Anesthetic Action Research Articles

Association Between Anesthesia Provider Education and Carbon Footprint Related to the Use of Inhaled Halogenated Anesthetics.

Inhaled halogenated anesthetics are responsible for half of operating room total greenhouse gas emissions. Sustainable anesthesia groups were set up in 4 Lyon, France, university hospitals (Hospices Civils de Lyon) in January 2018 and have supported a specific information campaign about the carbon footprint related to the use of inhaled halogenated anesthetics in June 2019. We aimed to assess whether implementing such information campaigns was associated with a decrease in the carbon footprint related to inhaled halogenated anesthetics. This retrospective cohort study was conducted from January 1, 2015, to February 29, 2020, in 4 hospitals of the Hospices Civils de Lyon in France. Information meetings on sustainable anesthesia practices were organized by sustainable anesthesia groups that were set up in January 2018. In addition, a specific information campaign about the carbon footprint related to inhaled halogenated anesthetics was conducted in June 2019; it was followed by a questionnaire to be completed online. The monthly purchase of sevoflurane, desflurane, and propofol was recorded, and the estimated monthly carbon footprint from desflurane- and sevoflurane-related perioperative emissions was calculated. The interrupted time-series data from January 2015 to February 2020 were analyzed by segmented regression, considering both interventions (setting up of the sustainable anesthesia groups and specific information campaign) in the analysis and adjusting for 2 confounding factors (seasonality of the data and number of general anesthesia uses). Among the 641 anesthesia providers from the study hospitals, 121 (19%) attended the information meetings about the carbon footprint of inhaled halogenated anesthetics, and 180 (28%) completed the questionnaire. The anesthetic activity from all 641 providers was considered in the analysis. After the sustainable anesthesia groups were set up, the carbon footprint of sevoflurane and desflurane started decreasing: the slope significantly changed ( P < .01) and became significantly negative, from -0.27 (95% confidence interval [CI], -1.08 to 0.54) tons.month -1 to -14.16 (95% CI, -16.67 to -11.65) tons.month -1 . After the specific information campaign, the carbon footprint kept decreasing, with a slope of -7.58 (95% CI, -13.74 to -1.41) tons.month -1 ( P = .02), which was not significantly different from the previous period ( P = .07). The setup of the sustainable anesthesia groups was associated with a dramatic reduction in the carbon footprint related to halogenated anesthetics. These results should encourage health care institutions to undertake information campaigns toward anesthesia providers so that they also take into account the environmental impact in the choice of anesthetic drugs, in addition to the benefits for the patient and economic concerns.

The state of anesthesia in South Korea: a national survey of the status of anesthetic service activity in 2014-2016.

BackgroundBecause the quality of anesthesia affects the surgical outcome, the aim of this study was to investigate the current status of anesthetic services performed by anesthesiologists and non-anesthesiologists in South Korea from 2014 to 2016 and to compare the results with data from 2011 to 2013.MethodsThe claimed anesthesia services at medical institutions with employed anesthesiologists and the claims for an invitation fee for an anesthesiologist at medical institutions without employed anesthesiologists were regarded as anesthetic services performed by an anesthesiologist. From 2014 to 2016, the employment of anesthesiologists according to the type of medical institution, the status of anesthetic services according to the presence or absence of employed anesthesiologists, and status of anesthetic services at medical institutions without employed anesthesiologists were analyzed.ResultsThe proportion of medical institutions that employed anesthesiologists slightly increased from 27.8% in 2014 to 28.8% in 2016. General anesthesia was more concentrated at higher medical institutions, and most anesthesias were performed by an anesthesiologist. The proportion of spinal anesthesia, epidural anesthesia, and brachial plexus performed by non-anesthesiologists was 11%, 15%, and 16.5%, respectively. Intravenous anesthesia performed by non-anesthesiologists was 58% and has increased compared to the past.ConclusionsThe employment of anesthesiologists has increased with time, and general anesthesiology was mostly performed by anesthesiologists. However, since the proportion of anesthetic services performed by non-anesthesiologists in regional anesthesia and intravenous anesthesia was maintained high, it is necessary to find ways to expand the safety of anesthetic services.

