Relato de caso de lombalgia inflamatória com extenso comprometimento anatômico-funcional: a importância de uma adequada abordagem da dor lombar na Atenção Primária à Saúde / Case report of inflammatory low back pain with extensive anatomical-functional impairment: The importance of an adequate approach to low back pain in Primary Care / Presentación de un caso de lumbalgia inflamatoria con afectación anatómico-funcional extensa: La importancia de un abordaje adecuado de la lumbalgia en Atención Primaria de Salud

Introdução: A lombalgia é uma condição prevalente e que apresenta importante impacto na capacidade funcional e na qualidade de vida, sendo a sua correta abordagem na Atenção Primária à Saúde fundamental para a identificação e o estabelecimento de um diagnóstico etiológico precoce de possíveis patologias que possam estar relacionadas a desfechos mórbidos e a graves limitações funcionais. Apresentação do caso: Paciente de 56 anos, sexo masculino, hipertenso, foi encaminhado para serviço especializado de reumatologia com histórico de lombalgia havia mais de 20 anos. Ao exame físico foi constatada presença de deformidades da coluna vertebral e extensa limitação de movimentos. Exames radiográficos mostravam esclerose de articulações sacroilíacas, osteopenia difusa e coluna vertebral em aspecto de "bambu". Conclusões: Constata-se a importância de que na abordagem das lombalgias na atenção primária se busque o reconhecimento de possíveis etiologias graves e potencialmente incapacitantes que possam estar subjacentes à queixa de dor lombar. Com esse objetivo, é fundamental o reconhecimento das chamadas red flags relacionadas às lombalgias, além de sua caracterização como mecânica ou inflamatória. Perante a atuação da atenção primária no oferecimento de um cuidado pautado na integralidade e na prevenção de agravos, reafirma-se a importância de uma avaliação clínica pormenorizada das lombalgias nesse nível de atenção à saúde.

Introduction: Low back pain is a prevalent condition that has an important impact on functional capacity and quality of life, and its correct approach in Primary Care is fundamental to the identification and establishment of an early etiological diagnosis of possible pathologies that may be related to outcomes morbid conditions and serious functional limitations. Case presentation: 56-year-old male patient, hypertensive, referred to a specialized rheumatology service with a history of low back pain for over 20 years. Physical examination revealed the presence of spinal deformities and extensive movement limitations. Radiographic examinations showing sclerosis of the sacro-iliac joints, diffuse osteopenia and a "bamboo" appearance of the spine. Conclusions: It is important that in the approach of low back pain in Primary Care, we seek to recognize possible serious and potentially disabling etiologies that may underlie the complaint of low back pain. For that, it is essential to recognize the so-called "red flags" related to low back pain, in addition to its characterization as mechanical or inflammatory. Given the role of Primary Care in offering care based on integrality and in the prevention of injuries, the importance of a detailed clinical assessment of low back pain at this level of health care is reaffirmed.

Introducción: La lumbalgia es una patología prevalente que tiene un impacto importante en la capacidad funcional y la calidad de vida, y su correcto abordaje en Atención Primaria de Salud es fundamental para la identificación y establecimiento de un diagnóstico etiológico precoz de posibles patologías que puedan estar relacionadas con los resultados, condiciones morbosas y limitaciones funcionales graves. Presentación del caso: Paciente masculino de 56 años, hipertenso, remitido a servicio especializado de reumatología con antecedentes de dolor lumbar de más de 20 años. El examen físico reveló la presencia de deformidades de la columna y amplias limitaciones de movimiento. Los exámenes radiológicos muestran esclerosis de las articulaciones sacroilíacas, osteopenia difusa y una apariencia de "bambú" de la columna. Conclusiones: Es importante que al abordar la lumbalgia en Atención Primaria de Salud busquemos reconocer las posibles etiologías graves y potencialmente incapacitantes que pueden subyacer a la queja de lumbalgia. Con este objetivo, es fundamental reconocer las llamadas "banderas rojas" relacionadas con la lumbalgia, además de su caracterización como mecánica o inflamatoria. Dado el papel de Atención Primaria de Salud a la hora de ofrecer una atención basada en la integralidad y prevención de enfermedades, se reafirma la importancia de una evaluación clínica detallada de la lumbalgia en este nivel de atención sanitaria.

