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An evaluation of the inflammatory enzymatic interactions related to pulmonary function can help identify biomarkers for interventions or prophylactic measures to improve patient prognosis. This study aimed to determine the effect of epoxide hydrolase inhibition by GSK2256294 in different pulmonary inflammation models. A secondary search was performed using Medline/PubMed, Web of Science, SciELO, Cochrane Library, Embase, Academic Google, and gray literature by two independent reviewers, who analyzed the methodological quality and consistency of the data. Different variables were compared using a meta-analysis. A total of 86 studies were found, 4 of which were selected from the gray literature. Based on the eligibility criteria, two clinical and one preclinical studies were evaluated. GSK2256294 inhibited the soluble epoxide hydrolase enzyme in both clinical and preclinical models, exhibiting greater effectiveness in clinical studies and contributing to the anti-inflammatory activity mediated by the eicosatrienoic pathway by reducing the levels of dihydroxyeicosatrienoic acids and leukotoxin-diol. Overall, GSK2256294 was identified as a promising drug for controlling the deleterious manifestations of lung inflammation. Further clinical and preclinical studies are required to ensure consistency among the evidence and identify other biological activities mediated by GSK2256294.
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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.
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COVID-19 , SARS-CoV-2 , Humanos , Linfócitos T CD8-Positivos , Linfócitos T Auxiliares-Indutores , PulmãoRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1-7), and angiotensin (1-9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1-7), and angiotensin (1-9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.
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O angioedema hereditário é uma doença autossômica dominante caracterizada por crises recorrentes de edema que acometem o tecido subcutâneo e o submucoso, com envolvimento de diversos órgãos. Os principais locais afetados são face, membros superiores e inferiores, as alças intestinais e as vias respiratórias superiores. Em decorrência da falta de conhecimento dessa condição por profissionais de saúde, ocorre atraso importante no seu diagnóstico, comprometendo a qualidade de vida dos indivíduos afetados. Além disso, o retardo no diagnóstico pode resultar em aumento da mortalidade por asfixia devido ao edema de laringe. A natureza errática das crises com variação do quadro clínico e gravidade dos sintomas entre diferentes pacientes, e no mesmo paciente ao longo da vida, se constitui em desafio no cuidado dos doentes que têm angioedema hereditário. O principal tipo de angioedema hereditário é resultante de mais de 700 variantes patogênicas do gene SERPING1 com deficiência funcional ou quantitativa da proteína inibidor de C1, porém nos últimos anos outras mutações foram descritas em seis outros genes. Ocorreram avanços importantes na fisiopatologia da doença e novas drogas para o tratamento do angioedema hereditário foram desenvolvidas. Nesse contexto, o Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) em conjunto com a Associação Brasileira de Alergia e Imunologia (ASBAI) atualizou as diretrizes brasileiras do angioedema hereditário. O maior conhecimento dos diversos aspectos resultou na divisão das diretrizes em duas partes, sendo nessa primeira parte abordados a definição, a classificação e o diagnóstico.
Hereditary angioedema is an autosomal dominant disease characterized by recurrent attacks of edema that affect the subcutaneous tissue and the submucosa, involving several organs. The main affected sites are the face, upper and lower limbs, gastrointestinal tract, and upper airways. Because health professionals lack knowledge about this condition, there is a significant delay in diagnosis, compromising the quality of life of affected individuals. Furthermore, delayed diagnosis may result in increased mortality from asphyxia due to laryngeal edema. The erratic nature of the attacks with variations in clinical course and severity of symptoms among different patients and in one patient throughout life constitutes a challenge in the care of patients with hereditary angioedema. The main type of hereditary angioedema results from more than 700 pathogenic variants of the SERPING1 gene with functional or quantitative deficiency of the C1 inhibitor protein, but in recent years other mutations have been described in six other genes. Important advances have been made in the pathophysiology of the disease, and new drugs for the treatment of hereditary angioedema have been developed. In this context, the Brazilian Study Group on Hereditary Angioedema (GEBRAEH) in conjunction with the Brazilian Association of Allergy and Immunology (ASBAI) updated the Brazilian guidelines on hereditary angioedema. Greater knowledge of different aspects resulted in the division of the guidelines into two parts, with definition, classification, and diagnosis being addressed in this first part.
