Discriminating aspects of global metabolism of neonatal cardiomyocytes from wild type and KO-CSRP3 rats using proton magnetic resonance spectroscopy of culture media samples.

Knockout of multifunction gene cysteine- and glycine-rich protein 3 (CSRP3) in cardiomyocytes (CMs) of mice leads to heart dilation, severely affecting its functions. In humans, CSRP3 mutations are associated with hypertrophic (HCM) and dilated cardiomyopathy (DCM). The absence of the CSRP3 expression produces unknown effects on in vitro neonatal CMs' metabolism. The metabolome changes in culture media conditioned by CSRP3 knockout (KO-CSRP3), and wild type (WT) neonatal cardiomyocytes were investigated under untreated or after metabolic challenging conditions produced by isoproterenol (ISO) stimulation, by in vitro high-resolution proton magnetic resonance spectroscopy (1H-MRS)-based metabolomics. Metabolic differences between neonatal KO-CSRP3 and WT rats' CMs were identified. After 72 h of culture, ISO administration was associated with increased CMs' energy requirements and increased levels of threonine, alanine, and 3-hydroxybutyrate in both neonatal KO-CSRP3 and WT CMs conditioned media. When compared with KO-CSRP3, culture media derived from WT cells presented higher lactate concentrations either under basal or ISO-stimulated conditions. The higher activity of ketogenic biochemical pathways met the elevated energy requirements of the contractile cells. Both cells are considered phenotypically indistinguishable in the neonatal period of animal lives, but the observed metabolic stress responses of KO-CSRP3 and WT CMs to ISO were different. KO-CSRP3 CMs produced less lactate than WT CMs in both basal and stimulated conditions. Mainly, ISO-stimulated conditions produced evidence for lactate overload within KO-CSRP3 CMs, while WT CMs succeeded to manage the metabolic stress. Thus, 1H-MRS-based metabolomics was suitable to identify early inefficient energetic metabolism in neonatal KO-CSRP3 CMs. These results may reflect an apparent lower lactate transport and consumption, in association with protein catabolism.

Impaired vascular smooth muscle cell force-generating capacity and phenotypic deregulation in Marfan Syndrome mice.

Mechanisms whereby fibrillin-1 mutations determine thoracic aorta aneurysms/dissections (TAAD) in Marfan Syndrome (MFS) are unclear. Most aortic aneurysms evolve from mechanosignaling deregulation, converging to impaired vascular smooth muscle cell (VSMC) force-generating capacity accompanied by synthetic phenotype switch. However, little is known on VSMC mechanoresponses in MFS pathophysiology. Here, we investigated traction force-generating capacity in aortic VSMC cultured from 3-month old mg∆lpn MFS mice, together with morpho-functional and proteomic data. Cultured MFS-VSMC depicted marked phenotype changes vs. wild-type (WT) VSMC, with overexpressed cell proliferation markers but either lower (calponin-1) or higher (SM alpha-actin and SM22) differentiation marker expression. In parallel, the increased cell area and its complex non-fusiform shape suggested possible transition towards a mesenchymal-like phenotype, confirmed through several markers (e.g. N-cadherin, Slug). MFS-VSMC proteomic profile diverged from that of WT-VSMC particularly regarding lower expression of actin cytoskeleton-regulatory proteins. Accordingly, MFS-VSMC displayed lower traction force-generating capacity and impaired contractile moment at physiological substrate stiffness, and markedly attenuated traction force responses to enhanced substrate rigidity. Such impaired mechanoresponses correlated with decreased number, altered morphology and delocalization of focal adhesions, as well as disorganized actin stress fiber network vs. WT-VSMC. In VSMC cultured from 6-month-old mice, phenotype changes were attenuated and both WT-VSMC and MFS-VSMC generated less traction force, presumably involving VSMC aging, but without evident senescence. In summary, MFS-VSMC display impaired force-generating capacity accompanying a mesenchymal-like phenotype switch connected to impaired cytoskeleton/focal adhesion organization. Thus, MFS-associated TAAD involves mechanoresponse impairment common to other TAAD types, but through distinct mechanisms.

