EGF加强大鼠胃壁细胞的泌酸活动

以氨基比林聚集为间接的泌酸指标，本实验观察了急性分离的大鼠胃粘膜壁细胞对ＥＧＦ的反应。结果表明：１．急性分离后３０分钟左右，壁细胞对较大剂量的ＥＧＦ（１００ｎＭ）的反应为胃酸分泌的减少；２．急性分离后６０分钟左右，壁细胞对ＥＧＦ（０．１－１００ｎＭ）的反应为泌酸活动的加强。结果提示壁细胞被分离后经历一功能恢复的过程，ＥＧＦ对壁细胞的生理作用可能是加强其泌酸活动。     

New method for quantitative measurement of N-nitrosodimethylamine formation in the whole mouse

A simple method for the quantitative estimation of the formation of N-nitrosodimethylamine (NDMA) in mice has been developed. Mice were frozen in liquid nitrogen and homogenized. NDMA was then extracted and analyzed by a gas chromatograph equipped with a thermal energy analyzer. In normal mice NDMA (100 nmole) administered orally was rapidly metabolized and recovery of NDMA was about 10% after 60 min. However, when pyrazole (300 mg/kg) was injected i.p. to mice 60 min before the administration of NDMA, more than 80% of the administered NDMA could be recovered within 60 min. This result suggested that in pyrazole pretreated mice the accurate amount of NDMA formed could be estimated. Therefore the NDMA formation was measured in the pyrazole pretreated mice. When 0.25 mole of aminopyrine and from 0.25 to 2.0 umole of sodium nitrite were simultaneously administered orally, the amount of the NDMA formation in 20 min was found to be from 8.2 to 60.3 nmole. These values are equal to about from 30 to 200 g/kg of body weight which are nearly daily doses expected to cause the carcinogenic effect on mice or rats. This method of measuring NDMA in pyrazole pretreated mice appears to be useful for investigating the in vivo formation of NDMA quantitatively.     

Adrenergic stimulation of isolated rat gastric mucosal cells

Summary Adrenergic stimulation of the adenylate cyclase (AC)-cAMP-system and ¹⁴C-aminopyrine accumulation, an indirect measure of parietal cell H⁺-production, was studied in different preparations of gastric mucosal cells.The ₂-adrenoceptor agonist hexoprenaline activated AC of crude homogenates from the gastric corpus of mouse, rat, guinea-pig, hog, dog and man. In isolated rat gastric cells (20% parietal cells), treated by low power sonication, 10^–8 to 10^–3 mol/l adrenaline and hexoprenaline activated AC equally potently and efficaciously by maximally 170%. Isoprenaline proved to be less effective activating up to 80%. 5·10^–5 mol/l GMP-PNP augmented basal activity 8.5 times and reduced the maximal efficacy. Adrenaline and hexoprenaline activated AC by maximally 120%, isoprenaline by 40%. The potency of adrenaline was 4 times lower, that of hexoprenaline 2 and that of isoprenaline 4 times higher in the presence of GMP-PNP. Adrenergic stimulation was inhibited by the -adrenoceptor antagonist propranolol, the effect of -adrenoceptor-blockade by phenoxybenzamine was less pronounced. In fractions with 7–80% of parietal cells, prepared by isopycnic centrifugation with Percoll, adrenaline and hexoprenaline activated AC or hexoprenaline enhanced the cellular level of cAMP in parietal cell poor and rich fractions. The degree of activation in response to histamine correlated with the number of parietal cells. ¹⁴C-Aminopyrine uptake was increasingly stimulated through 10^–8 to 10^–5 mol/l hexoprenaline, maximally by doubling the basal accumulation. 10^–4 mol/l histamine was 8 times more effective. 3·10^–7 mol/l propranolol inhibited the effect of 10^–5 mol/l hexoprenaline by 80%.The data suggest the localization of -adrenoceptors (likely -adrenoceptor) on parietal and other nonidentified gastric cells. At the parietal cell, adrenaline and hexoprenaline initiate activation of AC and hexoprenaline leads to H⁺-production. The responses are small compared to the effect of histamine. Thus, -adrenoceptor agonists exert intrinsic activity in relation to H⁺-production. Their influence on stimulated secretion of isolated cells remains to be elucidated.     

