RESUMEN
Mesenchymal stem cells (MSCs) pretreatment is an effective route for improving cell-based therapy of endothelial cell survival, vascular stabilization, and angiogenesis. We hypothesized that the application of human umbilical cord-MSCs (hUC-MSCs) pretreated with angiotensin-II (Ang-II) might be a potential therapeutic approach for severe acute pancreatitis (SAP). Therefore, the effect of Ang-II pretreated hUC-MSCs on SAP was investigated in vitro and in vivo. METHODS: In the present study, human umbilical cord-derived MSCs pretreated with or without Ang-II were delivered through the tail vein of rats 12â¯h after induction of SAP. Pancreatitis severity scores and serum lipase levels, as well as the levels of VEGF and VEGFR2 were evaluated. RESULTS: We found that the administration of Ang-II-MSCs significantly inhibited pancreatic injury, as reflected by reductions of pancreatitis severity scores, serum amylase and serum lipase levels. Furthermore, the reduced apoptotic rate and increased tube formation in human umbilical vein endothelial Cells (HUVEC) were found resulting from the administration of Ang-II-MSC-CM. Moreover, knockdown of VEGFR2 can block the effect of Ang-II-MSC-CM on preventing HUVEC from apoptosis, as well as the capacity of tube formation was also suppressed. In addition, the expression of increased Bcl-2 and alleviated caspase-3 were observed in HUVEC and HUVEC transfectants exposure to Ang-II-MSC-CM. CONCLUSION: Collectively, these results elucidated that the pretreatment of hUC-MSCs with Ang-II improved the outcome of MSC-based therapy for SAP via enhancing angiogenesis and ameliorating endothelial cell dysfunction in a VEGFR2 dependent manner.
Asunto(s)
Angiotensina II/farmacología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Páncreas/lesiones , Páncreas/patología , Pancreatitis/terapia , Cordón Umbilical/citología , Enfermedad Aguda , Animales , Apoptosis/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Humanos , Modelos Biológicos , Neovascularización Fisiológica/efectos de los fármacos , Páncreas/efectos de los fármacos , Pancreatitis/patología , Comunicación Paracrina/efectos de los fármacos , Ratas , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Extravascular lung water (EVLW) is a sensitive prognostic indicator of pulmonary edema. Thus, EVLW may be an advantageous method of fluid management. This study aims to evaluate the outcomes of using EVLW and pulmonary artery wedge pressure (PAWP) as strategies for fluid management in patients with acute respiratory distress syndrome (ARDS). METHODS: Twenty-nine patients were randomly divided into the EVLW and PAWP groups. The survival rate, ICU (Intensive Care Unit) length of stay, duration of mechanical ventilation, acute lung injury scores, and oxygenation index of the EVLW and PAWP groups were compared. RESULTS: No significant difference in the survival rates at 28 and 60 days (d) after treatment was found between the two groups (p = 0.542). The duration of mechanical ventilation and ICU length of stay were significantly lower (p < 0.05) in the EVLW group than in the PAWP group. The 7 d cumulative fluid balance was -783 ± 391 ml in the EVLW group and -256 ± 514 ml in the PAWP group (p < 0.05). Compared with the PAWP group, the EVLW group showed improved oxygenation index (p = 0.006). CONCLUSIONS: EVLW for fluid management improved clinical results in patients with ARDS better than PAWP.
RESUMEN
Visfatin has been associated with some inflammatory disease. This study aimed to compare plasma visfatin levels in patients with community-acquired pneumonia and healthy controls and to furthermore investigate the relationship between their concentrations and 30-day mortality in patients. Plasma visfatin concentrations were measured in 176 patients and 95 healthy controls. The admission visfatin levels were significantly increased in all patients, survivals and non-survivals with community-acquired pneumonia compared with healthy control individuals, associated with pneumonia severity index score, Acute Physiology and Chronic Health Evaluation II score, white blood cell count, and plasma C-reactive protein level, and identified as an independent predictor for 30-day mortality. Its predictive value was similar to those of pneumonia severity index score and Acute Physiology and Chronic Health Evaluation II score. However, visfatin did not statistically significantly improve the predictive values of pneumonia severity index score and Acute Physiology and Chronic Health Evaluation II score. Thus, higher plasma visfatin level correlates with disease severity and markers of system inflammation and represent a novel biomarker for predicting 30-day mortality in patients with community-acquired pneumonia.