OBJECTIVETo determine the impact of adjunctive Buchang Naoxintong Capsule (, NXT) on dual antiplatelet therapy in patients with cytochrome P450 2C19*2 (CYP2C19*2) polymorphism undergoing percutaneous coronary intervention (PCI).

METHODSNinety patients with CYP2C19*2 polymorphism were enrolled, and their genotypes were confirmed by polymerase chain reaction (PCR). The patients were randomly assigned to receive either adjunctive NXT (triple group, 45 cases) or dual antiplatelet therapy (dual group, 45 cases) using a computer-generated randomization sequence and sealed envelopes. Platelet function was assessed at baseline and 7 days after treatment with conventional aggregometry. Subsequent major adverse cardiovascular events (MACE, including sudden cardiac arrest and acute coronary syndrome) were recorded during a 12-month follow-up.

RESULTSBaseline platelet function measurements were similar in both groups. After 7 days, percent inhibitions of maximum platelet aggregation and late platelet aggregation were significantly greater in the triple versus dual group (42.3%±16.0% vs. 20.8%±15.2%, P<0.01, and 54.7%±18.3% vs. 21.5%±29.2%, P<0.01, respectively). During the 12-month follow-up, the rate of subsequent MACE (6/45) was significantly lower in the triple group compared with the dual group (14/45; P<0.05).

CONCLUSIONAdjunctive NXT to maintenance dose clopidogrel (75 g) could enhance the antiplatelet effect and decrease subsequent MACE in patients with the CYP2C19*2 polymorphism undergoing PCI.

Adenosine Diphosphate ; pharmacology ; Cytochrome P-450 CYP2C19 ; genetics ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Maintenance Chemotherapy ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; adverse effects ; pharmacology ; Platelet Function Tests ; Polymorphism, Genetic ; Ticlopidine ; adverse effects ; analogs & derivatives ; pharmacology ; Treatment Outcome

OBJECTIVETo study the changes of adenosine diphosphate (ADP)-induced platelet aggregation rate, and evaluate the effects of Maixuekang Capsule (, MKC) on platelet aggregation rate and long-term prognosis of patients with acute coronary syndrome after percutaneous coronary intervention (PCI).

METHODSA total of 236 patients with acute coronary syndrome, who received successful PCI, were randomly assigned to a trial group (116 cases) and a control group (120 cases) according to random numbers; treatment allocation occurred when the participants met the inclusion criteria and signed the informed consent forms. In the trial group, the patients were treated with MKC combined with routine medication, and in the control group the patients were treated with routine medication. The therapeutic course for the two groups was 12 months and the follow-up was 12 months. The levels of ADP-induced platelet aggregation rate and serum high-sensitive C-reactive protein (hs-CRP) were determined before PCI, 12 h and 30 days after PCI. In the meantime, the incidence of cardio-/cerebrovascular events was recorded during the 12-month follow-up.

RESULTSCompared with before PCI, the levels of ADP-induced platelet aggregation rate and serum hs-CRP were significantly higher at 12 h after PCI (P<0.05). They were significantly reduced after 30-day-treatment of MKC, showing statistical differences when compared with those in the control group (P<0.05). During the 12-month follow-up, the incidence of cardio-/cerebrovascular events was significantly lower in the trial group than in the control group (6.9% vs. 12.5%, P<0.01).

CONCLUSIONSADP-induced platelet aggregation function was significantly elevated after PCI. MKC improved the prognosis of patients with acute coronary syndrome, possibly through inhibiting the platelet aggregation, fighting against inflammation, and protecting the vascular endothelial function.

Acute Coronary Syndrome ; drug therapy ; surgery ; Adenosine Diphosphate ; pharmacology ; Aged ; C-Reactive Protein ; metabolism ; Capsules ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Percutaneous Coronary Intervention ; Platelet Aggregation ; drug effects ; Prognosis

OBJECTIVETo investigate the effects of Qushuanling Capsule ( QSLC) on thrombus formation and platelet aggregation in rats.

