Inhibition by Seeds of Phalaris canariensis Extracts of Key Enzymes Linked to Obesity.

CONTEXT: Obesity and its associated diseases are an increasing problem around the world. One hyperglycemic remedy is reduction of glucose absorption performed by suppressing digestion of carbohydrates and lipids through the use of inhibitors. Phalaris canariensis (P canariensis) is a species belonging to the Graminaceae family and is used in traditional medicine in Mexico for treatment of diabetes and obesity. OBJECTIVE: The aim of the study was to evaluate the effects of different extracts of the seeds of P canariensis on enzymes metabolizing fat and carbohydrates, obtained using 3 solvents. DESIGN: The seeds of P canariensis were extracted using hexane (ALH), chloroform (ALC), and methanol (ALM) and were investigated for their antiobesity potential. SETTING: This research was conducted in the Laboratory of Research of Natural Products in the School of Chemical Engineering at the National Polytechnic Institute and in the Research Laboratory of Enzymology in the National School of Biological Sciences. OUTCOME MEASURES: Different concentrations of the extracts were used to study the inhibition of enzymatic activity by porcine pancreatic α-amylase, with carbose as a positive control. The inhibitory activity of α-glucosidase was determined using the standard method with bovine serum albumin (BSA). Pancreatic lipase (PL) activity was measured by absorbance at 412 nm, and the data obtained were compared with orlistat. The PL activity was assessed using a second method measuring the rate of release of oleic acid from triolein. Lipoprotein lipase (LPL) activity was measured by released (3H)-oleic acid. Lipolytic activity in cultured, mouse, 3T3-Ll adipocytes was used as a measure of hormone-sensitive lipase activity. The inhibitory activity of rat intestinal sucrase was determined by measuring the glucose released. A Caco-2 cell assay determined the content of free glucose. RESULTS: The ALH extract of P canariensis showed potent inhibitory activity with IC50 values of 2.13 and 1.25 mg/mL as compared with α-amylase and α-glucosidase, respectively, and produced inhibition in rat intestinal sucrose. Further, the ALM extract showed significantly inhibitory effects against PL, LPL, and lipolysis of 3T3-LI adipocytes. CONCLUSIONS: The results provide evidence for the effects of the seeds of P canariensis for a retarded absorption of carbohydrates and lipids through the inhibition of enzymes that are related to obesity and diabetes mellitus type 2.

A new reduced-order observer for the synchronization of nonlinear chaotic systems: An application to secure communications.

This paper deals with the master-slave synchronization scheme for partially known nonlinear chaotic systems, where the unknown dynamics is considered as the master system and we propose the slave system structure which estimates the unknown states. It introduced a new reduced order observer, using the concept of Algebraic Observability; we applied the results to a Sundarapandian chaotic system, and by means of some numerical simulations we show the effectiveness of the suggested approach. Finally, the proposed observer is utilized for encryption, where encryption key is the master system and decryption key is the slave system.

Systematic review of existing literature regarding the prevalence of pediatric atopic dermatitis in Honduras.

Background: Atopic dermatitis (AD) is an inflammatory skin condition, often multifactorial in origin, and most commonly manifests during childhood. Although there remains a deficit in literature, current data suggest Honduras may have the highest prevalence and severity of AD among all Latin American countries. Objective: To assess the current prevalence of pediatric AD in Honduras and evaluate existing gaps in available literature to monitor disease burden. Methods: A comprehensive literature search was performed in March 2023. Articles were removed if they were published before 2007, were of the incorrect study design, or were focused on countries outside of Honduras. The articles were independently reviewed by 2 authors. Results: The initial literature search yielded 174 studies, of which 7 met inclusion criteria. AD prevalence rates in children in Honduras ranged from 0.7% to 40.0%. Limitations: Limitations include elements of study design, analytic methods, study populations, and limited articles. Conclusion: There appears to be a disproportionately higher prevalence and disease burden of pediatric AD in Honduras. Future research should acquire accurate data to further understand the prevalence, incidence, and severity of AD in Honduras.

Analysis of Diffusion Coefficients of Iron Monoboride and Diiron Boride Coating Formed on the Surface of AISI 420 Steel by Two Different Models: Experiments and Modelling.

