Neutrophil elastase:From mechanisms to therapeutic potential / 药物分析学报

Neutrophil elastase(NE),a major protease in the primary granules of neutrophils,is involved in microbicidal activity.NE is an important factor promoting inflammation,has bactericidal effects,and shortens the inflammatory process.NE also regulates tumor growth by promoting metastasis and tumor microenvironment remodeling.However,NE plays a role in killing tumors under certain conditions and promotes other diseases such as pulmonary ventilation dysfunction.Additionally,it plays a complex role in various physiological processes and mediates several diseases.Sivelestat,a specific NE inhibitor,has strong potential for clinical application,particularly in the treatment of coronavirus disease 2019(COVID-19).This review discusses the pathophysiological processes associated with NE and the potential clinical applications of sivelestat.

Progressive neuropathy in patients with lepromatous leprosy after multidrug therapy

BACKGROUND The lepromatous pole is a stigmatising prototype for patients with leprosy. Generally, these patients have little or no symptoms of peripheral nerve involvement at the time of their diagnosis. However, signs of advanced peripheral neuropathy would be visible during the initial neurological evaluation and could worsen during and after multidrug therapy (MDT). Disabilities caused by peripheral nerve injuries greatly affect these patients' lives, and the pathophysiological mechanisms underlying nerve damage remain unclear. OBJECTIVES To evaluate the outcome of peripheral neuropathy in patients with lepromatous leprosy (LL) and persistent neuropathic symptoms years after completing MDT. METHODS We evaluated the medical records of 14 patients with LL who underwent nerve biopsies due to worsening neuropathy at least four years after MDT. FINDINGS Neuropathic pain developed in 64.3% of the patients, and a neurological examination showed that most patients had alterations in the medium- and large-caliber fibers at the beginning of treatment. Neurological symptoms and signs deteriorated despite complete MDT and prednisone or thalidomide use for years. Nerve conduction studies showed that sensory nerves were the most affected. MAIN CONCLUSIONS Patients with LL can develop progressive peripheral neuropathy, which continues to develop even when they are on long-term anti-inflammatory and immunosuppressive therapy.

Daño renal en pacientes con COVID-19 / Kidney damage in COVID-19 patients

Introducción: La COVID-19 es una enfermedad relativamente nueva, que puede causar afecciones en diferentes órganos. El daño renal se asocia a la mortalidad, por lo que debe ser identificado precozmente. Objetivo: Describir el daño renal en pacientes de COVID-19. Métodos: Se realizó una revisión bibliográfica de materiales publicados durante el periodo comprendido entre el 20 de abril al 25 de agosto de 2020. Se consultaron las bases de datos PubMed, SciELO, Ebsco y Clinical Key, así como el motor de búsqueda Google Académico. Los métodos utilizados fueron análisis-síntesis, inducción-deducción e histórico-lógico. Análisis e integración de la información: Para realizar un diagnóstico precoz que permita modificar el pronóstico y la historia natural de la mortalidad, se realizan numerosas investigaciones en los pacientes portadores de la COVID-19. En la literatura científica se reportan artículos sobre la importancia de la detección del daño renal. Se ha identificado que, tanto el daño renal previo, como el desarrollo de este durante la COVID-19, desempeñan un rol importante en el aumento de la tasa de letalidad. Conclusiones: La Afección renal crónica es una agravante en pacientes que padecen COVID-19. La descripción de los mecanismos causantes de la lesión renal es fundamental para establecer el pronóstico de estos pacientes, sin embargo, luego de la revisión, se comprobó que aún es escasa la literatura científica que aborde la relación del daño renal durante la COVID-19(AU)

Introduction: COVID-19 is a relatively new disease that affects various organs. Associated as it is to mortality, kidney damage should be identified as early as possible. Objective: Conduct a bibliographic review aimed at describing kidney damage in COVID-19 patients. Methods: A bibliographic review was conducted of materials about the topic published from 20 April to 25 August 2020. The search was carried out in the databases PubMed, SciELO, Ebsco and Clinical Key, as well as the search engine Google Scholar. Analytic-synthetic, inductive-deductive and historical-logical methods were used. Data analysis and integration: In order to obtain an early diagnosis allowing to modify the prognosis and natural evolution of mortality, a large number of studies are performed on patients carrying COVID-19. Papers are found in the scientific literature which refer to the importance of detecting kidney damage. It has been found that kidney damage, either developing before or during the course of the disease, plays an important role in the increase in lethality. Conclusions: Kidney damage is common in COVID-19 patients. Describing the mechanisms causing the kidney injury is a fundamental pillar to establish the prognosis for these patients. The description of kidney damage during COVID-19 is still scarce in the scientific literature(AU)