METHODSArteriovenous bypass, venous thrombosis, and middle cerebral artery thrombosis models were used in rats to investigate the anti-thrombotic effects of QSLC, a compound of nine Chinese herbs. The platelet aggregation induced by adenosine diphosphate (ADP), thrombin or arachidonic acid (AA), as well as the contents of thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1α (6-keto-PGF1α) in rat plasma and aortic walls, were determined to investigate the possible mechanisms of the anti-thrombotic effects of QSLC.

RESULTSAfter oral administration with QSLC for 7 days, arteriovenous bypass thrombosis was obviously suppressed compared with the model group, venous thrombosis was also obviously suppressed, rat behaviors were obviously improved, and brain infarct size as well as water content were also reduced. The platelet aggregation induced by ADP or thrombin was inhibited by QSLC, but the drug had no effect on AA-induced platelet aggregation and content of TXB(2) and 6-keto-PGF1α in plasma and the aortic wall.

CONCLUSIONThese results suggest that QSLC can be used in the prevention and treatment of thrombotic diseases, and that its mechanism of action may be related to inhibition of platelet aggregation.

6-Ketoprostaglandin F1 alpha ; blood ; Adenosine Diphosphate ; pharmacology ; Animals ; Aorta ; drug effects ; metabolism ; pathology ; Cerebral Infarction ; blood ; drug therapy ; pathology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Middle Cerebral Artery ; drug effects ; pathology ; Platelet Aggregation ; drug effects ; Rats ; Rats, Sprague-Dawley ; Thrombosis ; drug therapy ; pathology ; Thromboxane B2 ; blood ; Venous Thrombosis ; drug therapy ; pathology

There are growing evidences that pinocembrin has better neuroprotective effect. In the present study, the effect of pinocembrin on mitochondrial respiratory function was evaluated in global brain ischemia/ reperfusion (4-vessel occlusion, 4-VO) rats. The results showed that pinocembrin improved the respiratory activity of 4-VO brain mitochondria, through increasing ADP/O, state 3 respiration state (V3), respiration control rate index (RCI) and oxidative phosphorylation rate (OPR). And then, the effect of pinocembrin on brain mitochondria was verified in vitro. The results showed that pinocembrin increased ADP/O, state 3 respiration state, respiration control rate index, oxidative phosphorylation rate in NADH/FADH2 dependent respiratory chain and decreased state 4 respiration state (V4) in NADH dependent respiratory chain. Pinocembrin improved ATP content in brain mitochondria in vitro and in SH-SY5Y cells.
Adenosine Diphosphate ; metabolism ; Adenosine Triphosphate ; biosynthesis ; Animals ; Brain Ischemia ; pathology ; physiopathology ; Cell Line, Tumor ; Cell Respiration ; drug effects ; Flavanones ; pharmacology ; Hippocampus ; pathology ; Male ; Mitochondria ; drug effects ; physiology ; Neuroblastoma ; metabolism ; pathology ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Oxygen ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of benzo(a)pyrene (BaP) on platelet aggregation and expression of P-selectin.

METHODSBlood samples were collected from healthy volunteers and the platelets was washed. Platelet aggregation was monitored by aggregometer and the expression of P-seletin was detected by whole blood flow cytometry.

RESULTBaP (10 μmol/L, 1 μmol/L and 0.1 μmol/L) did not induce platelet aggregation; however, preincubation with BaP (10 μmol/L) significantly enhanced ADP-induced platelet aggregation (P < 0.01) and platelet aggregation was (80 ± 10)%, while BaP-preincubation failed to enhance platelet aggregation under collagen and thrombin stimulation. Flow cytometry showed that preincubation with BaP increased ADP-induced, but not thrombin-induced P-selectin expression (P < 0.01).

CONCLUSIONBaP can stimulate ADP-induced platelet aggregation and P-selectin expression, probably through the interaction with ADP-mediated signal pathway.

