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ACE
Terms modified by ACE Selected AbstractsON SOCIAL LEARNING AND ROBUST EVOLUTIONARY ALGORITHM DESIGN IN THE COURNOT OLIGOPOLY GAMECOMPUTATIONAL INTELLIGENCE, Issue 2 2007Floortje Alkemade Agent-based computational economics (ACE) combines elements from economics and computer science. In this article, the focus is on the relation between the evolutionary technique that is used and the economic problem that is modeled. In the field of ACE, economic simulations often derive parameter settings for the genetic algorithm directly from the values of the economic model parameters. This article compares two important approaches that are dominating in ACE and shows that the above practice may hinder the performance of the genetic algorithm and thereby hinder agent learning. More specifically, it is shown that economic model parameters and evolutionary algorithm parameters should be treated separately by comparing the two widely used approaches to social learning with respect to their convergence properties and robustness. This leads to new considerations for the methodological aspects of evolutionary algorithm design within the field of ACE. [source] HYBRID ACE: COMBINING SEARCH DIRECTIONS FOR HEURISTIC PLANNINGCOMPUTATIONAL INTELLIGENCE, Issue 3 2005Dimitris Vrakas One of the most promising trends in Domain-Independent AI Planning, nowadays, is state-space heuristic planning. The planners of this category construct general but efficient heuristic functions, which are used as a guide to traverse the state space either in a forward or in a backward direction. Although specific problems may favor one or the other direction, there is no clear evidence why any of them should be generally preferred. This paper presents Hybrid-AcE, a domain-independent planning system that combines search in both directions utilizing a complex criterion that monitors the progress of the search, to switch between them. Hybrid AcE embodies two powerful domain-independent heuristic functions extending one of the AcE planning systems. Moreover, the system is equipped with a fact-ordering technique and two methods for problem simplification that limit the search space and guide the algorithm to the most promising states. The bi-directional system has been tested on a variety of problems adopted from the AIPS planning competitions with quite promising results. [source] Heart Failure Drug Utilization Patterns for Medicaid Patients Before and After a Heart Failure-Related HospitalizationCONGESTIVE HEART FAILURE, Issue 3 2005Patricia A. Howard PharmD The authors examined heart failure (HF) drug utilization patterns in Medicaid patients before and after a HF-related hospitalization. This was a retrospective claims analysis of Kansas Medicaid beneficiaries hospitalized for HF between July 1, 2000, and March 31, 2001. HF drugs were tracked 6 months prior and 6 months following the admission. Angiotensin-converting enzyme (ACE) inhibitor doses were compared with target ranges. The cohort of 135 patients had a mean age of 53.6 years and was predominantly female (66.7%) and Caucasian (70.4%) with a high prevalence of cardiovascular comorbidities. Before hospitalization, less than one third of patients were receiving ACE inhibitors, angiotensin receptor blockers, , blockers, digoxin, or vasodilators. Following hospitalization, increased utilization was observed for , blockers, digoxin, and angiotensin receptor blockers, but overall usage remained low. ACE inhibitors and vasodilator use remained constant. ACE-inhibitor doses were below target ranges before and after hospitalization. In this Medicaid cohort, HF-related hospitalizations did not lead to improved HF therapy. [source] Possible Interaction Between Aspirin and ACE Inhibitors: Update on Unresolved ControversyCONGESTIVE HEART FAILURE, Issue 6 2000Israel M. Barbash BmedSc The widespread use of aspirin and angiotensin converting enzyme (ACE) inhibitors in patients with coronary artery disease contributes significantly to the reduction in morbidity and mortality from this common health problem. These agents are widely and concomitantly used, and they share mechanisms that may interact in negative or positive pathways. Data derived from in vitro preparations, animal studies, human studies, and case-control studies are inconsistent. No study has established firm evidence regarding the safety or adverse effect of aspirin on patients who are on ACE inhibitors. The efficacy and safety of aspirin in combination with ACE inhibitors has been questioned and debated. If a negative interaction does exist, it will affect daily practice in treating patients with coronary artery disease and heart failure. This article reviews the available data regarding the safety