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New Strategy (new + strategy)
Kinds of New Strategy Selected AbstractsPDK1 and PKB/Akt: Ideal Targets for Development of New Strategies to Structure-Based Drug DesignIUBMB LIFE, Issue 3 2003Thomas Harris Abstract Growth factor binding events to receptor tyrosine kinases result in activation of phosphatidylinositol 3-kinase (PI3K), and activated PI3K generates the membrane-bound second messengers phosphatidylinositol 3,4-diphosphate [PI(3,4)P2] and PI(3,4,5)P3, which mediate membrane translocation of the phosphoinositide-dependent kinase-1 (PDK1) and protein kinase B (PKB, also known as Akt). In addition to the kinase domain, PDK1 and PKB contain a pleckstrin homology (PH) domain that binds to the second messenger, resulting in the phosphorylation and activation of PKB by PDK1. Recent evidence indicates that constitutive activation of PKB contributes to cancer progression by promoting proliferation and increased cell survival. The indicating of PDK1 and PKB as primary targets for discovery of anticancer drugs, together with the observations that both PDK1 and PKB contain small-molecule regulatory binding sites that may be in proximity to the kinase active site, make PDK1 and PKB ideal targets for the development of new strategies to structure-based drug design. While X-ray structures have been reported for the kinase domains of PDK1 and PKB, no suitable crystals have been obtained for either PDK1 or PKB with their PH domains intact. In this regard, a novel structure-based strategy is proposed, which utilizes segmental isotopic labeling of the PH domain in combination with site-directed spin labeling of the kinase active site. Then, long-range distance restraints between the 15N-labeled backbone amide groups of the PH domain and the unpaired electron of the active site spin label can be determined from magnetic resonance studies of the enhancement effect that the paramagnetic spin label has on the nuclear relaxation rates of the amide protons. The determination of the structure and position of the PH domain with respect to the known X-ray structure of the kinase active site could be useful in the rational design of potent and selective inhibitors of PDK1 and PKB by 'linking' the free energies of binding of substrate (ATP) analogs with analogs of the inositol polar head group of the phospholipid second messenger. The combined use of X-ray crystallography, segmental isotopic and spin labeling, and magnetic resonance studies can be further extended to the study of other dynamic multidomain proteins and targets for structure-based drug design. IUBMB Life, 55: 117-126, 2003 [source] ChemInform Abstract: New Strategies for Organic Catalysis: The First Enantioselective Organocatalytic 1,3-Dipolar Cycloaddition.CHEMINFORM, Issue 3 2001Wendy S. Jen Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] What Leads Children to Adopt New Strategies?CHILD DEVELOPMENT, Issue 4 2006A Microgenetic/Cross-Sectional Study of Class Inclusion Learning of class inclusion by 5-year-olds in response to empirical and logical explanations of an adult's answers was examined. Contrary to the view that young children possess an empirical bias, 5-year-olds learned more, and continued learning for longer, when given logical explanations of correct answers than when given empirical explanations. Once children discovered how to solve the problems, they showed few regressions. Many children in the microgenetic experiment followed the path of change anticipated from previous cross-sectional studies, but children in the cross-sectional part of the study seemed to follow a different path. Reasons for the superior effectiveness of the logical explanations were discussed. [source] New Strategy for Dehydrogenase Amperometric Biosensors Using Surfactant to Enhance the Sensitivity of Diaphorase/Ferrocene Modified Carbon Paste Electrodes for Electrocatalytic Oxidation of NADHELECTROANALYSIS, Issue 13 2003César Ramírez-Molina Abstract A carbon paste electrode (CPE) modified with diaphorase (DAP) and ferrocene (FcH) has been developed for determination of NADH at low working potential. The sensitivity and operational stability, towards the detection of the reduced form of the nicotinamide adenine dinucleotide (NADH) in flow injection analysis (FIA), were greatly improved (5 times) upon adding Tween 20 into the electrode matrix. The magnitude of the amperometric signal was dependent on DAP, FcH and surfactant loading, into the modified carbon paste electrode. A rapid