氯氮平、氟哌啶醇和氯丙嗪对慢性精神分裂症患者糖、脂代谢及体质量的影响

目的 探讨氯氮平、氟哌啶醇和氯丙嗪对慢性精神分裂症患者的糖、脂代谢和体质量的影响。方法 对服用氯氮平（89例，氯氮平组），服用氟哌啶醇（87例，氟哌啶醇组）及服用氯丙嗪（83例，氯丙嗪组）治疗的慢性精神分裂症患者于治疗前后的不同时间进行血糖、胰岛素、血脂及体质量测定，并做相关因素分析。结果 氯氮平组治疗第90天和第180天空腹血糖异常（空腹血浆血糖〉7.0mmo/L）的发生率分别为8％及24％，氟哌啶醇组分别为1％和2％，氯丙嗪组分别为1％及4％。治疗第90天氯氮平组和氯丙嗪组的空腹及餐后2h血糖浓度均较治疗前升高，治疗第180天的血糖浓度高于第90天，氟哌啶醇组各时点的变化则不明显；差异均有统计学意义（P均〈0．01）。治疗第90天，氯氮平组的体质量平均高于治疗前5．5％，氯丙嗪组高于治疗前4．8％；治疗第180天两组分别高于治疗前9．1％和7．4％；氟哌啶醇组则无明显变化；三组间的差异有统计学意义（P〈0．01）。三组患者治疗第180天的胰岛素浓度均高于治疗前，差异均有统计学意义（P均〈0．01），但三组间的差异无统计学意义（P〉0．05）。氯氮平组和氯丙嗪组的胆固醇和甘油三酯浓度均高于治疗前，差异均有统计学意义（P均〈0．01），氟哌啶醇组则无明显变化。治疗第180天氯氮平组和氯丙嗪组患者血糖、胰岛素、血脂浓度与体质量均有一定相关性（r=0．23-0．39）；氯氮平组的血糖、体质量、血脂代谢还与血药浓度呈显著性相关（r=0．28-0．62），差异均有统计学意义（P〈0．05或〈0．01）。结论 氯氮平和氯丙嗪治疗影响慢性精神分裂症患者的糖、脂代谢及体质量。     

Functional mechanism underlying cyclooxygenase-2 expression in rat small intestine following administration of indomethacin: Relation to intestinal hypermotility

Background and Aim:  We recently reported that cyclooxygenase (COX)-2 is upregulated in the rat small intestine after administration of indomethacin, and this may be the key to non-steroidal anti-inflammatory drug (NSAID)-induced intestinal damage. The present study investigated the mechanism for COX-2 expression induced in the rat small intestine by indomethacin, in relation with ulcerogenic processes.
Methods:  Animals were given indomethacin or SC-560 p.o., and the intestinal mucosa was examined 24 h later.
Results:  Indomethacin caused hemorrhagic lesions in the small intestine, accompanied with an increase in intestinal motility, bacterial invasion and inducible nitric oxide synthase (iNOS) activity, as well as the expression of COX-2 mRNA in the mucosa. Although SC-560 did not cause any damage, this agent caused intestinal hypermotility, the bacterial invasion and the upregulation of COX-2 expression. The mucosal PGE₂ content was decreased by SC-560 at 3 h but recovered 12 h later, and this recovery of PGE₂ was attenuated by both atropine and ampicillin, in addition to rofecoxib. The intestinal hypermotility response to indomethacin was prevented by both 16,16-dimethyl PGE₂ and atropine, but not ampicillin. Yet all these agents inhibited not only the bacterial invasion but also the expression of COX-2 and iNOS activity in the intestinal mucosa following indomethacin treatment, resulting in the prevention of intestinal lesions.
Conclusion:  These results suggest that COX-2 expression in the intestinal mucosa following the administration of indomethacin is associated with intestinal hypermotility and bacterial invasion. The intestinal hypermotility caused by COX-1 inhibition may be a key to COX-2 expression after administration of NSAIDs and their intestinal ulcerogenic properties.     

