Maximum Aggregation Rate Research Articles

Changes of platelet aggregability in patients with subcortical ischemic vascular disease

Objective: To explore the change and value of platelet aggregability(PA)in patients with subcortical ischemic vascular disease (SIVD). Methods: A total of 108 patients with SIVD hospitalized in the Department of Neurology of the First Affiliated Hospital of Anhui Medical University from October 2015 to July 2017 were enrolled as SIVD group and 30 healthy cases were also in cluded as normal controlgroup (NC). According to magnetic resonance imaging(MRI), the SIVD group was further divided into two subtypes: lacunar infarction(LI) (n=31)and leukoaraiosis(LA) (n=77). The severity of LA was further graded according to the Fazekas scale. The maximum aggregation rate of platelets was measured by optical turbidimetry, respectively, using four arachidonic acid (ACA), two adenosine monophosphate (ADP) and collagen (COLL) as inducerin all subjects. The change of PA between the subtypes of SIVD and NC were compared, and the relationship between PA and the severity of LA was analyzed. Results: The level of PA in SIVD was significantly higher than those in NC (P<0.001). In comparison with NC, the level of PA was significantly higher in both LI and LA subgroups(P<0.05). Meanwhile, there was no significant difference between LA group and LI group (P>0.05). Moreover, between LA groups, the PA induced by COLL were significantly different between the LA3 group and the LA1 group (P=0.026). Correlation analysis showed that ageand the level of PA induced by COLL was positively correlated with LA grade (r=0.382, P=0.001; r=0.260, P=0.026). Multivariate logistic regression analysis revealed that after controlling for various factors, when induced by ACA, the risk of SIVD in the highest group (>86.80%) and higher group (82.63%-86.80%) was 13.95 and 3.09 times respectively higher than in the normal group(<82.63%), the differences were statistically significant (P<0.001, P=0.038); when induced by ADP, the risk of SIVD in the highest group (>87.63%) and higher group (82.80%-87.63%) was 20.78 and 5.85 times respectively higher than in the normal group (<82.80%), the differences were statistically significant (P<0.001, P=0.003); When induced by COLL, the risk of SIVD in the highest group (>87.60%) and higher group (83.80%-87.60%)was 28.53 and 9.02 times respectively higher than in the normal group (<83.80%), the differences were statistically significant (P<0.001, P=0.002). Conclusions: The increasedlevel of PA is an independent risk factor of SIVD and closely related with the severity of LA .This study provides a theoretical basis for further understanding of the SIVD's pathogenesis and for the prevention and treatment of SIVD in the clinical practice.

PXR polymorphisms have impact on the clinical efficacy of clopidogrel in patients undergoing percutaneous coronary intervention

BackgroundsClopidogrel is widely used in Coronary Heart Disease (CHD) patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic events. However, clopidogrel response variability (CRV) may affect the patients' clinical outcomes. The current data have shown that genetic factors play an important role in CRV. The aim of this research is to investigate the association of pregnane X receptor (PXR, also called NR1I2) genetic polymorphisms with the clinical efficacy of clopidogrel in patients undergoing PCI. MethodsA total of 384 patients undergoing PCI were recruited and treated with dual antiplatelet therapy (DAPT) for 12 months. The plasma concentration of clopidogrel carboxylic acid metabolites (CLPM) was measured by High Performance Liquid Chromatography (HPLC). The maximum aggregation rate (MAR) of platelet were measured by PL-11 analyzer. PXR genetic polymorphisms were determined by Sequenom MassArray system. The clinical outcomes were observed by readmission, outpatient and calling back interview within 12 months after PCI. ResultsAmong all 384 patients, a total of 153 patients were occurred with major adverse cardiovascular events (MACE), 29 patients were occurred with bleeding events, the other patients had a favorable prognosis. The polymprphisms of PXR rs3814057A > C [OR(95%CI): 0.71(0.527–0.957), P = 0.024], rs3814058T > C [OR (95%CI): 1.395(1.034–1.883), P = 0.029] and rs6785049 A > G [OR(95%CI): 0.724 (0.535–0.979), P = 0.036] were significantly associated with MACE. The haplotype h1 (GCC) was associated with a higher risk of MACE [OR (95%CI): 1.385 (1.028–1.866), P = 0.031]. Whereas, the haplotype h2 (AAT) was associated with a lower risk of MACE [OR (95%CI): 0.711(0.525–0.962), P = 0.027]. ConclusionsThe genotypes and haplotypes of PXR rs3814057, rs3814058 and rs6785049 have impact on the MACE in clopidogrel treated patients after PCI.

Increased Thrombogenicity in Chronic Renal Failure in a Rat Model Induced by 5/6 Ablation/Infarction.

