RESUMEN
BACKGROUND: Antimicrobial resistance is increasing and there is an urgent international imperative to optimise use within hospitals. Antibiotic use at the end of life is frequent in the hospital setting, but data on use in Australian hospitals in this context is limited, and optimisation is complicated by clinical/diagnostic, ethical and humanistic considerations. As yet there is little data available on baseline use in hospital end of life settings, an empirical gap we sought to begin to fill here. METHODS: A retrospective review of antibiotic use in patients who died in a Queensland hospital between January 2015 and July 2015. RESULTS: One hundred and thirty-seven patients were included, of which 73 were male (53.3%) and the median age was 81 years. Of these patients, 86 received antibiotics at the end of life. The most common antibiotic prescribed was piperacillin/tazobactam (41.9%). The most common site of infection was pulmonary (32.8%). Of 86 patients prescribed antibiotics, 29 patients (33.7%) received antibiotics after futility was documented. 83 patients (96.5%) were administered their antibiotics intravenously. CONCLUSION: Antimicrobial use at the end of life is frequent, with greater than one third of the patients who died in hospital having their antibiotics continued after discussion of futility. Antimicrobial use in this setting is complex with significant clinical, social and ethical considerations which need to be addressed if antibiotic optimization in this area (and more broadly in the hospital) is to be achieved.
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Antibacterianos/efectos adversos , Cuidado Terminal/estadística & datos numéricos , Enfermo Terminal , Adulto , Anciano , Anciano de 80 o más Años , Programas de Optimización del Uso de los Antimicrobianos/estadística & datos numéricos , Australia , Femenino , Hospitales/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Queensland , Estudios Retrospectivos , Cuidado Terminal/métodosRESUMEN
BACKGROUND AND PURPOSE: While over a million international students attend U.S. universities, there is little information to guide providers on their care. Differences in language and health beliefs can lead to misunderstandings and poor outcomes. The purpose of this study was to describe the health practices and healthcare experiences of international students before and after they move to the United States to carve out specific quality improvement activities at a student health center. METHODS: International students volunteered to attend focus groups. Data were analyzed using text coding software (Dedoose) to identify salient themes that reflected participants' experiences. CONCLUSIONS: Participants (N = 19) identified four areas of health maintenance: exercise, nutrition, yearly checkups, and self-care for minor ailments. While participants described health care in their home countries as accessible and affordable, they described health care in the United States as less accessible, more expensive, and laden with communication mishaps. IMPLICATIONS FOR PRACTICE: A broader educational message to international students, that is, how to maintain healthy habits in the United States and how to access/navigate U.S. health care, coupled with staff training on effective health communication and the use of interpreter services would enhance the health and healthcare experience of this vital population.
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Servicios de Salud para Estudiantes/estadística & datos numéricos , Estudiantes/psicología , Universidades/normas , Adulto , Dieta/normas , Ejercicio Físico/psicología , Femenino , Grupos Focales , Sistemas Prepagos de Salud , Humanos , Masculino , Medicina Preventiva/métodos , Investigación Cualitativa , Estados Unidos , Universidades/organización & administraciónRESUMEN
Identifying challenges to progression for a health care profession student who is not meeting expectations in a busy clinical practice can be challenging yet can lead to assisting the student toward success. Preceptor preparation includes acquiring knowledge about the student's education program, understanding federal regulations designed to protect students, gathering background information about a student, learning to provide feedback, structuring the clinical experience, and completing student evaluations. Students in health care professions may have difficulties with cognitive, affective, or psychomotor learning, and the clinical preceptor can identify problems for student progression within these learning domains. Subsequently, specific solutions that are tailored to the individual student's needs can be developed, implemented, and evaluated. A structured evaluation of the student's performance by the clinical preceptor, in accordance with the education program's parameters, is essential. Through a structured process, preceptors can assist many students to achieve success, in spite of challenges. This article describes how the preceptor can prepare, identify the type(s) of problem(s), and develop learning solutions for students who are experiencing difficulties in clinical settings.
