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1.
Telemed Rep ; 4(1): 327-335, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37908625

RESUMEN

Background: e-Health interventions can potentially improve health care. My Viva Plan® (MVP) is a web-based program that focuses on mindfulness, nutrition, and physical fitness. The aim of this study was to evaluate the effects of this platform on stress indicators and diet quality among first-year university students. Methods: Ninety-seven university students were enrolled in a randomized, controlled clinical trial. Participants were randomized into control (n = 49) and MVP (n = 48) groups. Perceived stress was measured using the self-report Stress Indicator Questionnaire. Diet quality was assessed by the nutrient-rich foods index, and body composition was assessed by a hand-to-foot, multifrequency, bioelectrical impedance analysis. Results: There were no differences in physical, sleep, behavioral, emotional, and personal habit indicators between groups. Diet quality and body composition were similar between groups, except among women in the MVP group with decreased body fat (-1.2 ± 2.6 kg, p < 0.05). Participant engagement was low: 50% of the MVP group did not access the platform. Conclusions: The MVP web-based intervention was not associated with improvements in stress indicators, diet quality, and body composition, likely due to the characteristics of our cohort of healthy young individuals. Future studies should focus on enhancing motivational approaches to explore the potential of e-health interventions that improve health behavior.Clinical Trial Registration number: NCT03579264A.

2.
Am J Clin Nutr ; 118(2): 422-432, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37290740

RESUMEN

BACKGROUND: Total energy expenditure (TEE) determines energy requirements, but objective data in patients with cancer are limited. OBJECTIVES: We aimed to characterize TEE, investigate its predictors, and compare TEE with cancer-specific predicted energy requirements. METHODS: This cross-sectional analysis included patients with stages II-IV colorectal cancer from the Protein Recommendation to Increase Muscle (PRIMe) trial. TEE was assessed by 24-h stay in a whole-room indirect calorimeter before dietary intervention and compared with cancer-specific predicted energy requirements (25-30 kcal/kg). Generalized linear models, paired-samples t tests, and Pearson correlation were applied. RESULTS: Thirty-one patients (56 ± 10 y; body mass index [BMI]: 27.9 ± 5.5 kg/m2; 68% male) were included. Absolute TEE was higher in males (mean difference: 391 kcal/d; 95% CI: 167, 616 kcal/d; P < 0.001), patients with colon cancer (mean difference: 279 kcal/d; 95% CI: 73, 485 kcal/d; P = 0.010), and patients with obesity (mean difference: 393 kcal/d; 95% CI: 182, 604 kcal/d; P < 0.001). Appendicular lean soft tissue (ß: 46.72; 95% CI: 34.27, 59.17; P < 0.001) and tumor location (colon-ß: 139.69; 95% CI: 19.44, 259.95; P = 0.023) independently predicted TEE when adjusted for sex. Error between measured TEE and energy requirements predicted by 25 kcal/kg (mean difference: 241 kcal/d; 95% CI: 76, 405 kcal/d; P = 0.010) or 30 kcal/kg (mean difference: 367 kcal/d; 95% CI: 163, 571 kcal/d; P < 0.001) was higher for patients with obesity, and proportional error was observed (25 kcal/kg: r = -0.587; P < 0.001; and 30 kcal/kg: r = -0.751; P < 0.001). TEE (mean difference: 25 kcal/kg; 95% CI: 24, 27 kcal/kg) was below predicted requirements using 30 kcal/kg (-430 ± 322 kcal/d; P < 0.001). CONCLUSIONS: This is the largest study to assess TEE of patients with cancer using whole-room indirect calorimeter and highlights the need for improved assessment of energy requirements in this population. Energy requirements predicted using 30 kcal/kg overestimated TEE by 1.44 times in a controlled sedentary environment and TEE was outside of the predicted requirement range for most. Special considerations are warranted when determining TEE of patients with colorectal cancer, such as BMI, body composition, and tumor location. This is a baseline cross-sectional analysis from a clinical trial registered at clinicaltrials.gov as NCT02788955 (https://clinicaltrials.gov/ct2/show/NCT02788955).


