Platelet membrane alterations induced by the local anesthetic dibucaine

Tertiary amine local anesthetics modify a variety of platelet membrane- related functions. The present study explored dibucaine (DB)-induced inhibition of platelet cohesion by examining structural and functional alterations of the human platelet membrane glycoprotein IIb-IIIa complex (GPIIb-IIIa) and platelet Ca2+ homeostasis. Complete inhibition of ADP-induced aggregation was achieved five minutes after platelet exposure to 0.10 to 0.25 mmol/L of DB when fibrinogen binding was reduced by 50%. At higher concentrations of DB (approximately 1 mmol/L), ADP-induced fibrinogen binding was completely blocked. Scatchard analysis revealed loss of high-affinity binding sites in addition to reduction in Bmax. In contrast, chymotrypsin-treated platelets sustained 50% inhibition of fibrinogen binding when incubated with 0.4 to 0.5 mmol/L DB, and kinetic analysis showed that the high- affinity platelet-fibrinogen interactions were reduced but not absent. Fibrinogen binding to chymotrypsin-treated platelets could not be completely inhibited even at high DB concentrations (1 mmol/L). The inhibition of fibrinogen binding to chymotrypsin-treated platelets correlated with changes in binding of a monoclonal antibody (10E5) specific for an epitope on the GPIIb-IIIa complex. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and radioelectroimmunoassay of DB-treated platelets, however, showed no evidence of a reduction or degradation of GP IIb or IIIa. Platelet incubation with DB (five minutes, 0.1 to 1.0 mmol/L) was also accompanied by: increased platelet membrane-associated Ca2+ involving low-affinity binding sites [Kd = 5 X 10(-5) mol/L-]; increased 45Ca2+ uptake which correlated with degradation of actin-binding protein (ABP) and digestion of GPIb as visualized on periodic-acid Schiff (PAS)- stained SDS gels and as inferred from decreased binding of a monoclonal antibody (6D1) directed against this glycoprotein; and enhanced Ca2+ exchange. Thus, exposure of platelets to DB results in membrane-related alterations that may contribute to inhibition of platelet cohesion: Decreased fibrinogen receptor exposure by traditional agonists and diminished accessibility of the GPIIb-IIIa complex to extracellular ligands correlate with DB-induced inhibition of platelet aggregation; and increased calcium uptake and exchange across the platelet membrane likely leads to activation of the calcium-dependent protease(s) which was previously shown to correlate with DB-induced inhibition of ristocetin-induced platelet agglutination.     

艾司洛尔联合胺碘酮治疗心室电风暴160例临床分析

目的：探讨和分析盐酸艾司洛尔与胺碘酮联合使用在治疗心室电风暴患者的效果。方法整群选取该院在2011年9月-2014年6月期间所收治的329例心室电风暴患者,遵照随机与知情自愿原则,分为观察组(160例)和对照组(169例)。给予药物胺碘酮治疗,对观察组患者采用盐酸艾司洛尔与胺碘酮联合治疗方案,疗程结束后,认真观察和对比两组患者所取得治疗的效果。结果观察组患者总有效率为95.0%,明显高于对照组的70.4%,该两组患者总有效率对比,差异有统计学意义(P<0.01);治疗后观察组患者收缩压与心率分别为(104.0±15.0)mmHg、(84.0±13.0)次/min全部低于对照组,该两组患者治疗后的收缩压与心率对比,差异有统计学意义(P<0.05)。结论采用盐酸艾司洛尔联合药物胺碘酮共同治疗心室电风暴患者的临床效果满意,能够提高心室风暴患者的治愈率,具有临床推广价值。     

Evaluation of the systematic set-up errors using electronic portal image device in the radiotherapy procedures

Objective： The aim of this work was to quantify the extent of set-up errors to conduct a quality assurance （QA） aspect of treatment delivery, verification of the treatment field＇s position on different days using electronic portal. Methods： This study was carried out on 12 patients, treated for pelvis tumor; and total of 240 images obtained by electronic portal image device （EPID） were analyzed. The EPIs acquire using EPID attached to the Siemens linear accelerator. The anatomy match- ing software （Theraview） was used and displacement in two dimensions were noted for each treatment field to study patient setup errors. Results： The percentages of mean deviations less than 5 mm in X direction were 65% ＆ 92%, from 5-10 mm were 31% ＆ 19% and more than 10 mm were 11% ＆ 9% forNP and lateral direction respectively. The percentages of mean deviations less than 5 mm in Y direction were 65% ＆ 63%, from 5-10 mm were 33% ＆ 28% and more than 10 mm were 22% ＆ 29%. The mean deviations in 2D-vector errors were 〈 5 mm in 47% and 46%, 5-10 mm in 36% and 37% and 〉 10 mm in 37% and 37% of images in the NP and lateral direction respectively. Conclusion： The results revealed that the ranges of set up errors are immobilization method to improve reproducibility. The observed variations were not within the limits..     

