青蒿素及其衍生物的药理作用

青蒿素及其衍生物是我国科学工作者研究开发的一类抗疟疾新药,具有自主知识产权.由于青蒿素类药具有抗疟疾、抗孕、抗纤维化、抗血吸虫、抗弓形虫、抗心律失常和肿瘤细胞毒性等作用,并且有安全、高效、无耐药性等优点,备受国内外学者关注.但其作用机制、毒副作用和应用等方面有待更深入的研究.     

青蒿素类药物的药理作用研究进展

青蒿素是从植物黄花蒿中提取的抗疟疾活性成分,在临床上广泛用于治疗疟疾。由于青蒿素类药物还具有抗疟疾、抗孕、抗纤维化、抗血吸虫、抗弓形虫、抗心律失常和肿瘤细胞毒性等药理作用,且具有安全、高效、无耐药性等优点,备受国内外学者关注。笔者对近年来青蒿素类药物的其他主要药理学作用研究的现状进行了综述。     

白花蛇舌草抗炎、抗肿瘤作用研究进展

摘要：慢性炎症与肿瘤的发生、发展、侵袭、转移等密切相关,清热解毒中药白花蛇舌草兼具抗炎、抗肿瘤作用,在临床上常用于各种炎症、肿瘤的预防与治疗。白花蛇舌草抗炎机制研究主要涉及NF-κB、MAPK、5-LOX等信号通路,抗肿瘤研究主要为抗肠癌、抗肺癌、抗肝癌、抗乳腺癌、抗胃癌等,机制涉及PI3K/AKT、TGF-β/Smad、MAPK、STAT3等信号通路,并可能通过NF-κB、MAPK、VEGF等途径在“炎-癌”转化过程中发挥重要作用。本综述为白花蛇舌草抗炎、抗肿瘤及干预“炎-癌转化”深入研究提供参考。     

鳢肠属植物的化学成分和药理作用

鳢肠属植物含有三萜皂苷、芳杂环类、甾体生物碱等化学成分,具有保肝、免疫调节、抗炎、抗蛇毒和抗诱变等生物活性。综述了该属的鳢肠和白鳢肠的化学成分、药理作用等研究进展。     

砂仁临床药理作用的研究进展

砂仁不仅具有温里类中药的共同药效谱,也具有温里药的辛温归脾胃经的共同中药药性。现代研究显示砂仁具有抗溃疡、抗腹泻、促进胃排空和胃肠推进运动、利胆、镇痛、抗炎、抗血小板聚集和延长凝血时间等药理作用。综述砂仁在消化系统、血液系统以及镇痛抗炎等方面的临床药理作用的研究进展。     

翻开抗微生物药物厚厚的“族谱”

抗微生物药物是一个很大的“家族”,包括很多成员,按照药物作用的对象（即八大类微生物）可分为：抗茵药物、抗病毒药物、抗真菌药物、抗支原体药物、抗衣原体药物、抗立克次体药物、抗分支杆菌药物、抗螺旋体药物等,通常不包括抗寄生虫药物,但广义的抗微生物药物有时把抗寄生虫药物也包括在内。     

宁夏苦豆子主要活性成分及治疗肝脏疾病的研究进展

苦豆子是豆科槐属植物,为宁夏的道地药材之一.苦豆子有着丰富而复杂的活性成分,主要有生物碱、黄酮、挥发油、甾体、多糖、脂肪酸等.近年来,国内外对苦豆子生物碱开展了大量研究,该类生物碱具有抗肝炎、抗肝纤维化、抗肝硬化、抗肝衰竭、抗肝癌等药理作用,其中,苦参碱相关药物已经获批在临床用于治疗乙型肝炎病毒感染等疾病.鉴于苦豆子在...     

