Changes of plasma 6-keto-PGF1.ALPHA. and thromboxane B2 levels and platelet aggregation after tourniquet ischemia on the upper limb in normal subjects and patients with ischemic heart disease.

Aim: Polymorphisms in cytochrome P450 (CYP) 2C19 and paraoxonase-1 (PON-1) genes are thought to be involved in clopidogrel high on treatment reactivity in ischemic heart disease (IHD) patients. Methods: A total of 240 patients with IHD were screened for CYP2C19 loss-of-function alleles (LOF; *2, *3) and PON-1 Q192R. Patients were classified as responders and nonresponders to clopidogrel based upon platelet aggregation studies. Genotyping of the CYP2C19 and PON-1 allele was carried out by PCR-RFLP. Results: Results showed that 14.3% of the patients were nonresponders, whereas 85.7% were responders to the clopidogrel therapy. CYP2C19*3 allele showed significant association with clopidogrel high on treatment reactivity in IHD patients. Conclusion: Result of our study demonstrate that IHD patients with CYP2C19*3 allele can face the problem of clopidogrel high on treatment reactivity in Punjabi Pakistani population.

Download Full-text

Novel perspective substances with selective anti-aggregant action

Kazan medical journal ◽

10.17816/kmj1923 ◽

2013 ◽

Vol 94 (5) ◽

pp. 700-704

Author(s):

S V Kiselev ◽

L E Nikitina ◽

M M Vorontsova ◽

R G Turaev

Keyword(s):

Heart Disease ◽

Platelet Aggregation ◽

Ischemic Heart Disease ◽

Venous Blood ◽

International Normalized Ratio ◽

Water Soluble ◽

System Structure ◽

Ischemic Heart ◽

Hemostasis System

Aim. To study the influence of new sulfur-containing derivatives of β-pinene on the platelet aggregation ability and coagulant activity of human serum in vitro. Methods. A series of sulfides and sulfoxides have been synthesized based on β-pinene. Sulfides have been synthesized by the electrophilic addition reaction of thiols to the double bond of β-pinene in the presence of ZnCl 2. Sulfides were oxidized to sulfoxides by such oxidizing agents as sodium periodate, meta-Chloroperoxybenzoic acid, selenium dioxide with hydrogen peroxide and sulfuryl chloride in combination with ethyl alcohol. The best result was achieved by asymmetric oxidation method using the Ti(O-i-Pr) 4/(R)-mandelic acid /t-BuOOH oxidation system. Structure of synthesized compounds was ascertained by 1Н and 13С nuclear magnetic resonance, chromatomass spectrometry and X-ray structural analysis. Clotting activity of synthesized substances was evaluated by platelets aggregating rates and standard surface-dependent coagulation tests. Venous blood from patients with ischemic heart disease and evident changes in hemostasis system were used to determine spontaneous platelets aggregation and serum clotting activity. The induced platelets aggregation was studied on serum obtained from healthy donors. Results. The basic substance (β-pinene) did not influence the hemostasis system status in patients with ischemic heart disease. The substances synthesized on its basis have shown high anti-aggregatory activity: spontaneous velocity and aggregation coefficient reduced significantly and even reached normal values in some cases. Besides, they reduced the serum clotting activity, normalized activated partial thromboplastin time, prothrombin time international normalized ratio. However, the activity of thrombin was not influenced. The most water-soluble sulfoxide showed the most activity and almost completely inhibited spontaneous and collagen-induced and arachidonic acid-induced platelet aggregation, as well as better reduced the serum clotting activity in patients with ischemic heart disease compared to other synthesized substances. Conclusion. Taking into account low toxicity of thioterpenoids, the novel substances can be described as potentially promising drugs for medical treatment and prevention of thrombophilia and as agents for blood stabilization.

Download Full-text

Polyphenols and Oxidative Stress in Atherosclerosis-Related Ischemic Heart Disease and Stroke

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/8526438 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 51

Author(s):

Yu-Chen Cheng ◽

Jer-Ming Sheen ◽

Wen Long Hu ◽

Yu-Chiang Hung

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Heart Disease ◽

Platelet Aggregation ◽

Ischemic Heart Disease ◽

Radical Scavenging ◽

Ischemic Heart ◽

Vsmc Proliferation

Good nutrition could maintain health and life. Polyphenols are common nutrient mainly derived from fruits, vegetables, tea, coffee, cocoa, mushrooms, beverages, and traditional medicinal herbs. They are potential substances against oxidative-related diseases, for example, cardiovascular disease, specifically, atherosclerosis-related ischemic heart disease and stroke, which are health and economic problems recognized worldwide. In this study, we reviewed the risk factors for atherosclerosis, including hypertension, diabetes mellitus, hyperlipidemia, obesity, and cigarette smoking as well as the antioxidative activity of polyphenols, which could prevent the pathology of atherosclerosis, including endothelial dysfunction, low-density lipoprotein oxidation, vascular smooth muscle cell proliferation, inflammatory process by monocytes, macrophages or T lymphocytes, and platelet aggregation. The strong radical-scavenging properties of polyphenols would exhibit antioxidative and anti-inflammation effects. Polyphenols reduce ROS production by inhibiting oxidases, reducing the production of superoxide, inhibiting OxLDL formation, suppressing VSMC proliferation and migration, reducing platelet aggregation, and improving mitochondrial oxidative stress. Polyphenol consumption also inhibits the development of hypertension, diabetes mellitus, hyperlipidemia, and obesity. Despite the numerousin vivoandin vitrostudies, more advanced clinical trials are necessary to confirm the efficacy of polyphenols in the treatment of atherosclerosis-related vascular diseases.

Download Full-text