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

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 lacking.Methods: 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 < 16, neither group showed a rebound rise of isoagglutinin titers. For patients with initial isoagglutinin titers ≥ 16, the rebound rise of isoagglutinin titers was more prominent in the RP group. There was no difference in time-dependent changes in B cell subpopulations and ABO-I-related complications.Conclusions: Sufficient 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.

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

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.

Influence of an emulsifier on the pressure desensitization of emulsion explosives

The desensitization degree of emulsion explosives （EE） was calculated with the peak pressure of explosion shock waves tested in water. To an explosive, the less the desensitization degree, the better the compression resistance, so the compression resistance of an explosive can be compared and analyzed quantificationally with the desensitization degree. The influence of an emulsifier on the pressure desensitization of EE was studied, including the content and category of emulsifiers. Three kinds of emulsifiers （Span-80, compound emulsifier, and T-152） were used in the tests. The experimental results show that both the content and category of emulsifiers make a great effect on the pressure desensitization of EE. The desensitization degree of EE reduces with the emulsifier content being increased, but there is an optimal content of an emulsifier for the compression resistance of EE. While the content of Span-80 reaches 4wt%, the desensitization degree of EE becomes a minimal value, and augments somewhat if the emulsifier content is increased more. That is to say, the compression resistance of EE becomes the highest while the content of Span-80 is 4wt%, and the compression resistance will decline if the content of Span-80 is increased more. The compression resistance of the explosive emulsified by compound emulsifier is the highest among all the explosives, when the content of the whole components and manufacturing engineering are kept invariable.

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

Nitrocellulose,or cellulose nitrate,has received considerable interest due to its various applications,such as propellants,coating agents and gas generators.However,its high mechanical sensitivity caused many accidents during its storage and usage in ammunition.In this work,two kinds of insensitive step ladderstructured nitrocellulose(LNC)with different nitrogen contents were synthesized.The 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 performance.Compared with raw nitrocellulose,LNC has a sharper exothermic peak in the DSC and ARC curves.The 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,respectively.The 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.Insensitive LNC provides an alternative to be used as a binder in insensitive propellants formulation.

EFFECTS OF DESENSITIZATION AND REBOUND TO ADENOSINE ON ACTION POTENTIAL AND CONTRACTILITY IN ATRIAL CELLS IN GUINEA-PIGS

Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10, 100μ mol·L -1Ado, the ratio of shortened APD was ( 9.58± 1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1 μ mol·L -1Ado had no desensitization ( P >0.05), but the time of desensitization of 10μ mol·L -1 Ado and 100μ mol·L -1 Ado was 1 minute( P <0.05) and 5 minutes( P < 0.05), respectively. The desensitization of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility of 10?μ mol·L -1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4± 16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100 μ mol·L -1 Ado was (12.38±7.50)%,(19.00± 8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.

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

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 (P<0.05). However, as the intervals were 20 and 120 seconds, the effects of twice ACh administration had no significant dif ference (P>0.05). 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.

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

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 of the controls, and this phenomenon was not shown in the cirrhotic rats. Norepinephrine significantly increased the activity of ROCK-1 in normal rats but not in cirrhotic ones. Norepinephrine significantly increased ROCK-1 activity in cirrhotic rats when GRK-2 inhibitor was used. CONCLUSIONS: β-arrestin-2 expression and its interaction with GPCRs are significantly upregulated in the mesenteric arteries in patients and rats with cirrhosis. These upregulations result in GPCR desensitization, G-protein dysfunction and ROCK inhibition. These may explain the decreased contractility of the mesenteric artery in response to vasoconstrictors.

Successful interferon desensitization in a patient with chronic hepatitis C infection

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.

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

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.

