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Abstract Background Evidence has shown that patients with chronic obstructive pulmonary disease present significant deficits in the control of postural balance when compared to healthy subjects. In view of this, it is pertinent to investigate the effects of different therapeutic strategies used alone or in association with pulmonary rehabilitation with the potential to improve postural balance and other outcomes with clinical significance in patients with chronic obstructive pulmonary disease. This study will investigate the effects of an 8-week (short-term) multimodal exercise program [inspiratory muscle training (IMT) plus neuromuscular electrical stimulation (NMES)] on postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation program compared to individualized addition of IMT or NMES to pulmonary rehabilitation or standard pulmonary rehabilitation. Methods This is a randomized, single-blind, 4-parallel-group trial. Forty patients with chronic obstructive pulmonary disease will be included prospectively to this study during a pulmonary rehabilitation program. Patients will be randomly assigned to one of four groups: multimodal exercise program (IMT + NMES + pulmonary rehabilitation group) or (IMT + pulmonary rehabilitation group) or (NMES + pulmonary rehabilitation group) or standard pulmonary rehabilitation group. Patients will receive two sessions per week for 8 weeks. The primary outcome will be static postural balance and secondary outcomes will include as follows: static and dynamic postural balance, fear of falling, muscle strength and endurance (peripheral and respiratory), functional capacity, health-related quality of life, muscle architecture (quadriceps femoris and diaphragm), and laboratory biomarkers. Discussion This randomized clinical trial will investigate the effects of adding of short-term multimodal exercise program, in addition to pulmonary rehabilitation program, in postural balance in patients with chronic obstructive pulmonary disease enrolled in a pulmonary rehabilitation. Furthermore, this randomized control trial will enable important directions regarding the effectiveness of short-term intervention as part of the need to expand the focus of pulmonary rehabilitation to include balance management in chronic obstructive pulmonary disease patients which will be generated. Trial registration ClinicalTrials.gov NCT04387318. Registered on May 13, 2020.

Bisphenol-A (BPA) is an endocrine-disrupting molecule associated with the risk of several non-transmissible chronic diseases. We postulated that BPA triggers oxidative alterations, altering immunocompetence and contributing to physiological dysfunction. To evaluate the effects of BPA on the oxidative and immune system, Californian earthworms were reared in a culture medium containing different BPA concentrations for 24 and 72 h. Coelomocytes were used to evaluate the effects of BPA on oxidative markers, cellular proliferation, and apoptosis, and immunocompetence effects were investigated by yeast-exposure assay and the modulation of genes related to immune response. Low BPA concentrations induced coelomocyte proliferation, imbalanced superoxide/NO levels, higher micronucleus frequency, and apoptosis. BPA also induced Amp1 gene overexpression and a low efficiency of dead yeast capture. The association between DNA damage and changes in innate immune metabolism could be related to the action of BPA, which is associated with the risk of physiological disturbances and non-transmissible chronic diseases.

Resumo Objetivos Neste estudo prospectivo, avaliamos o impacto do uso de medicamentos potencialmente inapropriados prescritos antes da internação (PIM-ph) na mortalidade de idosos. Métodos Foram incluídos 318 pacientes com idade ≥ 65 anos que procuraram atendimento de emergência e foram internados por qualquer motivo clínico. As informações sobre os indicadores clínicos e sociais foram obtidas por meio de entrevistas estruturadas, 24 a 48 horas após a internação. Os medicamentos usados por esses pacientes foram registrados e o uso de PIM-ph foi identificado pela análise brasileira baseada em consenso de uso de PIM. A análise considerou a influência de todo conjunto de PIM-ph, bem como de alguns PIM-ph específicos. O impacto do uso de PIM-ph na sobrevida de idosos hospitalizados foi determinado por meio da análise multivariada de regressão de Cox. Resultados A prevalência de PIM-ph foi 49,7% (n = 158). Um total de 85 (26,7%) pacientes faleceram durante a internação ou até 30 dias após a alta. Dezoito classes farmacológicas de uso de PIM-ph foram identificadas. O uso de PIM-ph, benzodiazepínico (IC: 1.055-3.365, p= 0.032), digoxina (IC: 1.623-7.048, p=0.001) e diuréticos de alça (IC: 1.000-3.455, p=0.05) aumentou o risco relativo de mortalidade independente de sexo, idade, causas clínicas de hospitalização, risco de fragilidade, suporte social, presença de sintomas de confusão, polifarmácia e evolução intra-hospitalar de complicações geriátricas. Conclusão O uso de PIM-ph (Benzodiazepínicos, digoxina e diuréticos de alça) pode contribuir para o risco de mortalidade em idosos hospitalizados. Esses resultados podem ser relevantes no manejo e cuidado terapêutico de pacientes hospitalizados.

