Neuroinflammation is one of the mechanisms leading to neurodegenerative brain damage induced by chronic alcohol (ethanol) exposure. Microglia play a major role in the development of innate immune responses to environmental injuries including ethanol. Adenosine 5″-triphosphate (ATP)-activated purinergic P2X receptor (P2XR) subtypes, P2X4Rs and P2X7Rs, are endogenously expressed in microglia and can modulate their activity. These 2 P2XR subtypes differ pharmacologically and functionally: 1) P2X4Rs are activated at lower (≤0.1 mM) whereas P2X7Rs - at higher (≥1.0 mM) ATP concentrations; 2) P2X4R activation contributes to the release of brain derived neurotrophic factor and its role in tactile allodynia and neuropathic pain is demonstrated; 3) Due to its role in the secretion of pro-inflammatory IL-1β, P2X7Rs have been implicated in the development of neurodegenerative pathologies, pain and morphine tolerance. To date, the roles of individual P2XR subtypes in ethanol effects on microglia and the functional consequences are not completely understood. Based on the existing knowledge on the pharmacological and functional differences between P2X4Rs and P2X7Rs, the present work tested the hypothesis that P2X4Rs and P2X7Rs play differential roles in ethanol action in microglia. Effects of ethanol on P2X4R and P2X7R activity, expression and functional consequences were determined using murine BV2 microglial cells. Ethanol (≥100 mM) inhibited P2X4Rs but was inactive on P2X7 channel activity. Ethanol (25, 100 mM) inhibited P2X4R-mediated microglia migration whereas it potentiated pore formation in P2X7Rs. Furthermore, ethanol (25, 100 mM) potentiated P2X7R-mediated IL-1β secretion from BV2 microglia. Ethanol also induced protein expression for both P2XR subtypes. Overall, the findings identify differential roles for P2X4Rs and P2X7Rs in regards to ethanol effects on microglia which may be linked to different stages of ethanol exposure.

Background Enhanced recovery after surgery (ERAS) protocols have been associated with improved postoperative outcomes but require further validation in thoracic surgery. This study evaluated outcomes of patients undergoing pulmonary resection before and after implementation of an ERAS protocol. Methods Electronic medical records were queried for all patients undergoing pulmonary resection between April 2017 and April 2019. Patients were grouped into pre-and post-ERAS cohorts based on dates of operation. The ERAS protocol prioritized early mobilization, limited invasive monitoring, euvolemia, and non-narcotic analgesia. Primary outcome measures included intensive care unit (ICU) utilization, postoperative pain metrics, and perioperative morbidity. Regression analyses were performed to identify predictors of morbidity. Subgroup analyses were performed by pulmonary risk profile and surgical approach. Results A total of 64 pre-and 67 post-ERAS patients were included in the study. ERAS implementation was associated with reduced postoperative ICU admission (pre: 65.6% vs. post: 19.4%, p \ 0.0001), shorter ICU median length of stay (LOS) (pre: 1 vs. post: 0, p \ 0.0001), and decreased opioid usage measured by median morphine milligram equivalents (pre: 40.5 vs. post: 20.0, p \ 0.0001). Post-ERAS patients also reported lower visual analog scale (VAS) pain scores on postoperative days (POD) 1 and 2 (pre: 6.3/5.6 vs. post: 5.3/4.2, p = 0.04/0.01) as well as average VAS pain score over POD0-2 (pre: 6.2 vs. post: 5.2, p = 0.005). Conclusions Implementation of an ERAS protocol for pulmonary resection, which dictated reduced ICU admissions, did not increase major postoperative morbidity. Additionally, ERAS-enrolled patients reported improved postoperative pain control despite decreased opioid utilization.

Prior to testing novel therapeutics in humans, short and long term preclinical (i.e., animal), repetitive pharmacological and toxicological testing is required. In most cases, the preferred route of administration is via oral delivery. At the present time, oral delivery is mostly accomplished using an oral gavage procedure, in part, because it can achieve consistent and precise dosing in the animal model. Although this method is well established it does have complications that can result in a high rate of animal attrition. To this end, the procedure introduced here describes an alternative to the oral gavage method in which the desired drug is incorporated into a tastant, orally dissolving strip (ODS) that can simply be presented to the test animal where it is then rapidly taken up with minimal manipulation of the test subject. Herein, we demonstrate that preclinical, oral drug delivery using the ODS method represents a safe, convenient, and humane alternative to oral gavage.

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