The Amazonian Camu-Camu Fruit Modulates the Development of Drosophila melanogaster and the Neural Function of Adult Flies under Oxidative Stress Conditions.

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.

Polifarmácia, medicamentos potencialmente inapropriados e a vulnerabilidade de pessoas idosas / Polypharmacy, potentially inappropriate medications, and the vulnerability of older adults

Resumo Objetivo Analisar a frequência de polifarmácia e prescrição de medicamentos potencialmente inapropriados (MPI) segundo os Critérios de Beers e CBMPI em pessoas idosas com vulnerabilidade clínico-funcional. Método Trata-se de um estudo transversal onde analisou-se os prontuários de 496 participantes com 60 anos ou mais, atendidos em primeira consulta em uma Policlínica Gerontológica. Os dados sociodemográficos, medicamentos, e o Índice de Vulnerabilidade Clínico Funcional 20 (IVCF-20) e quedas foram extraídos dos prontuários. A polifarmácia foi definida como o uso simultâneo de cinco ou mais medicamentos. Os participantes foram classificados em três grupos: robusto, em risco e vulnerável. Resultados A análise demonstrou que 69 (13,91%) dos participantes faziam uso de polifarmácia. Entre os usuários de polifarmácia, 40 (57,97%) faziam uso de pelo menos um MPI. Os MPIs mais encontrados foram a glibenclamida e o omeprazol, respectivamente. Pessoas idosas com vulnerabilidade apresentaram um risco três vezes maior de apresentar polifarmácia (RP 3,59; IC95% 2,109-6,092). Conclusão O uso de polifarmácia e MPI neste estudo estavam associados à vulnerabilidade da pessoa idosa, reforçando a necessidade de avaliação criteriosa de prescrições medicamentosas para essa população.

Abstract Objective To analyze the frequency of polypharmacy and the prescription of Potentially Inappropriate Medications (PIM) according to the Beers Criteria and CBMPI in older adults with clinical-functional vulnerability. Method This is a cross-sectional study where the medical records of 496 participants aged 60 and older, seen in their first appointment at a Gerontological Polyclinic, were analyzed. Sociodemographic data, medications, the Clinical-Functional Vulnerability Index-20 (IVCF-20), and falls were extracted from the medical records. Polypharmacy was defined as the simultaneous use of five or more medications. Participants were classified into three groups: robust, at risk, and vulnerable. Results The analysis revealed that 69 (13.91%) participants were using polypharmacy. Among polypharmacy users, 40 (57.97%) were using at least one PIM. The most commonly found PIM were glibenclamide and omeprazole, respectively. Older adults with vulnerability were three times more likely to have polypharmacy (OR 3.59; 95% CI 2.109-6.092). Conclusion The use of polypharmacy and PIM in this study was associated with the vulnerability of older adults, emphasizing the need for a thorough evaluation of medication prescriptions for this population.

A coffee enriched with guarana, selenium, and l-carnitine (GSC) has nutrigenomic effects on oxi-inflammatory markers of relapsing-remitting multiple sclerosis patients: A pilot study.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1ß, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions.

Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats.

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.

Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells.

INTRODUCTION: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress. Additionally, patients also have increased peripheral and neural chronic inflammation. The Brazilian fruit, açaí, has been demonstrated to be a neuroprotective agent through its recovery of mitochondrial complex I activity. This extract has previously shown anti-inflammatory effects in inflammatory cells. However, there is a lack of understanding of potential anti-neuroinflammatory mechanisms, such as cell cycle involvement. OBJECTIVE: The objective of this study is to evaluate the anti-neuroinflammatory potential of an açaí extract in lipopolysaccharide-activated BV-2 microglia cells. METHODS: Açaí extract was produced and characterized through high performance liquid chromatography. Following açaí extraction and characterization, BV-2 microglia cells were activated with LPS and a dose-response curve was generated to select the most effective açaí dose to reduce cellular proliferation. This dose was then used to assess reactive oxygen species (ROS) production, double-strand DNA release, cell cycle modulation, and cytokine and caspase protein expression. RESULTS: Characterization of the açaí extract revealed 10 bioactive molecules. The extract reduced cellular proliferation, ROS production, and reduced pro-inflammatory cytokines and caspase 1 protein expression under 1 µg/mL in LPS-activated BV-2 microglia cells but had no effect on double strand DNA release. Additionally, açaí treatment caused cell cycle arrest, specifically within synthesis and G2/Mitosis phases. CONCLUSION: These results suggest that the freeze-dried hydroalcoholic açaí extract presents high anti-neuroinflammatory potential.

