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1.
Sci Rep ; 14(1): 15749, 2024 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977767

RESUMO

Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.


Assuntos
Anabolizantes , Proteína Morfogenética Óssea 2 , Técnicas de Movimentação Dentária , Microtomografia por Raio-X , Animais , Camundongos , Técnicas de Movimentação Dentária/efeitos adversos , Anabolizantes/farmacologia , Anabolizantes/administração & dosagem , Masculino , Osteogênese/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Ligante RANK/metabolismo , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/patologia , Modelos Animais de Doenças
2.
Neurosci Biobehav Rev ; 163: 105772, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38879097

RESUMO

The prevalence of anabolic androgenic steroids (AAS) is rising, especially in recreational sports and the general population. While body image significantly influences AAS use, gender differences remain unclear. We examined gender-related connections between AAS use, body image, eating behavior, and physical activity. Following PRISMA guidelines, we analyzed 22 studies: 14 with male-only samples, 5 mixed-gender, 2 with sexual and gender minorities, and 1 with a female-only sample. FINDINGS: confirm body image as a key predictor of AAS use. Though AAS use correlates with eating disorders, outcomes vary by context; for instance, no discernible difference in eating behavior was observed between AAS users and non-users in bodybuilding. Physical activity findings varied, with some studies showing no significant differences between AAS users and non-users. Due to limited gender-comparison studies, conclusive gender-related differences cannot be drawn. This systematic review underscores the complex interplay between AAS use, body image, eating behavior, and physical activity, emphasizing the necessity for further research to develop targeted interventions for diverse populations, addressing AAS-related concerns and promoting overall well-being.


Assuntos
Imagem Corporal , Exercício Físico , Comportamento Alimentar , Humanos , Comportamento Alimentar/efeitos dos fármacos , Anabolizantes/administração & dosagem , Anabolizantes/efeitos adversos , Masculino , Feminino , Caracteres Sexuais , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Esteróides Androgênicos Anabolizantes
3.
Int J Mol Sci ; 23(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35055125

RESUMO

PTH induces phosphorylation of the transcriptional coregulator NACA on serine 99 through Gαs and PKA. This leads to nuclear translocation of NACA and expression of the target gene Lrp6, encoding a coreceptor of the PTH receptor (PTH1R) necessary for full anabolic response to intermittent PTH (iPTH) treatment. We hypothesized that maintaining enough functional PTH1R/LRP6 coreceptor complexes at the plasma membrane through NACA-dependent Lrp6 transcription is important to ensure maximal response to iPTH. To test this model, we generated compound heterozygous mice in which one allele each of Naca and Lrp6 is inactivated in osteoblasts and osteocytes, using a knock-in strain with a Naca99 Ser-to-Ala mutation and an Lrp6 floxed strain (test genotype: Naca99S/A; Lrp6+/fl;OCN-Cre). Four-month-old females were injected with vehicle or 100 µg/kg PTH(1-34) once daily, 5 days a week for 4 weeks. Control mice showed significant increases in vertebral trabecular bone mass and biomechanical properties that were abolished in compound heterozygotes. Lrp6 expression was reduced in compound heterozygotes vs. controls. The iPTH treatment increased Alpl and Col1a1 mRNA levels in the control but not in the test group. These results confirm that NACA and LRP6 form part of a common genetic pathway that is necessary for the full anabolic effect of iPTH.


Assuntos
Anabolizantes/administração & dosagem , Células-Tronco Embrionárias/citologia , Proteína-6 Relacionada a Receptor de Lipoproteína de Baixa Densidade/genética , Chaperonas Moleculares/genética , Hormônio Paratireóideo/administração & dosagem , Anabolizantes/farmacologia , Animais , Linhagem Celular , Membrana Celular/metabolismo , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Introdução de Genes , Camundongos , Chaperonas Moleculares/metabolismo , Mutagênese Sítio-Dirigida , Osteoblastos/metabolismo , Osteócitos/metabolismo , Hormônio Paratireóideo/farmacologia , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X
4.
Meat Sci ; 182: 108615, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34352620

RESUMO

The impacts of several hormonal growth promotants (HGP) on Warner-Bratzler Shear Force (WBSF), desmin degradation ratio (DDR) and collagen content (COLL) were assessed. Treatments within feedlot and pasture finished steer carcasses (n = 60, n = 40, respectively) were control (CON-100-F and CON-400-P), oestradiol HGPs (OES-100-F and OES-400-P) and trenbolone acetate/oestradiol HGPs (TBA+OES-100-F only). The longissimus lumborum (LL), gluteus medius (GM), infraspinatus (IS), semitendinosus (ST,) and the LL and biceps femoris (BF) were collected from feedlot and pasture finished steers, respectively. All muscles were aged between 3 and 35 days. The LL from TBA+OES-100-F carcasses had increased WBSF and decreased DDR, which varied in magnitude with ageing (P < 0.05). The GM from OES-100-F steers also had lower DDR (P < 0.05). The feedlot HGP treatments had no impact on the WBSF of the IS, ST or GM and no impact on COLL in the LL. The OES-400-P had no impact on WBSF, DDRor COLL for both muscles (P > 0.05).


