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Whitehead Thorsen posted an update 6 months, 3 weeks ago
CONCLUSIONS There was no evidence that treatment with HFNO at flow rates of up to 70 L min-1 for 30 min resulted in gastric distension or an increase in gastric secretions in healthy individuals breathing spontaneously. The generalisability of these findings to subjects under anaesthesia and patients with incompetence of the lower oesophageal sphincter or impaired gastric emptying requires further investigation. CLINICAL TRIAL REGISTRATION NCT03134937. BACKGROUND We hypothesised that Calabadion 1, an acyclic cucurbituril molecular container, reverses fentanyl-induced respiratory depression and dysfunction of the CNS. METHODS Experiments were conducted in male Sprague-Dawley rats. A constant-rate i.v. infusion of fentanyl (12.5 or 25 μg kg-1 over 15 min) was administered followed by an i.v. bolus of Calabadion 1 (0.5-200 mg kg-1) or placebo. The primary outcome was reversal of ventilatory and respiratory depression, assessed by pneumotachography and arterial blood gas analysis, respectively. Key secondary outcomes were effects on fentanyl-induced central nervous dysfunction quantified by righting reflex, balance beam test, and electromyography (EMG). RESULTS Calabadion 1 reversed fentanyl-induced respiratory depression across the endpoints minute ventilation, pH, and Paco2 (P=0.001). Compared with placebo, Calabadion 1 dose dependently (P for trend less then 0.001) reversed fentanyl-induced hypoventilation 81.9 (mean ) vs 45.5 ml min-1; P less then 0.001, acidosis (pH 7.43 vs 7.28 ; P=0.005), and hypercarbia (Paco2 43.4 vs 63.4 mm Hg; P=0.018). The effective Calabadion 1 doses required to reverse respiratory depression by 50% and 90% (ED50Res and ED90Res) were 1.7 and 15.6 mg kg-1, respectively. Higher effective doses were needed for recovery of righting reflex (ED50CNS 9.6 mg kg-1; ED90CNS 86.1 mg kg-1), which was accelerated by Calabadion 1 (4.6 vs 9.0 min; P less then 0.001). Calabadion 1 also significantly accelerated recovery of full functional mobility and reversal of muscle rigidity. CONCLUSIONS Calabadion 1 selectively and dose dependently reversed the respiratory system and CNS side-effects of fentanyl. The action of anxiolytic compounds that act on selective serotonin receptors (SSRIs) have been scarcely evaluated. Serotonergic drugs have been shown to be effective in treating anxiety without presenting adverse effects as benzodiazepines. However, the anxiolytic effects take days to occur. This study aimed to evaluate the anxiolytic effect of the synthetic chalcone, 4′- acetamide (PAAMNBA), and its possible mechanism of action in adult zebrafish (Danio rerio). PAAMNBA was synthesized with a yield of 51.3% and its chemical structure was determined by 1H and 13C NMR. Initially, PAAPMNBA was intraperitoneally administered to zebrafish (n = 6/group) at doses of 4, 12, or 40 mg/kg, and the animals were subsequently subjected to acute and open field toxicity tests. PAAMNBA was administered to the other groups (n = 6/group) for analyzing its effect in the light and dark test. The involvement of the serotonergic (5HT) system was also evaluated using 5-HTR 1, 5-HTR 2A/2C, and 5-HTR 3A/3B receptor antagonists, namely, pizotifeo, granizetron, and ciproeptadina, respectively. Molecular coupling was performed using the 5-HT1 receptor. PAAMNBA was found to be non-toxic, reduced the locomotor activity, and had an anxiolytic effect in adult zebrafish. The effect was reduced by pretreatment with pizotifene and was not reversed by treatment with granizetron and cyproeptadine. A previous in vivo molecular coupling study indicated that chalcones interact with the 5-HT1 receptor. The results suggested that the chalcone, PAAPMNBA, has anxiolytic activity, that is mediated by the serotonergic system via the 5-HT1 receptor. The interaction of PAAPMNBA with the 5-HT1 receptor was confirmed by molecular docking studies. Cervical cancer is an aggressive human cancer with poor prognosis among women, and urgently requires effective treatments. Engeletin (ENG, dihydrokaempferol 3-rhamnoside), as a flavanonol glycoside, could be found in various kinds of vegetables and fruits, exerting significant anti-inflammatory biological activities. However, its role in regulating cervical cancer, as well as the underlying molecular mechanisms are still unknown. In this study, we found that ENG treatments dose-dependently reduced the proliferation of cervical cancer cells. Epithelial to mesenchymal transition (EMT) process in cervical cancer was also restrained by ENG using transwell analysis, as evidenced by the significantly reduced migration and invasion. In addition, ENG treatments restricted vascular endothelial growth factor-A (VEGFA) expression in cervical cancer cells, contributing to the suppression of angiogenesis. Mechanistically, ENG significantly reduced the expression of chemokine (C-C motif) ligand 2 (CCL2) in cervical cancer cells associated with the blockage of nuclear factor-κB (NF-κB) signaling pathway. Moreover, ENG functioned as an inhibitor of NF-κB, which was involved in the repression of angiogenesis. In xenograft model, ENG treatment effectively reduced the tumor volume and weight, accompanied with decreased expression of phosphorylated NF-κB, CCL2 and VEGFA, and showed little influence on the body weight change. Therefore, ENG might be a potential therapeutic strategy for the treatment of cervical cancer. OBJECTIVES This study presents the largest clinical experience of percutaneously placed axillary intra-aortic balloon pump (IABP) in patients with advanced heart failure. Trichostatin A HDAC inhibitor BACKGROUND Transfemoral placement of IABP limits mobility and recuperation in patients who need prolonged support. We had previously reported a novel percutaneous method of IABP placement in the axillary artery and now present our expanded experience with this technique. METHODS We performed a retrospective chart review of patients with advanced heart failure with percutaneous axillary IABP placement from November 2007 to June 2018 at Houston Methodist Hospital. We defined successful cardiac replacement therapy as heart transplant or left ventricular assist device implantation. We compared patients who had successful cardiac replacement with those who died and those who needed unplanned escalation of mechanical circulatory support. RESULTS Of the 195 patients identified, 133 (68%) underwent successful cardiac replacement (120 transplants and 13 left ventricular assist device) as planned.
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