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The aim of this study was to determine the effect of prolactin (PRL) on intracellular calcium (Ca2+) concentration and its neuroprotective role in a model of kainic acid (KA) excitotoxicity in primary cultures of hippocampal neurons. Cell viability and intracellular Ca2+ concentrations were determined by MTT and Fura-2 assays, respectively, either after induction by KA as an agonist or after treatment with NBQX antagonist alone or in combination with PRL administration. Expression of ionotropic glutamatergic receptors (iGluRs) subunits in neuronal cells was determined by RT-qPCR. Dose-response treatments with KA or glutamate (Glu), the latter used as endogenous agonist control, induced a significant increase in neuronal intracellular Ca2+ concentration followed by a significant decrease in hippocampal neuronal viability. Administration of PRL induced a significant increase in neuronal viability after treatment with KA. Furthermore, administration of PRL decreased intracellular Ca2+ concentrations induced by KA treatment. Independent administration of the AMPAR-KAR antagonist reversed cell death and reduced intracellular Ca2+ concentration in a similar manner as PRL. Additionally, mRNA expression of AMPAR, KAR and NMDAR subtypes were detected in hippocampal neurons; however, no significant changes in iGluRs subunit expression were observed due to excitotoxicity or PRL treatment. The results suggest that PRL inhibits the increase in intracellular Ca2+ concentration induced by KA, leading to neuroprotection.
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Ácido Kaínico , Prolactina , Prolactina/farmacología , Ácido Kaínico/toxicidad , Neuroprotección , Hipocampo/metabolismo , Neuronas/metabolismoRESUMEN
Urban tourist beach ecosystems provide the essential service of recreation. These ecosystems also support critical ecological functions where biodiversity conservation is not usually a priority. The sudden lockdown due to the COVID-19 pandemic created a unique opportunity to evaluate the effects of human absence in these urban-coastal ecosystems. This study examined bioindicators from 29 urban tourist beaches in seven Latin-American countries and assesses their response to lockdown about some relevant anthropogenic stressors such as pollution, noise, human activities, and user density. The presence of animals and plants, as well as the intensity of stressors, were assessed through a standardized protocol during lockdown conditions. Additionally, the environmental conditions of the beaches before and during lockdown were qualitatively compared using multivariate non-parametric statistics. We found notable positive changes in biological components and a clear decrease in human stressors on almost all the beaches. Dune vegetation increased on most sites. Similarly, high burrow densities of ghost crabs were observed on beaches, except those where cleaning activity persisted. Because of the lockdown, there was an exceptionally low frequency of beach users, which in turn reduced litter, noise and unnatural odors. The observed patterns suggest that tourist beaches can be restored to natural settings relatively quickly. We propose several indicators to measure changes in beaches once lockdown is relaxed. Adequate conservation strategies will render the recreational service of tourist beaches more environmental-friendly.
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Resumen: Este es un ensayo en el cual se hace la reflexión sobre el tiempo y la duración de la consulta médica, vistos como procesos sociales que están determinados por macro estructuras, siguiendo la lógica productiva y las demandas del tiempo moderno. La duración de la consulta médica es heterogénea a nivel mundial. Por el contrario, si hay algo en común es la percepción tanto de los profesionales como de los pacientes que el tiempo de interacción es breve, lo cual permea en la relación médico-paciente, perpetuando un ciclo de insatisfacción-tensión-ansiedad en ambos actores. Bajo la premisa de una sociología del tiempo y apelando a los principios éticos de la medicina, proponemos que la estimación en la duración de una consulta considere este recurso como indispensable para una adecuada interacción, teniendo presente las opiniones tanto de los pacientes como de los profesionales en cuanto a sus necesidades de dignidad para la atención y para la prestación de un servicio profesional, ya que ambos tienen derechos y obligaciones a respetarse. Además, las instituciones deberán garantizarlas a fin de preservar una adecuada relación médico-paciente-institución. La organización en los horarios de las jornadas laborales no basta. Es necesario realizar las asignaciones de consulta y tareas correlativas con los tiempos de dedicación necesarios con el objeto de humanizar los procesos, considerando las lógicas sociales y económicas sin ignorar la otredad y la alteridad de los sujetos involucrados.
