药学监护与护与人类基因

人类基因组科学是一门跨学科的科学.这门科学揭示生命的奥秘,可推动医药学的发展,也为药学监护提供最大的帮助. 1药学监护的重要性 药学监护(pharmaceutical care,PC)是20世纪80年代兴起的一个药学工作模式.它要求药师不应单纯面对药物,更重要的是应面对病人.不但要治愈病人,还要对病人的生命质量负责.因而,除了疾病的诊断之外,药师要参与病人的整个治疗过程.要选择药物;要决定用药途径和剂量;要进行血药浓度监测;要预测药物对病人个体有没有潜在的不良反应,以及如何预防和消除这些不良反应等.     

战汗与脱汗的鉴别与护理

战汗与脱汗属祖国医学“汗证”范畴,临床上提高战汗与脱汗的鉴别与辩证施护能力十分必要,兹将笔者体会介绍如下。 1 战汗与脱汗的鉴别 战汗是指病人先恶寒战栗,几经挣扎,而后汗出者。多见于疾病邪正相争剧烈之时,是疾病发展的转折点。如汗出后热退脉缓,则邪去正安,疾病好转;若汗出后身仍高热,脉来急疾,则表示邪盛正衰,疾病恶化。     

生姜与大枣的治疗与保健作用

目的：介绍生姜与大枣配伍对心脑血管疾病及其他疾病的治疗和保健预防作用。方法：大枣粉500g,生姜粉100g混匀,每服15g,日2次。结果：脑梗死患者病程1个月以内,疗程1个月治疗46例,痊愈40例,显效6例,有效率为100.0%;病程1~6个月,疗程6个月的治疗35例,痊愈20例,显效15例,有效率为100.0%;病程6个月以上服药1年的治疗19例,好转13例,无效4例,复发2例,有效率为68.4%。冠心病心绞痛Ⅰ级治疗59例,疗程3个月,痊愈59例;心绞痛Ⅱ级治疗36例,疗程6个月,痊愈30例,显效6例;心绞痛Ⅲ级治疗5例,疗程1年,显效5例。结论：应用脑梗死的辅助治疗疗效明显提高,用于脑梗死后遗症可改善症状,防止复发,应用冠心病疗效高而稳定可靠,对心脑血管疾病的辅助治疗和应用愈早愈好,疗程愈长疗效愈巩固,复发率愈低。     

妊娠与性传播性疾病诊断与治疗

近年来性传播疾病(sexually transmitted diseases.STD)迅速蔓延,妊娠妇女受染的机会越来越多,由于妊娠期一些激素的变化,如脑垂体、甲状腺、肾上腺等均有不同程度增大及功能增加,以致使孕妇对STD的易感性增加,随着胎儿的逐渐成熟,孕妇不同程度的贫血,组织水肿、膀胱受压.输尿管受雌激素及孕激素的影响导致肌张力懦动减弱,尿液滞留,阴道粘膜充血,粘膜皱褶加深上皮细胞蓄积多量糖元,阴道内酸度增加等,这些都有利于STD各种病原体的生长繁殖,故妊娠与STD是有着密切的关系,本文简介在门诊常见的几种STD的诊断及治疗进行探讨.     

五加皮与香加皮的混用与区分

最近我们在基层检查中发现,临床上以香加皮代五加皮混用,情况比较普遍,在此有必要提醒大家注意二者的区分. 五加皮为五加科植物细柱五加A canthopanax grxacilistylus W. Wsmith的干燥根皮,又名南五加;香加皮为萝艹摩科植物杠柳periploca sepium Bge的干燥根皮,又名北五加皮.临床上五加皮以祛风湿、强筋骨、补肝肾为主要功效,尤以补肝肾见长;而香加皮则以祛风湿,强筋骨为主,有毒,不宜用量过大,且小儿不宜服用.二者在功能、主治、用量上都有区别,所以香加皮不能代五加皮混用.二者区别详见表1.     

苦杏仁与桃仁的鉴别与应用

通过比较和分析的方法,对苦杏仁和桃仁进行性状特点、主要显微鉴别、蛋白电泳鉴别方面比较,为其准确药用提供依据.     

