RESUMEN
Caligus rogercresseyi is the dominant sea louse parasite affecting the salmon and trout industry in southern Chile. This parasite has a wide range of native and endemic fish hosts. The Patagonian blenny Eleginops maclovinus, which is parasitized mostly by the caligid species Lepeophtheirus spp. and C. rogercresseyi, is presumably responsible for the transmission of C. rogercresseyi to salmonids. The aim of this study was to characterize the transmission of parasites between different fish species and parasite cohort development under laboratory conditions. Parasite abundances and intensities were quantified. Transmission of parasites from Patagonian blenny to Atlantic salmon Salmo salar was lower (~9%, mainly corresponding to C. rogercresseyi) than from salmon to Patagonian blenny (14.7-26.9%, where only C. rogercresseyi were observed). This suggests that the transmission of C. rogercresseyi from salmon individuals is higher than the transmission from a native fish. Parasite cohorts developed successfully on both fish species, but apparently under different developmental rates. Water temperature, oxygen, and juvenile abundances were the variables that better explained cohort development success and variation in C. rogercresseyi adult abundances over time.
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Copépodos , Enfermedades de los Peces , Salmo salar , Salmonidae , Animales , Chile/epidemiología , Enfermedades de los Peces/epidemiología , SalmónRESUMEN
High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent ß-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated ß-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 ß-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 ß-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 ß-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 ß-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.
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Células Secretoras de Insulina/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Transcriptoma/genética , Acetilserotonina O-Metiltransferasa/efectos de los fármacos , Acetilserotonina O-Metiltransferasa/genética , Animales , N-Acetiltransferasa de Arilalquilamina/efectos de los fármacos , N-Acetiltransferasa de Arilalquilamina/genética , Catecol O-Metiltransferasa/efectos de los fármacos , Catecol O-Metiltransferasa/genética , Línea Celular , Dopa-Decarboxilasa/efectos de los fármacos , Dopa-Decarboxilasa/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/efectos de los fármacos , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Dopamina beta-Hidroxilasa/efectos de los fármacos , Dopamina beta-Hidroxilasa/genética , Insulina/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/metabolismo , Ratones , Monoaminooxidasa/efectos de los fármacos , Monoaminooxidasa/genética , Ácido Oléico/farmacología , Ácido Palmítico/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Serotonina/metabolismo , Proteínas de Transporte de Serotonina en la Membrana Plasmática/efectos de los fármacos , Proteínas de Transporte de Serotonina en la Membrana Plasmática/genética , Transcriptoma/efectos de los fármacos , Triptófano Hidroxilasa/efectos de los fármacos , Triptófano Hidroxilasa/genética , Tirosina 3-Monooxigenasa/efectos de los fármacos , Tirosina 3-Monooxigenasa/genéticaRESUMEN
Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation (AU)
No disponible
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Humanos , Masculino , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/diagnóstico , Insulina , Glucemia/análisis , Intolerancia a la Glucosa/diagnóstico , Estado Prediabético/diagnóstico , Resistencia a la Insulina/etnología , Células Secretoras de Insulina , Chile , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etnología , Insulina/sangre , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/etnología , Estado Prediabético/sangre , Estado Prediabético/etnología , Salud de la Familia/etnología , Prueba de Tolerancia a la GlucosaRESUMEN
Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/diagnóstico , Intolerancia a la Glucosa/diagnóstico , Resistencia a la Insulina , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Estado Prediabético/diagnóstico , Adolescente , Adulto , Chile , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/metabolismo , Salud de la Familia/etnología , Femenino , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/etnología , Intolerancia a la Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina/etnología , Secreción de Insulina , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Estado Prediabético/sangre , Estado Prediabético/etnología , Estado Prediabético/metabolismo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
