RESUMEN
Compared to competitive runners, recreational runners appear to be more prone to injuries, which have been associated with foot strike patterns. Surprisingly, only few studies had examined the foot strike patterns outside laboratories. Therefore, this study compared the foot strike patterns in recreational runners at outdoor tracks with previously reported data. We also investigated the relationship between foot strike pattern, speed, and footwear in this cohort. Among 434 recreational runners analysed, 89.6% of them landed with rearfoot strike (RFS). Only 6.9 and 3.5% landed with midfoot and forefoot, respectively. A significant shift towards non-RFS was observed in our cohort, when compared with previously reported data. When speed increased by 1 m/s, the odds of having forefoot strike and midfoot strike relative to RFS increased by 2.3 times and 2.6 times, respectively. Runners were 9.2 times more likely to run with a forefoot strike in minimalists compared to regular running shoes, although 70% of runners in minimalists continued to use a RFS. These findings suggest that foot strike pattern may differ across running conditions and runners should consider these factors in order to mitigate potential injury.
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Pie/fisiología , Marcha/fisiología , Carrera/fisiología , Zapatos , Adulto , Traumatismos en Atletas/prevención & control , Fenómenos Biomecánicos , Diseño de Equipo , Femenino , Humanos , Masculino , Carrera/lesionesRESUMEN
BACKGROUND: Recent consensus on variant angina defines significant spasm as total or subtotal occlusion of a coronary artery. However, the clinical significance of "less-than-subtotal" spasm needs to be reappraised, especially if the coronary spasm is combined with chest pain. Therefore, we evaluated the feasibility of left ventricular end diastolic pressure (LVEDP) as a tool to detect myocardial ischemia during ergonovine provocation testing. METHODS: After achieving two access sites, 29 patients underwent successful LVEDP monitoring using 5-Fr pigtail catheters during ergonovine provocation tests. Patients were divided into two groups based on the occurrence of anginal symptoms. RESULTS: Of the 29 patients, 16 (55 %) patients had anginal symptoms. LVEDP was significantly increased in the symptomatic group compared with the nonsymptomatic group (∆LVEDP 5.6 ± 4.2 vs. 1.2 ± 2.0 mmHg, p = 0.002). However, of the 16 patients with anginal symptoms, positive provocation test results were confirmed in only six patients (38 %) as per the traditional standard (> 90 % inducible spasm of the epicardial coronary artery). CONCLUSION: Compared with the traditional standard, LVEDP may have advantages in terms of elucidating anginal symptoms in patients suspected of having coronary vasospasm when performing ergonovine provocation tests.
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Angina Pectoris Variable/diagnóstico , Determinación de la Presión Sanguínea/métodos , Presión Sanguínea/efectos de los fármacos , Ergonovina/administración & dosificación , Isquemia Miocárdica/diagnóstico , Volumen Sistólico/efectos de los fármacos , Vasos Coronarios/efectos de los fármacos , Femenino , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Vasoconstrictores/administración & dosificaciónRESUMEN
The new allele, HLA-B*40:301 differs from B*40:01:02 by one nucleotide substitution at codon 239 (AGA â AAA).
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Alelos , Antígenos HLA-B/genética , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Secuencia de Bases , Exones/genética , Humanos , Masculino , Datos de Secuencia Molecular , Alineación de SecuenciaRESUMEN
BACKGROUND: Chronic mitral valvular insufficiency (CMVI) in dogs is very common and might cause clinical signs of congestion and poor tissue perfusion. HYPOTHESIS: Poor tissue perfusion from CMVI causes pancreatitis in dogs, as indicated by serum pancreatic lipase concentrations. ANIMALS: Sixty-two client-owned dogs consisting of 40 dogs with different stages of heart failure from CMVI and 22 age-matched healthy dogs, based on full cardiac exam and routine laboratory tests. METHODS: Prospective, controlled, observational study. Serum canine pancreatic lipase immunoreactivity (cPLI) concentrations were determined by quantitative cPLI test in healthy and CMVI groups. RESULTS: Serum cPLI concentrations were 54.0 µg/L (IQR: 38.0-78.8 µg/L) in control, 55.0 µg/L (IQR: 38.3-88.8 µg/L) in ISACHC I, 115.0 µg/L (IQR: 45.0-179.0 µg/L) in ISACHC II and 223.0 µg/L (IQR: 119.5-817.5 µg/L) in ISACHC III. Close correlation to serum cPLI concentration was found in the left atrial to aorta (LA/Ao) ratio (r = 0.597; P = .000) and the severity of heart failure (r = 0.530; P = .000). CONCLUSIONS AND CLINICAL IMPORTANCE: This study found CMVI is associated with pancreatic injury in congestive heart failure caused by CMVI. Therefore, periodic monitoring on cPLI could be useful in monitoring dogs in heart failure.