Camu-camu (Myrciaria dubia) is known for its antioxidant properties, although little is known about its developmental safety effects, particularly on adult neural function under basal redox and oxidative stress conditions. Therefore, this study sought to address this gap by conducting three complementary protocols using Drosophila melanogaster to investigate these effects. The initial assays revealed that second-stage larvae consumed diets supplemented with various concentrations of camu-camu uniformly, establishing a 50% lethal concentration at 4.799 mg/mL. Hence, non-lethal (0.1, 0.5, and 1 mg/mL) and sub-lethal (5 and 10 mg/mL) concentrations were then chosen to evaluate the effects of camu-camu on preimaginal development and adult neural function. Our observations showed that camu-camu impacts the expression of antioxidant enzymes, reactive species, and lipoperoxidation. Notably, sub-lethal concentrations decreased preimaginal viability and locomotor activity, negatively influenced geotaxis and acetylcholinesterase activity, and increased reactive species, catalase, and glutathione S-transferase activity in flies. Additionally, the protective effects of camu-camu against oxidative stress induced by iron (20 mM) were assessed. Flies supplemented with 0.5 mg/mL of camu-camu during the larval period showed improved neural viability and function, and this supplementation was found to protect against oxidative stress. These findings are instrumental in evaluating the safety and efficacy of commercial supplements based on camu-camu, offering significant insights for future research and application.

Abstract Tamoxifen (TMX) is used as adjuvant therapy for estrogen receptor-positive (ER+) breast cancer cases due to its affinity and inhibitory effects. However, about 30% of cases show drug resistance, resulting in recurrence and metastasis, the leading causes of death. A literature review can help to elucidate the main cellular processes involved in TMX resistance. A scoping review was performed to find clinical studies investigating the association of expression of molecular markers profiles with long-term outcomes in ER+ patients treated with TMX. In silico analysis was performed to assess the interrelationship among the selected markers, evaluating the joint involvement with the biological processes. Forty-five studies were selected according to the inclusion and exclusion criteria. After clustering and gene ontology analysis, 23 molecular markers were significantly associated, forming three clusters of strong correlation with cell cycle regulation, signal transduction of proliferative stimuli, and hormone response involved in morphogenesis and differentiation of mammary gland. Also, it was found that overexpression of markers in selected clusters is a significant indicator of poor overall survival. The proposed review offered a better understanding of independent data from the literature, revealing an integrative network of markers involved in cellular processes that could modulate the response of TMX. Analysis of these mechanisms and their molecular components could improve the effectiveness of TMX.

The objective of this study was to analyze the in vitro stability and toxicity of liposomes containing guarana in skin cell lines. The liposomes were produced by the reverse phase evaporation method containing 1 mg/mL guarana. The stability of the liposomes was evaluated by physical-chemical parameters for up to 90 days using three different storage conditions. The cytotoxicity of guarana (GL), liposomes (B-Lip), and guarana-loaded liposomes (G-Lip) was evaluated on spontaneously immortalized human keratinocyte cell lines (HaCaT), murine Swiss albino fibroblasts (3T3), and human fibroblasts (1BR.3.G). The evaluation was performed using cellular viability analysis. The techniques used were 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutral red capturing (NRU), and the analyses were conducted after 24, 48, and 72 h of exposure of these cells to the different treatments. The G-Lip exhibited physical-chemical stability for 60 days when the samples were stored in a refrigerator. The GL, B-Lip, and G-Lip demonstrated low cytotoxicity in the three different cell cultures tested since a small reduction in cell viability was only observed at the highest concentrations. In addition, greater cell damage was observed for B-Lip; however, guarana protected the cells from this damage. Thus, G-Lip structures can be considered promising systems for topical applications.

There are several diseases, such as bipolar disorder, for example, where a chronic inflammation related to NLRP3 inflammasome is present. So, it is important to search for new anti-inflammatory agents. Açaí (Euterpe oleracea Mart.) is a Brazilian fruit with antioxidant and anti-inflammatory activities. However, the mechanism of açaí anti-inflammatory potential is still unclear. The objective of this study was to evaluate the anti-inflammatory effect of açaí extract and its mechanism. Macrophages were exposed to phytohemagglutinin to induce inflammation and treated with different concentrations of açaí extract. Cellular proliferation, cell cycle, oxidative metabolism parameters, inflammatory cytokines and NLRP3 have been assessed. 1 μg/mL of açaí extract was able to act as an antioxidant agent. Açaí extract decreased NLRP3 inflammasome levels and reduced pro-inflammatory cytokines. The extract caused cell cycle arresting and decreased proliferation. Obtained results suggest that açaí extract has anti-inflammatory effect and its mechanism of action involve NLRP3 inflammasome modulation.

Aluminum (Al) is ubiquitously present in the environment and known to be a neurotoxin for humans. The trivalent free Al anion (Al3+) can cross the blood-brain barrier (BBB), accumulate in the brain, and elicit harmful effects to the central nervous system (CNS) cells. Thus, evidence has suggested that Al increases the risk of developing neurodegenerative diseases, particularly Alzheimer’s disease (AD). Purinergic signaling has been shown to play a role in several neurological conditions as it can modulate the functioning of several cell types, such as microglial cells, the main resident immune cells of the CNS. However, Al effects on microglial cells and the role of the purinergic system remain elusive. Based on this background, this study is aimed at assessing the modulation of Al on purinergic system parameters of microglial cells. An in vitro study was performed using brain microglial cells exposed to Al chloride (AlCl3) and lipopolysaccharide (LPS) for 96 h. The uptake of Al, metabolism of nucleotides (ATP, ADP, and AMP) and nucleoside (adenosine), and the gene expression and protein density of purinoceptors were investigated. The results showed that both Al and LPS increased the breakdown of adenosine, whereas they decreased nucleotide hydrolysis. Furthermore, the findings revealed that both Al and LPS triggered an increase in gene expression and protein density of P2X7R and A2AR receptors, whereas reduced the A1R receptor expression and density. Taken together, the results showed that Al and LPS altered the setup of the purinergic system of microglial cells. Thus, this study provides new insights into the involvement of the purinergic system in the mechanisms underlying Al toxicity in microglial cells.

