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1.
Cardiovasc Diabetol ; 23(1): 109, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553758

RESUMO

BACKGROUND: In this study, we evaluated the lipidome alterations caused by type 1 diabetes (T1D) and type 2 diabetes (T2D), by determining lipids significantly associated with diabetes overall and in both sexes, and lipids associated with the glycaemic state. METHODS: An untargeted lipidomic analysis was performed to measure the lipid profiles of 360 subjects (91 T1D, 91 T2D, 74 with prediabetes and 104 controls (CT)) without cardiovascular and/or chronic kidney disease. Ultra-high performance liquid chromatography-electrospray ionization mass spectrometry (UHPLC-ESI-MS) was conducted in two ion modes (positive and negative). We used multiple linear regression models to (1) assess the association between each lipid feature and each condition, (2) determine sex-specific differences related to diabetes, and (3) identify lipids associated with the glycaemic state by considering the prediabetes stage. The models were adjusted by sex, age, hypertension, dyslipidaemia, body mass index, glucose, smoking, systolic blood pressure, triglycerides, HDL cholesterol, LDL cholesterol, alternate Mediterranean diet score (aMED) and estimated glomerular filtration rate (eGFR); diabetes duration and glycated haemoglobin (HbA1c) were also included in the comparison between T1D and T2D. RESULTS: A total of 54 unique lipid subspecies from 15 unique lipid classes were annotated. Lysophosphatidylcholines (LPC) and ceramides (Cer) showed opposite effects in subjects with T1D and subjects with T2D, LPCs being mainly up-regulated in T1D and down-regulated in T2D, and Cer being up-regulated in T2D and down-regulated in T1D. Also, Phosphatidylcholines were clearly down-regulated in subjects with T1D. Regarding sex-specific differences, ceramides and phosphatidylcholines exhibited important diabetes-associated differences due to sex. Concerning the glycaemic state, we found a gradual increase of a panel of 1-deoxyceramides from normoglycemia to prediabetes to T2D. CONCLUSIONS: Our findings revealed an extensive disruption of lipid metabolism in both T1D and T2D. Additionally, we found sex-specific lipidome changes associated with diabetes, and lipids associated with the glycaemic state that can be linked to previously described molecular mechanisms in diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Masculino , Feminino , Humanos , Lipidômica , Estado Pré-Diabético/diagnóstico , Estado Pré-Diabético/complicações , HDL-Colesterol , Ceramidas , Fosfatidilcolinas
2.
J Mol Endocrinol ; 72(4)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38240302

RESUMO

Enteroendocrine cells located along the gastrointestinal epithelium sense different nutrients/luminal contents that trigger the secretion of a variety of gut hormones with different roles in glucose homeostasis and appetite regulation. The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are involved in the regulation of insulin secretion, appetite, food intake and body weight after their nutrient-induced secretion from the gut. GLP-1 mimetics have been developed and used in the treatment of type 2 diabetes mellitus and obesity. Modulating the release of endogenous intestinal hormones may be a promising approach for the treatment of obesity and type 2 diabetes without surgery. For that reason, current understanding of the cellular mechanisms underlying intestinal hormone secretion will be the focus of this review. The mechanisms controlling hormone secretion depend on the nature of the stimulus, involving a variety of signalling pathways including ion channels, nutrient transporters and G-protein-coupled receptors.


Assuntos
Diabetes Mellitus Tipo 2 , Incretinas , Humanos , Incretinas/fisiologia , Diabetes Mellitus Tipo 2/metabolismo , Polipeptídeo Inibidor Gástrico/metabolismo , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Obesidade/metabolismo , Glucose/metabolismo , Insulina/metabolismo
3.
J Foot Ankle Surg ; 63(1): 36-41, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37633486

RESUMO

The goal of our study is to compare the stability of the anatomic reconstruction of the anterior talofibular ligament (ATFL) with direct repair of the ATFL, in a cadaver model. We performed the following techniques in 18 cadaveric ankles: the intact ATFL was cut, after which a direct repair using 2 anchors was performed. The repair was sectioned, and anatomic reconstruction was then performed with a tendon autograft. We measured angular displacement in 3 anatomic planes (axial, coronal, sagittal) for each situation in response to the anterior drawer test (ADT), talar tilt test (TTT) and pivot test (PT), using a specifically constructed arthrometer. The sectioned ATFL was inferior to the intact ATFL in the axial plane with the ADT (p = .012), in the axial plane with the PT (p = .001) and in the axial and coronal planes with the TTT (p = .013 and p = .016, respectively). Direct anatomic repair was inferior to the intact ATFL in the axial plane upon the PT (p = .009). No differences could be found between anatomic graft reconstructions and the intact ATFL with any manoeuver, nor when comparing anatomic graft reconstruction and direct repair with 2 anchors. We were able to conclude that anatomic graft reconstruction of the ATFL reproduces angular stability of the native ligament in a cadaver model. While we could not detect if anatomic graft reconstruction was superior to direct repair, the latter proved to be less stable in the axial plane upon internal rotation (pivot test) versus the intact ATFL.


Assuntos
Instabilidade Articular , Ligamentos Laterais do Tornozelo , Humanos , Ligamentos Laterais do Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Tornozelo , Tendões/transplante , Cadáver , Instabilidade Articular/cirurgia , Fenômenos Biomecânicos
4.
Front Endocrinol (Lausanne) ; 14: 1269787, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027102

RESUMO

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) . Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to <3SDS from normal value were considered responders and those whose IGF1 was ≥3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively. Results: In all, 30 patients were responders and 17 were non-responders. GH2h was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH2h = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH2h = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH2h than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 ± 4.2 vs 3.3 ± 2.1; p=0.01). Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly.


