Short-term elevation of intracranial pressure does neither influence duodenal motility nor frequency of bolus transport events: a porcine model

BACKGROUND: Patients with traumatic brain injuries and raised intracranial pressure (ICP) display biphasic response with faster gastric emptying during the early stage followed by a prolonged gastric transit time later. While duodenal contractile activity plays a pivotal role in transpyloric transit we investigated the effects of raised intracranial pressure on duodenal motility during the early phase. In order to exclude significant deterioration of mucosal blood supply which might also influence duodenal motility, luminal microdialysis was used in conjunction. METHODS: During general anaesthesia, 11 pigs (32–37 kg, German Landrace) were instrumented with both a luminal catheter for impedancometry and a luminal catheter for microdialysis into the proximal duodenum. Additionally, a catheter was inserted into the left ventricle to increase the intracranial pressure from baseline up to 50 mmHg in steps of 10 mmHg each hour by injection of artificial cerebrospinal fluid. At the same time, duodenal motility was recorded continuously. Duodenal luminal lactate, pyruvate, and glucose concentrations were measured during physiological state and during elevated intracranial pressure of 10, 20, 30, 40, and 50 mmHg in six pigs. Five pigs served as controls. RESULTS: Although there was a trend towards shortened migrating motor cycle (MMC) length in pigs with raised ICP, the interdigestive phase I–III and the MMC cycle length were comparable in the groups. Spontaneous MMC cycles were not disrupted during intracranial hypertension. The mean concentration of lactate and glucose was comparable in the groups, while the concentration of pyruvate was partially higher in the study group than in the controls (p < 0.05). This was associated with a decrease in lactate to pyruvate ratio (p < 0.05). CONCLUSION: The present study suggests that a stepwise and hourly increase of the intracranial pressure of up to 50 mmHg, does not influence duodenal motility activity in a significant manner. A considerable deterioration of the duodenal mucosal blood flow was excluded by determining the lactate to pyruvate ratio

Short-term elevation of intracranial pressure does neither influence duodenal motility nor frequency of bolus transport events: a porcine model

Abstract Background Patients with traumatic brain injuries and raised intracranial pressure (ICP) display biphasic response with faster gastric emptying during the early stage followed by a prolonged gastric transit time later. While duodenal contractile activity plays a pivotal role in transpyloric transit we investigated the effects of raised intracranial pressure on duodenal motility during the early phase. In order to exclude significant deterioration of mucosal blood supply which might also influence duodenal motility, luminal microdialysis was used in conjunction. Methods During general anaesthesia, 11 pigs (32–37 kg, German Landrace) were instrumented with both a luminal catheter for impedancometry and a luminal catheter for microdialysis into the proximal duodenum. Additionally, a catheter was inserted into the left ventricle to increase the intracranial pressure from baseline up to 50 mmHg in steps of 10 mmHg each hour by injection of artificial cerebrospinal fluid. At the same time, duodenal motility was recorded continuously. Duodenal luminal lactate, pyruvate, and glucose concentrations were measured during physiological state and during elevated intracranial pressure of 10, 20, 30, 40, and 50 mmHg in six pigs. Five pigs served as controls. Results Although there was a trend towards shortened migrating motor cycle (MMC) length in pigs with raised ICP, the interdigestive phase I–III and the MMC cycle length were comparable in the groups. Spontaneous MMC cycles were not disrupted during intracranial hypertension. The mean concentration of lactate and glucose was comparable in the groups, while the concentration of pyruvate was partially higher in the study group than in the controls (p Conclusion The present study suggests that a stepwise and hourly increase of the intracranial pressure of up to 50 mmHg, does not influence duodenal motility activity in a significant manner. A considerable deterioration of the duodenal mucosal blood flow was excluded by determining the lactate to pyruvate ratio.</p

The Global Phosphorylation Landscape of SARS-CoV-2 Infection

International audienceThe causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies