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1.
Environ Toxicol Chem ; 43(6): 1242-1249, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38557972

RESUMEN

Fragrance encapsulates are widely used in consumer care applications such as fabric softeners or other liquid laundry products; they provide multiple benefits, from fragrance protection in the commercial product to a controlled release and improved sensorial experience for the consumers. Polymeric fragrance encapsulates are in the scope of the EU regulation restricting the use of intentionally added microplastic particles, and industry is actively working on innovation programs to find biodegradable alternatives. However, particular attention needs to be paid to claims that a fragrance encapsulation system is biodegradable, because biodegradation test results can vary considerably depending on how a test material is prepared, which can even lead to false-positive biodegradation test results, as shown in our study. We demonstrate the importance of the sample preparation phase of the process. We show how the biodegradation level can fluctuate from 0% to 91%, depending on how the test material is isolated from a given microcapsule slurry system, and we present a method that can be used to obtain trustworthy biodegradation results. Environ Toxicol Chem 2024;43:1242-1249. © 2024 Givaudan France SAS. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Asunto(s)
Biodegradación Ambiental , Polímeros , Perfumes
2.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1559728

RESUMEN

Introducción: El amniocele es una hernia del saco amniótico a través de un defecto en la pared del útero, el cual puede deberse a ruptura uterina, secundario a daños preexistentes, anomalías uterinas o en un útero sin cicatrices. Caso clínico: Presentamos el caso de una paciente de 37 años, con antecedente de dos partos por cesárea, a quien en la semana 25,5 de embarazo se le diagnostica por ecografía amniocele en la pared anterior de útero contenido por la vejiga, además de signos ecográficos de acretismo placentario. La posterior realización de resonancia magnética confirma el diagnóstico. Se realiza manejo expectante con estancia continua intrahospitalaria estricta. Resolución obstétrica a las 34 semanas por cesárea, con extracción fetal por fondo uterino sin complicaciones, con posterior realización de histerectomía con placenta in situ. Conclusiones: Este reporte de caso ilustra la importancia de la identificación temprana de esta condición por ser una complicación infrecuente, pero de grave pronóstico fetomaterno en ausencia de atención inmediata.


Introduction: Amniocele is a hernia of the amniotic sac through a defect in the uterine wall, which can be caused by uterine rupture secondary to preexisting damage, uterine anomalies, or a scarless uterus. Case report: We present a case of a 37-year-old patient with a history of two previous cesarean deliveries. At 25.5 weeks of gestation, the diagnosis of amniocele in the anterior uterine wall, contained by the bladder, along with ultrasound signs of placenta accreta, was confirmed through ultrasound. Subsequent magnetic resonance imaging further confirmed the diagnosis. Expectant management with strict continuous intrahospital stay was implemented. Obstetric resolution was achieved at 34 weeks through cesarean delivery, with uncomplicated fetal extraction through the uterine fundus. Subsequently, a hysterectomy was performed with the placenta left in situ. Conclusions: This case report illustrates the importance of early identification of this condition due to its infrequent but serious feto-maternal prognosis in the absence of immediate attention.

3.
Curr Top Med Chem ; 24(2): 89-108, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37842892

RESUMEN

Recent developments in the use of natural product-based molecules as antiparasitic agents for Malaria, leishmaniasis (LE), Chagas disease (CD), and Human African trypanosomiasis (HAT) are reviewed. The role of diverse plants in developing bioactive species is discussed in addition to analyzing the structural diversity of natural products as active agents and the diverse biological applications in CD, HAT, LE, and Malaria. This review focuses on medicinal chemistry, emphasizing the structural characteristics of natural molecules as bioactive agents against parasitic infections caused by Leishmania, Trypanosoma, and Plasmodium parasites.


