对HBVHBeAg/HBeAb血清的探讨

对１０１例ＨＢＶ血清中ＨＢＶＤＮＡ进行检测，发现４５例ＨＢｅＡｇ（＋）／ＨＢｅＡｂ（－）血清检出８８．８８％ＨＢＶＤＮＡ（＋），５６例ＨＢｅＡｂ（－）／ＨＢｅＡｂ（＋）血清检出４６．４２％ＨＢＶＤＮＡ（＋），ＨＢｅＡｇ／ＨＢｅＡｂ与ＨＢＶＤＮＡ关系显著性检验，差别无显著性（χ２＝１．１６，Ｐ＞０．０５），ＨＢｓＡｇ滴度与ＨＢｅＡｇ检出无相关性（ｒ＝０，Ｐ＞０．０５）。     

膦甲酸钠联合干扰素治疗慢性乙型病毒性肝炎的临床疗效

目的：比较膦甲酸钠与干扰素联用和单用干扰素治疗慢性乙型肝炎的疗效。方法：选择慢性乙型肝炎患者６１例，分为联合组２３例和干扰素组３８例；联合组用膦甲酸钠４．８ｇ静滴，ｑｄ，疗程１月，合并用干扰素α－１ｂ３００万ｕ，ｉｍ，隔日１次，疗程３个月。干扰素组单用干扰素，以谷丙转氨酶（ＡＬＴ）、乙肝病毒标志物（ＨＢＶＭ）、乙肝病毒ＤＮＡ及前Ｃ区基因野生株和变异株为观察指标，比较不同治疗方案对指标的影响。结果：治疗３个月后联合组与干扰素组对慢性乙肝患者血清ＨＢｅＡｇ／抗－ＨＢｅ转换率分别为４７．８％和２８．９％（Ｐ〉０．０５）。对慢性乙肝患者血清ＨＢＶ－ＤＮＡ的阴转率分别为６９．５％和３４．２％（Ｐ〈０．０１）。对慢性乙肝患者的ＨＢＶ前Ｃ区基因野生株及变异株总阴转率分别为６９．６％和３６．８％（Ｐ〈０．０５），联合组对慢性乙     

舌下含服干扰素单磷酸阿糖腺苷及两药联合抗乙肝病毒疗效追踪观察

本文报告慢性乙肝病人及携带者共４０例。随机分干扰素组２０例，舌下含服２００ＩＵ／次，每日一次，疗程３个月；单磷酸阿糖腺苷组１０例，第１天～５天按１０ｍｇ·ｋｇ￣（－１）·ｄ￣（－１），２次肌注。第６天～２８天按５ｍｇ·ｋｇ￣（－１）·ｄ￣（－１），１次肌注。两药联合组１０例，两药剂量和疗程同上。疗程结束后，经６个月追踪观察，干扰素组ＨＢｅＡｇ转阴８例，伴抗－ＨＢｅ转阳７例；单磷酸阿糖腺苷组ＨＢｅＡｇ转阴２例，伴抗－ＨＢｅ转阳。追踪期部分标记回升，远期效果不及两药联合组。两药联合组血清病毒复制标记转阴早，有６例ＨＢｅＡｇ转阴伴抗－ＨＢｅ转阳。有４例ＨＢＶ－ＤＮＡ转阴。其近期和追踪期效果均比两药单用好。初步提示两药联合治疗组抗病毒效果优于两药单用组。     

拉米夫定治疗慢性乙型肝炎的多中心、随机双盲、安慰剂对照研究

目的：研究拉米夫定对血清乙型肝炎病毒＿脱氧核糖核酸（ＨＢＶ＿ＤＮＡ）阳性的慢性乙型肝炎病毒感染病人的疗效和安全性。方法：４２９例病人,随机分成拉米夫定治疗组（３２２例）和安慰剂对照组（１０７例）。治疗组每日口服拉米夫定１００ｍｇ,对照组服用外形相同的安慰剂每日１片,共１２ｗｋ。结果：治疗组累计９２．２％病人血清ＨＢＶ＿ＤＮＡ阴转（低于１．６ｎｇ／Ｌ）,最终持续阴转率为７８．５％。对照组ＨＢＶ＿ＤＮＡ累计阴转率为１４．１％,最终阴转率为１１％。２组疗效比较Ｐ＜０．０１。治疗前丙氨酸转氨酶（ＡＬＴ）增高的病人,１２ｗｋ时治疗组的ＡＬＴ复常率为６０．３％,对照组为２７％,Ｐ＜０．０１。２组ＨＢｅＡｇ／抗ＨＢｅ的血清转换率差别无显著意义（Ｐ＞０．０５）。２组的不良反应发生率比较,差别无显著意义（Ｐ＞０．０５）。结论：拉米夫定能明显降低血清ＨＢＶ＿ＤＮＡ水平,促使ＡＬＴ恢复正常,不良反应轻,耐受性好。     

