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desensitization of G-protein-coupled receptors induces vascular hypocontractility in response to norepinephrine in the mesenteric arteries of cirrhotic patients and rats

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 295-304页

作者： Wei Chen Jiang-Yong Sang De-Jun Liu Jun Qin Yan-Miao Huo Jia Xu Zhi-Yong Wu Department of Surgery Renji Hospital School of Medicine Shanghai Jiaotong University Department of Surgery Xinjiang Kashi District Second People's Hospital

BACKGROUND: The increased β-arrestin-2 and its combination with G-protein-coupled receptors (GPCRs) lead to GPCRs desensitization. The latter may be responsible for decreased contractile reactivity in the mesenteric arteries of cirrhotic patients and rats. The present study is to investigate the machinery changes of α-adrenergic receptors and G proteins and their roles in the contractility of mesenteric arteries of cirrhotic patients and animal models. METHODS: Patients with cirrhosis due to hepatitis B and cirrhotic rats induced by CCl 4 were studied. Mesenteric artery contractility in response to norepinephrine was determined by a vessel perfusion system. The contractile effect of G protein-coupled receptor kinase-2 (GRK-2) inhibitor on the mesenteric artery was evaluated. The protein expression of the α 1 adrenergic receptor, G proteins, β-arrestin-2, GRK-2 as well as the activity of Rho associated coiled-coil forming protein kinase-1 (ROCK-1) were measured by Western blot. In addition, the interaction of α 1 adrenergic receptor with β-arrestin-2 was assessed by co-immunoprecipitation. RESULTS: The portal vein pressure of cirrhotic patients and rats was significantly higher than that of controls. The doseresponse curve to norepinephrine in mesenteric arteriole was shifted to the right, and EC 50 was significantly increased in cirrhotic patients and rats. There were no significant differences in the expressions of the α 1 adrenergic receptor and G proteins in the cirrhotic group compared with the controls. However, the protein expressions of GRK-2 and β-arrestin-2 were significantly elevated in cirrhotic patients and rats compared with those of the controls. The interaction of the α 1 adrenergic receptor and β-arrestin-2 was significantly aggravated. This interaction was significantly reversed by GRK-2 inhibitor. Both the protein expression and activity of ROCK-1 were significantly decreased in the mesenteric artery in patients with cirrhosis compared with those o

关键词： portal hypertension desensitization G-protein-coupled receptors β-arrestin-2 Rho associated coiled-coil forming protein kinase

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Investigation on thermal characteristics and desensitization mechanism of improved step ladder-structured nitrocellulose

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Defence Technology（防务技术） 2023年第2期20卷 93-102页

作者： Cheng-kai Pu Yu Luan Ming-jun Yi Zheng-gang Xiao Key Laboratory of Special Energy Materials Ministry of EducationSchool of Chemistry and Chemical EngineeringNanjing University of Science and TechnologyNanjing210094People's Republic of China

Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas ***,its high mechanical sensitivity caused many accidents during its storage and usage in *** this work,two kinds of insensitive step ladderstructured nitrocellulose(LNC)with different nitrogen contents were *** products were characterized by FT-IR,Raman,XRD,SEM,elemental analysis,TGA,DSC,accelerating rate calorimeter analysis(ARC),and drop weight test to study their molecular structure,thermal characteristics and desensitization *** with raw nitrocellulose,LNC has a sharper exothermic peak in the DSC and ARC *** H50values of the two kinds of LNC increased from 25.76 to 30.01 cm for low nitrogen content and from 18.02 to 21.84 cm for high nitrogen content,*** results show that the ladder-structure of LNC which provides regular molecular arrangement and a soft buffer made with polyethylene glycol could affect the energy releasing process of LNC and reduce the sensitivity of *** LNC provides an alternative to be used as a binder in insensitive propellants formulation.

