Short Duration Of Action Research Articles

Efficacy of Intrathecal 0.75% Hyperbaric Ropivacaine versus 0.5% Hyperbaric Bupivacaine for Elective Inguinal and Perineal Surgery: A Randomised Double-blinded Clinical Study

Introduction: Ropivacaine, an amide local anaesthesia, often considered safer alternative to bupivacaine. Bupivacaine, a longer-acting agent that provides dense motor blockade, is known to carry a higher risk of re-entrant arrhythmias and cardiac depression with accidental intravascular injection. The shorter duration of action, coupled with profound sensory block and comparatively less side-effects, makes ropivacaine useful in tackling cases of day care surgery. Aim: To compare the efficacy of hyperbaric ropivacaine versus bupivacaine for elective inguinal and perineal surgery under spinal anaesthesia in terms of time of sensory and motor block, time taken to reach peak T8 level sensory block, total duration of both sensory and motor block, time of first micturition, and any associated side-effects. Materials and Methods: The present randomised double-blind clinical study, was carried out in the Department of Anaesthesia, Dr. D. Y Patil Medical College, Hospital and Research Centre (tertiary healthcare centre), Pune, Maharashtra, India, from March 2023 to August 2023. Study involved 30 patients aged 18-60, classified as American Society of Anaesthesiologists (ASA) grade I and II. Patients were randomly assigned to group RH (receiving hyperbaric ropivacaine) or group BH (receiving hyperbaric bupivacaine). The study assessed for onset and duration of sensory block at T-8 dermatome. The study also assessed motor block onset and duration using modified Bromage scale, observing postoperative micturition, intraoperative haemodynamic changes and adverse effects. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software version 16.0, with a p-value of <0.05 considered significant. Results: Demographic profile in terms of age {Mean±Standard Deviation (SD) in group RH: 42.93±14.73 years vs group BH: 39.06±11.94 years), gender distribution, type of surgery performed and its duration (group RH: 85.67±39.5 minutes vs group BH: 98.4±32.8 minutes) was not significant. The onset of sensory block (2.09±0.69 min) and motor block (3.52±0.66 min), the time taken to reach T8 level (3.40±0.93 min), was faster in the hyperbaric ropivacaine group. Similarly, the duration of motor block (261.93±73.21 min), time taken for the recession of the sensory block to S2 (351.4±66.78 min), and the recession of the motor block to Bromage scale 0 (291.93±64.93 min) were faster in ropivacaine group. The time taken for the passage of first micturition post-subarachnoid block was earlier (338.73±31.29 min) in ropivacaine group. Conclusion: A 0.75% hyperbaric ropivacaine is more efficacious, with faster onset of sensory and motor blockade, relatively quick recovery profile, and an earlier time of first micturition in comparison to 0.5% hyperbaric bupivacaine.

Preparation and evaluation of oral insulin nanocapsule delivery systems.

Insulin therapy is essential for regulating blood sugar levels. Conventional subcutaneous injection is prone to psychological stress, local tissue damage and severe blood glucose fluctuations, and thus the development of oral insulin technology has become an alternative therapy. However, oral insulin faces challenges such as difficult absorption, poor adhesion, low bioavailability, and short duration of action, due to the large molecular weight, low permeability, and easily degradable by enzymes and gastric acids. In this study, oral insulin nanocapsule delivery systems (Orl-Ins-NPs) were developed by using polylactic acid-co-glycolic acid (PLGA) as the encapsulation material for insulin loading. After preparation, optimization and characterization, the mean size of Orl-Ins-NPs was 140.08 nm, the encapsulation efficiency of the system was 54.3 %, and the loading capacity of insulin was 2.2 %. In addition, cationic modification with chitosan/ polyethyleneimine promoted adhesion and permeation of the intestinal mucus layer, and surface coating with pH-responsive methyl methacrylate trimethylamine ethyl chloride copolymer achieved 100 % gastric protection. The results of rat blood glucose test showed that, subcutaneous injection of the control group reduced blood glucose concentrations within 1 h and returned to initial levels within 4 h, while Orl-Ins-NPs slowly reduced blood glucose concentration to 51.3 % of the initial level and maintains stability within 10 h. Orl-Ins-NPs exhibited good physicochemical stabilities, sustained release property, improved in vitro acid resistance, as well as long-term in vivo hypoglycemic effect. This system demonstrates its potential clinical application in oral insulin and other protein drugs delivery.

