HDAC inhibitors in parasitic diseases

Parasitic diseases cause significant global morbidity and mortality, particularly in underdeveloped regions of the world. Malaria alone causes ~800000 deaths each year, with children and pregnant women being at highest risk. There is no licensed vaccine available for any human parasitic disease and drug resistance is compromising the efficacy of many available anti-parasitic drugs. This is driving drug discovery research on new agents with novel modes of action. Histone deacetylase (HDAC) inhibitors are being investigated as drugs for a range of diseases, including cancers and infectious diseases such as HIV/AIDS, and several parasitic diseases. This review focuses on the current state of knowledge of HDAC inhibitors targeted to the major human parasitic diseases malaria, schistosomiasis, trypanosomiasis, toxoplasmosis and leishmaniasis. Insights are provided into the unique challenges that will need to be considered if HDAC inhibitors are to be progressed towards clinical development as potential new anti-parasitic drugs.     

The evolution of parasitic diseases

Parasites are characterized by their fitness-reducing effect on their hosts. Studying the evolution of parasitic diseases is an attempt to understand these negative effects as an adaptation of the parasite, the host, both or neither. Dieter Ebert and E. Allen Herre here discuss how the underlying concepts are general and are applicable for all types of disease-producing organisms, broadly defined here as parasites. The evolutionary processes that lead to the maintenance of the harmful effects are believed to be characterized by genetic correlations with other fitness components of the parasite. Depending on the shape of these correlations, any level of virulence can evolve.     

Altered drug metabolism in parasitic diseases

While the immune system represents the main line of host defence against parasite infections, mixed function oxidase (MFO) systems (Box 1) offer the main line of defence against drugs and other biologically active substances. But, as this review shows, many parasites can exert a profound effect on the host MFO system by altering the microsomal drug-metabolizing enzymes and electron transport carriers such as cytochrome P-450. This can markedly affect the host's ability to metabolize biologically active compounds, often with adverse physiological, pharmacological and toxicological consequences. In mammals, drug metabolism occurs predominantly in the liver, and to a lesser extent in the spleen, lungs, kidneys, intestine and cerebral tissues. Thus those parasites that occupy sites in these tissues - such as amoebae, Fasciola, schistosomes and malaria - tend to be those with greatest effects on the host's ability to metabolize drugs. The effects can modify the host response to substances unrelated to the infection, and to drugs which may be administered under a chemotherapeutic regime.     

DNA-binding antibodies and parasitic diseases

DNA-binding antibodies are produced during the course of many parasitic infections, including malaria, leprosy and schistosomiasis. These antibodies are also present in certain autoimmune diseases, such as systemic lupus erythematosus, and much information is available about their properties and contribution to related disease processes Here, Anne Wozencraft and Norman Staines consider how DNA-binding antibodies might arise during parasitic infection and discuss how an increased knowledge of their properties and functions could lead to a greater understanding of mechanisms of immuno-pathology in these diseases.     

鱼类的寄生虫和寄生虫病

鱼类有多种各类寄生虫分割造成寄生虫病,其中很多会引起鱼类大量死亡。本文就主要的鱼病和病原做了简要的介绍。     

Immunogenic glycoconjugates implicated in parasitic nematode diseases

Parasitic nematodes infect billions of people world-wide, often causing chronic infections associated with high morbidity. The greatest interface between the parasite and its host is the cuticle surface, the outer layer of which in many species is covered by a carbohydrate-rich glycocalyx or cuticle surface coat. In addition many nematodes excrete or secrete antigenic glycoconjugates (ES antigens) which can either help to form the glycocalyx or dissipate more extensively into the nematode's environment. The glycocalyx and ES antigens represent the main immunogenic challenge to the host and could therefore be crucial in determining if successful parasitism is established. This review focuses on a few selected model systems where detailed structural data on glycoconjugates have been obtained over the last few years and where this structural information is starting to provide insight into possible molecular functions.