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Competencia Clínica , Educación en Enfermería , Partería/educación , Enfermeras Obstetrices , Preceptoría , Solución de Problemas , Estudiantes de Enfermería , Femenino , Humanos , Embarazo , EnseñanzaRESUMEN
Individuals overdue for recommended cancer screenings may not be receiving adequate cancer prevention education. Since Latinas have the highest incidence of cervical cancer among all racial/ethnic groups, human papillomavirus (HPV) vaccination education is especially important for this population. The correlates of HPV vaccine-related awareness and knowledge were assessed among Latinas who were overdue for recommended cancer screenings. N = 206 Latinas who were overdue for recommended cancer screenings were recruited by health educators from local community groups. Bivariate analyses and multivariable regression models were used to investigate factors associated with HPV vaccine-related awareness and knowledge among participants as well as to assess correlates of HPV vaccine receipt for eligible children of participants. In multivariable regression analyses, years living in the U.S. (p = 0.05) and health insurance status (p = 0.03) were significantly related to HPV vaccine-related knowledge measures. Age (p < 0.01), birthplace (p = 0.02), years living in the U.S. (p = 0.05), annual household income (p = 0.05), cervical cancer screening status (p = 0.03), and HPV vaccine-related knowledge measures (p < 0.01) were significantly associated with HPV vaccination outcomes for eligible daughters of participants. Cervical cancer screening status (p = 0.02) and HPV vaccine-related knowledge measures (p = 0.01) were significantly associated with HPV vaccination outcomes for eligible sons of participants. Results indicate poor HPV vaccine-related awareness and knowledge among Latinas. Interventions to improve HPV vaccine-related awareness and knowledge in Utah's growing Latino population should target vulnerable individuals (e.g., not employed outside the home, less educated, less acculturated, poor, uninsured, overdue for cervical cancer screening) by using materials that are culturally sensitive, linguistically appropriate, and easily accessible.
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Detección Precoz del Cáncer , Conocimientos, Actitudes y Práctica en Salud , Hispánicos o Latinos/estadística & datos numéricos , Vacunas contra Papillomavirus , Adulto , Femenino , Humanos , Persona de Mediana Edad , Utah/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Vacunación/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND: Maternal psychosocial factors contribute to adverse pregnancy outcome, but very few studies have assessed associations of duration and experiences of stress, depression, and intimate partner violence (IPV) with maternal and newborn outcomes. OBJECTIVES: It was hypothesized that duration and level of maternal stress, depression, and IPV would predict increased risk of adverse maternal/newborn outcomes. METHODS: A secondary data analysis of a population-based data set collected by the Utah Department of Health Pregnancy Risk Assessment and Monitoring System and birth certificates for 4682 live births was conducted, reflecting a total population size of 143,373 live births in 2009-2011. Exposures of interest were experiences and duration of maternal stress, depression, and IPV before and during pregnancy. Outcomes were gestational age, birth weight, newborn admission to the neonatal intensive care unit (NICU), and postpartum depression (PPD) symptoms and diagnosis. RESULTS: After controlling for maternal demographics, body mass index, and smoking, women with greater duration of depression before and during pregnancy showed an increase in admission of their newborn to NICU (adjusted odds ratios [aORs] = 1.66-2.48, p < .001), PPD symptoms (aORs = 3.94-9.13, p < .001), and diagnosis of PPD (aORs = 7.72-59.60, p < .001). More kinds of experiences of maternal stress were associated with higher odds of PPD symptoms (aORs = 1.34-5.51, p < .001), but not PPD diagnosis or NICU admissions. DISCUSSION: Longer lasting maternal depression and stress are associated with poorer outcomes for mothers and newborns. Future prospective studies should evaluate the usefulness of preconception and continuous prenatal risk identification of maternal depression and stress. This would facilitate timely psychosocial interventions as an approach to improving maternal/newborn outcomes for these higher risk women.