Epidemiological study of Hepatitis C in people deprived of liberty / Estudo epidemiológico da Hepatite C em pessoas privadas de liberdade

INTRODUCTION: The prevalence of hepatitis C (HCV) is high among prisoners. If untreated, a substantial number of patients progress to cirrhosis, hepatocarcinoma, or liver failure. World Health Organization aims to reduce the incidence of infection by 90% by 2030. OBJECTIVE: To describe the prevalence of anti-HCV and sociodemographic and clinical aspects, related to the presence of the antibody, in the population deprived of liberty. METHODS: Cross-sectional and epidemiological survey, with exploratory, observational, quantitative-analytical components. A simple random sample of 233 participants, with 95% Confidence Interval (CI) and, a 4% margin of error, was calculated for a population of 1,564 prisoners. The relationship between sociodemographic and clinical variables was evaluated, considering as outcome of the rapid test for anti-HCV results, using the associative measure Prevalence Ratio (PR) with a 95% CI. RESULTS: 240 people participated. The prevalence of anti-HCV was 2%, and the use of injectable drugs (PR 14.75; PRIC95% 2.09-104.28), being born in the decades of 1951 to 1980 (PR 9.28; PRIC95% 1.06-81.57) and be co-infected with hepatitis B virus (PR 10.75; PRIC95% 1.66-69.65) were the aspects that presented a relevant prevalence ratio for the presence of the virus, which could be generalized to the population. CONCLUSION: This is a population that is difficult to access, the study is relevant because it contributes to preventive measures of public health in the prison system. Moreover, it shows the need to implement measures to prevent and contain the spread of HCV, aiming at the elimination of hepatitis C in this population.

INTRODUÇÃO: A prevalência da hepatite C (HCV) é elevada entre os prisioneiros. Se não tratada, proporção substancial das infecções progride para cirrose, hepatocarcinoma ou insuficiência hepática. Organização Mundial de Saúde tem a meta de reduzir a incidência da infecção em 90% até 2030. OBJETIVO: Descrever a prevalência do anti-HCV e os aspectos sociodemográficos e clínicos, relacionados à presença do anticorpo, na população privada de liberdade. MÉTODOS: Estudo transversal por inquérito epidemiológico, com componente exploratório, observacional, quantitativo-analítico. Foi calculada amostra aleatória simples de 233 pessoas, Intervalo de Confiança (IC) 95%, margem de erro 4% para população de 1564 prisioneiros. Foi avaliada a relação entre os aspectos sociodemográficos e clínicos com o desfecho obtido pelo teste rápido para anti-HCV por meio da medida associativa Razão de Prevalência (RP) e IC de 95% para essa estimativa. RESULTADOS: Participaram 240 pessoas. A prevalência do anti-HCV foi de 2%, sendo que o uso de drogas injetáveis (RP 14,75; RPIC95% 2,09-104,28), ter nascido nas décadas de 1951 a 1980 (RP 9,28; RPIC95% 1,06-81,57) e ser coinfectado com o vírus da hepatite B (RP 10,75; RPIC95% 1,66-69,65) foram os aspectos que apresentaram razão de prevalência para a presença do vírus, passível de generalização para a população. CONCLUSÃO: Trata-se de população de difícil acesso, o estudo é relevante por contribuir para medidas preventivas de saúde pública no sistema prisional. Outrossim, mostra a necessidade de se implementar medidas para evitar e conter a disseminação de HCV, visando a microeliminação da hepatite C na população carcerária.

G20’s commitment to telehealth for reducing global health disparities: from a global commitment to regional actions