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Humanos , Terapêutica , Classificação , Diagnóstico , Angioedemas Hereditários , Qualidade de Vida , Asfixia , Sinais e Sintomas , Sociedades Médicas , Preparações Farmacêuticas , Glicoproteínas , Edema Laríngeo , Alergia e Imunologia , MutaçãoRESUMO
O tratamento do angioedema hereditário tem início com a educação dos pacientes e familiares sobre a doença, pois é fundamental o conhecimento da imprevisibilidade das crises, assim como os seus fatores desencadeantes. O tratamento medicamentoso se divide em terapia das crises e profilaxia das manifestações clínicas. As crises devem ser tratadas o mais precocemente possível com o uso do antagonista do receptor de bradicinina, o icatibanto ou o concentrado de C1-inibidor. É necessário estabeler um plano de ação em caso de crises para todos os pacientes. A profilaxia de longo prazo dos sintomas deve ser realizada preferencialmente com medicamentos de primeira linha, como concentrado do C1-inibidor ou o anticorpo monoclonal anti-calicreína, lanadelumabe. Como segunda linha de tratamento temos os andrógenos atenuados. Na profilaxia de curto prazo, antes de procedimentos que podem desencadear crises, o uso do concentrado de C1-inibidor é preconizado. Existem algumas restrições para uso desses tratamentos em crianças e gestantes que devem ser consideradas. Novos medicamentos baseados nos avanços do conhecimento da fisiopatologia do angioedema hereditário estão em desenvolvimento, devendo melhorar a qualidade de vida dos pacientes. O uso de ferramentas padronizadas para monitorização da qualidade de vida, do controle e da atividade da doença são fundamentais no acompanhamento destes pacientes. A criação de associações de pacientes e familiares de pacientes com angioedema hereditário tem desempenhado um papel muito importante no cuidado destes pacientes no nosso país.
The treatment of hereditary angioedema begins with the education of patients and their families about the disease, as it is essential to know the unpredictability of attacks as well as their triggering factors. Drug treatment is divided into attack therapy and prophylaxis of clinical manifestations. Attacks should be treated as early as possible with the bradykinin receptor antagonist icatibant or C1-inhibitor concentrate. An action plan needs to be established for all patients with attacks. Long-term prophylaxis of symptoms should preferably be performed with first-line drugs such as C1-inhibitor concentrate or the anti-kallikrein monoclonal antibody lanadelumab. Attenuated androgens are the second line of treatment. In short-term prophylaxis, before procedures that can trigger attacks, the use of C1-inhibitor concentrate is recommended. There are some restrictions for the use of these treatments in children and pregnant women that should be considered. New drugs based on advances in knowledge of the pathophysiology of hereditary angioedema are under development and are expected to improve patient quality of life. The use of standardized tools for monitoring quality of life and controlling disease activity is essential in the follow-up of these patients. The creation of associations of patients and families of patients with hereditary angioedema has played a very important role in the care of these patients in Brazil.
