77 research outputs found

    Neurophysiological Repercussions of Anabolic Steroid Abuse: A Road into Neurodegenerative Disorders

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    Since its discovery, several chemical modifications in the testosterone molecule have been done by pharmaceutical industry in order to improve its pharmacological effects, resulting in the creation of anabolic steroids (AS). Despite the therapeutic benefits, AS abuse has spread among elite and recreational athletes in the search for improvements on physical appearance and physical performance. Illicit use of anabolic AS has been correlated with several adverse effects, such as cardiovascular, endocrine, reproductive, and neurobehavioral dysfunctions. Recently, declines on cognitive and mnemonic performance have been demonstrated clinically and experimentally. Experimental studies have demonstrated that these neurological dysfunctions are correlated to spread neuronal apoptosis throughout important areas of the central nervous system (CNS), such as hippocampus and cortex. Several pathophysiological mechanisms have been linked to the AS-induced neurotoxicity, including redox imbalance and recruitment of pro-apoptotic downstream pathways. Furthermore, exposure to AS has arisen as a potential risk factor to the development of Alzheimer’s disease. Altogether, these evidences imply that AS abuse per se induces neurodegeneration and can aggravate the prognosis of neurodegenerative diseases

    Eugenol mitigated acute lung but not spermatic toxicity of C60 fullerene emulsion in mice

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    C60 fullerene (C60) is a nano-pollutant that can damage the respiratory system. Eugenol exhibits significant anti-inflammatory and antioxidant properties. We aimed to investigate the time course of C60 emulsion-induced pulmonary and spermatic harms, as well as the effect of eugenol on C60 emulsion toxicity. The first group of mice (protocol 1) received intratracheally C60 emulsion (1.0 mg/kg BW) or vehicle and were tested at 12, 24, 72 and 96 h (F groups) thereafter. The second group of mice (protocol 2) received intratracheally C60 emulsion or vehicle, 1 h later were gavaged with eugenol (150 mg/kg) or vehicle, and experiments were done 24 h after instillation. Lung mechanics, morphology, redox markers, cytokines and epididymal spermatozoa were analyzed. Protocol 1: Tissue damping (G) and elastance (H) were significantly higher in F24 than in others groups, except for H in F72. Morphological and inflammatory parameters were worst at 24 h and subsequently declined until 96 h, whereas redox and spermatic parameters worsened over the whole period. Eugenol eliminated the increase in G, H, cellularity, and cytokines, attenuated oxidative stress induced by C60 exposure, but had no effect on sperm. Hence, exposure to C60 emulsion deteriorated lung morphofunctional, redox and inflammatory characteristics and increased the risk of infertility. Furthermore, eugenol avoided those changes, but did not prevent sperm damage

    ENERGIA METABOLIZÁVEL PARA SUÍNOS IMUNOCASTRADOS EM TERMINAÇÃO

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    Objetivou-se estimar a exigĂȘncia de energia metabolizĂĄvel (EM) para suĂ­nos machos imunocastrados na fase de terminação. O experimento foi conduzido na Universidade Estadual Norte Fluminense Darcy Ribeiro. Foram utilizados 60 suĂ­nos machos distribuĂ­dos em delineamento de blocos casualizados, sendo 50 suĂ­nos imunocastrados – IM (tratamento 1 a 5) e 10 castrados cirurgicamente – CC (tratamento 3b). Os tratamentos diferiram quanto ao nĂ­vel de EM utilizada, sendo T1 – 3030, T2 – 3130, T3a – 3230, T3b – 3230, T4 – 3330 e T5 – 3430 Kcal de EM/Kg. Foram avaliadas caracterĂ­sticas de desempenho em diferentes perĂ­odos (A – intervalo entre a primeira e a segunda imunização, B – intervalo entre a segunda imunização e o abate e T – perĂ­odo total, da primeira imunização ao abate) e de carcaça, alĂ©m de anĂĄlise sensorial da carne dos suĂ­nos. Os dados mĂ©dios obtidos nos diferentes nĂ­veis de energia foram submetidos Ă  anĂĄlise de variĂąncia e anĂĄlise de regressĂŁo linear em nĂ­vel de 5% de significĂąncia. A anĂĄlise foi realizada com o auxĂ­lio do programa de anĂĄlises estatĂ­sticas SAEG. Foi observado efeito linear crescente (P0,05) entre as caracterĂ­sticas de carcaça avaliadas. Na anĂĄlise sensorial, embora os avaliadores tenham detectado diferenças no odor das carnes de suĂ­nos CC e IM, tais diferenças nĂŁo foram devidas ao odor sexual. NĂŁo foi possĂ­vel estimar o nĂ­vel de energia metabolizĂĄvel para a categoria de suĂ­nos imunocastrados em fase de terminação