Assuntos
Anabolizantes/administração & dosagem , Colágeno/análise , Desmina/metabolismo , Estradiol/administração & dosagem , Músculo Esquelético/química , Acetato de Trembolona/administração & dosagem , Animais , Bovinos , Dieta/veterinária , Masculino , Carne Vermelha/análise , Resistência ao Cisalhamento
5.
Behav Brain Res ; 414: 113475, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34280460

RESUMO

Oxandrolone (OXA) is an androgen and anabolic steroid (AAS) that is used to reverse weight loss associated with some medical conditions. One of the side effects of OXA is its potential to induce depressive symptoms. Growing evidence suggested that neuroinflammation and cytokines play crucial roles in sickness behavioral and associated mood disturbances. Previous studies showed that metformin attenuated neuroinflammation. This study investigated the potential protective role of metformin against OXA-induced depression-like behavior and neuroinflammation. Twenty- four Wistar male rats were randomly grouped into four groups: the control group (Control) received only vehicle; the oxandrolone group (OXA) received oxandrolone (0.28 mg/kg, i.p); the metformin group (MET) received metformin (100 mg/kg, i.p); and the oxandrolone / metformin group (OXA + MET) received both oxandrolone (0.28 mg/kg, i.p) and metformin (100 mg/kg, i.p). These treatments were administered for fourteen consecutive days. Behavioral tests to measure depression-like behavior were conducted before and after treatments. qRT-PCR was used to measure the relative expression of proinflammatory and anti-inflammatory cytokines in the hippocampus and hypothalamus. The results showed that oxandrolone induced depression-like behavior and dysregulated pro-/anti-inflammatory cytokines, while metformin attenuated these effects. These findings suggest that metformin is a potential treatment to reverse the depressive effects induced by oxandrolone that involve neuroinflammatory effects.


Assuntos
Anabolizantes/efeitos adversos , Anti-Inflamatórios/farmacologia , Citocinas/efeitos dos fármacos , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Metformina/farmacologia , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/tratamento farmacológico , Oxandrolona/efeitos adversos , Anabolizantes/administração & dosagem , Animais , Anti-Inflamatórios/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Depressão/imunologia , Depressão/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/imunologia , Hipocampo/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/imunologia , Hipotálamo/metabolismo , Interleucina-10 , Interleucina-1beta/efeitos dos fármacos , Interleucina-6 , Masculino , Metformina/administração & dosagem , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/metabolismo , Oxandrolona/administração & dosagem , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/efeitos dos fármacos
6.
Neurosci Lett ; 761: 136104, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34256105

RESUMO

AIMS: Oxandrolone (OXA) is a synthetic steroid used for the treatment of clinical conditions associated with catabolic states in humans, including children. However, its behavioral effects are not well known. Our goal was to evaluate the anxiety-like behavior induced in young adult rats after the treatment of juvenile animals with OXA. METHODS: Four-week-old male rats were separated into three groups: Control (CON), therapeutic-like OXA dose (TD), and excessive OXA dose (ED), in which 2.5 and 37.5 mg/kg/day of OXA were administered via gavage for four weeks for TD and ED, respectively. Behavior was evaluated through the elevated plus maze (EPM) and open field (OF) tests. Protein expression of catalase (CAT), superoxide dismutase (SOD), Tumor necrosis factor-α (TNF-α), and dopamine receptor 2 (DrD2) were analyzed in tissue samples of the hippocampus, amygdala, and prefrontal cortex by Western Blot. RESULTS: OXA induced anxiety-like behaviors in both TD and ED animals; it decreased the time spent in the open arms of the EPM in both groups and reduced the time spent in the central zone of the OF in the TD group. In the hippocampus, CAT expression was higher in TD compared with both control and ED animals. No differences were found in the amygdala and prefrontal cortex. TNF-α, SOD, and DrD2 levels were not altered in any of the assessed areas. CONCLUSIONS: Treatment of juvenile rats with OXA led to anxiety-like behavior in young adult animals regardless of the dose used, with minor changes in the antioxidant machinery located in the hippocampus.


