Plos One
-
Warm ischemia-reperfusion injury remains a crucial issue in transplantation following the cardiac death of donors. Previously, we showed that surfactant inhalation during warm ischemia mitigated ischemia-reperfusion injury. This study investigated the mechanisms of surfactant inhalation protection of the warm ischemic lung after reoxygenation with ventilation alone. ⋯ Immunohistochemically, lungs in the SURF group showed weaker staining for 8-hydroxy-2'-deoxyguanosine, inducible nitric oxide synthase, and apoptosis, and stronger staining for Bcl-2 and surfactant protein-C. Our results indicate that surfactant inhalation in the last phase of warm ischemia mitigated the injury resulting from reoxygenation after warm ischemia. The reduction in oxidative damage and the inhibition of apoptosis might contribute to the protection of the warm ischemic lungs.
-
Bilateral destruction of the olfactory bulbs is known to cause behavioral changes analogous to symptoms of depression. Curcumin, a traditional Indian spice is currently being investigated in different psychiatric problems including depression. Dietary phytochemicals are currently used as an adjuvant therapy to accelerate their therapeutic efficacy. Therefore, the present study is an attempt to elucidate the neuroprotective mechanism of curcumin and its co-administration with piperine against olfactory bulbectomy induced depression in rats. ⋯ The present study highlights that curcumin along with piperine exhibits neuroprotection against olfactory bulbectomy induced depression possibly by modulating oxidative-nitrosative stress induced neuroinflammation and apoptosis.
-
Cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR) is associated with poor survival rate and neurofunctional outcome. Toll-like receptor 2 (TLR2) plays an important role in conditions of sterile inflammation such as reperfusion injury. Recent data demonstrated beneficial effects of the administration of TLR2-blocking antibodies in ischemia/reperfusion injury. In this study we investigated the role of TLR2 for survival and neurofunctional outcome after CA/CPR in mice. ⋯ Deficiency or functional blockade of TLR2 is associated with increased survival and improved neurofunctional outcome in a mouse model of CA/CPR. Thus, TLR2 inhibition could provide a novel therapeutic approach for reducing mortality and morbidity after cardiac arrest and cardiopulmonary resuscitation.
-
Aberrant epidermal growth factor (EGF) signaling is associated with tumor growth in squamous cell carcinoma of the head and neck in humans (HNSCC), and is a major focus of targeted therapy. Cetuximab, a monoclonal antibody against EGFR, has been successful at prolonging survival but has only a 10% tumor shrinkage response rate in a clinical setting. The goal of this study was to compare dacomitinib (PF-00299804), a next generation small molecule tyrosine kinase inhibitor that irreversibly blocks multiple HER family receptors (HER-1 (EGFR), HER-2 and HER-4 tyrosine kinases), to cetuximab, the current FDA approved anti-EGFR medication for HNSCC and erlotinib, an EGFR specific small molecule tyrosine kinase inhibitor. ⋯ Phosphorylated and total EGFR and ERK levels correlate with sensitivity to both cetuximab and dacomitinib. Three of the four lines in the exquisitely sensitive group had the highest levels of phosphorylated and total EGFR and ERK among the ten lines selected, while the three resistant lines collectively had the lowest levels. Neither pAKT nor tAKT was associated with sensitivity.
-
Warao Amerindians, who inhabit the Orinoco Delta, are the second largest indigenous group in Venezuela. High Warao general mortality rates were mentioned in a limited study 21 years ago. However, there have been no comprehensive studies addressing child survival across the entire population. ⋯ The Warao have a low CSI which is correlated with MPI and maternal age. Infectious diseases are responsible for 85% of childhood deaths. The low socioeconomic development, lack of infrastructure and geographic and cultural isolation suggest that an integrated approach is urgently needed to improve the child survival and overall health of the Warao Amerindians.