L—赖氢酸高产菌株筛选

本实验以Ｌ－赖氨酸产生菌钝齿棒杆菌ＯＭ－４（ＨＳ＾＋，ＡＥＳ＾ｒ，Ｍｅｔ＾ｒ）为出发菌株，经硫酸二乙酯和氯化钾锂复合诱变处理，用ＡＥＣ（Ｓ－２氨乙基）－Ｌ－半胱氨酸）和苏氨酸定向筛选获得了高抗ＡＥＣ的突变株ＡＴ－５（ＨＳ＾＋，ＡＥＣ＾ｒ，ＡＥＣ＾ｒ）菌株，ＡＴ－５为出发菌株经亚硝基胍诱变处理，获得一株产Ｌ－赖氨酸的ＴＡ（２－噻唑－ＤＬ－丙氨酸）抗性突变株（ＡＴＴ－６８号），菌株产酸量由原来ＯＭ－４     

病毒性肝炎血清中可溶性IL－2受体水平动态观察

用ＥＬＩＳＡ方法检测了４２例甲型肝炎（ＨＡ）、２１例戊型肝炎（ＨＥ）、５５例乙型肝炎（ＨＢ）、１５例丙型肝炎（ＨＣ）、５例了型肝炎（ＨＤ）患者血清中ｓＩＬ－２Ｒ水平，同时设１００例健康对照组。并对各组病例进行了急性期、恢复期及慢性化（指ＨＢ、ＨＣ、ＨＤ）血清中ｓＩＬ－２Ｒ水平动态观察。结果显示，健康对照组为２１４．６±９７．３Ｕ／ｍｌ，各类急性、慢性肝炎血清中ｓＩＬ－２Ｒ水平明显高于对照组（Ｐ＜０．０５）。恢复期病例ｓＩＬ－２Ｒ水平，接近对照组。提示血清中ｓＩＬ－２Ｒ水平的高低可作为疾病慢性化与否的一项辅助指标。说明ｓＩＬ－２Ｒ水平的变化与肝损伤程度是一致的。     

2，2，6，6－四氯环己酮的制备

２，２，６，６－四氯环己酮的制备叶发青，周和平（咸宁医学院，湖北４３７１００）ＰＲＥＰＡＲＡＴＩＯＮＯＦ２，２．６，６－ＴＥＴＲＡＣＨＬＯＲＯＣＹＣＬＯＨＥＸＡＮＯＮＥ￥ＹＥＦａ－Ｑｉｎｇ，ＺＨＯＵＨｅ－Ｐｉｎｇ（ＸｉａｎｎｉｎｇＭｅｄｉｃａｌＣｏｌ...     

老年原发性高血压患者血尿β2微球蛋白及尿微白蛋白的变化

目的 探讨老年原发性高血压（ＥＨ）血、尿β２微球蛋白（β２－ＭＣ）及尿微白蛋白（Ｍ－Ａ１ｂ）的变化。方法 对血尿素氮（ＢＵＮ）、肌酐（Ｃｒ）正常的老年ＥＨ患者７７例对照组２４例测定血、尿β２－ＭＣ及尿Ｍ－Ａ１ｂ水平,进行对照分析。结果 ＥＨⅠ级对照组无差异（Ｐ〉０．０５）;ＥＨⅡ级组血、尿β２－ＭＧ及尿Ｍ－Ａ１ｂ均明显高于对照组（Ｐ〈０．０５）;ＥＨⅢ级组与对照组有显著性差异（Ｐ〈０．０１）,且明     

抗溃疡药乙酰胺基己酸锌的合成

抗溃疡药乙酰胺基己酸锌的合成何伍，罗宣德（中国医药研究开发中心，北京１０２２０６）ＳＹＮＴＨＥＳＩＳＯＦＡＮＴＩＵＬＣＥＲＡＴＩＶＥＺＩＮＣ６－ＡＣＥＴＡＭＩＤＯＣＡＰＲＯＡＴＥ￥ＨＥＷｕ；ＬＵＯＸｕａｎ－Ｄｅ（ＮａｔｉｏｎａｌＩｎｓｔｉｔｕｔｅｏｆ...     