Fabrication of Hypoxia-Mimicking Supramolecular Hydrogels for Cartilage Repair.

Despite advancements in chronic arthritis treatment, there remains a significant demand for advanced nanotechnologies capable of efficiently delivering a wide range of therapeutic agents to provide symptomatic relief and facilitate the healing of inflamed cartilage tissue. Considering the significant impact of hypoxia on the development and maintenance of chondral tissue, replicating its effects on stem cells could be a potential approach for the treatment of osteoarthritis (OA). Cobalt is a prominent hypoxia-inducing agent, owing to its ability to activate the hypoxia-inducible factor (HIF) pathway regardless of cellular oxygen levels. The intra-articular (IA) injection of dexamethasone (Dex) is often used to alleviate inflammation and pain associated with OA. Nevertheless, several obstacles impede the drug's efficacy, including its short duration of action and rapid elimination from the joint space. Considering these research problems, the study brings an advanced strategy for the development of a three-dimensional (3D) bioprintable hypoxia-mimicking supramolecular hydrogel (HMSG) through the self-assembly of Dex-loaded poly(ethylene glycol) diacrylate (PEGDA) guest polymers with acryloyl β-cyclodextrin (AβCD) host monomers, in combination with cobalt nanowires (Co NWs). Through the process of photo-cross-linking, HMSG can generate multivalent host-guest nanoclusters, making it an excellent candidate for 3D bioprinting, showcasing remarkable mechanical properties. By effectively delivering Dex and Co2+ in a sustained manner, the HMSG affords a suitable microenvironment for the encapsulated umbilical cord-derived mesenchymal stem cells (UMSCs), thereby promoting the synthesis of matrix components and decreasing the release of catabolic factors. Moreover, the HMSG ameliorates OA severity by increasing the M2 macrophage polarization, which can ultimately contribute to immunomodulatory effects. In conclusion, the results propose potential approaches for utilizing HMSG as efficient carriers to transport various therapeutic molecules to the injury site, thereby assimilating into nearby tissues and promoting successful tissue repair without the need for external growth factors.

Pharmacokinetics and pharmacodynamics of ciprofol after continuous infusion in elderly patients

BackgroundCiprofol, a novel intravenous anesthetic, which has primarily been used for the induction and maintenance of general anesthesia in adults, is characterized by rapid onset, short duration of action, and quick and smooth recovery. However, the pharmacokinetic characteristics of continuous infusions and the correlation between the plasma concentration and the bispectral index (BIS) in elderly patients are still unknown.MethodIn this randomized, controlled study, thirty elderly patients (62–78 years old) undergoing elective gastrointestinal tumor resection were treated with propofol (N = 15) or ciprofol (N = 15) as sedatives during anesthesia. After induction, ciprofol/propofol was continuously infused intravenously until the end of the operation. Perioperative vital signs, injection pain, adverse events (AEs), BIS values, eyelid reflex disappearance times, and recovery times were recorded. The plasma concentrations of ciprofol and propofol were measured by liquid chromatography tandem mass spectrometry (LC‒MS/MS) and the pharmacokinetics were determined by noncompartmental analysis.ResultsBoth drugs caused a decrease in blood pressure and heart rate after induction. Eight cases (53. 3%) of hypotension and 3 cases (20%) of bradycardia occurred in the propofol group, while 8 cases (53. 3%) of hypotension and 5 cases (33. 3%) of bradycardia occurred in the ciprofol group. At intubation, the ciprofol group experienced fewer fluctuations in blood pressure than the propofol group. Ciprofol resulted in only one case (6.7%) of mild injection pain, less than that produced by propofol (10/15, 66.7%) (P < 0.05). Anesthesia induction was successfully completed with both drugs, and there were no significant differences in eyelash reflex disappearance or recovery time between the two groups. The plasma concentrations during maintenance were relatively stable in both groups (propofol 1.78 ± 0.67 μg/mL, ciprofol 0.71 ± 0.23 μg/mL), and a suitable depth of sedation was achieved with a BIS of 40–60. The pharmacokinetic (PK) parameters for ciprofol are listed as follows: Maximum Plasma Concentration (Cmax) 6.02 ± 2.13 μg/ml; Time to Maximum Concentration (Tmax) 0.18 ± 0.62 min; Apparent Volume of Distribution (Vz) 3.96 ± 0.84 L/kg; Total Clearance (CL) 0.83 ± 0.14 L/h/kg; Half-life (t½) 3.47 ± 1.85 h; Area Under the Curve (AUC) 5000 ± 900 L/h/kg; Terminal Elimination Rate Constant (λz) 0.23 ± 0.07 1/h. Similar to propofol, the plasma concentration of ciprofol was linearly correlated with the BIS.ConclusionCiprofol, a novel intravenous anesthetic, can be safely and effectively used in elderly patient continuous infusion with minimal injection pain. Plasma concentrations of ciprofol correlate well with BIS values, helping control sedation depth. For elderly patients undergoing gastrointestinal tumor surgery, an optimal maintenance dose of 0.8 mg/kg/h is recommended.Trial registrationThis clinical trial (registration No: ChiCTR2100047580, https://www.chictr.org.cn. The pre-registration date was June 20, 2021, and the review approval and official case solicitation began in December 2021; Retrospectively registered) was conducted in accordance with the World Medical Congress Declaration of Helsinki and Good Clinical Practice guidelines. All study subjects provided written informed consent.

