暂无摘要。

Noradrenaline (NA) and serotonin (5-HT) induce nociception and antinociception. This antagonistic effect can be explained by the dose and type of activated receptors. We investigated the existence of synergism between the noradrenergic and serotonergic systems during peripheral antinociception. The paw pressure test was performed in mice that had increased sensitivity by intraplantar injection of prostaglandin E2 (PGE2). Noradrenaline (80 ng) administered intraplantarly induced an antinociceptive effect, that was reversed by the administration of selective antagonists of serotoninergic receptors 5-HT1B isamoltan, 5-HT1D BRL15572, 5-HT2A ketanserin, 5-HT3 ondansetron, but not by selective receptor antagonist 5-HT7 SB-269970. The administration of escitalopram, a serotonin reuptake inhibitor, potentiated the antinociceptive effect at a submaximal dose of NA. These results, indicate the existence of synergism between the noradrenergic and serotonergic systems in peripheral antinociception in mice.

BACKGROUND: The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section.
METHODS: Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery.
RESULTS: No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes.
CONCLUSIONS: Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section.

暂无摘要。

UNASSIGNED: Post-discharge nausea and vomiting (PDNV) is a pertinent problem in patients undergoing ambulatory surgery. The objective of this study was to assess the efficacy of the novel drug olanzapine, which has proved its efficiency in patients undergoing highly emetogenic chemotherapy for PDNV prevention.
UNASSIGNED: This randomised controlled trial recruited 106 adult patients (18-65 years) undergoing highly emetogenic daycare surgeries with propofol-based general anaesthesia (GA). Group O received preoperative oral olanzapine 10 mg, and Group C, acting as a control, received 8 mg of intravenous dexamethasone and 4 mg of ondansetron intraoperatively. The primary outcome was nausea (numeric rating scale >3) and/or vomiting 24 h after discharge. Secondary outcomes included nausea and vomiting in the post-anaesthesia care unit (PACU), severe nausea, vomiting and side effects. Normality was assessed using the Shapiro-Wilk test, and the independent samples t-test or the Mann-Whitney U test was used to compare continuous variables. Fisher\'s exact test was used to assess any non-random associations between the categorical variables.
UNASSIGNED: The incidence and severity of postoperative nausea and vomiting were similar in both groups within PACU (four patients experienced nausea and vomiting, three had severe symptoms in Group O, P = 0.057) and in the post-discharge period (three patients in Group O had nausea and vomiting compared to five patients in Group C, of which four were severe, P = 0.484). The side effects (sedation, dizziness, and light-headedness) were comparable between the two groups.
UNASSIGNED: A single preoperative oral olanzapine can be an effective alternative to standard antiemetic prophylaxis involving dexamethasone and ondansetron for preventing PDNV in highly emetogenic daycare surgeries with propofol-based GA.

UNASSIGNED: Common postoperative complications following surgery, particularly acute appendicitis surgery, include postoperative pain and vomiting, which can cause discomfort and delay recovery time.
UNASSIGNED: A randomized double-blinded placebo-controlled clinical trial was conducted with 80 cases of acute appendicitis of American Society of Anesthesiologists (ASA) physical status I or II and aged 18-60 y/o scheduled for appendectomy under general anesthesia. Patients were randomly divided into two equal groups: group A received 4 mg of ondansetron IV (2 ml) and group B received 2 ml of normal slain IV (placebo). Pain according to VAS, nausea and vomiting according to clinical symptoms, shivering and sedation according to the Bedside Shivering Assessment Scale (BSAS), and the Ramsay Sedation Scale (RSS) at 2, 6, 12, and 24 hours after surgery were evaluated and compared between the groups.
UNASSIGNED: There was a significant decline in the severity of pain only at 2 hours after surgery between the ondansetron and control groups (5.3 ± 1.0 vs. 6.0 ± 1.0; p=0.01), not showing a difference between the groups at 6, 12, and 24 hours after appendectomy. Postoperative nausea and vomiting at 2 (5% vs. 25%; p=0.03) and 6 (7.5% vs. 27.5%; p=0.04) hours after appendectomy in the ondansetron group. At different times, the ondansetron and control groups did not differ in terms of pethidine consumption or sedation.
UNASSIGNED: In conclusion, our study found that ondansetron was effective in reducing postoperative vomiting after acute appendicitis surgery. However, it did not show a clinically significant effect on postoperative pain. This trial is registered with IRCT20230722058883N1.

