中国抗生素杂志 第26卷1～6期(2001年)目次检索

进展与述评组合生物合成研究进展　胡又佳 ,朱春宝 ,朱宝泉 2 6 (5 ) :32 1超广谱 β-内酰胺酶分子生物学基础的研究进展　陆坚 ,唐英春2 6 (6 ) :40 1金葡球菌对糖肽类抗生素敏感性降低的研究进展　陈智鸿 ,范昕建 ,吕晓菊 2 6 (1) :75喹诺酮类药物抗结核治疗的研究进展　张沂 ,段蕴铀 ,张沂扬2 6 (3) :2 34微生物 (新抗生素、微生物药物筛选、育种和发酵 )微生物来源的 Azole类抗真菌活性增强剂—— FKI- 0 0 76 A、B和 C的研究　王海燕 ,荒井雅吉 ,供田洋 ,等 2 6 (2 ) :89新蒽环类抗生素 G0 0 41- 3c的理化性质及结构分析　肖春玲 ,…     

微生物来源的Azole类抗真菌活性增强剂——FKI-0076A、B和C的研究

FKI-0076A、B和C是从真菌培养液中筛选Azole类抗真菌活性增强剂过程中获得的．每6ram纸片10μg FKI-0076A、B或1．Oμg FKI-0076C就显示增强活性。真菌Talaromyces sp．FKI-0076培养5d后．经有机溶媒提取,常压ODS柱层析和制备HPLC柱层析分离．得到FKI-0076A、B和C纯品。又经过测定其HR-MS、UV、IR、^1H-NMR、^13C-NMR、DEPT、^1H-^3H COSY、HMQC和HMBC等光谱数据。将FKI-0076A的结构定为BK223-A．FKI-0076B的结构定为vermistatin．FKI-0076C的结构定为deoxyfunicone。     

委内瑞拉马脑炎病毒基因工程减毒活疫苗:动物模型试验

目前的委内瑞拉马脑炎病毒 ( VEEV)减毒疫苗TC- 83和灭活疫苗 C- 84都尚欠完善 ,美国陆军医学传染病研究所 Pratt等对新型 VEEV基因工程减毒活疫苗通过动物模型试验来评价其安全性、免疫性和有效性。　　作者以 VEEV野毒株 V30 0 0全长 c DNA为模板 ,利用改良 Kunkel定点突变技术构建了 8个候选疫苗株 ,包括糖蛋白区三种减毒突变不同组合构成的V35 1 9( E12 72、 E2 76、 E2 2 0 9突变 )、 V35 2 0 ( E181、E2 76、 E2 2 0 9突变 )、V35 2 2 ( nt3A、E2 76、 E2 2 0 9突变 )、V35 2 4 ( nt3A、E12 72、E2 2 0 9突变 ) ,PE2…     

莲心碱在大鼠体内的药物动力学研究

用反向HPLC法 ,以己酮可可碱为内标 ,建立了血浆中莲心碱的测定方法 ,血浆标准曲线为A1/A2 =0 3188C - 0 0 6 77,相关系数r =0 9999,回收率及日内、日间精密度均符合要求。根据大鼠颈静脉给药 (8 5 4mg/kg)后测得的血药浓度 ,用 3P87处理后求得的莲心碱的主要药动学参数为 :t1/ 2 (α) =2 5 14min ,t1/ 2 ( β) =49 5 2 2min ,AUC =114 878min·μg/mL ,CL =0 0 743L/ (kg·min) -1,V(c) =0 76 6L/kg。     

气相色谱法测定鱼油多烯乙酯的含量

目的用气相色谱法测定鱼油多烯乙酯中二十碳五烯酸乙酯 (EPA E)和二十二碳六烯酸乙酯 (DHA E)的含量。方法采用气相色谱法 ,聚二乙二醇酯为固定相 ,涂布浓度为 10 % ,载体为ChromosorbWAWDMCS 80～ 10 0目的气相柱。结果EPA E平均回收率为 10 0 .31% ,RSD为 2 .5 4 % ;DHA E平均回收率为 10 3.37% ,RSD为 2 .76 %。结论此法操作简便、准确、重现性、稳定性好 ,是一种可行的含量测定方法     