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Enfermedades de los Perros/etiología , Insuficiencia Cardíaca/veterinaria , Lipasa/sangre , Insuficiencia de la Válvula Mitral/veterinaria , Páncreas/enzimología , Animales , Estudios de Casos y Controles , Enfermedades de los Perros/enzimología , Perros , Insuficiencia Cardíaca/complicaciones , Lipasa/metabolismo , Insuficiencia de la Válvula Mitral/complicaciones , Pancreatitis/enzimología , Pancreatitis/etiología , Pancreatitis/veterinariaRESUMEN
Developmental dyslexia, the most common childhood learning disorder, is highly heritable, and recent studies have identified KIAA0319-Like (KIAA0319L) as a candidate dyslexia susceptibility gene at the 1p36-34 (DYX8) locus. In this experiment, we investigated the anatomical effects of knocking down this gene during rat corticogenesis. Cortical progenitor cells were transfected using in utero electroporation on embryonic day (E) 15.5 with plasmids encoding either: (1) Kiaa0319l small hairpin RNA (shRNA), (2) an expression construct for human KIAA0319L, (3) Kiaa0319l shRNA+KIAA0319L expression construct (rescue), or (4) controls (scrambled Kiaa0319l shRNA or empty expression vector). Mothers were injected with 5-bromo-2-deoxyuridine (BrdU) at either E13.5, E15.5, or E17.5. Disruption of Kiaa0319l function (by knockdown, overexpression, or rescue) resulted in the formation of large nodular periventricular heterotopia in approximately 25% of the rats, which can be seen as early as postnatal day 1. Only a small subset of heterotopic neurons had been transfected, indicating non-cell autonomous effects of the transfection. Most heterotopic neurons were generated in mid- to late-gestation, and laminar markers suggest that they were destined for upper cortical laminae. Finally, we found that transfected neurons in the cerebral cortex were located in their expected laminae. These results indicate that KIAA0319L is the fourth of four candidate dyslexia susceptibility genes that is involved in neuronal migration, which supports the association of abnormal neuronal migration with developmental dyslexia.
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Corteza Cerebral/crecimiento & desarrollo , Dislexia/genética , Regulación del Desarrollo de la Expresión Génica , Malformaciones del Desarrollo Cortical del Grupo II/genética , Células-Madre Neurales/metabolismo , Proteínas Nucleares/metabolismo , Animales , Animales Recién Nacidos , Susceptibilidad a Enfermedades , Electroporación , Humanos , Neurogénesis/genética , Proteínas Nucleares/genética , ARN Interferente Pequeño , Ratas , Ratas Transgénicas , Receptores de Superficie Celular , TransfecciónRESUMEN
Imprinting control regions (ICRs) play a fundamental role in establishing and maintaining the non-random monoallelic expression of certain genes, via common regulatory elements such as non-coding RNAs and differentially methylated regions (DMRs) of DNA. We recently surveyed DNA methylation levels within four ICRs (H19-ICR, IGF2-DMR, KvDMR, and NESPAS-ICR) in whole-blood genomic DNA from 128 monozygotic (MZ) and 128 dizygotic (DZ) human twin pairs. Our analyses revealed high individual variation and intra-domain covariation in methylation levels across CpGs and emphasized the interaction between epigenetic variation and the underlying genetic sequence in a parent-of-origin fashion. Here, we extend our analysis to conduct two genome-wide screenings of single nucleotide polymorphisms (SNPs) underlying either intra-domain covariation or parent-of-origin-dependent association with methylation status at individual CpG sites located within ICRs. Although genome-wide significance was not surpassed due to sample size limitations, the most significantly associated SNPs found through multiple-trait genome-wide association (MQFAM) included the previously described rs10732516, which is located in the vicinity of the H19-ICR. Similarly, we identified an association between rs965808 and methylation status within the NESPAS-ICR. This SNP is positioned within an intronic region of the overlapping genes GNAS and GNAS-AS1, which are imprinted genes regulated by the NESPAS-ICR. Sixteen other SNPs located in regions apart from the analyzed regions displayed suggestive association with intra-domain methylation. Additionally, we identified 13 SNPs displaying parent-of-origin association with individual methylation sites through family-based association testing. In this exploratory study, we show the value and feasibility of using alternative GWAS approaches in the study of the interaction between epigenetic state and genetic sequence within imprinting regulatory domains. Despite the relatively small sample size, we identified a number of SNPs displaying suggestive association either in a domain-wide or in a parent-of-origin fashion. Nevertheless, these associations will require future experimental validation or replication in larger and independent samples.