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Depresión Posparto/epidemiología , Depresión/epidemiología , Unidades de Cuidado Intensivo Neonatal , Madres/psicología , Admisión del Paciente , Estrés Psicológico/epidemiología , Adolescente , Adulto , Peso al Nacer , Bases de Datos como Asunto , Depresión Posparto/diagnóstico , Violencia Doméstica , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Embarazo , Medición de Riesgo , Muestreo , Encuestas y Cuestionarios , Factores de Tiempo , Utah/epidemiología , Adulto JovenRESUMEN
OBJECTIVE: To determine the best sociodemographic and behavioral predictors for gestational diabetes mellitus (GDM) and birth weight (BW) and whether stress, depression, or abuse influences GDM and BW after controlling for sociodemographic variables. DESIGN: Retrospective correlational. SETTING: Utah Pregnancy Risk Monitoring System and birth certificate data. PARTICIPANTS: We analyzed data from the birth certificates of 4,682 women with live births between 2009 and 2011 in Utah. During that time, a total of 143,373 live births occurred in the state. Data were predominantly from non-Hispanic White, married, or partnered women with average age of 27.5 years and average body mass index (BMI) of 25.1. METHODS: Stress, cumulative depression, and abuse were operationalized based on previous analysis, and control and covariate data (e.g., age, BMI, race, ethnicity, education, marital status) were collected. Bivariate analysis was used to identify associations between variables, and a hierarchical stepwise logistical regression was conducted to identify best predictors of GDM and BW. RESULTS: We did not find that cumulative depression, stress, or abuse was a predictor of GDM, and only cumulative stress was a predictor of BW. More incidences of GDM were observed in women who were poor, older, less educated, non-White, obese, or experienced depression during pregnancy. CONCLUSION: Unlike depression or abuse, stress is often overlooked by providers. This finding represents an unmet opportunity for nurses to screen for and assist women with stressors to positively affect birth weight.
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Peso al Nacer , Diabetes Gestacional/epidemiología , Diabetes Gestacional/psicología , Resultado del Embarazo , Atención Prenatal/organización & administración , Adolescente , Adulto , Índice de Masa Corporal , Estudios de Cohortes , Bases de Datos Factuales , Depresión/complicaciones , Diabetes Gestacional/etiología , Femenino , Humanos , Recién Nacido , Valor Predictivo de las Pruebas , Embarazo , Psicología , Estudios Retrospectivos , Medición de Riesgo , Maltrato Conyugal/estadística & datos numéricos , Estrés Psicológico/complicaciones , Utah , Adulto JovenRESUMEN
OBJECTIVES: Urinary catheter associated bloodstream infection (UCABSI) causes significant morbidity, mortality and healthcare costs. We aimed to define the risk factors for UCABSI. METHODS: A case-control study was conducted at two Australian tertiary hospitals. Patients with urinary source bloodstream infection associated with an indwelling urinary catheter (IDC) were compared to controls with an IDC who did not develop urinary source bloodstream infection. RESULTS: There were 491 controls and 67 cases included in the analysis. Independent statistically significant risk factors for the development of UCABSI included insertion of the catheter in operating theatre, chronic kidney disease, age-adjusted Charlson comorbidity index, accurate urinary measurements as reason for IDC insertion and dementia. IDCs were inserted for valid reasons in nearly all patients, however an appropriate indication at 48 h post-insertion was found in only 44% of patients. Initial empiric antibiotics were deemed inappropriate in 23 patients (34%). CONCLUSION: To our knowledge, this is the first study to look specifically at the risk factors for bloodstream infection in urinary catheterised patients. Several risk factors were identified. IDC management and empiric management of UCABSI could be improved and is likely to result in a decreased incidence of infection and its complications.