and repeatable response was observed to the variation of NADH concentration in the vicinity of the electrode surface. Such advantages of the DAP/FcH/Tween 20 modified carbon paste were successfully used in the construction of L -lactate dehydrogenase modified electrodes. The use of this new approach can be generalized to other dehydrogenases and represents a decisive step for a versatile preparation method of amperometric biosensors. [source] A New Strategy for the Synthesis of Polyaniline Nanostructures: From Nanofibers to NanowiresMACROMOLECULAR RAPID COMMUNICATIONS, Issue 6 2007Jing Li Abstract A new approach for the synthesis of polyaniline (PANI) nanostructures under UV light illumination has been developed, which is the first report of a templateless chemical process for preparing pure PANI nanowires. The acceleration effect of photo-assistance on the polymerization can promote the homogeneous nucleation and elongation of the nanofibers and nanowires, leading to easy preparation of tunable diameters of the nanowires and nanofibers of PANI. [source] Time to make up your mind: why choosing is difficultBRITISH JOURNAL OF LEARNING DISABILITIES, Issue 1 2003John Harris Summary For many years, the promotion of choice has been a core objective for virtually every service provider working to support people with learning disability. This is confirmed by the 2001 English White Paper Valuing People, A New Strategy for Learning Disability for the 21st Century, which describes choice as one of four key principles at the heart of the UK Government's proposals, and the 2000 review of learning disability services commissioned by the Scottish Executive, People Like Us, which places a similarly high priority on the creation of choice. The present paper gives an overview of our current understanding of the concept of choice. It concludes that our aspirations to promote choice for people with learning disability are undermined by conceptual confusion about the meaning of choice, inappropriate methods for helping people to make choices and an absence of applied research to guide practice in service settings. This review is designed to establish a conceptual framework for examining choice and empowerment for people with learning disability, and to describe the implications for future research and practice. [source] ChemInform Abstract: A New Strategy for Asymmetric Synthesis of Aminophosphonic Acid Derivatives: The First Enantioselective Catalytic Reduction of C-Phosphorylated Imines.CHEMINFORM, Issue 17 2009Yuliya Rassukana Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: A New Strategy for the Synthesis of Pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines and Pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines.CHEMINFORM, Issue 11 2009Ahmad Sami Shawali Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: A New Strategy of the Chemical Route to the Cyclopropane Structure: Direct Transformation of Benzylidenemalononitriles and Malononitrile into 1,1,2,2-Tetracyanocyclopropanes.CHEMINFORM, Issue 22 2008Michail N. Elinson Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] ChemInform Abstract: New Strategy for the Oxidation of Hantzsch 1,4-Dihydropyridines and Dihydropyrido[2,3-d]pyrimidines Catalyzed by DMSO under Aerobic Conditions.CHEMINFORM, Issue 1 2008Anil Saini Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] A New Strategy for the Diastereoselective Synthesis of Polyfunctionalized Pyrrolidines.CHEMINFORM, Issue 21 2004Andrew S. Davis Abstract For Abstract see ChemInform Abstract in Full Text. [source] Glyco-SeS: Selenenylsulfide-Mediated Protein Glycoconjugation , A New Strategy in Post-Translational Modification.CHEMINFORM, Issue 20 2004David P. Gamblin No abstract is available for this article. [source] A New Strategy for the Synthesis of ,-Nitro Alcohols from Aliphatic Nitro Compounds.CHEMINFORM, Issue 47 2003Roman A. Kunetsky Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: Direct Catalytic Asymmetric Aldol Reactions Promoted by Novel Heterobimetallic Catalysts Possessing Strong Broensted Base: A New Strategy for the Development of Lewis Acid,Broensted Base Bifunctional Catalysts.CHEMINFORM, Issue 32 2001Naoki Yoshikawa Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Preconditioning and postconditioning: new strategies for cardioprotectionDIABETES OBESITY & METABOLISM, Issue 6 2008D. J. Hausenloy Despite optimal therapy, the morbidity and mortality of coronary heart disease (CHD) remains significant, particularly in patients with diabetes or