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Humanos , Tratamento Farmacológico , Angioedemas Hereditários , Anticorpos Monoclonais Humanizados , Antagonistas dos Receptores da Bradicinina , Pacientes , Qualidade de Vida , Terapêutica , Bradicinina , Preparações Farmacêuticas , Calicreínas , Medicamentos de ReferênciaRESUMO
BACKGROUND: Acquired deficiency of C1 inhibitor (AAE-C1-INH) is a very rare cause of recurrent angioedema, with few cases reported in the literature. We aimed to describe a series of patients with AAE-C1-INH who were diagnosed and received care at angioedema reference centers in Brazil, affiliated to the Brazilian Group of Studies on Hereditary Angioedema. METHODS: Fourteen patients from 8 Brazilian Angioedema Reference Centers, diagnosed with AAE-C1-INH, were included in this study. Clinical data collected included sex, date of birth, date of onset of symptoms, date of diagnosis, plasma levels of antigenic and/or functional C1-INH, levels of C4 and C1q, location and treatment of angioedema attacks, long-term prophylaxis, associated diseases, and definitive treatment. RESULTS: Fourteen patients were identified with AAE-C1-INH. Most patients (10/14; 71.4%) were female. The median age at onset of symptoms was 56.5 years (range, 14-74 years; interquartile range [IQR], 32-64 years), and median age at diagnosis was 58.0 years (range, 20-76 years; IQR, 38-65 years), with a median time until diagnosis of 2 years (range, 0-6 years; IQR, 1-3 years). The most common manifestations were cutaneous (face, eyelids, lips, trunk, hands, feet, and genitals). Most patient had low levels of C4 (13/14; 92.8%) and of antigenic C1-INH (8/14; 57.1%). Four had decreased functional activity of C1-INH (4/7; 57.1%) and C1q levels were low in 5 patients (5/12; 41.6%). Underlying diseases were identified in all 14 patients, with lymphoma of the splenic marginal zone and monoclonal gammopathy of undetermined significance being the most frequent. Nine patients (64.2%) needed long-term prophylactic treatment for recurrent angioedema and 5 patients (46.7%) required treatment for angioedema attacks. Most of them (12/14; 85.7%) had resolution of angioedema. CONCLUSION: Therapy of AAE-C1-INH aims to control symptoms; however, diagnosis and treatment of the underlying disease, when present, should be an important target and may lead to the resolution of angioedema in patients with AAE-C1-INH.
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Angioedema , Angioedemas Hereditários , Adolescente , Adulto , Idoso , Angioedema/diagnóstico , Angioedema/etiologia , Angioedemas Hereditários/terapia , Brasil/epidemiologia , Proteína Inibidora do Complemento C1/genética , Complemento C1q/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Coffea arabica is commonly known for its cardiotonic and neurotonic activities, but in some places' folk medicine, like in Arabia and Africa, C. arabica is used to treat headache, migraine, the flu, anemia, oedema, asthenia, asthma, inflammation and wounds. AIMS OF THE STUDY: The aims were to evaluate if the aqueous extracts of Coffea arabica, prepared from beans with different degrees of roasting, and their main chemical constituents could exert an in vivo anti-gouty effect. MATERIALS AND METHODS: Coffea extracts were obtained from the beans of not roasted, light, medium and dark roasted coffee and from decaffeinated and traditional coffees and were prepared with water at 25°C and at 98°C. C57BL/6 mice were induced to gout by an injection of monosodium urate crystals and treated with coffee extracts at doses of 25, 75 and 225 mg/kg and their chemical constituents at a dose of 10 mg/kg. The antinociceptive and anti-inflammatory effects were evaluated. RESULTS: Treatments with Coffea extracts prepared with water at 98°C were more effective to exert antinociceptive and anti-inflammatory activities than the ones prepared with water at 25°C. Caffeic and chlorogenic acids reduced hypernociception in animals when compared with negative control group (7.79 and 5.69 vs 18.53; P < 0.05 and P < 0.001, respectively), inhibited neutrophil migration (1.59 × 104 and 0.38 × 104 vs 9.47 × 104; P < 0.0001 both) and decreased pro-inflammatory cytokines concentration (IL-1ß, IL-6 and TNF-α). CONCLUSIONS: We have demonstrated that our treatments attenuated gout, and this effect could be attributed to a reducement in hypernociception, neutrophil migration and cytokines concentration. These results suggest coffee as a potential candidate for studies in acute gout therapy.
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Coffea/química , Gota/tratamento farmacológico , Inflamação/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Analgésicos/química , Analgésicos/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fitoterapia , Distribuição AleatóriaRESUMO
This paper presents the main results of a study developed in a Graduate Program from 2016 to 2018 with all workers from the Intra-Hospital Commission for Donating Organs and Tissues for Transplants of a Public Tertiary Hospital, in which the general proposal was to analyze the organization and the work process of this team, investigating mental strain in the workers involved. This qualitative exploratory research in Occupational Health focused on Work-Related Mental Health. The material selected for the study was retrieved by bibliographic survey, participant observation, social questionnaire, and semi-directed individual interview. It was subjected to thematic content analysis and referred to the theoretical category of mental strain. The organization and work process analysis evidenced that workers are subject to biomechanical, biological, and mental health accident risks. This condition characterizes the wear process of these workers, in particular the mental strain, which can lead to health loss. Nevertheless, workers are emotionally connected to work, which can be a source of sublimation, providing pleasure and satisfaction.
