Effect of combined supplementation with vitamin E and alpha-lipoic acid on myocardial performance during in vivo ischaemia-reperfusion

Reactive oxygen species (ROS) contribute significantly to myocardial ischaemia-reperfusion (I-R) injury. Recently the combination of the antioxidants vitamin E (VE) and alpha-lipoic acid (alpha-LA) has been reported to improve cardiac performance and reduce myocardial lipid peroxidation during in vitro I-R. The purpose of these experiments was to investigate the effects of VE and alpha-LA supplementation on cardiac performance, incidence of dysrhythmias and biochemical alterations during an in vivo myocardial I-R insult. Female Sprague-Dawley rats (4-months old) were assigned to one of the two dietary treatments: (1) control diet (CON) or (2) VE and alpha-LA supplementation (ANTIOXID). The CON diet was prepared to meet AIN-93M standards, which contains 75 IU VE kg-1 diet. The ANTIOXID diet contained 10 000 IU VE kg(-1) diet and 1.65 g alpha-LA kg(-1) diet. After the 14-week feeding period, significant differences (P<0.05) existed in mean myocardial VE levels between dietary groups. Animals in each experimental group were subjected to an in vivo I-R protocol which included 25 min of left anterior coronary artery occlusion followed by 10 min of reperfusion. No group differences (P>0.05) existed in cardiac performance (e.g. peak arterial pressure or ventricular work) or the incidence of ventricular dysrhythmias during the I-R protocol. Following I-R, two markers of lipid peroxidation were lower (P<0.05) in the ANTIOXID animals compared with CON. These data indicate that dietary supplementation of the antioxidants, VE and alpha-LA do not influence cardiac performance or the incidence of dysrhythmias but do decrease lipid peroxidation during in vivo I-R in young adult rats.     

人IL-12表达质粒联合含信号肽Mtb8.4基因疫苗对小鼠结核杆菌感染的免疫保护效果

目的研究结核分枝杆菌含信号肽Mtb8.4(MS)基因疫苗与人白细胞介素12(hIL-12)联合免疫小鼠后,诱导的细胞免疫应答及对小鼠结核杆菌感染的免疫保护效果。方法将40只C57BL/6N小鼠随机分为联合免疫组(MS基因疫苗 hIL-12组)、MS基因疫苗组、卡介苗(BCG)组、空载体组和PBS组。将基因疫苗、空载体和PBS,经肌内注射免疫各组小鼠,每隔3周免疫1次,共免疫3次;BCG组经尾部皮下注射1×106CFU BCG免疫1次。采用ELISA法检测小鼠脾细胞培养上清中细胞因子的水平;用乳酸脱氢酶(LDH)释放法检测免疫小鼠细胞毒性T细胞的杀伤活性。用结核杆菌强毒株H37Rv静脉攻击小鼠后,计数肺和脾组织中结核杆菌的菌落数。对小鼠的部分肺和脾组织作病理切片,经HE染色观察组织病变的程度,经ZN染色检查抗酸杆菌,观察该疫苗对小鼠结核杆菌感染的免疫保护效果。结果联合免疫组能诱导较强的抗原特异性Th1型细胞免疫应答,免疫小鼠脾细胞培养上清液中IFN-γ和IL-2的水平,与BCG组相当,显著高于MS基因疫苗组,IL-4分泌减少,特异性CTL的杀伤活性增强,对小鼠结核杆菌感染有较好的免疫保护效果。表现为小鼠肺和脾组织中结核杆菌的菌落数显著减少,组织病变明显减轻,其效果与卡介苗(BCG)组相当,但优于MS基因疫苗组。结论以hIL-12表达质粒与MS基因疫苗联合免疫后,能显著增强MS基因疫苗对小鼠结核杆菌感染的免疫保护效果。     

