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1.
Front Mol Biosci ; 10: 1100486, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36936993

RESUMO

Introduction: Similar to what it has been reported with preceding viral epidemics (such as MERS, SARS, or influenza), SARS-CoV-2 infection is also affecting the human immunometabolism with long-term consequences. Even with underreporting, an accumulated of almost 650 million people have been infected and 620 million recovered since the start of the pandemic; therefore, the impact of these long-term consequences in the world population could be significant. Recently, the World Health Organization recognized the post-COVID syndrome as a new entity, and guidelines are being established to manage and treat this new condition. However, there is still uncertainty about the molecular mechanisms behind the large number of symptoms reported worldwide. Aims and Methods: In this study we aimed to evaluate the clinical and lipidomic profiles (using non-targeted lipidomics) of recovered patients who had a mild and severe COVID-19 infection (acute phase, first epidemic wave); the assessment was made two years after the initial infection. Results: Fatigue (59%) and musculoskeletal (50%) symptoms as the most relevant and persistent. Functional analyses revealed that sterols, bile acids, isoprenoids, and fatty esters were the predicted metabolic pathways affected in both COVID-19 and post-COVID-19 patients. Principal Component Analysis showed differences between study groups. Several species of phosphatidylcholines and sphingomyelins were identified and expressed in higher levels in post-COVID-19 patients compared to controls. The paired analysis (comparing patients with an active infection and 2 years after recovery) show 170 dysregulated features. The relationship of such metabolic dysregulations with the clinical symptoms, point to the importance of developing diagnostic and therapeuthic markers based on cell signaling pathways.

2.
Appl Opt ; 61(27): 7875-7882, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36255907

RESUMO

A method adding phase-shifting capacity in two mutually perpendicular axes to the Ronchi test is presented in this work. The phase of the object with the position of the reflected ray on the grating was identified and used to solve the equation of reflection in two orthogonal directions. In this manner, the test-surface figure was obtained. The procedure was demonstrated with an inverse qualitative test and a direct, quantitative test. Both tests give results comparable to Fizeau interferometry, with the precision of the order of 25 nm peak to valley. This technique is a good alternative to interferometry because, in addition to its inherent high-resolution, it is possible to obtain the radius of curvature and conic constant, which interferometers, requiring auxiliary optics, cannot provide. This method also has a high dynamic range and is not as susceptible to vibrations or turbulence. The setup can be built with low-cost, readily available components, is easily aligned, uses a white light source, and can be made very lightweight and compact, which makes it ideal for mounting onto existing polishing machines in any optical fabrication workshop, to perform in situ surface metrology.

3.
Zootaxa ; 5214(4): 496-506, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37044893

RESUMO

Larvae of an unidentified Lepidopteran hepialid were found boring stems and crown roots of blackberry (Rubus sp.) in Michoacán, Mexico. In this study, the morphological and molecular identification of larvae and adults of this insect was performed. Preliminary aspects of biology, including information on parasitoids associated to larval stage, are also recorded. A total of 109 larvae of various instars were collected and three were reared to adult. The two females and one male were identified as Phassus huebneri (Geyer) (Lepidoptera: Hepialidae) following morphological characters. This identification was corroborated by comparing the cytochrome oxidase I (COI) barcode of two field-collected larvae (IIAFL1 and IIAFL2) with sequences of Phassus spp. obtained from GenBank. A Neighbor-Joining similarity analysis yielded a phenogram with two subclades. The first subclade grouped the IIAFL1 and IIAFL2 sequences with two other Mexican sequences categorized as P. huebneri, whereas in the second subclade other species belonging to the genus Phassus from Guatemala and Costa Rica were grouped together. Larval development of nine instars took about 14 months. Larvae reached a maximum length of 10 cm. The pupal stage lasted 39-41 days. Each of the two females laid over 1,000 unfertilized eggs within a period of 48 h. Larvae were parasitized by Dinera grisescens Fallen (Diptera: Tachinidae) and another unidentified Dinera sp. This study provides additional evidences on the distribution pattern of P. huebneri in western Mexico and presents the first record of this species feeding on one of the most economically important crops in Mexico.