Amazon-derived nutraceuticals: Promises to mitigate chronic inflammatory states and neuroinflammation.

Nutraceuticals have been the focus of numerous research in recent years and accumulating data support their use for promoting some health benefits. Several nutraceuticals have been widely studied as supplements due to their functional properties ameliorating symptoms associated with neurological disorders, such as oxidative stress and chronic inflammatory states. This seems to be the case of some fruits and seeds from the Amazon Biome consumed since the pre-Columbian period that could have potential beneficial impact on the human nervous system. The beneficial activities of these food sources are possibly related to a large number of bioactive molecules including polyphenols, carotenoids, unsaturated fatty acids, vitamins, and trace elements. In this context, this review compiled the research on six Amazonian fruits and seeds species and some of the major nutraceuticals found in their composition, presenting brief mechanisms related to their protagonist action in improving inflammatory responses and neuroinflammation.

Açaí (Euterpe oleracea Mart.) as a Potential Anti-neuroinflammatory Agent: NLRP3 Priming and Activating Signal Pathway Modulation.

Neurological disorders have been demonstrated to be associated with mitochondrial dysfunction. This impairment may lead to oxidative stress and neuroinflammation, specifically promoted by NLRP3 expression. Açaí (Euterpe oleracea Mart.) has been studied in this field, since it presents important biological activities. We investigated açaí extract's anti-neuroinflammatory capacity, through NLRP3 inflammasome modulation. Microglia (EOC 13.31) were exposed to LPS and nigericin, as agents of inflammatory induction, and treated with açaí extract. Additionally, we used lithium (Li) as an anti-inflammatory control. Three different experiment models were conducted: (1) isolated NLRP3 priming and activation signals; (2) combined NLRP3 priming and activation signals followed by açaí extract as a therapeutic agent; and (3) combined NLRP3 priming and activation signals with açaí extract as a preventive agent. Cells exposed to 0.1 µg/mL of LPS presented high proliferation and increased levels of NO, and ROS, while 0.1 µg/mL of açaí extract was capable to reduce cellular proliferation and recover levels of NO and ROS. Primed and activated cells presented increased levels of NLRP3, caspase-1, and IL-1ß, while açaí, Li, and orientin treatments reversed this impairment. We found that açaí, Li, and orientin were effective prophylactic treatments. Preventative treatment with Li and orientin was unable to avoid overexpression of IL-1ß compared to the positive control. However, orientin downregulated NLRP3 and caspase-1. Lastly, primed and activated cells impaired ATP production, which was prevented by pre-treatment with açaí, Li, and orientin. In conclusion, we suggest that açaí could be a potential agent to treat or prevent neuropsychiatric diseases related to neuroinflammation.

Physical activity is associated with low-level stress among a sample of seniors during COVID-19 outbreak? / Atividade física está associada com baixos níveis de estresse em uma amostra de idosos durante a pandemia de COVID-19?