Cannabis and driving: A new perspective

Cannabis and driving is an emerging injury‐prevention concern. The incidence of driving while affected by cannabis is rising in parallel with increased cannabis use in the community. Younger drivers are at particular risk. Improvements in research methodology, technology and laboratory testing methods have occurred in the last 10 years. These cast doubt on earlier results and conclusions. Studies now show that cannabis has a significant impairing effect on driving when used alone and that this effect is exaggerated when combined with alcohol. Of particular concern is the presence of cannabis as the sole psychoactive drug in an increasing number of road fatalities and the lack of any structural response to this problem. A review of testing methods, laboratory and real driving studies, and recent epidemiological studies is presented. Suggestions for methods of further data collection and future public policy are made.     

免疫调节药在肿瘤患者住院治疗中的应用分析

目的 了解肿瘤住院患者使用免疫调节药的现状，为临床合理用药提供参考。方法对2003～2005年免疫调节药应用情况运用药物使用频度（DDDs）、年均增率（AARG）等分析方法，进行统计分析。结果 免疫调节药销售金额年均增长率达106.69%。生物反应修饰剂销售金额占总金额的65.93%。生物反应修饰剂和增强免疫功能中成药用药频度相当。排序靠前的是金黄色葡萄球菌滤液注射液、参芪扶正注射液，用量上升最快的是香菇多糖注射液、胸腺素α1注射液。结论 免疫调节药是肿瘤放化疗必备用药，在肿瘤患者住院治疗中应用广泛。整体上该类药物的应用基本合理。疗效显著且作用广泛的药物成为临床首选。     

Studies on Toxicity of Nitroquine-Dapsone Compound and Therapeutic Effects of Folic or Folinic Acid on Toxicated Animals

The toxic effects of nitroquine-dapsone compound(NQD)in mice and dogs were studied.The therapeutic index of NQDin mice is 1911,the greatest among the 6 antimalarials tested.Thetoxic effects of NQD(50 mg/kg/day for 3 days per os)and nitro-quine in dogs were manifested by injuries on the adrenal cortexand intestinal epithelium.When folic acid(4 mg/kg/day for 4 days)or calcium leucovorinum(0.3 mg/kg/day for 4 days)were usedconcomitantly with NQD,the death rate and the incidence of dia-rrhea in the toxicated dogs were greatly reduced,the injury on theintestinal epithelium was much milder,and the goblet cells weremuch more numerous than those without treatment.The results suggestthat folic acid and calcium leucovorinum can protect the undifferen-tiated cells in the intestinal crypts from being injured by NQD.     

中药血清化学在中药及中药复方研究中的应用

中药血清化学是在传统的口服给药模式的基础上,依据中药口服后只有移行入血的成分才可能发挥药效的思路,通过综合运用现代的提取、分析技术,对药物口服吸收后含药血清中的原型药物及其代谢产物进行分析研究,从而可直接筛选和判断出中药及复方中的有效成分并据此较快速地探明其药效物质基础,同时辅助阐明中药复方的配伍机制和意义,对中药新药的研发起到加速和推动作用。文中作者总结了一些血清药物化学的成功实践经验,并对血清药物化学的研究方法进行了归纳和概述。     

Flavocoxid is as effective as naproxen for managing the signs and symptoms of osteoarthritis of the knee in humans: a short-term randomized,double-blind pilot study