INTRODUCTION: Pancreatic ß-cells synthetize and store Serotonin (5-Hydroxytriptamine, 5HT) which is co-released with insulin. It has been proposed that extracellular 5HT binds to specific cell surface receptors and modulate insulin secretion. On the other hand, Selective Serotonin Reuptake Inhibitor (SSRI) fluoxetine seems to reduce Glucose-Stimulated Insulin Secretion (GSIS). However, it is unknown whether this effect results from changes in extracellular 5HT concentration owed to the blockade of 5HT transporter (SERT) or from non-5HT dependent actions. The aims of this work were: 1) to quantify extracellular 5HT levels and GSIS in ß-cell lines, 2) to determine whether extracellular 5HT levels and GSIS are changed by fluoxetine or 5-Hydroxytryptophan (5HTP, the immediate 5HT biosynthetic precursor), and 3) to quantify the expression of Slc6a4 gene (encoding SERT) in ß-cell lines in relation to other genes involved in 5HT system. MATERIAL AND METHODS: ß-cell lines MIN6 and RINm5f were subjected to GSIS protocols, after treatment with fluoxetine, 5HTP or 5HT. Insulin and 5HT were quantified by ELISA and HPLC, respectively. Relative mRNA expression was quantified by RT-qPCR. RESULTS: MIN6 ß-cells secretes 5HT in response to glucose, showing a sharp increase in 5HT release when cells were preloaded with 5HTP. Treatment with 5HT or fluoxetine reduces GSIS. Fluoxetine fails to further increases 5HTP-induced elevation of secreted 5HT. MIN6 ß-cells express both isoforms of Tryptophan Hydroxylase (Tph1 and Tph2), and have high expression levels of L-Dopa decarboxylase (Ddc), both enzymes involved in 5HT biosynthetic pathway, but do not express the 5HT transporters Slc6a4 or Slc6a3 (the Dopamine-5HT transporter) genes. CONCLUSION: The inhibitory effect of fluoxetine on ß-cell glucose stimulated insulin secretion is not mediated by blockage of 5HT transporter through SERT.
Asunto(s)
Fluoxetina/farmacología , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Serotonina/metabolismo , Animales , Descarboxilasas de Aminoácido-L-Aromático/metabolismo , Línea Celular Tumoral , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Secreción de Insulina , Células Secretoras de Insulina/citología , Ratones , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Triptófano Hidroxilasa/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Recent and ongoing clinical studies have indicated that topiramate (Topamax®) could be effective in treating ethanol or cocaine abuse. However, the effects of topiramate on the co-administration of ethanol and cocaine remain largely unknown. EXPERIMENTAL APPROACH: We studied the effects of topiramate, in Wistar rats, on operant ethanol self-administration with the co-administration of cocaine (i.p.). The psychomotor effects of topiramate were examined before ethanol self-administration and cocaine exposure. Blood samples were collected to analyse ethanol and cocaine metabolism (blood ethanol levels and benzoylecgonine). Quantitative real-time PCR was used to characterize the gene expression in the prefrontal cortex. KEY RESULTS: Topiramate prevented the cocaine-induced increased response to ethanol in a dose-dependent manner without causing any motor impairment by itself. This effect was observed when topiramate was administered before ethanol access, but not when topiramate was administered before the cocaine injection. Topiramate did not block cocaine-induced psychomotor stimulation. Topiramate reduced blood ethanol levels but did not affect cocaine metabolism. Ethanol increased the gene expression of DNA methyltransferases (Dnmt1 and Dnmt3a), the corepressor Dnmt1-associated protein 1 (Dmap1), and the RNA methyltransferase Trdmt1. These effects were prevented by topiramate or cocaine. Gene expression of histone deacetylase-2 and glutamate receptor kainate-1 were only increased by cocaine treatment. Topiramate and cocaine co-administration caused an up-regulation of dopamine (Drd1, Th) and opioid (Oprm1) receptor genes. Topiramate showed a tendency to alter episodic-like memory. CONCLUSIONS AND IMPLICATIONS: Topiramate is an effective inhibitor of the cocaine-induced increase in operant ethanol self-administration.
