红霉素环11,12-碳酸酯与罗红霉素双盲双模拟随机对照治疗细菌性感染

目的：评价红霉素环11，12－碳酸酯治疗呼吸系统和皮肤软组织细菌性感染的安全性和有效性。方法：以罗红霉素为对照，进行多中心、区组随机、双盲双模拟对照试验。红霉素环11，12－碳酸酯片250－500mg/次，每日2次，口服，疗程5－10d。罗红霉素片150－300mg／次，每2次，疗程5－10d。结果：试验组、对照组各病种的极效率分别为90.00%与77.27％；不同细菌感染者的临床有效率分别为89.47%与76.19%；细菌清除率分别为100％（19／19）与95.24%（20／21），试验组与对照组各对应指标差异无统计学意义（P＞0.05）；不良反应结果显示，红霉素环11，12－碳酸酯可引起轻微消化道症状，及实验室肝功能的异常，其不良反应发生率为12.00%，罗红霉素可引起轻微肝功能异常，无需处理可自行缓解，不良反应发生率为3.85%，两组指标差异无统计学显著性（P＞0.05），试验期间未出现严重不良反应。结论：红霉素环11，12－碳酸酯作为一种新型大环内酯类抗菌药物，抗菌活性较强，使用方便，可安全有效地治疗由敏感菌引起的轻、中度感染，值得临床推广应用。     

红霉素环11,12-碳酸酯于小鼠体内的抗菌活性研究

目的 评价红霉素环11，12-碳酸酯的体内抗菌活性。方法 采用小鼠腹腔感染模型，观察红霉素环11，12-碳酸酯口服对临床分离的金葡菌、化脓链球菌、肺炎链球菌感染小鼠的体内疗效，并与罗红霉素、红霉素进行比较。结果 红霉素环11，12-碳酸酯口服对金葡菌15、金葡菌91—29、化脓链球菌94—3、化脓链球菌556、肺炎链球菌9—9、肺炎链球菌9—5感染小鼠的ED50值分别为38．84、37．08、8．62、9．15、12．76、31，42mg／kg，抗菌活性比红霉素强2～8倍，与罗红霉素相近。结论 红霉素环11，12-碳酸酯对金葡菌、化脓链球菌和肺炎链球菌感染小鼠均有较强的保护作用，抗菌活性明显优于红霉素，与罗红霉素相近。     

阿奇霉素与红霉素治疗急性细菌性感染的临床评价

目的：评价阿奇霉素注射液治疗急性呼吸道感染、泌尿道感染及皮肤软组织感染的安全性和有效性。方法：阿奇霉素注射液静脉滴注，每次250mg,qd，首次剂量加倍，疗程5d。对照药红霉素每日1—1．5g，分1—2次静脉滴注，疗程7—14d。结果：阿奇霉素注射液与红霉素随机对照治疗呼吸道、泌尿道及皮肤软组织感染32例，其中试验组17例，对照组15例。试验组与对照组的临床有效率分别为94．1％与86．7％，细菌清除率分别为100．0％与76．9％；不良反应发生率分别为10．53％与20．00％。以上结果经统计学处理差异无显著性。结论：阿奇霉素注射液静脉点滴，每次250mg，qd，首次剂量加倍，对敏感致病菌及支原体引起的轻、中度呼吸道感染，泌尿系感染及皮肤软组织感染均有很好临床疗效和细菌学疗效，不良反应低。     

阿奇红霉素与罗红霉素随机对照治疗30对细菌性感染的临床评价

阿奇红霉素为一新的ａｚａｌｉｄｅ类抗生素，为评价其安全性及有效性，我们以罗红霉素为对照药，进行随机对照试验治疗细菌性感染６０例，阿奇红霉素组３０例，剂量第一日５００ｍｇ，以后４日２５０ｍｇ，每日一次；罗红霉素组３０例，第一日３００ｍｇ ｂｉｄ，以后４日１５０ｍｇ ｂｉｄ，疗程均为５ｄ。两组痊愈显效率分别为９３．３％及９０．０％，细菌清除率分别为９３．３％及８６．７％，不良反应发生率均为１０．０％。     

