2000年医药研究进展

本文简述2000年医药研究的最新进展，包括：新上市的具有代表性药物和新的治疗方法，当年的热点研究领域，同时也对一些治疗领域中新药开发面临的困难和重要的药物不良反应进行简述。

Novel approaches towards conquering hepatitis B virus infection

Currently approved treatments for hepatitis B virus （HBV） infection include the immunomodulatory agent, IFN-α, and nucleos（t）ide analogues. Their efficacy is limited by their side effects, as well as the induction of viral mutations that render them less potent. It is thus necessary to develop drugs that target additional viral antigens. Chemicals and biomaterials by unique methods of preventing HBV replication are currently being developed, including novel nucleosides and newly synthesized compounds such as capsid assembling and mRNA transcription inhibitors. Molecular therapies that target different stages of the HBV life cycle will aid current methods to manage chronic hepatitis B （CriB） infection. The use of immunomodulators and gene therapy are also under consideration. This report summarizes the most recent treatment possibilities for CHB infection. Emerging therapies and their potential mechanisms, efficacy, and pitfalls are discussed.

Interaction or relationship between Helicobacter pylori and non-steroidal anti-inflammatory drugs in upper gastrointestinal diseases

According to a meta-analysis, H pylori and non-steroidal anti-inflammatory drugs （NSAID） independently and significantly increase the risk of gastroduodenal ulcer and ulcer bleeding. Their coincidence is frequent, demonstration of a possible relationship and consequent attitude is of important implications. But unfortunately, no consensus has been approved in the past years and their interactions are still controversial. H pylori and NSAID are known to share a number of pathogenic mechanisms, but there is no evidence for the significant synergic action between these two risk factors. Their relationship is independent, additive, synergistic or antagonistic without considering the influence of other factors because studies on this subject are different in almost all aspects of their methodology, including the definition of a NSAID user as well as the types, doses, duration and their indications for NSAID use, as well as their end-points, definition of dyspepsia and regimes used for eradication of H pylori. These might contribute to the conflicting results and opinions. H pylori infection in humans does not act synergistically with NSAID on ulcer healing, and there is no need to eradicate it. This notion is supported by the finding that the eradication of H pylori does not affect NSAID induced gastropathy treated with omeprazole and that H pylori infection induces a strong cyclooxygenase-2 （COX-2） expression resulting in excessive biosynthesis of gastroprotective prostaglandin which in turn counteracts NSAID-induced gastropathy and heals the existing ulcer. Other investigators claimed that H pylori infection acts synergistically with NSAID on ulcer development, and H pylori should be eradicated, particularly at the start of long-term NSAID therapy. Eradication of H pylori prior to NSAID treatment does not appear to accelerate ulcer healing or to prevent recurrent ulcers in NSAID users. However, some recommendations can be drawn from the results of clinical trails.

Strategies for Antiviral Screening Targeting Early Steps of Virus Infection

Viral infection begins with the entry of the virus into the host target cell and initiates replication. For this reason, the virus entry machinery is an excellent target for antiviral therapeutics. In general, a virus life cycle includes several major steps: cell-surface attachment, entry, replication, assembly, and egress, while some viruses involve another stage called latency. The early steps of the virus life cycle include virus attachment, receptor binding, and entry. These steps involve the initial interactions between a virus and the host cell and thus are major determinants of the tropism of the virus infection, the nature of the virus replication, and the diseases resulting from the infection. Owing to the pathological importance of these early steps in the progress of viral infectious diseases, the development of inhibitors against these steps has been the focus of the pharmaceutical industry. In this review, Herpes Simplex Virus (HSV), Hepatitis C Virus (HCV), and Human Enterovirus 71 (EV71) were used as representatives of enveloped DNA, enveloped RNA, and non-enveloped viruses, respectively. The current mechanistic understanding of their attachment and entry, and the strategies for antagonist screenings are summarized herein.

Sarcoidosis and chronic hepatitis C:A case report

Several case reports deal with the relationship between hepatitis C virus （HCV） infection and pulmonary or he- patic sarcoidosis. Most publications describe interferon m-induced sarcoidosis. However, HCV infection per se is also suggested to cause sarcoqdosis. The present case report describes a case of biopsy-verified lung and liver sarcoidosis and HCV infection, and the out- come of antiviral therapy. In March 2009, a 25-year-old man presented with moderately elevated liver enzymes without any clinical symptoms. The patient was posi- tive for HCV antibodies and HCV RNA of genotype lb. Four months later the patient became dyspnoic and pulmonary sarcoidosis was diagnosed by lung biopsy and radiography. A short course of corticosteroid treat- ment relieved symptoms. Three months later, liver biopsy showed noncaseating granulomas consisting of epithelioid histiocytes and giant cells with a small amount of peripheral lymphocyte infiltration, without any signs of fibrosis. Chronic HCV infection with co- existence of pulmonary and hepatic sarcoidosis was diagnosed. Antiviral therapy with peginterferon ~ and ribavirin at standard doses was started, which lasted 48 wk, and sustained viral response was achieved. A second liver biopsy showed disappearance of granulo- mas and chest radiography revealed normalization of mediastinal and perihilar glands. The hypothesis that HCV infection perse may have triggered systemic sar- coidosis was proposed. Successful treatment of HCV infection led to continuous remission of pulmonary and hepatic sarcoidosis. Further studies are required to un- derstand the relationship between systemic sarcoidosis and HCV infection.

Analysis of a sex-structured HIV/AIDS model with the effect of screening of infectives

This paper presents a nonlinear sex-structured mathematical model to study the spread of HIV/AIDS by considering transmission of disease by heterosexual contact. The epidemic threshold and equilibria for the model are determined, local stability and global stability of both the “Disease-Free Equilibrium” （DFE） and “Endemic Equilibrium” （EE） are discussed in detail. The DFE is shown to be locally and globally stable when the basic reproductive number R0 is less than unity. We also prove that the EE is locally and globally asymptotically stable under some conditions. Finally, numerical simulations are reported to support the analytical findings.