Memory Deficits in Aged Cebus Monkeys and Facilitation With Central Cholinomimetics

Cebus monkeys of 3 different age groups were trained to perform an automated behavioral task (delayed response), intended to measure recent memory ability. In in initial study, the aged monkeys (18 years and older) exhibit prprogressively greater performance impairments (relative to young monkeys) as they were required to remember the location of a visual stimulus for increasingly longer durations (0 to 20 sec). This deficits replicated previously published results from aged Rhesus monkeys and appeared similar to the primary memory deficits reported in elderly humans and demented patients. In subsequent studies, the effects of three different cholinomimetics were evaluated for their ability to improve the aged monkey's performance on this task. Each monkey was tested under several acute doses of the cholinergic precursor, choline, the anticholinesterase, physostigmine, and the cholinergic muscarinic receptor agonist, arecoline. The results revealed clear differences in the ability of these drugs to improve performance on this task. Choline exerted no apparent effects in the aged monkeys at any dose tested. Physostigmine clearly enhanced performance in certain aged monkeys, but the optimal dose varied dramatically between subjects, replicating previously published results with aged Rhesus monkeys and humans. Arecoline produced clear improvement within a restricted dose range, with little variation in optimal dose between subjects. In addition to demonstrating differences in the effects of different cholinomimetics on memory performance in aged primates, these data also suggest a possible rationale for future investigations. Assuming that each of these drugs primarily affected cholinergic function in the manner conventionally attributed, these data suggest that, within the cholinergic system, the more directly one stimulates the receptor, the more one might expect robust and consistent effects on memory performance in aged subjects.     

高效液相色谱法测定氢溴酸樟柳碱含量

目的：建立了高效液相色谱法测定氢溴酸樟柳碱的含量。方法：采用ＯＤＳ柱,以０．２％十二烷基硫酸钠的甲醇－０．０１ｍｏｌ．Ｌ^-1磷酸二拚钾（用磷酸调节ｐＨ为３．５（ ６０：４０）为流动相,对羟基苯甲酸丁酯为内标物,用紫外检测器于２１０ｎｍ波长处检测。结果：氢溴酸樟柳碱进样量在０．５～３μｇ范围内有良好线笥关系（ｒ＝０．９９９９）。平均回收率为９９．５％,ＲＳＤ为２．６％（ｎ＝３）。最低检出量为０．００６     

Noradrenergic influences on catalepsy

Widespread depletion of forebrain noradrenaline, produced by the intracerebral injection of 4 g of 6-hydroxydopamine into the fibres of the dorsal noradrenergic bundle, potentiated the catalepsy induced by 20 mg/kg of morphine and severely attenuated the catalepsy induced by two separate cholinergic agonists, arecoline and pilocarpine. It did not, however, affect haloperidol catalepsy at any of the four doses tested. These results suggest that cholinergic catalepsy may be critically dependent on an intact noradrenergic substrate, perhaps through cholinergic receptors located either presynaptically on noradrenergic terminals or on the cell bodies of origin in the locus coeruleus. Noradrenaline appears to play a modulatory role in morphine catalepsy, although other sites of action must also be involved. Ascending noradrenergic systems do not appear to influence haloperidol catalepsy.     

HPLC法测定氢溴酸加兰他敏分散片的含量

目的 :建立氢溴酸加兰他敏及其分散片的HPLC分析方法。方法 :采用ODS色谱柱 (15 0mm× 4 .6mm ,5 μm) ,以甲醇 水 冰醋酸 (75∶92 5∶10 )为流动相 ;流速 :1.0ml·min-1,检测波长 :2 89nm ;采用外标法测定氢溴酸加兰他敏分散片的含量。结果 :氢溴酸加兰他敏在 10～ 10 0 μg·ml-1范围内 ,线性关系良好 (r =0 .9998) ;平均回收率为 10 0 .2 % ;日内精密度(RSD =0 .6 % ,n =5 )良好。结论 :本法适用于氢溴酸加兰他敏及其分散片的含量测定 ,方法简便、准确、快速。     

高效液相色谱法测定美息伪麻拉明分散片中组分含量的研究

目的:采用高效液相色谱法考察并建立了测定复方制剂美息伪麻拉明分散片中对乙酰氨基酚(Par)、氢溴酸右美沙芬(Dex)、盐酸苯海拉明(Dip)和盐酸伪麻黄碱(Pse)的含量。方法:色谱柱为Diamonsil-C_(18)(200mm×4.6mm,5μm),测定Par用乙腈-甲醇-0.05mol·L~(-1)磷酸二氢钾溶液(5:1:25)为流动相,检测波长为245nm,测定Dex、Dip和Pse用pH3.3甲酸钠缓冲液-乙腈-甲醇-十二烷基硫酸钠(32:28:5:0.06=V:V:V:W)为流动相,检测波长为256nm。结果:Par、Dex、Pse、Dip浓度在2.06～20.60μg·mL~(-1),0.11～1.06,0.20～2.02,0.10～1.01mg·mL~(-1)范围内与峰面积呈良好的线性关系,r分别为0.999 7,0.999 4,0.999 5,0.999 7。平均回收率依次为100.2％,99.28％,100.6％,100.7％。结论:本法精密度好,结果准确可靠。适用于该复方制剂的质量检验分析。     