Assuntos
Dípteros , Lepidópteros , Mariposas , Rubus , Feminino , Masculino , Animais , Mariposas/genética , México , Larva/genética , Biologia
4.
Alerta (San Salvador) ; 4(3): 108-103, jul. 29, 2021. ilus
Artigo em Espanhol | LILACS, BISSAL | ID: biblio-1282080

RESUMO

La intubación submentoniana es útil en procedimientos quirúrgicos en donde la intubación nasotraqueal está contraindicada y la intubación orotraqueal no es ideal debido a la fijación intermaxilar. Este informe describe dos pacientes masculinos que se presentaron al Hospital Nacional Rosales, en el servicio de Cirugía Maxilofacial de El Salvador, con historia de sufrir accidente de tránsito. El primer caso evidenció al examen radiológico fractura simple y desplazada de sínfisis mandibular, fractura simple huesos propios nasales y desviación del tabique nasal. El segundo caso es un paciente con fractura de sínfisis y doble cóndilo mandibular que presentaba imposibilidad a la apertura bucal. A través de la técnica del cirujano maxilofacial Hernández Altemir (España), el tubo endotraqueal atraviesa una incisión extraoral en la región submentoniana del suelo de la boca, para poder practicar reducción abierta de fracturas faciales, logrando adecuada oclusión, con mínimos cuidados posoperatorios y con una cicatriz estética. Al terminar la cirugía, la posición del tubo endotraqueal regresa a su posición original y el paciente evoluciona satisfactoriamente


Submental intubation is useful in surgical procedures where nasotracheal intubation is contraindicated and orotracheal intubation is not ideal due to intermaxillary fixation. This report describes two male patients who presented to the Rosales National Hospital, in the Maxillofacial Surgery service of El Salvador, with a history of suffering a traffic accident. The first case showed a simple and displaced fracture of the mandibular symphysis, simple nasal bone fracture and deviation of the nasal septum on radiological examination. The second case is a patient with a symphysis fracture and a double mandibular condyle that presented an inability to open the mouth. Through the technique of the maxillofacial surgeon Hernández Altemir (Spain), the endotracheal tube passes through an extraoral incision in the submental region of the floor of the mouth, in order to perform open reduction of facial fractures, achieving adequate occlusion, with minimal postoperative care and with an aesthetic scar. At the end of the surgery, the position of the endotracheal tube returns to its original position and the patient evolves satisfactorily


Assuntos
Humanos , Manuseio das Vias Aéreas , Intubação , Traumatismos Maxilofaciais
5.
Blood Adv ; 5(7): 1977-1990, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33843988

RESUMO

The production of in vitro-derived platelets has great potential for transfusion medicine. Here, we build on our experience in the forward programming (FoP) of human pluripotent stem cells (hPSCs) to megakaryocytes (MKs) and address several aspects of the complex challenges to bring this technology to the bedside. We first identify clinical-grade hPSC lines that generate MKs efficiently. We design a bespoke media to maximize both production and maturity of MKs and improve platelet output. Crucially, we transition the lentiviral-based FoP of hPSCs to a nonviral inducible system. We also show how small molecules promote a definitive hematopoiesis phenotype during the differentiation process, thereby increasing the quality of the final product. Finally, we generate platelets using a bioreactor designed to reproduce the physical cues that promote platelet production in the bone marrow. We show that these platelets are able to contribute to both thrombus formation in vitro and have a hemostatic effect in thrombocytopenic mice in vivo.


Assuntos
Megacariócitos , Células-Tronco Pluripotentes , Animais , Reatores Biológicos , Plaquetas , Camundongos , Trombopoese
6.
Alerta (San Salvador) ; 3(2): 50-56, ago.12, 2020. ilus
Artigo em Espanhol | LILACS, BISSAL | ID: biblio-1117075

RESUMO

El ameloblastoma es un tumor de origen odontogénico, con un comportamiento altamente agresivo. Estos pueden ser sólidos o multiquístico, uniquístico, periférico o extraóseo y desmoplásico. Dentro de las alternativas de manejo, se pre!ere un tratamiento que garantice seguridad para el paciente, como la resección radical o en bloque. Cada vez se utiliza menos el tratamiento conservador debido a una alta tasa de recidiva. Se presenta un caso de paciente masculino de 13 años, que fue visto en el Hospital Nacional Rosales, en el servicio de cirugía maxilofacial de El Salvador, por una in"amación en la región posterior mandibular en el lado izquierdo de la cara. El examen intraoral reveló leve extrusión y movilidad grado 2 de pieza 36 y 37. Los análisis clínicos, radiográ!cos e histopatológicos con!rmaron el diagnóstico de ameloblastoma. Fue tratado de forma conservadora mediante curetaje, ostectomía periférica y marsupialización. Se tuvo buen resultado estético y funcional, con un adecuado proceso de cicatrización y regeneración ósea !siológica, sin la necesidad de materiales de injerto óseo. Después de un seguimiento de 8 años, no hubo evidencia de recurrencia. Esta decisión depende de la variante clínica, la extensión tumoral y el adecuado control postoperatorio del paciente