Abstract: This essay is a reflection of the time and duration of the medical consultation, seen as a social process that is determined by macro structures following the productive logic and the demands of modern time. The length of the medical discussion is heterogeneous worldwide; in contrast, what is standard is the perception of the professionals and the patients that the time for interaction is short. Such a perception pervades the doctor-patient relationship, perpetuating a cycle of dissatisfaction-tension-anxiety in these actors. Under the premise of the sociology of time and appealing to the ethical principles of medicine, we propose that the estimation in the length of a medical consultation must be considered. Time is indispensable for an adequate interaction to account for the needs of patients and professionals in a dignified manner since both have rights and obligations to be respected.
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Humanos , Relaciones Médico-Paciente , Médicos/organización & administración , Atención a la Salud/organización & administración , Factores de Tiempo , Satisfacción del Paciente , Evaluación de Necesidades , Derechos del PacienteAsunto(s)
Cíclidos , Enfermedades de los Peces/microbiología , Francisella/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/veterinaria , Animales , Acuicultura , Brasil/epidemiología , Enfermedades de los Peces/diagnóstico , Francisella/genética , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinariaRESUMEN
Salmonellae are Gram-negative zoonotic bacteria that are frequently part of the normal reptilian gastrointestinal flora. The main objective of this project was to estimate the prevalence of non-typhoidal Salmonella enterica in the nesting and foraging populations of sea turtles on St. Kitts and in sand from known nesting beaches. Results suggest a higher prevalence of Salmonella in nesting leatherback sea turtles compared with foraging green and hawksbill sea turtles. Salmonella was cultured from 2/9 and identified by molecular diagnostic methods in 3/9 leatherback sea turtle samples. Salmonella DNA was detected in one hawksbill turtle, but viable isolates were not recovered from any hawksbill sea turtles. No Salmonella was detected in green sea turtles. In samples collected from nesting beaches, Salmonella was only recovered from a single dry sand sample. All recovered isolates were positive for the wzx gene, consistent with the O:7 serogroup. Further serotyping characterized serovars Montevideo and Newport present in cloacal and sand samples. Repetitive-element palindromic PCR (rep-PCR) fingerprint analysis and pulsed-field gel electrophoresis of the 2014 isolates from turtles and sand as well as archived Salmonella isolates recovered from leatherback sea turtles in 2012 and 2013, identified two distinct genotypes and four different pulsotypes, respectively. The genotyping and serotyping were directly correlated. To determine the persistence of representative strains of each serotype/genotype in these environments, laboratory-controlled microcosm studies were performed in water and sand (dry and wet) incubated at 25 or 35°C. Isolates persisted for at least 32 days in most microcosms, although there were significant decreases in culturable bacteria in several microcosms, with the greatest reduction in dry sand incubated at 35°C. This information provides a better understanding of the epizootiology of Salmonella in free-ranging marine reptiles and the potential public health risks associated with human interactions with these animals in the Caribbean.
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Playas , Salmonella enterica/aislamiento & purificación , Agua de Mar/microbiología , Microbiología del Suelo , Tortugas/microbiología , Animales , Cloaca/microbiología , San Kitts y Nevis , Microbiología del AguaRESUMEN
An outbreak of Streptococcus iniae occurred in the early months of 2008 among wild reef fish in the waters of the Federation of St Kitts and Nevis, lasting almost 2 months. Moribund and dead fish were collected for gross, histological, bacteriological, and molecular analysis. Necropsy findings included diffuse fibrinous pericarditis, pale friable livers, and serosal petechiation. Cytological and histological analysis revealed granulocytic and granulomatous inflammation with abundant coccoid bacterial organisms forming long chains. Necrosis, inflammation, and vasculitis were most severe in the pericardium, meninges, liver, kidneys, and gills. Bacterial isolates revealed ß-hemolytic, Gram-positive coccoid bacteria identified as S. iniae by amplification and 16S ribosomal RNA gene sequencing. Results from biochemical and antimicrobial susceptibility analysis, together with repetitive element palindromic polymerase chain reaction fingerprinting, suggest that a single strain was responsible for the outbreak. The inciting cause for this S. iniae-associated cluster of mortalities is unknown.
