Search

The neuromuscular junction is a complex structure consisting of the muscle cell, the nerve terminal of a motor neuron and the synaptic cleft. It is the site of action for neuromuscular blocking drugs, which are a cornerstone of anaesthetic practice. These drugs can be divided into depolarizing and non-depolarizing drugs; the latter can be further subdivided into benzylisoquinolinium and aminosteroid compounds. Reversal agents are also discussed. The pharmacology of neuromuscular blocking drugs and reversal agents is discussed including mechanism of action, metabolism, factors influencing choice of drug as well as adverse effect profile. [ABSTRACT FROM AUTHOR]

Background: Patients with neurologic injuries often receive neuromuscular blocking agents to facilitate airway management. The urgent nature of intubation may result in paralytic administration prior to neurologic examination, delaying clinical assessment, prognostication, and surgical interventions. Objective: In October 2018, an institutional guideline was implemented to extend institutional sugammadex use to include patients with uncertain neurologic examinations with recent rocuronium administration. The guideline allowed for a dose range of 2 mg/kg to 16 mg/kg. The objective of this continuous quality improvement project was to describe the use of sugammadex after implementation of an institutional guideline. Methods: Patient records between October 2018 and March 2020 were reviewed for guideline adherence and outcomes. Information assessed included patient weight, injury mechanism, the dosage and timing of rocuronium and sugammadex administration, and neurologic examination findings. Descriptive statistics were used to assess outcomes. Results: During the study period, eleven patients received sugammadex to facilitate neurologic examinations. The most common dose of sugammadex was 4 mg/kg with a mean total dose of 498.4 ± 333.5 mg. The mean time between rocuronium and sugammadex administration was 73.9 ± 41 minutes. Most patients (72.7%) had definitive changes in neurologic examination after sugammadex administration. Five patients had neurosurgical interventions offered and performed, with 1 of the patients surviving. Conclusions: This case series suggests that sugammadex is useful for reversing rocuronium induced paralysis to facilitate neurologic examination needed to determine management strategies for patients with a neurologic injury. [ABSTRACT FROM AUTHOR]

Background: Prolong effects of non-depolarizing neuromuscular blocking agents after rapid sequence intubation may prevent meaningful neurological examination, delaying appropriate diagnosis and neurosurgical intervention. Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium. Objective: The objective of this study was to evaluate low- (2 mg/kg) vs standard-dose (4 mg/kg) sugammadex for rocuronium-induced deep neuromuscular blockade reversal in the emergency department (ED) by achieving a post-treatment train-of-four (TOF) of 4 to facilitate neurological examination. Methods: This was a single-center, retrospective, cohort study evaluating low-vs standard-dose sugammadex for neuromuscular blockade reversal in the ED. Results: 34 patients were identified within the designated time period, 24 of which were included in the final analysis ([n = 9 low-dose], [n = 15 standard-dose]). Median sugammadex doses were 2.3 mg/kg and 4.1 mg/kg for low- and standard-dose, respectively. The majority of patients presented for intraparenchymal hemorrhage (54.2%). No significant difference in success rate of NMBA reversal was found between low- and standard-dose sugammadex ([100.0% vs 93.3%], P = 1.000). A total of 9 patients had a neurosurgical procedure performed after sugammadex administration. Low-dose sugammadex was associated with significantly less acquisition cost compared to the standard dose (P <.001). Conclusion: Low- (2 mg/kg) and standard-dose (4 mg/kg) sugammadex successfully reversed rocuronium-induced deep neuromuscular blockade in the ED by achieving a post-treatment TOF of 4 to facilitate neurologic examination. Low-dose sugammadex may be a viable option for deep NMBA reversal in the ED and is associated with decreased institutional cost. [ABSTRACT FROM AUTHOR]

Purpose: Post-operative urinary retention (POUR) is a known complication of hernia surgery. Minimally invasive inguinal hernia repair (IHR) is typically done under general anesthesia with neuromuscular blockade (NMB), which is commonly reversed with an anticholinesterase inhibitor paired with an anticholinergic agent. Sugammadex is a unique NMB reversal agent that does not have to be paired with an anticholinergic. We sought to explore the role of sugammadex in reducing the rate of POUR following these procedures. Methods: Data were collected retrospectively at a single institution between February 2016 and October 2019. We identified and studied patients who underwent minimally invasive IHR and received either sugammadex or neostigmine/glycopyrrolate for NMB reversal. The primary endpoint was POUR requiring bladder catheterization. Secondary endpoints included post-operative and 30-day readmissions. Results: 274 patients were included in this study (143 received neostigmine and glycopyrrolate, 131 sugammadex). The sugammadex patients were on average 5 years older than the neostigmine/ glycopyrrolate patients (63.2 vs 58.2, p = 0.003), and received less median intravenous fluids (IVF) (900 ml vs 1000 ml; p = 0.015). There was a significant difference in the rate of POUR between the sugammadex and neostigmine/glycopyrrolate patients (0.0% vs 8.4%, p ≤ 0.001). The difference remained significant after controlling for age and IVF. The odds of POUR for those who received neostigmine/glycopyrrolate were 25 × higher than the odds of those who received sugammadex. Conclusion: The results of this study reflect the protective role of sugammadex against POUR in minimally invasive IHR cases. [ABSTRACT FROM AUTHOR]

Background: Opioid-induced rigidity is typically observed during rapid administration of fentanyl. Herein, we present a case in which rigidity occurred after reversal of rocuronium during emergence from anesthesia. Case presentation: A 73-year-old man underwent video-assisted partial lung resection. General anesthesia was induced with propofol, remimazolam, remifentanil, and rocuronium. Fentanyl was administered early during anesthesia. The surgery was completed without complications, and sugammadex sodium was administered for rocuronium reversal. The patient became agitated, but spontaneous breathing was maintained; therefore, the intratracheal tube was removed after the administration of flumazenil. The patient developed stiffness in the neck and jaw muscles along with remarkable skeletal muscle contractions. Dramatic improvement was observed immediately after administration of naloxone. Conclusions: Even as the simulated effect site concentration of fentanyl decreases during anesthesia emergence, opioid-induced rigidity may still occur. Rapid reversal of remimazolam by flumazenil might have contributed to the rigidity in this case. [ABSTRACT FROM AUTHOR]

