我院门诊和老年患者抗生素处方的调查分析

目的:了解门诊患者(包括老年患者)抗生素应用情况,并对其合理性进行分析。方法:回顾性调查一家综合性医院门诊患者抗生素使用情况。结果:4 313张门诊处方中含抗生素的比例为39.8%,其中单用抗生素的占57.8%,两药联用占35.3%,三药联用占6.35%,四药联合用占0.52%。老年患者中含抗生素处方比例为41.4%;其中含抗生素处方中单用率为72.5%,二联用药率为26.7%,三联用药率为0.8%,尚无四联使用情况。常用抗生素类药物有氟喹诺酮类、头孢菌素类、大环内酯类等。结论:该院老年患者抗生素选用基本合理。     

骨松灵对骨质疏松症的药效学研究

目的：以大鼠和小鼠观察骨松灵治疗骨质疏松症的药效。方法：采用小鼠扭体及耳廊肿胀,大鼠内芽肿,小鼠免疫器官及性器官增重,大鼠骨结构及钙磷含量测定等实验方法。结果：骨松灵能明显抑制小鼠耳廊肿胀及大鼠内芽组织增生;减少小鼠扭体次数;增加小鼠免疫器官的重量。减轻雌、雄性小鼠性器官的萎缩及重量减轻程度,能明显阻止髓腔面积增大及小梁骨面积减小;增加动物骨钙含量。结论：骨松灵具明确的抗炎止痛作用,能减轻性器官的萎缩程度;提高机体免疫力;通过调节钙磷代谢,保持骨矿含量,改善骨质疏松的骨结构,起到治疗骨质疏松的作用。     

抗抑郁药物对慢性应激抑郁模型大鼠海马胱天蛋白酶-9表达的影响

目的研究氟西汀与噻萘普汀对慢性应激抑郁模型大鼠海马胱天蛋白酶-9(Caspase-9)表达的影响。方法将大鼠随机分为抑郁模型组、氟西汀组、噻萘普汀组和对照组。模型组、氟西汀组和噻萘普汀组给予21d的应激刺激,此期间对照组正常饲养,刺激期间氟西汀组每天灌胃氟西汀(10mg/kg),噻萘普汀组每天灌胃噻萘普汀(50mg/kg),模型组和对照组每天灌胃等体积的生理盐水。行为学检测应用开场法和液体消耗实验。采用Western blot法检测各组大鼠海马Caspase-9的表达情况。结果模型组水平穿越格数、竖立次数、修饰次数、糖水消耗百分比均显著低于对照组(P<0.01)。氟西汀组水平穿越格数、竖立次数、修饰次数和糖水消耗百分比均高于模型组(P<0.05)。噻萘普汀组糖水消耗百分比高于模型组(P<0.05),水平穿越格数、竖立次数和修饰次数也高于模型组,但差异无统计学意义。慢性应激后模型组大鼠海马Caspase-9的表达水平显著高于对照组(P<0.01);氟西汀组大鼠海马Caspase-9的表达水平低于模型组(P<0.01),高于对照组(P<0.05);噻萘普汀组大鼠海马Caspase-9的表达水平低于模型组(P<0.01),高于对照组(P<0.01)。结论氟西汀和噻萘普汀2种抗抑郁药物均可以逆转慢性应激抑郁模型大鼠海马中Caspase-9表达的升高。     

