Sedative Effects Research Articles

A systematic review of effectiveness and safety of some herbal compounds as treatment for primary insomnia

Introduction Sleep related disorders affect around 30% of people all over the world, and evidence shows that 10% require therapeutic intervention. Insomnia represents the most common disturbance of sleep, defined as the experience of poor sleep for at least 1 month. Most of primary insomnia can be prevented by a proper lifestyle and sleep hygiene rules. Regardless, hypnotic drugs and widely prescribed, and most times, long-term used, which is not recommended because of its negative side effects.ObjectivesReview the scientific evidence about effectiveness of plant extracts for insomnia, natural products with practically no side-effects, and thus be possible to reduce or even avoid the use of hypnotic drugs.MethodsThe Medline database through the Pubmed search engine was used with the following keywords: “insomnia” and “herbal compounds”.ResultsValerian activity on sleep disturbances has been attributed to the presence of isovaleric acids and valepotriates with reported calming action and GABA reuptake inhibition with sedative effects. Considering the data presented in the literature, despite controversial and conflicting, several studies showed that valerian (160-600mg/day) improved sleep quality and reduced sleep latency and duration; also valerian seems more effective for chronic insomnia than acute episodes.Hop has different properties: calming, sleep inducing, gastric secretion stimulating and spasmolytic.Increasing GABAergic activity seems to be the main mechanism of action, thus inhibiting the central nervous system and also has demonstrated binding affinities to some of the melatonin and serotonin receptor. It’s sedative characteristics have been confirmed in a clinical trial in association with valerian, where sleep latency and quality were improved. However, monotherapy studies showed no relevant effectiveness in sleep.Kava Kava plant showed promising results, in rats and humans, with decrease sleep latency, better sleep quality and recuperation after sleep. However, raised concern about its potential of hepatotoxicity.There is also promising evidence of the lavender efficacy for sleep disorders in a wide variety of populations and diseases, it was actually mentioned to be as effective as lorazepam in adults with anxiety and sleeping problems. With studies with dose of 80mg it was observed a reduction in sleep awakenings, sleep duration and overall sleep quality and anxiety.Conclusions There is a clear preference from the patient to natural compounds, and with almost nonexistent side effects, some herbal derivates are showed to have positive effectiveness in mild insomnia, but nonetheless much more studies on this field are needed.Disclosure of InterestNone Declared

Small-Fiber Neuropathy

Small-fiber neuropathy (SFN) develops due to the impairment of fibers responsible for mediating temperature, pain, and autonomic functions. SFN complicates a number of common diseases such as diabetes mellitus, human immunodeficiency virus, and COVID-19, and is likely to be increasingly encountered. The associated pain contributes significantly to the morbidity of these diseases. Progression is slow, and most people affected by SFN do not develop large-fiber involvement over time. However, mixed polyneuropathies often start as SFN, and SFN often coexists with large fiber–predominant neuropathy. Symptoms of SFN, including painful paresthesia and dizziness, and sedative side effects of pain medications can negatively affect the quality of life. Standardized diagnostic criteria for SFN are not fully established, and skin biopsy remains the diagnostic test considered most reliable. Autonomic testing is useful when autonomic symptoms are present along with screening for associated conditions. Treatment should be individualized to control underlying causes and alleviate pain. Early diagnosis and individualized treatment are important for controlling SFN symptoms and optimizing daily functions. Here, we review the common but increasingly ignored condition, SFN, and discuss its diagnosis and management.

Comparative evaluation of intranasal dexmedetomidine, intranasal midazolam, and nitrous oxide for conscious sedation of anxious children undergoing dental treatment: A randomized cross-over trial.