This study aimed to explore whether differences exist in anesthesia care providers' use of intraoperative medication between African American and non-Hispanic White patients in adult surgical patients who underwent noncardiothoracic nonobstetric surgeries with general anesthesia. A retrospective observational cohort study used electronic health records between January 1, 2018 and August 31, 2019 at a large academic health system in the southeastern United States. To evaluate the isolated impact of race on intraoperative medication use, inverse probability of treatment weighting using the propensity scores was used to balance the covariates between African American and non-Hispanic White patients. Regression analyses were then performed to evaluate the impact of race on the total dose of opioid analgesia administered, and the use of midazolam, sugammadex, antihypotensive drugs, and antihypertensive drugs. Of the 31,790 patients included in the sample, 58.9% were non-Hispanic Whites and 13.6% were African American patients. After adjusting for significant covariates, African American patients were more likely to receive midazolam premedication (p <.0001; adjusted odds ratio [aOR] = 1.17, 99.9% CI [1.06, 1.30]), and antihypertensive drugs (p =.0002; aOR = 1.15, 99.9% CI [1.02, 1.30]), and less likely to receive antihypotensive drugs (p <.0001; aOR = 0.85, 99.9% CI [0.76, 0.95]) than non-Hispanic White patients. However, we did not find significant differences in the total dose of opioid analgesia administered, or sugammadex. This study identified differences in intraoperative anesthesia care delivery between African American and non-Hispanic White patients; however, future research is needed to understand mechanisms that contribute to these differences and whether these differences are associated with patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: neostigmine and sugammadex are alternatives for reversal of vecuroniuminduced neuromuscular relaxation. Material and methods: clinical trial, randomized in patients with neuromuscular relaxation induced by vecuronium at 0.1 mg/kg of ideal weight; to perform the reversion of neuromuscular relaxation (RRNM), they were divided into two groups: group A sugammadex of 2 mg/kg and group B neostigmine .04 mg/kg plus .02 mg/kg (both ideal weight). RRNM time, presence of adverse events and occurrence of residual relaxation in the post-anesthesia care area were compared. Statistical analysis was performed with Mann-Whitney U, χ² and the effect size was calculated with g Hedges. Results: 76 patients were included in two groups: sugammadex and neostigmine, group A presented RRNM at four minutes and group B at 12 minutes with a p < 0.01 with a correlation r = 0.08, also group A presented adverse events in 2.63% and group B 89.46% with a p < 0.001. Conclusions: sugammadex presented shorter time to vecuronium-induced NRRMR and lower adverse events. [ABSTRACT FROM AUTHOR]

Aims: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine. Methods: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis. Results: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P‐value for the reversal agents stratified by surgery duration was 0.011. Conclusion: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated. [ABSTRACT FROM AUTHOR]

Muscle relaxants and their reverse drugs should be carefully administered to patients with acute polymyositis and/or dermatomyositis. However, the use of these drugs in controlled polymyositis and/or dermatomyositis is controversial. This case report describes the use of rocuronium and sugammadex in a 27-year-old female patient with controlled polymyositis who was scheduled for minor oral surgery under general anesthesia. General anesthesia was induced rapidly, and 0.66 mg/kg of rocuronium was administered prior to nasotracheal intubation. No additional muscle relaxants were administered during the surgery. At the end of surgery, approximately 2 hours after the rocuronium was administered, her train-of-four (TOF) ratio was still 49%. A dose of 3.3 mg/kg of sugammadex was administered, and it took 12 minutes for the TOF ratio to exceed 90%. The prolonged duration of muscle relaxation in patients with polymyositis may be due to a decrease in skeletal muscle and capillary volume. The slow onset of sugammadex may be caused by slow diffusion of rocuronium from the neuromuscular junction. Patients with polymyositis require close perioperative neuromuscular function monitoring, regardless of their disease control status. [ABSTRACT FROM AUTHOR]

Pawe&lstrok; Radkowski,1– 3 Maria Agnieszka Derkaczew,2 Micha&lstrok; Adam Jacewicz,4,5 Dariusz Onichimowski1,2 1Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 2Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland; 3Hospital zum Heiligen Geist, Fritzlar, Germany; 4Regional Specialist Hospital in Olsztyn, Olsztyn, Poland; 5Department of Pharmacology and Toxicology, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, PolandCorrespondence: Maria Agnieszka Derkaczew, Department of Anaesthesiology and Intensive Care, Faculty of Medicine, Collegium Medicum University of Warmia and Mazury in Olsztyn, Olsztyn, Poland, Email m.derkaczew@gmail.comAbstract: The prevalence of morbid obesity in today’s population around the world is alarming. Morbid obesity involves substantial changes in body composition and function, which can affect the pharmacodynamics and pharmacokinetics of many drugs. This paper aims to discuss the application of muscle relaxants and their reversing agents in patients with morbid obesity. This work is based both on the available literature and the author’s personal experience. Dosage recommendations for muscle relaxants in morbidly obese patients are as follows: non-depolarizing relaxants like rocuronium, vecuronium, atracurium, and cisatracurium should be based on ideal body weight. Succinylcholine dosage should be adjusted to total body weight with a 200 mg maximum, while mivacurium should also be based on total body weight. Pancuronium is not used due to its long duration. Neostigmine dosing remains uncertain, but some suggest using total body weight. When it comes to Sugammadex opinions of the authors are divided, some indicate that it should be dosed based on ideal body weight, but more recent studies show that it should be based on 40% of corrected body weight.Keywords: muscle relaxants, muscle relaxants reversal agents, succinylcholine, sugammadex, morbid obesity, obese patients

