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BACKGROUND: MS severity may be affected by genetic, patient-related, disease-related and environmental factors. Socioeconomic status, including income and healthcare access, amongst others, may also have a role in affecting diagnostic delay or therapy prescription. In Chile, two main healthcare systems exist, public-healthcare and private-healthcare, nonetheless universal care laws (e.g., access to High Efficacy Therapy-HET), including both systems, have been recently enacted for people with MS. OBJECTIVE: To assess the role of Socioeconomic Conditions (SEC), clinical variables and public health policies on the impact of disease severity of MS patients in Chile. METHODS: Multicentric, observational, cross-sectional study including patients from two reference centres (1 national reference centre from the private-health system and 1 regional reference centre from the public-health system). SEC and clinical variables included healthcare insurance (private or public), subclassification of health insurance according to monthly income, sex, age at onset, diagnostic delay, disease duration, diagnosis before HET law (as a proxy of HET delay), and current HET treatment. Progression Index (PI), EDSS ≥6.0 and Progressive MS diagnosis were used as outcome measures. Multivariable binary logistic regression was performed. RESULTS: We included 604 patients (460 private-health, 144 public-health), 67% women, 100% white/mestizo, 88% RRMS, mean age 42±12 years, mean age at onset 32±11 years, mean disease duration 10±6 years, median diagnostic delay 0 (0-34) years, 86% currently receiving any DMT, 55% currently receiving HET, median EDSS at last visit of 2.0 (0-10), and median PI 0.17 (0-4.5). Lower monthly income was associated with higher EDSS and higher PI. In the multivariable analysis, public-healthcare (OR 10.2), being diagnosed before HET-law (OR 4.89), longer diagnostic delay (OR 1.26), and older age at onset (OR 1.05) were associated with a higher risk of PI>0.2, while current HET (OR 0.39) was a protective factor. Diagnosis before HET-law (OR 7.59), public-healthcare (OR 6.49), male sex (OR 2.56), longer disease duration (OR 1.2) and older age at onset (OR 1.1) were associated with a higher risk of Progressive MS. Public-healthcare (OR 5.54), longer disease duration (OR 1.14) and older age at onset (OR 1.08) were associated with a higher risk of EDSS ≥6.0 while current treatment with HET had a trend as being a protective factor (OR 0.44, p = 0.05). CONCLUSION: MS severity is impacted by non-modifiable factors such as sex and age at onset. Interventions focused on shortening diagnostic delay and encouraging early access to high-efficacy therapies, as well as initiatives that may reduce the disparities inherent to lower socioeconomic status, may improve outcomes in people with MS.
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Alzheimer disease (AD) is the main cause of dementia worldwide and a source of important population morbidity and mortality. It is estimate that its prevalence will increase dramatically in the upcoming years. The classical clinical presentation of AD is an amnesic hippocampal syndrome, and Mild Cognitive impairment (MCI) is considered the initial stage between normal cognition and dementia. The most accepted pathogenesis establishes amyloid beta (Ab) deposition in brain parenchyma as the initial mechanism, followed by the intracellular accumulation of hyperphosphorylated tau finally leading to the loss of synapses and neurons. Recently, the study of AD pathogenesis is focusing on immune mechanisms as main actors of disease development. Microglia is the macrophagic resident cell in the central nervous system (CNS), and initiates the inflammatory response and Ab phagocytosis, interacting with other glia and recruiting diverse immune cells to the CNS. The role of the adaptive immune system, and, especially T lymphocytes' role, is still controversial. We hypothesize that the pathogenesis of AD is dynamic; with a preponderant proinflammatory activity initially, but later on, the persistent presence of Ab due to the lack of its proper elimination leads to a phenomena of lymphocyte dysfunction and immunological tolerance that have a deleterious role at advanced stages of the disease. (AU)
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Humanos , Masculino , Femenino , Enfermedad de Alzheimer/fisiopatología , Enfermedad de Alzheimer/inmunología , Demencia/inmunologíaRESUMEN