This study aimed to verify the association of physical activity, behaviors, and health conditions with stress among a sample of older adults from Manaus, Brazil, during the COVID-19 outbreak. This is a cross-sectional analysis of 79 older adults (76% female; age: 68.24 ± 6.82 years) from Fundação Universidade Aberta da Terceira Idade (FUnATI). The perceived stress (PS) was assessed by the Per-ceived Stress Scale, while a questionnaire via telephone call. The variables also included physical ac-tivity, sleep quality, sociodemographic, and health condition variables. Linear Bayesian mixed-effects regression models were applied to verify the association between these correlates with PS. Older people who met the recommendations before the COVID-19 outbreak but did not meet the same recommendations during the COVID-19 outbreak have a higher PS score compared to those older people who did not meet the PA recommendations at either time. In contrast, those elderly people who met PA recommendations before and during the COVID-19 outbreak had a lower PS score compared to their peers who did not meet physical activity recommendations at either time. Those older people who did not meet the PA recommendations before the COVID-19 outbreak, but did meet the PA recommendations during the COVID-19 outbreak, did not have significant differences in the PS score compared to their peers who did not meet the PA recommendations in either mo-ment. Sleep changes and high BMI were negatively associated with PS. The maintenance of physical activity during the pandemic was associated with lower levels of stress in older people

Este estudo teve como objetivo verificar a associação de atividade física, comportamentos e condições de saúde associadas ao estresse em uma mostra de idosos de Manaus, Brasil, durante o surto COVID-19. Trata-se de uma análise transversal (n = 79 idosos; 76% mulheres; idade: 68,24 ± 6,82 anos) da Fundação Universi-dade Aberta da Terceira Idade (FUnATI). O estresse percebido (EP) foi avaliado utilizando a Escala de Estresse Percebido, aplicado via ligação telefônica. O questionário também incluiu atividade física, quali-dade do sono, variáveis sociodemográficas e de condição de saúde. Modelos de regressão linear Bayesiana de efeitos mistos foram aplicados para verificar a associação entre esses correlatos com EP. Idosos que atendiam às recomendações de AF antes do surto de COVID-19 mas não mantiveram a prática durante o surto apre-sentaram pontuação de EP mais alta em comparação com os idosos que não atendiam às recomendações em nenhum dos momentos. Em contraste, os idosos que mantiveram os níveis de AF tiveram uma pontuação de EP mais baixa. Idosos que não atenderam às recomendações de AF antes do surto de COVID-19, mas atenderam às recomendações de PA durante o surto de COVID-19 não tiveram diferenças significativas na pontuação de EP. Mudanças no sono e alto IMC foram associados negativamente com o EP. A manutenção da atividade física durante a pandemia foi associada a níveis mais baixos de estresse em pessoas mais velhas

Superoxide-anion triggers impairments of immune efficiency and stress response behaviors of Eisenia fetida earthworms.

Superoxide-hydrogen peroxide (S-HP), triggered by Val16Ala-SOD2 human polymorphism, may influence the risk of depression. Therefore, it is plausible that higher basal S-anion levels and chronic inflammatory states associated with the VV-SOD2 genotype can negatively modulate the stress response associated with resilience in various species, from primitive species to humans. To test this hypothesis, Eisenia fetida earthworms were exposed for 24 h to 30 nM rotenone, which causes mitochondrial dysfunction by generating high S-anion levels (known as the "VV-like phenotype"), and 10 µM porphyrin, a SOD2-like compound, which generates elevated HP levels (known as the "AA-like phenotype"). The results suggested that both S-anion and HP acted as signaling molecules, differentially altering the immune function and acute hydric stressful response. Although the AA-like phenotype improved the immune and stress response efficiencies, the VV-like phenotype showed a downregulated expression of the toll-like receptor (EaTLR, JX898685) and antimicrobial peptide (AMP) (AF060552) genes, which triggered the impairment of encapsulation and earthworms extracellular trap (EET) processes used by earthworms to trap and destroy microorganisms. When exposed to adverse environments and dangerous hydric stress, VV-like earthworms exhibited an impulsive behavior and failed to quickly identify and migrate to a protected environment, unlike control earthworms and AA-like earthworms. All results corroborated that the S-anion imbalance could concomitantly induce alterations in immune function and stress behavior related to earthworm survival. From a human perspective, this information may corroborate the potential specific role of superoxide anion in the modulation of the stress response, resilience, and risk of depression.