Ameloblastoma is a tumor of odontogenic origin and highly aggressive. Four clinical variants of ameloblastomas are known: solid or multicystic, unicystic, peripheral or extra- osseous and desmoplastic. Among the treatment alternatives, a treatment that ensures a high percentage of successful prognosis for the patient is preferred, being the most indicated, radical resection, or in bulk. Conservative treatment is less used due to its recurrence rate. A clinical case of a 13-year-old male patient is presented to the Rosales National Hospital, in the Maxillofacial Surgery service of El Salvador with an in"ammation in the posterior mandibular region on the left side of the face. Intraoral examination revealed mild extrusion and mobility grade 2 of parts 37 and 36. Clinical, radiographic and histopathological analyzes con!rmed the diagnosis of Ameloblastoma. It was treated conservatively by curettage, peripheral osteotomy and marsupialization. A good aesthetic and functional result was obtained, applying the conservative technique, with an adequate healing and physiological bone regeneration, without recourse to bone grafting materials. After an 8-year follow-up no evidence was found of tumor recurrence. The decision regarding the type of treatment to be applied, depends on the clinical variables, tumor extension and adequate postoperative monitoring and care of the patient


Assuntos
Humanos , Cirurgia Bucal , Ameloblastoma , Neoplasias , El Salvador
7.
Med Teach ; 42(8): 929-936, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32503386

RESUMO

Context: Social accountability of medical schools has emerged as a standard of excellence in medical education during the last decade. However, the lack of valid and reliable instruments to estimate social accountability has limited the possibility of measuring the impact that medical schools have in society. Our aim was to develop an instrument and validate its use for assessing social accountability in Latin American countries.Methods: We used a three-phase mixed methods research design to develop, validate and estimate social accountability in a diverse convenient sample of 49 medical schools from 16 Latin American countries. We used a qualitative framework approach and a Delphi consensus method to design an instrument with high content validity. Finally, we assessed the psychometric properties of the instrument.Results: The Social Accountability Instrument for Latin America (SAIL) contained 21 items in four domains: mission and quality improvement, public policy, community engagement, and professional integrity. Its reliability index, estimated using Cronbach's alpha, was very high (0.96). Most of the medical schools that had ranked over the 80th percentile on traditional national academic estimates did not reach the 80th percentile using SAIL.Conclusions: There are validity arguments (content and reliability) to support the measurement of social accountability using the SAIL instrument. Its application showed that it provides a complementary dimension to that traditionally obtained when estimating quality in medical schools.


Assuntos
Educação Médica , Faculdades de Medicina , Humanos , América Latina , Reprodutibilidade dos Testes , Responsabilidade Social
8.
Biomaterials ; 243: 119921, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32172030

RESUMO

In vitro tissue engineered models are poised to have significant impact on disease modeling and preclinical drug development. Reliable methods to induce microvascular networks in such microphysiological systems are needed to improve the size and physiological function of these models. By systematically engineering several physical and biomolecular properties of the cellular microenvironment (including crosslinking density, polymer density, adhesion ligand concentration, and degradability), we establish design principles that describe how synthetic matrix properties influence vascular morphogenesis in modular and tunable hydrogels based on commercial 8-arm poly (ethylene glycol) (PEG8a) macromers. We apply these design principles to generate endothelial networks that exhibit consistent morphology throughout depths of hydrogel greater than 1 mm. These PEG8a-based hydrogels have relatively high volumetric swelling ratios (>1.5), which limits their utility in confined environments such as microfluidic devices. To overcome this limitation, we mitigate swelling by incorporating a highly functional PEG-grafted alpha-helical poly (propargyl-l-glutamate) (PPLGgPEG) macromer along with the canonical 8-arm PEG8a macromer in gel formation. This hydrogel platform supports enhanced endothelial morphogenesis in neutral-swelling environments. Finally, we incorporate PEG8a-PPLGgPEG gels into microfluidic devices and demonstrate improved diffusion kinetics and microvascular network formation in situ compared to PEG8a-based gels.