某专科医院护理人员循证护理认知现状调查及对策

目的了解护理人员对循证护理（EBN）的认知现状，提出相应对策。方法采用自行设计的问卷对某专科医院当班护理人员进行EBN认知状况的调查。结果6．76％的护理人员熟悉EBN知识．21．71％的护理人员对EBN知识有所了解，43．06％的护理人员听说过EBN，28．47％的护理人员从未听说过。54．09％和38．79％的护理人员认为有机会可了解和希望了解EBN的相关知识。仅有8．54％的护理人员经常关注EBN。获得EBN知识的来源：医学讲座占56．94％、医学杂志占58．01％、网络信息占69．40％、高年资护士占46．26％。对EBN信息资源了解：29．18％的护理人员不知道，46．28％的护理人员听说过，21．00％的护理人员有所了解，仅有3．56％的护理人员熟悉。循证技能上，护理人员遇到临床护理问题的解决方法：45．20％的护理人员采用EBN的科学证据、57．65％的护理人员采取查阅文献、32．38％的护理人员凭个人经验解决、61．57％的护理人员采取向高年资护士请教。结论护理教育工作者应改革课程体系，重视、完善护生EBN的基础知识及EBN技能培养。医院应对临床护士给予行政支持，领导要重视EBN，确保EBN的实施。     

Non-reducible cyclic, and azaphenylalanyl6 analogues of somatostatin

SSeven new analogues of somatostatin are described, along with the effects of these analogues on pentagastrin-stimulated gastric acid and pepsin secretion in conscious cats. Replacement of the cystine disulphide bridge of somatostatin with an amide bridge, with or without deletion of the N-terminal dipeptide, resulted in analogues with approximately 20% of the potency of somatostatin. Simultaneous ommision of Lys4 in the amide-bridge analogues reduced the activity of the peptides to approximately 5% of somatostatin. Substitution of Phe6 of somatostatin or an amide-bridged analogue with azaphenylalanyl resulted in peptides with no detectable activity. The results illustrate the possible importance of the basic side-chain of Lys4 for the activity of somatostatin. The lack of activity of azaphenylalanyl6 analogues of somatostatin demonstrate the extreme importance of the orientation of the side-chain of Phe6 for the activity of somatostatin, possibly for the binding to somatostatin receptors.     

Effects of acute and chronic administration of fluoxetine on the activity of serotonergic neurons in the dorsal raphe nucleus of the rat

The gradual recovery of activity of serotonergic neurons following an initial inhibition has been hypothesized to play an important role in the delayed onset of efficacy of selective serotonin reuptake inhibitors. This study explored the clinical relevance of this hypothesis by examining the effects of different doses and routes of administration of fluoxetine on the recovery of activity of serotonergic neurons over the course of a 21-day exposure. Single-unit, extracellular recordings of serotonergic neurons were made in the dorsal raphe nucleus of anesthetized male rats. Acute i.v., s.c. and i.p. administration of fluoxetine inhibited the activity of serotonergic neurons. With chronic administration of fluoxetine, at clinically relevant doses, the activity of serotonergic neurons gradually recovered to baseline levels over the course of 14-21 days. The dose of fluoxetine (5, 10 or 20 mg/kg per day) did not make a significant difference in the time course of the recovery of activity of serotonergic neurons. A significant, non-parallel shift in the dose-response curve of serotonergic neurons to the serotonin-1A (5-HT1A) agonist 8-OH-DPAT occurred over the 21 days of treatment with fluoxetine, indicating a desensitization of the 5-HT1A receptor during this period. The recovery of firing did not correlate with either plasma or cerebrospinal fluid levels of fluoxetine or norfluoxetine. These results indicate that, similar to the effects of dose on the speed of onset of the clinical effects of SSRIs, increasing the dose of fluoxetine does not hasten the recovery of firing of serotonergic neurons during chronic administration. These results support the hypothesis that desensitization of the 5-HT1A receptor and consequent recovery of firing of 5-HT cells in the dorsal raphe nucleus plays a role in the delayed therapeutic onset of fluoxetine.     

