RESUMO
OBJECTIVES: Montelukast is a well-known leukotriene receptor antagonist commonly used in treating allergic rhinitis and asthma. Omega-3 fatty acid is also known as an antiallergic and immunomodulator molecule. This study aimed to elucidate the efficacy of systemic montelukast and omega-3 fatty acid treatment in allergic rhinitis models in Wistar Hannover rats. METHODS: This research was conducted on 28 healthy Wistar Hannover rats weighing 250-350â¯g. After establishing the allergic rhinitis model, nasal symptoms were observed and scored, and the nasal mucosa of all rats was investigated histologically. Light microscopy was utilized to evaluate the degree of ciliary loss, goblet cell hyperplasia, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration, and hypertrophy in chondrocytes. RESULTS: As a result of the analysis of the data obtained from the study, it was determined that typical allergic rhinitis symptoms such as nasal scratching and sneezing were significantly reduced in the rats in the montelukast and omega-3 treated group, and these symptoms did not increase after repeated intranasal OVA-protease applications. Histological examinations after fish oil treatment did not reveal typical inflammatory changes in allergic rhinitis. None of the rats in the montelukast and omega-3 groups had any increase in goblet cells, whereas 14.3% of the rats in the control group and 28.6% of the rats in the allergic rhinitis group had mild increase. Last but not least, 71.4% of rats in the allergic rhinitis group had a moderate increase. The difference between the groups was statistically significant (pâ¯<â¯0.001). CONCLUSION: Regarding the outcomes of this research, it was observed that w-3 fatty acids had antiallergic effects, both histopathological and clinical, in the allergic rhinitis model. We believe that further randomized controlled trials incorporating larger cohorts are warranted to verify the use of omega-3 fatty acids in treating allergic rhinitis. The level of evidence of this article is Level 2.
Assuntos
Acetatos , Ciclopropanos , Modelos Animais de Doenças , Ácidos Graxos Ômega-3 , Óleos de Peixe , Antagonistas de Leucotrienos , Ovalbumina , Quinolinas , Ratos Wistar , Rinite Alérgica , Sulfetos , Animais , Ciclopropanos/uso terapêutico , Sulfetos/uso terapêutico , Acetatos/uso terapêutico , Quinolinas/uso terapêutico , Ácidos Graxos Ômega-3/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/patologia , Ratos , Antagonistas de Leucotrienos/uso terapêutico , Óleos de Peixe/uso terapêutico , Masculino , Resultado do Tratamento , Mucosa Nasal/patologia , Mucosa Nasal/efeitos dos fármacosRESUMO
Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.
Assuntos
Carcinoma de Ehrlich , Metotrexato , Camundongos , Animais , Metotrexato/farmacologia , Carcinoma de Ehrlich/tratamento farmacológico , Coração , Fígado/patologia , Acetatos/farmacologia , Acetatos/uso terapêuticoRESUMO
OBJECTIVE: There is an urgent need for effective treatments to prevent or attenuate lung and systemic inflammation, endotheliitis, and thrombosis related to COVID-19. This study aimed to assess the effectiveness of a multidrug-therapy consisting of Ivermectin, Azithromycin, Montelukast, and Acetylsalicylic acid ("TNR4" therapy) to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico. DESIGN AND METHODS: A comparative effectiveness study was performed among 768 confirmed SARS-CoV-2 cases aged 18-80 years, who received ambulatory care at the Ministry of Health of Tlaxcala. A total of 481 cases received the TNR4 therapy, while 287 received another treatment (comparison group). All participants received home visits and/or phone calls for clinical evaluation during the 14 days after enrollment. RESULTS: Nearly 85% of cases who received the TNR4 recovered within 14 days compared to 59% in the comparison group. The likelihood of recovery within 14 days was 3.4 times greater among the TNR4 group than in the comparison group. Patients treated with TNR4 had a 75% and 81% lower risk of being hospitalized or death, respectively, than the comparison group. CONCLUSIONS: TNR4 therapy improved recovery and prevented the risk of hospitalization and death among ambulatory COVID-19 cases.
Assuntos
Acetatos/uso terapêutico , Antivirais/uso terapêutico , Aspirina/uso terapêutico , Azitromicina/uso terapêutico , Tratamento Farmacológico da COVID-19 , Ciclopropanos/uso terapêutico , Ivermectina/uso terapêutico , Quinolinas/uso terapêutico , Sulfetos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Hospitalização , Humanos , Masculino , México , Pessoa de Meia-Idade , SARS-CoV-2 , Resultado do Tratamento , Adulto JovemRESUMO
Inflammation is generally accepted as a component of the host defence system and a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Many endogenous mediators that drive the resolution of inflammation are now known. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro-resolution molecules, or strategies that promote their increase, tend to suppress inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti-inflammatory, pro-resolving, anti-thrombogenic and anti-microbial effects of such endogenous mediators of resolution may be useful in the treatment of the late stages of the disease in patients with COVID-19.