Flavocoxid (Limbrel), a proprietary mixture of flavonoid molecules (baicalin and catechin), was tested against a traditional nonsteroidal anti-inflammatory drug, naproxen, for the management of the signs and symptoms of moderate osteoarthritis (OA) in humans. Discomfort and global disease activity were used as the primary end points, and safety assessments were also taken for both treatments as a secondary endpoint. In this double-blind study, 103 subjects were randomly assigned to receive either flavocoxid [500 mg twice daily (BID)] or naproxen (500 mg BID) in a 1-month onset of action trial. Outcome measures included the short Western Ontario and McMaster University Osteoarthritis Index, subject Visual Analogue Scale for discomfort and global response, and investigator Visual Analogue Scale for global response and fecal occult blood. Both flavocoxid and naproxen showed significant reduction in the signs and symptoms of knee OA (P ≤ .001). There were no statistically detectable differences between the flavocoxid and naproxen groups with respect to any of the outcome variables. Similarly, there were no statistically detectable differences between the groups with respect to any adverse event, although there was a trend toward a higher incidence of edema and nonspecific musculoskeletal discomfort in the naproxen group. In this short-term pilot study, flavocoxid was as effective as naproxen in controlling the signs and symptoms of OA of the knee and would present a safe and effective option for those individuals on traditional nonsteroidal anti-inflammatory drugs or cyclooxygenase-2 inhibitors. A low incidence of adverse events was reported for both groups.     

Seizures induced by aminooxyacetic acid in mice: pharmacological characteristics

Systemic (s.c.) administration of aminooxyacetic acid (AOAA) in mice triggered clonic convulsions with a CD50 (convulsive dose) of 68 mg/kg (range 54-86). AOAA also induced clonic convulsions in mice subjected to intracerebroventricular administration of the drug with a CD50 of 0.04 mumols (range 0.028-0.06). At the onset of convulsions induced by systemic AOAA (CD97;150 mg/kg), the GAD activity in the frontal cortex and hippocampus was not affected. GABA mimetic drugs, progabide and gabaculine, had no effect on convulsions induced by AOAA. Convulsions induced by systemic administration of AOAA were blocked by diazepam, phenobarbital, and valproate. Ethosuximide, trimethadione, acetazolamide, diphenylhydantoin, and carbamazepine remained ineffective. L-Phenylisopropyladenosine was also found to protect mice against AOAA-induced convulsions, whereas atropine and baclofen had no effect. The seizures induced by intracerebroventricular administration of AOAA (CD97; 0.1 mumols) were blocked by coadministration of preferential N-methyl-D-aspartate antagonists, D-(-)-2-aminophosphonoheptanoic (AP7), 3-[+/-)-2-carboxypiperazine-4-yl)-propyl-1-phosphonic (CPP), and kynurenic acid (KYNA); preferential quisqualate/kainate antagonists, 6-cyano-7-nitro-quinoxaline-2,3-dione and gamma-D-glutamylaminomethylsulphonic acid, remained inactive in the range of dosages sufficient to block seizures induced by quisqualic acid or kainic acid. The antagonistic action of antiepileptic drugs effective against seizures induced by excitatory amino acids (diazepam and valproate), and drugs acting on excitatory amino acid receptors (AP7, CPP, and KYNA) upon seizures induced by AOAA suggests an involvement of excitatory neurotransmission in the convulsant action of the drug.     

Gold complex research in medical science. Difficulties with experimental design

Despite the use of gold complexes in modern medicine for over 100 years and the use of gold complexes in the management of rheumatoid disease for more than 60 years, the definitive mechanisms of action for efficacy and for toxicity have not been established. Gold is a group 1b metal in the periodic table with several oxidation states but it is only Au(I) which is active in the biological milieu. Gold sodium thiomalate is not only a polymeric structure, but also has the chiral ligand, thiomalic acid. Gold sodium thiomalate thus can exist in several different physical states which may have different biological activity. In addition the pharmacokinetic profile of gold complexes has been of little value in the understanding of either the mechanism of action, efficacy or toxicity for both the injectable and the oral gold complexes. Many authors have misinterpreted research data on the activities of gold complexes because they compared gold complexes of different structures, and gold complexes which exist at different pH. Experimental work in our laboratory has identified that gold sodium thiomalate is a mixture and can exist as either a yellow or a colourless solution. These have some similar but several different biological activities. Many factors contribute to the lack of understanding of the action of gold complexes. Some of these factors are related to the wide variation in physical structure and biological activities exhibited by these compounds.