the metabolic syndrome. New strategies for cardioprotection are therefore required to improve the clinical outcomes in patients with CHD. Ischaemic preconditioning (IPC) as a cardioprotective strategy has not fulfilled it clinical potential, primarily because of the need to intervene before the index ischaemic event, which is impossible to predict in patients presenting with an acute myocardial infarction (AMI). However, emerging studies suggest that IPC-induced protection is mediated in part by signalling transduction pathways recruited at time of myocardial reperfusion, creating the possibility of harnessing its cardioprotective potential by intervening at time of reperfusion. In this regard, the recently described phenomenon of ischaemic postconditioning (IPost) has attracted great interest, particularly as it represents an intervention, which can be applied at time of myocardial reperfusion for patients presenting with an AMI. Interestingly, the signal transduction pathways, which underlie its protection, are similar to those recruited by IPC, creating a potential common cardioprotective pathway, which can be recruited at time of myocardial reperfusion, through the use of appropriate pharmacological agents given as adjuvant therapy to current myocardial reperfusion strategies such as thrombolysis and primary percutaneous coronary intervention for patients presenting with an AMI. This article provides a brief overview of IPC and IPost and describes the common signal transduction pathway they both appear to recruit at time of myocardial reperfusion, the pharmacological manipulation of which has the potential to generate new strategies for cardioprotection. [source] Comparison of Different Strategies on DNA Chip Fabrication and DNA-Sensing: Optical and Electrochemical ApproachesELECTROANALYSIS, Issue 22 2005Sabine Szunerits Abstract New strategies for the construction of DNA chips and the detection of DNA hybridization will be discussed in this review. The focus will be on the use of polypyrrole as a linker between a substrate and oligonucleotide probes. The modification step is based on the electrochemical copolymerization of pyrrole and oligonucleotides bearing a pyrrole group on its 5, end. This strategy was employed for the immobilization of oligonucleotides on millimeter-sized electrodes, microelectrode arrays, as well as for the local structuring of homogeneous gold surfaces. Our approaches for the localized patterning of gold surfaces will be also discussed. Localized immobilization was achieved by using an electrospotting technique, where a micropipette served as an electrochemical cell where spot sizes with 800,,m diameters were fabricated. The use of a microcell using a Teflon covered metal needle with a cavity of 100,,m resulted in immobilized probe spots of 300,,m. Scanning electrochemical microscopy (SECM) was also used, and surface modifications of 100,,m were obtained depending on the experimental conditions. Different detection methods were employed for the reading of the hybridization event: fluorescence imaging, surface plasmon resonance imaging (SPRI), photocurrent measurements, and voltamperometric measurements using intercalators. Their advantages concerning the various immobilization strategies will also be discussed. [source] Zoledronate has an antitumor effect and induces actin rearrangement in dexamethasone-resistant myeloma cellsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2007Masayuki Koizumi Abstract New strategies are needed to overcome the resistance of multiple myeloma (MM) to dexamethasone (Dex). Several recent in vitro studies demonstrated the antitumor effect of nitrogen-containing amino-bisphosphonates (N-BPs) in various tumor cell lines. Inhibition of the prenylation of small G proteins is assumed to be one of the principal mechanisms by which N-BPs exert their effects. There have been few reports on N-BP treatment of MM cells that are resistant to Dex. Additionally, it is not known how small G proteins are altered in N-BP-treated MM cells. In this study, we evaluated the effect of the most potent N-BP, zoledronate (ZOL), on a Dex-resistant human MM cell subline (Dex-R) that we established from the well-documented RPMI8226 cell line. ZOL reduced the viability and induced apoptosis of Dex-R cells. Some of the ZOL-treated RPMI8226 cells and ZOL-treated Dex-R cells were elongated; however, elongated cells were not seen among the Dex-treated RPMI8226 cells. Furthermore, we found that portions of the small G proteins, Rho and