膦甲酸治疗慢性乙,丙型肝炎近期疗效观察小结

从１９９５年６月至１９９６年２月，我们用解放军３０２医院华星制药厂生产的膦甲酸注射液治疗了２１例慢性乙型及／或丙型肝炎患者，以评价该药对乙、丙型肝炎的临床抗病毒疗效及不良反应。其中１４例单纯乙型，３例乙、丙型重叠感染，４例单纯丙型。治疗方法为２５００ｍｇ静滴（２ｈ输完）ｑ１２ｈ，疗程２８ｄ。结果：治疗前ＨＢｓＡｇ（＋）１７例，ＨＢｅＡｇ（＋）１２例，ＨＢＶＤＮＡ（＋）１３例，治疗结束时ＨＢｓＡｇ、ＨＢｅＡｇ及ＨＢＶＤＮＡ分别有１例（５．９％）、７例（５８．３％）及１０例（７６．９％）转阴。治疗前抗－ＨＣＶ（＋）５例，ＨＣＶＲＮＡ（＋）７例，治疗结束时抗－ＨＣＶ及ＨＣＶＲＮＡ分别有１例（２０．０％）及４例（５７．１％）转阴，另有２例用药后血清ＨＣＶＲＮＡ浓度下降约９０％。不良反应大多较轻，发生率为４２．９％，主要为纳差、恶心、腹胀、乏力等消化道及全身症状。３例血钾轻至中度降低，仅１例因恶心、呕吐较重于用药第１７天停药。本研究结果提示，按本文给药方法静点膦甲酸可以达到较好的抑制乙肝病毒复制的效果，对丙肝病毒复制很可能也有抑制作用。     

受体异向药物L—HAS—Ara—AMP抗HBV效应的临床研究

目的;观察去唾液酸糖蛋白受体导向药物Ｌ－ＨＡＳ－Ａｒａ－ＡＭＰ的抗ＨＢＶ的临床疗效。方法：应用５ｄ和２８ｄ疗程治疗慢性乙型肝炎２９例,以Ａｒａ－ＡＭＰ治疗２７例为对照。结果：Ｌ－ＨＳＡ－Ａｒａ－ＡＭＰ ５ｄ疗程,１０例ＨＢｅＡｇ阳性阴转３例,８例ＨＢＶ－ＤＮＡ阳性阴转４例。２８ｄ疗程ＨＢｅＡｇ阴转率３１．６％,ＨＢｅＡｇ滴度下降率４７．４％,有治疗效应者７９．０％．;ＨＢＶ－ＤＮＡ阴转率３１．６％     

聚合酶链反应技术检测血清乙肝病毒DNA的结果报告

应用ＰＣＲ技术和ＥＬＩＳＡ法同时检测了乙肝患者血清９７例。结果显示：ＨＢＶ－ＤＮＡ－ＰＣＲ阳性率６７．０％，乙肝五项一项以上阳性率９７．９％，ＨＢｅＡｇ阳性者ＨＢＶ－ＤＮＡ阳性率８９．７％，ＨＢｅＡｇ阴性仍有５１．７％ＨＢＶ－ＤＮＡ阳性，抗－ＨＢｓ阳性者ＨＢＶ－ＤＮＡ阳性率２５．０％，献血员有４．０％ＨＢＶ－ＤＮＡ阳性。结果提示，在乙肝病毒感染检出率方面，乙肝五项高于ＰＣＲ，ＨＢＶ－ＤＮＡ－ＰＣＲ     

苷必妥治疗慢性乙型肝炎及活动性肝硬化的疗效观察

目的：观察苷必妥治疗慢性乙型肝炎及活动性肝硬化的临床疗效。方法：治疗组、对照组各６０例，给予常规护肝药物，治疗组加用苷必妥２ｍｇ，每日１次肌注。疗程３上月。结果：疗程结束时，治疗组ＡＬＴ、ＳＢ复常率明显优于对照组（Ｐ〈０．０１），ＨＢｅＡｇ和ＨＢＶ－ＤＮＡ的阴转率分别为４７．５％和４３．６％，而对照组则分别为１５．４％和５．４％，两组之间有显著性差异（Ｐ〈０．０１）。治疗组活动性肝硬化患者的血清Ⅲ     

诺西肽抗乙肝病毒体外实验研究

以ＨｅｐＧ２．２．２．１５细胞株为模型，以其分泌的ＨＢｓＡｇ、ＨＢｅＡｇ、ＨＢＶＤＮＡ及细胞存活率为观察指标，综合评价了诺西肽体外抗ＨＢＶ效果。结果表明：诺西肽对ＨＢｓＡｇ和ＨＢｅＡｇ的５０％抑制浓度ＩＣ５０分别为＜１２．５和４１．６μｇ／ｍｌ，治疗指数（ＴＩ）分别为＞１６和＞４．８。Ｓｏｕｔｈｅｒｎ结果显示，诺西肽在１２．５μｇ／ｍｌ浓度下对细胞内ＨＢＶＤＮＡ的抑制率为２６．４％。     

羟乙桂胺在肌肉挛缩患者及健康志愿者体内的药物动力学

９名肌肉挛缩患者和６名健康志愿者口服羟乙桂胺片１５ｍｇ／ｋｇ，用ＨＰＬＣ测定血药浓度并计算动力学参数。９名肌肉挛缩患者口服后的达峰时间Ｔｍａｘ（约１ｈ），峰浓度Ｃｍａｘ（５．５±０．８μｇ／ｍｌ）；ｋａ（１．１９±０．１４ｈ－１），ｔ１／２α（１．０８±０．３１ｈ），ｔ１／２β（３．３７±１．０５ｈ），与健康志愿者无显著差异（ｐ＞０．０５）。     

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.