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ABSTRACT Orthotopic liver transplantation (OLT) is the standard of care for patients suffering from end stage liver disease (ESLD). This is a high-risk procedure with the potential for hemorrhage, large shifts in preload and afterload, and release of vasoactive mediators that can have profound effects on hemodynamic equilibrium. In addition, patients with ESLD can have preexisting coronary artery disease, cirrhotic cardiomyopathy, porto-pulomary hypertension and imbalanced coagulation. As cardiovascular involvement is invariable and patient are at an appreciable risk of intraoperative cardiac arrest, Trans esophageal echocardiography (TEE) is increasingly becoming a routinely utilized monitor during OLT in patients without contraindications to its use. A comprehensive TEE assessment performed by trained operators provides a wealth of information on baseline cardiac function, while a focused study specific for the ESLD patients can help in prompt diagnosis and treatment of critical events. Future studies utilizing TEE will eventually optimize examination safety, quality, permit patient risk stratification, provide intraoperative guidance, and allow for evaluation of graft vasculature.

Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect.

Orthotopic liver transplantation (OLT) is the standard of care for patients suffering from end stage liver disease (ESLD). This is a high-risk procedure with the potential for hemorrhage, large shifts in preload and afterload, and release of vasoactive mediators that can have profound effects on hemodynamic equilibrium. In addition, patients with ESLD can have preexisting coronary artery disease, cirrhotic cardiomyopathy, porto-pulomary hypertension and imbalanced coagulation. As cardiovascular involvement is invariable and patient are at an appreciable risk of intraoperative cardiac arrest, Trans esophageal echocardiography (TEE) is increasingly becoming a routinely utilized monitor during OLT in patients without contraindications to its use. A comprehensive TEE assessment performed by trained operators provides a wealth of information on baseline cardiac function, while a focused study specific for the ESLD patients can help in prompt diagnosis and treatment of critical events. Future studies utilizing TEE will eventually optimize examination safety, quality, permit patient risk stratification, provide intraoperative guidance, and allow for evaluation of graft vasculature.

Previous studies have shown that transplanted enteric glia enhance axonal regeneration, reduce tissue damage, and promote functional recovery following spinal cord injury. However, the mechanisms by which enteric glia mediate these beneficial effects are unknown. Neurotrophic factors can promote neuronal differentiation, survival and neurite extension. We hypothesized that enteric glia may exert their protective effects against spinal cord injury partially through the secretion of neurotrophic factors. In the present study, we demonstrated that primary enteric glia cells release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor over time with their concentrations reaching approximately 250, 100 and 50 pg/mL of culture medium respectively after 48 hours. The biological relevance of this secretion was assessed by incubating dissociated dorsal root ganglion neuronal cultures in enteric glia-conditioned medium with and/or without neutralizing antibodies to each of these proteins and evaluating the differences in neurite growth. We discovered that conditioned medium enhances neurite outgrowth in dorsal root ganglion neurons. Even though there was no detectable amount of neurotrophin-3 secretion using ELISA analysis, the neurite outgrowth effect can be attenuated by the antibody-mediated neutralization of each of the aforementioned neurotrophic factors. Therefore, enteric glia secrete nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor and neurotrophin-3 into their surrounding environment in concentrations that can cause a biological effect. Research Highlights (1) Primary enteric glia release nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor into culture medium. (2) Enteric glia stimulate neurite branching of dorsal root ganglion neurons. (3) The beneficial effect of enteric glia on neurite of dorsal root ganglion neurons is, in part, regulated by the release of neurotrophic factors including nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor, and neurotrophin-3. (4) This study provides new insight and a foundation for further study on mechanisms by which enteric glia exert their beneficial effects in vitro and in vivo. Abbreviations ENS, enteric nervous system; EG, enteric glia; CNS, central nervous system; DRG, dorsal root ganglion; NGF, nerve growth factor; BDNF, brain-derived neurotrophic factor; NT-3, neurotrophin-3; Trk, tropomyosin-related kinase; GDNF, glial cell line-derived neurotrophic factor; MPZ, myelin protein zero