Disfunciones quimiosensoriales del olfato y el gusto provocadas por el SARS-CoV-2 / Chemosensory dysfunctions of taste and smell caused by SARS-CoV-2 / Disfunções quimiossensoriais de olfato e paladar causadas pelo SARS-CoV-2

RESUMEN Introducción: Múltiples reportes de la literatura científica avalan, que los trastornos del olfato y el gusto son cada vez más frecuentes desde el inicio de la COVID-19, ofreciendo diversos mecanismos fisiopatológicos para explicar estas alteraciones. Objetivo: Sistematizar las evidencias científicas disponibles, relacionadas con alteraciones del olfato y gusto producidas por SARS-CoV-2. Método: Se desarrolló una revisión bibliográfica basada en el análisis documental, la sistematización y contrastación de la información científica realizada sobre el tema. Las búsquedas se realizaron en bases de datos disponibles (SciELO, Medline, Scopus, Medscape), con el buscador Google Académico. Desarrollo: La información se estructuró en aspectos morfofuncionales de los sistemas del olfato y el gusto; estructura y replicación del SARS-CoV-2; interacción del virus con el sistema renina-angiotensina-aldosterona, su afinidad por el receptor enzima convertidora; mecanismos fisiopatológicos de estas disfunciones. Conclusiones: Aunque se describen las alteraciones del olfato y el gusto en pacientes con COVID-19, no están totalmente esclarecidos los mecanismos fisiopatogénicos relacionados con estas disfunciones quimiosensoriales. No obstante, su aparición en ausencia de otras enfermedades respiratorias, debe alertar al personal de salud sobre la posibilidad de infección por SARS-CoV-2.

ABSTRACT Introduction: Multiple scientific reports certified that disorders of taste and smell are more frequent since COVID-19 onset, reporting various pathophysiological mechanisms to explain these alterations. Objective: To methodize the available scientific evidence related to smell and taste disorders caused by SARS-CoV-2. Method: A bibliographic review, based on the documentary analyses, systematization and contrasting view of scientific information on the topic, was carried out. Search was conducted on available databases (SciELO, Medline, Scopus, Medscape), using the web search engine Academic Google. Development: Information gathered was performed based on taste and smell morphofunctional aspects; structure and replication of SARS-CoV-2; virus interaction with renin-angiotensin-aldosterone system and its affinity for the converting enzyme receptor; pathophysiological mechanisms of these dysfunctions. Conclusions: Although alterations of smell and taste are described in patients with COVID-19, the pathophysiological mechanisms associated with these chemosensory dysfunctions are not totally clarified. However, the onset of these symptoms in absence of other respiratory illnesses should alert health care personnel concerning to a possible SARS-CoV-2 infection.

RESUMO Introdução: Diversos relatos da literatura científica sustentam que os distúrbios do olfato e do paladar são cada vez mais frequentes desde o início da COVID-19, oferecendo vários mecanismos fisiopatológicos para explicar essas alterações. Objetivo: Sistematizar as evidências científicas disponíveis relacionadas às alterações de olfato e paladar produzidas pelo SARS-CoV-2. Método: Foi desenvolvida uma revisão bibliográfica a partir da análise documental, da sistematização e do contraste das informações científicas realizadas sobre o assunto. As buscas foram realizadas nas bases de dados disponíveis (SciELO, Medline, Scopus, Medscape), com a ferramenta de busca Google Scholar. Desenvolvimento: A informação foi estruturada em aspectos morfofuncionais dos sistemas olfativo e gustativo; estrutura e replicação de SARS-CoV-2; interação do vírus com o sistema renina-angiotensina-aldosterona, sua afinidade pelo receptor enzima conversora; mecanismos fisiopatológicos dessas disfunções. Conclusões: Embora as alterações do olfato e do paladar sejam descritas em pacientes com COVID-19, os mecanismos fisiopatogênicos relacionados a essas disfunções quimiossensoriais não estão totalmente esclarecidos. No entanto, seu aparecimento na ausência de outras doenças respiratórias deve alertar o pessoal de saúde para a possibilidade de infecção pelo SARS-CoV-2.