关键词： Nitrocellulose Decomposition desensitization Ladder structure Thermal characteristic Polyethylene glycol

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A comparison of desensitization methods: Rituximab with/without plasmapheresis in ABO-incompatible living donor liver transplantation

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Hepatobiliary & Pancreatic Diseases International 2018年第2期17卷 119-125页

作者： Eung Chang Lee Seong Hoon Kim Jae Ryong Shim Sang-Jae Park Center for Liver Cancer National Cancer Center

Background: Plasmapheresis is a desensitization method used prior to ABO-incompatible(ABO-I) living donor liver transplantation. However, studies on its usefulness in the rituximab era are ***: Fifty-six adult patients underwent ABO-I living donor liver transplantation between January2012 and October 2015. A single dose of rituximab(300 mg/m~2) was administered 2 weeks before surgery with plasmapheresis in all patients until February 2014(RP group, n = 26). Patients were administered rituximab only, without plasmapheresis between March 2014 and October 2015(RO group, n = 30).Results: The 6-, 12-and 18-month overall survival rates were 92.3%, 80.8% and 76.9% in the RP group and 96.6%, 85.4% and 85.4% in the RO group, respectively(P = 0.574). When the initial isoagglutinin titers desensitization for ABO-I living donor liver transplantation can be achieved using rituximab alone. This desensitization strategy does not affect the isoagglutinin titers, ABO-I-related complications and patient survival.

关键词： desensitization Rituximab Plasmapheresis ABO-incompatibility Living donor Liver transplantation

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desensitization OF ACETYLCHOLINE ON THE INHIBITION EFFECTS OF BLOOD PRE SSURE IN ANESTHETIZED CANINE

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Journal of Pharmaceutical Analysis 2004年第2期16卷 167-170页

作者：陈莉娜吕军臧伟进于晓江孙晓东高小利 Department of Cardiovascular Physiology and Pharmacology Medical School of Xi'an Jiaotong University Xi'an 710061 China Department of Cardiovascular Physiology and Pharmacology Medical School of Xi'an Jiaotong University Xi'an 710061 ChinaKey Laboratory of Environment and GenesRelatedto Diseases(Xian jiaotong University)Ministry of EducationXian710061China

Objective To investigate the desensitization of acetylcholine (ACh) on the inhibition effects of blood pressure (BP) in anesthe tized canine and build a model for studying desensitization in vivo. Methods Through changing the intervals (120, 100, 80, 60, 40, 20 seconds) of twice ACh administration (each was 15μg·kg -1,i.v.), the desensitization on the effect of systemic blood pressure of the first ACh in jection towards the subsequent ACh administration was observed. Results When ACh administration intervals were 40, 60, 80 , 100 seconds, the percentages of desensitization of ACh on systemic blood press ure were significantly increased (P0.05). Conclusion The results indicated that ACh contents in blo od might influence the action of next ACh administration. To some extent, the hi gher the concentration of ACh in blood, the bigger the ratio of desensitization of exogenous ACh is. In addition, this method of twice drug administration could be used as a model of studying desensitization in vivo.

关键词： acetylcholine desensitization canine blood pre ssure

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Abstinence Following a Motivation-Skill-desensitization-Mental Energy Intervention for Heroin Dependence: A Three-year Follow-up Result of a Randomized Controlled Trial

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Current Medical Science 2019年第3期39卷 472-482页

作者： Jia-yan CHEN Jin-cong YU Jie-pin CAO Yang XIAO Hong GU Rui-lin ZHONG Fang DING Zeng-zhen WANG Department of Epidemiology and Biostatistics School of Public Health Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 China Psychological Health Education and Counseling Center Zhongnan University of Economics and Law Wuhan 430073China School of Nursing Duke University Durham NC 27710 USA Wuhan Shiwu Research Institute of Science on Modem Psychology Wuhan 430062 China Xiangyang Drug Rehabilitation Center Xiangyang 441100 China

The high rate of relapse among heroin users remains a significant public concern in China. In the present study, we utilized a Motivation-Skill-desensitization-Mental Energy (MSDE) intervention and evaluated its effects on abstinence and mental health. Eighty-nine male heroin users in a drug rehabilitation center were enrolled in the study. The participants in the MSDE intervention group (n=46) received MSDE intervention, which included motivational interviewing, coping skills training, eye movement desensitization and reprocessing, and mindfulness-based psychotherapy. The participants in the control group (h=43) received a series of lectures on skills training. A significant increase in Contemplation Ladder score (P<0.001) and decreases in scores on the Obsessive Compulsive Drug Use Scale (P<0.001), Beck Depression Inventory (P<0.001), and Aggression Questionnaire (P=O.O33) were found immediately after intervention. Compared to the control group, the MSDE intervention group reported significantly higher abstinence rates (P=0.027) and retention rates (P<0.001) at follow-up. Overall, the MSDE intervention, which uses a combined strategy for relapse prevention, could be a promising approach for preventing relapse among heroin users in China.