96例冠心病患者静滴前列腺素E1不良反应的观察及护理

1998年 1月～ 1999年 12月 ,我们配合医生观察护理 96例采用前列腺素 E1 静滴治疗冠心病的患者 ,现将观察护理体会报告如下。1　临床资料本组 96例均为住院冠心病人 ,给予前列腺素 E1 (PGE1 )治疗。其中男性 6 4例 ,女性 32例 ;年龄最大 81岁 ,最小 5 2岁 ,平均 6 5岁。在治疗期间 ,出现静脉炎 76例 ,占 79.2 % ;消化道反应 (腹痛、恶心、呕吐 ) 10例 ,占 10 .4% ;发热、头痛 5例 ,占 5 .2 ;心悸 5例 ,占 5 .2 %。给予 5 %葡萄糖 2 5 0 ml+ PGE1 10 0 μg或 0 .9%生理盐水 2 5 0 ml+ PGE1 10 0 μg,每日 1次静滴 ,14天为一个疗程 ,据血…     

成分输血 测验题(第四套题)

1 二级医院成分输血率应达A 70 %以上　　B 5 0 %以上C 2 0 %D 10 0 %E 4 0 %以上2 全血储存数日后 ,其中的有效成分主要为A 凝血因子　　B 粒细胞C 血小板　　　D 红细胞E 白蛋白3 全血的保存温度为A 2 2℃　　　B 10℃C 37℃　　　D 2～ 6℃E - 2 0℃4 TA -GVHD是指A 输血反应　　B 发热反应C 输血相关性移植物抗宿主病D 成分输血E 溶血反应5 体重 6 0kg的成年人 ,手术失血90 0mL应输入A 全血　　B 浓缩红细胞C 血浆　　D 晶体溶液E 白蛋白6 浓缩红细胞的Hct为A 5 0 %　　　B 95 %C 70 %～ 90 %D 10 0 %　　E 4 0 %7 …     

荧光PCR定量检测外周血中β-葡萄醛酶mRNA方法及临床应用

目的探讨荧光PCR定量检测外周血中β-葡萄醛酶mRNA探讨临床意义。方法荧光PCR定量检测外周血中β-葡萄醛酶mRNA。结果30例肝胆结石患者外周血中β—GmRNA1．46E3～1．47E6Copies／L；Ⅰ（高分化肝癌）1．37E3～2．76E6 Copies／L；Ⅱ-Ⅲ（中分化肝癌）9．38E3．1-98E7Copies／L；Ⅳ（低分化肝癌）9．76E7～9．86E8Copies／L。结论内源性β-G与肝胆管结石形成有关、β—GmRNA检测可成为肝癌诊断的辅助指标。     

HPLC法测定维生素E搽剂中维生素E的含量

目的：建立HPLC法测定维生素E搽剂中维生素E含量的方法。方法：色谱柱为SHIMADZU VP-ODS C18柱（4．6mm×150mm）;流动相为甲醇-水（98：2）,流速为1．0ml／min,检测波长为284nm。结果：线性范围为0．025-0．200mg／ml,r=0．9999,平均回收率为98．80％,RSD为0．5％。结论：HPLC法测定维生素E搽剂中维生素E的含量,方法准确可靠,简单可行,可用于维生素E搽剂中维生素E的含量测定。     

厄贝沙坦对高血压并发心力衰竭患者心功能的影响

目的 :观察血管紧张素Ⅱ受体阻滞剂厄贝沙坦的降压疗效和对心功能的影响。方法 :试验组 (n =4 0 )口服厄贝沙坦 15 0mg ,qd ,连用 4周 ;对照组 (n =36 )口服卡托普利 12 .5mg ,bid或tid ,连用 4周 ,用药期间仔细检查体格及心电图 ,给药前后行超声心动图计算射血分数 (EF)和E/A比值 ,评定心功能变化。结果 :试验组SBP和DBP都有明显降低 ,而对照组改变不明显 ,2组间比较差异非常显著 ;2组治疗后心功能都有明显改善 ,试验组总有效率为 80 % ,对照组为 6 1% ,2组比较差异有显著性 ;2组治疗后LVEF均升高 :试验组 0 .4 6± 0 .0 7vs 0 .4 1±0 .0 6 (P <0 .0 5 ) ,对照组 0 .4 2± 0 .0 6vs 0 .4 0± 0 .0 5 (P >0 .0 5 ) ;E/A比值升高 :试验组为 1.0 6± 0 .13vs 0 .5 8±0 .15 (P <0 .0 1) ,对照组 0 .76± 0 .12vs 0 .5 7± 0 .14 (P <0 .0 5 )。试验组好转更明显。结论 :厄贝沙坦有利于缓解心衰症状 ,改善其收缩功能和舒张功能 ;其疗效优于卡托普利。     

Funicone-related compounds,potentiators of antifungal miconazole activity,produced by Talaromycesflavus FKI-0076