氢溴酸高乌甲素大鼠在体胃肠的吸收动力学研究

 目的：考察氢溴酸高乌甲素(LH)在大鼠胃肠道的吸收动力学特征及促进剂对其的吸收促进效果。方法：采用大鼠在体胃肠吸收实验模型,用HPLC法测定循环液中药物的浓度。结果：LH在胃、十二指肠、空肠、回肠、结肠的吸收百分率分别为9.67%,19.61%,11.83%,12.95%,9.51%;不同质量浓度的LH(10～40 mg?L-1)与小肠吸收量呈线性关系,吸收速率常数Ka几乎不变。P-糖蛋白抑制剂维拉帕米可增加药物从小肠的吸收。促进剂对药物在小肠内的吸收促进效果均比较明显,癸酸钠吸收促进效果最好。组织病理学观察结果显示,癸酸钠对小肠黏膜造成的损伤最小。结论：药物在整个胃肠道中的吸收均比较有限,在小肠中的吸收呈一级动力学过程,吸收机制有可能为被动扩散;吸收促进剂癸酸钠吸收促进效果最好,且毒性最小,有望作为药用辅料用于口服制剂中提高LH的生物利用度。     

Interacting with α7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages

Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.     

复方樟柳碱对早期糖尿病视网膜病变多焦视网膜电图的影响

目的：观察复方樟柳碱穴位注射对早期DR的多焦视网膜电图(mfERG)一阶Kernel反应的改变。

方法：连续选取Ⅰ～Ⅱ期糖尿病视网膜病变患者48例48眼,分为对照组和注射组,其中对照组采用控制血糖药物治疗,注射组除采用药物控制血糖外接受复方樟柳碱穴位注射。治疗后行多焦电生理检查,分析参数为mfERG产生的4个象限、6环以及总和反应的波形,对总和反应平均密度、P1和N1的潜伏期与振幅结果进行统计学分析。

结果：注药组和对照组P1波的总和反应平均密度为39.42±6.46、28.50±3.73nV/deg²,N1波为11.12±1.34、6.33±1.14nV/deg²。注药组P1波和N1波总和反应平均密度均高于对照组(P1：t=6.230,P<0.01; N1：t=3.526,P<0.01)。注药组SN、IN、IT和ST象限P1反应波平均密度分别为32.61±9.62、32.31±7.94、29.24±7.84、28.09±5.38nV/deg²,均高于对照组(P<0.05),各象限两组N1反应波平均密度比较均无明显差异。注药组R1～R6 P1、R1～R3 N1反应波平均密度分别为98.11±17.53、73.95±17.20、64.09±14.13、49.43±10.08、40.24±11.55、36.86±6.43、25.27±12.81、21.31±6.76、14.86±5.06nV/deg²,均高于对照组(P<0.05),两组R4～R6 N1反应波平均密度比较无明显差异。注药组IT和ST中P1和N1波幅值1.37±0.35、1.28±0.29、0.31±0.05和0.30±0.10μV,明显高于对照组(P<0.05),两组SN和IN中P1和N1波幅值差异无统计学意义。

结论：复方樟柳碱穴位注射可以改善早期DR部分视网膜功能损伤。     

Differential roles of hypothalamic serotonin receptor subtypes in the regulation of prolactin secretion in the turkey hen

In the turkey, exogenous serotonin (5-hydroxytryptamine, 5-HT) increases prolactin (PRL) secretion by acting through the dopaminergic (DAergic) system. In the present study, infusion of the 5-HT_2C receptor agonist, (R)(−)-DOI hydrochloride (DOI), into the third ventricle stimulates PRL secretion, whereas the 5-HT_1A receptor agonist, (+/−)-8-OH-DPAT hydrobromide (DPAT), inhibits PRL secretion. Using the immediate-early gene, c-fos, as an indicator of neuronal activity, in situ hybridization histochemistry showed preferential c-fos co-localization within tyrosine hydroxylase immunoreactive neurons (the rate limiting enzyme in DA synthesis) in the areas of the nucleus preopticus medialis (POM) and the nucleus premammillaris (PMM), in response to DPAT and DOI, respectively. To clarify the involvement of 5-HT_1A and 5-HT_2C receptors in PRL regulation, their mRNA expression was determined on hypothalamic tissue sections from birds in different reproductive stages. A significant difference in 5-HT_1A receptor was observed, with the POM of hypoprolactinemic short day and photorefractory birds showing the highest expression. 5-HT_2C receptors mRNA did not change during the reproductive cycle. The data presented support the notion that DA neurons in the PMM and POM mediate the stimulatory and inhibitory effects of 5-HT, respectively, on PRL secretion and the 5-HTergic system can both stimulate and inhibit PRL secretion.     

气相色谱法测定氢溴酸替格列汀中溴乙烷残留量

目的 建立氢溴酸替格列汀中遗传毒性杂质溴乙烷残留量的气相色谱（GC）检测方法。方法 采用迪马DM-624色谱柱（30 m×0.53 mm×3.0 μm）;电子捕获检测器（ECD）;程序升温：初始柱温40 ℃,保持3 min,以20 ℃/min升温至200 ℃,保持5 min;进样口温度：210 ℃;检测器温度：210 ℃;载气：氮气;分流比：3：1;进样量1 μL。结果 溴乙烷在0.75～6.75 μg/mL与峰面积呈良好的线性关系（r=0.999 7）,最低检测限为0.26 μg/mL。平均回收率为99.4%,RSD值为0.3%（n=9）。3批氢溴酸替格列汀样品中均未检测出溴乙烷。结论 该方法简便、准确,重复性好,适用于氢溴酸替格列汀中溴乙烷残留量的控制。