Asunto(s)
Neoplasias Colorrectales , Metabolismo Energético , Femenino , Humanos , Masculino , Índice de Masa Corporal , Calorimetría Indirecta , Estudios Transversales , Metabolismo Energético/fisiología , Obesidad , Persona de Mediana Edad , Anciano
3.
J Acad Nutr Diet ; 123(3): 407-416, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36002111

RESUMEN

BACKGROUND: Dietary changes often accompany management of a cancer diagnosis, but how and why patients with colorectal cancer (CRC) make dietary decisions requires further investigation. OBJECTIVE: To learn about patients' food-related beliefs and understand whether and why dietary changes were made by patients starting chemotherapy after a CRC diagnosis. DESIGN: A qualitative semi-structured interview study was conducted as a secondary analysis among a subset of patients with stages II-IV CRC enrolled at baseline in a randomized controlled trial. PARTICIPANTS/SETTING: Twenty-nine patients participated in the interview. Data were collected at the University of Alberta (Edmonton, Alberta, Canada) from 2016-2019 before any trial intervention. QUALITATIVE DATA ANALYSIS: Audio-recorded interviews were transcribed verbatim then coded inductively by two research team members. Qualitative content analysis was applied to capture emergent themes. RESULTS: Patients reported varied degrees of dietary change that stemmed from internal and external influences. Four main themes emerged to describe patients' dietary decisions after a CRC diagnosis: 1) Medical Influences: eating to live; 2) Health Beliefs: connecting lived experiences with new realities; 3) Static Diets: no changes postdiagnosis; and 4) Navigating External Influences: confluence of personal agency and social constraints. CONCLUSION: The extent to which patients altered their dietary choices depended on perspectives and beliefs. These included the degree to which dietary decisions provided some agency (ie, feeling of control) for dealing with physical ramifications of cancer treatment, individuals' personal understandings of healthy foods, and the role of diet in managing their new physical reality postdiagnosis. This information provides registered dietitian nutritionists and health care providers with insight into dietary intentions of select patients being treated for CRC. These findings can guide future research focused on effective strategies for streamlined nutritional support that aligns with patient needs.


Asunto(s)
Neoplasias Colorrectales , Dieta , Humanos , Alimentos , Neoplasias Colorrectales/diagnóstico , Investigación Cualitativa , Alberta
4.
Sex Transm Infect ; 98(8): 549-556, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35039437

RESUMEN

OBJECTIVES: Use of illicit substances during sex (chemsex) may increase transmission of HIV and other STIs. Pre-exposure prophylaxis (PrEP) is highly effective at preventing HIV transmission, providing an important prevention tool for those who practise chemsex. However, it does not prevent acquisition of other STIs. We aim to examine the impact of chemsex on STI incidence among gay, bisexual and other men who have sex with men (gbMSM), and transgender women using PrEP in Montréal, Canada. METHODS: We linked baseline sociodemographic and behavioural data with follow-up STI testing from 2013 to 2020 among PrEP users in the l'Actuel PrEP Cohort (Canada). Focusing on the 24 months following PrEP initiation, we estimated the effect of chemsex reported at baseline on cumulative incidence of gonorrhoea and chlamydia using Kaplan-Meier curves and survival analyses. We investigated the role of polysubstance use and effect modification by sociodemographic factors. RESULTS: There were 2086 clients (2079 cisgender gbMSM, 3 transgender gbMSM, 4 transgender women) who initiated PrEP, contributing 1477 years of follow-up. There were no incident HIV infections among clients on PrEP. Controlling for sociodemographic confounders, clients reporting chemsex at baseline had a 32% higher hazard of gonorrhoea/chlamydia diagnosis (adjusted HR=1.32; 95% CI: 1.10 to 1.57), equivalent to a risk increase of 8.9 percentage points (95% CI: 8.5 to 9.4) at 12 months. The effect was greater for clients who reported polysubstance use (adjusted HR=1.51; 95% CI: 1.21 to 1.89). The strength of the effect of chemsex on STI incidence varied by age, education and income. CONCLUSION: Among PrEP users, chemsex at baseline was linked to increased incidence of gonorrhoea and chlamydia. This effect was stronger for people reporting multiple chemsex substances. The high STI incidence among gbMSM who report chemsex highlights the importance of PrEP for this population and the need for integrated services that address the complexities of sexualised substance use.