Pharmacological methods, specifically sedatives, have gained popularity in managing the behavior of children during dental appointments. The aim of this study was to compare 1 m/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide in evaluating the level of sedation, behavior of the child, onset of sedation, physiologic signs, and adverse effects. In this cross-over trial, 15 children aged 6-8 years were randomized to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhalation nitrous oxide at three separate visits. After administering the sedative agent, a single pulpectomy was performed during each appointment, and the outcomes were recorded. The washout period between each visit was 1 week. All three sedative agents were equally effective in controlling overall behavior. Dexmedetomidine showed lower sedation level scores (agitated; score 9) than the other groups. There was a statistically significant difference in the onset of sedation, with dexmedetomidine having the longest onset of 36.2 ± 9.47 min. Coughing and sneezing were predominantly observed after administration of intranasal midazolam. Oxygen saturation levels were statistically lower in the intranasal midazolam group during local anesthesia administration and post-treatment. 0.3 mg/kg intranasal midazolam is as effective as nitrous oxide sedation for controlling behavior and providing adequate sedation in pediatric dental patients. However, 1 m/kg dexmedetomidine did not provide the same level of sedation and had a significantly longer onset. 0.3 mg/kg intranasal midazolam is an effective alternative to nitrous oxide sedation in anxious children.

Sleep architecture disturbance due to the use of benzodiazepines

Introduction Insomnia, which is characterized by difficulty in initiating or maintaining a physiological sleep, is a relevant clinical issue, affecting not only the elderly population (from 20% to 40%), but also the general population since 30% of adults report problems in sleeping properly. In addition, 30-40% of adults report complaints about sleep quality lifetime, and10-15% report chronic insomniaBenzodiazepines (BZDs) are commonly prescribed to treat insomnia and sleep disorders. BZDs show a rapid sedative and anxiolytic effect, successfully used in the acute treatment of insomnia as well as anxiety, agitation, or anxiety associated with any type of psychiatric disorder. Their use is associated with potential side effects such as residual daytime sleepiness, ataxia, and dizziness. Long-term BZDs use may lead to drug abuse, tolerance, drug dependency, and abstinence. For instance, BZDs abrupt withdrawal can lead to severe symptoms such as insomnia and/or rebound anxiety, an increase in heart rate and blood pressure, nausea and/or vomiting, sweating, diarrhea, convulsions, and other neurological and psychiatric symptoms.ObjectivesThis e-poster aimed to summarize evidence regarding the effect of BZDs treatment on human Sleep Architecture.MethodsA bibliopgraphical review was performed using PubMed platform. All relevant articles were found using the keywords: benzodiazepines, sleep architecture, insomnia.ResultsProlonged use of benzodiazepines leads to an increase of time spent in stages 2 and a decrease of time in stages 1, 3, and 4. The increased NREM stage 2 is associated with a subjective improvement in sleep quality. The decrease in NREM sleep time in stages 3 and 4 is usually associated with lesser “rest” for the brain, which leads to a lack of concentration.ConclusionsBZDs use modified sleep architecture in the short and long term.Disclosure of InterestNone Declared

Clinical Application and Research Progress of Remimazolam for Pediatric Patients.

Remimazolam is a novel ultrashort-acting benzodiazepine that allosterically modulates γ-aminobutyric acid type A (GABAA) receptors to exert sedative effects. Remimazolam has the properties of controllable sedation, rapid onset, and a short duration of action, along with minor depression of circulation and respiration. Remimazolam has been approved for clinical use since 2020 in Japan, and it has been applied for procedural sedation, general anesthesia induction and maintenance, and sedation in ICU patients, and has been proven to be safe and effective. Currently, no consensus has been reached on the clinical application of remimazolam in pediatric patients. This review introduces the clinical research progress and limitations of remimazolam in recent years, aiming to supply scientific guidance and a theoretical reference for the application of remimazolam in pediatric anaesthesia.