Assuntos
Materiais Biocompatíveis , Hidrogéis , Polietilenoglicóis , Engenharia Tecidual
9.
Medicina (B Aires) ; 79 Suppl 3: 66-70, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31603847

RESUMO

The two main demyelinating diseases in children are reviewed. Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). For its physiopathological characteristics, probable etiologies, clinical manifestations, diagnosis, treatment, prognosis, evolution, as well as atypical alterations that complicate its diagnosis, the smaller the child is, more study is needed before reaching the diagnosis. The International Study Group of Multiple Pediatric Sclerosis, published the operating definitions for demyelinating diseases acquired from the central nervous system in children: the ADEM is monophasic, polysymptomatic and with encephalopathy. Its duration is up to 3 months, with fluctuating symptoms and magnetic resonance findings. MS is an isolated monofocal or polyfocal syndrome, without encephalopathy. Currently, two different and distinguishable diseases are considered from the onset of symptoms.


Se revisan dos de las principales enfermedades desmielinizantes en niños, la encefalomielitis aguda diseminada (EAD) y la esclerosis múltiple (EM). Por sus características fisiopatológicas, etiologías probables, manifestaciones clínicas, diagnóstico, tratamiento, pronóstico, evolución, así como alteraciones atípicas que complican su diagnóstico; cuanto más pequeño es el paciente se necesita estudiar más, antes de llegar al diagnóstico. El Grupo Internacional de Estudio de Esclerosis Múltiple Pediátrica publicó las definiciones operativas para enfermedades desmielinizantes adquiridas del sistema nervioso central: la EAD es monofásica, polisintomática y con encefalopatía. Su duración es de hasta 3 meses, con síntomas fluctuantes y hallazgos en resonancia magnética. La EM se define como síndrome aislado monofocal o polifocal, sin encefalopatía. Actualmente se consideran dos enfermedades diferentes y distinguibles desde el inicio de los síntomas.


Assuntos
Encefalomielite Aguda Disseminada/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Criança , Quimioterapia Combinada , Encefalomielite Aguda Disseminada/tratamento farmacológico , Humanos , Imunoterapia , Imageamento por Ressonância Magnética , Esclerose Múltipla/tratamento farmacológico , Esteroides/uso terapêutico , Síndrome
10.
Medicina (B.Aires) ; 79(supl.3): 66-70, set. 2019. ilus
Artigo em Espanhol | LILACS | ID: biblio-1040553

RESUMO

Se revisan dos de las principales enfermedades desmielinizantes en niños, la encefalomielitis aguda diseminada (EAD) y la esclerosis múltiple (EM). Por sus características fisiopatológicas, etiologías probables, manifestaciones clínicas, diagnóstico, tratamiento, pronóstico, evolución, así como alteraciones atípicas que complican su diagnóstico; cuanto más pequeño es el paciente se necesita estudiar más, antes de llegar al diagnóstico. El Grupo Internacional de Estudio de Esclerosis Múltiple Pediátrica publicó las definiciones operativas para enfermedades desmielinizantes adquiridas del sistema nervioso central: la EAD es monofásica, polisintomática y con encefalopatía. Su duración es de hasta 3 meses, con síntomas fluctuantes y hallazgos en resonancia magnética. La EM se define como síndrome aislado monofocal o polifocal, sin encefalopatía. Actualmente se consideran dos enfermedades diferentes y distinguibles desde el inicio de los síntomas.


The two main demyelinating diseases in children are reviewed. Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). For its physiopathological characteristics, probable etiologies, clinical manifestations, diagnosis, treatment, prognosis, evolution, as well as atypical alterations that complicate its diagnosis, the smaller the child is, more study is needed before reaching the diagnosis. The International Study Group of Multiple Pediatric Sclerosis, published the operating definitions for demyelinating diseases acquired from the central nervous system in children: the ADEM is monophasic, polysymptomatic and with encephalopathy. Its duration is up to 3 months, with fluctuating symptoms and magnetic resonance findings. MS is an isolated monofocal or polyfocal syndrome, without encephalopathy. Currently, two different and distinguishable diseases are considered from the onset of symptoms.


