Enhanced physical stability of human calcitonin after methionine oxidation

Calcitonin is a blood-calcium-lowering peptide, present in different species, which inhibits the resorption of bone by osteoclasts. Human calcitonin (hCT) is one of the few calcitonin peptides, which contains a methionine residue; this residue is in position 8. Methionines are known to be readily oxidized to sulfoxides both in vivo and in vitro. The current work describes the effect of methionine oxidation on the physical stability of hCT. Aggregation kinetics of human calcitonin were studied at different pH values by intrinsic fluorescence spectroscopy, turbidity at 350 nm, microscopy analyses, Nile Red, and 1,8-ANS fluorescence emission. In all the experiments, methionine oxidation reduced the aggregation rate of human calcitonin. The effect of methionine oxidation was independent of pH. Fluorescence lifetime data also showed that the conformation of hCT in the aggregated state can be influenced by methionine oxidation. A hypothesis for the enhanced physical stability of oxidized hCT is presented and discussed.     

THE THEORY OF THE BASIC ASSUMPTION OF INCOHESION: AGGREGATION/MASSIFICATION OR (BA) I:A/M

Presented in honour of Dr Estela Welldon as a friend and colleague, and in acknowledgement of her contributions to forensic psychotherapy and group analysis for people who suffer from extreme anxieties associated with confused sex and gender identifications and choices, sado-masochism and criminality, this article integrates Bionian and Foulkesian perspectives in group analysis by conceptualizing a fourth basic assumption in the unconscious life of social systems. The basic assumption of Incohesion: Aggregation/Massification or (ba) I:A/M is derived from a relational rather than an instinctual metapsychology, and assumes that helplessness and the fear of annihilation precede the emergence of envy, thus emphasizing the importance of traumatogenic processes. Traumatized people with crustacean and amoeboid defences/protections against the fear of annihilation are likely to personify aggregation and massification processes, respectively. This theory can be applied in the group treatments of our most disturbed patients, and in understanding the dynamics of traumatized social systems, ranging from families to organizations and even societies.     

体外反搏对冠心病血小板聚集,TXB_2和6-酮-PGF_(1α)的影响

体外反搏(ECP)治疗16例冠心病人,其中11例测定了治疗前,治疗中1小时,1.5小时,2小时和停机后1小时,2小时以及一疗程后第二天清晨的血小板聚集,13例测定了治疗前,治疗中和一疗程结束时TXB_2和6-酮-PGF_(1a)。发现治疗2小时及以后各时段的血小板聚集率,TXB_2与治疗前比较有明显下降(P<0.01,P<0.05各自),6-酮PGF_(1a)明显升高(P<0.05)。本文指出,血流动力学的改变可影响血小板聚集,但主要是ECP治疗改善了微循环和组织代谢,保护了血管内皮使PGI_2合成增多,从而抑制了血栓的形成和冠状动脉痉挛,扩张了冠状动脉,此可能是ECP治疗冠心病的作用机制之一,并且在治疗心绞痛病人中防止了冠状动脉的进一步受损。     

Effect of ultrafiltration and plasma osmolarity upon the flow properties of blood: A possible mechanism for control of blood flow in the renal medullary vasa recta

Summary The normal flow properties of human blood are severely altered when its chemical composition is altered by ultrafiltration or by making plasma hypertonic with NaCl or Mannitol. As a result of ultrafiltration, the viscosity of plasma is increased and so is the concentration of high molecular weight plasma proteins (e.g. fibrinogen), causing red cell aggregation. The crenation of erythrocytes reduces their physiological fluidity and thereby greatly increases apparent blood viscosity. The combined effects of NaCl induced hypertonicity (600 mOsmol/l) and ultrafiltration (FF 0.4) increased apparent blood viscosity between 110 and 4 times (depending on hematocrit value). These effects are especially pronounced in models of the microcirculation (Millipore^® filters, 514 m mean pore diameter) and are operating at low hematocrit values. Since the renal medullary vasa recta are the only part of the circulatory bed where such chemical changes of the blood occur, the hypothesis is presented that the hypertonicity of the vasa plasma via its effect on red cells rheology controls the relatively low rate of vasa recta blood flow in antidiuresis.Presented in parts before the Spring Meeting of the Federation of American Societies of Experimental Biology (Atlantic City 1969) and the 36^th Meeting of the German Physiological Society (Mainz, 1969).Supported by grants from the Max Kade Foundation (New York, N.Y.), the John A. Hartford Foundation, Public Health Service Grant 5 P01-H.E. 11306, and from the Deutsche Forschungsgemeinschaft (Schm 84/1).     

