RESUMEN
Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.
Asunto(s)
Quinolinas/uso terapéutico , Asma/tratamiento farmacológico , Antiasmáticos/uso terapéutico , Sustancias Protectoras/uso terapéutico , Tos/tratamiento farmacológico , ARN Largo no Codificante/metabolismo , Acetatos/uso terapéutico , Asma/sangre , Tos/sangre , Modelos Animales de Enfermedad , Ratones Endogámicos BALB CRESUMEN
Este artículo resume las diferentes formas de presentación clínica de la enfermedad COVID-19 causada por el virus SARS-Co-2 documentadas fundamentalmente en las tres principales revisiones sistemáticas disponibles. Entre las manifestaciones clínicas de frecuente aparición se destacan la fiebre (83 %), la tos (60 %) y la fatiga (38 %), seguidas por las mialgias (29 %), el aumento de la producción del esputo (27 %) y la disnea (25 %). Entre los hallazgos de laboratorio,predominan el aumento de los valores de proteína C reactiva (69 %), la linfopenia (57 %) y el aumento de los niveles de lactato-deshidrogenasa (52 %). Respecto de las manifestaciones radiológicas, tienen especial importancia las opacificaciones en vidrio esmerilado (80 %), la neumonía bilateral (73 %) y la afectación de tres lóbulos pulmonares o más (57 %).Si bien la evidencia sintetizada tiene limitaciones, permite una aproximación actualizada a los conocimientos disponibles sobre la clínica de esta nueva enfermedad en la población adulta. (AU)
This article summarizes the different forms of clinical presentation of COVID-19, caused by the SARS-Co-2 virus, synthesizing the information collected mainly by three published systematic reviews. Frequent clinical manifestations include fever(83 %), cough (60 %), and fatigue (38 %), followed by myalgia (29 %), increased sputum production (27 %) and dyspnea(25 %). Among the laboratory findings, the most common are the increase in C-reactive protein values (69 %), lymphopenia (57 %) and the increase in lactate dehydrogenase levels (52 %).. Most remarkable radiological features include ground glass opacifications (80 %), bilateral pneumonia (73 %) and the involvement of three or more lung lobes (57 %). Although the synthesized evidence has limitations, it allows an updated approach to the available knowledge about the clinical symptoms of this new disease in the adult population. (AU)
Asunto(s)
Humanos , Adulto , Adulto Joven , Neumonía Viral/fisiopatología , Infecciones por Coronavirus/fisiopatología , Betacoronavirus/patogenicidad , Neumonía Viral/complicaciones , Neumonía Viral/etiología , Neumonía Viral/diagnóstico por imagen , Esputo , Proteína C-Reactiva/metabolismo , China , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/etiología , Infecciones por Coronavirus/diagnóstico por imagen , Tos/diagnóstico , Tos/fisiopatología , Tos/sangre , Disnea/diagnóstico , Disnea/fisiopatología , Disnea/sangre , Fatiga/diagnóstico , Fatiga/fisiopatología , Fatiga/sangre , Pandemias , Fiebre/diagnóstico , Fiebre/fisiopatología , Fiebre/sangre , Mialgia/diagnóstico , Mialgia/fisiopatología , Mialgia/sangre , L-Lactato Deshidrogenasa/sangre , Linfopenia/sangreRESUMEN
OBJETIVO: Determinar a concentração de alfa 1-antitripsina (AAT) e a prevalência dos alelos S e Z em indivíduos sintomáticos respiratórios crônicos. MÉTODOS: Pacientes com tosse crônica e dispnéia foram submetidos à avaliação clínica, espirometria, tomografia computadorizada de tórax, dosagem de AAT por nefelometria e pesquisa das mutações S e Z por reação em cadeia da polimerase. Foram consideradas como variáveis dependentes a concentração de AAT e o tabagismo. RESULTADOS: Dos 89 pacientes incluídos no estudo (44 mulheres; idade média, 51,3 ± 18,2 anos), os alelos S e Z foram detectados em 33,3 por cento e 5,7 por cento, respectivamente, com freqüência gênica dos alelos S e Z de 0,16 e 0,028. Dois pacientes tinham genótipo SZ (AAT < 89 mg/dL). Os pacientes foram divididos em grupos segundo a concentração de AAT: < 89 mg/dL (deficiência, nenhum grupo); 90-140 mg/dL (faixa intermediária, Grupo 1, n = 30); e > 141 mg/dL (normal, Grupo 2, n = 57). A freqüência de fumantes foi igual nos dois grupos, com carga tabágica maior no Grupo 2. O alelo S estava presente em 13 e 14 pacientes dos Grupos 1 e 2, respectivamente, enquanto que o alelo Z estava presente em 2 e 1 paciente dos mesmos grupos. Não houve diferença nos testes de função pulmonar, nem na freqüência de bronquiectasias ou enfisema entre os dois grupos. Os valores espirométricos e as concentrações de AAT foram similares entre fumantes e não-fumantes. Bronquiectasias foram mais freqüentes entre os não fumantes, e enfisema foi mais freqüente entre os fumantes. CONCLUSÕES: Trinta pacientes apresentaram níveis de AAT abaixo da média esperada para os genótipos MM e MS, e este fato não pode ser explicado por uma freqüência maior dos alelos S e Z.
OBJECTIVE: To determine the levels of alpha-1 antitrypsin (AAT) and the presence of S and Z alleles in patients with chronic respiratory symptoms. METHODS: Patients with chronic cough and dyspnea were submitted to clinical evaluation, pulmonary function tests, high-resolution computed tomography, nephelometric determination of AAT and determination of S and Z alleles by polymerase chain reaction. Smoking and AAT levels were considered the dependent variables. RESULTS: Of the 89 patients included in the study, 44 were female. The mean age was 51.3 ± 18.2 years. The S and Z alleles were detected in 33.3 percent and 5.7 percent, respectively, and the gene frequency was 0.16 and 0.028, respectively. Two patients were SZ heterozygotes (AAT levels < 89 mg/dL). The patients were divided into groups based on AAT level: < 89 mg/dL (deficiency, no group); 90-140 mg/dL (intermediate, Group 1, n = 30); and > 141 mg/dL (normal, Group 2, n = 57). The frequency of smokers was the same in both groups, although tobacco intake was greater in Group 2. The S allele was present in 13 and 14 patients in Groups 1 and 2, respectively, whereas the Z allele was present in 2 and 1 patient in the same groups. There was no difference in the results of pulmonary function tests or in the frequency of bronchiectasis or emphysema between the two groups. Spirometric values and AAT levels were similar in smokers and nonsmokers. Bronchiectasis was more common in nonsmokers, and emphysema was more common in smokers. CONCLUSIONS: Thirty patients presented AAT levels lower than the mean values found in patients with the MM or MS genotype, and this fact could not be explained by an increased frequency of S and Z alleles.