N-Ethylnorketamine has anesthetic and analgesic effects with abuse liability

Arylcyclohexylamines is an ever-growing class of new psychoactive substances, including an increasing number of ketamine analogs. N-Ethylnorketamine (NENK) is a new synthetic ketamine analog that has emerged as an abused drug, but little is known about the pharmacological profile of NENK. In this study, we investigated the anesthetic and analgesic activity, abuse liability of NENK compared with ketamine. The ED50 values of anesthetic activity for NENK and ketamine were 96.9, 69.4 mg/kg, respectively. The ED50 values of analgesic activity for NENK and ketamine were 45.9 and 23.6 mg/kg, respectively. NENK induced significant conditioned place preference at a minimum dose of 10.0 mg/kg in mice, an effect comparable to that of ketamine (3.0 mg/kg). Acute injections of NENK or ketamine at 30.0 mg/kg enhanced locomotor activity, and repeated treatments with this dose induced locomotor sensitization after withdrawal. Taken together, these results clearly demonstrated that NENK has lower anesthetic and analgesic activity compared to ketamine, but has significant abuse liability.

Utilization of propranolol hydrochloride mucoadhesive invasomes as a locally acting contraceptive: in-vitro, ex-vivo, and in-vivo evaluation

It was found that propranolol hydrochloride (PNL), which is a beta-blocker used for hypertension treatment, has a potent spermicidal activity through local anesthetic activity or beta-blocking effect on sperm cells subsequently it could be used as a contraceptive remedy. This study aimed to entrap PNL into invasomes (INVs) and then formulate it as a locally acting contraceptive gel. PNL-loaded mucoadhesive INVs were prepared via the thin-film hydration technique. The D-optimal design was utilized to fabricate INVs employing lipid concentration (X1), terpenes concentration (X2), terpenes type (X3), and chitosan concentration (X4) as independent variables, while their impact was observed for entrapment efficiency percent (Y1; EE%), particle size (Y2; PS), zeta potential (Y3; ZP), and amount of drug released after 6 h (Y4; Q6h). Design Expert® was bestowed to nominate the desired formula. The selected INV was subjected to further studies and formulated into a mucoadhesive gel for ex-vivo and in-vivo investigations. The optimum INV showed a spherical shape with EE% of 65.01 ± 1.24%, PS of 243.75 ± 8.13 nm, PDI of 0.203 ± 0.01, ZP of 49.80 ± 0.42 mV, and Q6h of 53.16 ± 0.73%. Differential scanning calorimetry study asserted the capability of INVs to entrap PNL. Permeation studies confirmed the desired sustained effect of PNL-loaded INVs-gel compared to PNL-gel, INVs, and PNL solution. Sperm motility assay proved the potency of INVs-gel to inhibit sperm motility. Besides, the histopathological investigation verified the tolerability of the prepared INVs-gel. Taken together, the gained data justified the efficacy of PNL-loaded INVs-gel as a potential locally acting contraceptive.

Design, synthesis and antibacterial activity of novel metal complex of 3-amino-2-methyl 6-1odo quinazolin-4(3H)-one

Introduction: 4(3H)-quinazolinone rings have been reported to possess different biological activities such as antibacterial, antifungal, antitubercular, antiviral, anticancer. These activities also include antihypertensive, diuretic, antimicrobial, pesticidal, anticonvulsant, anaesthetic and sedative activities, anti-malarial, and anti-diabetic.The above observations and findings stimulated my interest to synthesize these novel, Co (ll) , Cu (ll) and Zn (ll) complexes of 3-amino-2-methyl-6-lodo-quinazolin-4 (3H)-one compounds. Methods: A new Ligand 3-amino-2-methyl 6-Iodo quinazolin-4(3H)-One (L) has been synthesized in good yield by the reaction of methyl 2-amino 5-Iodo benzoate with acetic anhydride, then replace the oxygen with nitrogen of hydrazine. When the ligand react with Co (11), Zn (11) and Cu (11) new complexes are formed. The chemical structure of all prepared compounds were characterized by elemental analysis, IR, UV/visible, 1H-NMR, 13C-NMR, and GCMS, moreover, molar ration M: L were also determined. The free Ligand and their metal complexes were tested in vitro against a number of microorganisms, gram positive bacteria (Staphylococcus aureus, Bacillus species and Enterococcus feacalis), gram negative bacteria (Escherichia coli, Klebsiella pneumonia, and pseudomonas aeruginosa) and fungi (Candida albicans) in order to assess their antibacterial properties. All our complexes showed considerable activity against all bacteria. Conclusions: From our findings, all the complexes synthesized have higher activities against the test microorganisms as compared to the ligand activity.

