Studies on the Mechanism of Hyaluronate Lyase Action

Hyaluronate lyase from streptococci group A was purified by chromatography on DEAE-Sephadex A-50 and on Biogel P-150, thereby enriching it about 1,000-fold and separating it into two enzyme fractions with the same amino acid composition. The photooxidation of hyaluronate lyase in the presence of methylene blue results in rapid inactivation of the enzyme. The histidine content of the enzyme is decreased considerably, but also the content of methionine, tyrosine, and lysine is lowered. The enzyme is inhibited, but incompletely so, by N-tosyl-L-phenyl-alanine-chloromethyl ketone (TPCK) and N-α-p-tosyl-L-lysine chloromethyl ketone (TLCK). Hyaluronic acid methyl ester, prepared from hyaluronic acid and diazomethane, is not split by hyaluronate lyase (EC 4.2.2.1). Hyaluronic acid methyl ester is not a competitive inhibitor of hyaluronate lyase. For the mechanism of the enzymatic elimination reaction a proton transfer between histidine of the enzyme and the carboxylate group of hyaluronate is proposed.     

IL-17在鼻息肉形成中的作用机制

目的 检测白介素-17（IL-17）及其受体（IL-17R）在鼻息肉和正常鼻黏膜中的表达及IL-17在鼻息肉患者血清中的表达,观察IL-17 在鼻息肉发病过程中可能的作用机制和意义。方法 鼻息肉组织及血清标本来自青岛大学附属医院耳鼻咽喉科2016年11月~2017年11月行鼻息肉切除术的42例患者,选取10例同期行上颌窦囊肿手术切除的正常中鼻道黏膜组织作为正常鼻粘膜对照,10例健康成年人血清作为正常对照。HE 染色用于常规组织病理学检查,免疫组织化学染色观察IL-17及其受体表达水平及部位,双重免疫组织化学染色观察表达IL-17的细胞,ELISA法检测血清中IL-17蛋白表达水平。结果 ①42例鼻息肉组织中IL-17和IL-17R阳性细胞数较正常鼻黏膜组织中多,差异有统计学意义（P＜0.05）;巨噬细胞表面标志（CD68）在鼻息肉组织中的表达比正常鼻黏膜组织高,差异有统计学意义（P＜0.05）。②IL-17及CD68双重免疫组化染色显示IL-17主要表达于鼻息肉巨噬细胞上,IL-17R主要表达于上皮层基底细胞、腺管基底细胞及血管内皮细胞。③42例鼻息肉患者血清中IL-17蛋白水平和健康成年人比较,差异无统计学意义（P＞0.05）。结论 IL-17对鼻息肉的形成作用可能是通过影响巨噬细胞的功能及相关细胞因子实现的,IL-17与IL-17受体的相互作用可能参与鼻息肉的病理改变,如上皮细胞基底膜增厚及腺体增生等。     

Mechanism of Action of Cyclosporin A

Previous studies have shown that cyclosporin A (CyA) prevents the elaboration of the lymphokine leucocyte migration inhibitory factor (LIF). Since LIF production is interleukin 1 (IL-1)-dependent, we carried out experiments using partially and highly purified IL-1 preparations to study the effect of CyA. We found that (a) IL-1 was consistently depleted during a 1-h incubation with human blood T lymphocytes but not with B lymphocytes or erythrocytes; (b) the depletion could not be ascribed to pinocytosis, cell functions requiring active metabolism, or enzyme-mediated destruction of IL-1; (c) CyA, but not biologically inactive cyclosporin, antagonized the apparent absorption of IL-1; (d) T cells pre-exposed to CyA were rendered incapable of removing the monokine; and (e) CyA was capable of displacing IL-1 once absorbed by T cells. Because the putative binding of IL-1 showed saturability, reversibility (with CyA as a probe), and tissue specificity consistent with a known target for the monokine, we propose that IL-1 interacts with a receptor-like structure on T cells. Finally, we found that insulin interfered with the function of CyA at the very early macrophage-T-cell co-operative stage, even at physiological concentrations.     

Mechanism of Action of Suppressor Cells

The addition of a small proportion (10%) of in vivo concanavalin-A (Con-A)-activated spleen cells to normal spleen cell cultures suppressed the primary immune response to sheep erythrocytes (SRBC) but had no effect on the thymus-independent primary immune response to 3,5-dinitro-4-hydroxy-phenacetyl-conjugated lipopolysaccharide. When Con-A-activated cells were added after 24 h, there was no suppression of the anti-SRBC response but rather an enhanced response when few cells were admixed. Con-A-activated cells did not influence activation of normal cells by polyclonal T- and B-cell activators. It is concluded that Con-A-induced suppressor cells do not act on B cells but rather on helper cells (T cells or macrophages) at a very early stage of the immune response to thymus-dependent antigens.     

