPs). Setting and participants  Data were gathered from a convenience sample of 40 depressed patients to understand key aspects of treatment decision‐making from the patient perspective. The sample varied in depression severity and type of setting in which treatment was sought. Main variables studied  Semi‐structured interview questions focused on patients’ prior experiences with depression and treatment, perceptions of the treatment decision‐making process, and needs and expectations about treatment. Current depression severity was also assessed. Results  Patient lack of insight regarding depression severity substantially delayed patient engagement in treatment seeking and decision‐making. Patients expected their GPs to be a first and main source of objective information and discussion about depression and treatment and to provide emotional support for decision‐making. Patients also identified needs for additional information about depression and its treatment, as well as concerns about certain aspects of treatment. Conclusions  The depression treatment context has some aspects that differ from treatment decision‐making for other types of health conditions. SDM approaches for depression treatment should be adapted based on depression severity and patient‐identified needs. PMID:17324195

Beliefs and attitudes regarding drug treatment: application of the theory of planned behavior in African-American cocaine users.

PubMed

Booth, Brenda M; Stewart, Katharine E; Curran, Geoffrey M; Cheney, Ann M; Borders, Tyrone F

2014-10-01

The Theory of Planned Behavior (TPB) can provide insights into perceived need for cocaine treatment among African American cocaine users. A cross-sectional community sample of 400 (50% rural) not-in-treatment African-American cocaine users was identified through respondent-driven sampling in one urban and two rural counties in Arkansas. Measures included self-reports of attitudes and beliefs about cocaine treatment, perceived need and perceived effectiveness of treatment, and positive and negative cocaine expectancies. Normative beliefs were measured by perceived stigma and consequences of stigma regarding drug use and drug treatment. Perceived control was measured by readiness for treatment, prior drug treatment, and perceived ability to cut down on cocaine use without treatment. Multiple regression analysis found that older age (standardized regression coefficient β=0.15, P<0.001), rural residence (β=-0.09, P=0.025), effectiveness of treatment (β=0.39, P<0.001), negative cocaine expectancies (β=0.138, P=0.003), experiences of rejection (β=0.18, P<0.001), need for secrecy (β=0.12, P=0.002), and readiness for treatment (β=0.15, P<0.001) were independently associated with perceived need for cocaine treatment. TPB is a relevant model for understanding perceived need for treatment among African-American cocaine users. Research has shown perceived need to be a major correlate of treatment participation. Study results should be applicable for designing interventions to encourage treatment participation. Copyright © 2014. Published by Elsevier Ltd.

Analysis of External Treatment Methods and Technical Characteristics of External Treatment

NASA Astrophysics Data System (ADS)

Zhang, Rui; Miao, Mingsan; Bai, Ming

2018-01-01

Chinese medicine external therapy is a treatment method of Chinese medicine with Chinese characteristics. The effect of traditional Chinese medicine external treatment, convenient operation, external treatment and technology has great prospects for development. The traditional Chinese medicine external treatment method and technical characteristics were analyzed.

40 CFR 63.1581 - Does the subpart distinguish between different types of POTW treatment plants?

Code of Federal Regulations, 2010 CFR

2010-07-01

... different types of POTW treatment plants? 63.1581 Section 63.1581 Protection of Environment ENVIRONMENTAL... treatment plants? Yes, POTW treatment plants are divided into two subcategories. A POTW treatment plant which does not meet the characteristics of an industrial POTW treatment plant belongs in the non...

40 CFR 133.105 - Treatment equivalent to secondary treatment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... through proper operation and maintenance of the treatment works, based on an analysis of the past... treatment works, considering the design capability of the treatment process and geographical and climatic...

Choice of unconventional treatment by patients with cancer.