Resumen Introducción Las fístulas aorto-entéricas (FAE) son una causa infrecuente de hemorragia digestiva. El pronóstico, generalmente ominoso, depende de una alta sospecha clínica y diagnóstico oportuno. Caso clínico Reportamos el caso de una mujer de 66 años intervenida por un aneurisma sacular aórtico abdominal (AAA) yuxtarrenal, con rotura contenida, fistulizado al duodeno. Presentó una hemorragia digestiva en el preoperatorio; sin embargo, el diagnóstico de la fístula se hizo en el intraoperatorio. La paciente fue sometida a reparación quirúrgica urgente con instalación de una prótesis aórtica bifemoral y resección duodenal. En el postoperatorio inmediato presentó una trombosis parcial de las ramas de la prótesis aórtica e isquemia de extremidades, siendo reintervenida exitosamente. Discusión La FAE es una causa potencialmente fatal de hemorragia digestiva. El diagnóstico continúa siendo un desafío debido a su presentación inespecífica y siempre debiese ser considerado frente a una hemorragia digestiva sin causa aparente. Existen varias opciones para el enfrentamiento quirúrgico que deben ser analizadas caso a caso, sin retrasar la reparación de la fístula. Es preferible la resección duodenal ante la simple duodenorrafia.
Introduction Aorto-enteric fistulae (AEF) are a rare cause of gastrointestinal bleeding. The prognosis tends to be ominous, depending greatly in a high level of clinical suspicion and prompt diagnosis. Clinical case We report a case of a 66-year-old female with a saccular juxta-renal abdominal aortic aneurysm (AAA), with a contained rupture. The patient was urgently submitted to surgical repair using an bifemoral aortic prosthesis. A duodenal partial resection was performed. During the immediate postoperative time she presented partial thrombosis of prosthesis and ischemia of lower extremities so she was reoperated successfully. Discussion AEF is a potentially fatal cause of gastrointestinal bleeding. Diagnosis is still troublesome due to its vague presentation and it should always be considered when facing gastrointestinal haemorrhage with no apparent cause. There are several surgical approaches that should be pondered case to case without delaying the repair of the defect.
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Humanos , Femenino , Anciano , Enfermedades de la Aorta/complicaciones , Fístula Intestinal/cirugía , Fístula Intestinal/complicaciones , Enfermedades Duodenales/complicaciones , Hemorragia Gastrointestinal/cirugía , Fístula Intestinal/diagnóstico , Resultado del Tratamiento , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Implantación de Prótesis Vascular/métodos , Periodo Perioperatorio , Hemorragia Gastrointestinal/diagnósticoRESUMEN
INTRODUCTION: The new 2015 criteria for neuromyelitis optica spectrum disorders (NMOSD) have been recently incorporated in the study of different international cohorts. AIM: To describe clinical-radiological characteristics and prognostic factors in patients with NMOSD according to the 2015 criteria. PATIENTS AND METHODS: Retrospective analysis of 36 patients diagnosed with NMOSD according to serologic AQP4 status (positive, negative, unknown and negative + unknown). Clinical and radiological characteristics were compared and possible disability prognostic factors were evaluated. RESULTS: AQP4 were positive in 7 patients, negative in 12 and unknown in 17. Age of presentation was 36.6 ± 16 years, with higher female proportion (4:1). Mean disease duration was 7.4 ± 7.6 years. Most frequent presenting symptoms were acute myelitis (61%), optic neuritis (33%) and area postrema syndrome (11%). Most frequent MRI lesion was longitudinally extensive transverse myelitis (75%). All patients received acute treatment during attacks, and preventive treatment was used in 81% (azathioprine and rituximab mostly prescribed). Median EDSS was 2.0 at the end of follow-up. No differences were observed in any of the variables comparing serologic status. Age of first attack was prognostic, with direct correlation with EDSS. First attack in < 30 years was protective, meanwhile > 50 years old patients had increased risk of disability. CONCLUSIONS: The 2015 criteria allow the description and classification of NMOSD patients within different cohorts. Age of first attack seems to be a prognostic factor for developing disability.
