Propofol suppresses hormones levels more obviously than sevoflurane in pediatric patients with craniopharyngioma: A prospective randomized controlled clinical trial.

OBJECTIVE: General anesthesia can disturb the hormone levels in surgical patients. Hormone deficiency is one of the major symptoms of craniopharyngioma (CP) in pediatric patients. The aim of this prospective randomized controlled clinical study is to evaluate whether propofol and sevoflurane influence the perioperative hormone levels in these patients and to determine which anesthesia technique causes less impact on hormone levels. MATERIALS: Sixty-four ASA I and II pediatric patients with CP undergoing elective neurosurgery were randomly divided into the sevoflurane group (S group, n = 32) and the propofol group (P group, n = 32). Anesthesia was maintained with sevoflurane and propofol until the end of the operation. Demographic information, operation information and hemodynamic variables were recorded. The levels of hormones were evaluated preoperatively as the baseline (T0), 1h after the beginning of the operation (T1), immediately at the end of the operation (T2) and 72 h postoperatively (T3). RESULTS: There were no significant differences in the two groups in terms of patients' demographics and intraoperative information, such as operation duration, blood loss and transfusion volumes, and fluid infusion volume (P>0.05). In both groups, compared to those at T0, the levels of TSH, FT3, TT3 and ACTH at T1, T2 and T3 were significantly lower. The levels of FSH, PRL and GH at T3 were also significantly lower (P<0.05). The FT3 and TT3 levels of both groups at T2 and T3 were significantly lower than those at T1, but the ACTH level was significantly increased (P<0.05). Compared to the levels at T2, the TSH, FT3, FT4 and ACTH levels of the two groups at T3 were significantly reduced (P<0.05). The baseline hormone levels of both groups were similar (P>0.05). At T1, the FT3, TT3, FT4, TT4 and ACTH levels in the P group were significantly lower than those in the S group (P<0.05). At T2, the TT3 and ACTH levels of the P group were significantly lower than those of the S group (P<0.05) At T3, the TT4 level in the P group was significantly lower than that of the S group (P<0.05). CONCLUSION: Propofol and sevoflurane could reduce the levels of hormones intraoperatively and postoperatively in pediatric patients with craniopharyngioma. However, propofol reduced hormone levels more intensively, mainly intraoperatively. Postoperatively, propofol and sevoflurane had similar inhibition effects on the shift in hormone levels. Therefore, in pediatric patients with craniopharyngioma undergoing neurosurgery, sevoflurane might be the preferred anesthetic because it causes less interruption of hormone levels. However, because of their similar postoperative effects, which long-term effects of sevoflurane or propofol could produce optimal clinical situations? Thus more extensive clinical studies are needed. TRIAL REGISTRATION: Clinical trial registration. This trail was registered at Chinese Clinical Trial Registry (http://www.chictr.org.cn, Jun Xiong) on 28/12/2021, registration number was ChiCTR2100054885.

Effects of Pharmacological Intervention on Recovery After Sevoflurane Anesthesia in Children: a Network Meta-analysis of Randomized Controlled Trials.

Sevoflurane, commonly administered to children as anesthesia, often leads to emergence delirium (ED). Currently, a consensus is lacking among clinicians regarding pharmacological interventions to improve recovery. To determine an effective approach, we compared the effects of several drugs in lowering the incidence of ED after sevoflurane anesthesia in children.We searched online databases for relevant randomized controlled trials (59 studies selected; 5199 NMA-eligible participants) and performed a frequentist network meta-analysis (NMA). This study was registered on PROSPERO (number CRD: 42022329939).All included studies had a low to moderate risk of overall bias. The incidence of ED after sevoflurane anesthesia in children differed according to other drugs administered, and were ranked from high to low according to the surface under the cumulative ranking curve (SUCRA).Sufentanil (91.2%) and dexmedetomidine (77.6%) were more likely to reduce the incidence (SUCRA value) of ED, whereas the placebo (6.5%), ramelteon (11.1%), and magnesium (18%) were less likely to reduce the incidence of ED. Remifentanil (89.3%) ranked first in shortening emergence time, followed by placebo (82.4%) and ketamine (69.7%). Placebo shortened extubation time, followed by remifentanil (66.5%) and alfentanil (61.4%).Sufentanil and remifentanil lowered sevoflurane-induced ED incidences among children and shortened the emergence time more effectively than other drugs. Most adjuvant drugs that are combined with sevoflurane either do not change or may even prolong extubation time. Further research and clinical trials are required to support and update these conclusions.

