Current Medicinal Chemistry - Volume 14, Issue 18, 2007

Highly active antiretroviral treatment (HAART), i.e. the combination of three or more drugs against human immunodeficiency virus type 1 (HIV-1), has greatly improved the clinical outcome of HIV-1-infected individuals. However, HAART is unable to reconstitute HIV-specific immunity and eradicate the virus. Several observations in primate models and in humans support the notion that cell-mediated immunity can control v Read More

The role of the Human Immunodeficiency Virus (HIV) in the pathogenesis of the Acquired Immune-Deficiency Syndrome (AIDS) is changed. Direct HIV-mediated killing of CD4+ T cells is not the only mechanism leading to lymphocyte depletion. There is increasing evidence that, during the chronic phases of infection, T cell activation, accelerated cell turnover, and cytokines imbalance induce the so-called cell cycle dysregul Read More

Eosinophils are a minority subpopulation of leukocytes whose roles in host defense against infection remain controversial, but which have been implicated in the pathogenesis of both acute allergic inflammation and the chronic bronchopulmonary remodelling in asthma. Eosinophilia, a hallmark of both helminth infections and atopic diseases, is maintained through upregulation of eosinophilopoiesis by means of increase Read More

Inducible nitric oxide synthase (iNOS) is expressed in a variety of cell types, in particular in inflammatory cells, in response to diverse pro-inflammatory stimuli. This process requires critical levels of arachidonic acid (AA), generated by constitutive phospholipase A2 (PLA2), promoting tyrosine kinase-dependent phosphorylation, and inhibition, of constitutive NOS. Lowering basal NO levels is indeed critical for the activati Read More

Peripheral inflammation enhances the antinociceptive effects of opioid receptor agonists through the activation of peripheral opioid receptors whose expression also increases during inflammatory pain. Similarly, intestinal inflammation also increases the antitransit and antiexudative effects of opioids as well as the expression of neuronal and extra-neuronal opioid receptors located in the gut. Nitric oxide has been described e Read More

Multiple sclerosis (MS) is the most common disabling neurological disease in young adults and is thought to result from an autoimmune attack against autoantigens within the myelin sheath. A characteristic feature of MS is the broad heterogeneity of clinical, histopathological and immunological phenotypes, which urges a more differentiated defining of patients by biological markers that reflect the underlying disea Read More

Cysteinyl leukotrienes (Cys-LTs) are potent proinflammatory mediators derived from arachidonic acid through the 5- lypoxigenase (5-LO) pathway. They exert important pharmacological effects by interaction with at least two different receptors: Cys-LT1 and Cys-LT2. By competitive binding to the Cys-LT1 receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast, and pranlukast, block the effects of Cys-LTs Read More

The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billio Read More

In recent years, there has been an increasing prevalence of obesity and related diseases. This epidemiological change has increased the interest of researchers in the molecular and biochemical pathways involved in the pathogenesis of hepatic and biliary diseases. Insulin resistance is considered the major mechanism involved in the hepatic and biliary manifestations of obesity. Epidemiological, clinical, and basic research demonst Read More

The goals of tuberculosis control are to cure active disease, prevent relapse, reduce transmission and avert the emergence of drug resistance. However, since the 1960s, there have been few developments in available therapies. Currently available agents are complicated by numerous side-effects, drug interactions and the need for a long duration of therapy. Rifampicin-containing regimes lead to hepatic enzyme induction w Read More