Rap1A, were unprenylated in the ZOL-treated MM cells. Geranylgeraniol reduced the above-mentioned ZOL-induced effects. These findings suggest that ZOL may be beneficial for the treatment of Dex-resistant MM by suppressing the processing of RhoA and Rap1A. [source] Driving in the melanoma landscapeEXPERIMENTAL DERMATOLOGY, Issue 6 2009Meenhard Herlyn Abstract:, The melanoma landscape is rapidly evolving. The melanoma oncologists have now the first successful targets for therapy that have a genetic base , albeit in rare forms of the malignancy. Once melanoma becomes part of the Cancer Genome Atlas consortium, a comprehensive map of genetic changes will be established to point the field to true drivers of the disease that will become new targets for therapy. The same abnormalities will also serve as biomarkers for diagnosis, prognosis and therapy follow-up. Melanomas as a group are heterogenous as are tumor cells within one lesion. New strategies will move towards individualized therapies and combination therapies to target all cells within a tumor. [source] New strategies in insulin treatment: analogues and noninvasive routes of administrationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2005Jørgen Rungby Abstract Recent years have seen the development of alternatives to human insulin for the treatment of diabetes. Both rapid-acting and long-acting analogues are available. Alternative routes of insulin administration are emerging. The present review briefly summarizes the present knowledge on insulin analogues and alternative administration routes. [source] Effectiveness of hepatitis C treatment with pegylated interferon and ribavirin in urban minority patients,HEPATOLOGY, Issue 4 2010Paul Feuerstadt Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naïve, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority patients. We evaluated 2,370 outpatients for HCV therapy from 2001 to 2006 in the Faculty Practice of the Albert Einstein College of Medicine or the attending-supervised Montefiore Medical Center Liver Clinic. Care was supervised by one experienced physician under conditions of everyday clinical practice, and appropriate ancillary resources were made available to all patients. Two hundred fifty-five patients were treated with a mean age of 50 years (60% male, 40% female; 58% Hispanic, 20% African American, 9% Caucasian, 13% other; 68% genotype 1, the remainder genotypes 2 or 3). Patients had at least one liver biopsy. Intention-to-treat analysis (ITT) showed SVR in 14% of genotype 1 patients and 37% in genotype 2/3 patients (P < 0.001). SVR was significantly higher in faculty practice (27%) than in clinic patients (15%) by intention-to-treat (P = 0.01) but not per-protocol analysis (46% faculty practice, 34% clinic). 3.3% of 1,656 treatment-naïve, HIV antibody,negative individuals ultimately achieved SVR. Current hepatitis C therapies may sometimes be unavailable to, inappropriate for, and ineffective in United States urban patients. Treatment with pegylated interferon and ribavirin was less effective in this population than is implied by multinational phase III controlled trials. New strategies are needed to care for such patients. (HEPATOLOGY 2010.) [source] Radical-scavenging polyphenols: new strategies for their synthesisJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2007Paolo Bovicelli New strategies for the synthesis of polyphenols, compounds with antioxidant properties contained in every kind of plants, are discussed. Syntheses of different classes of polyphenols, namely ubiquinones, present in many natural systems in which electron-transfer mechanisms are involved, hydroxy-tyrosol, one of the main components of the phenol fraction in olives, and flavonoids, widespread in the plant kingdom, were approached by simple and environmentally sustainable methods. [source] New strategies for polymer development in pharmaceutical science , a short reviewJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 9 2001A. Godwin We are developing synthetic polymers for pharmaceutical and medical applications. These applications can be broadly grouped on how the polymer will be utilized e.g. material, excipient or molecule. Our focus is to develop polymers with more defined structures that are based on biological, physicochemical and/or materials criteria. Strategies are being developed to more efficiently optimize structure,property correlations during preclinical development. We describe two examples of our research on pharmaceutical polymer development: narrow