[ABSTRACT]. The G20, representing the world’s largest economies, plays a critical role in shaping global health policies, initiatives and innovative solutions. As these nations navigate the complexities of digital transformation in the health sector, engagement with the Global Initiative on Digital Health (2), aligned with the Pan American Health Organization ́s (PAHO) eight guiding principles for the digital transformation of the health sector (3), becomes imperative not only for advancing technology adoption but also for promoting health equity and universal access to health and universal health coverage. The inclusion of telehealth in the G20 agenda, championed by Brazil’s presidency, underscores the group’s commitment to leveraging digital innovations to improve health outcomes in G20 countries and globally, as telehealth is a key area of the digital transformation of the health sector. Because countries worldwide vary widely in the capacity of their digital health infrastructure and their development stages, there lies a unique opportunity to foster international collaboration, share knowledge and drive global standards that support the widespread adoption of telehealth solutions for leaving no one behind. This strategic focus is predicated on the understand- ing that telehealth serves as both a catalyst for health equity and a critical tool for reinforcing health systems grounded in primary health care (PHC). The scientific rationale behind this concerted effort is clear: by enhancing digital infrastructure and fostering the adoption of telehealth solutions, there is potential to bridge the global digital divide and democratize access to health services. The G20, representing the world’s largest economies, plays a critical role in shaping global health policies, initiatives and innovative solutions (1). As these nations navigate the complexities of digital transformation in the health sector, engagement with the Global Initiative on Digital Health (2), aligned with the Pan American Health Organization ́s (PAHO) eight guiding principles for the digital transformation of the health sector (3), becomes imperative not only for advancing technology adoption but also for promoting health equity and universal access to health and universal health coverage. The inclusion of telehealth in the G20 agenda, championed by Brazil’s presidency, underscores the group’s commitment to leveraging digital innovations to improve health outcomes in G20 countries and globally, as telehealth is a key area of the digital transformation of the health sector. Because countries worldwide vary widely in the capacity of their digital health infrastructure and their development stages, there lies a unique opportunity to foster international collaboration, share knowledge and drive global standards that support the widespread adoption of telehealth solutions for leaving no one behind. This strategic focus is predicated on the understand- ing that telehealth serves as both a catalyst for health equity and a critical tool for reinforcing health systems grounded in primary health care (PHC). The scientific rationale behind this concerted effort is clear: by enhancing digital infrastructure and fostering the adoption of telehealth solutions, there is potential to bridge the global digital divide and democratize access to health services. In envisioning the future of global health, the fourth pillar of the vision of PAHO’s Director emerges with critical importance: the construction of resilient national health systems is firmly rooted in the implementation of the PHC strategy. This vision is not just an aspiration but a necessary evolution, with PAHO standing ready to guide countries towards achieving this goal. PAHO’s commitment involves supporting countries in the organization of health services networks based on PHC, targeting public financing to foster universal access and coverage, and bolstering governance in health under the leadership of health ministries. Moreover, it calls for the rapid deployment of technological innovations such as telehealth and also broader digital transformation initiatives (4). Digital transformation, emerging as a key innovative strategy, offers significant improvements to the strengthening of PHC. Through the adoption of inclusive digital health solutions, it is possible to enhance the delivery of health services, ensuring they become more accessible, efficient and equitable for everyone, everywhere (5, 6). Among the priorities leading this transformation, telehealth emerged at the G20 as a key opportunity in the mission to leave no one behind and as a cornerstone of the digital transformation of the health sector. Telehealth improves access to care and health information, thereby empowering individuals and communities (7). It effectively extends health services to underserved populations, encourages collaborative practices among health professionals, and broadens access to health for the wider community. It can support reduced waiting times and costs through efficiencies in care management. Through telehealth, the transition to a new era of PHC can be accelerated through technological advancements that drive us towards a more inclusive and accessible health care system for all. Concrete efforts should be focused on modernizing normative and legislative frameworks, investment in digital infrastructure, prioritizing the development of robust digital health infrastructures while ensuring that reliable internet access and digital tools are available across urban and rural areas alike. Enhancing digital literacy and telehealth competencies among health professionals and the population will maximize the utilization and effectiveness of digital health services. However, the lack of standardized policies and frameworks for telehealth is a significant barrier to its global adoption and, therefore, G20 nations can lead by example, working towards (a) developing international telehealth guidelines that consider ethical, privacy and security standards for telehealth services to facilitate cross-border healthcare delivery and secure data exchange; and (b) promoting interoperable telehealth platforms that can seamlessly exchange information, thus enhancing the continuity and quality of care. The G20’s leadership and commitment to integrating telehealth into the global health agenda can set an unprecedented opportunity for international cooperation in digital health. G20 countries can significantly impact global health outcomes by integrating telehealth at all levels of care and health service delivery networks, impacting the lives of billions around the world. Equity must remain central to our efforts as telehealth services are integrated into the model of care. This means ensuring the adoption of differentiated approaches in digital health based on (a) the characteristics of a territory (geographical dis- persion, status of infrastructure), (b) the beneficiary population to be served (their health needs, and cultural, racial and ethnic considerations) and (c) the health system capacities and organization (the health services network, coverage capacity and availability of multiprofessional teams). Health outcomes can be significantly positively impacted by undertaking bottom-up planning processes that take into account the latter considerations and by adapting the model of care to leverage the capacity of digital health. Embracing the Regional Roadmap for the Digital Transformation of the Health Sector in the Region of the Americas is imperative for countries aiming to develop expansive, resilient and inclusive health systems based on PHC (8,9). This comprehensive framework, backed by lessons learned and suc- cessful experiences, underscores the significant potential that digital transformation holds for improving health outcomes. Brazil's commitment to the consolidation of the Unified Health System (the Sistema Único de Saúde, or SUS) and its well-established Family Health Strategy as the foundation for the health and well-being of its population is being expressed through the rapid deployment of telehealth, and serves as a model of innovation and effectiveness, showcasing the transformative impact of digital health solutions on accessibility, efficiency and quality of care (10). This editorial, jointly prepared by rep- resentatives of the government of Brazil and PAHO advocates for global standardization of telehealth practices that ensures the scalability and sustainability of health interventions while addressing the core determinants of health equity.