Quantification of alignment of vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) are essential components that keep the tonus of the arterial network, which is the channel used to conduct the blood from the heart to the peripheral areas of the body. It is known that mechanical and architectural changes in VSMCs may lead to functional modifications in the cardiovascular system; therefore, the quantitative characterization of these changes can help to elucidate questions that remain unclear in pathological situations, such as hypertension, vasospasm, vascular hypertrophy, and atherosclerosis. In this work, we have developed a new framework of image processing using the Sobel operator, associated with statistical analysis, to determine the degree of local alignment of actin filaments, which we found to be directly related with the distensibility of the arterial wall. We have also compared these results with the rigidity of the cytoskeleton of VSMCs. The results suggest that the alignment degree increases from peripheral arteries, such as carotid and femoral, to central arteries, as well coronary and thoracic aorta, which can indicate that the level of local alignment of the actin fibers in VSMCs is related with the mechanical behavior of the arterial wall. © 2018 International Society for Advancement of Cytometry.

Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy.

Radiation retinopathy (RR) is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab). One must be aware of distant side effects after intravitreal injections.

Frequência etiológica da hipertensão pulmonar em ambulatório de referência na Bahia / Etiological frequency of pulmonary hypertension in a reference outpatient clinic in Bahia, Brazil / Frecuencia etiológica de la hipertensión pulmonar en un ambulatorio de referencia en Bahia

Fundamento: A hipertensão pulmonar (HP) resulta de diversas etiologias com possíveis influências geográficas, porém poucos trabalhos descrevem a frequência etiológica da HP, especialmente em nosso meio. Não está claro se existe associação entre etiologia e nível de pressão pulmonar ou intensidade da sintomatologia. Objetivo: 1) descrever a prevalência etiológica da HP na Bahia; 2) avaliar se a etiologia é fator determinante no nível de pressão pulmonar; 3) avaliar se a etiologia é fator determinante na classe funcional; 4) identificar os demais preditores do nível de pressão pulmonar e da classe funcional. Métodos: Estudo observacional, de corte transversal, em portadores de HP atendidos no Ambulatório Magalhães Neto, entre junho de 2005 e dezembro de 2007. A HP foi definida como pressão sistólica da artéria pulmonar (PSAP) > 40 mmHg pelo ecocardiograma. Pacientes com doença pulmonar obstrutiva crônica ou doença ventricular esquerda não foram incluídos. Resultados: Foram estudados 48 pacientes com PSAP de 86 ± 24 mmHg. Quanto à etiologia, 42 por cento dos pacientes foram classificados como idiopáticos, seguidos de 25 por cento de esquistossomose, 19 por cento de cardiopatia congênita e 10 por cento de embolia pulmonar crônica. O maior tempo de doença prediz pressões mais elevadas em cardiopatas. Indivíduos com esquistossomose tiveram melhor desempenho funcional quando comparados aos demais (456 ± 58 vs. 299 ± 138 metros, p = 0,005). Etiologia esquistossomótica e idades menores apresentam melhor classe funcional. Conclusão: 1) Prevalece a classificação idiopática, sendo a esquistossomose a causa específica mais frequente em nosso meio; 2) pacientes com etiologia esquistossomótica e de idades menores apresentam melhor classe funcional; 3) cardiopatia congênita resulta em maior nível de pressão na artéria pulmonar, provavelmente devido ao maior tempo de doença.

Background: Pulmonary hypertension (PH) results from several etiologies, with possible geographic influences; however, few studies have described the etiological frequency of PH, especially in our country. It is not clear whether there is an association between etiology and pulmonary pressure level or symptom intensity. Objectives: 1) to describe the etiological prevalence of PH in the state of Bahia, Brazil; 2) to evaluate whether the etiology is a determinant factor for the pulmonary pressure level; 3) to evaluate whether the etiology is a determinant factor for functional class; 4) to identify the other predictors of pulmonary pressure level and functional class. Methods: The present was an observational, cross-sectional study that analyzed individuals with PH treated at the Magalhaes Neto Outpatient Clinic, between June 2005 and December 2007. PH was defined as pulmonary artery systolic pressure (PASP) > 40 mmHg measure at the echocardiogram. Patients with chronic obstructive pulmonary disease or ventricular disease were excluded from the study. RESULTS: A total of 48 patients with PASP = 86 ± 24 mmHg were studied. Regarding the etiology, 42 percent of the patients were classified as idiopathic, followed by 25 percent as schistosomatic, 19 percent as congenital cardiopathy and 10 percent of chronic pulmonary embolism. A longer time of disease predicted higher pressures in patients with cardiopathy. Individuals with schistosomiasis had the best functional performance when compared to the others (456 ± 58 vs. 299 ± 138 meters, p=0.005). The schistosomatic etiology and younger age presented better functional class. Conclusions: 1) the idiopathic classification is the most prevalent, with schistosomiasis being the most frequent specific cause in our country; 2) patients with schistosomatic etiology and of younger age present better functional class. 3) the congenital cardiopathy results in a higher pressure level in the pulmonary artery, ...

