Calcitonin gene-related peptide increases blood flow and potentiates plasma protein extravasation in the rat knee joint.

1. The effects of calcitonin gene-related peptide (CGRP) and other vasoactive mediators of inflammation on blood flow in the synovial vessels and plasma protein extravasation into the knee (femoro-tibial) joint of the pentobarbitone-anaesthetized rat were measured. 2. Changes in synovial blood flow were estimated by 133xenon clearance from the synovial cavity. CGRP (0.1 pmol and 10 pmol) and prostaglandin E1 (PGE1; 3 pmol and 300 pmol) significantly increased clearance from the knee joint measured 5 min after intra-articular injection. Substance P (10 pmol) had no effect on synovial blood flow. 3. Intra-articular perfusion of the rat knee with CGRP at concentrations up to 0.1 mM, or PGE1 at concentrations up to 10 microM, did not increase plasma extravasation into the synovial cavity measured by accumulation of intravenously injected 125I-albumin in the perfusate. 4. Plasma extravasation into the knee was significantly increased by infusion of bradykinin (0.1 microM), 5-hydroxytryptamine (1 microM) and histamine (0.1 mM), compared with the contralateral joints in the same animals which were perfused with Tyrode solution. 5. Perfusion of the knee joint with substance P did not specifically induce 125I-labelled albumin accumulation in the synovial cavity even at doses that had systemic effects as observed by marked plasma extravasation into other tissues. 6. The increase in plasma extravasation induced by histamine (0.1 mM) was potentiated by co-infusion with CGRP (0.1 microM) and PGE1 (3 microM). However the response to a submaximal dose (0.1 microM) of bradykinin, which induced similar plasma extravasation to histamine (0.1 mM), was not increased by co-infusion with CGRP or PGE1.(ABSTRACT TRUNCATED AT 250 WORDS)     

银杏叶提取物活血通络作用的药效学研究

目的：观察银杏叶提取物(EGb)的活血通络功效。方法：小鼠耳廓微循环实验、胶原蛋白-肾上腺素诱导的小鼠体内血栓形成实验、大鼠血液流变学实验及离体兔耳灌流实验。结果：银杏叶提取物经口给药．能显著改善小鼠耳廓微循环，抑制胶原蛋白-肾上腺素诱导的小鼠体内血栓形成，降低大鼠血液粘度，并能显著扩张离体兔耳血管。结论：银杏叶提取物有显著的活血化瘀功效。     

Studies on the effects of the antiandrogen cyproterone acetate on social encounters between pairs of male mice

An attempt was made in two experiments to reinvestigate the effects of the antiandrogen cyproterone acetate (CA) on mouse social behavior in a variety of ethologically-assessed paired encounters. The data confirm that CA reduces offense (threat and attack) in animals when both subjects receive the material but that CA has no such action in other pairings. This suggests that CA's major suppressive effect on "hostility" is expressed in mice via a reduction in "attack-promoting" pheromone production. Indeed, there was evidence in the more chronic study that CA, could augment (via a central mechanism?) offense in subjects paired with docile anosmic opponents. Changes in defense were largely responses to variations in the degree of attack to which animals were subjected. The antihormone also had actions on other aspects of behavior including sexual activity, social investigation and immobility in such tests. CA had a potent suppressive action on the weights of sex accessory glands. The data do not suggest that CA can be used as a specific antihostility agent.     

Human fibroblast tissue factor is inhibited by lipoprotein-associated coagulation inhibitor and placental anticoagulant protein but not by apolipoprotein A-II

Studies of proteins that inhibit tissue factor activity have generally been conducted using either an extracted tissue homogenate ("thromboplastin") or tissue factor protein reconstituted into phospholipid vesicles rather than with tissue factor expressed in cell membranes (its physiological environment). In the present study, a human fibroblast cell strain was used to evaluate the effects of lipoprotein associated coagulation inhibitor (LACI), placental anticoagulant protein (PAP), and apolipoprotein A-II (apo A-II) on human tissue factor in cell membranes. LACI was tested from 7.8 to 500 pmol/L on fibroblasts cultured at cell densities ranging from 3,500 to 9,925 cells/well, and caused a progressive inhibition of tissue factor activity. PAP was tested from 3.9 nmol/L to 1 mumol/L at cell densities ranging from 4,500 to 15,400 cells/well and caused up to 83% inhibition of tissue factor activity. Inhibition by these proteins appeared to be influenced by cell density as well as whether the cells were intact or disrupted. Apo A-II, up to 1 mumol/L, did not inhibit the tissue factor activity of intact or disrupted fibroblasts at any cell density examined even though it did inhibit the activity of tissue factor in phospholipid vesicles. Of these inhibitors of tissue factor-dependent activation of factor X, LACI was the most effective in suppressing the generation of factor Xa activity. The effects obtained with apo A-II are clearly dependent on the nature of the tissue factor preparation with which it is tested. The disparity between the inhibitory effect of apo A-II on the activity of tissue factor reconstituted into lipid vesicles and the absence of effect on the activity of tissue factor remaining in cell membranes serves to reemphasize the necessity of reexamining results obtained with model systems using as nearly physiological reagents as possible.     

