Antiaggregatory Effects Research Articles

Identification of dibenzyl imidazolidine and triazole acetamide derivatives through virtual screening targeting amyloid beta aggregation and neurotoxicity in PC12 cells

Aggregation and neurotoxicity of amyloid β (Aβ) protein is a hallmark characteristic of Alzheimer's disease (AD). In this study we compared the anti-aggregatory and neuroprotective effects of five synthetic compounds against Aβ protein; four of which possessed a five membered heterocycle ring scaffold (two dibenzyl phenyl imidazolidines and two triazole sulfanyl acetamides) and one with a fused five membered heterocycle (benzoxazole) ring, selected thorough virtual screening from ZINC database. Molecular docking of their optimized structures was used to study Aβ binding characteristics. As predicted from molecular docking, strong steric binding of imidazolidines and H-bonding of both triazoles to Aβ were translated into anti Aβ aggregation properties. Subsequent transmission electron microscopy (TEM) was used to assess their effects on Aβ1-42 fibril formation. Four compounds variably altered morphology of Aβ fibrils from long, intertwined fibrils to short, loose structures. Thioflavin T assay of Aβ fibrillisation kinetics demonstrated that one imidazolidine and both triazole compounds inhibited Aβ aggregation. Rat pheochromocytoma (PC12) cells were exposed to Aβ1-42, alone and in combination with the heterocyclic compounds to assess neuroprotective effects. Aβ1-42-evoked loss of neuronal cell viability was significantly attenuated in the presence of both imidazolidine compounds, while the triazole acetamides and benzoxazole compound were toxic to PC12 cells. These findings highlight the Aβ anti-aggregative and neuroprotective propensity of a dibenzyl phenyl imidazolidine scaffold (Compound 1 and 2). While the triazole sulfanyl acetamide scaffold also possessed Aβ anti-aggregation properties, they also demonstrated significant intrinsic neurotoxicity. Overall, the predictive efficacy of in silico methods enables the identification of novel imidazolidines that act both as inhibitors of Aβ aggregation and neurotoxicity, and may provide a further platform for the development of novel Alzheimer's disease-modifying pharmacotherapies.

A novel indication of platonin, a therapeutic immunomodulating medicine, on neuroprotection against ischemic stroke in mice

Thrombosis and stroke are major causes of disability and death worldwide. However, the regular antithrombotic drugs may have unsatisfactory results and side effects. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers and some acute inflammation. Here, we explored the neuroprotective effects of platonin against middle cerebral artery occlusion (MCAO)-induced ischemic stroke in mice. Platonin(200 μg/kg) substantially reduced cerebral infarct volume, brain edema, neuronal cell death and neurological deficit scores, and improved the MCAO-reduced locomotor activity and rotarod performance. Platonin(5–10 μM) potently inhibited platelet aggregation and c-Jun NH2-terminal kinase (JNK) phosphorylation in collagen-activated platelets. The antiaggregation effect did not affect bleeding time but increased occlusion time in platonin(100 and 200 μg/kg)-treated mice. Platonin(2–10 μM) was potent in diminishing collagen- and Fenton reaction-induced ∙OH formation. Platonin(5–10 μM) also suppressed the expression of nitric oxide, inducible nitric oxide synthase, cyclooxygenase-2, interleukin-1β, and JNK phosphorylation in lipopolysaccharide-stimulated macrophages. MCAO-induced expression of 3-nitrotyrosine and Iba1 was apparently attenuated in platonin(200 μg/kg)-treated mice. In conclusion, platonin exhibited remarkable neuroprotective properties against MCAO-induced ischemia in a mouse model through its antiaggregation, antiinflammatory and antiradical properties. The observed therapeutic efficacy of platonin may consider being a novel medcine against ischemic stroke.