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Bacteriemia/veterinaria , Brotes de Enfermedades/veterinaria , Enfermedades de los Peces/epidemiología , Infecciones Estreptocócicas/veterinaria , Streptococcus/aislamiento & purificación , Animales , Bacteriemia/epidemiología , Bacteriemia/microbiología , Bacteriemia/patología , Arrecifes de Coral , ADN Ribosómico/química , ADN Ribosómico/genética , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/mortalidad , Enfermedades de los Peces/patología , Peces , Humanos , Pruebas de Sensibilidad Microbiana/veterinaria , Reacción en Cadena de la Polimerasa/veterinaria , ARN Ribosómico 16S/genética , San Kitts y Nevis/epidemiología , Análisis de Secuencia de ADN/veterinaria , Infecciones Estreptocócicas/epidemiología , Infecciones Estreptocócicas/microbiología , Infecciones Estreptocócicas/patología , Streptococcus/clasificación , Streptococcus/efectos de los fármacos , Streptococcus/genética , ZoonosisRESUMEN
Modalities of questionnaire administration may affect data quality, particularly when conducting Biological and Behavioral Surveillance Surveys (BBSS) of uniformed personnel. We aimed to examine differences in administration, reporting and data quality across several common modalities of administration for BBSS endeavors. Prior to a large-scale BBSS endeavor with the uniformed services of Peru, we pilot tested three modes of questionnaire administration among personnel engaged in internal combat: face-to-face interview (FFI), self-administered paper-based interview (SAPI), and audio computer-assisted self-interview (ACASI). Individuals who took the survey using ACASI were less likely to have missing data on measures of sexual risk and alcohol abuse and were more likely to report sexual risk behaviours and symptoms of alcohol abuse; however, more individuals took the survey using SAPI given inadequate time to devote to sitting through an entire FFI or ACASI. Sexually transmitted infections did not vary significantly across modes of questionnaire administration. While more logistically complicated for BBSS efforts in resource-constrained settings, we recommend the use of ACASI in collecting BBSS data from uniformed personnel if conditions are permissible.
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Entrevistas como Asunto/métodos , Personal Militar , Asunción de Riesgos , Conducta Sexual , Encuestas y Cuestionarios , Análisis de Varianza , Recolección de Datos/instrumentación , Femenino , Humanos , Masculino , Perú , Reproducibilidad de los Resultados , Autoevaluación (Psicología)RESUMEN
Vestibular afferent neurons (VANs) transmit information from the vestibular end organs to the central nuclei. This information is encoded within the firing pattern of these cells and is heavily influenced by the K⺠conductances expressed by vestibular neurons. In the present study, we describe the presence of a previously unidentified Naâº-activated K⺠conductance (KNa) in these cells. We observed that the blocking of Na⺠channels by tetrodotoxin (TTX) or the substitution of choline for Na⺠in the extracellular solution during voltage clamp pulses resulted in the reduction of a sustained outward current that was dependent on the Na⺠current. Furthermore, increases in the intracellular concentration of Na⺠that were made by blocking the Naâº/K⺠ATPase with ouabain increased the amplitude of the outward current, and reduction of the intracellular Clâ» concentration reduced the TTX-sensitive outward current. The substitution of Li⺠for Na⺠in the extracellular solution significantly reduced the amplitude of the outward current in voltage clamp pulses and decreased the afterhyperpolarization (AHP) of the action potentials in current clamp experiments. These electrophysiological results are consistent with the presence of mRNA transcripts for the KNa subunits Slick and Slack in the vestibular ganglia and in the sensory epithelium, which were detected using reverse-transcription polymerase chain reaction (RT-PCR). These results are also consistent with the immunolabeling of Slick and Slack protein in isolated vestibular neurons, in the vestibular ganglion and in the vestibular sensory epithelium. These results indicate that KNa channels are expressed in VANs and in their terminals. Furthermore, these data indicate that these channels may contribute to the firing pattern of vestibular neurons.