In Vitro Biological Properties of Solanum sessiliflorum (Dunal), an Amazonian Fruit.

Solanum sessiliflorum is an Amazonian fruit (cubiu) that has been domesticated since pre-Colombian era. It is also used in folk medicine to treat some clinical conditions. This investigation chemically characterized and analyzed the in vitro antioxidant and antitumoral effect of a cubiu pulp/seed hydroalcoholic extract. Cubiu extract was chemically characterized by high-performance liquid chromatography with diode array detector (HPLC-DAD), its antioxidant capacity measured by 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the following complementary in vitro protocols were performed: (1) cytoprotective effect of cubiu on human peripheral blood mononuclear cells (PBMCs) exposed to H2O2, a genotoxic and procarcinogen molecule; (2) effect of cubiu on low density lipoproteins oxidation; and (3) cytotoxic and antiproliferative effect on breast (MCF-7) and colorectal (HT-29) cancer cell lines. Biochemical and flow cytometry analyses were conducted in these protocols. Cubiu extract presented high concentrations of caffeic and gallic acids, beta-carotene, catechin, quercetin, and rutin, and its antioxidant capacity was confirmed. Cubiu attenuated H2O2 cytotoxicity on PBMCs, presented lowering effect on LDL oxidation, and induced mortality and proliferative inhibition of colorectal cancer cells. In cancer cells, cubiu extract at 10 µg/mL showed similar effects to 5-fluorouracil chemo drug reducing its viability and frequency of S-phase, indicating that cells are undergoing mitosis. In summary, despite the limitations of in vitro protocols, our results suggest that cubiu has several biological properties that affect human health.

Violência intrafamiliar contra a pessoa idosa em área urbana com suporte de proteção social e de saúde / Interfamily violence against elderly people in urban area with support of social and health protection

Este estudo tem como objetivo estimar a prevalência da violência contra a pessoa idosa e investigar como ela se apresenta em área urbana com suporte de serviços de proteção social e de saúde destinados ao atendimento do idoso. Pesquisa quantitativa, trans- versal e descritiva realizada com 380 idosos residentes na zona sul da cidade de Manaus, área mais equipada com serviços de proteção social e de saúde para idosos. Foi calculada uma margem de erro de 5% e Coeficiente de Confiança de 95%. Utilizou-se Instrumento de Avaliação de Violência e Maus-Tratos Contra a Pessoa Idosa usado pelo Ministério da Saúde nos Cadernos de Atenção Básica. A prevalência de violência foi de 30,3% e ultrapassou a média de muitos estudos brasileiros. A violência psicológica foi a mais preva- lente, com taxa acima da média nacional, seguida da financeira e da física. As variáveis "idade", "renda familiar", "violência financeira" e "violência física" apresentaram forte associação (p < 0,05). O número ampliado de unidades de acolhimento e notificação de violência não garantiu prevalência significantemente menor em relação à taxa nacional, indicando que o problema possa estar nas relações intrafamiliares conflituosas. Sugerem-se estudos que possam identificar a disfuncionalidade familiar como preditora de violência contra pessoa idosa e uma maior atuação das instituições que lidam com a problemática, na promoção de uma cultura de paz no âmbito da família e da comunidade.(AU)

The objective was to estimate the prevalence of violence against the elderly and to investigate how it presents itself in an urban area with support from social protection and health services for the elderly. Quantitative, cross-sectional and descriptive research carried out with 380 elderly people living in the southern area of the city of Manaus, an area more equipped with social protection and health services for the elderly. A 5% margin of error and a 95% confidence coefficient were calculated. An Instrument for the Assessment of Violence and Mistreatment against the Elderly, used by the Ministry of Health in the Primary Care Notebooks, was applied. The prevalence of violence was 30.3% and exceeded the average of many Brazilian studies. The psychological violence was the most prevalent with a rate above the national average, followed by financial and physical. The variables age, family income, financial and physical violence showed a strong association (p<0.05). The increased number of reception units and notification of violence did not guarantee a significantly lower prevalence in relation to the national rate, indicating that the problem may be in conflicting interfamily relationships. It suggests studies that can identify family dysfunctionality as a predictor of violence against the elderly and the greater role of institutions that deal with the problem, in promoting a culture of peace within the family and community.(AU)

