甘利欣注射液治疗酒精性肝病临床研究

目的研究甘利欣注射液治疗酒精性肝病临床疗效。方法选择酒精性肝病住院病人200例,随机分为治疗组120例,给予甘利欣注射液治疗;对照组80例,给予门冬氨酸钾镁+肌苷静脉滴注。结果治疗组总有效率98.0%,对照组总有效率64.1%,2组相比差异显著(P<0.01),治疗组显效所需时间为(9.7±3.2)d,明显少于对照组(P<0.01)。1个疗程结束,治疗组ALT、AST、GGT、TG、CHO下降幅度均明显高于对照组(P均<0.01),治疗组ALT、AST、GGT、TG、CHO复常率分别为97.6%、95.5%、89.5%、87.6%、78.5%,与对照组相比也有明显差异(P均<0.01)。结论甘利欣注射液治疗酒精性肝病疗效明显,优于门氨酸钾镁+肌苷治疗     

Evidence for increased dorsal hippocampal adenosine release and metabolism during pharmacologically induced seizures in rats

There is growing pharmacological evidence from several animal models of seizure disorder that adenosine possesses endogenous anticonvulsant activity. In order to further evaluate the role of adenosine in seizure activity, we monitored adenosine and its major biochemical metabolites inosine, xanthine, and hypoxanthine in the dorsal hippocampus by in vivo microdialysis before and during the induction of generalized seizures. Seizures were induced pharmacologically in groups of urethane-anesthetized rats by the administration of bicuculline (0.5 mg/kg, i.v.), kainic acid (12.0 mg/kg, i.v.) or pentylenetetrazol (100–250 mg/kg, i.p). Seizure activity was monitored electrophysiologically from the dorsal hippocampus. Dialysate hippocampal purine levels increased during all three seizure types. The largest increases were for the adenosine metabolites hypoxanthine and inosine, with smaller increases observed for adenosine and xanthine. Intra-hippocampal perfusion with the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl-adenine, (EHNA, 300 μM), only slightly increased basal hippocampal adenosine. Guanosine levels in the hippocampus, a purine not directly related to adenosine metabolism, were unaffected by all treatments. These findings demonstrate that an increase in hippocampal adenosine release and metabolism is associated with seizure activity and support the hypothesis that the increased adenosine levels may attenuate hippocampal seizure activity, possibly by terminating ongoing seizures and altering the pattern of subsequent seizures.     

Nicotinamide,inosine and hypoxanthine,putative endogenous ligands of the benzodiazepine receptor,opposite to diazepam are much more effective against kynurenine-induced seizures than against pentylenetetrazol-induced seizures

Nicotinamide (NAM, 1000 mg/kg), inosine (INS, 1000 mg/kg), hypoxanthine (HXT, 500 mg/kg), putative endogenous ligands of the benzodiazepine receptor, and nicotinic acid (NA, 500 mg/kg) diminished DL-kynurenine-(DL-K, 50 μg ICV) induced seizures in C57BL/6 adult male mice and only prolonged the latency of pentylenetetrazol (PTZ, 500 μg ICV) seizures. The same effect was previously observed when PTZ was administered IP. In albino male BALB/c and SHR (bred from Swiss) mice only NA was effective against DL-K. Diazepam in a dose of 0.5 mg/kg prevented PTZ-induced seizures in half of the animals but even in dose of 10 and 20 mg/kg it was ineffective against DL-K. When injected ICV NAM (1 and 10 μg), INS (10 μg) and HXT (10 μg) prevented seizures induced by DL-K and were ineffective against seizures induced by PTZ. It is suggested that if NAM, INS and HXT are of functional importance in the central nervous system, they can act as antagonists of endogenous brain kynurenine. NA and NAM are suggested to be functional feedback inhibitory regulators of the kynurenine pathway of metabolism of tryptophan.     

Effect of Inosine on Seizures Induced with Pentylenetetrazole, Bicuculline, or Picrotoxin

The effect in mice of inosine administered subcutaneously on the threshold of seizures induced with pentylenetetrazole (PTZ), bicuculline, and picrotoxin was studied, and brain inosine levels were measured. Following inosine, 1,000 mg/kg, the threshold to PTZ was increased at 10-30 min after injection as determined by a tail vein infusion method. Bicuculline and picrotoxin thresholds were significantly elevated only at 5 min. The time to the first myoclonic jerk after intraperitoneal administration of each of these convulsants was significantly prolonged by the lowest dose of inosine tested (250 mg/kg for PTZ, 100 mg/kg for bicuculline, and 500 mg/kg for picrotoxin). Inosine was given subcutaneously 10 min before the convulsant. The mean control brain inosine concentration was 2.9 microM. After subcutaneous inosine, 1,000, 500, and 250 mg/kg, the highest levels reached were 14.4, 7.9, and 4.3 microM, respectively. It is concluded that micromolar concentrations of inosine in brain are antiepileptic.     