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Regulación del Desarrollo de la Expresión Génica/fisiología , Potenciales de la Membrana/efectos de los fármacos , Canales de Potasio/metabolismo , Células Receptoras Sensoriales/metabolismo , Sodio/metabolismo , Factores de Edad , Animales , Animales Recién Nacidos , Fenómenos Biofísicos/efectos de los fármacos , Fenómenos Biofísicos/genética , Biofisica , Células Cultivadas , Relación Dosis-Respuesta a Droga , Estimulación Eléctrica , Inhibidores Enzimáticos/farmacología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Litio/metabolismo , Potenciales de la Membrana/fisiología , Proteínas del Tejido Nervioso/metabolismo , Ouabaína/farmacología , Técnicas de Placa-Clamp , Canales de potasio activados por Sodio , ARN Mensajero , Ratas , Ratas Wistar , Células Receptoras Sensoriales/efectos de los fármacos , Sodio/farmacología , Bloqueadores de los Canales de Sodio/farmacología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Ganglio Espiral de la Cóclea/citología , Tetrodotoxina/farmacologíaRESUMEN
OBJECTIVE: Few Latin American studies have described menopausal symptoms in detail by means of a standardized assessment tool. The objective of this study was to assess the prevalence and severity of menopausal symptoms and their impact over quality of life among mid-aged Latin American women. METHOD: In this cross-sectional study, 8373 otherwise healthy women aged 40-59 years from 12 Latin American countries were asked to fill out the Menopause Rating Scale (MRS) and a questionnaire containing personal sociodemographic data. Menopause status (pre-, peri- and postmenopausal) was defined according to the criteria of the Stages of Reproductive Aging Workshop. RESULTS: Of all the studied women, 90.9% had at least one menopausal symptom (complaint) that they rated. Muscle and joint discomfort, physical and mental exhaustion and depressive mood were highly prevalent and rated as severe-very severe (scores of 3 and 4), at a higher rate than vasomotor symptoms (15.6%, 13.8% and 13.7% vs. 9.6%, respectively). Of premenopausal women (40-44 years), 77.0% reported at least one rated complaint, with 12.9% displaying MRS scores defined as severe (> 16). The latter rate increased to 26.4% in perimenopausal, 31.6% in early postmenopausal and 29.9% among late postmenopausal women. As measured with the MRS, the presence of hot flushes increased the risk of impairment of overall quality of life in both premenopausal (odds ratio 12.67; 95% confidence interval 9.53-16.83) and peri/postmenopausal women (odds ratio 9.37; 95% confidence interval 7.85-11.19). CONCLUSION: In this large, mid-aged, female Latin American series, muscle/joint discomfort and psychological symptoms were the most prevalent and severely rated menopausal symptoms. The symptoms appear early in the premenopause, significantly impair quality of life and persist 5 years beyond the menopause.
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Perimenopausia/fisiología , Posmenopausia/fisiología , Premenopausia/fisiología , Evaluación de Síntomas , Adulto , Artralgia , Síntomas Conductuales/epidemiología , Estudios Transversales , Depresión , Femenino , Sofocos/epidemiología , Humanos , América Latina/epidemiología , Persona de Mediana Edad , Músculos , Dolor , Calidad de Vida , Encuestas y Cuestionarios , Sudoración , Enfermedades de la Vejiga Urinaria/epidemiología , Enfermedades Vaginales/epidemiologíaRESUMEN
Enhanced endometrial proliferation correlates obesity to type-I (estrogen-dependent) endometrial cancer (EC). Our aim was to distinguish obese women (without EC) with differing endometrial proliferation. Endometrial and blood samples were obtained from normal-weight and obese women without EC. Type-I EC samples were obtained from obese patients. On measuring endometrial proliferation (Ki67 and phosphorylated histone H3 (p-H3)), two groups of obese women without EC were identified: obese(High Proliferating) (O(HP)) and obese(Low Proliferating) (O(LP)). Increased Ki67 (88.5%, P<0.001), p-H3 (62.6%, P<0.01), 17ß-estradiol/progesterone ratio (46.3%, P<0.01) and endometrial estrogen receptor alpha (ERα) (82.2%, P<0.001) were observed in O(HP) compared with O(LP) patients. ECs possessed similar ERα and enhanced proliferation as O(HP), suggesting that O(HP) women are at higher risk of type-I EC. O(LP) women were indistinguishable from normal-weight women regarding these determinants of endometrial proliferation, ERα and 17ß-estradiol/progesterone ratio. Our data may further define the obesity phenotype in regards to type-I EC risk and may help identify obese women more susceptible to develop type-I EC, allowing early intervention and a potential reduction in mortality.