Justificativa e Objetivos: Muitos avanços ocorreram em prevenção, diagnóstico e tratamento das doenças infecciosas, porém elas ainda são as principais causas de hospitalização e morte em idosos. O objetivo deste trabalho foi verificar o benefício do uso de antimicrobianos e sua associação com a implementação de outras medidas terapêuticas e com a indicação de cuidados paliativos nas duas últimas semanas de vida de idosos em internação hospitalar, a fim de subsidiar o desenvolvimento de modelos racionais de prescrição para este grupo. Métodos: Foi desenvolvido um estudo retrospectivo realizado pela análise de prontuários dos idosos participantes do estudo epidemiológico do tipo coorte ―Desenvolvimento de uma linha de cuidados para o idoso no Hospital Universitário de Santa Maria‖ que apresentaram óbito como desfecho. Resultados: Dos 97 indivíduos avaliados, 89,7% (n = 87) fizeram uso de antibiótico nas duas últimas semanas de vida. Entre aqueles que utilizaram antibacteriano, 38,9% apresentaram sinais clínicos de melhora após o início do tratamento (n = 28). Assim, foi possível afirmar que não houve associação entre o alívio dos sintomas e o uso de antibacteriano (p = 0,377). Entre aqueles que se beneficiaram da antibioticoterapia, 46,4% foram indicados para infecção respiratória e 14,3% para infecção do trato urinário. Não foi encontrada dependência entre o uso de antibacteriano e as outras medidas terapêuticas adotadas (p = 0,057), nem com a indicação de cuidado paliativo (p = 0,065). Conclusão: Observou-se pouca evidência de benefício no uso de antibacteriano no grupo estudado, o que sinaliza a necessidade de uma adequação de plano de cuidado diferenciada para esse perfil de pacientes.

Mesenchymal stem cells are a population of somatic cells found in several tissues of an adult organism, including adipose tissue. Reactive oxygen species (ROS) can cause cellular alterations, including mutagenesis and genomic instability and the development of diseases. Thus, it is important to understand ROS-induced damage to cell macromolecules such as DNA, proteins, and lipids. In this study, we investigated oxidative stress rates and viability of adipose tissue-derived mesenchymal stem cells (ADSCs) from the greater omentum of rabbits. Cell cultures were analyzed at different passages (1-5) using the dichlorofluorescein acetate assay for measuring ROS production and cell viability tests. ROS levels were highest at passage 2 and cell viability was highest at passage 4.

Ageing can cause disorders such as age-related macular degeneration (AMD), which leads to irreversible visual loss in elderly people. Given that nutrition may influence some age-related disorders, this study investigated, in vivo, the association between self-reported eyesight quality and daily guarana intake in riparian elderly subjects and, in vitro, the effects of guarana (Paullinia cupana) on retinal pigmented epithelium (RPE) cells exposed to paraquat. Just over half of the elderly subjects self-reported poor vision (n = 320, 50.8%), 234 (37.1%) self-reported regular eyesight, whereas just 76 (12.1%) self-reported good vision. Subjects that self-reported good vision presented a higher frequency of habitual guarana consumption. Guarana treatment was able to decrease apoptosis and necrosis events and differentially modulate gene expression and protein levels of caspases 1, 3 and 8 in RPE cells. This work provides new perspectives on the potential use of guarana against eye diseases due to its cytoprotective effects.

Comprender las relaciones de los factores que tienen influencia directa o indirectamente en la obesidad y en el estado nutricional de individuos tendría como resultado una visión amplia y bastante completa de esta relevante cuestión de salud pública. El objetivo de este estudio es evaluar el estado nutricional e identificar los niveles de obesidad en individuos de edades comprendidas entre 30 y 59 años, residentes en la zona urbana de la ciudad de Manaos, Amazonas. Se trata de un estudio transversal, de enfoque cuantitativo y carácter descriptivo. Se calculó la muestra en base a una proporción esperada del 51%, error de muestra de un 2% e intervalo de confianza del 95%, totalizando 2.500 individuos de edades comprendidas entre 30 y 59 años. Se analizaron las siguientes variables demográficas: género, edad, raza, nacionalidad, situación matrimonial y religión; variables relacionadas al estado nutricional y otros agravios: Índice de Masa Corporal (IMC), Circunferencia de la Cintura (CC), Presión Arterial (PA) y Glucemia Capilar (GC). Los resultados de la investigación demostraron que, sumándose a los porcentuales de obesidad I, II y III, el índice alcanzado fue del 32,3% y, sumándose este porcentual a los individuos con sobrepeso, el resultado fue de 73,4%. La investigación ha encontrado un resultado del 24,1% de individuos con PAS≥ 140 / PAD ≥ 80 y 16,3% con índice glicémico elevado. El desarrollo de este estudio nos ha posibilitado una percepción de los envejecientes en la ciudad de Manaos en lo que respecta a la obesidad y estado nutricional. Frente a esto, se observa la necesidad de ofrecer informaciones acerca de este fenómeno.

