蝙蝠葛碱抑制凝血酶诱导的血小板膜糖蛋白Ⅳ再分布和胞内α—颗？…

探讨蝙蝠葛碱对血小板聚集功能的影响。观察Ｄａｕ对血小板膜糖蛋白Ⅳ再分布和胞内α－颗粒凝血酶敏感蛋白释放的抑制作用。方法：应用流式细胞仪分别检测静息血小板ＧＰⅣ分布,ＴＳＰ释放。结果;Ｄａｕ并不影响静息血小板膜ＧＰⅣ和ＴＳＰ分布。而对活化血小板膜ＧＰⅣ再分布和细胞内α－颗粒ＴＳＰ释放具有明显的抑制作用,且两者的抑制作用呈显著正相关,这种抑制作用并不受Ｃａ＾２＋浓度的影响。     

左旋四氢巴马汀对单个豚鼠心室肌细胞钙电流的阻滞作用

AIM: To study the effect of l-tetrahydropalmatine (l-THP) on L-type calcium channel. METHODS: Patch clamp technique (whole cell recording) was used to record L-Ca2+ current in single cardiac myocyte. RESULTS: 1) l-THP 1, 10, and 100 micromol.L-1 reduced ICa-max from (999 +/- 93) pA to (700 +/- 111) pA, (582 +/- 66) pA, and (420 +/- 112) pA (n = 6, P < 0.01), respectively. 2) l-THP reduced the voltage at half-maximal inactivation (V1/2) of L-Ca2+ channel to more negative potentials by 9 mV (n = 5, P < 0.05). 3) l-THP caused both tonic and use-dependent reduction of Ca2+ current. Tonic block of l-THP on Ca2+ current was 46% +/- 8% (n = 6, P < 0.01). The degree of use dependent blocking was 13.5% +/- 2.4% (n = 6, P < 0.05) at 1 Hz, the degree increased to 44% +/- 5% (n = 6, P < 0.01) at 3 Hz. 4) l-THP delayed half-recovery time of Ca2+ channel recovery from inactivity from (94 +/- 39) ms to (170 +/- 42) ms(n = 6, P < 0.01). CONCLUSION: l-THP has a moderate inhibitory effect on L-Ca2+ current.     

Diagnosis and management of organic ovarian cysts: indications and procedures for laparoscopy

In the field of gynaecological surgery, the past few years have been significant due to the development of operative laparoscopy. Originally recommended for the diagnosis of female infertility, over the past 15 years laparoscopy has acquired the standing of a surgical discipline in its own right. Laparoscopic surgical treatment of ovarian cysts, whether conservative or radical, has now been completely standardized. The aim of this work is to specify the indications, procedures and risks involved with this surgery as applied to organic ovarian cysts. Only benign ovarian cysts are suitable for treatment by laparoscopic surgery; ovarian cancer must always be handled by classic surgery using a mid-line laparotomy. Given that clinical and other pre-operative investigations can give only an indication, ovarian lesions require surgical investigation to diagnose the histological type. Laparoscopy appears to be as reliable as laparotomy when assessing whether an ovarian tumour is malignant. The risk of parietal contamination and peritoneal dissemination if a malignancy is not recognized means that, if there are no signs of extra-ovarian extension, adnexectomy is mandatory whenever there is the slightest doubt. This adnexectomy must obey two important rules: it must be accomplished without rupturing the cyst, and the cyst must be placed, intact, inside an endoscopic bag before being extracted. Provided that all stages of the procedure, from pre-operative work-up to the initial diagnostic phase of the laparoscopy, are carried out meticulously, laparoscopic surgery is reliable for both the diagnosis and the management of benign organic-ovarian cysts.     

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).     

Excitotoxic damage in neurotrauma: fact or fiction

Secondary brain injury is a well-demonstrated contributor to the morbidity and mortality of severe head injury. At least ten new compounds which antagonize the effects of glutamate in the brain are currently undergoing clinical evaluation as putative protectants against this secondary injury. None have yet shown clear benefit in humans. It is accepted that excitatory amino acids, glutamate in particular, have 'neurotoxic' effects on the brain, especially when present in excessive amounts. Whether or not this excitatory amino acid toxicity represents the major pathway for secondary damage is disputed. In the laboratory, over 300 studies have now demonstrated the ability of glutamate antagonist drugs of various types to prevent ischemic and post-traumatic acute brain damage. The magnitude and consistency of protection afforded by this group of compounds exceeds that which has ever been shown with any other mechanisms. Laboratory studies using in vitro neuronal models have implicated glutamate as a promoter of ionic flux and calcium entry across the cell membrane, which may then initiate astrocytic swelling and neuronal necrosis. In vivo animal models of brain trauma and ischemia have demonstrated glutamate release and potassium efflux into the extracellular fluid (ECF). Outcome in these models is improved, as assessed by both histopathology and behavioral studies, when glutamate antagonists are used. Additionally, presynaptic glutamate blockade in animal models such as middle cerebral artery (MCA) occlusion and subdural hematoma, creates reduction in lesion size which is paralleled by reduced glutamate production. In bridging the gap between the laboratory and the patient care setting, human microdialysis studies have shown massive release of excitatory amino acids into the ECF after severe head injury. Early studies with TV-methyl-D-aspartate (NMDA) antagonists in head injured humans have demonstrated a reduction of intracranial pressure and an improvement in cerebral perfusion. Future studies are needed to examine further the value of protection from excitatory amino acid induced injury.     