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

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 schizophrenia.Star⁃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 efficacy.However,it is still not fully understanding howγ-2 modu⁃late AMPAR gating.METHODS AND RESULTS The desensitization for different mutation of AMPAR andγ-2 was compared.It was shown that the electric attraction was involved in the interaction of AMPAR andγ-2.In addition,the interaction of KGK motif in ligand binding domain and pre-M1 chain of AMPAR and EX1 ofγ-2 modulate AMPAR opening and desensitization.Substitution of these charged residues had sur⁃prisingly effects on AMPAR desensitization kinet⁃ics.CONCLUSION 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.

Establishment and verification of theβ_(2)-AR desensitization asthma mice

Objective:To establish and verify aβ_(2)-AR desensitization asthma mice model.Methods:A total of 30 SPF male BALB/c mice were randomly divided into blank group,the common asthma group,andβ_(2)-AR desensitization asthma model group.Asthma model was established,and on this basis,the method of atom-izing inhalation and intraperitoneal injections of salbutamol was used to prepareβ_(2)-AR desensitization asthma model.After the last stimulation on the 21st day of modeling,the airway resistance of mice was measured.ELISA was used to detect the content of serum IgE;HE staining was used to observe the lung organization degree of infla-mmatory cell infiltration;Western blot method was used to detect theβ_(2)-AR content in lung tissue,RT-PCR was used to detect theβ_(2)-ARmRNA expressionin lung tissue.Results:Compared with the blank group,as acetyl choline(Mch)levels increased,groups of OVA induced airway resistance increases;but theβ_(2)-AR desensitization asthma model group increased airway resistance was more significant(P<0.05);compared with the blank group,IgE levels of common asthma group andβ_(2)-AR desensitization asthma model group elevated(P<0.01).The pathological histology observation found theβ_(2)-AR desensitization asthma airway inflammation infiltration in mice,the excessive mucus secretion and collagen deposition,and the pathological performance obviously increase compared with the common asthma group;β_(2)-AR content in the lung tissue ofβ_(2)-AR desensitization asthma model in mice,β_(2)-AR mRNA expression level in the blank group and common asthma model group were significantly decreased(P<0.05).Conclusion:Theβ_(2)-AR desensitization asthma mouse model was successfully established,and the buildingcycle was short.

Effect of desensitization treatment for highly sensitized uremic patients before kidney transplantation

Objective To explore the feasibility and efficacy of desensitization protocol for highly sensitized renal transplant patients ( HSP ) . Methods Thirty - five HSPs ( HLA class - I panel reactive antibody 2〉50 % ) , including 27 patients with a positive T and/or B cell cy-

Progress on the application of graphene-based composites toward energetic materials:A review

Carbon material is an important additive in energetic materials.Graphene is a monolayer carbon material in which carbon atoms are arranged in two-dimensional honeycomb structure,who has special optical,electrical,and mechanical properties.Recently,the application of graphene-based composites in energetic materials has received extensive attention.This review mainly summarizes the applications of graphene and graphene-based nanomaterials in energetic materials.The effects of these materials on the thermal stability,sensitivity,mechanical property,ignition and combustion of energetic materials were discussed.Furthermore,the progress of functionalized modification of graphene has been summarized,including covalent bonding modification and doping modification.These studies show that graphenebased materials exhibit excellent performances and might emerge as promising candidate for energetic materials.

Hybrid HMX multi-level assembled under the constraint of 2D materials with efficiently reduced sensitivity and optimized thermal stability

The interfacial interaction between HMX molecules and coating materials is the key to the safety performance of explosives and has received extensive attention.However,screening suitable coating agents to enhance the interfacial effect to obtain high-energy and low-sensitivity explosives has long been a major challenge.In this work,HMX-PEI/rGO/g-C_(3)N_(4)(HPrGC)composites were innovatively prepared by a multi-level coating strategy of two-dimensional graphite rGO and g-C_(3)N_(4).The g-C_(3)N_(4) used for desensitization has a richπ-conjugated system and shows outstanding ability in reducing friction sensitivity.The hierarchical structure of HPrGC formed by electrostatic self-assembly andπ-πstacking can effectively dissipate energy accumulation under heat and mechanical stimulation through structural evolution,thus exhibiting a prominent synergistic desensitization effect on HMX.The results show that rGO/gC_(3)N_(4) coating has no effect on the crystal structure and chemical structure of HMX.More importantly,the perfect combination of g-C_(3)N_(4) and rGO endows HPrGC with enhanced thermal stability and ideal mechanical sensitivity(IS:21 J,FS:216 N).Obviously,the new fabrication of HPrGC enriches the variety of desensitizer materials and helps to deepen the understanding of the interaction between explosives and coatings.