The Effect of Cadmium Pretreatment on the Nephrotoxic Action and Kidney Uptake of Mercury in Male and Female Rats

Pretreatment of female rats with cadmium (2 × 2·46 mg Cd²⁺/kg as CdCl₂) protected them against the nephrotoxic effect of Hg²⁺ (0·5, 1·0 and 1·5 mg/kg as HgCl₂) given 6 days after the second dose of Cd²⁺. Male rats were more sensitive than females to HgCl₂ and were protected by the Cd²⁺ pretreatment against only 0·5 mg Hg²⁺/kg.Protection by Cd²⁺ was not associated with decreased accumulation of Hg²⁺ in the kidneys; on the contrary, uptake was increased by Cd²⁺ and, at the two higher dose levels, was greater in the kidney of the less sensitive female rat than in the male. Also, in control female rats the renal burden of Hg²⁺ seemed to be independent of the dose within the range 0·5-1·5 mg Hg²⁺/kg, whereas the tubular damage was dose dependent.     

Studies on the Mechanism of Action of Lithium Ions

When the extracellular Na⁺ was replaced by lithium (Li⁺) the frequency of the impulses elicited by stretching the stretch receptor of crayfish was changed and then inhibited. This effect was not due to the lack of extracellular Na⁺. Higher firing rate facilitated and low extracellular K⁺ delayed the Li⁺ effect. Ouabain alone (10^-4 M) changed the impulse activity in a similar manner to Li⁺ replacement. Ouabain (10^-5 M) decreased the rate of recovery during wash-out after Li⁺ replacement. The Li⁺-induced increase in the frequency of the impulse activity was probably the result of a lower intracellular K⁺ concentration, the block of the spike activity being due to the accumulation of Li⁺ in the cell. The Na⁺ pump participated in the recovery of the spike activity after Li⁺ replacement.     

卟啉及其衍生物抗癌活性机理研究进展

综述卟啉类抗癌活性化合物在肿瘤细胞中的优先聚集机理及抗癌活性机理,为进一步研发卟啉类抗癌新药提供参考。     

二甲双胍药理作用及其机制研究

二甲双胍属于临床最常用的药物之一,主要通过轻度抑制线粒全呼吸链复合物,从而激活磷酸腺苷活化蛋白激酶（AMPK）,减少肝脏葡萄糖输出,具有显著的降糖效果,还在多种疾病的治疗中发挥作用,如肿瘤疾病、大血管并发症、促甲状腺素激素水平、保护脑组织与心脏等,均有针对性治疗效果。临床对二甲双胍药物作用与药理机制研究较少,不能充分展现其临床效果。故本研究主要针对二甲双胍药理作用及其机制研究作一综述,为临床用药提供参考与借鉴,从而提高临床用药效果。     

The Mechanism of Action of Anaphylatoxin. Its Effect on Guinea Pig Mast Cells

In the guinea pig anaphylatoxin produces mast cell damage that is similar to that produced by antigen-antibody reaction but is different from that produced by chemical histamine liberators. This damage is inhibited by iodoacetate, p-chloromercuribenzoate, phenol and cold, but is not inhibited by calcium lack or previous heating of the tissue to 45° C. Mepyramine reduces but does not abolish the contraction of the ileum produced by anaphylatoxin. Previous heating of a sensitized ileum to 45° C., although completely abolishing the anaphylactic response, does not interfere with the contraction induced by anaphylatoxin. Furthermore desensitization to anaphylatoxin does not modify the anaphylactic contraction. The implication of anaphylatoxin with the anaphylactic reaction is discussed. It is concluded: (a) that anaphylatoxin shares with the anaphylactic reaction part of the pathway leading to histamine release; (b) that the mechanism of action of anaphylatoxin is quite different from that of the chemical histamine liberators.     

抗菌生物材料的抗细菌黏附能力

背景：由于生物材料和人工器官在临床应用逐渐增多,给临床患者进行治疗疾病的同时还存在着一些问题,最为常见的是生物材料植入人体后引起的细菌感染。 目的：探讨生物材料在抗细菌黏附中的作用,抗菌生物材料的分类及特点。 方法：生物材料在机体引起各种感染的原因是由于细菌生物膜的形成,防止生物材料置入后感染的关键是抑制细菌在生物材料表面的黏附以及防止细菌在生物材料表面形成细菌生物膜。细菌表面黏附重点是改变细菌自身的特性和材料表面的物理化学性质,通过改变材料的物理化学性质来减小材料和细菌之间的相互作用力,主要采用化学接枝法、等离子体法、气相沉淀法等。预防细菌黏附首先要增强机体的免疫防御能力,其次要使界面快速的被组织覆盖,形成严密的连结界面。 结果与结论：抗菌生物材料分为无机抗菌生物材料、天然抗菌生物材料和合成抗菌生物材料,无机抗菌材料以银系材料为主,天然抗菌生物材料以壳聚糖研究为较多,合成抗菌生物材料以季铵盐类材料为代表,各种材料都具有各自的优缺点,需要进一步的体内外基础实验和临床研究来验证和推动抗菌生物材料的发展。     

Mechanism of Action of the Enteropathogenic Factor of Clostridium perfringens Type A

