Low T3 syndrome as a prognostic factor in patients in the intensive care unit: an observational cohort study. / Síndrome do T3 baixo como fator prognóstico em pacientes na unidade de terapia intensiva: estudo de coorte observacional.

OBJECTIVE: To assess euthyroid sick syndrome as a prognostic factor in patients in the intensive care unit; to detect factors that may affect mortality; and to develop an equation to calculate death probability. METHODS: This was a longitudinal, observational, nonconcurrent cohort study developed in the intensive care unit of Fundação Santa Casa de Misericórdia do Pará. One hundred adults with no prior documented endocrinopathy were submitted to a 20mL blood sample collection for the measurement of thyroid stimulating hormone, free tetraiodothyronine, free triiodothyronine and reverse triiodothyronine. RESULTS: Most patients were female, aged 20 to 29 years. Most patients who died were older (median age of 48 years), and euthyroid sick syndrome was present in 97.5% of them. Euthyroid sick syndrome was related to death, comorbidities, age and length of stay in the intensive care unit (median of 7.5 days).There was an association between lower thyroid stimulating hormone and death. Patients with free triiodothyronine levels below 2.9pg/mL were more likely to die; reverse triiodothyronine rates were above 0.2ng/mL in those who died. Free triiodothyronine had greater sensitivity and accuracy, and reverse triiodothyronine had greater specificity to predict mortality. Based on the results and cutoff points, a multiple logistic regression formula was developed to calculate the probability of death. CONCLUSION: The main limitation of this study is the fact that it was conducted in a reference hospital for maternal and child care; therefore, there was a greater number of female patients and, consequently, a sampling bias existed. However, opportune measurement of free and reverse triiodothyronine levels in critical patients and application of the proposed equation are suggested.

OBJETIVO: Avaliar a síndrome do doente eutireóideo como fator prognóstico em pacientes na unidade de terapia intensiva, detectar fatores que possam influenciar a mortalidade e desenvolver uma equação para calcular a probabilidade de morte. MÉTODOS: Este foi um estudo de coorte longitudinal, observacional e não concorrente realizado na unidade de terapia intensiva da Fundação Santa Casa de Misericórdia do Pará. Realizou-se coleta de 20mL de sangue em 100 adultos sem endocrinopatia previamente documentada para a dosagem do hormônio estimulante da tireoide, da tetraiodotironina livre, da tri-iodotironina livre e da tri-iodotironina reversa. RESULTADOS: A maioria dos pacientes era do sexo feminino, com idades entre 20 e 29 anos. A maioria dos pacientes que morreram era mais velha (idade mediana de 48 anos), e 97,5% deles possuíam a síndrome do doente eutireóideo.A síndrome do doente eutireóideo esteve relacionada à morte, às comorbidades, à idade e ao tempo de internação (mediana de 7,5 dias) na unidade de terapia intensiva. A baixa dosagem de hormônio estimulante da tireoide estava associada à morte. Os pacientes com dosagem da tri-iodotironina livre menor que 2,9pg/mL tinham maior probabilidade de morrer e, naqueles que morreram, a dosagem de tri-iodotironina reversa era maior que 0,2ng/mL. A tri-iodotironina livre apresentou maior sensibilidade e acurácia, e a tri-iodotironina reversa teve maior especificidade para prever a mortalidade. Com base nos resultados e pontos de corte, desenvolveu-se uma fórmula de regressão logística múltipla para calcular a probabilidade de morte. CONCLUSÃO: Sugere-se verificar oportunamente a dosagem da triiodotironina livre e reversa em pacientes graves e aplicar a equação proposta.

Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment.

Síndrome do T3 baixo como fator prognóstico em pacientes na unidade de terapia intensiva: estudo de coorte observacional / Low T3 syndrome as a prognostic factor in patients in the intensive care unit: an observational cohort study