WHOQOL-Bref is widely used to assess quality of life. The present study estimated the prevalence of elderly people with low quality of life and the association of socio-cultural, economic and health variables. The elderly were classified as low (< 60 points) or regular/good (> 60 points). The elderly (1431) were investigated, most of the elderly were married, with low schooling, with own income and lived with their spouse or other relatives. A large part (20.8%) reported having performed some habitual physical activity, (24.7%) smoked and (7.1%) ingested high amounts of alcohol. The mean WHOQOL-Bref score was 87.9 ± 11.6 points, with 6.1% having poor quality of life and 93.9% regular/good. There was a high number of elderly people with hypertension, type 2 diabetes, cardiovascular diseases and stroke in the low quality of life group. Also, it showed a high frequency in the elderly who reported very poor/poor vision, hearing and the prevalence of hospitalizations. The results suggested that the quality of life standards assessed by the WHOQOL-Bref are similar to the Southern Brazilian regions and the cut-off point used here was reliable for detecting poor quality of life associated with chronic morbidities.

BACKGROUND:Olanzapine (OLZ) is a second-generation antipsychotic drug used for treatment of schizophrenia, bipolar disorder, and other neuropsychiatric conditions. Undesirable side effects of OLZ include metabolic alterations associated with chronic oxidative-inflammation events. It is possible that lithium (Li), a mood modulator that exhibits anti-inflammatory properties may attenuate OLZ-induced oxi-inflammatory effects. METHODOLOGY:To test this hypothesis we activated RAW 264.7 immortalized macrophages with OLZ and evaluated oxidation and inflammation at the gene and protein levels. Li and OLZ concentrations were determined using estimated plasma therapeutic concentrations. RESULTS:OLZ triggered a significant increase in macrophage proliferation at 72 h. Higher levels of oxidative markers and proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, with a concomitant reduction in IL-10, were observed in OLZ-exposed macrophages. Lithium (Li) exposure triggered a short and attenuated inflammatory response demonstrated by elevation of superoxide anion (SA), reactive oxygen species (ROS), IL-1β, and cellular proliferation followed by elevation of anti-inflammatory IL-10 levels. Li treatment of OLZ-supplemented macrophages was able to reverse elevation of oxidative and inflammatory markers and increase IL-10 levels. CONCLUSIONS:Despite methodological limitations related to in vitro protocols, results suggested that Li may attenuate OLZ-induced oxidative and inflammatory responses that result from metabolic side effects associated with OLZ.

Células-tronco mesenquimais são uma população de células somáticas encontradas em vários tecidos de um organismo adulto, incluindo o tecido adiposo. Espécies reativas de oxigênio (ROS) podem causar alterações celulares, incluindo mutagênese e instabilidade genômica e o desenvolvimento de doenças. Assim, é importante entender o dano induzido pelas EROs às macromoléculas celulares, como DNA, proteínas e lipídios. Neste estudo, investigamos as taxas de estresse oxidativo e viabilidade de células-tronco mesenquimais derivadas do tecido adiposo (ADSCs) a partir do omento maior de coelhos. As culturas celulares foram analisadas em diferentes passagens (1-5) utilizando o ensaio de acetato de diclorofluoresceína para medir a produção de ROS e testes de viabilidade celular. Os níveis de EROs foram mais altos na 2ª passagem e a viabilidade celular foi maior na 4ª passagem.

Abstract: Stem cells in regenerative therapy have received attention from researchers in recent decades. The culture of these cells allows studies about their behavior and metabolism. Thus, cell culture is the basis for cell therapy and tissue engineering researches. A major concern regarding the use of cultivated stem cell in human or veterinary clinical routine is the risk of carcinogenesis. Cellular activities require a balanced redox state. However, when there is an imbalance in this state, oxidative stress occurs. Oxidative stress contributes to cytotoxicity, which may result in cell death or genomic alterations, favoring the development of cancer cells. The aim of this study was to determine whether there are differences in the behavior of cultured mesenchymal stem cells from canine adipose tissue according to its site of collection (omentum and subcutaneous) evaluating the rate of proliferation, viability, level of oxidative stress and cytotoxicity over six passages. For this experiment, two samples of adipose tissue from subcutaneous and omentum where taken from a female dog corpse, 13 years old, Pitbull. The results showed greater levels of oxidative stress in the first and last passages of both groups, favoring cytotoxicity and cell death.

