Sedative Effects Research Articles

Effects of moderate sedation induced by propofol or midazolam on intracranial pressure

Introduction: Propofol and midazolam are the main options for moderate sedation in clinical practice. In addition, these drugs are used to reduce intracranial pressure in cases of intracranial hypertension, and their use in these situations is guided by limited evidence. Objective: To compare the effects of propofol and midazolam on intracranial pressure wave morphology in moderate sedation in patients undergoing upper digestive endoscopy. Methods: Sixty patients were included in this study, being divided into two groups, propofol and midazolam group. Intracranial pressure was monitored during and after upper digestive endoscopy, using non-invasive monitoring equipment developed by the company Brain4care. Arterial pressure was measured before and after the exam. Results: The propofol group had lower intracranial pressure (p=0.037) during moderate sedation compared to intracranial pressure after endoscopy and a significant decrease in systolic (p=0.0001) and diastolic pressure (p=0.001) after sedation. Midazolam, on the other hand, reduced systolic pressure (p=0.001), but didn’t change the other parameters after the procedure. There wasn’t a significant difference between the propofol and midazolam groups. Conclusion: There was no significant difference between the groups studied, however, analyses within the propofol and midazolam groups indicate that propofol, but not midazolam, causes changes in intracranial pressure in moderate sedation.

Synthetic cannabinoid identification in cases associated with blue lotus and valerian root vaping products.

Synthetic cannabinoids emerged in the early 21st century and have continued to evolve and flourish to present day. Like other novel psychoactive substances (NPS), synthetic cannabinoids have been sold under the guise of legitimate products. Some examples include "potpourri," "incense," and herbal material. Between May 2020 and December 2023, the United States Army Criminal Investigation Laboratory, Drug Chemistry Division (USACIL) received 29 seized drug cases mentioning "blue lotus" or "valerian root." In 90% of these cases, at least one exhibit contained one or more synthetic cannabinoids. During the same timeframe, the Armed Forces Medical Examiner System, Division of Forensic Toxicology received 65 toxicology cases that contained synthetic cannabinoids and/or their corresponding metabolites where case history mentioned "blue lotus." The most frequently observed synthetic cannabinoids between laboratories were 5F-MDMB-PICA, ADB-BUTINACA, and MDMB-4en-PINACA. Innocuous branding and marketing may deceive law enforcement, investigators, and healthcare providers into believing that the adverse effects of erratic behavior, sedation, slurred speech, and hallucinations are a result of toxicity from botanical extracts (e.g. apomorphine and nuciferine in blue lotus). Due to the dangerous nature of these NPS, synthetic cannabinoid screening is recommended for all cases where there is suspected use of vaping products suggested to contain "blue lotus" or "valerian root" as vendors continue to conceal the presence of these compounds.

ADVANTAGES OF USING DEXMEDETOMIDINE AS AN ADJUVANT IN LAPAROSCOPIC BARIATRIC SURGERIES

The global rise in obesity rates has necessitated an increased frequency of bariatric surgeries, posing intricate challenges in anesthesia management. Dexmedetomidine, an α2-adrenergic receptor agonist, has emerged as a potential adjunct to general anesthesia in this context. This study aimed to evaluate the efficacy and safety of dexmedetomidine in 1306 adult patients undergoing elective bariatric surgery between January 2017 and September 2023, comparing outcomes with a placebo group.Dexmedetomidine was administered during both the maintenance phase of anesthesia. Key parameters including intraoperative and postoperative complications, analgesic requirements, hemodynamics, and recovery profiles were meticulously monitored and analyzed. Dexmedetomidine demonstrated sedative and analgesic-sparing effects, coupled with cardiovascular stabilization and preservation of respiratory function. Notably, it significantly reduced the utilization of anesthetic drugs, postoperative opioids, and propofol during the surgical procedure. Furthermore, dexmedetomidine exhibited efficacy in attenuating propofol injection pain, mitigating stress responses during the critical phase of extubation, and diminishing postoperative pain along with associated analgesic requirements. However, a nuanced approach to dosage was imperative, as higher doses correlated with delayed respiratory recovery and an increased incidence of bradycardia.To summarize, dexmedetomidine as an adjuvant to general anesthesia in bariatric surgery presents notable advantages in enhancing recovery profiles, mitigating complications, and improving patient comfort. Optimal dosing strategies are paramount to harnessing its benefits while mitigating potential adverse effects, thereby optimizing perioperative care in this patient population.

