Pathogenesis of different diseases


A.V. Sorokina, L.P. Kovalenko, E.V. Shipaeva, T.A. Gudasheva, R.U. Ostrovskaya, S.B. Seredenin. State Zakusov’s Institute of Pharmacology RAMS, Moscow, Russia

The prooxidant mechanism involved in the action of adjuvant- type immunomodulating drugs exerts positive effect during chronic infectious processes in patients with secondary immunodeficiency. Neutrophils form the forefront line of defense of an organism exposed to infectious processes, although during most non-infectious diseases the activated neurotrophils produce notable cyto- and organotoxic action. Neutrophils have a powerful aggressive potential inducing infectious (purulent) and non-infectious inflammations (during post- traumatic disorders of different genesis, vascular dementia, brain ischemia).

Neutrophils are involved in middle and late phase of autoimmune, and probably allergic inflammation of different forms. During stroke there is observed the infiltration of cerebral microves- sels by leukocytes, which induce remarkable perivascular edema, an enhanced adhesion of leukocytes to microvessels endothelium and brain tissue infiltration. All these events result in ischemic area enlargement. Free radical activity of neutrophilic leukocytes leads to the expression of iNOS-synthase in neutrophils, COX-2 in cel- lular membranes thus triggering eukozanoids synthesis, and namely PGE2.

One of valuable constutuent of multicomponent action produced by cardiotropic and psychotropic drugs is their differently oriented effect upon membranes of various cells and their mediator con- trol. It may induce an anti-inflammatory effect or pseudoallergic response. Therefore, it appears beneficial when experimental testing the immunotoxicity of novel membrane-active substances to use the chemoluminescence for evaluating their effect on neutrophic lykocytes activated by phorbolmiristatacetate or other enhacers.

It is also of value to estimate acute exudative (carragenan- and Con A-induced edema) and chronic (adjuvant arthritis) immune inflam- mations. After single dosage of psychotropic adaptogenic agent estriglutone (per os) and DNA-containing compound AVP (subcu- taneously) a significant dose-depended increase in the inflammatory response to Con A was observed. The inflammatory action was found in 2-mercaptobenzimidasole derivatives, an antiarrhythmic agent Bradisole and selective anxiolytic Afobazol. Pronounced an- tioxidant and anti-inflammatory properties were shown in dipeptide nootropic Noopept.

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