Assuntos
Humanos , Criança , Encefalomielite Aguda Disseminada/diagnóstico por imagem , Esclerose Múltipla/diagnóstico por imagem , Esteroides/uso terapêutico , Síndrome , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Quimioterapia Combinada , Encefalomielite Aguda Disseminada/tratamento farmacológico , Imunoterapia , Esclerose Múltipla/tratamento farmacológico
11.
Medicina (B Aires) ; 78 Suppl 2: 2-5, 2018.
Artigo em Espanhol | MEDLINE | ID: mdl-30199357

RESUMO

West syndrome or infantile spasms is an epileptic encephalopathy, classified as generalized epilepsies and syndromes. There are multiple reports of the evolution from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is determined. It has been reported that they may be only an epileptic entity age dependent that it would be in relation to the degree of brain immaturity. In this retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us suppose that the low incidence could be related to the use of this drug. Given that vigabatrin has a gabaergic action and increased levels of ACTH, may explain this relationship but this must be confirmed with the best knowledge of the intimate mechanisms of these serious epileptic encephalopathies.


Assuntos
Síndrome de Lennox-Gastaut/etiologia , Espasmos Infantis/complicações , Anticonvulsivantes/uso terapêutico , Progressão da Doença , Eletroencefalografia , Feminino , Humanos , Lactente , Síndrome de Lennox-Gastaut/diagnóstico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Imageamento por Ressonância Magnética , Metilprednisolona/uso terapêutico , Estudos Retrospectivos , Espasmos Infantis/diagnóstico , Espasmos Infantis/tratamento farmacológico , Síndrome , Vigabatrina/uso terapêutico
12.
Medicina (B.Aires) ; 78(supl.2): 2-5, set. 2018. ilus, tab
Artigo em Espanhol | LILACS | ID: biblio-955006

RESUMO

El síndrome de West o espasmos infantiles, es una encefalopatía epiléptica clasificada como epilepsias y síndromes generalizados. Hay múltiples informes de la evolución de síndrome de West a síndrome de Lennox-Gastaut de un 25 hasta 60%, sin reconocerse una causa específica. Se ha comunicado que pueden ser solo una entidad epiléptica dependiente de la edad y que estaría en relación con el grado de inmadurez cerebral. En esta revisión retrospectiva de 130 casos de espasmos infantiles, solo 14 (10.7%) evolucionaron a Lennox-Gastaut. El haber recibido en todos los casos vigabatrina como tratamiento nos hace suponer que la baja incidencia podría estar relacionada con el uso de este fármaco. Dado que la vigabatrina tiene una acción gabaérgica y aumenta los niveles de ACTH podría explicar esta relación, pero esto deberá confirmarse con el mejor conocimiento de los mecanismos íntimos de estas graves encefalopatías.


West syndrome or infantile spasms is an epileptic encephalopathy, classified as generalized epilepsies and syndromes. There are multiple reports of the evolution from West to Lennox-Gastaut syndrome of 25 up to 60%, without a specific cause is determined. It has been reported that they may be only an epileptic entity age dependent that it would be in relation to the degree of brain immaturity. In this retrospective review of 130 cases of West syndrome, only 14 (10.7%) evolved to Lennox-Gastaut. Having received in all cases vigabatrin as a treatment, makes us suppose that the low incidence could be related to the use of this drug. Given that vigabatrin has a gabaergic action and increased levels of ACTH, may explain this relationship but this must be confirmed with the best knowledge of the intimate mechanisms of these serious epileptic encephalopathies.