Neste artigo apresentamos os principais resultados de um estudo desenvolvido em um Programa de Pós-Graduação, entre 2016 e 2018, com todos os trabalhadores da Comissão Intra-Hospitalar de Doação de Órgãos e Tecidos para Transplantes, de um Hospital Público Terciário, em que a proposta geral foi analisar a organização e o processo de trabalho desta equipe, procurando investigar se havia desgaste mental nos trabalhadores envolvidos. Trata-se de uma pesquisa exploratória de base qualitativa no campo Saúde do Trabalhador, com foco na Saúde Mental Relacionada ao Trabalho, em que o material selecionado para o estudo, obtido por meio de levantamento bibliográfico, observação-participante, questionário social e entrevista individual semidirigida, foi submetido à análise de conteúdo temática e remetido à categoria teórica de desgaste mental. A análise da organização e do processo de trabalho demonstrou que os trabalhadores estão submetidos a riscos de acidentes, biomecânicos, biológicos e para saúde mental, quadro que caracteriza o processo de desgaste destes trabalhadores, em particular, o desgaste mental, podendo levá-los a perda da saúde. Apesar disso, os trabalhadores estão afetivamente ligados ao trabalho, que pode ser fonte de sublimação, propiciando prazer e satisfação.
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Saúde Ocupacional , Obtenção de Tecidos e Órgãos , Humanos , Saúde Mental , Organizações , Inquéritos e QuestionáriosRESUMO
Resumo Neste artigo apresentamos os principais resultados de um estudo desenvolvido em um Programa de Pós-Graduação, entre 2016 e 2018, com todos os trabalhadores da Comissão Intra-Hospitalar de Doação de Órgãos e Tecidos para Transplantes, de um Hospital Público Terciário, em que a proposta geral foi analisar a organização e o processo de trabalho desta equipe, procurando investigar se havia desgaste mental nos trabalhadores envolvidos. Trata-se de uma pesquisa exploratória de base qualitativa no campo Saúde do Trabalhador, com foco na Saúde Mental Relacionada ao Trabalho, em que o material selecionado para o estudo, obtido por meio de levantamento bibliográfico, observação-participante, questionário social e entrevista individual semidirigida, foi submetido à análise de conteúdo temática e remetido à categoria teórica de desgaste mental. A análise da organização e do processo de trabalho demonstrou que os trabalhadores estão submetidos a riscos de acidentes, biomecânicos, biológicos e para saúde mental, quadro que caracteriza o processo de desgaste destes trabalhadores, em particular, o desgaste mental, podendo levá-los a perda da saúde. Apesar disso, os trabalhadores estão afetivamente ligados ao trabalho, que pode ser fonte de sublimação, propiciando prazer e satisfação.
Abstract This paper presents the main results of a study developed in a Graduate Program from 2016 to 2018 with all workers from the Intra-Hospital Commission for Donating Organs and Tissues for Transplants of a Public Tertiary Hospital, in which the general proposal was to analyze the organization and the work process of this team, investigating mental strain in the workers involved. This qualitative exploratory research in Occupational Health focused on Work-Related Mental Health. The material selected for the study was retrieved by bibliographic survey, participant observation, social questionnaire, and semi-directed individual interview. It was subjected to thematic content analysis and referred to the theoretical category of mental strain. The organization and work process analysis evidenced that workers are subject to biomechanical, biological, and mental health accident risks. This condition characterizes the wear process of these workers, in particular the mental strain, which can lead to health loss. Nevertheless, workers are emotionally connected to work, which can be a source of sublimation, providing pleasure and satisfaction.
