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Anabolic Androgenic Steroids : Effects on Neuropeptide Systems in the Rat BrainHallberg, Mathias January 2005 (has links)
Anabolic-androgenic steroids (AAS) have been used in clinics for decades. The misuse of AAS has previously been attributed merely to sport athletes, taking AAS with intentions to increase muscle mass, enhance physical performance and to improve results in competitions. Today, the misuse of AAS has spread to adolescents and young adults not connected to sports. Alarmingly, many reports are pointing at severe psychiatric adverse effects among AAS abusers, which include mood swings, mania, anxiety, depression and aggression. Numerous examples of severe and often unprovoked violence and brutal crimes have been connected to AAS abuse and there is a strong need for a better understanding of the underlying biochemical events that might account for the adverse behaviors induced by AAS. The general aim of this thesis was to study the effect of chronic AAS administration on neuropeptide circuits in the rat brain associated with the regulation of rewarding effects, memory, anxiety, depression and aggression, using nandrolone decanoate as a prototype AAS. Results demonstrated that daily administration of AAS to rats in doses comparable to those taken by AAS abusers, in certain brain structures significantly affected, a) the levels of the opioid peptides dynorphin B and Met-enkephalin-Arg6Phe7, b) the levels of the tachykinin substance P (SP), c) the density of the SP neurokinin 1 (NK1) receptor, d) the level of the SP metabolite SP1-7 that frequently exerts opposite effects to SP, e) the SP1-7 generating enzyme substance P endopeptidase (SPE) and finally, f) the levels of the neuropeptide calcitonin gene-related peptide (CGRP) often co-localized with SP. The alterations seen in the levels and activities of these neurochemical components are in many aspects compatible with behaviors typified among AAS abusers.
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Harnessing the anabolic properties of dark respiration to enhance sink activity at elevated CO2 using Arabidopsis thaliana L. with partially-suppressed mitochondrial pyruvate dehydrogenase kinaseWeraduwage, Sarathi 17 May 2013 (has links)
Sink limitations in plants reduce the potential for photosynthesis and yield, particularly under conditions that favour enhanced source activity such as elevated CO2 (EC). Dark respiration, considered catabolic, has rarely been exploited to enhance sink activity in plants. Arabidopsis thaliana L. lines with partially-suppressed mitochondrial pyruvate dehydrogenase (mtPDH) kinase (mtPDHK), a negative post-translational regulator of the mtPDH complex, was shown previously to have both elevated mtPDH complex activity and increased seed weight and oil content at ambient CO2 (AC), suggesting an enhancement of sink activity. The mtPDH links glycolysis with the tricarboxylic acid (TCA) cycle. It was hypothesized that Arabidopsis having suppressed mtPDHK will display their greatest plant productivity at EC through a combined enhancement of source and sink activities. Control and transgenic Arabidopsis having either constitutive or seed-specific expression of antisense mtPDHK were grown at either AC or EC. Expression of mtPDHK and mtPDH complex activity in rosette leaves and reproductive tissues were measured, which required the development of an assay to quantify mtPDH activity. Vegetative and reproductive growth over time, seed oil
parameters, and leaf net C exchange were also quantified. A parabolic relationship was found between mtPDHK expression and mtPDH activity, reflecting a role for mtPDH in balancing photosynthetic and respiratory processes. A number of growth and seed oil parameters were improved in transgenic lines, particularly at EC; many of these parameters showed a
significant linear or quadratic correlation with mtPDHK expression and mtPDH activity. The proportion of very long chain fatty acids was increased in transgenic lines. Leaf net C exchange was enhanced at AC and EC, and particularly in lines showing repression of mtPDHK. The greatest enhancement in total seed and oil productivity was found for the constitutive lines 104 and 31 at EC (up to 2.8 times). These two lines exhibited a significant increase in inflorescence size, an increase in leaf water use efficiency, the lowest rate of mtPDH complex inactivation by ATP, and an intermediary enhancement of mtPDH complex
activity in seeds. Thus, it is concluded that the mtPDH plays a key role in regulating sink and source activities in plants. / Natural Sciences and Engineering Research Council (NSERC) through the Green Crop Networks Research Network; Ontario Graduate Scholarship;
Syngenta Graduate Scholarship; Ball Farm Services and Agrico Canada Ltd. Scholarship; Mrs. Fred Ball Scholarship; Arthur D. Latornell Scholarship; Hoskins Scholarship; Robb Travel Grant; Registrars and the Deans Scholarship and travel awards and bursaries from the University of Guelph, and the Ontario Agricultural College.