Assuntos
Anabolizantes/toxicidade , Ansiedade/etiologia , Hipocampo/efeitos dos fármacos , Oxandrolona/toxicidade , Anabolizantes/administração & dosagem , Animais , Catalase/metabolismo , Hipocampo/crescimento & desenvolvimento , Hipocampo/metabolismo , Masculino , Oxandrolona/administração & dosagem , Ratos , Ratos Wistar , Receptores de Dopamina D2/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
7.
Front Endocrinol (Lausanne) ; 12: 678797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177807

RESUMO

Background: Gonadotropin-releasing hormone agonist (GnRHa) is the gold standard in the treatment of Central Precocious Puberty (CPP) with progressive puberty and accelerative growth. However, GnRHa treatment is reported to result in growth deceleration and prevents growth plate development which leads to a reduction in height velocity. Stanozolol (ST) has been used to stimulate growth in patients with delayed growth and puberty, nevertheless, the effects and mechanisms of ST on CPP with GnRHa treatment are currently unclear. Methods and Results: In the current study, we recorded the following vital observations that provided insights into ST induced chondrogenic differentiation and the maintenance of normal growth plate development: (1) ST efficiently prevented growth deceleration and maintained normal growth plate development in rats undergoing GnRHa treatment; (2) ST suppressed the inhibitory effect of GnRHa to promote chondrogenic differentiation; (3) ST induced chondrogenic differentiation through the activation of the JNK/c-Jun/Sox9 signaling pathway; (4) ST promoted chondrogenic differentiation and growth plate development through the JNK/Sox9 signaling pathway in vivo. Conclusions: ST mitigated the inhibitory effects of GnRHa and promoted growth plate development in rats. ST induced the differentiation of chondrocytes and maintained normal growth plate development through the activation of JNK/c-Jun/Sox9 signaling. These novel findings indicated that ST could be a potential agent for maintaining normal bone growth in cases of CPP undergoing GnRHa treatment.


Assuntos
Anabolizantes/uso terapêutico , Desenvolvimento Ósseo/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/agonistas , Puberdade Precoce/tratamento farmacológico , Estanozolol/uso terapêutico , Anabolizantes/administração & dosagem , Animais , Linhagem Celular , Condrócitos/efeitos dos fármacos , Quimioterapia Combinada , Lâmina de Crescimento/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estanozolol/administração & dosagem
8.
Curr Osteoporos Rep ; 18(5): 449-459, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32860563

RESUMO

PURPOSE OF REVIEW: Compared with the current standard of implanting bone anabolics for fracture repair, bone fracture-targeted anabolics would be more effective, less invasive, and less toxic and would allow for control over what phase of fracture healing is being affected. We therefore sought to identify the optimal bone-targeting molecule to allow for systemic administration of therapeutics to bone fractures. RECENT FINDINGS: We found that many bone-targeting molecules exist, but most have been developed for the treatment of bone cancers, osteomyelitis, or osteoporosis. There are a few examples of bone-targeting ligands that have been developed for bone fractures that are selective for the bone fracture over the body and skeleton. Acidic oligopeptides have the ideal half-life, toxicity profile, and selectivity for a bone fracture-targeting ligand and are the most developed and promising of these bone fracture-targeting ligands. However, many other promising ligands have been developed that could be used for bone fractures.


Assuntos
Anabolizantes/administração & dosagem , Sistemas de Liberação de Medicamentos , Consolidação da Fratura , Fraturas Ósseas/tratamento farmacológico , Fosfatase Alcalina , Aminoácidos Acídicos , Difosfonatos , Durapatita , Humanos , Imunoglobulina G , Oligopeptídeos , Proteínas Recombinantes de Fusão , Fosfatase Ácida Resistente a Tartarato , Tetraciclina
9.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1295-1304, July-Aug. 2020. tab, graf, ilus
Artigo em Português | LILACS, VETINDEX | ID: biblio-1131466