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Humanos , Obtenção de Tecidos e Órgãos , Saúde Ocupacional , Organizações , Saúde Mental , Inquéritos e QuestionáriosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ethanolic extract of aerial parts from Lychnophora pinaster Mart. are used in traditional Brazilian medicine for treating pain, rheumatism and inflammation. AIM OF THE STUDY: Drugs for the treatment of gout present severe adverse effects, justifying the need to search for new therapeutic options. The aim of the present study was to evaluate the effects of the ethanolic extract of L. pinaster and its main constituents in arthritis induced in mice by the injection of monosodium urate (MSU) crystals. MATERIALS AND METHODS: Antinociceptive effect was investigated using an electronic pressure-meter nociception paw test in C57BL/6 mice. Anti-gouty arthritis was investigated in mice induced with gout by the injection of MSU crystals into their femur-tibial tissue. Ethanolic extract of the aerial parts of Lychnophora pinaster and its main chemical constituents were evaluated as treatment. RESULTS: The ethanolic extract and their main chemical constituents inhibited neutrophil migration, reduced IL-1ß and TNF-α concentrations in the inflamed tissue and showed antinociceptive activity. CONCLUSIONS: Gouty arthritis effects of the ethanolic extract can be attached to a synergistic effect of terpenes, flavonoids and phenolic acids present in the extract. Results obtained support the use of this extract and its main chemical constituents in the treatment of gout, inflammation, and pain.
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Artrite Gotosa/tratamento farmacológico , Asteraceae/química , Gota/tratamento farmacológico , Extratos Vegetais/farmacologia , Analgésicos/química , Analgésicos/isolamento & purificação , Analgésicos/farmacologia , Animais , Artrite Gotosa/patologia , Brasil , Modelos Animais de Doenças , Gota/patologia , Inflamação/tratamento farmacológico , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Dor/tratamento farmacológico , Dor/etiologia , Extratos Vegetais/químicaRESUMO
Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin-kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin-kallikrein system in two markers that indicate improved disease recovery.
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Bradicinina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Proteína Inibidora do Complemento C1/uso terapêutico , Sistema Calicreína-Cinina/efeitos dos fármacos , Calicreínas/antagonistas & inibidores , Adulto , Idoso , Bradicinina/uso terapêutico , Estudos de Casos e Controles , Reposicionamento de Medicamentos , Feminino , Humanos , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: SARS-CoV-2, the virus that causes COVID-19, enters the cells through a mechanism dependent on its binding to angiotensin-converting enzyme 2 (ACE2), a protein highly expressed in the lungs. The putative viral-induced inhibition of ACE2 could result in the defective degradation of bradykinin, a potent inflammatory substance. We hypothesize that increased bradykinin in the lungs is an important mechanism driving the development of pneumonia and respiratory failure in COVID-19. METHODS: This is a phase II, single-center, three-armed parallel-group, open-label, active control superiority randomized clinical trial. One hundred eighty eligible patients will be randomly assigned in a 1:1:1 ratio to receive either the inhibitor of C1e/kallikrein 20 U/kg intravenously on day 1 and day 4 plus standard care; or icatibant 30 mg subcutaneously, three doses/day for 4 days plus standard care; or standard care alone, as recommended in the clinical trials published to date, which includes supplemental oxygen, non-invasive and invasive ventilation, antibiotic agents, anti-inflammatory agents, prophylactic antithrombotic therapy, vasopressor support, and renal replacement therapy. DISCUSSION: Accumulation of bradykinin in the lungs is a common side effect of ACE inhibitors leading to cough. In animal models, the inactivation of ACE2 leads to severe acute pneumonitis in response to lipopolysaccharide (LPS), and the inhibition of bradykinin almost completely restores the lung structure. We believe that inhibition of bradykinin in severe COVID-19 patients could reduce the lung inflammatory response, impacting positively on the severity of disease and mortality rates. TRIAL REGISTRATION: Brazilian Clinical Trials Registry Universal Trial Number (UTN) U1111-1250-1843. Registered on May/5/2020.