[RESUMEN]. Sin resumen disponible Texto completo en inglés

[RESUMO]. Não existe resumo disponível Texto completo em inglês

From national and regional commitments to global impact: artificial intelligence for equitable public health at the G20

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Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin.

Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1960s. It was effectively banned in 2003 but remains in the environment to this day due to several factors that increase its half-life and its misuse despite the bans. In addition to the endocrine-disrupting effect of TBT, which may lead to imposex induction in some invertebrate species, there are several studies that demonstrate that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms; mainly, there are alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, and we discuss issues that still need to be explored to fill the knowledge gaps regarding the impact of this endocrine-disrupting chemical on immune system homeostasis.

Outbreak of leishmaniasis caused by Leishmania enriettii in guinea pigs (Cavia porcellus) / Surto de leishmaniose causada por Leishmania enriettii em cobaias (Cavia porcellus)

We describe an outbreak of leishmaniasis in seven guinea pigs (Cavia porcellus) in which nodular ulcerated skin lesions of varying sizes were observed in the nasal cavity, upper lip, pinnae, vulva, and periarticular region of the limbs. Cytologic exam of collected samples of the lesions in the auricle of one of the animals revealed macrophages containing parasitophorous vacuoles of approximately 4.0μm in diameter in their cytoplasm with morphology suggestive of Leishmania sp. Although skin lesions spontaneously regressed in two of the Guinea pigs, only one survived. All six animals that died were necropsied. Grossly, all animals showed bloody nodular cutaneous lesions with crusts. One of the guinea pigs had distended dark red and firm lungs. Histopathology of the skin lesions revealed histiocytic interstitial acanthotic dermatitis associated with a myriad of Leishmania organisms within macrophages cytoplasm. In the lung, the lesions were characteristic of broncho-interstitial pneumonia with focal infiltrates of neutrophils, epithelioid macrophages, and multinucleated giant cells containing 2µm basophilic amastigotes with morphology compatible with Leishmania spp. A focal granulomatous lesion ,associated with the causal agent in the lung is a novel description of leishmaniasis in guinea pigs caused by L. enriettii. The polymerase chain reaction (PCR) technique with mini-exon primer performed in samples of lesions from two affected guinea pigs was positive and equal to the reference strain, identifying Leishmania enriettii. The cytological, macroscopic, and histological lesions associated with the PCR technique allowed the diagnosis of leishmaniasis and the identification of the specie L. enriettii.