The Val16Ala-SOD2 polymorphism affects cyto-genotoxicity of pyridostigmine bromide on human peripheral blood mononuclear cells.

Pyridostigmine bromide (PB), an acetylcholinesterase (AChE) enzyme inhibitor. Experimental evidence showed that when combined with other drugs or exercise, PB caused extensive neural and/or systemic oxidative stress. However, no studies have been conducted on the genetic influence associated with basal oxidative superoxide-hydrogen peroxide (S-HP) imbalance, such as that triggered by Val16Ala-SOD2 single nucleotide polymorphism (SNP, rs4880). This SNP, (homozygous genotypes) has been associated with several chronic degenerative disorders. Therefore, we evaluated whether the SOD-SNP could alter cyto-genotoxic effects triggered by different PB-concentrations in peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from volunteers carrying different SOD2-genotypes and were cultured with various concentrations of PB. PB effects in quantity of enzyme AChE, mortality rate, oxidative stress markers, and DNA damage were assessed. Protein and gene expression of antioxidant enzymes, apoptotic markers and DNA repair enzyme, were evaluated in 24 h cultures. In general, PB up-regulated expression of antioxidant enzymes, and did not trigger apoptotic events. However, AA-PBMCs seemed more sensitive to PB exposure, in a protein decrease of the enzyme AChE by 10%, cell-mortality at concentrations of 20 and 40 ng/mL, protein carbonylation, and DNA damage, as analyzed by the Comet assay. Contrarily, PB demonstrated cyto-genoprotective effects on V-allele cells. These results indicated that genetic factors that increase HP-release may affect PB efficiency and safety.

Guarana improves behavior and inflammatory alterations triggered by methylmercury exposure: an in vivo fruit fly and in vitro neural cells study.

Methylmercury (MeHg) is a well-known environmental pollutant associated with neurological and developmental deficits in animals and humans. However, epidemiological data showed that people living in the Amazon region although exposed to MeHg do not present these effects probably due to the protective effect of certain foods. We hypothesized here if guarana, a highly caffeinated fruit and consumed on a daily basis by Amazon people, could have some protective effect against MeHg toxicity using two complementary approaches. To assess locomotor impairment and sleep disruption, we used fruit fly (Drosophila melanogaster) model, and to evaluate neuroinflammation, we used human SH-SY5Y neural cells by measuring inflammatory cytokines levels. Results showed that guarana had a protective effect on the locomotor activity of male fruit flies reducing the excessive sleepiness caused by MeHg and increasing daily activity. Also, guarana increased the viability of flies and attenuated neural cells mortality. In addition, guarana reduced all pro-inflammatory cytokines levels increased by MeHg, along with caspase-1, caspase -3, caspase-8, and 8-dOHG levels, whereas increased the anti-inflammatory (IL-10) cytokine levels, which was decreased by MeHg. Our study provides new insights on the protective effects of guarana on the viability, locomotor activity, sleep, and activity patterns in vivo and the in vitro neuronal anti-inflammatory effect against MeHg toxicity.

Correction to: The Influence of a Xanthine-Catechin Chemical Matrix on in vitro Macrophage-Activation Triggered by Antipsychotic Ziprasidone.

After publication of our article it came to our attention that it contains a number of errors with regard to the citations. The details are provided below.

The Influence of a Xanthine-Catechin Chemical Matrix on in vitro Macrophage-Activation Triggered by Antipsychotic Ziprasidone.

