Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs.

Conscious pigs underwent a sequence of 10 2-min coronary occlusions, each separated by 2 min of reperfusion, for three consecutive days (days 1, 2, and 3). On day 1, pigs received an i.v. infusion of a combination of antioxidants (superoxide dismutase, catalase, and N-2 mercaptopropionyl glycine; group II, n = 9), nisoldipine (group III, n = 6), or vehicle (group I [controls], n = 9). In the control group, systolic wall thickening (WTh) in the ischemic-reperfused region on day 1 remained significantly depressed for 4 h after the 10th reperfusion, indicating myocardial "stunning." On days 2 and 3, however, the recovery of WTh improved markedly, so that the total deficit of WTh decreased by 53% on day 2 and 56% on day 3 compared with day 1 (P < 0.01), indicating the development of a powerful cardioprotective response (late preconditioning against stunning). In the anti-oxidant-treated group, the total deficit of WTh on day 1 was 54% less than in the control group (P < 0.01). On day 2, the total deficit of WTh was 85% greater than that observed on day 1 and similar to that observed on day 1 in the control group. On day 3, the total deficit of WTh was 58% less than that noted on day 2 (P < 0.01). In the nisoldipine-treated group, the total deficit of WTh on day 1 was 53% less than that noted in controls (P < 0.01). On days 2 and 3, the total deficit of WTh was similar to the corresponding values in the control group. These results demonstrate that: (a) in the conscious pig, antioxidant therapy completely blocks the development of late preconditioning against stunning, indicating that the production of reactive oxygen species (ROS) on day 1 is the mechanism whereby ischemia induces the protective response observed on day 2; (b) antioxidant therapy markedly attenuates myocardial stunning on day 1, indicating that ROS play an important pathogenetic role in postischemic dysfunction in the porcine heart despite the lack of xanthine oxidase; (c) although the administration of a calcium-channel antagonist (nisoldipine) is as effective as antioxidant therapy in attenuating myocardial stunning on day 1, it has no effect on late preconditioning on day 2, indicating that the ability of antioxidants to block late preconditioning is not a nonspecific result of the mitigation of postischemic dysfunction on day 1. Generation of ROS during reperfusion is generally viewed as a deleterious process. Our finding that ROS contribute to the genesis of myocardial stunning but, at the same time, trigger the development of late preconditioning against stunning supports a complex pathophysiological paradigm, in which ROS play an immediate injurious role (as mediators of stunning) followed by a useful function (as mediators of subsequent preconditioning).     

子宫内膜癌端粒酶活性研究

目的探索端粒酶活性与子宫内膜癌发生发展的关系。方法采用ＰＣＲ－ＴＲＡＰ方法检测３４例子宫内膜癌和６例正常子宫内膜组织的端粒酶活性。结果在３４例子宫内膜癌中,２８例端粒酶活性阳性;６例正常子宫内膜组织中,有１例端粒酶活性阳性。结论端粒酶激活与子宫内膜癌的发生发展有密切关系,并有可能成为子宫内膜癌的临床肿瘤标记物     

Rapid modulation of keratinocyte differentiation by the external environment

The ultrastructural differentiation of epidermal keratinocytes cultured in the presence of 3T3 feeder cells is significantly different from that of the epidermis in vivo. Several markers of keratinization, including keratohyaline granules (KGs), membrane-coating granules (MCGs), and an enucleated stratum corneum are essentially absent from cultured cells. When cultured rabbit epidermal cells were trypsinized and injected subcutaneously into athymic mice, the cells reaggregated and formed cysts lined with a stratified squamous epithelium morphologically resembling the in vivo epidermis. In this paper, we examined the differentiation of the injected cells by electron microscopy. Within 24 h after injection, MCGs and KGs appeared in the reaggregated epidermal cells. Horny cells were noted within 48 h. Since basement membrane formation was not completed until much later (between 4-9 days), a direct contact between epidermal cells and a continuous basal lamina structure was not required for the formation of various keratinization markers. Glycogen and lipid droplets, which were abundant in the early (10-48 h) cystic epithelia, gradually disappeared from the basal through the granular layers during days 2-9. By 16 days, the ultrastructure of the cystic epithelium appeared similar to the in vivo rabbit epidermis including the formation of "rabbit-type" KGs, MCGs, and normal enucleated horny cells. These results provided further evidence that the differentiation of epidermal cells can be modulated significantly and reversibly by the external environment. Moreover, the expression of certain morphologic markers of keratinization (KGs and MCGs) can be modulated rapidly by the growth environment.     