Comparative local anaesthetic activity of lignocaine, lignocaine-adrenaline and water extracts of Annona muricata during castration in dogs

Comparative local anaesthetic activity of lignocaine, lignocaine-adrenaline and water extracts of Annona muricata during castration in dogs

The role of voltage-gated calcium channels in the mechanisms of anesthesia and perioperative analgesia.

A family of neuronal voltage-gated calcium channels (VGCCs) have received only recently a significant consideration regarding the mechanisms of anesthesia because VGCC inhibition may be important in anesthetic action by decreasing neuronal excitability and presynaptic excitatory transmission. The T-type VGCCs channels (T-channels), although rarely involved in synaptic neurotransmitter release, play an important role in controlling neuronal excitability and in generating spontaneous oscillatory bursting of groups of neurons in the thalamus thought to be involved in regulating the state of arousal and sleep. Furthermore, these channels are important regulators of neuronal excitability in pain pathway. This review will provide an overview of historic perspective and the recent literature on the role of VGCCs and T-channel inhibition in particular in the mechanisms of action of anesthetics and analgesics. Recent research in the field of novel mechanisms of hypnotic action of anesthetics revealed significant contribution of the Ca V 3.1 isoform of T-channels expressed in the thalamus. Furthermore, perioperative analgesia can be achieved by targeting Ca V 3.2 isoform of these channels that is abundantly expressed in pain pathways. The review summarizes current knowledge regarding the contribution of T-channels in hypnosis and analgesia. Further preclinical and clinical studies are needed to validate their potential for developing novel anesthetics and new perioperative pain therapies.

Obstetric Anesthesia Procedure-Based Workload and Facility Utilization of Society of Obstetric Anesthesia and Perinatology Centers of Excellence Designated Institutions.

Optimal workload and staffing for obstetric anesthesia services have yet to be determined. We surveyed Society of Obstetric Anesthesia and Perinatology (SOAP) Centers of Excellence (COE) for Obstetric Anesthesia Care institutions to evaluate procedure-based obstetric anesthesia workload and facility use. After institutional review board (IRB) exemption, an online survey instrument (REDCap) was sent by email (1 initial and 2 reminders) to all SOAP COEs. Survey data included the number of deliveries, cesarean delivery rate, neuraxial labor analgesia rate, the number of labor and operating rooms, and the number of in-house and backup obstetric anesthesia providers. Obstetric anesthesia activity was estimated using a time-based workload ratio per provider (Stanford Work Index, 1.0 = clinically working every minute of every hour on duty) during weekday, weeknight, and weekend shifts. We compared workload between academic and nonacademic centers and correlated operating and labor rooms with cesarean and vaginal delivery volume. Fifty-one of 53 surveys were returned (96% response rate). Data from 33 academic and 14 nonacademic US institutions were analyzed. For academic centers, median Stanford Work Index for all staff (included trainees and Certified Registered Nurse Anesthetists) was 0.20 (weekday) and 0.19 (weeknight and weekends); nonacademic centers were 0.33 (weekday, P < .001 versus academic), 0.23 (weeknight, P = .009 versus academic), and 0.23 (weekends, P = .03 versus academic practices). Attending-only Stanford Work Indices were similar between academic and nonacademic centers. Total number of rooms on the obstetric suite (operating, labor, or triage room) was strongly correlated with delivery volume ( R2 = 0.55). The results outline staffing procedure-based workload ratios and facility utilization at SOAP COEs in the United States. These data can be used by other institutions that provide obstetric anesthesia services to guide their obstetric anesthesia staffing. The importance of considering the workload associated with different shifts and between academic and nonacademic centers is also highlighted. The results show that approximately one-third of an obstetric anesthesiologist's workload is spent on performing procedures. We did not, however, measure the other tasks anesthesiologists practice as peripartum physicians (eg, managing critically ill parturients, doing pre- and postprocedural evaluations, or performing emergent and unexpected procedures), and future studies are required to determine the time required to perform these tasks. Studies to determine the optimal staffing models to handle workload fluctuations and improve outcomes are also required.