Assuntos
Acromegalia , Adenoma , Neoplasias Hipofisárias , Humanos , Octreotida/uso terapêutico , Acromegalia/diagnóstico , Acromegalia/tratamento farmacológico , Acromegalia/metabolismo , Somatostatina/uso terapêutico , Resultado do Tratamento , Neoplasias Hipofisárias/metabolismo , Adenoma/tratamento farmacológico , Caderinas
5.
Front Immunol ; 14: 1285743, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901253

RESUMO

B-cell acute lymphoblastic leukemia (B-ALL) stands as the primary contributor to childhood cancer-related mortality on a global scale. The development of the most conventional forms of this disease has been proposed to be conducted by two different steps influenced by different types of risk factors. The first step is led by a genetic insult that is presumably acquired before birth that transforms a healthy cell into a preleukemic one, which is maintained untransformed until the second step takes place. This necessary next step to leukemia development will be triggered by different risk factors to which children are exposed after birth. Murine models that recap the stepwise progression of B-ALL have been instrumental in identifying environmental and genetic factors that contribute to disease risk. Recent evidence from these models has demonstrated that specific environmental risk factors, such as common infections or gut microbiome dysbiosis, induce immune stress, driving the transformation of preleukemic cells, and harboring genetic alterations, into fully transformed leukemic cells. Such models serve as valuable tools for investigating the mechanisms underlying preleukemic events and can aid in the development of preventive approaches for leukemia in child. Here, we discuss the existing knowledge, learned from mouse models, of the impact of genetic and environmental risk factors on childhood B-ALL evolution and how B-ALL prevention could be reached by interfering with preleukemic cells.


Assuntos
Leucemia de Células B , Leucemia Linfocítica Crônica de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Camundongos , Animais , Leucemia-Linfoma Linfoblástico de Células Precursoras/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Fatores de Risco
6.
Eur J Hosp Pharm ; 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798087

RESUMO

We present the case of a patient with failed desensitisation to paclitaxel that was ultimately successful with omalizumab treatment. Our patient, a female aged between 20-25 and diagnosed with a triple negative breast cancer, received first-line treatment with carboplatin and paclitaxel. During the second cycle of paclitaxel, she experienced heat, dyspnoea, facial angioedema and vomiting. Skin tests for allergic reactions returned negative results, and drug provocation tests showed a positive result (anaphylaxis). Rapid drug desensitisation (RDD) was carried out with two bags of dilutions but at the beginning of the infusion, the patient experienced symptoms again, so the infusion was stopped. Therefore, the use of omalizumab, already reported as a successful adjuvant in desensitisation to other drugs, was considered. The anti-immunoglobulin E (IgE) monoclonal antibody was administered off-label before the first programmed desensitisation with success: total dose of paclitaxel was infused without any reaction. The patient was able to receive the complete chemotherapy treatment.

7.
Cochrane Database Syst Rev ; 8: CD007315, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37526194

RESUMO

BACKGROUND: People with diabetes mellitus are at increased risk of postoperative complications. Data from randomised clinical trials and meta-analyses point to a potential benefit of intensive glycaemic control, targeting near-normal blood glucose, in people with hyperglycaemia (with and without diabetes mellitus) being submitted for surgical procedures. However, there is limited evidence concerning this question in people with diabetes mellitus undergoing surgery. OBJECTIVES: To assess the effects of perioperative glycaemic control for people with diabetes undergoing surgery. SEARCH METHODS: For this update, we searched the databases CENTRAL, MEDLINE, LILACS, WHO ICTRP and ClinicalTrials.gov. The date of last search for all databases was 25 July 2022. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) that prespecified different targets of perioperative glycaemic control for participants with diabetes (intensive versus conventional or standard care). DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the risk of bias. Our primary outcomes were all-cause mortality, hypoglycaemic events and infectious complications. Secondary outcomes were cardiovascular events, renal failure, length of hospital and intensive care unit (ICU) stay, health-related quality of life, socioeconomic effects, weight gain and mean blood glucose during the intervention. We summarised studies using meta-analysis with a random-effects model and calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes, using a 95% confidence interval (CI), or summarised outcomes with descriptive methods. We used the GRADE approach to evaluate the certainty of the evidence (CoE). MAIN RESULTS: A total of eight additional studies were added to the 12 included studies in the previous review leading to 20 RCTs included in this update. A total of 2670 participants were randomised, of which 1320 were allocated to the intensive treatment group and 1350 to the comparison group. The duration of the intervention varied from during surgery to five days postoperative. No included trial had an overall low risk of bias. Intensive glycaemic control resulted in little or no difference in all-cause mortality compared to conventional glycaemic control (130/1263 (10.3%) and 117/1288 (9.1%) events, RR 1.08, 95% CI 0.88 to 1.33; I2 = 0%; 2551 participants, 18 studies; high CoE). Hypoglycaemic events, both severe and non-severe, were mainly experienced in the intensive glycaemic control group. Intensive glycaemic control may slightly increase hypoglycaemic events compared to conventional glycaemic control (141/1184 (11.9%) and 41/1226 (3.3%) events, RR 3.36, 95% CI 1.69 to 6.67; I2 = 64%; 2410 participants, 17 studies; low CoE), as well as those considered severe events (37/927 (4.0%) and 6/969 (0.6%), RR 4.73, 95% CI 2.12 to 10.55; I2 = 0%; 1896 participants, 11 studies; low CoE). Intensive glycaemic control, compared to conventional glycaemic control, may result in little to no difference in the rate of infectious complications (160/1228 (13.0%) versus 224/1225 (18.2%) events, RR 0.75, 95% CI 0.55 to 1.04; P = 0.09; I2 = 55%; 2453 participants, 18 studies; low CoE). Analysis of the predefined secondary outcomes revealed that intensive glycaemic control may result in a decrease in cardiovascular events compared to conventional glycaemic control (107/955 (11.2%) versus 125/978 (12.7%) events, RR 0.73, 95% CI 0.55 to 0.97; P = 0.03; I2 = 44%; 1454 participants, 12 studies; low CoE). Further, intensive glycaemic control resulted in little or no difference in renal failure events compared to conventional glycaemic control (137/1029 (13.3%) and 158/1057 (14.9%), RR 0.92, 95% CI 0.69 to 1.22; P = 0.56; I2 = 38%; 2086 participants, 14 studies; low CoE). We found little to no difference between intensive glycaemic control and conventional glycaemic control in length of ICU stay (MD -0.10 days, 95% CI -0.57 to 0.38; P = 0.69; I2 = 69%; 1687 participants, 11 studies; low CoE), and length of hospital stay (MD -0.79 days, 95% CI -1.79 to 0.21; P = 0.12; I2 = 77%; 1520 participants, 12 studies; very low CoE). Due to the differences within included studies, we did not pool data for the reduction of mean blood glucose. Intensive glycaemic control resulted in a mean lowering of blood glucose, ranging from 13.42 mg/dL to 91.30 mg/dL. One trial assessed health-related quality of life in 12/37 participants in the intensive glycaemic control group, and 13/44 participants in the conventional glycaemic control group; no important difference was shown in the measured physical health composite score of the short-form 12-item health survey (SF-12). One substudy reported a cost analysis of the population of an included study showing a higher total hospital cost in the conventional glycaemic control group, USD 42,052 (32,858 to 56,421) compared to the intensive glycaemic control group, USD 40,884 (31.216 to 49,992). It is important to point out that there is relevant heterogeneity between studies for several outcomes. We identified two ongoing trials. The results of these studies could add new information in future updates on this topic. AUTHORS' CONCLUSIONS: High-certainty evidence indicates that perioperative intensive glycaemic control in people with diabetes undergoing surgery does not reduce all-cause mortality compared to conventional glycaemic control. There is low-certainty evidence that intensive glycaemic control may reduce the risk of cardiovascular events, but cause little to no difference to the risk of infectious complications after the intervention, while it may increase the risk of hypoglycaemia. There are no clear differences between the groups for the other outcomes. There are uncertainties among the intensive and conventional groups regarding the optimal glycaemic algorithm and target blood glucose concentrations. In addition, we found poor data on health-related quality of life, socio-economic effects and weight gain. It is also relevant to underline the heterogeneity among studies regarding clinical outcomes and methodological approaches. More studies are needed that consider these factors and provide a higher quality of evidence, especially for outcomes such as hypoglycaemia and infectious complications.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Glicemia/análise , Diabetes Mellitus Tipo 2/complicações , Controle Glicêmico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Nat Commun ; 14(1): 5159, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620322