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzyme δ-aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

INTRODUÇÃO: a sarcopenia é caracterizada pela perda de massa e funcionalidade muscular e está associada a uma série de disfunções e doenças sistêmicas que acometem os idosos. Também é um dos parâmetros utilizados para definição da síndrome de fragilidade, que é altamente prevalente em idosos, conferindo maior risco para quedas, fraturas, incapacidade, dependência, hospitalização recorrente e mortalidade. Recentemente, a literatura tem reportado que a etiopatogenia da sarcopenia está intimamente relacionada com um aumento na taxa de produção de espécie reativa de oxigênio (ERO), o que pode ocasionar a denervação, perda e atrofia de fibras musculares e consequente perda da força muscular. OBJETIVO: realizar uma revisão narrativa da literatura sobre o papel do estresse oxidativo na gênese da sarcopenia. MÉTODO: revisão narrativa. Foram consultadas as bases de dados MEDLINE, LILACS e SciElo. As buscas foram feitas através das expressões: sarcopenia e envelhecimento, perda de massa muscular em idosos, estresse oxidativo, inflamação e sarcopenia e epidemiologia da sarcopenia. Resultados: a etiologia da sarcopenia é multifatorial e envolve a interação de diversos fatores, incluindo aspectos genéticos, metabólicos, estilo de vida, como os hábitos alimentares (ingestão protéica) e de gasto energético (atividade física), e as EROs desempenham papel-chave na mediação do processo de perda de massa e função muscular associado ao envelhecimento. CONCLUSÃO: ao longo do processo de envelhecimento, o estresse oxidativo torna-se mais perigoso, uma vez que, associado ao declínio dos hormônios sexuais, que exercem efeitos anabólicos sobre o tecido músculo-esquelético, pode acelerar a perda e atrofia desse tecido.

The polyphenol contents and antioxidant capacity of Brazilian red grape juices and wine vinegars were analyzed. Additionally, it was analyzed the human polyphenol absorption and acute effect in plasmatic oxidative metabolism biomarkers after juice ingestion. The organic Bordo grape juice (GBO) presented a higher level of trans-resveratrol, quercitin, rutin, gallic acid, caffeic acid and total flavonoids then other juices and vinegars as well as antioxidant capacity. The plasmatic polyphenol increased 27.2% after GBO juice ingestion. The results showed that juices and vinegars from Brazilian crops present similar chemical and functional properties described in studies performed in other countries.

INTRODUCTION: One of the several metabolic pathways involved in breast carcinogenesis is the human polymorphism in the mitochondrial targeting sequence Ala-9Val of the manganese superoxide dismutase (MnSOD) gene, which has been previously associated with increased risk of breast cancer in females. Since there is no previous report on this polymorphism in male breast cancer, the objective of this study is to analyze MnSOD polymorphism in a population of males and females with breast cancer from the southernmost state of Brazil, compared to healthy controls. METHODS: A case-control study of one hundred patients affected by breast cancer (11 men and 89 women) and 370 healthy age-adjusted database controls was performed. DNA was extracted from paraffin-embedded tumoral tissue. MnSOD polymorphism was determined by PCR-RFLP techniques using restriction enzyme Hae III. Chi-square test was used to compare MnSOD frequency distribution. RESULTS: MnSOD genotypic frequencies in all patients with breast cancer were AA = 15%; AV = 56%; VV = 29% and controls AA = 6.5%; AV = 68.1% and VV = 25.4%. Both male and female patients with breast cancer presented significantly higher AA frequencies compared to controls (p = 0.035), suggesting strong association of this genotype with breast cancer. A 2.15-fold (95% confidence interval [CI] 1.393-4.541) risk of breast cancer was found among individuals carrying the MnSOD AA allele-containing genotypes compared with the MnSOD VV and AV genotypes. DISCUSSION: These results confirm the already established association of MnSOD AA genotype with female breast cancer and further indicate a similar frequency distribution and increased risk in the male population.INTRODUÇÃO: Uma das diversas rotas metabólicas envolvidas no processo de carcinogênese da mama é o polimorfismo Ala-9Val do gene da superóxido dismutase dependente de manganês, cuja associação com o aumento do risco de câncer de mama em mulheres já é bem estabelecida na literatura. Contudo, não existem estudos envolvendo esse polimorfismo no carcinoma de mama em homens, principalmente devido à baixa prevalência dessa neoplasia. O objetivo deste estudo é analisar o polimorfismo da MnSOD em uma população de homens e mulheres com câncer de mama no sul do Brasil, comparando tais achados com controles saudáveis. MÉTODOS: Foi realizado um estudo de caso-controle em cem pacientes com câncer de mama (11 homens e 89 mulheres) e 370 controles saudáveis. O DNA foi extraído do tecido tumoral emblocado em parafina. O polimorfismo da MnSOD foi determinado por técnicas de PCR-RFLP usando a enzima de restrição Hae III. O teste do qui quadrado foi usado para comparar a distribuição das freqüências dos polimorfismos. RESULTADOS: As freqüências genotípicas dos pacientes com câncer de mama foram AA = 15%; AV = 56%; VV = 29% e dos controles AA = 6,5%; AV = 68,1% e VV = 25,4%. Os pacientes com câncer de mama, tanto as mulheres como os homens, apresentaram freqüências significativamente mais elevadas do genótipo AA quando comparadas aos controles (p = 0,035), sugerindo associação forte desse genótipo com o câncer de mama. O intervalo de confiança foi de 1,393-4,541 (95%) e o risco encontrado foi de 2,15 para indivíduos portadores do genótipo AA, quando comparados com os controles que tinham os genótipos VV e AV da MnSOD. DISCUSSÃO: Esses resultados confirmam a associação já estabelecida do genótipo da MnSOD AA com câncer de mama em mulheres e indicam distribuição de freqüência similar e risco aumentado na população masculina.

