Efeitos do uso de Decanoato de Nandrolona sobre a junção neuromuscular de ratos em processo de envelhecimento submetidos ao exercício resistido

O envelhecimento populacional tem sido considerado um dos maiores desafios de saúde pública contemporânea, entre outros fatores leva à diminuição de hormônios, à perda progressiva da massa muscular e diminuição da força muscular. O exercício físico atua positivamente sobre esse sistema, bem como os derivados sintéticos da testosterona, os quais apresentam um efeito anabólico. Assim este trabalho teve como objetivo avaliar se a associação do exercício físico potencializado ou não por dose supra-fisiológica de decanoato de nandrolona previnem alterações decorrentes da idade no músculo sóleo de ratos e nas junções neuromusculares associadas. Foram utilizados 40 ratos Sprague-Dawley machos, com 90 dias de idade, os quais foram tratados durante 8 semanas e distribuídos, de acordo com o tratamento, em grupos de animais sedentários ou treinados, com ou sem o uso deDN. O treinamento físico foi realizado por sessões de saltos em água, três vezes por semana. Após atingirem 300 dias de idade, os músculos sóleos foram coletados e realizadas as seguintes análises: Análise morfológica e morfométrica das junções neuromusculares; Análise ultraestrutural das fibras musculares e junções neuromusculares associadas; Análise Imunohistoquímica e morfométrica das fibras Fast e Slow; Análise da Distribuição dos nAChRs por meio de microscopia confocal. Os resultados mostraram que houve diminuição do peso dos animais que fizeram uso de DN, embora o peso do músculo sóleo não tenha se alterado. A morfologia geral e morfometria das JNM se mantiveram constante nos grupos estudados, sendo que ultraestruturalmente as dobras juncionais eram escassas. Quanto à distribuição dos nAChRs , os animais que realizaram exercício, apresentaram um padrão de distribuição em de braços contínuos dos nAChR, nos demais o padrão em "ilha" estava presente. Na análise das fibras fast e Slow, o padrão morfométrico e quantitativo se mantiveram em todos os grupos experimentais. Sendo que núcleos centrais e áreas focais de lesão, bem como desorganização miofibrilar, foram observadas ultraestruturalmente nos animais que usaram DN. Os resultados permitem concluir que as alterações observadas neste estudo referem-se ao fator idade e que o exercício físico realizado na juventude manteve o padrão estrutural dos nAChR presentes nos jovens, já o DN não preveniu alterações morfológicas no sistema neuromuscular decorrente da idade.Population aging has been considered one of the greatest challenges of contemporary public health; among other factors there is decreased hormone release, progressive loss of muscle mass, and decreased muscle strength. Physical exercise has a beneficial effect on that system, as well as synthetic testosterone derivatives, which have anabolic effect. This study had the objective of evaluating whether the association of physical exercise enhanced or not by supraphysiological dose of nandrolone decanoate prevents age-related alterations in the soleus muscle of rats and in the associated neuromuscular junctions. 40 male Sprague-Dawley rats, 90 days old, were treated for 8 weeks and distributed according to the treatment in sedentary or exercised group, with or without the use of ND. Physical training was conducted by jumps in water three times per week. At the age of 300 days, the soleus muscles were collected and analyzed as follows: morphologic and morphometric analysis of neuromuscular junctions; ultrastructural analysis of muscle fibers and associated neuromuscular junctions; immunohistochemistry and morphometric analysis of fast and slow-twitch fibers; analysis of the distribution of nAChRs by confocal microscopy. The results demonstrated that there was a decreased weight in the animals that used ND, although the weight of the soleus muscle did not change. The general morphology and morphometry of the NMJ remained constant in the groups studied, and in regard to ultrastructure the junctional folds were scarce. The animals that performed exercise had a pattern of nAChRs in continuous branches, in all the other animals the "island" pattern was present. The morphometric and quantitative pattern of slow and fast-twitch fibers remained stable in all groups. Central nuclei and focal areas of injury, as well as myofibrillar disorganization were observed in the animals that used ND. The results enable the conclusion that the alterations observed in this study were consequent to aging, and that physical exercise performed in youth maintained the structural pattern of nAChR present in the young animals. ND did not prevent morphological changes in the neuromuscular system consequent to aging

Effects of Nandrolone Decanoate on Skeletal Muscle and Neuromuscular Junction of Sedentary and Exercised Rats

Background and Objectives: Nandrolone decanoate (ND) is the most widely used among the anabolic androgenic steroids (AAS), synthetic substances derived from testosterone, to improve muscular and health gains associated with exercises. The AAS leads to physical performance enhancement and presents anti-aging properties, but its abuse is associated with several adverse effects. Supraphysiological doses of AAS with or without physical exercise can cause morphological and functional alterations in neuromuscular interactions. This study aims to investigate the effects of ND supraphysiological doses in neuromuscular interactions, focusing on the soleus muscle and its neuromuscular junctions (NMJs) in rats, associated or not with physical exercise. Materials and Methods: Forty male Sprague Dawley rats were divided into four groups: sedentary and exercised groups, with or without ND at the dose of 10 mg/kg/week. The animals were treated for eight weeks, with intramuscular injections, and the soleus muscle was collected for morphological analyses. Results: The supraphysiological doses of ND in the sedentary group caused muscle degeneration, evidenced by splitting fibers, clusters of small fibers, irregular myofibrils, altered sarcomeres, an increase in collagen deposition and in the number of type I muscle fibers (slow-twitch) and central nuclei, as well as a decrease in fibers with peripheral nuclei. On the other hand, in the ND exercise group, there was an increase in the NMJs diameter with scattering of its acetylcholine receptors, although no major morphological changes were found in the skeletal muscle. Thus, the alterations caused by ND in sedentary rats were partially reversed by physical exercise. Conclusions: The supraphysiological ND exposure in the sedentary rats promoted an increase in muscle oxidative pattern and adverse morphological alterations in skeletal muscle, resulting from damage or post-injury regeneration. In the ND-exercised rats, no major morphological changes were found. Thus, the physical exercise partially reversed the alterations caused by ND in sedentary rats

Listening to patients, for the patients: The COVAD Study-Vision, organizational structure, and challenges

Background: The pandemic presented unique challenges for individuals with autoimmune and rheumatic diseases (AIRDs) due to their underlying condition, the effects of immunosuppressive treatments, and increased vaccine hesitancy. Objectives: The COVID-19 vaccination in autoimmune diseases (COVAD) study, a series of ongoing, patient self-reported surveys were conceived with the vision of being a unique tool to gather patient perspectives on AIRDs. It involved a multinational, multicenter collaborative effort amidst a global lockdown. Methods: Leveraging social media as a research tool, COVAD collected data using validated patient-reported outcomes (PROs). The study, comprising a core team, steering committee, and global collaborators, facilitated data collection and analysis. A pilot-tested, validated survey, featuring questions regarding COVID-19 infection, vaccination and outcomes, patient demographics, and PROs was circulated to patients with AIRDs and healthy controls (HCs). Discussion: We present the challenges encountered during this international collaborative project, including coordination, data management, funding constraints, language barriers, and authorship concerns, while highlighting the measures taken to address them. Conclusion: Collaborative virtual models offer a dynamic new frontier in medical research and are vital to studying rare diseases. The COVAD study demonstrates the potential of online platforms for conducting large-scale, patient-focused research and underscores the importance of integrating patient perspective into clinical care. Care of patients is our central motivation, and it is essential to recognize their voices as equal stakeholders and valued partners in the study of the conditions that affect them

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)