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This study characterized a nanosupplement based on coenzyme Q10 containing guarana (Paullinia cupana) and Brazil nuts oil (Bertholetia excelsa) (G-Nut). Determined cytotoxic and oxi-immunomodulatory effects on human peripheral blood mononuclear cells (PBMCs) and its effect on mortality of red Californian earthworms (Eisenia fetida) and on the immune efficiency of its coelomocytes immune by in vitro exposure to yeast dead microorganism. The cytotoxic and immunomodulatory effects of G-Nut and the GN-Free extract (0.25-3 mg/mL) were determined in PBMC cultures. Apoptotic, oxidative, and inflammatory markers were determined using biochemical, immunological, and molecular protocols. The effects of G-Nut and GN-Free extracts on mortality and immune efficiency were investigated in earthworms. G-Nut and GN-Free did not induce cytotoxic events in PBMCs, triggering the decrease in apoptotic (caspases 3 and 8) gene expression, lipid and protein oxidation levels, or pro-inflammatory cytokine levels. G-Nut and GN-Free did not trigger earthworm mortality and improved coelomocyte immune efficiency by increasing Eisenia neutrophil extracellular DNA traps and brown body formation when exposed to dead yeasts. The G-Nut nanoformulation is safe and can be used as a new form of food supplement by oral or transdermal delivery.
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Bertholletia , Leucócitos Mononucleares , Nanopartículas , Oligoquetos , Paullinia , Extratos Vegetais , Ubiquinona , Animais , Oligoquetos/química , Humanos , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Nanopartículas/química , Bertholletia/química , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Paullinia/química , Apoptose/efeitos dos fármacosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional harvest of Achyrocline satureioides (AS) occurs at dawn on Good Friday in some South American countries. Inflorescences are traditionally used as infusions for several disorders, including neuropsychiatric disorders. Pillows and cushions are popularly filled with AS to attenuate the symptoms of depression, anxiety, and sleep disturbances. However, evidence for the potential beneficial effects of AS on human neural cells remains unclear. AIM OF THE STUDY: An in vitro model of SH-SY5Y human neural cells was applied to evaluate the effect of AS infusion, prepared as commonly used, on cells exposed to rotenone and to investigate its potential for neuropsychiatric disorders. MATERIALS AND METHODS: A hot aqueous extract was obtained from a traditionally prepared AS inflorescence infusion and chemically characterized by high-resolution mass spectrometry and spectrophotometric quantification of total polyphenols, tannins, and flavonoids. The SH-SY5Y cell cultures were treated with AS extract at concentrations of 1, 3, 5, 10, 50, 100, and 300 µL/mL to determine the potential cyto- and genotoxic effects of AS on neural cells using MTT, Neutral Red, and GEMO assays. Apoptosis modulation was assessed using flow cytometry and apoptosis-modulating genes were evaluated by qRT-PCR. The protective effect of AS on the neurotoxicity triggered by rotenone exposure (30 nM) was determined by analyzing cellular viability and oxidative markers such as lipid peroxidation and protein carbonylation, and DNA damage was assessed by micronucleus assay. RESULTS: The AS extract, as traditionally prepared, had estimated concentrations of 409.973 ± 31.107 µg/mL, 0.1041 ± 0.0246 mg GAE/mL, and 63.309 ± 3.178 mg QE/mL of total tannins, total polyphenols, and flavonoids, respectively. At concentrations of 30 and 100 µl/mL, AS decreased apoptotic events, whereas the highest concentration (300 µl/mL) increased apoptosis compared to that in the control (p < 0.05). In cells exposed to rotenone, AS treatment induced cell proliferation, reduced DNA damage (as evaluated by micronuclei), and reduced lipid and protein oxidation. CONCLUSIONS: The data indicate the non-cytotoxic and beneficial effects of AS extract on human neural cells by reducing cellular mortality and oxidative stress in neural cells triggered by rotenone exposure.
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Achyrocline , Apoptose , Neurônios , Fármacos Neuroprotetores , Extratos Vegetais , Rotenona , Humanos , Rotenona/toxicidade , Extratos Vegetais/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Neurônios/efeitos dos fármacos , Achyrocline/química , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Dano ao DNA/efeitos dos fármacos , Antioxidantes/farmacologiaRESUMO
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.