X-ray Responsive Antioxidant Drug-Free Hydrogel for Treatment of Radiation Skin Injury.

Radiotherapy (RT) is widely applied in tumor therapy, but inevitable side effects, especially for skin radiation injury, are still a fatal problem and life-threatening challenge for tumor patients. The main components of topical radiation protection preparations currently available on the market are antioxidants, such as SOD, which are limited by their unstable activity and short duration of action, making it difficult to achieve the effects of radiation protection and skin radiation damage treatment. Therefore, we designed a drug-free antioxidant hydrogel patch with encapsulated bioactive epidermal growth factor (EGF) for the treatment of radiation skin injury. The X-ray responsive hydrogel formed by copolymerization of the disulfide-containing hyperbranched poly(β-hydrazide ester) macromer polymer (PBAE), methacryloylated hyaluronic acid, and acrylamide exhibits continuous antioxidant activity through the oxidation of disulfide bonds in PBAE as well as the triggered release of EGF after X-ray responsive breakage of the polymer network to finally promote radioactive wound healing. Upon radiotherapy, the antioxidant hydrogel is able to alleviate local oxidative stress by continuously eliminating excessive ROS and can prevent deterioration of radiation skin injury. Moreover, the drug-free hydrogel with its excellent antioxidant property can overcome the disadvantages of traditional medicine (such as poor solubility, random diffusion, rapid drug clearance, and interference with tumor efficacy). Notably, the drug-free hydrogel exhibits a negligible effect for tumor therapy because the antioxidant hydrogel acts only on the epidermis and displays no shielding effect for ionization radiation. Ultimately, in vivo animal studies affirm the efficacy of our methodology, wherein the administration of the antioxidant hydrogel on acute irradiated skin attenuates the progression of radiation skin injury and promotes radioactive wound healing. This innovative strategy points out a new inspiration for the precise treatment of skin radiation damage with X-ray responsive antioxidant drug-free hydrogels.

Remimazolam, a novel drug, for safe and effective endoscopic sedation.

Remimazolam is a novel benzodiazepine with unique pharmacokinetic and pharmacodynamic properties, making it an ideal candidate for sedation during endoscopic procedures. Distinguished by its rapid onset and short duration of action, remimazolam offers a safer and more efficient alternative to traditional sedatives, such as midazolam and propofol, with fewer side effects, such as hypotension, bradycardia, and respiratory depression. This article reviews the characteristics of remimazolam and its practical advantages, including ease of use, quick recovery time, and minimal residual sedation, emphasizing its potential to improve patient safety and procedural efficiency in clinical endoscopy settings.

Pharmacokinetic and Pharmacodynamic Equivalence of Biosimilar and Reference Ultra-Rapid Lispro: A Comparative Clamp Study in Healthy Volunteers.