Efficacy and safety of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) in patients with neuromuscular diseases remains unclear. We summarised the available evidence and evaluated the quality of data reporting and the validity of published reports. We searched for reports (any design) on the usage of sugammadex (any regimen) for the reversal of an NMBA in patients (any age) with any neuromuscular disease. We used a modified CARE checklist (maximum score 23) to assess the quality of data reporting and an original specific validity checklist (maximum score 41) that was developed through a Delphi process. We retrieved 126 observational reports (386 patients). Most dealt with myasthenia gravis patients receiving rocuronium. The train-of-four ratio returned to ≥0.9 in 258 of 265 (97.4%) patients in whom neuromonitoring was used. Adverse events occurred in 14 of 332 (4.2%) patients in whom adverse events were reported as present or absent. In 90 case reports, the median score of the 23-point CARE checklist was 13.5 (inter-quartile range [IQR] 11–16). In all 126 reports, the median score of the 41-point validity checklist was 23 (IQR 20–27). Scores were positively correlated. These uncontrolled observations (of mainly low to moderate quality and validity) do not allow confident assessment of the efficacy and safety of sugammadex for the reversal of NMBAs in patients with neuromuscular diseases. Reporting of observational data should follow established guidelines, include specific information to ensure validity, and emphasise what the new data add to current knowledge. PROSPERO 2019 (CRD42019119924). [ABSTRACT FROM AUTHOR]

Abstract Background Sugammadex is a pharmacologic agent that provides rapid reversal of neuromuscular blockade via encapsulation of the neuromuscular blocking agent (NMBA). The sugammadex-NMBA complex is primarily cleared through glomerular filtration from the kidney, raising the possibility that alterations in renal function could affect its elimination. In pediatric patients, the benefits of sugammadex have led to widespread utilization; however, there is limited information on its application in pediatric renal impairment. This study examined sugammadex use and postoperative outcomes in pediatric patients with severe chronic renal impairment at our quaternary pediatric referral hospital. Methods After IRB approval, we performed a retrospective analysis in pediatric patients with stage IV and V chronic kidney disease who received sugammadex from January 2017 to March 2022. Postoperative outcomes studied included new or increased respiratory requirement, unplanned intensive care unit (ICU) admission, postoperative pneumonia, anaphylaxis, and death within 48 h postoperatively, unplanned deferral of intraoperative extubation, and repeat administrations of NMBA reversal after leaving the operating room. Results The final cohort included 17 patients ranging from 8 months to 16 years old. One patient required new postoperative noninvasive ventilation on postoperative day 2, which was credited to hypervolemia. Another patient had bronchospasm intraoperatively resolving with medication, which could not definitively be associated sugammadex administration. There were no instances of deferred extubation, unplanned ICU or need for supplemental oxygen after tracheal extubation identified. Conclusion No adverse effects directly attributable to sugammadex in pediatric patients with severe renal impairment were detected. There may be a role for utilization of sugammadex for neuromuscular reversal in this population.

Bleeding events are common in patients prescribed anticoagulants and can have devastating consequences. Several specific and nonspecific agents have been developed to reverse the effects of anticoagulant drugs or toxins. Vitamin K, as the oldest of these antidotes, specifically counteracts the effects of pharmaceuticals and rodenticides designed to deplete stores of vitamin K‐dependent factors. In cases of life‐threatening bleeding, the addition of prothrombin complex concentrates (PCCs) allows for the immediate replacement of coagulation factors. While the use of PCCs has been extended to the non‐specific reversal of the effects of newer direct oral anticoagulants, the specific agents idarucizumab, targeting dabigatran and andexanet‐α, binding factor Xa inhibitors, have recently been developed and are being preferentially recommended by most guidelines. However, despite having rapid effects on correcting coagulopathy, there is to date a lack of robust evidence establishing the clear superiority of direct oral anticoagulant‐specific reversal agents over PCCs in terms of haemostatic efficacy, safety or mortality. For andexanet‐α, a potential signal of increased thromboembolic risks, comparatively high costs and low availability might also limit its use, even though emerging evidence appears to bolster its role in intracranial haemorrhage. Protamine is the specific agent for the reversal of unfractionated heparin anticoagulation used mainly in cardiovascular surgery. It is much less effective for low molecular weight heparin fragments and is usually reserved for cases with life‐threatening bleeding. [ABSTRACT FROM AUTHOR]

Background: Prenatal alcohol exposure (PAE) has serious physical consequences for children such as behavioral disabilities, growth disorders, neuromuscular problems, impaired motor coordination, and decreased muscle tone. However, it is not known whether loss of muscle strength occurs, and which interventions will effectively mitigate physical PAE impairments. We aimed to investigate whether physical alteration persists during adolescence and whether exercise is an effective intervention. Results: Using paradigms to evaluate different physical qualities, we described that early adolescent PAE animals have significant alterations in agility and strength, without alterations in balance and coordination compared to CTRL animals. We evaluated the effectiveness of 3 different exercise protocols for 4 weeks: Enrichment environment (EE), Endurance exercise (EEX), and Resistance exercise (REX). The enriched environment significantly improved the strength in the PAE group but not in the CTRL group whose strength parameters were maintained even during exercise. Resistance exercise showed the greatest benefits in gaining strength, and endurance exercise did not. Conclusion: PAE induced a significant decrease in strength compared to CTRL in PND21. Resistance exercise is the most effective to reverse the effects of PAE on muscular strength. Our data suggests that individualized, scheduled, and supervised training of resistance is more beneficial than endurance or enriched environment exercise for adolescents FASD. [ABSTRACT FROM AUTHOR]

We developed a system to adjust the rate of a continuous rocuronium (Rb) infusion to achieve 3 ≤ %T1 ≤ 10 with a closed-loop control. Samples were collected from 15 patients, and Rb blood concentrations were measured at the following time points: (1) when %T1 recovered to 3% or more after the initial Rb infusion; (2) when %T1 stabilized within the target range; (3) at the cessation of the Rb infusion; (4) 5 min after the sugammadex administration. The predicted Rb blood concentration at each time point was calculated and recorded using the pharmacokinetic parameters of Weirda et al. At time points (1), (2), and (3), the predicted blood concentrations were in good agreement with the measured values, but after the administration of sugammadex, the blood concentrations were higher than the predicted values because the Rb distributed in the tissues migrated into the blood. From the above, it was confirmed that the predicted blood concentration of Rb can be a good indicator for the automatic Rb administration control. [ABSTRACT FROM AUTHOR]