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Background and objectives: The COVID-19 pandemic and its consequent severe acute respiratory syndrome (SARS) have taken the lives of millions since 2020. The use of neuraminidase inhibitors is a promising alternative in treating this disease, with several studies on off-label use being conducted since the beginning of the pandemic, but none of them have a large sample size and analyze multiple risk factors. The purpose of this article is to identify possible associations between various factors and risk of hospitalization, need for ventilation and death, as well as the influence of the prescription of Zanamivir and Oseltamivir on these same indicators. Methods: In this transversal study, approximately 900,000 medical records from all regions of Brazil were collected from the Ministry of Health database, and after that, proper statistical analysis of the variables was performed. Results: Hospitalization was associated with gender, ethnicity, education, local urbanization, State, and its percentage of elderly, as well as the climate. The prescription of Zanamivir and Oseltamivir was associated with higher incidence of symptoms, lower hospitalization and death rate, and lower need for invasive and non-invasive ventilation. Medical records from146,160 patients were excluded due to SARS not caused by COVID-19. Conclusion: From this data, it is possible to draw a risk profile for hospitalization by SARS and consider the use of Zanamivir and Oseltamivir as a treatment for these patients.(AU)
Justificativa e objetivos: A pandemia de COVID-19 e sua consequente síndrome respiratória aguda grave (SRAG) levaram milhões de pessoas a óbito desde 2020. O uso de inibidores da neuraminidase é uma alternativa promissora no tratamento dessa doença, com vários estudos sobre o uso off-label sendo conduzidos desde o início da pandemia, mas nenhum que tenha um grande tamanho amostral e que analise vários fatores de risco. O objetivo deste artigo é identificar possíveis associações entre diversos fatores e risco de hospitalização, necessidade de ventilação e óbito, assim como a influência da prescrição de Zanamivir e Oseltamivir nos mesmos indicadores. Métodos: Neste estudo transversal, foi feito o levantamento de aproximadamente 900 mil prontuários de todas as regiões do Brasil, provenientes de dados do Ministério da Saúde, e em seguida foi realizado o tratamento estatístico adequado das variáveis. Resultados: A hospitalização foi associada a sexo, etnia, escolaridade, urbanização do local, Estado e porcentagem de idosos do mesmo, assim como o clima. Já a prescrição de Zanamivir e Oseltamivir foi associada a maior incidência de sintomas, menor taxa de hospitalização e óbito e menor necessidade de ventilação invasiva e não-invasiva. Foram excluídos 146.160 prontuários devido a SRAG não ocasionada pela COVID-19. Conclusão: Com esses dados, é possível traçar um perfil de risco para hospitalização por SRAG e considerar o uso de Zanamivir e Oseltamivir como tratamento para esses pacientes.(AU)
Justificación y objetivos: la pandemia Covid-19 y su consiguiente síndrome respiratorio agudo severo (SRAS) han muerto millones de personas desde 2020. El uso de inhibidores de la neuraminidasa es una alternativa prometedora en el tratamiento de esta enfermedad, con varios estudios sobre el uso off-label que se realiza desde el principio de la pandemia, pero ninguno que tenga un tamaño de muestra grande y analice múltiples factores de riesgo. El propósito de este artículo es identificar posibles asociaciones entre varios factores y el riesgo de hospitalización, necesidad de ventilación y muerte, así como la influencia de la prescripción de Zanamivir y Oseltamivir en los mismos indicadores. Métodos: En este estudio transversal, se encuestaron a los datos del Ministerio de Salud de aproximadamente 900,000 registros de todas las regiones de Brasil, después de que se realizó un tratamiento estadístico adecuado de las variables. Resultados: La hospitalización se asoció con género, etnia, educación, urbanización del sitio, Estado y porcentaje de ancianos, así como el clima. La prescripción de zanamivir y oseltamivir se asoció con la mayor incidencia de síntomas, menor hospitalización y tasa de mortalidad y menor necesidad de ventilación invasiva y no invasiva. Se excluyeron 146,160 registros médicos debido a SRAS no causado por Covid-19. Conclusión: con estos datos, es posible dibujar un perfil de riesgo para la hospitalización por SRAS y considerar el uso de zanamivir y oseltamivir como tratamiento para estos pacientes.(AU)
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Humanos , Síndrome Respiratória Aguda Grave , Oseltamivir/uso terapêutico , Zanamivir/uso terapêutico , COVID-19 , Brasil , Estudos Transversais , Fatores de RiscoRESUMO
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.