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Neoplasias Endometriales/patología , Endometrio/patología , Estradiol/metabolismo , Receptor alfa de Estrógeno/metabolismo , Obesidad/patología , Progesterona/metabolismo , Adulto , Anciano , Proliferación Celular , Neoplasias Endometriales/etiología , Neoplasias Endometriales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Antígeno Ki-67/metabolismo , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/metabolismo , FenotipoRESUMEN
Although, the Yaqui and Mayo valleys are the most important agricultural areas in Sonora, there is only limited data of the pesticides residue in soils in these valleys. This study measured the organochlorine pesticides (OCPs) in 234 soil samples (residential and agricultural) from 24 communities. The global results (mean, range) indicated that benzene hexachloride (19.2, ND-938.5 µg g(-1)), endrin (6.6, ND-377.3 µg g(-1)) and DDTs (36.45, ND-679.7 µg g(-1)) were the dominant contaminants. Soil is one of the most important routes of exposure to OCPs in the population of southern Sonora and this study can be used to establish background levels of OCPs.
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Hidrocarburos Clorados/análisis , Residuos de Plaguicidas/análisis , Contaminantes del Suelo/análisis , Monitoreo del Ambiente , Contaminación Ambiental/estadística & datos numéricos , MéxicoRESUMEN
The objective was to determine the effect of oxytocin treatments after calving on the incidence of RFM and reproductive performance in dual purpose cows under tropical conditions. Five hundred thirty six pluriparous, crossbred Zebu cows were randomly assigned to two groups: Oxy (n = 280): cows were given 30 IU of oxytocin im immediately after normal unassisted calving, and again 6 h later; C (n = 256): control. Expulsion of fetal membranes was evaluated 24 h after delivery. After a 30-d voluntary waiting period, AI was done 12 h after cows were detected in estrus. Oxytocin had no effect on the incidence of RFM (4.6 vs. 3.1% for Oxy and C, respectively, P > 0.05). Cows in Oxy and C had similar first service and overall pregnancy rates (54.0 vs. 47.8% and 75.4 vs. 73.4%; respectively, P > 0.05). There were no differences between Oxy and C for calving to first estrus (83.6 ± 3.7 vs. 77.2 ± 3.8 d) and calving to conception intervals (113.6 ± 5.0 vs. 110.5 ± 5.2 d), as well as rates of anestrus (13.6 vs. 13.7%), repeat breeding (21.8 vs. 20.7%), and culling (15.7 vs. 16.4%). In conclusion, oxytocin treatment after normal unassisted calving did not significantly reduce the incidence of RFM or improve reproductive performance in crossbred Zebu cows under tropical conditions.
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Enfermedades de los Bovinos/tratamiento farmacológico , Oxitocina/uso terapéutico , Retención de la Placenta/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/epidemiología , Femenino , Hibridación Genética , Incidencia , Retención de la Placenta/tratamiento farmacológico , Retención de la Placenta/epidemiología , Periodo Posparto , Embarazo , Índice de EmbarazoRESUMEN
Cactophilic Drosophila flies are excellent models to study adaptation to a relatively narrow spectrum of potential host plants and host-driven evolutionary diversification. Previous studies suggested a complex genetic architecture of wing and male genital morphology in phylogenetically basal species of the D. buzzatii cluster. In this work, we investigate the effect of experimental hybridization and host plant shifts on male genital and wing morphology in D. gouveai Tidon-Sklorz and Sene and D. antonietae Tidon-Sklorz and Sene, a pair of more recently derived species. We explicitly tested the hypotheses that wing and male genital morphology in interspecific hybrids depend on the host plant in which flies were grown. Our study shows that cactus hosts exert a strong effect on genital and wing morphology and that hybrids can be clearly differentiated on the basis of wing and genital morphology from both parental species. However, the extent of morphological differentiation between hybrids and pure species as well as plasticity patterns varied across organs, suggesting a complex genetic architecture for the studied traits.