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Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Urinario/efectos adversos , Catéteres Urinarios/efectos adversos , Infecciones Urinarias/epidemiología , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Australia/epidemiología , Bacteriemia , Estudios de Casos y Controles , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Infecciones Urinarias/tratamiento farmacológicoRESUMEN
BACKGROUND: The "Latina epidemiologic paradox" postulates that despite socioeconomic disadvantages, Latina mothers have a lower risk for delivering low birth weight (LBW) babies than non-Latina Whites. However, these patterns may be changing over time and may differ depending on the mother's birthplace and legal status in the United States. This study investigates differences in risk for three birth outcomes among Whites, U.S.-born Latinas, and foreign-born Latinas. METHODS: We undertook a cross-sectional study of rates of LBW, preterm, and small-for-gestational-age (SGA) births among 196,617 women delivering live, singleton births in Utah from 2004 to 2007. Each group was compared using logistic regression. RESULTS: U.S.-born Latinas had a similar or greater risk for all three outcomes when compared with Whites. Foreign-born Latinas had lower risk for preterm birth (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.80-0.90) compared with Whites, but not for LBW and SGA; foreign-born Latinas had a lower risk for LBW (OR, 0.82; 95% CI, 0.74-0.92), preterm birth (OR, 0.81; 95% CI, 0.74-0.89), and SGA (OR, 0.91; 95% CI, 0.83-0.99) compared with U.S.-born Latinas. Among foreign-born Latinas only, there was no difference in risk between documented (i.e., those who had a legal social security number) and undocumented women for LBW, preterm birth, or SGA. CONCLUSIONS: These data support the existence of a variation of the "Latina paradox" among Latinas according to birthplace, where U.S.-born Latinas do not experience better birth outcomes than Whites, but foreign-born Latinas experience better birth outcomes for several endpoints compared with U.S.-born Latinas. Prevention efforts may prove more effective by considering the different composition of risk factors among foreign- and U.S.-born Latina populations.
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Emigración e Inmigración/estadística & datos numéricos , Hispánicos o Latinos/estadística & datos numéricos , Resultado del Embarazo/etnología , Nacimiento Prematuro/etnología , Intervalos de Confianza , Estudios Transversales , Femenino , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Modelos Logísticos , Madres , Oportunidad Relativa , Embarazo , Prevalencia , Factores de Riesgo , Utah/epidemiología , Población Blanca/estadística & datos numéricosRESUMEN
We aimed to determine the effects of variations in dietary composition on equine gut microbiota and their fermentation products, and proposed that dietary modifications profoundly affect microbial ecosystems and their metabolites. Bacterial communities within the large intestine of three groups of horses were compared using oligonucleotide-RNA hybridisation methodology. Each group consisting of six horses was maintained on (1) a grass-only diet, (2) a concentrate diet (i.e. supplemented with hydrolysable carbohydrates) and (3) a concentrate diet but horses were affected by simple colonic obstruction and distension (SCOD), a prevalent form of dietary-induced intestinal disease. We show that in response to dietary change and intestinal disease, there is a progressive and significant increase in Lachnospiraceae, the Bacteroidetes assemblage and the lactic acid-producing, Bacillus-Lactobacillus-Streptococcus (BLS) group. In contrast, there is a corresponding decrease in the proportion of obligate fibrolytic, acid-intolerant bacteria, Fibrobacter and Ruminococcaceae. Assessment of monocarboxylic acids indicated that there are significantly higher concentrations of lactic acid in the colonic contents of horses maintained on a concentrate diet and those suffering from SCOD, correlating with the observed increase in the population abundance of the BLS group. However, the population size of the Veillonellaceae (lactate utilisers) remained constant in each study group. The inability of this group to respond to increased lactic acid may be a contributory factor to the build-up of lactic acid observed in horses fed a concentrate diet and those suffering from SCOD.
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Dieta , Caballos/metabolismo , Caballos/microbiología , Intestino Grueso/metabolismo , Intestino Grueso/microbiología , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Bacillus/aislamiento & purificación , Carga Bacteriana , Bacteroidetes/aislamiento & purificación , Fermentación , Fibrobacter/aislamiento & purificación , Enfermedades de los Caballos/metabolismo , Enfermedades de los Caballos/microbiología , Enfermedades Intestinales/metabolismo , Enfermedades Intestinales/microbiología , Enfermedades Intestinales/veterinaria , Lactobacillus/aislamiento & purificación , Metagenoma , ARN Bacteriano/genética , ARN Bacteriano/aislamiento & purificación , Streptococcus/aislamiento & purificaciónRESUMEN
The "Latina paradox" describes the phenomenon of women born in Mexico having their babies in the US deliver fewer low birth weight babies than White US born women. Social support and networks have been suggested as factors in this paradox. Network size was included in Utah's Pregnancy Risk Assessment Monitoring Survey (PRAMS) for 4 years. Through an analysis of linked Birth Certificate and PRAMS data, the relationship between birth weight and social networks of four groups of women were examined. Perhaps due to Utah's unique population characteristics and service-oriented culture, the "Latina paradox" was not demonstrated. However, the study did demonstrate that specific social network size options were positively associated with birth weight, and husbands in either culture (White or Hispanic) appear to be the main source of social support. In addition, this study reinforced the importance of carefully planned and executed surveys that are culturally appropriate.
