RESUMO
(1) Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) reduce adipose tissue and cardiovascular events in patients with type 2 diabetes (T2D). Accumulation of epicardial adipose tissue (EAT) is associated with increased cardio-metabolic risks and obstructive coronary disease events in patients with T2D. (2) We performed a systematic review and meta-analysis of SGLT2-i therapy on T2D patients, reporting data on changes in EAT after searching the PubMed/MEDLINE, Embase, Science Direct, Scopus, Google Scholar, and Cochrane databases. A random effects or fixed effects model meta-analysis was then applied. (3) Results: A total of three studies (n = 64 patients with SGLT2-i, n = 62 with standard therapy) were included in the final analysis. SGLT2 inhibitors reduced EAT (SMD: -0.82 (-1.49; -0.15); p < 0.0001). An exploratory analysis showed that HbA1c was significantly reduced with SGLT2-i use, while body mass index was not significantly reduced with this drug. (4) Conclusions: This meta-analysis suggests that the amount of EAT is significantly reduced in T2D patients with SGLT2-i treatment.
Assuntos
Tecido Adiposo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/antagonistas & inibidores , Pericárdio/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Tecido Adiposo/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/metabolismo , Humanos , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pericárdio/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de RiscoRESUMO
OBJECTIVES: Patients with univentricular hearts who require permanent pacing systems typically require placement of epicardial leads. It is frequently difficult to find a position with good thresholds due to epimyocardial fibrosis or fat. The goal of the study is to assess the progression of capture thresholds (CT), sensing parameters (P waves and R waves), and impedances (imp) of steroid eluting epicardial pacing leads in young adults who underwent Fontan conversion and a pacemaker implant. METHODS: All patients undergoing Fontan conversion in two institutions were retrospectively identified. Demographic data, congenital heart defects, pacing leads used, and pacing parameters were analyzed at implant, at 6 weeks and 12 months after implant. RESULTS: Twenty patients were identified (twelve males); mean age at conversion was 24.9 ± 5.4 years (range 18-35). Epicardial bipolar steroid eluting leads were used. The site of implant both in the atria and the ventricles varied depending on the parameters. At implant, mean atrial and ventricular impedances were 617 ± 171 Ω and 1061 ± 771 Ω, respectively, mean P wave amplitude was 2 ± 0.7 mV, and mean R wave amplitude was 12.5 ± 7.7 mV. Mean CT was 1.7 ± 0.8 V at 0.5 ms for the atrium and 2.2 ± 1.2 V at 0.5 ms for the ventricle. Ventricular CT and impedance showed an improvement within the first 12 months after implant, with four patients having a decrease in threshold of more than 2 V. CONCLUSION: In patients undergoing Fontan conversion, implant ventricular CT and impedances are frequently higher than expected but typically improve during follow-up. Acceptance of higher initial threshold values may be a potential strategy in this patient population.
OBJETIVO: Los pacientes con corazón univentricular que requieren estimulación cardíaca reciben sistemas de estimulación epicárdicos. Debido a la presencia de fibrosis o grasa epi-miocárdica es dificultoso en esta población encontrar sitios con adecuados parámetros de estimulación. El objetivo de este estudio es determinar la progresión de los umbrales de captura, los parámetros de sensado (medición de las ondas P y R) e impedancias (imp) de los catéteres epicárdicos con liberación de esteroides implantados en adultos jóvenes sometidos a cirugía de reconversión de Fontan e implante de marcapasos. MÉTODOS: Los pacientes sometidos a cirugía de reconversión de Fontan en dos instituciones fueron analizados retrospectivamente. Los datos demográficos, el tipo de cardiopatía congénita, de catéteres de estimulación y los parámetros de estimulación fueron analizados al momento del implante, a las 6 semanas y al año. RESULTADOS: Se identificaron 20 pacientes (12 de ellos de sexo masculino); la edad media al momento de la reconversión fue de 24.9 ± 5.4 años (rango 18-35). Se utilizaron catéteres epicárdicos bipolares de fijación pasiva y con liberación de esteroides en todos los casos. El sitio de implante en las aurículas y en los ventrículos fue variable de acuerdo a los parámetros. En el momento del implante las impedancias medias fueron 617 ± 171 W y 1061 ± 771 W respectivamente, la amplitud media de la onda P fue 2 ± 0.7 mV y la media de amplitud de la onda R fue de 12.5 ± 7.7 mV. Las medias de los umbrales de captura fueron 1.7 ± 0.8 V at 0.5 ms para los catéteres auriculares y 2.2 ± 1.2 V at 0.5 ms para los ventriculares. Los umbrales de captura y las impedancias ventriculares mostraron una mejoría en los 12 meses posteriores al implante, y en 4 pacientes esa mejoría en el umbral de captura ventricular fue mayor a 2 V. CONCLUSIONES: En pacientes sometidos a una cirugía de reconversión de Fontan e implante de marcapasos, los umbrales de captura e impedancias ventriculares son más elevados que los esperados, pero mejoran durante el seguimiento. La aceptación de valores más elevados puede potencialmente constituir una alternativa en esta población de pacientes.