Abstract Objectives We aimed to evaluate the impact of potentially inappropriate medications prescribed prior to hospitalization (PIM-ph) on the mortality Methods We included 318 patients, aged ≥65 who sought emergency care and were hospitalized for any clinical reasons. Information on patients' clinical and social indicators was obtained via structured interviews conducted 24 to 48 hours after hospitalization. All medications used by older adults prior to hospitalization were recorded, and PIM-ph were identified using the Brazilian PIM Consensus. The study considered the influence of the entire set of PIM-ph and specific PIM-ph used by these patients. The impact of PIM-ph use during hospitalization and after 30 days of this event was statistically determined by multivariable Cox proportional hazard regression analysis, which included sex, age, and other clinical and functional indicators as intervening variables. Results The prevalence of PIM-ph use was 49.7% (n=158). A total of 85 (26.7%) patients died during hospitalization or within 30 days after discharge. Eighteen pharmacological classes of PIM-ph use were identified. The use of total PIM-ph, benzodiazepines (IC: 1.055-3.365, p= 0.032), digoxin(IC: 1.623-7.048, p=0.001), and loop diuretics (IC: 1.000-3.455, p=0.05) increased the relative risk of mortality independent of sex, age, clinical causes of hospitalization, frailty risk, social support, presence of confusion symptoms, polypharmacy, and in-hospital evolution of geriatric complications. Conclusion PIM-ph use, especially benzodiazepines, digoxin, and loop diuretics, could contribute to mortality risk in hospitalized older adults. These results could be relevant in the management and therapeutic care of hospitalized patients.
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RESUMO Objetivo Investigar os efeitos da suplementação antioxidante com extrato de açaí no incômodo com o zumbido crônico e a relação com os níveis de ansiedade e metabolismo oxidativo, não excluindo a sobreposição de enfermidades. Método Ensaio clínico, randomizado, controlado por placebo. Participaram 30 indivíduos, com média de 50,5 anos, 14 do sexo masculino e 16 do feminino, com limiares auditivos normais ou perda auditiva sensorioneural até grau leve bilateralmente, divididos em dois grupos: Grupo Placebo (sem ativo) e Grupo Açaí (100mg de extrato de açaí). Aplicaram-se os seguintes procedimentos antes e após três meses dos tratamentos: Tinnitus Handicap Inventory (THI), Inventário de Ansiedade de Beck (BAI) e amostras de sangue para avaliação de biomarcadores de estresse oxidativo (Peroxidação Lipídica e Carbonilação de proteínas). Resultados Houve redução do incômodo do zumbido para o grupo açaí, verificado por meio do THI (p=0,006). Diferenças significativas foram constatadas na pontuação dos sintomas comuns para os quadros de ansiedade no grupo placebo (p=0,016) porém, o mesmo não foi observado para os biomarcadores de metabolismo oxidativo, apesar de haver uma diminuição dos valores pós-tratamento para os grupos. Conclusão A suplementação antioxidante oral, com extrato de açaí, manifestou efeitos favoráveis no zumbido, reduzindo o desconforto com o sintoma, independente da etiologia de base, podendo ser considerada uma modalidade de tratamento. Entretanto, o efeito dessa suplementação nos sintomas de ansiedade e em biomarcadores de estresse oxidativo precisa de maior investigação.