INTRODUÇÃO: A mediastinite é uma grave complicação da cirurgia cardíaca, com incidência de 0,4% a 5%, mortalidade de 10% a 47% e elevada morbidade. OBJETIVO: Identificar os fatores de risco pré e transoperatórios para mediastinite após a cirurgia cardíaca em nosso hospital. MÉTODO: Estudo prospectivo de 1298 pacientes submetidos à cirurgia cardíaca no Hospital São Lucas no período de março de 1997 a maio de 2000. Foram avaliados nove potenciais fatores de risco associados a mediastinite (obesidade, diabetes mellitus, doença pulmonar obstrutiva crônica, ponte mamária, tempo de bypass cardiopulmonar, tabagismo, sexo, fração de ejeção e cirurgia cardíaca prévia), através de análise univariada, seguida de análise multivariada de regressão logística. RESULTADOS: Dos 1298 pacientes estudados, 62,6% eram homens e 18,3% eram diabéticos. Trinta e oito (2,9%) pacientes apresentaram mediastinite e seis (15,8%) destes morreram. Quatro variáveis foram selecionadas por análise univariada (pOBJECTIVE: Mediastinitis is a serious complication of open-heart surgery, with an incidence that varies from 0.4% to 5%, mortality from 10% to 47% and a high morbidity rate. OBJECTIVE: To identify preoperative and trans-operative risk factors of mediastinitis after open-heart surgery in our hospital. METHOD: This was a prospective study of 1298 patients submitted to the open-heart surgery in São Lucas hospital in the period from March 1997 to May 2000. Nine potential risk factors associated with mediastinitis were studied (obesity, diabetes mellitus, chronic obstructive pulmonary disease -COPD-, internal mammary artery, cardiopulmonary bypass time, smoking, gender, ejection fraction and previous heart surgery) using univariate analysis, where necessary followed by multivariate logistic regression. RESULTS: Of the 1298 studied patients, 62.6% were men and 18.3 suffered from diabetes. Thirty-eight patients (2.9%) presented with mediastinitis postoperatively, and six (15.8%) of these died. Four variables identified as risk factors by univariate analysis (p

Methotrexate (MTX) is a folic acid antagonist used in high doses as an anti-cancer treatment and in low doses for the treatment of some autoimmune diseases. MTX use has been linked to oxidative imbalance, which may cause multi-organ toxicities that can be attenuated by antioxidant supplementation. Despite the oxidative effect of MTX, the influence of antioxidant gene polymorphisms on MTX toxicity is not well studied. Therefore, we analyzed here whether a genetic imbalance of the manganese-dependent superoxide dismutase (SOD2) gene could have some impact on the MTX cytotoxic response. An in vitro study using human peripheral blood mononuclear cells (PBMCs) obtained from carriers with different Ala16Val-SOD2 genotypes (AA, VV and AV) was carried out, and the effect on cell viability and proliferation was analyzed, as well as the effect on oxidative, inflammatory and apoptotic markers. AA-PBMCs that present higher SOD2 efficiencies were more resistance to high MTX doses (10 and 100 µM) than were the VV and AV genotypes. Both lipoperoxidation and ROS levels increased significantly in PBMCs exposed to MTX independent of Ala16Val-SOD2 genotypes, whereas increased protein carbonylation was observed only in PBMCs from V allele carriers. The AA-PBMCs exposed to MTX showed decreasing SOD2 activity, but a concomitant up regulation of the SOD2 gene was observed. A significant increase in glutathione peroxidase (GPX) levels was observed in all PBMCs exposed to MTX. However, this effect was more intense in AA-PBMCs. Caspase-8 and -3 levels were increased in cells exposed to MTX, but the modulation of these genes, as well as that of the Bax and Bcl-2 genes involved in the apoptosis pathway, presented a modulation that was dependent on the SOD2 genotype. MTX at a concentration of 10 µM also increased inflammatory cytokines (IL-1β, IL-6, TNFα and Igγ) and decreased the level of IL-10 anti-inflammatory cytokine, independent of SOD2 genetic background. The results suggest that potential pharmacogenetic effect on the cytotoxic response to MTX due differential redox status of cells carriers different SOD2 genotypes.

Theories of lifespan evolution are a source of confusion amongst aging researchers. After a century of aging research the dispute over whether the aging process is active or passive persists and a comprehensive and universally accepted theoretical model remains elusive. Evolutionary aging theories primarily dispute whether the aging process is exclusively adapted to favor the kin or exclusively non-adapted to favor the individual. Interestingly, contradictory data and theories supporting both exclusively programmed and exclusively non-programmed theories continue to grow. However, this is a false dichotomy; natural selection favors traits resulting in efficient reproduction whether they benefit the individual or the kin. Thus, to understand the evolution of aging, first we must understand the environment-dependent balance between the advantages and disadvantages of extended lifespan in the process of spreading genes. As described by distinct theories, different niches and environmental conditions confer on extended lifespan a range of fitness values varying from highly beneficial to highly detrimental. Here, we considered the range of fitness values for extended lifespan and develop a fitness-based framework for categorizing existing theories. We show that all theories can be classified into four basic types: secondary (beneficial), maladaptive (neutral), assisted death (detrimental) and senemorphic aging (varying between beneficial to detrimental). We anticipate that this classification system will assist with understanding and interpreting aging/death by providing a way of considering theories as members of one of these classes rather than consideration of their individual details.

