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Abstract Almost every person has to deal with transgressions committed by a romantic partner and faces their negative psychological outcomes, and coping strategies might be key to understanding post-transgression dynamics and forgiveness. We tested the construct validity of the Inventory of Strategies for Coping with a Partner's Transgression which include the emotion (E-FCS), problem (P-FCS), and meaning-focused coping strategies (M-FCS) scales. Results replicated the factor structure of each of the three scales through confirmatory factor analysis techniques, tested its reliability with the McDonald's omega coefficient, and then correlated the scales with forgiveness and resentment, strengthening its construct validity. In general, the validity and reliability of scales were confirmed. Emotion-focused strategies showed a negative correlation with forgiveness, while problem and meaning-focused strategies had a positive correlation. These findings were discussed in the context of theory and their practical implications.
Resumen Las personas tienden a lidiar con transgresiones cometidas por su pareja y enfrentar sus consecuencias psicológicas aversivas, por lo que las estrategias de afrontamiento pueden ser clave para la dinámica post-transgresión, y el perdón. Validamos tres escalas para medir estrategias de afrontamiento ante las transgresiones cometidas por la pareja: Estrategias enfocadas en la emoción (E-FCS), el problema (P-FCS) y el sentido (M-FCS). Los resultados muestran que las estructuras factoriales se replicaron en mediante análisis factoriales confirmatorios, se puso a prueba su confiabilidad mediante el coeficiente omega de McDonald, y finalmente se correlacionaron con el perdón y resentimiento, fortaleciendo su validez de constructo. En general los resultados muestran evidencia de validez de constructo y confiabilidad, en general los factores de la E-FCS se correlacionaron negativamente con al perdón, mientras que de P-FCS Y M-FSC lo hicieron positivamente. Se discuten los hallazgos a la luz de la teoría, y sus implicaciones prácticas.
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ABSTRACT Introduction: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. Methods: Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. Results: The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p = 0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p = 0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p = 0.0007 and p = 0.004, respectively). Conclusion: ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.
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Leucemia-Linfoma Linfoblástico de Células PrecursorasRESUMO
The gut has been suggested as the first organ to be affected by unbalanced diets contributing to the obesogenic process. This study aimed to test a short time-course exposition model to a known pro- or anti-inflammatory enriched fatty diet to understand the early gut alterations. Male mice were exposed to the chow diet (CT), high-fat (HF) diet, or a high-fat diet partially replaced on flaxseed oil (FS), rich in omega-3 (ω3), for 14 days. HF and FS increased the total body weight mass compared with the CT group, but FS reduced the epididymal fat depot compared to HF. The bioinformatics from mice and human databases showed the Zo1-Ocln-Cldn7 tight junctions as the main protein-triad. In the ileum, the HF diet has increased IL1ß transcript and IL1ß, TNFα, and CD11b proteins, but reduced the tight junctions (Zo1, Ocln, and Cld7) compared to the CT group. Despite the FS diet being partially efficient in protecting the ileum against inflammation, the tight junctions were increased, compared to the HF group. The GPR120 and GPR40 receptors were unaffected by diets, but GPR120 was colocalized on the surface of ileum macrophages. The short period of a high-fat diet was enough to start the obesogenic process, ileum inflammation, and reduce the tight junctions. Flaxseed oil did not protect efficiently against dysmetabolism. Still, it increased the tight junctions, even without alteration on inflammatory parameters, suggesting the protection against gut permeability during early obesity development.
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Ácidos Graxos Ômega-3 , Óleo de Semente do Linho , Humanos , Masculino , Animais , Camundongos , Óleo de Semente do Linho/farmacologia , Junções Íntimas/metabolismo , Ácidos Graxos Insaturados , Inflamação/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Ácidos GraxosRESUMO
INTRODUCTION: Improving survival of Acute Lymphoblastic Leukemia (ALL) in adult patients has been a challenge. Despite intensive chemotherapy treatment, overall survival is poor. However, several studies demonstrate that young adult patients have better survival when treated with pediatric-based intensive regimens. Considering these results, We decided to treat newly diagnosed ALL patients according to age and risk factors. The goal of this study was to describe the results of this intensive chemotherapy treatment approach for ALL adult patients diagnosed at our institution. METHODS: Fifty-eight ALL patients, diagnosed from 2004 to 2013, were included in the analysis. Patients were assigned to either the St. Jude Total Therapy XIIIB high-risk arm (St Jude) or the CALGB 8811 (CALGB). The Kaplan-Meier survival curve was used for the survival analyses and the Cox proportional hazard regression, for multivariable analysis. RESULTS: The overall survival was 22.9% at 10 years. The St. Jude improved survival, compared to the CALGB (p = 0.007), with 32.6% vs. 7.4% survival rate at 10 years. However, no survival benefit was found for patients younger than 20 years old (p = 0.32). The multivariable analysis demonstrated that undetectable minimal residual disease (MRD) and hematopoietic stem cell transplantation (HSCT) had beneficial impact on survival (p = 0.0007 and p = 0.004, respectively). CONCLUSION: ALL is a disease of poor prognosis for adults. The joint effort to standardize treatment and seek solutions is the way to start improving this scenario.