Assuntos
Cardiopatias Congênitas , Marca-Passo Artificial , Adolescente , Adulto , Desfibriladores Implantáveis/normas , Impedância Elétrica , Eletrodos Implantados , Técnica de Fontan , Glucocorticoides/farmacologia , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/cirurgia , Humanos , Masculino , Pericárdio/efeitos dos fármacos , Pericárdio/patologia , Pericárdio/cirurgia , Estudos Retrospectivos , Taquicardia Ventricular/terapia , Resultado do Tratamento , Adulto JovemRESUMO
The decline of the Bombus population is closely related to the presence of environmental pollutants. Among these pollutants, trace metals represent a major concern, which includes mercury, a known genotoxic substance. The induction of genotoxicity may be demonstrated by the comet assay (a.k.a. single-cell gel electrophoresis), a simple and sensitive method for DNA damage estimating. The current work provided, for the first time, a protocol of comet assay for Bombus atratus using mercury as a standard chemical at safe concentrations according to the Environment National Council of Brazil, and the World Health Organization. Bees were collected and divided into three groups (n = 11 each), in which the exposed groups received a 0.2 ppb or a 1 ppb of mercury solution, and the control group received water. The bioassay was performed for 48 h at controlled temperature and humidity conditions, according to the OECD guideline toxicological test method for B. terrestris. The samples were stained with different dyes to observe the efficacy of each one. Variations of parameters in methodology, such as concentration and time of exposure to lysis solution as well as the electrophoretic process, allowed the observation of comets at different levels. DAPI and acridine orange presented an unstable fluorescence, and silver nitrate dye was more effective. Therefore, the comet assay was shown to be an effective method to evaluate genotoxic effects in bees. The obtained results may be helpful for the establishment of a suitable protocol for future genotoxicity assessment in neotropical bees using different doses of xenobiotics.
Assuntos
Abelhas/efeitos dos fármacos , Dano ao DNA , Poluentes Ambientais/toxicidade , Corpo Adiposo/efeitos dos fármacos , Mercúrio/toxicidade , Pericárdio/efeitos dos fármacos , Animais , Abelhas/genética , Abelhas/crescimento & desenvolvimento , Brasil , Células Cultivadas , Ensaio Cometa/métodos , Corpo Adiposo/patologia , Pericárdio/patologiaRESUMO
The objective of this study was to evaluate the effect of chemical treatment with glutamic acid to avoid calcification of biological cardiac valves. The bovine pericardium (BP) tissues were fixed with 0.5% glutaraldehyde (BP/GA), followed by treatment with glutamic acid (BP/GA + Glu) for neutralization of the free aldehyde groups. Microscopic analysis showed that the wavy structure of collagen fibrils was preserved, but changes in elastin's integrity occurred. However, the treatment did not promote undesirable changes in the thermal and mechanical properties of the modified BPs. These samples were systematically studied in rat subcutaneous tissue: control (BP/GA) and anticalcificant (BP/GA + Glu). After 60 days, both groups induced similar inflammatory reactions. In terms of calcification, BP/GA + Glu remained more stable with a lower index (3.1 ± 0.2 µg Ca2+ /mg dry tissue), whereas for BP/GA it was 5.7 ± 1.3 µg Ca2+ /mg dry tissue. Bioprostheses made from BP/GA + Glu were implanted in the pulmonary position in sheep, and in vivo echocardiographic analyses revealed maintenance of valvar function after 180 days, with low gradients and minimal valve insufficiency. The explanted tissues of the BP/GA + Glu group had a lower average calcium content 3.8 ± 3.0 µg Ca2+ /mg dry tissue. The results indicated high anticalcification efficiency of BP/GA + Glu in both subcutaneous implant in rats and in the experimental sheep model, which is an advantage that should encourage the industrial application of these materials for the manufacture of bioprostheses.