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Hispánicos o Latinos , Recién Nacido de Bajo Peso , Apoyo Social , Adulto , Certificado de Nacimiento , Femenino , Humanos , Recién Nacido , Masculino , Estudios Retrospectivos , Encuestas y Cuestionarios , Utah , Adulto JovenRESUMEN
Experimental and epidemiological evidence suggests that consumption of hydrolyzable carbohydrate, hCHO (grain), by horses is an important risk factor for colic, a common cause of equine mortality. It is unknown whether the small intestinal capacity to digest hCHO and/or to absorb monosaccharides is limiting, or even if horses can adapt to increased carbohydrate load. We investigated changes in the brush-border membrane carbohydrate digestive enzymes and glucose absorptive capacity of horse small intestine in response to increased hCHO. Expression of the Na(+)/glucose co-transporter, SGLT1, was assessed by Western blotting, immunohistochemistry, Northern blotting, QPCR, and Na(+)-dependent D-glucose transport. Glucose transport rates, SGLT1 protein, and mRNA expression were all 2-fold higher in the jejunum and 3- to 5-fold higher in the ileum of horses maintained on a hCHO-enriched diet compared to pasture forage. Activity of the disaccharidases was unaltered by diet. In a well-controlled study, we determined SGLT1 expression in the duodenal and ileal biopsies of horses switched, gradually over a 2-month period, from low (<1.0 g/kg bwt/day) to high hCHO (6.0 g/kg bwt/day) diets of known composition. We show that SGLT1 expression is enhanced, with time, 2-fold in the duodenum and 3.3-fold in the ileum. The study has important implications for dietary management of the horse.
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Carbohidratos de la Dieta/farmacología , Transportador 1 de Sodio-Glucosa/metabolismo , Adaptación Fisiológica , Animales , Femenino , Transportador de Glucosa de Tipo 2/biosíntesis , Caballos , Íleon/efectos de los fármacos , Íleon/metabolismo , Inmunohistoquímica , Yeyuno/efectos de los fármacos , Yeyuno/metabolismo , Masculino , Microvellosidades/metabolismo , ARN Mensajero/metabolismo , Transportador 1 de Sodio-Glucosa/biosíntesis , Solubilidad , Sacarasa/metabolismo , alfa-Glucosidasas/metabolismoRESUMEN
The purpose of this study was to determine how closely certified nurse-midwives in the United States follow contemporary cervical cancer screening guidelines. A survey was sent to 264 randomly selected certified nurse-midwives. Survey questions included demographics and clinical scenarios addressing initiation, frequency, and cessation of screening. Responses were received from 60% of the sampled certified nurse-midwives who had valid mailing addresses; 127 were eligible for the analytic sample. Many nurse-midwives initiate cervical cancer screening earlier than guidelines recommend; 72% would initiate screening in an 18-year-old within 1 month of coitarche, while 36% would begin screening virginal girls at age 18, and many continue cervical cancer screening after guidelines recommend cessation. More than 60% of the respondents would continue screening a woman who had undergone total hysterectomy for symptomatic fibroids who had no history of dysplasia, and half would continue to screen a 70-year-old woman with a 30-year history of previous normal Pap tests. In addition, despite guidelines which recommend less frequent screening, more than one-quarter (28%) would continue annual screening in a 35-year-old woman with three or more normal tests. Certified nurse-midwives are performing cervical cancer screening more frequently than current guidelines recommend. Comparisons to the practice of other providers are offered. Education to limit unnecessary testing is needed.