良姜的化学成分及药理活性研究进展

高良姜的化学活性成分主要包括二苯基庚烷类(diarylheptanoid)、挥发油类、糖苷类、苯丙素类和黄酮类等。高良姜有广泛的药理作用,如止呕、抗溃疡、抗腹泻、镇痛抗炎、抗血栓形成、抗缺氧、抗氧化、抗促癌作用等。本文就近年来高良姜的化学成分及药理活性的研究进展进行了综述,并展望了下一步研究的方向。     

术类的药理和药效

本文综述了近十年来术类在抗胃溃疡、利水、抗糖尿病、抗肿瘤、抗炎及对神经系统等方面的药理作用的研究成果。     

黄芪甲苷抗凋亡作用机制的研究进展

黄芪甲苷是黄芪的主要活性成分,具有众多的生物活性,如抗神经退行性疾病（阿尔海默病,帕金森）、抗应激、抗纤维化、抗病毒、抗炎等。通过查阅国内外文献,发现抗细胞凋亡作用与多种疾病密切相关。本文从细胞凋亡产生的重要途径如死亡受体途径、线粒体途径、内质网途径、PI3K/Akt途径、MAPK途径等多个方面对黄芪甲苷抗凋亡作用机制进行综述,为黄芪甲苷在抗细胞凋亡的相关研究提供参考。     

Daily fluctuation of hepatic P450 monooxygenase activities in male rats is controlled by the suprachiasmatic nucleus but remains unaffected by adrenal hormones

Hepatic P450 monooxygenase activities, which strongly influence the efficacy and/or toxicity of drugs, are known to fluctuate daily. We also know that the P450 activities assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities fluctuate daily, with apparently high values during the dark period in male rats. However, there is little knowledge about the factors that regulate daily fluctuation of P450 monooxygenase activities. In the present study using rats, we induced lesions in the suprachiasmatic nucleus (SCN) of the brain, the known site of the body's internal clock, and examined the effects on the daily fluctuation of the ACD activities to clarify the relationship between the SCN and the daily fluctuation of P450 monooxygenase activities. In addition, adrenalectomy was performed to re-evaluate the influence of adrenal hormones on the P450 activities. Our results indicated that daily fluctuations of the hepatic ACD activities were completely eliminated in the SCN-lesioned rats. However, the ACD activities in the adrenalectomized rats showed apparent daily fluctuations with high values during the dark period and low values during the light period. Therefore, this study demonstrated that the daily fluctuation of the hepatic P450 monooxygenase activities in male rats is controlled by the SCN but remains unaffected by the adrenal hormones. Received: 11 May 1999 / Accepted: 19 July 1999     

Daily fluctuation of 7-alkoxycoumarin O-dealkylase activities in the liver of male F344 rats under ad libitum-feeding or fasting condition.

It has been reported that drug metabolizing enzyme activities in the liver fluctuate daily, though the daily fluctuation of 7-alkoxycoumarin O-dealkylase (ACD) activities catalyzed by P450 has not been examined. The ACD activities are known to be useful to clarify the extensive induction of P450-dependent oxygenases. In the present study, the hepatic ACD activities, as well as P450 content, were investigated periodically in male F344 rats under ad libitum-feeding or fasting condition. The ACD activities in ad libitum-fed rats were found to follow obvious daily fluctuations with high values during dark periods and with low values during light periods. This agreed with the other previous results of drug metabolizing enzyme activities measured with other substrates. Because the daily fluctuation was also observed in fasted rats, the fluctuation in ACD activities was clearly not affected by feeding, an external factor. P450 content, however, showed different fluctuation patterns from the ACD activities. This suggests that the fluctuation of ACD activities might not be related to the quantitative variation of P450 proteins.     

Elucidation of anti-allergic activities of curcumin-related compounds with a special reference to their anti-oxidative activities

The anti-allergic and anti-oxidative activities of curcumin-related compounds (glycosides, reductants and bis-demethoxy analogs) were investigated to elucidate the underlying active mechanisms and structural features of curcumin in exerting these activities. The anti-allergic activities were assessed by measurement of histamine release from rat basophilic leukemia cells, RBL-2H3. Curcumin and tetrahydrocurcumin (THC) caused a marked decrease in histamine release. Glycosides of curcumin, bis-demethoxycurcumin and THC also inhibited the release of histamine, though less potently than curcumin did. The anti-oxidative activities were assessed by measurement of cell-free or cellular radical scavenging. All compounds but diglycosides or bis-demethoxycurcumin analogs distinctly exerted anti-oxidative effects. The relationship between both of these activities revealed that all compounds with potent radical scavenging activities caused a definite decrease in histamine release, but some compounds with non-potent radical scavenging activities also inhibited the histamine release. These results suggest that the hydroxy groups of curcumin play a significant role in exerting both the anti-oxidative and anti-allergic activities, and that most of the compounds develop the anti-allergic activities through mechanisms related to anti-oxidative activities, but some through mechanisms unrelated to anti-oxidation activity.     