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Efeitos dos esteróides anabólicos androgênicos sobre a bioquímica, morfologia, biomecânica e expressão gênica de diferentes tendões de ratos submetidos ao exercício de cargaMarqueti, Rita de Cássia 30 April 2010 (has links)
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Previous issue date: 2010-04-30 / Universidade Federal de Minas Gerais / The aim of this study was to evaluate the effects of vertical jump associated with anabolic androgenic steroids (AAS) on the biochemical, biomechanical and morphological properties, and the expression of the main genes responsible for remodeling in the calcaneal tendon (CT), superficial flexor tendon (TFS) and deep flexor tendon (TFP) in rats Animals were divided into four experimental groups: Sedentary (S), Trained (T) (vertical jump, 50 80% body weight load, 7 weeks, 5 days/week), AAS-treated sedentary rats (AAS) (5 mg/kg of body mass, twice a week).), and AAS-treated and trained animals (AAST). The techniques performed were: zymography (to analyze the metalopeptidase activity - MMP-2); biomechanical test (cross-sectional area, displacement at maximum load, maximum stress, maximum strain, and elastic modulus); morphology and real time PCR. The training promoted an increased in MMP-2 activity in the three regions of TFS, while the AAS treatment or the combination of training and AAS decreased both MMP-2 concentration and active form in all regions of the SFT. The biomechanical test showed that AAS increased tendon rigidity (i.e., lower elasticity and capacity to resist load) and the effects were enhanced by the combination of AAS and training. The DFT was the most affected by training, AAS, and the interaction of both. Take together the morphology and stereology showed that training increases the vascularity and cellularity, while the AAS combined with training reduced these two parameters in the three evaluated tendons. Gene expression showed that training did not increase the main genes expression responsible for tissue resistance: collagen type I and III, but the AAS or the association with training promoted a downregulation of expression in these genes on all tendons regions. In conclusion, the exercise increased remodeling and differently modulates the genes expression related to ECM remodeling in tendon. The AAS administration and combination with exercise induce negative effects, providing a poor remodeling and increasing risk of tendons injury. / O objetivo desse estudo foi avaliar os efeitos do salto vertical em associação com esteróide anabólico androgênico (EAA) nas propriedades bioquímicas, biomecânicas, morfológicas e a expressão dos principais genes responsáveis pelo remodelamento do tendão calcâneo (TC), tendão flexor superficial (TFS) e tendão flexor profundo (TFP) de ratos. Ratos Wistar foram divididos em quatro grupos experimentais: animais sedentários (S); animais sedentários com a administração de EAA (EAA) (5 mg/kg de peso corporal, duas vezes por semana); animais treinados (T) (salto vertical na água com carga de 50 a 80% do peso corporal do animal, duração de 7 semanas 5 dias/semana) e animais treinados com a administração de EAA (EAAT). Foram utilizadas as técnicas: de zimografia (para analisar a atividade da metalopeptidase - MMP-2); teste biomecânico (área de secção transversa, deslocamento até a carga máxima, tensão máxima, deformação máxima, e módulo de elasticidade); morfologia dos tendões e real time PCR. A zimografia mostrou que o treinamento aumentou a atividade da MMP-2 em todas as regiões do TFS enquanto o EAA ou associação de ambos reduziu a atividade da mesma em todas as regiões analisadas. O teste biomecânico mostrou que o EAA aumentou a rigidez dos tendões (baixa elasticidade e capacidade de resistir carga), e os efeitos foram reforçados pela associação de ambos, EAA e treino. O TFP foi o mais afetado pelo treinamento, EAA, e pela interação de ambos. A morfologia juntamente com a estereologia mostrou que o treinamento aumenta a vascularização e celularidade, enquanto o EAA associado ao treinamento reduz esses dois parâmetros nos 3 tendões avaliados. A expressão gênica mostrou que o treinamento não aumentou a expressão dos principais genes responsáveis pela resistência tecidual: colágeno tipo I e III, mas o EAA ou a associação com o treinamento promoveram uma redução na expressão desses genes em todas as regiões dos tendões. Assim, conclui-se que o exercício aumentou o remodelamento e modulou diferentemente a expressão de genes relacionados com o remodelamento da MEC no tendão. Já a administração de EAA e associação com o exercício acarretaram efeitos negativos no tendão, propiciando um remodelamento deficiente que pode estar relacionado com a ocorrência de lesões.