Pathogenic, biallelic variants in SORD were identified in 2020 as a novel cause for autosomal-recessive Charcot-Marie-Tooth disease (CMT) type 2, an inherited neuropathy. SORD codes for the enzyme sorbitol dehydrogenase. Loss of this enzyme's activity leads to an increase of sorbitol in serum. We retrospectively screened 166 patients with axonal neuropathy (predominantly CMT type 2, but including intermediate form of CMT and distal hereditary motor neuropathy (dHMN)) without identified genetic etiology for SORD mutations at a single large German neuromuscular center. Clinical and electrophysiology exam findings were analyzed for genotype–phenotype correlation. Five patients of the total cohort of 166 patients harbored pathogenic variants in SORD (3%). The homozygous frameshift variant c.757delG (p.Ala253Glnfs*27) was the most common (4/5). One additional case carried this variant on one allele only and an additional pathogenic missense variant c.458C > A (p.Ala153Asp) on the other allele. Age of onset ranged from early infancy to mid-twenties, and phenotypes comprised axonal CMT (4) and dHMN (1). Our findings strengthen the importance of screening for pathogenic variants in SORD, especially in patients with genetically unconfirmed axonal neuropathy, especially CMT type 2 and dHMN. [ABSTRACT FROM AUTHOR]

Background: Postoperative gastrointestinal dysfunction (POGD) commonly occurs following gastrointestinal (GI) surgery and is associated with specific anesthetic agents. Cholinesterase inhibitors employed for reversing neuromuscular blockade have been implicated in development of POGD. Sugammadex, a novel reversal agent, is linked with reduced POGD. However, there is a lack of comprehensive comparative review between these agents regarding their impact on POGD following GI surgery. This study aims to systematically review the effects of sugammadex on POGD compared to cholinesterase inhibitors following GI surgery. Methods: MEDLINE, EMBASE, and CENTRAL were searched as of July 2022 to identify articles comparing sugammadex with cholinesterase inhibitors in patients undergoing gastrointestinal surgery, specifically in relation to POGD. Secondary endpoints included length of hospital stay, readmission rates, pulmonary complications, and postoperative morbidity. Results: From 198 citations, 2 randomized controlled trials (RCTs) and 3 retrospective cohorts with 717 patients receiving sugammadex and 812 patients receiving cholinesterase inhibitors were included. Significantly lower rates of prolonged postoperative ileus (OR.44, 95% CI.25-.77, P <.05, I2 = 56%, low certainty evidence) was observed with sugammadex. No significant difference in any other outcome was observed. Narrative review of readmission data demonstrated no significant difference. Conclusion: The use of sugammadex following gastrointestinal surgery is associated with significantly lower rates of prolonged postoperative ileus compared to cholinesterase inhibitors. However, these do not translate into a significant reduction in length of stay, morbidity, or postoperative nausea and vomiting. Results are limited by the numer of studies included and missing data, more robust RCTs are needed before recommendations can be made. [ABSTRACT FROM AUTHOR]

Organophosphate pesticide poisoning challenges health care systems worldwide. Furthermore, nerve agents remain a continuous threat. The treatment options for organophosphate poisoning have virtually been unchanged for decades, relying on symptomatic treatment and the use of oximes to indirectly restore neuromuscular function. Hence, compounds targeting directly nicotinic acetylcholine receptors (nAChRs) might substantially improve treatment options. The current study investigated a series of bispyridinium analogues with a trimethylene or 2,2′-diethyloxy linker in a rat hemidiaphragm model, using indirect field stimulation. Methyl- and ethyl-substituted bispyridinium analogues restored neuromuscular function up to 37 ± 17% (MB419, a 3-methyl analogue) at a stimulation frequency of 20 Hz. The bispyridinium analogues with a 2- or 3-methyl group, or a 2- or 3-ethyl group, tended towards a higher restoration of neuromuscular function than those with a 4-methyl or 4-ethyl group, respectively. The current data can be used for future studies to optimize structure-based molecular modeling of compounds targeting the nAChR. [Display omitted] • Bispyridinium non-oximes analogues with a trimethylene or 2,2′-diethyloxy linker and various substituents were studied. • Methyl- and ethyl- substituted compounds with a trimethylene linker were able to partially restore muscle force. • The investigated bispyridinium analogues can be used for future studies to optimize structure-based molecular modeling. [ABSTRACT FROM AUTHOR]

Sugammadex (SUG) is a modified γ-cyclodextrin molecule used in patients under general anesthesia to reverse the effects of neuromuscular blocking agents. Besides, recent studies have shown that SUG positively affects the nervous system. However, its effect on seizures is still unclear. The current study aimed to examine the effects of SUG on pentylenetetrazole (PTZ)-induced epileptic seizures in mice. The mice were randomly divided into four groups. Group 1 was controlled, group 2 was administered saline (1 mL/kg serum physiologic), and Groups 3 and 4 were administered Sugammadex (150 and 300 mg/kg). Pentylenetetrazole (60 mg/kg) was given to induce seizures 30 min after saline or drug administration except for the control group. Total oxidant status (TOS) and total antioxidant status (TAS) levels in the hippocampus and cortex were measured using a commercial kit. 8-hydroxydeoxyguanosine (8-OHdG), 4-hydroxynonenal (4‑HNE), 3,3 dityrosine, caspase-3, apoptosis-inducing factor (AIF), and light chain 3 (LC3B) levels in the hippocampal CA1 region and cortex after seizures were evaluated immunohistochemical staining. SUG reduced seizure stages and increased epileptic seizure onset times. Moreover, it decreased TOS levels and increased TAS levels in the hippocampus and cortex. Besides, after seizures, it reduced 4-HNE, 3,3 dityrosandine, caspase-3, and LC3B immunohistochemical scores in the hippocampal CA1 region and cortex. SUG has protective effects on pentylenetetrazole-induced seizures in mice, alleviating seizures, oxidative stress, apoptosis, and autophagy. The anticonvulsant mechanism of SUG may be related to the inhibition of the oxidative stress pathway. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) poses a significant global health and economic challenge, with atherosclerosis being a primary cause. Over the past 40 years, substantial research has been conducted into the prevention and reversal of atherosclerosis, resulting in the development of lipid-lowering agents such as statins and fibrates. Despite the extensive literature and formulation of numerous therapeutic guidelines in this domain, a comprehensive bibliometric analysis of the current research landscape and trends has not been performed. This study aimed to elucidate the evolution and milestones of research into lipid-lowering treatments for coronary heart disease (CHD) in conjunction with hyperlipidemia through bibliometric analysis, offering insights into future directions for treatment strategies. Methods: This study examined publications from 1986 to 2023 retrieved from the Web of Science database (Core Collection). Utilizing tools such as VOSviewer, Pajek, and CiteSpace, we analyzed publication and citation numbers, H-indexes, contributions by countries and institutions, authorship, journal sources, and keyword usage to uncover research trajectories and areas of focus. Results: Our analysis of 587 publications revealed a recent surge in research output, particularly post-2003. The American Journal of Cardiology published the highest number of studies, with 40 articles, whereas Circulation received the highest number of citations (6,266). Key contributors included the United States, Japan, and China, with the United States leading in citation numbers and the H-index. Harvard University and Leiden University emerged as pivotal institutions, and Professors J. Wouter Jukema and Robert P. Giugliano were identified as leading experts. Keyword analysis disclosed five thematic clusters, indicating a shift in research towards new drug combinations and strategies, signaling future research directions. Conclusion: The last 4 decades have seen a notable rise in publications on lipidlowering therapies for CHD and hyperlipidemia, with the United States retaining world-leading status. The increase in international collaboration aids the shift towards research into innovative lipid-lowering agents and therapeutic approaches. PCSK9 inhibitors and innovative combination therapies, including antisense oligonucleotides and angiopoietin-like protein 3 inhibitors, provide avenues for future research, intending to maximize the safety and efficacy of treatment approaches. [ABSTRACT FROM AUTHOR]