molecular weight distribution (MWD) homopolymeric precursors which can be functionalized to give families of narrow MWD homo- and co-polymers, and hydrolytically degradable polymers. [source] New strategies for the control of arthropod vectors of disease in dogs and catsMEDICAL AND VETERINARY ENTOMOLOGY, Issue 4 2008D. OTRANTO Abstract Arthropod-borne diseases (ABDs) in cats and dogs have a major impact on animal health and welfare and, in many cases, also on human health. Many ABDs are expected to increase in prevalence as a result of changing social habits, habitat modifications, introductions of exotic vectors and climate change. Control has, historically, focused on the use of insecticides and chemotherapy. We review alternative, emerging approaches to ABDs that currently offer promise, particularly modelling and molecular techniques and the development of novel vaccines that target molecules produced by arthropods during the bloodmeal. We argue that there is an urgent need to establish effective surveillance systems for most ABDs across various countries in order to facilitate a detailed risk analysis, which should include evaluation of potential spread to new areas and the possible introduction of new exotic species or disease agents. This will require clear and exhaustive knowledge on the distribution of ABDs in different areas, understanding of the diagnostic limitations pertaining to ABDs and standardization of techniques among reference laboratories in different countries. Continuous monitoring of insecticide resistance and the development of management strategies to minimize its onset are also essential. Ultimately, it is probable that approaches which attempt to reduce vector abundance or treat hosts with chemotherapy alone are unlikely to be effective in the long term. More suitable approaches may include greater use of a range of mutually compatible options in integrated management programmes. [source] Decrease in Tumor Apparent Permeability-Surface Area Product to a MRI Macromolecular Contrast Medium Following Angiogenesis Inhibition with Correlations to Cytotoxic Drug AccumulationMICROCIRCULATION, Issue 5 2004HEIKE E. DALDRUP-LINK ABSTRACT Background: New strategies for cancer therapy include the combination of angiogenesis inhibitors with cytotoxins. However, angiogenesis inhibitors may alter tumor microvessel structure and transendothelial permeability thereby reducing tumoral delivery of cytotoxic agents. The aim of this study was to estimate quantitatively the apparent permeability-surface area product (KPS) in tumors to a macromolecular contrast medium (MMCM), to follow changes in KPS induced by antibodies to vascular endothelial growth factor (anti-VEGF), and to correlate the findings with tumor accumulation of cisplatin, a highly protein-bound cytotoxin, and 5-fluorouracil (5-FU), a small unbound cytotoxin. Methods: Dynamic MRI enhanced with a MMCM (albumin-(Gd-DTPA)30) was analyzed using a two-compartment tumor tissue model (plasma and interstitial water) to quantitatively estimate KPS. These estimates of KPS were correlated with cytotoxic drug accumulations in the tumors. Results: Anti-VEGF treatment reduced KPS to MMCM in tumor tissue from 0.013 mL h,1 cm,3 (n = 9) at baseline to 0.003 mL h,1 cm,3 (n = 9) 24 h later (p < .05). The KPS values correlated significantly (r2 = .78; p < .0001) with the tumor cisplatin accumulation. No correlation (r2 = .001; p = .89) was found between KPS and tumor accumulation of the substantially smaller 5-FU molecule. Conclusions: MMCM-enhanced MRI can be used to detect and estimate changes in KPS to this contrast agent following a single dose of anti-VEGF antibody. The decline in KPS induced by this inhibitor of angiogenesis is associated with reduced tumor concentration of a protein-bound cytotoxin, similar in molecular weight to the contrast agent. MRI assays of microvascular status as performed here may be useful to clinically monitor responses to anti-angiogenesis drugs and to optimize the choice and timing of cytotoxic drug administration. [source] Inhibition of platelet phospholipase A2 activity by catuaba extract suggests antiin,ammatory propertiesPHYTOTHERAPY RESEARCH, Issue 11 2004Nádia R. Barbosa Abstract In the in,ammation process, phospholipase A2 (PLA2) catalyses the cleavage of the sn -2 ester-linked fatty acids from phospholipids, being the enzyme responsible for arachidonic acid (AA) release by cells for the biosynthesis of the prostaglandins and thromboxanes via the cyclooxygenase system, and the