RESUMO Objetivo: Avaliar a síndrome do doente eutireóideo como fator prognóstico em pacientes na unidade de terapia intensiva, detectar fatores que possam influenciar a mortalidade e desenvolver uma equação para calcular a probabilidade de morte. Métodos: Este foi um estudo de coorte longitudinal, observacional e não concorrente realizado na unidade de terapia intensiva da Fundação Santa Casa de Misericórdia do Pará. Realizou-se coleta de 20mL de sangue em 100 adultos sem endocrinopatia previamente documentada para a dosagem do hormônio estimulante da tireoide, da tetraiodotironina livre, da tri-iodotironina livre e da tri-iodotironina reversa. Resultados: A maioria dos pacientes era do sexo feminino, com idades entre 20 e 29 anos. A maioria dos pacientes que morreram era mais velha (idade mediana de 48 anos), e 97,5% deles possuíam a síndrome do doente eutireóideo. A síndrome do doente eutireóideo esteve relacionada à morte, às comorbidades, à idade e ao tempo de internação (mediana de 7,5 dias) na unidade de terapia intensiva. A baixa dosagem de hormônio estimulante da tireoide estava associada à morte. Os pacientes com dosagem da tri-iodotironina livre menor que 2,9pg/mL tinham maior probabilidade de morrer e, naqueles que morreram, a dosagem de tri-iodotironina reversa era maior que 0,2ng/mL. A tri-iodotironina livre apresentou maior sensibilidade e acurácia, e a tri-iodotironina reversa teve maior especificidade para prever a mortalidade. Com base nos resultados e pontos de corte, desenvolveu-se uma fórmula de regressão logística múltipla para calcular a probabilidade de morte. Conclusão: Sugere-se verificar oportunamente a dosagem da triiodotironina livre e reversa em pacientes graves e aplicar a equação proposta.

ABSTRACT Objective: To assess euthyroid sick syndrome as a prognostic factor in patients in the intensive care unit; to detect factors that may affect mortality; and to develop an equation to calculate death probability. Methods: This was a longitudinal, observational, nonconcurrent cohort study developed in the intensive care unit of Fundação Santa Casa de Misericórdia do Pará. One hundred adults with no prior documented endocrinopathy were submitted to a 20mL blood sample collection for the measurement of thyroid stimulating hormone, free tetraiodothyronine, free triiodothyronine and reverse triiodothyronine. Results: Most patients were female, aged 20 to 29 years. Most patients who died were older (median age of 48 years), and euthyroid sick syndrome was present in 97.5% of them. Euthyroid sick syndrome was related to death, comorbidities, age and length of stay in the intensive care unit (median of 7.5 days). There was an association between lower thyroid stimulating hormone and death. Patients with free triiodothyronine levels below 2.9pg/mL were more likely to die; reverse triiodothyronine rates were above 0.2ng/mL in those who died. Free triiodothyronine had greater sensitivity and accuracy, and reverse triiodothyronine had greater specificity to predict mortality. Based on the results and cutoff points, a multiple logistic regression formula was developed to calculate the probability of death. Conclusion: The main limitation of this study is the fact that it was conducted in a reference hospital for maternal and child care; therefore, there was a greater number of female patients and, consequently, a sampling bias existed. However, opportune measurement of free and reverse triiodothyronine levels in critical patients and application of the proposed equation are suggested.

SARS-CoV-2 triggered neutrophil extracellular traps (NETs) mediate COVID-19 pathology

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to respiratory failure. These patients also develop cytokine storm syndrome, and organ dysfunctions, which is a clinical picture that resembles sepsis. Considering that neutrophil extracellular traps (NETs) have been described as an important factors of tissue damage in sepsis, we investigated whether NETs would be produced in COVID-19 patients and participate in the lung tissue damage. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and respective healthy controls were enrolled. NETs concentration was assessed by MPO-DNA PicoGreen assay or by confocal immunofluorescence. The cytotoxic effect of SARS-CoV-2-induced NETs was analyzed in human epithelial lung cells (A549 cells). The concentration of NETs was augmented in plasma and tracheal aspirate from COVID-19 patients and their neutrophils spontaneously released higher levels of NETs. NETs were also found in the lung tissue specimens from autopsies of COVID-19 patients. Notably, viable SARS-CoV-2 can directly induce in vitro release of NETs by healthy neutrophils in a PAD-4-dependent manner. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represent a potential therapeutic target for COVID-19.

Phytomedicines containing Matricaria species for the treatment of skin diseases: A biotechnological approach.

