RESUMO
BPC 157, a pentadecapeptide with extensive healing effects, has recently been suggested to contribute to angiogenesis. However, the underlying mechanism is not yet clear. The present study aimed to explore the potential therapeutic effect and pro-angiogenic mechanism of BPC 157. As demonstrated by the chick chorioallantoic membrane (CAM) assay and endothelial tube formation assay, BPC 157 could increase the vessel density both in vivo and in vitro, respectively. BPC 157 could also accelerate the recovery of blood flow in the ischemic muscle of the rat hind limb as detected by laser Doppler scanning, indicating the promotion of angiogenesis. Histological analysis of the hind limb muscle confirmed the increased number of vessels and the enhanced vascular expression of vascular endothelial growth factor receptor 2 (VEGFR2) in rat with BPC 157 treatment. In vitro study using human vascular endothelial cells further confirmed the increased mRNA and protein expressions of VEGFR2 but not VEGF-A by BPC 157. In addition, BPC 157 could promote VEGFR2 internalization in vascular endothelial cells which was blocked in the presence of dynasore, an inhibitor of endocytosis. BPC 157 time dependently activated the VEGFR2-Akt-eNOS signaling pathway which could also be suppressed by dynasore. The increase of endothelial tube formation induced by BPC 157 was also inhibited by dynasore. This study demonstrates the pro-angiogenic effects of BPC 157 that is associated with the increased expression, internalization of VEGFR2, and the activation of VEGFR2-Akt-eNOS signaling pathway. BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation. KEY MESSAGE: BPC 157 promotes angiogenesis in CAM assay and tube formation assay. BPC 157 accelerates the blood flow recovery and vessel number in rats with hind limb ischemia. BPC 157 up-regulates VEGFR2 expression in rats with hind limb ischemia and endothelial cell culture. BPC 157 promotes VEGFR2 internalization in association with VEGFR2-Akt-eNOS activation.
Assuntos
Indutores da Angiogênese/uso terapêutico , Membro Posterior/irrigação sanguínea , Isquemia/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Galinhas , Membro Posterior/efeitos dos fármacos , Membro Posterior/metabolismo , Membro Posterior/fisiopatologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Isquemia/genética , Isquemia/metabolismo , Isquemia/fisiopatologia , Ratos , Regulação para Cima/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
AIM: To assess the efficacy of intranasal corticosteroid therapy in the treatment of obstructive sleep apnea (OSA) based on current evidence. METHODS: A number of medical literature data bases: PubMed, Cochrane Library, Scopus, and CINAHL, were searched comprehensively to identify randomized controlled trials (RCT) that reported on the efficacy of intranasal corticosteroid therapy for OSA. The selected studies were subjected to a meta-analysis and a risk-of-bias assessment. RESULTS: Seven RCTs met our eligibility criteria, five of these were included in our meta-analysis. The results indicated that intranasal corticosteroid therapy has a better effect in decreasing the apnea-hypopnea index compared with those participants who received placebo (standard mean difference 0.95 [95% confidence interval, -1.42 to -0.47]) (n = 221, I(2) = 62%). CONCLUSION: Our study results showed that patients who received intranasal corticosteroid therapy had a significant improvement in OSA. However, this evidence was limited by the potential risk of bias and heterogeneity of the selected RCTs.
Assuntos
Corticosteroides/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Apneia Obstrutiva do Sono/tratamento farmacológico , Administração Intranasal , Medicina Baseada em Evidências , Feminino , Humanos , MasculinoRESUMO
The current study presents a case of persistent hypoglycemia as the initial manifestation of advanced hepatocellular carcinoma (HCC), as well as a systematic review of the management of hypoglycemia associated with HCC. A 42-year-old female presented with loss of consciousness and a blood glucose level of 30 mg/dl (normal range, 80-140 mg/dl). Abdominal ultrasound and computed tomography were performed to investigate tenderness in the right upper quadrant, and the results revealed a hepatic mass of 15 cm in diameter, with metastasis. A diagnosis of insulinoma was ruled out by examining the insulin level. Prednisolone treatment was ineffective for relieving the persistent hypoglycemia, however, a single dose of palliative radiotherapy reduced the hypoglycemic episodes to once monthly. Due to the advanced disease, the patient refused further treatment, with the exception of a palliative therapy with glucose fluid. The patient succumbed to pneumonia with sepsis. A systematic review of the literature indicated that steroids were the most commonly used drug for hypoglycemia associated with HCC, however, in the majority of cases no effect was noted as observed in this study. Cytoreduction by surgery or systemic chemotherapy has been the most effective treatment. Although rare, hypoglycemia may be the initial symptom of HCC. Cytoreduction is the most effective method of treating hypoglycemia associated with HCC.