Isoflurane inhibition of endocytosis is an anesthetic mechanism of action

The mechanisms of volatile anesthetic action remain among the most perplexing mysteries of medicine. Across phylogeny, volatile anesthetics selectively inhibit mitochondrial complex I, and they also depress presynaptic excitatory signaling. To explore how these effects are linked, we studied isoflurane effects on presynaptic vesicle cycling and ATP levels in hippocampal cultured neurons from wild-type and complex Imutant (Ndufs4(KO)) mice. To bypass complex I, we measured isoflurane effects on anesthetic sensitivity in mice expressing NADH dehydrogenase (NDi1). Endocytosis in physiologic concentrations of glucose was delayed by effective behavioral concentrations of isoflurane in both wild-type (τ [unexposed] 44.8± 24.2 s;τ [exposed] 116.1± 28.1 s; p<0.01) and Ndufs4(KO) cultures (τ [unexposed] 67.6± 16.0 s;τ [exposed] 128.4± 42.9 s; p= 0.028). Increasing glucose, to enhance glycolysis and increase ATP production, led to maintenance of both ATP levels and endocytosis (τ [unexposed] 28.0± 14.4;τ [exposed] 38.2± 5.7; reducing glucose worsened ATP levels and depressed endocytosis (τ [unexposed] 85.4± 69.3; τ [exposed]>1,000; p<0.001). The block in recycling occurred at the level of reuptake of synaptic vesicles into the presynaptic cell. Expression of NDi1 in wild-type mice caused behavioral resistance to isoflurane for tail clamp response (EC50 Ndi1(-) 1.27%± 0.14%; Ndi1(+) 1.55%± 0.13%) and halothane (EC50 Ndi1(-) 1.20%± 0.11%; Ndi1(+) 1.46%± 0.10%); expression of NDi1 in neurons improved hippocampal function, alleviated inhibition of presynaptic recycling, and increased ATP levels during isoflurane exposure. The clear alignment of cell culture data to invivo phenotypes of both isoflurane-sensitive and -resistant mice indicates that inhibition of mitochondrial complex I is a primary mechanism of action of volatile anesthetics.

The Use of Cinnamon Essential Oils in Aquaculture: Antibacterial, Anesthetic, Growth-Promoting, and Antioxidant Effects

Cinnamon essential oils (EOs) are widely known for their pharmaceutical properties; however, studies investigating the use of these EOs in aquaculture are scarce. The aims of this study were to evaluate the anesthetic effect of bathing silver catfish (Rhamdia quelen) with Cinnamomum cassia EO (CCEO) and its nanoemulsion (NCCEO); the growth-promoting and antioxidant effects of dietary supplementation with CCEO in silver catfish; and the in vitro antibacterial effect of CCEO, NCCEO, and Cinnamomum zeylanicum EO (CZEO) against bacteria isolated from diseased silver catfish. The two cinnamon EOs showed promising antibacterial activity, which was potentiated by the nanoemulsion. CCEO showed satisfactory anesthetic activity in silver catfish, and its nanoemulsion intensified the sedative activity. Supplementation of 1.0 mL CCEO per kg of diet for 60 days increased weight, length, and weight gain when compared to the control group, evidencing the growth-promoting activity of this EO. Dietary supplementation of CCEO for 30 and 60 days also showed an antioxidant effect, as it decreased levels of thiobarbituric acid reactive species and increased the superoxide dismutase activity in the liver of silver catfish. Therefore, cinnamon EOs have a promising use in aquaculture.

Effect of Local Anesthetics on Dipole Potential of Different Phase Membranes: A Fluorescence Study.

The molecular mechanism behind the action of local anesthetics is not well understood. Phenylethanol (PEtOH) is an ingredient of essential oils with a rose-like odor, and it has previously been used as a local anesthetic. In this work, we explored the effect of PEtOH on dipole potential in membranes representing biologically relevant phases, employing the dual-wavelength ratiometric method utilizing the potential-sensitive probe di-8-ANEPPS. Our results show that PEtOH reduces membrane dipole potential in membranes of all biologically relevant phases (gel, liquid-ordered, and fluid) in a concentration-dependent manner. To the best of our knowledge, these results constitute one of the early reports describing reduction of membrane dipole potential induced by local anesthetics, irrespective of membrane phase.