ABSTRACT Purpose To investigate the effects of antioxidant supplementation with açaí extract on the discomfort with chronic tinnitus and the relationship with the levels of anxiety and oxidative metabolism, not excluding the overlap of diseases. Methods Randomized, placebo-controlled clinical trial. 30 individuals participated, with an average of 50.5 years, 14 males and 16 females, with normal hearing thresholds or sensorineural hearing loss up to mild degree, divided into two groups: Placebo Group (without active) and, Açaí Group (100mg of açaí extract). The following procedures were applied before and after three months of treatments: Tinnitus Handicap Inventory (THI), Beck's Anxiety Inventory (BAI) and blood samples for evaluation of oxidative stress biomarkers (Lipid Peroxidation and Protein Carbonylation). Results There was a reduction in the discomfort of tinnitus for the açaí group verified through THI (p = 0.006). Significant differences were found in the score of common symptoms for anxiety disorders in the placebo group (p = 0.016), however, the same was not observed for oxidative metabolism biomarkers, although there was a decrease in post-treatment values for all groups. Conclusion Oral antioxidant supplementation, with açaí extract, showed favorable effects on tinnitus, reducing discomfort with the symptom, regardless of the underlying etiology, and can be considered a treatment modality. However, the effect of this supplementation on anxiety symptoms and oxidative stress biomarkers needs further investigation.
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Abstract Fibromyalgia (FM) is a nonarticular rheumatic syndrome that leads to diffuse myalgia, sleep disturbances and morning stiffness. Balneotherapy has been shown an effective strategy to improve the health conditions of patients; however, the treatment follow-up is based on patient report due to the lack of biomarkers. Thus, this study evaluated the application of cytokines and phosphoglycerate mutase I (PGAM-I) to monitoring FM patient underwent to balneotherapy treatment. Eleven healthy and eleven women with FM were submitted to daily sessions of balneotherapy during 10 days. Clinical and quality of life parameters were assessed through a FIQ questionnaire. Blood levels of TNF-(, interleukins (IL-1, IL-2 and IL-10) and PGAM-I expression in patients' saliva were also evaluated. Patients with FM showed significant improvements in their clinical status after treatment. Also, FM patients has IL-10 levels lower than healthy women and the balneotherapy increased the expression of this cytokine in both groups, concomitantly to pain relief. Although inflammatory cytokines (IL-1, IL-2 and TNF-() were more expressed in FM patients than healthy patients their levels did not reduce after treatment. A slight increase of PGAM-I expression was observed. In conclusion, IL-10 levels could be a useful biomarker to balneotherapy follow-up of FM patients. However, these findings must be analyzed in a larger number of patients in order to validate IL-10 as an effective biomarker.
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Humanos , Feminino , Biomarcadores , Fibromialgia/diagnóstico , Interleucina-10/sangue , Qualidade de Vida , Saliva , Balneologia , Fibromialgia/terapia , Estudos de Casos e Controles , Inquéritos e Questionários , Interleucina-1/sangue , Interleucina-2/sangue , Fosfoglicerato Mutase/sangueAssuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Qualidade de Vida , Brasil , Envelhecimento , Saúde Pública , Inquéritos e Questionários , MorbidadeRESUMO
OBJETIVO: avaliar a associação entre a função do sistema olivococlear medial e biomarcadores genotóxicos em escolares residentes de região fumicultora. MÉTODOS: trata-se de um estudo observacional, prospectivo e transversal. O grupo estudo foi composto por 21 escolares normo-ouvintes residentes de região fumicultora e o grupo controle por 25 escolares normo-ouvintes que não residiam na zona rural. O sistema olivococlear medial foi avaliado por meio da supressão das Emissões otoacústicas produto de distorção, e os biomarcadores genotóxicos foram: ensaio cometa, teste de micronúcleos e ensaio fluorimétrico de quantificação de DNA. Os dados obtidos foram submetidos à análise estatística. RESULTADOS: ao comparar a ocorrência do efeito de supressão das emissões entre os grupos, não foi detectada associação significante. Tanto no ensaio cometa como no ensaio fluorimétrico de quantificação de DNA a média do grupo estudo mostrou-se significantemente mais elevada que a do grupo controle. No teste de micronúcleos, verificou-se diferença significante quanto ao somatório de células alteradas e à frequência de células binucleadas, sendo a média do grupo estudo mais elevada que a do grupo controle. Já referente à frequência de células com micronúcleo, não se observou diferença significante entre os grupos. Não foi detectada associação entre ocorrência do efeito de supressão e os resultados dos biomarcadores genotóxicos. CONCLUSÃO: o grupo estudo não apresentou alterações no sistema olivococlear medial, evidenciado pela presença de supressão das emissões, porém apresentou índices de dano significantemente mais elevados dos biomarcadores genotóxicos. Entretanto, não se verificou associação entre supressão das emissões e genotoxicidade. .
