Role of high mobility group box-1 and protection of growth hormone and somatostatin in severe acute pancreatitis

In this study, we investigated the potential role of high-mobility group box 1 (HMGB1) in severe acute pancreatitis (SAP) and the effects of growth hormone (G) and somatostatin (S) in SAP rats. The rats were randomly divided into 6 groups of 20 each: sham-operated, SAP, SAP+saline, SAP+G, SAP+S and SAP+G+S. Ileum and pancreas tissues of rats in each group were evaluated histologically. HMGB1 mRNA expression was measured by reverse transcription-PCR. Levels of circulating TNF-α, IL-1, IL-6, and endotoxin were also measured. In the SAP group, interstitial congestion and edema, inflammatory cell infiltration, and interstitial hemorrhage occurred in ileum and pancreas tissues. The levels of HMGB1, TNF-α, IL-1, IL-6 and endotoxin were significantly up-regulated in the SAP group compared with those in the sham-operated group, and the 7-day survival rate was 0%. In the SAP+G and SAP+S groups, the inflammatory response of the morphological structures was alleviated, the levels of HMGB1, TNF-α, IL-1, IL-6, and endotoxin were significantly decreased compared with those in the SAP group, and the survival rate was increased. Moreover, in the SAP+G+S group, all histological scores were significantly improved and the survival rate was significantly higher compared with the SAP group. In conclusion, HMGB1 might participate in pancreas and ileum injury in SAP. Growth hormone and somatostatin might play a therapeutic role in the inflammatory response of SAP.

Notch ligand Delta-like 1 promotes the metastasis of melanoma by enhancing tumor adhesion

Notch signaling plays a vital role in tumorigenicity and tumor progression by regulating proliferation, invasion, and the tumor microenvironment. Previous research by our group indicated that Notch ligand Delta-like 1 (Dll1) is involved in angiogenesis in melanoma, and we noticed that it took a longer time to trypsinize Dll1-expressing B16 melanoma cells than the control cells. In this article, we extended our study to investigate the effects of Dll1 on tumor cell adhesion and metastasis. Dll1 overexpression activated Notch signaling in B16 tumor cells and significantly enhanced the adhering capacity of B16 tumor cells both in vitro and in vivo. B16-Dll1 cells also had a higher metastatic potential than their counterpart in the mouse model of lung metastasis. Along with increased Dll1 expression, N-cadherin, but not E-cadherin, was upregulated in B16-Dll1 cells. These data suggested that Notch ligand Dll1 may enhance the adhesion and metastasis of melanoma cells by upregulation of N-cadherin.

Effect of clopidogrel with or without omeprazole in patients with carotid artery stenting / Efecto del clopidogrel con o sin omeprazol en pacientes con stent en la arteria carótida

BACKGROUND: Recent concerns have been raised about the potential for proton pump inhibitors (PPIs) to blunt the efficacy of clopidogrel. We observed the effect of clopidogrel plus aspirin with or without omeprazole in patients with carotid stenoses after they received placement of carotid stents. METHODS: Sixty-four consecutive patients treated with percutaneous carotid artery stenting (CAS) comprised the sample. All enrolled patients underwent the C13 urea breath test (C13 UBT) before CAS. Patients with Helicobacter pylori infection and a history of peptic ulcer were assigned dual antiplatelet combination with omeprazole. Others received dual antiplatelet without omeprazole. Transcranial Doppler and ultrasonography were performed to assess the middle cerebral artery and carotid artery in follow-up at three months and six months. RESULTS: Eight patients had gastrointestinal bleeding; the event rate was 22.6% without omeprazole and 3.8% with omeprazole. The rate of gastrointestinal bleeding was reduced with omeprazole as compared without omeprazole (p = 0.026, p < 0.05). The two groups did not differ significantly in the rate of instent restenosis and thrombus through transcranial Doppler and ultrasonography. CONCLUSION: Among patients receiving dual antiplatelet therapy, prophylactic use of omeprazole reduced the rate of upper gastrointestinal bleeding. There was no apparent interaction between clopidogrel and omeprazole in patients with carotid artery stenting.

ANTECEDENTES: Recientemente se han expresado preocupaciones acerca de la posibilidad de que los inhibidores de la bomba de protones (IBP) para debilitar la eficacia del clopidogrel. Observamos el efecto del clopidogrel más aspirina con o sin omeprazol en pacientes con estenosis de la arteria carótida después de que recibieran la colocación de stents carotídeos. MÉTODOS: Sesenta y cuatro pacientes consecutivos tratados con stent percutáneo de la arteria carótida (SAC) fueron seleccionados para formar la muestra. A todos los pacientes inscritos se les realizó la prueba de aliento con urea C13 (C13 UBT) antes de CAS. A pacientes con infección por Helicobacter pylori y antecedentes de úlcera péptica les fue asignada una combinación antiplaquetaria dual con omeprazol. Otros recibieron tratamiento antiplaquetario dual sin omeprazol. Se realizaron una prueba Transcranial Doppler y una ultrasonografía a fin de evaluar la arteria cerebral media y la arteria carótida en seguimientos a los tres meses y a los seis meses. RESULTADOS: Ocho pacientes tuvieron hemorragia gastrointerstinal; la tasa de eventos fue 22.6% sin omeprazol y 3.8% con omeprazol. La tasa de hemorragia gastrointerstinal se redujo con omeprazol en comparación con la obtenida sin omeprazol (p = 0,026, p < 0.05). Los dos grupos no difirieron significativamente con respecto a la tasa de restenosis en stent y trombos a través de la prueba Transcranial Doppler y la ultrasonografía. CONCLUSIÓN: Entre los pacientes que reciben terapia antiplaquetaria dual, el uso profiláctico de omeprazol redujo la tasa de hemorragia gastrointestinal superior. No hubo interacción ostensible entre el clopidogrel y el omeprazol en pacientes con stent de la arteria carótida.

Effects of inhibitors of the tyrosine kinase signaling cascade on an in vitro model of allergic airways.

It has been shown that activation of protein tyrosine kinases (PTKs) is the earliest detectable signaling response to FcepsilonRI cross-linking on mast cells. Following tyrosine kinase activation, a family of mitogen-activated protein kinases (MAPKs) was found to be activated as well. Activation of this PTK signaling cascade will lead to mast cell degranulation. This review summarizes our recent studies on the role of PTK signaling cascade in an in vitro guinea pig model of allergic asthma using PTK inhibitors, genistein and tyrphostin 47, and MAPK kinase inhibitor, PD098059. Inhibitors of the PTK and MAPK signaling pathways significantly attenuated the ovalbumin (OVA)-induced bronchial anaphylactic contraction and enhanced relaxation of constricted airways, respectively, and substantially blocked the release of histamine and peptidoleukotrienes from chopped lung preparations induced by OVA. Based upon their substantial inhibitory effects on the Schultz-Dale reaction, further examination on the potential anti-asthmatic effects of PTK cascade inhibitors in an in vivo model of allergic asthma is recommended.