PurposeAbnormalities in hemostasis and coagulation have been suggested in chronic renal failure (CRF). In this study, we compared processes of thrombus formation between rats with CRF and those with normal kidney function.Materials and MethodsCRF was induced by 5/6 ablation/infarction of the kidneys in Sprague-Dawley rats, and surviving rats after 4 weeks were used. Ferric chloride (FeCl3)-induced thrombosis in the carotid artery was induced to assess thrombus formation. Whole blood clot formation was evaluated using rotational thromboelastometry (ROTEM). Platelet aggregation was assessed with impedance platelet aggregometry.ResultsFeCl3-induced thrombus formation was initiated faster in the CRF group than in the control group (13.2±1.1 sec vs. 17.8±1.0 sec, p=0.027). On histological examination, the maximal diameters of thrombi were larger in the CRF group than in the control group (394.2±201.1 µm vs. 114.0±145.1 µm, p=0.039). In extrinsic pathway ROTEM, the CRF group showed faster clot initiation (clotting time, 59.0±7.3 sec vs. 72.8±5.0 sec, p=0.032) and increased clot growth kinetics (α angle, 84.8±0.2° vs. 82.0±0.6°, p=0.008), compared to the control group. Maximal platelet aggregation rate was higher in the CRF group than in the control group (58.2±0.2% vs. 44.6±1.2%, p=0.006).ConclusionOur study demonstrated that thrombogenicity is increased in rats with CRF. An activated extrinsic coagulation pathway may play an important role in increasing thrombogenicity in CRF.

Features of functioning of trombocytic layer of hemostasis in experimental parodontitis modeling

The purpose of the study is to identify the peculiarities of the functioning of the vascular-thrombocyte linkage of hemostasis in the experimental periodontitis.Material and methods. Experimental manipulations were performed on white nonlinear male rats weighing 260.0 ± 30.0 g, in which experimental periodontitis was induced. Determination of total, free and bound oxyproline in urine was carried out using the method of P. N. Sharaev. Analysis of the aggregation curve included the definition of such indicators: 1) the degree of aggregation — the maximum% of light transmission of the plasma; 2) time to achieve maximum aggregation rate — time to achieve maximum% light transmission; 3) the rate of aggregation, which was calculated 30 seconds after the beginning of platelet aggregation. Results. Studying the functional activity of platelets in rats with experimental periodontitis revealed signs of changes in the functions of the platelet linkage hemostasis. In periodontitis in connective tissue periodontium and thrombocyte hemostasis, metabolic disorders of the connective tissue were revealed, which is the level of oxyproline in the urine of animals.Conclusions. In the experimental periodontitis, clear changes in the functional activity of the platelets were detected. In parallel with the decrease in the functional activity of platelets in the periodontitis, the level of urine in all three oxyproline fractions is reduced. The obtained results testify to the commonality of processes occurring in the blood and connective tissue and associated with metabolic disorders in it, decrease in the synthesis and collagen collapse.

Influence of aspirin/clopidogrel treatment on platelet aggregation rate and analysis of drug resistance in the patients with coronary heart disease

Objective To investigate the influence of aspirin and/or clopidogrel treatment on platelet aggregation rate in coronary heart disease (CHD) patients, and discuss the factors related to anti-platelet drug resistance. Methods A total of 160 patients with CHD and received aspirin and/or clopidogrel treatment were enrolled in the Second Xiangya Hospital, Central South University, and were divided into stable coronary heart disease (SCHD) group (n=90) and acute coronary syndrome (ACS) group (n=70). Meanwhile, non-coronary heart disease (NCHD) patients who did not receive anti-platelet drug treatment were enrolled as controls (n=50). Clinical data of the subjects were recorded. The maximum platelet aggregation rate induced by arachidonic acid (MAR-AA) and adenosine diphosphate (MAR-ADP) were evaluated with sequential platelet counting method. The factors related to drug resistance were analyzed with Logistic regression analysis. Results Compared to NCHD group, there were lower MAR-AA and MAR-ADP in two groups of CHD (all P<0.05). In ACS patients, MAR-AA and MAR-ADP are significantly lower (P<0.05) in patients who receive the aspirin and clopidogrel. The rate of anti-platelet drug resistance in ACS group was significantly higher than that in SCHD group (20.0% vs 10.0%, P<0.05). Multivariate logistic regression analysis showed that low HDL-C (<1.0 mmol/L) was an independent risk factor related to the anti-platelet drug resistance (OR=4.36, 95% CI: 1.36-14.02, P=0.025). Conclusions The antiplatelet treatment with aspirin and/or clopidogrel can significantly reduce the platelet reactivity in CHD patients, but some patients still present anti-platelet drug resistance. The combination of aspirin and clopidogrel is better. The rate of drug resistance in ACS patients is high. Low HDL-C might be associated with anti-platelet drug resistance. Key words: Aspirin/TU; Ticlopidine/AA/TU; Coronary disease/DT; Platelet aggregation/DE; Drug resistance