Talaromyces flavus FKI-0076, a soil isolate, was found to produce compounds which reinforce the anti-Candida albicans activity of miconazole. Four structurally related compounds, a novel one, designated actofunicone, and the knowns deoxyfunicone, vermistatin and NG-012, were isolated from the culture broth by solvent extraction, ODS column chromatography and HPLC. The structure of actofunicone was elucidated as benzoic acid, 3,5-dimethoxy-2-[[4-oxo-6-(2-acetyloxy propyl)-4H-pyran-3-yl]carbonyl]-, methyl ester by various spectroscopic analyses including NMR experiments. These compounds potentiated the anti-C. albicans activity of miconazole, decreasing the IC50 value of miconazole from 19 microM to 1.6 approximately 3.7 microM in the presence of the funicones.     

New beauvericins, potentiators of antifungal miconazole activity, Produced by Beauveria sp. FKI-1366. II. Structure elucidation

The structures of beauvericins D, E and F, novel potentiators of miconazole activity against Candida albicans produced by Beauveria sp. FKI 1366, were elucidated by various spectroscopic analyses including UV, NMR, and MS and degradation experiments. They have the common skeleton of the 18-membered cyclodepsipeptides.     

Characterization of a novel binding site for 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]bradykinin on epithelial membranes of guinea pig ileum.

We have recently shown that (a) [125I-Tyr8]bradykinin (BK) recognized bradykinin binding sites in guinea pig epithelium membranes with a Kd value of 1.6 nM and a Bmax of 156 fmol/mg protein, and (b) B2 agonists and some B2 antagonists, such as D-Arg-[Hyp3,D-Phe7,Leu8]BK, inhibited this specific binding with a Ki value of 32 nM. In the present study, we have radioiodinated the B2 antagonist Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK and have performed a full characterization of the binding properties of this tracer in the same membrane preparation. Equilibrium experiments performed in the absence or presence of an excess of BK (10(-5) M) showed that 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK specifically labelled two different sites. One of these is the same as the site labelled by [125I-Tyr8]BK, and this indicates that 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK interacts specifically with kinin B2 receptors. Equilibrium experiment performed in the presence of an excess of BK (10(-5) M) indicated that specific binding of 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK to the second site is also saturable and Scatchard analysis showed that the site is of high affinity with a Kd of 16.8 nM and a Bmax of 2.08 pmol/mg protein. Surprisingly, unlabelled B2 agonists such as bradykinin, [Tyr8]BK, [Leu8]BK, [Hyp3,Tyr8(OMe)]BK, D-Arg-[Hyp3]BK and kallidin were found to be inactive on this second site. A series of B2 receptor antagonists, Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK, D-Arg-[Hyp3,D-Phe7,Leu8]BK, D-Arg-[Hyp3,Leu5,8,D-Phe7]BK, D-Arg-[Hyp3,Gly6,D-Phe7,Leu8]BK and D-Arg-[Hyp3,Thi5,8,D-Phe7]BK inhibited 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK binding with Ki values of 25.0, 20.9, 15.8, 64.6 and 6606.9 nM respectively. On the other hand, [Thi5,8,D-Phe7]BK did not interfere with 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK but was found to be a potent inhibitor of [125I-Tyr8]BK binding (Ki = 53.7 nM). As expected, B1 receptor agonists, antagonists and peptides non-related to BK such as substance P, neurokinin A, neurokinin B, angiotensin II, bombesin, vasopressin and the calcitonin gene related peptide were unable to compete with 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK. The results show that 125I-Tyr-D-Arg-[Hyp3,D-Phe7,Leu8]BK is interacting with two distinct binding sites in the guinea pig epithelium: one is the well known bradykinin B2 receptor and the other is a new, non-characterized binding site that interacts exclusively with some bradykinin receptor antagonists.     

In vitro and in vivo effects of kinin B(1) and B(2) receptor agonists and antagonists in inbred control and cardiomyopathic hamsters