ОСНОВНЫЕ АСПЕКТЫ ФАРМАЦЕВТИЧЕСКОГО КОНСУЛЬТИРОВАНИЯ СЕДАТИВНЫМИ ЛЕКАРСТВЕННЫМИ СРЕДСТВАМИ

Preserving human health, increasing life expectancy, reducing diseases and preventing them are the most important tasks of the modern medical and pharmaceutical community, the achievement of which, among other things, is impossible without the provision of proper pharmaceutical consultation and the availability of affordable and high-quality medicines. Providing incomplete or inaccessible information when providing information and consulting services threatens pharmacy visitors not only with the lack of a positive effect in treatment, but also with the possibility of causing harm to the body. The purpose of the work is to compile a recommendatory algorithm for the provision of pharmaceutical consultation using the example of drugs with a sedative effect. The materials of the study are instructions for the medical use of drugs, as well as leaflets with information for patients on the state of the state register of registered drugs for December 2023. In the course of the work, the main aspects of pharmaceutical consulting were identified, the regulatory framework relating to the provision of information and consulting services represented by the following documents: Order of the Ministry of Health of the Russian Federation dated August 31, 2016 No. 647n “On approval of the Rules for Good Pharmacy Practice of Medicines for Medical Use”; Order of the Ministry of Labor and Social Protection of the Russian Federation dated March 9, 2016 No. 91n “On approval of the professional standard “Pharmacist””; Order of the Ministry of Labor and Social Protection of the Russian Federation dated May 31, 2021 N 349n “On approval of the professional standard “Pharmacist””. Based on the results of the study, the characteristics of the selection and offer of sedative drugs are presented in detail, and an algorithm for the selection and offer of drugs with a sedative effect from the group of over-the-counter anxiolytics is compiled.

Green synthesis and multifaceted characterization of iron oxide nanoparticles derived from Senna bicapsularis for enhanced in vitro and in vivo biological investigation

Abstract Iron oxide nanoparticles have garnered significant interest in recent years due to their diverse applications, particularly in the therapeutic field. We present a green synthesis method using the extract of Senna bicapsularis, the production of iron oxide nanoparticles (IONPs). The successful synthesis of IONPs was confirmed by UV–visible spectroscopy, revealing the characteristic peak at 295 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy were employed to elucidate the functional groups involved in the synthesis and characterize the morphological features of the nanoparticles. Subsequently, the synthesized IONPs were subjected to biological assays to assess their anticancer, enzyme inhibitory, analgesic, and sedative activities, following standardized protocols. The IONPs exhibited potent anticancer activity against the MDR 2780AD cell line, with IC50 values of 0.85 (extract) and 0.55 (iron oxide nanoparticles). Remarkable inhibitory effects were also observed against urease (IC50 = 12.98 ± 0.98) and xanthine oxidase (IC50 = 96.09 ± 0.65). Additionally, they demonstrated moderate carbonic anhydrase II inhibition, with 42.09% inhibition at a concentration of 0.25 mM. Furthermore, the extract and IONPs demonstrated a significant analgesic effect in a dose-dependent manner, while the sedative effect was also significant (p < 0.001).

Comparison of methods of non-mechanical pressure measurement in the cuff of an endotracheal tube

Bronchoscopy is a diagnostic and follow-up procedure. Despite the fact that this manipulation itself is minimally invasive, it can be a difficult test for both the patient and the doctor. Therefore, this manipulation definitely requires anesthesia and sedation. This study compared dexmedetomidine and propofol sedation methods during diagnostic bronchoscopy to assess their safety, effectiveness, and satisfaction. The results show a high level of safety of both methods, although some significant differences affecting the choice of sedation method were found. 32 patients participated in the study, divided into two groups depending on the used method of sedation: propofol or dexmedetomidine. Pulse oximetry, heart rate, capnography parameters were measured, the number and severity of iatrogenic lesions of the trachea, as well as the satisfaction of care and doctors were assessed. In some groups, there was a high level of safety of sedation. Dexmedetomidine sedation was associated with fewer cough episodes and greater satisfaction, but had a longer induction time with propofol. A low incidence of serious complications was observed in both groups. Dexmedetomidine can be considered a safe and effective sedation option for diagnostic bronchoscopy, offering additional benefits such as reduced cough episodes and increased patient satisfaction. The choice of the sedation method is based on the individual characteristics of the patient and the available resources of the hospital.