Assuntos
Anti-Inflamatórios/uso terapêutico , Tratamento Farmacológico da COVID-19 , Inflamação/tratamento farmacológico , Acetatos/uso terapêutico , Angiotensina I/uso terapêutico , Animais , Anexina A1/uso terapêutico , COVID-19/imunologia , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/uso terapêutico , Humanos , Peróxido de Hidrogênio/uso terapêutico , Inflamação/imunologia , Mediadores da Inflamação/imunologia , Camundongos , Infecções por Orthomyxoviridae/tratamento farmacológico , Infecções por Orthomyxoviridae/imunologia , Oxidantes/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , Peptídeos/uso terapêutico , Inibidores da Fosfodiesterase 4/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Rolipram/uso terapêutico , Vasodilatadores/uso terapêuticoRESUMO
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.
Assuntos
Acetatos/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Tosse/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Quinolinas/uso terapêutico , RNA Longo não Codificante/metabolismo , Animais , Asma/sangue , Criança , Pré-Escolar , Tosse/sangue , Ciclopropanos , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , SulfetosRESUMO
Introduction: Sphingosine-1-phosphate (S1P) is a membrane-derived lysophospholipid signaling molecule implicated in various physiological and pathological processes, such as regulation of the immune, cardiovascular, pulmonary, and nervous systems and theoretical cancer-related risks, through extracellular activation of S1P1-5 receptors.Areas covered: S1P receptor agonism is a novel strategy for the treatment of UC targeting lymphocyte recirculation, through blockade of lymphocyte egress from lymph nodes. We conducted an extensive literature review on PUBMED on currently available data on molecular aspects of S1P modulation, the mechanisms of action of S1PR agonists (fingolimod, ozanimod, etrasimod, and KRP-203), and their potential efficacy and safety for the treatment of patients with ulcerative colitis.Expert opinion: Selective S1P modulators have emerged to enlarge the efficacy and safety profile of this class of agents. Phase 3 programs should add the potential body of evidence to prove their benefit for the management of UC patients.
Assuntos
Colite Ulcerativa/tratamento farmacológico , Moduladores do Receptor de Esfingosina 1 Fosfato/uso terapêutico , Receptores de Esfingosina-1-Fosfato/agonistas , Acetatos/uso terapêutico , Ensaios Clínicos como Assunto , Colite Ulcerativa/patologia , Humanos , Indanos/uso terapêutico , Indóis/uso terapêutico , Lisofosfolipídeos/metabolismo , Oxidiazóis/uso terapêutico , Esfingosina/análogos & derivados , Esfingosina/metabolismo , Receptores de Esfingosina-1-Fosfato/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.
Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Histamina/sangue , Leucotrieno D4/sangue , Quimioterapia Combinada/métodos , Medicina de Precisão/métodos , Rinite Alérgica/sangue , Quinolinas/uso terapêutico , Espirro , RNA Mensageiro/genética , Receptores Histamínicos H1/genética , Obstrução Nasal/tratamento farmacológico , Resultado do Tratamento , Loratadina/uso terapêutico , Receptores de Leucotrienos/genética , Antialérgicos/uso terapêutico , Rinite Alérgica/diagnóstico , Rinite Alérgica/tratamento farmacológico , Furoato de Mometasona/uso terapêutico , Acetatos/uso terapêutico , Mucosa NasalRESUMO
INTRODUCTION: The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. OBJECTIVE: To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. METHODS: A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. RESULTS: Loratadine+mometasone furoate and loratadine+mometasone furoate+montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p<0.05). Meanwhile, montelukast+mometasone furoate and montelukast+mometasone furoate+loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p<0.05). CONCLUSION: Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.
Assuntos
Quimioterapia Combinada/métodos , Histamina/sangue , Leucotrieno D4/sangue , Medicina de Precisão/métodos , Rinite Alérgica/sangue , Acetatos/uso terapêutico , Adolescente , Adulto , Idoso , Antialérgicos/uso terapêutico , Ciclopropanos , Feminino , Humanos , Loratadina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Furoato de Mometasona/uso terapêutico , Mucosa Nasal , Obstrução Nasal/tratamento farmacológico , Quinolinas/uso terapêutico , RNA Mensageiro/genética , Receptores Histamínicos H1/genética , Receptores de Leucotrienos/genética , Rinite Alérgica/diagnóstico , Rinite Alérgica/tratamento farmacológico , Espirro , Sulfetos , Resultado do Tratamento , Adulto JovemRESUMO
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.
Assuntos
Quinolinas/uso terapêutico , Asma/tratamento farmacológico , Antiasmáticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Tosse/tratamento farmacológico , RNA Longo não Codificante/metabolismo , Acetatos/uso terapêutico , Asma/sangue , Tosse/sangue , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
PURPOSE: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). METHODS: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. RESULTS: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. CONCLUSION: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.