Anesthetic Preferences for Cardiac Anesthesia: A Survey of the Society of Cardiovascular Anesthesiologists.

BACKGROUND: Volatile anesthetics have been historically preferred for cardiac anesthesia, but the evidence for their superiority to intravenous agents is mixed. We conducted a survey to better understand the current state of practice and the rationale behind provider preferences for anesthesia for cardiac surgery with cardiopulmonary bypass. We hypothesized that anesthetic preference would vary considerably among surveyed providers without a clear majority, as would the rationale behind those preferences. METHODS: Email invitations were sent to members of the Society of Cardiovascular Anesthesiologists, who were asked to identify the anesthetics or sedatives they typically prefer to administer during induction, prebypass, bypass, postbypass, and postoperative periods and why they prefer those agents. Members' beliefs regarding the importance of anesthetics on postoperative outcomes were also assessed. RESULTS: Invitations were sent on 2 separate dates to 3328 and 3274 members, of whom 689 (21%) responded. The median (interquartile range [IQR]) respondent age was 45 (37-56) years, 79% were men, and 75% were fellowship trained. The most frequently chosen drug for induction was propofol (80%). Isoflurane was the most frequently selected primary agent for the prebypass (57%), bypass (62%), and postbypass periods (50%). Sevoflurane was the second most frequently selected (30%; 17%, and 24%, respectively). Propofol was the third most frequently selected agent for the bypass (14%) and postbypass periods (17%). Ease of use was the most frequently selected reason for administering isoflurane and sevoflurane for each period. During bypass, the second most frequently selected rationale for using isoflurane and sevoflurane was institutional practice. A total of 76% responded that the perfusionist typically delivers the bypass anesthetic. Ischemic preconditioning, organ protection, and postoperative cognitive function were infrequently selected as rationales for preferring the volatile anesthetics. Most respondents (73%) think that anesthetics have organ-protective properties, especially isoflurane (74%) and sevoflurane (59%), and 72% believed that anesthetic choice contributes to patient outcome. The median (IQR) agreement (0 = strongly disagree to 100 = strongly agree) was 72 (63-85) for the statement that "inhaled anesthetics are an optimal maintenance anesthetic for cardiac surgery." CONCLUSIONS: In a survey of cardiac anesthesiologists, a majority of respondents indicated that they prefer volatile anesthetics for maintenance of anesthesia, that anesthetic selection impacts patient outcomes, and that volatile anesthetics have organ-protective properties. The members' rationales for preferring these agents possibly reflect that practical considerations, such as ease of use, effectiveness, and institutional practice, also influence anesthetic selection during cardiac surgery in addition to considerations such as organ protection.

The equilibrated blood sevoflurane concentrations show a rapid decrease after switching from ventilation for the human lung to cardiopulmonary bypass.

Volatile anesthetics (VAs) protect myocardial cells during cardiovascular surgeries, including cardiopulmonary bypass (CPB). In CPB, blood is gradually transferred from the body to a CPB unit until the target cardiac index is achieved, following which human lung (HL) ventilation is stopped. This pilot study aimed to evaluate changes in the blood sevoflurane concentrations 5 min after the start of CPB when its delivery to the oxygenator began after HL ventilation with sevoflurane was completed. Six patients were recruited and participated in this study. For each patient, the equilibrated blood sample, collected 20 min after starting the delivery of 1.7% sevoflurane (HL group), and another blood sample, collected 5 min after starting the CPB, were analyzed using gas chromatography equipped with a flame ionization detector. The mean (± standard deviation) sevoflurane concentrations in the HL and 5 min after starting CPB groups were 58.6 ± 4.7 and 14.5 ± 5.0 µg/ml, respectively (P < 0.01). In conclusion, the equilibrated blood sevoflurane concentrations showed a rapid decrease when switching from sevoflurane ventilation for the HL to CPB unless it was introduced to the oxygenator until completion of the switch.

Effect of Dexmedetomidine in children undergoing general anaesthesia with sevoflurane: a meta-analysis and systematic review.