Asunto(s)
Antiprotozoarios , Productos Biológicos , Enfermedad de Chagas , Leishmaniasis , Malaria , Tripanosomiasis Africana , Animales , Humanos , Antiparasitarios/farmacología , Antiparasitarios/uso terapéutico , Antiparasitarios/química , Antiprotozoarios/farmacología , Antiprotozoarios/uso terapéutico , Antiprotozoarios/química , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Productos Biológicos/química , Enfermedades Desatendidas/tratamiento farmacológico , Enfermedades Desatendidas/parasitología , Tripanosomiasis Africana/tratamiento farmacológico , Leishmaniasis/tratamiento farmacológico , Enfermedad de Chagas/tratamiento farmacológico , Malaria/tratamiento farmacológico
4.
Ginecol. obstet. Méx ; 92(1): 27-40, ene. 2024. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1557851

RESUMEN

Resumen OBJETIVO: Describir un esquema de atención no quirúrgica en pacientes con embarazo en cicatriz de cesárea en el contexto de un sistema de salud con bajos recursos. Además, describir la tolerancia, vigilancia, evolución y desenlace de cada una de las pacientes tratadas con el esquema propuesto. MATERIALES Y MÉTODOS: Estudio retrospectivo, descriptivo de serie de casos de pacientes que acudieron al servicio de Urgencias de una institución de tercer nivel de atención en Barranquilla, Colombia, entre los meses de mayo de 2020 a marzo 2023 debido a síntomas obstétricos o fueron remitidas a la institución con diagnóstico, confirmado por ultrasonografía, de embarazo en cicatriz de cesárea. Parámetros de estudio: medición de variables sociodemográficas, obstétricas, de evolución clínica y complicaciones maternas. Se efectuó el análisis descriptivo de los datos. RESULTADOS: Se documentaron 11 pacientes que dieron una incidencia de 1.85 casos por cada 5000 embarazos. El dolor pélvico y el sangrado fueron los síntomas más prevalentes. Cinco pacientes tuvieron dos o más cesáreas, el resto una sola previa y cinco antecedente de legrado obstétrico. Nueve de 11 pacientes se atendieron con menos de 8 semanas de embarazo. La tasa de éxito alcanzada fue en las 11 pacientes, con negativización de la beta hCG a los 38.7 días en promedio. No se registraron complicaciones severas ni requerimiento de atención quirúrgica. CONCLUSIONES: Se describió la implementación de un esquema combinado sistémico y local con metotrexato que resultó seguro y efectivo, con preservación de la fertilidad.


Abstract OBJECTIVE: To report a scheme of non-surgical care in patients with cesarean scar pregnancy in the context of a health system with low resources. In addition, to describe the tolerance, monitoring, evolution and outcome of each of the patients treated with the proposed scheme. MATERIALS AND METHODS: Descriptive study of a case series of patients who, between May 2020 and March 2023, attended the emergency room of a tertiary care institution in Barranquilla, Colombia, because of obstetric symptoms or were referred to the institution with a diagnosis of cesarean scar pregnancy confirmed by ultrasound. Study parameters: measurement of sociodemographic, obstetric, clinical evolution and maternal complication variables. Descriptive analysis of data was performed. Results: Eleven patients were documented, giving an incidence of 1.85 cases per 5000 pregnancies. Pelvic pain and bleeding were the most common symptoms. Five patients had two or more previous cesarean sections, the remainder had only one previous cesarean section, and five had a history of obstetric curettage. Nine of the 11 patients were treated at less than 8 weeks'; gestation. The success rate was 100%, with a mean beta-hCG negativity of 38.7 days. There were no major complications and no surgical intervention was required. CONCLUSIONS: We describe the implementation of a combined systemic and local regimen with methotrexate that was safe and effective, with preservation of fertility.