In the present work, two mathematical diffusion models have been used to estimate the growth of the iron monoboride and diiron boride coating formed on AISI 420 steel. The boronizing of the steel was carried out with the solid diffusion packing method at a boronizing temperature of 1123 K-1273 K. Experimental results show the two-coating system consists of an outer monoboride and an inner diiron boride coating with a predominantly planar structure at the propagation front. The depth of the boride coating increases according to temperature and treatment time. A parabolic curve characterizes the propagation of the boride coatings. The two proposed mathematical models of mass transfer diffusion are founded on the solution corresponding to Fick's second fundamental law. The first is based on a linear boron concentration-penetration profile without time dependence, and the second model with time dependence (exact solution). For both models, the theoretical law of parabolic propagation and the average flux of boron atoms (Fick's first fundamental law) at the growth interfaces (monoboride/diiron boride and diiron boride/substrate) are considered to estimate the propagation of the boride coatings (monoboride and diiron boride). To validate the mathematical models, a programming code is written in the MATLAB program (adaptation 7.5) designed to simulate the growth of the boride coatings (monoboride and diiron boride). The following parameters are used as input data for this computer code: (the layer thicknesses of the FeB and Fe2B phases, the operating temperature, the boronizing time, initial formation time of the boride coating, the surface boron concentration limits, FeB/Fe2B and Fe2B/Fe growth interfaces, and the mass transfer diffusion coefficient of boron in the iron monoboride and diiron boride phases). The outputs of the computer code are the constants εFeB and εFe2B. The assessment of activation energies of AISI 420 steel for the two mathematical models of mass transfer is coincident (QFeB=221.9 kJ∙mol-1 and QFe2B=209.1 kJ∙mol-1). A numerical analysis was performed using a standard Taylor series for clarification of the proximity between the two models. SEM micrographs exhibited a strong propensity toward a flat-fronted composition at expansion interfaces of the iron monoboride and diiron boride coating, confirmed by XRD analysis. Tribological characterizations included the Vickers hardness test method, pin-on-disc, and Daimler-Benz Rockwell-C indentation adhesion tests. After thorough analysis, the energies were compared to the existing literature to validate our experiment. We found that our models and experimental results agreed. The diffusion models we utilized were crucial in gaining a deeper understanding of the boronizing behavior of AISI 420 steel, and they also allowed us to predict the thicknesses of the iron monoboride and diiron boride coating. These models provide helpful approaches for predicting the behavior of these steels.

Stalking Victimization and Emotional Consequences: A Cross-Cultural Comparison Between American and Spanish University Students.

This paper entails a comparative study between a country that has criminalized stalking for almost three decades (the U.S.) and a nation that just recently outlawed the phenomenon (Spain). Employing a sample of American and Spanish university students, we examined the prevalence and types of stalking behaviors and victims' emotional responses to their victimization. We also explored whether experiencing a particular category of stalking behaviors (i.e., surveillance and approach stalking) triggers specific emotional responses similarly among American and Spanish victims. We found more than two-thirds (36%) of the Spanish students (n = 638) and almost half (48%) of the American students (n = 411) reported that they have experienced the unwanted or intrusive behaviors included in our study. We also found relative to Spanish victims, American victims were significantly more likely to encounter approach stalking and report feeling anxious, angry, depressed, sick, and suicidal as a result of their victimization. Implications of our findings and directions for future research are discussed.

Axl-mediated activation of TBK1 drives epithelial plasticity in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is characterized by an activating mutation in KRAS. Direct inhibition of KRAS through pharmacological means remains a challenge; however, targeting key KRAS effectors has therapeutic potential. We investigated the contribution of TANK-binding kinase 1 (TBK1), a critical downstream effector of mutant active KRAS, to PDA progression. We report that TBK1 supports the growth and metastasis of KRAS-mutant PDA by driving an epithelial plasticity program in tumor cells that enhances invasive and metastatic capacity. Further, we identify that the receptor tyrosine kinase Axl induces TBK1 activity in a Ras-RalB-dependent manner. These findings demonstrate that TBK1 is central to an Axl-driven epithelial-mesenchymal transition in KRAS-mutant PDA and suggest that interruption of the Axl-TBK1 signaling cascade above or below KRAS has potential therapeutic efficacy in this recalcitrant disease.

Assessment of TANK-binding kinase 1 as a therapeutic target in cancer.

TANK-binding kinase 1 (TBK1) is central to multiple biological processes that promote tumorigenesis including cell division, autophagy, innate immune response and AKT-pro survival signaling. TBK1 is well studied and most known for its function in innate immunity. However, the serine threonine protein kinase received significant attention as a synthetic lethal partner and effector of the major oncogene, RAS. This review summarizes newly identified cancer promoting functions of TBK1 and evaluates the therapeutic potential of targeting TBK1 in cancer.

