二羧乙基锗倍半氧化物的抗大鼠实验性胃溃疡作用及其作用机理研究

二羧乙基锗倍半氧物(Dicarboxyethyl GermaniumSesquioxide,DEG)是人工合成的有机锗化合物。它能对抗Shay幽门结扎性溃疡的形成,使胃液中PGE_2含量增加,胃蛋白酶活性和游离酸度明显降低。DEG还能对抗消炎痛型,五肽胃泌素型和酒精型溃疡的形成,促进醋酸型溃疡的愈合,但对应激型和利血平型溃疡无对抗作用。DEG的主细胞分泌功能比对照组明显减弱。实验结果表明,DEG的抗溃疡作用可能与增加胃内PGE_2含量、抑制胃液分泌和促进蛋白质合成有关。     

Inhibition of GABA-gated chloride channel function by arachidonic acid

The effects of arachidonic acid and its metabolites on gamma-aminobutyric acid (GABAA) receptor function were determined in rat cerebral cortical synaptoneurosomes. Incubation of synaptoneurosomes with phospholipase A2 decreased muscimol-induced 36Cl- uptake. Arachidonic acid, the major unsaturated fatty acid released by phospholipase A2, also inhibited muscimol-induced 36Cl uptake. Similar inhibition was obtained with other unsaturated fatty acids (docosahexaenoic, oleic) but not with saturated fatty acids (stearic, palmitic). The effect of arachidonic acid on muscimol responses was inhibited by bovine serum albumin (BSA), and BSA enhanced muscimol responses directly, indicating the generation of endogenous arachidonic acid in the synaptoneurosome preparation. The generation of endogenous arachidonic acid was also indicated by the ability of 2 inhibitors of arachidonic acid metabolism, indomethacin and nordihydroguaiaretic acid (NDGA), to inhibit muscimol-induced 36Cl uptake. We conclude that arachidonic acid probably has both direct and indirect actions on muscimol responses since both enzyme inhibitors inhibited muscimol responses but did not prevent the effect of exogenously added arachidonic acid. In additional experiments, arachidonic acid metabolites generated by cyclooxygenase, prostaglandins D2, E2 and F2 alpha, each decreased muscimol responses; prostaglandins F2 alpha was the most potent inhibitor. Since the unsaturated fatty acids and their metabolites are most susceptible to peroxidation, a generating system of superoxide radicals was tested on muscimol responses. A combination of xanthine and xanthine oxidase inhibited muscimol-induced 36Cl uptake in a concentration-dependent manner. We propose that the inhibition of GABAA neurotransmission by arachidonic acid and its metabolites can lead to increased neuronal excitability. This mechanism may play an important role in the development of neuronal damage following seizures or cerebral ischemia.     

前列腺素E1对大鼠肝移植肾功能的保护作用

目的探讨术中应用前列腺素E1（prostaglandin E1，PGE1）对大鼠肝移植肾功能的保护作用。方法大鼠原位肝移植术中经颈内静脉灌注PGE1为治疗组，生理盐水和空白为对照组，观察术后1周存活率、1h的尿量，测定血浆肌酐、尿素氮和肾组织中丙二醛（malondjaldehyde，MDA）、谷胱甘肽（glutathione，GSH）含量，肾组织病理检查。结果PGE1治疗组术后1h尿量较对照组明显增加，肌酐和尿素氮水平均较对照组降低，PGE1治疗组肾组织中GSH含量显著高于两对照组，MDA含量低于两对照组。病理检查PGE1治疗组肾脏组织形态学损伤明显减轻。结论术中应用PGE1能显著改善大鼠肝移植后的肾功能，其机制可能与对抗氧自由基损伤作用有关。     

消旋17-苯-18,19,20-失三碳前列腺素F2α甲酯及其15-差向异构体的合成

从中间体(4)出发,经醛(5),与鏻叶立德(3)或2-酮-4-苯丁烷磷酸酯(11)钠缩合成(6),再钠硼氢还原得3′α-醇(7A)及其差向异构体(7B),经硅胶柱色谱分开,分别经二异丁基铝氢还原,与溴化5-三苯鏻戊酸之Wittig试剂缩合,得17-苯-18,19,20-失三碳前列腺素F_2α(9A)及其15-差向异构体(9B),再用重氮甲烷甲酯化,分别得相应的17-苯-18,19,20-失三碳前列腺素F_2α甲酯(10A)及其15-差向异构体(10B)。     

Effect of prostaglandin E1 on graft function of kidneys from living related donors