抗凝剂与抗血小板药物与麻醉

对于合并心血管疾病的老年患者或是血管外科患者而言，血栓与血栓相关并发症成为致死致残的重要原因之一。抗凝剂与抗血小板药物的应用使血栓相关并发症的发生率大大降低。然而在临床麻醉中，服用此类药物患者的麻醉相关问题为麻醉医生提出了一定的挑战。本文就抗凝剂与抗血小板药物与麻醉的相关进展进行综述。     

妊娠与性传播性疾病诊断与治疗

近年来性传播疾病(Sexually transmitted diseaess STD)迅速蔓延,妊娠妇女受染的机会越来越多,由于妊娠期一些激素的变化,如脑垂体、甲状腺,肾上腺等均有不同程度增大及功能增加,以致使孕妇对STD的易感性增加,随着胎儿的逐渐成熟,孕妇不同程度的贫血,组织水肿、膀胱受压。输尿管受雌激素及孕激素的影响导致肌 张力懦动减弱,尿液滞留,阴道粘膜充血,粘膜皱褶加深上皮细胞蓄积多量糖元,阴道内酸度增加等,这些都有利于STD各种病原体的生长繁殖,故妊娠与STD是有着密切的关系,本文简介在门诊常见的几种STD的诊断及治疗进行探讨。     

龙骨与龙齿的来源与鉴别

龙是古代传说中被神化的一种巨型动物。古人把远古时代多种人型哺乳动物骨骼化石,看作是龙的遗物,故名龙骨,龙的牙肉,故名龙齿。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Strain-dependency in motor activity and in concentration and turnover of catecholamines in synchronized rats

Circadian rhythm in motor activity was studied with an Animex motimeter in six strains of rats (ACI, BH, BS, DA, LEW, TNO) synchronized by a 12 hr light: 12 hr dark cycle. ANOVA revealed significant interstrain differences in motor activity as well as in the concentration and turnover of central noradrenaline and dopamine. Strain-dependent differences were also found with regard to tyrosine hydroxylase inhibition on motor activity. However, no significant interstrain correlations were found between endogenous concentration and/or turnover rates of the catecholamines and motor activity in normal and drug-treated rats.     

Pharmacokinetics and tolerability of artesunate and amodiaquine alone and in combination in healthy volunteers

Objectives  The WHO recommends artemisinin-based combination therapies for treatment of uncomplicated falciparum malaria. At least 15 African countries have adopted artesunate plus amodiaquine as treatment policy. As no pharmacokinetic data on this combination have been published to date, we investigated its pharmacokinetic interactions and tolerability in healthy volunteers in Africa. Methods  In a randomized, three-phase, cross-over study, amodiaquine (10 mg/kg) and artesunate (4 mg/kg) were given as single oral doses to 15 healthy volunteers. Artesunate was given to all volunteers on day 0. On day 7 they received either amodiaquine or amodiaquine plus artesunate and the alternative regimen on day 28. The pharmacokinetics of artesunate and amodiaquine and their main active metabolites dihydroartemisinin and desethylamodiaquine were compared following monotherapy and combination therapy using analysis of variance. Results  Thirteen volunteers completed the study, and pharmacokinetic parameters could be determined for twelve volunteers. When given in combination, the mean AUC was lower for dihydroartemisinin [ratio 67% (95% CI 51–88%); P = 0.008] and desethylamodiaquine [ratio 65% (95% CI 46–90%); P = 0.015] when compared with monotherapy. Adverse events of concern occurred in four volunteers (27%): grade 3 transaminitis (n = 1), neutropaenia (n = 2), and hypersensitivity (n = 1). Conclusion  The total drug exposure to both drugs was reduced significantly when they were given in combination. The clinical significance of these interactions is unclear and must be studied in malaria patients. The frequency and nature of adverse events among the healthy volunteers were of concern, and suggest laboratory monitoring would be needed in malaria patients treated with artesunate plus amodiaquine.     