of combined aspirin and ACE-inhibitor treatment among patients with ischemic heart disease, to assess the possible interaction between the two drugs and to discuss thesignificance and implications of the data. [source] Acute exercise causes an enhancement of tissue renin,angiotensin system in the kidney in ratsACTA PHYSIOLOGICA, Issue 1 2005S. Maeda Abstract Aims:, Initially, the renin,angiotensin system (RAS) produced through the classical endocrine pathway was well known for its regulation of blood pressure. However, it was revealed that a local autocrine and/or paracrine RAS may exist in a number of tissues (such as kidney). Exercise causes a redistribution of tissue blood flow, by which the blood flow is greatly increased in active muscles, whereas it is decreased in the splanchnic circulation (such as in the kidney). We hypothesized that exercise causes an enhancement of tissue RAS in the kidney. Methods:, We studied whether exercise affects expression of angiotensinogen and angiotensin-converting enzyme (ACE) and tissue angiotensin II level in the kidney. The rats performed treadmill running for 30-min. Immediately after this exercise, kidney was quickly removed. Control rats remained at rest during this 30-min period. Results:, The expression of angiotensinogen mRNA in the kidney was markedly higher in the exercise rats than in the control rats. ACE mRNA in the kidney was significantly higher in the exercise rats than in the control rats. Western blot analysis confirmed significant upregulation of ACE protein in the kidney after exercise. Tissue angiotensin II level was also increased by exercise. Conclusion:, The present study suggests that the exercise-induced enhancement of tissue RAS in the kidney causes vasoconstriction and hence decreases blood flow in the kidney, which are helpful in increasing blood flow in active muscles, thereby contributing to the redistribution of blood flow during exercise. [source] Modeling the Effects of a Service Guarantee on Perceived Service Quality Using Alternating Conditional Expectations (ACE),DECISION SCIENCES, Issue 3 2002Chee-Chuong Sum ABSTRACT This paper addresses the dearth of empirical research on the relationship between service guarantee and perceived service quality (PSQ). In particular, we examine the moderating effects of a service guarantee on PSQ. While a recent study provided empirical evidence that service quality is affected by service guarantee and employee variables such as employee motivation/vision and learning through service failure, the nature and form of the relationships between these variables remain unclear. Knowledge of these relationships can assist service managers to allocate resources more judiciously, avoid pitfalls, and establish more realistic expectations. Data was obtained from employees and customers of a multinational hotel chain that has implemented a service guarantee program in 89 of its hotels in America and Canada. As the employee variables could affect performance in a non-linear fashion, we relaxed the assumption of model linearity by using the Alternating Conditional Expectations (ACE) algorithm to arrive at a better-fitting, non-linear regression model for PSQ. Our findings indicate the existence of significant non-linear relationships between PSQ and its determinant variables. The ACE model also revealed that service guarantee interacts with the employee variables to affect PSQ in a non-linear fashion. The non-linear relationships present new insights into the management of service guarantees and PSQ. Explanations and managerial implications of our results are presented and discussed. [source] Factors regulating renal angiotensin-converting enzyme activity in the ratACTA PHYSIOLOGICA, Issue 1 2000Changes in angiotensin-converting enzyme (ACE) activity appear to be important in mediating the natriuresis which ensues after administration of an oral or gastric sodium load. In this study, we sought to determine the time course of the changes in ACE activity in the kidney which occur after sodium ingestion. In addition, we sought to investigate mechanisms which might underlie these changes. Angiotensin-converting enzyme activity was measured by generation of histidyl-leucine in homogenates of kidneys harvested at varying time-points after gastric sodium administration. The effects of intravenous sodium loading, solution osmolality and of changes in renal nerve activity were also investigated. Intragastric instillation of both the sodium-containing solution and its iso-osmotic urea control solution resulted in significant increases in renal ACE activity (NaCl: P < 0.0005; Urea: P < 0.01). The increase in renal ACE activity after gastric sodium loading was more prolonged than after the urea control (P < 0.025, NaCl vs. urea