A Systematic Review on Sedative and Hypnotics

Abstract: Sedative and hypnotic drugs are central nervous system depressants primarily used to induce calmness, reduce anxiety, and promote sleep. These medications include benzodiazepines, barbiturates, and various non-benzodiazepine sleep aids, each varying in their mechanism of action, efficacy, and safety profiles. Benzodiazepines, such as diazepam and alprazolam, enhance the effect of the neurotransmitter gamma-aminobutyric acid (GABA) at the GABA-A receptor, resulting in sedative, anxiolytic, muscle relaxant, and anticonvulsant effects. They are commonly prescribed for anxiety disorders, insomnia, seizures, and muscle spasms. However, their use is associated with risks of tolerance, dependence, and withdrawal symptoms. Barbiturates, such as phenobarbital, were once widely used for their sedative and hypnotic properties but have largely been replaced by benzodiazepines and other safer alternatives due to their higher risk of overdose and dependence. Barbiturates enhance GABAergic transmission but also directly activate GABA receptors, leading to more profound central nervous system depression. Non-benzodiazepine sleep aids, including drugs like zolpidem, eszopiclone, and zaleplon, act on the benzodiazepine receptor site but have a different chemical structure. These drugs are often preferred for short-term treatment of insomnia due to their relatively lower risk of dependence and adverse effects compared to benzodiazepines.

DEXMEDETOMIDINE: A VERSATILE, MULTITASKING ANESTHETIC AGENT FOR PERIOPERATIVE MANAGEMENT, A NARRATIVE REVIEW

Dexmedetomidine stands out as a versatile anesthetic agent with a unique combination of sedative, analgesic, and sympatholytic properties, making it highly suitable for various perioperative applications. Its ability to provide arousable sedation, reduce opioid requirements, and maintain hemodynamic stability offers significant advantages in the perioperative management of surgical patients, particularly those with cardiovascular risks or a history of opioid use. The neuroprotective potential of dexmedetomidine further broadens its clinical applicability, especially in neurosurgical and trauma settings. While generally well-tolerated, its use necessitates careful monitoring to mitigate side effects such as bradycardia and hypotension, particularly in patients with hepatic impairment. The availability of atipamezole as an antidote enhances the safety profile of dexmedetomidine, allowing for rapid and effective reversal of its sedative and cardiovascular effects. Given the comprehensive benefits and the evolving evidence supporting its use, dexmedetomidine represents a valuable addition to the anesthesiologists toolkit, warranting its continued exploration and integration into perioperative care protocols.

Dexmedetomidine Promotes NREM Sleep by Depressing Oxytocin Neurons in the Paraventricular Nucleus in Mice.

Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist with sedative effects on sleep homeostasis. Oxytocin-expressing (OXT) neurons in the paraventricular nucleus (PVN) of the hypothalamus (PVNOXT) regulate sexual reproduction, drinking, sleep-wakefulness, and other instinctive behaviors. To investigate the effect of DEX on the activity and signal transmission of PVNOXT in regulating the sleep-wakefulness cycle. Here, we employed OXT-cre mice to selectively target and express the designer receptors exclusively activated by designer drugs (DREADD)-based chemogenetic tool hM3D(Gq) in PVNOXT neurons. Combining chemogenetic methods with electroencephalogram (EEG) /electromyogram (EMG) recordings, we found that cannula injection of DEX in PVN significantly increased the duration of non-rapid eye movement (NREM) sleep in mice. Furthermore, the chemogenetic activation of PVNOXT neurons using i.p. injection of clozapine N-oxide (CNO) after cannula injection of DEX to PVN led to a substantial increase in wakefulness. Electrophysiological results showed that DEX decreased the frequency of action potential (AP) and the spontaneous excitatory postsynaptic current (sEPSC) of PVNOXT neurons through α2-adrenoceptors. Therefore, these results identify that DEX promotes sleep and maintains sleep homeostasis by inhibiting PVNOXT neurons through the α2-adrenoceptor.