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Bradicinina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Proteína Inibidora do Complemento C1/administração & dosagem , Insuficiência Respiratória/tratamento farmacológico , Adulto , Enzima de Conversão de Angiotensina 2/metabolismo , Bradicinina/administração & dosagem , Bradicinina/efeitos adversos , Bradicinina/antagonistas & inibidores , Bradicinina/imunologia , Bradicinina/metabolismo , Antagonistas de Receptor B2 da Bradicinina/administração & dosagem , Antagonistas de Receptor B2 da Bradicinina/efeitos adversos , Brasil , COVID-19/complicações , COVID-19/imunologia , COVID-19/virologia , Ensaios Clínicos Fase II como Assunto , Proteína Inibidora do Complemento C1/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Humanos , Injeções Intravenosas , Injeções Subcutâneas , Calicreínas/antagonistas & inibidores , Calicreínas/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Respiratória/imunologia , Insuficiência Respiratória/virologia , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the anti-inflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity. AIM OF THE STUDY: Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-α and IL-1ß cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis. MATERIALS AND METHODS: The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lactones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1ß and TNF-α concentrations, and SOD and CAT activities. RESULTS: Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-α production. These compounds also demonstrated antinociceptive and antioxidant activities. CONCLUSION: Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the pro-inflammatory cytokine TNF-α. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Gotosa/tratamento farmacológico , Asteraceae/química , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Artrite Gotosa/induzido quimicamente , Hidrocarbonetos Aromáticos com Pontes/isolamento & purificação , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Catalase/metabolismo , Furanos/isolamento & purificação , Furanos/farmacologia , Furanos/uso terapêutico , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Articulações/efeitos dos fármacos , Lactonas/isolamento & purificação , Lactonas/uso terapêutico , Masculino , Medicina Tradicional/métodos , Camundongos Endogâmicos C57BL , Neutrófilos/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/uso terapêutico , Sesterterpenos/isolamento & purificação , Sesterterpenos/farmacologia , Sesterterpenos/uso terapêutico , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/toxicidadeRESUMO
After the formation of Itaipu Reservoir, the invader Trachelyopterus galeatus colonized the upper Paraná River. Light microscopy was used to describe gametogenesis and the reproductive phases of females and males. The following data were verified: diameter of the oocytes, spawning type, batch fecundity by ovary weight, standard length, and total weight of the fish, along with the regions where this species reproduced in the upper Paraná River floodplain. A total of 470 specimens were collected quarterly in 2016, 2018 and 2019, and bimonthly in 2017. The gonads were fixed in a Karnovsky solution, dehydrated, infiltrated, and embedded in historesin. The histological slides were stained using PAS + iron hematoxylin + metanil yellow, analyzed and photographed under an image-capturing microscope. As regards diameter of the oocytes and fecundity estimates, ovaries whose oocytes were measured under a stereomicroscope were sampled. In the oogenesis, undifferentiated and differentiated oogonia, early primary growth oocytes, secondary growth oocytes, full-grown oocytes and maturing oocytes were recorded. In the spermatogenesis, primary and secondary spermatogonia, primary and secondary spermatocytes, spermatids and spermatozoa were recorded. The reproductive phases found for females and males were: immature, early development, late development, spawning/sperm-releasing capable, regression, and regeneration. Trachelyopterus galeatus prefers to occupy and reproduce in the Ventura, Patos, Guaraná, Fechada, Garças, and Pau Véio lagoons. The diameter of the oocytes varied from 0.4 to 2.9 mm. Females spawn, on average, 113 oocytes per batch. Batch fecundity variation shows that the larger the ovary, standard length, and total weight, the larger the number of oocytes to be spawned. This invader possesses reproductive success in the upper Paraná River floodplain, especially in lagoons.(AU)
Assuntos
Animais , Peixes-Gato/embriologia , Peixes-Gato/crescimento & desenvolvimento , Inseminação , Reprodução , Fertilidade , EspermatogêneseRESUMO
After the formation of Itaipu Reservoir, the invader Trachelyopterus galeatus colonized the upper Paraná River. Light microscopy was used to describe gametogenesis and the reproductive phases of females and males. The following data were verified: diameter of the oocytes, spawning type, batch fecundity by ovary weight, standard length, and total weight of the fish, along with the regions where this species reproduced in the upper Paraná River floodplain. A total of 470 specimens were collected quarterly in 2016, 2018 and 2019, and bimonthly in 2017. The gonads were fixed in a Karnovsky solution, dehydrated, infiltrated, and embedded in historesin. The histological slides were stained using PAS + iron hematoxylin + metanil yellow, analyzed and photographed under an image-capturing microscope. As regards diameter of the oocytes and fecundity estimates, ovaries whose oocytes were measured under a stereomicroscope were sampled. In the oogenesis, undifferentiated and differentiated oogonia, early primary growth oocytes, secondary growth oocytes, full-grown oocytes and maturing oocytes were recorded. In the spermatogenesis, primary and secondary spermatogonia, primary and secondary spermatocytes, spermatids and spermatozoa were recorded. The reproductive phases found for females and males were: immature, early development, late development, spawning/sperm-releasing capable, regression, and regeneration. Trachelyopterus galeatus prefers to occupy and reproduce in the Ventura, Patos, Guaraná, Fechada, Garças, and Pau Véio lagoons. The diameter of the oocytes varied from 0.4 to 2.9 mm. Females spawn, on average, 113 oocytes per batch. Batch fecundity variation shows that the larger the ovary, standard length, and total weight, the larger the number of oocytes to be spawned. This invader possesses reproductive success in the upper Paraná River floodplain, especially in lagoons.