Ultra-rapid insulin lispro is an innovative insulin analogue designed to achieve rapid onset and short duration of action, aimed at optimizing glycemic control in patients with diabetes. This was a double-blind, randomized, 2-period, crossover clamp study to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD), along with safety profiles, of a potential biosimilar ultra-rapid insulin lispro compared to the reference product in healthy White men. A total of 35 healthy volunteers completed hyperinsulinemic euglycemic clamp procedures across both study periods. Blood samples were collected at predefined intervals up to 8hours to assess PK parameters. Plasma glucose levels were monitored every 5minutes during the 8-hour clamps, with adjustments to the glucose infusion rate to maintain the target range. Insulin quantification in plasma was conducted using a validated enzyme-linked immunosorbent assay method. PD assessment was based on glucose infusion rate profiles during both clamps. Geometric mean ratios for maximum plasma concentration and area under the concentration-time curve from insulin administration to the last measurable concentration for the test and reference drugs fell within the bioequivalence range of 80%-125%. Furthermore, the investigational drugs demonstrated comparable PK/PD profiles of insulin lispro. Both formulations exhibited similar safety profiles primarily characterized by mild injection site reactions.

Ciprofol: A Comprehensive Review of Its Pharmacological Profile, Clinical Efficacy, and Future Directions in Anesthetic Practice

Background: Intravenous anesthetic agents are essential for the induction and maintenance of anesthesia, acting on the central nervous system (CNS) to induce unconsciousness, immobility, and amnesia. Propofol is widely used due to its rapid onset, short duration of action, and smooth recovery profile. However, its use can be associated with adverse effects, including injection site pain, dose-dependent hypotension, and respiratory depression. The need to address these limitations has driven the development of ciprofol (HSK3486), a novel intravenous anesthetic agent designed to retain propofol’s efficacy while improving its safety profile. Objectives: This review evaluates the pharmacological profile, clinical efficacy, safety, and tolerability of ciprofol and its potential advantages over propofol. It also highlights knowledge gaps and future research directions. Methods: A comprehensive review of peer-reviewed studies, clinical trials, and systematic reviews was performed to assess ciprofol’s pharmacodynamics, pharmacokinetics, and clinical performance in surgical and diagnostic settings. Results: Ciprofol exerts its anesthetic effects by modulating GABA_A receptors, enhancing inhibitory neurotransmission. Structural modifications, including the incorporation of a cyclopropyl group, increase its receptor binding affinity, contributing to reduced injection pain and improved hemodynamic stability. Clinical studies indicate that ciprofol provides effective sedation and anesthesia at lower doses, with fewer incidences of hypotension, bradycardia, and respiratory depression compared to propofol. It demonstrated consistent efficacy in elderly patients and those with hepatic or renal impairments, with minimal need for dose adjustments. Conclusion: Ciprofol represents a significant advancement in intravenous anesthetic agents, offering enhanced patient safety and comfort. Its reduced side effect profile and favorable pharmacokinetics support its use as an alternative to propofol, particularly in high-risk and critically ill patients. However, further research is needed to address long-term safety, evaluate its role in intensive care unit sedation, and explore potential neuroprotective effects.

Comparative analysis of weed management techniques in taro (Colocasia esculenta (L.) Schott)

Weed management poses a significant challenge in taro cultivation since it’s a long-duration crop grown during the monsoon season. The warm, humid conditions of its extended growing period promote rapid weed germination and growth, complicating weed management efforts. To address this issue, a study was conducted at the Bangladesh Agricultural Research Institute, Jashore, in 2021 and 2022 to evaluate sustainable weed management strategies for taro. The experiment, designed as a randomized complete block (RCB) with three replications, tested seven weed control methods: T1= straw mulching (SM), T2= pre-emergence herbicide+SM, T3= poly mulching (PM), T4= pre-emergence herbicide+PM, T5= intercropping+two hand-weeding, T6= pre-emergence herbicide, and T7= four hand-weeding, alongside T8= weed-free and T9= weedy control treatments. Results indicated that all mulching treatments achieved 70% to 80% weed control efficiency, significantly reducing weed growth up to 120 days after emergence (DAE). The intercropping+hand-weeding treatment provided 75% to 80% weed control up to 90 DAE. Among the mulches, straw mulching resulted in the tallest and widest plant base girths, leading to the highest yield and benefit-cost ratio, followed by other mulch and intercropping+hand-weeding treatments. Pre-emergence herbicide treatments were ineffective due to their short duration of action. Additionally, combining mulching (SM &amp; PM) with pre-emergence herbicide offered no advantage over mulching alone. These findings highlight straw mulch as the most effective weed management strategy for taro, eliminating the need for herbicides. Where mulch is unavailable, intercropping combined with hand weeding can be a viable alternative for effective weed control.