土木香中纯化的五种倍半萜类化合物抑制肿瘤增殖活性的研究

目的检测土木香中纯化的五种倍半萜化合物抑制肿瘤增殖的活性,并探讨化合物结构与活性之间的关系。方法应用MTT法测定五种倍半萜类化合物对体外培养人肿瘤细胞增殖的影响;应用小鼠移植性肝癌模型测定了异土木香内酯的抗肿瘤活性。结果化合物1(异土木香内酯)对U251SP细胞、HLE细胞和MM1-CB细胞的增殖显示较强的抑制活性;化合物2～5对各种实验用肿瘤细胞的增殖不显示抑制活性;化合物1对移植性肿瘤(肝癌H22)具有明显的抑制作用,并呈现较好的剂量依赖关系。结论异土木香内酯具有较强的肿瘤抑制活性;化合物2～5对肿瘤细胞增殖抑制活性丧失可能由于A-环和B-环之间的键裂开,形成一个大10元环,改变了原来的构象所致。     

Relationships between plasma and tissue transaminase activities in rats maintained under different feeding conditions

In order to verify the nutritional aspect of alterations of the plasma and tissue transaminase activities, rats were fed 4 hr per day for 35 days (the spaced-fed (SF) rats) and the time course of the alterations in plasma and tissue transaminase activity was compared with those in the ad libitum fed (ALF) rats. Plasma transaminase activities were stable throughout the experiment period in the ALF rats. In the SF rats there were alterations in the plasma alanine aminotransferase (ALT) activities, the direction of which was different between the early phase and late phase of the experiment period; plasma ALT activities decreased in the early phase and gradually increased in the late phase. Plasma aspartate aminotransferase (AST) activities were stable in the SF rats throughout the experiment period as well as the ALF rats. The decreases in plasma ALT activities in the early phase were considered to be related to decreases in ALT activities in the small intestinal mucosa (SI mucosa). On the other hand, the increases in plasma ALT activities in the late phase were considered to be related to increases in ALT activities in the liver. Multiple regression analyses (MRAs) revealed that plasma ALT activities in the SF rats could be estimated by the ALT activities in the SI mucosa and liver. From these results, the alterations of the plasma ALT activities in the SF rats could be explained by those in the SI mucosa and liver under the conditions in our study.     

Microsomal lauric acid hydroxylase activities after treatment of rats with three classical cytochrome P450 inducers and peroxisome proliferating compounds.

In order to investigate a proposed relationship between induction of hepatic microsomal lauric acid hydroxylase activity and peroxisome proliferation in the liver, male Wistar rats were treated with peroxisome proliferating compounds, and the lauric acid hydroxylase activity, the immunochemical detectable levels of cytochrome P450 4A1 and the activities of peroxisomal enzymes were determined. In addition, the levels of cytochrome P450 4A1 and lauric acid hydroxylase activities were studied after treatment of rats with three cytochrome P450 inducers. After treatment with aroclor-1254, phenobarbital or 3-methylcholanthrene total cytochrome P450 was 1.7-2.7 times induced. However, no induction of lauric acid omega-hydroxylase activities or P450 4A1 levels were found. After treatment of rats with di(2-ethylhexyl)phthalate (DEHP) a dose-dependent induction of lauric acid omega-hydroxylase activities, levels of cytochrome P450 4A1 and peroxisomal fatty acid beta-oxidation was found. Even at a dose-level of 100 mg DEPH/kg body weight per day a significant induction of these activities was observed. The main metabolites of DEHP, mono(2-ethylhexyl)phthalate and 2-ethyl-1-hexanol, also caused an induction of levels of P450 4A1, lauric acid omega-hydroxylase activities and the activity of peroxisomal palmitoyl-CoA oxidase. 2-Ethyl-1-hexanoic acid did not influence lauric acid omega-hydroxylase activities, but did induce levels of P450 4A1 and palmitoyl-CoA oxidase activities. Three other compounds (perfluoro-octanoic acid, valproate and nafenopin) induced both lauric acid omega-hydroxylase activity and peroxisomal palmitoyl-CoA oxidase activity. The plasticizer, di(2-ethylhexyl)adipate, did not induce levels of P450 4A1, lauric acid omega-hydroxylase activities or palmitoyl-CoA oxidase activities. With the compounds tested a close association between the induction of lauric acid omega-hydroxylase activities and peroxisomal palmitoyl-CoA oxidase activity was found. These data support the theory that peroxisome proliferating compounds do induce lauric acid omega-hydroxylase activities and that there might be a mechanistic inter-relationship between peroxisome proliferation and induction of lauric acid omega-hydroxylase activities.     