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Outside of clinical trials, few studies have addressed the outcomes of Ph+ acute lymphoblastic leukemia (ALL) in adults, especially from developing world. In this study, we conducted a multicenter analysis on the outcomes of patients aged > 15 years with Ph+ ALL, aiming to get to know an overview of the Brazilian experience as well as to explore baseline factors associated with relapse and mortality in our setting. Over these 10 years, patients were treated with diverse protocols, all of them always combined with a frontline tyrosine-kinase inhibitor. A total of 123 Ph+ ALL patients was included. Imatinib was the first line TKI in 97 %. The complete response rate was 79 %. The early death rate was 15 %, being associated with increasing age at diagnosis (p = 0.06). The use of intensive versus attenuated induction regimen was not associated with higher induction mortality (p = 0.99). Overall, 29 % of patients aged ≤ 60 years underwent allogeneic transplantation, 87 % in first CR. 4-year overall survival (OS) and relapse-free survival were 25 % and 24 %, respectively. The incidence of relapse (death as a competitor) was 29 %, while the non-relapse mortality was 42 %. Only age was independently associated with OS, and lactate dehydrogenase level and central nervous disease at diagnosis were related to relapse in our cohort. This is the first historical cohort multicenter study on Ph+ ALL from Brazil. Reporting these outcomes is essential to encourage public policies to expand access to new drugs and transplantation in middle-income countries.
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Transplante de Células-Tronco Hematopoéticas/mortalidade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Adulto JovemRESUMO
Electrocardiographic imaging (ECGI) is a technique to reconstruct non-invasively the electrical activity on the heart surface from body-surface potential recordings and geometric information of the torso and the heart. ECGI has shown scientific and clinical value when used to characterize and treat both atrial and ventricular arrhythmias. Regarding atrial fibrillation (AF), the characterization of the electrical propagation and the underlying substrate favoring AF is inherently more challenging than for ventricular arrhythmias, due to the progressive and heterogeneous nature of the disease and its manifestation, the small volume and wall thickness of the atria, and the relatively large role of microstructural abnormalities in AF. At the same time, ECGI has the advantage over other mapping technologies of allowing a global characterization of atrial electrical activity at every atrial beat and non-invasively. However, since ECGI is time-consuming and costly and the use of electrical mapping to guide AF ablation is still not fully established, the clinical value of ECGI for AF is still under assessment. Nonetheless, AF is known to be the manifestation of a complex interaction between electrical and structural abnormalities and therefore, true electro-anatomical-structural imaging may elucidate important key factors of AF development, progression, and treatment. Therefore, it is paramount to identify which clinical questions could be successfully addressed by ECGI when it comes to AF characterization and treatment, and which questions may be beyond its technical limitations. In this manuscript we review the questions that researchers have tried to address on the use of ECGI for AF characterization and treatment guidance (for example, localization of AF triggers and sustaining mechanisms), and we discuss the technological requirements and validation. We address experimental and clinical results, limitations, and future challenges for fruitful application of ECGI for AF understanding and management. We pay attention to existing techniques and clinical application, to computer models and (animal or human) experiments, to challenges of methodological and clinical validation. The overall objective of the study is to provide a consensus on valuable directions that ECGI research may take to provide future improvements in AF characterization and treatment guidance.
