Pathogenesis of congenital pyrimidine 5′ -nucleotidase | deficiency: A study on relationship among erythrocyte morphology, enzyme protein content and activity

Objective: To further explore the mechanism of congenital pyrimidine 5'-nucleotidase I deficiency. Methods; The samples were collected from the family members of a patient with P5'N- I deficiency. The enzyme activities were measured by UMP method and the enzyme proteins were quantified by ELISA while the morphology of peripheral blood cells was observed. Results: The enzyme contents reduced as their enzyme activities decreased in the family especially in four members. There was a significant positive correlation(r =0. 955) between the activity and the content of P 5'N- I . The count of the stippling cell was varied in the family. Conclusion.- One of the reasons for congenital P5' N- I deficiency might be the deficiency in the enzyme content. The morphology of peripheral blood erythrocyte may be an assistant diagnotic index. The P5'N- I activities and contents were measured simultaneously may be a effective method in clinic diagnosis.     

Th2细胞因子调节哮喘炎症细胞转运机制的研究

目的 探讨Th2细胞因子IL-5、IL-13调节哮喘炎症过程中肺和骨髓之间的细胞转运机制。方法 建立哮喘动物模型,获取肺泡灌洗液,检测IL-5、IFN-γ,浓度并进行病理分析;应用原位杂交技术检测肺组织IL-5、IL-13 mRNA表达和骨髓IL-5mRNA表达;免疫组化法观察肺、骨髓IL-5免疫反应细胞;流式细胞仪检测骨髓CD34、CD3阳性细胞。结果 哮喘组肺泡灌洗液IL-5浓度明显高于对照组(P<0.001);哮喘组肺组织病理改变显示小气道痉挛,管壁周围炎性细胞浸润,以嗜酸粒细胞、淋巴细胞为主;哮喘组肺组织IL-5、IL-13 mRNA表达较对照组显著增加(P<0.01);哮喘组骨髓IL-5 mRNA阳性细胞明显增加(P<0.001),与肺组织IL-5 mRNA表达的增高密切相关(P<0.05);此外,哮喘组肺组织和骨髓IL-5免疫反应细胞显著增加(P<0.01),骨髓CD34、CD3细胞均显著增高(P<0.01),并且CD34增高与骨髓细胞表达IL-5 mRNA密切相关(P<0.05)。结论IL-5可能在转录和转录后水平均参与调节骨髓嗜酸粒细胞的功能和炎症细胞在肺和骨髓之间的转运。     

5-单硝异山梨酯缓释剂治疗老年单纯收缩期高血压疗效观察

目的 观察5-单硝异山梨酯缓释剂（ISMN）对老年单纯收缩期高血压（ISH）患者降压治疗的疗效。方法 80例ISH患者随机分为对照组39例和治疗组41例，对照组给予氨氯地平5mg，吲达帕安2．5mg每日1次口服，治疗组在上述治疗的基础上给予5-单硝异山梨酯缓释剂40mg每日1次口服，疗程4周。结果 （1）治疗组从第一周开始收缩压（SBP）下降幅度即大于对照组，先于对照组于第二周降至正常，差异有显著性（P〈0．05）；（2）从第一周开始治疗组舒张压（DBP）下降幅度即小于对照组（P〈0．05），第三周开始差距加大，差异有非常显著性（P〈0．01），整个观察期内治疗组DBP下降幅度始终小于对照组，且从第二周开始处于相对稳定状态；（3）第一周开始治疗组脉压（PP）下降幅度即大于对照组（P〈0．05），第二周开始差距进一步加大，差异有非常显著性（P〈0．01）。结论 硝酸酯类药物能降低ISH患者的SBP,而对DBP影响不大，使PP减小，对ISH患者降压治疗有益。     

Metabolism and binding of androgens in the spinal cord of the rat

The binding of [3H]androgens and estrogens, and the metabolism of [3H]androgens, were studied in the spinal cord of the adult rat. High-affinity, specific binding sites for [3H]testosterone and [3H]estradiol were detected in cytosol fractions from the spinal cords of castrate animals. Equilibrium dissociation constants for reaction of these sites with their respective ligands were similar to those of androgen and estrogen receptors from other regions of the central nervous system. Nuclear binding of [3H]estradiol was observed in the spinal cord 1 h after intravenous administration of the isotope. Likewise, exchange assay demonstrated the presence of high-affinity androgen binding sites in spinal cord nuclei from orchidectomized, testosterone propionate treated animals. 5 alpha-Reductase activity in homogenates of the spinal cord was relatively high, approximately 3 times that in the pooled hypothalamus, preoptic area, septum and amygdala. However, in contrast to the latter brain regions, estrogen formation was not detectable in spinal cord tissue. No sex differences were observed in the metabolism of [3H]testosterone by spinal cord homogenates. These results confirm the presence of androgen and estrogen receptors in the rat spinal cord. The lack of detectable aromatase activity in the spinal cord is consistent with the hypothesis that the effects of circulating testosterone on spinal reflex function are mediated primarily through the androgen receptor system.     