L-赖氨酸高产菌株筛选

本实验以Ｌ－赖氨酸产生菌钝齿棒杆菌（Ｃｏｒｙｎｅｂａｃｔｅｒｉｕｍｃｒｅｎａｔｕｍ）ＯＭ－４（ＨＳ＋，ＡＥＳｒ，Ｍｅｔｒ）为出发菌株，经硫酸二乙酯和氯化锂复合诱变处理，用ＡＥＣ（Ｓ－［２－氨乙基）－Ｌ－半胱氨酸）和苏氨酸定向筛选获得了高抗ＡＥＣ的突变株ＡＴ－５（ＨＳ＋，ＡＥＣｒ，Ｍｅｔｒ）菌株，再以ＡＴ－５为出发菌株经亚硝基胍诱变处理，获得一株产Ｌ－赖氨酸的ＴＡ（２－噻唑－ＤＬ－丙氨酸）抗性突变株（ＡＴＴ一６８号），菌株产酸量由原来ＯＭ一４菌株的４６．３ｍｇ／ｍＬ提高到７４．８ｍｇ／ｍＬ提高１６１．５％，在筛选结构类似物抗性突变株时采用小钢杯法，可大大节省结构类似物药品．     

Du柿果脂溶性成分的提取分离与鉴定

本实验用东北产的笃斯越桔ＶａｃｃｉｎｉｃｍＵｌｉｇｉｎｏｓｕｍＬ的成熟果实。经乙醇提取，回收乙醇，用不同极性溶剂萃取（ｐｅｔ．ｅｔ。ＣＨＣｌ３、ＥｔｏＡｃＥｔＯＨ）把Ｐｅｔ、ｅｔ部分上硅胶柱以Ｐｅｔ、ｅｔ、Ｐｅｔ、ｅｔ：Ｅｔ２Ｏ＝９：１与Ｄｅｔ、ｅｔ：Ｅｔ２Ｏ＝９：２     

AUTHENTICATIONOFTHECHINESEDRUG“KUDIDAN”（HERBAELEPHANTOPI）ANDITSSUBSTITUTESUSINGRANDOMPRIMEDPOLYMERASECHAINREACTION（PCR）

ＡＵＴＨＥＮＴＩＣＡＴＩＯＮＯＦＴＨＥＣＨＩＮＥＳＥＤＲＵＧ“ＫＵＤＩＤＡＮ”（ＨＥＲＢＡＥＬＥＰＨＡＮＴＯＰＩ）ＡＮＤＩＴＳＳＵＢＳＴＩＴＵＴＥＳＵＳＩＮＧＲＡＮＤＯＭＰＲＩＭＥＤＰＯＬＹＭＥＲＡＳＥＣＨＡＩＮＲＥＡＣＴＩＯＮ（ＰＣＲ）ＨＣａ...     

亚硫酸氢钠裂解6－甲氧基－2－萘乙酮肟

亚硫酸氢钠裂解６－甲氧基－２－萘乙酮肟赵文超，沙耀武（清华大学化学系，北京１０００８４）ＣＬＥＡＶＡＧＥＯＦ６－ＭＥＴＨＯＸＹ－２－ＡＣＥＴＯＮＡＰＨＴＨＯＮＯＸＩＭＥＢＹＳＯＤＩＵＭＢＩＳＵＬＦＩＴＥ￥ＺＨＡＯＷｅｎ－Ｃｈａｏ；ＳＨＡＹａｏ－Ｗｕ（...     

金丝桃甙诱变性研究

金丝桃甙诱变性研究余素贞，王家骥，宋必卫，马传庚，徐叔云（安徽医科大学，合肥２３００３２）ＭＵＴＡＧＥＮＩＣＩＴＹＴＥＳＴＳＯＦＨＹＰＥＲＩＮ￥ＳＨＥＳｕ－Ｚｈｅｎ；ＷＡＮＧＪｉａ－Ｊｉ；ＳＯＮＧＢｉ－Ｗｅｉ；ＭＡＣｈｕａｎＧｅｎｇ；ＸＵＳｈｕ－Ｙｕ...     