RESUMO

No presente estudo, foram analisados os efeitos do estanozolol, associado ou não à atividade física, sobre o hemograma, o peso ponderal, a ingestão líquida e sólida, a urinálise, a expressão do VEGF-A renal e o glicogênio hepático, além da histopatologia hepática e renal em ratos Wistar. Foram utilizados 32 ratos Wistar, machos, jovens, separados em quatro grupos: GC (grupo controle); GCE (grupo controle-exercício); GT (grupo tratamento-esteroide); GTE (grupo tratamento-esteroide-exercício). Os animais dos grupos GT e GTE (n=16) foram submetidos a injeções subcutâneas, cinco dias/semana, durante 30 dias, na concentração de 5mg/kg de estanozolol diluído em 1mL de óleo de gergelim, utilizado como veículo. A natação foi definida como exercício físico. Houve aumento no peso dos animais submetidos ao estanozolol e ao exercício a partir da terceira semana de uso e aumento da excreção urinária a partir da quinta semana; os demais parâmetros da urinálise foram semelhantes entre os grupos. O uso de estanozolol associado ou não à atividade física promoveu redução da expressão do VEGF-A nos rins e do glicogênio hepático, além de alterações histopatológicas nesses órgãos. Quanto à hematologia, houve uma diminuição dos leucócitos no GTE em relação aos grupos GT e GCE. Quanto aos linfócitos, houve um aumento no GT e uma diminuição no GTE, e, em relação ao número de plaquetas, houve diminuição no GTE quando comparado ao GT e ao GCE Assim, conclui-se que estanozolol na dose de 5,0mg/kg causa alterações renais e hepáticas em ratos Wistar, podendo levar à falência dos rins e do fígado.(AU)


The goal of this study was to determine the effect of stanozolol (ST) on kidney and liver of Wistar rats. Thirty-two male animals were divided into the following four groups: control group (CG); Control group-exercise (GCE); Group-steroid treatment (GT); Group treatment-steroid-exercise (GTE). Swimming was defined as exercise. The animals GT and GTE was submitted to subcutaneous injections, five days/week for 30 days, at a concentration of 5mg/kg ST diluted in 1mL/kg of sesame oil. The results showed an increase in weight gain in all animals submitted to ST and exercise from the 3rd week of use and increase in urinary excretion from the 5th week and the other urinalysis parameters were similar. The ST associated or not with physical activity reduced VEGF-A expression in the kidneys and hepatic glycogen, as well as histopathological changes in these organs. Regarding hematology, there was a decrease in leukocytes in the GTE. As for lymphocytes there was an increase in GT and a decrease in GTE, and in relation to the number of platelets, there was a decrease in GTE. In conclusion, the administration of stanozolol at 5.0mg/kg caused a structural change of kidney and liver in treated animals.(AU)


Assuntos
Animais , Ratos , Estanozolol/administração & dosagem , Natação , Rim/anatomia & histologia , Fígado/efeitos dos fármacos , Ratos Wistar/fisiologia , Anabolizantes/administração & dosagem , Testes de Função Renal/veterinária
10.
Expert Opin Investig Drugs ; 29(8): 881-891, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32476495

RESUMO

INTRODUCTION: Skeletal muscle wasting is a frequent clinical problem encountered in patients with chronic diseases. Increased levels of inflammatory markers play a role in the imbalance between muscle protein synthesis and degradation. Although testosterone has long been proposed as a treatment for patients with muscle wasting, undesirable side effects have raised concerns about prostatic hypertrophy in men as well as virilization in women. Selective androgen receptor modulators (SARMs) have demonstrated similar results like testosterone at improving lean body mass (LBM) with less side effects on androgen-dependent tissue. AREAS COVERED: This review outlines the ongoing clinical development in the field of SARMs and their effectiveness in improving body composition and physical function. The included articles were collected at pubmed.gov and analyzed integrally. EXPERT OPINION: There is an unmet clinical need for safe and effective anabolic compounds such as SARMs. Despite the effect on LBM shown by SARMs in phase II clinical trials, results on improved physical function and muscle strength are still lacking and long-term outcomes have to be assessed in these patients. Moreover, there is a need to determine the effect of resistance exercise training and protein intake associated with SARMs in the treatment of patients with muscle wasting.


Assuntos
Anabolizantes/administração & dosagem , Atrofia Muscular/tratamento farmacológico , Receptores Androgênicos/efeitos dos fármacos , Anabolizantes/efeitos adversos , Anabolizantes/farmacologia , Animais , Desenvolvimento de Medicamentos , Humanos , Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Proteínas/administração & dosagem , Receptores Androgênicos/metabolismo , Treinamento Resistido/métodos , Testosterona/administração & dosagem , Testosterona/farmacologia
11.
J Clin Endocrinol Metab ; 105(8)2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32453819