OBJECTIVE: The sedative effects of dexmedetomidine (Dex) are similar to natural sleep, with easy wakening following Dex administration, and Dex has minor effects on breathing, reducing emergence agitation in children. The aim of this study was to systematically evaluate the effects of Dex on recovery quality in children following general anaesthesia with sevoflurane, to aid clinical decision making. METHODS: Relevant randomized controlled trials published before August 2019 were searched and selected from databases. Two researchers independently screened the literature, extracted data, and assessed included studies for bias risk. Meta-analysis was performed using Stata 14.0 software. RESULTS: The study included 24 publications. Following general anaesthesia by sevoflurane, Dex was associated with reduced occurrence of emergence agitation (odds ratio [OR] 0.16, 95% confidence interval [CI] 0.11, 0.25) and nausea and vomiting (OR 0.40, 95% CI 0.24, 0.60), along with shortened eye-opening time (standardized mean difference [SMD] 0.72, 95% CI 0.41, 1.03), shortened extubation time (SMD 0.54, 95% CI 0.28, 0.81), and reduced duration of post-anaesthesia care unit (PACU) stay (SMD 0.29, 95% CI 0.08, 0.51) versus placebo. CONCLUSION: Dexmedetomidine has positive effects on recovery quality in children undergoing general anaesthesia with sevoflurane.

Biochemical significance of limonene and its metabolites: future prospects for designing and developing highly potent anticancer drugs.

Monocyclic monoterpenes have been recognized as useful pharmacological ingredients due to their ability to treat numerous diseases. Limonene and perillyl alcohol as well as their metabolites (especially perillic acid and its methyl ester) possess bioactivities such as antitumor, antiviral, anti-inflammatory, and antibacterial agents. These therapeutic properties have been well documented. Based on the aforementioned biological properties of limonene and its metabolites, their structural modification and development into effective drugs could be rewarding. However, utilization of these monocyclic monoterpenes as scaffolds for the design and developments of more effective chemoprotective agents has not received the needed attention by medicinal scientists. Recently, some derivatives of limonene metabolites have been synthesized. Nonetheless, there have been no thorough studies on their pharmacokinetic and pharmacodynamic properties as well as their inhibition against isoprenylation enzymes. In this review, recent research progress in the biochemical significance of limonene and its metabolites was summarized with emphasis on their antitumor effects. Future prospects of these bioactive monoterpenes for drug design and development are also highlighted.

Investigating the efficacy of a new intravenous (IV) nanoemulsified sevoflurane/arginine formulation for maintenance of general anesthesia for embolization of cerebral aneurysm.

The aim of this research investigation was to profound analysis the mitigating impact of sevoflurane/arginine post-molding on cerebral ischemia-reperfusion damage in rats. The authors fabricated emulsions fusing sevoflurane, perfluorooctyl bromide as a settling specialist, and mixes of arginine polymer. Cell suitability and gene expression of tubulin and NeuN were assessed. The stability, morphology and functional group were evaluated utilizing dynamic light scattering (DLS), Transmission Electron Microscope (TEM), atomic force microscopy (AFM), and Fourier-transform infrared spectroscopy (FTIR). Cerebral aneurysms were prompted through hypertension and a solitary stereotactic infusion of elastase into the basal storage in rat. The capacity of the emulsions to decreased cerebral aneurysm was tried in vivo by regulating them IV delivery of Se/Arg samples to rats. Se/Arg pre-conditioning expanded cell feasibility in neuroblast (SK-N-DZ) cells. Se/Arg pre-conditioning diminished infarct volume and enhanced neurological result in rats subjected to cerebral hypoxia-ischemia. Se/Arg preconditioning expanded levels of tubulin and NeuN. The prepared sevoflurane/arginine material pre-conditioning-incited neuroprotective impacts in vitro as well as in vivo analyses. Sevoflurane/arginine post-molding decreased cerebral tissue misfortune detected 7 days after cerebrum hypoxia-ischemia. This impact was prompted by clinically significant focuses and canceled by Sevoflurane/arginine. These outcomes recommend that Sevoflurane/arginine post-conditioning ensures neonatal cerebrum against cerebrum hypoxia-ischemia.

Efficacy Of Intravenous Lignocain Vs Sevoflurane In Prevention Of Coughing And Desaturation At Extubation In Children.