RESUMO

The initial steps of B-cell acute lymphoblastic leukemia (B-ALL) development usually pass unnoticed in children. Several preclinical studies have shown that exposure to immune stressors triggers the transformation of preleukemic B cells to full-blown B-ALL, but how this takes place is still a longstanding and unsolved challenge. Here we show that dysregulation of innate immunity plays a driving role in the clonal evolution of pre-malignant Pax5+/- B-cell precursors toward leukemia. Transcriptional profiling reveals that Myd88 is downregulated in immune-stressed pre-malignant B-cell precursors and in leukemic cells. Genetic reduction of Myd88 expression leads to a significant increase in leukemia incidence in Pax5+/-Myd88+/- mice through an inflammation-dependent mechanism. Early induction of Myd88-independent Toll-like receptor 3 signaling results in a significant delay of leukemia development in Pax5+/- mice. Altogether, these findings identify a role for innate immunity dysregulation in leukemia, with important implications for understanding and therapeutic targeting of the preleukemic state in children.


Assuntos
Linfoma de Burkitt , Leucemia , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Animais , Camundongos , Células Precursoras de Linfócitos B , Fator 88 de Diferenciação Mieloide/genética , Transdução de Sinais , Proteínas Adaptadoras de Transdução de Sinal , Imunidade Inata , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
9.
Podium (Pinar Río) ; 18(2)ago. 2023.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1448877

RESUMO

El presente trabajo investiga sobre los estudios de percepción en atletas del equipo nacional de tenis de mesa. Tuvo como objetivo proponer ejercicios perceptivo-visuales para la mejora de la percepción de la distancia central y periférica en dicho equipo, a partir de la detección de las dificultades presentadas en el juego en los controles clasificatorios, 2019. La necesidad de realizar estudios que exploren la percepción de la distancia central y periférica en el ámbito de la psicología del deporte revela la importancia y actualidad del tema, por la contribución de este componente del sistema psicorregulador de las acciones motrices, al rendimiento de los atletas durante el proceso de entrenamiento y competencia. Se utilizaron métodos del nivel teórico como el análisis-síntesis y del nivel empírico la observación, la entrevista, la prueba de Vera y Saínz de la Torre para la determinación de la percepción de la distancia ajustada a las características específicas del tenis de mesa y el criterio de especialistas. Los principales resultados permitieron constatar un nivel inadecuado de desarrollo de la percepción de la distancia, en lo referente a los cálculos ópticos motriz, la visión central-periférica y los movimientos desequilibrados en los desplazamientos. Además, se aprecian dificultades en la coordinación y en las reacciones que afectan la precisión, potencia y colocación de los golpeos. Se elaboraron ejercicios perceptivo-visuales para la mejora de la percepción de la distancia central y periférica en el equipo nacional de tenis de mesa que fueron valoradas de muy adecuadas por los especialistas.


O presente trabalho investiga os estudos da percepção em atletas da seleção nacional de tênis de mesa. Teve como objetivo propor exercícios perceptivo-visuais para a melhoria da percepção da distância central e periférica nessa equipe, a partir da detecção das dificuldades apresentadas no jogo nos controles classificatórios de 2019. A necessidade de realizar estudos que explorem a percepção da distância central e periférica no campo da psicologia do esporte revela a importância e a atualidade do tema, devido à contribuição desse componente do sistema psicorregulatório das ações motoras para o desempenho dos atletas durante o processo de treinamento e competição. Foram utilizados métodos teóricos como análise-síntese e métodos empíricos como observação, entrevista, teste de Vera e Saínz de la Torre para a determinação da percepção da distância ajustada às características específicas do tênis de mesa e aos critérios dos especialistas. Os principais resultados mostraram um nível inadequado de desenvolvimento da percepção de distância, com relação a cálculos ópticos motores, visão centro-periférica e movimentos desequilibrados ao se movimentar. Além disso, há dificuldades na coordenação e nas reações que afetam a precisão, a potência e a colocação dos chutes. Exercícios perceptivo-visuais para a melhoria da percepção da distância central e periférica na equipe nacional de tênis de mesa foram elaborados e avaliados como muito adequados pelos especialistas.