Dual action effects of morphine on the electrical activity of the dorsal tegmentum

The midbrain tegmentum has been identified as an important locus for development of negative reinforcement with electrical stimulation of the brain. It also plays a central role in the motivational-affective component of pain, and is a site of the analgesic action of morphine. The present study reports the effects of morphine on the electrical activity of areas of the dorsal tegmentum of rats that were also tested for the aversive effects of brain stimulation. The results of spectral analysis of the EEG indicated that IP injections of 16 mg/kg of morphine significantly depressed intensity of EEG, while 8 mg/kg of morphine tended to increase intensity. The results were interpreted in terms of the dual action hypothesis of morphine action and Winter's model of drug effects of electrical activity of the brain. It was concluded that morphine may produce complementary inhibitory and excitatory effects on the negative and positive reinforcement systems of the brain respectively.     

Biochemical characteristics of the anti-ischemic action of the new structural analog of gamma-butyrobetaine 3-(2,2,2,-trimethylhydrazine)propionate

A structural analogue of gamma-butyrobetaine 3-(2,2,2-trimethylhydrazine)propionate (THP) administered orally in doses of 50 and 150 mg/kg for 10 days prevented isoproterenol-induced increase of the activity of the hepatic isoform of lactate dehydrogenase in the rat blood serum and in a dose of 150 mg/kg prevented an increase of creatine phosphokinase activity. Against a background of the course administration of THP isoproterenol failed to cause the accumulation of acyl-insoluble acylcarnitine in the myocardium. In this case a dose-dependent decrease of free carnitine concentration and accumulation of fatty acids in the myocardium were noted. The cardioprotective effect of THP manifested itself in prevention of a decrease of ATP and ADP concentrations, accumulation of AMP and a reduction of energy charge under the influence of isoproterenol. The ability of THP to decrease the intracellular concentration of free carnitine and to depress as a result carnitine-dependent oxidation of free fatty acids may underlie the anti-ischemic effect of THP.     

Effect of corazole on the dynamics of oxidative-reductive processes in cerebral cortical neurons

By using the complex of techniques on the basis of life-time microscopy and spectrophotometry of the structures of II, III layers of the cat brain motor cortex there was studied the effect of ionophoretically delivered corazole on the dynamics of integral redox-state of pyramidal cells bodies, the surrounding neuropil as compared to the changed bioelectrical activity. The development of the convulsant activity of neurons coincided with the shift of their redox-state towards the accumulation of intracellular reducing equivalents. Both in the bodies of neurons and in the structures of neuropil a stable pronounced increase of restoration of intracellular redox-systems was preceded by the process of wave-like fluctuating changes in the content of reducing equivalents. The role of the revealed disturbances of oxidation-reduction processes in the mechanisms of corazole-induced lesions of neurons is discussed.     

经皮穿钉固定骶髂关节针道参数的解剖学研究

目的:计算经皮穿钉治疗骶髂关节脱位的螺钉针道参数。方法:通过对十具防腐尸体的解剖学研究,确定椎弓根最窄处在髂骨后外侧的投影区,将骶1椎体纵形剖开,自一侧骶1椎体通过椎弓根向投影区逆行穿针,确定闭合打钉时拉力螺钉的置入范围、角度、螺钉长度,根据测量数值自另侧骨盆顺行打钉,验证螺钉针道参数。结果:在所有进行实验的尸体骨盆中椎弓根最窄处在髂骨后外侧投射区相对固定,在骶骨翼及S1锥体置入1根长拉力螺钉达骶1锥体1/2,置入螺钉最小长度为6.99厘米(为骶髂关节穿钉点髂骨最小厚度+骶骨体横径+第1骶椎体上面最大横径的1/2),置入螺钉最大长度为7.71厘米(为骶骨翼前缘耳状面骶1椎体外侧缘间距+骶1椎体横径的1/2+骶髂关节穿钉点髂骨最大厚度)。钉道范围:骶1进针点为以髂后上棘、髂后下棘连线为底的等边三角形的顶点,进针方向与冠状面夹角为20～25度,与水平位夹角为20度。结论:闭合打钉治疗骶髂关节脱位从解剖学研究角度认为是可行的的,但进针点及方向、螺钉长度需要根据椎弓根在骨盆壁体表投影数值及与骶1椎体的夹角确定。在不具备导航系统的情况下,以上参数可供临床参考。     

Blockade of dopamine autoreceptors by haloperidol and the apparent dynamics of potassium-stimulated endogenous release of dopamine from and reuptake into striatal suspensions in the rat.