Asunto(s)
Chlamydia , Gonorrea , Infecciones por VIH , Profilaxis Pre-Exposición , Minorías Sexuales y de Género , Enfermedades de Transmisión Sexual , Masculino , Femenino , Humanos , Incidencia , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Canadá/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control
5.
Eur J Clin Nutr ; 76(2): 212-219, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-33986493

RESUMEN

BACKGROUND: Bioelectrical impedance analysis (BIA) is a widely used method for estimating body composition. Avoiding foods/beverages containing caffeine is a frequently enforced pre-test protocol to ensure reliability of BIA measurements. However, few studies have evaluated whether this is necessary, with conflicting results. We aimed to determine whether the coffee consumption differing in caffeine content influences BIA parameters in healthy adults. METHODS: Twenty-five healthy adults were enrolled in a randomized, double-blind cross-over trial. Three amounts of caffeine were given with 200 mL of coffee: 0 mg (11 g of decaffeinated), 200 mg (5.5 g of caffeinated plus 5.5 g of decaffeinated), and 400 mg of caffeine (11 g of caffeinated). BIA measurements were conducted at 6 different times, and coefficient variations (CV) explored. RESULTS: No differences were observed for group × time interaction on impedance, resistance, or reactance (p > 0.05). Values of BIA parameters increased after 30-min of coffee consumption, independently of the caffeine dosage (all p < 0.001). Body fat percentage followed the same pattern and increased after 45-min (p < 0.05). Median CV for consecutive impedance, resistance, and reactance measurements were >95%CI of expected device measurement error over 70-min, without difference between groups. Urine output volume was not different between groups (decaffeinated: 440.45 ± 197.57 mL; 200 mg: 471.80 ± 171.88 mL; 400 mg: 489.30 ± 204.10 mL, p > 0.05). CONCLUSION: Coffee consumption influenced BIA-derived results after 70-min but was not related to caffeine content, likely due to water intake.


Asunto(s)
Cafeína , Café , Adulto , Estudios Cruzados , Método Doble Ciego , Impedancia Eléctrica , Humanos , Reproducibilidad de los Resultados
6.
Drug Alcohol Depend ; 226: 108875, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34218004

RESUMEN

INTRODUCTION: Chemsex among gay, bisexual and other men who have sex with men (gbMSM) has raised public health concerns because of its association with sexual behaviours that can increase transmission of sexually transmitted infections, including HIV. Pre-exposure prophylaxis (PrEP) is highly effective at blocking HIV acquisition, addressing important prevention needs among individuals practicing chemsex. This study aims to improve our understanding of chemsex practices and PrEP trajectories of gbMSM and transgender women consulting for PrEP. METHODS: We used data from the PrEP cohort of Clinique médicale l'Actuel, a major sexual health clinic in Montréal. We describe the sociodemographic profile of clients consulting for PrEP, characterize chemsex and polysubstance use trends over time, and evaluate PrEP trajectories using Kaplan-Meier curves. RESULTS: Among 2923 clients who consulted for PrEP between 2013-2020 (2910 cisgender gbMSM, 6 transgender gbMSM, 7 transgender women), 24 % reported chemsex in the past year and 13 % reported polysubstance use. The most common chemsex substances were ecstasy (14 %), GHB (13 %), and cocaine (12 %). The proportion of clients reporting chemsex and polysubstance use decreased over time. In both the chemsex and no-chemsex group, 73 % of clients initiated PrEP. The median time to discontinuation was similar between the chemsex (6.5 months; 95 %CI: 5.3-7.2) and no-chemsex group (6.9 months; 95 %CI: 6.3-7.5). CONCLUSION: Chemsex is not a barrier to PrEP initiation or persistence. However, these results suggest a high prevalence of chemsex among gbMSM consulting for PrEP, highlighting the need for services addressing the intersection of sexual health and substance use for this population.