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Metilación de ADN , Estudio de Asociación del Genoma Completo , Impresión Genómica , Padres , Polimorfismo de Nucleótido Simple/genética , Sitios de Carácter Cuantitativo , ARN Largo no Codificante/genética , Gemelos/genética , Adolescente , Adulto , Niño , Mapeo Cromosómico , Epigénesis Genética , Femenino , Subunidades alfa de la Proteína de Unión al GTP Gs/genética , Humanos , Factor II del Crecimiento Similar a la Insulina/genética , Masculino , Canales de Potasio con Entrada de Voltaje/genética , Secuencias Reguladoras de Ácidos Nucleicos , Adulto JovenRESUMEN
BACKGROUND: For treating dogs with heavy heartworm infection, mechanical removal using various retrieval devices is useful. However, the efficacy and safety of retrieval devices have rarely been studied. HYPOTHESIS: Catheter-based heartworm removal using 2 retrieval devices (basket and tripod grasping forceps) is efficient and safe for treating dogs with heavy worm burden. ANIMALS: Fifty-two client-owned dogs with heavy (Class III and IV) worm burden. METHODS: A retrospective study was performed on 52 dogs, using a catheter-based heartworm removal approach using 2 types of retrieval devices (ie, the basket and the tripod grasping forceps). The efficacy and complications associated with the 2 devices were assessed. RESULTS: The basket device was used on 22 of the study group dogs, and the tripod grasping forceps was used on 30 of the dogs. The postoperative survival rate was 95.5% for the basket device and 80% for the tripod grasping forceps, but the difference was not statistically significant. The worm number captured per attempt was 3.5 ± 1.7 using the basket device and 1.9 ± 0.85 for the tripod grasping forceps (P < .05). Various complications associated with heartworm removal were noticed with both retrieval devices. CONCLUSIONS AND CLINICAL IMPORTANCE: This study suggests that catheter-based heartworm removal is not only a relatively safe and efficient therapeutic method in dogs with heavy worm burden, but more efficient using the basket device. Our data do not indicate a clear safety advantage between the 2 devices evaluated, although the survival rate was numerically higher in dogs undergoing a basket intervention.
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Dirofilariasis/cirugía , Enfermedades de los Perros/cirugía , Instrumentos Quirúrgicos/veterinaria , Animales , Dirofilariasis/patología , Enfermedades de los Perros/patología , Perros , Diseño de Equipo , Femenino , Masculino , Estudios RetrospectivosRESUMEN
The C868T single nucleotide polymorphism (SNP) in the CD4 receptor encodes an amino acid change that could alter its structure and influence human immunodeficiency virus (HIV-1) infection risk. HIV-1-infected pregnant women in Nairobi were followed with their infants for 1 year postpartum. Among 131 infants, those with the 868T allele were more likely than wild-type infants to acquire HIV-1 overall [hazard ratio (HR) = 1.92, 95% confidence interval (CI) 1.05, 3.50, P = 0.03; adjusted HR = 2.03, 95% CI 1.03, 3.98, P = 0.04], after adjusting for maternal viral load. This SNP (an allele frequency of approximately 15% in our cohort) was associated with increased susceptibility to mother-to-child HIV-1 transmission, consistent with a previous study on this polymorphism among Nairobi sex workers.