Synergistic action of cefodizime and other antimicrobial agents on clinically isolated microorganisms. III. Synergistic action with gentamicin]

An in vitro investigation was done on antimicrobial activities of cefodizime (CDZM) in combination with gentamicin (GM) against clinically isolated Gram-negative rods. The results are summarized as follows. 1. Combined antimicrobial activities were dependent on antimicrobial activities of GM, similar to the CDZM + sisomicin (SISO) combination. The combined activities were concentration dependent, and they were more strongly dependent on GM concentrations than on CDZM concentrations. The obtained results suggested that synergistic or cooperative antimicrobial activities of the combination would be expected when GM concentrations in blood are at or somewhat lower than 1 MIC, and clinical activities would be exerted regardless of the presence of CDZM resistant organisms, similarly to CDZM+SISO combination. 2. It seems possible that, with regard to combinations of beta-lactam antibiotics and aminoglycoside antibiotics, there exist universal rules that combined activities are dependent on activities of aminoglycoside antibiotics, and that stronger concentration dependencies on aminoglycosides would be observed than those on beta-lactams.     

The isoenzyme pattern of cytochrome P450 in rat hepatocytes in primary culture, comparing different enzyme activities in microsomal incubations and in intact monolayers

Changes in the isoenzyme pattern of cytochrome P450 during culture were investigated in primary cultures of rat hepatocytes, measuring specific enzyme activities in microsomes prepared from cultured cells as well as in intact monolayers. Assays of 7-ethoxyresorufin O-deethylation (EROD), 7-pentoxyresorufin O-depentylation (PROD), aniline 4-hydroxylation (AH) and the specific regioselective hydroxylation of testosterone were used as representatives of the activities of seven isoenzymes of cytochrome P450. The isoenzyme profile expressed as catalytic activities was qualitatively and quantitatively similar in microsomes obtained from freshly isolated hepatocytes in comparison with microsomes obtained from whole livers of untreated rats. There was a relatively high activity in EROD, AH and the oxidation of testosterone at the 7 alpha, 2 alpha, 6 beta, 16 alpha and 17 sites (androstenedione). During culture, these microsomal enzyme activities declined at a similar rate to ca. 50% of the activities of microsomes prepared from freshly isolated hepatocytes after 24 hr and to 15% after 96 hr. The overall decline of cytochrome P450-dependent activities during culture was not accompanied with gross changes in catalytic profile. Determining the same drug-metabolizing activities directly in intact hepatocyte monolayers revealed a much higher metabolic rate for all measured P450-dependent activities. The profile of the catalytic activities was essentially the same as measured in microsomes prepared from cultured hepatocytes. The relatively low activity towards the 7 alpha site of testosterone measured in intact hepatocytes, however, remained constant during culture. Determination of enzyme activities directly in intact hepatocytes is a convenient way of studying changes in monooxygenase activities of different P450 isoenzymes in vitro.     

运用品管圈活动降低急诊不合理处方发生率的实践

目的：运用品管圈活动降低我院急诊不合理处方发生率,促进急诊合理用药,保障患者用药安全。方法：按照品管圈十大步骤及七大手法开展活动,分别调取我院2016年8月至9月（活动前）和2016年12月至2017年1月（活动后）的急诊处方,对处方进行点评,通过所得数据对此次活动进行效果确认。结果：急诊不合理处方发生率由活动前的46.28%降低至改善后的15.17%。结论：通过开展此次活动,再次印证了品管圈是推动医疗质量持续改进的有效管理工具,在降低急诊不合理处方发生率方面效果显著,提升了药学服务质量,体现了药师的价值。