Spirostanol saponins from Ypsilandra parviflora induce platelet aggregation

Phytochemical investigation on the whole plants of Ypsilandra parviflora led to the isolation of seven new spirostanol saponins, named ypsiparosides A–G, together with 14 known saponins. Their structures were unambiguously established based on extensive spectroscopic evidence and chemical methods. The induced rabbit platelet aggregation activities of the isolates were tested. Compounds 4, 15, and 17 showed maximal platelet aggregation rates ranging from 43 to 55% at a concentration of 300μg/mL. Further experiments exhibited that compounds 4, 15, and 17 possessed EC50 values of 642.9, 95.3, and 300.8μg/mL, respectively.

Shen-Cao granules formulated based on traditional Chinese medicine alleviates bone marrow suppression caused by platinum-based anticancer reagents.

Background:The aim of this study was to evaluate effects of Shen-Cao granules for the prevention of thrombocytopenia caused by anticancer chemotherapy.Methods:In this prospective study, a total of 200 patients with various malignant tumors were enrolled and evenly divided into a Shen-Cao granule treatment (n = 100) and a control group (n = 100). After 2 cycles chemotherapy with any combination of platinum-based drugs (cisplatin, carboplatin, and nedaplatin), the blood platelet (PLT) counts, levels of the PLT production regulator thrombopoietin (TPO), PLT aggregation rates, and the PLT activation marker CD62P expressions were monitored for 2 weeks.Results:During 2 weeks of post-chemotherapy, the mean values of the minimum PLT count were 49.65 ± 7.35 × 109/L in the treatment group and 31.56 ± 9.32 × 109/L in the control group. The PLT count in the treatment group reached the lowest value 1.8 days later and recovered to a concentration ≥100 × 109/L 3 days earlier than in the control group. The concentrations of the TPO were 71.43 ± 1.74 and 87.24 ± 0.92 ng/mL in the treatment group and 65.75 ± 1.39 and 67.75 ± 0.67 ng/mL in the control group at 7 and 14 days post-chemotherapy, respectively. The maximum PLT aggregation rate declined after chemotherapy in the treatment group from 58.14 ± 11.46% to 52.89 ± 10.52%, while it increased in the control group from 56.94 ± 10.55% to 61.75 ± 12.26%. Coordinately, the expression of CD62P in the treatment group decreased from 6.17 ± 0.59% to 4.89 ± 0.72%, while it increased from 6.09 ± 0.75% to 7.75 ± 0.67% in the control group.Conclusion:Our study demonstrated that Shen-Cao granule treatment alleviated thrombocytopenia after chemotherapy, and reduced tumor-induced PLT activation and aggregation.

Protective effects of traditional Chinese herbal formula Compound Xueshuantong Capsule (CXC) on rats with blood circulation disorders

ABSTRACTCompound Xueshuantong Capsule (CXC) is a traditional Chinese herbal formula composed of root of Panax pseudoginseng var. notoginseng (Burkill) G. Hoo & C.L. Tseng, root of Astragalus membranaceus var. mongholicus (Bunge) P.K. Hsiao, root of Salvia miltiorrhiza var. charbonnelii (H. Lév.) C.Y. Wu, and root of Scrophularia ningpoensis Hemsl. CXC was approved by the China Food and Drug Administration in 2003 (No. Z20030017) based on the positive clinical effect in the treatment of cardiovascular diseases. The present study was designed to elucidate the mode of action of CXC in the regulation of the haemorheology, blood coagulation, oxidative stress and energy metabolism. Rats were placed in ice-cold water (0–4 °C) for 5 min during the time interval (4 h) between two adrenaline injections to induce blood circulation disorders. Blood was collected from abdominal aorta to detect whole blood viscosity, plasma viscosity, maximum platelet aggregation rate, erythrocyte aggregation index, red corpuscle electrophoresis index, activated partial thromboplastin time and prothrombin time. Myocardial tissue was homogenized to detect total antioxidant capacity, myeloperoxidase, Na+–K+ ATPase, and Ca2+ ATPase. The results indicated that, in addition to preventing haemorheological disorders, CXC could perform anti-platelet and anticoagulant effects, promote total antioxidant capacity and regulate myocardial energy metabolism, which might partly account for its mechanisms of action against cardiovascular diseases.