关键词： heroin dependence relapse prevention motivational interviewing cognitive therapy eye movement desensitization and reprocessing

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Essential roles of exosome and circRNA_101093 on ferroptosis desensitization in lung adenocarcinoma

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Cancer Communications 2022年第4期42卷 287-313页

作者： Xiao Zhang Yunhua Xu Lifang Ma Keke Yu Yongjie Niu Xin Xu Yi Shi Susu Guo Xiangfei Xue Yikun Wang Shiyu Qiu Jiangtao Cui Hong Wang Xiaoting Tian Yayou Miao Fanyu Meng Yongxia Qiao Yongchun Yu Jiayi Wang Department of Laboratory Medicine Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030P.R.China Department of Thoracic Surgery Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030P.R.China Shanghai Institute of Thoracic Oncology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030P.R.China Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030P.R.China Department of Bio-bank Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030P.R.China Shanghai Municipal Hospital of Traditional Chinese Medicine Shanghai University of Traditional Chinese MedicineShanghai 200071P.R.China Bio-X Institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric disorderShanghai Jiao Tong UniversityShanghai 200030P.R.China Department of Clinical Laboratory Medicine Shanghai Tenth People’s Hospital of Tongji UniversityShanghai 200072P.R.China School of Public Health Shanghai Jiao Tong University School of MedicineShanghai 200025P.R.China

Background:Resistance to ferroptosis,a regulated cell death caused by irondependent excessive accumulation of lipid peroxides,has recently been linked to lung adenocarcinoma(LUAD).Intracellular antioxidant systems are required for protection against *** purpose of the present studywas to investigate whether and how extracellular system desensitizes LUAD cells to ***:Established human lung fibroblasts MRC-5,WI38,and human LUAD H1650,PC9,H1975,H358,A549,and H1299 cell lines,tumor and matched normal adjacent tissues of LUAD,and plasma from healthy individuals and LUAD patients were used in this *** and immunoblotting were used to analyze protein expression,and quantitative reverse transcription-PCR was used to analyze mRNA *** viability,cell death,and the lipid reactive oxygen species generationwere measured to evaluate the responses to *** were observed using transmission electron *** localization of arachidonic acid(AA)was detected using click chemistry labeling followed by confocal *** between RNAs and proteins were detected using RNA pull-down,RNA immunoprecipitation and photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation *** analysis was used to investigate RNA-regulated proteins,and metabolomic analysis was performed to analyze *** xenograft,patient-derived xenograft,cell-implanted intrapulmonary LUAD mouse models and plasma/tissue specimens from LUAD patients were used to validate the molecular ***:Plasma exosome from LUAD patients specifically reduced lipid peroxidation and desensitized LUAD cells to ferroptosis.A potential explanation is that exosomal circRNA_101093(cir93)maintained an elevation in intracellular cir93 in LUAD to modulate AA,a poly-unsaturated fatty acid critical for ferroptosisassociated increased peroxidation in the plasma ***,cir93 interac

关键词： exosome circRNA_101093 ferroptosis desensitization lung adenocarcinoma lipid peroxidation poly-unsaturated fatty acid taurine N-arachidonoyl taurine RNA-protein interaction

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Successful interferon desensitization in a patient with chronic hepatitis C infection

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World Journal of Gastroenterology 2009年第33期15卷 4196-4198页

作者： Seyed Alireza Taghavi Ahad Eshraghian Gastroentero-hepatology Research Center of Shiraz University of Medical Science Nemazee Hospital

Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment, with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.

