Vascular damage and

P2Y receptors that are found on endothelial cells elicit a Ca2+-dependent release of endothelium-dependent relaxing factor (EDRF) and vasodilation. A secondary activation of a Ca2+-sensitive phospholipase A2 increases the synthesis of endothelial prostacyclin, which limits the extent of intravascular platelet aggregation following vascular damage and platelet stimulation. The P2Y-mediated vasodilation opposes a vasoconstriction evoked by P2X receptors located on vascular smooth muscle cells. The latter elicit an endothelial-independent excitation (i.e. constriction). P2Y receptors are also found on adrenal chromaffin cells and platelets, where they modulate catecholamine release and aggregation respectively. 

Arterial hypertension (high blood pressure) generally does not impair the well-being of the affected individual however, in the long term it leads to vascular damage and secondary complications (A). The aim of antihypertensive therapy is to prevent the latter and, thus, to prolong life expectancy. 

Gi effects Vomiting, diarrhea, abdominal pain, and nausea may occur, especially with maximum doses. These may be particularly troublesome in the presence of peptic ulcer or spastic colon. At toxic doses, colchicine may cause severe diarrhea, generalized vascular damage, and renal damage with hematuria and oliguria. To avoid more serious toxicity, discontinue use when these symptoms appear, regardless of whether joint pain has been relieved. 

Pathophysiologically, although vascular damage and platelet involvement occurs, the major component in the clot is fibrin. 

Systemic arterial hypertension ( high blood pressure ) does not typically make the afflicted individual feel unwell however, after many years, it leads to vascular damage and to the secondary complications thereof hence, the designation of hypertension as the silent killer. The ultimate aim of the pharmacological management of hypertension is to prevent these complications and thus to prolong not only life expectancy but also quality of life. 

The therapeutic effect of PDT may be due to direct cell killing or vascular damage, and there are also indications of the importance of immune responses. The relative importance of these pathways to therapeutic effects depends on the photosensitizer and its formulation, the way of administration, and the time between administration of the photosensitizer and exposure to light. 

Spokas and Wun (1992) produced venous thrombosis in the vena cava of rabbits by vascular damage and stasis. The vascular wall was damaged by crushing with hemostat clamps. A segment of the vena cava was looped with two ligatures, 2.5 cm apart. At 2 h after ligation, the isolated venous sac was dissected and the clot removed for determination of dry weight. 

Spokas EG, Wun TC (1992) Venous thrombosis produced in the vena cava of rabbits by vascular damage and stasis. J Pharm Toxicol Meth 27 225-232... 

Platelet adhesion to the extracellular matrix exposed at sites of vascular damage, and subsequent platelet aggreption are integral parts of the hemostatic system designed to... 

Generalized vascular damage and endothelial lesions, followed by disseminated intravascular coagulation and formation of microthrombi with subsequent tissue infarction... 

Hepatocellular and renal damage is at least partly secondary to vascular damage and impaired tissue perfusion, rather than a direct effect of the toxin itself. Animal studies have... 

The ability of combretastatin A-4 disodium phosphate to induce vascular damage and enhance the radiation response of murine tumors was investigated [97]. A C3H mouse mammary carcinoma transplanted in the foot of CD FI mice and the KHT mouse sarcoma growing in the legmuscleofC3H/HeJ mice were used. CA-4-DP was dissolved in saline and injected intraperitoneally. Tumor blood perfusion was... 

Long-term Studies - Any therapeutic approach cannot be considered successful if it only lowers serum lipids. It must prevent further deposition in the tissues and hopefully also reduce existing atheromata. The final criterion of any treatment is its effect on the Incidence of clinical vascular damage and useful life span. It has long been recognized that the efficacy of medical approaches to atherosclerosis can best be evaluated in long-tem studies. 

Although Clostridia produce potent toxins, the pure collagenase is not very toxic (Mandl, 1961). However, administration of ma.ssive doses into tail veins of mice caused vascular damage and death resulted from pulmonary hemorrhage (Howes el al., 1960). 

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