Asunto(s)
Infecciones por VIH , Profilaxis Pre-Exposición , Salud Sexual , Minorías Sexuales y de Género , Canadá , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino , Conducta Sexual
7.
J Acad Nutr Diet ; 121(12): 2409-2418.e3, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34119458

RESUMEN

BACKGROUND: My Viva Plan (MVP) (https://www.myvivainc.com/) is a web-based application developed by a dietitian that aims to support healthy living by providing resources and self-monitoring tools to help promote a healthy diet, healthy mind, and physical fitness. First-year university students have the potential to benefit because poor dietary choices, limited physical activity, and high stress are prevalent in this population. In addition, they are also active technology users. OBJECTIVE: This study aims to understand experiences and perception of MVP by first-year university students using this tool as part of a 12-week randomized controlled trial. DESIGN: One-on-one semistructured interviews were conducted following a 12-week intervention involving use of MVP. PARTICIPANTS/SETTING: First-year university students from the University of Alberta, Edmonton, Canada (n = 32). INTERVENTION: Participants were instructed to use MVP as much as possible for 12 weeks in either the fall/2018 or winter/2019 semesters. QUALITATIVE DATA ANALYSIS: Interviews were audio-recorded, transcribed verbatim, and analyzed abductively using content analysis. RESULTS: Participants reported varied use of MVP across the 12-week period. Data were categorized using the HealthChange Methodology (Behaviors, Emotions, 37 Situations, Thinking) framework. Participants provided various examples of emotions (eg, motivation, stress), situations (eg, time, living arrangements, finances), and thinking (eg, self-awareness, level of satisfaction with MVP, and how MVP was or could be better tailored for students) that acted as either facilitators or barriers to MVP use and explained their behaviors associated with this tool. CONCLUSIONS: Overall, participant behaviors regarding MVP varied and were influenced by several factors, including their emotions, situations, and thinking. The Behaviors, Emotions, Situations, Thinking framework may be helpful for dietitians to identify barriers and facilitators affecting their client's use of ehealth tools for lifestyle behavior change. This information can be used to optimize client support when using these tools.


Asunto(s)
Dieta Saludable/psicología , Intervención basada en la Internet , Atención Plena , Aptitud Física/psicología , Estudiantes/psicología , Canadá , Emociones , Ejercicio Físico , Conducta Alimentaria/psicología , Femenino , Monitores de Ejercicio , Humanos , Masculino , Motivación , Aceptación de la Atención de Salud/psicología , Percepción , Investigación Cualitativa , Características de la Residencia , Estrés Psicológico/psicología , Universidades , Adulto Joven
8.
JMIR Res Protoc ; 10(3): e24534, 2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33688844

RESUMEN

BACKGROUND: First-year university students are at an increased risk for developing mental health issues and a poor nutritional status. Self-care plays an essential role in optimizing mental health and can prevent or manage stress, anxiety, and depression. Web-based self-monitoring of diet and physical activity can lead to similar or improved health outcomes compared with conventional methods. Such tools are also popular among university students. OBJECTIVE: The primary aim of this 12-week randomized controlled trial is to assess the impact of a web-based wellness platform on perceived stress among first-year university students. The secondary aim is to assess the effects of the platform on diet quality. The exploratory objectives are to explore the effects of the platform on body composition, health-related quality of life, mindfulness, mental well-being, and physical activity. METHODS: A total of 97 first-year undergraduate students were randomized to either the intervention (n=48) or control (n=49) group. The intervention consisted of access to a web-based platform called My Viva Plan (MVP), which aims to support healthy living by focusing on the topics of mindfulness, nutrition, and physical activity. The platform is fully automated and guided by the principles of cognitive behavioral theory. Participants in the intervention group were instructed to use the MVP as frequently as possible over 12 weeks. The control group did not receive access to MVP. Perceived stress was assessed using the Stress Indicators Questionnaire at baseline, week 6, and week 12. Three-day food records were used to analyze the dietary intake at baseline and week 12. Health-related quality of life, mindfulness, mental well-being, and physical activity questionnaires were completed at baseline, week 6, and week 12. Body composition was assessed at baseline and week 12. Study assessments were completed in person at baseline and week 12 and electronically at week 6. RESULTS: Study recruitment started in August 2018, with batch enrollment for students registered in the fall (September 2018 to December 2018) and winter (January 2019 to April 2019) academic terms at the University of Alberta, Edmonton, Alberta. CONCLUSIONS: This study is the first to explore the impact of a web-based platform designed to promote health and wellness on perceived stress and diet quality among first-year university students. TRIAL REGISTRATION: ClinicalTrials.gov NCT03579264; https://clinicaltrials.gov/ct2/show/NCT03579264. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24534.