Effects of lithium carbonate on apomorphine-induced sniffing behaviour in rats

Effects of lithium carbonate (Li2CO3) on sniffing induced by apomorphine have been tested in rats. Intraperitoneal administration of different doses of apomorphine (0.25, 0.5 and 1 mg/kg) induced a dose-dependent sniffing response. Chronic Li2CO3 exposure (0.1% in drinking water for 30-35 days) but not acute administration of the drug (320 mg/kg, intraperitoneally) decreased the response of apomorphine. The response to chronic Li2CO3 exposure was observed when apomorphine was injected 60 min., 24 hr or 72 hr after Li2CO3withdrawal, with maximum effect observed when the drug was administered 72 hr after withdrawal of Li2CO3. Blockade of sniffing induced by apomorphine by the D1 dopamine receptor antagonist, SCH23390 (0.005 mg/kg, intraperitoneally) or the D2 dopamine receptor antagonist, sulpiride (25 mg/kg, intraperitoneally) was not increased in acute Li2CO3-treated animals. In animals which were treated chronically with Li2CO3, the blockade of apomorphine response by sulpiride but not by SCH23390 was potentiated. It is concluded that chronic treatment of animals with Li2CO3 is able to alter D2 dopamine receptors response.     

Effect of co-administration of subchronic lithium pretreatment and acute MAO inhibitors on extracellular monoamine levels and the expression of contextual conditioned fear in rats

We investigated the effects of clorgyline [a selective MAO (monoamine oxidase inhibitor)-A inhibitor] and lazabemide (a selective MAO-B inhibitor) on extracellular serotonin, dopamine and noradrenaline concentrations in the medial prefrontal cortex after 1-week treatment with subchronic 0.2% or 0.05% Li2CO3 (p.o.) and the effects on expression of contextual conditioned fear, previously reported to be reduced by facilitation of serotonin neurotransmission. As compared to normal diet controls, the subchronic 0.2% Li2CO3 group showed significantly higher levels of extracellular serotonin, but not noradrenaline. No changes were observed in the 0.05% Li2CO3 group. Acute clorgyline (10 mg/kg) treatments combined with subchronic 0.2% Li2CO3 treatments showed significant increases in extracellular serotonin concentrations, but not in dopamine or noradrenaline, as compared with clorgyline treatment alone. There was an additive effect with combined treatment of subchronic 0.2% Li2CO3 and acute clorgyline on the reduction of conditioned freezing, an index of conditioned fear, and this was not observed with subchronic 0.05% Li2CO3. These behavioral data indicate the functional significance of increased extracellular serotonin concentrations due to combined use of a MAO-A inhibitor with subchronic lithium. Effects of lazabemide (10 mg/kg) on extracellular monoamine concentrations and conditioned fear were slight or negligible, and were not affected by subchronic lithium treatment. The present study suggests that lithium augmentation of the antidepressant effect of MAO inhibitors is mediated by additional increases in the extracellular serotonin concentrations induced by MAO-A inhibition and suggests that the anxiolytic action of MAO inhibitors may be enhanced by lithium.     

碳酸锂对抗化学诱导大鼠肝癌前病变过程中GST-P的表达及意义

目的观察碳酸锂 (Li2 CO3)对抗黄曲霉毒素B1(AFB1)诱发的大鼠肝癌前病变的组织形态学变化及胎盘型谷胱甘肽硫转移酶 (GST P)的表达。方法采用肝癌发生的动物模型。 144只Wistar大鼠 ,随机分为A、B、C、D四组 (A组为阴性对照组 ;B组为阳性对照组 ;C组为Li2 CO3 同时给药组 ;D组为Li2 CO3 先期给药组 ) ,于实验第 6、9、10周分批断头处死动物 ,取动物肝脏进行肝组织学检查和GST P的免疫组化染色。结果C、D两组动物健康状况明显改善 ,肝癌前期病变程度明显减轻 ;肝癌标志酶GST P表达减弱 (P <0 0 1) ;D组动物一般状况明显好于C组 ,GST P阳性灶的下降趋势优于C组。结论Li2 CO3 对化学诱导肝癌有明显对抗作用 ,并有一定的预防作用。GST P的动态检测有助于肝癌的早期发现及追踪观察     

Changes in the pharmacokinetics of digoxin in polyuria in streptozotocin-induced diabetic mice and lithium carbonate-treated mice