5.
ACS Omega ; 8(31): 28060-28079, 2023 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-37576656

RESUMEN

In situ combustion (ISC) is one of the oldest thermal enhanced oil recovery methods to have been applied in Venezuela to increase the production of highly viscous crude oils, with a first field application in 1959 in the Tia Juana Field-Lake Maracaibo Basin. This method, which is characterized by high energy efficiency, consists of injecting air into the reservoir where exothermic oxidation reactions initiate to increase the mobility of the oil. Compared to other thermal enhanced oil recovery methods such as steam injection, ISC has a lower environmental impact in terms of water and fuel consumption, and emission of gases as the produced gases can be reinjected or stored. Several ISC projects have been carried out in Venezuela in Tia Juana, Morichal, Miga, and Melones fields. Although the technical results have been satisfactory in terms of viscosity reduction and improved crude oil properties (such as °API), other important aspects of project evaluations have not been convincing due to the following factors: high temperatures in producing wells, acid gases management, generation of complex emulsions, corrosion, and high CAPEX and OPEX costs. Nevertheless, additional research work has been conducted on process optimization, using catalysts and hydrogen donors, to better address these other factors. Due to the great need to increase hydrocarbon production in Venezuela and to the advantages of ISC as an upgrading technique where low-carbon fuels and hydrogen as byproducts are generated, this paper presents a revisit of ISC projects in Venezuela from R&D technical aspects to field applications. It seeks to identify the main insights regarding the success and failure of the evaluated projects and make substantiated recommendations in the case of future applications of this technology.

6.
JACC Case Rep ; 11: 101790, 2023 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-37077433

RESUMEN

We present a 22-week fetus with isolated absent aortic valve and inverse circular shunt. The pregnancy was interrupted. Here, echocardiography and pathology images demonstrate this rare entity. Whole genome sequencing revealed a potentially disease-causing variant in the APC gene. Whole genome sequencing should be considered in severe and rare fetal diseases. (Level of Difficulty: Advanced.).

7.
Rev. Fed. Centroam. Ginecol. Obstet. ; 27 (1), 2023;27(1): 22-26, 30 de abril de 2023.
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1426980

RESUMEN

La placenta acreta se define como una invasión trofoblástica anormal de una parte o de toda la placenta a nivel de las paredes miometriales del útero. La incidencia de acretismo placentario viene cada vez más y más en aumento. El factor de riesgo más común es la presencia de cesárea y la posibilidad de cursar con acretismo placentario aumenta entre más cesáreas tenga la paciente. Hay pocos datos acerca de acretismo placentario localizado en mioma uterino, sobre todo en el contexto de una paciente primigestante. Se presenta el caso de una primigestante tardía, quien cursó con embarazo de alto riesgo dado por acretismo placentario localizado en mioma intramural; asimismo, hacemos una revisión de la literatura acerca del diagnóstico oportuno y pronóstico de esta condición. (provisto por Infomedic International)


Placenta accreta is defined as an abnormal trophoblastic invasion of part or all of the placenta at the level of the myometrial walls of the uterus. The incidence of placental accreta is increasingly on the rise. The most common risk factor is the presence of cesarean section and the likelihood of placental accreta increases the more cesarean sections the patient has. There is little data on placental accreta located in uterine myoma, especially in the context of a primigestational patient. We present the case of a late primigestation, who had a high-risk pregnancy due to placental accreta located in an intramural myoma; we also review the literature on the timely diagnosis and prognosis of this condition. (provided by Infomedic International)

8.
J Bionic Eng ; 19(5): 1374-1391, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35756166

RESUMEN

This paper presents an upper limb exoskeleton that allows cognitive (through electromyography signals) and physical user interaction (through load cells sensors) for passive and active exercises that can activate neuroplasticity in the rehabilitation process of people who suffer from a neurological injury. For the exoskeleton to be easily accepted by patients who suffer from a neurological injury, we used the ISO9241-210:2010 as a methodology design process. As the first steps of the design process, design requirements were collected from previous usability tests and literature. Then, as a second step, a technological solution is proposed, and as a third step, the system was evaluated through performance and user testing. As part of the technological solution and to allow patient participation during the rehabilitation process, we have proposed a hybrid admittance control whose input is load cell or electromyography signals. The hybrid admittance control is intended for active therapy exercises, is easily implemented, and does not need musculoskeletal modeling to work. Furthermore, electromyography signals classification models and features were evaluated to identify the best settings for the cognitive human-robot interaction.

