Edited by Dietmar Fuchs
and Okezie I Aruoma
Readership: Aimed at Research and Development in Academia and Industry, in particular pharmaceutical Research, Virologists, Public Health Professionals, Clinicians, Biochemists, Molecular Biologists, Physiologists and all those with an interest in the molecular mechanisms of gene expression and human diseases.
PHARMACOLOGY OF HIV INFECTION AND AIDS
The book begins with a discussion of the neuropathology of HIV infection. The nervous system (NS) is the second major target of infection by the human immunodeficiency virus type 1 (HIV-1) just following the immune system. Clinical studies have shown that about half of patients with AIDS have neurological disorders which represent the principal cause of death and of disabling in this group. Neuropathological studies have further shown that 80 to 100% of cases have CNS lesions. The neurological complications of AIDS are multiple and result from various causes; they frequently have an atypical clinical and morphological presentation, and may be associated in the same patient. Host cell activation appears to be the basis of a permanent infection with the human immunodeficiency virus (HIV) Next to virus replication numerous signals are hereby initiated, including the production of cytokines i.e. interferon gamma (IFN-g) and host cell death. Elevated levels of IFN-g produced by T-lymphocytes, constitute a hallmark of activated cell-mediated immunity. It further initiates the expression of proinflammatory cytokines such as interleukin-1 (IL-1), IL-6 and tumor necrosis factor-a (TNF-a) and enhances macrophage capacity to secrete reactive oxygen intermediates. In addition, IFN-g is the major stimulator for the biosynthesis of the immune activation markers neopterin and 7,8-dihydroneopterin from guanosine triphosphate (GTP). The book continues with a discussion of the role of immune activation in the induction of apoptosis of host cells.
Retroviruses have RNA genome that is not replicated into RNA. Instead, their replication is mediated by a double-stranded DNA intermediate that is integrated in the nuclear genome of the infected cell. The retroviridae family is divided in three groups: the oncoviridae, the lentiviridae and the spumaviridae. The pathological effect of these groups has allowed their sub-classification. Oncoviridae are responsible for some types of leukemia and sarcomas in different animal species. Lentiviridae are associated with neurological disorders, as well as with other pathological manifestations, like the acquired immunodeficiency syndrome (AIDS) in humans.However, no pathogenicity has been found associated with spumaviridae. AIDS is a viral pathology characterized by the progressive loss of the human immune natural defenses and the emergence of skin cancer (Kaposi sarcoma) and several other opportunistic infections. The main retrovirus involved in AIDS is the human immunodeficiency virus type-1 (HIV-1). A second virus (HIV-2) is also known. Both viruses belong to the family of retroviridae and their characteristics allow them to be classified as lentiviridae.
In the 17 years since the first cases of AIDS were diagnosed and the 14 years since the human immunodeficiency virus (HIV), the causative agent was discovered, the epidemic has continued to spread throughout the world. An extraordinary research effort has been mounted in order to better understand HIV pathogenesis, to design effective therapies, and to develop an efficacious vaccine. The latter goal is the only effective means to fight the epidemic on a worldwide level. In this book, rather than attempting an exhaustive review of every approach, the challenges peculiar to HIV vaccine development are outlined with a summary of the evolution of strategies attempting to meet the various challenges. The book turns to the long-term impact of Zidovudine monotherapy and Pneumocystis carinii prophylaxis on HIV disease. Many studies and clinical trials found that zidovudine and P. carinii prophylaxis each significantly reduced short-term mor-bidity and mortality from HIV-1 disease. In human immunodeficiency virus (HIV-1) infection the production of neopterin increases in parallel with progression of the disease. Neopterins are suggested as independent predictors of the progression of HIV-1 infection. A significant inverse correlation exists between neopterin levels in serum and urine and absolute CD4+.
Herbal medicines are being used world wide for the treatment of various diseases including acquired immunodeficiency syndrome (AIDS). Anti-HIV properties of different types of compounds isolated from a large number of medicinal plants. These include ketones and aldehydes isolated from Houttuynia cordata, phorbol esters from Excoecaria agallocha, tetracyclic diterpene tetraesters from Euphorbia myrsinites, pentacyclic triterpenes, galloyl and caffeoyl quinic acid derivatives isolated from commercially available tannic acid, or from plants Securidaca longipedunculata and Guiera senegalensis, triterpenoids from Syzigium claviflorum, novel kaurane type diterpene lactone neotripterifordin and triterpenes from Tripterygium wilfordii and Polyalthia suberosa, atropisomeric naphthylisoquinoline alkaloid. dimers, from a newly described species of Ancistrocladus, bergenins and 6-hydroxy tremetone from Ardisia japonica and Werneria ciliolata, novel chromone alkaloids from Schumanniophyton magnificumm and many related compounds. Flavanoids are the most commonly found constituents of many medicinal plants. Interestingly, they structurally resemble nucleosides, isoalloxazine and folic acid. Flavonoids show strong affinity for binding to proteins and heavy metals, have the ability to catalyse electron transport and to scavenge free radicals.
Viral diseases, reactive oxygen species (ROS) including the reactive nitrogen intermediates (RNI) play a dichotomous role as a host defence mechanism and as a contributor to host pathology. In addition to this aspect which they share with the biology of parasitic and bacterial infections, it has in recent years become clear that ROS play an important role in the regulation of metabolism. The role of free radical metabolism in viral pathogenesis may have both negative and positive aspects not only for the viruses but also for their host cells and, at a higher level, for an individual. This conveniently leads to discussions on micronutrient and antioxidant deficiencies in HIV and AIDS patients: A role for nutrient-based immune therapy.
Early HIV infection has been also linked to increased oxidative stress and specific nutrient deficiencies that are present at the time of detection of immune derangements. Nutrient abnormalities may potentiate immune dysfunction, increasing the risk of AIDS development. Thus nutrient/antioxidant therapy may play a vital role in treatment of this immunodeficiency disease, providing a complimentary approach to antiviral drug therapy.
In the light of this, the potential of HIV-1 Encoded selenoproteins as a basis for antioxidant therapy is extensively discussed. Finally, Pharmacology of HIV Infection and AIDS looks at a clinical update on nutrition and HIV/AIDS. Malnutrition is multifactorial and common in patients with HIV infection and AIDS. The etiology and background of malnutrition in HIV infection and AIDS are discussed. The parameters to identify and monitor nutritional health in this patient population are assessed. Finally, the various intervention strategies to promote weight gain and lean body mass (LBM) through dietary intake, pharmacological agents, and exercise are discussed with a view to emphasizing the importance of nutrition in this patient population.
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