Early sevoflurane sedation in severe COVID-19-related lung injury patients. A pilot randomized controlled trial

BackgroundThis study aimed to assess a potential organ protective effect of volatile sedation in a scenario of severe inflammation with an early cytokine storm (in particular IL-6 elevation) in patients suffering from COVID-19-related lung injury with invasive mechanical ventilation and sedation.MethodsThis is a small-scale pilot multicenter randomized controlled trial from four tertiary hospitals in Switzerland, conducted between April 2020 and May 2021. 60 patients requiring mechanical ventilation due to severe COVID-19-related lung injury were included and randomized to 48-hour sedation with sevoflurane vs. continuous intravenous sedation (= control) within 24 h after intubation. The primary composite outcome was determined as mortality or persistent organ dysfunction (POD), defined as the need for mechanical ventilation, vasopressors, or renal replacement therapy at day 28. Secondary outcomes were the length of ICU and hospital stay, adverse events, routine laboratory parameters (creatinine, urea), and plasma inflammatory mediators.Results28 patients were randomized to sevoflurane, 32 to the control arm. The intention-to-treat analysis revealed no difference in the primary endpoint with 11 (39%) sevoflurane and 13 (41%) control patients (p = 0.916) reaching the primary outcome. Five patients died within 28 days in each group (16% vs. 18%, p = 0.817). Of the 28-day survivors, 6 (26%) and 8 (30%) presented with POD (p = 0.781). There was a significant difference regarding the need for vasopressors (1 (4%) patient in the sevoflurane arm, 7 (26%) in the control one (p = 0.028)). Length of ICU stay, hospital stay, and registered adverse events within 28 days were comparable, except for acute kidney injury (AKI), with 11 (39%) sevoflurane vs. 2 (6%) control patients (p = 0.001). The blood levels of IL-6 in the first few days after the onset of the lung injury were less distinctly elevated than expected.ConclusionsNo evident benefits were observed with short sevoflurane sedation on mortality and POD. Unexpectedly low blood levels of IL-6 might indicate a moderate injury with therefore limited improvement options of sevoflurane. Acute renal issues suggest caution in using sevoflurane for sedation in COVID-19.Trial registrationThe trial was registered on ClinicalTrials.gov (NCT04355962) on 2020/04/21.

Comparative Analysis of the Sedative and Hypnotic Effects among Various Parts of Zizyphus spinosus Hu and Their Chemical Analysis.

Zizyphus spinosus Hu (ZS), as a "medicinal and food-homologous" plant, has been used for a long history. The study was to assess the sedative and hypnotic effects among various parts of ZS. The model, diazepam (DZP), ZS kernel (ZSS), ZS flesh (ZSF), and ZS husk (ZSKS) group occurred subsequent to the successful establishment of the para-chlorophenylalanine induced insomnia model via intraperitoneal injection. The latency and duration of sleep in mice in each group were recorded. The substance basis of various parts of ZS was analyzed by the UPLC-QTOF-MS technique. The results showed that relative to the model group, DZP, ZSS, ZSF, and ZSKS groups demonstrated shortened sleep latency (p < 0.05) and extended sleep duration (p < 0.01). The GABA, 5-HT, and BDNF levels were significantly upregulated in the brain tissues of the mice in the DZP, ZSF, and ZSS groups (p < 0.01). However, the improvement in ZSKS was non-significant. Additionally, the mRNA and protein expression levels of 5-HT1AR, GABAARα1, and BDNF in mice in the DZP, ZSS, and ZSF groups were significantly enhanced (p < 0.01). However, the improvement in the ZSKS group was insignificant (p < 0.05). The examination of the substance composition across different parts revealed that the shared chemical basis contributing to the sedative and hypnotic potency of different parts of ZS may involve the presence of compounds such as (1) magnoflorine, (8) betulinic acid, (9) ceanothic acid, and (10) alphitolic acid. It provides a basis for further elucidation of the substance basis responsible for the functional and medicinal effects of ZS.