Comparison of the effect of ticagrelor and clopidogrel on platelet functions and inflammation factor in patients with acute coronary syndrome after PCI

Objective To compare the effect of ticagrelor and clopidogrel on platelet functions and inflammation factor in patients with acute coronary syndrome(ACS) after PCI. Methods 180 patients with ACS who taken PCI were chosen and randomly divided into the observation group and the control group(90 cases in each group). All patients of the two groups were given conventional treatment, and the control group received clopidogrel treatment on the basis of routine therapy preoperation and postoperation, while the observation group received clopidogrel treatment on the basis of the control group treatment.Before treatment and 24 h, 7 d, 28 d after treatment, the C-reactive protein(CRP), interleukin 6(IL-6), tumor necrosis factor alpha(TNF-α), myeloperoxidase(MPO), soluble CD40 receptor(sCD40L), platelet maximum aggregation rate(MPAR) and P2Y12 response unit(PRU) in the two groups were recorded and compared, as well as the main cerebrovascular events after six months follow-up. Results In the two groups before treatment, MPAR and PRU had no statistically significant differences(t=0.41, 0.19, all P>0.05).24h, 7d and 28d after operation, MPAR and PRU were significantly decreased compared with before treatment(t≥2.09, all P 0.05).24h after treatment, CRP, sCD40L, IL-6 and TNF-α in the two groups all significantly increased(all P<0.05), and then decreased.24h, 7d, 28d after treatment, DCRP, sCD40L, IL-6 and TNF-α in the observation group were all significantly lower than those in the control group (t=60.79, 50.30, 27.95, 12.98, 40.29, 16.73, 15.03, 7.30, all P<0.05). And, the incidence rate of cardiovascular adverse events of the observation group was 2.22%, which was significantly lower than 10.00% of the control group(χ2=5.714, P<0.05). Conclusion Compared with clopidogrel, using ticagrelor to treat ACS patients after PCI has better antiplatelet aggregation and inflammation effects, which can reduce the incidence of cardiovascular adverse events. Key words: Coronary artery disease; Ticagrelor; Blood platelets; Chemokines

Adequate Platelet Function Inhibition Confirmed by Two Inductive Agents Predicts Lower Recurrence of Ischemic Stroke/Transient Ischemic Attack.

Background The correlation between platelet function and recurrent ischemic stroke or TIA remains uncertain. Objective To investigate two inductive agents to detect platelet functions and assess associations with recurrent ischemic stroke/TIA. Method The study included 738 ischemic stroke/TIA patients. On days 0, 3, and 9 after antiplatelet therapy, platelet function tests were determined by maximum aggregation rate (MAR) using a PL-11 platelet function analyzer and phase matching reagents. Two induction agents were used: arachidonic acid (AA) and adenosine diphosphate (ADP). At 3-month follow-up, recurrence of stroke/TIA was recorded. Result Cut-off values of adequate platelet function inhibition were MARADP < 35% and MARAA < 35%. Data showed that antiplatelet therapy could reduce the maximum aggregation rate. More importantly, adequate platelet function inhibition of either MARADP or MARAA was not associated with the recurrence of stroke/TIA, but adequate platelet function inhibition of not only MARADP but also MARAA predicts lower recurrence (0/121 (0.00%) versus 18/459 (3.92%), P = 0.0188). Conclusion The platelet function tested by PL-11 demonstrated that adequate inhibition of both MARADP and MARAA could predict lower risk of ischemic stroke/TIA recurrence.

Effects of astaxanthin on blood coagulation, fibrinolysis and platelet aggregation in hyperlipidemic rats

Context: Astaxanthin (ASTX) is a xanthophyll carotenoid that reduces hemostasis in hyperlipidemic organisms. Its antihemostatic mechanisms remain unclear. Objective: The effects of ASTX on coagulation, the fibrinolytic system and platelet aggregation were investigated in hyperlipidemic rats. Materials and methods: Different doses of ASTX (5, 10 and 30 mg/kg/day, p.o.) were administered for four weeks to high-fat diet-induced hyperlipidemic rats. Serum lipid and lipoprotein levels were measured with an automatic biochemical analyzer. The prothrombin time (PT), activated partial thromboplastin time (APTT) and maximum platelet aggregation rate (MAR) were determined by a coagulation analyzer. The activities of the tissue-type plasminogen activator (t-PA), type-1 plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS), as well as the levels of thromboxane B(2) [TXB(2)], 6-keto prostaglandin F(1α) [6-keto-PGF(1α)] and platelet granule membrane protein (GMP-140), were measured with enzyme-linked immunosorbent assay kits. Gene and protein expression levels were analyzed by reverse transcriptase polymerase chain reaction and Western blot, respectively. Results: ASTX (30 mg/kg) treatment in hyperlipidemic rats reduced serum TG (0.58 ± 0.14 versus 1.12 ± 0.24 mmol/L), serum TC (1.77 ± 0.22 versus 2.24 ± 0.21 mmol/L), serum LDL-C (1.13 ± 0.32 versus 2.04 ± 0.48 mmol/L), serum MDA (69%), plasma MAR (55%), serum TXB2/6-keto-PGF1α (34%) and serum GMP-140 levels (25%), plasma PAI-1 activity (48%) and downregulated the mRNA (33%) and protein (23%) expression of aorta eNOS, the mRNA (79%) and protein (72%) expression levels of aorta PAI-1. However, ASTX (30 mg/kg/d) treatment increased serum SOD activity (2.1 fold), serum GPx activity (1.8 fold), plasma PT (1.3 fold), plasma APTT (1.7 fold), serum NO (1.4-fold), serum 6-keto-PGF1α (1.3 fold). Conclusions: ASTX reduced blood coagulation and platelet aggregation and promoted fibrinolytic activity in hyperlipidemic rats. These activities were closely correlated with ASTX, maintaining the balance of t-PA/PAI-1, NO/ROS and TXA2/PGI2 in vivo.