Rapid and high-throughput colorimetric screening for anti-aggregation reagents of protein conformational diseases by using gold nanoplasmonic particles

Cellular deposition of destabilized proteins and their aggregates is considered one of the most indisputable factors implicated in protein conformational diseases. Here, we report an innovative high-throughput screening method for discovering anti-aggregation reagents out of numerous potential candidates by using gold nanoplasmonic particles. In our method, nanoparticles act as catalytic activators to accelerate protein aggregation and simultaneously exhibit a colorimetric response according to their embedded shape on the protein aggregates. Using this principle, we observed the colorimetric response to the anti-aggregation effect of amyloid β (Aβ) with the naked eye within a few minutes. Investigation of the anti-aggregation effects of select candidates under three different protein aggregation stages showed that the anti-aggregation efficiency could relate to disease progression. Finally, results obtained with spiked samples in cerebrospinal fluid as well as under various denaturation conditions and different Aβ compositions show the feasibility of future personalized medicine considering individual patient's disease progression.

PARAMETERS OF ARACHYDONIC ACID CYCLE METABOLISM IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION ON THE BACKGROUND OF COMPLEX THERAPY OF OMEGA-3 POLYUNSATURATED FATTY ACIDS

The aim of the study was to evaluate the effect of omega-3 polyunsaturated fatty acids on the main metabolic rates of the arachydonic acid cycle in patients with acute myocardial infarction in the context of traditional complex therapy. Materials and methods of research. We conducted an open, randomized study of two groups of patients (n=59) with acute myocardial infarction (MI), which did not undergo angioplastic and thrombolysis: in the main group (n=26) traditional complex therapy (including double antiaggregant therapy) from the first day supplemented with Omega-3 triglycerides [EPA/DGA — 1.2/1-90%] 1g. per day. In the control group (n=33) only complex therapy was performed. The main components of the arachydonic acid cycle — thromboxane B2 (TxB2) and prostaglandin I2 (PgI2), as well as their analogues, thromboxane B3 (TxB3) and prostaglandin I3 (PgI3), resulting from the replacement of arachidonic acid by omega-3 PUFAs, were evaluated for all patients on the 1st, 7th, 14th days after the onset of MI in the blood plasma. Results of the study. On day 14, an increase in the level of prostaglandin I3 in the Omega-3 triglycerides [EPA/DGA — 1.2/1-90%] group was observed in 10 times, the level of thromboxane B3 was increased in 15.9 times, in the absence of significant differences between the groups in the thromboxane B2 and prostaglandin I2 level. A decrease in the ratios of PgI2 / PgI3 and TxB2 / TxB3 in the main group also was noted. Conclusion. Given the lower functional activity of thromboxane B3 and the decrease in the ratio of TxB2 / TxB3, against the background of Omega-3 triglycerides [EPA/DGA — 1.2/1-90%] therapy, one can judge the presence of an independent antiaggregant effect of omega-3-polyunsaturated fatty acids as a result of their use in patients with MI.

Safety and Efficacy of Ventriculostomy Procedures under Dual Antiplatelet Therapy in Patients Treated With Stent Assisted Coiling In Subarachnoid Hemorrhage.

Stent assisted coilling (SAC) is an alternative in the treatment of ruptured aneurysms. Stenting requires the use of dual antiplatelet agents. Hydrocephaly is a complication of subarachnoid hemorrhage (SAH) requiring ventriculostomy. Antiplatelet treatment reveal a risk of hemorrhage in ventriculostomy. Anti-aggregant effect starts at least four hours after the initial doses of treatment. However, in many studies, ventriculostomy was performed before antiplatelet treatment and the hemorrhagic complications were related to the procedure. The aim of this study was to determine the risk of ventriculostomy related hemorrhage in patients with impaired thrombocyte function and to contribute to the literature. Between 2011 and 2016, 53 patients treated with SAC due to SAH in our clinic were retrospectively evaluated. Hemorrhagic complication risks due to antiplatelet therapy related to ventriculostomy were retrospectively evaluated Results: All of the ventricular catheter procedures were performed at least 1 day after the dual therapy (in average 4,3 days after SAC). On 5 patients 1 ventriculostomy was performed, on 2 patients 2, and on 1 patient 6 ventriculostomies were performed. Although radiological hemorrhage was present on the catheter tract in 4 patients, no temporary or permanent neruologic deficit was observed. Impaired thrombocyte functions pose a risk in ventriculostomy. Also, evaluating the risk of hemorrhage before the antiplatelet treatment reaches its full effect may lead to false results. Studies with small patient groups with antiagregant therapy and impaired thrombocyte functions also contribute to the literature. Larger studies regarding this subject are needed.