This paper research perception studies in athletes from the national table tennis team. Its objective was to propose perceptual-visual exercises to improve the perception of central and peripheral distance in said team, based on the detection of the difficulties presented in the game in the qualifying controls, 2019. The need to carry out studies that explore the perception of central and peripheral distance in the field of sports psychology reveals the importance and topicality of the subject, due to the contribution of this component of the psychoregulatory system of motor actions, to the performance of athletes during the training and competition process. Theoretical level methods such as analysis-synthesis, as well as observation, interview and Vera and Saínz de la Torre test from the empirical level were used to determine the perception of distance adjusted to the specific characteristics of table tennis and tennis, also the specialist criteria method was used. The main results allowed to verify an inadequate level of development of the perception of distance, in relation to optical motor calculations, central-peripheral vision and unbalanced movements in displacements. In addition, there are difficulties in coordination and reactions that affect the precision, power and placement of the shots. Perceptual-visual exercises were developed to improve the perception of central and peripheral distance in the national table tennis team, which were valued as very adequate by specialists.

10.
Food Chem ; 402: 134225, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36137376

RESUMO

The strong effect of protein digestion products on gastrointestinal-released hormones is recognised. However, little is known about the specific peptide sequences able to induce gastrointestinal hormone secretion and the receptors involved. Our objective was to identify peptides able to induce the secretion of cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1) in the enteroendocrine cell line STC-1, and to evaluate the involvement of the calcium-sensing receptor and G-protein coupled receptor-93 in this cell signalling. The key role of the amino acidic sequence on CCK and GLP-1 secretion is demonstrated. Removing Ser from the N-terminus of κ-casein 33SRYPS37, or the N-terminal Trp-Ile in lysozyme 123WIRGCRL129 decreased the secretion of both hormones. However, substituting Tyr by Ala in peptide αs1-CN 90RYLG93 enhanced the CCK secretion levels but not the GLP-1 ones. In addition, the involvement of CaSR and GPR93 was evidenced, but our results pointed to the contribution of additional receptors or transporters.


Assuntos
Colecistocinina , Hormônios Gastrointestinais , Colecistocinina/genética , Colecistocinina/metabolismo , Colecistocinina/farmacologia , Peptídeo 1 Semelhante ao Glucagon/genética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Muramidase/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Caseínas/metabolismo , Células Enteroendócrinas , Peptídeos/metabolismo , Hormônios Gastrointestinais/metabolismo , Hormônios Gastrointestinais/farmacologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
11.
Podium (Pinar Río) ; 17(3): 911-924, sept.-dic. 2022. tab
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1406279

RESUMO

RESUMEN Introducción: El establecimiento de metas es un proceso fundamental en el entrenamiento deportivo y puede ser utilizado como una técnica motivacional en el deporte para manejar los recursos psicológicos del deportista y el equipo en aras de potenciar la cohesión y lograr sus aspiraciones. Objetivo: Analizar la pertinencia de la aplicación de un programa de intervención psicológica sustentado en el establecimiento de metas como técnica motivacional en el equipo femenino categoría 13-14 años de Polo Acuático de la Escuela de Iniciación Deportiva Escolar Eide "Marcelo Salado", de Villa Clara, Cuba. Materiales y métodos: La metodología empleada incluye diversos métodos y técnicas de investigación de naturaleza cuantitativa y cualitativa. Se utilizaron el análisis ssíntesis, observación, entrevista, cuestionario de establecimiento de metas, técnica de completamiento de frases, el cuestionario de estilo de dirección, la triangulación y el preexperimento. Se calcularon medidas descriptivas de posición como la media y la moda. Se utilizó la prueba de hipótesis no paramétrica de rangos señalados de Wilcoxon para comprobar si los cambios antes y después de la intervención eran significativos. Resultados: Los datos susceptibles de medición fueron procesados estadísticamente mediante el software SPSS para Windows versión 17.0 Los resultados demuestran la influencia del programa de intervención aplicado para el mejoramiento del establecimiento de metas del equipo. Conclusiones: Valoran la contribución de la aplicación del programa de intervención psicológica, en el establecimiento de metas de manera más objetivas, claras y comprensibles en las deportistas y en el desarrollo de la esfera motivacional al utilizar las potencialidades del trabajo del equipo deportivo como grupo.


SÍNTESE Introdução: O estabelecimento de metas é um processo fundamental no treinamento esportivo e pode ser usado como uma técnica motivacional no esporte para administrar os recursos psicológicos do atleta e da equipe, a fim de aumentar a coesão e alcançar suas aspirações. Objetivo: analisar a relevância da aplicação de um programa de intervenção psicológica baseado no estabelecimento de metas como técnica motivacional na equipe de pólo aquático feminina de 13-14 anos da Escuela de Iniciación Deportiva Escolar Eide "Marcelo Salado", em Villa Clara, Cuba. Materiais e métodos: a metodologia empregada inclui vários métodos e técnicas de pesquisa de natureza quantitativa e qualitativa. Foram utilizadas análise-síntese, observação, entrevista, questionário de estabelecimento de metas, técnica de preenchimento de frases, questionário de estilo de gestão, triangulação e pré-experimentação. Foram calculadas medidas descritivas de posição, tais como média e modo. O teste de hipóteses Wilcoxon não paramétrico assinado foi usado para testar se as mudanças antes e depois da intervenção eram significativas. Resultados: Os dados mensuráveis foram processados estatisticamente usando o software SPSS para Windows versão 17.0. Os resultados demonstram a influência do programa de intervenção aplicado na melhoria da definição das metas da equipe. Conclusões: a contribuição da aplicação do programa de intervenção psicológica no estabelecimento de metas mais objetivas, claras e compreensíveis para as atletas e no desenvolvimento da esfera motivacional, utilizando o potencial do trabalho da equipe esportiva como um grupo.