    LISINA DIGESTÍVEL PARA MARRÃS NO TERÇO FINAL DA GESTAÇÃO

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    Objetivou-se verificar com esse trabalho se o aumento do nĂ­vel de lisina digestĂ­vel na dieta de marrĂŁs, fornecidas a partir do 75Âș dia de gestação atĂ© o parto influencia o desempenho reprodutivo das matrizes, especialmente sobre o peso dos leitĂ”es e a uniformidade do lote e avaliar a condição corporal das fĂȘmeas para a segunda cobertura. Foram utilizadas 6 marrĂŁs da linhagem Fertilis 20 (Genetiporc), alojadas em baias individuais de alvenaria, sem acesso a piquetes, com pĂ©-direito de 2,5m, com telhado em duas ĂĄguas e telha de barro tipo francesa. As matrizes receberam o mesmo tratamento atĂ© 75Âș dia de gestação. Os animais foram distribuĂ­dos em delineamento experimental de blocos inteiramente casualizados, com dois tratamentos: 0,63 e 0,78% de lisina digestĂ­vel na ração, com trĂȘs repetiçÔes. As raçÔes experimentais foram elaboradas com milho e farelo de soja como ingredientes principais e foram formuladas para atender as exigĂȘncias nutricionais de marrĂŁs, exceto lisina. As matrizes receberam alimentação “ad libitum” atĂ© a fase gestacional na qual se iniciou o experimento. No perĂ­odo experimental, o arraçoamento foi realizado duas vezes ao dia (de manhĂŁ e a tarde), totalizando aproximadamente 3,4 kg. As raçÔes, sobras e os animais foram pesados para determinação do ganho de peso mĂ©dio diĂĄrio (GPD), do consumo mĂ©dio de ração diĂĄrio (CRD). As matrizes foram pesadas apĂłs a confirmação de gestação (21 dias apĂłs a cobertura), aos 75 dias de gestação, no parto e na desmama dos leitĂ”es. Os leitĂ”es foram pesados ao nascer e Ă  desmama, realizada aos 21 dias de idade, para determinação do desempenho da leitegada. Foi avaliada a perda de peso da porca durante o perĂ­odo de lactação. Os dados obtidos foram submetidos Ă  anĂĄlise de variĂąncia. NĂŁo foi detectado efeito (p>0,05) da elevação do nĂ­vel de lisina digestĂ­vel da ração de 0,62 para 0,78% sobre nenhum dos parĂąmetros avaliados. O aumento do nĂ­vel de lisina digestĂ­vel nĂŁo influenciou o desempenho reprodutivo das marrĂŁs ou da leitegada

    Bisphenol A increases hydrogen peroxide generation by thyrocytes both in vivo and in vitro

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    Bisphenol A (BPA) is the most common monomer in polycarbonate plastics and an endocrine disruptor. Though some effects of BPA on thyroid hormone (TH) synthesis and action have been described, the impact of this compound on thyroid H2O2 generation remains elusive. H2O2 is a reactive oxygen species (ROS), which could have deleterious effect on thyrocytes if in excess. Therefore, herein we aimed at evaluating the effect of BPA exposition both in vivo and in vitro on H2O2 generation in thyrocytes, besides other essential steps for TH synthesis. Female Wistar rats were treated with vehicle (control) or BPA 40 mg/kg BW for 15 days, by gavage. We then evaluated thyroid iodide uptake, mediated by sodium-iodide symporter (NIS), thyroperoxidase (TPO) and dual oxidase (DOUX) activities (H2O2 generation). Hydrogen peroxide generation was increased, while iodide uptake and TPO activity were reduced by BPA exposition. We have also incubated the rat thyroid cell line PCCL3 with 10−9 M BPA and evaluated Nis and Duox mRNA levels, besides H2O2 generation. Similar to that found in vivo, BPA treatment also led to increased H2O2 generation in PCCL3. Nis mRNA levels were reduced and Duox2 mRNA levels were increased in BPA-exposed cells. To evaluate the importance of oxidative stress on BPA-induced Nis reduction, PCCL3 was treated with BPA in association to N-acetylcysteine, an antioxidant, which reversed the effect of BPA on Nis. Our data suggest that BPA increases ROS production in thyrocytes, what could lead to oxidative damage thus possibly predisposing to thyroid disease

    Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

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    Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≄1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≀6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362
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