Identification of Anti-Inflammatory and Anti-Hypertensive Drugs as Inhibitors of Bacterial Diguanylate Cyclases

Biofilms are widely present in many human chronic infections, often more resistant to treatment with antibiotics. Bacterial diguanylate cyclases (DGCs) synthesize cyclic dimeric guanosine monophosphate (c-di-GMP) from two guanosine-5'-triphosphate (GTP) molecules. c-di-GMP is a central second messenger controlling biofilm formation, turning this class of enzymes an attractive target to prevent and disrupt biofilms of pathogenic bacteria. Here, we apply an in silico ligand- and target-based hybrid method to screen potential DGC inhibitors from an FDA-approved drug databank. Mass spectrometry assays confirmed that seven screened compounds selectively bound to the GTP active site of P. aeruginosa WspR GGDEF domain. Four out of those, including the anti-inflammatory sulfasalazine and the anti-hypertensive eprosartan, inhibited distinct DGCs (P. aeruginosa WspR and E. coli YdeH) in the micromolar range. Sulfasalazine and eprosartan reduced aggregation in solution of E. coli overexpressing WspR or YdeH. Similar anti-aggregation effects were also observed for sulfasalazine-related anti-inflammatory drugs sulfadiazine and sulfathiazole, the latter a previously described anti-biofilm agent. The optimized pharmacokinetic properties and toxicological profiles of the DGC inhibitors could be promising candidates for new anti-microbial agents based on the drug reposition strategy.

Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention.

Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST-ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n=725) or non-CYP3A4-metabolized statin group (group B, n=462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: -15±79, p<0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, -62±78, p<0.001; group B, -59±69, p<0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.

Basic therapy efficacy in children with pulmonary hypertension related to congenital heart defects: place of endothelial dysfunction and systemic inflammation markers

Aim. To evaluate efficacy of the specific therapy by results of 4-year observation of patients with pulmonary arterial hypertension associated with congenital heart defects (PH-CHD) Material and methods. The evaluation is provided, of endothelium condition dynamics during one year (baseline, in 6 and 12 months) by the level of endothelium dysfunction markers, cells reparation and proinflammatory factor — interleukin-1. Dynamics of clinical status of patients and of the condition of the right heart chambers by echocardiography with Doppler study, was monitored during 4 years. Results. In severe PH patients under bosentan complex therapy the clinical improvement was marked as exercise tolerance improvement, decreased rate of pulmonary crises and decreased functional class of the disease, tendency to increase life duration. In bosentan group, there was 10-time reduction of vascular endothelial growth factor level, double decrease of sPECAM-1 and by 70% — of proinflammatory cytokine interleukin-1. In moderate and severe PH without bosentan therapy there was statistically significant increase of sPECAM-1, increase of vascular endothelial growth factor by 5 and 2 times, respectively, and progression of the disease. Conclusion. For infants with PH-CHD, complex bosentan therapy makes it for clear clinical improvement related to antiproliferative and antiaggregant effects, which are mediated by non-selective inhibition of endothelin-1 receptors. Absence of PH-specific therapy determines the progression of disease, irrelevant to functional class.