leukotrienes and eicosatetraenoids via the lipoxygenase pathway. AA mobilization by PLA2 and subsequent prostaglandins synthesis is considered to be a pivotal event in in,ammation. Therefore, drugs that inhibit PLA2, thus blocking the COX and LOX pathways in the AA cascade, may be effective in the treatment of in,ammatory processes. New strategies for the treatment of in,ammatory processes could be detected by a search for active principles of vegetal origin that control the lipid mediator production by inhibition of PLA2. The present data are part of a wide explorative investigation on the effects of Trichilia catigua (catuaba), which found that PLA2 activity was totally inhibited by catuaba at a concentration of 120 µg/mL, suggesting that this natural substance may have antiin,ammatory properties. Copyright © 2004 John Wiley & Sons, Ltd. [source] Non-attendance at a diabetes transitional clinic and glycaemic controlPRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 3 2010FRCP, MG Masding MB BS Abstract Young patients with diabetes are particularly vulnerable to long-term complications, and require a carefully planned transition to adult diabetes care. As clinic non-attendance has been identified as an issue for transitional clinics, we audited our well established clinic to look at non-attendance rates, and to examine the characteristics of those who miss transitional clinic appointments. We conducted a retrospective analysis of audit data from the diabetes transitional clinic in January to December 2004, and September 2007 to September 2008. The results showed that 40/53 patients missed at least one appointment in 2004, compared to 19/61 in 2007,8 (p<0.0001). There was no reduction in HbA1c in this group (2004: median HbA1c 9.4% [range 6.8,13.2%]; 2007,8: median HbA1c 9.7% [range 5.7,14.0%[). In 2007,8, the non-attender group had higher HbA1c (full attenders: median [range] HbA1c 8.9% [5.7,12.7%]; those who missed at least one appointment: HbA1c 10.3% [7.7,14.0%]; p<0.001), and were older (non-attenders mean [SD] 18.0 [1.10] years, full attenders 17.3 [1.17] years). Sex and type of diabetes did not affect ,did not attend' rates. Those who miss diabetes transitional clinic appointments have poorer glycaemic control, although non-attendance is complex and may be due to a variety of reasons. New strategies to help young people deal with their diabetes are needed. Copyright © 2010 John Wiley & Sons. [source] Point/Counterpoint: The Role of Carotid UltrasoundPREVENTIVE CARDIOLOGY, Issue 2 2005Point: Uses Of Carotid Plaque Measurement As A Predictor Of Cardiovascular Events Vascular prevention is most cost-effective in high-risk patients, but secondary prevention misses many opportunities. The high-risk strategy-identifying patients with high levels of risk factors-is problematic because traditional risk factors predict only half of vascular events. In multiple regression, traditional risk factors explained only half of carotid atherosclerosis. New strategies are being explored, such as electron-beam computerized tomographic measurement of coronary calcification, to identify high-risk patients. Carotid plaque is a powerful tool for identifying and managing high-risk vascular patients, as it explains twice as much of unexplained vascular risk as coronary calcium by electron beam computerized tomography, and it has significant advantages compared with intimal-medial thickness. After adjustment for risk factors, patients in the highest quartile of baseline plaque area have 3.5 times the risk of stroke, death, or myocardial infarction compared with those in the lowest quartile. Those with regression or stable plaque have half the risk of those with progression after adjustment for the same panel of risk factors. The therapeutic target is plaque regression or stabilization, not just control of traditional risk factors. Trying to treat arteries without measuring plaque is like trying to treat hypertension without measuring the pressure, or hyperlipidemia without measuring the lipids. [source] Computer-Based Analysis of Dynamic QT Changes: Toward High Precision and Individual Rate CorrectionANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 4 2002Corina Dota M.D. Background: New strategies are needed to improve the results of automatic measurement of the various parts of the ECG signal and their dynamic changes. Methods: The EClysis software processes digitally-recorded ECGs from up to 12 leads at 500 Hz, using strictly defined algorithms to detect the PQRSTU points and to