Assuntos
Bioprótese , Calcificação Fisiológica/efeitos dos fármacos , Bovinos , Ácido Glutâmico/farmacologia , Próteses Valvulares Cardíacas , Animais , Bovinos/fisiologia , Glutaral/farmacologia , Valvas Cardíacas/efeitos dos fármacos , Valvas Cardíacas/fisiologia , Pericárdio/efeitos dos fármacos , Pericárdio/fisiologiaAssuntos
Albendazol/uso terapêutico , Anticestoides/uso terapêutico , Cardiomiopatias/tratamento farmacológico , Equinococose/tratamento farmacológico , Cisto Mediastínico/tratamento farmacológico , Pericárdio/efeitos dos fármacos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/parasitologia , Equinococose/diagnóstico por imagem , Equinococose/parasitologia , Humanos , Masculino , Cisto Mediastínico/diagnóstico por imagem , Cisto Mediastínico/parasitologia , Pessoa de Meia-Idade , Pericárdio/diagnóstico por imagem , Pericárdio/parasitologia , Resultado do TratamentoAssuntos
Tecido Adiposo/efeitos dos fármacos , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Toxinas Botulínicas/administração & dosagem , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pericárdio/efeitos dos fármacos , Complicações Pós-Operatórias/prevenção & controle , Humanos , Injeções , Reprodutibilidade dos TestesAssuntos
Humanos , Pericárdio/efeitos dos fármacos , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Toxinas Botulínicas/administração & dosagem , Tecido Adiposo/efeitos dos fármacos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Reprodutibilidade dos Testes , InjeçõesRESUMO
BACKGROUND: Pericardium tissue allograft can be used for surgical repair in several procedures. One of the tissue engineering strategies is the process of decellularization. This process decreases immunogenic response, but it may modify the natural extracellular matrix composition and behavior. OBJECTIVE: The aim of this study was to evaluate the effectiveness of cell removal, maintenance of extracellular matrix properties and mechanical integrity of decellularized human pericardium using a low concentration solution of sodium dodecyl sulfate. METHODS: Decellularization was performed with sodium dodecyl sulfate and ethylenediaminetetraacetic acid. Histological analysis, DNA quantification, evaluation of glycosaminoglycans and collagen were performed. Biomechanical assay was performed using tensile test to compare the decellularization effects on tissue properties of tensile strength, elongation and elastic modulus. P < 0.05 was considered significant. RESULTS: There was reduction in visible nuclei present in pericardium tissue after decellularization, but it retained collagen and elastin bundles similar to fresh pericardium. The DNA contents of the decellularized pericardium were significantly reduced to less than 511.23 ± 120.4 ng per mg of dry weight (p < 0.001). The biomechanical assay showed no significant difference for fresh or decellularized tissue. CONCLUSION: The decellularization process reduces cell content as well as extracellular matrix components without changing its biomechanical properties.
Assuntos
Separação Celular/métodos , Pericárdio/citologia , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologia , Engenharia Tecidual/métodos , Adolescente , Adulto , Fenômenos Biomecânicos , Humanos , Pessoa de Meia-Idade , Pericárdio/efeitos dos fármacos , Medicina Regenerativa , Alicerces Teciduais , Adulto JovemRESUMO
Abstract Background: Pericardium tissue allograft can be used for surgical repair in several procedures. One of the tissue engineering strategies is the process of decellularization. This process decreases immunogenic response, but it may modify the natural extracellular matrix composition and behavior. Objective: The aim of this study was to evaluate the effectiveness of cell removal, maintenance of extracellular matrix properties and mechanical integrity of decellularized human pericardium using a low concentration solution of sodium dodecyl sulfate. Methods: Decellularization was performed with sodium dodecyl sulfate and ethylenediaminetetraacetic acid. Histological analysis, DNA quantification, evaluation of glycosaminoglycans and collagen were performed. Biomechanical assay was performed using tensile test to compare the decellularization effects on tissue properties of tensile strength, elongation and elastic modulus. P < 0.05 was considered significant. Results: There was reduction in visible nuclei present in pericardium tissue after decellularization, but it retained collagen and elastin bundles similar to fresh pericardium. The DNA contents of the decellularized pericardium were significantly reduced to less than 511.23 ± 120.4 ng per mg of dry weight (p < 0.001). The biomechanical assay showed no significant difference for fresh or decellularized tissue. Conclusion: The decellularization process reduces cell content as well as extracellular matrix components without changing its biomechanical properties.
