The pancreas is essential for digestion and glucose homeostasis. Diseases associated with the pancreas (e.g., pancreatitis, pancreatic cancer, diabetes) are generally debilitating for the patient. Diabetes is particularly prominent in the United States, affecting nearly 6 percent of the population, with associated annual health costs in the billions of dollars. Pancreas development is a complex process that requires the timely expression of numerous factors. Among them, a basic Helix-Loop-Helix factor, BETA2, was shown to be important for terminal differentiation of islet cells including insulin- and glucagon-producing cells. Expression studies demonstrated the presence of BETA2 in islet cells and specific neurons. Targeted deletion of the BETA2 gene in mice revealed its significance in pancreas development. In addition, BETA2 is important in granule cell development of the hippocampus and cerebellum. This chapter will focus on the role of BETA2 in pancreas physiology, neuronal development, and its molecular biology.
Bone morphogenetic proteins (BMPs), members of the transforming growth factor-b subfamily, function as instructive signals for neuronal lineage commitment and promote neuronal differentiation. However, the mechanism of BMP7 action in vivo after peripheral nerve injury is poorly understood. This study examines the efficacy of gene transfer of adenoviral (Ad) BMP7 on peripheral neuropathy. Transgene expression was found in both Ad-infected sciatic nerves and their respective remote neurons, indicating Ad transduction by a retrograde transport. After AdBMP7 infection to nerves, the sciatic nerves were crushed or transected. Hind limb functional behavior, including rotarod test and sciatic functional index, were conducted in rats weekly after nerve injury. Interestingly, enhanced BMP7 expression significantly improved hind limb functional recovery in AdBMP7-transduced rats when compared with AdGFPtransduced nerve-crushed or transected rats. Furthermore, AdBMP7 transduction reduced injury-induced macrophage activation, nerve demyelination and axonal degeneration. By contrast, AdBMP7 infection did not affect the hyperalgesia paw-withdrawal latency after nerve injury. We further examined the effect of AdBMP7 infection on sciatic nerve explant and Schwann cell cultures. Enhanced cell proliferation was significantly increased by AdBMP7 transduction in both cultures. Taken together, BMP7 overexpression by Ad gene transfer was beneficial in both nerves and Schwann cells on functional recovery after sciatic nerve injury in rats.
Peripheral nerve graft supported sensory re-innervation and partial protection of the grey matter, but up-regulated CSPG in the graft-stump junction compared to non-grafted rats. The reduction of CSPG was caused by FGF-1-PN synergy, and did not involve dissociation of CSPG or the suppression of a general immune response.
Objective
Protobothrops mucrosquamatus, a Crotalinae snake with haemorrhagic venom, is responsible for the most common poisoning snakebites in Taiwan. Although a specific antivenin has been developed to treat this snakebite, surgical intervention is still needed in some patients because of the progression of tissue injury. Early risk stratification is important to identify the early signs of need for surgery. The purpose of this study was to investigate the early predictors for surgery in patients with P. mucrosquamatus envenomation.
Methods
The medical records of inpatients with P. mucrosquamatus envenomation between 2008 and 2013 were retrospectively reviewed. Clinical information was collected and analysed between surgical and nonsurgical patients.
Results
A total of 60 patients with P. mucrosquamatus envenomation, including 8 surgical patients (13.3%) and 52 non-surgical patients (86.7%), presented to the emergency department during the study period. Compartment syndrome (62.5%) and tissue necrosis (37.5%) were the main reasons for surgery. Comparison between surgical and non-surgical patients showed significantly higher white blood cell count (17.1 × 103/μL vs. 8.5 × 103/μL; p=0.002) and peak D-dimer level (1924.8 ng/mL vs. 730.0 ng/mL; p=0.006) in the surgical group. Ecchymosis (p=0.009), haemorrhagic bulla formation (p=0.002), leukocytosis (p=0.002), elevated peak D-dimer level (>1000 ng/mL) (p=0.005), and rhabdomyolysis (creatine kinase level >1000 IU/L) (p=0.007) were the significant signs relevant to surgery. On multivariate analysis, leukocytosis and ecchymosis were the most significant predictors of surgery in patients with P. mucrosquamatus envenomation.
Conclusions
Patients with P. mucrosquamatus envenomation presenting with leukocytosis and wound ecchymosis will have a high probability of requiring surgical therapy. (Hong Kong j.emerg.med. 2016;23:210-219)
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