Analysis of the Potential Topical Anti-Inflammatory Activity of Averrhoa carambola L. in Mice

Inflammatory skin disorders, such as psoriasis and atopic dermatitis, are very common in the population; however, the treatments currently available are not well tolerated and are often ineffective. Averrhoa carambola L. (Oxalidaceae) is an Asian tree that has been used in traditional folk medicine in the treatment of several skin disorders. The present study evaluates the topical anti-inflammatory effects of the crude ethanolic extract of A. carambola leaves, its hexane, ethyl acetate, and butanol fractions and two isolated flavonoids on skin inflammation. Anti-inflammatory activity was measured using a croton oil-induced ear edema model of inflammation in mice. Topically applied ethanolic extract reduced edema in a dose-dependent manner, resulting in a maximum inhibition of 73 ± 3% and an ID50 value of 0.05 (range: 0.02–0.13) mg/ear. Myeloperoxidase (MPO) activity was also inhibited by the extract, resulting in a maximum inhibition of 60 ± 6% (0.6 mg/ear). All of the fractions tested caused inhibition of edema formation and of MPO activity. Treatment with the ethyl acetate fraction was the most effective, resulting in inhibition levels of 75 ± 5 and 54 ± 8% for edema formation and MPO activity, respectively. However, treatment of mice with isolated compounds [apigenin-6-C-β-l-fucopyranoside and apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-β-l-fucopyranoside] did not yield successful results. Apigenin-6-C-(2″-O-α-l-rhamnopyranosyl)-β-l-fucopyranoside caused only a mild reduction in edema formation (28 ± 11%). Taken together, these preliminary results support the popular use of A. carambola as an anti-inflammatory agent and open up new possibilities for its use in skin disorders

Tratamento da tuberculose pulmonar sensível a drogas : uma revisão sistemática com meta-análise em rede

Orientador: Prof. Dr. Roberto Pontarolo.Coorientadora: Dra. Fernanda Stumpf ToninDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Ciências Farmacêuticas. Defesa : Curitiba, 16/12/2020Inclui referências: p. 96-98Área de concentração: Insumos, Medicamentos e CorrelatosResumo: A tuberculose, causada pelo agente Mycobacterium tuberculosis. Atualmente, o seu tratamento é realizado com o uso de quatro antimicrobianos por um período de seis meses. Entretanto, muitas vezes, esse protocolo terapêutico não se mostra eficaz e a doença evolui para a forma resistente. Isso ocorre, principalmente, pela falta de adesão do paciente que, por motivos socioeconômicos ou relacionados ao medicamento (p. ex. efeitos adversos, duração do tratamento, recorrência dos sintomas), interrompe o tratamento sem a completa cura da doença. Logo, a necessidade de retratamento é comum, e por isso, novos esquemas terapêuticos têm sido desenvolvidos com o objetivo de encurtar o tempo da terapia medicamentosa e melhorar a adesão. Nesse contexto, é importante avaliar, por meio da Saúde Baseada em Evidências, os riscos e benefícios da disponibilização de tecnologias à população, a fim de gerar dados científicos passíveis de guiar tomadas de decisão mais assertivas por gestores de saúde. Assim, o objetivo deste estudo foi avaliar as evidências da eficácia e segurança comparativas dos regimes de medicamentos disponíveis para o tratamento da tuberculose pulmonar droga-sensível (TB-DS). Para isso foi realizada uma revisão sistemática de ensaios clínicos randomizados (ECRs) de acordo com o PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) e Colaboração Cochrane. A busca de artigos foi realizada nas bases de dados PubMed e Scopus. Foram elegíveis estudos avaliando qualquer tratamento antimicrobiano para TB-DS com duração de pelo menos duas semanas em adultos. Os desfechos avaliados foram a cultura de escarro, a conversão da cultura de escarro, os efeitos adversos e efeitos adversos graves. A abordagem bayesiana foi usada para elaboração das meta-análises em rede, que permitem comparações diretas e indiretas entre os tratamentos para cada um dos desfechos. Adicionalmente, os tratamentos foram classificados de acordo com seu perfil através da análise pela superfície sob a curva de classificação cumulativa (SUCRA). As meta-análises de rede foram conduzidas usando Addis versão 1.16.6. A avaliação da qualidade dos ECRs incluídos foi realizada com emprego da ferramenta da Cochrane e escala de Jadad. Vinte e quatro estudos foram incluídos na revisão e quinze nas meta-análises. Os estudos demonstraram uma qualidade metodológica geral baixa-moderada tanto na ferramenta Cochrane como na escala de Jadad (escore médio de 2,75). Nenhum regime foi estatisticamente mais eficaz do que o regime padrão da Organização Mundial de Saúde - OMS (rifampicina + isoniazida + etambutol + pirazinamida). No entanto, as composições contendo rifapentina e moxifloxacino na fase intensiva (8 semanas) apresentaram bons resultados de eficácia (cultura de escarro negativa), apesar de ser necessária cautela no seu uso pela baixa segurança de algumas dosagens. Devido a elevada heterogeneidade dos estudos e falta de reporte padronizado de alguns resultados, outras conclusões não foram possíveis. Logo, outros estudos comparando diretamente as terapias mais promissoras são necessários para confirmar as evidências existentes. Palavras-chave: Tuberculose. Agentes antituberculosos. Droga-sensível. Revisão sistemática. Meta-análise de rede.Abstract: Tuberculosis, caused by the agent Mycobacterium tuberculosis. Currently, its treatment is carried out with the use of four antimicrobial drugs for a period of six months. However, this therapeutic protocol is oftenly not effective and the disease evolves to a resistant form. This is mainly due to the patient's lack of adherence, which, for socioeconomic reasons or related to the medication (eg adverse effects, duration of treatment, recurrence of symptoms), interrupts treatment without the complete cure of the disease. Therefore, the need for retreatment is common, and for this reason, new therapeutic regimens have been developed with the aim of shortening the total time of drug therapy and improving adherence. In this context, it is important to assess, through Evidence-Based Health, the risks and benefits of making technologies available to the population, in order to generate scientific data that can guide more assertive decision-making by health professionals and managers. Thus, the objective of this study was to evaluate the evidence of the comparative efficacy and safety of antimicrobial drug regimens available for the treatment of drug-sensitive pulmonary tuberculosis (DS-TB). For that, a systematic review of randomized clinical trials (RCTs) was carried out according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Collaboration recommendations. The search for articles was carried out in the PubMed and Scopus databases. Studies evaluating any antimicrobial treatment for DS-TB lasting at least two weeks in adults were eligible. The evaluated outcomes were sputum culture, sputum culture conversion, adverse effects and serious adverse effects. The Bayesian approach was used to develop the network meta-analyses, which allow direct and indirect comparisons between treatments for each of the outcomes. Additionally, treatments were classified according to their profile through surface analyses under the cumulative classification curve (SUCRA). Network meta-analyses were conducted using Addis version 1.16.6. The quality assessment of the included RCTs was performed using the Cochrane tool and Jadad scale. Twenty-four studies were included in the review and fifteen in the meta-analyses. The studies demonstrated a general low-moderate methodological quality both in the Cochrane tool and in the Jadad scale (mean score of 2.75). No regimen was statistically more effective than the standard regimen of the World Health Organization - WHO (rifampicin + isoniazid + ethambutol + pyrazinamide). However, compositions containing rifapentine and moxifloxacin in the intensive phase (8 weeks) showed good efficacy results (negative sputum culture), although caution is needed in their use due to the low safety of some dosages (amount of adverse effects). Due to high heterogeneity of studies and lack of standardized reporting of some results, other conclusions were not possible, so further studies directly comparing the most promising therapies are needed to confirm the existing evidence. Keywords: Tuberculosis. Antituberculous agents. Drug-sensitive. Systematic review. Network meta-analysis