Anesthetic effects of eugenol on adult ridgetail white prawn (Exopalaemon carinicauda) and its protective effects under simulated transportation

Anesthesia is a common practice used to improve animal welfare and reduce the negative impacts of stress factors in aquaculture settings. However, few studies have been conducted to investigate the application of anesthetics in ridgetail white prawn (Exopalaemon carinicauda). In the present study, the anesthetic efficacy and protective effects of eugenol in adults of this species were evaluated. When the prawns (n = 5) were immersed in different concentrations of eugenol in the range of 0–240 μL/L for 30 min, the results showed that 180 and 240 μL/L could lead to quick sedative and anesthesia effects with 100% mortality after 30 min exposure, while 30 μL/L failed to induce any sedative and anesthesia effects. Further tests showed that adult individuals were quickly anesthetized by eugenol at a concentration of 60–90 μL/L with a 30 min immersion, while half of the prawns were sedated in 30 μL/L eugenol after 4 h exposure, then recovered at 2 h without any mortality. Furthermore, we checked the water quality parameters after the adult prawns were immersed in four eugenol concentrations (0, 10, 20, 30 μL/L) for 8 h of simulated transportation followed by a 96 h recovery, we found that 30 μL/L eugenol treatment could significantly decrease the ammonia nitrogen concentration, and increased the survival rate at 96 h post recovery. The oxidative responses of the prawns during the 8 h transportation at 30 μL/L eugenol followed by 96 h recovery period were analyzed. The results showed that eugenol administration significantly decreased the malonaldehyde (MDA) concentration and the activities of most antioxidant-related enzymes immediately. The present data indicated that eugenol was an efficient anesthetic, which could be used for long-distance transportation of this species. It exhibited excellent protective effects to improve the animal's welfare by improving water quality and alleviating oxidative stress.

The Effect of a Subsequent Dose of Dexmedetomidine or Other Sedatives following an Initial Dose of Dexmedetomidine on Electrolytes, Acid-Base Balance, Creatinine, Glucose, and Cardiac Troponin I in Cats: Part II.

The administered dose of dexmedetomidine may occasionally fail to produce the anticipated sedative effects. Therefore, a subsequent dose or administration of another sedative may enhance sedation; however, patient safety may be affected. The safety of seven different drugs administered at the following time point after an insufficient dose of dexmedetomidine was evaluated in a crossover, blind, experimental study that included six healthy adult cats. All cats received an initial dose of dexmedetomidine and a subsequent dose of either dexmedetomidine (Group DD), NS 0.9% (DC), tramadol (DT), butorphanol (DBT), buprenorphine (DBP), ketamine (DK), or midazolam (DM). Animal safety was assessed using repeated blood gas analysis and measurement of electrolytes, glucose, cardiac troponin I, and creatinine to evaluate cardiac, respiratory, and renal function. The median values of creatinine, cardiac troponin I, pH, partial pressure of carbon dioxide, potassium, and sodium did not change significantly throughout the study. Heart rate was significantly decreased in all groups after administration of the drug combinations, except for in the DK group. Respiratory rate decreased significantly after administration of the initial dose of dexmedetomidine and in the DBP and DM groups. The partial pressure of oxygen, although normal, decreased significantly after the administration of dexmedetomidine, whereas the median concentration of glucose increased significantly following the administration of dexmedetomidine. The results of our study suggest that the drug combinations used did not alter the blood parameters above normal limits, while cardiac and renal function were not compromised. Therefore, a safe level of sedation was achieved. However, the administration of dexmedetomidine reduced the partial pressure of oxygen; thus, oxygen supplementation during sedation may be advantageous. Additionally, the increase in glucose concentration indicates that dexmedetomidine should not be used in cats with hyperglycaemia, whereas the decrease in haematocrit suggests that dexmedetomidine is not recommended in anaemic cats.

Anxiolytic and Sedative Properties of Melatonin Premedication in Pediatrics Undergoing Elective Cardiac Catheterization: A Randomized Placebo Study.