The levels of adenosine and its metabolites in the guinea pig and rat brain during complete ischemia-in vivo study

Changes in levels of adenosine, inosine, hypoxanthine and ATP during complete ischemia after decapitation were determined in various areas of the guinea pig and rat brain using an HPLC method. These results were compared with levels in brains fixed by microwave irradiation. The levels of adenosine during 60 min of complete ischemia were extremely high and unevenly distributed while levels in the microwaved brains were very low and evenly distributed. The ratios of inosine plus hypoxanthine levels to adenosine which indicate the rate of metabolic degradation from adenosine into inosine and hypoxanthine, were also unevenly distributed during complete ischemia in the cerebellum, superior colliculus, cerebral cortex and hippocampus of the guinea pig and rat, and the highest ratio was observed in the cerebellum of the guinea pig and the superior colliculus of the rat. The activities of adenosine deaminase (ADA), one of the enzymes involved in adenosine metabolism, were measured in the four regions of the guinea pig. The ADA activities were unevenly distributed and the highest ADA activity was found in the cerebellum. These regional differences in ADA activities are in good agreement with the regional differences in the ratio of inosine plus hypoxanthine levels to adenosine during complete ischemia. Furthermore, the administration of EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride] (10 mg/kg, i.p.), an ADA inhibitor, caused a significant increase of adenosine and decrease of inosine formation in all four regions and a drastic effect on the cerebellum with high ADA activity compared with the other regions in the guinea pig brain. These results indicate that the changes in concentrations of adenosine and its metabolites (inosine and hypoxanthine) during complete ischemia depend on ADA activity in each brain region.     

Increase of adenosine content in cerebral cortex of the cat during bicuculline-induced seizure

In order to elucidate whether adenosine may be involved in the increase in cerebral blood flow (CBF) during functional hyperemia, cortical tissue levels of adenosine, inosine and hypoxanthine were measured in the cat following bicuculline (3 mg/kg)-induced seizure. In addition, the subcellular distribution of 5-nucleotidase in the cortex was determined by histochemical techniques. Experiments were performed on anaesthetized and immobilized cats and tissue samples to be analyzed for the different purine compounds were obtained by freezing through the trepanized and non-trepanized skull. Control values for adenosine, inosine and hypoxanthine on the trepanized side were 1.31, 1.12 and 3.79 nmoles/g, respectively. The cortical content of adenosine increased to 3.85 nmoles/g, 15 s after beginning of seizure activity and remained elevated for 20 min. Inosine and hypoxanthine also increased, exhibiting highest values after 20 min. Values for adenosine and lactate were found to be generally higher when analysis was performed from tissue frozen through the intact skull bone. In all experiments the adenosine content correlated with lactate levels. From measurements of plasma concentrations of adenosine and inosine in the sinus sagittalis superior it is concluded that seizure is also accompanied by an enhanced release of adenosine from the brain. Localization of 5-nucleotidase by electron-microscopic cytochemistry revealed that this enzyme is associated almost exclusively with plasma membranes of glial cell membranes including perivascular astrocytes. Thus high concentration of adenosine can be expected to accumulate locally in the brain cortex. In view of the well known increase in CBF during onset of seizure and the time course of adenosine formation, our findings support the view that adenosine may be involved in the initial phase of seizure-induced functional hyperemia of the brain.A preliminary report of this investigation was presented at the 49th Meeting of the German Physiological Society at Göttingen (Pflügers Archiv 373: 74, 1978) and at the first conference of the studygroup for neurochemistry (Hoppe-Seyler's Z. Physiol. Chemie 359: 461–462, 1978)     