RESUMO

CONTEXT: Consensus regarding diagnosis and management of osteoporosis in premenopausal women (PW) is still lacking due to few studies carried out in this population. DESIGN: The European Calcified Tissue Society and the International Osteoporosis Foundation convened a working group to produce an updated review of literature published after 2017 on this topic. RESULTS: Fragility fractures in PW are rare and mostly due to secondary osteoporosis (ie, in presence of an underlying disease such as hormonal, inflammatory, or digestive disorders). In absence of another disorder, low bone mineral density (BMD) together with fragility fractures qualifies as idiopathic osteoporosis. In contrast, low BMD alone does not necessarily represent osteoporosis in absence of bone microarchitectural abnormalities. BMD increases in PW with osteoporosis when the underlying disease is treated. For example, in celiac disease, an increase of 9% in radius trabecular volumetric density was achieved after 1 year of gluten-free diet, while anti-tumor necrosis factor alpha improved BMD in PW with inflammatory bowel diseases. In amenorrhea, including anorexia nervosa, appropriately delivered estrogen replacement therapy can also improve BMD. Alternatively, antiresorptive or anabolic therapy has been shown to improve BMD in a variety of conditions, the range of improvement (3%-16%) depending on skeletal site and the nature of the secondary cause. No studies were powered to demonstrate fracture reduction. The effects of bisphosphonates in childbearing women have been scantly studied and caution is needed. CONCLUSION: The majority of PW with osteoporosis have an underlying disease. Specific therapy of these diseases, as well as antiresorptive and anabolic drugs, improve BMD, but without evidence of fracture reduction.


Assuntos
Reabsorção Óssea/prevenção & controle , Osteoporose/etiologia , Fraturas por Osteoporose/prevenção & controle , Pré-Menopausa/fisiologia , Amenorreia/complicações , Amenorreia/fisiopatologia , Amenorreia/terapia , Anabolizantes/administração & dosagem , Anorexia Nervosa/complicações , Anorexia Nervosa/fisiopatologia , Anorexia Nervosa/terapia , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Conservadores da Densidade Óssea/administração & dosagem , Reabsorção Óssea/complicações , Reabsorção Óssea/etiologia , Reabsorção Óssea/fisiopatologia , Doença Celíaca/complicações , Doença Celíaca/fisiopatologia , Doença Celíaca/terapia , Terapia de Reposição de Estrogênios , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/fisiopatologia , Doenças Inflamatórias Intestinais/terapia , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Resultado do Tratamento
12.
Sci Rep ; 10(1): 2287, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32041983

RESUMO

Nandrolone is a testosterone analogue with anabolic properties commonly abused worldwide, recently utilized also as therapeutic agent in chronic diseases, cancer included. Here we investigated the impact of nandrolone on the metabolic phenotype in HepG2 cell line. The results attained show that pharmacological dosage of nandrolone, slowing cell growth, repressed mitochondrial respiration, inhibited the respiratory chain complexes I and III and enhanced mitochondrial reactive oxygen species (ROS) production. Intriguingly, nandrolone caused a significant increase of stemness-markers in both 2D and 3D cultures, which resulted to be CxIII-ROS dependent. Notably, nandrolone negatively affected differentiation both in healthy hematopoietic and mesenchymal stem cells. Finally, nandrolone administration in mice confirmed the up-regulation of stemness-markers in liver, spleen and kidney. Our observations show, for the first time, that chronic administration of nandrolone, favoring maintenance of stem cells in different tissues would represent a precondition that, in addition to multiple hits, might enhance risk of carcinogenesis raising warnings about its abuse and therapeutic utilization.


Assuntos
Anabolizantes/efeitos adversos , Carcinogênese/induzido quimicamente , Mitocôndrias/efeitos dos fármacos , Nandrolona/efeitos adversos , Células-Tronco Neoplásicas/efeitos dos fármacos , Anabolizantes/administração & dosagem , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/patologia , Técnicas de Cultura de Células , Diferenciação Celular/efeitos dos fármacos , Respiração Celular/efeitos dos fármacos , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/fisiologia , Células Hep G2 , Humanos , Rim/citologia , Rim/efeitos dos fármacos , Fígado/citologia , Fígado/efeitos dos fármacos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/fisiologia , Camundongos , Mitocôndrias/metabolismo , Modelos Animais , Nandrolona/administração & dosagem , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Esferoides Celulares , Baço/citologia , Baço/efeitos dos fármacos , Ensaio Tumoral de Célula-Tronco , Regulação para Cima/efeitos dos fármacos
13.
Dermatol Ther ; 33(1): e13200, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31854482