at 90 min). This prolonged increase in renal ACE activity appeared to reflect a response to absorbed sodium as intravenous sodium administration caused a significant increase in renal ACE activity at 90 min (P < 0.0005). In contrast to these stimuli which increased renal ACE activity, renal denervation caused a significant decrease in ACE activity in the kidney (P < 0.05). We conclude that gastric sodium loading increases renal ACE activity. This effect appears to be due initially to a response to an increase in gastric lumenal osmolality and later to absorbed sodium. These changes in renal ACE activity are not mediated by a decrease in renal nerve activity. [source] Effects of insulin resistance on endothelial function: possible mechanisms and clinical implicationsDIABETES OBESITY & METABOLISM, Issue 10 2008D Tousoulis Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin,angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials. [source] Treatment of high-risk diabetic patients with angiotensin II receptor blockersDIABETES OBESITY & METABOLISM, Issue 6 2001R. Estacio Summary In the United States, , 16 million people have diabetes; 90,95% have type 2 diabetes. They are at increased risk of developing hypertension and cardiovascular disease (CVD). The benefits of treating hypertension in diabetic patients and the potential to delay complications and reduce mortality have been demonstrated in clinical trials. Increasing evidence shows that angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) receptor blockers (ARBs) may be equally effective in delaying progressive renal disease in diabetic patients. Large, multicentre trials are ongoing to confirm the efficacy and superior safety profile of ARBs in this population. [source] Serum angiotensin-converting enzyme and frequency of severe hypoglycaemia in Type 1 diabetes: does a relationship exist?DIABETIC MEDICINE, Issue 12 2007N. N. Zammitt Abstract Aims An association has been described between elevated serum angiotensin-converting enzyme (ACE) and an increased risk of severe hypoglycaemia (SH). To ascertain whether this reported association could be replicated in a different country, it was re-examined in 300 individuals with Type 1 diabetes. Methods People with Type 1 diabetes, none of whom was taking renin,angiotensin system blocking drugs, were recruited. Participants recorded the frequency with which they had experienced SH. Glycated haemoglobin (HbA1c) and serum ACE were measured. The difference in the incidence of SH between different quartiles of ACE activity and the relationship between serum ACE and SH were examined using non-parametric statistical tests and a negative binomial model. Results Data were obtained from 300 patients [158 male; HbA1c median (range) 8.2% (5.2,12.8%), median age 36 years (16,88); duration of diabetes 14.5 years (2,49)]. The incidence of SH was 0.93 episodes per patient year. The mean incidence of SH in the top and bottom quartiles of ACE activity was 0.5 and 1.7 episodes per patient year, respectively, but this difference was not statistically significant (P = 0.075). Spearman's test showed a very weak, although statistically significant, association between serum ACE level and SH incidence (r = 0.115, P = 0.047). The binomial model also showed a statistically significant (P = 0.002), but clinically weak, relationship between serum ACE and SH. Conclusions The present survey showed a weak relationship between serum ACE and the frequency of SH, the clinical relevance of which is unclear. This limits the proposed role for serum ACE as an index of risk for SH. [source] Association analysis of genes in the renin-angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart StudyDIABETIC MEDICINE, Issue 3 2006K. P. Burdon Abstract Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin-angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima-media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population. [source] The renin,angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerationsDIABETIC MEDICINE, Issue 8 2003R. E. Gilbert Abstract The relationship between the renin,angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS. [source] Angiotensin-I-converting enzyme insertion/deletion polymorphism and high urinary albumin concentration in French Type 2 diabetes patientsDIABETIC MEDICINE, Issue 8 2003S. Hadjadj Abstract Aims Family-based studies suggest a genetic basis for nephropathy in Type 2 diabetes. The angiotensin-I-converting enzyme (ACE) gene is a candidate gene for Type 1 diabetes nephropathy. We assessed the association between high urinary albumin concentration and ACE insertion/deletion (I/D) polymorphism, in French Type 2 diabetes patients. Methods We studied 3139 micro/macroalbuminuric French patients