PURPOSE: to evaluate the association between the function of the medial olivocochlear system and the biomarkers of genotoxicity in resident students from the tobacco-producing region. METHODS: the study group was composed by 21 normal-hearing students from the tobacco-producing region and the control group by 25 normal-hearing students who did not live in the countryside. The medial olivocochlear system was assessed by the distortion of product otoacoustic emissions and genotoxic biomarkers, such as: comet assay, micronucleus test and fluorimetric assay for the quantification of DNA. The data were subjected to statistical analysis. RESULTS: by comparing the occurrence of suppression of emissions between the groups, no significant association was detected. Considering the comet assay and the fluorimetric assay for quantitation of DNA, the mean of the study group was considerate significantly higher than the mean of the control group. In the micronucleus test, it was found a significant difference in the sum of abnormal cells and in the frequency of binucleated cells, with the mean of the study group higher than the one found in the control group. And, in relation to the frequency of cells with micronucleus, it showed no significant difference between both groups. No association was found between the occurrence of suppression and the results of genotoxicity biomarkers. CONCLUSION: the study group had no alteration in medial olivocochlear system, which was evidenced by the presence of emissions suppression, but it presented injury rates considerate significantly higher in relation to the genotoxic biomarkers. However, there was no association between suppression of emissions and genotoxicity. .
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PURPOSE: To verify the association between the amplitude of distortion-product otoacoustic emissions (DPOAE) and biomarkers of oxidative stress (OS) in resident students of the tobacco-producing region. METHODS: Participated in the study group (SG) 21 normal-hearing students from the tobacco-producing region, and in the control group (CG) 25 normal-hearing students who did not live in the countryside. The auditory system was assessed by DPOAE and the following biomarkers: dichlorofluorescein diacetate (DCFH-DA) and micronucleus test (MN). RESULTS: Both groups showed DPOAE present in both ears. Significant difference was detected between groups - in the right ear in the frequency of 4.000 Hz and in the left ear in the frequency of 2.000 Hz - with the mean amplitude of the DPOAE of the SG lower than the one found in the CG. Considering both ears, the SG presented lower mean across all frequencies and it was found a significant difference in the frequencies of 2.000 and 4.000 Hz. The overall mean of DPOAE, by ear, no significant differences were observed. In relation to the rate of production of free radicals, the mean of the SG was significantly higher than that of the mean of the CG. For the frequency of abnormal cells in the MN test, the mean of the SG was also considerate significantly higher than the mean of the CG. CONCLUSION: The SG showed a lower response level of DPOAE at all frequencies and high levels of biomarkers of EO, however there was no association between assessments. .
OBJETIVO: Verificar a associação entre a amplitude das Emissões Otoacústicas Produto de Distorção (EOAPD) e biomarcadores do estresse oxidativo (EO) em escolares residentes de região fumicultora. MÉTODOS: Participaram do grupo estudo (GE) 21 escolares normo-ouvintes residentes de região fumicultora, e do grupo controle (GC), 25 escolares normo-ouvintes que não residiam na zona rural. O sistema auditivo foi avaliado por meio das EOAPD, e os biomarcadores do EO foram: Diclorofluoresceína diacetato (DCFH-DA) e teste de micronúcleos (MN). RESULTADOS: Os dois grupos apresentaram EOAPD presentes em ambas as orelhas. Detectou-se diferença significativa entre os grupos - na orelha direita, a frequência foi 4.000 Hz, e na esquerda, 2.000 Hz -, sendo a média de amplitude das EOAPD do GE menor que a do GC. Quanto às duas orelhas, o GE apresentou média inferior em todas as frequências, verificando-se diferença significativa em 2.000 e 4.000 Hz. Na média geral das EOAPD por orelha não foi observada diferença significativa. Na taxa de produção de radicais livres, a média do GE mostrou-se significativamente mais elevada que a do GC. Quanto à frequência de células alteradas no teste de MN, a média do GE também se apresentou significativamente mais elevada que a do GC. CONCLUSÃO: O GE apresentou nível de resposta das EOAPD menor em todas as frequências e índices elevados dos biomarcadores do EO, porém não foi verificada associação entre as avaliações. .