Adenosine Diphosphate ; pharmacology ; Benzo(a)pyrene ; pharmacology ; Blood Platelets ; drug effects ; metabolism ; Collagen ; pharmacology ; Humans ; P-Selectin ; blood ; drug effects ; Platelet Aggregation ; drug effects ; Thrombin ; pharmacology

The purpose of this study was to evaluate in vitro the effects of hydrocortisone and aminophylline on adenosine diphosphate (ADP)-induced platelet aggregation in horses. Blood samples from 30 healthy Thoroughbred horses were collected by via jugular venipuncture to assess platelet aggregation. Platelet-rich and platelet-poor plasma were prepared from all samples by centrifugation and divided into three different aliquots. In the first aliquot, platelet aggregation was measured after platelet activation with 1 microM and 0.5 microM ADP (Group A). In the other two aliquots, the effect of a 10 min preincubation with hydrocortisone (Group B) or aminophylline (Group C) on ADP-induced aggregation at final ADP concentrations of 1 microM and 0.5 microM was observed. Platelet aggregation, recorded by an aggregometer, was evaluated by measuring the maximum degree of platelet aggregation and the initial velocities of platelet aggregation were obtained. Our results demonstrated the inhibitory effect of hydrocortisone and the induction effect of aminophylline on equine platelet responses in vitro.
Adenosine Diphosphate/pharmacology ; Aminophylline/*pharmacology ; Animals ; Anti-Inflammatory Agents/*pharmacology ; Female ; Horses/*physiology ; Hydrocortisone/*pharmacology ; Male ; Platelet Aggregation/*drug effects

OBJECTIVETo investigate the effect of Tongxinluo Capsule (TXLC) on platelet aggregation in patients of coronary heart disease (CHD) with aspirin resistance (AR).

METHODSPatients with AR were screened out from 330 CHD patients, who had regularly taken aspirin (100 mg/d) for more than one month, by testing platelet aggregation level after adenosine diphosphate (ADP) and collagen (COL) induction. They were randomly assigned to three groups: the combined treatment group treated by TXLC + aspirin, the TXL group treated by TXLC alone and the AS group treated by aspirin alone, at the dose of TXLC 3 capsules thrice a day, and that of aspirin 100 mg/d. The therapeutic course for all was one month. Patients' platelet aggregation was measured before and after 1-month treatment.

RESULTSEighty-nine patients with AR were screened out from the 330 CHD patients, the occurrence rate being 26.97%. Platelet aggregation was significantly decreased after 1-month treatment in the combined treatment group and the TXL groups (P < 0.05), but changed insignificantly in the AS group, the difference between the former two and the latter group was statistically significant (P < 0.05).

CONCLUSIONTXLC has definite effect in reducing the ADP + COL induced platelet aggregation.

Adenosine Diphosphate ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Aspirin ; pharmacology ; Collagen ; metabolism ; Coronary Disease ; blood ; drug therapy ; Drug Resistance ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; drug effects

BACKGROUNDAdenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.

METHODSA total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel (n = 104) served as the Talcom (Taijia) group; others (n = 101) received Plavix, the Plavix group. Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% (the primary endpoint) compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.

RESULTSCompared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a > 50% decrease in adenosine phosphate-mediated platelet aggregation (rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P = 0.028). There was no significant difference in the eligible index between the Talcom and Plavix groups (47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P > 0.05) based on a standard adenosine diphosphate-mediated platelet aggregation decrease of > 50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events (2.5% vs. 2.9%, P = 5.43). No acute or subacute stent thrombosis events occurred.

CONCLUSIONAn adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Adenosine Diphosphate ; pharmacology ; Aged ; Angioplasty, Balloon, Coronary ; Female ; Humans ; Male ; Middle Aged ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; administration & dosage ; Prospective Studies ; Ticlopidine ; administration & dosage ; adverse effects ; analogs & derivatives