ABSTRACT Introduction: Goal setting is a fundamental process in sports training and can be used as a motivational technique in sports to manage the resources of the athlete and the team in order to enhance cohesion and achieve their aspirations. Objective: To analyze the relevance of the application of a psychological intervention program based on the establishment of goals as a motivational technique in the women's team category 13-14 years of Water Polo of the School of Sports Initiation School Eide " Marcelo Salado", of Villa Clare, Cuba. Materials and methods: The methodology used includes various research methods and techniques of a quantitative and qualitative nature. Analysis-synthesis, observation, interview, goal setting questionnaire, sentence completion technique, management style questionnaire, triangulation and pre-experiment were used. Descriptive measures of position such as the mean and mode were calculated. The Wilcoxon signed ranks nonparametric hypothesis test was used to test whether the changes before and after the intervention were significant. Results: The measurable data were statistically processed using the SPSS software for Windows version 17.0. The results demonstrate the influence of the intervention program applied to improve the team's goal setting. Conclusions: They value the contribution of the application of the psychological intervention program, in the establishment of goals in a more objective, clear and understandable way in the athletes and in the development of the motivational sphere when using the potentialities of the work of the sports team as a group.

12.
Podium (Pinar Río) ; 17(3): 1124-1140, sept.-dic. 2022. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1406294

RESUMO

RESUMEN Introducción: La concentración de la atención es fundamental en el boxeo, actividad donde el deportista se enfrenta a un contrario a corta distancia, en un combate que transcurre en un tiempo limitado, planteándole elevadas exigencias al proceso de atención. Objetivo: El presente trabajo tuvo como objetivo comparar la concentración de la atención en boxeadores categoría 15 - 16 años de la Eide "Mártires de Barbados" de La Habana, antes y después de la intervención psicológica del proceso. Materiales y métodos: La muestra fue de 20 deportistas de interés competitivo. La evaluación se realizó en dos momentos durante la etapa de preparación especial; el primero antes de realizar acciones de intervención psicológica del proceso y el segundo luego de ocho semanas realizándolas. Para el diagnóstico inicial se utilizaron las siguientes técnicas: Test de Anillos de Landolt, escala de autovaloración a deportistas, escala de valoración externa a entrenadores, entrevista a deportistas y observación estructurada a entrenamientos y competencias. En el retest, se repitieron las tres primeras técnicas mencionadas. Resultados: Los principales resultados arrojados inicialmente fueron una concentración evaluada de mal y de regular en el 50 % y 40 % de la muestra respectivamente, expresadas fundamentalmente en reiteración de errores ya corregidos por los entrenadores y en dificultad para mantener la focalización. Post intervención se comprobó una mejora de la concentración de la atención, al obtenerse un diagnóstico de bien, muy bien y excelente en el 35 %, 20 % y 20 % de la muestra respectivamente. Conclusiones: Se concluye que la intervención propuesta contribuyó a una mejoría en el diagnóstico del proceso.


SÍNTESE Introdução: A concentração da atenção é fundamental no boxe, uma atividade onde o atleta enfrenta um adversário a curta distância, em um combate que ocorre em um tempo limitado, colocando altas exigências no processo de atenção. Objetivo: O objetivo deste estudo foi comparar a concentração de atenção nos boxeadores da categoria "Mártires de Barbados" Eide em Havana, antes e depois da intervenção psicológica do processo. Materiais e métodos: A amostra consistiu de 20 atletas de interesse competitivo. A avaliação foi realizada em dois momentos durante a fase de preparação especial; o primeiro antes de realizar as ações de intervenção sicológica do processo e o segundo após oito semanas de realização das mesmas. Para o diagnóstico inicial, foram utilizadas as seguintes técnicas: Landolt's Ring Test, escala de auto-avaliação para atletas, escala de avaliação externa para treinadores, entrevista com atletas e observação estruturada de sessões de treinamento e competições. No novo teste, as três primeiras técnicas mencionadas acima foram repetidas. Resultados: Os principais resultados mostraram inicialmente uma concentração fraca e justa em 50% e 40% da amostra respectivamente, expressa principalmente na repetição de erros já corrigidos pelos treinadores e na dificuldade de manter o foco. Após a intervenção, verificou-se uma melhora na concentração da atenção, obtendo-se um diagnóstico de bom, muito bom e excelente em 35%, 20% e 20% da amostra, respectivamente. Conclusões: Conclui-se que a intervenção proposta contribuiu para uma melhoria no diagnóstico do processo.


ABSTRACT Introduction: The concentration of attention is essential in boxing, an activity where the athlete faces an opponent at close range, in a fight that takes place in a limited time, placing high demands on the attention process. Objective: The present study aimed to compare the concentration of attention in boxers category 15 - 16 years of the Sport Initiation School (Eide in Spanish) "Mártires de Barbados" in Havana, before and after the psychological intervention of the process. Materials and methods: The sample consisted of 20 athletes of competitive interest. The evaluation was carried out at two moments during the special preparation stage; the first before carrying out psychological intervention actions of the process and the second after eight weeks carrying them out. For the initial diagnosis, the following techniques were used: Landolt Ring Test, self-assessment scale for athletes, external assessment scale for coaches, interviews with athletes, and structured observation of training and competitions. In the retest, the first three techniques mentioned were repeated. Results: The main results initially obtained were a concentration evaluated as bad and regular in 50 % and 40 % of the sample, respectively, expressed mainly in the repetition of errors already corrected by the coaches and in difficulty in maintaining focus. Post-intervention, an improvement in attention concentration was verified, obtaining a diagnosis of good, very good and excellent in 35 %, 20 % and 20 % of the sample, respectively. Conclusions: It is concluded that the proposed intervention contributed to an improvement in the diagnosis of the process.