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Cactaceae , Drosophila/anatomía & histología , Genitales Masculinos/anatomía & histología , Hibridación Genética , Alas de Animales/anatomía & histología , Adaptación Biológica , Animales , Drosophila/genética , Drosophila/crecimiento & desarrollo , Femenino , Genitales Masculinos/crecimiento & desarrollo , Masculino , Especificidad de la Especie , Alas de Animales/crecimiento & desarrolloRESUMEN
Understanding linkages between household behavior and Aedes aegypti (L.) larval ecology is essential for community-based dengue mitigation. Here we associate water storage behaviors with the rate of A. aegypti pupal production in three dengue-endemic Colombian cities with different mean temperatures. Qualitative, semi-structured interviews and pupal counts were conducted over a 7-15-day period in 235 households containing a water storage vessel infested with larvae. Emptying vessels more often than every 7 days strongly reduced pupal production in all three cities. Emptying every 7-15 days reduced production by a similar magnitude as emptying <7 days in Armenia (21.9 degrees C), has a threefold smaller reduction as compared to <7 days in Bucaramanga (23.9 degrees C), and did not reduce production in Barranquilla (29.0 degrees C). Lidding vessels reduced mosquito production and was most feasible in Barranquilla because of container structure. Vessel emptying strongly correlated with usage in Barranquilla, where many households stored water in case of interruptions in piped service rather than for regular use. In the cooler cities, >90% of households regularly used stored water for washing clothes, generating a weaker correlation between emptying and usage. Emptying was less frequent in the households surveyed in the dry season in all three cities. These results show that A. aegypti production and human behaviors are coupled in a temperature-dependent manner. In addition to biological effects on aquatic stages, climate change may impact A. aegypti production through human behavioral adaptations. Vector control programs should account for geographic variation in temperature and water usage behaviors in designing targeted interventions.
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Aedes/crecimiento & desarrollo , Dengue , Insectos Vectores/crecimiento & desarrollo , Control de Mosquitos/métodos , Agua , Animales , Colombia , Dengue/prevención & control , Dengue/transmisión , Ecología , Composición Familiar , Artículos Domésticos , Humanos , Masculino , Pupa , Estaciones del Año , Temperatura , Abastecimiento de AguaRESUMEN
In rats, iron deficiency produces an alteration in myelin formation. However, there is limited information on the effects of this condition on oligodendroglial cell (OLGc) proliferation and maturation. In the present study, we further analyzed the hypomyelination associated with iron deficiency by studying the dynamics of oligodendrogenesis. Rats were fed control (40 mg Fe/kg) or iron-deficient (4 mg Fe/kg) diets from gestation day 5 until postnatal day 3 (P3) or 11 (P11). OLGc proliferation, migration and differentiation were investigated before and after an intracranial injection of apotransferrin at 3 days of age (P3). The proliferating cell population was evaluated at P3. Iron-deficient (ID) animals showed an increase in the oligodendrocyte precursors cell (OPC) population in comparison with controls. The overall pattern of migration of cells labeled with BrdU was investigated at P11. Iron deficiency increased the amount of BrdU(+) cells in the corpus callosum (CC) and decreased OLGc maturation and myelin formation. Changes in nerve conduction were analyzed by measuring visual evoked potentials. Latency and amplitude were significantly disturbed in ID rats compared with controls. Both parameters were substantially normalized when animals were treated with a single intracranial injection of 350 ng apotransferrin (aTf). The current results give support to the idea that iron deficiency increases the number of proliferating and undifferentiated cells in the CC compared with the control. Treatment with aTf almost completely reverted the effects of iron deficiency, both changing the migration pattern and increasing the number of mature cells in the CC and myelin formation.