Loss of Tbk1 kinase activity protects mice from diet-induced metabolic dysfunction.

OBJECTIVE: TANK Binding Kinase 1 (TBK1) has been implicated in the regulation of metabolism through studies with the drug amlexanox, an inhibitor of the IκB kinase (IKK)-related kinases. Amlexanox induced weight loss, reduced fatty liver and insulin resistance in high fat diet (HFD) fed mice and has now progressed into clinical testing for the treatment and prevention of obesity and type 2 diabetes. However, since amlexanox is a dual IKKε/TBK1 inhibitor, the specific metabolic contribution of TBK1 is not clear. METHODS: To distinguish metabolic functions unique to TBK1, we examined the metabolic profile of global Tbk1 mutant mice challenged with an obesogenic diet and investigated potential mechanisms for the improved metabolic phenotype. RESULTS AND CONCLUSION: We report that systemic loss of TBK1 kinase function has an overall protective effect on metabolic readouts in mice on an obesogenic diet, which is mediated by loss of an inhibitory interaction between TBK1 and the insulin receptor.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders.

BACKGROUND: Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. METHODS: The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. RESULTS: We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. CONCLUSIONS: People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.

Small-Molecule Inhibition of Axl Targets Tumor Immune Suppression and Enhances Chemotherapy in Pancreatic Cancer.

Activation of the receptor tyrosine kinase Axl is associated with poor outcomes in pancreatic cancer (PDAC), where it coordinately mediates immune evasion and drug resistance. Here, we demonstrate that the selective Axl kinase inhibitor BGB324 targets the tumor-immune interface to blunt the aggressive traits of PDAC cells in vitro and enhance gemcitibine efficacy in vivo Axl signaling stimulates the TBK1-NFκB pathway and innate immune suppression in the tumor microenvironment. In tumor cells, BGB324 treatment drove epithelial differentiation, expression of nucleoside transporters affecting gemcitabine response, and an immune stimulatory microenvironment. Our results establish a preclinical mechanistic rationale for the clinical development of Axl inhibitors to improve the treatment of PDAC patients.Significance: These results establish a preclinical mechanistic rationale for the clinical development of AXL inhibitors to improve the treatment of PDAC patients. Cancer Res; 78(1); 246-55. ©2017 AACR.

Knowledge on fibromyalgia among general practitioners, from Chiclayo-Peru, 2016. / Conocimientos de fibromialgia en médicos de atención primaria de la provincia de Chiclayo-Perú, 2016.

OBJECTIVE: Knowledge about fibromyalgia in general practitioners in the province of Chiclayo, Peru, 2016. MATERIALS AND METHODS: Cross sectional descriptive study. Non-probability sampling, census type. In all, 145 physicians were evaluated through a questionnaire of 14 questions, validated by experts and a pilot. The analysis was performed using STATA v. 13. RESULTS: Accuracy in questions involving diagnosis was 41.1% and in questions about treatment: 65%; 75.1% 'had seen patients with fibromyalgia' previously. The average on locating pain points was 2.2±2.8. Only 2.8% identified 11 or more painful points; 54.5% answered that 'the diagnosis is clinical and exams are for the differential diagnosis'; 46.1% in Ministerio de Salud (MINSA) and 28.3% in Seguro Social de Salud (EsSalud) answered the item about diagnostic criteria (P=.021); 65.7% said that psychotherapy, pregabalin and aerobic exercise were the most effective therapeutic triad, with no differences between MINSA and EsSalud: 61.5% vs. 68.6% (P=.23); 59.3% responded that drugs that had proved to be useful were: Pregabalin, duloxetine and amitriptyline; 66.2% responded that the most effective physical therapy is aerobic exercise. CONCLUSIONS: Knowledge of the diagnosis and treatment of fibromyalgia by general doctors in Chiclayo is poor. There are some differences in knowledge depending on the age and type of institution to which each belongs.

Comprehensive Ex Vivo Transposon Mutagenesis Identifies Genes That Promote Growth Factor Independence and Leukemogenesis.