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PURPOSE: Atrial tachycardia (AT), flutter (AFL) and fibrillation (AF) are very common cardiac arrhythmias and are driven by localized sources that can be ablation targets. Non-invasive body surface potential mapping (BSPM) can be useful for early diagnosis and ablation planning. We aimed to characterize and differentiate the arrhythmic mechanisms behind AT, AFL and AF from the BSPM perspective using basic features reflecting their electrophysiology. METHODS: 19 simulations of 567-lead BSPMs were used to obtain dominant frequency (DF) maps and estimate the atrial driving frequencies using the highest DF (HDF). Regions with |DF-HDF|≤1Hz were segmented and characterized (size, area); the spatial distribution of the differences |DF-atrialHDFestimate| was qualitatively analyzed. Phase singularity points (SPs) were detected on maps generated with Hilbert transform after band-pass filtering around the HDF (±1Hz). Connected SPs along time (filaments) and their histogram (heatmaps) were used for rotational activity characterization (duration, spatiotemporal stability). Results were reproduced in clinical layouts (252 to 12 leads) and with different rotations and translations of the atria within the torso, and compared with the original 567-lead outcomes using structural similarity index (SSIM) between maps, sensitivity and precision in SP detection and direct feature comparison. Random forest and least-square based algorithms were used to classify the arrhythmias and their mechanisms' location, respectively, based on the obtained features. RESULTS: Frequency and phase analyses revealed distinct behavior between arrhythmias. AT and AFL presented uniform DF maps with low variance, while AF maps were more heterogeneous. Lower differences from the atrial HDF regions correlated with the driver location. Rotational activity was most stable in AFL, followed by AT and AF. Features were robust to lower spatial resolution layouts and modifications in the atrial geometry; DF and heatmaps presented decreasing SSIM along the layouts. The classification of the arrhythmias and their mechanisms' location achieved balanced accuracy of 72.0% and 73.9%, respectively. CONCLUSION: Non-invasive characterization of AT, AFL and AF based on realistic models highlights intrinsic differences between the arrhythmias, enhancing the BSPM utility as an auxiliary clinical tool.
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Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Algoritmos , Fibrilação Atrial/cirurgia , Mapeamento Potencial de Superfície Corporal , Átrios do Coração , HumanosRESUMO
ABSTRACT Introduction: Acute promyelocytic leukemia (APL) is caused by t(15;17)(q24;q21) translocation, which product is the fusion oncoprotein PML-RARa (promyelocytic leukemia-retinoic acid receptor alpha). The morphology of leukemic promyelocytes is usually characteristic, with the presence of faggot cells and coarse cytoplasmic granulations; immunophenotype is characteristic in most cases. However, definitive laboratory diagnosis should be performed by detecting t(15;17) or by PML-RARa fusion protein. Objectives: To compare cytomorphology, flow cytometry, and classical cytogenetic of bone marrow samples from patients with APL, treated at the Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), as well as describe the possible discrepancies between the methodologies. Method: Retrospective analysis of APL cases treated at the CHC-UFPR from January 2000 to July 2018. Results: Eighty-eight patients (42 man/ 46 woman; mean age: 34 years), 42.1% of them presented a high-risk prognosis. Flow cytometry was performed in 83 cases (94.3%); karyotype was performed in 79 cases (89.7%), but translocation t(15;17) was confirmed in only 53 cases (60.2%). From the 28 patients with a non-conclusive karyotype; fourteen (15.9%) of them presented the PML-RARa transcript in the molecular analysis. In total, 35 patients (39 8%) performed research of the PML-RARa gene by molecular biology. Only 45 patients (51.1%) presented concordant diagnosis among the three technical exams (morphology, flow cytometry and cytogenetics). Overall survival was 67% at 4.8 years, with 29 deaths. Conclusion: Genetic confirmation was observed in 76.1% of samples, 60.2% by conventional cytogenetics and 15.9% by molecular biology. There was a disagreement between the methodologies, and a low sensibility of the conventional cytogenetics, demonstrating the importance of performing molecular techniques for diagnostic confirmation.
