Effects of low-dose epinephrine on perioperative hemostasis and inflammatory reaction in major surgical operations: a randomized clinical trial.

Essentials Blood loss and immune reaction are closely related to morbidity and recovery after surgery. We studied the effect of epinephrine plus tranexamic acid on blood loss and immune reaction. Epinephrine plus tranexamic acid reduced postoperative total blood loss and immune reaction. Epinephrine plus tranexamic acid did not increase the incidence of complications. SUMMARY: Background Hemostasis, thrombosis and surgical stress-induced immune reactions are important for perioperative morbidity and recovery after major surgical operations. Objectives To evaluate the effects of combined administration of low-dose epinephrine (LDEPI) and tranexamic acid (TXA) on perioperative blood loss, thromboembolic complications and inflammatory responses in patients undergoing total hip arthroplasty (THA). Patients/Methods Patients scheduled for THA (n = 195) were randomized into three interventions: intravenous LDEPI plus TXA (group IV); topical diluted epinephrine plus TXA (group TP); and TXA alone as control (group CT). The primary outcome was perioperative blood loss on postoperative day (POD) 1. Secondary outcomes included perioperative blood loss on POD 3, intraoperative blood loss, volume of drainage, transfusion values, coagulation and fibrinolysis parameters, inflammatory cytokine levels, cases of thrombosis, intravenous fluid on the operation day, and length of hospital stay. Results The mean calculated amounts of total blood loss in groups IV, TP and CT were 631.2 mL, 760.5 mL, and 825.6 mL, respectively, on POD 1; treatment effects (differences) were 194.4 mL (95% confidence interval [CI] 146.7-242.0) and 65.0 mL (95% CI 17.4-112.7). Groups IV and TP had lower levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin [IL]-1ß) and higher levels of the anti-inflammatory cytokine IL-10, and showed faster development of coagulation and fibrinolysis (without change in peak levels), than group CT early postoperation. No differences were observed in transfusion, thromboembolic and other outcomes among the groups. Conclusion The combined administration of LDEPI and TXA was more effective in reducing perioperative blood loss and alleviating the inflammatory response than TXA alone, without increasing the incidence of thromboembolic and other complications.

Influence of dexmedetomidine to cognitive function during recovery period for children with general anesthesia.

OBJECTIVE: We studied the influence of Dexmedetomidine on cognitive function in children during the recovery period of general anesthesia. PATIENTS AND METHODS: Ninety-three children who underwent general anesthesia were selected and randomly divided into (1) the control group, (2) the dexmedetomidine group, and (3) the dezocine group. Fentanyl, propofol, and rocuronium were used in all patients to induce anesthesia, while sevoflurane inhalation and propofol were used to maintain anesthesia. In the control group, 20 ml NS were infused intravenously 10 min before anesthetic induction. In the dexmedetomidine group, 1.0 µg/kg dexmedetomidine in 20 ml was infused for 10 min. In the dezocine group, 0.1 mg/kg dezocine in 20 ml was infused for 10 min. Mean arterial blood pressure, average heart rate, and average oxygen saturation (SaO2) were compared at the following time points: end of surgery (T0), before extubation (T1), during extubation (T2), and 30 min after extubation (T3). The VAS scale, Ramsay sedation score, delirium grading scale and occurrence of adverse reactions at 30 min after extubation were recorded. The occurrence of postoperative cognitive dysfunction (POCD) and the expression of serum neuron-specific enolase (NSE) and IL-6 at postoperative days 1 and 7 were recorded. RESULTS: Comparing mean arterial blood pressure, average heart rate, and average oxygen saturation (SaO2) at the different time points in the dexmedetomidine group, there were no statistically significant differences (p>0.05). The difference in the occurrence of adverse reactions in the different groups was statistically significant (p<0.05). The occurrence of postoperative cognitive dysfunction (POCD) at postoperative day 1 was significantly higher in the control group than the other two groups (p<0.05), and on the postoperative day 7th, the differences were not statistically significant (p>0.05). Regarding the expression of neuron-specific enolase (NSE) and IL-6, the levels were the highest in the control group, followed by the dezocine group (p<0.05). CONCLUSIONS: The dexmedetomidine is safer than dezocine in aspects of hemodynamics, sedation, analgesia, degree of delirium, occurrence of adverse reactions, and postoperative cognitive dysfunction (POCD). The improvement in the occurrence of postoperative cognitive dysfunction (POCD) is related to the levels of serum neuron-specific enolase (NSE) and IL-6.

Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis.

The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a key component of tumor necrosis factor (TNF)-induced necroptosis and plays a crucial role in necroptosis execution. However, the mechanisms that control MLKL activity are not completely understood. Here, we identify the molecular chaperone Hsp90 as a novel MLKL-interacting protein. We show that Hsp90 associates with MLKL and is required for MLKL stability. Moreover, we find that Hsp90 also regulates the stability of the upstream RIP3 kinase. Interference with Hsp90 function with the 17AAG inhibitor destabilizes MLKL and RIP3, resulting in their degradation by the proteasome pathway. Furthermore, we find that Hsp90 is required for TNF-stimulated necrosome assembly. Disruption of Hsp90 function prevents necrosome formation and strongly reduces MLKL phosphorylation and inhibits TNF-induced necroptosis. Consistent with a positive role of Hsp90 in necroptosis, coexpression of Hsp90 increases MLKL oligomerization and plasma membrane translocation and enhances MLKL-mediated necroptosis. Our findings demonstrate that an efficient necrotic response requires a functional Hsp90.

Polymorphisms associated with egg number at 300 days of age in chickens.

We looked for variations that could be associated with chicken egg number at 300 days of age (EN300) in seven genes of the hypothalamic-pituitary-gonadal axis, including gonadotrophin-releasing hormone-I (GnRH-I), GnRH receptor (GnRHR), neuropeptide Y (NPY), dopamine D2 receptor (DRD2), vasoactive intestinal polypeptide (VIP), VIP receptor-1 (VIPR-1), prolactin (PRL), and the QTL region between 87 and 105 cM of the Z chromosome. Ten mutations in the seven genes were chosen to do marker-trait association analyses in a population comprising 1310 chickens, which were obtained from a company located in Guangdong Province of China. The C1704887T of VIPR-1 was found to have a highly significant association with EN300. The T5841629C of DRD2 and the C1715301T of VIPR-1 were significantly associated with EN300. A highly significant association was also found between the C1704887T-C1715301T haplotypes of VIPR-1 and EN300. H1H3 had the highest EN300. Four PCR-RFLP variations in the candidate QTL region were selected to investigate their genetic effects on EN300. The haplotypes of T32742468C-G32742603A in this region showed a highly significant association with EN300. Bioinformatics analyses showed that both T32742468C and G32742603A were located in intron 1 of the SH3-domain GRB2-like 2 (SH3GL2) gene. We conclude that five SNPs, including C1704887T and C1715301T of VIPR-1, T5841629C of DRD2, and T32742468C and G32742603A of SH3GL2, would be useful as markers for breeding to increase chicken EN300.