Background: We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed. Results: We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts. Conclusions: For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: This study was aimed at determining the effect of sugammadex versus a combination of glycopyrrolate and neostigmine (GN) for neuromuscular reversal blockage on transient postoperative urinary retention (TPOUR) in patients undergoing a laparoscopic and robot-assisted laparoscopic hysterectomy. Methods: We conducted a retrospective cohort study in patients undergoing a laparoscopic or robotic hysterectomy between February 2017 and December 2021. Patients with and without concomitant procedures were included. Demographics and perioperative data were extracted from the patient's medical record. Before discharge, all patients were required to spontaneously void and have a post-void residual of less than 150 ml. Results: We identified 500 patients and 485 were included in the final analysis. We had 319 subjects who received sugammadex and 166 GN combination. Both groups had overall similar demographics and perioperative characteristics. Most patients had a conventional laparoscopy procedure (391 [82.5%]) compared with robotic (83 [17.5%]). Patients who received GN were significantly more likely to be discharged home with an indwelling catheter (odds ratio [OR], 1.82; 95% confidence interval [CI], 1.09—3.05). After adjusting for perioperative medications and sling implantation during the surgery a logistic regression model continued to demonstrate that patients who received GN had significantly higher odds of being discharged with a catheter (OR, 1.79; 95% CI, 1.03–3.12). Conclusions: Our findings suggest that sugammadex decreases the odds of TPOUR after laparoscopic hysterectomies with and without slings compared with the combination of GN. Additional prospective trials are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Copyright of INSPILIP. Revista Ecuatoriana de Ciencia, Tecnología e Innovacion en Salud Pública is the property of Instituto Nacional de Investigacion en Salud Publica (INSPI) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This article discusses the importance of quantitative neuromuscular monitoring in anesthesia practice. It highlights the historical development of neuromuscular blocking drugs and the introduction of sugammadex, which offers the potential for antagonism of neuromuscular block. The article emphasizes the dangers of residual neuromuscular block, including prolonged recovery and postoperative complications. It also addresses the barriers to adopting quantitative monitoring, such as cost and lack of training. The authors argue that the use of quantitative monitoring is essential for optimizing neuromuscular block management and improving patient outcomes. [Extracted from the article]

Postoperative urinary retention (POUR) is defined as the inability to void in the presence of a full bladder after surgery. Complications include delirium, pain, prolonged hospitalization, and long-term altered bladder contractility. Comorbidities, type of surgery and anesthesia influence the development of POUR. The incidence varies between 5% and 70%. History and clinical examination, the need for bladder catheterization and ultrasonographic evaluation are three methods used to diagnose POUR. The prevention of POUR currently involves identifying patients with pre-operative risk factors and then modifying them where possible. Bladder catheterization is the standard treatment of POUR, however, further studies are necessary to establish patients who need a bladder catheter, bladder volume thresholds and duration of catheterization. [ABSTRACT FROM AUTHOR]

Background: Using soybean oil–based lipid emulsions (Intralipid), which contain higher amounts of ω‐6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition–associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. Methods: The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late‐onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. Results: Forty‐four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] μmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. Conclusion: SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition. [ABSTRACT FROM AUTHOR]

Anaesthesia induced with remimazolam and a fentanyl-series opioid can be reversed with flumazenil and naloxone. Concomitant paralysis with rocuronium can facilitate tracheal intubation whilst being reversible with sugammadex. Together, this combination might offer full reversibility of a 'routine' or a 'rapid-sequence' induction anaesthesia. Whether this is useful, or even safe, requires careful evaluation. [ABSTRACT FROM AUTHOR]

The article focuses on the usage of sugammadex in emergency departments (EDs) within a large regional health system. Topics include the demographic and clinical characteristics of patients receiving sugammadex, the primary indications for its use (especially for neurological examination post-intubation), and the variation in administration practices between academic and community hospitals.

