chondroitin-sulfates and Carotid-Artery-Diseases

Fucosylated chondroitin sulfate (FucCS) is a potent anticoagulant polysaccharide extracted from sea cucumber. Its anticoagulant activity is attributed to the presence of unique branches of sulfated fucose. Although this glycosaminoglycan exerts an antithrombotic effect following oral administration, high doses are necessary to achieve the maximum effect. The diminished activity of FucCS following oral administration is likely due to its degradation in the gastrointestinal tract and its limited ability to cross the intestinal cell membranes. The latter aspect is particularly difficult to overcome. However, gastro-resistant tablet formulation may help limit the degradation of FucCS in the gastrointestinal tract. In the present work, we found that the oral administration of FucCS as gastro-resistant tablets produces a more potent and prolonged anticoagulant effect compared with its administration as an aqueous solution, with no significant changes in the bleeding tendency or arterial blood pressure. Experiments using animal models of arterial thrombosis initiated by endothelial injury demonstrated that FucCS delivered as gastro-protective tablets produced a potent antithrombotic effect, whereas its aqueous solution was ineffective. However, there was no significant difference between the effects of FucCS delivered as gastro-resistant tablets or as aqueous solution in a venous thrombosis model, likely due to the high dose of thromboplastin used. New oral anticoagulants tested in these experimental models for comparison showed significantly increased bleeding tendencies. Our study provides a framework for developing effective oral anticoagulants based on sulfated polysaccharides from marine organisms. The present results suggest that FucCS is a promising oral anticoagulant.

Topics: Administration, Oral; Animals; Anticoagulants; Blood Coagulation; Carotid Artery Diseases; Chondroitin Sulfates; Disease Models, Animal; Drug Compounding; Female; Hemorrhage; Male; Rats, Wistar; Tablets, Enteric-Coated; Thrombosis; Time Factors; Venous Thrombosis

Ischemic stroke patients subtyped as of undetermined cause (SUC) usually outnumber those with determined cause subtypes. Etiological stroke classifications may lead to neglect of parallel, noncausative findings. Atherosclerosis progresses over decades and is associated with high morbidity and mortality in young stroke patients in long-term follow-up studies. We compared the prevalence of carotid atherosclerosis in all TOAST subtypes among young patients with acute ischemic stroke.. We investigated 150 patients aged 15-60 years with documented acute ischemic stroke, and 84 controls free of cardiovascular disease. Stroke etiology was classified according to TOAST criteria. Carotid intima-media thickness (cIMT) measurements were obtained from 12 standardized multiangle measurements in the common carotid artery, carotid bifurcation, and internal carotid artery.. The causes of stroke were 5.3% large-artery atherosclerosis (LAA), 26.7% cardioembolism, 21.3% small-artery occlusion (SAO), 10% stroke of other determined cause, and 36.7% stroke of undetermined cause (SUC). cIMT was increased in patients with LAA (1.56 mm, P = .002), SAO (1.11 mm, P = .006), and SUC (1.10 mm, P = .004) compared to controls (cIMT 0.86 mm). Segmental cIMT distribution differed across stroke subtypes, age groups, and sexes.. Atherosclerotic disease is prevalent in the majority of young and middle-aged ischemic stroke patients, requiring determined investigation and aggressive treatment of modifiable risk factors.

Topics: Adolescent; Adult; Age Factors; Carotid Artery Diseases; Carotid Intima-Media Thickness; Chondroitin Sulfates; Dermatan Sulfate; Female; Fibrinolytic Agents; Heparitin Sulfate; Humans; Longitudinal Studies; Male; Middle Aged; Neuroimaging; Norway; Stroke; Young Adult