13.
Cardiovasc Diabetol ; 21(1): 207, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221075

RESUMO

BACKGROUND: Compelling evidence suggests that the fibroblast growth factor 23 (FGF23) / α-klotho axis is impaired in subjects with diabetes mellitus. We examined the relationship between parameters related to calcium/phosphate homeostasis, including FGF23 and α-klotho, and subclinical carotid atherosclerosis burden in type 1 diabetes mellitus (T1D) subjects. METHODS: This cross-sectional study involved 226 subjects with T1D and 147 age-, sex- and plaque-matched, non-diabetic (non-T1D) subjects, both with normal renal function. Carotid ultrasound was performed to determine the presence and burden of atheromatous plaques. Concentrations of the intact form of FGF23 and α-klotho were assessed by ELISA. Calcium, phosphate, parathyroid hormone, and vitamin D levels were also determined. Negative binomial regression models were used to examine relationship between parameters studied and subclinical carotid atherosclerosis. RESULTS: Only FGF23 was increased in T1D compared with non-diabetic subjects (> 2-fold; p < 0.05). α-klotho was higher in subjects with subclinical carotid atherosclerosis (1.4-fold, p < 0.05). Regression analysis revealed that the log α-klotho concentration was positively associated with the presence of subclinical carotid atherosclerosis both in T1D subjects (incidence rate ratio [IRR]: 1.41; 95% confidence interval [CI], 1.06-1.89; p < 0.05) and in non-T1D subjects (IRR: 1.65; 95% CI, 1.02-2.75; p < 0.05). The models also showed that age, smoking and albuminuria-to-creatinine ratio were positively associated with subclinical carotid atherosclerosis in T1D subjects. Interestingly, sex-related protection against plaque was also revealed in T1D women. CONCLUSION: Higher α-klotho was associated with subclinical carotid atherosclerotic in the absence of kidney dysfunction. This finding also points to a new pathophysiological pathway involved in the development and progression of this complication.


Assuntos
Doenças das Artérias Carótidas , Diabetes Mellitus Tipo 1 , Placa Aterosclerótica , Cálcio , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/etiologia , Creatinina , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Fatores de Crescimento de Fibroblastos , Glucuronidase , Humanos , Hormônio Paratireóideo , Fosfatos , Vitamina D
14.
Circulation ; 146(11): 851-867, 2022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-35959657

RESUMO

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by high propensity to life-threatening arrhythmias and progressive loss of heart muscle. More than 40% of reported genetic variants linked to ARVC reside in the PKP2 gene, which encodes the PKP2 protein (plakophilin-2). METHODS: We describe a comprehensive characterization of the ARVC molecular landscape as determined by high-resolution mass spectrometry, RNA sequencing, and transmission electron microscopy of right ventricular biopsy samples obtained from patients with ARVC with PKP2 mutations and left ventricular ejection fraction >45%. Samples from healthy relatives served as controls. The observations led to experimental work using multiple imaging and biochemical techniques in mice with a cardiac-specific deletion of Pkp2 studied at a time of preserved left ventricular ejection fraction and in human induced pluripotent stem cell-derived PKP2-deficient myocytes. RESULTS: Samples from patients with ARVC present a loss of nuclear envelope integrity, molecular signatures indicative of increased DNA damage, and a deficit in transcripts coding for proteins in the electron transport chain. Mice with a cardiac-specific deletion of Pkp2 also present a loss of nuclear envelope integrity, which leads to DNA damage and subsequent excess oxidant production (O2.- and H2O2), the latter increased further under mechanical stress (isoproterenol or exercise). Increased oxidant production and DNA damage is recapitulated in human induced pluripotent stem cell-derived PKP2-deficient myocytes. Furthermore, PKP2-deficient cells release H2O2 into the extracellular environment, causing DNA damage and increased oxidant production in neighboring myocytes in a paracrine manner. Treatment with honokiol increases SIRT3 (mitochondrial nicotinamide adenine dinucleotide-dependent protein deacetylase sirtuin-3) activity, reduces oxidant levels and DNA damage in vitro and in vivo, reduces collagen abundance in the right ventricular free wall, and has a protective effect on right ventricular function. CONCLUSIONS: Loss of nuclear envelope integrity and subsequent DNA damage is a key substrate in the molecular pathology of ARVC. We show transcriptional downregulation of proteins of the electron transcript chain as an early event in the molecular pathophysiology of the disease (before loss of left ventricular ejection fraction <45%), which associates with increased oxidant production (O2.- and H2O2). We propose therapies that limit oxidant formation as a possible intervention to restrict DNA damage in ARVC.


Assuntos
Displasia Arritmogênica Ventricular Direita , Células-Tronco Pluripotentes Induzidas , Placofilinas , Adulto , Animais , Displasia Arritmogênica Ventricular Direita/patologia , Dano ao DNA , Humanos , Peróxido de Hidrogênio , Células-Tronco Pluripotentes Induzidas/metabolismo , Camundongos , Mutação , Miócitos Cardíacos/metabolismo , Membrana Nuclear/metabolismo , Membrana Nuclear/patologia , Oxidantes/metabolismo , Placofilinas/genética , Placofilinas/metabolismo , Volume Sistólico , Função Ventricular Esquerda
15.
Int J Mol Sci ; 23(14)2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35886910

RESUMO

Leukemia is the most usual childhood cancer, and B-cell acute lymphoblastic leukemia (B-ALL) is its most common presentation. It has been proposed that pediatric leukemogenesis occurs through a "multi-step" or "multi-hit" mechanism that includes both in utero and postnatal steps. Many childhood leukemia-initiating events, such as chromosomal translocations, originate in utero, and studies so far suggest that these "first-hits" occur at a far higher frequency than the incidence of childhood leukemia itself. The reason why only a small percentage of the children born with such preleukemic "hits" will develop full-blown leukemia is still a mystery. In order to better understand childhood leukemia, mouse modeling is essential, but only if the multistage process of leukemia can be recapitulated in the model. Therefore, mouse models naturally reproducing the "multi-step" process of childhood B-ALL will be essential to identify environmental or other factors that are directly linked to increased risk of disease.