卡巴胆碱抑制肿瘤坏死因子所致微血管内皮细胞通透性增高

目的探讨卡巴胆碱对肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）诱导的增加微血管通透性的作用。方法采用FITC标记白蛋白漏出法、考马斯亮蓝染色法观察卡巴胆碱对TNF-α诱导微血管内皮细胞通透性，细胞形态和细胞骨架变化的影响。结果与对照组比较，TNF-α明显增加微血管内皮细胞通透性（P〈0．05），诱导细胞皱缩，细胞间隙增大和细胞骨架排列紊乱。给予卡巴胆碱可以明显抑制TNF-α诱导微血管内皮细胞通透性增加，并呈剂量依赖性，同时可以使细胞间隙明显减小，细胞骨架排列有序。结论卡巴胆碱可能通过抑制TNF-α对细胞骨架的损伤，进而抑制微血管通透性增加。     

Molecular genetic methods in the diagnosis of hematologic neoplasms

Leukemias and lymphomas are monoclonal neoplasms that arise as a result of molecular abnormalities. These abnormalites are diverse but can be grouped into two general categories, chromosomal translocations that usually result in oncogene activation and inactivation of tumor suppressor genes. Recent advances in our understanding of chromosomal translocations have led to improved classification of leukemias and lymphomas. For example, the t(9;22)(q34;q11) is now considered a defining feature of chronic myeloid leukemia, and the t(2;5)(p23;q35) defines a clinically and biologically unique subset of anaplastic large cell lymphomas. In this review, we focus on chromosomal translocations in hematologic neoplasms and the techniques used for their detection. We also briefly discuss tumor suppressor genes and assessment of clonality in lymphoid neoplasms.     

Abnormal B cell function in haemophiliacs and their relationship with factor concentrates administration.

The present study was performed to evaluate B cell function in haemophiliacs. Spontaneous and pokeweed mitogen (PWM)-induced immunoglobulin (Ig) production was determined by ELISA in the supernatants of cultured peripheral blood lymphocytes (PBL) from 14 haemophiliacs and 17 normal donors. Spontaneous IgM, IgA and IgG production was three times higher in patients than normal controls, while PWM-induced IgM, IgA and IgG production was markedly reduced in patients compared to normal donors (P less than 0.025). Allogeneic co-cultures of haemophiliacs and normal B plus T cell fractions revealed that these results are due to a defect of the patients' T cell depleted fraction. These abnormalities were not found in three patients who had received no clotting factor concentrates for at least 1 year prior to the study. Additionally, the annual amount of clotting factor concentrates received by treated patients correlates well with the enhancement of spontaneous Ig production (r = +0.688, P less than 0.02), the decrease of PWM-induced Ig secretion (r = -0.655, P less than 0.02), and the elevation of serum IgG levels (r = +0.610, P less than 0.05). These findings suggest that the administration of clotting factor concentrates play an important role in the altered B cell function in haemophiliacs.     

Evaluation of three simple and rapid immunological tests for detection of heat-labile enterotoxin of enterotoxigenic Escherichia coli.

Three simple immunological tests, the modified Elek (Biken) test, the modified staphylococcal coagglutination test, and the rapid GM1-horseradish peroxidase-enzyme-linked immunosorbent assay have been evaluated for detection of heat-labile enterotoxin of enterotoxigenic Escherichia coli. Of the 100 coded E. coli strains tested, 94 gave consistent results with all the three immunological tests; a discrepancy was observed in only 6 strains. Identical results were obtained when the Biken test was conducted with complete and incomplete Biken kits (Meguro Institute Ltd., Osaka, Japan). All three immunological tests evaluated in this study were found to be sensitive and simple and can be easily adopted by any laboratory for detection of heat-labile enterotoxins of enterotoxigenic E. coli strains.     

Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload.