国产与进口azithromycin随机对照试验的临床评价

为评价国产ａｚｉｔｈｒｏｍｙｃｉｎ（ＡＺＭ）在临床治疗急性细菌性感染病人的有效性与安全性，我们以进口ＡＺＭ为对照药，进行随机对照试验治疗细菌性感染２００例。国产与进口ＡＺＭ组各１００例，治疗呼吸系统和皮肤软组织感染均为每日１次，首次５００ｍｇ，以后每次２５０ｍｇ，疗程７ｄ，治疗淋病均为单次口服１ｇ即可。两组痊愈率分别为８０．０％及８４．０％，有效率分别为９３．０％及９１．０％，细菌清除率分别为９３．３％及９２．１％，不良反应发生率分别为７％及６％，以上结果经统计学处理无显著性差异。国产ＡＺＭ临床疗效肯定，使用安全、方便。     

红霉素环11,12-碳酸酯的体外抗菌活性研究

目的评 价红霉素环11，12-碳酸酯的体外抗菌活性。方法 采用琼脂平皿二倍稀释法测定国产和进口红霉素环11，12-碳酸酯对临床分离致病菌的体外抗菌作用，并与红霉素、罗红霉素、克拉霉素、地红霉素、阿奇霉素和乙酰螺旋霉素进行了比较。结果 国产和进口红霉素环11，12-碳酸酯对579株临床分离菌的抗菌活性相近，对革兰氏阳性菌和厌氧菌的抗菌活性比红霉素强2～8倍，优于罗红霉素、克拉霉素、地红霉索、阿奇霉素、乙酰螺旋霉素，但对革兰氏阴性菌的抗菌活性稍弱于阿奇霉素。红霉索环11，12-碳酸酯对金葡菌显示抑菌作用，对化脓链球菌在2～4倍MIC浓度时显示杀菌作用；红霉素环11，12-碳酸酯抗金葡菌和化脓链球菌的活性随着pH的增加而增强，接种量和血清浓度对国产红霉素环11，12-碳酸酯抗金葡菌和化脓链球菌的活性无明显影响。结论 红霉素环11，12-碳酸酯具有较强的体外抗菌活性，国产红霉素环11，12-碳酸酯抗菌活性与进口相近，优于红霉素、罗红霉素、克拉霉素、地红霉素、阿奇霉素和乙酰螺旋霉素。     

帕珠沙星与左氧氟沙星治疗急性细菌性感染临床评价

目的：评价甲磺酸帕珠沙星氯化钠注射液治疗急性细菌性感染包括呼吸道感染、泌尿道感染以及皮肤软组织的安全性和有效性。方法：采用区组随机化、盲法对照、多中心临床试验的设计方法，选用左氧氟沙星作为对照药，其中皮肤软组织感染病例采用开放性试验设计方法。结果：在本次随机临床试验中共入选257例使用帕珠沙星或其对照药左氧沙星治疗急性呼吸系统、泌尿系统感染的病例，有243例进入PP分析，其临床总痊愈率分别为65．3％和66．4％，总有效率分别为93．2％和96．0％，细菌清除率分别为87．1％和90．6％，相关不良反应发生率分别为10．3％和7．6％，两组间的临床疗效、细菌清除率和不良反应发生率比较均无显著差异，另外入选30例使用帕珠沙星治疗皮肤软组织感染的开放病例，有29例进入PP分析，其临床痊愈率为51．7％，临床有效率为86．2％，细菌清除率为95．8％，不良反应发生率为3．3％。结论：甲磺酸帕珠沙星是治疗常见急性细菌性呼吸道感染、泌尿系统感染及皮肤软组织感染较为安全、有效的抗菌药物。     