The aims of this study were to examine the possible alterations occurring in the effects of kinins on isolated aortae of inbred control (CHF 148) and cardiomyopathic (CHF 146) hamsters of 150 - 175 and 350 - 375 days of age. Bradykinin (BK) and desArg(9)BK contracted isolated aortae (with or without endothelium) of hamsters of both strains and ages. After tissue equilibration (90 min), responses elicited by both kinin agonists were stable over the time of experiments. The patterns of isometric contractions of BK and desArg(9)BK were however found to be different; desArg(9)BK had a slower onset and a longer duration of action than BK. Potencies (pEC(50) values) of BK in all groups of hamsters were significantly increased by preincubating the tissues with captopril (10(-5) M). No differences in the pEC(50) values and the E(max) values for BK or desArg(9)BK were seen between isolated vessels from inbred control and cardiomyopathic hamsters. The myotropic effect of BK was inhibited by the selective non peptide antagonist, FR 173657 (pIC(50) 7.25+/-0.12 at the bradykinin B(2) receptor subtype (B(2) receptor)). Those of desArg(9)BK, at the bradykinin B(1) receptor subtype (B(1) receptor) were abolished by either R 715 (pIC(50) of 7. 55+/-0.05; alpha(E) = 0), Lys[Leu(8)]desArg(9)BK (pIC(50) of 7.21+/-0. 01; alpha(E) = 0.22) or [Leu(8)]desArg(9)BK (pIC(50) of 7.25+/-0.02; alpha(E) = 0.18). FR 173657 had no agonistic activity, exerted a non competitive type of antagonism and was poorly reversible (lasting more than 5 h) from B(2) receptor. In vivo, FR 173657 (given per os at 1 and 5 mg kg(-1), 1 h before the experiment) antagonized the acute hypotensive effect of BK in anaesthetized hamsters. It is concluded that aging and/or the presence of a congenital cardiovascular disorder in hamsters are not associated with changes in the in vitro aortic responses to either BK or desArg(9)BK.     

Pharmacological characterization of RMP-7, a novel bradykinin agonist in smooth muscle

RMP-7 is a bradykinin (BK) agonist designed to be resistant to kininases such as angiotensin-converting enzyme (ACE). Pharmacological assays were performed with RMP-7 in isolated guinea-pig ileum and rat mesenteric artery. RMP-7 induced contractile responses in the guinea-pig ileum, where the apparent affinity of the peptide (pD2) was significantly lower than that determined for BK (7.3 +/- 0.07 vs. 8.3 +/- 0.05, respectively). HOE-140 blocked this effect indicating that B2 receptor was involved. Captopril (1 microM) had no potentiating effect on RMP-7 but increased pD2 value determined for BK (8.8 +/- 0.1), confirming a high resistance of RMP-7 to the ACE. In rat mesenteric artery, RMP-7 induced endothelium-dependent relaxation (7.8 +/- 0.4), with a higher affinity than that of BK which induced vasodilatation only in the presence of 1 microM captopril (6.9 +/- 0.36). Nevertheless, the maximum effect induced by RMP-7 was lower than that of BK in contrast to that observed in guinea-pig ileum although B2 receptor was involved in both cases. We concluded that: RMP-7 is greatly resistant to the ACE and that the receptor sites activated by RMP-7 and BK show important differences in vascular and non-vascular preparations probably due to the different sensitivity of the B2 receptor to RMP-7.     

Characterization of kinin receptors in human cultured detrusor smooth muscle cells

BACKGROUND AND PURPOSE: Kinins have an important role in inflammatory cystitis and in animal pathophysiological models, by acting on epithelium, fibroblasts, sensory innervation and smooth muscle. The aim of this study was to characterize the receptors responsible for direct motor responses induced by kinins on human detrusor. EXPERIMENTAL APPROACH: Human detrusor cells from biopsies were isolated and maintained in culture. B(1) and B(2) kinin receptors were characterized by means of radioligand and functional experiments (PI accumulation and PGE(2) release). KEY RESULTS: [(3)H]-[desArg(9)]-Lys-BK and [(3)H]-BK saturation studies indicated receptor density (B(max)) and K (d) values of 19 or 113 fmol mg(-1), and 0.16 or 0.11 nM for the B(1) or B(2) receptors, respectively. Inhibition binding studies indicated the selectivity of the B(1) receptor antagonist [desArg(9)Leu(8)]-Lys-BK and of the B(2) receptor antagonists Icatibant and MEN16132. [DesArg(9)]-Lys-BK and BK induced PI accumulation with an EC(50) of 1.6 and 1.4 nM and different maximal responses (E(max) of [desArg(9)]-Lys-BK was 10% of BK). BK also induced prostaglandin E(2) release (EC(50) 2.3 nM), whereas no response was detected with the B(1) receptor agonist. The incubation of detrusor smooth muscle cells with interleukin 1beta (IL-1beta) or tumour necrosis factor-alpha (TNF-alpha) (10 ng ml(-1)) induced a time-dependent increase in radioligand-specific binding, which was greater for the B(1) than for the B(2) receptor. CONCLUSIONS AND IMPLICATIONS: Human detrusor smooth muscle cells in culture retain kinin receptors, and represent a suitable model to investigate the mechanisms and changes that occur under chronic inflammatory conditions.     

Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea-pig small intestine

1. Electrophysiologic methods were used to study actions of bradykinin (BK) in neurones of the myenteric plexus of guinea-pig small intestine in vitro. Exposure to BK depolarized the membrane potential and elevated excitability in AH- and S-type neurones. Neuronal input resistance associated with the depolarizing responses was either decreased or unchanged in S-type and increased in AH-type neurones. 2. The selective B(2) BK receptor antagonist HOE-140, but not the selective B(1) receptor antagonist des-arg(10)-HOE-140, suppressed the BK-evoked responses. RT-PCR confirmed the expression of B(2) receptor mRNA, but not B(1) receptor mRNA. 3. Binding of fluorescently- labeled HOE-140 (HOE741) was localized to ganglion cells in whole-mount preparations. BK B(2) receptors were coexpressed with immunoreactivity for calbindin or nitric oxide synthase. 4. Exposure to BK suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. Depolarizing responses evoked by application of serotonin or substance P and nicotinic responses to acetylcholine were not reduced by BK. This suggested that BK action on neurotransmission was presynaptic suppression of neurotransmitter release. Presence of HOE-140 in the bathing solution suppressed or abolished the presynaptic inhibitory action of BK. 5. The cyclooxygenase inhibitor, piroxicam, suppressed both the direct excitatory action of BK and its presynaptic inhibitory action. Application of prostaglandin E(2), D(2), F(2alpha) or I(2) mimicked the BK-evoked responses. 6. The results suggest that BK acts at B(2) BK receptors on myenteric neurones to stimulate the formation of prostaglandins. Once formed and released, the prostaglandins act to elevate the excitability of ganglion cells in the myenteric plexus and to suppress the synaptic release of neurotransmitters.     

DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin (desArg10-[Hoe140]) is a potent bradykinin B1 receptor antagonist.

DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK is a potent and stable B1 bradykinin (BK) receptor antagonist which was one order of magnitude more potent (IC50 1.2 x 10(-8) M) in the isolated rabbit aorta than the known selective B1 BK receptor antagonist, desArg9-[Leu8]BK (IC50 1.1 x 10(-7) M). DesArg9-D-Arg[Hyp3,Thi5,D-Tic7,Oic8]BK is the desArg10 derivative of Hoe140, a new, potent, stable, selective and long-acting B2 BK receptor antagonist. In B2 organ preparation it was three orders of magnitude less potent than Hoe140. Since it is potent and stable it could contribute to the investigation of B1 BK receptor function.     

New sesquicillins, insecticidal antibiotics produced by Albophoma sp. FKI-1778

Four new antibiotics, sesquicillins B to E were isolated from the culture broth of Albophoma sp. FKI-1778 together with known sesquicillin (sesquicillin A in this paper). The structures of sesquicillins were elucidated by spectroscopic studies including various NMR experiments. All sesquicillins have a common pyrano-diterpene skeleton. Sesquicillins showed moderate inhibitory activity against the growth of Artemia salina (brine shrimps) and Jurkat cells.     

Bradykinin B1 and B2 receptors, tumour necrosis factor alpha and inflammatory hyperalgesia

The effects of BK agonists and antagonists, and other hyperalgesic/antihyperalgesic drugs were measured (3 h after injection of hyperalgesic drugs) in a model of mechanical hyperalgesia (the end-point of which was indicated by a brief apnoea, the retraction of the head and forepaws, and muscular tremor). DALBK inhibited responses to carrageenin, bradykinin, DABK, and kallidin. Responses to kallidin and DABK were inhibited by indomethacin or atenolol and abolished by the combination of indomethacin + atenolol. DALBK or HOE 140, given 30 min before, but not 2 h after, carrageenin, BK, DABK and kallidin reduced hyperalgesic responses to these agents. A small dose of DABK+ a small dose of BK evoked a response similar to the response to a much larger dose of DABK or BK, given alone. Responses to BK were antagonized by HOE 140 whereas DALBK antagonized only responses to larger doses of BK. The combination of a small dose of DALBK with a small dose of HOE 140 abolished the response to BK. The hyperalgesic response to LPS (1 microg) was inhibited by DALBK or HOE 140 and abolished by DALBK + HOE 140. The hyperalgesic response to LPS (5 microg) was not antagonized by DALBK + HOE 140. These data suggest: (a) a predominant role for B2 receptors in mediating hyperalgesic responses to BK and to drugs that stimulate BK release, and (b) activation of the hyperalgesic cytokine cascade independently of both B1 and B2 receptors if the hyperalgesic stimulus is of sufficient magnitude.