PubMed

Kimby, Charlotte Kira; Launsø, Laila; Henningsen, Inge; Langgaard, Henrik

2003-08-01

Previous studies conducted on the use of unconventional treatment by patients with cancer have focused on unconventional treatment as a joint group of therapies. The objective of this study is to gather preliminary information about the use of different modes of unconventional cancer treatment by patients with cancer and to describe user profiles of standardized and individualized treatments. Data originate from an ongoing explorative 5-year study of 441 consecutively registered cancer patients who have consulted medical doctors and alternative therapists practicing unconventional treatment in Denmark. This paper is based on data from the first and second of six questionnaires. The unconventional treatments included in this study are categorized into two forms of treatment: standardized and individualized treatment. Four hundred and forty-one (441) Danish patients with cancer who use unconventional cancer treatment. The analysis shows significant correlations between type of treatment and the following variables: gender, education, occupational status, type of cancer, purpose of seeking unconventional treatment, metastatic spread, opinion regarding appropriate unconventional treatment, and simultaneous use of unconventional treatment. The study shows that there are significant differences between patients with cancer choosing standardized and those choosing individualized unconventional treatment. The probability of choosing standardized unconventional treatment is greatest among male participants, patients having shorter school education, and for patients who have recovery as the goal of seeking unconventional treatment. The probability of choosing individualized unconventional treatment is greatest among women, for patients with longer school education, and for patients wanting relief from symptoms, information, and improvement of general condition as the purpose of seeking unconventional cancer treatment. Patients with breast and gynecologic cancer are more inclined to seek individualized treatment than patients with all other cancer diseases. The study points to the fact that it might be essential to differentiate between different forms of unconventional treatment to understand the use by patients with cancer and the outcomes of these treatments.

Interdisciplinary treatment for an adult patient with anterior open bite, severe periodontitis, and intellectual disability.

PubMed

Kang, Da-Young; Choi, Sung-Hwan; Jung, Young-Soo; Hwang, Chung-Ju

2015-05-01

This case report describes the beneficial effects of the interdisciplinary treatment of an adult patient with severe skeletal periodontal problems. A 30-year-old female patient presented with anterior open bite, gummy smile, and facial asymmetry. The patient had chronic generalized severe periodontitis with pathologic maxillary anterior teeth migration and mild intellectual disability. Treatment included 6 months of periodontal treatment, followed by presurgical orthodontic treatment, a Le Fort I osteotomy with anterior segmental osteotomy, a bilateral sagittal split ramus osteotomy, and postsurgical orthodontic treatment. After treatment completion, the patient exhibited functional and aesthetic improvements. Her periodontal condition improved and was maintained after the treatment. Here, we demonstrate a successful treatment outcome in a complicated case following a systematic interdisciplinary approach performed with the correct diagnosis and treatment planning.

Repeated addiction treatment use in Sweden: a National Register Database study.

PubMed

Grahn, Robert; Chassler, Deborah; Lundgren, Lena

2014-11-01

Sweden has a free, universal addiction treatment system, yet few studies exist examining utilization of treatment in this country. This study identified predisposing, enabling, and need factors associated with history of number of voluntary addiction treatment episodes for a national sample of 12,009 individuals assessed for an alcohol and/or drug use disorder in Sweden. On average, people reported 4.3 prior treatment episodes. Linear regression methods identified that predisposing factors such as older age and being male were associated with more voluntary addiction treatment episodes compared to younger and female clients; a higher Addiction Severity Index (ASI) employment score (an enabling factor) was associated with more voluntary addiction treatment episodes; and need factors including a history of inpatient mental health treatment, a higher ASI psychiatric score, a higher ASI alcohol score, higher levels of illicit drug use, more compulsory addiction treatment episodes, a lower ASI legal score, and a history of criminal justice involvement were all associated with more voluntary addiction treatment episodes compared to their counterparts.. There were no differences in the number of treatment episodes by education or immigrant status. (1) Need is a key factor associated with more treatment use. (2) Further studies are needed to identify gender differences in access/use of treatment. (3) Given multiple treatment histories, Swedish addiction treatment policy should reflect a chronic care model rather than an acute care model.

Effects of Treatment Type on Alcohol Consumption Partially Mediated by Alcoholics Anonymous Attendance.

PubMed

Karriker-Jaffe, Katherine J; Klinger, Jamie L; Witbrodt, Jane; Kaskutas, Lee Ann

2018-03-21

As insurance coverage, funding sources and venues for drug and alcohol treatment evolve in the United States, it is important to assess how the type of treatment received may impact long-term outcomes. The current study aims were to examine effects of treatment type on alcohol consumption in the year after treatment intake and to test mediators of effects of treatment type on later alcohol use. Longitudinal data from clients in inpatient and outpatient alcohol treatment programs in California (n = 560) were used in ordinary least squares path analysis adjusting for respondent characteristics typically associated with both treatment completion and alcohol use. The primary outcome was amount of alcohol consumed in the 12 months after treatment entry; hypothesized mediators were treatment duration and participation in Alcoholics Anonymous (AA). Despite higher baseline problem severity and a shorter treatment duration, inpatient clients consumed less alcohol after treatment than outpatient clients (B [95% CI] = -0.95 [-1.67, -0.23]). AA involvement was a significant mediator of the relationship between treatment type and alcohol consumption, with inpatient clients being more involved in AA and also drinking less after treatment than outpatient clients; the bias-corrected bootstrap 95% confidence interval for the indirect effect (B = -0.20) was entirely below zero (-0.43 to -0.05). Outpatient clients may benefit from customized posttreatment recommendations to identify additional resources to assist in the recovery process during the first year after treatment.