9.
Sci Signal ; 14(709): eabh3839, 2021 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-34784250

RESUMEN

Thyroid hormone (TH) action is essential for hepatic lipid synthesis and oxidation. Analysis of hepatocyte-specific thyroid receptor ß1 (TRß1) knockout mice confirmed a role for TH in stimulating de novo lipogenesis and fatty acid oxidation through its nuclear receptor. Specifically, TRß1 and its principal corepressor NCoR1 in hepatocytes repressed de novo lipogenesis, whereas the TH-mediated induction of lipogenic genes depended on the transcription factor ChREBP. Mice with a hepatocyte-specific deficiency in ChREBP lost TH-mediated stimulation of the lipogenic program, which, in turn, impaired the regulation of fatty acid oxidation. TH regulated ChREBP activation and recruitment to DNA, revealing a mechanism by which TH regulates specific signaling pathways. Regulation of the lipogenic pathway by TH through ChREBP was conserved in hepatocytes derived from human induced pluripotent stem cells. These results demonstrate that TH signaling in the liver acts simultaneously to enhance both lipogenesis and fatty acid oxidation.


Asunto(s)
Células Madre Pluripotentes Inducidas , Lipogénesis , Hormonas Tiroideas , Animales , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Lipogénesis/genética , Hígado/metabolismo , Ratones , Hormonas Tiroideas/metabolismo
10.
Arch Pathol Lab Med ; 144(10): 1245-1253, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-32057275

RESUMEN

CONTEXT.­: The adoption of digital capture of pathology slides as whole slide images (WSI) for educational and research applications has proven utility. OBJECTIVE.­: To compare pathologists' primary diagnoses derived from WSI versus the standard microscope. Because WSIs differ in format and method of observation compared with the current standard glass slide microscopy, this study is critical to potential clinical adoption of digital pathology. DESIGN.­: The study enrolled a total of 2045 cases enriched for more difficult diagnostic categories and represented as 5849 slides were curated and provided for diagnosis by a team of 19 reading pathologists separately as WSI or as glass slides viewed by light microscope. Cases were reviewed by each pathologist in both modalities in randomized order with a minimum 31-day washout between modality reads for each case. Each diagnosis was compared with the original clinical reference diagnosis by an independent central adjudication review. RESULTS.­: The overall major discrepancy rates were 3.64% for WSI review and 3.20% for manual slide review diagnosis methods, a difference of 0.44% (95% CI, -0.15 to 1.03). The time to review a case averaged 5.20 minutes for WSI and 4.95 minutes for glass slides. There was no specific subset of diagnostic category that showed higher rates of modality-specific discrepancy, though some categories showed greater discrepancy than others in both modalities. CONCLUSIONS.­: WSIs are noninferior to traditional glass slides for primary diagnosis in anatomic pathology.


Asunto(s)
Interpretación de Imagen Asistida por Computador/métodos , Microscopía/métodos , Patología Quirúrgica/métodos , Método Doble Ciego , Humanos , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados
11.
Nanoscale Adv ; 2(5): 2052-2062, 2020 May 19.
Artículo en Inglés | MEDLINE | ID: mdl-36132494

RESUMEN

Gas diffusion electrocrystallization (GDEx) was explored for the synthesis of iron oxide nanoparticles (IONPs). A gas-diffusion cathode was employed to reduce oxygen, producing hydroxyl ions (OH-) and oxidants (H2O2 and HO2 -), which acted as reactive intermediates for the formation of stable IONPs. The IONPs were mainly composed of pure magnetite. However, their composition strongly depended on the presence of a weak acid, i.e., ammonium chloride (NH4Cl), and on the applied electrode potential. Pure magnetite was obtained due to the simultaneous action of H2O2 and the buffer capacity of the added NH4Cl. Magnetite and goethite were identified as products under different operating conditions. The presence of NH4Cl facilitated an acid-base reaction and, in some cases, led to cathodic deprotonation, forming a surplus of hydrogen peroxide, while adding the weak acid promoted gradual changes in the pH by slightly enhancing H2O2 production when increasing the applied potential. This also resulted in smaller average crystallite sizes as follows: 20.3 ± 0.6 at -0.350 V, 14.7 ± 2.1 at -0.550 and 12.0 ± 2.0 at -0.750 V. GDEx is also demonstrated to be a green, effective, and efficient cathodic process to recover soluble iron to IONPs, being capable of removing >99% of the iron initially present in the solution.