Assuntos
Humanos , Feminino , Lactente , Espasmos Infantis/complicações , Síndrome de Lennox-Gastaut/etiologia , Espasmos Infantis/diagnóstico , Espasmos Infantis/tratamento farmacológico , Síndrome , Metilprednisolona/uso terapêutico , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Progressão da Doença , Vigabatrina/uso terapêutico , Eletroencefalografia , Síndrome de Lennox-Gastaut/diagnóstico , Síndrome de Lennox-Gastaut/tratamento farmacológico , Anticonvulsivantes/uso terapêutico
13.
Sci Rep ; 8(1): 8015, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29789564

RESUMO

Microphysiological systems (MPS), consisting of tissue constructs, biomaterials, and culture media, aim to recapitulate relevant organ functions in vitro. MPS components are housed in fluidic hardware with operational protocols, such as periodic complete media replacement. Such batch-like operations provide relevant nutrients and remove waste products but also reset cell-secreted mediators (e.g. cytokines, hormones) and potentially limit exposure to drugs (and metabolites). While each component plays an essential role for tissue functionality, MPS-specific nutrient needs are not yet well-characterized nor utilized to operate MPSs at more physiologically-relevant conditions. MPS-specific nutrient needs for gut (immortalized cancer cells), liver (human primary hepatocytes) and cardiac (iPSC-derived cardiomyocytes) MPSs were experimentally quantified. In a long-term study of the gut MPS (10 days), this knowledge was used to design operational protocols to maintain glucose and lactate at desired levels. This quasi-steady state operation was experimentally validated by monitoring glucose and lactate as well as MPS functionality. In a theoretical study, nutrient needs of an integrated multi-MPS platform (gut, liver, cardiac MPSs) were computationally simulated to identify long-term quasi-steady state operations. This integrative experimental and computational approach demonstrates the utilization of quantitative multi-scale characterization of MPSs and incorporating MPS-specific information to establish more physiologically-relevant experimental operations.


Assuntos
Técnicas de Cultura de Células/métodos , Metabolismo Energético/fisiologia , Microtecnologia/métodos , Especificidade de Órgãos/fisiologia , Integração de Sistemas , Fenômenos Bioquímicos , Células CACO-2 , Técnicas de Cultura de Células/instrumentação , Células Cultivadas , Simulação por Computador , Meios de Cultura/química , Meios de Cultura/farmacologia , Ecossistema , Glucose/metabolismo , Células HT29 , Humanos , Células-Tronco Pluripotentes Induzidas/fisiologia , Intestinos/citologia , Ácido Láctico/metabolismo , Fígado/citologia , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Microtecnologia/instrumentação , Miócitos Cardíacos/citologia , Biologia de Sistemas
14.
Sci Rep ; 8(1): 4530, 2018 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-29540740

RESUMO

Microphysiological systems (MPSs) are in vitro models that capture facets of in vivo organ function through use of specialized culture microenvironments, including 3D matrices and microperfusion. Here, we report an approach to co-culture multiple different MPSs linked together physiologically on re-useable, open-system microfluidic platforms that are compatible with the quantitative study of a range of compounds, including lipophilic drugs. We describe three different platform designs - "4-way", "7-way", and "10-way" - each accommodating a mixing chamber and up to 4, 7, or 10 MPSs. Platforms accommodate multiple different MPS flow configurations, each with internal re-circulation to enhance molecular exchange, and feature on-board pneumatically-driven pumps with independently programmable flow rates to provide precise control over both intra- and inter-MPS flow partitioning and drug distribution. We first developed a 4-MPS system, showing accurate prediction of secreted liver protein distribution and 2-week maintenance of phenotypic markers. We then developed 7-MPS and 10-MPS platforms, demonstrating reliable, robust operation and maintenance of MPS phenotypic function for 3 weeks (7-way) and 4 weeks (10-way) of continuous interaction, as well as PK analysis of diclofenac metabolism. This study illustrates several generalizable design and operational principles for implementing multi-MPS "physiome-on-a-chip" approaches in drug discovery.


Assuntos
Técnicas de Cocultura/métodos , Diclofenaco/farmacocinética , Dispositivos Lab-On-A-Chip , Fígado/metabolismo , Animais , Avaliação Pré-Clínica de Medicamentos , Humanos , Procedimentos Analíticos em Microchip , Modelos Biológicos , Fenótipo , Ratos
15.
Pediátr. Panamá ; 46(2): 58-62, agosto-septiembre 2017.
Artigo em Espanhol | LILACS | ID: biblio-848276