麦白霉素与麦迪霉素随机双盲对照治疗细菌性感染101例临床观察

麦白霉素为一大环内酯类抗生素，为评价其安全性及有效性，我们以进口麦迪霉素为对照药，进行多中心随机双盲对照试验（药品包装盒上仅标名Ａ、Ｂ），治疗呼吸道感染及皮肤软组织感染１０１例．其中５１例用Ａ药治疗，５０例用Ｂ药治疗（每次２００～４００ｍｇ口服，每日３次，疗程７～１４天）。两组有效率分别为８０．４％和８２．０％，细菌清除率均为８３．３％，两组不良反应发生率分别为７．８４％与６．００％，不良反应轻微，以上结果经统计学处理无显著性差异。     

麦白霉素与麦迪霉素随机双盲对照治疗细菌性感染101例…

麦白霉素为一大环内酯类抗生素，为评价其安全性及有效性，我们以进口麦迪霉素为对照药，进行多中心随机双盲对照试验（药品包装盒上仅标名Ａ、Ｂ），治疗呼吸道感染及皮肤软组织感染１０１例，其中５１例用Ａ药治疗，５０例用Ｂ药治疗（每次２００￣４００ｍｇ口服，每日３次，疗程７￣１４天）。两组有效率分别为８０．４％和８２．０％，细菌清除率均为８３．３％，两组不良反应发生率分别为７．８４％和６．００％，不良反应轻微     

盐酸左氧氟沙星氯化钠注射液与氧氟沙星注射液随机对照治疗细菌性感染207例疗效及不良反应观察

为评价国产盐酸氟沙星氯化钠注射液治疗细菌性感染的有效性和;安全性,采用多中心随机对照平行开放试验方法,以氧氟沙星注射液为对照药,治疗呼吸系统、消化系统、泌尿生殖系统及皮肤软组织感染患者２０７例,其中试验组１０４例,对照组１０３例。盐酸左氧氧氟沙星氯化钠注射液２００ｍｇ静脉滴注,每日１次,对照药氧氟沙星注射液２００ｍｇ静脉滴注,每天２次,疗程消化系统感染为５～１０天,呼吸系统、泌尿生殖系统及皮肤软组     

Polymorphism, pseudopolymorphism, and amorphism of peracetylated alpha-, beta-, and gamma-cyclodextrins

Polymorphism, pseudopolymorphism, and amorphism of hexakis(2,3,6-tri-O-acetyl)-alpha-cyclodextrin (TAalphaCyD), heptakis(2,3,6-tri-O-acetyl)-beta-cyclodextrin (TAbetaCyD), and octakis(2,3,6-tri-O-acetyl)-gamma-cyclodextrin (TAgammaCyD) were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffractometry (XRPD), Fourier transform infrared spectroscopy (FTIR) and optical microscopy. An anhydrous and a bi-hydrate crystalline forms of TAalphaCyD, two monotropic anhydrous polymorphs and three pseudopolymorphs (i.e. methanolate, hydrate, and isopropanolate-hydrate) of TAbetaCyD, as well as two monotropic anhydrous polymorphs and isostructural pseudopolymorphs (e.g. hydrate and isopropanolate-hydrate) of TAgammaCyD were isolated and characterized. The amorphous forms of each TACyD were also obtained. Thermal data for desolvation of TAalphaCyD.2H2O and TAbetaCyD.CH3OH were reconciled with their crystal packing features. Melting temperatures and enthalpies of the crystalline forms of each TACyD can be referred to for possible solid-state interactions with drugs.     

