NO偶联双氯芬酸衍生物抗炎、镇痛、解热作用实验研究

目的：考察NO偶联双氯芬酸衍生物(澳通，CO-3)的抗炎、镇痛、解热作用。方法：通过小鼠耳二甲苯致炎、角叉菜胶致大鼠足跖肿胀、大鼠棉球肉芽肿及Ⅱ型胶原所致的大鼠关节炎等实验模型，观察CO-3的抗炎作用；通过小鼠醋酸扭体、热板刺激和大鼠甩尾等实验模型，观察CO-3的镇痛作用；通过大鼠啤酒酵母致热实验模型，观察CO-3的解热作用。结果：CO-3可明显抑制二甲苯所致小鼠耳肿胀、角叉菜胶致大鼠足跖肿胀、大鼠棉球肉芽组织增生及Ⅱ型胶原所致的大鼠关节炎；能显著抑制醋酸引起的小鼠扭体反应及提高甩尾及热板刺激的致痛阈值；对啤酒酵母致热大鼠有明显的解热作用。结论：CO-3具有良好的抗炎、镇痛、解热作用。     

三叶青提取物抗炎、镇痛及解热作用的实验研究

目的:探讨三叶青提取物(ERT)的抗炎、镇痛及解热作用,并验证其相关功效.方法:以小鼠腹腔毛细血管通透法、小鼠耳肿胀法及大鼠足肿胀法观察其抗炎作用;以小鼠扭体法、热板法观察其镇痛作用;以干酵母致热法及2,4-二硝基苯酚致热法观察其解热作用.结果:三叶青提取物能明显抑制小鼠腹腔毛细血管炎性渗出,抑制二甲苯所致小鼠耳廓肿胀及10%蛋清致大鼠足跖肿胀;减少醋酸致小鼠扭体次数,提高热板法小鼠痛阈值;并降低干酵母和2,4-二硝基苯酚致大鼠发热模型的体温.结论:三叶青提取物具有较好的抗炎、镇痛及解热作用,与其相关的中医临床功效及主治相符.     

穿心莲内酯衍生物DAP-Na的药效学研究

目的考察穿心莲内酯衍生物DAP-Na的解热、抗炎、抗菌作用.方法采用干酵母致大鼠发热及内毒素致家兔发热两种模型观察DAP-Na的解热作用;蛋清致大鼠足肿胀及二甲苯致小鼠耳肿胀两种炎症模型观察DAP-Na的抗炎作用;试管培养法观察DAP-Na的抗菌作用.结果DAP-Na量效关系明显:300,150mg/kg对干酵母所致的大鼠发热及内毒素所致的家兔发热均有良好的解热作用;400,200,100mg/kg对蛋清所致的大鼠足肿胀及二甲苯所致的小鼠耳肿胀均有良好抗炎作用;试管培养法观察显示DAP-Na对大肠杆菌、痢疾杆菌、金葡菌及肺炎球菌均无作用.结论 DAP-Na有较好的解热及抗炎作用,但体外无抗菌作用.     

金苓痛风舒微丸抗炎镇痛作用的实验研究

目的探讨金苓痛风舒微丸的抗炎、镇痛作用。方法采用二甲苯致小鼠耳廓肿胀实验、角叉菜胶致大鼠足跖肿胀实验观察其抗炎作用;采用冰醋酸致痛小鼠扭体实验、小鼠尾根部加压致痛实验观察其镇痛作用。结果金苓痛风舒微丸可明显抑制二甲苯所致的小鼠耳廓的炎症肿胀（P〈0.05）;有效抑制角叉菜胶致大鼠足跖肿胀程度（P〈0.05）;对醋酸致小鼠扭体反应有明显对抗作用（P〈0.05）;显著升高小鼠痛阈值。结论金苓痛风舒微丸具有显著的抗炎、镇痛作用。     

穿心莲内酯衍生物DAP-Na的药效学研究

目的　考察穿心莲内酯衍生物DAP-Na的解热、抗炎、抗菌作用。方法　采用干酵母致大鼠发热及内毒素致家兔发热两种模型观察DAP- Na的解热作用;蛋清致大鼠足肿胀及二甲苯致小鼠耳肿胀两种炎症模型观察DAP -Na的抗炎作用;试管培养法观察DAP- Na的抗菌作用。结果　DAP- Na量效关系明显: 300, 150mg/kg对干酵母所致的大鼠发热及内毒素所致的家兔发热均有良好的解热作用; 400, 200, 100mg/kg对蛋清所致的大鼠足肿胀及二甲苯所致的小鼠耳肿胀均有良好抗炎作用;试管培养法观察显示DAP -Na对大肠杆菌、痢疾杆菌、金葡菌及肺炎球菌均无作用。结论　DAP -Na有较好的解热及抗炎作用,但体外无抗菌作用。     