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Efeito do decanoato de nandrolona associado ao exercício de carga na expressão do fator de crescimento de endotélio vascular (VEGF) no músculo sóleo de ratosPaschoal, Milena de Moura 11 August 2008 (has links)
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Previous issue date: 2008-08-11 / Universidade Federal de Sao Carlos / Androgenic-anabolic steroids have been used both for performance improvement and aesthetic reasons. It is well know that high doses of AAS can raise serious adverse effects such as skeletal muscle injuries including increase in the rate of muscle strains/ruptures. The aim of this study was to investigate VEGF mRNA expression in the rat soleus muscle after jumping training associated with androgenic-anabolic
steroids (AAS) administration. Wistar rats were grouped into: sedentary (S); trained without AAS (T); nandrolone decanoate (ND)-treated sedentary (AAS); and trained with AAS (AAST). The trained groups have carried out jumps in water at 32°C.: 4 series of 10 jumps each, with a 30-second interval among series, for 7 weeks, with 50- 80% overload of the animal corporal mass. The AAS (Decadurabolin® - 5mg/kg) was injected via subcutaneous in animal back twice a week. Real-time PCR analyses have shown that training significantly increased VEGF mRNA expression in comparison
with the S, AAS groups. When training exercise was associated with nandrolone decanoate, the VEGF mRNA expression was inhibit compared with T group. The inhibited expression of VEGF by AAS administration could cause diminished angiogenesis in skeletal muscle. These results suggest that the AAS may be strongly prejudicial to muscle remodeling and performance. / Muitos estudos vêm mostrando os efeitos nocivos para o organismo do abuso de esteróides anabólicos androgênicos (EAA) por atletas e freqüentadores de academia. Entretanto há poucas pesquisas relatando os efeitos prejudiciais dessas substâncias no músculo esquelético. O objetivo desse trabalho foi analisar a expressão do fator de crescimento de endotélio vascular (VEGF) no músculo sóleo de ratos submetidos ao tratamento com EAA e ao exercício de carga. Os animais foram divididos em quatro grupos: S (sedentário controle), T (treinado controle), EAA (sedentário com administração de decanoato de nandrolona) e EAAT (treinado com administração de decanoato de nandrolona). O treinamento foi constituído por saltos em meio líquido à 32°C: 4 séries de 10 saltos cada, com intervalo de 30 segundos entre as séries, em 5 dias da semana, durante 7 semanas, com carga variando de 50 80% da massa corporal do animal. O decanoato de nandrolona (Decadurabolin® - mg/kg) foi injetado via subcutânea no dorso dos animais, duas vezes por semana. A análise da expressão de mRNA de VEGF, por PCR em tempo real mostrou que no grupo que treinou e que não recebeu a injeção de EAA houve aumento significante na expressão desse fator em relação aos grupos que não treinaram (S e EAA). Por outro lado, quando o treino foi associado com a administração de EAA houve inibição da expressão de VEGF em relação ao grupo treinado controle. VEGF é um fator chave na indução da angiogênese, processo de formação de novos vasos sangüíneos a partir de vasos pré-existentes e essa é uma das primeiras adaptações do músculo ao exercício. Em conclusão a diminuição da expressão de VEGF com o uso de EAA poderia provocar uma redução na formação desses novos vasos, promovendo possivelmente uma redução na performance.
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Esteroides anabólicos androgênicos e seus efeitos associados ao treinamento de força de ratas wistar eutróficas / Androgenic anabolic steroids and their effects associated with wistar eutrophic rat strength trainingSantos, Wiliane Nery 17 April 2017 (has links)
Introduction: Strength training has been consistently demonstrated in studies as
responsible for significant increases in lean mass and metabolic rate, accompanied by
significant reductions in body fat weight, using strategies to accelerate this process
androgenic anabolic steroids has been enough used by practitioners of this modality.
Objective: To evaluate the strength training acting in conjunction with Androgenic
Anabolic Steroids on the percentage of body fat of eutrophic rats. Methods: Twentyfour
female rats randomly distributed in four groups were used: 1) Sedentary Control
(CS) 2) Trained Control (CT) 3) Sedentary Nandrolone Decanoate (DS) 4) Trained
Nandrolone Decanoate (DT). Strength training was performed in a squatting apparatus
composed of four sets of 12 repetitions, with intensity of 70% of 1RM for eight weeks.
