Background: Articaine is an amide local anaesthetic, which is gaining popularity for use in dental and oral surgical anaesthesia in the United Kingdom. Hitherto there has been insufficient evidence to recommend artica...Background: Articaine is an amide local anaesthetic, which is gaining popularity for use in dental and oral surgical anaesthesia in the United Kingdom. Hitherto there has been insufficient evidence to recommend articaine above the more commonly used lidocaine for dental procedures. The aim of this study is to compare the efficacy of 4% articaine with 1:100,000 adrenaline (4AA) with that of 2% lidocaine with 1:100,000 adrenaline (2LA) administered as buccal infiltrations for anaesthesia in mandibular permanent first molar teeth. Any significant advantage noted may obviate the need for regional blockage of the inferior dental nerve in dental or minor oral surgical procedure under local anaesthesia. Objectives: To review the published literature comparing the efficacies of 4AA and 2LA for achieving pulpal anaesthesia in human mandibular permanent first molar teeth. Null Hypothesis: 4AA and 2LA are of equal efficacy when used to anaesthetize mandibular permanent first molar teeth by buccal infiltration. Method: An electronic search encompassing Ovid MEDLINE?, PubMed (National Center for Biotechnology Information, US National Library of Medicine), SCOPUS?, SCIRUS?, EMBASE? databases and the Cochrane Library was performed to identify trials relating to the efficacy of 4AA and 2LA local anaesthetic solutions on mandibular first molars in adult participants. Study characteristics and outcome data were extracted as a basis for meta-analysis. Results: Three randomised controlled trials were identified for this meta-analysis. The relative efficacy of 4AA over 2LA in anesthetizing permanent first mandibular molars was calculated at 1.57 (95% CI = 1.27 to 1.95). Conclusion: Despite the promising results shown in the meta-analysis it is difficult to say from the evidence presented that 4AA should be used clinically in preference over 2LA.展开更多
Background and Aims: Erector spinae plane block, Paravertebral block and serratus anterior block are three formats for analgesia post-operatively following radical mastectomy. This study compares the analgesic efficac...Background and Aims: Erector spinae plane block, Paravertebral block and serratus anterior block are three formats for analgesia post-operatively following radical mastectomy. This study compares the analgesic efficacy of these modalities for analgesia post-operatively by articaine 2% with adrenaline. Methods: Seventy-five patients with ASA physical status I or II subjected to modified radical mastectomy with axillary clearance were enrolled for the study. After induction of general anaesthesia all patients received 20 mL 2% articaine with adrenaline in each technique of the study. Patients in Group 1 (Erector spinae block [ESB], n = 25), Group 2 paravertebral block [PVB] n = 25), Group 3 (serratus anterior plane block [SAPB] n = 25) were ultrasound-guided on ipsilateral side. Patients were estimated for pain scores at 0, 2, 4, 6, 12 and 24 h, and duration of analgesia post-operatively and relieve analgesic doses required of morphine up to 24 h. Results: Visual analogue scale scores post-operatively were lower in ESB and PVB group compared with SAPB at 4, 6, 12 and 24 h (P P Conclusion: Sonar-guided erector spinae block and thoracic paravertebral block minimize post-operative pain scores, prolongs the duration of analgesia and diminishes requirements for assigning analgesics in the first 24 h of post-operative period compared to ultrasound-guided serratus anterior plane block but, ESB technique was more potent, easily and less side effect in compared with PVB.展开更多
Local anesthetics(LAs),such as articaine(AT),exhibit limited efficacy in inflammatory environments,which constitutes a significant limitation in their clinical application within oral medicine.In our prior research,we...Local anesthetics(LAs),such as articaine(AT),exhibit limited efficacy in inflammatory environments,which constitutes a significant limitation in their clinical application within oral medicine.In our prior research,we developed AT-17,which demonstrated effective properties in chronic inflamma-tory conditions and appears to function as a novel oral LA that could address this challenge.In the present study,we further elucidated the beneficial effects of AT-17 in acute inflammation,particularly in oral acute inflammation,where mitochondrial-related apoptosis played a crucial role.Our findings indicated that AT-17 effectively inhibited lipopolysaccharide(LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro.This process involved the inhibition of mitochondrial reactive oxygen species(mtROS)production and the subsequent activation of the NRF2 pathway.Most notably,improve-ments in mitochondria-related apoptosis were key contributors to AT-17’s inhibition of voltage-gated sodium channels.Additionally,AT-17 was shown to reduce mtROS production in nerve cells through the Na+/NCLX/ETC signaling axis.In conclusion,we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis.This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.展开更多
The development of novel local anesthetics has long been mired in a cycle of incremental optimization,primarily focusing on sodium channel kinetics and pharmacokinetic refinement.The work by Hao et al.^(1),featured in...The development of novel local anesthetics has long been mired in a cycle of incremental optimization,primarily focusing on sodium channel kinetics and pharmacokinetic refinement.The work by Hao et al.^(1),featured in this issue,constitutes a genuine paradigm shift that fundamentally redefines the potential of local anes-thetics.Their compound,AT-17,transcends the conventional category of sodium channel blockers;it represents a multifunc-tional therapeutic agent that directly addresses the core patho-physiology responsible for anesthetic failure under inflammatory conditions.展开更多
Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects.The primary challenge is to integrate diverse pharmacophores within a singl...Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects.The primary challenge is to integrate diverse pharmacophores within a single-molecule framework.To address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local anesthetic.DeepSA integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound generation.This framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent constraints.Through a sequence of local editing to navigate the molecular space,DeepSA successfully identified AT-17,a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models.Mechanistic insights into AT-17 revealed its dual mode of action:selective inhibition of NaV1.7 and 1.8 channels,contributing to its prolonged local anesthetic effects,and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway.These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery,particularly within stringent chemical constraints.展开更多
文摘Background: Articaine is an amide local anaesthetic, which is gaining popularity for use in dental and oral surgical anaesthesia in the United Kingdom. Hitherto there has been insufficient evidence to recommend articaine above the more commonly used lidocaine for dental procedures. The aim of this study is to compare the efficacy of 4% articaine with 1:100,000 adrenaline (4AA) with that of 2% lidocaine with 1:100,000 adrenaline (2LA) administered as buccal infiltrations for anaesthesia in mandibular permanent first molar teeth. Any significant advantage noted may obviate the need for regional blockage of the inferior dental nerve in dental or minor oral surgical procedure under local anaesthesia. Objectives: To review the published literature comparing the efficacies of 4AA and 2LA for achieving pulpal anaesthesia in human mandibular permanent first molar teeth. Null Hypothesis: 4AA and 2LA are of equal efficacy when used to anaesthetize mandibular permanent first molar teeth by buccal infiltration. Method: An electronic search encompassing Ovid MEDLINE?, PubMed (National Center for Biotechnology Information, US National Library of Medicine), SCOPUS?, SCIRUS?, EMBASE? databases and the Cochrane Library was performed to identify trials relating to the efficacy of 4AA and 2LA local anaesthetic solutions on mandibular first molars in adult participants. Study characteristics and outcome data were extracted as a basis for meta-analysis. Results: Three randomised controlled trials were identified for this meta-analysis. The relative efficacy of 4AA over 2LA in anesthetizing permanent first mandibular molars was calculated at 1.57 (95% CI = 1.27 to 1.95). Conclusion: Despite the promising results shown in the meta-analysis it is difficult to say from the evidence presented that 4AA should be used clinically in preference over 2LA.
文摘Background and Aims: Erector spinae plane block, Paravertebral block and serratus anterior block are three formats for analgesia post-operatively following radical mastectomy. This study compares the analgesic efficacy of these modalities for analgesia post-operatively by articaine 2% with adrenaline. Methods: Seventy-five patients with ASA physical status I or II subjected to modified radical mastectomy with axillary clearance were enrolled for the study. After induction of general anaesthesia all patients received 20 mL 2% articaine with adrenaline in each technique of the study. Patients in Group 1 (Erector spinae block [ESB], n = 25), Group 2 paravertebral block [PVB] n = 25), Group 3 (serratus anterior plane block [SAPB] n = 25) were ultrasound-guided on ipsilateral side. Patients were estimated for pain scores at 0, 2, 4, 6, 12 and 24 h, and duration of analgesia post-operatively and relieve analgesic doses required of morphine up to 24 h. Results: Visual analogue scale scores post-operatively were lower in ESB and PVB group compared with SAPB at 4, 6, 12 and 24 h (P P Conclusion: Sonar-guided erector spinae block and thoracic paravertebral block minimize post-operative pain scores, prolongs the duration of analgesia and diminishes requirements for assigning analgesics in the first 24 h of post-operative period compared to ultrasound-guided serratus anterior plane block but, ESB technique was more potent, easily and less side effect in compared with PVB.