Abstract Background Thoracic surgery is a high-risk surgery especially for the risk of postoperative pulmonary complications. Postoperative residual paralysis has been shown to be a risk factor for pulmonary complications. Nevertheless, there are few data in the literature concerning the use of neuromuscular blocking agent antagonists in patients undergoing lung surgery. Methods Seventy patients were randomized in three Italian centers to receive sugammadex or neostigmine at the end of thoracic surgery according to the depth of the residual neuromuscular block. The primary outcome was the time from reversal administration to a train-of-four ratio (TOFR) of 0.9. Secondary outcomes were the time to TOFR of 1.0, to extubation, to postanesthesia unit (PACU) discharge, postoperative complications until 30 days after surgery, and length of hospital stay. Results Median time to recovery to a TOFR of 0.9 was significantly shorter in the sugammadex group compared to the neostigmine one (88 vs. 278 s — P

Background Charcot-Marie-Tooth disease (CMTD) is a hereditary polyneuropathy associated with a life-threatening risk of pulmonary complications. Case A 61-year-old male with CMTD for 40 years was admitted for the drainage of an abscess in his left ankle. Total intravenous anesthesia was administered, and an electromyography device was attached to the hand for neuromuscular monitoring; however, the response was not measured. Kinemyography and acceleromyography devices were attached to both hands, and responses were obtained. After neuromuscular blockade (NMB) with rocuronium 0.6 mg/kg, the train-of-four (TOF) response on kinemyography was normally measured, but the post-tetanic count on acceleromyography consistently showed 0 during anesthesia. Sugammadex 200 mg was injected to reverse the NMB. After 5 min, the TOF ratios for kinemyography and acceleromyography exceeded 90%. The patient recovered without any complications. Conclusions For CMTD patients, acceleromyography or kinemyography is superior to electromyography, and sugammadex can be used to reverse NMB successfully.

We investigate the statistical properties of fluctuations in active systems that are governed by nonsymmetric responses. Both an underdamped Langevin system with an odd resistance tensor and an overdamped Langevin system with an odd elastic tensor are studied. For a system in thermal equilibrium, the time-correlation functions should satisfy time-reversal symmetry and the antisymmetric parts of the correlation functions should vanish. For the odd Langevin systems, however, we find that the antisymmetric parts of the time-correlation functions can exist and that they are proportional to either the odd resistance coefficient or the odd elastic constant. This means that the time-reversal invariance of the correlation functions is broken due to the presence of odd responses in active systems. Using the short-time asymptotic expressions of the time-correlation functions, one can estimate an odd elastic constant of an active material such as an enzyme or a motor protein. [ABSTRACT FROM AUTHOR]

Background: Residual neuromuscular blockade (rNMB) remains a persistent and preventable problem, with serious risks. Methods: Our objective was to describe and assess patterns in the use of neuromuscular blocking agents (NMBAs), neuromuscular transmission (NMT) monitoring, and factors associated with the use of sugammadex. We performed a retrospective, observational cohort study based on electronic medical records in a large teaching hospital in the Netherlands that introduced an integrated NMT monitoring module with automatic recording in 2017. A total of 22,000 cases were randomly selected from all surgeries between January 2015 and December 2019 that required endotracheal intubation with the use of an NMBA. A total of 14,592 cases fulfilled all the inclusion criteria for complete analyses. Results: Relative NMBA usage remained the same over time. For rocuronium, spontaneous reversal decreased from 86 to 81%, sugammadex reversal increased from 12 to 18%. There was a decline in patients extubated in the operating room (OR) with neither documented NMT monitoring nor sugammadex-mediated reversal from 46 to 31%. The percentage of patients extubated in the OR without a documented train-of-four ratio ≥ 0.9, decreased from 77 to 56%. Several factors were independently associated with the use of sugammadex, including BMI > 30 kg/m2 (odds ratio: 1.41; 95% CI: 1.24–1.60), ASA class 3 or 4 (1.20; 1.07–1.34), age > 60 years (1.37; 1.23–1.53), duration of surgery < 120 min (3.01; 2.68–3.38), emergency surgery (1.83; 1.60–2.09), laparoscopic surgery (2.01; 1.71–2.36), open abdominal/thoracic surgery (1.56; 1.38–1.78), NMT monitoring used (5.31; 4.63–6.08), total dose of rocuronium (1.99; 1.76–2.25), and (inversely) use of inhalational anaesthetics (0.88; 0.79–0.99). Conclusion: Our data demonstrate that the implementation of NMT monitoring with automatic recording coincides with a gradual increase in the (documented) use of NMT monitoring and an increased use of sugammadex with a more precise dose. Factors associated with sugammadex use include higher age, ASA score, BMI, abdominal and thoracic surgery, higher rocuronium doses, emergency surgery and the use of NMT monitoring. Trial registration N/A. Key points: • Introduction of NMT monitoring with automatic recording coincides with an increase in (documented) use of NMT monitoring. • Sugammadex is more frequently used in patients with a presumed higher a priori risk of pulmonary complications. • Despite increased NMT monitoring and use of sugammadex a significant percentage of patients remain at potential risk of rNMB. [ABSTRACT FROM AUTHOR]

Small molecules, including therapeutic drugs and tracer molecules, play a vital role in biological processing, disease treatment and diagnosis, and have inspired various nanobiotechnology approaches to realize their biological function, particularly in drug delivery. Desirable features of a delivery system for functional small molecules (FSMs) include high biocompatibility, high loading capacity, and simple manufacturing processes, without the need for chemical modification of the FSM itself. Herein, we report a simple and versatile approach, based on metal–phenolic‐mediated assembly, for assembling FSMs into nanoparticles (i.e. FSM‐MPN NPs) under aqueous and ambient conditions. We demonstrate loading of anticancer drugs, latency reversal agents, and fluorophores at up to ~80 % that is mostly facilitated by π and hydrophobic interactions between the FSM and nanoparticle components. Secondary nanoparticle engineering involving coating with a polyphenol–antibody thin film or sequential co‐loading of multiple FSMs enables cancer cell targeting and combination delivery, respectively. Incorporating fluorophores into FSM‐MPN NPs enables the visualization of biodistribution at different time points, revealing that most of these NPs are retained in the kidney and heart 24 h post intravenous administration. This work provides a viable pathway for the rational design of small molecule nanoparticle delivery platforms for diverse biological applications. [ABSTRACT FROM AUTHOR]