Structured Polymers Enable the Sustained Delivery of Glucocorticoids within the Intra-Articular Space.

Intra-articular glucocorticoid injections are effective in controlling inflammation and pain in arthritides but restricted by short duration of action and risk of joint degeneration. Controlled drug release using biocompatible hydrogels offers a unique solution, but limitations of in situ gelation restrict their application. Gellan sheared hydrogels (GSHs) retain the advantages of hydrogels, however their unique microstructures lend themselves to intra-articular application - capable of shear thinning under force but restructuring at rest to enhance residence. This study examined GSHs for extended intra-articular glucocorticoid delivery of prednisolone (10 mgmL-1); demonstrating links between material mechanics, steroid release, and preclinical assessment of efficacy in synoviocyte culture and transgenic(TNF)197Gkl (TNFtg) murine model of arthritis. GSHs demonstrated sustained release, with typical Fickian profiles over 18 days. Moreover, systems showed good stability under extended culture, with inherent cell-compatibility and suppression of inflammatory synoviocyte activation. In TNFtg animals, GSHs suppressed synovitis (70.08%, p < 0.05), pannus formation (45.01%, p < 0.05), and increased articular cartilage (82.23%, p < 0.05) relative to vehicle controls. The extended profile of steroid release from injectable GSH formulations holds promise in the treatment and management of inflammatory arthritides such as rheumatoid and osteoarthritis, representing a step-change in intra-articular drug delivery to suppress long-term joint inflammation.

Intranasal trimethyl chitosan-coated emulsomes containing tizanidine as brain-targeted therapy in spasticity: formulation, optimization, and pharmacokinetic assessment.

Tizanidine HCl (TZN) is an FDA-approved medication for treating spasticity. However, its oral administration presents obstacles to its efficacy, as it has a short duration of action and a low rate of absorption into the circulation (less than 40%) due to its rapid breakdown in the liver. In addition, its hydrophilic properties limit its capacity to cross the blood-brain barrier, thereby prohibiting it from reaching the central nervous system, where it can exert its intended therapeutic effects. Furthermore, diet-dependent absorption leads to fluctuations in bioavailability. Thus, this work aimed to create TZN-loaded chitosan-coated emulsomes (TZN-CTS-EMS) for intranasal administration, bypassing hepatic metabolism and boosting brain bioavailability. TZN-CTS-EMS were made using a thin film hydration approach. The influence of the independent parameters on the vesicle characteristics was examined and optimized using a Box-Behnken experimental methodology. The optimized formulation expected by the experimental design exhibited a greater desirability factor, characterized by a smaller particle size (127.63 nm), higher encapsulation efficiency (67.36%), and higher zeta potential (32.49 mV). As a result, it was chosen for additional in vivo assessment. Histopathological examinations showed no structural injury or toxicity to the nasal mucosa. Compared to intranasal TZN solution (TZN-SOL), the pharmacokinetics analysis demonstrated that intranasal TZN-CTS-EMS had a relative bioavailability of 191.9% in the plasma and459.3% in the brain. According to these findings, intranasal administration of the optimized TZN-CTS-EMS may represent a viable, noninvasive substitute for effective TZN delivery to brain tissues, potentially leading to improved safety and pharmacological efficiency.