Effect of timing of count events on estimates of sea lice abundance and interpretation of effectiveness following bath treatments.

PubMed

Gautam, R; Vanderstichel, R; Boerlage, A S; Revie, C W; Hammell, K L

2017-03-01

Effectiveness of sea lice bath treatment is often assessed by comparing pre- and post-treatment counts. However, in practice, the post-treatment counting window varies from the day of treatment to several days after treatment. In this study, we assess the effect of post-treatment lag time on sea lice abundance estimates after chemical bath treatment using data from the sea lice data management program (Fish-iTrends) between 2010 and 2014. Data on two life stages, (i) adult female (AF) and (ii) pre-adult and adult male (PAAM), were aggregated at the cage level and log-transformed. Average sea lice counts by post-treatment lag time were computed for AF and PAAM and compared relative to treatment day, using linear mixed models. There were 720 observations (treatment events) that uniquely matched pre- and post-treatment counts from 53 farms. Lag time had a significant effect on the estimated sea lice abundance, which was influenced by season and pre-treatment sea lice levels. During summer, sea lice were at a minimum when counted 1 day post-treatment irrespective of pre-treatment sea lice levels, whereas in the spring and autumn, low levels were observed for PAAM over a longer interval of time, provided the pre-treatment sea lice levels were >5-10. © 2016 John Wiley & Sons Ltd.

Characteristics of treatment provided for amphetamine use in New South Wales, Australia.

PubMed

McKetin, Rebecca; Kelly, Erin; Indig, Devon

2005-09-01

The purpose of this study was to examine the types of treatment services provided for amphetamine use, the characteristics of amphetamine treatment clients and the geographic areas most affected by amphetamine treatment provision within New South Wales (NSW), Australia. Data on completed amphetamine treatment episodes were extracted from the NSW Minimum Data Set for Alcohol and Other Drug Treatment Services for the year 2002/03 (n = 4,337). The geographic area of treatment presentations was based on the location of the treatment service, and was categorized as metropolitan, regional or rural. Treatment disproportionately affected regional and rural NSW, and treatment clients often presented with concurrent cannabis and/or alcohol problems. Clients were overwhelmingly injecting drug users with poor socio-demographic characteristics. Counselling was the most common treatment service provided, followed by detoxification and residential rehabilitation. Detoxification was usually provided in an in-patient setting, particularly within metropolitan NSW. Compliance with residential rehabilitation was notably poor. In conclusion, the development of appropriate interventions for amphetamine use needs to consider that the majority of treatment recipients will be based in a regional or rural setting, and treating amphetamine users will often involve treatment of concurrent cannabis and alcohol problems. The nature and appropriateness of treatment services provided for amphetamine use needs to be reviewed in detail, and further research is needed into the nature of problematic amphetamine use and factors affecting treatment demand in regional and rural NSW.

Treatment of anorexia nervosa in children and adolescents.

PubMed

Weaver, Laurel; Sit, Lydia; Liebman, Ronald

2012-04-01

In this review, we discuss the treatment of anorexia nervosa (AN) in children and adolescents, highlighting inpatient and outpatient psychiatric treatment. AN is an illness that involves medical and psychological issues; hence, treatment often requires the seamless integration of several medical professionals. It is important that the treatment model be unified and consistent as patients transition from inpatient to outpatient treatment. We briefly describe the therapeutic principles involved in treatment of AN and then give examples of how we employ these principles across treatment settings and with multiple medical professionals.

Substance abuse treatment response in a Latino sample: the influence of family conflict.