On alternate days, the DS and DT groups received daily 5 mg/kg nandrolone decanoate
intraperitoneally and the CS and CT groups received only saline solution (0.9%). The
data represent the mean ± standard error of the mean. Student's t-test was used for
analysis between groups, ns = no statistical difference. Results: After eight weeks of
training, the weight between the CS and CT groups were different when compared to
the DS and DT groups (there was no statistical difference between groups (CS vs CT,
DS vs DT), in this sense, the CT group Who underwent strength training had a 10.8%
and 11.2% increase in strength, in the 6th and 8th weeks, respectively, when compared
to the CS group. The fatty contents of different territories were evaluated as follows:
subcutaneous (SUB), retroperitoneal (RETRO) and periovarian (PERI) fats, which did
not identify statistical differences between the groups evaluated. Conclusion: The use of
Nandrolone Decanoate in trained rats did not cause changes in weight, strength and
adipose tissue. / Introdução: Treinamentos de força têm sido consistentemente demonstrado em estudos
como responsáveis por aumentos significativos na massa magra e da taxa metabólica,
acompanhada por reduções significativas no peso de gordura corporal, utilizando-se de
estratégias para acelerar este processos os esteroides anabólicos androgênicos tem sido
bastante utilizados por praticantes desta modalidade. Objetivo: Avaliar o treinamento
de força atuando de forma conjunta com Esteroides Anabólicos Androgênicos sobre o
percentual de gordura corporal de ratas eutróficas. Métodos: Foram utilizados 24 ratas
fêmeas distribuídas randomicamente em quatro grupos: 1) Controle Sedentário (CS) 2)
Controle Treinado (CT) 3) Decanoato de Nandrolona Sedentário (DS) 4) Decanoato de
Nandrolona Treinado (DT). O treinamento de força foi realizado em aparelho de
agachamento composto por quatro séries de 12 repetições, com intensidade de 70% de
1RM durante oito semanas. Em dias alternados, os grupos DS e DT recebiam
diariamente Decanoato de nandrolona intraperitoneal 5mg/kg por secção e os grupos CS
e CT recebiam somente solução salina (0,9%). Os dados representam a média ± erro
padrão da média. Utilizou-se o teste t de Student para análise entre os grupos, ns = sem
diferença estatística. Resultados: Após oito semanas de treinamento, o peso entre os
grupos CS e CT foram diferentes quando comparados com os grupos DS e DT (não foi
observado diferença estatística intergrupos (CS vs CT; DS vs DT)), neste sentido, o
grupo CT que foram submetidos ao treinamento de força apresentaram um incremento
da força de 10,8% e 11,2%, nas 6ª e 8ª semanas, respectivamente, quando comparado ao
grupo CS. Foram avaliados os conteúdos gordurosos de diferentes territórios conforme
segue: gorduras subcutâneas (SUB), retroperitoneal (RETRO) e periovariana (PERI) o
qual não identificamos diferenças estatísticas entre os grupos avaliados. Conclusão: O
uso de Decanoato de Nandrolona nas ratas treinadas não causou alteração, no peso, na
força e no tecido adiposo.
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Bad to the Bone: The Effects of Therapeutic Glucocorticoids on Osteoblasts and OsteocytesGado, Manuel, Baschant, Ulrike, Hofbauer, Lorenz C., Henneicke, Holger 04 April 2024 (has links)
Despite the continued development of specialized immunosuppressive therapies in the form of monoclonal antibodies, glucocorticoids remain a mainstay in the treatment of rheumatological and auto-inflammatory disorders. Therapeutic glucocorticoids are unmatched in the breadth of their immunosuppressive properties and deliver their anti-inflammatory effects at unparalleled speed. However, long-term exposure to therapeutic doses of glucocorticoids decreases bone mass and increases the risk of fractures – particularly in the spine – thus limiting their clinical use. Due to the abundant expression of glucocorticoid receptors across all skeletal cell populations and their respective progenitors, therapeutic glucocorticoids affect skeletal quality through a plethora of cellular targets and molecular mechanisms. However, recent evidence from rodent studies, supported by clinical data, highlights the considerable role of cells of the osteoblast lineage in the pathogenesis of glucocorticoid-induced osteoporosis: it is now appreciated that cells of the osteoblast lineage are key targets of therapeutic glucocorticoids and have an outsized role in mediating their undesirable skeletal effects. As part of this article, we review the molecular mechanisms underpinning the detrimental effects of supraphysiological levels of glucocorticoids on cells of the osteoblast lineage including osteocytes and highlight the clinical implications of recent discoveries in the field.