Impact of CYP2C19 Variants on Clinical Efficacy of Clopidogrel and 1-Year Clinical Outcomes in Coronary Heart Patients Undergoing Percutaneous Coronary Intervention

The impact of pharmacogenetic variants of cytochrome P450 2C19 (CYP2C19) on clopidogrel-mediated effects on platelet inhibition, inflammatory response and endothelial function, as well as risk of major adverse cardiovascular events (MACE), in coronary heart patients undergoing percutaneous coronary intervention (PCI) was investigated. To this end, we assessed the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 h of PCI in 559 patients treated with clopidogrel and followed up for 1 year for evidence of MACE. CYP2C19 *2 and *3 variants were identified using a clopidogrel-sensitive gene detection kit. Our results showed higher RPA and MAR as well as increased sE-selectin, sCD40L, sP-selectin, MMP-9, and sVCAM-1 levels in CYP2C19 intermediate metabolizer (IM, CYP2C19*1/*2, or *1/*3), poor metabolizer (PM, CYP2C19*2/*2, *2/*3, or *3/*3) and combined IM+PM groups, relative to those in extensive metabolizers (EM, CYP2C19*1/*1). In total, 519 patients completed 1 year of follow-up, among which 69 (13.3%) experienced MACE. The risk of MACE in CYP2C19 IM+PM patients was 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664 (1.397–5.193), P = 0.004). The data suggest that CYP2C19*2 and *3 variants modulate the drug efficacy of clopidogrel in coronary heart patients undergoing PCI and further enhance the risk of MACE. Accordingly, CYP2C19 pharmacogenetic profiling may be beneficial for coronary heart patients undergoing PCI to predict the efficacy of treatment with clopidogrel. We propose that IM and PM patients should benefit from treatment with higher clopidogrel doses to improve efficacy and reduce the incidence of MACE.

Anti-atherosclerosis and cardio-protective effects of the Angong Niuhuang Pill on a high fat and vitamin D3 induced rodent model of atherosclerosis

Ethnopharmacological relevanceThe Angong Niuhuang Pill (ANP) is a well known Chinese traditional therapeutic for the treatment for diseases affecting the Central Nervous System (CNS). Components of the ANP formulation, including Bovis Calculus Sativus, Pulvis Bubali Comus Concentratus, Moschus, Margarita, Cinnabaris, Realgar, Coptidis Rhizoma, Scutellariae Radix, Gardeniae Fructus, Curcumae Radix, and Bomeolum Syntheticum, have been used for the treatment of stroke, encephalitis and emergency meningitis across Asia, especially in China for hundreds of years. ObjectiveThe goal of this study was to investigate the anti-atherosclerosis and cardio-protective effects of ANP administration using a rodent model of atherosclerosis induced by a high fat and vitamin D3. MethodsSpecific Pathogen-Free (SPF) 78 male SD rats were randomly divided into a control group and 5 atherosclerotic model groups. The atherosclerotic groups were divided to receive either Simvastatin (SVTT, 0.005g/kg), Low-dose ANP (0.125g/kg), Medium-dose ANP (0.25g/kg), and High-dose ANP (0.5g/kg). Following adaptive feeding for one week, atherosclerosis was induced and the atherosclerosis model was established. Experimental drugs (either simvastatin or ANP) or normal saline were administered intragastrically once daily for 9 weeks starting from the 8th week. A carotid artery ultrasound was performed at the 17th week to determine whether atherosclerosis had been induced. After the atherosclerosis model was successfully established, platelet aggregation rates, serum biochemical indices, apoptosis-related Bcl-2, Bax proteins levels in the heart were assayed. Pathological and histological analysis was completed using artery tissue from different experimental different groups to assess the effects of ANP. ResultsANP significantly decreased aortic membrane thickness, the maximum platelet aggregation rates, and the ratio of low density lipoprotein cholesterol (LDL) to high density lipoprotein cholesterol (HDL). In addition, ANP significantly reduced serum contents of total cholesterol, low density lipoprotein, malondialdehyde, troponin I, high-sensitivity C-reactive protein, and lactate dehydrogenase. ANP markedly improved abnormal pathological conditions of the aorta and heart, and helped to prevent myocardial apoptosis. ConclusionsWe have demonstrated that ANP has robust ant-atherosclerosis and cardio-protective effects on a high-fat and vitamin D3 – induced rodent model of atherosclerosis due to its antiplatelet aggregation, lipid regulatory, antioxidant, anti-inflammatory and anti-apoptotic properties.