12.
Nat Commun ; 10(1): 1684, 2019 04 11.
Artículo en Inglés | MEDLINE | ID: mdl-30975991

RESUMEN

Obesity triggers the development of non-alcoholic fatty liver disease (NAFLD), which involves alterations of regulatory transcription networks and epigenomes in hepatocytes. Here we demonstrate that G protein pathway suppressor 2 (GPS2), a subunit of the nuclear receptor corepressor (NCOR) and histone deacetylase 3 (HDAC3) complex, has a central role in these alterations and accelerates the progression of NAFLD towards non-alcoholic steatohepatitis (NASH). Hepatocyte-specific Gps2 knockout in mice alleviates the development of diet-induced steatosis and fibrosis and causes activation of lipid catabolic genes. Integrative cistrome, epigenome and transcriptome analysis identifies the lipid-sensing peroxisome proliferator-activated receptor α (PPARα, NR1C1) as a direct GPS2 target. Liver gene expression data from human patients reveal that Gps2 expression positively correlates with a NASH/fibrosis gene signature. Collectively, our data suggest that the GPS2-PPARα partnership in hepatocytes coordinates the progression of NAFLD in mice and in humans and thus might be of therapeutic interest.


Asunto(s)
Péptidos y Proteínas de Señalización Intracelular/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/patología , PPAR alfa/metabolismo , Animales , Biopsia , Conjuntos de Datos como Asunto , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Epigénesis Genética , Fibrosis , Células HEK293 , Hepatocitos/metabolismo , Humanos , Péptidos y Proteínas de Señalización Intracelular/genética , Metabolismo de los Lípidos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR alfa/genética
13.
Sci Signal ; 11(536)2018 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-29945885

RESUMEN

Thyroid hormone receptor ß1 (THRB1) and estrogen-related receptor α (ESRRA; also known as ERRα) both play important roles in mitochondrial activity. To understand their potential interactions, we performed transcriptome and ChIP-seq analyses and found that many genes that were co-regulated by both THRB1 and ESRRA were involved in mitochondrial metabolic pathways. These included oxidative phosphorylation (OXPHOS), the tricarboxylic acid (TCA) cycle, and ß-oxidation of fatty acids. TH increased ESRRA expression and activity in a THRB1-dependent manner through the induction of the transcriptional coactivator PPARGC1A (also known as PGC1α). Moreover, TH induced mitochondrial biogenesis, fission, and mitophagy in an ESRRA-dependent manner. TH also induced the expression of the autophagy-regulating kinase ULK1 through ESRRA, which then promoted DRP1-mediated mitochondrial fission. In addition, ULK1 activated the docking receptor protein FUNDC1 and its interaction with the autophagosomal protein MAP1LC3B-II to induce mitophagy. siRNA knockdown of ESRRA, ULK1, DRP1, or FUNDC1 inhibited TH-induced autophagic clearance of mitochondria through mitophagy and decreased OXPHOS. These findings show that many of the mitochondrial actions of TH are mediated through stimulation of ESRRA expression and activity, and co-regulation of mitochondrial turnover through the PPARGC1A-ESRRA-ULK1 pathway is mediated by their regulation of mitochondrial fission and mitophagy. Hormonal or pharmacologic induction of ESRRA expression or activity could improve mitochondrial quality in metabolic disorders.


Asunto(s)
Autofagia , Mitocondrias/fisiología , Dinámicas Mitocondriales , Mitofagia , Receptores de Estrógenos/metabolismo , Receptores beta de Hormona Tiroidea/fisiología , Animales , Homólogo de la Proteína 1 Relacionada con la Autofagia/genética , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Células Cultivadas , Dinaminas/genética , Dinaminas/metabolismo , Humanos , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Fosforilación , Receptores de Estrógenos/genética , Receptor Relacionado con Estrógeno ERRalfa
14.
Proc Natl Acad Sci U S A ; 114(40): E8458-E8467, 2017 10 03.
Artículo en Inglés | MEDLINE | ID: mdl-28923959