In vitro ex vivo assessment of Morinda citrifolia on drug metabolizing enzymes in spontaneously hypertensive rats

Morinda citrifolia Linn. (Rubiaceae), common name noni, has been used as a herbal medicine for over 2000 years. The consumption of noni, and especially the fruit, stresses the importance, urgency, and possibility of the examination of drug interaction when concomitantly administered with a drug. The objectives of this study were to determine the effects of noni juice (NJ) on aminopyrine N-demethylase (APND), uridine diphosphoglucuronosyl-transferase (UGT), and cytosolic glutathione S-transferase (GST) drug metabolizing enzymes and the molecular mechanism elucidation of NJ on APND using different inhibitors and stimulators. The in vitro results for APND showed that different concentrations of NJ significantly increased the activity in isolated hepatocytes at 1.0?ng/mL, 10?ng/mL, 10?μg/mL, 20?μg/mL, 50?μg/mL, and 100?μg/mL. The ex vivo results demonstrated that NJ (210?mg/kg) produced a statistically significant increase in APND activity following 1 day of NJ treatment. The results for UGT and GST showed a decrease in the activity of UGT at a dose of 21?mg/kg following 1 day of treatment, and at 2.1 and 21?mg/kg following 14 days of treatment. GST enzyme demonstrated an increase in activity by 100% for all doses following 1 day of treatment. Molecular mechanism elucidation of the ex vivo effect of NJ on phase I APND showed that KT5720 significantly reduced the activity as compared to control. A change in activity of APND, UGT, and GST following 1 day and 14 days of treatment suggests that all three metabolic pathways may play a role in herb–drug interaction by modulation of metabolic enzymes.     

Central monoamines and antinociceptive drug action

Experiments were perfomed in rats to elucidate the role of central 5-HT and catecholamines in the mediation of the antinociceptive effects of d-amphetamine, d-p-chloroamphetamine, morphine and aminopyrine. The method of Randall and Selitto (1957) was used for determining the antinociceptive effect.     

水溶性弱碱性药物的线性滴定

前文已谈及水溶性弱酸性药物的线性法测定。迄今为止所发表的各种文献中只涉及到用碱滴定各种弱酸性物质,对弱碱性物质的应用尚未见报道。本文对用盐酸滴定各种弱碱性药物作了尝试,获得了较好结果。     

HPLC法测定复方金刚烷胺氨基比林片中氨基比林的溶出度

目的建立一种用高效液相色谱法测定复方金刚烷胺氨基比林片中氨基比林溶出度的方法。方法以水为溶出介质,转速为100 r.min-1,30 min时取样。选用色谱柱SunfireC18(250 mm×4.6 mm,5μm);流动相为甲醇-水(56:44);检测波长:273 nm;流速:1.0 mL/min。结果氨基比林在11.9～71.47μg/mL浓度范围内与峰面积呈良好的线性关系(r=0.9999)。平均回收率为99.05%。结论本方法简单、快速、结果准确可靠。     

氨基比林原料药含量测定方法的研究

氨基比林属吡唑酮类解热镇痛药,其通过选择性的抑制下丘脑前部前列腺合成酶,减少前列腺素的生物合成,使体温恢复正常,而实现疗效.目前现行法定标准是用容量分析法来测定氨基比林的含量,但该法终点无明显突跃,难以准确判断.本实验通过紫外分光光度法直接测定氨基比林原料药中氨基比林的含量,其操作简便、快速、可行,通过对两种方法的简单比较说明紫外分光光度法测得的结果准确度较高.     

双波长一元线性回归分光光度法同时测定复方氨基比林注射液中三组分含量

本文依据一组含有不同比例待测和干扰组分的标准混合液的吸收值,采用一元线性回归方法,在选择最佳测定波长对的同时建立标准工作曲线方程,使其更符合实际作品测定时的情况,提高了结果的精度和可靠性,并使计算量和实验工作量得以降低。应用于复方氨基比林注射液中三组分氨基比林、安替比林和巴比妥的同时测定,其平均回收率分别为99.8%,100.4%和99.8%,变异系数分别为0.59,1.48和1.05,结果优于卡尔曼滤波法、偏最小二乘法和目标因子分析法。     

Ursodeoxycholate has no beneficial effect on liver function or histology in biliary cirrhosis in the rat

In different cholestatic conditions, the beneficial effects of the tertiary bile acid, ursodeoxycholate, have been described. It is unclear, however, whether ursodeoxycholate also affects the functional and structural alterations induced by chronic biliary obstruction. Therefore, we studied the effect of ursodeoxycholate (100 mg/kg/day) on microsomal function as assessed in vivo by the aminopyrine breath test, on portal hypertension and on the structural composition of the liver in rats with chronic (3-week) biliary obstruction. Hepatic composition was assessed stereologically. Ursodeoxycholate had no effect on any of the parameters measured. We conclude that this form of treatment does not affect advanced liver disease due to common bile duct obstruction. This finding supports one of the proposed mechanisms of action of ursodeoxycholate, namely that it interferes with the ileal absorption of more toxic endogenous bile salts.