3,15-二乙酰苯甲酰乌头原碱镇痛的作用部位

用大、小鼠四种测痛方法证实,ip DABA具有剂量依赖性镇痛作用ith DABA (527,1186 μR·kg~(-1)不产生镇痛作用;icv (35—75μS·kg~(-1)及水管周灰质注射DABA(20μg)均呈显著镇痛作用;损毁双侧蓝斑,DABA镇痛作用消失;蓝斑处注射DABA(20μg)不产生镇痛作用,揭示DABA的镇痛作用部位主要在中枢脊髓以上结构,水管周灰质是DABA镇痛的原发作用部位之一,蓝斑是其作用的中间环节之一。     

苯甲酰青藤碱的镇痛抗炎作用

目的:考察青藤碱衍生物苯甲酰青藤碱的镇痛、抗炎作用.方法:用小鼠扭体法、小鼠热板法、小鼠耳肿胀法、大鼠足跖肿胀法等试验观察.结果:苯甲酰青藤碱可抑制冰醋酸致小鼠疼痛的作用,提高小鼠热板痛阈值,抑制由二甲苯引起的小鼠耳肿胀,对角叉菜所致的足肿胀有抑制作用.结论:苯甲酰青藤碱具有镇痛、抗炎作用,且呈量效关系.     

N-（间马来酰亚胺苯甲酰）二棕榈酰磷脂酰乙醇胺的合成

间氨基苯甲酸与马来酸酐反应生成酰胺化合物,经脱水环合用N-羟基琥珀酰亚胺活化羧基,与二棕榈酰磷脂酰乙醇胺反应生成N-(间马来酰亚胺苯甲酰)二棕榈酰磷脂酰乙醇胺,总收率约29%.可用于制备主动靶向长循环脂质体.     

微生物来源的脂酰辅酶A：胆固醇酰转移酶抑制剂的研究进展

脂酰辅酶A：胆固醇脂酰转移酶(AcylCoA：Cholesterol Acyltransferase，简称ACAT)是催化胆固醇3位羟基，由长链脂酰CoA将脂酰基导人后，生成胆固醇酯(CE)的酶(图1)。ACAT在生物体内胆固醇代谢过程中起着重要的作用(图2)：(1)食物中的     

强效镇痛剂研究——Ⅴ.N-[1-(β-羟基-β-苯乙基)-3-甲基-4-哌啶基]-N-丙酰苯胺(7302)酯类衍生物的合成及镇痛活性

本文报道了一系列N-[1-(β-酰氧基-β-苯乙基)-3-甲基-4-哌啶基]-N-丙酰苯胺类衍生物及其化学结构与镇痛强度之间的关系,并测定了几个代表化合物的镇痛作用时间及与阿片受体亲和力。实验结果表明,7302的β-羟基酯化后,均能维持一定的镇痛强度,其镇痛作用时间与母体化合物7302相近。从受体结合试验来看,酯化后与受体亲和的能力显著下降。     

磷脂酰丝氨酸的中枢神经作用

磷脂酰丝氨酸(phosphatidylserine)是一种重要的细胞膜活性成分,可影响神经系统的多种生物学变化。此文介绍了磷脂酰丝氨酸的生化作用,对中枢神经系统的药理作用及其作用机制,其目的是总结目前对磷脂酰丝氨酸的认识,促进其生理学和药理学的研究。     

甘利欣联合多烯磷脂酰胆碱抗肝纤维化的疗效观察

目的 探讨甘利欣联合多烯磷脂酰胆碱对慢性肝炎肝纤维化的治疗作用.方法 将60例慢性乙型肝炎分为治疗组(予甘利欣150 mg和多烯磷脂酰胆碱15 ml治疗),甘利欣组(予甘利欣150 mg治疗)和多烯磷脂酰胆碱组(予多烯磷脂酰胆碱15 ml治疗).比较治疗前后检测各组肝功能及肝纤维化血清学指标.结果 治疗组治疗后肝功能及肝纤维化血清学指标明显好转,与治疗前及甘利欣组、多烯磷脂酰胆碱组比较,差异有统计学意义(P<0.05).结论 甘利欣联合多烯磷脂酰胆碱对慢性肝炎有明显的抗纤维化作用,比单用效果要好.     