recruited in the DIABHYCAR Study, an ACE inhibition trial in Type 2 diabetes patients with renal and cardiovascular outcomes. The main inclusion criteria were age , 50 years, urinary albumin concentration , 20 mg/l assessed centrally during two consecutive screening visits, and plasma creatinine concentration , 150 µmol/l. These patients were compared with 605 normoalbuminuric (NA; urinary albumin concentration < 10 mg/l at first screening for the DIABHYCAR Study) French patients. ACE I/D genotype was determined by nested polymerase chain reaction. Results The ACE I/D polymorphism was in Hardy,Weinberg equilibrium. The distribution of genotypes did not differ significantly between micro/macroalbuminuric and NA patients: 552 and 115 II, 1468 and 282 ID, 1119 and 208 DD (P = 0.67). However, the ACE D allele was more frequent among normotensive micro/macroalbuminuric patients than among NA patients (P = 0.039). Conclusions The ACE I/D polymorphism was not associated with high urinary albumin concentration in French Type 2 diabetes patients. [source] Role of Echocardiography in Assessing the Mechanism and Effect of Ramipril on Functional Mitral Regurgitation in Dilated CardiomyopathyECHOCARDIOGRAPHY, Issue 4 2005D.M. (Card), F.I.A.E., F.I.A.M.S., F.I.C.C., F.I.C.P., I.B. Vijayalakshmi M.D. The objectives of this article are to determine the possible mechanism of functional mitral regurgitation in patients with dilated cardiomyopathy (DCM) and to know the effect of ramipril on left ventricle (LV) and mitral regurgitation by ECHO. Several postulates are put forth for functional mitral regurgitation in DCM, and mitral annular dilatation is said to be the primary mechanism in the past, but the exact mechanism is not clear. Though angiotensin converting enzyme (ACE) inhibitors are known to remodel the LV, their beneficial effect in patients with DCM with functional mitral regurgitation is not known. Various cardiac dimensions and degree of mitral regurgitation were measured by echocardiography in 30 normal control group and in 30 patients with DCM of various etiologies except ischemic, before and after ramipril therapy. There was a significant difference in all parameters especially sphericity of left ventricle and position of papillary muscles (P < 0.0003) in DCM patients, but mitral valve annulus did not show significant change (P < 0.3) compared to control group. In 50% of the patients, the functional mitral regurgitation totally disappeared. In 30% of patients, it came down from grade II to I or became trivial. In 20% of patients, it remained unchanged. There was remarkable improvement in sphericity, LV dimension, volumes, and EF%, which increased from 31 ± 9.81 to 39.3 ± 8.3% (P < 0.0003). It is concluded that echocardiography clearly demonstrates the increased sphericity of LV in DCM. The lateral migration of papillary muscles possibly plays a major role in functional mitral regurgitation. Ramipril significantly reduces not only sphericity but also functional mitral regurgitation. [source] Cover Picture: Electrophoresis 4'2010ELECTROPHORESIS, Issue 4 2010Article first published online: 16 FEB 2010 Issue no. 4 is a regular issue with Emphasis on "Bioanalysis". Part I has 12 articles on bioanalysis featuring methodologies for proteomics, proteins, peptides and nucleic acids. Part II has 5 papers on interactive CE, e.g., MEEKC, MEKC and ACE. The remaining 2 articles make up Part III, and are concerned with the regulation of flow in microfluidics and sensitivity enhancement in CEC. Featured articles include: Identification of candidate biomarkers in ovarian cancer serum by depletion of highly abundant proteins and differential in gel electrophoresis. ((10.1002/elps.200900441.R1)) An effective SCAR-PCR method derived from restriction site amplified polymorphism (RSAP) for the identification of female Schistosoma japonicum of zoonotic significance. ((10.1002/elps.200900615.R1)) Rapid and sensitive DNA targets detection using enzyme amplified electrochemical detection based on microchip. ((10.1002/elps.200900538.R1)) [source] Interaction study of a lysozyme-binding aptamer with mono- and divalent cations by ACEELECTROPHORESIS, Issue 3 2010Marie Girardot Abstract Binding between an aptamer and its target is highly dependent on the conformation of the aptamer molecule, this latter seeming to be affected by a variety of cations. As only a few studies have reported on the interactions of monovalent or divalent cations with aptamers, we describe herein the use of ACE in its mobility shift format for investigating interactions between various monovalent (Na+, K+, Cs+) or divalent (Mg2+, Ca2+, Ba2+) cations and a 30-mer lysozyme-binding aptamer. This study was performed in BGEs of different natures (phosphate and MOPS buffers) and