PubMed

Fish, Jessica N; Maier, Candice A; Priest, Jacob B

2015-02-01

Latino Americans report underutilization of treatment and poor treatment response for substance use and abuse compared to other racial/ethnic groups; thus, it is important to assess factors that contribute to these disparities. The current study objective was to assess the influence of family conflict on substance abuse treatment response in a sample of Latino Americans using two different yet complementary analyses. First, ordinary least squares regression was used to assess the association between overall family conflict and pre- and post-treatment substance use. Second, repeated measures latent class analysis was used to identify groups based on family member conflict and timing of conflict during treatment. Findings indicated that family conflict contributed unique variance to concurrent substance use; however pre-treatment family conflict was not related to post-treatment outcomes. Results also identified three distinct family conflict groups: no/low conflict, pre-treatment conflict, and post-treatment conflict who differed in pre- and post-treatment substance use. Post hoc investigation revealed that those who experienced pre-treatment conflict but low post-treatment conflict showed the greatest decrease in substance use. Findings highlight the importance of considering family conflict during all stages of treatment for Latino American substance users. Copyright © 2015 Elsevier Inc. All rights reserved.

Recovery of calf muscle strength following acute achilles tendon rupture treatment: a comparison between minimally invasive surgery and conservative treatment.

PubMed

Metz, Roderik; van der Heijden, Geert J M G; Verleisdonk, Egbert-Jan M M; Tamminga, Rob; van der Werken, Christiaan

2009-10-01

The aim of this study was to measure the effect of treatment of acute Achilles tendon ruptures on calf muscle strength recovery. Eighty-three patients with acute Achilles tendon rupture were randomly allocated to either minimally invasive surgery with functional after-treatment or conservative treatment by functional bracing. Calf muscle strength using isokinetic testing was evaluated at 3 months and after 6 or more months posttreatment. To exclusively investigate the effect of treatment on outcome, the authors excluded patients with major complications from the analysis. In 31 of 39 patients in the surgical treatment group and 25 of 34 patients in the conservative treatment group, isokinetic strength tests were performed. In the analysis of differences in mean peak torque, no statistically significant differences were found between surgery and conservative treatment, except for plantar flexion strength at 90 degrees per second at the second measurement, favoring conservative treatment. After 8 to 10 months follow- up, loss of plantar flexion strength was still present in the injured leg in both treatment groups. In conclusion, isokinetic muscle strength testing did not detect a statistically significant difference between minimally invasive surgical treatment with functional after-treatment and conservative treatment by functional bracing of acute Achilles tendon ruptures.

Direct versus Indirect Treatment for Preschool Children who Stutter: The RESTART Randomized Trial.

PubMed

de Sonneville-Koedoot, Caroline; Stolk, Elly; Rietveld, Toni; Franken, Marie-Christine

2015-01-01

Stuttering is a common childhood disorder. There is limited high quality evidence regarding options for best treatment. The aim of the study was to compare the effectiveness of direct treatment with indirect treatment in preschool children who stutter. In this multicenter randomized controlled trial with an 18 month follow-up, preschool children who stutter who were referred for treatment were randomized to direct treatment (Lidcombe Program; n = 99) or indirect treatment (RESTART-DCM treatment; n = 100). Main inclusion criteria were age 3-6 years, ≥3% syllables stuttered (%SS), and time since onset ≥6 months. The primary outcome was the percentage of non-stuttering children at 18 months. Secondary outcomes included stuttering frequency (%SS), stuttering severity ratings by the parents and therapist, severity rating by the child, health-related quality of life, emotional and behavioral problems, and speech attitude. Percentage of non-stuttering children for direct treatment was 76.5% (65/85) versus 71.4% (65/91) for indirect treatment (Odds Ratio (OR), 0.6; 95% CI, 0.1-2.4, p = .42). At 3 months, children treated by direct treatment showed a greater decline in %SS (significant interaction time x therapy: β = -1.89; t(282.82) = -2.807, p = .005). At 18 months, stuttering frequency was 1.2% (SD 2.1) for direct treatment and 1.5% (SD 2.1) for indirect treatment. Direct treatment had slightly better scores on most other secondary outcome measures, but no differences between treatment approaches were significant. Direct treatment decreased stuttering more quickly during the first three months of treatment. At 18 months, however, clinical outcomes for direct and indirect treatment were comparable. These results imply that at 18 months post treatment onset, both treatments are roughly equal in treating developmental stuttering in ways that surpass expectations of natural recovery. Follow-up data are needed to confirm these findings in the longer term. isrctn.org ISRCTN24362190.