Ziprasidone (ZIP) is an effective antipsychotic with low side effects than other second-generation antipsychotics. Despite this, there are reports of adverse events and previous studies associating the use of ZIP the inflammatory response. It is possible to infer that bioactive molecules present in some foods could attenuate peripheral inflammatory and oxidative stress potentially triggered ZIP. This is the case of guaraná xanthine-catechin chemical matrix (XC-Mix) that presents caffeine, theobromine, and catechin. The in vitro protocols using murine RAW 264.7 cell macrophages were ZIP-exposure in culture medium supplemented with chemical isolated and admixture of Caf, The, and Cat. Main results showed that supplementation with isolated and XC-mix had a lowering effect on 72 h macrophages proliferation. XC-mix with 1:1:1 proportion at 25 µg/mL of each caffeine, theobromine, and catechin, molecules present lowering effect on nitric oxide levels, oxidative stress markers (DNA oxidation quantified by 8-hydroxy-2' -deoxyguanosine), lipoperoxidation, and protein carbonylation. XC-mix also decreased protein levels and downregulated genes of proinflammatory cytokines (IL-1ß, IL-6, TNF-α). At contrary, XC-Mix increased levels and upregulated gene of anti-inflammatory IL-10 cytokine. The results suggest that XC-matrix could present some beneficial action on peripheral proinflammatory effects ZIP-triggered. Complementary in vivo studies could be useful to confirm these in vitro findings described here.

Brazil nut improves the oxidative metabolism of superoxide-hydrogen peroxide chemically-imbalanced human fibroblasts in a nutrigenomic manner.

There are some genes associated to the risk of chronic diseases that present potential nutrigenetic response, such as the human manganese-dependent superoxide dismutase gene (Val16Ala-SOD2, rs4880) for which homozygous genotypes (VV and AA) are associated with higher basal superoxide (S) and hydrogen peroxide (HP) levels, respectively. It is possible that the VV- and AA-imbalance could be attenuated by selenium(Se)-rich foods such as Brazil nut (BN). To test this hypothesis, we conducted an in vitro protocol triggering a chemical S-HP imbalance by exposure of dermal fibroblast cells (HFF-1) to paraquat, which generates high S levels (VV-like treatment) and porphyrin (MnTBAP), which generates high HP levels (AA-like treatment). Modulation of cell growth and pro-oxidative and antioxidant markers were evaluated. BN aqueous extract (BNAE) most effective concentration which increased cell growth and decreased oxidative metabolism indicators of imbalanced cells was 75 ng Se/mL. However, this effect was not directly affected by the S-HP imbalance: in AA-SOD2-like cells, thioredoxin reductase (TrxR-1) gene was upregulated and in VV-SOD2-like cells an upregulation of glutathione peroxidase (GPx-1) gene expression was observed, however, this regulation occured in a homeostatic manner. These results suggest that BNAE was able to minimize negative effects in both directions of the S-HP imbalance, by modulation of different oxidative-metabolic pathways.

Cognitive function and its associations in older adults from Amazonas, Brazil / Função Cognitiva e suas associações em adultos-idosos do estado do Amazonas, Brasil

The objectives of this study were: (1) to investigate the age-related differences in cognitive function (CF), nutritional status (MNA), physical activity (AF), quality of life (QoL), depression, social sat-isfaction (SS) and socioeconomic status (SES), and (2) to explore the relationships between CF and the previous variables. This cross sectional study included 268 men and 433 women (aged 71.4 ± 7.0 years). CF was determined with the Cognitive Telephone Screening Instrument (COGTEL) and the Mini-Mental State Examination (MMSE). Correlates were as follows: Mini Nutritional Assessment (MNA), PA (Baecke questionnaire modified for older adults), Quality of life (QoL SF-12), Geriatrics Depression Scale (GDS), Satisfaction and Social Support Scale, and Socioeconomic status (SES). All instruments were applied in a face to face interview. An independent t-test identi-fied significantly higher scores in young-old adults (≤ 69 years) for CF (p < 0.001), PA (p= 0.046) and SES (p= 0.007), compared to old-old adults (≥ 70 years). The results of multiple linear regression analysis indicated that the most significant CF correlates were SES (ß = 0.45;p< 0.001), age (ß = -0.12;p< 0.001), SS (ß = 0.12;p= 0.001), GDS (ß = -0.11; p= 0.003) and QoL (ß = 0.08;p= 0.017). The overall regression model explained 36% of the total variance in the COGTEL. The oldest and the more depressed adults obtained lower scores for FC. The present study suggests that, between the correlates studied, SES was the strongest predictor in the explanation of CF in older adults