Comparison of the effects of child-centered playful companionship and pharmacological sedation in alleviating preoperative anxiety in preschool children

Objective: To investigate the effectiveness of child-centered playful companionship and sedative medication in alleviating preoperative anxiety in preschool children. Methods: A retrospective analysis was conducted on 3 825 preschool children (3-6 years) who underwent elective surgery at Shanghai Children's Medical Center from April 2021 to March 2022. The children were divided into three groups based on the preoperative anxiolytic intervention: child-centered playful companionship group (n=2 198), pharmacological sedation group (n=1 281), and no intervention group (n=346). The pharmacological sedation group received intranasal dexmedetomidine at 2 μg/kg or oral midazolam syrup at 0.5 mg/kg. The child-centered playful companionship group received care from certified preoperative sedation nurses using a child-centered playful nursing model. The no intervention group did not receive any anti-anxiety measures due to various subjective and objective reasons. Preoperative separation anxiety scores (PSAS), sedation medication usage, and Ramsay sedation scores were recorded for all children. The primary outcome was the success rate of separation based on PSAS scores across different anxiolytic intervention groups, while the secondary outcome was the Ramsay sedation score. Results: The child-centered playful companionship group included 1 462 boys and 736 girls, with a median age [M (Q1, Q3)]of 59 (49, 69) months. The pharmacological sedation group included 824 boys and 457 girls, with a median age of 52 (42, 61) months; and the no intervention group included 212 boys and 134 girls, with a median age of 57 (48, 69) months. The success rate of separation in the child-centered playful companionship group was 95.6% (2 102/2 198), and in the pharmacological sedation group was 93.8% (1 202/1 281), both significantly higher than the 43.6% (151/346) of the no intervention group (all P<0.05). Among the 1 281 children in the pharmacological sedation group, 785 received oral midazolam and 496 received intranasal dexmedetomidine. Compared to the intranasal dexmedetomidine group, the oral midazolam group was younger, had a lower body weight and a higher proportion of American Society of Anesthesiologists (ASA) class Ⅲ (all P<0.05). The success rate of separation was 93.4% (733/785) in the oral midazolam group and 94.6% (469/496) in the intranasal dexmedetomidine group, with no statistically significant difference (P=0.392). The Ramsay sedation score was 2 (2, 2) in the intranasal dexmedetomidine group, better than the 2 (2, 2) of the oral midazolam group (P=0.024). Conclusion: Both child-centered playful companionship and pharmacological sedation effectively alleviate preoperative anxiety in preschool children.

General Anestesi Intravena pada Tindakan Debridement dan Tangensial Eksisi Pasien Combustio 13.5% Grade Iia

It was reported that the patient, a 40 year old woman, weighing 53 kg, would undergo debridement and tangential excision. The patient said he had no history of previous illness. The patient also denied a history of allergies and dentures. The patient also does not currently have a cold, cough or fever. Therefore, the patient is classified as ASA I because he has no systemic abnormalities. In this operation, an intravenous general anesthesia technique was used because the duration of the surgery is not long, and it also avoids the effects of inhalation sedation. The patient did not use respiratory assistance and had strict intraoperative monitoring to maintain airway patency.The drugs used are midazolam and fentanyl as pre-medication, and propofol as an induction drug, which is then treated with propofol intermittently. After the operation is complete, the patient is immediately transferred to the recovery room, and his consciousness value is checked using the Aldrette score, which in this patient's score is 10, and therefore, the patient can be transferred to the treatment room.