Spirostanol glycosides with hemostatic and antimicrobial activities from Trillium kamtschaticum

Ten spirostanol glycosides, trillikamtosides A–J, together with eleven known analogues, were isolated from the hemostatic fraction of the 75% aqueous EtOH extract of the whole herbs of Trillium kamtschaticum. Their structures were established by extensive spectroscopic data analysis and chemical methods. The aglycones of three of these compounds had unique 3β,17α-dihydroxy-spirostanes featuring a double bond between C-4 and C-5, while two others represent a rare class of spirostanol glycosides which possess a 5(6 → 7) abeo-steroidal aglycone. All the compounds were evaluated for their hemostatic and antimicrobial activities. Three of the spirostanol glycosides exhibited induced-platelet aggregation at a concentration of 300 μg/mL with maximal induced-platelet aggregation rates of 72%, 71%, and 62% in rabbits, respectively, and their EC50 values were 492.7, 203.3, and 109.8 μM. Five of the spirostanol glycosides showed an anti-Candida albicans effect with MIC values of 21.1, 10.6, 8.8, 21.6, and 11.0 μM, respectively.

PS 05-55 IMPACT OF CYP2C19 VARIANTS ON DRUG EFFICACY OF CLOPIDOGREL AND 1-YEAR CLINICAL OUTCOMES IN CORONARY HEART PATIENTS UNDERGOING PCI

Objective: To investigate the following: 1) the association between CYP2C19 variants involved in clopidogrel-mediated platelet effects; 2) the association between CYP2C19 variants involved in clopidogrel-mediated inflammatory, endothelial effects; 3) CYP2C19 variants involved in the risk of major adverse cardiovascular events(MACE). Design and Method: We detected the residual platelet aggregation rate (RPA), maximal aggregation rate (MAR) and the plasma levels of sCD40L, sP-selectin, MMP-9, sVCAM-1 and sE-selectin after 24 hours of PCI in 559 patients undergoing PCI treated with clopidogrel, and followed up for one year for MACE. Results: The levels of RPA, MAR, sE-selectin, sCD40l, sP-selectin, MMP-9 and sVCAM-1 in CYP2C19 intermediate metabolizers (IM), poor metabolizers (PM) or both together patients were higher than those in extensive metabolizers (EM) patients. During one-year follow-up, there were 69 cases (13.3%) suffering MACE. The risk of MACE in CYP2C19 IM + PM patients is 2.664 times higher than that in CYP2C19 EM patients (OR = 2.664(1.397–5.193), P = 0.004). Our results suggest that CYP2C19 metabolizers modulate clopidogrel drug efficacy in coronary heart patients undergoing PCI and further impact on the risk of MACE. Conclusions: Thus it is benefit for coronary heart patients undergoing PCI treated with clopidogrel if carried out individualized treatment according to CYP2C19 metabolizers.

Anti-aggregant activity of new xanthine derivative under conditions of hyper aggregation of platelets in vitro

Aim. To study the anti-aggregant activity and the effectiveness of firstly synthesized cyclohexilammonium salt of 2-[1-ethil-3-methyl-7-(dioxotiethanyl-3)-xantinyl-8-thio]acetic acid as a potential antiplatelet agent under in vitro conditions.&#x0D; Methods. Experimental work was carried out on the blood of healthy donors and 74 male patients diagnosed with thrombosis of various localization. Thromboelastography of citrate blood samples was performed in the presence of the test substances on the device TEG 5000. The analysis determined the overall trend of coagulation, functional activity of platelets and fibrinogen, fibrinolytic activity and physico-mechanical properties of clots formed. ADP-, collagen-, and epinephrine-induced platelet aggregations were registered. Agregatogramm analysis was performed using software AGGR. We evaluated the general nature of the aggregation, the maximum aggregate, maximum aggregation rate, the average size of platelet aggregates.&#x0D; Results. Cyclohexilammonium salt of 2-[1-ethil-3-methyl-7-(dioxotiethanyl-3)-xantinyl-8-thio]acetic acid in in vitro conditions showed anti-aggregant activity greater than the reference substance, and effectively suppress hypercoagulation caused by an excess of thrombin and tissue factor.&#x0D; Conclusion. The results of the study make it possible to establish in a potentially high ex vivo therapeutic effect of a cyclohexilammonium salt of 2-[1-ethil-3-methyl-7-(dioxotiethanyl-3)-xantinyl-8-thio]acetic acid under conditions involving platelet hyperaggregation.