ionic strengths. First, the effective charges of the aptamer in 30,mM ionic strength phosphate and MOPS (pH 7.0) were estimated to be 7.4 and 3.6, respectively. Then, corrections for ionic strength and counterion condensation effects were performed for all studies. The effective mobility shift was attributed not only to these effects, but also to a possible interaction with the buffer components (binary or ternary complexes) as well as possible conformational changes of the aptamer. Finally, apparent binding constants were calculated for divalent cations with mathematical linearization methods, and the influence of the nature of the BGE was evidenced. [source] Cover Picture: Electrophoresis 16/2008ELECTROPHORESIS, Issue 16 2008Article first published online: 13 AUG 200 Issue no. 16 is a Special Issue on "Affinity and Immunoaffinity CE and CEC" consisting of 23 papers that are arranged into five parts. The first part has 4 review articles followed by a selection of 5 papers in the second part on the application of affinity CE and CEC assembled . The third part comprises a series of papers on more specialized applications of ACE and the fourth part deals with immunoaffinity applications. Finally, the fifth part is a collection of chip-based applications. [source] Use of chemometric methodology in optimizing conditions for competitive binding partial filling affinity capillary electrophoresisELECTROPHORESIS, Issue 16 2008Ruth E. Montes Abstract This work expands the knowledge of the use of chemometric response surface methodology (RSM) in optimizing conditions for competitive binding partial filling ACE (PFACE). Specifically, RSM in the form of a Box,Behnken design was implemented in flow-through PFACE (FTPFACE) to effectively predict the significance of injection time, voltage, and neutral ligand (neutral arylsulfonamide) concentration, [Lo], on protein,neutral ligand binding. Statistical analysis results were used to create a model for response surface prediction via contour and surface plots at a given maximum response (,RMTR) to reach a targeted Kb,=,2.50×106,M,1. The adequacy of the model was then validated by experimental runs at the optimal predicted solution (injection time,=,2.3,min, voltage,=,11.6,kV, [Lo],=,1.4,,M). The achieved results greatly extend the usefulness of chemometrics in ACE and provide a valuable statistical tool for the study of other receptor,ligand combinations. [source] Behavior of interacting species in vacancy affinity capillary electrophoresis described by mass balance equationELECTROPHORESIS, Issue 16 2008Ying Sun Abstract Vacancy ACE (VACE) is one of the ACE methods, and has been used to study binding interactions between different biomolecules. Thermodynamic binding constants can be estimated with nonlinear regression methods. With a highly efficient computer simulation program (SimDCCE), it is possible to demonstrate the detailed behaviors of each species during the interaction process under different conditions. In this work, thirteen scenarios in four different combinations of migration orders of the free protein, free drug, and complex formed are studied. The detailed interaction process between protein and ligand is discussed and illustrated based on the mass balance equation, also called mass transfer equation. By properly setting the parameters in the simulation model, the influence of different factors during the interaction process can be well understood. [source] High-sensitive determination of human ,-thrombin by its 29-mer aptamer in affinity probe capillary electrophoresisELECTROPHORESIS, Issue 12 2008Yilin Li Abstract ACE technique provides an effective tool for the separation and identification of disease-related biomarkers in clinical analysis. In recent years, a couple of synthetic DNA or RNA oligonucleotides, known as aptamers, rival the specificity and affinity for targets to antibodies and are employed as one kind of powerful affinity probe in ACE. In this work, based on high affinity between antithrombin aptamer and thrombin (their dissociation constant is 0.5,nM), a carboxyfluorescein-labeled 29-nucleotide (nt) aptamer (F29-mer) was used and an aptamer-based affinity probe CE (aptamer-based APCE) method was successfully established for high-sensitive detection and quantitative analysis of thrombin. Experimental conditions including incubation temperature and time, buffer composition, and concentration of cations were investigated and optimized. Under the optimized condition, the linear range was from 0 to 400,nM and the LOD was 2,nM (74,ng/mL, S/N,=,3), i.e., 40,amol, both in running buffer and in 5% v/v human serum. This LOD is the lowest one than those achieved by the previous APCE methods but based on a 15-mer aptamer. This approach offers a promising method