In vitro antiaggregation and deaggregation potential of Rhizophora mucronata and its bioactive compound (+)- catechin against Alzheimer’s beta amyloid peptide (25–35)

Objective: Amyloid hypothesis states that endogenous β-amyloid peptides (Aβ), especially its aggregated oligomers and fibrils are the key pathogenic factors leading to Alzheimer’s disease (AD). Therefore, inhibition of Aβ fibrillation rather than blocking its production is considered promising therapeutic intervention. Hence, the present study was carried out to assess the effect of methanolic leaf extract of R. mucronata (MERM) and its bioactive compound catechin on in vitro fibrillation of Aβ (25–35).Methodology: Antiaggregation and disaggregation effect by MERM and (+)- catechin against Aβ (25–35) were assessed in three different phases by thioflavin T (ThT) fluorescence assay and confocal microscopic analysis. The conformational changes in the aggregated Aβ fibrils in the presence and absence of MERM and catechin were analysed by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and CD spectroscopy.Results: Results of ThT and confocal microscopic studies showed decrease in fluorescence intensity in MERM and catechin-treated groups illustrating that both MERM and catechin effectively inhibited fibril aggregation as well as destabilized preformed Aβ fibril. TEM revealed that MERM incubated samples were virtually devoid of structured fibrils but had an amorphous-like consistency, whereas the control contained structured fibrils of various width and length. FTIR analysis showed decrease in absorbance at 1630 cm−1 (amide I region) in MERM-treated groups substantiating the results of ThT assay. Circular dichroism data indicate that catechin prevents the formation of β-structured aggregates of Aβ peptide.Conclusion: Results suggest that MERM and catechin might have direct interaction with Aβ peptide preventing its fibrillation.

Bioavailability of Quercetin

Quercetin is generally present as quercetin glycoside in nature and involves quercetin aglycone conjugated to sugar moieties such as glucose or rutinose. Quercetin has been reported to exhibit antioxidative, anti-carcinogenic, anti-inflammatory, anti-aggregatory and vasodilating effects. Unfortunately, quercetin bioavailability is generally poor and several factors affect its bioavailability. Quercetin bioavailability varies widely between individuals. Gender may affect quercetin bioavailability, but there is no clear evidence. There has been little research looking for the effects of age and vitamin C status on bioavailability of quercetin supplements, but there is no research seeking out the effects of age and vitamin C status on bioavailability of food-derived quercetin. Presence of sugar moieties increases bioavailability and differences in quercetin-conjugated glycosides affect bioavailability. For instance, onion-derived quercetin, which is mainly quercetin glucoside, is more bioavailable than apple-derived quercetin, which contains quercetin rhamnoside and quercetin galactoside. Quercetin is lipophilic compound, thus dietary fat enhances its bioavailability. Nondigestible fiber may also improve quercetin bioavailability. Quercetin bioavailability is greater when it is consumed as an integral food component. This study reviews and discusses factors affecting quercetin bioavailability.

Radiolabeled tirofiban - a potential radiopharmaceutical for detection of deep venous thrombosis.

AimThe aim of this study was to investigate the possibility of using 99mtechnetium (99mTc)-labeled tirofiban (a reversible antagonist of glycoprotein IIb/IIIa) for detection of deep venous thrombosis (DVT) in rats without causing an antiplatelet effect.MethodsThe ability of in vitro tirofiban to inhibit adenosine 5′-diphosphate (ADP)-induced platelet aggregation was evaluated using optical aggregometer. Binding of 99mTc-tirofiban to platelets was evaluated. Serum levels of unlabeled (a validated high performance liquid chromatography method) and 99mTc-tirofiban after single intravenous injection were evaluated in male Wistar rats with or without induced DVT (femoral vein ligation model), and the rats were also subjected to whole body scintigraphy.ResultsTirofiban in vitro inhibits ADP-induced aggregation of human platelets in a dose- and concentration-dependent manner (10 nM to 2 μM), but only if it is added before ADP and not after ADP. 99mTc labeling did not affect the ability of tirofiban to bind to either human or rat platelets, nor did it affect tirofiban pharmacokinetics in intact rats or in animals with induced DVT. When 99mTc-tirofiban was injected to rats after induction of DVT, at a molar dose lower than the one showing only a weak antiaggregatory effect in vitro, whole body scintigraphy indicated localization of 99mTc-tirofiban around the place of the induced DVT.Conclusion99mTc labeling of tirofiban does not affect its ability to bind to glycoprotein IIb/IIIa or its in vivo pharmacokinetics in rats, either intact or with DVT. A low, nonantiaggregatory dose of 99mTc-tirofiban may be used to visualize DVT at an early stage.