Alterations in triacylglycerol and phospholipid metabolism are known to occur during the evolution of myocardial ischemic injury. The purpose of this study was to explore potential relationships between the accumulation of arachidonic acid and other fatty acids, the accumulation of triacylglycerol, and the progression of myocardial injury. Measurements of the fatty acid levels in triacylglycerol, unesterified fatty acids, and calcium content were correlated with myocardial function during ischemia and ischemia with reflow in an isolated perfused rat heart preparation. After 10 minutes of ischemia in this model, myocardial dysfunction was reversible, with recovery of left ventricular +dP/dt to 82.0% +/- 4.8% of control values upon reperfusion. Hearts did not recover with reperfusion after 30 minutes of ischemia and displayed a significant increase in tissue calcium content. A significant, nearly threefold increase in the arachidonic acid content of triacylglycerol was found after 10 minutes of ischemia and continued to increase with longer periods of ischemia and reflow. Other fatty acids also showed increased levels in triacylglycerol. The time course of accumulation of unesterified arachidonic acid paralleled the loss of myocardial function. Levels of free arachidonic acid were (in nanomoles per gram wet weight) 11.1 +/- 2.1 (SEM) for control hearts, 17.3 +/- 1.9 after 10 minutes of ischemia, and 38.4 +/- 2.5 after 30 minutes of ischemia. Increases in other free fatty acids contributed to a significant increase in total free fatty acid accumulation after 30 minutes of ischemia. Thus, the content of arachidonic and other fatty acids in triacylglycerol was found to increase early during ischemia, and a major increase in free arachidonic and other unesterified fatty acids occurred after a longer period of ischemia. These findings are consistent with an initial reincorporation of free fatty acids into triacylglycerol after release from membrane phospholipids, suggesting that membrane fatty acids may be a major source of triacylglycerol that accumulates in ischemic myocardium. In addition, these results suggest that a major increase in free fatty acids during ischemia and ischemia with reflow correlates temporally with the development of severe contractile dysfunction and accumulation of calcium in the heart.     

An Analytic Model of Subminiature Auditory Sensation System for Sound Source Localization

It is reported that some types of insects have a remarkable ability to detect the direction of an incident sound even though its acoustic sensory organs are in very close proximity each other. Maybe the ears are jointed by a cuticular structure with which the separated motions can be coupled mechanically and thus be magnified. In this paper, a detailed model is setup to describe the principle of this type of localization using a mechanical coupled structure. The transfer functions and the responses of the model in terms of time and frequency are analyzed to describe the mechanism of its ability of directional hearing. This analytical model provides a method to design the experimental model for the predetermined incident sound pressure, and the analysis of this model shows that this structure have the ability to determine the direction of the incident stimulus.     

Face cooling-induced reduction of plasma prolactin response to exercise as part of an integrated response to thermal stress

Summary This study was designed to verify if the decrease in blood prolactin (PRL) induced by selective face cooling during exercise could be part of a response to specific body thermal stress. Five healthy trained male cyclists presenting a significant plasma PRL elevation to exercise were, on three occasions and at weekly interval, submitted to a submaximal exercise (approx. 65% ) on ergocycle with and without selective face cooling. In absence of face cooling a first trial served to establish reference values for workload, heart rate and plasma PRL levels, the latter increasing markedly (450% of resting values) in these conditions. On a second trial but with workload maintained at reference values (222±9 W), a significant bradycardia was observed with face cooling; furthermore, plasma PRL response to exercise was significantly reduced (to 31% of original response). On a third trial with face cooling, workload had to be significantly augmented (242±10 W) to maintain heart rate at reference level (78%HR _max); in addition, plasma PRL response to exercise was almost unchanged compared to the reference-value level. The absence of a significant face cooling-induced decrease in sympathetic tonus, as evaluated through peripheral plasma catecholamines response, does not indicate a role for the autonomic nervous system in the face cooling-induced reduction of both heart rate and PRL responses during exercise. Assay of circulating peripheral beta-endorphins could indicate that the face cooling-induced PRL blunted response does not necessarily involve an opioid mediation. It was concluded that decreased plasma PRL levels could be associated to bradycardia, hyposudation and peripheral vaso-constriction to constitute an integrated response to face cooling during thermal stress. This study was supported by grants from Natural Sciences and Engineering Research Council of Canada and from Régie de la Sécurité dans les Sports du Québec