Descrevemos um surto de leishmaniose em sete cobaias (Cavia porcellus), com lesões cutâneas nodulares ulceradas de tamanhos variados observadas na cavidade nasal, lábio superior, pavilhões auriculares, vulva e região periarticular dos membros. No exame citológico foram encontrados macrófagos contendo vacúolos parasitóforos no citoplasma de aproximadamente 4.0μm em diâmetro com morfologia sugestiva de Leishmania sp. Apesar de regressão espontânea das lesões cutâneas terem ocorrido em duas das sete cobaias, apenas um sobreviveu. Seis dos sete animais afetados morreram e foram necropsiados. Macroscopicamente, todos os animais apresentaram lesões cutâneas nodulares, crostosas e sanguinolentas. Uma das cobaias tinha pulmões vermelho-escuros, distendidos e firmes. A histopatologia das lesões cutâneas revelou dermatite acantótica intersticial histiocítica associada a miríades de organismos de Leishmania no citoplasma de macrófagos. Nos pulmões as lesões eram características de pneumonia bronco-intersticial com infiltrado focal de neutrófilos, eosinófilos, macrófagos epitelioides e células gigantes multinucleadas contendo amastigotas basofílicos de 2µm com morfologia compatível com Leishmania spp. Lesões granulomatosas focais associadas ao agente no pulmão são um achado inédito na leishmaniose causada por L. enriettii em cobaias. A técnica de reação em cadeia da polimerase (PCR) com primer mini-exon realizada em amostras de lesões de duas cobaias afetadas foi positiva, identificando Leishmania enriettii. Os aspectos macroscópicos, citológicos, e histológicos associados à técnica da (PCR), permitiram o diagnóstico da leishmaniose e a identificação da espécie L. enriettii.

Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells.

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients' survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain's effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile.

Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária / Experience in managing action research on hepatitis C survey in the prison community

Resumo Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

Abstract We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Experience in managing action research on hepatitis C survey in the prison community. / Experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária.

We aimed to report the experience in managing action research on hepatitis C investigation in the prison community in the Triângulo Mineiro region, Minas Gerais, Brazil. The proposal was developed from March 2019 to March 2020, reaching 240 people to contain the spread of the disease through a survey, testing, and monitoring of positive cases. We adopted intersectoral action with articulation between Universities, Medical Society, Teaching Hospital, and State Secretariat for Justice and Public Security. Strategies for the management of action research are described: study settings and stakeholders, registration and formalization of the activity, application of tests, and management of reagent inmates. We identified difficulties regarding the accommodation of routines among the research team and the proper functioning of the penitentiary, which required extensive training between the parties and managerial articulations. We consider that the report collaborates with the organization of future research aimed at accessing this still invisible population, the prison community when it highlights the strategies adopted to conduct the research.

Objetivou-se relatar a experiência no gerenciamento de pesquisa-ação sobre inquérito de hepatite C junto à comunidade carcerária no Triângulo Mineiro, Minas Gerais. A proposta foi desenvolvida entre março de 2019 e março de 2020, alcançando 240 pessoas, com o intuito de conter a disseminação do agravo por meio de inquérito, testagem e acompanhamento dos casos positivos. Adotou-se ação intersetorial, com articulação entre universidades, sociedade médica, hospital de ensino e Secretaria de Estado de Justiça e Segurança Pública. As estratégias para o gerenciamento da pesquisa-ação foram: cenários e atores do estudo, registro e formalização da atividade, aplicação dos testes e manejo dos internos reagentes. Dificuldades foram identificadas quanto à acomodação de rotinas entre equipe de pesquisadores e funcionamento próprio da penitenciária, o que exigiu treinamento ostensivo entre as partes e articulações gerenciais. Considera-se que o relato, quando destaca as estratégias adotadas para a condução da pesquisa, colabora para a organização de investigações futuras que visem acessar essa população ainda invisibilizada.

Environmentally relevant dose of the endocrine disruptor tributyltin disturbs redox balance in female thyroid gland.