COMPARATIVE STUDY OF INTRATHECAL HYPERBARIC BUPIVACAINE 0.5% VERSUS MIDAZOLAM PLUS HYPERBARIC BUPIVACAINE 0.5% MIXTURE FOR INFRAUMBILICAL SURGERIES.

Background: Sub arachnoid block is a commonly used anesthesia technique for all infra umbilical surgeries &amp; there is search for agents and techniques which would prolong local anesthetic action without its deleterious effects. The present study was designed to compare effect of 0.5% of hyperbaric bupivacaine intrathecal versus 0.4ml of intrathecal midazolam with 0.5% of hyperbaric bupivacaine for infra umbilical surgeries. Material And Methods: Present study was single-center, a double-blind trial, conducted in patients of age group 18-60 years with ASA grade I/II posted for elective infraumbilical surgery. 60 patients were divided into Group I received 3ml of 0.5% Bupivacaine heavy and 0.4 ml of 0.9% saline &amp; Group II received 3ml of 0.5% Bupivacaine heavy and 0.4 ml of midazolam (2mg). The meanResults: duration of maximum sensory blockade, maximum motor blockade was more in group II as compared to group I &amp; difference was statistically signicant (p&lt;0.05). Mean duration of surgery was less in group II as compared to group I &amp; difference was statistically signicant (p&lt;0.05). Duration of Motor blockade, duration of sensory blockade, time for two segment regression, time of rescue analgesia was more in group II as compared to group I &amp; difference was statistically signicant (p&lt;0.05). Patients complained of pain faster in Group I than in Group II, VAS score. Midazolam still nds a place in regularConclusion: clinical use as an intrathecal adjuvant with hyperbaric bupivacaine due to its hemodynamic stability and better post-operative analgesia with no signicant adverse effects.

ACE Question

Article| May 2022 ACE Question ASA Monitor May 2022, Vol. 86, 16. https://doi.org/10.1097/01.ASM.0000830808.15004.67 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Search Site Citation ACE Question. ASA Monitor 2022; 86:16 doi: https://doi.org/10.1097/01.ASM.0000830808.15004.67 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll PublicationsASA Monitor Search Advanced Search Topics: anesthesiology continuing education (ace) Due to national drug shortages, your facility is unable to obtain bupivacaine. You are planning a peripheral nerve block, and the only preservative-free local anesthetic available is 1.5% mepivacaine. What would be the MOST likely result of using mepivacaine in comparison to bupivacaine? Mepivacaine is an intermediate-potency amide local anesthetic that can be used for peripheral nerve blockade. It is commonly available in a 1.5% concentration. When compared to longer-duration agents such as bupivacaine, the following differences are commonly noted: The addition of epinephrine (1:200,000) will prolong the action of local anesthetics administered for a peripheral nerve block. The extent of this prolongation is greater with intermediate-acting agents such as mepivacaine than with longer-acting agents such as bupivacaine. Anesthesiology Continuing Education (ACE) is a self-study CME program that covers established medical knowledge in the field of anesthesiology. ACE can help fulfill the CME requirements of MOCA®. To learn... You do not currently have access to this content.

Dexmedetomidine attenuates oxygen-glucose deprivation/ reperfusion-induced inflammation through the miR-17-5p/ TLR4/ NF-\u03baB axis