The Trimeric Model: A New Model of Periodontal Treatment Planning

PubMed Central

Tarakji, Bassel

2014-01-01

Treatment of periodontal disease is a complex and multidisciplinary procedure, requiring periodontal, surgical, restorative, and orthodontic treatment modalities. Several authors attempted to formulate models for periodontal treatment that orders the treatment steps in a logical and easy to remember manner. In this article, we discuss two models of periodontal treatment planning from two of the most well-known textbook in the specialty of periodontics internationally. Then modify them to arrive at a new model of periodontal treatment planning, The Trimeric Model. Adding restorative and orthodontic interrelationships with periodontal treatment allows us to expand this model into the Extended Trimeric Model of periodontal treatment planning. These models will provide a logical framework and a clear order of the treatment of periodontal disease for general practitioners and periodontists alike. PMID:25177662

Direct versus Indirect Treatment for Preschool Children who Stutter: The RESTART Randomized Trial

PubMed Central

de Sonneville-Koedoot, Caroline; Stolk, Elly; Rietveld, Toni; Franken, Marie-Christine

2015-01-01

Objective Stuttering is a common childhood disorder. There is limited high quality evidence regarding options for best treatment. The aim of the study was to compare the effectiveness of direct treatment with indirect treatment in preschool children who stutter. Methods In this multicenter randomized controlled trial with an 18 month follow-up, preschool children who stutter who were referred for treatment were randomized to direct treatment (Lidcombe Program; n = 99) or indirect treatment (RESTART-DCM treatment; n = 100). Main inclusion criteria were age 3–6 years, ≥3% syllables stuttered (%SS), and time since onset ≥6 months. The primary outcome was the percentage of non-stuttering children at 18 months. Secondary outcomes included stuttering frequency (%SS), stuttering severity ratings by the parents and therapist, severity rating by the child, health-related quality of life, emotional and behavioral problems, and speech attitude. Results Percentage of non-stuttering children for direct treatment was 76.5% (65/85) versus 71.4% (65/91) for indirect treatment (Odds Ratio (OR), 0.6; 95% CI, 0.1–2.4, p = .42). At 3 months, children treated by direct treatment showed a greater decline in %SS (significant interaction time x therapy: β = -1.89; t(282.82) = -2.807, p = .005). At 18 months, stuttering frequency was 1.2% (SD 2.1) for direct treatment and 1.5% (SD 2.1) for indirect treatment. Direct treatment had slightly better scores on most other secondary outcome measures, but no differences between treatment approaches were significant. Conclusions Direct treatment decreased stuttering more quickly during the first three months of treatment. At 18 months, however, clinical outcomes for direct and indirect treatment were comparable. These results imply that at 18 months post treatment onset, both treatments are roughly equal in treating developmental stuttering in ways that surpass expectations of natural recovery. Follow-up data are needed to confirm these findings in the longer term. Trial Registration isrctn.org ISRCTN24362190 PMID:26218228

Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline.

PubMed

Sateia, Michael J; Buysse, Daniel J; Krystal, Andrew D; Neubauer, David N; Heald, Jonathan L

2017-02-15

The purpose of this guideline is to establish clinical practice recommendations for the pharmacologic treatment of chronic insomnia in adults, when such treatment is clinically indicated. Unlike previous meta-analyses, which focused on broad classes of drugs, this guideline focuses on individual drugs commonly used to treat insomnia. It includes drugs that are FDA-approved for the treatment of insomnia, as well as several drugs commonly used to treat insomnia without an FDA indication for this condition. This guideline should be used in conjunction with other AASM guidelines on the evaluation and treatment of chronic insomnia in adults. The American Academy of Sleep Medicine commissioned a task force of four experts in sleep medicine. A systematic review was conducted to identify randomized controlled trials, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process was used to assess the evidence. The task force developed recommendations and assigned strengths based on the quality of evidence, the balance of benefits and harms, and patient values and preferences. Literature reviews are provided for those pharmacologic agents for which sufficient evidence was available to establish recommendations. The AASM Board of Directors approved the final recommendations. The following recommendations are intended as a guideline for clinicians in choosing a specific pharmacological agent for treatment of chronic insomnia in adults, when such treatment is indicated. Under GRADE, a STRONG recommendation is one that clinicians should, under most circumstances, follow. A WEAK recommendation reflects a lower degree of certainty in the outcome and appropriateness of the patient-care strategy for all patients, but should not be construed as an indication of ineffectiveness. GRADE recommendation strengths do not refer to the magnitude of treatment effects in a particular patient, but rather, to the strength of evidence in published data. Downgrading the quality of evidence for these treatments is predictable in GRADE, due to the funding source for most pharmacological clinical trials and the attendant risk of publication bias; the relatively small number of eligible trials for each individual agent; and the observed heterogeneity in the data. The ultimate judgment regarding propriety of any specific care must be made by the clinician in light of the individual circumstances presented by the patient, available diagnostic tools, accessible treatment options, and resources. We suggest that clinicians use suvorexant as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use eszopiclone as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zaleplon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use zolpidem as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use triazolam as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use temazepam as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use ramelteon as a treatment for sleep onset insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians use doxepin as a treatment for sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use trazodone as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tiagabine as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use diphenhydramine as a treatment for sleep onset and sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use melatonin as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use tryptophan as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). We suggest that clinicians not use valerian as a treatment for sleep onset or sleep maintenance insomnia (versus no treatment) in adults. (WEAK). © 2017 American Academy of Sleep Medicine