关键词： Chronic hepatitis C desensitization Drug hypersensitivity Interferon a2b Ribavirin

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Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report

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World Journal of Clinical Cases 2016年第10期4卷 351-355页

作者： Vivek B Kute Himanshu V Patel Pankaj R Shah Pranjal R Modi Veena R Shah Sayyed J Rizvi Bipin C Pal Manisha P Modi Priya S Shah Umesh T Varyani Pavan S Wakhare Saiprasad G Shinde Viajay A Ghodela Minaxi H Patel Varsha B Trivedi Hargovind L Trivedi Department of Nephrology and Clinical Transplantation Institute of Kidney Diseases and Research CenterDr.HL Trivedi Institute of Transplantation Sciences(IKDRC-ITS) Department of Urology and Transplantation IKDRC-ITS Department of Anesthesia IKDRC-ITS Department of Pathology Laboratory MedicineTransfusion Services and ImmunohematologyIKDRC-ITS

The combination of kidney paired donation(KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation(LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.

关键词： Kidney failure Chronic desensitization Immunologic Kidney transplantation Blood group incompatibility Living donors Tissue and organ procurement

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A logarithmic rapid desensitization protocol: initial experience in carboplatin hypersensitivity reactions

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Journal of Cancer Metastasis and Treatment 2019年第8期4卷 21-28页

作者： Enrique Burches Jose-Alejandro Pérez-Fidalgo Francisco Ferriols Inés González-Barrallo AndrésCervantes Allergy Department Hospital Clinico UniversitarioValencia 46010Spain Oncology Department Hospital Clinico Universitario and INCLIVA Research InstituteValencia 46010Spain Pharmacy Department Hospital Clinico UniversitarioValencia 46010Spain

Aim: Hypersensitivity reactions to carboplatin are not an infrequent adverse event in ovarian cancer patients. However, reintroduction of platinum-containing schedules is the standard of care in platinum-sensitive recurrent ovarian cancer. Rapid desensitization is a procedure for gradual reintroduction of drug. It allows a safe administration of medications that are beneficial for the management of patients after certain types of hypersensitivity reactions. It is indicated in cases in which there are no reasonable therapeutic alternatives. Methods: We performed a descriptive retrospective study of high-grade ovarian cancer patients with known carboplatin hypersensitivity reactions that were treated with a 13-steps rapid desensitization protocol with 3 different solutions and infusion rates. The procedure followed a mathematic model (gradual increases with a relationship between doses following a geometric series) which is called logarithmic rapid desensitization protocol (LRDP). The aim was to describe the safety of the LRDP in terms of number and severity of infusion reactions and the effectiveness in the rate of cycles completely administered. Results: Four different patients diagnosed with recurrent platinum-sensitive ovarian cancer with a previous infusion reaction were included. LRDP was administered in 19 different cycles. LRDP was administered safety in all 19 cycles, only 2 patients had a mild cutaneous reaction in 4 different cycles during LRDP (21.05%). The foreseen dose of carboplatin was fully administered in all ***: LRDP with carboplatin is a feasible and safe protocol in patients with previous infusion reaction to carboplatin. The protocol might allow a safe administration of drugs, that are beneficial for the management of patients, after certain types of hypersensitivity reactions, and it is indicated in cases in which there are no reasonable therapeutic alternatives.

关键词： Drug allergy hypersensitivity desensitization rapid protocol logarithmic model carboplatin

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Mechanism of charged interface of stargazin EX1 on AMPAR opening and desensitization

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中国药理学与毒理学杂志 2021年第9期35卷 685-686页

作者： YANG Zu-xiao ZHANG Wei Department of Pharmacology of Chinese Materia Medica Institution of Chinese Integrative Medicinethe Key Laboratory of New Drug Pharmacology and ToxicologyHebei Medical UniversityShijiazhuang 050017China

OBJECTIVE AMPA-subtype iono⁃tropic glutamate receptors(iGluRs)mediate fast excitatory synaptic transmission in the mammali⁃an central nervous system(CNS).It plays the key role in many central nerves disorder such as epilepsy,depression and ***⁃gazin(STZ,also named TARP-γ2),as the first TARPs found in CNS,potentiates AMPAR activity by attenuating deactivation and desensitization,enhancing recovery from desensitization,and facilitating agonist affinity and ***,it is still not fully understanding howγ-2 modu⁃late AMPAR *** AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was *** was shown that the electric attraction was involved in the interaction of AMPAR andγ-*** addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and *** of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃*** The electric attraction has two impacts on the channels gating process the first destablizing the receptor closed state and enabling the channel opening,the second pro⁃moting the channels entering desensitization state upon the channel opening.

关键词： ionotropic glutamate receptors desensitization stargazin EX1

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