Os objetivos deste estudo foram: (1) investigar as diferenças associadas à idade na função cognitiva (FC), status nutricional (MNA), atividade física (AF), qualidade de vida (QV ), depressão, satisfação social (SS) e estatuto socioeconômico (ESSE), e (2) explorar as relações entre a FC e as varáveis anteriores. Este estudo, de natureza transversal, incluiu 268 homens e 433 mulheres (71,4 ± 7,0 anos de idade). A FC foi determinada a partir do Cognitive Telephone Screening Instrument (COGTEL) e do Mini-Mental State Examination (MMSE). Os preditores analisados incluíram: o Mini Nutritional Assessment (MNA), a AF (questionário de Baecke modificado para idosos), a QV (SF-12), a Escala de Depressão em Geriatria (GDS), a Escala de Satisfação com o Suporte Social e o ESSE (Estatuto Socioeconômico). Todos os instrumentos foram aplicados sob forma de entrevista. Um t-teste de medidas independentes identificou scores significativamente mais elevados nos adultos-idosos mais jovens (60 - 69 anos de idade) na FC (p < 0,001), AF (p = 0,046) e ESSE (p = 0,007), comparativamente aos mais idosos (70 - 91 anos de idade). Os resultados da análise de regressão linear múltipla indicaram que os preditores mais significativos da FC foram: ESSE (ß = 0,45; p < 0,001), idade (ß = -0,12; p < 0,001), SS (ß = 0,12; p = 0,001), GDS (ß = -0,11; p = 0,003) e QV (ß = 0,08; p = 0,017). O modelo de regressão testado, explicou 36% da variância total do COGTEL. As pessoas mais idosas e deprimidas obtiveram scores mais baixos na FC. Este estudo sugere que entre os preditores estudados, o ESSE é a variável mais forte na explicação da FC nos adultos idosos

Genetic or pharmacological superoxide-hydrogen peroxide imbalances modulate the in vitro effects of lithium on glycogen synthase kinase-3ß.

INTRODUCTION: Lithium (Li), a mood stabilizer used to treat bipolar disorder (BP) symptoms has important anti-inflammatory effects by downregulation of glycogen synthase kinase-3 beta (GSK-3ß). However, sometime Li effect is not efficient in some patients suggesting genetic interference. Previous investigations described association between a genetic superoxide­hydrogen (S-HP) imbalance caused by a superoxide dismutase manganese dependent gene polymorphism (Val16Ala-SOD2 SNP, rs4880) and differential anti-inflammatory response of some drugs and bioactive molecules. Therefore, we postulated here that S-HP imbalance could present some effect on GSK-3ß modulation by Li. METHODS: to test this hypothesis, a genetic and a pharmacological S-HP imbalance protocols were performed. In the two protocols, immune cells were activated by phythohemaglutin (PHA). The first one, used peripheral blood mononuclear cells (PBMCs) cultures carrying different Val16Ala-SOD2 genotypes, and the second used a commercial macrophage cell line RAW 264.7. Macrophages were exposed to paraquat to induce high S levels (VV-like cells) or porphyrin, that is a SOD2-like molecule that increase dismutation of S into HP (AA-like cells). In both protocols the Li effects on GSK-3ß gene and protein modulation as evaluated in 24 h cultures. The inflammatory activation was also analyzed by cellular proliferation in 72 h cell cultures. RESULTS: as expected PHA exposure triggered a strong upregulation of GSK-3ß gene expression (p ≤ 0.001), and Li exposure showed GSK-3ß gene downregulation from 0.7 mEq/L concentrations. However, Li modulatory effects on GSk-3ß gene and protein expression was directly influenced by basal S-HP balance. Presence of high S-basal levels (VV genotype and VV-like cells) induced attenuated Li anti-inflammatory effects in comparison with balanced and AA and AA-like cells (p < 0.001). Despite methodological limitations related to in vitro assays, the whole of results suggested that Li anti-inflammatory effects is influenced by S-HP basal state and is plausible that its influence could contributes to resistance of some patients to Li treatment or to increase of intensity of some side effects Li-associated.