The effects of remimazolam combined with sufentanil on respiration, circulation and sedation level in patients undergoing colonoscopy

BackgroundThe main sedative which is propofol in painless gastroenteroscopy, has a high risk of reducing blood pressure and respiratory depression. Remimazolam (a short-acting benzodiazepine) is expected to be widely used in painless gastroenteroscopy due to its rapid onset, rapid metabolism and light respiratory and circulation inhibition.MethodsA randomized, single-blind, parallel, controlled study, 123 outpatients who were undergoing painless colonoscopy and ramdomly divided into group A, B and C, in Hangzhou First People’s Hospital, July-December 2021. All patients were intravenously injected with 5 µg sufentanil for analgesic preconditioning. The group A was induced by 0.2 mg/kg remimazolam besylate. The group B was induced by 0.25 mg/kg remimazolam besylate. And the group C was inducted by 2.0 mg /kg propofol. If the patients had limb movement or MOAA/S score > 3 and so on, remimazolam besylate was added at 2.5 mg/ time in group A and B, and propofol emulsion injection was added at 0.5 mg/kg/ time in group C. During the operation, according to the actual situation, remimazolam was per added 2.5 mg in the experimental group, and propofol was 0.5 mg/kg in the control group. Heart rate (HR), non-invasive blood pressure (BP), respiratory rate (RR), pulse oxygen saturation (SpO2), and improved vigilance/sedation score (MOAA/S) of patients was recorded from entering endoscopy room to get out of the anesthesia recovery room, also including perioperative adverse events, other medications or treatments, the time of patients waking up and leaving the hospital.ResultsThe successful rate of induction in three groups was 100%. There was no significant difference in the sedation completion rate among the three groups (Group A:90.2%, Group B: 92.7%, Group C: 92.7%, P = 1.000). The rate of adverse events after administration: group A(27.0%) and B(36.8%) both lower than group C(71.0%),P < 0.001;There was no significant difference between group A and group B, P > 0.744;The average time from the last drug administration to meet the discharge criteria of the subjects in three groups was as follows: The average time of group A(16.2 min) and Group B(16.5 min) both shorter than group C(19.6 min), P = 0.001; There was no significant difference between group A and group B, P = 0.742. Conclusions: This study revealed that remimazolam is a safe and effective medication for colonoscopy sedation, the security of remimazolam is better than propofol, and the sedative effect with the initial dose of 0.25 mg/kg of remimazolam is optimal.Trial registrationChina Clinical Trial Center with registration number: 2100052615,02/11/2021.

Effective and safe pediatric sedation.

Pediatric sedation is a crucial tool for minimizing pain and anxiety during procedures and examinations in children. However, it is not without risks. This review provides a comprehensive review of pediatric sedation, including both established practices and recent advancements. A thorough pre-procedural evaluation is crucial to mitigate these risks. Skilled healthcare professionals trained in pediatric sedation are paramount to ensure a safe and effective procedure. The choice of sedative medication depends on various factors, such as the type of procedure and the patient's medical condition. Medications, used alone or in combination, offer sedation with varying onset times and durations. Non-pharmacological approaches can complement pharmacological sedation and further reduce potential complications. Preventing sedation-related complications requires a multidisciplinary approach. This includes collaborative decision-making, vigilant monitoring throughout the procedure, and a focus on patient safety. Recovery involves ensuring the child returns to their baseline status before discharge, following established criteria. In conclusion, successful pediatric sedation hinges on a comprehensive strategy. This strategy encompasses a thorough evaluation, skilled personnel, appropriate medication selection, vigilant monitoring, and a focus on patient safety throughout the process. By following these steps, we can minimize risks and achieve successful outcomes.