BACKGROUND: Inadvertent coughing and desaturation are the most commonly faced and feared respiratory complications in post-anaesthesia period. The study was done to compare the efficacy of intravenous lignocaine versus sevoflurane in prevention of coughing and desaturation at extubation in children less than 6 years of age. METHODS: This Randomized Control Trial was carried out from May 2013 to May 2016, at Combined Military Hospital Nowshera after obtaining approval from the hospital ethics committee (IREC-0003/5/13/Aneas). Children aged three months to six years undergoing surgical procedures requiring the placement of definitive airway were randomly assigned into two groups. Patients were anaesthetized by standardized balanced anaesthesia technique. In Group A (n=355), three minutes prior to extubation lignocaine 2% was used intravenously. In Group B (n=355), isoflurane was switched off, breathing circuit changed and sevoflurane started at minimum alveolar concentration (MAC 3-4%) for 3 minutes prior to extubation. Assessment for extubation was clinical. Oxygen saturation and severity of coughing were noted for 5 consecutive minutes, after extubation. RESULTS: In group-A, 156 patients were less than 2 years of age while in group-B, 135 patients were less than 2 years old. In group-A, 199 and in group-B, 220 children were 2-6 years of age respectively. Post stratification the p-value for weight was 0.17 (p-value >0.05) and t-statistic was 1.36. Post stratification p-value for gender was 0.12 (p-value>0.05) and chi square statistic was 2.49. Group A had more eventful extubation with 270 cases of cough (76%) as compared to group-B where it was noted in 199 cases (56%). Similarly, desaturation was observed in 85 cases in group-A (24%) as compared to 28 cases (8%) in group-B. The difference between the groups was statistically significant. CONCLUSIONS: Sevoflurane based anaesthetic vapours mixture causes statistical significant prevention from events like coughing episodes and desaturation in post-extubation in children less than six years of age undergoing elective surgery.

Impact of Volatile Anesthetic Agents on Early Clinical Outcomes in Liver Transplantation.

BACKGROUND: Few studies have assessed the ability of inhaled anesthetic agents to ameliorate ischemia-reperfusion injury (IRI) in liver transplantation (LT). This study compares inhaled anesthetics in early liver allograft IRI. LT recipient and organ donor data were extracted retrospectively for all LTs at a single center between 2001 and 2015. METHODS: LT recipient and organ donor data were extracted retrospectively for all LTs at a single center between 2001 and 2015. The choice of primary anesthetic agent was at the discretion of the anesthesiologist. Serum alanine aminotransferase (ALT) and total bilirubin (TB) levels were measured daily in the post-transplant period as measures of early graft injury and function. Survival and clinical outcomes are reported. RESULTS: There were 1291 primary LTs included in the analysis, with 3 primary inhaled agents: isoflurane (62%), desflurane (8%), and sevoflurane (30%). In the first 7 days post-transplant, the peak ALT level was lowest for desflurane (352), followed by sevoflurane (411) and isoflurane (481) (P = .09). All groups had similar ALT and TB by 7 days post-transplant. Graft survival for all 3 groups was statistically similar at 1, 7, and 30 days, with equivalent patient and graft survival at 1 year. CONCLUSIONS: All 3 agents had similar rates of early allograft dysfunction and renal dysfunction. Subgroup analysis of high-risk donor grafts showed no statistical difference. In conclusion, administration of desflurane or sevoflurane may provide some early hepatoprotection against IRI, but longer-term outcomes were equivalent for all agents.

Effect of sevoflurane preconditioning on light-induced retinal damage in diabetic rats.

Hyperglycemia and bright light are powerful stress agents that produce an enhanced retinal damage, when simultaneously acting on retina. Previous studies have shown that preconditioning with sevoflurane anesthesia offers a certain degree of protection to retinal cells against light damage. The objective of this study was to explore the effect of sevoflurane anesthetic preconditioning on a model of light-induced retinal degeneration in diabetic rats. Wistar rats that were randomly divided into four groups: control (rats exposed to photostress), group 1 (rats exposed to photostress and sevoflurane preconditioning), group 2 (diabetic rats exposed to photostress), group 3 (diabetic rats exposed to photostress and sevoflurane preconditioning) were used for this experiment. We recorded basal electroretinogram (ERG), at 36 h and 14 days after photostress and performed histological analysis of the retina. Results showed that sevoflurane has a protective effect on light-induced neuroretinal degeneration proved by significantly less variations of the ERG before and after photostress. Diabetes appears to increase the damaging effect of photostress on retina and attenuate the protection provided by sevoflurane preconditioning.

MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K/Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning.

BACKGROUND/AIMS: Ischemic heart disease is a leading cause of death in cardiovascular diseases, and microRNAs (miRs) have been reported to be potential therapeutic targets in heart disease. Herein, this study aims to investigate the effects of microRNA (miR)-374 on myocardial ischemia-reperfusion (I/R) injury in rat models pretreated with sevoflurane by targeting SP1 through the PI3K/Akt pathway. METHODS: SD rats were grouped into sham, I/R and sevoflurane + I/R (sevoflurane preconditioning and I/R) groups. The biochemical indicators, pathological changes, positive expression of SP1 protein, and apoptosis rates were measured using biochemical detection, Evans blue-TTC staining, immunohistochemistry and TUNEL staining. RT-qPCR and Western blotting were used to investigate the expression of miR-374 mRNA and the protein expression of SP1, PI3K, HO-1, p53, iNOS, c-fos, Akt/p-Akt, and GSK-3ß/p-GSK-3ß. Cardiomyocytes were treated with miR-374 mimics, miR-374 inhibitors, or siRNA-SP1. Cardiomyocyte proliferation and cycle distribution and apoptosis were studied by MTT and flow cytometry. RESULTS: Compared with the I/R group, in the sevoflurane + I/R group, serum SOD and IL-10 increased, while MDA, LDH, CK, TNF-α, IL-6 and IL-10 decreased, as did the percentage of infarct area, the positive rate of SP1 and the apoptosis index. The expression of SP1, p53, iNOS and c-fos decreased, and the miR-374 expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. With the upregulation of miR-374 and the downregulation of SP1, the expression of SP1, p53, iNOS and c-fos decreased, as did the proportion of cells in G1 phase and the apoptosis rate; the expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. The results in the miR-374 inhibitor group contrasted with the above results. CONCLUSION: The results indicated that miR-374 could alleviate myocardial I/R damage in rat models pretreated with sevoflurane by targeting SP1 by activating the PI3K/Akt pathway.

Pain and analgesic drugs in chronic venous ulcers with topical sevoflurane use.

OBJECTIVE: Pain in chronic venous ulcers (CVUs) notably increases with the usual cleaning of the wound. Chronic pain is usually poorly controlled even with the multiple analgesic treatments available. Analgesics can have different serious adverse effects and medical interactions in old patients with several comorbidities. This study reports the efficacy and safety of topical sevoflurane for treatment of pain in CVUs. METHODS: We report a descriptive and retrospective study of 30 patients older than 65 years with painful CVUs refractory to conventional analgesic treatments. Patients received topical sevoflurane treatment before the usual cleaning of the ulcer. Cleaning visits with sevoflurane every 2 days for a period of 1 month were scheduled. We compared the visual analog scale results and analgesic drugs for cleaning with and without topical sevoflurane. The systemic pharmacokinetics of sevoflurane after topical application has not been determined. RESULTS: Pain related to CVUs decreased with topical sevoflurane. Sevoflurane had an analgesic effect with latency time between 2 and 7 minutes. The duration of analgesia ranged between 8 and 18 hours. The time needed to take an analgesic treatment increased after application of sevoflurane. The use of other conventional analgesic drugs, including paracetamol, metamizole, nonsteroidal anti-inflammatory drugs, tramadol, and major opioids, was progressively reduced. The main local adverse effects were mild and transient, including heat, pruritus, and erythema. There were no systemic adverse effects. CONCLUSIONS: Topical sevoflurane has an intense, fast, and long-lasting local analgesic effect with an adequate safety profile. It also diminishes the taking of other conventional analgesic drugs. Topical sevoflurane is an efficient and safe therapeutic alternative for refractory painful CVUs.

Effect of preoperative visiting operation room on emergence agitation in preschool children under sevoflurane anesthesia.