Therapeutic Potential of Cannabinoids in Glaucoma – Hit or Myth? - A Review

Introduction: Glaucoma is a leading cause of irreversible blindness, characterized by elevated intraocular pressure (IOP) that damages the optic nerve. Current treatments mainly focus on reducing IOP, but some patients do not respond adequately to conventional therapies. Cannabinoids, particularly Δ9-tetrahydrocannabinol (Δ9-THC), have been investigated as potential adjunctive treatments for glaucoma. Studies have shown varying effects of cannabinoids on IOP regulation, though their precise mechanisms remain unclear. Aim of Study: This study aims to evaluate the therapeutic potential of cannabinoids in the treatment of glaucoma by examining their effects on IOP, their mechanisms of action, and the risks and benefits associated with their use. Material and methods: A comprehensive literature review of studies on the therapeutic potential of cannabinoids in glaucoma was conducted using the PubMed database. Results and Conclusions: Cannabinoids, especially Δ9-THC, have demonstrated the ability to reduce IOP in both healthy individuals and glaucoma patients. However, the effect is typically short-lived, lasting only 3-4 hours. The efficacy of cannabinoids in reducing IOP is influenced by the method of administration (oral, intravenous, inhalation) and the delivery system used for topical application. Despite some promising results, the use of cannabinoids as a mainstream glaucoma treatment is limited by factors such as the short duration of action, the potential for addiction, and the occurrence of adverse effects like tachycardia, hypotension, and cognitive impairment. Although cannabinoids offer a unique approach to glaucoma management, further research is necessary to address these limitations and determine their long-term therapeutic viability.

Safety Profiles Related to Dosing Errors of Rapid-Acting Insulin Analogs: A Comparative Analysis Using the EudraVigilance Database.

Diabetes is a widespread condition that can lead to multiple and severe complications. Rapid-acting insulin analogs (RAIAs) and long-acting insulin analogs are prescribed for the effective management of diabetes. RAIAs are expected to be associated with a higher number of dosing errors because of their rapid onset, short duration of action, and the need for frequent dosing, compared to other insulin analogs. There are three approved RAIAs on the market: insulin lispro (LIS), insulin aspart (ASP), and insulin glulisine (GLU). The aim of this study is to evaluate the real-world evidence on dosing errors reported for RAIAs in EudraVigilance (EV), an established pharmacovigilance database, in comparison to other insulin analogs and human insulins. A descriptive analysis and a disproportionality analysis were conducted. ASP and LIS were associated with high percentages of adverse drug reactions (ADRs) (22% and 17%, respectively), with over 70% of the reports involving serious ADRs. A higher frequency of cardiac and eye disorder ADRs was observed for LIS compared with ASP and GLU. GLU showed a higher frequency of ADRs in the skin and subcutaneous tissue disorders category. LIS dosing errors accounted for 5% of the total number of cases, while dosing errors for ASP and GLU were less than 3%. The most frequently reported dosing errors involved improper dosing (49%). Although there were fewer dosing errors of RAIAs in comparison to other insulins, the severity of the potential outcome highlights the importance of precise dosing and timing. Improved the monitoring and reporting of these dosing errors could enhance diabetes patient care. Additionally, smart medical devices could improve therapeutic outcomes.

Progress in the development of an Advax-adjuvanted protein capsular matrix vaccine against typhoid fever

Typhoid fever, caused by Salmonella Typhi, remains a significant global public health concern, with an estimated 11 &amp;ndash; 20 million cases annually. Vaccines are critical to controlling typhoid fever. Widespread vaccination diminishes the emergence of antibiotic-resistant strains of S. Typhi. The economic benefits of vaccination are also substantial, as the costs of treating typhoid fever and its complications can be significant. Ty21a&amp;reg;, a killed whole-cell vaccine, and Vivotif&amp;reg;, a live-attenuated vaccine, have been available for decades but have relatively short durations of action and only provide partial protection. Vi polysaccharide-conjugate vaccines have improved the durability of protection, but there is still room for improvement. Typhax&amp;trade;, a novel alternative to traditional conjugate vaccines, utilizes Vi polysaccharide that is non-covalently entrapped in a poly-L-lysine and CRM197 protein matrix crosslinked by glutaraldehyde. When formulated with Advax-CpG&amp;trade; adjuvant, Typhax demonstrated promising results in a range of animal models including mice, rabbits, and non-human primates in which it induces high and sustained serum anti-Vi immunoglobulin G and serum bactericidal activity, without any safety or reactogenicity issues. This novel vaccine approach offers the potential for a low-cost, more effective, and durable vaccine against typhoid fever, avoiding the need for frequent booster doses.

