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Aggregation Inhibitor (aggregation + inhibitor)
Kinds of Aggregation Inhibitor Selected AbstractsHighly Efficient Chemoenzymatic Synthesis of Methyl (R)- o -Chloromandelate, a Key Intermediate for Clopidogrel, via Asymmetric Reduction with Recombinant Escherichia coliADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2008Tadashi Ema Abstract Methyl (R)- o -chloromandelate [(R)- 1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o -chlorobenzoylformate (2) with recombinant Escherichia coli overproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the whole-cell reduction of 2, and the optimum productivity as high as 178,g/L was attained at 20,°C on a 2-g scale (1.0,M). The optimized reaction could be scaled up easily to transform 20,g of 2 in 100,mL of buffer. Three synthetic methods for 2 are compared. [source] Two subpopulations of thrombin-activated platelets differ in their binding of the components of the intrinsic factor X-activating complexJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 11 2005M. A. PANTELEEV Summary., Binding of fluorescein-labeled coagulation factors IXa, VIII, X, and allophycocyanin-labeled annexin V to thrombin-activated platelets was studied using flow cytometry. Upon activation, two platelet subpopulations were detected, which differed by 1,2 orders of magnitude in the binding of the coagulation factors and by 2,3 orders of magnitude in the binding of annexin V. The percentage of the high-binding platelets increased dose dependently of thrombin concentration. At 100 nm of thrombin, platelets with elevated binding capability constituted ,4% of total platelets and were responsible for the binding of ,50% of the total bound factor. Binding of factors to the high-binding subpopulation was calcium-dependent and specific as evidenced by experiments in the presence of excess unlabeled factor. The percentage of the high-binding platelets was not affected by echistatin, a potent aggregation inhibitor, confirming that the high-binding platelets were not platelet aggregates. Despite the difference in the coagulation factors binding, the subpopulations were indistinguishable by the expression of general platelet marker CD42b and activation markers PAC1 (an epitope of glycoprotein IIb/IIIa) and CD62P (P-selectin). Dual-labeling binding studies involving coagulation factors (IXa, VIII, or X) and annexin V demonstrated that the high-binding platelet subpopulation was identical for all coagulation factors and for annexin V. The high-binding subpopulation had lower mean forward and side scatters compared with the low-binding subpopulation (,80% and ,60%, respectively). In its turn, the high-binding subpopulation was not homogeneous and included two subpopulations with different scatter values. We conclude that activation by thrombin induces the formation of two distinct subpopulations of platelets different in their binding of the components of the intrinsic fX-activating complex, which may have certain physiological or pathological significance. [source] Recombinant decorsin: Dynamics of the RGD recognition sitePROTEIN SCIENCE, Issue 8 2000Andrzej M. Krezel Abstract Decorsin is an antagonist of integrin ,IIb,3 and a potent platelet aggregation inhibitor. A synthetic gene encoding decorsin, originally isolated from the leech Macrobdella decora, was designed, constructed, and expressed in Escherichia coli. The synthetic gene was fused to the stII signal sequence and expressed under the transcriptional control of the E. coli alkaline phosphatase promoter. The protein was purified by size-exclusion filtration of the periplasmic contents followed by reversed-phase high-performance liquid chromatography. Purified recombinant decorsin was found to be indistinguishable from leech-derived decorsin based on amino acid composition, mass spectral analysis, and biological activity assays. Complete sequential assignments of 1H and proton bound 13C resonances were established. Stereospecific assignments of 21 of 25 nondegenerate ,-methylene groups were determined. The RGD adhesion site recognized by integrin receptors was found at the apex of a most exposed hairpin loop. The dynamic behavior of decorsin was analyzed using several independent NMR parameters. Although the loop containing the RGD sequence is the most flexible one in decorsin, the conformation of the RGD site itself is more restricted than in other proteins with similar activities. [source] The common inhalation anesthetic isoflurane induces caspase activation and increases amyloid ,-protein level in vivoANNALS OF NEUROLOGY, Issue 6 2008Zhongcong Xie MD Objective An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of Alzheimer's disease,associated amyloid ,-protein (A,) in cultured cells. However, the in vivo relevance has not been addressed. Methods We therefore set out to determine effects of isoflurane on caspase activation and levels of ,-site amyloid precursor protein,cleaving enzyme (BACE) and A, in naive mice, using Western blot, immunohistochemistry, and reverse transcriptase polymerase chain reaction. Results Here we show for the first time that a clinically relevant isoflurane anesthesia (1.4% isoflurane for 2 hours) leads to caspase activation and modest increases in levels of BACE 6 hours after anesthesia in mouse brain. Isoflurane anesthesia induces caspase activation, and increases levels of BACE and A, up to 24 hours after anesthesia. Isoflurane may increase BACE levels by reducing BACE degradation. Moreover, the A, aggregation inhibitor, clioquinol, was able to attenuate isoflurane-induced caspase-3 activation in vivo. Interpretation Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane may promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation. Ann Neurol 2008 [source] Tau oligomers and aggregation in Alzheimer's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 6 2010Marco A. Meraz-Ríos J. Neurochem. (2010) 112, 1353,1367. Abstract We are analyzing the physiological function of Tau protein and its abnormal pathological behavior when this protein is self-assemble into pathological filaments. These aggregates of Tau protein are the main components in many diseases such as Alzheimer's disease (AD). Recent studies suggest that Tau acquires complex oligomeric