BACKGROUND: Emergence agitation (EA) is a common complication in children during recovery from sevoflurane anesthesia with an high incidence. The main objective of this study was to compare the effects of preoperative visiting operation room (PVOR) to administration of propofol at the end of anesthesia on EA in preschool children under sevoflurane anesthesia. METHODS: Sixty-nine preschool children aged from 3 to 6 years scheduled for tonsillectomy under sevoflurane anesthesia were randomly allocated to one of the three groups to receive either PVOR (Group PV), routine preoperative visit (Group RV) or routine preoperative visit plus propofol (Group RP), 23 patients were included in each group. General anesthesia was induced and maintained with sevoflurane. Parental separation status score, mask acceptance score, Aono's four point score and pediatric anesthesia emergence delirium (PAED) score and incidence of EA were recorded. PAED score >10 were regarded as EA. Recovery profile and adverse events were also recorded. RESULT: Parental separation status score and mask acceptance score in group PV was significantly lower than that in group RV and group RP (P < 0.05); Aono's four point score, PAED score and incidence of EA in group PV and group RP was significantly lower than that in group RV (P < 0.05); Time to extubation and time to interaction in group PV and group RV was significantly shorter than that in group RP (P < 0.05); POV and rescue by fentanyl in group PV and group RP was significantly lower than that in group RV(P < 0.05). CONCLUSION: PVOR can effectively reduce the incidence of EA as well as administration of propofol without additional medical expenses and other adverse effects.

Sevoflurane preconditioning ameliorates lipopolysaccharide-induced cognitive impairment in mice.

Systemic inflammation induces brain neuronal inflammation, in turn causing acute cognitive disorders. Furthermore, neuronal inflammation is one cause of postoperative cognitive disorder (POCD) and delirium. However, no sufficiently established pharmacological treatment is available for neurocognitive inflammation. This study evaluated the possible neuroprotective effects of preconditioning with sevoflurane anesthesia on cognition and neuroinflammatory changes in an animal model of lipopolysaccharide (LPS)-induced systemic inflammation. Adult mice were randomly divided into (1) control, (2) 2% sevoflurane preconditioning for 1 h, (3) intraperitoneal 5 mg/kg LPS injection, and (4) 2% sevoflurane preconditioning for 1 h + LPS injection groups. At 24 h after 5 mg/kg LPS injection, microglial activation based on ionized calcium-binding adapter molecule 1 (Iba-1) expression in the hippocampus was determined using immunostaining and immunoblotting. IL-1ß and IL-6 immunoblotting were used as inflammation markers, and ß-site of amyloid precursor protein cleaving enzyme 1 (BACE1) immunoblotting was performed to evaluate amyloid ß-protein (Aß) accumulation. Long-term cognitive impairment was evaluated using fear conditioning tests. Intraperitoneal LPS increased levels of Iba-1 (150%), inflammation markers (160%), and Aß accumulation (350%), and sevoflurane preconditioning suppressed these increases. Systemic LPS caused learning deficits. Sevoflurane also maintained long-term memory in mice receiving LPS injection. Sevoflurane preconditioning prevented long-term memory impairment in the mouse model administered systemic LPS by decreasing excessive microglial activation, inflammation, and Aß accumulation. This study supports the hypothesis that sevoflurane preconditioning might also be beneficial for neuronal inflammation. Sevoflurane might be beneficial for reducing delirium and POCD.

Methylated flavonoids as anti-seizure agents: Naringenin 4',7-dimethyl ether attenuates epileptic seizures in zebrafish and mouse models.

Epilepsy is a neurological disease that affects more than 70 million people worldwide and is characterized by the presence of spontaneous unprovoked recurrent seizures. Existing anti-seizure drugs (ASDs) have side effects and fail to control seizures in 30% of patients due to drug resistance. Hence, safer and more efficacious drugs are sorely needed. Flavonoids are polyphenolic structures naturally present in most plants and consumed daily with no adverse effects reported. These structures have shown activity in several seizure and epilepsy animal models through allosteric modulation of GABAA receptors, but also via potent anti-inflammatory action in the brain. As such, dietary flavonoids offer an interesting source for ASD and anti-epileptogenic drug (AED) discovery, but their pharmaceutical potential is often hampered by metabolic instability and low oral bioavailability. It has been argued that their drug-likeness can be improved via methylation of the free hydroxyl groups, thereby dramatically enhancing metabolic stability and membrane transport, facilitating absorption and highly increasing bioavailability. Since no scientific data is available regarding the use of methylated flavonoids in the fight against epilepsy, we studied naringenin (NRG), kaempferol (KFL), and three methylated derivatives, i.e., naringenin 7-O-methyl ether (NRG-M), naringenin 4',7-dimethyl ether (NRG-DM), and kaempferide (4'-O-methyl kaempferol) (KFD) in the zebrafish pentylenetetrazole (PTZ) seizure model. We demonstrate that the methylated flavanones NRG-DM and NRG-M are highly effective against PTZ-induced seizures in larval zebrafish, whereas NRG and the flavonols KFL and KFD possess only a limited activity. Moreover, we show that NRG-DM is active in two standard acute mouse seizure models, i.e., the timed i.v. PTZ seizure model and the 6-Hz psychomotor seizure model. Based on these results, NRG-DM is proposed as a lead compound that is worth further investigation for the treatment of generalized seizures and drug-resistant focal seizures. Our data therefore highlights the potential of methylated flavonoids in the search for new and improved ASDs.