TITLE: Espectro de neuromielitis optica: descripcion de una cohorte segun los criterios diagnosticos de 2015.Introduccion. Los nuevos criterios diagnosticos de 2015 del espectro de neuromielitis optica (NMO) estan comenzando a utilizarse en diferentes poblaciones en el mundo. Objetivo. Describir las caracteristicas clinicorradiologicas y pronosticas de pacientes diagnosticados de NMO con los criterios de 2015. Pacientes y metodos. Analizamos retrospectivamente 36 pacientes diagnosticados de NMO con los actuales criterios. Se generaron cuatro grupos segun la serologia de antiacuaporina 4 (positivos, negativos, desconocidos y negativos mas desconocidos agrupados). Se compararon sus caracteristicas clinicorradiologicas y se evaluaron posibles variables pronosticas de discapacidad. Resultados. Encontramos siete pacientes seropositivos, 12 negativos y 17 desconocidos. La edad de inicio fue de 36 ± 16 años, con mayor proporcion de mujeres (4 a 1). La duracion de la enfermedad fue de 7,4 ± 7,6 años. Los sintomas iniciales mas frecuentes fueron mielitis (61%), neuritis optica (33%) y sindrome del area postrema (11%). La lesion mas frecuente en la resonancia magnetica fue la mielitis longitudinalmente extensa (75%). Todos los pacientes recibieron tratamiento agudo, y el preventivo se utilizo en el 81%; la azatioprina y el rituximab fueron los que mas se usaron. La mediana de la Expanded Disability Status Scale (EDSS) fue de 2 al final del seguimiento. No hubo diferencias significativas en las variables clinicorradiologicas entre los distintos grupos de pacientes. La edad de inicio fue pronostica y presenta correlacion directa con la EDSS. El inicio antes de los 30 años fue protector y, despues de los 50 años, un factor de riesgo para mayor discapacidad. Conclusiones. Los actuales criterios permiten describir diferentes cohortes. La edad de inicio parece ser un factor pronostico para desarrollar discapacidad.
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Neuromielitis Óptica/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuromielitis Óptica/terapia , Estudios Retrospectivos , Adulto JovenRESUMEN
Introduction: Gastric cancer (GC) is the leading cause of cancer mortality in Chile. The development ofgastric adenocarcinoma its preceded by a histopathologic cascade composed of gastric atrophy, intestinal metaplasia and gastric dysplasia. Sydney protocol has been proposed as the standard method for diagnosingthese conditions. The aim of this research study was to establish whether Sydney protocol increase thedetection of premalignant gastric lesions, as gastric atrophy and intestinal metaplasia, compared to non protocolizedendoscopies/biopsies. Methods: Upper gastroduodenal endoscopies (GDE) from Hospital Clí-nico Universidad Católica de Chile between April-May 2015 and April-May 2016 was analyzed. Patientswith histological study with 18 years-old or older were included. Patients with history of GC or malignantlesions at GDE where excluded. Detection of gastric atrophy, intestinal metaplasia and suggestive findingsof autoimmune gastritis where compared between Sydney protocol and non-protocolized endoscopies/biopsies...
Introducción: El cáncer gástrico (CG) es la principal causa de muertes por cáncer en Chile. El desarrollo del adenocarcinoma gástrico es precedido por una cascada histopatológica (gastritis; atrofia gástrica/AG; metaplasia intestinal/MI). Se ha propuesto la biopsia del cuerpo, ángulo y antro a través del protocolo de Sydney para la búsqueda de estas condiciones. Objetivo: Determinar la diferencia en la detección delesiones premalignas gástricas a través del protocolo de Sydney comparado con el estudio endoscópico habitual. Métodos: Se analizaron las endoscopias digestivas altas (EDA) realizadas en el Centro de Endoscopia Digestiva del Hospital Clínico de la Universidad Católica en los períodos entre abril y mayo del 2015 y 2016. Se incluyeron las EDA de pacientes mayores de 18 años con estudio histológico. Fueron excluidos los pacientes con antecedente personal de CG o lesiones de aspecto maligno macroscópicas. Se comparó la detección de AG, MI y gastritis autoinmune (GA) en el estudio histológico entre los pacientes con protocolo Sydney y el estudio endoscópico no protocolizado...