变应性鼻炎特异性免疫治疗护理

变应性鼻炎是耳鼻咽喉科常见疾病,主要表现为鼻痒、喷嚏和流清涕等,严重影响患者的生活质量。相当一部分患者可发展为支气管哮喘。变应性鼻炎的治疗体系可分为避免接触变应原、药物治疗和变应原特异性免疫治疗3个部分。特异性免疫治疗又称为脱敏治疗，是世界卫生组织（World Health Organization，WHO）推荐使用的唯一的对因治疗手段。其具体方法为依据患者所敏感的变应原的不同，对患者定期进行皮下注射标准化变应原疫苗，浓度由低到高，剂量由小到大，使患者对该变应原逐渐产生耐受，从而表现为临床症状的改善。

过敏性疾病免疫治疗100年

1910年英国医师Noon（1877～1913）从法国巴斯德研究所来到英国伦敦St.Mary医院,第2年就完成了一项历史性工作。1911年6月11日他在《柳叶刀》上撰文介绍采用皮下注射逐渐增加剂量的禾本科梯牧草（Timothy）花粉浸出液的方式,治疗花粉过敏导致的过敏性鼻炎（AR）,

呼吸道变应性疾病免疫治疗的临床应用和发展前景

采用标准化的变应原疫苗对呼吸道变应性疾病进行免疫治疗,已经在临床上良好的效果,本文就其临床应用现状及发展前景做一介绍,为今后更深入的研究工作提供参考。

GLUMA Desensitizer在烤瓷牙备中的临床应用

目的研究GLUMADesensitizer在烤瓷牙备中的临床应用。方法选择双侧需行烤瓷修复治疗的患者,一侧直接用氧化锌粘冠,另一侧用GLUMADesensitizer脱敏后再用氧化锌粘冠,复诊时循问观察结果。结果用GLUMADesensitizer脱敏后再用氧化锌粘冠侧效果明显好于直接用氧化锌粘冠侧。结论用GLUMADe-sensitizer脱敏后再用氧化锌粘冠,方便,值得在烤瓷牙备中推广。

ABO incompatible renal transplants:Good or bad?

ABO incompatible kidney transplantation(ABOi-KT) was previously considered to be an absolute contraindication for patients with end-stage kidney disease(ESKD) due to hyperacute rejection related to blood type barrier. Since the first successful series of ABOi-KT was reported, ABOi-KT is performed increasingly all over the world. ABOi-KT has led to an expanded donor pool and reduced the number of patients with ESKD awaiting deceased kidney transplantation(KT). Intensified immunosuppression and immunological understanding has helped to shape current desensitization protocols. Consequently, in recent years, ABOi-KT outcome is comparable to ABO compatible KT(ABOc-KT). However, many questions still remain unanswered. In ABOi-KT, there is an additional residual immunological risk that maylead to allograft damage, despite using current diverse but usually intensified immunosuppressive protocols at the expense of increasing risk of infection and possibly malignancy. Notably, in ABOi-KT, desensitization and antibody reduction therapies have increased the cost of KT. Reassuringly, there has been an evolution in ABOiKT leading to a simplification of protocols over the last decade. This review provides an overview of the history, outcome, protocol, advantages and disadvantages in ABOi-KT, and focuses on whether ABOi-KT should be recommended as a therapeutic option of KT in the future.