Annotinolides A-C, Three Lycopodane-Derived 8,5-Lactones with Polycyclic Skeletons from Lycopodium annotinum.

Three novel 7,8-seco-lycopodane-derived 8,5-lactones (annotinolides A-C, 1-3) were isolated from Lycopodium annotinum. Their structures were elucidated by spectroscopic methods and single-crystal X-ray diffraction. Compound 1 possesses an unusual cyclopropane ring constructed through a hitherto unknown C-6/C-12 bond. Compound 2 represents the first 7,8-seco-lycopodane-derived alkaloid with a rare cyclobutane ring formed by a new C-12/C-15 linkage, while the C-8/C-15 bond remains. Compound 3 contains an unprecedented 12-spiro-9,12-γ-lactone moiety. Their plausible biosynthetic pathways and antiaggregation effects on amyloid-β1-42 are also presented.

The role of unfractionated heparin for the antiaggregatory effect of aspirin in patients undergoing carotid endarterectomy: Results of an observational clinical study.

The aims of the present study were to examine the influence of a low-dose unfractionated heparin regime on platelet aggregation and to additionally assess the prevalence of primary aspirin resistance in patients undergoing carotid endarterectomy. Therefore, 50 patients undergoing carotid endarterectomy were enrolled. A bolus of 3000 IU unfractionated heparin was administered 2 min before carotid cross-clamping additionally to standard antiaggregatory therapy. Haemostaseological point of care testing was performed twice, prior to surgery and 10 min after unfractionated heparin administration by the use of aggregometric and viscoelastic point of care testing. Following unfractionated heparin administration, the activated partial thromboplastin time increased significantly and clotting time in viscoelastic INTEM test was shown to be significantly prolonged. In contrast, the antiaggregatory effect of aspirin was not diminished in aggregometric ASPI test. A low-dose unfractionated heparin regime during carotid endarterectomy was therefore considered to be safe, without diminishing the antiplatelet effect of aspirin. Moreover, aggregometric point of care testing was identified to be a suitable tool for the identification of patients with primary aspirin resistance ( n = 3).

Iloprost as an acute kidney injury-triggering agent in severely atherosclerotic patients.

SummaryBackgroundIloprost, a stable prostacyclin analog, is used as a rescue therapy for severe peripheral arterial disease (PAD). It has systemic vasodilatory and anti-aggregant effects, with severe vasodilatation potentially causing organ ischaemia when severe atherosclerosis is the underlying cause. In this study, we retrospectively analysed renal outcomes after iloprost infusion therapy in 86 patients.MethodsEighty-six patients with PAD who received iloprost infusion therapy were retrospectively analysed. Clinical and biochemical parameters were recorded before (initial, Cr1), during (third day, Cr2), and after (14th day following the termination of infusion therapy, Cr3) treatment. Acute kidney injury (AKI) was defined according to KDIGO guidelines as a ≥ 0.3 mg/dl (26.52 μmol/l) increase in creatinine levels from baseline within 48 hours.Results:Cr2 (1.46 ± 0.1 mg/dl) (129.06 ± 8.84 μmol/l) and Cr3 (1.53 ± 0.12 mg/dl) (135.25 ± 10.61 μmol/l) creatinine levels were significantly higher compared to the initial value (1.15 ± 0.6 mg/dl) (101.66 ± 53.04 μmol/l). AKI was observed in 36 patients (41.86%) on the third day of iloprost infusion. Logistic regression analysis revealed smoking and not using acetylsalicylic acid as primary predictors (p = 0.02 and p = 0.008, respectively) of AKI during iloprost treatment. On the third infusion day, patients’ urinary output significantly increased (1813.30 ± 1123.46 vs 1545.17 ± 873.00 cm3) and diastolic blood pressure significantly decreased (70.07 ± 15.50 vs 74.14 ± 9.42 mmHg) from their initial values.ConclusionWhile iloprost treatment is effective in patients with PAD who are not suitable for surgery, severe systemic vasodilatation can cause renal ischaemia, resulting in nonoliguric AKI. Smoking, no acetylsalicylic acid use, and lower diastolic blood pressure are the clinical risk factors for AKI during iloprost treatment.