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Masculino , Femenino , Humanos , Adulto , Adulto Joven , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Biopsia/métodos , Lesiones Precancerosas/patología , Neoplasias Gástricas/patología , Atrofia/patología , Chile , Protocolos Clínicos , Endoscopía del Sistema Digestivo , Infecciones por Helicobacter/patología , Metaplasia/patología , Estudios RetrospectivosAsunto(s)
Femenino , Humanos , Adulto , Estenosis Esofágica/diagnóstico , Estenosis Esofágica/etiología , Várices Esofágicas y Gástricas/complicaciones , Stents , Cianoacrilatos/efectos adversos , Trastornos de Deglución/etiología , Estenosis Esofágica/terapia , Ligadura/efectos adversos , Escleroterapia/efectos adversosRESUMEN
The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-ß as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.
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5'-Nucleotidasa/metabolismo , 5'-Nucleotidasa/orina , Adenosina/orina , Diabetes Mellitus Experimental/orina , Nefropatías Diabéticas/orina , Riñón/patología , 5'-Nucleotidasa/análisis , Adenosina/análisis , Adenosina/metabolismo , Adenosina Monofosfato/metabolismo , Animales , Línea Celular , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/metabolismo , Nefropatías Diabéticas/patología , Humanos , Riñón/metabolismo , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Although Tissue Banks and their activities are not new in Mexico, the specific regulations for the activities of tissue banks and musculoskeletal tissues considered as health supplies are still under development. This review paper intends to provide information on the national situation of musculoskeletal tissue banks, major aspects concerning their regulation and organization, and the recognition of the national instances pertaining to the Coordination for Organ and Tissue Donation for Transplant Purposes for the obtention of (musculoskeletal) tissues from deceased donors.
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Huesos , Músculos , Bancos de Tejidos/legislación & jurisprudencia , Bancos de Tejidos/organización & administración , Humanos , MéxicoRESUMEN
Hypoxia relates with altered placental vasodilation, and in isolated endothelial cells, it reduces activity of the endothelial nitric oxide synthase (eNOS) and l-arginine transport. It has been reported that arginase-2 expression, an alternative pathway for l-arginine metabolism, is increased in adult endothelial cells exposed to hypoxia as well as in pre-eclamptic placentae. We studied in human umbilical vein endothelial cells (HUVEC) whether hypoxia-reduced NO synthesis results from increased arginase-mediated l-arginine metabolism and changes in subcellular localization of eNOS and arginase-2. In HUVEC exposed (24 h) to 5% (normoxia) or 2% (hypoxia) oxygen, l-arginine transport kinetics, arginase activity (urea assay), and NO synthase (NOS) activity (l-citrulline assay) were determined. Arginase-1, arginase-2 and eNOS expression were determined by RT-PCR and Western blot. Subcellular localization of arginase-2 and eNOS were studied using confocal microscopy and indirect immunofluorescence. Experiments were done in absence or presence of S-(2-boronoethyl)-l-cysteine-HCl (BEC, arginase inhibitor) or N(G)-nitro-l-arginine methyl ester (l-NAME). Hypoxia-induced reduction in eNOS activity was associated with a reduction in eNOS phosphorylation at Serine-1177 and increased phosphorylation at Threonine-495. This was paralleled with an induction in arginase-2 expression and activity, and decreased l-arginine transport. In hypoxia the arginase inhibition, restored NO synthesis and l-arginine transport, without changes in the eNOS post-translational modification status. Hypoxia increased arginase-2/eNOS colocalization, and eNOS redistribution to the cell periphery. Altogether these data reinforce the thought that eNOS cell location, post-translational modification and substrate availability are important mechanisms regulating eNOS activity. If these mechanisms occur in pregnancy diseases where feto-placental oxygen levels are reduced remains to be clarified.