A study was made to determine what effects the blockade of dopamine (DA) autoreceptors has on the dynamics of depolarization-stimulated release of DA from suspensions of the striatum. A rotating disk electrode voltammetric technique and a first order kinetic model were used to measure and quantify time-resolved depolarization-induced release of DA from and reuptake into the same striatal suspension. Multiphasic dose-response relationships between the magnitudes, rates and apparent rate constants of release of DA and the concentration of the autoreceptor antagonist, haloperidol, were observed. At small concentrations of haloperidol, less than or equal to 0.1 microM, the magnitude of release of DA and apparent release rate constants were increased, however, the duration of release, the initial rate of release and the rate constants of reuptake of DA were unaffected. At larger concentrations of haloperidol, greater than 1.0 microM, release of DA was prolonged and reuptake was decreased. The rate constants for release of DA correlated with the magnitude of release of DA at all of the concentrations of haloperidol studied. The concentrations of haloperidol in tissue were estimated and then correlated with functionally significant systemic doses of haloperidol by direct comparison to published data, relating total concentrations of haloperidol in tissue with systemic doses and their behavioral effects. At these doses, haloperidol was found to increase the release rate constant and magnitude of release of DA, without altering the duration of release or the timing of reuptake. Thus, at presumed functionally significant doses, autoreceptor antagonism resulted in a modulation of the amplitude of release of DA only.     

Effect of 22R-hydroxycholesterol on the action of sphingomyelinase from Bacillus cereus toward bovine erythrocytes.

The incorporation of 22R-hydroxycholesterol [(22R)-5-cholestene-3 beta,22-diol] into the bovine erythrocyte membranes remarkably enhanced the degradation of sphingomyelin in erythrocyte membranes by the action of sphingomyelinase from Bacillus cereus, causing much faster hemolysis of erythrocytes. The stimulative effect of 22R-hydroxycholesterol on the breakdown of sphingomyelin was maximal in the presence of Mg2+. On the other hand, in spite of the presence of 22R-hydroxycholesterol, the breakdown of sphingomyelin was inhibited by increasing concentrations of Ca2+. Also, the incorporation of 22R-hydroxycholesterol into the erythrocyte membranes facilitated the specific adsorption of the enzyme onto the surface of the erythrocyte membranes. The specific adsorption of sphingomyelinase amounted to 20-40% of the total activity in the presence of Mg2+ and the absence of divalent metal ions. In the presence of Ca2+, the incorporation of 22R-hydroxycholesterol enhanced the enzyme adsorption, exceeding more than 90% of the total activity. Therefore, the incorporation of 22R-hydroxycholesterol into bovine erythrocyte membranes remarkably accelerates the breakdown of sphingomyelin in the presence of Mg2+, and the specific adsorption of sphingomyelinase onto erythrocytes in the presence of Ca2+.     

医疗机构开展中药临床药学服务模式的探讨

摘 要 目的： 探讨中药临床药学服务模式,为开展中药临床药学提供参考。方法: 介绍当前开展中药临床药学服务模式现状,分析其面临的困境,提出完善中药临床药学开展模式的建议。结果与结论: 各医疗机构中药临床药学开展模式各不相同,开展的内容各异,大多服务层次较低,并未有建立起一套完善的中药临床药学服务工作模式。完善该工作模式主要面临中药临床药学学科体系的缺失、中药临床药师的缺乏、中药临床药学内容的复杂性等问题,需要从加强中药临床药学学科体系的研究与探索、加强中药临床药师的培养、建立多层次中药临床药学服务、探索多元化的中药临床药学开展模式等方面加强工作,促进中药临床药学开展,逐步丰富中药临床药学内容,建立更深入、更全面、更合理的中药临床药学服务模式。     