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Cocaína/farmacología , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Etanol/farmacología , Fructosa/análogos & derivados , Corteza Prefrontal/efectos de los fármacos , Animales , Conducta Animal/efectos de los fármacos , Cocaína/administración & dosificación , Cocaína/metabolismo , Condicionamiento Operante , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Etanol/administración & dosificación , Etanol/sangre , Fructosa/farmacología , Regulación Enzimológica de la Expresión Génica , Inyecciones Intraperitoneales , Masculino , Memoria Episódica , Corteza Prefrontal/enzimología , Desempeño Psicomotor/efectos de los fármacos , Ratas Wistar , Autoadministración , Factores de Tiempo , TopiramatoRESUMEN
The interaction of B7 family members with appropriate receptors is essential for an effective T cell response. CD80 and CD86 are the principal co-stimulatory molecules of this family and they are mainly expressed on professional antigen presenting cells (APCs), but also on several non-lymphoid cells. CD86 is constitutively expressed in keratinocytes from the spinous layer of normal cervical epithelium. However, the mechanisms that control the expression of this gene in epithelial cells remain unknown. We analyzed the DNA methylation status of the CD86 promoter and a CpG island located in the upstream intergenic region in keratinocyte-derived cell lines. In those cell lines where CD86 is expressed, a high degree of methylation in the CpG island was observed. However, a CpG dinucleotide within the cAMP response element (CRE) in the promoter region was consistently unmethylated and associated to the transcription factor CREB, as demonstrated by ChIP assays. The opposite methylation pattern was observed in cell lines where CD86 is not expressed, affecting also the binding of CREB. The analysis of the DNA methylation pattern of this gene in cells from the spinous and basal layers of normal cervical epithelium showed a similar profile to that observed in cell lines with and without expression of CD86 respectively. Our results indicate that the methylation pattern in the CD86 promoter and CpG island is closely related to the expression of this co-stimulatory molecule in keratinocytes.
Asunto(s)
Antígeno B7-2/genética , Islas de CpG/genética , Metilación de ADN/genética , Regulación de la Expresión Génica/genética , Queratinocitos/fisiología , Regiones Promotoras Genéticas/genética , Línea Celular , HumanosRESUMEN
The objective of this study was to evaluate the application of a TaqMan real-time reverse transcriptase PCR (RT-PCR) assay for the detection of infectious salmon anaemia virus (ISAV) in formalin-fixed paraffin-embedded (FFPE) fish tissues from Atlantic salmon Salmo salar with and without clinical signs of infection, and to compare it with histological and immunohistochemical (IHC) techniques. Sixteen fish samples obtained in 2007 and 2008 from 4 different farms in Chile were examined. The real-time RT-PCR allowed the detection of ISAV in FFPE samples from 9 of 16 fish, regardless of the organs analyzed, whereas 4 of the real-time RT-PCR negative fish were positive as indicated by histological examination and 3 of the real-time RT-PCR positive fish were negative as indicated by immunohistochemistry evaluation. The presence of ISAV in RT-PCR positive samples was confirmed by amplicon sequencing. This work constitutes the first report on the use of real-time RT-PCR for the detection of ISAV in FFPE sections. The assay is very useful for the examination of archival wax-embedded tissues, and allows for both prospective and retrospective evaluation of tissue samples for the presence of ISAV. However, the method only confirms the presence of the pathogen and should be used in combination with histopathology, which is a more precise tool. The combination of both techniques would be invaluable for confirmatory diagnosis of infectious salmon anaemia (ISA), which is essential for solving salmon farm problems.