RESUMO

Las hipersomnias son un grupo de trastornos caracterizados por una somnolencia excesiva durante al menos 1 mes, evidenciada tanto por episodios prolongados de sueño como por episodios de sueño diurno que se producen prácticamente cada día. Se dividen en primarios o centrales, (Hipersomnia idiopática, Narcolepsia y Síndrome de Klein-Levin) y secundarios (Privación del sueño crónica en niños). La somnolencia excesiva debe ser de su ciente gravedad como para provocar alteraciones clínicas significativas o deterioro social, escolar, laboral o de otras áreas importantes de la actividad del individuo; no aparece en el transcurso de otro trastorno del sueño o de otro trastorno mental ni se debe a los efectos fisiológicos directos de una sustancia o de una enfermedad médica. La somnolencia excesiva diurna (SDE) es una manifestación común, se presenta con una frecuencia variable; del 11% en niños hasta el 52,8% en adolescentes. La predominancia es igual en la narcolepsia con o sin cataplejía y en el Síndrome de Kleine-Levin. Su diagnóstico adecuado se basa en la historia clínica y estudios de polisomnografía. Y el tratamiento, ayudará al paciente a mejorar en sus actividades y a elevar su autoestima. La fisiopatología no es clara y su tratamiento va enfocado a disminuir el sueño diurno con fármacos como el Modafinil, Claritromicina o simpaticomiméticos y terapias de apoyo.


Abstract Hypersomnias are a group of disorders characterized by excessive drowsiness for at least 1 month, evidenced by both prolonged episodes of sleep and episodes of daytime sleep that occur almost every day. They are divided into primary or central, (idiopathic hypersomnia, Narcolepsy and Klein-Levin Syndrome) and secondary (Deprivation of chronic sleep in children). Excessive drowsiness should be of sufficient severity to cause significant cant clinical alterations or social, school, work or other important areas of the individual's activity; which does not appear in the course of another sleep disorder or other mental disorder, nor is it due to the direct physiological effects of substances or medical illness. Excessive daytime sleepiness (EDS) is a common manifestation; it occurs with a variable frequency; From 11% in children to 52.8% in adolescents. The predominance is the same in Narcolepsy with or without cataplexy and in Kleine-Levin Syndrome. The adequate diagnosis is based on clinical history and studies of polysomnography. The treatment will help the patient to improve their activities and raise their self-esteem. The pathophysiology is not clear and the treatment is focused on decreasing daytime sleep with drugs such as Modafinil, Clarithromycin or sympathomimetics and supportive therapies.


Assuntos
Pré-Escolar , Criança , Adolescente , Distúrbios do Sono por Sonolência Excessiva , Síndrome de Kleine-Levin , Narcolepsia
16.
Biomaterials ; 130: 90-103, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28371736

RESUMO

Methods to parse paracrine epithelial-stromal communication networks are a vital need in drug development, as disruption of these networks underlies diseases ranging from cancer to endometriosis. Here, we describe a modular, synthetic, and dissolvable extracellular matrix (MSD-ECM) hydrogel that fosters functional 3D epithelial-stromal co-culture, and that can be dissolved on-demand to recover cells and paracrine signaling proteins intact for subsequent analysis. Specifically, synthetic polymer hydrogels, modified with cell-interacting adhesion motifs and crosslinked with peptides that include a substrate for cell-mediated proteolytic remodeling, can be rapidly dissolved by an engineered version of the microbial transpeptidase Sortase A (SrtA) if the crosslinking peptide includes a SrtA substrate motif and a soluble second substrate. SrtA-mediated dissolution affected only 1 of 31 cytokines and growth factors assayed, whereas standard protease degradation methods destroyed about half of these same molecules. Using co-encapsulated endometrial epithelial and stromal cells as one model system, we show that the dynamic cytokine and growth factor response of co-cultures to an inflammatory cue is richer and more nuanced when measured from SrtA-dissolved gel microenvironments than from the culture supernate. This system employs accessible, reproducible reagents and facile protocols; hence, has potential as a tool in identifying and validating therapeutic targets in complex diseases.