Xanthine-Catechin Mixture Enhances Lithium-Induced Anti-Inflammatory Response in Activated Macrophages In Vitro.

Lithium (Li) is a chemical element used for treating and preventing bipolar disorder (BD) and exerts positive effects such as anti-inflammatory effects as well as undesirable side effects. These effects of Li can be influenced by interaction with some nutritional elements. Therefore, we investigated the potential effects of xanthine (caffeine and theobromine) and catechin molecules present in some food beverages broadly consumed worldwide, such as coffee and tea, on Li-induced anti-inflammatory effects. In the present study, we concomitantly exposed RAW 264.7 macrophages to Li, isolated xanthine and catechin molecules, and a xanthine-catechin mixture (XC mixture). We evaluated the effects of these treatments on cell proliferation, cell cycle progression, oxidative and antioxidant marker expression, cytokine levels, gene expression, and GSK-3ß enzyme expression. Treatment with the XC mixture potentialized Li-induced anti-inflammatory effects by intensification of the following: GSK-3ß inhibitory action, lowering effect on proinflammatory cytokines (IL-1ß, IL-6, and TNFα), and increase in the levels of IL-10 that is an anti-inflammatory cytokine. Despite the controversial nature of caffeine consumption by BD patients, these results suggested that consumption of caffeine, in low concentrations, mixed with other bioactive molecules along with Li may be safe.

A chemical compound based on methylxanthine-polyphenols lowers nitric oxide levels and increases post-thaw human sperm viability.

We produced a new chemical compound based on methylxanthines and polyphenols (CCMP) present in the chemical matrix of guaraná (Paullinia cupana), a seed extract with antioxidant properties. After supplementation with the standard extract of resveratrol, a well documented antioxidant found in other plant sources, we investigated whether this resveratrol-enriched compound could improve sperm viability and modulate differentially reactive oxygen species (ROS) and nitric oxide (NO) levels in thawed sperm. Sperm samples obtained from healthy young donors were treated with different concentrations of guaraná extract (0.1, 1, 5 or 10 mg/ml) and cells were frozen at -80°C for 24 h. In addition, the potential protective effects of guaraná treatment on sperm treated with pro-oxidant compound (200 µM hydrogen peroxide, H2O2) were assessed. Samples were also exposed to three concentrations of CCMP before being frozen in liquid nitrogen (-196°C) or in an ultrafreezer (-80°C) for 24 h, and both pre-freezing and post-thaw measurements of viability and oxidative stress were performed. Guaraná supplementation at 10 mg/ml significantly increased post-thaw viability and decreased oxidative metabolism of the sperm. Moreover, selected concentrations of CCMP improved viability and oxidative metabolism in sperm samples pre-freezing. Furthermore, CCMP showed cryoprotective activity by increasing viability and decreasing oxidative stress in post-thaw samples. In summary, these findings suggested that CCMP supplementation acts as a cryoprotectant to modulate ROS and NO levels in thawed sperm. CCMP could be used to enhance sperm quality and reproductive success.