This document is a list of references for a research article on the role of cyclodextrins in various biological processes. The references include studies on the solubilizing power of methyl-betacyclodextrins, the entry of fluorescently labeled methyl-beta-cyclodextrin into intestinal cells, the depletion of gangliosides and cholesterol by cyclodextrin derivatives, the effects of cyclodextrin-membrane interaction on drug delivery and membrane structure, the inhibitory effect of anandamide on sensory neuropeptide release, the antinociceptive effects of lipid raft disruptors, the effects of lipid raft disruptors on cell membrane fluidity, the analgesic effects of lipid raft disruption, the effect of cyclodextrin and membrane lipid structure on cyclodextrin-lipid interaction, the activation of capsaicin receptors by lipoxygenase products, the development of TRPV1-targeted drugs for pain conditions, the clearance of aggregated α-synuclein by TFEB activation, the cytotoxicity of beta-cyclodextrin derivatives, the regulation of membrane protein structure and function by lipid nano-environment, the depletion of cholesterol in model lipid membranes by cyclodextrin, the requirement of cholesterol for TRPV1 function and membrane expression, the effects of cyclodextrins on drug permeation through biological membranes, the molecular mechanism of cyclodextrin-mediated cholesterol extraction, the heterogeneity of lipid rafts, and [Extracted from the article]

Background: The MYH3‐associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3‐associated myosinopathy so far, with no more than two dozen cases being reported. Materials and Methods: A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole‐exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation. Results: The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161‐2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF‐B pathway, while the NM_002470.4: c.5161‐2A>C variant could affect the normal splicing of pre‐mRNA, resulting in the appearance of multiple abnormal transcripts. Conclusions: The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations. [ABSTRACT FROM AUTHOR]

Objective: This retrospective observational study aimed to investigate the effect of different doses of sugammadex used in reversing neuromuscular blockade in electroconvulsive therapy (ECT) procedures on patient recovery and hemodynamic measurements. Methods: Anesthesia induction was performed using propofol (1 mg/kg) and rocuronium (0.4 mg/kg). Patients were classified into group 2 (2 mg/kg) and group 3 (3 mg/kg) according to the dose of sugammadex used to reverse neuromuscular blockade. The patient's spontaneous breathing time, eye-opening time, time to comply with voluntary commands, time to reach Modified Aldrete score (MAS) 9, complications, and hemodynamic data were analyzed. Results: In total, 314 ECT sessions were performed on 46 patients. The average age of the patients was 38.3±12.6 years, and 56.6% (n=26) were male. While the average number of ECTs applied to the patients was 6.8±2.8, the average seizure duration was 28.2±12.7 seconds. The most common diagnosis (32.7%) in patients who underwent ECT was bipolar disorder. The average time to recovery of spontaneous breathing, eyeopening time, time to comply with voluntary commands, and time to reach MAS 9 were found to be significantly lower in group 3 (p<0.001, p<0.001, p<0.001, and p=0.002, respectively). Tooth damage was observed in 0.3% (n=1) and tongue abrasion in 0.6% (n=2) of the cases. Hemodynamic measurements were similar between groups (p>0.05). Conclusions: Sugammadex used at a dose of 3 mg/kg in ECT procedures significantly reduces recovery times compared with 2 mg/kg. However, both doses can be safely and cost-effectively used to reverse the neuromuscular blockade provided by 0.4 mg/kg rocuronium. [ABSTRACT FROM AUTHOR]

The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered. [ABSTRACT FROM AUTHOR]

Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. The aim of this study is to investigate the teratogenic effects of sugammadex on neural tube and embryonic development in early chick embryos. In this study, 50 0‐day fertile specific non‐pathogenic (SPF) eggs were used. Fifty eggs were divided into 5 different groups, each consisting of 10 pieces. While no substance was given to the control group at the 28th hour of the study, 4 different doses of sugammadex were administered to the experimental groups, respectively 2, 4, 8, 16 mg/kg. Cranio‐caudal lengths of embryos, somite numbers, average number of argyrophilic nucleolar regulatory regions (AgNOR) per nucleus, total AgNOR area/total nuclear area (TAA/NA) ratios, Caspase‐3 H‐Score results, and presence of neural tube defect were compared among the groups. While the mean cranio‐caudal lengths, somite counts, TAA/NA ratios and AgNOR counts of the embryos were found to be statistically significantly lower than the control group, Caspase‐3 H‐Score mean results were found to be significantly higher (p <.05). In addition, it was observed that there was an increase in neural tube patency and developmental delay. As a result, sugammadex crossing the placenta was revealed to increase the release of proapopitotic molecules and disrupt the developmental stages of embryos. Thus, it was determined that sugammadex in increased developmental delay and incidence of neural tube defects in early chick embryos with increased dose dependent. Despite these results, the effects of sugammadex on fetal development in in vivo and in vitro environments should be studied with further studies. Research Highlights: Sugammadex is a new generation drug that has led to significant changes in the practice of anesthesia. However, its effects on fetal development are not yet fully known. It has been observed that different doses of sugammadex increase the risk of neural tube defect development on chick embryos and slow the embryo development in a dose‐dependent manner. [ABSTRACT FROM AUTHOR]

Annona emarginata produces alkaloids of ecological and pharmacological interest and is tolerant to water and biotic stress, so it is used as rootstock for other Annonaceae fruits. There are few reports in the literature on how contrasting water stress impacts the production of specialized metabolites in Annonaceae and how primary metabolism adjusts to support such production. The objective of this investigation was to evaluate how drought and flooding stress affect alkaloid concentration and the primary metabolism of young A. emarginata plants. Three water levels (flooding, field capacity, and drought) were studied at two moments (stress and recovery). Variables analyzed were gas exchange levels, chlorophyll a fluorescence, leaf sugars, total alkaloid content, alkaloid profile, and Liriodenine concentration. The photosynthetic metabolism of A. emarginata was affected by water stress, with plants having a greater ability to adapt to drought conditions than to flooding. During the drought, a reduction in photosynthetic efficiency with subsequent recovery, higher starch and trehalose concentrations in leaves, and total alkaloids in roots (480 µg.g−1) were observed. Under flooding, there was a reduction in photochemical efficiency during stress, indicating damage to the photosynthetic apparatus, without reversal during the recovery period, as well as a higher concentration of total sugars, reducing sugars, sucrose, glucose, and fructose in leaves, and Liriodenine in roots (100 µg.g−1), with a lower concentration of total alkaloids (90 µg.g−1). It could be concluded that there is differential tolerance of A. emarginata to water stress, inducing the modulation of alkaloid production, while drought promotes a higher concentration of total alkaloids and flooding leads to an increase in the Liriodenine concentration. [ABSTRACT FROM AUTHOR]