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Benchmarking , Partería/normas , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/enfermería , Frotis Vaginal/estadística & datos numéricos , Adolescente , Adulto , Anciano , Certificación/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Encuestas y Cuestionarios , Estados Unidos/epidemiología , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/prevención & controlRESUMEN
Dietary sugars are transported from the intestinal lumen into absorptive enterocytes by the sodium-dependent glucose transporter isoform 1 (SGLT1). Regulation of this protein is important for the provision of glucose to the body and avoidance of intestinal malabsorption. Although expression of SGLT1 is regulated by luminal monosaccharides, the luminal glucose sensor mediating this process was unknown. Here, we show that the sweet taste receptor subunit T1R3 and the taste G protein gustducin, expressed in enteroendocrine cells, underlie intestinal sugar sensing and regulation of SGLT1 mRNA and protein. Dietary sugar and artificial sweeteners increased SGLT1 mRNA and protein expression, and glucose absorptive capacity in wild-type mice, but not in knockout mice lacking T1R3 or alpha-gustducin. Artificial sweeteners, acting on sweet taste receptors expressed on enteroendocrine GLUTag cells, stimulated secretion of gut hormones implicated in SGLT1 up-regulation. Gut-expressed taste signaling elements involved in regulating SGLT1 expression could provide novel therapeutic targets for modulating the gut's capacity to absorb sugars, with implications for the prevention and/or treatment of malabsorption syndromes and diet-related disorders including diabetes and obesity.
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Sacarosa en la Dieta/farmacología , Proteínas de Unión al GTP Heterotriméricas/metabolismo , Intestino Delgado/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transportador 1 de Sodio-Glucosa/metabolismo , Animales , Células Cultivadas , Glucosa/farmacología , Humanos , Ratones , Ratones Noqueados , ARN Mensajero/metabolismo , Transportador 1 de Sodio-Glucosa/genética , Sacarosa/análogos & derivados , Sacarosa/farmacología , Edulcorantes/farmacologíaRESUMEN
BACKGROUND & AIMS: Butyrate serves as the major source of energy for colonic epithelial cells, and has profound effects on their proliferation, differentiation, and apoptosis. Transport of butyrate across the colonocyte luminal membrane is mediated by the monocarboxylate transporter, MCT1; the expression of which is down-regulated dramatically during colon carcinogenesis. We have proposed that the decline in MCT1 expression during colon carcinogenesis may reduce the intracellular availability of butyrate required to regulate expression of genes associated with the processes maintaining tissue homeostasis within the colonic mucosa. METHODS: To test this hypothesis we used the technique of RNA interference to inhibit MCT1 expression specifically, and determined the consequences of this inhibition on the ability of butyrate to exert its recognized effects in vitro using flow cytometry, immunofluorescence, Northern analysis, and Western analysis. RESULTS: We show that inhibition of MCT1 expression, and hence butyrate uptake, has profound inhibitory effects on the ability of butyrate to regulate expression of key target genes: p21waf1/cip1 (p21), intestinal alkaline phosphatase (IAP), and cyclin D1, and their associated processes of proliferation and differentiation. In contrast, inhibition of MCT1 expression had no effect on the ability of butyrate to modulate expression of either bcl-XL or bak, and this was reflected in a corresponding lack of effect on butyrate induction of apoptosis. CONCLUSIONS: Collectively, these results show the importance of MCT1 to the ability of butyrate to induce cell-cycle arrest and differentiation, and suggest fundamental differences in the mechanisms by which butyrate modulates specific aspects of cell function.