Assuntos
Síndromes Mielodisplásicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Pré-Leucemia , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Pré-Leucemia/genética , Translocação Genética
16.
Reprod Biol ; 22(2): 100650, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35588659

RESUMO

Maternal obesity is associated with complications of pregnancy and increases the infant's risk of developing obesity, diabetes and cardiovascular disease later in life. The placenta has an important role in determining the pregnancy outcome, and the syncytiotrophoblast (ST) is the main component of the placenta that supports the relationship between the mother and fetus. The differentiation of the cytotrophoblast (CT) into the ST is accompanied by changes in mitochondrial functions and dynamics. The objective of the present study was to investigate the effects of maternal obesity (without gestational diabetes) on the in vitro differentiation capacities of human CT isolated from term placenta by focusing on mitochondrial status. We found that, during human CT differentiation process, maternal obesity is associated with (i) a lower progesterone secretion, (ii) a transient impairment in the ST's fusion potential (via syncytin-2 and its receptor), (iii) a lower mitochondrial content, and (iv) weaker mRNA expression of oestrogen-related receptor-gamma (a key mitobiogenesis gene). Moreover, maternal obesity altered the time course of ATP and reactive oxygen species production throughout CT differentiation. The mitochondrial dysfunctions observed in isolated human CTs of obese women might explain the observed decrease in progesterone production. Our results demonstrated that obesity in pregnancy is associated with a functional impairment of the ST which might alter the foetal-maternal dialogue.


Assuntos
Obesidade Materna , Trofoblastos , Diferenciação Celular , Feminino , Humanos , Mitocôndrias/metabolismo , Obesidade/complicações , Placenta/metabolismo , Gravidez , Progesterona/metabolismo , Trofoblastos/metabolismo
17.
Dig Liver Dis ; 54(9): 1209-1214, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35428580

RESUMO

BACKGROUND: Serum-based scores (SBS) appear to be a high applicability strategy for assessment of liver fibrosis in primary care. Aim of the study was to evaluate their performance to detect ≥F2 in a general population and to design a highly-applicable strategy for screening. METHODS: prospective population-based cohort study in randomly identified subjects, aged 40-70y. Medical history, blood tests and elastography were obtained, ≥F2 was determined by using LSM cutoff ≥9.2/7.8 kPa for M/XL probe and SBS diagnostic accuracies were evaluated. RESULTS: 986 patients were analyzed. LSM prevalence estimate suggestive of ≥F2 was 1.9% and Metabolic Sindrome (MS) (OR 3.4, 1.3-9.0;p = 0.01), was the only factor independently associated with ≥F2, with increasing prevalence according to the number of criteria (0 criterion:0%,1:0.3%,2:2.8%,3:2.4%,4:6.9%,5:14.3%;p<0.001). FLI and NFS were the two best-performing tests in the cross-sectional study, with AUROCs for ≥F2 of 0.89 (95%CI,0.84- 0.95) and 0.82 (95%CI,0.74-0.90), respectively. Predefined cutoff for FLI≥60 (Sn89.5%, Sp72.1%, NPV99.9%) and NFS≥-1.455 (Sn83.3%, Sp68%, NPV99.6%) showed adequate diagnostic accuracy. Based on these findings, a 3- step algorithm strategy to detect liver fibrosis in the community setting is proposed (Sn84.2%, Sp75.2%, NVP99.6%). CONCLUSIONS: A staged risk-stratification model improves the detection of ≥F2 in the community setting, while reducing unnecessary referrals.


Assuntos
Técnicas de Imagem por Elasticidade , Hepatopatias , Médicos , Adulto , Idoso , Biópsia , Estudos de Coortes , Estudos Transversais , Amigos , Humanos , Fígado , Cirrose Hepática , Pessoa de Meia-Idade , Estudos Prospectivos
18.
Podium (Pinar Río) ; 17(1)abr. 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1448870

RESUMO

La presente investigación se fundamentó en las teorías que exploran la resiliencia en el ámbito de la Psicología del Deporte, se planteó como objetivo analizar la manifestación de la resiliencia psicológica en atletas cubanos de alto rendimiento, específicamente en la exdeportista corredora de 800 metros Ana Fidelia Quiroz Moret y en deportistas de la categoría Juvenil y Mayores del equipo nacional de tenis de Mesa de Cuba. Se utilizaron métodos de investigación con predominio de la metodología cualitativa analítica como estudios de caso individual y de grupo, análisis-síntesis, entrevista, análisis de documentos y videos, observación, el cuestionario de Afrontamiento de estrés de Sandín y Chorot y la escala de Resiliencia de Wagnild y Young. Se utilizó el porcentaje como método matemático. Los resultados principales permitieron constatar la presencia de nivel alto de resiliencia en la exdeportista estudiada y niveles medio-alto y alto en los tenimesistas estudiados, se identificaron los factores protectores que influyen en el afrontamiento de eventos vitales y situaciones estresantes. Las conclusiones principales destacaron la necesidad de valorar en los deportistas de alto rendimiento estudiados, las manifestaciones de la resiliencia psicológica de manera particular: los factores protectores de la personalidad, la influencia de las redes de apoyo social así como las estrategias y estilos de afrontamiento al estrés que afloran ante situaciones adversas que se presentan en la vida deportiva, dificultades propias del entrenamiento y la competencia a las que se enfrentan con regularidad, que pueden constituir modelos a tener en cuenta para otros deportistas que se inician.