高效液相色谱法测定多烯磷脂酰胆碱软胶囊中磷脂酰胆碱和溶血磷脂酰胆碱的含量

目的建立HPLC法测定多烯磷脂酰胆碱软胶囊中磷脂酰胆碱和溶血磷脂酰胆碱的含量以及有关物质方法。方法采用蒸发光散射检测器SEDEX55,MERCK的Li Chrospher 100 Diol-5色谱柱(125mm×4.0 mm,5μm);流动相A为正己烷-异丙醇-冰醋酸-三乙胺(814∶170∶15∶0.8),流动相B为异丙醇-超纯水-冰醋酸-三乙胺(844∶140∶15∶0.8),梯度洗脱。结果磷脂酰胆碱在0.912~2.736mg·mL~(-1),溶血磷脂酰胆碱在0.072~0.216 mg·mL~(-1)内与峰面积线性关系良好(R~2均为0.999)。磷脂酰胆碱的平均回收率为101.2%,RSD为1.3%;溶血磷脂酰胆碱的平均回收率为100.5%,RSD为1.9%。溶血磷脂酰胆碱的检测限为0.57μg。结论本检测方法专属性强,结果可靠,专属性强,重复性良好,可用于多烯磷脂酰胆碱软胶囊的质量评价。     

老年人高三酰甘油血症的临床观察

目的观察临床上老年人三酰甘油(TG)的代谢情况,对老年人患高三酰甘油(TG)血症的预后进行对比分析,探讨三酰甘油与糖尿病(DM)、高血压(HP)、动脉粥样硬化性(AS)疾病和冠心病(CHD)的关系。方法运用BECKMAN全自动生化分析仪对老年人1080例高三酰甘油血症和880例三酰甘油正常的体检者进行三酰甘油和血糖的检测,结合临床的诊断结果,比较他们在糖尿病(DM)、冠心病(CHD)、动脉粥样硬化性(AS)疾病、高血压(HP)等疾病的发病情况。结果患有高三酰甘油(TG)血症的老年人的糖尿病(DM)、冠心病(CHD)、动脉粥样硬化性(AS)疾病、高血压(HP)的发病概率显著高于三酰甘油(TG)正常的老年人。结论老年人三酰甘油(TG)的代谢情况,直接影响老年人健康,高三酰甘油(TG)是导致糖尿病(DM)、冠心病(CHD)、动脉粥样硬化性(AS)疾病、高血压(HP)等疾病的重要因素之一,其中三酰甘油(TG)的代谢紊乱是病发的首要因素,所以我们应采取各种措施来控制三酰甘油(TG)的代谢紊乱,减少各种疾病的发生。     

丙氨酰谷氨酰胺对辐射照射大鼠蛋白质代谢的影响

目的:观察辐射对大鼠全身代谢的影响及丙氨酰谷氨酰胺(AlaGln)对辐射损伤引起的蛋白质损耗的恢复作用.方法:以60Co-γ射线照射大鼠造成全身辐射损伤,饲喂添加丙氨酰谷氨酰胺和放射性氨基酸的营养液,48h后收集脏器和血液样本并进行测定.结果:大鼠接受辐射后全身亮氨酸氧化上升,全身蛋白质合成和分解增加,丙氨酰谷氨酰胺可提高骨骼肌谷氨酰胺浓度,降低亮氨酸氧化.结论:通过给受辐射鼠添加丙氨酰谷氨酰胺可有效降低亮氨酸的氧化,影响重要分支侧链氨基酸(BCAA)的代谢,从而对蛋白质代谢产生积极作用.     

Cloning and characterization of the ddc homolog encoding L-2,4-diaminobutyrate decarboxylase in Enterobacter aerogenes

L-2,4-diaminobutyrate decarboxylase (DABA DC) catalyzes the formation of 1,3-diaminopropane (DAP) from DABA. In the present study, the ddc gene encoding DABA DC from Enterobacter aerogenes ATCC 13048 was cloned and characterized. Determination of the nucleotide sequence revealed an open reading frame of 1470 bp encoding a 53659-Da protein of 490 amino acids, whose deduced NH2-terminal sequence was identical to that of purified DABA DC from E. aerogenes. The deduced amino acid sequence was highly similar to those of Acinetobacter baumannii and Haemophilus influenzae DABA DCs encoded by the ddc genes. The lysine-307 of the E. aerogenes DABA DC was identified as the pyridoxal 5'-phosphate binding residue by site-directed mutagenesis. Furthermore, PCR analysis revealed the distribution of E. aerogenes ddc homologs in some other species of Enterobacteriaceae. Such a relatively wide occurrence of the ddc homologs implies biological significance of DABA DC and its product DAP.     