The research status of pathogenesis of sepsis related thrombocytopenia / 天津医药

Sepsis is a lethal organ dysfunction caused by infection induced reaction maladjustment. Thrombocytopenia is not only a common complication of sepsis, but also closely related to the patient's prognosis. In the clinical treatment, it is important to identify the etiology and pathogenesis of thrombocytopenia associated with sepsis and choose appropriate methods to correct thrombocytopenia in time to improve the prognosis of patients. This article gives an introduction to the research status of the etiology, pathophysiological mechanism and molecular mechanism of sepsis-related thrombocytopenia.

Depresión en insuficiencia cardíaca crónica:: causa o consecuencia / Depression in chronic heart failure: cause or consequence / Depressão na insuficiência cardíaca crônica: causa ou conseqüência

La depresión está presente entre el 17%-37% de los pacientes con insuficiencia cardíaca (IC), generando altos costos para la salud pública. Es importante considerar que los pacientes con diagnóstico de depresión presentan un incremento 4 veces mayor en términos de mortalidad comparado con aquellos que no la presentan. Los estudios en IC se han basado en las últimas décadas en los efectos de dicha enfermedad, rehospitalizaciones, calidad de vida y costos para la salud pública, dejándose de lado factores psicosociales como la depresión, la cual tendría un alto impacto nocivo sobre los pacientes. Aun se requiere de un mayor número de estudios e investigaciones para la comprensión de esta enfermedad. La depresión clínica es un desorden que consiste en una combinación de elementos que interfieren con la capacidad de las personas para realizar sus actividades habituales. Se debe tener en cuenta que los pacientes con IC presentan ciclos que varían de períodos de estabilización a períodos de hospitalización, provocando que los síntomas depresivos se modifiquen en el corto tiempo, dependiendo del estado de salud del paciente, ya sea que se encuentre hospitalizado o entre la cuarta y sexta semana posterior al alta. El objetivo de este trabajo es aportar información y datos basados en las investigaciones sobre depresión en IC, para considerar la necesidad de realizar el diagnóstico y aplicar un tratamiento precoz en los pacientes, mejorando la calidad de vida y evitando de esta manera la progresión de su enfermedad.

Depression is present in 17%-37% of patients with heart failure (HF), generating high costs for public health. It is important to consider that patients with a diagnosis of depression present a 4-fold increase in terms of mortality compared to those who do not. In the last decades, studies on HF have been based on the effects of this disease, rehospitalizations, quality of life and costs for public health, leaving aside psychosocial factors such as depression, which would have a high harmful impact on patients. Even more research and studies are needed to understand this disease. Clinical depression is a disorder consisting of a combination of elements that interfere with people's ability to perform their usual activities. It should be taken into account that patients with HF present cycles that vary from periods of stabilization to periods of hospitalization, causing depressive symptoms to be modified in the short time, depending on the patient's health status, whether hospitalized and between the fourth and sixth week after discharge. The aim of this paper is to provide information and data based on the research on depression in HF, to consider the need to make the diagnosis and to apply an early treatment in patients, improving the quality of life and avoiding the progression of their disease.

A depressão está presente entre 17%-37% dos pacientes com insuficiência cardíaca (IC), gerando altos custos para a saúde pública. É importante considerar que os pacientes diagnosticados com depressão têm um aumento de 4 vezes mais elevados em termos de mortalidade em comparação com aqueles que não sofrem desta doença. Nas últimas décadas, os estudos em IC foram com base nos efeitos da doença, reinternações, qualidade de vida e os custos para a saúde pública, deixando de lado fatores psicossociais, como depressão, o que teria um impacto negativo no alto de pacientes. Embora precise de um número maior de estudos e pesquisas para a compreensão desta doença. A depressão clínicaé uma doença que envolve uma combinação de elementos que interferem com a capacidade das pessoas para realizar suas atividades habituais. Deve notar-se que os pacientes com IC têm ciclos que variam de períodos de estabilização à períodos de hospitalização, causando sintomas depressivos alteradas no curto período de tempo, dependendo do estado de saúde do paciente, quer estejam hospitalizados e entre a quarta e a sexta semana após a alta. O objetivo deste estudo é fornecer informação detalhada e com base em pesquisa sobre depressão em dados de IC, a considerar a necessidade de diagnóstico e implementar o tratamento precoce em pacientes, melhorando a qualidade de vida e evitando assim a progressão da sua doença.