Platelet aggregation in hypothyroidism and graves’ disease

Aim. To study platelet aggregation in subclinical and symptomatic hypothyroidism and Graves’ disease.&#x0D; Methods. The results of clinical and laboratory study of 50 patients with hypothyroidism and 20 patients with Graves’ disease are described. To access platelets aggregation function aggregatogramms were decoded by setting the maximum aggregation value; maximum aggregation rate and platelet aggregates maximum size were evaluated according to the results of the dynamic measurements on aggregometer. A control group consisted of 40 healthy donors.&#x0D; Results. Patients with subclinical and symptomatic hypothyroidism had prolonged activated partial thromboplastin time, reflecting the propensity for hypocoagulation, reduced total platelets number, spontaneous and ADP-induced platelet aggregation, aggregates formation rate and their maximum size. Changes were more pronounced in patients with Graves’ disease: weakening of platelet component of hemostasis, reduction of the platelets total number and the maximum size of platelet aggregates, significant reduction of the rate to reach the maximum size of platelet aggregates and platelet aggregation were observed.&#x0D; Conclusion. Thyroid dysfunction is accompanied by dysfunction of hemocoagulation processes, signs of chronic disseminated intravascular coagulation syndrome; these changes are clinically more severe in patients with Graves’ disease.

Can Chinese Herbal Medicine Adjunctive Therapy Improve Outcomes of Senile Vascular Dementia? Systematic Review with Meta-analysis of Clinical Trials.

Many publications have reported the growing application of complementary and alternative medicine, particularly the use of Chinese herbal medicine (CHM) in combination with routine pharmacotherapy (RP) for senile vascular dementia (SVD), but its efficacy remains largely unexplored. The purpose of this study is to evaluate the efficacy of CHM adjunctive therapy (CHMAT), which is CHM combined with RP, in the treatment of SVD. Publications in seven electronic databases were searched extensively, and 27 trials with a total of 1961 patients were included for analysis. Compared with RP alone, CHMAT significantly increased the effective rate [odds ratio (OR) 2.98, 95% confidence interval (CI) 2.30, 3.86]. In addition, CHMAT showed benefits in detailed subgroups of the Mini-Mental State Exam (MMSE) score from time of onset to 4 weeks (WMD 3.01, 95% CI 2.15, 3.87), 8 weeks (weighted mean difference (WMD) 2.30, 95% CI 1.28, 3.32), 12 weeks (WMD 2.93, 95% CI 2.17, 3.69), and 24 weeks (WMD 3.25, 95% CI 2.61, 3.88), and in the activity of daily living scale score from time of onset to 4 weeks (WMD -4.64, 95% CI -6.12, -3.17), 8 weeks (WMD -4.30, 95% CI -6.04, -2.56), 12 weeks (WMD -3.89, 95% CI -4.68, -3.09), and 24 weeks (WMD -4.04, 95% CI -6.51, -1.57). Moreover, CHMAT had positive effects on changes in the Hasegawa dementia scale, National Institutes of Health Stroke Scale, Clinical Dementia Rating, and Montreal Cognitive Assessment scores, as well as blood fat levels (total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and apolipoprotein E), platelet aggregation rate (1-min platelet aggregation rate, 5-min platelet aggregation rate, and maximal platelet aggregation rate), and blood rheology (whole-blood viscosity and hematocrit). No serious or frequently occurring adverse effects were reported. Weaknesses of methodological quality in most trials were assessed using the Cochrane risk of bias tool, while the quality level of Grades of Recommendations Assessment Development and Evaluation (GRADE) evidence classification indicated 'very low'. This systematic review suggests that CHM as an adjunctive therapy can improve cognitive impairment and enhance immediate response and quality of life in SVD patients. However, because of limitations of methodological quality in the included studies, further research of rigorous design is needed.

Clinical study of low molecular heparin combined with mesalazine in treatment of patients with active ulcerative colitis