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Arginasa/biosíntesis , Células Endoteliales de la Vena Umbilical Humana/enzimología , Hipoxia/metabolismo , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Adulto , Arginasa/antagonistas & inhibidores , Arginina/metabolismo , Ácidos Borónicos/farmacología , Femenino , Técnica del Anticuerpo Fluorescente Indirecta , Humanos , Microscopía Confocal , NG-Nitroarginina Metil Éster/farmacología , Fosforilación , Embarazo , Procesamiento Proteico-Postraduccional , Fracciones Subcelulares/enzimologíaRESUMEN
Glioblastoma multiforme (GBM) is the most aggressive of brain tumors and is extremely insensitive to anticancer drugs. Studies have attributed the ABC transporter Mrp1 (ABCC1, multiple-drug resistance protein 1) with conferring chemoresistance in this tumor by extrusion of a wide spectrum of anticancer drugs. Therefore it is crucial to search for and investigate inhibitors of Mrp1 activity in GBM cells, particularly those that could be safe as chemosensitizers to anticancer drugs in clinical studies. We find that in primary cultured or T98G GBM cells exposed to therapeutic plasma concentrations of FK506 (tacrolimus), the expression of Mrp1 was decreased in a dose-dependent manner. The activity of this transporter, measured by CFDA fluorescent substrate extrusion, decreased significantly in primary cultured GBM cells on exposure to FK506 at concentrations of 15 ng/ml. When GBM cells were exposed to anticancer drugs vincristine, etoposide or taxol, cell viability was not affected. However when the anticancer drugs were assayed in combination with FK506, cell viability was significantly decreased by as much as 50% in GBM primary culture. We conclude that FK506 could be a valuable tool for chemosensitization of GBM cells, offering a possible improvement to the current poor therapy available for high-grade human gliomas.
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Antineoplásicos/farmacología , Neoplasias Encefálicas/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Glioblastoma/metabolismo , Inmunosupresores/farmacología , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/antagonistas & inhibidores , Tacrolimus/farmacología , Línea Celular Tumoral , Humanos , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/biosíntesisRESUMEN
Up regulation of the transforming growth factor-beta 1 (TGF-beta1) axis has been recognized as a pathogenic event for progression of glomerulosclerosis in diabetic nephropathy. We demonstrate that glomeruli isolated from diabetic rats accumulate up to sixfold more extracellular adenosine than normal rats. Both decreased nucleoside uptake activity by the equilibrative nucleoside transporter 1 and increased AMP hydrolysis contribute to raise extracellular adenosine. Ex vivo assays indicate that activation of the low affinity adenosine A2B receptor subtype (A2BAR) mediates TGF-beta1 release from glomeruli of diabetic rats, a pathogenic event that could support progression of glomerulopathy when the bioavailability of adenosine is increased.
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Adenosina/metabolismo , Nefropatías Diabéticas/metabolismo , Glomérulos Renales/metabolismo , Receptor de Adenosina A2B/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Adenosina Monofosfato/metabolismo , Animales , Disponibilidad Biológica , Tranportador Equilibrativo 1 de Nucleósido/metabolismo , Hidrólisis , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Progression of Alzheimer's disease (AD) is associated with chronic inflammation and microvascular alterations, which can induce impairment of brain perfusion because of vascular pathology and local acidosis. Acidosis can promote amyloidogenesis, which could further contribute to neurodegenerative changes. Nevertheless, there is also evidence that acidosis has neuroprotective effects in hypoxia models. Here we studied the effect of moderate acidosis on beta-amyloid (Abeta)-mediated neurotoxicity. We evaluated morphological changes, cell death, nitrite production and reductive metabolism of hippocampal cultures from Sprague-Dawley rats exposed to Abeta under physiological (pH 7.4) or moderate acidosis (pH 7.15-7.05). In addition, because transforming growth factor beta (TGFbeta) 1 is neuroprotective and is induced by several pathophysiological conditions, we assessed its presence at the different pHs. The exposure of hippocampal cells to Abeta induced a conspicuous reduction of neurites' arborization, as well as increased neuronal death and nitric oxide production. However, Abeta neurotoxicity was significantly attenuated when hippocampal cultures were kept at pH 7.15-7.05, showing a 68% reduction on lactate dehydrogenase release compared with cultures exposed to Abeta at pH 7.4 (P<0.01). Similarly, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction increased 3.5-fold (P<0.05), and Abeta-induced nitrite production was reduced by 65% when exposed to moderate acidosis compared with basal pH media (P<0.05). At the same time, moderate acidosis decreased intracellular TGFbeta1 precursor (latency associated protein-TGFbeta1) and increased up to fourfold TGFbeta1 bioactivity, detecting a 43% increase in the active TGFbeta levels in cultures exposed to Abeta and moderate acidosis. Inhibition of TGFbeta signaling abolished the neuroprotective effect of moderate acidosis. Our results show that moderate acidosis protected hippocampal cells from Abeta-mediated neurotoxicity through the increased activation and signaling potentiation of TGFbeta.