measure ECG intervals and amplitudes. Calculations are made on the averaged curve of each sampling period (beat group) or as means ± SD for beat groups, after being analyzed at the individual beat level in each lead. Resulting data sets can be exported for further statistical analyses. Using QT and R-R measured on beat level, an individual correction for the R-R dependence can be performed. Results: EClysis assigns PQRSTU points and intervals in a sensitive and highly reproducible manner, with coefficients of variation in ECG intervals corresponding to ca. 2 ms in the simulated ECG. In the normal ECG, the CVs are 2% for QRS, 0.8% for QT, and almost 6% for PQ intervals. EClysis highlights the increase in QT intervals and the decrease of T-wave amplitudes during almokalant infusion versus placebo. Using the observed linear or exponential relationships to adjust QT for R-R dependence in healthy subjects, one can eliminate this dependence almost completely by individualized correction. Conclusions: The EClysis system provides a precise and reproducible method to analyze ECGs. A.N.E. 2002;7(4):289,301 [source] Pro-apoptotic therapy with the oligonucleotide GenasenseTM (oblimersen sodium) targeting Bcl-2 protein expression enhances the biological anti-tumour activity of rituximabBRITISH JOURNAL OF HAEMATOLOGY, Issue 5 2004Jeyanthi Ramanarayanan Summary New strategies have evolved in the treatment of patients with non-Hodgkin's lymphoma (NHL). Anti-sense oligonucleotides (ASO) and monoclonal antibody (mAb) therapy, though proven to be safe and effective, have not demonstrated to be curative when used as single agents. We tested an innovative combination strategy involving various mAbs and ASO against Bcl-2 (G3139) in aggressive preclinical models. G3139, under optimal transfection conditions, decreased the proliferation rate of lymphoma cells by 60,75% when compared with controls. In addition, apoptosis was demonstrated in Raji (25%) and DHL-4 cells (30%) treated with Genasense following downregulation of Bcl-2 protein. Downregulation of Bcl-2 by G3139 was associated with a higher degree of rituximab-associated, complement-mediated cytotoxicity and antibody dependent cellular cytotoxicity when compared with rituximab alone-treated controls. In vivo studies in severe combined immunodeficiency (SCID) mice clearly demonstrated synergistic activity between G3139 and rituximab. Treatment of lymphoma-bearing SCID mice with G3139 for two consecutive days prior to each rituximab dose resulted in better disease control and survival than treatment with either agent alone or controls. Our findings suggest that Bcl-2 downregulation by G3139, followed by the administration of rituximab is an efficient anti-tumour strategy associated with improved survival in lymphoma-bearing SCID mice. [source] Migraine: a review and future directions for treatmentACTA NEUROLOGICA SCANDINAVICA, Issue 2 2006M. Linde Migraine is a chronic, neurological disorder generally manifesting itself in attacks with severe headache, nausea and an increased reactivity to sensory stimuli. A low migraine threshold is set by genetic factors, although the phenotype also modulates the manifestations. The 1-year prevalence is approximately 13% and is higher among women. Patients usually experience neuropsychological dysfunction, and sometimes also reversible focal neurological symptoms. The trajectories of the characteristic symptoms of acute migraine usually follow a similar time course, indicating a reciprocal underlying mechanism. A central nervous system hyperexcitability has been demonstrated in neurophysiological studies. The dibilitating effects of migraine are not confined to the attacks per se. Many individuals do not recover completely between the attacks and most report a negative impact on the most important life domains, and an interest in testing other treatments. Young persons have a higher frequency of attacks. Acute treatment should routinely be initiated with an analgesic plus a prokinetic anti-emetic. Triptans must not be provided early during the attack to ensure their efficacy. The natural course of attacks is commonly only temporarily altered by acute treatment. Non-pharmacological treatment and drugs may be equally viable in prophylaxis for migraine. In more complicated cases, conjoint therapy should be considered. New strategies to improve adherence with existing therapeutic regimens might yield greater benefits than will new pharmacological agents. [source] | ||||||||||||||||||||||||||||||||||||||||||||||