RESUMO

We present a 32-year-old man with successful treatment and remission of mycosis fungoides of both axillae in 2016 after PUVA therapy and systemic and local administration of corticosteroids. Subsequently, in 2017, the patient also achieved remission of a T-cell CD 30 positive, ALK-1 negative large-cell lymphoma of a retroperitoneal and inguinal lymph node after chemotherapy and radiotherapy. One year later, in 2018, the patient presented to our clinic with progression of skin lesions in both axillary areas and the appearance of а tumor in the right gluteal region.Dermatological examination showed livid-to-erythematous, partly sclerotic plaques in the right inguinal area, cutis laxa-like plaque formations in the right axillary region with similar but less-developed changes in the left axillary fold, a solitary subcutaneous tumor formation affecting the entire right gluteal region, and enlarged, palpable lymph nodes in the right para-axillary area. Biopsies were obtained from an axillary lesion and the surgically removed axillary lymph nodes, and histological examination revealed changes of granulomatous slack skin in the axilla and reactive inflammatory changes in the lymph nodes. Histology of gluteal tissue showed a "foreign body" type of reaction with sarcoid-like features, where the patient in the past have been injected with anabolic and steroidal drugs. Herein we describe a patient with simultaneous occurrence of granulomatous slack skin type mycosis fungoides and a sarcoid-like reaction. The question remains open whether this represents the so-called sarcoidosis-lymphoma syndrome or, more likely, granulomatous slack skin MF associated with a sarcoid-like reaction of "foreign body" type. The possibility that disturbance of tissue homeostasis by incorporation of certain adjuvants within injections (for example) in the past might have been an inducer of cutaneous T cell lymphoma and sarcoidosis/sarcoid like lesions seems reasonable but also speculative.


Assuntos
Anabolizantes/efeitos adversos , Linfoma Cutâneo de Células T/etiologia , Micose Fungoide/etiologia , Sarcoidose/etiologia , Adulto , Anabolizantes/administração & dosagem , Humanos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/patologia , Masculino , Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Sarcoidose/diagnóstico , Sarcoidose/patologia
14.
Arch Orthop Trauma Surg ; 140(3): 321-329, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31332508

RESUMO

INTRODUCTION: A recent randomized controlled trial has reported full patient compliance and no adverse events from therapy with parathyroid hormone (PTH) for osteoporosis and accelerated healing of fragility fractures of the pelvis. The purpose of the presented study was to evaluate if similar results can be achieved with comprehensive PTH therapy in routine clinical practice. We hypothesised that patients' burden of PTH therapy is underestimated in the literature. PATIENTS AND METHODS: Osteoanabolic PTH therapy was recommended to 79 patients suffering from an acute fragility fracture of the pelvis (FFP). Case finding, initiation of therapy and follow-up were performed by a fracture liaison service team. Primary outcome was PTH initiation rate. Secondary outcomes were implementation rate of alternative antiresorptive pharmaceutical therapy for osteoporosis and participation rate in a bone metabolic workup. Adverse events and effects potentially related to the therapy with bone-active drugs were documented as exploratory outcomes. RESULTS: Osteoanabolic PTH therapy as suggested was accepted by 32%, whereas antiresorptive therapy was implemented in another 14% of the patients. DEXA scans were available in 38% of the patients (+ 27% when compared to baseline). A bone-specific laboratory analysis was done in 18 patients, uncovering 7 pathological findings. Two patients terminated PTH therapy early because of side effects. CONCLUSION: The experiences with PTH therapy in FFP patients with respect to, implementation rate, frequency of side effects and of pathological findings in laboratory controls as reported from a previous RCT could not be reproduced in routine clinical practice.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas do Quadril/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Cooperação do Paciente/estatística & dados numéricos , Teriparatida/uso terapêutico , Idoso , Anabolizantes/administração & dosagem , Anabolizantes/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Feminino , Humanos , Masculino , Osteoporose/tratamento farmacológico , Estudos Retrospectivos , Teriparatida/administração & dosagem
15.
Neth J Med ; 77(7): 261-263, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31582578
16.
J Anim Sci ; 97(11): 4371-4385, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31541251