Resumo Fundameto: O enxerto de pericárdio pode ser usado em muitos procedimentos de correção cirúrgica. Uma das estratégias da engenharia tecidual é o processo de descelularização. No entanto, embora esse processo diminua a resposta imunogênica, a descelularização pode modificar tanto o comportamento como a composição da matriz extracelular natural. Objetivos: Avaliar a eficácia da descelularização usando baixa concentração de dodecil sulfato de sódio na remoção celular, na manutenção das propriedades da matriz extracelular e na integridade mecânica do pericárdio humano descelularizado. Métodos: A descelularização foi realizada com dodecil sulfato de sódio e ácido etilenodiamino tetra-acético. Foi realizada análise histológica, quantificação de DNA, e avaliação de glicosaminoglicanos e colágeno. O estudo biomecânico foi conduzido pelo teste de tração para comparar os efeitos da descelularização sobre as propriedades teciduais de resistência à tração, alongamento e módulo de elasticidade. Foi considerado um valor de p < 0,05 como estatisticamente significativo. Resultados: Observou-se uma redução na quantidade de núcleos presentes no pericárdio após a descelularização, apesar de manter quantidades similares de feixes de elastina e de colágeno. As concentrações de DNA do pericárdio descelularizado foram significativamente reduzidas para menos que 511,23 ± 120,4 ng por mg de peso seco (p < 0,001). O teste biomecânico não apontou diferenças entre os tecidos fresco e descelularizado. Conclusão: A descelularização reduziu a concentração de células bem como os componentes da matriz extracelular sem afetar suas propriedades biomecânicas.
Assuntos
Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Pericárdio/citologia , Dodecilsulfato de Sódio/farmacologia , Tensoativos/farmacologia , Separação Celular/métodos , Engenharia Tecidual/métodos , Pericárdio/efeitos dos fármacos , Fenômenos Biomecânicos , Medicina Regenerativa , Alicerces TeciduaisRESUMO
The aim of the study was to assess the effect of sitagliptin addition on the epicardial adipose tissue (EAT) thickness in subjects with type 2 diabetes mellitus inadequately controlled on metformin monotherapy. This was a 24-week interventional pilot study in 26 consecutive type 2 diabetic patients, 14 females and 12 males average age of 43.8 ± 9.0 years, with Hemoglobin A1c (HbA1c) ≥ 7% on metformin monotherapy. Subjects who met the inclusion criteria were added on sitagliptin and started on sitagliptin/metformin combination at the dosage of 50 mg/1000 mg twice daily. EAT and visceral and total body fat were measured, respectively, with echocardiography and bioelectrical impedance analysis at baseline and after 24 weeks of sitagliptin/metformin treatment in each subject. HbA1c and plasma lipids were also measured. EAT decreased significantly from 9.98 ± 2.63 to 8.10 ± 2.11 mm, p = 0.001, accounting for a percentage of reduction (∆%) of -15% after 24 weeks of sitagliptin addition, whereas total body fat percentage, visceral fat, and body mass index (BMI), decreased by 8, 12, and 7%, respectively (p = 0.001 for all). After 6 month, EAT ∆% was significantly correlated with ∆% of visceral fat (r = 0.456; p = 0.01), whereas no correlation with either BMI ∆% (r = 0.292; p = 0.147) or HbA1c ∆% was found. The addition of Sitagliptin produced a significant and rapid reduction of EAT, marker of organ-specific visceral fat, in overweight/obese individuals with type 2 diabetes inadequately controlled on metformin monotherapy. EAT as measured with ultrasound can serve as no invasive and accurate marker of visceral fat changes during pharmaceutical interventions targeting the fat.