BackgroundDexmedetomidine (DEX) is a selective agonist of α2-adrenergic receptors with anesthetic activity and neuroprotective benefits. However, its mechanism of action at the molecular level remains poorly defined. In this study, we investigated the protective effects of DEX on oxygen-glucose deprivation/ reperfusion (OGD/R)-induced neuronal apoptosis in PC12 cells, and evaluated its underlying mechanism(s) of neuroprotection and anti-inflammation.MethodsAn OGD/R model in PC12 cells was established. PC12 cells were cultured and divided into control, OGD/R, and OGD/R + DEX (1 μM, 10 μM, 50 μM) groups. Cell apoptosis was analyzed by flow cytometry and expression profiles were determined by qRT-PCR, western blot analysis, and enzyme linked immunosorbent assays (ELISA). The interaction between miRNA and its downstream targets was evaluated through luciferase reporter assays.ResultsDEX significantly decreased apoptosis rates and inhibited interleukin 1 beta (IL-1β), tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) release (P < 0.05). While expression of the pro-apoptotic proteins Bax and Caspase-3 was down-regulated, expression of Bcl-2 was upregulated in a dose-dependent manner (P < 0.05). Interestingly, miR-17-5p expression was down-regulated in the OGD/R group (compared to controls). Toll-like receptor 4 (TLR4), a key regulator of nuclear factor kappa-B (NF-κB) signaling, was identified as a novel target of miR-17-5p in PC12 cells. miR-17-5p expression was upregulated in the OGD/R + DEX group, suppressing TLR4 expression and reducing the secretion of proinflammatory cytokines.ConclusionDEX inhibits OGD/R-induced inflammation and apoptosis in PC12 cells by increasing miR-17-5p expression, downregulating TLR4, and inhibiting NF-κB signaling.

Clinical results of the using leucocyte interferon for the therapy of viral pathology of the oral mucous in somatic patients with combined dentistry pathology

Aim. To conduct a clinical test of the unguent form of human leukocyte interferon in somatic patients with relapsing of herpetic stomatitis.Material and methods. 98 somatic patients with viral pathology of the oral mucous at the age of 20 to 60 years and older were studied to identify the clinical efficiency of the leukocyte interferon. The order of the clinical studies was specified by a special program: preparations were decrypted, decryption was conducted after the analysis of the results of the clinical study. Preparation 1 – placebo (2% emulsion of lidocaine on vinilin), preparation 2 – interferon’s unguent, preparation 3 – 0.5% oxoline unguent. After active implementation of the complex treatment of patients with mucologic pathology were divided into 3 groups: 1st group included 31 patients who got a course of the treatment by preparation 1; 2nd - 34 persons, 2 have taken preparation; 3rd - 33 patients, 3 used preparation.Results. The most expressed clinical effect in the treatment of relapsing of herpetic stomatitis in somatic patients with combined dentistry pathology was shown by preparation 2, which had local anesthetic and anti-inflammation action. Indicators of the recovery of patients who got this preparation in contrast with patients of the third group decreased on average by 2 days, the 1st groups - by more than 1 day.Conclusion. Using oxolin’s unguent and preparation 1 in course of the treatment of herpetic stomatitis did not prevent the development of secondary elements in the oral mucous (24.0% and 44.0% accordingly) in most of the patients. Using preparation 2, new elements on oral mucous were observed only in 6.0% of cases, which shows it good antiviral effect.

Anesthetic care for electroconvulsive therapy.

Counselling and medication are often thought of as the only interventions for psychiatric disorders, but electroconvulsive therapy (ECT) has also been applied in clinical practice for over 80 years. ECT refers to the application of an electric stimulus through the patient’s scalp to treat psychiatric disorders such as treatment-resistant depression, catatonia, and schizophrenia. It is a safe, effective, and evidence-based therapy performed under general anesthesia with muscle relaxation. An appropriate level of anesthesia is essential for safe and successful ECT; however, little is known about this because of the limited interest from anesthesiologists. As the incidence of ECT increases, more anesthesiologists will be required to better understand the physiological changes, complications, and pharmacological actions of anesthetics and adjuvant drugs. Therefore, this review focuses on the fundamental physiological changes, management, and pharmacological actions associated with various drugs, such as anesthetics and neuromuscular blocking agents, as well as the comorbidities, indications, contraindications, and complications of using these agents as part of an ECT procedure through a literature review and our own experiences.

High-pressure crystallography shows noble gas intervention into protein-lipid interaction and suggests a model for anaesthetic action

In this work we examine how small hydrophobic molecules such as inert gases interact with membrane proteins (MPs) at a molecular level. High pressure atmospheres of argon and krypton were used to produce noble gas derivatives of crystals of three well studied MPs (two different proton pumps and a sodium light-driven ion pump). The structures obtained using X-ray crystallography showed that the vast majority of argon and krypton binding sites were located on the outer hydrophobic surface of the MPs – a surface usually accommodating hydrophobic chains of annular lipids (which are known structural and functional determinants for MPs). In conformity with these results, supplementary in silico molecular dynamics (MD) analysis predicted even greater numbers of argon and krypton binding positions on MP surface within the bilayer. These results indicate a potential importance of such interactions, particularly as related to the phenomenon of noble gas-induced anaesthesia.