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

BACKGROUND: During cardiopulmonary bypass (CPB) in children, anesthesia maintained by sevoflurane administered via the oxygenator is increasingly common. Anesthetic uptake and requirement may be influenced by the non-physiological conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may, therefore, be useful to guide the administration of sevoflurane during this phase. OBJECTIVE: The objective of this prospective, clinical, observational study was to assess the correlation between body temperature, Narcotrend Index (NI) and administered sevoflurane in children during CPB. METHODS: Forty-four children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied. On bypass, anesthesia was maintained with sevoflurane administered via the oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10 minutes. Expiratory gas was sampled from the oxygenator's sole expiratory port via a separate connecting line and the MAC was measured by the agent analyzer of the anesthesia machine. RESULTS: Raw (r = 0.74) and corrected (r = 0.73) r-values show that narcosis depth (as indicated by NI) can primarily be explained by the interaction of MAC and temperature. The analysis of variance (without the interaction term) confirms the significant and independent association of both factors, MAC (p<0.004, 95%CI: 0.19 to 0.46) and temperature (p<0.0001, 95%CI: 0.68 to 0.78), with the NI. During hypothermia, sevoflurane had been reduced significantly (r = 0.41, p<0.0001, 95%CI: 0.33 to 0.48). CONCLUSION: Perfusionists and anesthetists should be aware of the results of processed electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements differ inter-individually; they may decrease during cooling and increase during rewarming. Therefore, it seems reasonable to include the results of processed EEG monitoring when administering sevoflurane during CPB in children, but further studies are necessary to confirm this thesis.

[Study of sevoflurane/remifentanil coadministration on improving emergence and recovery characteristics of patients following general anaesthesia with sevoflurane].

Objective: To investigate the effects of remifentanil infusion on emergence and recovery characteristics of patients with thoracoscopic lobectomy following general anaesthesia with sevoflurane. Methods: One hundred patients, who were aged 37 to 65 years with American Society of Anesthesiologists (ASA) physical status 1-2, and scheduled for elective thoracoscopic lobectomy under general anaesthesia in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, from February 2016 to August 2016, were allocated to receive sevoflurane maintenance regimen(group S, n=50)or sevoflurane/remifentanil maintenance regimen(group SR, n=50)by random digital table. After routine induction and intubation, anaesthesia was maintained with 2% sevoflurane in group S and 1.5% sevoflurane/remifentanil(continuous intravenous injection at rate of 4 µg·kg(-1)·h(-1))coadministration in group SR respectively, with intermittent intravenous infusion of sulfentanil. Haemodynamic variables were collected at different time points and compared between two groups. Awaking time and extubation time, incidences of serious coughing and agitation were evaluated during emergence.Postoperative pain, nausea and cather-related bladder discomfort(CRBD)were evaluated in post anesthesia care unit. Results: Compared with group S, the arterial blood pressure and heart rate were significantly lower in group SR at extubation(all P<0.05). Time to awaking and to extubation in group SR were (4.2±2.1) min and (4.8±3.1)min respectively, in group S were (12.7±3.4) min and (15.4±4.1)min.The difference between two groups were statistically significant (t=-15.040, 14.582, all P<0.05). The incidences of serious coughing and agitation in group S were 48% and 58%, which were greater than those of group SR(6% and 10%). The difference were statistically significant(χ(2)=20.294, 23.574, all P<0.05). The NRS and incidence of complaining CRBD were similar in both groups(all P>0.05). Conclusion: Compared with sevoflurane maintenence, coadministration of remifentanil and sevoflurane maintenance regimen provides better emergence and recovery which are characterized by faster awakening and extubation with a lower incidence of emergence coughing and agitation.

