Recent advances in antifungal chemotherapy

For over 50 years, amphotericin B deoxycholate (AmBD) has been the 'gold standard' in antifungal chemotherapy, despite its frequent toxicities. However, improved treatment options for invasive fungal infections (IFIs) have been developed during the last 15 years. Newer antifungal agents, including less toxic lipid preparations of AmBD, triazoles and the echinocandins, have been added to our armamentarium against IFIs. Some of these newer drugs can now replace AmBD as primary therapy (e.g. caspofungin for candidiasis, voriconazole for aspergillosis), whilst others offer new therapeutic options for difficult-to-treat IFIs (e.g. posaconazole for zygomycosis, fusariosis and chromoblastomycosis). It is interesting that extended use of newer antifungals such as fluconazole, despite decreasing the mortality attributed to candidiasis, resulted in selection of species resistant to several antifungals (Candida krusei, Candida glabrata); whilst several publications suggest that prolonged use of voriconazole may expose severely immunocompromised patients to the risk of zygomycosis (breakthrough). On the other hand, the differences in the mode of action of newer antifungals such as echinocandins raise the question whether combination antifungal therapy is more effective than monotherapy. Finally, the availability of an oral formulation with excellent biosafety of several newer antifungals (e.g. posaconazole) makes them candidates for prophylactic or prolonged maintenance therapy.     

New advances in drug discovery

The conference covered the most exciting recent advances in industry and academia in areas related to drug discovery and development. Topics included candidates currently in clinical development, new technologies aimed at facilitating the drug discovery process and potential new targets. Targets in clinical development included inhibitors of lipoprotein-associated phospholipase A2 for atherosclerosis, IL-1beta converting enzyme inhibitors for inflammatory disorders and a novel proteasome inhibitor for cancer therapy. New technologies covered a novel system for screening ion channel function, various applications for RNA interference, different imaging modalities, as well as mRNA microarrays to facilitate toxicological assessment. New targets included the ATP-binding cassette family of transporters and the recently elucidated sulfation pathways.     

Recent advances in the chemotherapy of herpes virus infections

The main categories of antiherpes agents presently used in chemotherapy area reviewed according to the phase of virus replication affected : 1) virus adsorption (adamantane, nonionic surfactants) ; 2) eclipse (interferon) ; 3) virion maturation (nucleoside and nucleotide analogues and phosphonic acid derivatives). Mention is also made of other compounds--different synthetic organic derivatives, photodynamic dyes, metal ions, boric acid, hormones, antibiotics, other natural products (extracts from marine algae, propolis, garlic)--with promising antiviral properties. The difficulties and prospects of viral chemotherapy research are briefly discussed.     

Novel nucleoside strategies for anti-HIV and anti-HSV therapy.

This mini-review describes the structure-activity relationships of several series of new nucleoside analogues. It also points to the possibilities of finding new molecular modifications which could lead to antivirals with activity both against human immunodeficiency viruses (HIV) and herpesviruses.     

Isolation and characterization of an anti-HSV polysaccharide from Prunella vulgaris

A water soluble substance was isolated from a Chinese herb, Prunella vulgaris, by hot water extraction, ethanol precipitation and gel permeation column chromatography. Chemical tests showed that the substance was an anionic polysaccharide. Using a plaque reduction assay, the polysaccharide at 100 microg/ml was active against the herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), but was inactive against cytomegalovirus, the human influenza virus types A and B, the poliovirus type 1 or the vesicular stomatitis virus. The 50% plaque reduction dose of the polysaccharide for HSV-1 and HSV-2 was 10 microg/ml. Clinical isolates and known acyclovir-resistant (TK-deficient or polymerase-defective) strains of HSV-1 and HSV-2 were similarly inhibited by the polysaccharide. Pre-incubation of HSV-1 with the polysaccharide at 4, 25 or 37 degrees C completely abrogated the infectivity of HSV-1, but pre-treatment of Vero cells with the polysaccharide did not protect cells from infection by the virus. The addition of the polysaccharide at 0, 2, 5.5 and 8 h post-infection of Vero cells with HSV-1 at a multiplicity of infection (MOI) of five reduced the 20 h-yield of intracellular infectious virus by 100, 99, 99 and 94%, respectively. In contrast, a similar addition of heparin showed 85, 63, 53 and 3% reduction of intracellular virus yield, respectively. These results suggest that the polysaccharide may inhibit HSV by competing for cell receptors as well as by some unknown mechanisms after the virus has penetrated the cells. The Prunella polysaccharide was not cytotoxic to mammalian cells up to the highest concentration tested, 0.5 mg/ml and did not show any anti-coagulant activity. In conclusion, the polysaccharide isolated from P. vulgaris has specific activity against HSV and its mode of action appears to be different from other anionic carbohydrates, such as heparin.     