德国小蠊聚集信息素的组分及含量测定

德国小蠊的聚集行为是由个体分泌的聚集信息素引起的 ,德国小蠊若虫的体表和粪便中均含有聚集信息素。用气相色谱 (GC)和气 质谱 (GC MS)联用技术测定了德国小蠊体表的二氯甲烷提取物和粪便的正己烷提取物 ,结果表明体表提取物中的活性组分全部是外表皮分泌的一类碳氢化合物 ,而雌成虫和若虫的粪便提取物的GC MS谱图完全一致 ,与体表提取物相比 ,多了棕榈酸、亚油酸、油酸、十八碳酸、二十烷醇和二十二烷醇 6种组分 ,其余 2 5种组分则完全相同。这些结果表明德国小蠊聚集信息素的主要组分是表皮碳氢化合物。在体表提取物中含量最高的是 3 ,7 /3 ,9 /3 ,1 1 二甲基二十九碳烷 (占总量的 2 2 2 % )。其次是 9 1 1 /1 3 /1 5 甲基二十九碳烷、3 甲基二十九碳烷、 5 甲基二十九碳烷、正二十九碳烷、1 1 ,1 5 1 3 ,1 7 二甲基二十九碳烷和 5 ,9 /5 ,1 1 二甲基二十九碳烷 ,含量依次是 1 3 5 5 %、 1 0 46%、 7 93 % 6 48%、6 1 4%和 5 5 2 %。粪便提取物中也是 3 ,7 /3 ,9 /3 ,1 1二甲基二十九碳烷的含量最高 (占总量的 1 2 86% )其次是 9 1 1 /1 3 /1 5 甲基二十九碳烷、油酸、 3 甲基二十九碳烷、正二十九碳烷、 1 1 /1 3 /1 5 甲基三十一碳烷和 1 1 ,1 5 1 3 ,1 7 二甲基二十九碳     

气滞血瘀型输卵管炎性不孕大鼠病证结合模型的建立

目的探索气滞血瘀型输卵管炎性不孕大鼠病证结合模型的建立方法。方法将50只SD雌性大鼠按随机数字表法随机分为5组,分别为空白组、空白手术组、夹尾组、禁食水组、复合造模组。注射金黄色葡萄球菌制作输卵管炎性不孕模型,夹尾组给予夹尾、禁食水组给予禁食水、复合造模组给予夹尾+禁食水+声光电刺激复制气滞血瘀模型,观察造模后大鼠一般状态,受孕率及血流变指标。结果各模型组大鼠耳色、爪色出现不同程度的血瘀状态,夹尾组、复合造模组的全血黏度指标均有不同程度上升。夹尾组全血黏度低切、中切与空白组比较差异有统计学意义(P<0.01),复合造模组全血黏度低切、中切、高切与空白组、禁食水组比较差异有统计学意义(P<0.01)。刚性指数:禁食水组与空白组比较明显升高(P<0.01),复合造模组与空白组及夹尾组比较均有明显升高(P<0.01),聚集指数:夹尾组红细胞聚集指数与空白组比较明显升高(P<0.01),复合模型组与空白组及夹尾组比较均明显升高(P<0.01)。结论采取复合刺激结合金黄色葡萄球菌注射可以成功建立气滞血瘀型输卵管炎性不孕大鼠模型。     

Does platelet size correlate with function in patients undergoing cardiac surgery?