RESUMEN

Nuclear receptor corepressor 1 (NCoR1) is considered to be the major corepressor that mediates ligand-independent actions of the thyroid hormone receptor (TR) during development and in hypothyroidism. We tested this by expressing a hypomorphic NCoR1 allele (NCoR1ΔID), which cannot interact with the TR, in Pax8-KO mice, which make no thyroid hormone. Surprisingly, abrogation of NCoR1 function did not reverse the ligand-independent action of the TR on many gene targets and did not fully rescue the high mortality rate due to congenital hypothyroidism in these mice. To further examine NCoR1's role in repression by the unliganded TR, we deleted NCoR1 in the livers of euthyroid and hypothyroid mice and examined the effects on gene expression and enhancer activity measured by histone 3 lysine 27 (H3K27) acetylation. Even in the absence of NCoR1 function, we observed strong repression of more than 43% of positive T3 (3,3',5-triiodothyronine) targets in hypothyroid mice. Regulation of approximately half of those genes correlated with decreased H3K27 acetylation, and nearly 80% of these regions with affected H3K27 acetylation contained a bona fide TRß1-binding site. Moreover, using liver-specific TRß1-KO mice, we demonstrate that hypothyroidism-associated changes in gene expression and histone acetylation require TRß1. Thus, many of the genomic changes mediated by the TR in hypothyroidism are independent of NCoR1, suggesting a role for additional signaling modulators in hypothyroidism.


Asunto(s)
Hipotiroidismo/patología , Hígado/patología , Mutación , Co-Represor 1 de Receptor Nuclear/fisiología , Receptores beta de Hormona Tiroidea/fisiología , Hormonas Tiroideas/metabolismo , Acetilación , Animales , Células Cultivadas , Regulación de la Expresión Génica , Histonas/metabolismo , Hipotiroidismo/genética , Hipotiroidismo/metabolismo , Hígado/metabolismo , Ratones , Ratones Noqueados , Regiones Promotoras Genéticas , Transducción de Señal
15.
Pharmacol Ther ; 173: 135-145, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28174093

RESUMEN

Thyroid hormones (TH) are endocrine messengers essential for normal development and function of virtually every vertebrate. The hypothalamic-pituitary-thyroid axis is exquisitely modulated to maintain nearly constant TH (T4 and T3) levels in circulation. However peripheral tissues and the CNS control the intracellular availability of TH, suggesting that circulating concentrations of TH are not fully representative of what each cell type sees. Indeed, recent work in the field has identified that TH transporters, deiodinases and thyroid hormone receptor coregulators can strongly control tissue-specific sensitivity to a set amount of TH. Furthermore, the mechanism by which the thyroid hormone receptors regulate target gene expression can vary by gene, tissue and cellular context. This review will highlight novel insights into the machinery that controls the cellular response to TH, which include unique signaling cascades. These findings shed new light into the pathophysiology of human diseases caused by abnormal TH signaling.


Asunto(s)
Receptores de Hormona Tiroidea/metabolismo , Tiroxina/metabolismo , Triyodotironina/metabolismo , Animales , Regulación de la Expresión Génica/fisiología , Humanos , Sistema Hipotálamo-Hipofisario/fisiología , Transducción de Señal , Hormonas Tiroideas/metabolismo
16.
J Endocrinol ; 232(3): 451-459, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28053002

RESUMEN

Thyroid hormones (THs) induce pleiotropic effects in vertebrates, mainly through the activation or repression of gene expression. These mechanisms involve thyroid hormone binding to thyroid hormone receptors, an event that is followed by the sequential recruitment of coactivator or corepressor proteins, which in turn modify the rate of transcription. In the present study, we looked for specific coregulators recruited by the long isoform of the teleostean thyroid hormone receptor beta 1 (L-Trb1) when bound to the bioactive TH, 3,5-T2 (T2). We found that jun activation domain-binding protein1 (Jab1) interacts with L-Trb1 + T2 complex. Using both the teleostean and human TRB1 isoforms, we characterized the Jab1-TRB1 by yeast two-hybrid, pull-down and transactivation assays. Our results showed that the TRB1-Jab1 interaction was ligand dependent and involved the single Jab1 nuclear receptor box, as well as the ligand-binding and N-terminal domains of TRB1. We also provide evidence of ligand-dependent, dual coregulatory properties of Jab1. Indeed, when T2 is bound to L-Trb1 or hTRB1, Jab1 acts as a coactivator of transcription, whereas it has corepressor activity when interacting with the T3-bound S-Trb1 or hTRB1. These mechanisms could explain some of the pleiotropic actions exerted by THs to regulate diverse biological processes.