BACKGROUND: Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects.
METHODS: This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance.
RESULTS: There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo\'s.
CONCLUSIONS: In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04\'s adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.

BACKGROUND: Nonclinical evaluation of the cardiovascular effects of novel chemical or biological entities (NCE, NBEs) is crucial for supporting first-in-human clinical trials. One important aspect of these evaluations is the assessment of potential QT/QTc prolongation risk, as drug-induced QT prolongation can have catastrophic effects. The recent publication of E14/S7B Q&As allows for the situational incorporation of nonclinical QTc data as part of an integrated risk assessment for a Thorough QT (TQT) waiver application provided certain best practice criteria are met. Recent publications provided detailed characterization of nonclinical QTc telemetry data collected from the commonly used Latin square study design.
METHODS: To understand whether data from alternate telemetry study designs were sufficient to serve as part of the E14/S7B integrated risk assessment, we report the performance and translational sensitivity to identify clinical risk of QTc prolongation risk for an ascending dose telemetry design.
RESULTS: The data demonstrated low variability in QTci interval within animals from day to day, indicating a well-controlled study environment and limited concern for uncontrolled effects across dosing days. Historical study variances of the ascending dose design with n = 4 subjects, measured by least significant difference (LSD) and root mean square error (RMSE) values, were low enough to detect a + 10 ms QTci interval change, and the median minimum detectable difference (MDD) for QTci interval changes was <10 ms. Furthermore, concentration-QTci (C-QTci) assessments to determine +10 ms QTci increases for known hERG inhibitors were comparable to clinical CC values listed in the E14/S7B training materials, supporting the use of the ascending dose design in an E14/S7B integrated risk assessment.
CONCLUSIONS: These findings suggest that the ascending dose design can be a valuable tool in nonclinical evaluation of QT/QTc prolongation risk and the support of TQT waiver applications.

UNASSIGNED: Spinal anesthesia is commonly performed for cesarean section, however, postdural puncture headache (PDPH) is one of its most common adverse effects. Ondansetron is an antiemetic for cancer treatment and analgesia-induced nausea and vomiting. In this study, the authors aim to evaluate the effect of postoperative ondansetron on PDPH.
UNASSIGNED: In this randomized controlled clinical trial study, 120 pregnant patients are ASA ll, undergoing elective cesarean section, were randomized into two groups (placebo or study). The patients in the study group, immediately after the birth of a baby and 24 h after the operation, received ondansetron 4 mg IV while the placebo group received a placebo. The severity and incidence of headache, postoperative nausea and vomiting, dizziness, neck and lower back pain, and the use of analgesia was assessed in the two groups.
UNASSIGNED: The significant meaning of the time effect (P<0.001) indicated that regardless of the group, for each unit increase in time, the chance of developing a headache increased by 23%, which was statistically significant. Also, the significant meaning of the group effect indicated that regardless of time, patients who did not take indomethacin had ~4.11 times higher chances of developing a headache compared to those who received the medication, which was statistically significant (P=0.004).
UNASSIGNED: The administration of ondansetron significantly reduces the occurrence of postspinal anesthesia headaches and neck pain. There was no significant difference in headache severity between the two study groups.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or β-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats.
METHODS: This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2 Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8 Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40 mg/kg b.wt. /day, orally) or O (2 mg/kg) was given ip) or were kept untreated as model groups.
RESULTS: Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues.
CONCLUSIONS: The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.