for the rapid, selective, and sensitive detection of thrombin in practical utility. Further binding experiments using one carboxyfluorescein-labeled aptamer and the other nonlabeled aptamer or vice versa were carried out to deduce the formation of ternary complex when these two aptamers coexisted in the free solution with thrombin. [source] Implementation of chemometric methodology in ACE: Predictive investigation of protein,ligand bindingELECTROPHORESIS, Issue 16 2007Grady Hanrahan Abstract An ACE predictive investigation of protein,ligand binding using a highly effective chemometric response surface design technique is presented. Here, Kd was estimated using one noninteracting standard which relates to changes in the electrophoretic mobility of carbonic anhydrase B (CAB, EC 4.2.1.1) on complexation with the ligand 4-carboxybenzenesulfonamide (CBSA) present in the electrophoresis buffer. Experimental factors including injection time, capillary length, and applied voltage were selected and tested at three levels in a Box,Behnken design. Statistical analysis results were used to create a mathematical model for response surface prediction via contour and surface plots at a given target response (Kd,=,1.19×10,6,M). As expected, there were a number of predicted solutions that reached our target response based on the significance of each factor at appropriate levels. The adequacy of the model was validated by experimental runs with the predicted model solution (capillary length,=,47,cm, voltage,=,11,kV, injection time,=,0.01,min) presented in detail as an example. [source] Evaluation of enantioselective binding of antihistamines to human serum albumin by ACEELECTROPHORESIS, Issue 15 2007María Amparo Martínez-Gómez Abstract The drug binding to plasma and tissue proteins is a fundamental factor in determining the overall pharmacological activity of a drug. HSA, together with ,1 -acid glycoprotein, are the most important plasma proteins, which act as drug carriers, with implications on the pharmacokinetic of drugs. Among plasma proteins, HSA possesses the highest enantioselectivity. In this paper, a new methodology for the study of enantiodifferentiation of chiral drugs with HSA is developed and applied to evaluate the possible enantioselective binding of four antihistamines: brompheniramine, chlorpheniramine, hydroxyzine and orphenadrine to HSA. This study includes the determination of affinity constants of drug enantiomers to HSA and the evaluation of the binding sites of antihistamines on the HSA molecule. The developed methodology includes the ultrafiltration of samples containing HSA and racemic antihistaminic drugs and the analysis of the free or bound drug fraction using the affinity EKC-partial filling technique and HSA as chiral selector. The results shown in this paper represent the first evidence of the enantioselective binding of antihistamines to HSA, the major plasmatic protein. [source] Study of binding stoichiometries of the human immunodeficiency virus type,1 reverse transcriptase by capillary electrophoresis and laser-induced fluorescence polarization using aptamers as probesELECTROPHORESIS, Issue 2 2006Hao Fu Abstract Binding stoichiometries between four DNA aptamers (RT12, RT26, RTlt49, and ODN93) and the reverse transcriptase (RT) of the type,1 human immunodeficiency virus (HIV-1) were studied using affinity CE (ACE) coupled with LIF polarization and fluorescence polarization (FP). The ACE/LIF study showed evidence of two binding stoichiometries between the HIV-1,RT protein and aptamers RT12, RT26, and ODN93, suggesting that these aptamers can bind to both the p66 and p51 subunits of the HIV-1,RT. Only one binding stoichiometry for aptamer RTlt49 was found. The affinity complexes were easily separated from the unbound aptamers; however, the different stoichiometries were not well resolved. A complementary technique, FP, was able to provide additional information about the binding and supporting evidence for the ACE/LIF results. The ACE/LIFP study also revealed that the FP values of the 1:1 complexes of the HIV-1,RT protein with aptamers RT12, RT26, and ODN93 were always much greater than those of the 1:2 complexes. This was initially surprising because the larger molecular size of the 1:2 complexes was expected to result in higher FP values than the corresponding 1:1 complexes. This phenomenon was probably a result of fluorescence resonance energy transfer between the two fluorescent molecules bound to the HIV-1,RT protein. [source] Determination of protein-ligand affinity constants from direct migration time in capillary electrophoresisELECTROPHORESIS, Issue 12 2004Mikael Nilsson Abstract A simple method to calculate dissociation constants for protein-ligand interactions by partial-filling capillary