Possibility of Combined Use of Thymol and Carvacrol to Control the Number of Peach Aphids Myzus persicae (Sulzer, 1776)

The wide range of biological activity of essential oils in relation to pests gives reason to consider them as additional plant protection products and in other measures aimed at reducing the number of harmful arthropods. This paper presents the results of a study of the biological activity of a mixture of thymol and carvacrol, which are part of the essential oils of many plants, including oregano Origanum vulgare L. for the peach aphid Myzus persicae. The use of essential oil and a mixture of its components as fumigants has demonstrated their high aphidocidal potential. When processing the leaves of a forage plant (beans), the ability of a mixture of thymol and carvacrol to reduce the viability of female aphids and the number of offspring was established, and on vegetative plants (pepper) to negatively affect the survival of individuals of the daughter generation in the preimaginal period. The short duration of action allows the use of oils and individual components in conjunction with biological control agents and pollinators, and assumes a slight or complete absence of residues in food products. Preparations based on essential oils of plants can be used immediately before harvesting, due to the minimum waiting period.

Efficacy of QuickSleeper Intraosseous Injection of 4% Articaine in Mandibular First Molars With Symptomatic Irreversible Pulpitis: A Randomized Controlled Trial.

To evaluate the anesthetic efficacy of 4% articaine with 1:100,000 epinephrine via primary intraosseous (IO) injection with the QuickSleeper device vs inferior alveolar nerve block (IANB) for mandibular first molars diagnosed with symptomatic irreversible pulpitis (SIP). Sixty-four patients with a first mandibular molar with SIP were randomly divided into 2 groups: IO (n = 32) and IANB (n = 32). Each received either an IO injection with the 5th generation QuickSleeper device or a conventional IANB with 1.7 mL 4% articaine with 1:100,000 epinephrine. Success was defined as no/mild pain upon the access cavity preparation and initial filing. Injection pain, anesthetic onset, heart rate (HR) change, HR recovery time, and duration of anesthesia were also recorded and analyzed. The success rates were 40.6% for IANB and 81.2% for IO (P < .001). IO exhibited a significantly lower injection pain (P = .027), a shorter onset of action (P < .001), a greater heart rate increase (P < .001), a faster heart rate recovery time (P < .001), and a shorter duration of action (P < .001) vs IANB. Primary IO anesthesia using the fifth generation of the QuickSleeper device was more successful than IANB when using 4% articaine with 1:100,000 epinephrine to anesthetize mandibular first molars with SIP. The QuickSleeper device appeared to be a viable alternative to IANB for mandibular anesthesia.

Analysis of Intravenous Ketamine Bolus in Pediatric Emergency Care

Considering the increasing use of intravenous ketamine in pediatric emergency care, particularly for sedation, analgesia, and management of severe conditions such as traumatic brain injury and suicidal ideation, there is a need to critically evaluate its efficacy and safety in these settings. This study aims to systematically review and analyze various studies that have investigated the use of intravenous ketamine bolus in pediatric emergency care, focusing on its clinical outcomes, safety profile, and overall effectiveness. To achieve this, a narrative literature review was conducted, examining studies published between 2014 and 2023. The review included randomized controlled trials, observational studies, and case reports sourced from reputable databases such as PubMed, Scopus, and Web of Science. The results of the review indicate that intravenous ketamine is effective in providing rapid sedation and analgesia, with a favorable safety profile when administered by trained healthcare professionals. Specifically, it was observed that ketamine significantly reduces pain intensity, lowers suicidal ideation, and effectively manages intracranial pressure in children with severe traumatic brain injury. However, the review also highlights the variability in recovery times and the incidence of mild to moderate side effects, such as dizziness, nausea, and drowsiness. In addition, the need for rescue doses was more frequent in intravenous administration compared to intramuscular routes, though intravenous administration offered quicker onset and shorter duration of action. It is concluded that while intravenous ketamine is a valuable tool in pediatric emergency care, its administration should be carefully monitored, particularly in high-risk patients, to mitigate potential adverse effects. Further research is needed to refine dosing strategies, explore long-term outcomes, and establish standardized protocols to maximize the therapeutic benefits of ketamine while minimizing risks.