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Enfermedades de los Peces/virología , Isavirus/aislamiento & purificación , Infecciones por Orthomyxoviridae/veterinaria , Adhesión en Parafina/veterinaria , Salmo salar , Fijación del Tejido/veterinaria , Animales , Enfermedades de los Peces/diagnóstico , Fijadores/química , Formaldehído/química , Infecciones por Orthomyxoviridae/diagnóstico , Infecciones por Orthomyxoviridae/virología , Adhesión en Parafina/métodos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Fijación del Tejido/métodosRESUMEN
We report the first isolation, identification and characterization of a group of Chilean strains of atypical Aeromonas salmonicida isolated from freshwater farmed Atlantic salmon, Salmo salar. Affected fish showed superficial ulcers and pale liver with or without petechial haemorrhages. Outbreaks of the disease occurred in two farms in the south of Chile about 2200 km apart. Five strains were isolated in pure culture and identified by serological assays and immunofluorescence tests as belonging to Aeromonas salmonicida. Although the bacterial isolates were phenotypically homogeneous, minor differences with the reference strain A. salmonicida subsp. salmonicida ATCC 33658 were noted. Three specific primer sets and partial 16S rRNA gene sequencing allowed the identification of the Chilean isolates as atypical A. salmonicida, with A. salmonicida subsp. achromogenes and A. salmonicida subsp. masoucida as their closest relatives (100% sequence similarity). Molecular typing indicated that the atypical isolates belong to two genetic groups that were associated with the geographical origin.
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Aeromonas salmonicida/genética , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/patología , Agua Dulce , Forunculosis/veterinaria , Aeromonas salmonicida/aislamiento & purificación , Animales , Chile , Forunculosis/microbiología , Forunculosis/patología , Genes Bacterianos/genética , Datos de Secuencia Molecular , Fenotipo , Filogenia , Reacción en Cadena de la Polimerasa , ARN Ribosómico 16S/genética , Salmo salarRESUMEN
Keratinocytes have been traditionally considered as nonprofessional antigen presenting cells, since multipassaged cells from skin biopsies of healthy individuals do not constitutively express major histocompatibility complex (MHC) class II or costimulatory molecules, but can be induced to do so after exposure to interferon-gamma. In normal and human papillomavirus (HPV)-infected cervical epithelium, keratinocytes are affected by a variety of soluble mediators that could modulate the expression of molecules including costimulatory proteins; however, the presence of these molecules within the cervix has been poorly studied. Therefore, our aim was to further explore the presence of costimulatory molecules on normal cervical epithelium and HPV-16 positive low squamous intraepithelial lesions (LSIL). We found in situ CD86 (but not CD80) displayed on the surface of normal keratinocytes from the spinous layer of human cervical epithelium. The presence of the protein and its messenger RNA level (evaluated by in situ hybridization) was diminished in HPV-16 positive LSILs. Although downregulation of costimulatory molecules is frequently related to cytokines expression, we did not observe differences in the presence of interleukin-10, the main cytokine that inhibits CD86 expression. Expression of CD86 on keratinocytes from normal cervical epithelium could indicate the potentiality of these cells to activate cytotoxic T cells, while the shut-off of this molecule in HPV-16 positive lesions could be a mechanism for evading host immune surveillance, resulting in the persistent HPV infection and probable progression of cervical lesions.
Asunto(s)
Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Cuello del Útero/metabolismo , Papillomavirus Humano 16/aislamiento & purificación , Queratinocitos/metabolismo , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/virología , Displasia del Cuello del Útero/metabolismo , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/virología , Epitelio/metabolismo , Femenino , Humanos , Interleucina-10/metabolismo , Queratinocitos/patología , Neoplasias de Células Escamosas/patología , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patologíaRESUMEN
Objetivos: Valorar aspectos epidemiológicos, procedimientos diagnósticos, terapéuticos y factores de mal pronóstico implicados en la afectación visual final de pacientes con cuerpos extraños intraoculares.Métodos: Estudio descriptivo retrospectivo realizado en el Hospital Comarcal del Bierzo, León entre junio del 96 y mayo de 2001, con un período de seguimiento medio de 2 años. Abarca 86 pacientes con traumatismo ocular grave que precisaron ingreso e intervención quirúrgica, de los cuales, se recogieron datos de los 25 pacientes que presentaban cuerpo extraño intraocular (30%).Resultados: La edad media corresponde a 46 años donde el 88% era de predominio masculino. El 72% corresponde a accidentes laborales, el 24% a accidentes domésticos y el 4% a actividades de ocio. La naturaleza del material fue de