This study is to observe the difference in pharmacological characteristics between circular smooth muscles of rat isolated gastric body and gastric fundus, and to investigate the effects of nucleoside and nucleotide on circular smooth muscle of the rat gastric body and the involved receptors. Circular muscle strips of the rat gastric body and gastric fundus were prepared, and contractile responses to agonists were investigated with a technique of drug-receptor interaction in functional system. There was no significant difference between the circular muscle strips of the gastric body and gastric fundus in the responses to KCl, and no difference in EC50 values of contractile responses for 5-HT and His between the two kinds of preparations (P > 0.05). However, Emax values of contractile responses to 5-HT and His [(0.81 +/- 0.26) and (0.88 +/- 0.27) g] in gastric body were significantly smaller than those in gastric fundus [(2.67 +/- 0.61) and (1.90 +/- 0.68) g, P < 0.01], and EC50 value of CCh produced contractile response [(0.45 +/- 0.15) micromol x L(-1)] in gastric body was significantly higher than that in gastric fundus [(0.20 +/- 0.09) micromol x L(-1), P < 0.01]. In precontracted circular muscle strips of the gastric body, ATP (0.1-3000 micromol x L(-1)) produced only a contractile response concentration-dependently, but the same concentration of ATP induced a biphasic response (relaxation followed by a contraction) in precontracted circular muscle strips of the gastric fundus. ATP, UTP, ADP, 2-MeSATP and alpha,beta-MeATP produced contractile responses concentration-dependently in circular muscle strips of the rat gastric body. The EC50 value for 2-MeSATP [(7.2 +/- 5.2) nmol x L(-1)] was about 500 times lower than that for Ach [(3.47 +/- 1.20) micromol x L(-1)]. The rank order of potency for the contraction was 2-MeSATP>ADP>ATP=UTP>alpha,beta-MeATP>adenosine. The contractile responses to ATP and UTP were not significantly affected by phentolamine, propranolol, atropine or tetrodotoxin. In conclusion, there is a significant difference in pharmacological characteristics between the circular smooth muscles of the rat gastric body and gastric fundus and nucleotides might be important mediators responsible for the contraction via a specific P2Y receptor in circular smooth muscle of the rat gastric body.
Adenosine ; pharmacology ; Adenosine Diphosphate ; pharmacology ; Adenosine Triphosphate ; analogs & derivatives ; pharmacology ; Animals ; Gastric Fundus ; drug effects ; physiology ; Male ; Muscle Contraction ; drug effects ; Muscle, Smooth ; drug effects ; physiology ; Purinergic P2 Receptor Agonists ; Rats ; Rats, Wistar ; Receptors, Purinergic P2 ; drug effects ; Stomach ; drug effects ; physiology ; Thionucleotides ; pharmacology ; Uridine Triphosphate ; pharmacology

OBJECTIVETo investigate the effect of five traditional Chinese medicine formula for promoting blood circulation to remove stasis (Xuefuzhuyu Tang, Shaofuzhuyu Tang, Gexiazhuyu Tang, ShentongZhuyu Tang, Tongqiaohuoxue Tang) on platelet aggregation and clotting time in a dose-response relationship.

METHODThe platelet aggregation was tested with Born's method and thrombin time (TT) method was established to determine the clotting time.

RESULTThe formula for promoting blood circulation to remove stasis showed significant inhibitory effects on the platelet aggregation and prolonged clotting time, the supernate of 80% alcohol solution showed the most potent inhibitory activity among the three kinds of samples from one formula (P < 0.01), especially the supernate of Shaofuzhuyu Tang and Gexiazhuyu Tang were better than other formula on platelet aggregation. About the anticoagulant, the whole formula showed the evidently prolonging the clotting time than other two fractions (P < 0.01) and the precipitation were the worst.

CONCLUSIONThe formula for promoting blood circulation to remove stasis showed significant effect on platelet aggregation and clotting time, and different samples of the formula had different efficacy. The study established a foundation for further bio-activity evaluation of these formulae and provided evidence for the treatment of cardiovascular and cerebrovascular diseases.

Adenosine Diphosphate ; adverse effects ; Animals ; Blood Circulation ; drug effects ; Blood Coagulation ; drug effects ; Chemistry, Pharmaceutical ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; Female ; Male ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; pharmacology ; Rabbits ; Thrombin Time