小鼠静脉注射3，15－二乙酰苯甲酰乌头宁后血及脑中药物含量的变化

小鼠ｉｖ３，１５－二乙酰苯甲酰乌头宁５ｍｇ·ｋｇ－１后，血药－时曲线符合开放型二房室模型，其Ｔ　及Ｔ　分别为０．９９及２６．６２ｍｉｎ，脑药－时曲线表明给药后３０ｍｉｎ浓度达高峰，９０ｍｉｎ后浓度显著下降。     

小鼠静脉注射3，15－二乙酰苯甲酰乌头宁后血及脑中药物含量的变化

小鼠ｉｖ３，１５－二乙酰苯甲酰乌头宁５ｍｇ·ｋｇ－１后，血药－时曲线符合开放型二房室模型，其Ｔ　及Ｔ　分别为０．９９及２６．６２ｍｉｎ，脑药－时曲线表明给药后３０ｍｉｎ浓度达高峰，９０ｍｉｎ后浓度显著下降。     

Effects of bilateral injection of GABA into the substantia nigra on spontaneous behavior and measures of analgesia

Bilateral injection of gamma-aminobutyric acid (GABA, 10-300 micrograms) into the substantia nigra (pars reticulata) of rats produced stereotyped sniffing and had an analgesic-like effect on the hot-plate but not on the tail-flick test. These effects of GABA (30 micrograms) were suppressed by simultaneous administration of a sub-convulsant dose of bicuculline methiodide (100 ng). Significant increases in locomotion occurred when GABA (300 micrograms) was injected along with the inhibitor of GABA-transaminase, d,l-gamma-vinyl-GABA (GVG; 5 micrograms) and the inhibitor of the uptake of GABA, 1-2,4-diaminobutyric acid (DABA; 5 micrograms). No other behavioral effects were observed following injection of GABA into the nigra, either alone or in combination with GVG and DABA. Bilateral injection of bicuculline (100-600 ng) into the nigra had strong convulsant actions. When injected simultaneously with bicuculline, GABA reduced bicuculline-induced seizures. These results are discussed in terms of their relevance to understanding the mechanisms that underlie the behavioral effects produced by injection of muscimol into the nigra.     

Influence of cellular transport on the interaction of amino acids with gamma-aminobutyric acid (GABA)-receptors in the isolated olfactory cortex of the guinea-pig.

1 Freshly cut guniea-pig olfactory cortex slices contained 2.2 mmol gamma-aminobutyric acid (GABA)/kg tissue weight. This declined during in vitro incubation at 25 degrees C in the absence of exogenous GABA, but increased to 6.95 mmol/kg after 1.5 h incubation in 1 mM GABA. 2 Uptake of [3H]-GABA (1 microM) was inhibited by 1 mM (+/-)-nipecotic acid (-83%), beta-amino-n-butyric acid (BABA) (-59%), L-2,4-diaminobutyric acid (DABA) (-63%), (+/-)cis-3-aminocyclohexane carboxylic acid (ACHC) (-53%), and 3-aminopropanesulphonic acid (3-APS) (-26%), but was increased by beta-alanine (BALA) (+23%). 3 Autoradiographs showed steep concentration gradients of radioactivity across slices incubated for short periods in [3H]-GABA. 4 Efflux of [3H]-GABA from pre-loaded slices was accelerated strongly by nipecotic acid, BABA, DABA and ACHC but weakly or not all by BALA or 3-APS. 5 Nipecotic acid (1 mM) potentiated the surface-depolarization of the slice produced by GABA but not that produced by 3-APS. 6 The depolarizing actions of DABA, BABA, nipecotic acid and ACHC, but not that of 3-APS or BALA, were potentiated when the endogenous GABA content of slices was raised. 7 It is concluded that: (a) the depolarizing action of exogenous GABA is limited by cellular uptake; (b) surface-depolarizations produced by nipecotic acid, DABA, BABA and ACHC may be mediated by the release of GABA; and (c) neuronal, rather than glial, transport systems are responsible for these effects.     

Neuro‐ and hepatic toxicological profile of (S)‐2,4‐diaminobutanoic acid in embryonic,adolescent and adult zebrafish

(S)‐2,4‐Diaminobutanoic acid (DABA) is a noncanonical amino acid often co‐produced by cyanobacteria along with β‐N‐methylamino‐l ‐alanine (BMAA) in algal blooms. Although BMAA is a well‐established neurotoxin, the toxicity of DABA remains unclear. As part of our development of biocompatible materials, we wish to make use of DABA as both a building block and as the end‐product of enzymatically induced depolymerization; however, if it is toxic at very low concentrations, this would not be possible. We examined the toxicity of DABA using both in vivo embryonic and adult zebrafish models. At higher sublethal concentrations (700 μm ), the fish demonstrated early signs of cardiotoxicity. Adolescent zebrafish were able to tolerate a higher concentration. Post‐mortem histological analysis of juvenile zebrafish showed no liver or brain abnormalities associated with hepato‐ or neurotoxicity. Combined, these results show that DABA exhibits no overt toxicity at concentrations (100‐300 μm ) within an order of magnitude of those envisioned for its application. This study further highlights the low cost and ease of using zebrafish as an early‐stage toxicological screening tool.     