风热流浸膏解热镇痛和抗炎作用的实验研究

目的观察风热流浸膏的抗炎、镇痛和解热作用。方法采用二甲苯致小鼠耳肿胀、角叉菜胶致大鼠足趾肿胀的模型观察抗炎作用;采用乙酸和热刺激致小鼠疼痛的模型观察镇痛作用;采用2,4-二硝基酚和酵母粉致大鼠发热的模型观察解热作用。结果风热流浸膏能减轻小鼠耳肿胀和大鼠足趾肿胀炎症反应,缓解乙酸和热刺激所致疼痛,降低2,4-二硝基酚和酵母粉致大鼠发热的体温。结论风热流浸膏具有显著的抗炎、镇痛和解热作用。     

茶皂素抗炎镇痛作用的实验研究

目的探讨茶皂素的抗炎镇痛作用。方法采用二甲苯致小鼠耳廓肿胀、角叉菜胶致大鼠足跖肿胀、检测大鼠炎性组织中前列腺素E2（PGE2）含量、大鼠棉球肉芽肿实验观察茶皂素抗炎作用;通过小鼠热板致痛实验观察其镇痛作用。结果茶皂素能够明显抑制二甲苯致小鼠耳廓肿胀（P〈0.01）,减轻角叉菜胶致大鼠足跖肿胀（P〈0.01）,使其局部炎性组织中PGE2含量降低（P〈0.01）,抑制大鼠棉球肉芽肿的增重（P〈0.01）,延长小鼠热板痛反应时间（P〈0.05和P〈0.01）。结论茶皂素具有明显的抗炎镇痛作用。     

双花合剂解热抗炎作用的实验研究

目的研究双花合剂的解热抗炎作用。方法抗炎实验采用二甲苯致小鼠耳廓肿胀和角叉菜胶致大鼠足跖肿胀等常规抗炎实验法;观察酵母发热实验对大鼠体温的影响。结果双花合剂可明显抑制二甲苯致小鼠耳廓肿胀及角叉菜胶引起的大鼠足肿胀,可显著抑制大鼠发热。结论双花合剂有明显的解热、抗炎作用。     

前列宁栓抗炎镇痛作用实验

目的:研究前列宁栓的抗炎、镇痛作用。方法:采用二甲苯所致小鼠耳廓肿胀实验、角叉菜胶致大鼠足跖肿实验、大鼠棉球肉芽肿的影响实验、小鼠腹腔毛细血管通透性实验,细菌性(大肠杆菌)前列腺炎的抗炎作用。采用醋酸致小鼠扭体反应实验和小鼠热板法实验观察了前列宁栓的镇痛作用。结果:前列宁栓可明显抑制二甲苯所致的小鼠耳廓炎症;在多数时间降低角叉菜胶致大鼠足跖肿胀;明显抑制大鼠棉球肉芽肿的生成;明显降低小鼠腹腔毛细血管通透性;明显抑制大鼠细菌性前列腺炎;明显降低醋酸致小鼠扭体反应数;明显升高小鼠痛阈值。结论:前列宁栓具有明显的抗炎、镇痛作用。     

右旋布洛芬凝胶的抗炎镇痛作用

目的 考察右旋布洛芬凝胶的抗炎、镇痛作用。方法 以角叉菜胶致大鼠足跖肿胀、二甲苯致小鼠耳廓肿胀、大鼠辐射热刺激及小鼠醋酸扭体法，观察右旋布洛芬凝胶的局部抗炎、镇痛作用。结果 2.5%、4.0%右旋布洛芬凝胶局部涂药能显著抑制角叉菜胶所致大鼠足跖肿胀及二甲苯所致小鼠耳廓肿胀，并能明显提高大鼠对光热刺激的痛阈，减少小鼠醋酸刺激的扭体次数。结论 2.5%右旋布洛芬凝胶局部外用具有显著的抗炎、镇痛活性。     

Susceptibility to erythromycin of anaerobes of the genera Bacteroides, Fusobacterium, Sphaerophorus, Veillonella, Clostridium, Corynebacterium, Peptococcus, Peptostreptococcus

The minimal inhibitory concentrations (MIC) of erythromycin were determined by broth dilution tests for 313 anaerobic strains, most of which were clinical isolates. All the gram-positive anaerobes tested (84 Peptococcaceae, including 21 Peptostreptococcus anaerobius and 15 Peptococcus variabilis; 65 Corynebacterium acnes and 29 Clostridium strains, including 13 C. perfringens) were sensitive (MIC values 0.012 through 3.12 microgram erythromycin/ml); so were 111 cultures of gram-negative anaerobes (52 Bacteroides fragilis, 12 B. thetaiotaomicron, 7 B. vulgatus, 13 B. oralis, 4 B. melaninogenicus, 10 Sphaerophorus necrophorus, 2 Veillonella sp., 11 members of other species). Erythromycin at concentrations of 6.25 through 200.0 microgram/ml was active against 24 strains (1 B. fragilis, 4 Fusobacterium fusiforme, 9 Sph. freundi, 10 Sph. varius). The present results are compared to the limited number of reports existing with regard to the susceptibility of anaerobes to erythromycin.     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Strength of drug habits: For heroin,morphine, methadone,alcohol, barbiturates,pentobarbital, benzedrine,cocaine, and marijuana