RESUMEN Introducción: La leucemia promielocítica aguda (LPA) es causada por la translocación t(15;17)(q24;q21), cuyo producto es la oncoproteína de fusión PML-RARa (proteína de la leucemia promielocítica-receptor alfa de ácido retinoico). La morfología de los promielocitos leucémicos suele ser típica, con presencia de células faggot (células en haces) y gruesasgranulaciones citoplásmicas; el inmunofenotipo es característico en la mayor parte de los casos. No obstante, el diagnóstico final de laboratorio debe ser hecho por la detección de la t(15;17) o por la oncoproteína PML-RARa. Objetivos: Comparar la citomorfología, la citometría de flujo y la citogenética clásica de muestras de médula ósea de pacientes con LPA asistidos en el Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), así como describir lasposibles discrepancias entre los métodos. Método: Análisis retrospectivo de los casos de LPA asistidos en el CHC-UFPR entre enero de 2000 y julio de 2018. Resultados: De los 88 pacientes (42 hombres y 46 mujeres; edad promedio: 34 anos), 42,1% presentaron pronóstico de alto riesgo. Citometría de flujo se realizó en 83 casos (94,3%); cariotipo en 79 casos (89,7%),pero la translocación se confirmó en sólo53 (60,2%) casos. Entre los28 pacientes con cariotipo no concluyente, 14 (15,9%) presentaron el transcripto PML-RARa. En total, 35 pacientes (39,8%) realizaron la pesquisa del gen PML-RARa por biología molecular. Cuarenta y cinco pacientes (51,1%) tuvieron diagnóstico acorde entre los métodos (morfología, citometría de flujo y citogenética). La supervivencia global fue de 67% en 4,8 anos, con 29 muertes. Conclusión: Hubo confirmación genética en 76,1% de las muestras, siendo 60,2% por citogenética y 15,9%por biología celular. Hubo desacuerdo entre los métodos y baja sensibilidad de la citogenética convencional, lo que demuestra la importancia de la realización de técnicas moleculares para confirmación diagnóstica.
RESUMO Introdução: A leucemia promielocítica aguda (LPA) écausada pela translocação t(15;17)(q24;q21), cujo produto éa oncoproteína de fusão PML-RARa (leucemia promielocítica-receptor alfa do ácido retinoico). A morfologia dos promielócitos leucêmicos é habitualmente característica, com presença de faggot cells (células em maços ou feixes) e granulações citoplasmáticas grosseiras; o imunofenótipo é característico na maioria dos casos. Porém, o diagnóstico laboratorial definitivo deve ser feito pela detecção da t(15;17) ou pela oncoproteína PML-RARa. Objetivos: Comparar a citomorfologia, a citometria de fluxo e a citogenética clássica de amostras de medula óssea de pacientes com LPA atendidos no Complexo Hospital de Clínicas da Universidade Federal do Paraná (CHC-UFPR), bem como descrever as possíveis discrepâncias entre as metodologias. Método: Análise retrospectiva dos casos de LPA atendidos no CHC-UFPR entre janeiro de 2000 e julho de 2018. Resultados: Dos 88 pacientes (42 homens e 46 mulheres; média de idade: 34 anos), 42,1% apresentaram prognóstico de alto risco. A citometria de fluxo foi realizada em 83 casos (94,3%); o cariótipo, em 79 casos (89,7%), mas a translocação foi confirmada em apenas 53 (60,2%) casos. Dos 28 pacientes com cariótipo não conclusivo, 14 (15,9%) tinham a presença do transcrito PML-RARa. No total, 35 pacientes (39,8%) realizaram a pesquisa do gene PML-RARa por biologia molecular. Quarenta e cinco pacientes (51,1%) obtiveram diagnóstico concordante entre as metodologias (morfologia, citometria de fluxo e citogenética). A sobrevida global foi de 67% em 4,8 anos;com 29 óbitos. Conclusão: A confirmação genética foi realizada em 76,1% das amostras, sendo 60,2%por citogenética e 15,9% por biologia molecular. Houve discordância entre as metodologias e baixa sensibilidade da citogenética convencional, o que demonstra a importância da realização de técnicas moleculares para confirmação diagnóstica.
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Many species of the genus Croton have been used for anti-inflammatory, antiproliferative, antidiabetic, and antitumor purposes. The objective was to evaluate the effect of a hydroethanolic extract (HEE) from the inner bark of Croton argyrophyllus (Euphorbiaceae) on muscle damage and oxidative stress in rats after high intensity exercise. The animals were divided into four groups: (i) the sedentary group (SV; n = 7), (ii) the exercise vehicle group (EV, n = 7), (iii) the sedentary group HEE (SHG; n = 7) composed of sedentary animals and treated with the hydroethanolic extract of C. argyrophyllus (200 mg/kg, v.o.), and (iv) the HEE exercise group (HEE; n = 7) composed of animals submitted to resistance exercise (RE) and treated with the hydroethanolic extract of C. argyrophyllus (200 mg/kg, v.o.). In the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) test, the HEE showed lower values of inhibition potential (IP%) at 39.79% compared to gallic acid, 87.61%, and lipoperoxidation inhibition at 27.4% (100 µg/mL) or 28.6% (200 µg/mL) (p < 0.001). There was inhibition in free radicals in vivo. The HEE of C. argyrophyllus partially reduced the biomarkers of oxidative stress in muscle tissue and muscular damage (creatine kinase (CK) and Lactate Dehydrogenase (LDH)) (p < 0.05) in rats, and in this sense it can be an aid to the recovery process after exhaustive efforts.