Assuntos
Células Epiteliais/citologia , Matriz Extracelular/metabolismo , Sequência de Aminoácidos , Aminoaciltransferases/metabolismo , Proteínas de Bactérias/metabolismo , Comunicação Celular , Linhagem Celular Tumoral , Técnicas de Cocultura , Cisteína Endopeptidases/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Matriz Extracelular/efeitos dos fármacos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-1beta/metabolismo , Cinética , Peptídeos/química , Solubilidade , Células Estromais/citologia , Células Estromais/efeitos dos fármacos
17.
Urol Case Rep ; 10: 4-5, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27800297

RESUMO

There are several benign prostatic pathologies that can clinically mimic a prostate adenocarcinoma. Xanthogranulomatous prostatitis is a benign inflammatory condition of the prostate and a rare entity. A 47-year old male, with 3 years of lower urinary tract symptoms, with a palpable hypogastric tumor, digital rectal examination: solid prostate, of approximately 60 g. Initial PSA was 0.90 ng/mL. He underwent surgical excision of the lower abdominal nodule and prostatectomy. Histopathology showed xanthogranulomatous prostatitis, without malignancy. Xanthogranulomatous prostatitis is an extremely rare entity that can simulate prostate adenocarcinoma, therefore having a correct histopathological diagnosis is essential.

18.
Rev. argent. microbiol ; 47(2): 152-154, June 2015.
Artigo em Inglês | LILACS | ID: biblio-1147634

RESUMO

La cámara de Neubauer es un método ampliamente utilizado para cuantificar suspensiones de esporas. Sin embargo, esta técnica requiere personal entrenado y un tiempo considerable. La espectrofotometría demostró ser un método rápido, simple y preciso para estimar la concentración de esporas de aislados del género Fusarium. En este artículo breve presentamos una fórmula lineal ajustada para relacionar la absorbancia a 530nm con el número de conidios en suspensiones utilizadas en pruebas fitopatológicas


The use of a Neubauer chamber is a broadly employed method when cell suspensions need to be quantified. However, this technique may take a long time and needs trained personnel. Spectrophotometry has proved to be a rapid, simple and accurate method to estimate the concentration of spore suspensions of isolates of the genus Fusarium. In this work we present a linear formula to relate absorbance measurements at 530nm with the number of microconidia/ml in a suspension


Assuntos
Espectrofotometria/métodos , Esporos Fúngicos/isolamento & purificação , Fusarium/isolamento & purificação , Métodos
19.
Rev Argent Microbiol ; 47(2): 152-4, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25979149

RESUMO

The use of a Neubauer chamber is a broadly employed method when cell suspensions need to be quantified. However, this technique may take a long time and needs trained personnel. Spectrophotometry has proved to be a rapid, simple and accurate method to estimate the concentration of spore suspensions of isolates of the genus Fusarium. In this work we present a linear formula to relate absorbance measurements at 530nm with the number of microconidia/ml in a suspension.


Assuntos
Fusarium/isolamento & purificação , Micologia/métodos , Doenças das Plantas/microbiologia , Espectrofotometria/métodos , Esporos Fúngicos/isolamento & purificação , Cor , Fusarium/fisiologia , Humanos , Modelos Lineares , Técnicas de Tipagem Micológica , Cebolas/microbiologia , Especificidade da Espécie , Suspensões , Fatores de Tempo
20.
Stem Cell Rev Rep ; 11(3): 511-25, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25190668

RESUMO

Here we describe a strategy to model blood vessel development using a well-defined induced pluripotent stem cell-derived endothelial cell type (iPSC-EC) cultured within engineered platforms that mimic the 3D microenvironment. The iPSC-ECs used here were first characterized by expression of endothelial markers and functional properties that included VEGF responsiveness, TNF-α-induced upregulation of cell adhesion molecules (MCAM/CD146; ICAM1/CD54), thrombin-dependent barrier function, shear stress-induced alignment, and 2D and 3D capillary-like network formation in Matrigel. The iPSC-ECs also formed 3D vascular networks in a variety of engineering contexts, yielded perfusable, interconnected lumen when co-cultured with primary human fibroblasts, and aligned with flow in microfluidics devices. iPSC-EC function during tubule network formation, barrier formation, and sprouting was consistent with that of primary ECs, and the results suggest a VEGF-independent mechanism for sprouting, which is relevant to therapeutic anti-angiogenesis strategies. Our combined results demonstrate the feasibility of using a well-defined, stable source of iPSC-ECs to model blood vessel formation within a variety of contexts using standard in vitro formats.


Assuntos
Vasos Sanguíneos/crescimento & desenvolvimento , Diferenciação Celular/genética , Células-Tronco Pluripotentes Induzidas , Neovascularização Fisiológica/genética , Vasos Sanguíneos/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Fator de Necrose Tumoral alfa/biossíntese , Fator A de Crescimento do Endotélio Vascular/biossíntese
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