conformations which may be toxic. In this review, we emphasized the possible phenomena implicated in the formation of these oligomers. Studies with chemical inductors indicates that the microtubule-binding domain is the most important region involved in Tau aggregation and showed the requirement of a pre-arrange Tau in abnormal conformation to promote self-assembly. Transgenic animal models and AD neuropathology studies showed that post-translational modifications are also implicated in Tau aggregation and neural cell death during AD development. Therefore, we analyzed some events that could be present during Tau aggregation. Finally, we included a brief discussion of the possible relation between glucose metabolism dysfunction in AD, and data of Tau aggregation by using aggregation inhibitors. In conclusion, the process Tau aggregation deserves further investigations to design possible therapeutic targets to inhibit the toxicity of these aggregates and it is possible that could be extended to other diseases with similar etiology. [source] Synthesis of pathological and nonpathological human exon 1 huntingtinJOURNAL OF PEPTIDE SCIENCE, Issue 7 2010David Singer Abstract Huntington's disease (HD) is a neurodegenerative disorder that affects approximately 1 in 10 000 individuals. The underlying gene mutation was identified as a CAG-triplet repeat expansion in the gene huntingtin. The CAG sequence codes for glutamine, and in HD, an expansion of the polyglutamine (poly-Q) stretch above 35 glutamine residues results in pathogenicity. It has been demonstrated in various animal models that only the expression of exon 1 huntingtin, a 67-amino acid-long polypeptide plus a variable poly-Q stretch, is sufficient to cause full HD-like pathology. Therefore, a deeper understanding of exon 1 huntingtin, its structure, aggregation mechanism and interaction with other proteins is crucial for a better understanding of the disease. Here, we describe the synthesis of a 109-amino acid-long exon 1 huntingtin peptide including a poly-Q stretch of 42 glutamines. This microwave-assisted solid phase peptide synthesis resulted in milligram amounts of peptide with high purity. We also synthesized a nonpathogenic version of exon 1 huntingtin (90-amino acid long including a poly-Q stretch of 23 glutamine residues) using the same strategy. In circular dichroism spectroscopy, both polypeptides showed weak alpha-helical properties with the longer peptide showing a higher helical degree. These model peptides have great potential for further biomedical analyses, e.g. for large-scale pre-screenings for aggregation inhibitors, further structural analyses as well as protein,protein interaction studies. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd. [source] Prevalence of cardiovascular disease and risk factors in a type 2 diabetic population of the North Catalonia diabetes studyJOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS, Issue 3 2009DNS (Diabetes Nurse Specialist & Clinical Researcher), Jeronimo Jurado RN Abstract Purpose: The purpose of the study was to evaluate the prevalence of cardiovascular disease (CVD), cardiovascular risk factors (CVRFs), and their control in patients with type 2 diabetes mellitus (T2DM) at primary care settings from the North Catalonia Diabetes Study (NCDS). Data sources: In this multicentre cross-sectional descriptive study, data were collected from a random sample of 307 patients with T2DM. The prevalence of CVD, CVRF, metabolic syndrome (MS), coronary heart disease (CHD) risk at 10 years (Framingham Point Scores), and CVRF control was evaluated. MS and lipid profiles were established according to Adult Treatment Panel III criteria. Conclusions: CVD prevalence was 22.0% (CHD: 18.9% and peripheral ischemia: 4.5%) and more frequent in men. The prevalence of selected CVRF was: hypertension: 74.5%; dyslipidemia: 77.7%; smoking: 14.9%; obesity 44.9%, and familial CVD: 38.4%. Three or more CVRFs, including T2DM, were observed in 91.3%. MS prevalence was 68.7%. Framingham score was 10.0%, higher in men than in women. CVD prevalence was related to: age, number of CVRFs, duration of diabetes, familial history of CVD, waist circumference, hypertension, lipid profile, kidney disease, and Framingham score, but not to MS by itself. Correct lipid profiles and blood pressure were only observed in 18.9% and 24.0%, respectively, whereas platelet aggregation inhibitors were only recorded in 16.1% of the patient cohort. MS presence was not an independent risk factor of CVD in our study. Implications for practice: The high prevalence of CVD and an inadequate control of CVRF, which were apparent in the NCDS population, would suggest that advanced practice nurses should consider incorporating specific cardiovascular assessment in their routine care of persons with T2DM. [source] US4 Pharmacotherapy complicating dental surgeryORAL DISEASES, Issue 2006Boras Planning dental treatments for patients taking antithrombotic can be difficult for the general dental practitioner, particularly when surgical interventions are needed. The drugs employed in the long-term treatment of such patients include platelet aggregation inhibitors and oral anticoagulants. Platelet aggregation inhibitors do not represent a contraindication to oral surgery. The activity of oral anticoagulants can be affected by many substances, for this reason it is necessary to monitor by INR the patients taking those drugs. When INR is within therapeutic limits for the more common conditions, most of the oral surgery interventions do not need any special precaution. Evidence indicates that suspending antithrombotic drugs is not indicate, as complications following a thrombotic accident are more frequent and serious than bleedings following oral surgery. It is well known that systemic corticosteroid therapy due to the effect on adrenal suppression can interfere with dental surgical procedures. However, that is largely dependent on the type and dose of corticosteroid that patient is currently taking, or has been taking in the last 12 months and on the type and extent of surgical procedure which is to be performed. Surgical management of dental patients with history of systemic corticosteroid therapy is proposed from the existing literature. [source] | |||||||||||||