Direct cadiac electorphysiologic effects of sufentanil and vecuronium in isolated guinea-pig hearts

Sufentanil and vecuronium are commonly used simultaneously in anaesthesia. Bradycardia and asystole have been described immediately after the administration of these two compounds. Therefore, the purpose of the present study was to evaluate the direct cardiac effects of sufentanil and vecuronium in all parts of the cardiac pacemaker and conduction system.
The electrophysiological effects of sufentanil and vecuronium were studied in isolated spontaneously beating guinea-pig hearts perfused by the method of Langendorff. At a concentration of 0.1 μmol/1 sufentanil a significant reduction of the spontaneous sinus rate, prolongation of atrioventricular, intraventricular and His' bundle conduction could be observed. The highest concentration of 10 μmol/1 of sufentanil led to an overall slowing of conduction velocity and to an profound slowing of spontaneous sinus rate. AV nodal as well as atrial and ventricular refractoriness were markedly prolonged at this high concentration of sufentanil. In contrast, during perfusion with vecuronium at a concentration of 0.1 μmol/1 up to 10 μmol/1 no significant effects on cardiac conduction and pacemaker activity could be observed.
In conclusion, the electrophysiological effects of sufentanil are comparable to that of unspecific calcium antagonists. Therefore, especially in patients with a preexisting damage of the cardiac conduction system, the indirect effect of the combination of sufentanil and vecuronium which is predominantly responsible for bradycardia and asystole may be worsened by the direct effects of sufentanil.     

杂多阴离子对SiO_2细胞毒性的拮抗作用

本文采用离体细胞培养法,以细胞存活率、乳酸脱氢酶活性和酸性磷酸酶活性为指标,研究了几种α-Keggin结构的杂多阴离子对石英粉尘细胞毒性的影响。结果表明,与对照组比较,所用杂多阴离子无细胞毒性(P>0.05),石英尘经杂多阴离子作用后,细胞毒性显著降低,与石英尘组比较,上述三项指标差异均有显著意义(P<0.01),由此表明杂多阴离子对石英的细胞毒性有明显的拮抗作用。     

地衣芽胞杆菌对肠道致病菌的体内拮抗作用研究

目的:探讨地衣芽胞杆菌C01在模型小鼠体内对大肠杆菌、沙门氏菌抑制作用以及对乳杆菌等有益菌的促进作用。方法:用地衣芽胞杆菌C01灌胃肠道感染模型小鼠,采用体外活菌培养,分析粪便菌群数量的变化。结果:C01灌胃治疗组(EPEC C01)中乳杆菌的数量显著高于EPEC灌胃模型组(EPEC N)(P<0.01),肠杆菌数量下降极显著(P<0.01),而(EPEC N)组肠杆菌数显著高于正常对照组(NS)(P<0.05);肠炎沙门氏菌处理后C01灌胃治疗组(SL C01)和处理后肠炎沙门氏模型组(SL N)比较,乳杆菌、肠球菌和总厌氧菌的变化不明显,但肠杆菌数量下降极显著(P<0.01);形态病理学观察结果显示,C01芽胞杆菌灌胃治疗组肠粘膜病变明显减轻,肠粘膜及绒毛高度明显增加,绒毛轻度水肿,绒毛排列整齐、致密。结论:地衣芽胞杆菌C01在体内对肠炎沙门氏菌和致病性大肠杆菌有较强的抑制作用,能促进乳杆菌等生理性有益菌的增殖,可保护肠粘膜结构的完整性免受病原菌的侵袭。     

In-vitro interaction of azithromycin and fluoroquinolones against gram-positive and gram-negative bacteria