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Croton/química , Peroxidação de Lipídeos/efeitos dos fármacos , Condicionamento Físico Animal , Extratos Vegetais/farmacologia , Animais , Creatina Quinase , Radicais Livres/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Músculo Esquelético/metabolismo , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
Inducible nitric oxide (iNOS)-mediated S-nitrosation of the metabolic signaling pathway has emerged as a post-translational modification that triggers insulin resistance in obesity and aging. However, the effects of S-nitrosation in controlling energy homeostasis are unknown. Thus, in the present study we aimed to evaluate the effects of S-nitrosation in insulin signaling pathway in the hypothalamus of rodents. Herein, we demonstrated that the intracerebroventricular infusion of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) promoted hypothalamic insulin signaling resistance and replicated the food intake pattern of obese individuals. Indeed, obesity induced S-nitrosation of hypothalamic IR and Akt, whereas inhibition of iNOS or S-nitrosation of insulin signaling pathway protected against hypothalamic insulin resistance and normalized energy homeostasis. Overall, these findings indicated that S-nitrosation of insulin signaling pathway is required to sustain hypothalamic insulin resistance in obesity.
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Metabolismo Energético , Hipotálamo/metabolismo , Resistência à Insulina , Óxido Nítrico Sintase Tipo II/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Animais , Homeostase , Hipotálamo/efeitos dos fármacos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Knockout , Doadores de Óxido Nítrico/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Roedores , S-Nitrosoglutationa/metabolismo , S-Nitrosoglutationa/farmacologia , Transdução de SinaisRESUMO
Resumen: Se ha reportado que una transgresión interpersonal puede hacer que los individuos mantengan el resentimiento y experimenten más afecto negativo, ira, estrés, y depresión (Stackhouse, Ross y Boon, 2016). Dado su impacto en la salud física y mental, es importante estudiar el perdón desde la psicología científica, para lo cual es necesario contar con instrumentos válidos y confiables. Sin embargo, hay pocos en español, y no han sido suficientemente estudiados, por lo que en esta investigación se revisaron las propiedades psicométricas de tres escalas del perdón: la Escala de Capacidad de Perdón (CAPER; Casullo y Fernández-Liporacce, 2005), la Escala del Perdón (Vargas-Núñez y Pozos-Gutiérrez, 2005), y la Escala del Perdón en la Relación de Pareja (Rosales-Sarabia, 2013). Para el análisis de la escala CAPER y la Escala del Perdón participaron 253 adultos, mientras que en el caso de la Escala del Perdón en la Relación de Pareja participaron 238 personas involucradas en una relación de pareja, todos residentes del área metropolitana de la Ciudad de México. Los resultados mostraron que solo la Escala del Perdón en la Relación de Pareja replicó su estructura factorial en una muestra distinta. Se discuten los hallazgos a la luz de la literatura científica internacional.
Abstract: It has been reported that suffering from interpersonal transgressions may cause individuals to maintain resentment and experience more negative affect, anger, stress, and depression (Stackhouse, Ross, & Boon, 2016). Given its impact on physical and mental health, it is important to study forgiveness from a scientific perspective, for which counting on valid and reliable measure instruments is highly important. However, there are just a few in Spanish, and haven't been deeply studied, so in this research the psychometric properties of three scales of forgiveness were reviewed: The Forgiveness Capacity Scale (CAPER; Casullo & Fernández-Liporacce, 2005), the Forgiveness Scale (Vargas-Núñez & Pozos-Gutiérrez, 2005), and the Scale of Forgiveness in the Romantic Relationship (Rosales-Sarabia, 2013). For the psychometric analysis of CAPER and the Forgiveness Scale, 253 adults participated, while for the Scale of Forgiveness in the Romantic Relationship, 238 people involved in a relationship participated, all residents of the metropolitan area of the Mexico City. The results showed that only the Forgiveness Scale in the Romantic Relationship replicated its factorial structure in a different sample. Findings are discussed in the light of international scientific literature.