Tributyltin (TBT) is an endocrine disruptor used as a biocide in nautical paints. Even though many TBT effects in marine species are known, data in mammals are scarce, especially regarding the thyroid gland. The present study aimed to evaluate the effect of a subchronic exposure to TBT on thyroid oxidative stress of female Wistar rats. Rats received vehicle (control group), 200 or 1000 ng TBT/kg body weight/day for 40 days. After euthanasia, one part of the thyroids were collected in order to assess iodide uptake; activity and/or mRNA expression of thyroperoxidase (TPO) and dual oxidases (DUOXs); activity and/or mRNA expression of catalase, glutathione peroxidase, superoxide dismutase and NADPH oxidase 4 (CAT, GPx, SOD and NOX4); 4-hydroxynonenal (4-HNE) expression and total thiol groups levels; and mRNA expression of estrogen receptors alpha and beta (ERα and ERß). The remaining part of the thyroid was processed for morphological analysis of estrogen receptor alpha (ERα) and for collagen deposition. Iodide uptake was not changed with treatments. TPO activity and expression were increased in the TBT1000 group (259.81% and 95.17%). The activity, but not mRNA, of CAT (17.36% TBT200; 27.10% TBT1000) and GPx (29.24% TBT200; 28.97% TBT1000) were decreased by TBT. SOD and NADPH oxidase activity, as well as thiol group and 4-HNE levels remained unchanged. Interstitial collagen deposition increased in the TBT200 group (39.54%). The mRNA expression of ERα increased in TBT-treated rats (44.87% TBT200; 36.43% TBT1000), while protein expression was increased but not reaching significance (TBT1000, p = 0.056) by TBT. Therefore, our results show that TBT increases TPO expression and reduces antioxidant enzyme activities in the thyroid gland leading to oxidative stress. Some of these effects could be mediated by the ERα pathway.

Subacute and low-dose tributyltin exposure disturbs the mammalian hypothalamus-pituitary-thyroid axis in a sex-dependent manner.

Tributyltin (TBT) is an endocrine disruptor chemical (EDC) capable of altering the proper function of the hypothalamus-pituitary thyroid (HPT) axis. This study aimed to evaluate the subacute effects of TBT on the HPT axis of male and female rats. A dose of 100 ng/kg/day TBT was used in both sexes over a 15-day period, and the morphophysiology and gene expression of the HPT axis were assessed. TBT exposure increased the body weight in both sexes, while food efficiency increased - only in male rats. It was also possible to note alterations in the thyroid, with the presence of a stratified epithelium, cystic degeneration, and increased interstitial collagen deposition. A reduction in T3 and T4 levels was only observed in TBT male rats. A reduction in TSH levels was observed in TBT female rats. Evaluating mRNA expression, we observed a decrease in hepatic D1 and TRH mRNA levels in TBT female rats. An increase in D2 mRNA expression in the hypothalamus was observed in TBT male rats. Additionally, no significant changes in TRH or hepatic D1 mRNA expression in TBT male rats or in hypothalamic D1 and D2 mRNA expression in TBT female rats were observed. Thus, we can conclude that TBT has different toxicological effects on male and female rats by altering thyroid gland morphophysiology, leading to abnormal HPT axis function, and even at subacute and low doses, it may be involved in complex endocrine and metabolic disorders.

Clinical and Microbiological Profile of Diabetic Foot Ulcers Infected With Staphylococcus aureus in a Regional General Hospital in Bahia, Brazil.

It is necessary to know the resistance profile of Staphylococcus aureus to better control diabetic foot ulcer infections, to establish rational antibiotic therapy, and to avoid the development of resistant strains. This cross-sectional study evaluated the clinical parameters, virulence, and antimicrobial resistance profiles of S aureus in patients with diabetic foot disease admitted to a public hospital. S aureus strains were identified in patients with diabetes with amputation indication. Infected tissue samples were collected, microbes were isolated and identified. The microbial resistance profile was determined. Samples were also analyzed for biofilm formation and other virulence markers. The 34 individuals examined were mostly men, black, aged 60 years on average, and generally had a low income and education level. Most individuals had type 2 diabetes, and the mean time since diagnosis was 13.9 years. On an SF-36 (the Medical Outcomes Study 36-item short-form health survey) quality-of-life questionnaire, 75% of individuals obtained a score equal to 0 for physical impairment. S aureus specimens from 17 patients were isolated, corresponding to 50% of samples. Five isolates were classified as methicillin-resistant S aureus (MRSA). Molecular typing revealed that 20% of MRSA strains were SCCmec type V and 80% were type I. All isolates were sensitive to doxycycline; 61.5% were resistant to erythromycin, 38.5% to cefoxitin, 30.7% to clindamycin and ciprofloxacin, 23% to meropenem, 15.3% to gentamicin, 38.5% to oxacillin, and 7.7% (one strain) to vancomycin. Regarding biofilm production, 53% of samples were able to produce biofilms, and 84.6% had icaA and/or icaD genes. Additionally, the following enterotoxin genes were identified in the isolates: seb, sec, seg, and sei (5.9%, 5.9%, 11.8%, and 23.9%, respectively) and agr types 1 (5.9%) and 2 (11.8%). Genotypic evaluation made it possible to understand the pathogenicity of S aureus strains isolated from the diabetic foot; laboratory tests can assist in the monitoring of patients with systemic involvement.