Cell extract of an enteropathogenic strain of Clostridium perfringens type A was administered intravenously to lambs, rabbits, and guinea pigs. Lambs developed transitory diarrhea, lacrimation, salivation, nasal discharge, lassitude, and dyspnea in 1 to 5 hr after inoculation. Large doses of the inoculum caused rapid onset of the clinical signs and subsequent death. Examination of dead animals revealed intensely hyperemic small intestinal mucosa and some congestion in the liver, lungs, spleen, and kidneys. Rabbits showed excessive salivation, frequent defecation, tranquility, and dyspnea, followed by death. Guinea pigs became weak and died in 15 min to 7 hr. Congestion was evident in lungs, liver, spleen, and in the small intestine. In lambs and guinea pigs tested, atropine and epinephrine alleviated the clinical signs. Intradermally injected cell extract caused an immediate increase in capillary permeability and subsequent erythematous reaction without necrosis in the skin of guinea pigs. It is hypothesized that in the enteric infection C. perfringens enteropathogenic factor acts on the small intestine causing increased capillary permeability, vasodilation, and increased intestinal motility.     

microRNA-34家族在肺癌中的作用机制

在许多癌症中, miR?34家族成员充当着极具潜力的具有肿瘤抑制活性的作用。例如,在肺癌中,外源性高表达miR?34a能够抑制肺癌细胞的增殖并诱导其凋亡。预示着利用miR?34a的恢复疗法（ replace?ment therapy）治疗肺癌具有良好的前景,其作用机制也正在逐渐阐明。许多研究发现, miR?34a家族成员与肺癌细胞的增殖、转移、凋亡、细胞周期的调控息息相关。因此, miR?34a家族成员在肺癌的早期诊断、治疗、预后及发病机制的研究中发挥着重要作用。文章综述了miR?34家族的研究现状,重点总结了 miR?34家族在肺癌中的作用机制。     

川芎嗪对家兔肠系膜微血管作用机理的研究

目的：研究川穹嗪（Tetramethylpyarajine，TMP）对家兔肠系膜微循环血管动态变化的影响，以求进一步明确TMP对微血管作用的机理。方法：采取显微录像静画步进法观测TMP对休克、炎症时的家兔肠系膜毛细血管血流速度、血流量、内径及毛细血管前括约肌变化的影响。用血管运动诱导法观测TMP对微血管的血管运动的作用。同时用两点光电法测量微血管运动血流量的变化。结果：1．平均动脉压维持在5．33kPa时TMP组使10μm以下毛细血管血流量一直维持在（1．24±0．15）10－3μl／s，而生理盐水组由（1．10±0．20）10－3μ／s下降到（0．60±0．30）10－3μl／s（P＜0．01），但两组内径与正常比皆无显著变化。2．平均动脉压维持在5．33kPa时TMP组使红细胞通过毛细血管前括约肌的时间明显短于酚妥拉明组。3．在肠系膜局部滴入去甲肾上腺素（NA）诱发出微动脉自律性血管收缩舒张运动，TMP可抑制由NA引起的血管运动，并呈量效依赖关系。抑制后的血管血流量增加，与微动脉并行的微静脉和淋巴管无变化。结论：TMP对血管作用的机理是抑制由NA诱发的微动脉及毛细血管前括约肌局部血管收缩舒张运动，疏通局部血流，增加毛细血管床的灌流量，而不是以往认为的扩张毛细血管床的口径。     

Mechanism of Action of Isoniazid on Mycobacterium bovis Strain BCG

The mechanism of action of isoniazid (INH) on Mycobacterium bovis strain BCG was studied. The rates of synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein after the addition of INH to growing cultures were followed by measuring the incorporation of (3)H-thymidine, (3)H-uridine, and (14)C-l-valine, respectively. After the addition of INH, the rate of DNA synthesis began to decrease and was abolished within 4 hr. RNA synthesis ceased after 6 hr, and protein synthesis was inhibited after 7 hr. Thus, it appears that inhibition of the synthesis of DNA is one of the earliest events after INH addition. The inhibition of the synthesis of DNA was further found to correspond to losses in viability of treated cultures. Degradation of preexisting DNA in INH-treated strain BCG was not detected.     

垂体后叶素对心肌单相动作电位的影响及机理

用保持家兔处于闭胸状态记录心外膜心肌单相动作电位(MAP)的技术,研究垂体后叶素(Pt)对MAP的影响及机理。结果表明,Pt可致动物心率减慢、MAP振幅和V_(max)降低、MA时限延长和MAP间期不等以及室性早搏等。用阿托品(1mg/kg iv)或心得安、立其丁(各1mg/kg iv)或同时给予三种受体阻断剂后,再用Pt(2u/kg iv),出现与上述基本一致的电生理改变。结果提示:心肌MAP改变的机理是由于Pt直接作用于全身血管平滑肌使之收缩,外周阻力增加,心室的后负荷增大,心输出量减少和冠状动脉收缩血流阻力增加所致的全心性缺血。