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Acidosis/metabolismo , Péptidos beta-Amiloides/toxicidad , Hipocampo/citología , Neuronas/efectos de los fármacos , Fragmentos de Péptidos/toxicidad , Factor de Crecimiento Transformador beta/metabolismo , Péptidos beta-Amiloides/metabolismo , Análisis de Varianza , Animales , Azidas , Benzamidas/farmacología , Tamaño de la Célula/efectos de los fármacos , Dioxoles/farmacología , Embrión de Mamíferos , Femenino , Concentración de Iones de Hidrógeno , L-Lactato Deshidrogenasa/metabolismo , Óxido Nítrico/metabolismo , Embarazo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Sales de Tetrazolio , Tiazoles/antagonistas & inhibidores , Factor de Crecimiento Transformador beta/antagonistas & inhibidores , Tubulina (Proteína)/metabolismoRESUMEN
Up-regulation of the glomerular expression and the activity of vascular endothelial growth factor-A (VEGF) have been identified as an early pathogenic event for the progression of diabetic nephropathy. Currently, however the mediators are not yet clearly recognized. In this study we identified all four adenosine receptor (AR) subtypes, i.e. A(1), A(2A), A(2B) and A(3) in isolated rat kidney glomeruli. We localized the expression of A(2B)AR in podocytes, the primary VEGF producing cells. The ex vivo treatment of kidney glomeruli with adenosine or a general AR agonist NECA, increases VEGF protein content. In addition, NECA treatment elicits VEGF release. These effects were blocked by the A(2B)AR selective antagonist MRS1754 supplementation. Furthermore, we showed that A(2B)AR activation was necessary to promote a higher expression of VEGF in kidney glomeruli upon exposure to high d-glucose concentration, a pathogenic condition like those observed in diabetic nephropathy.
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Glomérulos Renales/metabolismo , Receptor de Adenosina A2B/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Células Cultivadas , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Altered endothelial cell function is a key factor associated with vascular disorders and is critical in the fetal growth and development. Pregnancies affected by diseases such as gestational diabetes are associated with human umbilical vein endothelial dysfunction, a finding that has been associated with a high incidence of vascular complications during the adult life. Limited information is available addressing cellular mechanisms associated with altered human umbilical vein endothelial function in gestational diabetes. One of the key signalling pathways associated with altered vascular physiology is the synthesis of the vasodilator nitric oxide (NO) from the cationic amino acid L-arginine by the endothelium (i.e. the endothelial L-arginine/NO pathway). The activity of this signalling pathway is modulated by D-glucose, adenosine, insulin, and ATP, among other molecules, and is upregulated (transcriptional, post-transcriptional and post-translational levels) in gestational diabetes. This review focuses on the cellular and molecular mechanisms involved with elevated adenosine levels in fetal umbilical vein blood and the endothelial L-arginine/NO pathway activity in gestational diabetes. We suggest that a lower capacity of adenosine transport by the fetal endothelium in gestational diabetes leads to extracellular accumulation of this nucleoside and its higher bio-availability activates endothelial P1 type purinoceptors. A functional association between A2a purinoceptor subtype signalling and the activity of the l-arginine transport mediated by human cationic amino acid transporters and endothelial NO synthase activity (i.e. 'ALANO pathway') is proposed, revealing in part the mechanisms that account for human umbilical vein endothelial cell dysfunction programmed through the development of the fetus in gestational diabetes.