Fundamento: La hipertensión pulmonar (HP) es la resultante de diversas etiologías con posibles influencias geográficas, pero pocos trabajos describen la frecuencia etiológica de la HP, especialmente en nuestro medio. No está claro si existe asociación entre etiología y nivel de presión pulmonar o intensidad de la sintomatología. Objetivo: (1) Describir la prevalencia etiológica de la HP en Bahía; (2) evaluar si la etiología es factor determinante en el nivel de presión pulmonar; (3) evaluar si la etiología es factor determinante en la clase funcional; (4) identificar los demás predictores del nivel de presión pulmonar y de la clase funcional. Métodos: Estudio observacional, de corte transversal, en portadores de HP atendidos en el Ambulatorio Magalhães Neto, entre junio de 2005 y diciembre de 2007. La HP fue definida como presión sistólica de la arteria pulmonar (PSAP) > 40 mmHg por ecocardiograma. No se incluyó a los pacientes con enfermedad pulmonar obstructiva crónica o deterioro del ventrículo izquierdo. Resultados: Se estudiaron a 48 pacientes con PSAP de 86±24 mmHg. En cuanto a la etiología, el 42 por ciento de los pacientes fue clasificado como idiopático, seguido del 25 por ciento por esquistosomiasis, el 19 por ciento por cardiopatía congénita y el 10 por ciento por embolia pulmonar crónica. El mayor tiempo de enfermedad predice presiones más elevadas en cardiópatas. Los individuos con esquistosomiasis tuvieron mejor desempeño funcional cuando se los comparó con los demás (456±58 vs. 299±138 metros, P = 0,005). Pacientes con etiología esquistosomiásica y edades más jóvenes cursan con mejor capacidad funcional. Conclusión: (1) Prevalece la clasificación idiopática, y la esquistosomiasis constituye la causa específica más frecuente en nuestro medio; (2) pacientes con etiología esquistosomiásica y de edades menores presentan mejor clase funcional; (3) la cardiopatía congénita resulta en mayor nivel de presión en la arteria pulmonar, ...

Etiological frequency of pulmonary hypertension in a reference outpatient clinic in Bahia, Brazil.

BACKGROUND: Pulmonary hypertension (PH) results from several etiologies, with possible geographic influences; however, few studies have described the etiological frequency of PH, especially in our country. It is not clear whether there is an association between etiology and pulmonary pressure level or symptom intensity. OBJECTIVES: 1) to describe the etiological prevalence of PH in the state of Bahia, Brazil; 2) to evaluate whether the etiology is a determinant factor for the pulmonary pressure level; 3) to evaluate whether the etiology is a determinant factor for functional class; 4) to identify the other predictors of pulmonary pressure level and functional class. METHODS: The present was an observational, cross-sectional study that analyzed individuals with PH treated at the Magalhaes Neto Outpatient Clinic, between June 2005 and December 2007. PH was defined as pulmonary artery systolic pressure (PASP) > 40 mmHg measure at the echocardiogram. Patients with chronic obstructive pulmonary disease or ventricular disease were excluded from the study. RESULTS: A total of 48 patients with PASP = 86 +/- 24 mmHg were studied. Regarding the etiology, 42% of the patients were classified as idiopathic, followed by 25% as schistosomatic, 19% as congenital cardiopathy and 10% of chronic pulmonary embolism. A longer time of disease predicted higher pressures in patients with cardiopathy. Individuals with schistosomiasis had the best functional performance when compared to the others (456 +/- 58 vs. 299 +/- 138 meters, p=0.005). The schistosomatic etiology and younger age presented better functional class. CONCLUSIONS: 1) the idiopathic classification is the most prevalent, with schistosomiasis being the most frequent specific cause in our country; 2) patients with schistosomatic etiology and of younger age present better functional class. 3) the congenital cardiopathy results in a higher pressure level in the pulmonary artery, probably due to the longer duration of the disease.