Objective: To determine the combined in-vitro effects of azithromycin plus the fluoroquinolone ofloxacin or lomefloxacin against gram-positive and gram-negative bacteria.
Methods: Fractional inhibitory (FIC) and fractional bactericidal concentration indices of azithromycin and the fluoroquinolone were determined using a microtiter-checkerboard method. Clinical isolates of Staphylococcus aureus, Streptococcus pneumoniae, Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Pseudomonas cepacia, Haemophilus influenzae, Xanthomonas maltophilia and Acinetobacter calcoaceticus were studied. Fourteen strains of S. aureus were also studied in time-kill curves with azithromycin (4 mg/L), lomefloxacin (6 mg/L) and the two in combination.
Results: No synergism or antagonism was found in inhibitory assays. However, bactericidal assays revealed antagonism with some strains of S. aureus, S. pneumoniae, X. maltophilia, A. calcoaceticus, P. aeruginosa, P. cepacia, K. pneumoniae and E. coli. Kill-curve results with 14 strains of S. aureus showed no antagonism with four strains of methicillin-resistant S. aureus (MRSA), and antagonism with one strain of MRSA and seven methicillin-susceptible S. aureus (MSSA).
Conclusions: In-vitro exposure to combinations of azithromycin and a fluoroquinolone does not produce a synergistic effect. Antagonism was found in bactericidal assays against some gram-negative bacteria and MSSA; caution is therefore recommended in the use of macrolides and quinolones against these organisms.     

Ketanserin causes surmountable antagonism of 5-hydroxytryptamine-induced contractions of large coronary arteries of dog

Summary Large coronary arteries of the dog were contracted with 5-hydroxytryptamine (5-HT). The 5-HT₂-receptor antagonist ketanserin antagonized the 5-HT-induced effects. Unlike Brazenor and Angus (Europ J Pharmacol 81: 569–576, 1982), who reported insurmountable antagonism of the effects of 5-HT in dog coronaries, we found that the antagonism by ketanserin can be surmounted, provided the concentrations of 5-HT are high enough. Ketanserin also unmasked a saturable component of the 5-HT-induced contractions. Although ketanserin (0.1–1 mol/l) depressed the maximal force of the saturable component, it did not change its EC₅₀ (-log mol/l 8.0). We conclude that large coronary arteries of dog are contracted by 5-HT mainly though 5-HT₂-receptors and to a smaller extent through receptors different from 5-HT₂.     

叶酸拮抗乙酰水杨酸致大鼠卵黄囊毒性作用的研究

以全胚胎培养模型结合免疫组化和电镜技术等探讨了乙酰水杨酸和叶酸对大鼠卵黄囊及胚胎的影响。结果表明：培养基含乙酰水杨酸３００μｇ／ｍｌ组的卵黄囊直径和胚胎体长均显著低于阴性对照组,胚胎畸形率明显增高。组织学检查发现卵黄囊厚度变薄。间质层血岛、微血管数量明显减少,血管壁细胞不连续,血管发育不良。卵黄囊内皮层细胞顶端微绒毛少见。内皮层细胞的溶酶体、内质网及核蛋白体等结构和数量均有明显改变。而６０ｍｇ／ｋｇ叶酸灌胃鼠血清与乙酰水杨酸联合应用后,则卵黄囊的上述毒性作用明显减轻或消失,提示叶酸能明显拮抗乙酰水杨酸致大鼠卵黄囊的毒性作用。     

β-Adrenoceptor blocking agents as partial agonists in isolated heart muscle: Dissociation of stimulation and blockade

Summary The cardiac stimulant actions of nine -adrenoceptor blocking agents were examined in kitten papillary muscles and in isolated atria of kittens and guinea pigs to determine to what extent these drugs behaved as classical partial agonists. In many ways the agents do appear to comprise a spectrum of partial agonists with widely differing efficacies. However, in one respect the actions of some of the -blockers did not fit into the classical mold. Several -blockers were found to exert stimulant effects only in concentrations appreciably higher than those required for substantial -adrenoceptor blockade. These observations suggest that more than one type of -adrenoceptor may be involved in the production of sympathomimetic effects on cardiac muscle.     