Nicotine induces calcium spikes in single nerve terminal varicosities: a role for intracellular calcium stores

We have previously shown that a large part of the D-amphetamine-induced release of dopamine in the nucleus accumbens is not associated with an increase in locomotor activity, and that "functional" dopamine release (i.e. release of dopamine associated with locomotor activity) requires the distal facilitation of noradrenergic transmission through alpha1-adrenergic receptors in the prefrontal cortex. To determine the role of monosynaptic or polysynaptic projections from the prefrontal cortex to the nucleus accumbens in these amphetamine responses, either AMPA/kainate (6-cyano-7-nitroquinoxaline-2,3-dione, CNQX, 300microM), N-methyl-D-aspartate (D(-)-2-amino-5-phosphono-pentanoic acid, APV, 500microM) or metabotropic [(+)-alpha-methyl-4-carboxy-phenylglycine, MCPG, 10mM] glutamate receptor antagonists were infused through a dialysis probe in the rat nucleus accumbens. CNQX and MCPG but not APV reduced the "non-functional" release of dopamine evoked by local (3microM) and systemic D-amphetamine (2mg/kg i.p.) treatments. However, the locomotor hyperactivity and functional dopamine release induced by systemic D-amphetamine were abolished by MCPG, but neither by CNQX nor by APV. MCPG treatment also abolished the hyperlocomotor activity and functional dopamine release evoked by bilateral morphine injection into the ventral tegmental area. The dopamine release evoked by this morphine treatment was 16-fold lower than that induced by the systemic D-amphetamine injection, although similar behavioral activations were observed. Altogether, our results further aid the discrimination of functional and non-functional release of dopamine. We suggest that the activation of metabotropic glutamate receptors in the nucleus accumbens is required for functional dopamine release following systemic D-amphetamine injection.     

癫痫儿童脑功能成像的临床应用研究进展

癫痫在儿童和青少年神经疾病中的发病率非常高 ,癫痫反复发作不仅影响患儿的运动功能 ,还影响其感知觉、记忆和语言等认知功能的健康发展。目前手术治疗是控制顽固性癫痫的重要手段 ,能否取得良好的手术效果有赖于癫痫灶的确定和认知功能皮层的准确定位。癫痫灶确定和认知功能皮层准确定位问题的解决不仅有利于癫痫儿童的诊断和治疗 ,也有利于更深入地了解癫痫发病机制 ,还有助于人类对语言、记忆等认知功能及其发展机制的深入认识。1　认知功能的手术前评估1.1　语言侧化与语言优势半球定位近三十年来 ,胼胝体切除术、脑叶切除术、大脑半球…     

Interaction of capsulate Haemophilus influenzae with human airway mucosa in vitro.

Two pairs of isogenic capsulate and noncapsulate and one pair of capsulate fimbriate and nonfimbriate strains of Haemophilus influenzae type b were studied in an organ culture of human respiratory mucosa. Over 24 h, the numbers of recovered bacteria increased from the original inoculum size of 10(5) to 10(8) CFU/ml. Transmission electron microscopy and scanning electron microscopy showed that noncapsulate organisms caused significant epithelial damage, whereas capsulate strains did not. Association of noncapsulate bacteria with damaged epithelial cells was observed by 14 h of incubation. In contrast, capsulate organisms were associated with a dense, thick, gel-like matrix which was observed above the epithelial surface. These capsulate organisms were not seen to associate with the epithelial surface (by transmission electron microscopy), though they were occasionally seen adhering to cells by scanning electron microscopy. Fimbriate capsulate H. influenzae showed increased adherence to buccal cells compared with nonfimbriate capsulate organisms. There was also association of fimbriate capsulate bacteria with damaged organ culture epithelium in one of four experiments. It is concluded that both capsule and fimbriae affect the interaction of H. influenzae with human airway mucosa in vitro by influencing adherence to and damage of the epithelium.     

HLA and Cancer in South African Indians

Two-hundred-and-forty-nine Indian cancer patients were tested for 39 HLA antigens and the antigen frequencies were compared with those of 603 control subjects. Comparisons were also made between cancer patients and controls for each ethnic group and for each site of cancer. There was an increase in the frequency of the HLA antigens A11 and Bw52 in patients with malignancies. Heterozygosity at the B locus was significantly increased in patients with cancer of the breast. The Aw24, B17 haplotype was also associated with breast cancer.     

Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB

Usher syndrome is recognized as the most frequent cause of hereditary deaf-blindness. Usher syndrome type I (USH1), the most severe form of the disease, is characterized by profound congenital sensorineural deafness, constant vestibular dysfunction, and retinitis pigmentosa of prepubertal onset. This form is genetically heterogeneous and five loci (USH1A-E) have been mapped thusfar. However, only the gene responsible for USH1 B (which accounts for approximately 75% of USH1 cases) has been characterized. It encodes a long-tailed unconventional myosin, myosin VIIA, with a predicted 2215 amino acid sequence. Primers covering the complete myosin VIIA coding sequence as well as the 3' non coding sequence were designed, allowing direct sequence analysis of each of the 48 coding exons and flanking splice sites in seven patients affected by USH1. Four novel mutations were thereby identified. The possibility should now be considered of a sequence-based prenatal diagnosis in some of the families affected by this very severe form of Usher syndrome.