New advances in microsphere-based single-dose vaccines

Polymer microspheres have shown great potential as a next generation adjuvant to replace or complement existing aluminum salts for vaccine potentiation. Microsphere-based systems can now be made to deliver subunit protein and peptide antigens in their native form in a continuous or pulsatile fashion for periods of weeks to months with reliable and reproducible kinetics, often obviating the need for booster immunizations in animal models. Microspheres have also shown potential as carriers for oral vaccine delivery due to their protective effects on encapsulated antigens and their ability to be taken up by the Peyer's patches in the intestine. The potency of these optimal depot formulations for antigen may be enhanced by the co-delivery of vaccine adjuvants, including cytokines, that are either entrapped in the polymer matrix or, alternatively, incorporated into the backbone of the polymer itself and released concomitantly with antigen as the polymer degrades. In this article we review the use of polymer microspheres for single-step immunization and discuss future applications for the improvement of vaccines and immunotherapies by utilizing encapsulation technology.     

New advances in NMDA receptor pharmacology

N-Methyl-D-aspartate (NMDA) receptors are tetrameric ion channels containing two of four possible GluN2 subunits. These receptors have been implicated for decades in neurological diseases such as stroke, traumatic brain injury, dementia and schizophrenia. The GluN2 subunits substantially contribute to functional diversity of NMDA receptors and are distinctly expressed during development and among brain regions. Thus, subunit-selective antagonists and modulators that differentially target the GluN2 subunit might provide an opportunity to pharmacologically modify the function of select groups of neurons for therapeutic gain. A flurry of clinical, functional and chemical studies have together reinvigorated efforts to identify subunit-selective modulators of NMDA receptor function, resulting in a handful of new compounds that appear to act at novel sites. Here, we review the properties of new emerging classes of subunit-selective NMDA receptor modulators, which we predict will mark the beginning of a productive period of progress for NMDA receptor pharmacology.     

抗抑郁症药物治疗靶标的研究进展

综述抑郁症发病新机制包括“神经营养学说”和“细胞因子学说”,并从神经可塑性、海马神经发生、下丘脑-垂体-肾上腺轴、免疫系统4个方面介绍了抑郁症药物治疗靶标和相关新药的研究进展。     

骨质疏松治疗药物研究新进展

正骨质疏松症是一种以骨量减少和骨组织微结构异常为特征,导致骨骼脆性增加和易发生骨折的代谢性骨病[1]。防治骨质疏松症的最终目的是减少骨折的发生。临床上采用延缓和减少骨量丢失,争取重获骨量,增加骨骼强度而达到此目的。骨质疏松症的治疗措施分为基     

前列腺癌免疫治疗的研究进展

前列腺癌已成为美国男性中最常见的恶性肿瘤之一,而在我国,随着老龄人口增加,其发病率也呈逐年上升趋势。传统的前列腺癌治疗方法包括外科手术治疗/放射治疗/化学治疗及激素疗法等。但患者经过上述治疗后易复发,或者确诊时肿瘤已发生转移,尽管雄激素阻断疗法使这些患者病情得到部分缓解,但大部分患者还是不可避免的发展到不     

专家论坛:焦虑症及其治疗药物

传统的药物(如苯二氮(艹卓)类、三环类药物)有很多不良反应10多年来焦虑症药物治疗有了实质性变化,研究证实.SSRI治疗抑郁症和焦虑症是有效和安全的.现在SSSI已成为治疗惊恐障碍的一线药物.同样在广泛性焦虑症的长期治疗中,文拉法辛.帕罗西汀和某些三环类药物优于苯二氮(艹卓)类.作者认为文拉法辛、帕罗西汀、曲唑酮、黛力新以及某些三环类药物可考虑作为广泛性焦虑症的一线药物.苯二氮(艹卓)类药起效快,能立即减轻焦虑症状可短期应用或与SSRI短期联用.     

New advances in antibiotic development and discovery

The development of new antibiotics is crucial to controlling current and future infectious diseases caused by antibiotic-resistant bacteria. Increased development costs, the difficulty in identifying new drug classes, unanticipated drug toxicities, the ease by which bacteria develop resistance to new antibiotics and the failure of many agents to address antibiotic resistance specifically, however, have all led to an overall decline in the number of antibiotics that are being introduced into clinical practice. Although there are few, if any, advances likely in the immediate future, there are agents in both clinical and preclinical development that can address some of the concerns of the infectious disease community. Many of these antibiotics will be tailored to specific infections caused by a relatively modest number of susceptible and resistant organisms.