多廿烷醇与普伐他汀治疗高脂血症的疗效和安全性

目的评价多廿烷醇治疗高脂血症,特别是高胆固醇血症的疗效和安全性。方法多甘烷醇组(试验组,多廿烷醇10mg·d~(-1))和普伐他汀组(对照组,普伐他汀10 mg·d~(-1))各119例。进行随机、双盲、双模拟、阳性药物平行对照试验。观察2组降脂疗效和不良反应发生情况。结果经过12 wk治疗,多廿烷醇组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL)、TC-高密度脂蛋白胆固醇(HDL-C)/ HDL-C、载脂蛋白B_(100)(Apo B_(100))、脂蛋白(Lpa)治疗前分别为(6.6±s0.7)、(4.0±0.6)、(0.10±0.03)、(3.3±0.5)mmol·L~(-1)、(260±184)mg·L~(-1),治疗后分别为(6.0±1.3)、(3.5±0.8)、(O.09±0.04)、(2.7±0.8)mmol·L~(-1)、(130±130)mg·L~(-1),治疗后各指标较治疗前均有非常显著差异(P<0.01)。普伐他汀组TC、LDL-C、TC-HDL-C/HDL-C、Apo B_(100)、Lpa治疗前分别为(6.7±0.8)、(4.1±0.7)、(0.10±0.03)、(3.4±0.5)mmol·L~(-1)、(279±240)mg·L~(-1),治疗后分别为(6.0±1.3)、(3.5±0.9)、(0.09±0.03)、(2.8±0.8)mmol·L~(-1)、(182±213)mg·L~(-1),治疗后各指标较治疗前均有非常显著差异(P<0.01)。但2组相比较,调脂作用相似,无显著差异(P>0.05)。不良反应方面,多廿烷醇组(9.2%)明显少于普伐他汀组(18.5%),2组有显著差异(P<0.05)。不良反应大多较轻微,不需停药能自行缓解。结论多廿烷醇10 mg·d~(-1)降脂效果与普伐他汀10 mg·d~(-1)的疗效相当,均能明显降低TC、LDL-C、TC-HDL-C/ HDL-C、Apo B_(100)、Lpa。多廿烷醇的安全性优于普伐他汀,不良反应轻微,耐受性好。     

Simultaneous Determination of Sulfation and Glucuronidation of Flavones in FVB Mouse Intestine in Vitro and in Vivo

Glucuronidation and sulfation are the two major phase II metabolic pathways for flavones, natural compounds that hold great potential for improving human health. We investigated the positional preference for sulfation and glucuronidation of seven structurally similar flavones in vitro and in situ. An FVB mouse intestinal perfusion model was used in addition to three small intestine S9 fractions catalyzing sulfation only (Sult enzymes), glucuronidation only (Ugt enzymes) or both (Sult and Ugt enzymes). In both the single and co‐reaction S9 systems, flavones containing 7‐OH groups were conjugated only at 7‐OH despite the presence of other hydroxyl groups, and 7‐OH glucuronidation was faster than sulfation (P < 0.05). The sulfation rate was enhanced in the Sult‐Ugt co‐reaction system, while glucuronidation was usually unchanged by the presence of Sult. In the intestinal perfusate, sulfation patterns were the same in the small intestine and colon, and the excretion rate of 7‐O‐sulfate was the fastest or second fastest. The excretion of 7‐O‐glucuronidates was faster in small intestine (P < 0.05) than in colon. The S9‐mediated sulfation rates of the different flavones were significantly correlated with the excretion rates of the same flavones from perfused intestine. In conclusion, flavone glucuronidation and sulfation rates were sensitive to minor changes in molecular structure. In intestinal S9 fractions, both Ugts and Sults preferentially catalyzed reactions at 7‐OH. The sulfation rate was significantly enhanced by simultaneous glucuronidation, but glucuronidation was unaltered by sulfation. Sulfation rates in mouse S9 fractions correlated with sulfation rates in perfused intestine. Copyright © 2011 John Wiley & Sons, Ltd.     

Stability and kinetics of hydrolysis of metronidazole monosuccinate in aqueous solution and in plasma

The kinetics of hydrolysis of metronidazole monosuccinate in aqueous solution at pH 1.5–10 and 60°C has been investigated. The decomposition was monitored by a high-performance liquid chromatographic method capable of determining the monosuccinate ester and the parent metronidazole simultaneously. At any given pH the reactions displayed strict first-order kinetics and were subject to specific acid-base catalysis; no general acid-base catalytic effect by various buffer substances was observed. Maximal stability was observed at pH 3–6, where the degradation rate was independent of pH indicating that intramolecular catalysis by the terminal carboxylate ion on the ester group is not involved in the hydrolysis reactions in this pH range. The lack of intramolecular catalysis is suggested to be due to the poor leaving ability of the strongly basic metronidazole alkoxide ion.The rates of conversion of the ester to metronidazole at 37°C in 80% human plasma and in 0.05 M phosphate buffer pH 7.40, respectively, were found to be nearly identical, $\text{t}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$~ 580 h, revealing that the degradation in plasma proceeds in the absence of enzymatic catalysis.     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.