9.
Clin Nutr ESPEN ; 41: 175-185, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33487262

RESUMEN

BACKGROUND: Severe muscle mass (MM) loss is a defining feature of cancer observed across all types and stages of disease and is an independent predictor of poor clinical outcomes including higher incidences of chemotherapy toxicity and decreased survival. Protein is essential to build MM, yet the optimal amount for preventing or treating muscle loss in patients with cancer remains undefined. METHODS: The Protein Recommendation to Increase Muscle (PRIMe) study is a single-center, two-armed, parallel, randomized, controlled pilot trial that assesses the feasibility of utilizing a high protein (HP) diet to positively impact clinical outcomes in people undergoing chemotherapy to treat colorectal cancer. Forty patients with newly diagnosed stage II-IV colorectal cancer who are scheduled to receive chemotherapy will be included. Participants are randomly assigned to a HP or normal protein (NP) diet for twelve weeks. The HP and NP groups receive nutrition recommendations to achieve 2.0 g of protein per kilogram of body weight per day (g∙kg-1∙d-1) and 1.0 g⋅kg-1⋅d-1, respectively. These values refer to the upper and lower recommended range of protein intake for people with cancer. Energy recommendations are based on measured energy expenditure. Assessments are completed within two weeks of starting chemotherapy (baseline), at week 6, and at week 12. Changes to skeletal MM, physical function, anthropometrics, body composition, muscle strength, physical activity, energy metabolism, metabolic markers, nutritional status, quality of life, readiness to change and psychosocial determinants of behavioural change are assessed between the HP and NP groups. Feasibility of the nutritional intervention is assessed by change in MM as a surrogate marker. CONCLUSIONS: This evidence-based study investigates the feasibility of increasing protein intake following a diagnosis of cancer on clinical outcomes during treatment for colorectal cancer. This study will inform larger trials assessing the impact of increasing protein intake in cancer to determine their importance and integration into standard clinical care for people with cancer.


Asunto(s)
Neoplasias Colorrectales , Dieta Rica en Proteínas , Neoplasias Colorrectales/tratamiento farmacológico , Estudios de Factibilidad , Humanos , Músculo Esquelético , Proyectos Piloto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
J Acquir Immune Defic Syndr ; 85(4): 408-415, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-33136737

RESUMEN

BACKGROUND: Reducing HIV transmission using pre-exposure prophylaxis (PrEP) requires focussing on individuals at high acquisition risk, such as men who have sex with men with a history of nonoccupational post-exposure prophylaxis (nPEP). This study aims to characterize longitudinal trends in PrEP uptake and its determinants among nPEP users in Montréal. METHODS: Eligible attendees at Clinique médicale l'Actuel were recruited prospectively starting in October 2000 (nPEP) and January 2013 (PrEP). Linking these cohorts, we characterized the nPEP-to-PrEP cascade, examined the determinants of PrEP uptake after nPEP consultation using a Cox proportional-hazard model, and assessed whether PrEP persistence differed by nPEP history using Kaplan-Meier curves. RESULTS: As of August 2019, 31% of 2682 nPEP cohort participants had 2 or more nPEP consultations. Subsequent PrEP consultations occurred among 36% of nPEP users, of which 17% sought nPEP again afterward. Among 2718 PrEP cohort participants, 46% reported previous nPEP use. Among nPEP users, those aged 25-49 years [hazard ratio (HR) = 1.3, 95% confidence interval (CI): 1.1 to 1.7], with more nPEP episodes (HR = 1.4, 95% CI: 1.3 to 1.5), who reported chemsex (HR = 1.3, 95% CI: 1.1 to 1.7), with a sexually transmitted infection history (HR = 1.5; 95% CI: 1.3 to 1.7), and who returned for their first nPEP follow-up visit (HR = 3.4, 95% CI: 2.7 to 4.2) had higher rates of PrEP linkage. There was no difference in PrEP persistence between nPEP-to-PrEP and PrEP only participants. CONCLUSION: Over one-third of nPEP users were subsequently prescribed PrEP. However, the large proportion of men who repeatedly use nPEP calls for more efficient PrEP-linkage services and, among those who use PrEP, improved persistence should be encouraged.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , VIH-1 , Homosexualidad Masculina , Profilaxis Pre-Exposición , Adulto , Canadá , Estudios de Cohortes , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Sexo Seguro
11.
Virol J ; 10: 337, 2013 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-24225020