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Alelos , Antígenos CD4/genética , Frecuencia de los Genes , Infecciones por VIH/genética , Infecciones por VIH/transmisión , VIH-1 , Transmisión Vertical de Enfermedad Infecciosa , Polimorfismo de Nucleótido Simple , Adulto , Antígenos CD4/inmunología , Estudios de Cohortes , Femenino , Infecciones por VIH/inmunología , Humanos , Lactante , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/genética , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/virologíaRESUMEN
Canine parvovirus type 2 (CPV-2) is a major pathogen inducing acute hemorrhagic gastroenteritis in dogs. Despite the identification of numerous CPV-2 variants (from CPV-2a to CPV-2c), the pathogenic differences among the CPV-2 variants in dogs have not been evaluated. The aim of this study was to compare the pathogenicity of CPV-2 variants (CPV-2a-I, CPV-2a-V and CPV-2b) isolated mainly from Korea. We evaluated the pathogenicity of three different CPV-2 variants, by performing clinical, hematological, serological and histopathological examinations after experimentally inoculating three types of CPV-2 variants into young puppies. We found that the overall pathogenicity of the CPV-2a variants (CPV-2a-I and 2a-V) was severer compared to the CPV-2b variant. In addition, there was no significant difference in pathogenicity between the two CPV-2a variants. Our findings indicate that there are differences in the pathogenicity of CPV-2 variants in dogs, which may be useful to understand the different pathobiology of the CPV-2 variants.
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Enfermedades de los Perros/patología , Enfermedades de los Perros/virología , Infecciones por Parvoviridae/veterinaria , Parvovirus Canino/patogenicidad , Análisis de Varianza , Animales , Animales Recién Nacidos , Anticuerpos Antivirales/sangre , Variación Antigénica , Antígenos Virales/inmunología , Diarrea/mortalidad , Diarrea/patología , Diarrea/veterinaria , Diarrea/virología , Enfermedades de los Perros/mortalidad , Perros , Pruebas de Inhibición de Hemaglutinación/veterinaria , Pruebas Hematológicas/veterinaria , Corea (Geográfico) , Infecciones por Parvoviridae/mortalidad , Infecciones por Parvoviridae/patología , Infecciones por Parvoviridae/virología , Parvovirus Canino/clasificación , Parvovirus Canino/inmunología , Filogenia , Distribución AleatoriaRESUMEN
AIM: To study the estrogenic activity of formononetin in vitro. METHODS: We have established a highly sensitive bioassay system by placing estrogen-responsive elements upstream of the luciferase reporter gene, and used this assay to determine the estrogenic activity of formononetin. Cell growth was measured by the MTT (3-(4,5-dimethylthioazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and MG-63 cell function was studied by measuring alkaline phosphatase activity. RESULTS: Formononetin activated expression of the estrogen-responsive reporter gene in human breast cell line MCF-7 in a concentration-dependent manner (0.5-500 microM), and this activation was inhibited by estrogen antagonist (ICI 182780 at 100 nM). Furthermore, it induced the proliferation of MCF-7 breast cancer cells and MG-63 osteosarcoma cells, and it also increased the alkaline phosphatase activity in MG-63 cells. CONCLUSION: Formononetin is a phytoestrogen that exhibits variable degrees of estrogen receptor agonism in different test systems.
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Bioensayo/métodos , Estrógenos/farmacología , Isoflavonas/farmacología , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Genes Reporteros/efectos de los fármacos , Humanos , Modelos Biológicos , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Fitoestrógenos/farmacología , Transcripción Genética/efectos de los fármacos , Transfección , Células Tumorales CultivadasRESUMEN
AIM: To study the effect of ginsenoside Re on PC12 cell damage induced by serum deprivation and beta-amyloid peptide. METHODS: PC 12 cell survival was measured by MTT and lactate dehydrogenase (LDH) assay. Results Serum-free medium and beta-amyloid peptide (10-100 microM) induced cytotoxicity in PC 12 cells. Ginsenoside Re (0.1-100 microM) attenuated the cytotoxic effects of serum-free medium and beta-amyloid peptide (50 microM) in a concentration-dependent manner. CONCLUSION: Ginsenoside Re prevented PC 12 cells from lesion induced by serum-free medium and beta-amyloid peptide.