electrophoresis is demonstrated. The method uses raw migration time data for the ligand and needs only additional information about capillary inner radius and the absolute amount of protein loaded. A theoretical study supported by experimental data also demonstrates that the retention of analyte in affinity capillary electrophoresis (ACE) using the partial-filling technique depends linearly on the absolute amount of selector added but is independent of both selector zone length and selector mobility. Factors such as field strength and electroosmotic flow are also cancelled out if they are kept constant. The theory is confirmed and the usefulness of the method is demonstrated by enantioseparations using ,-acid glycoprotein (AGP) and cellulase (Cel 7A) as chiral selectors. [source] ACE and angiotensinogen gene genotypes and left ventricular mass in athletesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2001F. Diet Background Genetic factors may be important in modifying heart size due to long-term athletic training. The significance of polymorphisms of genes of the renin,angiotensin system in myocardial mass in a population of athletes participating in different disciplines is not known. Methods The angiotensin I-converting enzyme gene insertion/deletion (I/D) polymorphism, angiotensinogen gene M235T polymorphism and angiotensin II type 1 receptor gene A1166C polymorphism were determined in 83 male Caucasian endurance athletes and associated with left ventricular mass. Results No association with left ventricular mass was found for the polymorphisms of angiotensin I-converting enzyme gene I/D, angiotensinogen gene M235T and angiotensin II type 1 gene A1166C when studied separately. However, combined analysis of the angiotensin I-converting enzyme gene I/D polymorphism and angiotensinogen gene M235T polymorphism genotypes suggested an association with left ventricular mass (g m,2) (P = 0·023). Athletes with the angiotensin I-converting enzyme gene DD/angiotensinogen gene TT genotype combination had greater left ventricular mass compared with all other genotype combinations (179·8 ± 26·1 g m,2 vs. 145·2 ± 27·3 g m,2, P = 0·003). Conclusions These results suggest an association of combined angiotensin I-converting enzyme gene I/D polymorphism genotypes, and angiotensinogen gene M235T polymorphism genotypes with left ventricular hypertrophy due to long-term athletic training. A synergistic effect of angiotensin I-converting enzyme gene DD genotype and angiotensinogen gene TT genotype on left ventricular mass in endurance athletes appears to occur. [source] Angiotensin-converting enzyme genotype and encephalopathy in Chernobyl cleanup workersEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2009A. D. Kehoe Background and purpose:, To identify, using a genetic model, a key role for the renin,angiotensin system (RAS) in the development of dyscirculatory encephalopathy (DE) in Chernobyl cleanup workers (CCW). The insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene denotes a substantial individual variation in RAS activity with the D-allele being associated with higher ACE activity. Methods:, Ninety-three male, Caucasian CCW were recruited from those under regular review at the All-Russia Centre of Emergency and Radiation Medicine, St. Petersburg. The presence or absence of DE was determined using existing institutional guidelines. ACE genotype was determined using internationally accepted methodologies. Results:, Angiotensin-converting enzyme genotype distribution in 59 subjects with DE was II: 10 (17%), ID: 31 (53%), DD: 18 (30%), D-allele frequency 56.8%. Whereas in those without the condition the distribution was II: 12 (35%), ID: 19 (56%), DD 3 (9%) and D-allele frequency 35.9% (P = 0.02). Conclusions:, These data are the first to identify an association between the ACE D-allele and DE in CCW. They provide evidence of a significant role for the RAS in the development of DE and suggest that clinical trials of ACE inhibition would be profitable in this group. [source] Angiotensin-converting enzyme polymorphisms and risk of spontaneous deep intracranial hemorrhage in TaiwanEUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2008C.