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Colon/metabolismo , Homeostasis , Transportadores de Ácidos Monocarboxílicos/metabolismo , Simportadores/metabolismo , Fosfatasa Alcalina/genética , Antígenos de Neoplasias/genética , Apoptosis/efectos de los fármacos , Butiratos/farmacología , Ciclo Celular/efectos de los fármacos , Proteínas de Ciclo Celular/genética , Diferenciación Celular/efectos de los fármacos , Línea Celular , Colon/efectos de los fármacos , Ciclina D1/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Proteínas Ligadas a GPI , Expresión Génica/efectos de los fármacos , Células HT29 , Humanos , Transportadores de Ácidos Monocarboxílicos/antagonistas & inhibidores , Interferencia de ARN , Simportadores/antagonistas & inhibidoresRESUMEN
OBJECTIVE: To confirm whether the plasma glucose concentration curve obtained during oral glucose tolerance tests (OGTTs) in horses with equine motor neuron disease (EMND) is decreased, compared with that obtained in clinically normal horses, and determine whether that decrease is a result of defective glucose metabolism or intestinal glucose transport dysfunction. ANIMALS: 8 horses with EMND and 44 matched control horses. PROCEDURE: Electromyography and OGTTs were performed in all 8 affected horses and 10 control horses. Intravenous GTTs (IVGTTs) were performed in 6 affected horses and another 11 control horses. The activity and levels of jejunal luminal membrane glucose transporter (Na+ / glucose cotransporter isoform 1 [SGLT1]) were measured in 2 affected horses and 23 control horses. RESULTS: In horses with EMND, generalized neuropathy was detected via quantitative electromyography; the mean increase in plasma glucose concentration during the OGTT was significantly decreased, compared with the value in control horses. During the IVGTT the mean increase in plasma glucose concentration was significantly lower than that of control horses. The activity and levels of SGLT1 in 2 affected horses were similar to those of control horses. Diagnosis of EMND was confirmed postmortem in all affected horses. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggest that the decreased plasma glucose curve obtained in horses with EMND during OGTTs (compared with control horses) is a result of overall enhanced glucose metabolism or abnormalities in the facilitated glucose transporters; definitive identification of the underlying mechanisms could aid in the development of appropriate treatments of EMND in horses.
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Glucemia/fisiología , Enfermedades de los Caballos/fisiopatología , Mucosa Intestinal/fisiopatología , Glicoproteínas de Membrana/fisiología , Proteínas de Transporte de Monosacáridos/fisiología , Enfermedad de la Neurona Motora/veterinaria , Animales , Electromiografía/veterinaria , Femenino , Prueba de Tolerancia a la Glucosa/veterinaria , Caballos , Masculino , Enfermedad de la Neurona Motora/fisiopatología , Transportador 1 de Sodio-GlucosaRESUMEN
Dietary sugars regulate expression of the intestinal Na+/glucose cotransporter, SGLT1, in many species. Using sheep intestine as a model, we showed that lumenal monosaccharides, both metabolisable and nonmetabolisable, regulate SGLT1 expression. This regulation occurs not only at the level of transcription, but also at the post-transcriptional level. Introduction of d-glucose and some d-glucose analogues into ruminant sheep intestine resulted in > 50-fold enhancement of SGLT1 expression. We aimed to determine if transport of sugar into the enterocytes is required for SGLT1 induction, and delineate the signal-transduction pathways involved. A membrane impermeable d-glucose analogue, di(glucos-6-yl)poly(ethylene glycol) 600, was synthesized and infused into the intestines of ruminant sheep. SGLT1 expression was determined using transport studies, Northern and Western blotting, and immunohistochemistry. An intestinal cell line, STC-1, was used to investigate the signalling pathways. Intestinal infusion with di(glucos-6-yl)poly(ethylene glycol) 600 led to induction of functional SGLT1, but the compound did not inhibit Na+/glucose transport into intestinal brush-border membrane vesicles. Studies using cells showed that increased medium glucose up-regulated SGLT1 abundance and SGLT1 promoter activity, and increased intracellular cAMP levels. Glucose-induced activation of the SGLT1 promoter was mimicked by the protein kinase A (PKA) agonist, 8Br-cAMP, and was inhibited by H-89, a PKA inhibitor. Pertussis toxin, a G-protein (Gi)-specific inhibitor, enhanced SGLT1 protein abundance to levels observed in response to glucose or 8Br-cAMP. We conclude that lumenal glucose is sensed by a glucose sensor, distinct from SGLT1, residing on the external face of the lumenal membrane. The glucose sensor initiates a signalling pathway, involving a G-protein-coupled receptor linked to a cAMP-PKA pathway resulting in enhancement of SGLT1 expression.