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Péptidos beta-Amiloides/farmacología , Ginsenósidos/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Medio de Cultivo Libre de Suero , L-Lactato Deshidrogenasa/metabolismo , Células PC12 , Panax/química , RatasRESUMEN
In vertebrate neuromuscular junctions, ATP is stored at the motor nerve terminals and is co-released with acetylcholine during neural stimulation. Here, we provide several lines of evidence that the synaptic ATP can act as a synapse-organizing factor to induce the expression of acetylcholinesterase (AChE) and acetylcholine receptor (AChR) in muscles, mediated by a metabotropic ATP receptor subtype, the P2Y(1) receptor. The activation of the P2Y(1) receptor by adenine nucleotides stimulated the accumulation of inositol phosphates and intracellular Ca(2+) mobilization in cultured chick myotubes. P2Y(1) receptor mRNA in chicken muscle is very abundant before hatching and again increases in the adult. The P2Y(1) receptor protein is shown to be restricted to the neuromuscular junctions and colocalized with AChRs in adult muscle (chicken, Xenopus, and rat) but not in the chick embryo. In chicks after hatching, this P2Y(1) localization develops over approximately 3 weeks. Denervation or crush of the motor nerve (in chicken or rat) caused up to 90% decrease in the muscle P2Y(1) transcript, which was restored on regeneration, whereas the AChR mRNA greatly increased. Last, mRNAs encoding the AChE catalytic subunit and the AChR alpha-subunit were induced when the P2Y(1) receptors were activated by specific agonists or by overexpression of P2Y(1) receptors in cultured myotubes; those agonists likewise induced the activity in the myotubes of promoter-reporter gene constructs for those subunits, actions that were blocked by a P2Y(1)-specific antagonist. These results provide evidence for a novel function of ATP in regulating the gene expression of those two postsynaptic effectors.
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Acetilcolinesterasa/metabolismo , Músculo Esquelético/metabolismo , Receptores Colinérgicos/metabolismo , Receptores Purinérgicos P2/biosíntesis , Nucleótidos de Adenina/farmacología , Adenosina Trifosfato/metabolismo , Envejecimiento/metabolismo , Animales , Células COS , Calcio/metabolismo , Células Cultivadas , Embrión de Pollo , Pollos , Fosfatos de Inositol/metabolismo , Neuronas Motoras/fisiología , Músculo Esquelético/citología , Compresión Nerviosa , Regeneración Nerviosa/fisiología , Unión Neuromuscular/metabolismo , ARN Mensajero/metabolismo , Ratas , Receptores Colinérgicos/genética , Receptores Purinérgicos P2/efectos de los fármacos , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2Y1 , Médula Espinal/metabolismo , Transfección , XenopusRESUMEN
Cell motility is likely to play a pivotal role in HIV infection by promoting the dissemination of infected cells. On the basis of observations indicating an interaction between HIV-1 Gag and target cell filamentous actin, we hypothesized that these interactions would promote cell motility of HIV-infected cells. Indeed, we have found that HIV-1 infection enhances the chemotactic response of macrophages. To specifically investigate the significance of the interactions between Gag and cellular actin, we transfected NIH 3T3 fibroblasts and HeLa cells with a construct that permits the expression of HIV-1 Gag in the absence of any other viral protein. Fractionation experiments showed that Gag was present in cytoskeletal fraction containing long actin filaments and in a high-speed postcytoskeletal fraction with short actin filaments. We have also localized HIV-1 Gag to the lamellipodia of chemoattractant-stimulated cells. Significantly, the motility of Gag-expressing cells was enhanced in chemotaxis assays. In vitro mutagenesis experiments showed that HIV-1 Gag binds filamentous actin through the nucleocapsid domain (NC). An NC-green fluorescent protein fusion had the same cellular distribution as the complete protein, and its expression increased cell motility. These data suggest that interactions between HIV-1 Gag and actin in infected cells enhance cell motility. Ultimately this enhanced motility of infected cells could promote the dissemination of virus into the brain and other tissues.