Aberrant signaling through cytokine receptors and their downstream signaling pathways is a major oncogenic mechanism underlying hematopoietic malignancies. To better understand how these pathways become pathologically activated and to potentially identify new drivers of hematopoietic cancers, we developed a high-throughput functional screening approach using ex vivo mutagenesis with the Sleeping Beauty transposon. We analyzed over 1,100 transposon-mutagenized pools of Ba/F3 cells, an IL3-dependent pro-B-cell line, which acquired cytokine independence and tumor-forming ability. Recurrent transposon insertions could be mapped to genes in the JAK/STAT and MAPK pathways, confirming the ability of this strategy to identify known oncogenic components of cytokine signaling pathways. In addition, recurrent insertions were identified in a large set of genes that have been found to be mutated in leukemia or associated with survival, but were not previously linked to the JAK/STAT or MAPK pathways nor shown to functionally contribute to leukemogenesis. Forced expression of these novel genes resulted in IL3-independent growth in vitro and tumorigenesis in vivo, validating this mutagenesis-based approach for identifying new genes that promote cytokine signaling and leukemogenesis. Therefore, our findings provide a broadly applicable approach for classifying functionally relevant genes in diverse malignancies and offer new insights into the impact of cytokine signaling on leukemia development.

A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics.

Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48(Cre);LSL-Kras(G12D);Cdkn2a(f/f)) mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR) signaling activates Kras. Regulators of G-protein signaling (RGS) proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC) transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a Kras(G12D)-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq) analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane) plus inhibitors of Axl signaling (warfarin and BGB324) have fewer tumor initiation sites and reduced tumor size compared with the standard-of-care treatment. Rgs16::GFP is therefore an in vivo reporter of PDA progression and sensitivity to new chemotherapeutic drug regimens such as Axl-targeted agents. This screening strategy can potentially be applied to identify improved therapeutics for other cancers.

Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice.

Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

Background Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. Methods The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. Results We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. Conclusions People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.

Heterophilic antibodies in sera from individuals without loxoscelism cross-react with phospholipase D from the venom of Loxosceles and Sicarius spiders

Loxoscelism is a severe human envenomation caused by Loxosceles spider venom. To the best of our knowledge, no study has evaluated the presence of antibodies against Loxosceles venom in loxoscelism patients without treatment with antivenom immunotherapy. We perform a comparative analysis for the presence of antibodies capable of recognizing Loxosceles venom in a group of patients diagnosed with loxoscelism and in a group of people without loxoscelism. Methods The detection of L. laeta venom, Sicarius venom and recombinant phospholipases D from Loxosceles (PLDs) in sera from people with loxoscelism (Group 1) and from healthy people with no history of loxoscelism (Group 2) was evaluated using immuno-dot blot, indirect ELISA, and Western blot. Results We found naturally heterophilic antibodies (IgG-type) in people without contact with Loxosceles spiders or any clinical history of loxoscelism. Either serum pools or single sera from Group 1 and Group 2 analyzed by dot blot tested positive for L. laeta venom. Indirect ELISA for venom recognition showed titles of 1:320 for Group 1 sera and 1:160 for Group 2 sera. Total IgG quantification showed no difference in sera from both groups. Pooled sera and purified IgG from sera of both groups revealed venom proteins between 25 and 32 kDa and the recombinant phospholipase D isoform 1 (rLlPLD1), specifically. Moreover, heterophile antibodies cross-react with PLDs from other Loxosceles species and the venom of Sicarius spider. Conclusions People without contact with the spider venom produced heterophilic antibodies capable of generating a cross-reaction against the venom of L. laeta and Sicarius spiders. Their presence and possible interference should be considered in the development of immunoassays for Loxosceles venom detection.(AU)

Prognostic value of coronary and microvascular flow reserve in patients with nonischemic dilated cardiomyopathy.

BACKGROUND: Coronary and microvascular blood flow reserve have been established as important predictors of prognosis in patients with cardiovascular disease. The aim of this study was to assess the value of coronary flow velocity reserve (CFVR) and real-time myocardial perfusion echocardiography (RTMPE) for predicting events in patients with nonischemic dilated cardiomyopathy. METHODS: One hundred ninety-five patients (mean age 54 ± 12 years; 66% men) with dilated cardiomyopathy (left ventricular ejection fraction < 35% and no obstructive coronary disease on invasive angiography or multidetector computed tomography) who underwent dipyridamole stress (0.84 mg/kg over 10 min) RTMPE were prospectively studied. CFVR was calculated as the ratio of hyperemic to baseline peak diastolic velocities in the distal left anterior coronary artery. The replenishment velocity (ß), plateau of acoustic intensity (A(N)), and myocardial blood flow reserve were obtained from RTMPE. RESULTS: Mean CFVR was 2.07 ± 0.52, mean A(N) reserve was 1.05 ± 0.09, mean ß reserve was 2.05 ± 0.39, and mean myocardial blood flow reserve (A(N) × ß) was 2.15 ± 0.48. During a median follow-up period of 29 months, 45 patients had events (43 deaths and two urgent transplantations). Independent predictors of events were left atrial diameter (relative risk, 1.16; 95% confidence interval, 1.08-1.26; P < .001) and ß reserve ≤ 2.0 (relative risk, 3.22; 95% confidence interval, 1.18-8.79; P < .001). After adjustment for ß reserve, CFVR and myocardial blood flow reserve no longer had predictive value. Left atrial diameter added prognostic value over clinical factors and left ventricular ejection fraction (χ2 = 36.8-58.5, P < .001). Beta reserve added additional power to the model (χ2 = 70.2, P < .001). CONCLUSIONS: Increased left atrial diameter and depressed ß reserve were independent predictors of cardiac death and transplantation in patients with nonischemic dilated cardiomyopathy. Beta reserve by RTMPE provided incremental predictive value beyond that provided by current known prognostic clinical and echocardiographic factors.