Efficacy and safety of daily treatments for drug-susceptible pulmonary tuberculosis: a systematic review and network meta-analysis

Objectives: To evaluate and update the evidence on the comparative efficacy and safety of antimicrobial drugs regimens for treating pulmonary drug-susceptible tuberculosis (DS-TB). Methods: A systematic review was performed with searches in PubMed and Scopus (PROSPERO-CRD42019141463). We included randomised controlled trials comparing the effect of any antimicrobial regimen lasting at least 2 weeks. The outcomes of interest were culture conversion and incidence of adverse events. Bayesian network meta-analyses and surface under the cumulative ranking curve (SUCRA) analyses were performed. Results were reported as odds ratio with 95% credibility intervals. Key findings: Fifteen studies were included in the meta-analysis (n = 7560 patients). No regimen was statistically more effective than the WHO standard approach (rifampicin, isoniazid, ethambutol, and pyrazinamide). The use of rifapentine 450 mg instead of rifampicin in the standard regimen demonstrated to be statistically safer than all other options for serious adverse events (e.g. hepatotoxicity, arthralgia) (OR ranging from 0.0 [Crl 0.00-0.04] to 0.0 [0.00-0.97]; SUCRA probabilities of 10%). Therapies containing rifapentine (Rp1500HEZ, Rp900HEZ) and moxifloxacin (RMEZ, RHMZ) are effective regarding culture conversion, but statistical uncertainty on their safety profile exists. Conclusion: The WHO standard regimen remains an overall effective and safe alternative for DS-TB. For intensive phase treatments, drugs combinations with rifapentine and moxifloxacin seem to reduce treatment duration while maintaining efficacy.info:eu-repo/semantics/publishedVersio

Systematic review with network meta-analysis on the treatments for latent tuberculosis infection in children and adolescents

Background: We aimed to synthesize the evidence on the efficacy and safety of different treatment regimens for latent tuberculosis infection (LTBI) in children and adolescents. Methods: A systematic review with network meta-analysis was performed (CRD142933). Searches were conducted in Pubmed and Scopus (Nov-2021). Randomized controlled trials comparing treatments for LTBI (patients up to 15 years), and reporting data on the incidence of the disease, death, or adverse events were included. Networks using the Bayesian framework were built for each outcome of interest. Results were reported as odds ratio (OR) with 95% credibility intervals (CrI). Rank probabilities were calculated via the surface under the cumulative ranking analysis (SUCRA) (Addis-v.1.16.8). GRADE approach was used to rate evidence's certainty. Results: Seven trials (n = 8696 patients) were included. Placebo was significantly associated with a higher incidence of tuberculosis compared to all active therapies. Combinations of isoniazid (15–25 mg/kg/week) plus rifapentine (300–900 mg/week), followed by isoniazid plus rifampicin (10 mg/kg/day) were ranked as best approaches with lower probabilities of disease incidence (10% and 19.5%, respectively in SUCRA) and death (20%). Higher doses of isoniazid monotherapy were significantly associated with more deaths (OR 18.28, 95% ICr [1.02, 48.60] of 4–6 mg/kg/day vs. 10 mg/kg/3x per week). Conclusions: Combined therapies of isoniazid plus rifapentine or rifampicin for short-term periods should be used as the first-line approach for treating LTBI in children and adolescents. The use of long-term isoniazid as monotherapy and at higher doses should be avoided for this population.info:eu-repo/semantics/publishedVersio