RELATIONSHIP BETWEEN CORNEAL DELLEN AND TEARFILM BREAKUP TIME

The BUT of 51 strabismus patients were measured before and after operation. The average pre-op BUT was 28.75 seconds(10.96"-91.80"). The post-op BUT in all operated eyes were reduced significantly, no matter what procedures had been performed and whether dellen appeared or not(P<0.01). The BUT in the group complicated dellen reduced from 23.22"(pre-op) to 8.61"(post-op). The incidence of dellen was 22.54% in this study. The incidence of dellen after rectus resection procedure(47.75%) was much higher than that after rectus recession(5.13%)(P<0.01). This study showed that dellen was closelyre related to the BUT and occurred more often in the eyes on which resection procedure was performed. It is considered that excessive lacrimation and elevation of the bulbar conjunctiva near the limbus may disturb the stability of the precornea tearfilm and cause the tearfilm break up earlier. Local corneal dehydration and dellen formation may be caused by reduced BUT. The incidence of dellen after operation may be higher if the cornea was carefully observed.     

中药厚朴及其类似品的有效成分分析

本文对中药厚朴及其类似品中的有效成分——厚朴酚、和厚朴酚及木兰箭毒碱分别进行了高效液相色谱法和双波长扫描法测定;对其挥发油中化学成分进行了气-质联用分离与鉴定。     

Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats

BACKGROUND AND PURPOSE: Studies show that blocking the activation of caspases by the caspase inhibitors z-VAD.FMK and z-DEVD.FMK can reduce ischemic neuronal injury after cerebral ischemia. Because the severity of ischemia was mild in some studies, we tested the efficacy of these caspase inhibitors on moderately severe but transient forebrain and focal ischemic insults in the rat. METHODS: Various regimens of z-VAD, z-DEVD, and control DMSO were given to rats subjected to either 4-vessel occlusion ischemia (4-VO, 10-minute occlusion, 7-day survival) or distal middle cerebral artery occlusion (MCAo, 90-minute occlusion, 22.5-hour survival). In global ischemia, treatments were given immediately after ischemia (experiment 1) or as preischemic and postischemic treatments (experiment 2). Three focal ischemia experiments were done. Injection times were 60 minutes into ischemia (experiment 1) and 60 minutes into ischemia plus 30 and 120 minutes after ischemia (experiment 2). Experiment 3 was identical to experiment 2 except that a 30-minute preischemia treatment was instituted. Core normothermia was maintained in all experiments during ischemia. However, in the last focal and global experiments, core and brain temperatures, respectively, were also measured after ischemia with telemetry probes. Because hyperthermia accompanied z-DEVD treatment, an extra z-DEVD-treated group (MCAo) was included with temperature clamped at normothermia. RESULTS: Neither z-VAD nor z-DEVD significantly reduced CA1 injury after global ischemia. In focal ischemia, both drugs significantly reduced infarction, but only in the third experiment, and the prevention of hyperthermia that accompanied z-DEVD treatment did not alter this. CONCLUSIONS: These results suggest a detrimental role of caspases in moderately severe focal but not global cerebral ischemia.     

胆管结石乳头局部组织中血管活性肠肽和一氧化氮合酶表达的改变及意义

目的 探讨胆管结石患者乳头局部组织中血管活性肠肽(VIP)和一氧化氮合酶(NOS)表达的改变及意义。方法 选择68例进行逆行胰胆管造影和/或乳头括约肌切开术的胆管结石患者,采用内镜下活检乳头局部组织。常规石蜡包埋,连续切片,免疫组化SABC法检测VIP及NOS。对照组为门诊胃镜检查胃粘膜大致正常者。结果 结石组乳头粘膜内 VlP和NOS阳性产物与对照组相比较显著降低(P相似文献