RESUMO
Platelet activity is essential in cardiovascular diseases. Therefore our objective was to evaluate the main effects of activating RAGE in platelets which are still unknown. A search for RAGE expression in different databases showed poor or a nonexistent presence in platelets. We confirmed the expression in platelets and secreted variable of RAGE (sRAGE). Platelets from elderly adults expressed in resting showed 3.2 fold more RAGE from young individuals (p < 0.01) and 3.3 fold with TRAP-6 (p < 0.001). These results could indicate that the expression of RAGE is more inducible in older adults. Then we found that activating RAGE with AGE-BSA-derived from methylglyoxal and subthreshold TRAP-6, showed a considerable increase with respect to the control in platelet aggregation and expression of P-selectin (respectively, p < 0.01). This effect was almost completely blocked by using a specific RAGE inhibitor (FSP-ZM1), confirming that RAGE is important for the function and activation platelet. Finally, we predict the region stimulated by AGE-BSA is located in region V of RAGE and 13 amino acids are critical for its binding. In conclusion, the activation of RAGE affects platelet activation and 13 amino acids are critical for its stimulation, this information is crucial for future possible treatments for CVD.
Assuntos
Produtos Finais de Glicação Avançada/metabolismo , Ativação Plaquetária , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de Sinais , Adulto , Idoso , Plaquetas/metabolismo , Simulação por Computador , Humanos , Soroalbumina Bovina/metabolismoRESUMO
INTRODUCTION/AIM: Levo-pantoprazole, the S-enantiomer of pantoprazole, is a proton pump inhibitor that has been shown in animal studies to be faster and stronger than its racemic formulation. There are no studies on humans and therefore our aim was to evaluate the effects of levo-pantoprazole versus racemic pantoprazole on intragastric pH. MATERIALS AND METHODS: A randomized controlled study was conducted on patients with erosive gastroesophageal reflux disease that were given 20mg of levo-pantoprazole (n = 15) versus 40mg of racemic pantoprazole (n = 15) for 7 days. Baseline and end-of-treatment symptom evaluation and intragastric pH measurement were carried out. RESULTS: There were no differences between the groups in the baseline evaluations. From 40 to 115min after the first dose of levo-pantoprazole, the mean intragastric pH was higher, compared with that of racemic pantoprazole (p < 0.05). After one week, levo-pantoprazole and racemic pantoprazole significantly reduced intragastric acid production and its esophageal exposure (p < 0.05). Even though there was no statistically significant difference, a larger number of patients that received levo-pantoprazole stated that their heartburn improved within the first 3 days. CONCLUSIONS: The S-enantiomer of pantoprazole (levo-pantoprazole) had a faster and stronger effect with respect to acid suppression, compared with its racemic formulation. Although the effect on symptoms was faster with levo-pantoprazole, occurring within the first days of treatment, it was equivalent to that of the racemate at one week of treatment.
Assuntos
Refluxo Gastroesofágico/tratamento farmacológico , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Pantoprazol/química , Pantoprazol/farmacologia , Inibidores da Bomba de Prótons/química , Inibidores da Bomba de Prótons/farmacologia , Adulto , Feminino , Refluxo Gastroesofágico/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/uso terapêutico , Inibidores da Bomba de Prótons/uso terapêutico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: A study of the intrafamilial transmission of the hepatitis B virus (HBV) and its relationship with the viral replication and epidemiological factors. METHODS: The intrafamilial transmission of 106 chronic carriers of HBV was evaluated: 79 were asymptomatic carriers (AC) and 27 had chronic liver disease (CLD). Overall 347 relatives of the first group individuals and 112 of the second group were investigated. In the index cases, all HBV markers were investigated, and also DNA-HBV in those with CLD. In the relatives, HBsAg, HBsAc and HBcAc were investigated. Also, a survey to evaluate the influence of socioeconomic and cultural factors was also carried out. RESULTS: The prevalence of markers was significantly higher in the relatives of patients with CLD (HBcAg, HBcAc and evidence of contact) followed by AC and controls. The most infective relation in AC was that of other contacts with significant differences from the mother-child relationship (HBsAc p less than 0.003, HBcAc p less than 0.01, and evidence of contact p less than 0.001). By contrast, in CLD the most infective relation was mother-child. The mother-child relation was more infective than the father-child one (HBsAg p less than 0.05, HBcAc p less than 0.03, and evidence of contact p less than 0.02). Regarding viral replication, it was found that the HBeAg and DNA positive patients were more infective. The prevalence of HBcAc and the evidence of contact increased with the time of living together of spouses. Finally, it can be stated in a general sense that, according to the results of the survey, the socioeconomic factors have a small influence on the familial transmission. CONCLUSIONS: The relatives of HBV carriers, particularly in the case of HC with high replication, have a high risk of transmission. Thus, their investigation and subsequent vaccination is mandatory.
Assuntos
Hepatite B/transmissão , Biomarcadores/sangue , Doadores de Sangue , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Portador Sadio/transmissão , Saúde da Família , Hepatite B/epidemiologia , Hepatite B/imunologia , Anticorpos Anti-Hepatite B/sangue , Antígenos da Hepatite B/sangue , Hepatite Crônica/epidemiologia , Hepatite Crônica/imunologia , Humanos , Prevalência , Estudos Soroepidemiológicos , Espanha/epidemiologiaRESUMO
We have studied in the present report 86 sera from healthy individuals from Granada province with the aim of determining the serum antibody threshold level which would correlate in our media with the absence of tuberculous disease. These antibodies were detected by an ELISA method (Anda Tb) which looks for the presence of antibodies against mycobacteria 60 antigen. We establish that in our media the threshold level should be established in 200 for healthy adults and in 100 IU for healthy children.