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Apoproteínas/uso terapéutico , Proliferación Celular/efectos de los fármacos , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/patología , Deficiencias de Hierro , Oligodendroglía/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Transferrina/uso terapéutico , Factores de Edad , Análisis de Varianza , Animales , Animales Recién Nacidos , Apoproteínas/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Peso Corporal/fisiología , Encéfalo , Bromodesoxiuridina/metabolismo , Recuento de Células , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Cuerpo Calloso/metabolismo , Cuerpo Calloso/patología , Enfermedades Desmielinizantes/etiología , Enfermedades Desmielinizantes/fisiopatología , Electroencefalografía/métodos , Potenciales Evocados Visuales/efectos de los fármacos , Potenciales Evocados Visuales/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Regulación del Desarrollo de la Expresión Génica/fisiología , Hematócrito/métodos , Proteína Básica de Mielina/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Oligodendroglía/fisiología , Estimulación Luminosa/métodos , Embarazo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas , Ácidos Siálicos/metabolismo , Transferrina/metabolismoRESUMEN
OBJECTIVE: To examine whether overweight and obesity could lead to increased endometrial proliferation and activation of AKT and ERK1,2 in cycling premenopausal women. METHODS: Endometrial and blood samples were obtained from women with normal endometrial histology, and allocated into three groups-normal-weight, overweight and obese-according to the subject's body mass index (BMI). Samples from obese patients with type-I endometrial cancer (EC) were included as a control. Cell proliferation was measured by immunohistochemical detection of Ki67 and phosphorylated histone H3 (p-H3). AKT and ERK1,2 activation was assessed by Western blot. Circulating steroids, leptin and insulin were measured by immunoassays. RESULTS: In endometrial samples with normal histology, epithelial cell proliferation was higher in the overweight and obese groups versus the normal-weight set (P<0.05). Proliferation indexes were positively correlated with the subject's BMI and serum levels of estrogen, leptin and insulin (P<0.05). Increased phosphorylated AKT (pAKT) (1.6-fold) and ERK1,2 (pERK1,2) (8.7-fold) were observed in endometria from obese with respect to normal-weight subjects (P<0.05). Similarly, increased phosphorylation of AKT (0.7-fold) and ERK1,2 (2.3-fold) was detected in endometria from overweight as compared with the normal-weight group (P<0.05). In women with EC, we found a significant increase in endometrial proliferation, and in pAKT and pERK1,2 expression levels when compared to patients with normal endometrial histology. CONCLUSION: These results show correlation between obesity (and overweight) and increased endometrial cell proliferation, and the activation of AKT and ERK1,2. These features could be related with the higher risk to develop type-I EC in overweight and obese women.
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Endometrio/enzimología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Obesidad/enzimología , Proteína Oncogénica v-akt/metabolismo , Sobrepeso/enzimología , Adulto , Anciano , Western Blotting , Procesos de Crecimiento Celular/fisiología , Endometrio/patología , Activación Enzimática , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Obesidad/sangre , Obesidad/patología , Sobrepeso/sangre , Sobrepeso/patologíaRESUMEN
To differentiate among different types of diabetes is becoming an increasingly challenging task. We investigated whether the patient's genetic profile is useful to identify the particular type of diabetes, to determine the corresponding hyperglycemia pathogenesis and treat accordingly. Three hundred and thirty-eight diabetic patients, diagnosed according to American Diabetes Association criteria, were recruited from 2004 to 2008 in diabetes health reference centers. We analyzed the major gene for type 1 diabetes susceptibility (HLA DQ/DR). In order to improve our understanding of the pathogenesis of the resulting hyperglycemia and to implement a more adequate treatment for the patients, we reclassified our sample according to the presence or absence of the genetic markers. We found that a higher percentage of people than expected have immunological disease, independent of their phenotype, with a relative risk of 4.62 (95% confidence interval). This methodology allowed us to establish an association between the genotype and its resulting phenotype. We found significant differences; the phenotypic classification did not reflect immunological disease based on genotype. Moreover, when we examined markers, body mass index and age of onset, we found that many people have an intermediate phenotype between type 1 and type 2. This genetic data can help provide an accurate definition of the disease and would therefore provide the physician a better possibility of providing adequate treatment.
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Diabetes Mellitus Tipo 1/genética , Adolescente , Adulto , Niño , Preescolar , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Lactante , Fenotipo , UruguayRESUMEN
Francisella sp. is an emergent bacterial pathogen that causes acute to chronic disease in warm and cold water cultured and wild fish species. During the past 3 years, the bacterium has been detected in tilapia, Oreochromis niloticus, cultured in Costa Rica. Infected fish presented non-specific clinical signs, such as erratic swimming, anorexia, anaemia, exophthalmia and high mortality. Upon macroscopic and microscopic examination, several internal organs (mainly spleen and kidney) were enlarged and contained white nodules. Histological examination revealed the presence of multifocal granulomatous lesions, with the presence of numerous small, pleomorphic, cocco-bacilli. The bacteria were isolated from infected tilapia on selective media and grown on several media with and without antibiotics. Specific PCR primers to the Francisella genus were used to confirm the preliminary diagnoses. In comparison with several bacterial 16S rRNA sequences, our isolate was found to share 99% identity with other Fransicella spp. isolated from fish, and more than 97% identity to the human pathogen Francisella tularensis. Koch's postulates were fulfilled after experimental intraperitoneal and gill exposure challenges.
