Envolvimento das vias de sinalização celular no efeito tipo-antidepressivo da quercetina em camundongos / Involvement of cellular signaling pathways in the antidepressant-like effect of quercetin in mice

A elevada prevalência do Transtorno Depressivo Maior (TDM) tem recebido atenção da comunidade científica pois acarreta considerável sofrimento aos acometidos. As bases neurobiológicas do TDM são pouco conhecidas e as opções de tratamento farmacológico disponíveis são escassas. Nesse sentido, investigar potenciais moléculas com efeito antidepressivo é crucial. A pesquisa objetivou elucidar o envolvimento das vias de sinalização celular no efeito tipo-antidepressivo da quercetina. Para isso, vários grupos de camundongos Swiss fêmeas foram tratados com veículo (solução salina 0,9% estéril), quercetina 25 mg/Kg (v.o.), inibidor (i.c.v.) ou quercetina + inibidor. Foram utilizados os inibidores: H-89 (inibidor da proteína cinase A, 1 µg/sítio, i.c.v.); KN-62 (inibidor da proteína cinase dependente de Ca2+/calmodulina, 1 µg/sítio, i.c.v.); LY294002, um inibidor da fosfatidilinositol 3 cinase (PI3K, 10 nmol/sítio, i.c.v.); e um inibidor da proteína cinase regulada por sinal extracelular (ERK), o PD98059 (5 µg/sítio, i.c.v.). Os animais foram submetidos ao Teste de Suspensão pela Cauda (TSC) e Teste do Aberto (TCA) para avaliação do efeito tipo-antidepressivo e possíveis interferências dos tratamentos na capacidade locomotora. Todos os procedimentos foram aprovados pelo CEUA/UNIVALI 021/2013. Os resultados obtidos apontaram que a quercetina foi capaz de reduzir o tempo de imobilidade dos camundongos no TSC, entretanto, sem comprometer a capacidade locomotora dos animais (TCA). Além disso, foi constatado que os inibidores H-89, KN-62, LY294002 e PD98059 revereteram o efeito anti-imobilidade da quercetina. A administração dos inibidores isolados ou em associação com a quercetina, não comprometeram a locomoção dos camundongos. De forma geral, os dados apontam que a quercetina desencadeia efeito tipo-antidepressivo por intermédio da modulação da proteína cinase A (PKA), proteína cinase dependente de Ca2+/calmodulina (CaMKII), fosfatidilinositol 3 cinase (PI3K) e proteína cinase regulada por sinal extracelular (MAPKs/ERK)

PROFILE OF PATIENTS WITH CHRONIC HEPATITIS C IN A PUBLIC HEALTH PROGRAM IN SOUTHERN BRAZIL

ABSTRACT BACKGROUND: Chronic hepatitis C (CHC) can progress to cirrhosis and its complications as hepatocellular carcinoma, leading to morbidity and mortality. To know the profile of patients with CHC virus is fundamental to optimize management. OBJECTIVE: To describe the profile of patients with CHC in a public health program in Southern Brazil. METHODS: A retrospective study was carried out in patients with CHC who underwent treatment against hepatitis C virus in a dispensation and pharmaceutical assistance center of the Public Health Department of the State of Rio Grande do Sul, South Brazil. All medical records of patients attended between December/2015 and December/2016 were evaluated. RESULTS: A total of 1,431 records of patients with CHC were evaluated. Males were the most prevalent (802; 56%) patients. The mean age was 58.6±9.9 years, ranging from 18 to 89 years. Genotype 1 was the most frequent (866;60.5%) of the patients. Ninety (6.3%) patients were transplanted from a solid organ, and of these, 73 (5.1%) were transplanted from the liver. The fibrosis evaluation was performed in 1,300 (90.8%) patients. Of these, 566 (39.6%) were evaluated through liver biopsy. Regarding the degree of fibrosis, 779 (54.4%) presented fibrosis grade 4 (cirrhosis). The genotype 3 was the most associated with fibrosis grade 4, and genotype 1 was associated with high viral load. CONCLUSION: The present study made possible the evaluation of the characteristics of patients with CHC in a public health program in South Brazil. There was a predominance of CHC in males, and the mean age was 59 years. They presented a predominance of genotype 1, higher viral load in patients with genotype 1 and greater degree of fibrosis in patients with genotype 3

Antidepressant-like effect of caffeic acid: Involvement of the cellular signaling pathways

Caffeic acid is a phenolic compound widely distributed in plants and beverages such as coffee. Although its mechanism of action is poorly understood, caffeic acid reportedly induces antidepressant-like and neuroprotective effects. This study aimed to investigate the involvement of cellular signaling pathways in acute antidepressant-like effect induced by caffeic acid in mice. All procedures were approved by the Institutional Animal Ethics Committee of the UNIVALI n. 021/2013. Female Swiss mice were administered with vehicle, caffeic acid (5 mg/ kg, p.o.), inhibitor (H-89, U0126, chelerythrine, or PD9859, i.c.v.) or caffeic acid plus inhibitor. The behavioral effects were evaluated 1h after the administration of compounds to mice using tail suspension test (TST) and open field test (OFT). The results showed that the antidepressant- like effect of caffeic acid in mice was possibly mediated by the activation of PKA, MEK 1/2, PKC and MAPK (as assessed using TST), without compromising their locomotor activity (as assessed using OFT). Our results demonstrated, at least in part, the pathways involved in the neuroprotective and behavioral effects of caffeic acid

Effectiveness of chronic hepatitis C treatment with direct-acting antivirals in the Public Health System in Brazil

ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients