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Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice

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Fundamental Research 2024年第4期4卷 820-828页

作者： Xiaqing Ma Qi Qi Wenying Wang Min Huang Haiyan Wang Limin Luo Xiaotao Xu Tifei Yuan Haibo Shi Wei Jiang Tao Xu Department of anesthesiology Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Department of anesthesiology Suzhou Hospital of Anhui Medical UniversitySuzhou 234000China Department of anesthesiology Affliated Hospital of Nantong UniversityMedical School of Nantong UniversityNantong 226001China Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Shanghai Key Laboratory of Sleep Disordered Breathing Shanghai 200233China

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain *** presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some neural function and *** aim of this study was to explore the role of ANLS in the occurrence and maintenance of *** 7 days consecutive morphine injection,a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4(PDK4),phosphorylated pyruvate dehydrogenase(p-PDH)and accumulation of L-lactate was elevated in the spinal dorsal *** administration of inhibitors of PDK,lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal *** astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in *** this study,we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal *** this process,PDK-p-PDH-lactate axis serves a pivotal role,which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

关键词： Pyruvate dehydrogenase kinase 4 Phosphorylated pyruvate dehydrogenase Astrocyte-neuron lactate shuttle Opioid-induced hyperalgesia Lactate

Lactate:a prospective target for therapeutic intervention in psychiatric disease

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Neural Regeneration Research 2024年第7期19卷 1473-1479页

作者： Yanhui Cai Haiyun Guo Tianle Han Huaning Wang Department of Psychiatry Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Department of anesthesiology and Perioperative Medicine Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina

Although antipsychotics that act via monoaminergic neurotransmitter modulation have considera ble therapeutic effect,they cannot completely relieve clinical symptoms in patients suffering from psychiatric disorde *** may be attributed to the limited range of neurotransmitters that are regulated by psychotropic *** findings indicate the need for investigation of psychotropic medications that target less-studied neurotransmitte *** these candidate neurotransmitters,lactate is developing from being a waste metabolite to a glial-neuronal signaling molecule in recent *** studies have suggested that cerebral lactate levels change considerably in numerous psychiatric illnesses;animal experiments have also shown that the supply of exogenous la ctate exerts an antidepressant *** this review,we have described how medications targeting newer neurotransmitte rs offer promise in psychiatric diseases;we have also summarized the advances in the use of lactate(and its corresponding signaling pathways)as a signaling *** addition,we have described the alterations in brain lactate levels in depression,anxiety,bipolar disorder,and schizophrenia and have indicated the challenges that need to be overcome before brain lactate can be used as a therapeutic target in psychopharmacology.

关键词： antidepressant anxiety bipolar disorder depression lactate psychiatric disease psychopharmacology schizophrenia signal molecular therapeutics

General anesthetic agents induce neurotoxicity through oligodendrocytes in the developing brain

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Zoological Research 2024年第3期45卷 691-703页

作者： Wen-Xin Hang Yan-Chang Yang Yu-Han Hu Fu-Quan Fang Lang Wang Xing-Hua Qian Patrick M.McQuillan Hui Xiong Jian-Hang Leng Zhi-Yong Hu Department of anesthesiology First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310003China Department of Cell Biology Yale UniversityNew HavenCT 06520USA Department of Neurology of the First Affiliated Hospital Interdisciplinary Institute of Neuroscience and TechnologySchool of Brain Science and Brain MedicineZhejiang University School of MedicineHangzhouZhejiang 310027China Department of anesthesiology Jiaxing Maternity and Childcare Health HospitalJiaxingZhejiang 314009China Department of anesthesiology Penn State Hershey Medical CentrePenn State College of MedicineHersheyPA 17033USA Department of Central Laboratory Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang 310006China

General anesthetic agents can impact brain function through interactions with neurons and their effects on glial *** perform essential roles in the central nervous system,including myelin sheath formation,axonal metabolism,and neuroplasticity *** are particularly vulnerable to the effects of general anesthetic agents resulting in impaired proliferation,differentiation,and *** are increasingly interested in the effects of general anesthetic agents on *** agents not only act on the surface receptors of oligodendrocytes to elicit neuroinflammation through modulation of signaling pathways,but also disrupt metabolic processes and alter the expression of genes involved in oligodendrocyte development and *** this review,we summarize the effects of general anesthetic agents on *** anticipate that future research will continue to explore these effects and develop strategies to decrease the incidence of adverse reactions associated with the use of general anesthetic agents.

关键词： Oligodendrocytes General anesthetic agents Neurotoxicity Central nervous system Perioperative neurocognitive disorders

A Comparative Study between Landmark Based and Real Time Ultrasound Guided Sub Arachnoid Block

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Open Journal of anesthesiology 2024年第4期14卷 118-125页

作者： Kunal Tewari Om Bahadur Thapa Deepak Mishra Manjot Multani Jyotsna Sharma Akash Ray Mohapatra Sandhya Khwaunju Department of anesthesiology and Critical Care Armed Forces Medical College Pune India Department of anesthesiology and Critical Care AFMC Pune India

Background: Sub arachnoid block (SAB) performed by traditional landmark palpation technique can be inaccurate. This problem is exacerbated by altered patient anatomy due to obesity and age-related changes. A pre-procedural ultrasound scan of the lumbar spine has been shown to be of benefit in guiding lumbar epidural insertion in obstetric patients. Information on the use of real-time ultrasound (RUS) guided SAB, to date, been limited. This study compared RUS guided SAB to traditional landmark guided technique in patients undergoing spinal anesthesia for different surgical procedures. Methods: This was a prospective, single center, comparative observational study conducted in the department of anesthesiology at our center. 560 patients who underwent spinal anesthesia either by landmark based technique or real-time ultrasound-guided methods. The primary outcome was the first attempt success rate of dural puncture when employing the two methods. Results: Baseline characteristics were similar in the two study groups. The first attempt success rate of dural puncture in landmark guided group was 64.3% compared to 72.6% in the ultrasound guided group. This difference was not statistically significant. The procedure performance time was significantly shorter with landmark palpation compared to use of real-time ultrasound guided method. Conclusion: Use of RUS-guided technique does not significantly improve the first attempt success rate of SAB dural puncture during spinal anesthesia compared to the traditional landmark-guided technique.

关键词： Sub Arachnoid Block (SAB) Real Time Ultrasound (RUS)

Deep simulated annealing for the discovery of novel dental anesthetics with local anesthesia and anti-inflammatory properties

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3086-3109页

作者： Yihang Hao Haofan Wang Xianggen Liu Wenrui Gai Shilong Hu Wencheng Liu Zhuang Miao Yu Gan Xianghua Yu Rongjia Shi Yongzhen Tan Ting Kang Ao Hai Yi Zhao Yihang Fu Yaling Tang Ling Ye Jin Liu Xinhua Liang Bowen Ke State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China College of Computer Science Sichuan UniversityChengdu 610065China Department of anesthesiology Laboratory of Anesthesia and Critical Care MedicineNational-Local Joint Engineering Research Centre of Translational Medicine of AnesthesiologyFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Multifunctional therapeutics have emerged as a solution to the constraints imposed by drugs with singular or insufficient therapeutic *** primary challenge is to integrate diverse pharmacophores within a single-molecule *** address this,we introduced DeepSA,a novel edit-based generative framework that utilizes deep simulated annealing for the modification of articaine,a wellknown local *** integrates deep neural networks into metaheuristics,effectively constraining molecular space during compound *** framework employs a sophisticated objective function that accounts for scaffold preservation,anti-inflammatory properties,and covalent *** 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 *** 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 *** 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.

关键词： Multifunctional drugs Deep simulated annealing Molecule generation Articaine derivatives AI-enhanced drug discovery

Comparison of efficacy of lung ultrasound and chest X-ray in diagnosing pulmonary edema and pleural effusion in ICU patients: A single centre, prospective, observational study

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Open Journal of anesthesiology 2024年第3期14卷 41-50页

作者： Kunal Tewari Sumanth Pelluru Deepak Mishra Nitin Pahuja Akash Ray Mohapatra Jyotsna Sharma Om Bahadur Thapa Manjot Multani Department of anesthesiology and Critical Care Armed Forces Medical College Pune India Department of anesthesiology and Critical Care Military Hospital Bhopal India

Background and Aims While chest X-ray (CXR) has been a conventional tool in intensive care units (ICUs) to identify lung pathologies, computed tomography (CT) scan remains the gold standard. Use of lung ultrasound (LUS) in resource-rich ICUs is still under investigation. The present study compares the utility of LUS to that of CXR in identifying pulmonary edema and pleural effusion in ICU patients. In addition, consolidation and pneumothorax were analyzed as secondary outcome measures. Material and Methods This is a prospective, single centric, observational study. Patients admitted in ICU were examined for lung pathologies, using LUS by a trained intensivist;and CXR done within 4 hours of each other. The final diagnosis was ascertained by an independent senior radiologist, based on the complete medical chart including clinical findings and the results of thoracic CT, if available. The results were compared and analyzed. Results Sensitivity, specificity and diagnostic accuracy of LUS was 95%, 94.4%, 94.67% for pleural effusion;and 98.33%, 97.78%, 98.00% for pulmonary edema respectively. Corresponding values with CXR were 48.33%, 76.67%, 65.33% for pleural effusion;and 36.67%, 82.22% and 64.00% for pulmonary edema respectively. Sensitivity, specificity and diagnostic accuracy of LUS was 91.30%, 96.85%, 96.00% for consolidation;and 100.00%, 79.02%, 80.00% for pneumothorax respectively. Corresponding values with CXR were 60.87%, 81.10%, 78.00% for consolidation;and 71.3%, 97.20%, 96.00% for pneumothorax respectively. Conclusion LUS has better diagnostic accuracy in diagnosis of pleural effusion and pulmonary edema when compared with CXR and is thus recommended as an effective alternative for diagnosis of these conditions in acute care settings. Our study recommends that a thoracic CT scan can be avoided in most of such cases.

关键词： Chest X ray (CXR) Consolidation Pulmonary edema Pleural effusion Lung ultrasound (LUS) Pneumothorax

anesthesiology:Advancing the Practice of Medicine

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Anesthesiology:Advancing the Practice of Medicine

Airway management of a patient with linear immunoglobulin A bullous dermatosis:A case report

2008年中华医学会全国麻醉学术年会

作者： James C.Eisenach FM James Ⅲ Professor of anesthesiology Wake Forest University School of Medicine Winston-Salem

What is anesthesiology? anesthesiology is a young specialty,with most academic departments tracing their beginnings to Ralph Waters,MD at the University of Wisconsin,USA,in the *** 1940 anesthesiology was not the prac... 详细信息

关键词：外科手术医学麻醉麻醉药物麻醉器械

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World Journal of Clinical Cases 2024年第13期12卷 2263-2268页

作者： Olga C Nin Robert Hutnik Neil N Chheda David Hutchinson Department of anesthesiology University of Florida College of MedicineGainesvilleFL 32610United States Department of Otolaryngology University of Florida College of MedicineGainesvilleFL 32610United States

BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable *** clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for *** SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous *** diagnosis of IgA dermatosis was recent,and the patient had been lost to *** severity of the disease and extent of airway involvement was unknown at the time of the *** airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating *** patient required transfer to the intensive care unit where a multidisciplinary team was involved in her *** patient was extubated on postoperative day *** A multidisciplinary approach to treating this disease is the best course of action before a surgical *** our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s *** surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

关键词： Airway management Bleeding risk Linear immunoglobulin A bullous dermatosis Multidisciplinary approach Outpatient procedure Case report

Activation of G-protein-coupled receptor 39 reduces neuropathic pain in a rat model

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Neural Regeneration Research 2024年第3期19卷 687-696页

作者： Longqing Zhang Xi Tan Fanhe Song Danyang Li Jiayi Wu Shaojie Gao Jia Sun Daiqiang Liu Yaqun Zhou Wei Mei Department of anesthesiology Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Healthand Wuhan Clinical Research Center for Geriatric AnesthesiaTongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains *** this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated *** injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated *** changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1α*** together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.

关键词： G-protein-coupled receptor 39(GPR39) neuroinflammation neuropathic pain nuclear respiratory factor 1(NRF1) peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α) sirtuin 1(SIRT1) spinal cord mitochondrial transcription factor A(TFAM)