Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Anti-Inflammatory and Anti-Allergy Agents) - Volume 5, Issue 2, 2006

Contrast medium (CM)-enhanced X-ray examinations are indispensable in clinical medicine. This is reflected by approximately 40-50 million CM-administrations per year worldwide. This number will probably increase due to increasing prevalence/incidence rates of malignant and cardio-vascular diseases, the need to monitor new therapeutic approaches (e.g. gene therapy), and last but not least, due to new technical app Read More

Contrast media (CM) are widely used substances that may lead to hypersensitivity reactions. Those adverse events can be classified as immediate reactions that occur within the first hour after administration of CM or delayed reactions that develop after more than one hour and during the following 7 days. The pathomechanisms for both types of reactions are still not fully clear. Only in a minority of cases with immediate re Read More

Iodinated contrast media (CM) are widely used in radiological procedures, and carry a risk of adverse reactions with possible sequelae or death. Various and numerous reactions have been reported, most of which are transient ones and do not threaten the patient's life. Immediate adverse reactions include adverse effects directly related to the osmotic load or to the CM chemotoxicity, and immediate hypersensitivity reactio Read More

Serious or fatal reactions to a contrast agent are usually unpredictable and the majority occurs within 20 min of administration. Incidence of very severe reactions with the use of low osmolar non ionic contrast media (CM) is very low (0.004%) and is reduced by a factor of 10 in comparison to high osmolar CM (0.04%). Fatality due to CM injection is rare and the incidence is similar with both types of CM (1 in 170,000 contrast ex Read More

Vascular reactions after administration of all classes of iodinated x-ray contrast media are well known side effects of these drugs. Both vasodilation and vasoconstriction have been observed. The manner and extent of the change in vessel tone depends on the type of contrast medium, species, vascular territory and contractile state of the vessels. The mechanisms underlying the vascular reaction induced by contrast media are Read More

Contrast-induced nephropathy (CIN) is a worrying concern in at-risk patients. Its pathophysiological mechanism remains speculative and is possibly modulated according to the risk factor(s) and clinical presentation of the patients. Overall, iodinated contrast media (CM) have been shown, in animal models, to induce medullary hypoxia. Furthermore, numerous studies have demonstrated that they have a direct cytotoxic poten Read More

Phospholipase A2 constitutes a large and diverse family of enzymes, which catalyze the hydrolysis of membrane glycerophospholipids at the sn-2 position to release fatty acids and lysophospholipids. When the fatty acid is the arachidonic acid, a complementary metabolism leads to pro-inflammatory mediators such as prostaglandins, leukotrienes, thromboxanes and platelet activating factors. Thus, modulating pro-infla Read More

Arachidonic acid derivatives, like prostaglandins and leukotrienes, and the platelet-activating factor (PAF) are highly active substances with diverse biological actions. Elevated levels of these lipid mediators in response to a variety of stimuli have been implicated in the pathology of many inflammatory diseases. The rate limiting step in the generation of prostaglandins, leukotrienes and the PAF, respectively, is the cleavage Read More

Inflammatory mediators contribute significantly to the induction and progression of cardiovascular diseases such as atherosclerosis and acute myocardial infarction (AMI). A mediator that has been shown to play a crucial role in both cardiovascular events is group-II secretory phospholipase A2 (sPLA2-II), as this mediator has been suggested to modulate atherosclerotic plaque formation, for example by increasing the accum Read More

High concentrations of human non pancreatic secretory phospholipase A2 (hnps-PLA2) have been reported as inducing factors in different inflammatory diseases. Thus, hnps-PLA2 inhibitors would be potential drugs against disorders generated by high levels of this enzyme. The latter has been crystallized with different ligands and several classes of inhibitors are known, but the optimization of their therapeutic properti Read More

PLA2 is an important signaling enzyme that generates multiple downstream effectors, such as arachidonic acid and PAF, which are key mediators of inflammation as well as other pathophysiological conditions. Inhibition of PLA2 is potentially an effective therapy for several inflammatory diseases. In this review, we discuss the various classes of synthetic inhibitors of Group IVA and Group VIA phospholipase A2.