Asunto(s)
Regulación de la Expresión Génica/efectos de los fármacos , Proteínas/metabolismo , Receptores beta de Hormona Tiroidea/metabolismo , Hormonas Tiroideas/farmacología , Animales , Complejo del Señalosoma COP9 , Línea Celular , Relación Dosis-Respuesta a Droga , Péptidos y Proteínas de Señalización Intracelular , Proteínas/genética , Ratas , Receptores de Hormona Tiroidea/metabolismo
17.
Genet Med ; 19(1): 83-89, 2017 01.
Artículo en Inglés | MEDLINE | ID: mdl-27337029

RESUMEN

PURPOSE: Chromosomal microarray analysis (CMA) is currently considered first-tier testing in pediatric care and prenatal diagnosis owing to its high diagnostic sensitivity for chromosomal imbalances. The aim of this study was to determine the efficacy and diagnostic power of CMA in both fresh and formalin-fixed paraffin-embedded (FFPE) samples of products of conception (POCs). METHODS: Over a 44-month period, 8,118 consecutive samples were received by our laboratory for CMA analysis. This included both fresh (76.4%) and FFPE samples (22.4%), most of which were ascertained for recurrent pregnancy loss and/or spontaneous abortion (83%). The majority of samples were evaluated by a whole-genome single-nucleotide polymorphism (SNP)-based array (81.6%); the remaining samples were evaluated by array-comparative genomic hybridization (CGH). RESULTS: A successful result was obtained in 7,396 of 8,118 (91.1%), with 92.4% of fresh tissue samples and 86.4% of FFPE samples successfully analyzed. Clinically significant abnormalities were identified in 53.7% of specimens (3,975 of 7,396), 94% of which were considered causative. CONCLUSION: Analysis of POC specimens by karyotyping fails in 20-40% of cases. SNP-based CMA is a robust platform, with successful results obtained in >90% of cases. SNP-based CMA can identify aneuploidy, polyploidy, whole-genome homozygosity, segmental genomic imbalances, and maternal cell contamination, thus maximizing sensitivity and decreasing false-negative results. Understanding the etiology of fetal loss enables clarification of recurrence risk and assists in determining appropriate management for future family planning.Genet Med 19 1, 83-89.


Asunto(s)
Aborto Espontáneo/genética , Hibridación Genómica Comparativa/métodos , Pruebas Genéticas , Diagnóstico Prenatal , Aborto Espontáneo/diagnóstico , Adulto , Factores de Edad , Aneuploidia , Aberraciones Cromosómicas , Femenino , Humanos , Hibridación Fluorescente in Situ/métodos , Cariotipificación/métodos , Persona de Mediana Edad , Adhesión en Parafina , Polimorfismo de Nucleótido Simple , Embarazo
18.
Mol Cell Endocrinol ; 425: 103-10, 2016 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-26820127

RESUMEN

T3 and cortisol activate or repress gene expression in virtually every vertebrate cell mainly by interacting with their nuclear hormone receptors. In contrast to the mechanisms for hormone gene activation, the mechanisms involved in gene repression remain elusive. In teleosts, the thyroid hormone receptor beta gene or thrb produces two isoforms of TRß1 that differ by nine amino acids in the ligand-binding domain of the long-TRß1, whereas the short-TRß1 lacks the insert. Previous reports have shown that the genomic effects exerted by 3,5-T2, a product of T3 outer-ring deiodination, are mediated by the long-TRß1. Furthermore, 3,5-T2 and T3 down-regulate the expression of long-TRß1 and short-TRß1, respectively. In contrast, cortisol has been shown to up-regulate the expression of thrb. To understand the molecular mechanisms for thrb modulation by thyroid hormones and cortisol, we used an in silico approach to identify thyroid- and cortisol-response elements within the proximal promoter of thrb from tilapia. We then characterized the identified response elements by EMSA and correlated our observations with the effects of THs and cortisol upon expression of thrb in tilapia. Our data show that 3,5-T2 represses thrb expression and impairs its up-regulation by cortisol possibly through a transrepression mechanism. We propose that for thrb down-regulation, ligands other than T3 are required to orchestrate the pleiotropic effects of thyroid hormones in vertebrates.