Cocaine: An Updated Overview on Chemistry, Detection, Biokinetics, and Pharmacotoxicological Aspects including Abuse Pattern.

Cocaine is one of the most consumed stimulants throughout the world, as official sources report. It is a naturally occurring sympathomimetic tropane alkaloid derived from the leaves of Erythroxylon coca, which has been used by South American locals for millennia. Cocaine can usually be found in two forms, cocaine hydrochloride, a white powder, or ‘crack’ cocaine, the free base. While the first is commonly administered by insufflation (‘snorting’) or intravenously, the second is adapted for inhalation (smoking). Cocaine can exert local anaesthetic action by inhibiting voltage-gated sodium channels, thus halting electrical impulse propagation; cocaine also impacts neurotransmission by hindering monoamine reuptake, particularly dopamine, from the synaptic cleft. The excess of available dopamine for postsynaptic activation mediates the pleasurable effects reported by users and contributes to the addictive potential and toxic effects of the drug. Cocaine is metabolised (mostly hepatically) into two main metabolites, ecgonine methyl ester and benzoylecgonine. Other metabolites include, for example, norcocaine and cocaethylene, both displaying pharmacological action, and the last one constituting a biomarker for co-consumption of cocaine with alcohol. This review provides a brief overview of cocaine’s prevalence and patterns of use, its physical-chemical properties and methods for analysis, pharmacokinetics, pharmacodynamics, and multi-level toxicity.

PHARMACOLOGICAL ACTIVITY OF NEW COMPOSITION WITH A DIMETHYLACETAMIDE DERIVATIVE IN INFRAORBITAL ANESTHESIA IN RATS WITH PERIODONTITIS

The safety and local anesthetic activity of the pharmaceutical composition LHT-15-13 containing a dimethylacetamide derivative, an antioxidant and a vasoconstrictor in rats with chronic periodontitis was studied in the work. White laboratory mice were used to determine acute toxicity with intravenous and subcutaneous administration of a 2% aqueous solution of LHT-15-32. In rats with experimental periodontitis, the threshold of pain sensitivity of the second upper molar was determined. The activity of oxidative stress and total antioxidant activity was determined in the mucous membrane of the gums of rats by the method of induced chemiluminescence. Local changes in periodontal tissues were assessed by quantitative enzyme immunoassay. The acute toxicity of the pharmaceutical composition when administered intravenously and subcutaneously was lower than that of the dimethylacetamide derivative with succinic acid LHT-600. LHT-15-13, when administered infraorbitally, caused deep anesthesia that lasted more than 70 minutes, activated the local antioxidant defense system and reduced the level of IL-1β in the gum tissue, caused tissue repair around the impacted upper molar in rats five days after injection. Thus, the pharmaceutical composition can be considered as an effective and safe agent for pain relief of the upper molars in periodontitis.

The Binding of Alpinia galanga Oil and Its Nanoemulsion to Mammal GABAA Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform.

The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A (GABAA) receptors in rat cortical membranes, was investigated using a [3H]muscimol binding assay and an in silico modeling platform. The results showed that only AGO and methyl eugenol displayed a positive modulation at the highest concentrations, whereas 1,8-cineole and 4-allylphenyl acetate were inactive. The result of AGO correlated well to the amount of methyl eugenol in AGO. Computational docking and dynamics simulations into the GABAA receptor complex model (PDB: 6X3T) showed the stable structure of the GABAA receptor–methyl eugenol complex with the lowest binding energy of −22.16 kcal/mol. This result shows that the anesthetic activity of AGO and methyl eugenol in mammals is associated with GABAA receptor modulation. An oil-in-water nanoemulsion containing 20% w/w AGO (NE-AGO) was formulated. NE-AGO showed a significant increase in specific [3H]muscimol binding, to 179% of the control, with an EC50 of 391 µg/mL. Intracellular studies show that normal human cells are highly tolerant to AGO and the nanoemulsion, indicating that NE-AGO may be useful for human anesthesia.