盐酸丙哌维林对豚鼠离体膀胱平滑肌条的钙拮抗作用

目的　研究盐酸丙哌维林 (P 4)对豚鼠离体膀胱平滑肌条的钙拮抗作用及作用机制。方法　采用离体平滑肌条浴槽实验方法 ,以维拉帕米为对照 ,测定P 4对CaCl2 和组胺 (His)所致离体膀胱平滑肌条的收缩及对乙酰胆碱 (ACh)所致膀胱平滑肌依赖细胞内钙、外钙收缩的影响。结果　P 41～ 1 0 0 μmol·L- 1 使CaCl2 累积量效曲线非平行右移 ,最大反应降低 ,pD2 ′为 4 73± 0 1 4。P 41 μmol·L- 1 使His量效曲线平行右移 ,最大效应不变 ,pA2 为 5 44± 0 1 4 ;1 0～ 1 0 0μmol·L- 1 使His量效曲线非平行右移 ,最大效应降低 ,pD2 ′为 4 71± 0 1 0。P 41、1 0和 1 0 0 μmol·L- 1 对ACh所致依赖细胞内钙收缩的抑制率分别为 45 77%± 6 54 %、86 2 6 %± 5 59%和 90 55 %± 3 1 1 % ,对依赖细胞外钙收缩的抑制率分别为 7 30 %± 2 89%、49 1 6 %± 6 0 9%和 88 2 5 %±3 70 %。结论　P 4低浓度时竞争性拮抗His所致膀胱平滑肌条的收缩反应 ,明显抑制膀胱平滑肌条依赖细胞内钙释放的收缩反应 ;高浓度时非竞争性拮抗His和CaCl2 所致膀胱平滑肌条的收缩反应 ,明显抑制膀胱平滑肌条依赖细胞内钙释放和外钙经钙通道内流所致收缩反应     

Opposite effects of glutamate antagonists and antiparkinsonian drugs on the activities of DOPA decarboxylase and 5-HTP decarboxylase in the rat brain

This study measured the activities of L-DOPA and 5-HTP decarboxylase (DDC and 5-HTPDC) in the substantia nigra and corpus striatum of reserpine-treated rats. Acute injection of the NMDA receptor antagonists CGP 40116 (5 mg/kg) and HA 966 (5 mg/kg), and to a lesser extent eliprodil (10 mg/kg), greatly elevated DDC in both structures, whilst having no effect on (nigra) or inhibiting (striatum) 5-HTPDC. L-DOPA (25 mg/kg) on its own inhibited both enzymes in either brain region. The weak NMDA receptor-channel blockers (and antiparkinsonian drugs) budipine (10 mg/kg), memantine (40 mg/kg) and amantadine (40 mg/kg) strongly increased DDC, whilst not affecting or decreasing 5-HTPDC activity in nigra and striatum. The L-DOPA-induced suppression of DDC was mostly reversed by all three antiparkinsonian drugs, whilst L-DOPA-induced inhibition of 5-HTPDC was only reversed by CGP 40116 (striatum only). It is concluded that glutamate exerts a differential physiological influence on the biosynthesis of dopamine and 5-HT in the brain, by tonically suppressing DDC and tonically stimulating 5-HTPDC. The L-DOPA-induced reduction in DDC may help to explain the eventual loss of efficacy of L-DOPA therapy in parkinsonian patients. It is suggested, however, that it may be possible to extend the lifetime of L-DOPA therapy with drugs which potentiate the activity of DDC, such as budipine and the 1-aminoadamantanes.     

锂的神经元保护作用及对铅神经毒性的拮抗效应

目的　探讨铅的神经毒性、锂的神经元保护作用以及锂对铅神经毒性的拮抗效应 ,研究不同浓度氯化锂和醋酸铅对原代培养皮层神经元生长及存活的影响。方法　建立新生大鼠皮层神经元原代培养技术 ,通过加入不同浓度氯化锂、醋酸铅及同时加入 5mmol L的氯化锂和不同浓度醋酸铅 ,显微镜下观察神经细胞的生长和存活情况 ,目镜测量神经元突起长度 ,噻唑蓝 (MTT)还原法检测细胞生长活力。结果　各浓度氯化锂均可促进神经元突起生长 (P <0 0 5 ) ,1 2 5mmol L以上浓度的氯化锂可使神经元生长活力降低 (P <0 0 5 ) ;醋酸铅 (≥ 10 - 7mol L)能抑制神经元生长 ,其神经元突起长度明显短于对照组 (P <0 0 1) ,各浓度的醋酸铅均可使神经元生长活力降低 (P <0 0 1) ;5mmol L浓度的锂对染铅神经元有明显的保护作用和促生长作用 ,表现为铅浓度为 10 - 6 mol L与 10 - 5mmol L组的神经元突起长度较单纯染铅组长 (P <0 0 1) ,使铅浓度为10 - 8～ 10 - 5mol L的神经元生长活力提高 (P <0 0 1)。结论　锂有神经元保护作用 ,而铅对神经元表现出毒性效应 ;锂对染铅神经元有一定的保护作用