Assuntos
Animais , Espermatogênese , Fertilidade , Inseminação , Peixes-Gato/crescimento & desenvolvimento , Peixes-Gato/embriologia , ReproduçãoRESUMO
COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1É may have great therapeutic potential for the development of novel drugs to treat COVID-19.
Assuntos
Betacoronavirus/fisiologia , Glicemia/metabolismo , Infecções por Coronavirus/complicações , Complicações do Diabetes/complicações , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Monócitos/metabolismo , Pneumonia Viral/complicações , Adulto , COVID-19 , Linhagem Celular , Infecções por Coronavirus/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Feminino , Glicólise , Humanos , Inflamação/complicações , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/virologia , Pandemias , Pneumonia Viral/metabolismo , Espécies Reativas de Oxigênio/metabolismo , SARS-CoV-2 , Transdução de SinaisRESUMO
Tabebuia species (Bignoniaceae) have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL) of Tabebuia roseoalba (Ridl.) Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase) by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate) crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species.
RESUMO
O estudo teve como objetivo investigar o cotidiano de gestantes em situação de rua e sua relação com as políticas públicas na cidade de Santos, litoral do Estado de São Paulo. A coleta de dados foi feita através do registro e estudo de narrativas de memórias de vida. A análise deu-se pelo agrupamento temático de trechos das narrativas, sendo identificadas quatro principais categorias: vida na rua; cuidado e gestação; projetos futuros; e rede pública de serviços. As narrativas revelam mulheres com capacidade criativa para desejar uma vida melhor a partir da possibilidade de ter um filho. Entretanto, a condição social em que vivem, envolvendo a luta diária pela sobrevivência e, em alguns casos, a dependência química dificultam o planejamento de estratégias que transformem o desejo em um projeto de vida. Dessa forma, na maioria das vezes perdem a guarda de seus filhos. Embora conheçam os serviços públicos, quase sempre os acessam apenas em casos de urgência. Não se identificaram na rede de serviços assistenciais - pública e do terceiro setor - programas focados na questão da gestante em situação de rua, ainda que o Brasil já viva, atualmente, histórias de famílias que têm a situação de rua como experiência intergeracional. Os resultados apontam para a necessidade de constituição de políticas intersetoriais, voltadas para gestantes em situação de rua.
The study aimed to investigate the daily routine of homeless pregnant women and their relation to public policies in the city of Santos, State of São Paulo. Data was collected through the record and study of narratives of life memories. The analysis was conducted through the thematic grouping of excerpts of narratives, and four main categories were identified: life on the street; care and pregnancy; future projects; and public services. The narratives reveal women with creative ability to desire a better life based on the possibility of having a child. However, the social condition in which they live, which involves the daily struggle for survival and, in some cases, drug addiction, hinders the planning of strategies to transform the desire into a life project. Thus, most of them lose custody of their children. Although they know the public services, they go to them only in emergencies, mostly. We have not identified, in the network of care services - public and third sector -, programs focusing on the issue of homeless pregnant women, even though Brazil already witnesses, today, stories of families who have the homeless situation as an intergenerational experience. The results point to the need of making intersectoral policies targeted at homeless pregnant women.