Treatment motivation among caregivers and adolescents with substance use disorders

PubMed Central

Cornelius, T.; Earnshaw, V. A.; Menino, D.; Bogart, L. M.; Levy, S.

2017-01-01

Substance use disorders (SUDs) in adolescence have negative long-term health effects, which can be mitigated through successful treatment. Caregivers play a central role in adolescent treatment involvement; however, studies have not examined treatment motivation and pressures to enter treatment in caregiver/adolescent dyads. Research suggests that internally motivated treatment (in contrast to coerced treatment) tends to lead to better outcomes. We used Self-Determination Theory (SDT) to examine intersecting motivational narratives among caregivers and adolescents in SUD treatment. Relationships between motivation, interpretation of caregiver pressures, adolescent autonomy, and relatedness were also explored. Adolescents in SUD treatment and their caregivers (NDyads = 15) were interviewed about treatment experiences. Interviews were coded for treatment motivation, including extrinsic (e.g., motivated by punishment), introjected (e.g., motivated by guilt), and identified/integrated motivation (e.g., seeing a behavior as integral to the self). Internalization of treatment motivation, autonomy support/competence (e.g., caregiver support for adolescent decisions), and relatedness (e.g., acceptance and support) were also coded. Four dyadic categories were identified: agreement that treatment was motivated by the adolescent (intrinsic); agreement that treatment was motivated by the caregiver (extrinsic); agreement that treatment was motivated by both, or a shift towards adolescent control (mixed/transitional); and disagreement (adolescents and caregivers each claimed they motivated treatment; conflicting). Autonomy support and relatedness were most prominent in intrinsic dyads, and least prominent in extrinsic dyads. The mixed/transitional group was also high in autonomy support and relatedness. The extrinsic group characterized caregiver rules as an unwelcome mechanism for behavioral control; caregivers in the other groups saw rules as a way to build adolescent competence and repair relationships, and adolescents saw rules as indicating care rather than control. Adolescents with intrinsic motivations were the most engaged in treatment. Results suggest the importance of intrinsically motivated treatment, and highlight autonomy support and relatedness as mechanisms that might facilitate treatment engagement. PMID:28237049

Treatment motivation among caregivers and adolescents with substance use disorders.

PubMed

Cornelius, T; Earnshaw, V A; Menino, D; Bogart, L M; Levy, S

2017-04-01

Substance use disorders (SUDs) in adolescence have negative long-term health effects, which can be mitigated through successful treatment. Caregivers play a central role in adolescent treatment involvement; however, studies have not examined treatment motivation and pressures to enter treatment in caregiver/adolescent dyads. Research suggests that internally motivated treatment (in contrast to coerced treatment) tends to lead to better outcomes. We used Self-determination theory (SDT) to examine intersecting motivational narratives among caregivers and adolescents in SUD treatment. Relationships between motivation, interpretation of caregiver pressures, adolescent autonomy, and relatedness were also explored. Adolescents in SUD treatment and their caregivers (N Dyads =15) were interviewed about treatment experiences. Interviews were coded for treatment motivation, including extrinsic (e.g., motivated by punishment), introjected (e.g., motivated by guilt), and identified/integrated motivation (e.g., seeing a behavior as integral to the self). Internalization of treatment motivation, autonomy support/competence (e.g., caregiver support for adolescent decisions), and relatedness (e.g., acceptance and support) were also coded. Four dyadic categories were identified: agreement that treatment was motivated by the adolescent (intrinsic); agreement that treatment was motivated by the caregiver (extrinsic); agreement that treatment was motivated by both, or a shift towards adolescent control (mixed/transitional); and disagreement (adolescents and caregivers each claimed they motivated treatment; conflicting). Autonomy support and relatedness were most prominent in intrinsic dyads, and least prominent in extrinsic dyads. The mixed/transitional group was also high in autonomy support and relatedness. The extrinsic group characterized caregiver rules as an unwelcome mechanism for behavioral control; caregivers in the other groups saw rules as a way to build adolescent competence and repair relationships, and adolescents saw rules as indicating care rather than control. Adolescents with intrinsic motivations were the most engaged in treatment. Results suggest the importance of intrinsically motivated treatment, and highlight autonomy support and relatedness as mechanisms that might facilitate treatment engagement. Copyright © 2017 Elsevier Inc. All rights reserved.