The monitoring of antiaggregation effect of acetylsalicylic acid therapy by measuring serum thromboxane B2 in patients with coronary artery bypass grafting.

Cardiovascular patients take acetylsalicylic acid (ASA) for preventing myocardial infarction and other thromboembolic complications. It is already known that in some patients this therapy is not effective. The aim of this study was to assess the percentage of ASA resistance on the sample of patients with coronary artery bypass grafting. Our study included 105 patients with coronary artery bypass grafting treated with ASA 150 mg/day or lesser. Platelet aggregation was measured by serum thromboxane B2 level as well as impedance aggregometry from whole blood to determine ASA antiaggregation effect. The percentage of ASA resistance was 41.9% with impedance aggregometry, and after determining the serum thromboxane B2 level this percentage was only 8.6%. The correlation between these two methods was weak (r = 0.443; P < 0.0001). Thromboembolic complications still occur in ASA-treated patients because some patients are resistant to ASA therapy. It would be useful to monitor the effectiveness of ASA therapy and give another antiaggregation drug to these patients to reduce adverse events. The problem is which test is ideal because different tests show different percentages of ASA resistance.

Modification-free and N-acetyl-L-cysteine-induced colorimetric response of AuNPs: A mechanistic study and sensitive Hg2+ detection

A facile yet sensitive and selective method was proposed for Hg2+ detection based on N-acetyl-L-cysteine(NAC)-induced colorimetric response of AuNPs. The proposed method can be easily performed by introducing the premixing of NAC and Hg2+ into as-prepared citrate-capped AuNPs solution. A combination of experimental and theoretical studies was applied to illustrate the mechanism of this AuNPs colorimetric system. The strong interaction of NAC and AuNPs through Au–S bond could lead to the aggregation of AuNPs, but the formation of NAC-Hg-NAC complex decreased the affinity between NAC and AuNPs and resulted in an anti-aggregation effect. Therefore, the color of the AuNPs solution would progress from purple to red with the increase of Hg2+ concentration. The proposed method had a high sensitivity with a limit of detection of 9.9nM. Coexistent metal ions, including Cd2+, Mn2+, Al3+, Ag+, K+, Mg2+, Ca2+, Cr3+, Cu2+, Fe3+, Pb2+, Ni2+ and Zn2+, did not interfere with the detection of Hg2+. This method can be used to monitor Hg2+ in tap water.

Antiplatelet Effect of Sequential Administration of Cilostazol in Patients with Acetylsalycilic Acid Resistance.

Acetylsalicylic acid (ASA) resistance in patients with coronary artery disease is an important medical problem that can affect treatment decision-making and outcomes. Cilostazol has been investigated to determine its effectiveness in patients with acetylsalicylic acid resistance. The aim of this study was to evaluate the antiplatelet efficacy of sequential administration of CLZ in patients with ASA resistance. A total of 180 patients were enrolled in our study. Patients with stable coronary artery disease were first given orally ASA 100 for 10 days, followed by collagen/epinephrine induced closure time (CTCEPI) measurements. Those who were found to be resistant to orally 100 mg of ASA were given orally 300 mg of ASA for an additional 10 days after which we repeated CTCEPI measurements. Those patients with resistance to orally 300 mg ASA were then given CLZ at a daily dose of orally 200 mg for 10 days followed by a final CTCEPI measurement. The rate of resistance to 100 mg ASA was 81/180 (45%) compared to a rate of 35/81 (43.2%) with 300 mg ASA. Of the 35 patients found to be resistant to 300 mg ASA, 22 (62.9%) also failed to respond to CLZ treatment. Overall, sequential administration of 300 mg ASA and 200 mg CLZ resulted in a reduction in the number of non-responders from 45% to 12.2%. Initiation of CLZ could be of benefit in some patients with ASA-resistance for whom an effective anti-aggregant effect is of clinical importance.