Prognostic value of qualitative and quantitative vasodilator stress myocardial perfusion echocardiography in patients with known or suspected coronary artery disease.

BACKGROUND: Quantification of myocardial blood flow reserve in patients with coronary artery disease using real-time myocardial perfusion echocardiography (RTMPE) has been demonstrated to further improve accuracy over the analysis of wall motion and qualitative analysis of myocardial perfusion. The aim of this study was to determine the prognostic value of qualitative and quantitative analyses obtained by RTMPE in patients with known or suspected coronary artery disease. METHODS: From March 2003 to December 2008, 227 consecutive patients with normal left ventricular function who underwent RTMPE were prospectively studied. Replenishment velocity reserve (ß) and myocardial blood flow reserve were derived from RTMPE. Primary outcomes were cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization, and secondary outcomes were coronary bypass graft surgery or angioplasty. RESULTS: During a median follow-up period of 32 months (range, 5 days to 6.9 years), 19 major events (two deaths, six myocardial infarctions, and 11 episodes of unstable angina) and 46 total events occurred. Wall motion (hazard ratio [HR], 2.8; 95% confidence interval [CI], 1.4-5.6; P = .003) and qualitative myocardial perfusion analysis (HR, 4.3; 95% CI, 2.1-8.5; P < .001) were predictors of total events but not primary events. Abnormal myocardial blood flow reserve and abnormal ß reserve were predictors of total events (HR, 8.1; 95% CI, 3-21; P < .001; and HR, 16.5; 95% CI, 5.5-49; P < .001) and primary events (HR, 3.8; 95% CI, 1-15; P = .048; and HR, 8.7; 95% CI, 1.8-40; P = .005). On multivariate analysis, only abnormal ß reserve was an independent predictor of total (HR, 10.6; 95% CI, 2.5-43; P = .001) and primary (HR, 10.5; 95% CI, 1.5-6; P = .015) events. Abnormal ß reserve added incremental value in predicting primary events (χ(2) = 2.0-13.2; P = .014). CONCLUSIONS: Quantitative adenosine stress RTMPE added independent and additional prognostic information over wall motion and qualitative myocardial perfusion analysis in patients with known or suspected coronary artery disease and normal left ventricular function.

Myocardial deformation by speckle tracking in severe dilated cardiomyopathy.

BACKGROUND: The high and increasing prevalence of Dilated Cardiomyopathy (DCM) represents a serious public health problem. New technologies are being used aiming at more accurate diagnoses in order to improve therapeutic approach. In this scenario, speckle tracking echocardiography (STE) uses natural myocardial markers to analyze the systolic deformation of the left ventricle (LV). OBJECTIVE: To measure the longitudinal transmural global strain (GS) of the LV through STE in patients with severe DCM, comparing the results with normal individuals and with echocardiographic parameters established for the analysis of LV systolic function, validating the method in this population. METHODS: We studied 71 patients with severe DCM (53 ± 12 years, 72% men) and 20 controls (30 ± 8 years, 45% men). We obtained LV volumes and ejection fraction by two and three-dimensional echocardiography, Doppler parameters, tissue Doppler and GS was obtained by STE. RESULTS: Compared to controls, LV volumes were higher in the DCM group; however, LVEF and peak velocity of E wave were lower in the latter. The myocardial performance index was higher among patients. Myocardial velocities at the tissue Doppler (S', e', a') were significantly lower and E/e' ratio was higher in the DCM group. The GS was decreased in the DCM group (-5.5% ± 2.3%) when compared to controls (-14.0% ± 1.8%). CONCLUSION: In this study, GS was significantly lower in patients with severe DCM, bringing new perspectives for therapeutic approaches in this specific population.