In humans, digoxin is mainly eliminated through the kidneys unchanged, and renal clearance represents approximately 70% of the total clearance. In this study, we used the mouse models to examine digoxin pharmacokinetics in polyuria induced by diabetes mellitus and lithium carbonate (Li(2)CO(3)) administration, including mechanistic evaluation of the contribution of glomerular filtration, tubular secretion, and tubular reabsorption. After digoxin administration to streptozotocin (STZ)-induced diabetic mice, digoxin CL/F increased to approximately 2.2 times that in normal mice. After treatment with Li(2)CO(3) (0.2%) for 10 days, the CL/F increased approximately 1.1 times for normal mice and 1.6 times for STZ mice. Creatinine clearance (CLcr) and the renal mRNA expression levels of mdr1a did not differ significantly between the normal, STZ, and Li(2)CO(3)-treated mice. The urine volume of STZ mice was approximately 26?mL/day, 22 times that of normal mice. The urine volume of Li(2)CO(3)-treated mice increased approximately 7.3 times for normal mice and 2.3 times for STZ mice. These results suggest that the therapeutic effect of digoxin may be significantly reduced in the presence of polyuria either induced by diabetes mellitus or manifested as an adverse effect of Li(2)CO(3) in diabetic patients, along with increased urine volume.     

Increases in the expression levels of aquaporin-2 and aquaporin-3 in the renal collecting tubules alleviate dehydration associated with polyuria in diabetes mellitus

Enhanced expression of renal aquaporin-2 (AQP2) has been reported when polyuria occurs in diabetic animal models. The purpose of this study was to clarify the possibility that increased AQP2 expression in the kidneys play a role as a compensatory mechanism to alleviate diabetic dehydration. Lithium carbonate (Li?CO?), which decreases the renal expression of AQPs, was administered to streptozotocin (STZ)-induced model mice of type I diabetes mellitus (STZ mice), to investigate the relationship between urine volume and renal AQP expression. Plasma glucose and urine glucose levels were similar between STZ mice given feed containing Li?CO? for 10 d and un-treated STZ mice. Urine volume increased to 70 ml/d for the Li?CO?-treated STZ mice, compared to 36 ml/d for un-treated STZ mice. No changes were observed in creatinine clearance or the mRNA expression levels of sodium myo-inositol transporter and taurine transporter, which are genes associated with the regulation of osmotic pressure in the kidney, in the Li?CO?-treated STZ mice relative to un-treated STZ mice. Protein expression levels of AQP2 and aquaporin-3 (AQP3) of the renal inner medulla were significantly decreased in the Li?CO?-treated STZ mice, compared to levels in the STZ group. This study revealed that the decreased expression levels of AQP2 and AQP3 in the kidney increased the urine volume in mice without a change in urinary osmotic pressure. The results of this study suggest that the increased renal AQP2 and AQP3 expression, in the setting of polyuria, physiologically serves as a compensatory mechanism to alleviate dehydration in diabetes mellitus.     

In vitro study of lithium carbonate adsorption by activated charcoal

The purpose of this study was to determine whether lithium carbonate (Li2CO3) is effectively adsorbed by activated charcoal (AC). Either 0 (control), 1.5, 3.0 or 9.0 grams of AC were added to Li2CO3 (300 mg) in distilled deionized water or simulated gastric fluid USP, filtered and and the filtrate analyzed for lithium by flame photometry. Adsorption of lithium was dependent on AC concentration and pH. In water, lithium was 14.7%, 26.5% and 40.4% adsorbed at AC:Li2CO3 ratios of 5:1, 10:1 and 30:1, respectively (p less than 0.05). In simulated gastric fluid, there was no significant adsorption at any of the AC concentrations studied. Since simulated gastric fluid more closely resembles in vivo conditions, the efficacy of AC in lithium carbonate overdoses is questionable but in vivo studies are needed to confirm these findings.     

In vitro interaction between psychotropic drugs and alcohol dehydrogenase activity

A series of CNS-stimulating and -depressant drugs have been studied for their in vitro interaction with horse liver alcohol dehydrogenase (ADH) activity. The depressant drugs studied included barbital, phenobarbital, thiopental, nitrazepam, chlorpromazine, sulpiride, clomethiazole, Li2CO3, diazepam, phenytoin, ethosuximide, morphine, and codeine. The stimulant drugs were theophylline, caffeine, amphetamine, imipramine, chlorimipramine, amitriptyline, and tranylcypromine. The results were as follows. First, ADH activity was inhibited by the action of chlorpromazine, tranylcypromine, imipramine, chlorimipramine, amitriptyline, sulpiride, amphetamine, codeine, ethosuximide, morphine, clomethiazole, nitrazepam, Li2CO3, theophylline, and phenobarbital, in descending order of inhibitory effect. Second, inhibition followed by activation of ADH activity was observed for imipramine and chlorimipramine. Third, activation of ADH activity was observed for phenytoin. Finally, the following drugs were not seen to exert any effect on ADH activity: barbital, thiopental, diazepam, and caffeine.     