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Adenosina/metabolismo , Arginina/metabolismo , Diabetes Gestacional/metabolismo , Endotelio/metabolismo , Óxido Nítrico/metabolismo , Transducción de Señal , Venas Umbilicales/metabolismo , Animales , Femenino , Humanos , EmbarazoRESUMEN
Caroli disease is a cystic congenital malformation of the intrahepatic biliary tract, frequently associated with lithiasis. Commonly, cystic dilatations are bilateral and infrequently they affect only one hepatic lobule or segment. We report six patients with localized Caroli disease, three in the right and three in the left hepatic lobule, that were subjected to a hepatic resection. There were no postoperative complications or mortality. After 28 months of follow up, patients are asymptomatic and with normal hepatic function and ultrasonography. The importance of diagnosing localized Caroli disease, in which hepatic resection can be curative, is emphasized
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Humanos , Adulto , Femenino , Persona de Mediana Edad , Enfermedad de Caroli , Hepatectomía , Colangiografía , Colelitiasis , Cálculos Biliares , Enfermedad de CaroliRESUMEN
La hiperplasia prostática benigna (HPB) es una patología de alta prevalencia en la consulta urológica. Una herramienta efectiva de tratamiento es la cirugía abierta transvesical, que en nuestro Servicio se indica principalmente a pacientes con volúmenes prostáticos superiores a 50 gramos. El objetivo de este estudio es conocer el manejo de los pacientes con HPB con indicación de cirugía abierta. Para esto, se efectúo un análisis retrospectivo de 328 fichas clínicas de pacientes intervenidos quirúrgicamente entre agosto de 1999 a julio de 2002. Dentro del estudio, el promedio de edad fue 68 años. El antígeno prostático específico (APE) promedio fue de 7,22 ng/ml, con antígeno menor a 4 ng/ml en el 41 por ciento y mayor a 10 ng/ml en el 19 por ciento. Dentro del estudio diagnóstico se practicó biopsia prostática transrectal ecodirigida al 32 por ciento. El volumen prostático promedio fue de 79,2 gramos, con un rango de 33 a 190 gramos. El principal motivo de consulta fue la sintomatología obstructiva baja (86 por ciento). Al momento de la cirugía, un 52 por ciento portaba sonda Foley uretrovesical. El 66 por ciento de las cirugías fueron realizadas por médicos residentes, asesorados por urólogo del servicio. Las complicaciones intra operatorias fueron 2,7 por ciento, siendo la principal el desgarro capsular. La sonda se retiró a los 6,3 días, con un promedio de estadía hospitalaria postoperatoria de 7,4 días. En el seguimiento, se destaca infección de herida operatoria (7,9 por ciento), hematuria (2,7 por ciento), infección del tracto urinario (ITU) (2,7 por ciento). El 1,2 por ciento fue reintervenido, principalmente por hemovejiga. Se encontró en forma incidental, cáncer prostático en 1,2 por ciento de los casos. No se registró mortalidad en esta revisión. El abordaje quirúrgico transvesical constituye la vía de elección en pacientes con volúmenes prostáticos superiores a 50 gramos. Es una técnica segura y presenta pocas complicaciones intra operatorias. Como complicación tardía más frecuente se presentó la infección de herida operatoria, no siendo significativo el uso de sonda Foley a permanencia en el preoperatorio. Las demás complicaciones están bajo los estándares mundiales esperados. En comparación con la literatura internacional, llama la atención el bajo porcentaje de adenocarcinoma prostático diagnosticado en forma incidental, a pesar de un APE promedio elevado.