Objective Platelet dysfunction secondary to cardiopulmonary bypass (CPB) is one of the major reasons for nonsurgical post-operative bleeding in cardiac surgery. Whether platelet size is an indicator for platelet function was investigated in patients undergoing coronary artery bypass grafting.Design Prospective study.Setting Intra-operative, cardiac surgery operations.Patients 80 consecutive patients undergoing coronary artery bypass grafting. Excluding criteria were pre-operative coagulation disorders and medication with anticoagulants within the last 10 days before the operation day.Measurements and results Platelet function was assessed by aggregometry using a turbidimetric method (inductors: ADP 2.0 mol/l, collagen 4 g/l, epinephrine 25 mol/l). Mean platelet volume (MPV) was measured by an electrical conductivity method. Measurements were carried out before, during, and after CPB until the 1st post-operative day on intensive care unit (ICU). Platelet size decreased significantly during CPB (max. –25% after weaning from bypass) and returned to baseline values on the 1st post-operative day. Platelet count (ranging from 93–304×10⁹/l) did not correlate significantly with MPV or aggregation variables. Maximum aggregation and maximum gradient of aggregation induced by ADP and collagen were significantly decreased by CPB with the most pronounced reduction at the end of CPB (ranging from –25% to –45%). Analyses of co-variance revealed a significant correlation between changes in MPV and changes in aggregation variables (ADP, collagen).Conclusion Platelet volume is easy to measure even in the operation room or in ICU and may indicate abnormalities in platelet function in the post-bypass period of cardiac surgery patients.     

活血舒通合剂对实验性高脂血症的保护作用

目的:研究活血舒通合剂对血脂的调节作用。方法:采用小鼠ig给予高脂乳剂法建立高脂血症模型,检测血清TC、TG、LDL-C、HDL-C含量。采用大鼠皮下注射肾上腺素和冰浴法建立急性血瘀模型,检测全血高切、中切、低切黏度,血浆黏度、全血还原黏度、红细胞压积。采用大鼠ig12天,测定血小板1min、5min的聚集率和最大聚集率。结果:活血舒通合剂高剂量组能降低血清TC、TG、LDL-C含量和升高HDL-C含量;降低全血高切、中切、低切黏度,血浆黏度、全血还原黏度、红细胞压积;降低血小板1min、5min的聚集率和最大聚集率。结论:活血舒通合剂具有调节血脂的作用。     

Inhibition of ��-amyloid1-40 Peptide Aggregation and Neurotoxicity by Citrate

The accumulation of β-amyloid (Aβ) aggregates is a characteristic of Alzheimer''s disease (AD). Furthermore, these aggregates have neurotoxic effects on cells, and thus, molecules that inhibit Aβ aggregate formation could be valuable therapeutics for AD. It is well known that aggregation of Aβ depends on its hydrophobicity, and thus, in order to increase the hydrophilicity of Aβ, we considered using citrate, an anionic surfactant with three carboxylic acid groups. We hypothesized that citrate could reduce hydrophobicity and increase hydrophilicity of Aβ_1-40 molecules via hydrophilic/electrostatic interactions. We found that citrate significantly inhibited Aβ_1-40 aggregation and significantly protected SH-SY5Y cell line against Aβ_1-40 aggregates-induced neurotoxicity. In details, we examined the effects of citrate on Aβ_1-40 aggregation and on Aβ_1-40 aggregates-induced cytotoxicity, cell viability, and apoptosis. Th-T assays showed that citrate significantly inhibited Aβ_1-40 aggregation in a concentration-dependent manner (Th-T intensity: from 91.3% in 0.01 mM citrate to 82.1% in 1.0 mM citrate vs. 100.0% in Aβ_1-40 alone). In cytotoxicity and viability assays, citrate reduced the toxicity of Aβ_1-40 in a concentration-dependent manner, in which the cytotoxicity decreased from 107.5 to 102.3% as compared with Aβ_1-40 aggregates alone treated cells (127.3%) and the cell viability increased from 84.6 to 93.8% as compared with the Aβ_1-40 aggregates alone treated cells (65.3%). Furthermore, Hoechst 33342 staining showed that citrate (1.0 mM) suppressed Aβ_1-40 aggregates-induced apoptosis in the cells. This study suggests that citrate can inhibit Aβ_1-40 aggregation and protect neurons from the apoptotic effects of Aβ_1-40 aggregates. Accordingly, our findings suggest that citrate administration should be viewed as a novel neuroprotective strategy for AD.