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Využití výživových suplementů v jednotlivých sportovních odvětvích / Use of Nutritional Supplements in Individual Sport SectorsWeiser, Martin January 2015 (has links)
The aim of the diploma thesis was to determine, which nutritional supplements are selected by athletes of strength and endurance sports branches and what is the reason for their option. The theoretical part characterizes the 8 selected sports sector from point of view of the sport performance structure. There is also mentioned the issue of nutritional supplements, their division, legislation or general recommendations for the use in sport. The last chapter deals with the requirements for the use of nutritional supplements in different periods with respect to the branche of sport. Research part has specifically determined the nutritional strategy for athletes in the field of mentioned food supplements at strength and endurance-oriented sports disciplines by using the questionnaire. The research is supported by an interview with an expert nutritionist and sports through collaboration with the staff of the Centre for Sports of the Ministry of Interior
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TARGETED DELIVERY OF BONE ANABOLICS TO BONE FRACTURES FOR ACCELERATED HEALINGJeffery J H Nielsen (8787002) 21 June 2022 (has links)
<div>Delayed fracture healing is a major health issue involved with aging. Therefore, strategies to improve the pace of repair and prevent non-union are needed in order to improve patient outcomes and lower healthcare costs. In order to accelerate bone fracture healing noninvasively, we sought to develop a drug delivery system that could safely and effectively be used to deliver therapeutics to the site of a bone fracture. We elected to pursue the promising strategy of using small-molecule drug conjugates that deliver therapeutics to bone in an attempt to increase the efficacy and safety of drugs for treating bone-related diseases.</div><div>This strategy also opened the door for new methods of administering drugs. Traditionally, administering bone anabolic agents to treat bone fractures has relied entirely on local surgical application. However, because it is so invasive, this method’s use and development has been limited. By conjugating bone anabolic agents to bone-homing molecules, bone fracture treatment can be performed through minimally invasive subcutaneous administration. The exposure of raw hydroxyapatite that occurs with a bone fracture allows these high-affinity molecules to chelate the calcium component of hydroxyapatite and localize primarily to the fracture site.</div><div>Many bone-homing molecules (such as bisphosphonates and tetracycline targeting) have been developed to treat osteoporosis. However, many of these molecules have toxicity associated with them. We have found that short oligopeptides of acidic amino acids can localize to bone fractures with high selectivity and with very low toxicity compared to bisphosphonates and tetracyclines.</div><div>We have also demonstrated that these molecules can be used to target peptides of all chemical classes: hydrophobic, neutral, cationic, anionic, short, and long. This ability is particularly useful because many bone anabolics are peptidic in nature. We have found that acidic oligopeptides have better persistence at the site of the fracture than bisphosphonate-targeted therapeutics. This method allows for a systemic administration of bone anabolics to treat bone fractures, which it achieves by accumulating the bone anabolic at the fracture site. It also opens the door for a new way of treating the prevalent afflictions of broken bones and the deaths associated with them.</div><div>We further developed this technology by using it to deliver anabolic peptides derived from growth factors, angiogenic agents, neuropeptides, and extracellular matrix fragments. We found several promising therapeutics that accelerated the healing of bone fractures by improving the mineralization of the callus and improving the overall strength. We optimized the performance of these molecules by improving their stability, targeting ligands, linkers, dose, and dosing frequency.</div><div>We also found that these therapeutics could be used to accelerate bone fracture repair even in the presence of severe comorbidities (such as diabetes and osteoporosis) that typically slow the repair process. We found that, unlike the currently approved therapeutic for fracture healing (BMP2), our therapeutics improved functionality and reduced pain in addition to strengthening the bone. These optimized targeted bone anabolics were not only effective at healing bone fractures but they also demonstrated that they could be used to speed up spinal fusion. Additionally, we demonstrated that acidic oligopeptides have potential to be used to treat other bone diseases with damaged bone.</div><div>With these targeted therapeutics, we no longer have to limit bone fracture healing to casts or invasive surgeries. Rather, we can apply these promising therapeutics that can be administered non-invasively to augment existing orthopedic practices. As these therapeutics move into clinical development, we anticipate that they will be able to reduce the immobilization time that is the source of so many of the deadly complications associated with bone fracture healing, particularly in the elderly.</div>
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