基金supported by the National Natural Science Foun-dation of China(82425054 and 82273784)the Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202004,China)+6 种基金Health Commission of Sichuan Province Medical Science and Technology Program(No.24CGZH05,China)the 1.3.5 Projects for Disciplines of Excel-lence,West China Hospital,Sichuan University(ZYGD25002 and ZYGD23025,China)the Sichuan Science and Technology Pro-grams(2024NSFSC0048,2023ZYD0168,2024YFFK0374 and 2023ZYD0168,China)the National Natural Science Foundation of China(82425054 and 82273784)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD25002 and ZYGD23025,China)Nature Science Foundation of Sichuan Province(2024NSFSC0048,China)Sichuan Science and Technology Program(2023ZYD0168,China).
文摘Local anesthetics(LAs),such as articaine(AT),exhibit limited efficacy in inflammatory environments,which constitutes a significant limitation in their clinical application within oral medicine.In our prior research,we developed AT-17,which demonstrated effective properties in chronic inflamma-tory conditions and appears to function as a novel oral LA that could address this challenge.In the present study,we further elucidated the beneficial effects of AT-17 in acute inflammation,particularly in oral acute inflammation,where mitochondrial-related apoptosis played a crucial role.Our findings indicated that AT-17 effectively inhibited lipopolysaccharide(LPS)-induced nerve cell apoptosis by ameliorating mitochondrial dysfunction in vitro.This process involved the inhibition of mitochondrial reactive oxygen species(mtROS)production and the subsequent activation of the NRF2 pathway.Most notably,improve-ments in mitochondria-related apoptosis were key contributors to AT-17’s inhibition of voltage-gated sodium channels.Additionally,AT-17 was shown to reduce mtROS production in nerve cells through the Na+/NCLX/ETC signaling axis.In conclusion,we have developed a novel local anesthetic that exhibits pronounced anesthetic functionality under inflammatory conditions by enhancing mitochondria-related apoptosis.This advancement holds considerable promise for future drug development and deepening our understanding of the underlying mechanisms of action.
文摘The development of novel local anesthetics has long been mired in a cycle of incremental optimization,primarily focusing on sodium channel kinetics and pharmacokinetic refinement.The work by Hao et al.^(1),featured in this issue,constitutes a genuine paradigm shift that fundamentally redefines the potential of local anes-thetics.Their compound,AT-17,transcends the conventional category of sodium channel blockers;it represents a multifunc-tional therapeutic agent that directly addresses the core patho-physiology responsible for anesthetic failure under inflammatory conditions.
基金supported by the National Natural Science Foundation of China(82273784,China)the Research and Develop Program,West China Hospital of Stomatology Sichuan University(RD-03-202004,China)+3 种基金the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYYC 21002,ZYGD23025,China)the Clinical Research Innovation Project,West China Hospital,Sichuan University(2019 HXCX006,China)the Science and Technology Major Project of Tibetan Autonomous Region of China(XZ202201ZD0001G,China)the Sichuan Science and Technology Program(2023 ZYD0168,China).
文摘Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic effects.The primary challenge is to integrate diverse pharmacophores within a single-molecule framework.To address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local anesthetic.DeepSA integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound generation.This framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent constraints.Through a sequence of local editing to navigate the molecular space,DeepSA successfully identified AT-17,a derivative exhibiting potent analgesic properties and significant anti-inflammatory activity in various animal models.Mechanistic insights into AT-17 revealed its dual mode of action:selective inhibition of NaV1.7 and 1.8 channels,contributing to its prolonged local anesthetic effects,and suppression of inflammatory mediators via modulation of the NLRP3 inflammasome pathway.These findings not only highlight the efficacy of AT-17 as a multifunctional drug candidate but also highlight the potential of DeepSA in facilitating AI-enhanced drug discovery,particularly within stringent chemical constraints.