metal en el 80% de los casos y el 20% de material no metálico. Se obtuvieron resultados de una agudeza visual menor al 0,5 en el 60% de los pacientes, donde influyeron factores de mal pronóstico de forma significativa.Conclusiones: Los accidentes laborales ocasionan traumatismos oculares con entrada de cuerpo extraño intraocular, que son la mayoría de características metálicas. El diagnóstico se realizó a través de exploración directa, radiografía orbitaria urgente, profilaxis antitetánica y antibiótica, así como, restauración del globo ocular.El resultado final fue una agudeza menor de 0,5 en el 60% de los pacientes donde destacan factores de mal pronóstico como una agudeza visual inicial disminuida, defecto pupilar aferente, cuerpos extraños de materia orgánica y complicaciones posteriores.Una buena actuación preventiva en el ámbito laboral disminuiría el número de accidentes y traumatismos oculares producidos. y que requieren la extracción en casi todos de los casos
Objectives: To evaluate the epidemiological aspects, diagnosis, therapeutical procedures, and factors of poor prognosis in patients with intraocular foreign bodies.Methods: A descriptive and retrospective study carried out at The Hospital Comarcal del Bierzo (León), between June 1996 and May 2001, with an average follow-up period of 2 years. It comprises 86 patients affected by serious ocular traumatism who required hospitalization and surgery, 25 of whom had an intraocular foreign body (30%).Results: The average age was 46, and 88% were males. Accidents at work account for 72% of cases, domestic accidents for 24%, and leisure activities for 4%. The nature of the material causing the accident was metallic in 80% of cases, and non-metallic materials in 20%. In 60% of patients, the final visual acuity was less than 0.5.Conclusions: Labour accidents cause ocular traumas with foreign body entrance. In most cases foreign bodies have a metallic composition.Diagnosis was made through direct exploration, roentgenography, CT scan and ultrasonography.We proceeded to carry out urgent admission, antitetanus and antibiotic prophylaxis as well as reconstruction of ocular globe.Main bad-prognosis factors were a diminished previous visual acuity, the presence of afferent pupillary defect, organic composition of foreign body and the occurrence of late complications
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Adulto , Anciano , Anciano de 80 o más Años , Humanos , Cuerpos Extraños en el Ojo/epidemiología , Lesiones Oculares Penetrantes/epidemiología , Técnicas de Diagnóstico Oftalmológico , Procedimientos Quirúrgicos Oftalmológicos/métodos , Agudeza Visual , Cuerpos Extraños en el Ojo/diagnóstico , Cuerpos Extraños en el Ojo/cirugía , Lesiones Oculares Penetrantes/diagnóstico , Lesiones Oculares Penetrantes/cirugía , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , España/epidemiología , Tomografía Computarizada por Rayos XAsunto(s)
Personal de Salud , Relaciones Interprofesionales , Ética Profesional , Guías como Asunto , Humanos , EspañaRESUMEN
A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.
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Aldehído Reductasa/genética , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Retinopatía Diabética/fisiopatología , Repeticiones de Minisatélite , Polimorfismo Genético , Edad de Inicio , Anciano , Secuencia de Bases , Estudios de Casos y Controles , Chile , Diabetes Mellitus Tipo 2/fisiopatología , Retinopatía Diabética/enzimología , Progresión de la Enfermedad , Hemoglobina Glucada/análisis , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Recent studies suggest that polymorphisms associated to the aldose reductase gene could be related to early retinopathy in noninsulin dependent diabetics (NIDDM). There is also new interest on the genetic modulation of coagulation factors in relation to this complication. AIM: To look for a possible relationship between the rate of appearance of retinopathy and the genotype of (AC)n polymorphic marker associated to aldose reductase gene. PATIENTS AND METHODS: A random sample of 27 NIDDM, aged 68.1 +/- 10.6 years, with a mean diabetes duration of 20.7 +/- 4.8 years and a mean glycosilated hemoglobin of 10.6 +/- 1.6%, was studied. The genotype of the (AC)n, polymorphic marker associated to the 5' end of the aldose reductase (ALR2) gene was determined by 32P-PCR plus sequenciation. Mutations of the factor XIII-A gene were studied by single stranded conformational polymorphism, sequenciation and restriction fragment length polymorphism. RESULTS: Four patients lacked the (AC)24 and had a higher rate of appearance of retinopathy than patients with the (AC)24 allele (0.0167 and 0.0907 score points per year respectively, p = 0.047). Both groups had similar glycosilated hemoglobin (11.7 +/- 0.2 and 10.5 +/- 1.6% respectively). Factor XIII gene mutations were not related to the rate of appearance of retinopathy. CONCLUSIONS: Our data suggest that the absence of the (AC)24 allele of the (AC)n polymorphic marker associated to the 5' end of the aldose reductase gene, is associated to a five fold reduction of retinopathy appearance rate.