Influence of serotonin on the development and migration of gonadotropin-releasing hormone neurones in rat foetuses

This study used a pharmacological approach to evaluate the consequences of the metabolic perturbations of neurotransmitters on brain development. Pregnant rats received p-chlorophenylalanine (pCPA), an inhibitor of serotonin (5-hydroxytryptamine, 5-HT) synthesis, or saline (control) from the 11th day of gestation once or daily up to the 15th, 17th and 20th day, followed by processing of the forebrain and/or nasal cranium of foetal males and females for high-performance liquid chromatography of monoamines, radioimmunoassay of gonadotropin-releasing hormone (GnRH) and quantitative and semiquantitative immunocytochemistry for GnRH. The pCPA treatment resulted in a 50-70% depletion of 5-HT in the nasal crania and forebrains at any studied age. Radioimmunoassay showed no change in GnRH content in 5-HT deficient foetuses at E16 compared to controls, being higher in both cases in the rostral forebrain than in the hypothalamus. In controls at E21, the GnRH content in the hypothalamus exceeded that in the rostral forebrain, whereas in the 5-HT deficient group the opposite was found. These data suggest that 5-HT provided a stimulating effect on GnRH neurone migration, and this was confirmed by quantification of GnRH-immunoreactive neurones in the forebrain along the trajectory of their migration. At E18 and E21, the fractions of GnRH neurones in the rostral part of the trajectory in pCPA-treated foetuses were greater than those in control foetuses but the opposite was true for the caudal part of the trajectory. Moreover, 5-HT appeared to control the proliferation of the precursor cells of GnRH neurones and their differentiation, as derived from the observations of the increased number of GnRH neurones in the forebrain of foetuses of both sexes, as well as the region-specific decreased neuronal size and content of GnRH in 5-HT-deficient females. Thus, 5-HT appears to contribute to the regulation of the origin, differentiation and migration of GnRH neurones.     

A murine monoclonal antibody that blocks fibrinogen binding to normal platelets also inhibits fibrinogen interactions with chymotrypsin- treated platelets

We recently described a monoclonal antibody, 10E5 , that completely blocks adenosine diphosphate (ADP) induced fibrinogen binding to platelets and aggregation induced by ADP, epinephrine, and thrombin. Multiple lines of evidence indicate that 10E5 binds to platelet membrane glycoproteins IIb and/or IIIa. Because it has been reported that platelets treated with chymotrypsin aggregate when fibrinogen is added, we tested the effect of 10E5 antibody on chymotrypsin-induced fibrinogen binding and platelet aggregation. Aspirin-treated human platelets were washed in modified Tyrode's buffer (pH 7.5), incubated for 5 minutes at 22 degrees C with 300 micrograms/mL chymotrypsin, and washed again. The amount of 10E5 antibody bound to these platelets (37,232 +/- 2,928 molecules/platelet; mean +/- SEM, N=9) was similar to that bound to unstimulated control platelets (36,910 +/- 2,669) and did not differ significantly from the amount of antibody bound to ADP- treated platelets (P less than .01, N = 5). The amount of 10E5 bound to chymotrypsin-treated platelets correlated directly with the amount of fibrinogen bound to separate aliquots of the same platelet samples (r = .876, P less than .001). The 10E5 antibody caused virtually complete inhibition of both the binding of fibrinogen to chymotrypsin-treated platelets and the aggregation induced by exogenous fibrinogen. Immunoprecipitation studies of 125I-labeled chymotrypsin-treated platelets revealed that the 10E5 antibody bound proteins with molecular weights characteristic of glycoproteins IIb and IIIa. These data suggest that the fibrinogen receptor on chymotrypsin-treated platelets is identical to that on ADP-treated platelets and that this receptor is either near to, or on, the glycoprotein IIb/IIIa complex.     

Results of percutaneous transluminal angioplasty

Percutaneous transluminal angioplasty (Dotter technique) was used in 2,942 cases of iliofemoral atheromatous disease. Results varied with the characteristics of the obstructing lesion (length and location) and the clinical stage of ischemia (claudication, rest pain, gangrene). Based on the foregoing, angioplasty is done either as the preferred primary treatment or for the relief of clinically advanced disease in patients unsuitable for high risk surgery. Success is favored by the use of aggregation inhibitors and single-use Teflon or balloon catheters; complications are few.