Storage,release, uptake,and inactivation of purines

Adenine nucleotides are released into the interstitial space during platelet thrombus formation and neurotransmission. ATP has also been reported to be released from the heart and endothelial cells in some studies. Ecto ATPase, ADPase, and 5′-nucleotidase activities capable of hydrolyzing ATP sequentially to adenosine are present in many cell types and may serve to terminate the actions of the nucleotides. The opposing effects of adenosine and ATP on the same cell types have suggested a modulatory role for adenosine of the actions of extracellular ATP and that the rates of hydrolysis of nucleotides might be regulated. Consistent with this it has been found that the balance between feedforward inhibition of 5′-nucleotidase by ADP and/or ATP and preferential delivery of AMP from ADPase to 5′-nucleotidase determines the rate of adenosine production and that this differs in different cell types. Alternatively, adenosine may be produced intracellularly as a result of an imbalance between energy demand and supply. There are at least two different cytosolic forms of 5′-nucleotidase. Degradation of ATP during increased metabolic activity results in an increase in intracellular AMP concentration. Either cytosolic enzyme has a high KM (2–5 mM) and would thus respond to this increase with a proportional rise in the rate of adenosine production. The nucleoside transporter is essential to allow the diffusion of adenosine to extracellular receptor sites. In general, adenosine must be taken up via the nucleoside transporter before it is inactivated either by phosphorylation by adenosine kinase in the micromolar range or by deamination by adenosine deaminase at higher concentrations. © 1993 Wiley-Liss, Inc.     

New synthesis of benzo-delta-carbolines, cryptolepines, and their salts: in vitro cytotoxic, antiplasmodial, and antitrypanosomal activities of delta-carbolines, benzo-delta-carbolines, and cryptolepines

The paper describes, in its first part, a new synthesis of benzo-delta-carbolines, cryptolepines, and their salts. The strategy is based on the association between halogen-dance and hetero-ring cross-coupling. It is fully convergent and regioselective with interesting overall yields from 27% to 70%. A halogen-dance mechanism in quinoline series is also proposed. The formal synthesis of potential antimalarial compounds and the first total synthesis of 11-isopropylcryptolepine are also described. In the second part, cytotoxic activity against mammalian cells and activities against Plasmodium falciparum and Trypanosoma cruzi of benzo-delta-carbolines and delta-carbolines were evaluated in vitro to study the structure-activity relationships. For benzo-delta-carbolines, methylation at N-5 increases the cytotoxic and antiparasitic activities. A further alkylation on C-11 generally increases the cytotoxic activity but not the antiparasitic activity, cryptolepine and 11-methylcryptolepine being the most active on both parasites. Taking advantage of the fluorescence of the indoloquinoline chromophore, cryptolepine was localized by fluorescence microscopy in parasite DNA-containing structures suggesting that these compounds act through interaction with parasite DNA as proposed for cryptolepine on melanoma cells. For delta-carbolines, methylation at N-1 is essential for the antimalarial activity. 1-Methyl-delta-carboline specifically accumulates in the intracellular parasite. It has weak cytotoxic activity and can be considered as a potential antimalarial compound.     

Stereospecific and circadian-phase-dependent kinetic behavior of d,l-, l-, and d-propranolol in plasma, heart, and brain of light--dark-synchronized rats

In light--dark-synchronized male rats, the kinetic behavior of d,l-, l-, and d-propranolol after single (1.78 and 8.89 mg/kg) or multiple drug administration (6 X 8.89 mg/kg) was studied in plasma, heart, and brain both in the light period (L) and in the dark period (D). With either dosage regimen the kinetics of racemic propranolol displayed a temporal dependency, elimination half-lives in plasma, heart, and brain being shorter during D than during L. This was observed with the stereoisomers only after single drug application with no circadian phase dependency at steady-state concentrations. On the other hand, the kinetic behavior of l- and d-propranolol exhibited pronounced stereospecificity in that t1/2 Beta, Vdbeta, plasma clearance, and drug accumulation in heart and brain were greater for l-propranolol than for the d-isomer. Stereospecific differences in t1/2 beta and elimination rate were more pronounced during D. In the light of the flow-dependent hepatic extraction of propranolol it is unlikely that daily variations in microsomal liver enzyme activity are responsible for the chronopharmacokinetics of propranolol. It is assumed that daily variations in liver blood flow, which is more effectively reduced by beta-receptor blockade in the period of increased sympathetic tone during D, are mainly responsible for the chronopharmocokinetics of the therapeutically used d,l-propranolol.     