Preoperative anxiety in children has been linked to various postoperative consequences, such as postoperative regressive behavioral issues, extended distress during the recovery period, eating disorders, and bedwetting. The current study aimed to investigate the efficacy of low-dose oral melatonin in alleviating preoperative anxiety among children in the Iraqi population. A randomized, double-blinded comparative study was undertaken, involving children aged four to 14 years scheduled for elective cardiac catheterization under general anesthesia. The study comprised a total of 80 children. The involved individuals were randomly assigned to two groups, each with 40 subjects. Group A received 0.5 mg/kg melatonin as premedication, while Group B received a placebo. The two groups demonstrated similarity in mean age, weight, cardiac disease, and gender distribution. Statistically significant reductions in anxiety scores were observed in the melatonin group compared to the placebo group. Particularly, children administered 0.5 mg/kg melatonin exhibited the most substantial anxiolysis and venipuncture compliance (P < 0.05). Additionally, children who were premedicated with melatonin experienced decreased cognition, maximum sedation, successful parental separation, and psychomotor impairment (P < 0.05). Melatonin demonstrated an effective sedation level without significant side effects, making it a preferred choice due to its efficacy, safety, current availability, and cost-effectiveness compared to other anesthetic agentsused in premedication procedures.

Brain protective effect of dexmedetomidine vs propofol for sedation during prolonged mechanical ventilation in non-brain injured patients.

Dexmedetomidine and propofol are two sedatives used for long-term sedation. It remains unclear whether dexmedetomidine provides superior cerebral protection for patients undergoing long-term mechanical ventilation. To compare the neuroprotective effects of dexmedetomidine and propofol for sedation during prolonged mechanical ventilation in patients without brain injury. Patients who underwent mechanical ventilation for > 72 h were randomly assigned to receive sedation with dexmedetomidine or propofol. The Richmond Agitation and Sedation Scale (RASS) was used to evaluate sedation effects, with a target range of -3 to 0. The primary outcomes were serum levels of S100-β and neuron-specific enolase (NSE) every 24 h. The secondary outcomes were remifentanil dosage, the proportion of patients requiring rescue sedation, and the time and frequency of RASS scores within the target range. A total of 52 and 63 patients were allocated to the dexmedetomidine group and propofol group, respectively. Baseline data were comparable between groups. No significant differences were identified between groups within the median duration of study drug infusion [52.0 (IQR: 36.0-73.5) h vs 53.0 (IQR: 37.0-72.0) h, P = 0.958], the median dose of remifentanil [4.5 (IQR: 4.0-5.0) μg/kg/h vs 4.6 (IQR: 4.0-5.0) μg/kg/h, P = 0.395], the median percentage of time in the target RASS range without rescue sedation [85.6% (IQR: 65.8%-96.6%) vs 86.7% (IQR: 72.3%-95.3), P = 0.592], and the median frequency within the target RASS range without rescue sedation [72.2% (60.8%-91.7%) vs 73.3% (60.0%-100.0%), P = 0.880]. The proportion of patients in the dexmedetomidine group who required rescue sedation was higher than in the propofol group with statistical significance (69.2% vs 50.8%, P = 0.045). Serum S100-β and NSE levels in the propofol group were higher than in the dexmedetomidine group with statistical significance during the first six and five days of mechanical ventilation, respectively (all P < 0.05). Dexmedetomidine demonstrated stronger protective effects on the brain compared to propofol for long-term mechanical ventilation in patients without brain injury.

Fospropofol disodium versus propofol for long-term sedation during invasive mechanical ventilation: A pilot randomized clinical trial

Study objectiveFospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). DesignSingle-centered, prospective, unblind, randomized, parallel-group clinical trial. SettingThe general ICU of university-affiliated teaching hospital. PatientsAdult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group.Interventions: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of −3 to 0 on the Richmond Agitation and Sedation Scale (RASS). MeasurementsThe primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. Main resultsThe median dose was 4.33 (IQR, 3.08–4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44–2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%–100.00%) in the fospropofol group and 83.33% (IQR, 77.45%–100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. ConclusionsFospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation.

Steroidal Saponins from Water Eggplant (Fruits of Solanum torvum) Exhibit Anti-Epileptic Activity against Pentylenetetrazole-Induced Seizure Model in Zebrafish.