Discovery, synthesis and SAR of 2-acyl-1-biarylmethyl pyrazolidines, dual orexin receptor antagonists designed as fast and short-acting sleeping drugs

Dual orexin receptor antagonists (DORAs) are approved for the treatment of sleep onset and/or sleep maintenance insomnia. In the present disclosure, we report the discovery of a new class of DORAs designed to treat sleep disorders requiring a fast onset and a short duration of action (<4 h). We used early human pharmacokinetic-pharmacodynamic (PK-PD) predictions and in vivo experiments to identify DORAs eliciting this specific hypnotic profile. A high-throughput screening campaign revealed hits based on a rarely precedented tricyclic pyrazolidine scaffold. After unsuccessful structure–activity-relationship (SAR) studies on this hit series, a scaffold hopping exercise, aimed at reducing the molecular complexity of the tricyclic scaffold, resulted in the discovery of the 2-acyl-1-biarylmethylpyrazolidine series. SAR studies on this achiral series gave rise to the lead compound DORA 42. In vitro and in vivo parameters of DORA 42, and its PK-PD simulation for human use are detailed.

Design and Evaluation of 3-Phenyloxetane Derivative Agonists of the Glucagon-Like Peptide-1 Receptor.

Various small molecule GLP1R agonists have been developed and tested for treating type 2 diabetes (T2DM) and obesity. However, many of these new compounds have drawbacks, such as potential hERG inhibition, lower activity compared to natural GLP-1, limited oral bioavailability in cynomolgus monkeys, and short duration of action. Recently, a new category of 3-phenyloxetane derivative GLP1R agonists with enhanced hERG inhibition has been discovered. Using an AIDD/CADD method, compound 14 (DD202-114) was identified as a potent and selective GLP1R agonist, which was chosen as a preclinical candidate (PCC). Compound 14 demonstrates full agonistic efficacy in promoting cAMP accumulation and possesses favorable drug-like characteristics compared to the clinical drug candidate Danuglipron. Additionally, in hGLP-1R knock-in mice, compound 14 displayed a sustained pharmacological effect, effectively reducing blood glucose levels and food intake. These findings suggest that compound 14 holds promise as a future treatment option for T2DM and obesity, offering improved properties.

Efficacy and Mechanism of Acupoint Catgut Embedding in the Treatment of Chronic Spontaneous Urticaria: Protocol for a Randomized Double-Blind Placebo-Controlled Trial.

Chronic spontaneous urticaria (CSU) is a common chronic inflammatory skin disease that manifests as itching and wheals, seriously affecting quality of life. Clinical observations and previous research trials have shown that acupuncture is safe and effective for the treatment of CSU. However, there are problems, such as a short duration of action and frequent treatment. Compared with traditional acupuncture, acupoint catgut embedding (ACE) has the advantages of a longer effect and higher compliance. Clinical trials are needed to prove its efficacy and mechanism of action. This trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. This is a randomized, double-blind, placebo-controlled trial. In this trial, 108 participants aged 18-60 years with a diagnosis of CSU and no history of ACE will be randomly assigned to 2 groups (1:1 ratio) using the Statistical Analysis System: treatment (ACE) and control (sham ACE). The participants and efficacy evaluators will be blinded to the grouping. Both the ACE and sham ACE groups will undergo acupuncture, but the sham ACE group will not receive catgut sutures. Treatment will be performed twice weekly for 8 weeks, with a 1-week run-in period and a 16-week follow-up period. Twenty patients will be randomly selected to undergo functional magnetic resonance imaging before and after the treatment period. The primary outcome will be the urticaria activity score over 7 days (UAS7). We will use R (version 4.0.1; R Project for Statistical Computing) to perform ANOVA and independent samples t tests to compare the differences within and between groups before and after treatment by judging the rejection range based on a significance level of .05. The study protocol has been approved by the Ethics Committee of Guang'anmen Hospital on September 7, 2022, and has been registered on November 30, 2022. Recruitment began on March 1, 2023. A total of 4-6 participants are expected to be recruited each month. The recruitment is planned to be completed on March 1, 2025, and we expect to publish our results by the winter of 2025. As of November 1, 2023, we have enrolled 25 participants with CSU. This randomized, double-blind, placebo-controlled trial aims to provide definitive evidence for the treatment of CSU with ACE and explore the mechanism of ACE. We hypothesize that wheals and itching will show greater improvement in participants receiving active therapy than in those receiving sham treatment. The limitations of this study include its single-center trial design, small sample size, and short treatment duration, which may have certain impacts on the research results. Chinese Clinical Trial Registry ChiCTR2200066274; https://www.chictr.org.cn/showprojEN.html?proj=179056. DERR1-10.2196/54376.