Schisandra chinensis inhibits the entry of BoHV-1 by blocking PI3K-Akt pathway and enhances the m6A methylation of gD to inhibit the entry of progeny virus.

Schisandra chinensis, a traditional Chinese medicine known for its antitussive and sedative effects, has shown promise in preventing various viral infections. Bovine herpesvirus-1 (BoHV-1) is an enveloped DNA virus that causes respiratory disease in cattle, leading to significant economic losses in the industry. Because the lack of previous reports on Schisandra chinensis resisting BoHV-1 infection, this study aimed to investigate the specific mechanisms involved. Results from TCID50, qPCR, IFA, and western blot analyses demonstrated that Schisandra chinensis could inhibit BoHV-1 entry into MDBK cells, primarily through its extract Methylgomisin O (Meth O). The specific mechanism involved Meth O blocking BoHV-1 entry into cells via clathrin- and caveolin-mediated endocytosis by suppressing the activation of PI3K-Akt signaling pathway. Additionally, findings from TCID50, qPCR, co-immunoprecipitation and western blot assays revealed that Schisandra chinensis blocked BoHV-1 gD transcription through enhancing m6A methylation of gD after virus entry, thereby hindering gD protein expression and preventing progeny virus entry into cells and ultimately inhibiting BoHV-1 replication. Overall, these results suggest that Schisandra chinensis can resist BoHV-1 infection by targeting the PI3K-Akt signaling pathway and inhibiting gD transcription.

Study on the preventive effect of dexmedetomidine on anesthetic associated sleep disturbance in young to middle-aged female patients undergoing hysteroscopy: a study protocol for a crossover randomized controlled trial

BackgroundPostoperative sleep disturbance has a potentially detrimental effect on postoperative recovery. Perioperative patients are affected by several factors. General anesthesia induces a non-physiological state that does not resemble natural sleep. Exposure to propofol/sevoflurane can lead to desynchronization of the circadian rhythm, which may result in postoperative sleep disturbance characterized by mid-cycle advancement of sleep and daytime sleepiness. Dexmedetomidine is a highly selective α2-adrenoceptor agonist with a unique sedative effect that facilitates the transition from sleep to wakefulness. Basic research has shown that dexmedetomidine induces deep sedation, similar to physical sleep, and helps maintain forebrain connectivity, which is likely to reduce delirium after surgery. The aim of this study is to evaluate the influence of exposure to the mono-anesthetic propofol on the development of postoperative sleep disturbance in young and middle-aged female patients undergoing hysteroscopy and whether prophylactic administration of dexmedetomidine influences reducing postoperative sleep disturbance.MethodsThis prospective randomized controlled trial (RCT) will include 150 patients undergoing hysteroscopy at the First Affiliated Hospital of Xiamen University. Participants will be randomly assigned to three groups in a 1:1:1 ratio. The dexmedetomidine group will have two subgroups and will receive a nasal spray of 0.2 µg/kg or 0.5 µg/kg 25 min before surgery, while the control group will receive a saline nasal spray. Three groups will undergo hysteroscopy with propofol-based TIVA according to the same scheme. Sleep quality will be measured using a wearable device and double-blind sleep assessments will be performed before surgery and 1, 3, and 7 days after surgery. SPSS 2.0 is used for statistical analysis. A χ2 test is used to compare groups, and t-test is used to determine statistical the significance of continuous variables.DiscussionThe purpose of this study is to investigate the incidence of propofol-associated sleep disorders and to test a combination of dexmedetomidine anesthesia regimen for the prevention of postoperative sleep disorders. This study will help to improve patients’ postoperative satisfaction and provide a new strategy for comfortable perioperative medical treatment.Trial registrationClinicalTrials.gov NCT06281561. Registered on February 24, 2024.

