The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors

Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.     

基于受体结构的药物分子设计系统:维甲类分子与其结合蛋白之间相互作用的研究

大分子解剖程序,配体分子契合适配和DOCK程序,以及计算化学的其它程序等,已集成为基于受体结构和分子间相互作用的进行分子设计的软件系统,定名为BIOS(Biomolecularinteractionsandorientationsimulator)。BIOS软件可在普通的微机上运行。使用BIOS分别剥离了细胞浆维甲结合蛋白(CRBP)和副睾维甲酸结合蛋白(E-RABP)两种蛋白的配体结合腔,剥离是围绕配体以同样的分子距离进行的。从而得到了芳香性残基分布相似的两个结合腔,其结合位点的几何排布却有相当差别。揭示出的结合腔已用于一系列的维甲类化合物的DOCK研究。E-RABP的结合腔可做为设计新维甲类分子的模板。     

Photic driving in migraine: correlations with clinical features

Fifty-eight migraineurs were. studied by intermediate frequency steady-state visual evoked potentials (SSVEPs) during headache-free periods. Sex, age, age of onset of migraine, duration of illness, type of migraine, side of pain, sleep .wake disorders, and frequency of migraine attacks did not correlate with any SSVEP abnormalities. On the other hand, visual responsiveness was significantly increased in subjects with family history of migraine, and in those with autonomic symptoms. Our results may indicate that a genetic predisposition to migraine underlies the observed abnormal visual response in migraineurs.     

Bupivacaine, 0.125 per cent, in obstetric epidural analgesia: experience in three thousand cases.

Bupivacaine, 0.125 per cent, with epinephrine, 1:800,000, was administered to 3,000 women in labor. Administration was in the lumbar epidural space for the purpose of achieving satisfactory analgesia with minimal or no motor paralysis. The usual initial dose of 12.5 mg (mean 13 +/- 2 SD) resulted in good sensory analgesia in 83 per cent of the patients and lasted for about and hour (mean 58 +/- 16 min). The mean total dose used for labor and delivery was 55 +/- 20 mg and the mean dose per hour 23 +/- 13 mg. Satisfactory analgesia for labor and delivery was obtained in 92 per cent of the patients, and in 66 per cent there was no discernible motor blockade. In the 3,000 patients, there was no adverse reaction to bupivacaine or epinephrine. No patient had a total spinal block or neurologic sequelae, and no neonatal depression could be attributed to the anesthetic.     

Levobupivacaine-sufentanil with or without epinephrine during epidural labor analgesia

In a prospective, randomized, double-blind study, we investigated whether epinephrine increased the efficacy of levobupivacaine and sufentanil during epidural labor analgesia. Seventy term parturients received an epidural injection of levobupivacaine 0.125% and sufentanil 0.75 microg/mL with or without 1:800,000 epinephrine. After an initial dose of 10 mL, a patient-controlled analgesia pump was started. Total and hourly drug consumption, pain scores using the visual analog scale, sensory and motor block, duration of labor, vital variables, maternal and neonatal outcome, and side effects were compared. If the parturients experienced insufficient pain relief during the study, even after a rescue dose of 10 mL, they were excluded from further study and received 10 mL of bupivacaine 0.125% and sufentanil 0.75 microg/mL with 1:800,000 epinephrine. Hourly drug consumption, rescue dosing, and pain scores at 15 min and 20 min were lower in the epinephrine group. The incidence of motor block and duration of the second stage of labor tended to be higher in the epinephrine group and were associated with lower Apgar scores at 1 and 5 min. These findings suggest that the addition of epinephrine intensifies the effects of epidural levobupivacaine and sufentanil but may cause more motor block.     

5种解热镇痛药的胶束电动毛细管色谱分离研究

报告了5种解热镇痛药——安替比林、4-氨基安替比林、安基比林、安乃近和保泰松的胶束电动毛细管色谱分离、紫外吸收检测法。研究了pH值、有机改性剂(甲醇)和十二烷基硫酸钠(SDS)浓度对分离的影响。在40mmol·L^-1SDS—25mmol·L^-1硼砂—15%甲醇(pH10.5)电泳介质中电泳,上述5组分可达基线分离。迁移时间批内和批间的RSD值分别小于1.3%和2.1%(n=5)。分离的理论塔板数在1.83×10⁴～4.15×10⁴之间。