The Acceptable Daily Intake of Food Additives

The Joint FAGWHO Expert Committee on Food Additives has evaluated in the past 15 years the acceptable daily intake of more than 200 food additives. This outstanding piece of work of major importance has marked a turning point in the field of the national and international public health policies concerning the control of the use of food additives and consequently the control also of food quality. It is of major importance therefore that the validity of such evaluations be fully recognized in scientific quarters. Because of certain aspects of the concept, namely the double range of safety margin of acceptable tolerance levels of these constituents in food, one unconditional and the other conditional, some doubt regarding the validity of the concept is liable to arise. A critical analysis of this aspect of the question is made, leading to the suggestion that with the exception of possibly a few cases, this double range of acceptability of an additive might usefully be dropped. At the same time a few other aspects of the problem are envisaged, namely, the necessity of evaluating the probable intake of the additives, short of which the acceptable daily intake concept fails to acquire practical significance.     

中药老字号专有技术的法律特征及保护对策

目的：尝试建立法律保护体系对中药老字号企业专有技术的有效覆盖。方法：检索相关数据和研究相关文献,在厘清中药老字号专有技术的法律特征的基础上,分析中药老字号企业专有技术保护存在的问题。结果与结论：分析发现目前我国中药老字号专有技术保护存在以下问题：专利对老字号保护效用欠缺;技术秘密保护手段受挤压;商标保护形式未得到中药老字号的重视;行政保护作用受限。而解决中药老字号专有技术的保护问题,有必要从完善专利、技术秘密和行政保护制度和商标保护等几个维度实现。     

Dynamics of behavioral sensitization induced by the dopamine agonist quinpirole and a proposed central energy control mechanism

The study characterizes the process of sensitization induced by intermittent administrations of quinpirole (0.5 mg/kg) in rats in a large open field. Sensitization was found to be self-limiting, with all measures of behavior reaching a plateau after the tenth twice-weekly injection. Kinetics of sensitization were a simple hyperbolic function of the number of drug injections for some measures (speed of locomotion, length of locomotor bouts) but showed positive co-operativity for others (distance travelled, duration of locomotion, frequency of stops, route stereotypy), suggesting potentiation of the effect by preceding injections. The pace of sensitization varied for different behaviors: locomotor speed changed fastest in the early portion of chronic treatment; stereotypy of route changed primarily during the late phase; mouthing did not sensitize. Sensitization evolved by a cascade of changes that included: advancing the onset of locomotor activation; prolonging the duration of locomotion; establishing new maxima of observable responses; altering the mode of locomotion; raising speed, rate and length of locomotor bouts; and increasing stereotypy of travel. These observations do not substantiate the prediction that development of behavioral sensitization is associated with emergence of disorganized activity and/or fractionation of response chains. Instead, it is proposed that development of sensitization may represent a build-up and strengthening of performance, reflecting enhanced central control of energy expenditure stimulated by repeated injections of quinpirole. Furthermore, it is suggested that for at least one response, the maximum observable amount of locomotion, development of sensitization requires only D₂ stimulation, independent of D₁ tone.     

The relationship between inhibition of phosphofructokinase activity and the mode of action of trivalent organic antimonials on schistosoma mansoni

The addition of purified mammalian phosphofructokinase to homogenates of schistosoma mansoni increased the rate of lactic acid production from glucose and reversed the inhibition of glycolysis produced by low concentrations of trivalent organic antimonials. Neither mammalian phosphofructokinase nor trivalent antimonials affected the rate of lactic acid production from fructose-1:6-diphosphate (HDP) by schistosome homogenates. Accordingly, in the schistosome, the rate of glycolysis of glucose is determined by the activity of phosphofructokinase.