肌苷片评价性抽验质量分析

目的对2012年军队评价性抽验肌苷片质量现状进行评价。方法对在全军范围内抽取的245批次肌苷片按《部颁标准》二部第六册(生化药品第一分册)1998年版、《中国药典》2005年版二部和2010年版二部进行全项检验,并对检验结果进行了统计分析。结果 245批次肌苷片样品质量均符合标准规定。结论目前国内肌苷片的生产工艺较为稳定,肌苷片质量总体较好,但个别生产厂家的产品需加强监督,其质量标准还需进一步充实和完善。     

软肝贴穴位贴敷神灯照射与消鼓软肝方联合西药治疗肝硬化腹水64例临床观察

[目的]观察软肝贴穴位贴敷神灯照射与消鼓软肝方联合西药治疗肝硬化腹水疗效。[方法]使用前瞻性设计方法,对64例住院患者使用软肝贴(水蛭、虻虫各5g,三棱、莪术、元胡、泽兰、马鞭草、大腹皮、姜黄、路路通各15g,共研成细末,醋调匀),穴位贴敷于肝区章门穴、期门穴、日月穴,并用神灯照射30min,1次/d;消鼓软肝方(柴胡、枳壳、陈皮、大腹皮、丹参、赤芍、鸡内金、益母草、泽兰、茯苓、泽泻、葫芦瓢各15g),150mL,1次/d,口服;0.9%氯化钠100mL+还原性谷胱甘肽1.2g,静点,1次/d;呋塞米20mg/次,3次/d,口服;螺内酯20mg/次,3次/d,口服;肌苷0.2/次,3次/d,口服;当白蛋白25g/L时,补充人血白蛋白10g/次,1次/d静点,连续3d。连续治疗30d为1疗程。观测临床症状、肝功能指标、脾脏状况、腹水、不良反应。连续治疗2疗程,判定疗效。[结果]显效39例,有效21例,无效4例,总有效率93.75%(60/64)。[结论]软肝贴穴位贴敷神灯照射与消鼓软肝方联合西药治疗肝硬化腹水,疗效满意,无副作用,值得推广。     

注射用辅酶A、三磷酸腺苷二钠及肌苷注射液配伍稳定性考察

摘 要 目的：考察注射用辅酶A、三磷酸腺苷二钠注射液及肌苷注射液在5%葡萄糖注射液中的配伍稳定性。 方法: 在室温条件下,模拟临床用药方法,配制3种药物与5%葡萄糖注射液的配伍溶液,采用HPLC法测定辅酶A、三磷酸腺苷二钠和肌苷的含量及有关物质变化情况,同时考察配伍溶液的外观、pH和不溶性微粒的变化情况。结果: 室温下4 h内,配伍溶液的外观、pH、不溶性微粒、各药物含量及有关物质均无明显变化;24 h后,配伍溶液出现浑浊絮状物,pH、不溶性微粒、含量及有关物质均明显发生变化。结论:在室温条件下,注射用辅酶A、三磷酸腺苷二钠注射液及肌苷注射液在5%葡萄糖注射液中的配伍溶液应于4 h内使用完。     

Inhibition of Junin virus RNA synthesis by an antiviral acridone derivative

There are no specific approved drugs for the treatment of agents of viral hemorrhagic fevers (HF) and antiviral therapies against these viruses are urgently needed. The present study characterizes the potent and selective antiviral activity against the HF causing arenavirus Junin virus (JUNV) of the compound 10-allyl-6-chloro-4-methoxy-9(10H)-acridone, designated 3f. The effectiveness of 3f to inhibit JUNV multiplication was not importantly affected by the initial multiplicity of infection, with similar effective concentration 50% (EC₅₀) values in virus yield inhibition assays performed in Vero cells in the range of 0.2-40 plaque forming units (PFU)/cell. Mechanistic studies demonstrated that 3f did not affect the initial steps of adsorption and internalization. The subsequent process of viral RNA synthesis was strongly inhibited, as quantified by real time RT-PCR in compound-treated cells relative to non-treated cells. The addition of exogenous guanosine rescued the infectivity and RNA synthesis of JUNV in 3f-treated cells in a dose-dependent manner, but the reversal was partial, suggesting that the reduction of the GTP pool contributed to the antiviral activity of 3f, but it was not the main operative mechanism. The comparison of 3f with two other viral RNA inhibitors, ribavirin and mycophenolic acid, showed that ribavirin did not act against JUNV through the cellular enzyme inosine monophosphate dehydrogenase (IMPDH) inhibition whereas the anti-JUNV activity of mycophenolic acid was mainly targeted at this enzyme.