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Quimiotaxis/fisiología , Citoesqueleto/metabolismo , Productos del Gen gag/metabolismo , VIH-1/patogenicidad , Macrófagos/fisiología , Nucleocápside/metabolismo , Células 3T3/fisiología , Células 3T3/virología , Actinas/metabolismo , Animales , Productos del Gen gag/genética , VIH-1/fisiología , Células HeLa/fisiología , Células HeLa/virología , Humanos , Macrófagos/virología , Ratones , Monocitos/fisiología , Monocitos/virología , TransfecciónRESUMEN
Intrauterine growth retardation (IUGR) affects almost 10% of infants born in the United States. It may be responsible for delayed gastrointestinal function and is an important cause of perinatal morbidity and mortality. The New Zealand White rabbit provides an optimal model for the study of naturally occurring IUGR. At term, birth weight is determined by fetal position within the bicornuate uterus. The small intestinal disaccharidase enzymes are indicators of bowel maturity and function. To examine potential differences in disaccharidase development between normal and IUGR fetuses, this rabbit model was investigated. Jejunum was harvested at multiple stages in rabbit development including the third trimester fetus, neonate, and adult. Lactase, maltase, and sucrase enzyme activity, as well as total protein content, was determined. Results were analyzed by the 2-tailed t test and ANOVA. Lactase activity appeared in the mid-third trimester, peaked in the early neonatal period, then declined to adult levels. Maltase activity appeared in the early third trimester and gradually rose to adult levels. Sucrase remained at trace levels until the mid-neonatal period, reaching adult levels by weaning. Both lactase and maltase activity were depressed in IUGR fetuses compared with their normal littermates. This pattern of disaccharidase depression continued into the neonatal period until catch-up growth occurred at 2 wk when levels equalized. This report describes differential small intestinal disaccharidase development between normal and growth-retarded rabbit fetuses in a naturally occurring model of IUGR.
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Disacaridasas/metabolismo , Modelos Animales de Enfermedad , Retardo del Crecimiento Fetal/enzimología , Animales , Intestino Delgado/embriología , Intestino Delgado/enzimología , ConejosRESUMEN
Biological diversity in the wound healing response is thought to be a major factor limiting the predictability of the outcome of refractive surgical procedures such as laser in situ keratomileusis and photorefractive keratectomy. Corneal wound healing is critical to the success of topography-linked or wave front-linked excimer laser ablation to optimize visual performance. This is because of the importance of retaining subtle features of custom ablation and the tendency of epithelial hyperplasia and stromal remodeling to obscure these features following either procedure. The corneal wound healing response is exceedingly complex. Keratocyte apoptosis, which occurs in response to epithelial injury, is the earliest observable event in the wound healing cascades and is therefore an excellent target for pharmacological intervention. Alterations of surgical technique can be designed to limit keratocyte apoptosis and the subsequent events in corneal wound healing. Abnormalities of the cascades could contribute to the pathogenesis of corneal diseases. For example, recent data have suggested that perturbation of the keratocyte apoptosis/mitosis balance could underlie the development of keratoconus in a proportion of patients.