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Aldehído Reductasa/genética , Diabetes Mellitus Tipo 2/genética , Retinopatía Diabética/genética , Polimorfismo Genético , Edad de Inicio , Anciano , Alelos , Marcadores Genéticos , Genotipo , Humanos , Persona de Mediana Edad , Mutación , Índice de Severidad de la Enfermedad , Caracteres SexualesRESUMEN
BACKGROUND: An immunological damage of beta cells in the islets of Langerhans, plays a role in the pathogenesis of type 1 diabetes. Recently, the identification of individuals in pre clinical phase and with high risk of developing type 1 diabetes, has become possible by means of the detection of immune markers such as islet cell antibodies (ICA) and the measurement of first phase response of insulin (FPRI). SUBJECTS AND METHODS: We studied 1,021 first degree relatives of type 1 diabetics, aged 4 to 35 years. ICA were measured using poly-IgG peroxidase in sections of human pancreas. In those subjects with positive ICA and normal oral glucose tolerance test, the FPRI was measured. FPRI was defined as the sum of insulinemias at minutes 1 and 3 after a three minutes 0.5 g/kg glucose load. RESULTS: Thirty subjects were ICA (+), defined as having more than 20 juvenile diabetes foundation units (prevalence of 2.9%). No differences in age, sex and closeness of familial relationship was found between ICA (+) and ICA (-) individuals. FPRI was measured in 24 subjects with normal oral glucose tolerance test and was normal in five. Seventeen subjects had a decreased response (between percentiles 1 and 5) and two had a response below percentile 1. No relationship between ICA levels and FPRI was found. CONCLUSIONS: The early detection of populations at risk of developing type 1 diabetes should be regarded as an important tool to better understand the natural history of the disease and to develop preventive programs in the future.
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Autoanticuerpos/sangre , Diabetes Mellitus Tipo 1/inmunología , Islotes Pancreáticos/inmunología , Adolescente , Adulto , Niño , Preescolar , Chile , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/genética , Femenino , Humanos , Masculino , Núcleo Familiar , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
53 HIV-positive patients, 66% of them zidovudine-experienced, were randomized to receive monotherapy with zidovudine or sequential therapy with zidovudine, didanosine and zalcitabine. Clinical end points, CD4 cell count change, and analysis abnormalities showed better results with sequential therapy.
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Didanosina/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Zalcitabina/uso terapéutico , Zidovudina/uso terapéutico , Adulto , Fármacos Anti-VIH/uso terapéutico , Recuento de Linfocito CD4 , Quimioterapia Combinada , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: The early detection of peripheral neuropathy in diabetics is important since it is the main risk factor for lower limb trophic lesions in diabetics. AIM: To assess the relationship between feet thermal sensation threshold and metabolic control in ambulatory non-insulin-dependent diabetics. PATIENTS AND METHODS: A random sample of 34 non-insulin-dependent diabetics followed for more than five years in a special clinic, out of 368 patients, was selected. Warmth sensation thresholds were measured in the dorsum of both feet using a MSTP-III thermostimulator. The average value of all glycosylated hemoglobins obtained during the 9.7 +/- 5.3 years of follow up for each patient was calculated. A multiple stepwise regression analysis was performed between thermal sensation as the dependent variable and glycosylated hemoglobin, fasting blood glucose, age and diabetes duration. RESULTS: The regression model disclosed glycosylated hemoglobin as the only independent predictor of warmth sensation threshold (partial r = 0.385; p = 0.043). Fifteen diabetic patients with good metabolic control, defined as those with a mean glycosylated hemoglobin of less than 9.5%, had a warmth sensation threshold of 35.6 +/- 3.7 degrees C, whereas 19 diabetics with a had control (glycosylated hemoglobin > or = 9.5%) had a threshold of 39 +/- 3.8 degrees C (p = 0.017). CONCLUSIONS: In this group of diabetics, there is a relationship between the severity of distal polyneuropathy and the metabolic control, assessed with glycosylated hemoglobin levels.