RESUMEN

BACKGROUND: Mumps virus (MuV) is a highly infectious paramyxovirus closely related to measles virus (MeV). Despite the availability of a mumps vaccine, outbreaks continue to occur and no treatment options are available. Vitamin A and other naturally occurring retinoids inhibit the replication of MeV in vitro. METHODS: Anti-viral effects of retinoids were observed in cell culture using the myelomonocytic U937, NB4/R4, and Huh7/7.5 cells. Observations of anti-viral effect were quantified using TCID50 analysis. Molecular properties of the antiviral effect were analysed using quantitative RT-PCR and western blot. RESULTS: The current work demonstrates that retinoids inhibit MuV in vitro due to up-regulation of type I interferon (IFN) and IFN stimulated genes. This effect is mediated by nuclear retinoid receptor signalling and RIG-I is required. The antiviral retinoid-induced state makes cells less permissive to viral replication from subsequent challenge with either MuV or MeV for less than 12 hours. CONCLUSIONS: These results demonstrate that retinoids inhibit MuV replication in uninfected bystander cells through a retinoid inducible gene I (RIG-I), retinoic acid receptor (RAR) and IFN dependent manner making them refractory to subsequent rounds of viral replication. These observations raise the possibility that pharmacological doses of retinoids might have clinical benefit in MuV infection.


Asunto(s)
Antivirales/farmacología , Virus de la Parotiditis/efectos de los fármacos , Retinoides/farmacología , Replicación Viral/efectos de los fármacos , Western Blotting , Línea Celular , Humanos , Pruebas de Sensibilidad Microbiana , Virus de la Parotiditis/fisiología , ARN Viral/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Proteínas Virales/análisis
12.
PLoS One ; 6(7): e22323, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21811588

RESUMEN

Vitamin A can significantly decrease measles-associated morbidity and mortality. Vitamin A can inhibit the replication of measles virus (MeV) in vitro through an RARα- and type I interferon (IFN)-dependent mechanism. Retinoid-induced gene I (RIG-I) expression is induced by retinoids, activated by MeV RNA and is important for IFN signaling. We hypothesized that RIG-I is central to retinoid-mediated inhibition of MeV in vitro. We demonstrate that RIG-I expression is increased in cells treated with retinoids and infected with MeV. The central role of RIG-I in the retinoid-anti-MeV effect was demonstrated in the Huh-7/7.5 model; the latter cells having non-functional RIG-I. RAR-dependent retinoid signaling was required for the induction of RIG-I by retinoids and MeV. Retinoid signaling was also found to act in combination with IFN to induce high levels of RIG-I expression. RIG-I promoter activation required both retinoids and MeV, as indicated by markers of active chromatin. IRF-1 is known to be regulated by retinoids and MeV, but we found recruitment of IRF-1 to the RIG-I promoter by retinoids alone. Using luciferase expression constructs, we further demonstrated that the IRF-1 response element of RIG-I was required for RIG-I activation by retinoids or IFN. These results reveal that retinoid treatment and MeV infection induces significant RIG-I. RIG-I is required for the retinoid-MeV antiviral response. The induction is dependent on IFN, retinoids and IRF-1.


