ABSTRACT
We analysed clinical and pharmacological factors influencing resistance to clopidogrel in 250 patients with cardiovascular diseases during 18 months. It was shown that the risk ofresistance depends on the form of coronary heart disease, carbohydrate metabolism, the AA genotype of CYP2C19*2 and TBS1 genes. The cardiovascular events significantly morefrequently occurred during 12 and 18 months in resistant diabetics and in the patients with an allele lacking the *2/*3 CYP2C9 gene function and AT/TT polymorphism of the thromboxane synthase gene TBS1.
Subject(s)
Cardiovascular Diseases/drug therapy , Cytochrome P-450 CYP2C19/genetics , DNA/genetics , Drug Resistance/genetics , Polymorphism, Genetic , Thromboxane-A Synthase/genetics , Ticlopidine/analogs & derivatives , Alleles , Cardiovascular Diseases/metabolism , Clopidogrel , Cytochrome P-450 CYP2C19/metabolism , Female , Genotype , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Thromboxane-A Synthase/metabolism , Ticlopidine/therapeutic useABSTRACT
AIM: To analyze the influence of clinical and pharmacogenetic factors on the risk of resistance to original or generic clopidogrel and that of cardiovascular events (CVE) during 12 months of follow-up. SUBJECTS AND METHODS: Two hundred and fifty patients admitted to Moscow hospitals in October 2011 to September 2012 were examined. All the patients received clopidogrel. During their stay at hospital, venous blood samples were collected twice (before and 7-10 days after continuous clopidogrel intake). Platelet function was determined by optical aggregometry. A less than 10% reduction in platelet aggregation was taken as a resistance criterion. In addition, CYP2C9 and CYP2C19 gene polymorphisms were investigated. RESULTS: Whether original or generic clopidogrel is used, the level of baseline or post-7-day ADP-induced platelet aggregation (ADP aggregation) fails to affect the risk of its resistance. Evaluation of ADP-induced platelet aggregation in patients with different CYP2C9 and CYP2C19 gene polymorphisms during the administration of original or generic clopidogrel also showed no significant differences in its resistance. During the 12-month follow-up, CVE significantly less frequently occurred as a result of the intake of original versus generic clopidogrel. CONCLUSION: The use of original clopidogrel does not affect the risk of resistance to antiplatelet drugs, but it is associated with the lower incidence of CVE during a year.
Subject(s)
Cardiovascular Diseases , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C9/genetics , Drug Resistance/genetics , Ticlopidine/analogs & derivatives , Aged , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/drug therapy , Cardiovascular Diseases/genetics , Clopidogrel , Drug Monitoring , Drug Substitution , Drugs, Generic/pharmacokinetics , Female , Humans , Male , Middle Aged , Pharmacogenetics , Platelet Aggregation/drug effects , Platelet Aggregation Inhibitors/pharmacokinetics , Platelet Function Tests/methods , Polymorphism, Genetic , Prognosis , Therapeutic Equivalency , Ticlopidine/pharmacokinetics , Treatment OutcomeSubject(s)
Collagen/physiology , Fibroblasts/transplantation , Laminin/physiology , Skin Transplantation , Skin/injuries , Surgical Flaps , Wound Healing , Animals , Culture Media, Conditioned , Humans , Male , RatsABSTRACT
The optimum composition of serum-free media has been established for cultivation of the continuous cell line Vero originated from kidney tissue of a normal African green monkey, in addition to the optimum composition of low-level serum media (2%) for cultivation of human embryonic fibroblasts. The medium DME (one of the basic media) appeared a medium of choice for both these cell types, and the best serum replacement consisted of insulin, bovine serum albumin, ethanolamine, epidermal growth factor and hydrocortisone. Under employment of this serum replacement together with the medium DME the proliferation indices for the Vero lineage and human embryonic fibroblasts were 76 and 71%, respectively. The developed serum replacement can serve the basis for a further optimization on cultivation of fibroblast-like cells, such as Vero and human embryonic fibroblasts, under serum-free or low-level serum conditions.
Subject(s)
Fibroblasts/cytology , Vero Cells/cytology , Animals , Cell Division , Chlorocebus aethiops , Culture Media , Culture Media, Serum-Free , Embryo, Mammalian , HumansABSTRACT
Low frequency ultrasound was applied to the treatment of suppurative maxillary sinusitis. The bactericidal activity of low frequency ultrasound was measured experimentally. Its effect on the mucous membrane of rabbit maxillary sinuses when they were sonicated from within was determined. This method allowed the therapeutic efficacy to be increased (83%). The method can be recommended for the treatment of drug intolerant patients.