Citral modulates virulence factors in methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for high morbidity and mortality rates. Citral has been studied in the pharmaceutical industry and has shown antimicrobial activity. This study aimed to analyze the antimicrobial activity of citral in inhibiting biofilm formation and modulating virulence genes, with the ultimate goal of finding a strategy for treating infections caused by MRSA strains. Citral showed antimicrobial activity against MRSA isolates with minimum inhibitory concentration (MIC) values between 5 mg/mL (0.5%) and 40 mg/mL (4%), and minimum bactericidal concentration (MBC) values between 10 mg/mL (1%) and 40 mg/mL (4%). The sub-inhibitory dose was 2.5 mg/mL (0.25%). Citral, in an antibiogram, modulated synergistically, antagonistically, or indifferent to the different antibiotics tested. Prior to evaluating the antibiofilm effects of citral, we classified the bacteria according to their biofilm production capacity. Citral showed greater efficacy in the initial stage, and there was a significant reduction in biofilm formation compared to the mature biofilm. qPCR was used to assess the modulation of virulence factor genes, and icaA underexpression was observed in isolates 20 and 48. For icaD, seg, and sei, an increase was observed in the expression of ATCC 33,591. No significant differences were found for eta and etb. Citral could be used as a supplement to conventional antibiotics for MRSA infections.

Experimental Multidisciplinary Approach Based on Compounded Capsule's Quality Evaluation for Pharmacy Undergraduate Courses.

Active learning is common in pharmacy school. However, such learning strategy rarely integrates more than one specific field. Here, we develop a new active multidisciplinary approach centered on compounded capsule's quality evaluation. Captopril capsules were chosen for their important role to control systemic arterial hypertension, a highly prevalent disease. The study design was developed and demonstrated by two undergraduate students. Four compounding pharmacies were selected randomly, and sixty capsules of captopril 25 mg were purchased from each pharmacy at three different periods (12 batches). The capsules were evaluated according to general aspects (visual observation), label information (according to the Brazilian Pharmacopoeia's regulation), weight variation (standard method), and uniformity of dosage units (iodine titration). All batches met the requirements expected for general aspects and one pharmacy did not meet minimum label criteria. Weight variation out of the standard limits was observed for three of the batches evaluated, and five batches were found to be out of the acceptable captopril's dosage. All stages of this activity resulted in important discussions pertaining to the education of pharmacists. The experimental multidisciplinary approach presented a lead to different discussions on several expertise fields and might have a great impact on the formation of future pharmacist. Several topics could be addressed using this activity, such as analytical chemistry, titration, stoichiometry, medicine preparation, pharmacological risks, et h i c a l aspects, and the pharmacist's role to guarantee health.

In vitro antitumoral effects of the steroid ouabain on human thyroid papillary carcinoma cell lines.

Ouabain is a steroid described as a compound extracted from plants that is capable of binding to Na+ , K+ -ATPase, inhibiting ion transport and triggering cell signaling pathways. Due to its positive ionotropic effect, ouabain was used for more than 200 years for the treatment of cardiac dysfunctions. Numerous antitumor effects of ouabain have been described so far; however, its role on thyroid cancer is still poorly understood. Therefore, the aim of the present work was to evaluate the effect of ouabain on the biology of human papillary thyroid cancer cells. For this, three human thyroid cell lines were used: NTHY-ori, a non-tumor lineage, BCPAP and TPC-1, both derived from papillary carcinomas. Cells were cultured in the presence or absence of ouabain. Subsequently, we evaluated its effects on the viability, cell death, cell cycle, and migratory ability of these cell lines. We also investigated the impact of ouabain in IL-6/IL-6R and epithelial to mesenchymal transition markers expression. Our results indicate that ouabain (10-7 M), decreased the number of NTHY-ori, TPC-1 and BCPAP viable cells and induced cell cycle arrest after in vitro culture, but did not appear to promote cell death. In TPC-1 cells ouabain also inhibited cell migration; increased IL-6/IL-6R expression and IL-6 secretion; and diminished vimentin and SNAIL-1 expression. Collectively, our results indicate that ouabain has an antitumoral role on human papillary thyroid carcinomas in vitro. Even though additional studies are necessary, our work contributes to the discussion of the possibility of new clinical trials of ouabain.