Efficacy and Safety of Combination of Noscapine and Chlorpheniramine in Management of Cold and Cough

Cough is one of the most common symptoms for which patients visit the doctor. Because of its broad differential diagnosis,cough is a challenging condition to manage. Antitussives or cough suppressants are indicated if cough interferes with dailyactivities. Cough suppressants not only provide symptomatic relief by decreasing cough, they also prevent the spread ofinfection. Noscapine is a non-narcotic cough suppressant, which relieves cough by acting at the level of the cough centerin the brain. It does not cause significant sedative, euphoric, or hypnotic effects, and other side effects such as respiratorysuppression and constipation that are typically associated with opioids. Hence, unlike other opioid antitussives such ascodeine, noscapine is nonaddictive.

Clerodendrum trichotomum Thunberg-An Ornamental Shrub with Medical Properties.

Harlequin glory bower (Clerodendrum trichotomum) is a shrub or small tree belonging to the Lamiaceae family, native to Japan, Korea, and eastern China. It has esthetic value and in Europe, it is cultivated as an ornamental plant. Its sweet-smelling flowers have a white or pink crown. The calyx turns from green to pink-purple over time, providing an especially decorative touch around surrounding the ripe deep-blue fruits that persist until winter. In the areas of its natural occurrence, the leaves and young shoots of C. trichotomum, and sometimes the roots, flowers and fruits, are used in folk medicine due to its anti-inflammatory, analgesic, anticancer, sedative, and hypotensive effects. Products based on Harlequin glory are also used in the treatment of rheumatoid arthritis, joint pain, skin inflammation, or asthma. Preliminary research on the composition of raw material suggests that its health-promoting effect is associated with the presence of numerous secondary metabolites, including phenylpropanoids, flavonoids, lignans, terpenoids, steroids, alkaloids, and anthraquinones. This work reviews the current state of knowledge about the phytochemistry and in vitro and in vivo pharmacological properties of the extracts and main active components isolated from C. trichotomum. It also indicates that before it can be used in modern medicine, further research is necessary regarding the safety and efficacy of the raw material, its mechanisms of action, and dosage.

Initial Characterization of the Viridisins' Biological Properties.

Viridisin A1 and A2 were previously heterologously expressed, purified, and characterized as ribosomally produced and post-translationally modified lanthipeptides. Such lanthipeptide operons are surprisingly common in Gram-negative bacteria, although their expression seems to be predominantly cryptic under laboratory conditions. However, the bioactivity and biological role of most lanthipeptide operons originating from marine-associated Pseudomonadota, such asThalassomonas viridans XOM25T, have not been described. Therefore, marine-associated Gram-negative lanthipeptide operons represent an untapped resource for novel structures, biochemistries, and bioactivities. Here, the upscaled production of viridisin A1 and A2 was performed for (methyl)lanthionine stereochemistry characterization, antibacterial, antifungal, and larval zebrafish behavioral screening. While antimicrobial activity was not observed, the VirBC modification machinery was found to install both dl- and ll-lanthionine stereoisomers. The VdsA1 and VdsA2 peptides induced sedative and stimulatory effects in zebrafish larvae, respectively, which is a bioactivity not previously reported from lanthipeptides. When combined, VdsA1 and VdsA2 counteracted the sedative and stimulatory effects observed when used individually.

Prehospital Use of Ketamine Versus Midazolam for Sedation in Acute Severe Agitation