RESUMO

Predominately Angus steers (n = 24; initial BW = 435 ± 28.3 kg) were used to evaluate non-coated (NC) and coated implants (CI) containing equal amounts of trenbolone acetate (TBA; 200 mg) and estradiol benzoate (EB; 28 mg) in finishing steers on sera metabolite responses, gene expression, and immunohistochemical analyses of the Longissimus muscle (LM). Performance data were analyzed as a randomized complete block design, and all other data were analyzed as repeated measures for a completely randomized design. Treatments were no implant (NI), NC (Synovex-PLUS; Zoetis, Parsippany, NJ), and CI (Synovex-One Feedlot) implant. There were 2 pen replicates per treatment (n = 4 steers/pen). LM biopsies, blood, and BW were collected before feeding on days 0, 14, 28, 56, 84, 112, and 133, with final BW being captured on day 140. Genes of interest were determined by RT-qPCR using two housekeeping genes. Sera was analyzed for estradiol-17ß (E2),17ß-trenbolone (TbOH), insulin-like growth factor 1 (IGF-I), NEFA, and urea-N (SUN). An α of 0.10 determined significance for performance and sera data; α of 0.05 was used for gene and histology data. No performance differences (P ≥ 0.10) were detected. An implant × day interaction (P ≤ 0.10) for E2, IGF-I, and SUN was detected; implants elevated (P ≤ 0.10) E2, 17ß-TbOH, and IGF-I; and decreased SUN across day of the study, meaning sera metabolites are not altered with time on feed. An implant × day interaction was detected for myogenic factor 5 (MYF-5) positive cells and proportions of MHCIIX. In LM, CI had greater (P < 0.10) IGF-I in LM over NI. CI increased (P < 0.05) G protein-coupled estrogen receptor 1 (GPER1) expression, as well as, GPER1 semi-quantitative scores over NI and NC. An implant × day interaction (P ≤ 0.05) for estrogen and androgen receptor-positive nuclei was detected; implants had increased (P ≤ 0.05) estrogen and androgen receptor-positive nuclei compared to NI. CIs increase genes associated with muscle tissue growth.


Assuntos
Anabolizantes/administração & dosagem , Bovinos/fisiologia , Estradiol/análogos & derivados , Esteroides/administração & dosagem , Acetato de Trembolona/administração & dosagem , Anabolizantes/sangue , Ração Animal , Animais , Bovinos/sangue , Dieta/veterinária , Implantes de Medicamento/administração & dosagem , Ingestão de Alimentos , Estradiol/administração & dosagem , Estradiol/sangue , Imuno-Histoquímica/veterinária , Fator de Crescimento Insulin-Like I/análise , Masculino , Músculo Esquelético/metabolismo , Distribuição Aleatória , Carne Vermelha/análise , Acetato de Trembolona/sangue
17.
Forensic Sci Med Pathol ; 15(4): 616-621, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31359306

RESUMO

Even if there are well-known consequences of anabolic androgenic steroid (AAS) abuse, their full pathway of action is still being investigated. In this context, the presented case report aims to discuss and provide evidence of unusual adverse effects linked to immunodeficiency in an AAS abuser. In fact, this kind of chronic complication, even if not usually considered, may lead sudden death. In this case a 31-year-old aesthetic weightlifter, who presented to the emergency department due to an accidental fall that resulted in left thigh trauma. This subsequently developed into left thigh necrotizing myofasciitis in the following few days. Although surgery and hyperbaric therapy were carried out, the man died. An autopsy with complete biological sampling for toxicological studies was performed. This case highlights the close relationship between AAS abuse and immunodeficiency and highlights it's importance for further studies. However, it should be considered that of all the dangerous effects produced by AAS use, necrotizing fasciitis is not such an unusual consequence.


Assuntos
Anabolizantes/efeitos adversos , Fasciite Necrosante/etiologia , Hospedeiro Imunocomprometido , Miosite/etiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Acidentes por Quedas , Adulto , Anabolizantes/administração & dosagem , Fasciite Necrosante/patologia , Evolução Fatal , Humanos , Injeções Intramusculares , Masculino , Miosite/patologia , Coxa da Perna , Levantamento de Peso
18.
Res Social Adm Pharm ; 15(8): 949-952, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31303195

RESUMO

BACKGROUND: Few anabolic-androgenic steroid (AAS) users disclose their performance enhancing drug (PED) use with their healthcare providers. AAS users practice polypharmacy with prescription medications to counter adverse effects of AAS, to further their muscular gains, or to lose weight. OBJECTIVES: To compare and contrast AAS using and non-AAS using gym clients regarding PED use, in particular prescription drugs. METHODS: The CASTRO (Castro Anabolic Steroid Research Observation) study was a 108-item cross-sectional survey that took place at four gyms in San Francisco, California between August 2015 and January 2016. 40 AAS users and 179 non-AAS users completed the survey. RESULTS: The prevalence of AAS use in the study cohort was 18.3%. AAS users reported using a greater number of total PEDs (8.7 ±â€¯4.2 vs. 3.7 ±â€¯2.1, p < 0.001) than non-AAS users. AAS users were more likely to misuse the following prescription drugs: antiestrogens (tamoxifen, anastrazole), fertility agents (clomiphene, human chorionic gonadotropin), erectile dysfunction drugs (tadalafil, sildenafil), anabolic drugs (clenbuterol, recombinant human growth hormone), and weight loss drugs (liothyronine). CONCLUSIONS: AAS users practice polypharmacy and misuse multiple prescription drugs. These findings allow researchers and clinicians to be more knowledgeable and to anticipate potential misuse of prescription medications that traditionally are not thought to be abused.


