VPA/PLGA microfibers produced by coaxial electrospinning for the treatment of central nervous system injury

The central nervous system shows limited regenerative capacity after injury. Spinal cord injury (SCI) is a devastating traumatic injury resulting in loss of sensory, motor, and autonomic function distal from the level of injury. An appropriate combination of biomaterials and bioactive substances is currently thought to be a promising approach to treat this condition. Systemic administration of valproic acid (VPA) has been previously shown to promote functional recovery in animal models of SCI. In this study, VPA was encapsulated in poly(lactic-co-glycolic acid) (PLGA) microfibers by the coaxial electrospinning technique. Fibers showed continuous and cylindrical morphology, randomly oriented fibers, and compatible morphological and mechanical characteristics for application in SCI. Drug-release analysis indicated a rapid release of VPA during the first day of the in vitro test. The coaxial fibers containing VPA supported adhesion, viability, and proliferation of PC12 cells. In addition, the VPA/PLGA microfibers induced the reduction of PC12 cell viability, as has already been described in the literature. The biomaterials were implanted in rats after SCI. The groups that received the implants did not show increased functional recovery or tissue regeneration compared to the control. These results indicated the cytocompatibility of the VPA/PLGA core-shell microfibers and that it may be a promising approach to treat SCI when combined with other strategies.

Compromiso cardiovascular en el síndrome de Marfan: reporte de caso / Cardiovascular compromise in Marfan syndrome: case report

El Síndrome de Marfan es una enfermedad del tejido conectivo causada por mutaciones en el gen FBN1, mismo que codifica la fibrilina-1, glucoproteína fundamental del componente de las microfibrillas. Entre las manifestaciones clínicas, la afectación cardiovascular merece una consideración especial, debido a su pronóstico. Se presenta un varón de 40 años quien acude al Instituto Nacional del Tórax por un cuadro clínico de 2 años de evolución caracterizado por clínica de insuficiencia cardiaca descompensada, insuficiencia aortica y criterios colagenopatía subyacente, ante lo cual tras los estudios de gabinete y el uso de los criterios pertinentes (Ghent modificados) se llega al diagnóstico de Síndrome de Marfan. La supervivencia de estos pacientes depende del diagnóstico temprano evitando las complicaciones que en su mayoría son mortales, el uso de los scores es de ayuda y la intervención oportuna lleva a un mejor pronóstico de vida y evita los procedimientos invasivos y por ende demás complicaciones

Marfan syndrome is a connective tissue disease caused by mutations in the FBN1 gene, which encodes fibrillin-1, a fundamental glycoprotein of the microfibril component. Among the clinical manifestations, cardiovascular involvement deserves special consideration, due to its prognosis. We present a 40-year-old man who came to the National Thorax Institute for a clinical picture of 2 years of evolution characterized by symptoms of decompensated heart failure, aortic insufficiency and underlying collagenous criteria, before which, after cabinet studies and the use of the relevant criteria (modified Ghent) leads to the diagnosis of Marfan Syndrome. The survival of these patients depends on early diagnosis, avoiding complications that are mostly fatal, the use of scores is helpful and timely intervention leads to a better prognosis for life and avoids invasive procedures and therefore other complications.

The microfibril-elastin fiber system distribution in left atrioventricular valve of the rat / Distribución del sistema de microfibrillas y fibras de elastina en la valva atrioventricular izquierda de la rata

The microfibril-elastin fiber system, an important constituent of the extracellular matrix, was studied in the rat left atrioventricular valve to investigate the interrelationship of oxytalan, elaunin and elastic fibers in left atrioventricular valve morphology. The elastin fibers forms continuous bundles observed along the length of the valve in atrial and ventricular layers and oriented parallel to endothelium. The elaunin and oxytalan fibers are distributed in the thickest fiber bundles along the length of the valve. The thinner fibers which radiated towards both the atrial and spongiosa layers, either as isolated or arborescent fiber bundles were identified as oxytalan fibers. With transmission electron microscopy elastic fibers were seen mainly in the atrial layer. The spongiosa layer was composed of elaunin and oxytalan fibers and ventricular layer showed elaunin fibers arranged in continuous bundles parallel to the endothelium. Both fibrillin and elastin were seen and identified by immunocytochemistry with colloidal gold in the left atrioventricular valve spongiosa and atrial layers. These observations allow us to suggest that the microfibril-elastin fiber system plays a role in the mechanical protection and maintenance of the integrity of the rat left atrioventricular valve.