CONTEXT AND OBJECTIVES: Despite the decline in the prevalence of tobacco use in many countries, including Brazil, there are growing numbers of smokers who continue to smoke at a low daily rate, or less frequently (non-daily smokers). This group needs to be better characterized in order to direct preventive actions and public health policies. The aim here was to compare lifestyle, health characteristics and alcoholism problems among young adult smokers, non-daily smokers and non-smokers. DESIGN AND SETTING: This was a cross-sectional study in which volunteers from the university community and its surrounds in Santa Maria, State of Rio Grande do Sul, Brazil, were included between October 2007 and January 2008. METHODS: Out of 1240 volunteers initially contacted in a university cafeteria, a total of 728 participants of mean age 22.45 ± 3.32 years were selected for final analysis. Data were collected using structured questionnaires. RESULTS: In general, it was observed that the non-daily smokers showed intermediate characteristics in relation to the smokers and non-smokers. However, there was a significant association between non-daily smoking and alcohol abuse. The non-daily smokers presented an odds ratio of 2.4 (95% confidence interval: 1.10-5.48) in relation to the daily smokers and an odds ratio of 3.3 (confidence interval: 1.7-6.5) in relation to the non-smokers, with regard to presenting a positive CAGE test, thereby indicating alcohol abuse or dependence. CONCLUSION: The study suggested that non-daily smoking and alcohol consumption were concomitant behaviors.

O Estado Rio Grande do Sul apresenta uma grande diversidade étnica e cultural na sua população. Entretanto, pouco se sabe sobre o perfil genético desta população em relação às doenças crônicas não-transmissíveis (DCNT) e o do padrão de herança de acordo com a origem étnica. Fatores como etnia e composição genética, em conjunto com a Reforma Sanitária brasileira e com o estilo de vida, têm possivelmente contribuído de forma substancial para o aumento da expectativa média de vida ao nascer e da longevidade dos gaúchos. A população do Rio Grande do Sul tem apresentado um acelerado processo de envelhecimento populacional e com um padrão diferenciado de morbi-mortalidade para as faixas etárias acima de 60 anos. O aumento da longevidade da população trouxe consigo um aumento não somente da incidência e prevalência, mas também da mortalidade por DCNT, tais como doenças cardiovasculares e neoplasias. Por isso, as políticas públicas de saúde precisam contemplar as peculiaridades étnicas, culturais e biológicas para que a população possa envelhecer com qualidade de vida. É dentro desse contexto que o presente artigo pretende contribuir na discussão do processo de envelhecimento populacional do Rio Grande do Sul.

INTRODUÇÃO: com o envelhecimento, ocorre perda gradual do volume da massa muscular, responsável por quase toda a perda da força nos idosos. Estudos têm mostrado que a atividade física pode diminuir a morbidade por doenças cardiovasculares, acidente vascular cerebral e aumentar a autonomia e independência. OBJETIVO: analisar a associação entre nível de atividade física, risco cardiovascular e o polimorfismo do gene da Apolipoproteína E em idosos. MÉTODOS: estudo retrospectivo, observacional a partir de um banco de dados de base populacional onde foram selecionados idosos sedentários e com histórico de atividade física regular que eram portadores e não portadores do alelo e4 do gene da apolipoproteína E. Foram aplicados os seguintes questionários: (a) International Physical Activity Questionnaire (IPAC); (b) recordatório 24 horas e miniquestionário de frequência alimentar; (c) análises bioquímicas do perfil lipídico e glicêmico. RESULTADOS: 255 idosos foram investigados; destes, 51 (20%) eram homens e 204, mulheres (80%). A idade média da amostra foi de 67,8±5.9 anos de idade (mínimo 60 máximo 86 anos). A frequência dos alelos foi de: alelo e3 =0.78, e4=0.16 e e2=0.06; 45 idosos (17.6%) possuíam pelo menos um alelo e4 e eram sedentários, 31 (12.2%) possuíam pelo menos um alelo e4 e apresentava atividade física regular (ativa), 50 (19.6%) foram classificados como tendo os demais alelos da apoE (e2/e3) e ativos enquanto 129 (60.6%) eram e2/e3 e sedentários. CONCLUSÃO: a atividade física poderia ser um fator importante na atenuação dos efeitos genéticos negativos associados ao alelo e4 do polimorfismo da apoE.