The fruits of Solanum torvum Swartz, a wild relative of eggplant, are consumed as a wild vegetable in tropical regions of Africa, Asia, and South America. In traditional Chinese medicine, it is believed to have anti-inflammatory and sedative effects. In the Philippines, water decoction is used to treat hyperactivity disorder. Twenty-two steroidal saponins were isolated and purified from the fruits grown in Yunnan, China, including six new compounds: torvosides U-Z (1-6). During drying and cooking, the saponins may undergo transformation, resulting in small amounts of sapogenins. These transformations can include dehydration of hydroxyl groups at position C22, formation of double bonds at position 20, 22 or 22, 23, and even formation of peroxide products. Saponin compounds torvoside X (4), torvoside Y (5), torvoside A (7), and (25S)-3-oxo-5α-spirostan-6α-yl-O-β-d-xylopyranoside (20), which are glycosylated at C-6, showed certain anti-epileptic activity in a pentylenetetrazole-induced zebrafish seizure model. No antiproliferative activity was detected when tested on the cancer cell line HepG2, and no hepatotoxic effect was noted on normal liver cell line LO2.

Comparison of the bispectral indices of patients receiving remimazolam and propofol for general anesthesia: a randomized crossover trial

BackgroundRemimazolam is a safe and effective new benzodiazepine sedative that has unique advantages in anesthesia induction and maintenance. The differences in the electroencephalogram bispectral index (BIS) during general anesthesia between propofol and remimazolam deserve further exploration. MethodsSingle-center randomized crossover study. Patients who required multiple hysteroscopic surgery were randomly assigned to use remimazolam (0.27 mg/kg for induction and 1 mg/kg/h for maintenance) first and then propofol (2.0 mg/kg for induction and 6 mg/kg/h for maintenance) during hysteroscopic surgery again 3 months later, or in the opposite order. Both drugs were used at the latest ED95 for unconsciousness. The BIS values (primary endpoint), intraoperative conditions, and incidence of adverse reactions (secondary endpoints) were compared at each time point. BIS values were analyzed with a mixed model of repeated measurements (MMRM). ResultsSeventeen patients completed the study. The lowest BIS value in the remimazolam regimen was significantly higher than that in the propofol regimen (p = 0.001). The MMRM analysis of the BIS values revealed significant differences between the regimens at each time point (p < 0.001). The intraoperative diastolic blood pressure and heart rate changes were smaller, the recovery was faster, and there were fewer adverse reactions and less injection pain, but a greater incidence of intraoperative body movement and hiccups, in the remimazolam regimen. ConclusionThe trial indicated that remimazolam maintained a higher BIS level than propofol. The correlation between the BIS and the depth of anesthesia induced by remimazolam needs to be further studied. Trial registrationThis trial is registered at ClinicalTrials.gov: ChiCTR2200064551

A randomised, placebo-controlled, double blind, crossover trial on the effect of a 20:1 cannabidiol: Δ9-tetrahydrocannabinol medical cannabis product on neurocognition, attention, and mood

As cannabinoid-based medications gain popularity in the treatment of refractory medical conditions, it is crucial to examine the neurocognitive effects of commonly prescribed products to ensure associated safety profiles. The present study aims to investigate the acute effects of a standard 1 mL sublingual dose of CannEpil®, a medicinal cannabis oil containing 100 mg cannabidiol (CBD) and 5 mg Δ9-tetrahydrocannabinol (THC) on neurocognition, attention, and mood. A randomised, double-blind, placebo-controlled, within-subjects design assessed 31 healthy participants (16 female, 15 male), aged between 21 and 58 years, over a two-week experimental protocol. Neurocognitive performance outcomes were assessed using the Cambridge Neuropsychological Test Automated Battery, with the Profile of Mood States questionnaire, and the Bond-Lader Visual Analogue Scale used to assess subjective state and mood. CannEpil increased Total Errors in Spatial Span and Correct Latency (median) in Pattern Recognition Memory, while also increasing Efficiency Score (lower score indicates greater efficiency) relative to placebo (all p < .05). Subjective Contentedness (p < .01) and Amicability (p < .05) were also increased at around 2.5 h post dosing, relative to placebo. Drowsiness or sedative effect was reported by 23 % of participants between three to six hours post CannEpil administration. Plasma concentrations of CBD, THC, and their metabolites were not significantly correlated with any observed alterations in neurocognition, subjective state, or adverse event occurrence. An acute dose of CannEpil impairs select aspects of visuospatial working memory and delayed pattern recognition, while largely preserving mood states among healthy individuals. Intermittent reports of drowsiness and sedation underscore the inter-individual variability of medicinal cannabis effects on subjective state. (ANZCTR; ACTRN12619000932167; https://www.anzctr.org.au)

Prospective Observational Study of Volatile Sedation with Sevoflurane After Aneurysmal Subarachnoid Hemorrhage Using the Sedaconda Anesthetic Conserving Device.