-M. Chen Background and purpose:, This study examines whether angiotensin-converting enzyme (ACE) gene polymorphisms are associated with the risk of spontaneous deep intracerebral hemorrhage (SDICH) in Taiwan using a case,control study. Methods:, Totally, 217 SDICH patients and 283 controls were recruited. Associations of ACE A-240T and ACE I/D polymorphisms with SDICH were examined under the additive model and adjusted for gender, age, body mass index, total cholesterol level, smoking history, alcohol use, hypertension, and use of ACE inhibitors. Results:, Hypertension, diabetes mellitus, family history of spontaneous intracerebral hemorrhage (SICH), and low cholesterol level increase risk of female SDICH, whereas hypertension, alcohol use, smoking history, family history of SICH, and low cholesterol level are an important risk factor for male SDICH. After adjusting for covariates, only haplotype ACE T-D (OR = 2.7, 95% CI, 1.1,6.5, P = 0.02) was associated with female SDICH. Conclusions:, This study demonstrates that environmental risk factors play a major role and ACE polymorphisms play a minor role in contributing risk of SDICH in Taiwan. [source] Monitoring neuropeptide-specific proteases: processing of the proopiomelanocortin peptides adrenocorticotropin and , -melanocyte-stimulating hormone in the skinEXPERIMENTAL DERMATOLOGY, Issue 10 2006Simone König Abstract:, The neuroendocrine precursor protein proopiomelanocortin (POMC) and its derived neuropeptides are involved in a number of important regulatory processes in the central nervous system as well as in peripheral tissues. Despite its important role in controlling the local activation of melanocortin (MC) receptors, the extracellular proteolytic processing of POMC peptides has received little attention. The mechanisms relevant for controlling the bioavailability of adrenocorticotropin and melanocyte-stimulating hormones for the corresponding MC receptors in the skin by specific peptidases such as neprilysin (neutral endopeptidase; NEP) or angiotensin-converting enzyme (ACE) have been addressed in a number of recent investigations. This review summarizes the current body of knowledge concerning the qualitative and quantitative POMC peptide processing with respect to the action and specificity of NEP and ACE and discusses relevant recent analytical methodologies. [source] Human skin: source of and target organ for angiotensin IIEXPERIMENTAL DERMATOLOGY, Issue 3 2004U. Muscha Steckelings Abstract:, The present study examined the expression of angiotensin receptors in human skin, the potential synthesis of angiotensin II (Ang II) in this location and looked for a first insight into physiological functions. AT1 and AT2 receptors were found within the epidermis and in dermal vessel walls. The same expression pattern was found for angiotensinogen, renin and angiotensin-converting enzyme (ACE). All components could additionally be demonstrated at mRNA level in cultured primary keratinocytes, melanocytes, dermal fibroblasts and dermal microvascular endothelial cells, except for AT2 receptors in melanocytes. The ability of cutaneous cells to synthesize Ang II was proved by identifying the molecule in cultured keratinocytes. Furthermore, in artificially wounded keratinocyte monolayers, ACE-mRNA expression was rapidly increased, and enhanced ACE expression was still found in cutaneous human scars 3 months after wounding. These findings suggest that the complete renin,angiotensin system is present in human skin and plays a role in normal cutaneous homeostasis as well as in human cutaneous wound healing. [source] Functional angiotensin-converting enzyme 2 is expressed in human cardiac myofibroblastsEXPERIMENTAL PHYSIOLOGY, Issue 5 2008Jodie L. Guy The renin,angiotensin system (RAS), in particular angiotensin II, plays an important role in cardiac remodelling. Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) are key players in the RAS and act antagonistically to regulate the levels of angiotensin II. In this study, we reveal the functional expression of ACE2 in human cardiac myofibroblasts, cells that are essential to the maintenance of normal cardiac architecture and also play a key role in myocardial remodelling. The observed reciprocal expression of ACE and ACE2 in these cells may reflect the possible opposing activity of these two enzymes. In this study, we demonstrate the presence of ACE2 as an ectoenzyme and reveal that ACE2 undergoes phorbol-12-myristate-13-acetate-inducible ectodomain shedding from the membrane. When cells were exposed to a number of pathophysiological stimuli, modulation of ACE2 levels was not detected. Importantly, whilst we found ACE2 to be expressed constitutively in cardiac myofibroblasts there were no detectable levels in either vascular smooth muscle cells or vascular endothelium, indicating that ACE2 expression is not ubiquitous. In paraffin sections of atrial appendage tissue, we observed a distinct staining pattern for ACE2 which appeared different from that of ACE. In conclusion, this study is the first to report co-expression of ACE and ACE2 in human cardiac myofibroblasts and may therefore present a model primary system for study of the comparative cell biology of ACE2 and ACE and their potentially opposing roles in myocardial remodelling. [source] | |||||||||||||||||||||||||||||||||||||||||||