Asunto(s)
Cíclidos , Enfermedades Transmisibles Emergentes/veterinaria , Enfermedades de los Peces/epidemiología , Enfermedades de los Peces/microbiología , Francisella/genética , Infecciones por Bacterias Gramnegativas/veterinaria , Animales , Acuicultura , Secuencia de Bases , Costa Rica/epidemiología , Cartilla de ADN/genética , Enfermedades de los Peces/patología , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/patología , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN/veterinaria , Homología de SecuenciaRESUMEN
We have previously shown that low concentrations of a specific proteasome inhibitor accelerate exit from the cell cycle and enhance oligodendroglial cell (OLGc) differentiation. To elucidate the mechanisms involved in this process, OLGcs of the N20.1 cell line, transfected with a reporter gene driven by the MBP promoter, were treated with proteasome inhibitors and/or inhibitors of different signaling pathways. Partial proteasome inhibition resulted in enhanced activation of the MBP promoter which involved the tyrosine kinase, PI3-Akt and PKC pathways, accompanied by an increase in the levels of p21(Cip1), p27(Kip1) and Sp1 and by a decrease in Nkx2.2. Binding of Sp1 to DNA was also increased. These results were not observed when the Sp1 binding site was mutated. We conclude that the enhanced activation of the MBP promoter induced by partial inhibition of the proteasome could be due, at least in part, to the stabilization of p27(Kip1) and Sp1.
Asunto(s)
Diferenciación Celular/genética , Proteína Básica de Mielina/genética , Oligodendroglía/citología , Oligodendroglía/metabolismo , Transducción de Señal/fisiología , Animales , Western Blotting , Línea Celular , Supervivencia Celular/efectos de los fármacos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Ensayo de Cambio de Movilidad Electroforética , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/fisiología , Proteína Homeobox Nkx-2.2 , Inmunoprecipitación , Ratones , Proteína Básica de Mielina/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Regiones Promotoras Genéticas , Complejo de la Endopetidasa Proteasomal/efectos de los fármacos , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteína Quinasa C/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/efectos de los fármacos , Factor de Transcripción Sp1/metabolismo , TransfecciónRESUMEN
Mechanisms that regulate oligodendroglial cell (OLGc) differentiation are the focus of intensive research in the field of cellular and molecular neurobiology. We have previously shown that the addition of apotransferrin (aTf) to primary OLGc cultures accelerates their differentiation and induces an increase in the expression of different components of the myelin cytoskeleton (CSK) such as actin, tubulin, and some of the microtubule-associated proteins, particularly the stable tubulin only peptide (STOP). Fyn protein-tyrosine kinase (Fyn kinase), a member of the Src family, participates in signalling pathways that regulate OLGs/myelin cytoskeletal reorganization. It is essential for myelin development in the central nervous system (CNS), and its absence results in hypomyelination. In the present study, we used both primary cell and N19 cell line cultures to investigate further the mechanisms of action involved in the accelerated differentiation of OLGcs induced by aTf. In particular, we were interested in studying the participation of Fyn kinase in the different pathways involved in the reorganization of the OLGc/myelin cytoskeleton. In agreement with results already published, we found that in OLGcs, Fyn kinase is associated with Tau and tubulin. Using a dominant-negative of Tau in which the Fyn-Tau-microtubules (MTs) interaction is blocked, we found that aTf was unable to induce OLGc morphological differentiation. It was also observed that aTf decreases the activated RhoA content in coincidence with a redistribution of actin immunoreactivity. These results give support to our hypothesis that Fyn kinase plays a key role in the differentiation process of OLGcs promoted by aTf.