Skin diseases have a notable impact on the life of the affected and in their health conditions. In order to allow a more effective and economical treatment for such disorders, new therapeutic approaches have been continuously investigated. Due to its high therapeutic and phytochemical potential, Matricaria species emerges as a pleasant alternative, since it is an important source of bioactive secondary metabolites suitable for the treatment of varied skin diseases. Therefore, this review aimed to catalog inventions that have used Matricaria species as the active component for skin disease treatment in order to assess the status of the technological development of the fitomedicines. For this, a search of patents was performed in four specialized patent database, which have reported the discovery of pharmaceutical bioproducts that used Matricaria species in its composition for skin treatment. Therefore, it is possible to notice that the pharmaceutical industry has driven efforts and investment to produce medicines for the dermatopathies, using species of this genus as an active principle. Besides, a trend of growth has been identified for the last years, which is accompanied by the continuous publication of scientific articles on the subject. It is known that a long journey is traversed between the scientific findings and their applications in the pharmaceutical market, creating the perspective that new Matricaria-based medicines may reach the pharmaceutical market in the coming years.

Natural products as a perspective for cancer pain management: A systematic review.

BACKGROUND: Cancer is the leading cause of death in the world and one of the main symptoms affecting these individuals is chronic pain, which must be evaluated and treated in its various components. Several drugs are currently used, but beyond the high cost, they have harmful side effects to patients or are transitorily effective. Ergo, there is a need to look for new options for cancer pain relief. Natural products (NPs) present themselves as strong candidates for the development of new drugs for the treatment of chronic pain, such as cancer pain. PURPOSE: This systematic review aimed to summarize current knowledge about the analgesic profile of NPs in cancer pain. METHODS: The search included PubMed, Scopus and Web of Science (from inception to June 2018) sought to summarize the articles studying new proposals with NPs for the management of oncological pain. Two independent reviewers extracted data on study characteristics, methods and outcomes. RESULTS: After an extensive survey, 21 articles were selected, which described the analgesic potential of 15 natural compounds to relieve cancer pain. After analyzing the data, it can be suggested that these NPs, which have targets in central and peripheral mechanisms, are interesting candidates for the treatment of cancer pain for addressing different pharmacological mechanisms (even innovative), but ensuring the safety of these compounds is still a challenge. Likewise, the cannabinoids compounds leave the front as the most promising compounds for direct applicability due to the clinical studies that have already been developed and the background already established about these effects on chronic pain. CONCLUSION: Regarding these findings, it can be concluded that the variability of possible biological sites of action is strategic for new perspectives in the development of therapeutic proposals different from those available in the current market.

α-Terpineol reduces cancer pain via modulation of oxidative stress and inhibition of iNOS.

α-Terpineol (TP) is present in a wide range of essential oils of the genus Eucalyptus, with recognized potential for a range of biological effects, such as analgesic. Hence, our study aimed to investigate the effect of TP on cancer pain induced by sarcoma 180 in Swiss mice. Our results showed that TP reduced significantly mechanical hyperalgesia and spontaneous and palpation-induced nociception, improved paw use without reducing tumor growth and grip strength. Importantly, no evident biochemical and hematological toxicity was oberved. Furthermore, TP increased the tissue antioxidant capacity due to ferric-reducing antioxidant power (FRAP) and glutathione (GSH). TP also reduced inducible nitric oxide synthase (iNOS) immunocontent in the tumors. Molecular docking estimated that TP binds within the same range of iNOS regions (other iNOS inhibitors), such as N-Nitroarginine methyl ester (L-NAME). These data provide strong evidence that TP may be an interesting candidate for the development of new safe analgesic drugs that are effective for cancer pain control.

Monoterpenes as Perspective to Chronic Pain Management: A Systematic Review.

BACKGROUND: Individuals with chronic diseases have persistent pain as the main symptom, which can often reduce their life quality and functional capacity. The suffering of patients results from the interaction of aversive perception of pain with physical disability, social and family isolation, financial worries and fear of mutilation and death. As an individual and subjective phenomenon that involves many complex aspects, chronic pain should be evaluated and treated in its various components. Several drugs are currently used, but besides the high cost, they have side effects that are harmful to patients. Therefore, there is the need to search for new options for pain relief. Natural products as monoterpenes have been the target of many researchers. OBJECTIVE: This systematic review aimed to briefly summarize the knowledge of the analgesic potential of monoterpenes facing chronic pain. RESULTS: After a search in PubMed, Lilacs, Scopus and Cochrane, 27 articles were selected, which described the analgesic potential of 16 monoterpenes for relief of chronic pain. CONCLUSION: After analyzing the data, it can be suggested that these compounds are strong candidates for the treatment of painful states.