Organochlorine residues in tissues of striped dolphins affected by the 1990 mediterranean epizootic: Relationships with the fatty acid composition

A simple and rapid method was developed for the simultaneous determination of fatty acids, organochlorine pesticides, and polychlorinated biphenyl (PCB) congeners in the same sample in order to explore possible connections between levels of contaminants and fatty acid composition. The method was applied to samples of melon, cerebrum, cerebellum, lung, liver, kidneys, and skeletal muscle obtained from 5 male and 5 female striped dolphins (Stenella coeruleoalba) found stranded in 1990 in the northeastern Spanish coasts during the morbillivirus epizootic that affected this cetacean in the Mediterranean Sea. The results indicate that PCBs were dominant in all tissues, with the highest geometric mean concentration being found in melon (903 g g^–1 wet wt); DDTs were also found at high concentrations (111 g g^–1 wet wt, in melon). Statistical analysis indicate that organochlorine concentration was correlated with the fatty acid composition of tissues, although some of these variations can be interpreted as a consequence of a shift in the diet produced in the striped dolphin population. However, other changes such as the negative correlation with arachidonic acid may suggest that the eicosanoid production could have been affected by the extremely high concentrations of PCBs and DDTs.     

Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption

For almost a half century scientists have striven to develop a theoretical model capable of predicting oral drug absorption in humans. From the pH-partition hypothesis to the compartmental absorption and transit (CAT) model, various qualitative/quantitative approaches have been proposed, revised and extended. In this review, these models are classified into three categories; quasi-equilibrium models, steady-state models and dynamic models. The quasi-equilibrium models include the pH-partition hypothesis and the absorption potential concept, the steady-state models include the film model and the mass balance approaches, and the dynamic models include the dispersion, mixing tank and CAT models. The quasi-equilibrium models generally provide a basic guideline for understanding drug absorption trends. The steady-state models can be used to estimate the fraction of dose absorbed. The dynamic models predict both the fraction of dose absorbed and the rate of drug absorption and can be related to pharmacokinetic models to evaluate plasma concentration profiles.     

Alterations of striatal monoamine metabolites in young rats following pre- and postnatal lead exposure

Dam rats were given lead (0, 0.58, 1.76, and 5.27 mmol/l) containing water ad lib from day 16 of gestation to weaning of the offspring on day 21 postpartum. The pups continued drinking the same lead containing water until the postnatal day 30. At the 30th day postpartum, the pups in each lead treated group were divided into four groups. The first group contains six male pups (PN30M). The second, third, and fourth groups contain six female pups (PN30F, PN60a, PN60b), respectively. The six female pups from control group formed the fifth group (PN60c). PN60a continued drinking the same lead-containing water until the postnatal day 60. PN60b were dosed with distilled water instead of lead-containing water from the 30th day to the 60th day postpartum. PN60c began to expose to 5.27 mmol Pb/l from the 30th day to the 60th day postpartum. The rats in PN30M and PN30F were decapitated on the 30th day postartum, whereas PN60a, PN60b, and PN60c were decapitated on the 60th day postpartum. The contents of metabolites of monoamine neurotransmitters: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyin-doleacetic acid (5-HIAA) in striatum were determined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). There were significant increases in the concentrations of HVA (1.58 ± 0.30 vs. 1.17 ± 0.12 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.01; and 1.44 ± 0.08 vs. 1.17 ± 0.10 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) and DOPAC (2.39 ± 0.25, 2.47 ± 0.28, 2.39 ± 0.44 vs. 1.82 ± 0.24 ng/mg wet tissue in three lead treated groups of PN60a, p < 0.05). The significant decreases in the concentration of MHPG (37.33 ± 5.53, 32.02 ± 6.87, 33.31 ± 2.41 vs. 43.85 ± 4.93 ng/mg wet tissue in the 0.58 mmol Pb/l group of PN60a, p < 0.05; in the 1.76 and the 5.27 mmol Pb/l group of PN60a, p < 0.01) and 5-HIAA (0.23 ± 0.04 vs. 0.38 ± 0.05 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.05; 0.26 ± 0.09 vs. 0.45 ± 0.09 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30F, p < 0.05; 0.31 ± 0.08 vs. 0.44 ± 0.08 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) were observed. No significant changes in the concentration of monoamine metabolites were observed either in rats of PN60b or PN60c. The results demonstrated the disturbances of monoamine metabolism in the striatum of developmental lead exposed rats.     

Prognostic relevance of detection of ligands for vertebrate galectins and a Lewis(Y)-specific monoclonal antibody

Tissue sections taken from 157 potentially curatively operated lung carcinoma patients (70 epidermoid carcinomas, 68 adenocarcinomas, 15 large cell anaplastic, and 4 small cell anaplastic carcinomas) were examined by a standardized histochemical protocol in a prospective study evaluating the extent of various types of probes to serve as prognostic indicators in lung cancer. Detailed clinical records and survival data (minimum 56 weeks, maximum 96 weeks) were correlated to the results of the histochemical reactions. The study centres on monitoring the expression of galactoside-containing epitopes in tumor cells by human, animal and plant lectins: and with a monoclonal antibody. In addition, affinity-purified subfractions of natural antibodies from human serum with preferential affinity to alpha- and beta-galactosides, respectively, were employed. Significant contributions to the estimation of the survival of patients are given by clinical parameters (pT, pN stage), number of resected and positive lymph nodes and presence of tumor metastases into specific lymph nodes (No. 5 and No. 6 right and left). With respect to the relevance of subsets of beta-galactosides, the galectin from chicken liver (CL-16) and the Le(y)-specific monoclonal antibody unveiled a negative correlation at a statistically significant level. The predictive value of binding of the animal lectin CL-16 was especially pronounced for patients with advanced tumor stages, pointing to a potential role of such lectin-reactive beta-galactosides in late tumor stages or progression.     

Colonic pseudo-tumor linked to Ogilvie's syndrome

We present a case of a giant colonic pseudolipoma in a patient with colonic dysmotility due to chronic Ogilvie's syndrome.