Progress on the protective effect of compounds from natural medicines on cerebral ischemia / 中国天然药物

The treatment of cerebral ischemic disease by natural medicines has a long history, and has accumulated a rich theoretical knowledge and treatment experience. The objective of this review is to critically evaluate the experimental research situation of the protective effect of the individual compounds from natural medicine on cerebral ischemia in the past ten years, emphasizing the major mechanisms underlying cerebral ischemic pathophysiology. Sixteen representative compounds from natural medicines which are often used to treat stroke are discussed. The results indicate that these components possess a protective effect on cerebral ischemia, and that these components have different mechanisms, including inhibiting excitotoxicity by ginkgolide B, antiapoptosis of breviscapine, influencing astrocytic activation and proliferation of tanshinone IIA, influencing free radicals by ginsenoside Rd, impairing blood-brain barrier disruption by baicalin, and the anti-inflammatory activity of tetramethylpyrazine. Moreover, some components have multiple neuroprotective mechanisms. Therefore, the combination of individual compounds from natural medicines, considering the mechanisms of cerebral ischemia, may be beneficial to patients with cerebral ischemia in the future. This approach will provide a direction for the further application and exploitation of new drug development in the treatment of cerebral ischemia.

Mecanismos de ação dos corticosteróides na polipose rinossinusal: [revisão] / Mechanism of action of glucocorticoids in nasal polyposis: [review]

Os glicocorticóides (GC) são drogas de escolha no tratamento clínico da polipose nasossinusal conforme recomendação da literatura. Entretanto, seus mecanismos de ação nas regressões dos sintomas clínicos e dos pólipos não são totalmente compreendidos. Sabe-se que a administração tópica e ou sistêmica dos glicocorticóides leva a variações na expressão de citocinas, quimiocinas e linfocinas, além das alterações celulares. Assim, os GC suprimem a expressão de citocinas pró-inflamatórias, de quimiocinas, de moléculas de adesão, além de estimular a transcrição de citocinas antiinflamatórias. Citocinas pró-fibróticas como a IL-11, fator básico de crescimento do fibroblasto (b-FGF) e fator de crescimento endotelial vascular (VEGF), relacionados com o crescimento do pólipo, também são suprimidos pela ação do GC. Tal ação depende fundamentalmente da interação com os seus receptores (GR), pois alguns indivíduos apresentam algum grau de resistência celular ao seu efeito, que parece estar relacionada com a presença da isoforma b do GR. Genes envolvidos nas fases de produção de imunoglobulinas, apresentação e processamento do antígeno também sofrem ação dos GC de forma variada. OBJETIVOS: Fazer uma revisão da literatura sobre os mecanismos de ação do GC na PNS. CONCLUSÃO: A compreensão desses mecanismos implicará no desenvolvimento de drogas mais eficazes na sua terapêutica.

Glucocorticoids (GC) are the drugs of choice for the clinical treatment of nasal polyposis, according to the medical literature. Its mechanism of action in the regression of clinical symptoms and polyps, however, is not fully understood. The topical and/or systemic use of glucocorticoids lead to variable expression of cytokines, chemokines and lymphokines, as well as changes in cells. It is known that GC suppresses the expression of pro-inflammatory cytokines, chemokines and adhesion molecules such as ICAM-1 and E-selectin; GC also stimulate the transcription of anti-inflammatory cytokines such as TGF-b. GC suppress pro-fibrotic cytokines related to polyp growth, such as IL-11, the basic fibroblast growth factor (b-FGF), and the vascular endotelial growth factor (VEGF). The action of GC depends fundamentally on their interaction with receptors (GR); certain subjects have a degree of resistance to its effect, which appears to be related with the presence of a b isoform of GR. GC also act variably on the genes involved in immunoglobulin production, presentation, and antigen processing. AIM: We present a review of the literature on the mechanisms of GC action in nasal polyosis. CONCLUSION: Understanding the mechanism of action of GC in nasal polyposis will aid in the development of new, more efficient, drugs.