Background: The impact of regular and irregular physical activity in body composition, muscle mass and strength of the elderly is not well studied yet. Objective: To compare anthropometric variables, muscle and fat thickness, mobility, handgrip and lower limb strength between regularly and irregularly active elderly classified by the International Physical Questionnaire Activity Questionnaire. Methods: A cross-sectional study conducted with 75 elderly people (14 males and 61 females) who practiced regular (RPA=10) or irregular physical activity (IPA=65). Anthropometric variables (body mass index, circumferences and skinfolds), muscular and fat thickness (triceps, vastus lateralis and medial gastrocnemius [ultrasound]), handgrip strength (Crown dynamometer), lower limb strength (sit and stand up test) and mobility were collected from the sample. Physical activity was assessed by the International Physical Questionnaire Activity Questionnaire. Results: No significant differences were found in the anthropometric, skeletal muscle and fat mass and force variables between two groups (p>0.05). However, elders who practiced irregular physical activity presented best performance in the time up and go test than those who practiced regular physical activity (p=0.008). Results were independent of sex and age of subjects (p=0.017). Conclusion: The study showed no significant differences between elderly that performed physical activity in regular or irregular way in relation body composition and force parameters. However, the results suggest that even irregular physical activity can help the elderly individuals in the mobility, and prevent falls.

Resumo Introdução: estudos sobre o idoso que vive na Região Norte do Brasil ainda são incipientes e necessários para subsidiar programas de saúde pública. Objetivos: o estudo aqui apresentado descreve o delineamento geral do Projeto Idoso da Floresta, analisando os principais indicadores de saúde de idosos inseridos no ESF-SUS em Manaus-AM, distribuídos nos quatro distritos de saúde investigados. Metodologia: foi feita análise amostral por conglomerados em dois estágios: (1º) seleção das unidades básicas de saúde da família (UBS) como unidades de seleção; (2º) seleção do idoso como unidade amostral, escolhido randomicamente entre as famílias atendidas nas UBSs. Resultados: 1.509 idosos foram incluídos, sendo 810 (53,6%) mulheres (67,6±7,7 anos) e 699 (46,4%) homens com idade média de 66,8± 6,9 anos. Em geral, o idoso investigado era casado/viúvo (94,8%), com nenhuma ou baixíssima escolaridade (46,5%), vivia em casas (94,7%), recebia algum auxílio (57,5%), era aposentado (64,5%), sem renda ou recebia até um salário-mínimo (67,9%). Destes, 85,5% eram autônomos e 10,3% possuíam mais de quatro morbidades. Os indicadores tenderam a ser significativamente diferenciados conforme o distrito investigado. Conclusão: em geral, os perfis socioeconômico e cultural, da prevalência de morbidades e dependência tenderam a ser similares ao descrito em outros estudos brasileiros. Entretanto, existiram diferenças entre os distritos que devem ser consideradas nas estratégias de atenção e saúde do idoso. Análises complementares que estratifiquem a amostra por sexo, idade e perfil socioeconômico e cultural precisam ser conduzidas.

ABSTRACT Advances in the studies with adult mesenchymal stem cells (MSCs) have turned tissue regenerative therapy into a promising tool in many areas of medicine. In orthopedics, one of the main challenges has been the regeneration of cartilage tissue, mainly in diarthroses. In the induction of the MSCs, in addition to cytodifferentiation, the microenvironmental context of the tissue to be regenerated and an appropriate spatial arrangement are extremely important factors. Furthermore, it is known that MSC differentiation is fundamentally determined by mechanisms such as cell proliferation (mitosis), biochemical-molecular interactions, movement, cell adhesion, and apoptosis. Although the use of MSCs for cartilage regeneration remains at a research level, there are important questions to be resolved in order to make this therapy efficient and safe. It is known, for instance, that the expansion of chondrocytes in cultivation, needed to increase the number of cells, could end up producing fibrocartilage instead of hyaline cartilage. However, the latest results are promising. In 2014, the first stage I/II clinical trial to evaluate the efficacy and safety of the intra-articular injection of MSCs in femorotibial cartilage regeneration was published, indicating a decrease in injured areas. One issue to be explored is how many modifications in the articulate inflammatory environment could induce differentiation of MSCs already allocated in that region. Such issue arose from studies that suggested that the suppression of the inflammation may increase the efficiency of tissue regeneration. Considering the complexity of the events related to the chondrogenesis and cartilage repair, it can be concluded that the road ahead is still long, and that further studies are needed.

Moringa stenopetala is often consumed as food and used in folkloric medicine for the management of several diseases including neurodegenerative diseases. This study investigated the protective effect and antioxidant efficacy of aqueous extract of Moringa stenopetala in BV-2 microglial cells. Aqueous extracts of M. stenopetala were prepared, lyophilized and reconstituted in 0.5% dimethylsulphoxide (DMSO). Cells were treated with M. stenopetala extracts (0.1–100 µg/ml) for cell viability assay and nitric oxide (NO) production tests. However, M. stenopetala extract (50 µg/ml) was used in the treatment of cells for the determination of protein carbonyl content and reactive oxygen species (ROS) level. Incubation of BV-2 microglia cell with M. stenopetala extract maintained cell viability, diminished NO and ROS levels, and reduced protein carbonyl contents. Chlorogenic acid, rutin, kaempferol and quercetin derivatives were the main phenolic compounds identified in M. stenopetala leaf extract. In conclusion, this study suggests that M. stenopetala extract is rich in antioxidant and contains bioactive neuroprotective agents.