Synthesis,anti-inflammatory,analgesic, and antibacterial activities of some triazole,triazolothiadiazole, and triazolothiadiazine derivatives

This study is concerned with the synthesis of new 1,2,4-triazoles, 1,3,4-thiadiazoles, and 1,3,4-thiadiazines derivatives. Derivatives 3a–i were obtained by condensation of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole 1 with the appropriate aldehyde. Compounds 4a–i were synthesized in a one pot reaction involving compounds 3a–i, formaldehyde, and morpholine. Condensation of compound 1 with the appropriate acids or 4-substituted phenacyl bromide gave compounds 6a–d and 8a–f respectively. The chemical structures of the newly synthesized derivatives were elucidated using different spectral and elemental methods of analysis. All compounds were evaluated for their anti-inflammatory activity and the most potent derivatives were tested for their analgesic activity using indomethacin as a reference drug. In addition, ulcerogenicity and LD₅₀ for the most active compounds were evaluated. Moreover, the antibacterial activities of the newly synthesized derivatives were investigated.     

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.     

Thyroid hormone, glucocorticoids, and prolactin at the nexus of physiology, reproduction, and toxicology

A symposium at the 2003 Annual Meeting of the Society of Toxicology brought together an expert group of endocrinologists to review how non-reproductive hormones can affect the endocrine system. This publication captures the essence of those presentations. Paul Cooke and Denise Holsberger recapitulate the evidence of how thyroid hormones affect male and female reproduction, and reproductive development. Ray Witorsch summarizes the many effects of glucocorticoids on the reproductive system. Finally, Paul Sylvester reviews the mechanism of action of prolactin, and reminds us that this ancient hormone has many functions beyond lactation.     

Pharmacokinetics of Liquiritigenin in Mice,Rats, Rabbits,and Dogs,and Animal Scale-Up

Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC_0?t) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r > 0.968) between log CL (or CL/f_u) (L/h) and log species body weight (W) (kg) [CL (or CL/f_u) = 3.29 (34.0) W^{0.723 (0.789)}] and log V_ss (or V_ss/f_u) (L) and log W (kg) [V_ss (or V_ss/f_u) = 0.340 (3.52) W^{0.882 (0.948)}]. Interspecies scale-up of plasma concentration–time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration–time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4327–4342, 2009     

Comparison of natriuretic, uricosuric, and antihypertensive properties of tienilic acid, bendrofluazide, and spironolactone.

The antihypertensive properties of the new diuretic tienilic acid were investigated. Thirteen previously untreated hypertensive patients took part in a double-blind crossover study in which 30 days' treatment with tienilic acid 250 mg, bendrofluazide 5 mg, and spironolactone 100 mg were compared. Bendrofluazide caused the greatest natriuresis on the first treatment day and the most rapid fall in blood pressure. The ultimate antihypertensive effect of all three drugs was similar. Tienilic acid caused a noticeable reduction in serum urate concentrations and a rise in urate clearance, in contrast to the other two agents, which caused slight urate retention. Tienilic acid and bendrofluazide caused falls and spironolactone a rise in plasma potassium concentrations. No untoward effects were seen from any of the drugs. It is concluded that tienilic acid is a moderately potent diuretic that lowers plasma urate concentrations. It may be the drug of first choice for hypertensive patients who already have gout or are likely to develop it when taking thiazide diuretics.     

Combination action of sisomicin, dibekacin and cefotetan, cefotaxime, latamoxef, and cefsulodin against Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa

The combined actions of sisomicin (SISO), dibekacin (DKB) and cefotetan (CTT), cefotaxime (CTX), latamoxef (LMOX), cefsulodin (CFS) against E coli KC-14, S. marcescens T-55 and P. aeruginosa E-2 were studied. The following results were obtained. The combination of SISO-CTT, SISO-CTX, SISO-LMOX, SISO-CFS, DKB-CTT, DKB-CTX, DKB-LMOX and DKB-CFS using the checker board dilution method on E. coli KC-14, S. marcescens T-55, P. aeruginosa E-2 were found to have a synergistic effect and the minimum FIC index values were 0.26--0.50 for SISO and 0.28--0.75 for DKB, respectively. With the killing kinetic method, all combinations tested showed a synergistic effect.