Volatile sedation is still used with caution in patients with acute brain injury because of safety concerns. We analyzed the effects of sevoflurane sedation on systemic and cerebral parameters measured by multimodal neuromonitoring in patients after aneurysmal subarachnoid hemorrhage (aSAH) with normal baseline intracranial pressure (ICP). In this prospective observational study, we analyzed a 12-h period before and after the switch from intravenous to volatile sedation with sevoflurane using the Sedaconda Anesthetic Conserving Device with a target Richmond Agitation Sedation Scale score of - 5 to - 4. ICP, cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), metabolic values of cerebral microdialysis, systemic cardiopulmonary parameters, and the administered drugs before and after the sedation switch were analyzed. We included 19 patients with a median age of 61years (range 46-78years), 74% of whom presented with World Federation of Neurosurgical Societies grade 4 or 5 aSAH. We observed no significant changes in the mean ICP (9.3 ± 4.2 vs. 9.7 ± 4.2mm Hg), PBrO2 (31.0 ± 13.2 vs. 32.2 ± 12.4mm Hg), cerebral lactate (5.0 ± 2.2 vs. 5.0 ± 1.9mmol/L), pyruvate (136.6 ± 55.9 vs. 134.1 ± 53.6µmol/L), and lactate/pyruvate ratio (37.4 ± 8.7 vs. 39.8 ± 9.2) after the sedation switch to sevoflurane. We found a significant decrease in mean arterial pressure (MAP) (88.6 ± 7.6 vs. 86.3 ± 5.8mm Hg) and CPP (78.8 ± 8.5 vs. 76.6 ± 6.6mm Hg) after the initiation of sevoflurane, but the decrease was still within the physiological range requiring no additional hemodynamic support. Sevoflurane appears to be a feasible alternative to intravenous sedation in patients with aSAH without intracranial hypertension, as our study did not show negative effects on ICP, cerebral oxygenation, or brain metabolism. Nevertheless, the risk of a decrease of MAP leading to a consecutive CPP decrease should be considered.

Nerolidol reduces depression-like behavior in mice and suppresses microglia activation by down-regulating DNA methyltransferase 1.

Modern medicine has unveiled that essential oil made from Aquilaria possesses sedative and hypnotic effects. Among the chemical components in Aquilaria, nerolidol, a natural sesquiterpene alcohol, has shown promising effects. This study aimed to unravel the potential of nerolidol in treating depression. Chronic unpredictable mild stress (CUMS) was utilized to induce depression-like behavior in mice, and open field test, sucrose preference, and tail suspension test was conducted. The impacts of nerolidol on the inflammatory response, microglial activation, and DNA methyltransferase 1 (DNMT1) were assessed. To study the regulatory role of DNMT1, lipopolysaccharide (LPS) was used to treat BV2 cells, followed by the evaluation of cell viability and DNMT1 level. Additionally, the influence of DNMT1 overexpression on BV2 cell activation was determined. Behavioral analysis revealed that nerolidol reduced depression-like behavior in mice. Nerolidol reduced the levels of inflammatory factors and microglial activation caused by CUMS. Nerolidol treatment was found to reduce DNMT1 levels in mouse brain tissue and it also decrease the LPS-induced increase in DNMT1 levels in BV2 cells. DNMT1 overexpression reversed the impacts of nerolidol on the inflammation response and cell activation. This study underscores the potential of nerolidol in reducing CUMS-induced depressive-like behavior and inhibiting microglial activation by downregulating DNMT1. These findings offer valuable insights into the potential of nerolidol as a therapeutic option for depression.