Assuntos
Anabolizantes/administração & dosagem , Academias de Ginástica/estatística & dados numéricos , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Congêneres da Testosterona/administração & dosagem , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , São Francisco , Inquéritos e Questionários
19.
Ann Anat ; 224: 142-152, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31108192

RESUMO

Nandrolone decanoate is an anabolic androgenic steroid that is abused worldwide by young athletes and bodybuilders to enhance their physical performance. Many clinical reports among those abusers demonstrated a variety of renal disorders. Lycopene is one of the dietary carotenoids found in fruits like tomato, watermelon, and grapefruit and has attracted considerable attention as an antioxidant. Therefore, the present study was designed to evaluate the protective effect of lycopene against nandrolone decanoate induced renal cortical damage. Forty adult male rats were equally divided into four main groups: group I served as the control, group II received lycopene 4 mg/kg/day, group III received nandrolone 10 mg/kg/week, and group IV received nandrolone and lycopene at a dose similar to the previous groups. At the end of the experiment, urea, creatinine and oxidative stress indicators were measured, then the kidneys were sampled for histopathological and immunohistochemical studies. Sections of the group (ПI) showed variable histopathological alterations in the form of distorted shrunken glomeruli and almost complete loss of the glomerular capillaries, in addition to vacuolation and shedding of the tubular epithelium. In conclusion, these results showed that nandrolone decanoate induced toxic effects in the kidney of rats and lycopene had protective effects versus such evoked renal damage.


Assuntos
Anabolizantes/toxicidade , Córtex Renal/efeitos dos fármacos , Licopeno/farmacologia , Decanoato de Nandrolona/toxicidade , Administração Oral , Anabolizantes/administração & dosagem , Análise de Variância , Animais , Peso Corporal , Creatinina/sangue , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Imuno-Histoquímica , Injeções Intramusculares , Córtex Renal/metabolismo , Córtex Renal/patologia , Licopeno/administração & dosagem , Masculino , Malondialdeído/metabolismo , Decanoato de Nandrolona/administração & dosagem , Tamanho do Órgão , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Ureia/sangue
20.
Arch Toxicol ; 93(7): 1807-1816, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31123801

RESUMO

Recent studies suggest that the anabolic effect of ecdysterone, a naturally occurring steroid hormone claimed to enhance physical performance, is mediated by estrogen receptor (ER) binding. In comparison with the prohibited anabolic agents (e.g., metandienone and others), ecdysterone revealed to be even more effective in a recent study performed in rats. However, scientific studies in humans are very rarely accessible. Thus, our project aimed at investigating the effects of ecdysterone-containing products on human sport exercise. A 10-week intervention study of strength training of young men (n = 46) was carried out. Different doses of ecdysterone-containing supplements have been administered during the study to evaluate the performance-enhancing effect. Analysis of blood and urine samples for ecdysterone and potential biomarkers of performance enhancement has been conducted. To ensure the specificity of the effects measured, a comprehensive screening for prohibited performance-enhancing substances was also carried out. Furthermore, the administered supplement has been tested for the absence of anabolic steroid contaminations prior to administration. Significantly higher increases in muscle mass were observed in those participants that were dosed with ecdysterone. The same hypertrophic effects were also detected in vitro in C2C12 myotubes. Even more relevant with respect to sports performance, significantly more pronounced increases in one-repetition bench press performance were observed. No increase in biomarkers for liver or kidney toxicity was noticed. These data underline the effectivity of an ecdysterone supplementation with respect to sports performance. Our results strongly suggest the inclusion of ecdysterone in the list of prohibited substances and methods in sports in class S1.2 "other anabolic agents".


Assuntos
Anabolizantes/farmacologia , Suplementos Nutricionais , Ecdisterona/farmacologia , Substâncias para Melhoria do Desempenho/farmacologia , Adulto , Anabolizantes/administração & dosagem , Animais , Desempenho Atlético/fisiologia , Biomarcadores/metabolismo , Linhagem Celular , Método Duplo-Cego , Ecdisterona/administração & dosagem , Humanos , Masculino , Camundongos , Mioblastos/efeitos dos fármacos , Substâncias para Melhoria do Desempenho/administração & dosagem , Treinamento Resistido , Adulto Jovem
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