Asunto(s)
Diyodotironinas/farmacología , Hidrocortisona/farmacología , Receptores beta de Hormona Tiroidea/genética , Tilapia/metabolismo , Animales , Simulación por Computador , Proteínas de Peces/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Regiones Promotoras Genéticas , Elementos de Respuesta , Transducción de Señal/efectos de los fármacos , Receptores beta de Hormona Tiroidea/metabolismo , Tilapia/genética , Transcripción Genética/efectos de los fármacos
19.
Surg Endosc ; 30(2): 649-656, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26091993

RESUMEN

BACKGROUND: Laparoscopic distal pancreatectomy (LDP) is a treatment option for benign and borderline pancreatic tumors. However, pancreatic fistula (PF) remains a significant morbidity, contributing to the length of hospital stay and overall costs. In a consecutive series of 143 patients at a single institution, the predictive factors associated with PF after LDP were identified. METHODS: A retrospective study of patients who had undergone LDP between January 2003 and December 2013 was conducted. Patient demographic data and clinicopathological parameters were analyzed to evaluate their correlation with the incidence of PF. RESULTS: Among the 143 patients, the indications for surgery were benign disease in 117 (82%) and malignant tumors in 26 (18%). PF occurred in 25 (17%) patients, 10 (40%) of whom had clinically significant (grade B) PF. No grade C PF was observed. Multivariable analysis showed that pancreatic thickness was a significant predictive factor for PF (P < 0.001). A 12-mm cutoff value was based on the median pancreatic thickness in this series. Pancreatic texture alone was not a significant risk factor (P = 0.30); however, it became significant in patients with pancreatic thickness exceeding 12 mm (P = 0.005). CONCLUSIONS: Pancreatic thickness exceeding 12 mm significantly increases the likelihood of PF after LDP. Pancreatic texture alone is not an independent risk factor for PF, but when combined with a thick parenchyma (>12 mm), a soft pancreas is predictive of PF.


Asunto(s)
Laparoscopía , Pancreatectomía/métodos , Fístula Pancreática/etiología , Complicaciones Posoperatorias/etiología , Adulto , Anciano , Femenino , Humanos , Incidencia , Tiempo de Internación , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedades Pancreáticas/cirugía , Fístula Pancreática/epidemiología , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
20.
J Hepatobiliary Pancreat Sci ; 22(12): 819-24, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26455716

RESUMEN

BACKGROUND: Few reports have described laparoscopy-assisted pancreaticoduodenectomy (LAPD) as an alternative to the conventional open approach for periampullary tumors. The safety and feasibility of this procedure remain to be determined. In this study, we compared the short-term clinical outcomes of LAPD with those of open pancreaticoduodenectomy (OPD). METHODS: A retrospective review of patients who had undergone pancreaticoduodenectomy for periampullary tumors between June and December 2014 was conducted. Patient demographic data and their pathological and short-term clinical parameters were compared between the LAPD and OPD groups. RESULTS: Fifty-two patients were included in the study: 18 had undergone LAPD and 34 had undergone OPD. The mean operation time was longer for LAPD than for OPD (531.1 vs. 383.2 min, P < 0.001). The estimated blood loss, rate of blood transfusion, surgical resection margin status, and number of lymph nodes retrieved were similar in both groups. Overall morbidity and the incidence of pancreatic fistula did not differ significantly between the two groups. However, the mean length of hospital stay was significantly shorter in the LAPD group (12.6 vs. 18.6 days, P = 0.001). CONCLUSION: LAPD is a technically safe and feasible alternative treatment for periampullary tumors, with short-term clinical outcomes equivalent to those of OPD, with a shorter hospital stay.


Asunto(s)
Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco/cirugía , Laparoscopía/métodos , Neoplasias Pancreáticas/cirugía , Pancreaticoduodenectomía/métodos , Anciano , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Transfusión Sanguínea/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Humanos , Incidencia , Tiempo de Internación/estadística & datos numéricos , Escisión del Ganglio Linfático , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Tempo Operativo , Seguridad del Paciente , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
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