Fue estudiado el sistema de fibras microfibrillas-elastina, un componente importante de la matriz extracelular, en la valva atrioventricular izquierda de rata, con la finalidad de investigar la interrelación de oxitalán, elaunin y fibras elásticas en la morfología de dicha valva. Las fibras de elastina forman paquetes continuos a lo largo de la valva en las capas atriales y ventriculares, orientadas paralelamente al endotelio. Las fibras de elaunin y oxitalán se distribuyen en haces de fibras más gruesas a lo largo de la valva. Las fibras más delgadas, las cuales se irradiaban hacia las capas atrial y esponjosa, ya sea como haces de fibras aisladas o arborescentes, fueron identificadas como fibras oxitalán. En la capa atrial a través de microscopía electrónica de transmisión se observaron principalmente fibras elásticas. La capa esponjosa estaba compuesta por fibras de elaunin y oxitalán; la capa ventricular mostró fibras de elaunin dispuestas en haces continuos paralelos al endotelio. Tanto fibrilina y elastina se observaron e identificaron por inmunocitoquímica con oro coloidal en las capas esponjosa y atrial de la valva atrioventricular izquierda. Estas observaciones nos permiten sugerir que el sistema de fibras de elastina-microfibrillas tienen participación en la protección mecánica y la mantención de la integridad de la valva atrioventricular izquierda en la rata.

Structural characterization and distribution of elastic system fibers in the human prostate and some prostatic lesions

Prostatic disorders are accompanied by extensive but poorly understood modifications of the cells and surrounding extracellular matrix. In this study, we examined the distribution of the elastic system fibers in prostatic disorders compared to normal tissue. Sections of prostatic transurethral resections and/or radical prostatectomies were examined after staining with hematoxylin-eosin plus fluorescence microscopy and after Weigert's staining for elastic fibers. Transmission electron microscopy was used to examine the ultrastructure of tissues from radical prostatectomy. A concentric fibrous extracellular matrix and smooth muscle cells were observed surrounding normal acini. The elastic fibers were thin and inconspicuous. In benign prostatic hyperplasia (BPH) the elastic components were of variable thickness and formed a three-dimensional network at the base of the epithelium. Conversely, increased variability in the elastic fiber distribution was observed in adenocarcinomas, depending on the tumor grade. In adenocarcinomas with little differentiation, in some hyperplasic acini, and in the stroma adjacent to tumoral mass, ruptured and residual elastic fibers indicative of matrix degradation or remodeling were seen. In more undifferentiated tumors, a pre-elastic network, perhaps indicative of a new extracellular matrix microenvironment was seen. These results indicate that prostate cancer cell invasion involves extensive remodeling of the fibers of the elastic system.

Estudo histoquímico de fibras oxitalânicas no ligamento periodontal de ratos normais e submetidos a forças mecânicas excessivas / Histochemical study of oxytalan fibers in the normal and repaired periodontal ligament of rats submitted to an excessive mechanical force

Os incisivos inferiores de sete ratos foram comprimidos um contra o outro por 7 dias para detectar a fibra oxitalânica na reparaçäo do ligamento periodontal. Retirados os aparelhos, três animais foram sacrificados imediatamente e os outros em 7, 14, 28 e 52 dias. Foi demonstrado, por histoquímica, que a força mecânica empregada promoveu a degeneraçäo do ligamento periodontal. As fibras oxitalânicas apresentavam-se aumentadas no período de reparaçäo, principalmente após 28 dias. Portanto, essas fibras podem ter um importante papel no suporte do ligamento periodontal normal em em reparaçäo

Avaliaçäo histológica e molecular dos grandes vasos de base em portadores de valva aórtica bicúspide / Histologic and molecular evaluation of the great vessels in patients with bicuspid aortic valve disease

Esta investigaçäo avaliou, através de microscopia ótica, as alterações histológicas nos grandes vasos da base em portadores de valva aórtica bicúspide (VAB) e valva aórtica pulmonar (AP) de 20 portadores de VAB, 11 portadores de VAT e 21 espécimens de indivíduos sem doença cardíaca. As alterações histológicas foram classificadas de 1 a 3 de acordo com sua intensidade. Na AA, a necrose cística da média (p<0,0001), a fragmentaçäo elástica (p=0,0020) e a alteraçäo na orientaçäo das células musculares lisas (p=0,0017) foram significativamente mais intensas (moderadas a graves) nos portadores VAB. Na AP, essas mesmas alterações histológicas também foram mais intensas no grupo VAB (p<0,0001,p=0,0304 e p=0,0420, respectivamente). Posteriormente, empregou-se imunofluorescência indireta e análise computadorizada das imagens para a quantificaçäo de fibrilina-1 e elastina na camada média dos grandes vasos, expressas como densidade óptica integrada média (DOI). Foram avaliados espécimens de 24 portadores aórticos e 6 de artéria pulmonar provenientes de indivíduos sem doença cardíaca. Os portadores de VAB apresentaram reduçäo significativa de fibrilina-1 na AA (p=0,0017). Näo foi observada diferença significativa na quantidade de elastina na AA (p=0,09597) e AP (p=0,09374), bem como associaçäo entre a reduçäo de fibrilina-1 e a idade dos portadores de VAB (p=0,887). Conclui-se que os portadores de VAB apresentaram alterações hsitológicas mais intensas nos vasos da base que os portadores de VAT, principalmente necrose cística da camada média. Na aorta ascendente, essas alterações histológicas podem estar associadas à reduçäo significativa de fibrilina-1 e näo associadas à idade. A reduçäo de fibrilina-1 ocorreu, provavelmente, na matriz extracelular