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Córnea/fisiología , Queratomileusis por Láser In Situ , Queratectomía Fotorrefractiva , Cicatrización de Heridas/fisiología , Animales , Apoptosis/fisiología , Córnea/citología , Células Epiteliales/fisiología , Fibroblastos/fisiología , Humanos , Láseres de Excímeros , Mitosis/fisiología , Errores de Refracción/metabolismo , Procedimientos Quirúrgicos RefractivosRESUMEN
PURPOSE: To retrospectively analyze the safety and efficacy of hyperopic laser in situ keratomileusis (LASIK) treatment of eyes with primary hyperopia and consecutive hyperopia after initial myopic treatment. METHODS: Thirty-two eyes of 19 patients with primary hyperopia (group 1) and 37 eyes of 26 patients with consecutive hyperopia after initial myopic LASIK overcorrection (group 2) that had LASIK for hyperopia with the Hansatome microkeratome and VISX S2 Smoothscan excimer laser with 6 months' follow-up after surgery were analyzed. Uncorrected visual acuity, best spectacle-corrected visual acuity, fogged manifest refraction, and corneal topography with corneal irregularity measurement (CIM) were evaluated 1 month, 3 months, and 6 months after surgery. RESULTS: In group 1, the mean preoperative cycloplegic spherical equivalent was +4.0 +/- 4.5 diopters (D) (range, +1.5 to + 8.75 D) and the 6-month postoperative cycloplegic spherical equivalent was +0.26 +/- 1.74 D (range, -3.00 to +2.75 D). Fifty-three percent of eyes (n= 17) in group 1 were within 1 D of emmetropia. Sixty-six percent of eyes (n= 21) had uncorrected visual acuity of at least 20/40. Three eyes (9%) lost two lines of best spectacle-corrected visual acuity. Changes in uncorrected visual acuity, best spectacle-corrected visual acuity, spherical equivalent, and the CIM topographic index 6 months after surgery were statistically significant compared with the preoperative values. In group 2, the mean preoperative cycloplegic spherical equivalent was +1.58 +/- 0.35 D (range, +0.125 to +2.75 D), and the mean postoperative cycloplegic spherical equivalent was -0.48 +/- 0.46 (range, -2.75 to +0.38 D). Eighty-six percent of eyes (n= 32) were within 1 D of emmetropia. Eighty-four percent of eyes (n= 31) in group 2 had uncorrected visual acuity of at least 20/40. One eye (2.7%) lost two lines of best spectacle-corrected visual acuity. Complications included an epithelial nest that resolved 3 months after surgery in one eye in group 2. CONCLUSIONS: LASIK is a relatively safe treatment of primary hyperopia and hyperopia resulting from overcorrection after initial LASIK treatment of myopia (consecutive hyperopia). Patients with high hyperopia (>5 D) are at risk for loss of two lines of best spectacle-corrected visual acuity. A reduction in the level of attempted correction appears to be necessary in the treatment of consecutive hyperopia.
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Córnea/cirugía , Hiperopía/cirugía , Queratomileusis por Láser In Situ , Adulto , Anciano , Topografía de la Córnea , Femenino , Humanos , Hiperopía/etiología , Masculino , Persona de Mediana Edad , Miopía/cirugía , Complicaciones Posoperatorias/cirugía , Refracción Ocular , Reoperación , Estudios Retrospectivos , Seguridad , Agudeza VisualRESUMEN
Cyclic adenosine 3',5'-monophosphate (cAMP)-dependent signalling pathway has been proposed to regulate acetylcholinesterase (AChE) expression in chick muscle; however, its role in mammalian enzyme is not known. We provide several lines of evidence to suggest that the cAMP-mediated AChE expression in myotube is oppositely regulated between avian and mammalian enzymes. Human AChE promoter was tagged with luciferase, namely Hp-Luc, which was transfected into cultured chick myotubes. Application of cAMP and forskolin induced the expression of chick AChE but reduced human AChE promoter-driven luciferase activity. Transfection of cDNAs encoding active mutants of G proteins altered the intracellular cAMP level in myotubes as well as the expression of chick and human AChE. When the constitutively active forms of Activating Transcription Factor-1 (EWS/ATF-1 oncogene) were over expressed in Hp-Luc transfected myotubes, the expression of chick AChE transcript and protein increased from approximately 1.8- to approximately 2.5-fold, but the luciferase activity was decreased by over 60%. Overexpression of cAMP-responsive element binding protein (CREB) in Hp-Luc transfected myotubes markedly enhanced the cAMP-mediated AChE expression in up- and downregulated chick and human enzymes, respectively. In addition, CREB bound the CRE sequence of human AChE promoter. Mutation on the CRE site markedly enhanced the expression of the promoter-driven luciferase; however, its response to cAMP inhibition in cultured myotubes was still retained. These findings suggest that a cAMP-dependent pathway is contrasting activation and repression of AChE expression in chick and human muscles.