The features of sulfonylurea’s usе in the general practice: a systematic review of glimepiride researches

Diabetes mellitus (DM) is on the third place by the prevalence after cardiovascular and oncologic diseases in the world. The choice of drug treatment DM is a complex process in the general practice. Background: identify the features of use, pharmacocinetics and pharmacodynamics of glimepiride in patients with DM type 2 in the general practice. A systematic review of publications in JAMA, Scholar and PubMed, as well as in journals and conference publications from 2005 till 2015 was conducted. It was found, that glimepiride, as a drug of 3rd generation sulfonylurea, has hypoglycemic, antiatherosclerotic, antiatherogenic, anti-inflammatory, antiapoptotic, antiaggregatory effects. High safety of glimepiride was proved by lower risk of severe and hidden hipoglycemia, positive results of use in patients with concomitant cardiovascular pathology. Proved high efficiency and safety of glimepiride as monotherapy and in combination allows its wide use in general practice

Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation.

BackgroundFemale patients with atrial fibrillation (AF) experience increased risk of thromboembolism compared to males, an observation that is reflected by its inclusion in the CHA2DS2VASc score. New onset AF (often associated with tachycardia) also confers upon patients increased thromboembolic risk. The mechanisms underlying this risk are uncertain, but new onset AF is associated with profound impairment of platelet nitric oxide (NO) signalling. Given that cardiovascular responses to catecholamines are gender-dependent, and that the presence of tachycardia in new onset AF may represent a response to catecholaminergic stimulation, we explored the potential impact of gender and tachycardia on platelet aggregation and NO signalling.MethodsInteractions were sought in 87 AF patients between the extent of adenosine diphosphate (ADP)-induced platelet aggregation, the anti-aggregatory effects of the NO donor, sodium nitroprusside, gender, and admission heart rate. The potential impact of platelet expression of thioredoxin-interacting protein (Txnip) was also evaluated.ResultsAnalysis of covariance confirmed the presence of physiological antagonism between platelet ADP and NO responses [F (1, 74) = 12.212, P < 0.01], while female sex correlated with impaired NO responses independent of platelet aggregability [F (2, 74) = 8.313, P < 0.01]. Admission heart rate correlated directly with platelet aggregation (r = 0.235, P < 0.05), and inversely with NO response (r = −0.331, P < 0.01). Txnip expression varied neither with gender nor with heart rate.ConclusionsThese results indicate that gender and heart rate are independent determinants of platelet function. Prospective studies of the putative benefit of reversal of tachycardia on restoration of normal platelet function are therefore a priority.

A selective, sensitive and label-free visual assay of fructose using anti-aggregation of gold nanoparticles as a colorimetric probe

Abstract A new convenient colorimetric sensor for fructose based on anti-aggregation of citrate-capped gold nanoparticles (AuNPs) is presented. 4-Mercaptophenylboronic acid (MPBA) induces the aggregation of AuNPs, leading to a color change from red to blue. Fructose as a potent competitor has strong affinity for MPBA and a borate ester is formed between MPBA and fructose. There is an obvious color change from blue to red with increasing the concentration of fructose. The anti-aggregation effect of fructose on AuNPs was seen by the naked eye and monitored by UV–vis spectra. Our results showed that the absorbance ratio (A 519 /A 640 ) was linear with fructose concentration in the range of 0.032–0.96 mmol/L ( R 2 = 0.996), with a low detection limit of 0.01 mmol/L (S/N = 3). Notably, a highly selective recognition of fructose was shown against other monosaccharide and disaccharide (glucose, mannose, galactose, lactose and saccharose). With anti-aggregation assays higher selectivity is achievable. The results of this work provide a rapid method for evaluating the quantitative analysis of fructose in human plasma at physiologically meaningful concentrations and at neutral pH. The proposed procedure can be used as an efficient method for the precise and accurate determination of fructose.