Prostaglandin E₁ (PGE₁) was used in renal transplant recipients with living related donors. The drug was given intravenously from day 1 to day 7 after transplantation at a dose of 40 µg/kg twice a day. A total of 45 patients were studied divided into two groups: 25 patients were treated with PGE₁ (group B) and the remaining 20 patients did not receive the drug (group A). In group B, 24-h creatinine clearance (Ccr) was 66 ± 12.8 ml/min compared with 40.3 ± 13.4 ml/min in group A on the fifth postoperative day (P < 0.05). Urinary levels of N-acetyl-β-d -glucosaminidase (NAG) and serum levels of platelet factor 4 (PF4) in group B were significantly lower than in group A. On the fourth postoperative day, the urinary excretion of thromboxan B₂ (TxB₂) in group A was higher than in group B, but not significantly (5.1 ± 3.0 ng/day and 2.8 ± 1.1 ng/day, respectively). Acute rejection occurred in four patients in group B and in 10 patients (40%) in group A. The percentage of Leu2a-positive lymphocytes in group B was higher than in group A. We conclude that postoperative administration of PGE₁ improves graft function in kidneys from living related donors.     

Prostaglandin E1 and dibutyryl cyclic AMP enhance platelet resistance to deformation

The effect of prostaglandin E₁ (PGE₁) on platelets is mediated through the PGE₁ receptor and the consequent maintenance of the platelet's discoid shape. The effects of PGE₁ and dibutyryl cAMP (dbcAMP) on the deformability of human platelets were studied. Deformability tests based upon the micropipette aspiration on the platelets were performed by using pipettes with radii (Rp) of 0.26-0.36 gm. The time course of the extension length (Dp, in μg) of the platelets in response to aspiration with a negative pressure (ΔP) of 5 cm H₂ O (ΔP × Rp = 0.15 dynes/cm) was analyzed. PGE₁ treatment (0.1 μM) resulted in a decrease of platelet deformability as compared with results obtained for apparently non-activated, control platelets. The deformation index, i.e., Dp/Rp (PGE₁ -treated) / Dp/Rp (control), was significantly reduced to 0.90 ± 0.04. DbcAMP treatment also significantly decreased the deformability of platelets and this decrease was dbcAMP dose dependent. In contrast, colchicine- or cytochalasin D-treated platelets increased deformability. PGE₁ -treated platelets had a higher [cAMP]_i than controls. Platelets treated with PGE₁ or dbcAMP showed a reduced [Ca²⁺]i increment induced by thrombin as compared to non-treated controls. These results indicate that PGE₁ and dbcAMP treatment of platelets is accompanied by an enhancement of platelet resistance to deformation. The increased [cAMP]_i and low [Ca²⁺]_i after PGE₁ treatment may limit the rearrangement of cytoskeleton and thus enhance platelet resistance to deformation.     

前列腺素E1治疗慢性乙型肝炎黄疸的观察

目的观察前列腺素E1治疗慢性乙型肝炎重度黄疸的疗效。方法在综合治疗基础上，分别使用前列腺素E1（治疗组）和门冬氨酸钾镁（对照组）治疗慢性乙型肝炎重度黄疸患者各35例，并观察其症状、体征及肝、肾功能等，疗程4周。结果治疗组的症状、体征及肝功能指标及总有效率，均显著优于对照组，两组比较差异有显著意义（P〈0．05）。结论前列腺素E1治疗慢性乙型肝炎重度黄疸能显著地促进黄疸消退和改善肝功能。     

Intrauterine fetal death

Sadly, intrauterine fetal death is a common occurrence and one that all labour ward personnel should be trained to manage. Recent advances have improved the likelihood of identifying a cause. The key to this is a logical and methodical approach to investigation. Postmortem examination remains a critical aspect of investigation and labour ward teams require a clear understanding of the legal aspects of this. Sympathetic and supportive care of parents should respect parental wishes and allow choice wherever possible. However, maternal safety should also be a central aspect of this care.     

前列腺素E1抑制血吸虫病家兔肝脏Ⅰ，Ⅲ型胶原生成的研究

目的:探讨前列腺素E1对血吸虫病家兔肝脏Ⅰ，Ⅲ型胶原的生成及分子伴侣Grp78/BiP基因表达的影响。 方法:用血吸虫尾蚴皮肤敷贴法感染14只家兔，构建血吸虫病肝纤维化动物模型。其中7只兔于感染后60d开始静脉注射PGE1［2.5μg/（kg.d）］至120d。用RT-PCR检测肝组织Ⅰ，Ⅲ型胶原和Grp78/BiP基因mRNA的表达水平。 结果:血吸虫病家兔肝纤维化形成过程中Ⅰ，Ⅲ型胶原基因表达水平明显增加，分别为(14.81±3.57)%和(12.9±3.25) %;Grp78/BiP mRNA表达显著上调(P<0.05)。外源性PGE1与模型组比较显著降低胶原Ⅰ，ⅢmRNA，分别为(5.79±1.26)%和(5.34±1.08) % （P<0.01)。分子伴侣Grp78/BiP mRNA水平显著下调，分别为(0.43±0.07)%和(0.29±0.02) % （P<0.05)。结论:PGE1可通过抑制基因表达和阻遏胶原成熟而有效地降低血吸虫病家兔肝脏胶原纤维的生成。