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Acetilcolinesterasa/genética , AMP Cíclico/metabolismo , Proteínas de Unión al ADN , Regulación Enzimológica de la Expresión Génica/fisiología , Fibras Musculares Esqueléticas/enzimología , Factor de Transcripción Activador 1 , Animales , Células Cultivadas , Embrión de Pollo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Humanos , Mamíferos , Fibras Musculares Esqueléticas/citología , Mutagénesis Sitio-Dirigida/fisiología , Regiones Promotoras Genéticas/fisiología , Unión Proteica/genética , Especificidad de la Especie , Factores de Transcripción/metabolismo , TransfecciónRESUMEN
The importance of cholesterol ester synthesis by acyl CoA:cholesterol acyltransferase (ACAT) enzymes in intestinal and hepatic cholesterol metabolism has been unclear. We now demonstrate that ACAT2 is the major ACAT in mouse small intestine and liver, and suggest that ACAT2 deficiency has profound effects on cholesterol metabolism in mice fed a cholesterol-rich diet, including complete resistance to diet-induced hypercholesterolemia and cholesterol gallstone formation. The underlying mechanism involves the lack of cholesterol ester synthesis in the intestine and a resultant reduced capacity to absorb cholesterol. Our results indicate that ACAT2 has an important role in the response to dietary cholesterol, and suggest that ACAT2 inhibition may be a useful strategy for treating hypercholesterolemia or cholesterol gallstones.
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Colelitiasis/etiología , Colesterol en la Dieta/efectos adversos , Hipercolesterolemia/etiología , Esterol O-Aciltransferasa/metabolismo , Animales , Vesícula Biliar/patología , Inmunidad Innata , Absorción Intestinal , Lipoproteínas/sangre , Lipoproteínas/ultraestructura , Hígado/patología , Masculino , Ratones , Ratones Mutantes , Esterol O-Aciltransferasa/genéticaRESUMEN
Different transcription elements have been proposed to play a role in the regulation of acetylcholinesterase (AChE) in muscle and neuron, and cyclic adenosine 3',5'-monophosphate (cAMP)-dependent pathway is one of them. In order to test the possible role of cAMP in regulating the expression of human AChE, an approximately 2.2 kb DNA fragment of human AChE promoter was linked up stream to a luciferase reporter. The chimeric DNA was transfected into cultured NG108-15 neuroblastoma cells. Application of Bt(2)-cAMP and forskolin increased the promoter driven luciferase activity over 2-fold in the transfected NG108-15 cells; the increase was parallel to the activation of endogenous AChE protein and enzymatic activity. The intracellular cAMP level was increased in the Galpha(sQL) (constitutively active mutant of Galpha(s)) cDNA transfected NG108-15 cells. The Galpha(sQL) cDNA transfected cells showed an increase of over 10-fold in the luciferase activity. In addition, a constitutively active mutant of activating transcription factor-1 (ATF-1) was able to turn on human AChE promoter by approximately 4-fold when they were co-expressed in the neuroblastoma cells. These results support the involvement of a cAMP-dependent pathway in regulating the expression of human AChE.
Asunto(s)
Acetilcolinesterasa/genética , AMP Cíclico/metabolismo , Regulación Enzimológica de la Expresión Génica/fisiología , Neuronas/enzimología , Regiones Promotoras Genéticas/fisiología , Animales , Bucladesina/farmacología , Diferenciación Celular/fisiología , Colforsina/farmacología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Genes Reporteros , Humanos , Luciferasas/genética , Neuroblastoma , Neuronas/citología , Transducción de Señal/fisiología , Sinapsis/fisiología , Transcripción Genética/efectos de los fármacos , Transcripción Genética/fisiología , Transfección , Células Tumorales CultivadasRESUMEN
Calcitonin gene-related peptide (CGRP), a neuropeptide synthesized by motor neurons, stimulates the expression of AChR and AChE at the vertebrate neuromuscular junctions. The signaling mechanism of CGRP-induced AChE expression in muscle was determined both in vitro and in vivo. In cultured chick myotubes, the intracellular cAMP-dependent protein kinase (PKA) activity increased to approximately 2-fold after the application of CGRP or PKA activators; the induction was blocked by PKA inhibitors. in vivo transfection analysis on chick gastrocnemius muscles showed that the transfection of cDNA encoding constitutively active mutant Galphas increased the expression of AChE mRNA and protein to approximately 2-fold, while the constitutively active mutant Galphai cDNA transfection showed an opposite effect. The induced catalytic subunit of AChE at approximately 105 kDa was determined by specific antibody. These findings indicate that the CGRP-induced AChE expression in chick muscle is mediated by a PKA-dependent pathway.