Tricarbonyldichlororuthenium (II) dimer (CORM2) activates non-selective cation current in human endothelial cells independently of carbon monoxide releasing

Tricarbonyldichlororuthenium (II) dimer (CORM2) has been developed as carbon monoxide (CO) donor. We found that CORM2 activated a type of specific current which was distinct from the big-conductance Ca(2+)-activated K(+) current activated by CO in human umbilical vein endothelial cells (HUVECs). So the aim of the present study was to characterize the CORM2-induced current and to access the relation with CO releasing. CORM2 (100 microM) activated a kind of bi-directional current in HUVECs when the ramp protocol (holding potential 0 mV, from -120 mV to +120 mV) was applied. The current was not blocked by apamin, TRAM-34 and iberiotoxin, the small, intermediate and big-conductance Ca(2+) -activated K(+) channel blockers, and it was not sensitive to the pipette solution chelated with EGTA. CORM2 still activated the current when the chloride in the pipette solution was substituted by equal mol gluconic acid. Substitution of the sodium in the bath with choline significantly reduced the current activated by CORM2. The current was regarded as the non-selective cation current. The current showed slightly inward rectifier property and was not sensitive to Gd(3+) (100 microM), La(3+) (10 microM) or 2-aminoethoxydiphenyl borate (100 microM). CO (10 microM), CORM3 (100, 200 microM) and RuCl(3) (100 microM) were used as controls and showed no effect of the current activation. In conclusion, CORM2 activated the non-selective cation current in HUVECs independently of its CO releasing.     

EFFECT OF MAGNESIUM ON PASSIVE FLUXES OF LITHIUM IN THE HUMAN ERYTHROCYTE

Extracellular Mg2+ is known to inhibit the passive Na+ and K+ fluxes in the human erythrocyte. In this study the effect of extracellular Mg2+ on Li+ efflux was measured in erythrocytes from 29 normotensive and essential hypertensive subjects. Magnesium produced a variable inhibition of between 0 and 47% in Li+ efflux in different subjects and this effect was unrelated to initial cell Li+, blood pressure or to an action on the co- or counter-transport pathways for this cation. A positive correlation was observed between the magnitude of the passive Li+ efflux and its inhibition (0 to 47%) by Mg2+ ions. Thus Mg2+ has an inhibitory effect on passive Li+ permeability which is unrelated to essential hypertension.     

Inhibition of platelet aggregation by carbon monoxide-releasing molecules (CO-RMs): comparison with NO donors

Carbon monoxide (CO) and CO-releasing molecules (CO-RMs) inhibit platelet aggregation in vitro. Herein, we compare the anti-platelet action of CORM-3, which releases CO rapidly (t (?) 1?min), and CORM-A1, which slowly releases CO (t(?)?=?21?min). The anti-platelet effects of NO donors with various kinetics of NO release were studied for comparison. The effects of CO-RMs and NO donors were analyzed in washed human platelets (WP), platelets rich plasma (PRP), or whole blood (WB) using aggregometry technique. CORM-3 and CORM-A1 inhibited platelet aggregation in human PRP, WP, or WB, in a concentration-dependent manner. In all three preparations, CORM-A1 was more potent than CORM-3. Inhibition of platelets aggregation by CORM-A1 was not significantly affected by a guanylate cyclase inhibitor (ODQ) and a phosphodiesterase-5 inhibitor, sildenafil. In contrast, inhibition of platelet aggregation by NO donors was more potent with a fast NO releaser (DEA-NO, t (?)?=?2?min) than slow NO releasers such as PAPA-NO (t (?)?=?15?min) or other slow NO donors. Predictably, the anti-platelet effect of DEA-NO and other NO donors was reversed by ODQ while potentiated by sildenafil. In contrast to NO donors which inhibit platelets proportionally to the kinetics of NO released via activation of soluble guanylate cyclase (sGC), the slow CO-releaser CORM-A1 is a superior anti-platelet agent as compared to CORM-3 which releases CO instantly. The anti-platelet action of CO-RMs does not involve sGC activation. Importantly, CORM-A1 or its derivatives representing the class of slow CO releasers display promising pharmacological profile as anti-platelet agents.