Inhibition of Laser-Induced Choroidal Neovascularization by Hematoporphyrin Dimethylether-Mediated Photodynamic Therapy in Rats.

This study aimed to investigate the effect of hematoporphyrin dimethylether (HDME)-mediated photodynamic therapy for laser-induced choroidal neovascularization (CNV) in adult Brown Norway rats. HDME was administered via tail vein at 14 d after the laser photocoagulation, and the rats received irradiance with a laser light at 570 nm at 15 min after injection. CNV was evaluated by fundus photography, fundus fluorescein angiography, optical coherence tomography, and hematoxylin and eosin staining. We found that CNV was occurred at 7 d after photocoagulation and reaching peak activity at 14 d after photocoagulation. There is a significant reduction in the total area of the fluorescein leakage and the number of strong fluorescein leakage spots on 7 d after HDME-mediated photodynamic therapy (PDT). The results suggest that HDME-mediated PDT inhibits laser-induced CNV in rats, representing a promising therapy for wet age-related macular degeneration.

Acute Dystonic Reaction Following General Anesthetic Agent Use.

Background: A 36-year-old Thai female who underwent a thymectomy under general anesthesia developed acute abnormal movements in the craniofacial region immediately after awakening with preserved consciousness. Phenomenology: Intermittent abnormal movements included oculogyric crisis; tongue protrusion; blepharospasm; and oro-mandibular dystonia consisting of risus sardonicus, jaw opening, and right torticollis. Educational value: An acute dystonic reaction can be a complication of either single or combined general anesthetic agents.

Downregulation of Na+/Ca2+ Exchanger Isoform 1 Protects Isolated Hearts by Sevoflurane Postconditioning but Not by Delayed Remote Ischemic Preconditioning in Rats.

BACKGROUND:: Calcium regulatory proteins-L-type Ca2+ channels (LTCCs), ryanodine receptor 2 (RyR2), and Na+/Ca2+ exchanger isoform 1 (NCX1) have been recognized as important protective mechanisms during myocardial ischemia-reperfusion injury (I/RI). Both sevoflurane postconditioning (SevoPoC) and delayed remote ischemic preconditioning (DRIPC) have been shown to protect the heart against I/RI. In this study, we aimed to compare the effects of SevoPoC and DRIPC on the expression of the three calcium regulatory proteins in an isolated rat heart model. METHODS:: After 30-min balanced perfusion, isolated hearts from rats were subjected to 30-min ischemia followed by 60-min reperfusion. Totally 40 isolated hearts were randomly assigned to four groups (n = 10/group): time control group, I/RI group, SevoPoC group, and DRIPC group. The effect of SevoPoC (3% v/v) and DRIPC were observed. Myocardial infarct size (IS), cardiac troponin I level, and heart function were measured. The protein and messenger RNA levels of LTCCs, RyR2, and NCX1 were determined. RESULTS:: Both SevoPoC and DRIPC improved the recovery of myocardial function, and reduced cardiac troponin I release after I/RI. The decrease in IS was more significant in the SevoPoC group than that in the DRIPC group (16.50% ± 4.54% in the SevoPoC group [P = 0.0006], and 22.34% ± 4.02% in the DRIPC group [P = 0.0007] vs. 35.00% ± 5.24% in the I/RI group, respectively). SevoPoC, but not DRIPC significantly inhibited the activity of NCX1 (0.59 ± 0.09 in the I/RI group vs. 0.32 ± 0.16 in the SevoPoC group, P = 0.006; vs. 0.57 ± 0.14 in the DRIPC group, P = 0.072). No statistical significant differences were observed in the expression of LTCCs and RyR2 between SevoPoC and DRIPC. In addition, subsequent correlation analysis showed a significantly positive relationship between the cardiac troponin I level and the protein expression of NCX1 (r = 0.505, P = 0.023). CONCLUSION:: SevoPoC may be more effective in the cardioprotection than DRIPC partly due to the deactivation of NCX1.