Objective: Acute severe agitation often requires pharmacologic sedation. While benzodiazepines and antipsychotics are traditional first-line medications for this purpose, recent evidence has shown that prehospital intramuscular (IM) administration of ketamine results in rapid, effective sedation. However, ketamine may be associated with adverse clinical events including a higher intubation rate. The purpose of this study is to compare the efficacy and safety of IM ketamine versus IM midazolam as medications to achieve sedation in the prehospital setting. Methods: This is a retrospective cohort study of agitated patients with an initial Richmond Agitation-Sedation Scale (RASS) score of at least 3, who were sedated and transported by ambulance to Hartford Hospital. The primary endpoint was incidence of endotracheal intubation occurring during transportation and within one hour after arrival to the emergency department (ED). Secondary endpoints included the percentage of patients who achieved an improved RASS score post drug administration, the use of additional sedating agents and the need for airway and breathing support, and differences in adverse events. Results: 66 patients in the ketamine group and 68 patients in the midazolam group met inclusion criteria. While more patients in the midazolam group achieved target RASS score of -1, 0, or 1 post drug administration, patients in the ketamine group had a lower mean RASS score post drug administration. There was no difference in endotracheal intubation rates between the two groups (6.1% versus 2.9%, respectively; p = 0.383). However, upon arrival to the ED, more patients in the ketamine group required additional sedating agents as well as airway or respiratory support Conclusion: Both ketamine and midazolam are relatively safe and efficacious in the prehospital environment. IM ketamine resulted in deeper sedation without increasing intubation rate. However, ED providers receiving patients treated with IM ketamine should prepare for additional sedating agents and airway interventions.

Study of biologically active substances of plants of the North-West Caucasus that produce a sedative effect

Medicinal plants have always arised an interest because they usually have pharmacological effects, low toxicity and high safety. Herbal preparations can be used both for the prevention of certain diseases and for the treatment of chronic and slowly developing ones. At the same time, practically healthy people can also use them to improve their quality of life. The experience of using medicinal plants in traditional medicine in the North-West Caucasus (in particular, in the Republic of Adygea) contributed to their active study with the aim of introducing official scientific medicine into clinical practice.For the treatment, prevention and diagnosis of many diseases, the medications are widely used that have a sedative effect in various neurotic conditions and have a regulatory effect on the central nervous system, reducing excitatory processes, enhancing inhibitory processes or eliminating the consequences of stressful situations. In this regard, there is a need to expand the local raw material base of medicinal plants, which accumulate biologically active substances in high concentrations.The article provides data on the study of wild North Caucasian populations of medicinal plants (valerian officinalis, common hop, motherwort and peppermint), which are promising producers of biologically active compounds. The results obtained indicate the safety of the raw material, allow us to evaluate its quality and prove the promise of ongoing scientific research, which has not only theoretical but also practical significance for the purpose of creating drugs that have a sedative effect, as well as for processing without restrictions.

The Role of Glucocorticoid and Nicotinic Acetylcholine Receptors in the Reward-Enhancing Effects of Nicotine in the ICSS Procedure in Male and Female Rats.

Tobacco use disorder is a chronic disorder that affects more than one billion people worldwide and causes the death of millions each year. The rewarding properties of nicotine are critical for the initiation of smoking. Previous research has shown that the activation of glucocorticoid receptors (GRs) plays a role in nicotine self-administration in rats. However, the role of GRs in the acute rewarding effects of nicotine are unknown. In this study, we investigated the effects of the GR antagonist mifepristone and the nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine on the reward-enhancing effects of nicotine using the intracranial self-stimulation (ICSS) procedure in adult male and female rats. The rats were prepared with ICSS electrodes in the medial forebrain bundle and then trained on the ICSS procedure. Nicotine lowered the brain reward thresholds and decreased response latencies similarly in male and female rats. These findings suggest that nicotine enhances the rewarding effects of ICSS and has stimulant properties. Treatment with the GR antagonist mifepristone did not affect the reward-enhancing effects of nicotine but increased response latencies, suggesting a sedative effect. Mecamylamine did not affect the brain reward thresholds or response latencies of the control rats, but prevented the nicotine-induced decrease in brain reward thresholds and reward latencies. These findings indicate that the rewarding effects of nicotine are mediated via the activation of nAChRs, and that the activation of GRs does not contribute to the acute rewarding effects of nicotine. These studies enhance our understanding of the neurobiological mechanisms underlying tobacco use disorder.

In vivo biological screening of extract and bioactive compound from Ficus benghalensis L. and their in silico molecular docking analysis.