The action of(±)-MDMA on medial prefrontal cortical neurons is mediated through the serotonergic system

The mechanism of action of systemitically administered(±)-MDMA (3, 4-methylenedioxymethamphetamine) on spontaneously active neurons in the medial prefrontal cortex (mPFc) of chloral hydrate anesthetized rats was examined using standard single unit extracellular recording techniques. Intravenously administered MDMA dose-dependently decreased the firing rates of the majority of mPFc neurons in control rats. In contrast, in rats that were pretreated withp-chlorophenylalanine (PCPA), which depletes the brain serotonin (5-hydroxytryptamine, 5-HT) content by inhibiting tryptophan hydroxylase, the rate-limiting enzyme in the synthesis of 5-HT, MDMA was largely ineffective in inhibiting the firing of mPFc cells. In PCPA-treated animals, the administration of 5-hydroxytryptophan (5-HTP), which presumably restored the brain 5-HT content, but notl-DOPA, reinstated MDMA's inhibitory action in PCPA-treated rats. In rats that were pretreated withα-methyl-p-tyrosine (AMPT), which depletes the brain dopamine (DA) content by inhibiting tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of DA, MDMA inhibited the firing of all of the mPFc cells. MDMA's effect on mPFc neurons was reversed by 5-HT receptor antagonists such as granisetron and metergoline. These results strongly suggest that MDMA exerts its action on mPFc cells indirectly by releasing endogenous 5-HT.     

唾液富组蛋白5抗白念珠菌作用实验性研究

目的探讨不同浓度的富组蛋白5（histidine rich protein5，HRPs5）在体外杀灭白念珠菌孢子、芽管的作用及抑制孢子形成芽管的作用。方法将一定数量的孢子和芽管分别与不同浓度的HRPs5混合培养后，置于400倍的倒置显微下观察菌落数，得出杀孢子率、杀芽管率和抑制孢子不形成芽管率。结果当25μml或更高浓度的HRPs5和白色念珠菌孢子作用后，可使90％以上的孢子丧失活力；100μml的HRPs5和白色念珠菌芽管作用后，可使90％以上的孢子丧失活力；400μg／ml的HRPs5和白色念珠菌孢子作用后，可使100％孢子受到抑制而不形成芽管。而50μg／ml的HRPs5对白色念珠菌孢子形成芽管仅有轻微的抑制作用。结论HRPs5在体外具有较强杀灭白念珠菌孢子、芽管的作用及抑制孢子形成芽管的作用，且随着HRPs5浓度的升高其作用愈强。     

Expression of epithelial matrix molecules collagen and laminin and corresponding integrins in chronic wounds

Re-epithelialization of cutaneous wounds is a coordinated process of proliferation and migration of keratinocytes at the wound edge. The study objective was to identify the differences in epidermal morphology, keratinocyte proliferation and matrix molecules (laminin 1, laminin 5, type IV collagen) and their specific integrin (α3, α6) expression in biopsies of meshed split thickness grafted and chronic wounds. The mean mitotic index of keratinocytes (ratio of cell cycle associated antigen Ki-67 expressing keratinocytes to basal keratinocytes) was highest in chronic wounds (38.7%) compared to acute wounds (22.25%, range 5.7% to 54%). The mean thickness of the hyper-proliferative epithelium at the wound edge of chronic wounds was 0.69 mm compared to 0.15 mm at the wound margin of split thickness grafted wounds. Both chronic wounds and skin grafted wounds exhibited strong laminin 5 immunoreactivity at the basal side of the epithelium, which extended under the most forward keratinocytes. Laminin 1 and type IV collagen immunoreactivity did not extend to the wound margin in either skin grafted or chronic wounds. In both transplanted skin and chronic wounds, the integrin sub-units α3 and α6 exhibited a strong pericellular immunoreactivity on the leading keratinocytes of the wound margin. Our data demonstrates that the proliferation of keratinocytes and the expression of associated integrins are not impaired in chronic wounds. Presented at the 33rd Congress of the Association of German Plastic Surgeons, Germany, 18–21 September, 2002.     

血小板激活因子拮抗剂YM-264对抗原引起气道嗜酸性粒细胞浸润的影响

应用鸡卵清蛋白致敏和刺激小鼠复制过敏性气道炎症反应模型研究血小板激活因子选择性拮抗剂ＹＭ－２６４对抗原引起气道嗜酸性粒细胞（ＥＯＳ）浸润的影响。结果发现，正常小鼠支气管肺泡灌洗液（ＢＡＬＦ）中未见到ＥＯＳ；致敏小鼠给予抗原多次反复吸入刺激后，ＢＡＬＦ中ＥＯＳ急剧增多。在ＹＭ－２６４治疗各组中，ＹＭ－２６４的不同剂量分别导致ＥＯＳ数下降２７．０％、４８．２％及６７．９％。还发现ＹＭ－２６４抑制ＥＯＳ对气道的浸润伴随着白细胞介素（ＩＬ）－５水平的明显下降。提示ＹＭ－２６４通过抑制ＩＬ－５的产生从而抑制了ＥＯＳ在气道的聚集。     

Correlation between 5-HT7 receptor affinity and protection against sound-induced seizures in DBA/2J mice

Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including 5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken to determine whether antagonism of the newly identified 5-HT₇ receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their affinity at the 5-HT₇ receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT₇ receptor and a statistically significant correlation was observed between 5-HT₇ affinity and doses for half-maximal response (ED₅₀) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT_1A, 5-HT_2A or 5-HT_2C receptors. It is also unlikely that interactions between the 5-ht₅ receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this in vivo model have no affinity for the 5-ht₅ receptor. There are similarities between the pharmacology of the 5-HT₇ receptor and that of the 5-HT_1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT_1A affinity was not significant. Furthermore, the 5-HT_1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT_1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT₇ receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with selective 5-HT₇ antagonists. Received: 20 March 1997 / Accepted: 10 August 1997