Objective To investigate the clinical effect of low molecular heparin combined with mesalazine in patients with active ulcerative colitis(UC). Methods 90 cases of patients with UC were randomly divided into three groups:A group,B group and C group,with 30 cases in each group.A group was given oral treatment with sulfasalazine enteric-coated tablets,B group was given oral treatment with mesalazine and C group was given low molecular heparin calcium combined with mesalazine(4100 iu, 1/d).The three groups were treated for 2 weeks.Coagulant function index such as activated partial prothrombin time(APTT),fibrinogen(FIB),platelet count(PLT),platelet maximum aggregation rate(PAG(Max)),D-dimer(D-D),C-reactive protein(CRP) were detected in the two groups before and after treatment of 7 and 1 4 d.Mayo disease activity index score was also recorded before and after treatment of 7 and 14d.And the differences among three groups were compared .Results There were significant differences in APTT,FIB,PLT and PAG(Max)after 7d,14d treatment among A,B and C groups(7d:F value were 17.652,12.427,42.873,14.318 respectively;14d:F value were 43.804,139.172,51.932,79.440 respectively,all P value< 0.05).APTT of C group after 7d,14d[(36.32±3.56)μg/m L,(40.15±4.24)μg/m L]were higher than B group[(32.14±2.86)μg/m L,(33.04±3.32)μg/m L]and A group[(31.82±3.36)μg/m L,(32.15± 3.24)μg/m L];FIB of C group after 7d,14d[(4.07±0.41)g/L,(3.14±0.28)g/L]were lower than B group [(4.47±0.40)g/L,(4.06±0.33)g/L]and A group[(4.58±0.44)g/L,(4.23±0.37)g/L];PLT of C group after 7d,14d[(262.22±60.61)×109/L,(201.38±49.42)×109/L]were lower than B group[(296.34±63.51)× 109/L,(253.25±55.47)×109/L]and A group[(301.71±70.62)×109/L,(262.05±64.11)×109/L];PAG (Max)of C group after 7d,14d[(0.46±0.08),(0.30±0.05)]were lower than B group[(0.57±0.10),(0.46±0.06)]and A group[(0.59±0.12),(0.51±0.08)].There were significant differences in CRP,D-D after 14d treatment among A,B and C groups(F value were 91.967,139.172 respectively,all P value<0.05).CRP of C group after 14d[(7.50±1.35)mg/L]were lower than B group[(10.80±1.37)mg/L]and A group[(12.12±1.64)mg/L];DD of C group after 14d[(0.26±0.02)mg/L]were lower than B group[(0.47±0.03)mg/L]and A group[(0.51±0.04)mg/L].There were significant differences in Mayo index score,△Mayo index score after 14d treatment among A,B and C groups(F value were 182.170,89.802 respectively,all P value<0.05).Mayo index score of C group after 14d(1.51±0.33) were lower than B group(2.93±0.46)and A group(3.42±0.63);.△Mayo index score of C group after 14d(5.67±1.60)were lower than B group(4.25±1.32)and A group(3.79±1.21);Pearson correlation analysis showed that△Mayo Mayo index score were positively correlated with PAG(Max) reduction△PAG(Max),△D-D,△CRP,△PTL(r value were 0.616,0.702,0.734,0.569,respectively,all P< 0.05).Multiple stepwise linear regression analysis showed that△PAG(Max),△D-D,△CRP,△PTL were closely related to△Mayo Mayo index score(partial regression coefficient were 4.209,2.451,0.801 respectively;t value were 7.890,4.787,2.201,respectively,all P<0.05). Conclusion The clinical effect of low molecular heparin combined with mesalazine in patients with active ulcerative colitis is effective,and the method can significantly improve the inflammation in patients with UC and high coagulation state,improving the clinical symptoms is better than the single drug,and worth clinical recommendations. Key words: Colitis; Ulcerative; Low molecular heparin; Mesalazine

The relationship between on-clopidogrel platelet reactivity, genotype, and post-percutaneous coronary intervention outcomes in Chinese patients

Background. High on-clopidogrel platelet reactivity reflects a poor response to clopidogrel and is associated with ischemic events, which has been attributed to several factors such as demographic, clinical characteristics and a polymorphism of CYP2C19. Some new platelet assays monitoring on-clopidogrel platelet reactivity are currently available in China, but their relevance to the CYP2C19 genotype and post-percutaneous coronary intervention outcomes remain to be elucidated. Methods. Patients were prospectively included if they had a successful percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) and received clopidogrel and aspirin. CYP2C19 loss-of function genotype, adenosine diphosphate (ADP)-induced maximum platelet aggregation rate (MPAADP) measured by light transmittance aggregometry, ADP-induced platelet-fibrin clot strength (MAADP) measured by thrombelastography, platelet reactivity index (PRI) measured by vasodilator-stimulated phosphoprotein phosphorylation (VASP), and the occurrence of 6-month major adverse cardiovascular events (MACE) were assessed in 178 patients. Results. High on-treatment platelet reactivity prevalence defined by MPAADP > 46.0%, MAADP > 47 mm and PRI > 50.0% was 27.0%, 24.2%, and 61.2%, respectively. ADP-specific assays (VASP PRI) differed according to CYP2C19 genotype, with a significant gene–dose effect (PMs > IMs > EMs, p < 0.05). Multivariate analysis showed MPAADP > 46.0% and MAADP > 47 mm to be independent predictors of MACE at 6 months. Conclusions. CYP2C19 loss-of function genotypes with the *2 and/or *3 allele are highly prevalent in the Chinese population and are associated with higher residual platelet reactivity. High on-treatment platelet reactivity defined by MPAADP or MAADP predicts an increased risk of MACE for ACS patients undergoing PCI.