The drug habits for 78 confirmed opiate addicts were studied on eight scales from the Process Association Test of Addiction (PATA) for many drug names. Through cluster analysis eight stages of addiction were defined: “to be clean”, “to learn about drugs”, “to hustle”, “to chip” (also “to be high”), to be psychologically dependent or “to need a shot”, “to be hooked”, “to kick a habit” and “to be in treatment”. Associations stimulated by the words heroin and morphine were very similar over the eight stages of addiction in opiate addicts. The subjects were especially inclined to associate morphine and heroin with the most severe level of addiction, “to be hooked”. Associations to both methadone and cocaine were elevated at the “hooked” stage, but in other respects associations to these drugs were opposite. Thus, associations to cocaine were focused on the stage of psychological dependence and the lower intermediate stage of addiction, “to chip” and “to be high”, whereas associations to methadone suggested a turning away from addiction as indicated by avoidance associations (“to come down” and “to kick a habit”) as well as associations to “treatment” and “to be clean”. Marijuana, Benzedrine, “goofball” (barbiturates) and alcohol habits were prominent at an intermediate stage of addiction (“to chip” and “to be high”). Avoidance associations were common for Benzedrine and “goofballs” (also pentobarbital) but not for marijuana or alcohol. “Hustling” associations were frequent for marijuana but not for alcohol.     

Simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone

A gas-liquid chromatographic method for the simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone in serum is described. The drugs and the internal standard, prilocaine, are extracted from 1 ml of serum. The procedure involves a two-step extraction and injection of the extract into a gas chromatograph equipped with a 10-ft OV-11 glass column and a nitrogen-phosphorus detector. The temperature gradient program results in a run time of 16 min and retention times for meperidine, prilocaine (internal standard), lidocaine, etidocaine, mepivacaine, methadone, and bupivacaine of 3.8, 5.4, 6.0, 8.7, 11.0, 11.7, and 14.8 min, respectively. Standard curves for all drugs were linear over the 80 to 2,000-ng/ml range and recovery of all components averaged 97 +/- 2% with the lowest detection limit of 10 ng/ml for all drugs except meperidine and methadone, which were 20 ng/ml. The within-day coefficients of variation ranged from 12 to 8% at 500 ng/ml. The day-to-day coefficients of variation of the slope and intercept values ranged from 2 to 0% and 130 to 3%, respectively. Response factors of the nitrogen-specific collector varied with the drug analyzed and resulted in peak area variation at constant offset and attenuation of 30%. This method is intended and adequate for therapeutic monitoring of chronically treated pain patients who are being given various combinations of local anesthetic and/or narcotic agents.     

New antiretroviral drugs: a review of the efficacy,safety, pharmacokinetics,and resistance profile of tipranavir,darunavir, etravirine,rilpivirine, maraviroc,and raltegravir

Background: The introduction and approval of new antiretroviral agents in the US and Canada bring new opportunities and new challenges. Arguably, for the first time ever, clinicians have the drugs necessary to achieve the goal of suppressing HIV RNA to levels less than 50 copies/mL in even the most treatment-experienced patients and in those with extensive drug-limiting resistance mutations. However, the use of these new agents is complicated by many drug–drug interactions and – to some extent – pre-existing mutations. To derive maximum durability from the use of these newer drugs, a thorough understanding of their indications and limitations is critical. Objective: To thoroughly review the six most recently approved or soon-to-be-approved antiretroviral drugs in the US and Canada: tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Methods: Discussion of the indications for, and pharmacokinetics, resistance profile, activity, toxicity, and clinical trials results of, the six new agents. Results/conclusions: These six new agents have resulted in marked progress towards the goal of being able to provide HIV-infected individuals with the drugs necessary to achieve decades of durable suppression of HIV without substantial toxicity.     

Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey

The physiological disposition of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, has been studied in the mouse, rat, dog, and monkey using 14C- or 3H-labeled drug. Oral doses of fluvastatin were absorbed at a moderate to rapid rate. The extent of absorption was dose-independent and was essentially complete in all four species studied. However, the drug was subject to extensive presystemic hepatic extraction followed by direct excretion via the bile, thus minimizing the systemic burden and yielding high liver/peripheral tissue concentration gradients for fluvastatin and its metabolites. Only at high doses far exceeding the intended human daily dose of ca 0.6 mg kg-1 did fluvastatin bioavailability approach unity, apparently due to saturation of the first-pass effect. Dose-normalized blood levels of fluvastatin and total radioactivity were higher in the dog than in the other species, suggesting a smaller distribution volume in the former. Fluvastatin was partially metabolized before excretion, the extent of metabolism being smallest in the dog and greatest in the mouse. The half-life of intact fluvastatin ranged from 1-2h in the monkey to 4-7h in the dog. Regardless of the dose or dose route, the administered radioactivity was recovered predominantly in feces, with the renal route accounting for less than 8 per cent of the dose. No tissue retention of radioactivity was observed, and material balance was essentially achieved within 96h after dosing.