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Diabetes Mellitus Tipo 2/metabolismo , Pie Diabético/prevención & control , Sensación Térmica/fisiología , Anciano , Atención Ambulatoria , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Pie Diabético/sangre , Pie Diabético/etiología , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Estudios Retrospectivos , Umbral SensorialRESUMEN
The frequency of bleeding complaints during the first year of use and their influence on removal rate were analyzed in a retrospective cohort study of 491 Norplant implants acceptors. Removal rates were significantly higher in women having menstrual complaints (1.98% and 29.23% in the first and fourth trimester) than in those who did not mention them (0.79 and 5.07% in the same periods). In all periods of observation, most women who mentioned menstrual problems decided to continue using the method. Two possible explanations for this are that 1) the complaints did not persist for very long, and 2) the most frequent complaint mentioned was bleeding irregularity, which was not as strongly associated with removals as increased or decreased bleeding. The authors conclude that bleeding problems are the most important factor limiting the acceptability of Norplant implants, either being the main reason for removal (3.9 per 100 women) or influencing the rate of removal for other reasons. Adequate counseling appears to be critical for reducing the impact of bleeding problems on removal rates, and thereby increasing the acceptability of the method. The importance of research aimed at preventing or treating menstrual problems to improve the acceptability of the method is emphasized.
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Levonorgestrel/efectos adversos , Hemorragia Uterina/inducido químicamente , Adulto , Estudios de Cohortes , Implantes de Medicamentos , Femenino , Humanos , Levonorgestrel/administración & dosificación , Satisfacción del Paciente , Estudios RetrospectivosRESUMEN
The objective was to evaluate the Semmes-Weinstein monofilament as a potential predictor of foot ulceration. A case-control study was carried out in a teaching hospital clinic specializing in diabetes and hyperlipidemic disorders. Two groups of patients with noninsulin-dependent diabetes mellitus were studied: 168 with no history of foot lesions (No-Ulcer group, aged 58.1 +/- 9.7 years, duration 11.5 +/- 7.8 years) and 14 who had at least one foot ulceration during the last year (foot ulcer group, aged 60.8 +/- 7.8 years', duration 17.1 +/- 10.5 years). The authors defined and measured a "monofilament index" using a size 5.07 Semmes-Weinstein monofilament on three locations on each foot and then measured peroneal nerve current perception thresholds using the Neurometer at three frequencies: 5 Hz, 250 Hz, and 2,000 Hz. The monofilament index score was lower in patients in the foot ulcer group than in patients in the No-Ulcer group (1.71 +/- 2.36 vs 5.21 +/- 1.81, P < 0.001). A cutoff point at an index of 5 out of 6 yielded a sensitivity rate of 85.71% and a false-positive rate of 16.07%. The peroneal nerve current perception threshold was higher (P < 0.005) in patients in the foot ulcer group than in patients in the No-Ulcer group for all frequencies (605.8 +/- 414.6 vs 181.5 +/- 272.3 for 5 Hz; 743.2 +/- 361.7 vs 251.6 +/- 283.7 for 250 Hz; 859.4 +/- 220.2 vs 423.3 +/- 252.6 for 2,000 Hz). (ABSTRACT TRUNCATED AT 250 WORDS)