Delinquency and association with behavioral disorders and substance abuse.

OBJECTIVE: to determine the incidence and associations of attention deficit-hyperactivity disorder (ADHD), conduct disorder (CD), and substance abuse disorder (SAD) in adolescents in conflict with the law in a Brazilian cohort. METHODS: the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School Aged-Children (K-SADS-PL) was administered to 69 adolescent boys who were incarcerated for 45 days in the city of Curitiba, Brazil. RESULTS: mean age was 15.5 years (range, 12-16.9 years) and most adolescents originated from disadvantaged social classes (87%). They resided in neighborhoods on the outskirts of the city or towns in the greater metropolitan area. Truancy and low educational achievement were common, with 73.9% not currently attending school and 43.4% not having finished the 5th grade. The great majority lived in single-parent families and many had relatives who themselves had problems with the law. Psychiatric disorders were apparent in 81.1% of the subjects, with the most common disorders being CD (59.4%), SAD (53.6%), and ADHD (43.5%). Both ADHD (p <0.001) and CD (p <0.01) had significant associations with substance abuse. CONCLUSION: in male adolescents in conflict with the law, ADHD, CD, and SAD were all found to be associated with delinquency.

Delinquency and association with behavioral disorders and substance abuse / Delinquência e associação de transtornos comportamentais com abuso de substâncias

Objective: to determine the incidence and associations of attention deficit-hyperactivity disorder (ADHD), conduct disorder (CD), and substance abuse disorder (SAD) in adolescents in conflict with the law in a Brazilian cohort. Methods: the Brazilian version of the Schedule for Affective Disorders and Schizophrenia for School Aged-Children (K-SADS-PL) was administered to 69 adolescent boys who were incarcerated for 45 days in the city of Curitiba, Brazil. Results: mean age was 15.5 years (range, 12-16.9 years) and most adolescents originated from disadvantaged social classes (87%). They resided in neighborhoods on the outskirts of the city or towns in the greater metropolitan area. Truancy and low educational achievement were common, with 73.9% not currently attending school and 43.4% not having finished the 5th grade. The great majority lived in single-parent families and many had relatives who themselves had problems with the law. Psychiatric disorders were apparent in 81.1% of the subjects, with the most common disorders being CD (59.4%), SAD (53.6%), and ADHD (43.5%). Both ADHD (p <0.001) and CD (p <0.01) had significant associations with substance abuse. Conclusion: in male adolescents in conflict with the law, ADHD, CD, and SAD were all found to be associated with delinquency. .

Objetivo: determinar a incidência e a associação entre transtorno de déficit de atenção e hiperatividade (TDAH), transtorno de conduta (TC) e transtorno de abuso de substâncias (TAS) em adolescentes brasileiros em conflito com a lei. Métodos: a versão brasileira do Schedule for Affective Disorders and Schizophrenia for School Aged-Children (K-SADS-PL) foi aplicada em 69 adolescentes do sexo masculino, encarcerados por 45 dias na cidade de Curitiba, Brasil. Resultados: a média de idade foi de 15,5 anos (variação 12 a 16,9 anos ) e a maioria dos adolescentes (87%) era procedente de classes sociais desfavorecidas e residia em bairros na periferia da cidade ou cidades da região metropolitana. Evasão escolar e baixo rendimento escolar foram comuns. Ao todo, 73,9% não frequentavam a escola e 43,4% não concluíram a 5ª série. A grande maioria vivia em famílias monoparentais e muitos tinham parentes de primeiro grau também com problemas com a lei. 81,1% dos adolescentes apresentaram problemas psiquiátricos, e os transtornos mais comuns foram TC (59,4%), TAS (53,6%) e TDAH (43,5%). Nos adolescentes, tanto com TDAH (p < 0,001) quanto com TC (p < 0,01), houve associação significativa com abuso de substâncias. Conclusão: em adolescentes do sexo masculino em conflito com a lei, houve uma associação significativa de TDAH e TC com TAS. .