A role for 5-hydroxytryptamine in the GABA-mimetic potentiation of alpha-flupenthixol-induced catalepsy in the rat

1 alpha-Flupenthixol (alpha-FPT)-induced catalepsy in the rat was potentiated by diaminobutyric acid (DABA), an inhibitor of the neuronal high affinity uptake of gamma-aminobutyric acid (GABA). 2 The depletion of 5-hydroxytryptamine (5-HT) with p-chlorophenylalanine (PCPA) abolished the DABA potentiation of alpha-FPT-induced catalepsy; this response was restored with 5-hydroxytryptophan. 3 Potentiation of alpha-FPT-induced catalepsy by clonazepam was significantly reduced by methysergide. Conversely, the potentiation of catalepsy by clomipramine was significantly reduced by picrotoxin. 4 These results are interpreted as evidence supporting a role for 5-HT in modifying the GABA-ergic inhibition of dopaminergic pathways, possibly by regulating the release of GABA.     

尿苷肽类抗生素生物合成研究进展

尿苷肽类抗生素是一类具有相同母核结构的化合物,其化学结构独特、作用机制新颖、抗菌谱窄,是寻找新型低毒、窄谱抗菌药物的先导化合物或候选药物的最佳选择之一。本文介绍了尿苷肽类抗生素的化学结构特征以及构效关系,着重介绍了其生物合成机制的最新研究进展。尿苷肽类抗生素肽链的合成由非核糖体肽合成酶（non-ribosomal peptide synthetase,NRPS）以非线性机制催化完成,肽链的组装始于中心模块2,3-二氨基丁酸（2,3-diaminobutyric acid,DABA）,其后的延伸包括N端氨基酸或二肽与DABAβ-氨基间的缩合,以及C端的脲二肽与DABAα-氨基间的缩合。3′-脱氧-4′,5′-烯酰胺尿苷由尿苷经过3步反应转化而来,并在NRPS的催化下与四肽或五肽缩合形成尿苷肽类抗生素。尿苷肽类抗生素生物合成机制的阐明为利用组合生物合成技术获得新结构的尿苷肽类化合物奠定了基础。     

Gamma-aminobutyric acid and the high pressure neurological syndrome

Sodium valproate, nipecotic acid, diaminobutyric acid (DABA) and beta-alanine are drugs which enhance transmission mediated by gamma-aminobutyric acid (GABA) by a variety of mechanisms. They were used to study the role of GABA in the high pressure neurological syndrome (HPNS) in the rat. Sodium valproate, nipecotic acid and DABA reduced the increase in slow waves seen in the electroencephalogram (EEG) of control rats at pressures above 10-20 ATA; however, only sodium valproate had a beneficial effect on the behavioural signs of the high pressure neurological syndrome (tremor, myoclonus and convulsions). Sodium valproate is also thought to decrease neurotransmission produced by excitatory amino acids; thus, these results suggest that GABA is not one of the major neurotransmitters involved in all aspects of the high pressure neurological syndrome and that changes in excitatory neurotransmission may affect the behavioural signs.     

Involvement of GABAergic mechanisms in chloroquine-induced seizures in mice.

1. The influence of some GABAergic agents on tonic seizures elicited by chloroquine was investigated in mice. 2. Chloroquine (45-100 mg/kg) elicited seizures in mice in a dose related manner. 3. Muscimol (1-2 mg/kg), DABA (8-16 mg/kg) and baclofen (4-16 mg/kg) profoundly delayed the onset of chloroquine (65 mg/kg)-induced seizures. The incidence of the seizures was also significantly reduced by muscimol (1-2 mg/kg), DABA (8 mg/kg) and baclofen (4-8 mg/kg). 4. AOAA (10 mg/kg) profoundly reduced the proportion of mice that convulsed while AOAA (20 mg/kg) completely protected mice against chloroquine (65 mg/kg)-induced seizures. 5. Bicuculline (5 mg/kg) and picrotoxin (0.5-1 mg/kg) significantly potentiated chloroquine (50 mg/kg)-induced seizures. The onset of seizures and the number of mice that convulsed were shortened and increased respectively. The onset of chloroquine (65 mg/kg)-elicited seizures was also profoundly shortened. Bicuculline (5 mg/kg) and picrotoxin (0.5 mg/kg) effectively antagonised the protective effects of muscimol (2 mg/kg), AOAA (10 mg/kg) and DABA (8 mg/kg) against chloroquine (65 mg/kg)-elicited seizures. 6. Diazepam (1 mg/kg) and phenobarbitone (20 mg/kg) significantly antagonised chloroquine (65 mg/kg) seizures. The onset of seizures was significantly delayed by both diazepam (0.25-1 mg/kg) and phenobarbitone (10-20 mg/kg). 7. These data suggest that enhancement and inhibition of GABAergic neurotransmission respectively attenuate and potentiate chloroquine seizures in mice.