The nonpharmacological sequence method provides a reliable evaluation of baroreflex sensitivity in fish.

The most commonly used technique to study the barostatic regulation of blood pressure in ectothermic vertebrates consists of determining the heart rate response to pharmacological manipulations of blood pressure, the so-called "Oxford method." Although well established, the Oxford method has some important limitations, such as induction of hypervolemia in small animals and undesired effects of vasoactive drugs on central and peripheral baroreflex components. As an alternative, the sequence method, which consists in the computerized evaluation of naturally-occurring baroreflex adjustments of heart rate without the need for pharmacological administrations, was developed to study baroreflexes. In the present study, we compare this sequence method with the Oxford technique in two teleost species with different life styles, and we assess the optimal software configuration for the employment of the sequence method in fish. Calculation of baroreflex gain through the sequence method was adequate and reliable when the software was configured to search for baroreflex sequences with a minimum length of three cardiac cycles with a delay of one cardiac cycle between fluctuations in mean ventral aortic blood pressure and reflex changes in pulse interval. When properly configured, the sequence and the Oxford methods yielded similar determinations of the baroreflex gain in fish.

Ouabain pre-treatment modulates B and T lymphocytes and improves survival of melanoma-bearing animals.

Ouabain (OUA) is a glycoside shown to modulate B and T lymphocytes. Nevertheless, ouabain effects on B16F10 melanoma immune response, a mouse lineage that mimics human melanoma, are still unknown. Our aim was to study how OUA in vivo treatment modulates lymphocytes and if it improves the response against B16F10 cells. C57BL/6 mice were pre-treated with intraperitoneal (i.p) injection of OUA (0.56 mg/Kg) for three consecutive days. On the 4th day, 106 B16F10 cells or vehicle were i.p. injected. Animals were euthanized on days 4th and 21st for organs removal and subsequent lymphocyte analyses by flow cytometry. In vivo ouabain-treatment reduced regulatory T cells in the spleen in both melanoma and non-melanoma groups. Ouabain preserved the number and percentage of B lymphocytes in peripheral organs of melanoma-injected mice. Melanoma-injected mice pre-treated with OUA also survive longer. Our findings contribute to a better understanding of OUA immunological effects in a melanoma model.

Multiple metastases of a transmissible venereal tumor in a dog

Background: Transmissible venereal tumor (TVT) is a common contagious neoplasm in dogs that spreads through coitus.Extra-genital presentations of this tumor are frequent and usually develop through implantation of neoplastic cells onexposed mucosae. TVT metastasis is rare, and when it happens its usually affecting regional lymph nodes and adjacentcutaneous tissue.Case: A female mixed breed dog, with estimated age of 7 to 11 months old, was rescued from the streets and taken to aveterinary clinic in the city of Porto Alegre, RS. The animal had multiple nodules on its body, vulva, ocular mucosa, andgingiva, along with signs of malnutrition and apathy. Cytological examination of the nodules and vulva was done andyielded a cytologic picture compatible with TVT. Weakly treatment with 0,3mg/m² vincristine sulphate was used untilclinical cure was noted. Approximately two weeks after clinical cure, the dog showed a blue colored eye and was referredfor ophthalmological, where it was diagnosed with vision loss due to glaucoma secondary to a neoplasm. The eye wasthen removed and sent for histopathological evaluation. Histopathology of the eye was compatible with TVT diagnosis.One month after enucleation the animal display dispenia, pain, aggressiveness and epistaxis. The animal was euthanizedand submitted for post-mortem evaluation. At necropsy there was a well-defined grayish-white, nodule near the thalamus.Similar nodules were also found on the lung, and anterior chamber of the eye. Histologically, all the nodules were compatible with TVT. Immunohistochemical examination was done, with the neoplastic cells being positive for vimentin andnegative for cytokeratin, CD79a, CD3 and CD117. Based on the post-mortem examination and clinical history, diagnosisof TVT...(AU)