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Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-α and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor γ (PPARγ) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARγ/Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARγ/CuZn-SOD axis expression.
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Fabaceae/química , Regulação da Expressão Gênica/efeitos dos fármacos , Resistência à Insulina , Obesidade/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/biossíntese , Extratos Vegetais/farmacologia , Superóxido Dismutase/biossíntese , Animais , Dieta/efeitos adversos , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Obesidade/induzido quimicamente , Obesidade/metabolismo , Obesidade/patologia , Extratos Vegetais/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The search for natural agents that minimize obesity-associated disorders is receiving special attention. Parkinsonia aculeata L. (Caesalpineaceae) has long been used in Brazil as a hypoglycaemic herbal medicine, without any scientific basis. AIMS OF THE STUDY: In this context, we aimed to use molecular and physiological methods to study the effect of a hydroethanolic extract partitioned with ethyl acetate from the aerial parts of Parkinsonia aculeata (HEPa/EtOAc) on insulin resistance in a mouse model of diet-induced obesity (DIO). MATERIAL AND METHODS: Firstly, C57BL/6J mice were fed either with standard rodent chow diet or a high-fat diet (HFD) for 12 consecutive weeks. Then, the animals were treated with HEPa/EtOAc at two doses (125 and 250mg/kg/day) or metformin (200mg/kg/day) for 16 days. At the end of the experiment, body weight, fat pad weight, fasting serum glucose (FSG), insulin (FSI) and leptin were measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. Glucose, insulin and pyruvate tolerance tests were performed. The expression and phosphorylation of IRß(tyr), Akt(ser473), AMPKα and PGC1α in liver, muscle and adipose tissue were determined by Western blot analyses. RESULTS: Herein we demonstrate for the first time an improvement in insulin resistance following HEPa/EtOAc administration in obese mice, as shown by increased glucose, insulin and pyruvate tolerance, as well as an improvement in FSG, FSI, HOMA-IR and circulating leptin levels, which together are in part due to enhancement of the insulin signaling pathway in its main target tissues. Surprisingly, the increase in activation of the AMPKα-PGC1-α axis by HEPa/EtOAc was similar to that produced by metformin treatment in the liver and muscle tissues. CONCLUSION: In conclusion, P. aculeata appears to be a source of therapeutic agent against obesity-related complications.
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Fabaceae/química , Resistência à Insulina/fisiologia , Insulina/metabolismo , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Brasil , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Jejum , Teste de Tolerância a Glucose/métodos , Leptina/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Obesidade/metabolismo , Extratos Vegetais/químicaRESUMO
An RP-HPLC method for the analysis of adenosine (ADO) has been developed and validated. In the present study, we report an RP-HPLC-based method with modifications of mobile phase and shorter retention time that substantially improved the efficiency of ADO analysis. The HPLC separation of the ADO was achieved on a C18 column, using a mobile phase consisting of water, containing 7% v/v ACN, at a flow rate of 0.8 mL/min. The column effluent was monitored by UV detection at 260 nm. A linear response was achieved over the concentration range of 0.25-100.00 micromol/L. The analytical method inter- and intra-run accuracy and precision were better than +/- 15%. The LOQ was 0.25 micromol/L, with ADO detection in the range of 6.25 pmol per sample. The method has been applied to the study of adenosine kinase (AK) kinetics.
Assuntos
Adenosina Quinase/metabolismo , Adenosina/análise , Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Água/química , Animais , Cromatografia/métodos , Cinética , Camundongos , Controle de Qualidade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta , Fatores de TempoRESUMO
The quinazoline derivative, 4-N-(3'-bromo-phenyl)amino-6,7-dimethoxyquinazoline (PD153035), has recently been identified as a potential drug for the treatment of proliferative disease. Here, we report a sensitive high performance liquid chromatography (HPLC)-based quantitative detection method for measurement of PD153035 levels in rat plasma. Sample pretreatment involved a two-step extraction with chloroform. The analytes were separated on a column packed with OmniSpher C18 material and eluted with acetonitrile-0.1 M ammonium acetate, pH 7.2 (70:30, v/v). The column effluent was monitored by UV detection at 330 nm. A linear response was achieved over the concentration range 0.50-100.00 microM using multilevel calibration with an internal standard. The analytical method inter- and intra-run accuracy and precision were better than +/-15%. The lower limit of quantification was 0.50 microM. The method has been applied to study the preclinical pharmacokinetics of this compound in rats.