The aldolase of S. mansoni has a high requirement for HDP; relatively slight reductions in the concentration of this substrate below the optimum resulted in a sharp decline of aldolase activity. Therefore, decreased formation of HDP, due to inhibition of schistosome phosphofructokinase activity by antimonials, reduced the activity of aldolase and resulted in an inhibition of glycolysis of schistosome homogenates.

Kinetic data revealed differences in the nature of the phosphofructokinase of S. mansoni and that of the enzyme catalysing the same reaction in the host. Exposure of schistosomes to low concentrations of potassium antimonyl tartrate or administration of subcurative doses of stibophen to the host resulted in an accumulation of the substrate (fructose-6-phosphate), and a reduction of the product (HDP) of the phosphofructokinase reaction, indicating that the activity of this enzyme was inhibited by antimonials in the intact parasite. It is concluded that inhibition of phosphofructokinase activity can account for the mechanism of the chemotherapeutic action of trivalent organic antimonials in schistosomiasis.

     

番泻苷对小鼠肠道运动功能的影响及相关机制研究

目的 :评价大黄提取二蒽酮类衍生物 (番泻苷 ,sennoside ,SEN)对小鼠肠道运动功能的影响 ,并探讨其相关机制。方法 :采用小鼠湿粪记数试验观察番泻苷对小鼠肠道运动功能的影响 ;采用放射免疫分析法检测小鼠小肠组织胃动素 (motilin ,MTL)、生长抑素 (somatostatin,SS)的水平 ;采用分光光度法测定小肠粘膜Na K ATP酶的活性。结果 :番泻苷各剂量均能增强小鼠的排便功能 ,与正常对照组相比有显著差异 ;番泻苷各剂量均能显著提高小鼠小肠组织胃动素的含量 ,而降低生长抑素的水平 ;番泻苷各剂量组小鼠小肠粘膜Na K ATP酶活性显著低于正常对照组。结论 :番泻苷能增强小鼠的肠道运动功能 ,具有润肠通便之功效 ,其机制可能与促进肠道胃动素释放 ,降低肠道生长抑素水平和抑制小肠粘膜Na K ATP酶的活性有关     

Effect of lipid composition on insulin-mediated fusion of small unilamellar liposomes: a kinetic study

Liposome-entrapped insulin could be used to prolong the hypoglycemic action of insulin. Also, the conjugation of insulin to the surface of liposomes allows the potential application of using insulin as a transporting molecule to deliver liposome-entrapped drugs to insulin-receptor rich tissues. The success of these two approaches of drug delivery depends on how insulin may interact with liposomes. The present study describes the application of the principle of kinetics to investigate the effect of insulin on the stability of various preparations of liposomal drug carriers. The technique of fluorescence resonance energy transfer was employed to study the destabilization of liposomal formulations through the process of insulin-mediated fusion of liposomes. The kinetics of insulin-mediated fusion appeared to be compatible with a model whereby the initial rate of fusion is governed by the mechanism of fusion of two small unilamellar, unfused liposomal particles. The rate constants of insulin-mediated fusion of various liposomal formulations were estimated from the initial rate of fusion, using the model of two-particle fusion. Arrhenius analysis of the rate constants of fusion at different temperatures suggests that the mechanism of insulin-mediated fusion of small unilamellar vesicles is not governed merely by the energy and frequency of collision between liposomal particles. Other factors, such as the binding of insulin with the surface of liposomes and the temperature effect on the dynamics of the liposomal membrane, as well as conformation of insulin, could potentially be important.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of organophosphates on bioelectrical activity of the brain

Effects on electroencephalogram of acute and chronic exposure of two main groups of organophosphates: classic anticholinesterases (OP) and new bicyclic organophosphates (PTBO) are described. The role of muscarinic receptors of the midbrain reticular formation in the mechanism of action of OP and the possible mechanism of action of PTBO as blockers of a chloride ionophore of the GABA receptor complex are presented. The mechanism of convulsive activity of both groups are also discussed.