Ficus benghalensis has been used by local health care practitioners to treat pain, inflammation, rheumatism, and other health issues. In this study, the crude extract and diverse fractions, along with the isolated compound of F. benghalensis were examined for their roles as muscle relaxants, analgesics, and sedatives. The extract and isolated compound 1 were screened for muscle-relaxant, analgesic, and sedative actions. The acetic acid-mediated writhing model was utilized for analgesic assessment, the muscle relaxant potential was quantified through traction and inclined plan tests, and the open field test was applied for sedative effects. The extract/fractions (25, 50, and 100 mg/kg) and isolated compounds (2.5, 5, 10, and 20 mg/kg) were tested at various doses. A profound (p< 0.001) reduce in the acetic acid-mediated writhing model was observed against carpachromene (64.44%), followed by ethyl acetate (60.67%) and methanol (58.42%) fractions. A marked (p< 0.001) muscle relaxant activity was noticed against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Regarding the sedative effect, a significant action was noted against the isolated compound (71.09%), followed by ethyl acetate (66.98%) and methanol (67.10%) fractions. Furthermore, the binding modes of the isolated compounds were explored using molecular docking. The molecular docking study revealed that the isolated compound possessed good binding affinity for COX2 and GABA. Our isolated compound may possess inhibitory activity against COX2 and GABA receptors. The extract and isolated compounds of Ficus benghalensis can be used as analgesics, muscle relaxants, and sedatives. However, detailed molecular and functional analyses are essential to ascertain their function as muscle relaxants, analgesics, and sedatives.

Use of Dexmedetomidine versus Nitroglycerine to Provide Hypotensive Anesthesia in ENT Surgeries (Functional Endoscopic Sinus Surgery)

Abstract Background controlled (deliberate/induced) hypotension is a technique by which the arterial blood pressure is lowered in a controllable manner to reduce surgical blood loss and improve the operative field visibility. There are pharmacological and nonpharmacological techniques for inducing hypotension. The nonpharmacological methods for deliberate hypotension include positioning and positive pressure ventilation to control venous return. Aim of the Work to evaluate the efficacy of dexmedetomidine (DEX) as a hypotensive agent in comparison to nitroglycerin (NTG) in FESS regarding the bloodless field, reduction of mean arterial blood pressure, decrease inhalational anesthetic requirements (MAC), decrease perioperative opioid requirements, increase the time to first postoperative analgesic request and recovery profile and increase hemodynamics stability. Patients and Methods we conducted this study on 20 patients who were planned to perform functional endoscopic sinus surgery and were randomly distributed into 2 equal groups: 10 patients received dexamedotomidine and equal number of patients received nitroglycerine. Serial measurements of mean arterial blood pressure and heart rate were obtained and records between both groups were compared. Results There were statistically significant differences between both groups regarding heart rate as mean values of heart rate were lower among dexamedotomidine group. There were no statistically significant differences between both groups regarding mean arterial blood pressure values at different time points during the operation. Regarding the period after stopping infusion, mean values of heart rate and blood pressure were lower among dexamedotomidine group than nitroglycerine group after 5 minutes and after 10 minutes and the differences had statistically significant differences. Regarding postoperative period, both groups were comparable regarding heart rate and blood pressure immediately postoperative. Conclusion From the results of this study, we could conclude that both Dexmedetomidine and Nitroglycerin can be effectively used in induced hypotensive anesthesia for ENT surgery as FESS. Both groups were comparable with intra operative MAP with no statistically significant differences. This study also show that Dexmedetomidine has added advantages as better haemodynamic stability than Nitroglycerin (No rebound HTN, no tachycardia). Has sedative and analgesic effect, reduce requirement of anesthetic agents and perioperative analgesia. Postoperative recovery score (Time to reach modified Aldert score more than nine significantly higher. Postoperative complication as nausea and vomiting is less.