O objetivo desta pesquisa foi analisar a manifestação da resiliência psicológica em atletas cubanos de alto rendimento, especificamente na ex-corredora Ana Fidelia Quiroz Moret, de 800m, e em atletas da seleção nacional cubana de tênis de mesa, nas categorias jovem e sênior. Foram utilizados métodos de pesquisa com predominância de metodologia analítica qualitativa, como estudos de casos individuais e de grupo, análise-síntese, entrevista, análise de documentos e vídeos, observação, o questionário de Cópia de Estresse de Sandin e Chorot e a escala de Resiliência de Wagnild e Young. A porcentagem foi utilizada como um método matemático. Os principais resultados mostraram a presença de um alto nível de resiliência na ex-esportista estudada e níveis médios-altos e altos nos tenistas estudados. Os fatores de proteção que influenciam o enfrentamento de eventos da vida e situações estressantes foram identificados. As principais conclusões destacaram a necessidade de avaliar nos atletas de alto rendimento estudados, as manifestações de resiliência psicológica em particular: os fatores protetores da personalidade, a influência das redes de apoio social, assim como as estratégias e estilos de lidar com o estresse que surgem em situações adversas que surgem na vida esportiva, as dificuldades de treinamento e competição que enfrentam regularmente, que podem constituir modelos a serem levados em conta para outros atletas que estão começando.


The present research was based on the theories that explore resilience in the field of Sport Psychology. The objective was to analyze the manifestation of psychological resilience in Cuban high-performance athletes, specifically in the former 800-meter runner Ana Fidelia Quiroz Moret and in athletes of the Cuban national Table Tennis team in the Juvenile and Senior categories. Research methods were used with a predominance of analytical qualitative methodology such as individual and group case studies, analysis-synthesis, interview, analysis of documents and videos, observation, the Stress Coping questionnaire of Sandin and Chorot and the Resilience scale of Wagnild and Young. The percentage was used as a mathematical method. The main results showed the presence of a high level of resilience in the ex-sportswoman studied and medium-high and high levels in the tennis players studied. The main conclusions highlighted the need to assess in the high performance athletes studied, the manifestations of psychological resilience in particular: the protective factors of the personality, the influence of social support networks as well as the strategies and styles of coping with stress that emerge in adverse situations that arise in sports life, difficulties of training and competition that they face regularly, which may constitute models to be taken into account for other athletes who are starting out.

19.
Cancer Res ; 82(6): 1098-1109, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35131871

RESUMO

Preventing development of childhood B-cell acute lymphoblastic leukemia (B-ALL), a disease with devastating effects, is a longstanding and unsolved challenge. Heterozygous germline alterations in the PAX5 gene can lead to B-ALL upon accumulation of secondary mutations affecting the JAK/STAT signaling pathway. Preclinical studies have shown that this malignant transformation occurs only under immune stress such as exposure to infectious pathogens. Here we show in Pax5+/- mice that transient, early-life administration of clinically relevant doses of ruxolitinib, a JAK1/2 inhibitor, significantly mitigates the risk of B-ALL following exposure to infection; 1 of 29 animals treated with ruxolitinib developed B-ALL versus 8 of 34 untreated mice. Ruxolitinib treatment preferentially targeted Pax5+/- versus wild-type B-cell progenitors and exerted unique effects on the Pax5+/- B-cell progenitor transcriptional program. These findings provide the first in vivo evidence for a potential strategy to prevent B-ALL development. SIGNIFICANCE: JAK/STAT inhibition suppresses tumorigenesis in a B-ALL-susceptible mouse model, presenting a novel approach to prevent B-ALL onset.


Assuntos
Janus Quinases , Leucemia-Linfoma Linfoblástico de Células Precursoras , Animais , Humanos , Janus Quinases/genética , Camundongos , Fator de Transcrição PAX5/genética , Fatores de Transcrição STAT , Transdução de Sinais/genética
20.
Ann Anat ; 239: 151726, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33798691

RESUMO

Insulin receptor substrate (Irs) belongs to a family of proteins that mediate the intracellular signaling of insulin and IGF-1. Insulin receptor substrate 2 (Irs2) is necessary for retinal function, since its failure in Irs2-deficient mice in hyperglycemic situation promotes photoreceptor degeneration and visual dysfunction, like in diabetic retinopathy. The expression of P450 aromatase, which catalyzes androgen aromatization to form 17ß-estradiol, increases in some neurodegenerative diseases thus promoting the local synthesis of neuroestrogens that exert relevant neuroprotective functions. Aromatase is also expressed in neurons and glial cells of the central nervous system (CNS), including the retina. To further understand the role of Irs2 at the retinal level, we performed an immunocytochemical study in adult normoglycemic Irs2-deficient mice. For this aim, the retinal immunoexpression of neuromodulators, such as aromatase, glutamine synthetase (GS), and tyrosine hydroxylase (TH) was analyzed, joint to a morphometric and planimetric study of the retinal layers. Comparing with wild-type (WT) control mice, the Irs2-knockout (Irs2-KO) animals showed a significant increase in the immunopositivity to aromatase in almost all of the retinal layers. Besides, Irs2-KO mice exhibited a decreased immunopositive reaction for GS and TH, in Müller and amacrine cells, respectively; morphological variations were also found in these retinal cell types. Furthermore, the retina of Irs2-KO mice displayed alterations in the structural organization, and a generalized decrease in the retinal thickness was observed in each of the layers, except for the inner nuclear layer. Our findings suggest that the absence of Irs2 induces retinal neurodegenerative changes in Müller and amacrine cells that are unrelated to hyperglycemia. Accordingly, in the Irs2-KO mice, the increased retinal immunocytochemical reactivity of aromatase could be associated with an attempt to repair such neural retina injuries by promoting local neuroprotective mediators.


Assuntos
Aromatase , Proteínas Substratos do Receptor de Insulina , Retina , Células Amácrinas/metabolismo , Animais , Aromatase/genética , Células Ependimogliais , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Retina/metabolismo
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