Asunto(s)
ARN Helicasas DEAD-box/metabolismo , Virus del Sarampión/efectos de los fármacos , Retinoides/farmacología , Animales , Antivirales/farmacología , Efecto Espectador/efectos de los fármacos , Línea Celular , Proteína 58 DEAD Box , Humanos , Factor 1 Regulador del Interferón/metabolismo , Sarampión/tratamiento farmacológico , Regiones Promotoras Genéticas/genética , Receptores Inmunológicos , Receptores de Ácido Retinoico/metabolismo , Receptor alfa de Ácido Retinoico , Transducción de Señal/efectos de los fármacos , Tretinoina/farmacología , Regulación hacia Arriba/efectos de los fármacos
13.
FASEB J ; 23(9): 3203-12, 2009 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-19447880

RESUMEN

Measles-associated mortality can be decreased in response to treatment with vitamin A. Our goal was to understand the mechanism by which vitamin A and other retinoids reduce measles virus (MeV) replication in vitro. MeV is known to inhibit type I interferon (IFN) signaling, and retinoids are increasingly implicated in modulating innate immunity. Type I IFN blocking antibodies abrogated the inhibitory effects of all-trans retinoic acid (ATRA) on MeV replication (EC(50) of ATRA: 3.17 x 10(-8) M). IFN-stimulated genes (ISGs) are up-regulated by ATRA in MeV-infected U937 cell cultures starting at 12 h and reaching a plateau at 24 h postinfection when compared to either treatment or infection alone. We found that this increased gene expression occurs in uninfected cells by using a transwell system where the uninfected cells were separated from infected cells by a membrane with 0.02-muM pores. Uninfected bystander cells from the ATRA-treated transwells did not support substantial viral replication when subsequently infected with MeV. In the absence of ATRA, the cells from the uninfected chamber did not up-regulate ISG expression and were not protected from subsequent challenge with virus. These results demonstrate that retinoids inhibit MeV replication by up-regulating elements of the innate immune response in uninfected bystander cells, making them refractory to productive infection during subsequent rounds of viral replication.


Asunto(s)
Efecto Espectador/efectos de los fármacos , Interferón Tipo I/inmunología , Virus del Sarampión/efectos de los fármacos , Retinoides/farmacología , Línea Celular , Humanos , Inmunidad Innata , Sarampión/dietoterapia , Sarampión/prevención & control , Transducción de Señal/inmunología , Tretinoina/farmacología , Replicación Viral/efectos de los fármacos , Vitamina A/farmacología
14.
Antiviral Res ; 80(1): 45-53, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18547655

RESUMEN

Measles virus (MV) infects 30 million children every year, resulting in more than half a million deaths. Vitamin A (retinol) treatment of acute measles can reduce measles-associated mortality by 50-80%. We sought to determine whether or not retinoids can act directly to limit MV output from infected cells. Physiologic concentrations of retinol were found to inhibit MV output in PBMC and a range of cell lines of epithelial and endothelial origin (40-50%). Near complete inhibition of viral output was achieved in some cells/lines treated with all-trans retinoic acid (ATRA) and 9-cis RA (9cRA). Important attenuation of the anti-MV effect of retinoids in R4 cells, a subclone of a retinoid-responsive cell line (NB4) deficient in RAR signaling, demonstrates that this effect is mediated at least in part by nuclear retinoid receptor signaling pathways. Inhibition of MV replication could not be fully explained as a result of retinoid effects on cell differentiation, proliferation or viability, particularly at low retinoid concentrations (1-10nM). These data provide the first evidence that retinoids can directly inhibit MV in vitro, and raise the possibility that retinoids may have similar actions in vivo.


Asunto(s)
Antivirales/farmacología , Virus del Sarampión/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Ácido Retinoico/metabolismo , Retinoides/farmacología , Transducción de Señal , Células CACO-2 , Línea Celular , Células Cultivadas , Células Endoteliales/virología , Células Epiteliales/virología , Humanos , Células Jurkat , Leucocitos Mononucleares/virología , Virus del Sarampión/metabolismo , Virus del Sarampión/fisiología , Transducción de Señal/efectos de los fármacos , Células U937
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