Recent studies have shown that sugammadex's effects on the nervous system are controversial and its effect on nociception, morphine analgesia and tolerance is still unclear. The current study aimed to examine the possible involvement of sugammadex on nociception, morphine analgesia, and morphine tolerance development involving oxidative stress and NOD-like receptor protein 3 (NLRP3)/Interleukin-1β (IL-1β) signaling pathways in rats. The animals, thirty-six male Wistar Albino rats, were separated into six groups (n = 6 for each group): saline, sugammadex, morphine, morphine + sugammadex, morphine tolerance, and morphine tolerance + sugammadex. The analgesic effects were measured by analgesia tests (the tail-flick and hot plate). Oxidative stress parameters, NLRP3/IL-1β signaling pathway, and apoptotic proteins in the dorsal root ganglion (DRG) tissues were measured using Enzyme-Linked ImmunoSorbent Assay (ELISA) kits. Sugammadex had no antinociceptive activity when administered alone. However, it improved morphine's analgesic efficacy and inhibited the development of morphine tolerance. In addition, it decreased oxidative stress and NLRP3/IL-1β signaling pathway proteins in the DRG when administered with single and repeated doses of morphine. Besides, sugammadex lowered apoptotic proteins in the DRG following tolerance development. Thus, we may conclude that the ability of sugammadex to affect morphine pharmacological activity may be mediated by the suppression of oxidative stress and the NLRP3/IL-1β pathway. [ABSTRACT FROM AUTHOR]

Background: The pathophysiological mechanisms of diabetic retinopathy (DR), a blinding disease, are intricate. DR was thought to be a microvascular disease previously. However, growing studies have indicated that the retinal microglia-induced inflammation precedes microangiopathy. The binary concept of microglial M1/M2 polarization paradigms during inflammatory activation has been debated. In this study, we confirmed microglia had the most significant changes in early DR using single-cell RNA sequencing. Methods: A total of five retinal specimens were collected from donor SD rats. Changes in various cells of the retina at the early stage of DR were analyzed using single-cell sequencing technology. Results: We defined three new microglial subtypes at cellular level, including two M1 types (Egr2+ M1 and Egr2− M1) and one M2 type. We also revealed the anatomical location between these subtypes, the dynamic changes of polarization phenotypes, and the possible activation sequence and mutual activation regulatory mechanism of different cells. Furthermore, we constructed an inflammatory network involving microglia, blood-derived macrophages and other retinal nonneuronal cells. The targeted study of new disease-specific microglial subtypes can shorten the time for drug screening and clinical application, which provided insight for the early control and reversal of DR. Conclusions: We found that microglia show the most obvious differential expression changes in early DR and reveal the changes in microglia in a high-glucose microenvironment at the single-cell level. Our comprehensive analysis will help achieve early reversal and control the occurrence and progression of DR. [ABSTRACT FROM AUTHOR]

Introduction: Severe acute global cerebral hypoxia can lead to significant disability in humans. Although different animal models have been described to study hypoxia, there is no endogenous model that considers hypoxia and its effect on the brain as an independent factor. Thus, we developed a minimally invasive rat model, which is based on the non-depolarizing muscle blocking agent rocuronium in anesthetized animals. This drug causes respiratory insufficiency by paralysis of the striated muscles. Methods: In this study, 14 rats underwent 12 min of hypoxemia with an oxygen saturation of approximately 60% measured by pulse oximetry; thereafter, animals obtained sugammadex to antagonize rocuronium immediately. Results: Compared to controls (14 rats, anesthesia only), hypoxic animals demonstrated significant morphological alterations in the hippocampus (cell decrease in the CA 1 region) and the cerebellum (Purkinje cell decrease), as well as significant changes in hypoxia markers in blood (Hif2α, Il1β, Tgf1β, Tnfα, S100b, cspg2, neuron-specific enolase), hippocampus (Il1β, Tnfα, S100b, cspg2, NSE), and cerebellum (Hif1α, Tnfα, S100b, cspg2, NSE). Effects were more pronounced in females than in males. Discussion: Consequently, this model is suitable to induce hypoxemia with consecutive global cerebral hypoxia. As significant morphological and biochemical changes were proven, it can be used to investigate therapeutic and preventive drugs for global cerebral hypoxia. [ABSTRACT FROM AUTHOR]

Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity. The RAD51 recombinase plays a pivotal role in replication fork reversal during replication stress. Here, the authors show that the GCFC domain-containing protein TFIP11 interacts with BLM helicase and is important for fork reversal during replication stress to preserve genome stability. [ABSTRACT FROM AUTHOR]

Background: Thoracic surgery is a high-risk surgery especially for the risk of postoperative pulmonary complications. Postoperative residual paralysis has been shown to be a risk factor for pulmonary complications. Nevertheless, there are few data in the literature concerning the use of neuromuscular blocking agent antagonists in patients undergoing lung surgery. Methods: Seventy patients were randomized in three Italian centers to receive sugammadex or neostigmine at the end of thoracic surgery according to the depth of the residual neuromuscular block. The primary outcome was the time from reversal administration to a train-of-four ratio (TOFR) of 0.9. Secondary outcomes were the time to TOFR of 1.0, to extubation, to postanesthesia unit (PACU) discharge, postoperative complications until 30 days after surgery, and length of hospital stay. Results: Median time to recovery to a TOFR of 0.9 was significantly shorter in the sugammadex group compared to the neostigmine one (88 vs. 278 s — P < 0.001). The percentage of patients who recovered to a TOFR of 0.9 within 5 min from reversal administration was 94.4% and 58.8% in the sugammadex and neostigmine groups, respectively (P < 0.001). The time to extubation, but not the PACU stay time, was significantly shorter in the sugammadex group. No differences were found between the study groups as regards postoperative complications and length of hospital stay. The superiority of sugammadex in shortening the recovery time was confirmed for both deep/moderate and shallow/minimal neuromuscular block. Conclusions: Among patients undergoing thoracic surgery, sugammadex ensures a faster recovery from the neuromuscular block and earlier extubation compared to neostigmine. [ABSTRACT FROM AUTHOR]