New developments in chemotherapy for non-invasive fungal infections

Dermatomycosis and subcutaneous mycosis comprise the non-invasive fungal infections commonly encountered in clinical practice around the world. The limited activity of early topical antifungal agents prompted the development of more effective systemic agents. While griseofulvin has been used for more than four decades, the use of early azoles, such as ketoconazole have resulted in better patient compliance and thus greater success. However, poor response and recurrence in dermatomycosis, as well as toxicity associated with ketoconazole therapy, has led to the search for newer antifungal agents and more effective treatment strategies. Terbinafine, itraconazole and fluconazole have the advantage of non-toxicity and a broad spectrum of activity. An overview of non-invasive fungal infections, antifungal agents in clinical use and recent developments in antifungal therapy is reviewed in this article.     

艾滋病治疗药物的研究进展

作者全面系统地阐述了近年来抗艾滋病新药的研发策略和研究进展,并根据药物作用靶点分别介绍了新上市的抗艾滋病药物的作用机制和结构特点,如第二代HIV-1逆转录酶抑制剂和HIV-1蛋白酶抑制剂,以及全新作用机制的HIV-1进入抑制剂和HIV-1整合酶抑制剂,并对今后抗艾滋病药物的发展方向进行了展望。     

Recent developments in the chemotherapy of malaria

Malaria remains a major infectious disease and is worsening in some areas, partly because of the spread of resistance to established antimalarial drugs. New drugs are urgently needed to combat the protozoan parasite, Plasmodium. This review covers new developments, including artemisinin derivatives, synthetic peroxides, folate pathway inhibitors, primaquine analogs and proteinase inhibitors. However, few of these agents are in clinical trials and many are derived from chemical classes already used extensively against malaria. The emerging understanding of parasite biology and new technological developments in drug discovery offer hope of improvement, but this will require increased interest from the pharmaceutical industry.     

Recent developments in the chemotherapy of Chagas disease

Chagas disease remains an important health problem in the Americas. Advances are being made in parts of South America in blocking transmission from insect vectors or blood transfusion, but more effective chemotherapy is needed for the millions who are already infected. This is especially important since recent results have indicated that treatment is beneficial for the elimination of the chronic course of the disease. The rational development of new drugs depends on the identification of differences between human metabolism and that of the causative parasite, Trypanosoma cruzi. Recent developments in the study of the basic biochemistry of the parasite have allowed the identification of novel targets for chemotherapy, such as sterol metabolism, protein prenylation, proteases, and phospholipid metabolism, and these are the subject of this review.     

New developments in aerosol dosimetry

Dosimetry provides information linking environmental exposures to sites of deposition, removal from these sites, and translocation of deposited materials. Dosimetry also aids in extrapolating laboratory animal and in vitro data to humans. Recent progress has shed light on: properties of particles in relation to their fates in the body; influence of age, gender, body size, and lung diseases on inhaled particle doses; particle movement to the brain via the olfactory nerves; and particle deposition hot spots in the respiratory tract. Ultrafine size has emerged as an important dosimetric characteristic. Particle count, composition, and surface properties are recognized as potentially important toxicology-related considerations. Differences in body size influence airway sizes, inhaled particle deposition, specific ventilation, and specific doses (e.g. per unit body mass). Related to body size, age, gender, species, and strain are also dosimetric considerations. Diseases, such as chronic obstructive pulmonary disease (COPD) and bronchitis, produce uneven doses within the respiratory tract. Traditional concepts of the translocation and clearance of deposited particles have been challenged. Ultrafine particles can translocate to the brain via olfactory nerves, and from the lung to other organs. The clearance rates of particles from tracheobronchial airways are slowed by respiratory tract infections, but newer evidence implies that slow particle clearance from this region also exists in healthy lungs. Finally, hot spots of particle deposition are seen in hollow models, lung tissue, and dosimetric simulations. Local doses to groups of epithelial cells can be much greater than those to surrounding cells. The new insights challenge dosimetry scientists.     

New developments in thrombosis therapy

Researchers presenting at the 16th International Congress on Thrombosis (Mediterranean League against Thromboembolic Disease), held May 58, 2000, in Porto, Portugal, reviewed the latest developments in the treatment of thrombosis. Several symposia focused attention on the new indications for low-molecular-weight heparins and provided updates on trials. The roles of tissue factor and tissue factor pathway inhibitor were extensively reviewed, and a number of late-stage developmental anticoagulants were presented.