Patient- and provider-level risk factors associated with default from tuberculosis treatment, South Africa, 2002: a case-control study

PubMed Central

2012-01-01

Background Persons who default from tuberculosis treatment are at risk for clinical deterioration and complications including worsening drug resistance and death. Our objective was to identify risk factors associated with tuberculosis (TB) treatment default in South Africa. Methods We conducted a national retrospective case control study to identify factors associated with treatment default using program data from 2002 and a standardized patient questionnaire. We defined default as interrupting TB treatment for two or more consecutive months during treatment. Cases were a sample of registered TB patients receiving treatment under DOTS that defaulted from treatment. Controls were those who began therapy and were cured, completed or failed treatment. Two respective multivariable models were constructed, stratified by history of TB treatment (new and re-treatment patients), to identify independent risk factors associated with default. Results The sample included 3165 TB patients from 8 provinces; 1164 were traceable and interviewed (232 cases and 932 controls). Significant risk factors associated with default among both groups included poor health care worker attitude (new: AOR 2.1, 95% CI 1.1-4.4; re-treatment: AOR 12, 95% CI 2.2-66.0) and changing residence during TB treatment (new: AOR 2.0, 95% CI 1.1-3.7; re-treatment: AOR 3.4, 95% CI 1.1-9.9). Among new patients, cases were more likely than controls to report having no formal education (AOR 2.3, 95% CI 1.2-4.2), feeling ashamed to have TB (AOR 2.0, 95% CI 1.3-3.0), not receiving adequate counseling about their treatment (AOR 1.9, 95% CI 1.2-2.8), drinking any alcohol during TB treatment (AOR 1.9, 95% CI 1.2-3.0), and seeing a traditional healer during TB treatment (AOR 1.9, 95% CI 1.1-3.4). Among re-treatment patients, risk factors included stopping TB treatment because they felt better (AOR 21, 95% CI 5.2-84), having a previous history of TB treatment default (AOR 6.4, 95% CI 2.9-14), and feeling that food provisions might have helped them finish treatment (AOR 5.0, 95% CI 1.3-19). Conclusions Risk factors for default differ between new and re-treatment TB patients in South Africa. Addressing default in both populations with targeted interventions is critical to overall program success. PMID:22264339

Failure-free survival after second-line systemic treatment of chronic graft-versus-host disease

PubMed Central

Storer, Barry E.; Lee, Stephanie J.; Carpenter, Paul A.; Sandmaier, Brenda M.; Flowers, Mary E. D.; Martin, Paul J.

2013-01-01

This study attempted to characterize causes of treatment failure, identify associated prognostic factors, and develop shorter-term end points for trials testing investigational products or regimens for second-line systemic treatment of chronic graft-versus-host disease (GVHD). The study cohort (312 patients) received second-line systemic treatment of chronic GVHD. The primary end point was failure-free survival (FFS) defined by the absence of third-line treatment, nonrelapse mortality, and recurrent malignancy during second-line treatment. Treatment change was the major cause of treatment failure. FFS was 56% at 6 months after second-line treatment. Lower steroid doses at 6 months correlated with subsequent withdrawal of immunosuppressive treatment. Multivariate analysis showed that high-risk disease at transplantation, lower gastrointestinal involvement at second-line treatment, and severe NIH global score at second-line treatment were associated with increased risks of treatment failure. These three factors were used to define risk groups, and success rates at 6 months were calculated for each risk group either without or with various steroid dose limits at 6 months as an additional criterion of success. These success rates could be used as the basis for a clinically relevant and efficient shorter-term end point in clinical studies that evaluate agents for second-line systemic treatment of chronic GVHD. PMID:23321253