RESUMEN
The purpose of this paper is to describe a process and technical requirements for the development of a video and related communications strategy that CBPR partnerships can use to recruit policymakers to participatory research. Policymakers play a critical role in social change agendas, yet are often difficult to engage for a variety of reasons, including limited availability and multiple, competing demands and constituencies. This paper draws on the experience of the Healthy Jacksonville Childhood Obesity Prevention Coalition, a 10-year-old partnership with a large membership and strong community roots in Duval County, Florida. The objectives of the communications strategy were to engage local and state policymakers in policy change that would positively affect childhood obesity prevention; educate policymakers about the social determinants of health, particularly those related to childhood obesity; and to do so in a way that elicited champions for the coalition's goals.
Asunto(s)
Política de Salud , Promoción de la Salud , Obesidad Infantil/prevención & control , Grabación en Video , Investigación Participativa Basada en la Comunidad , Florida , Humanos , Desarrollo de Programa , Recursos HumanosRESUMEN
The aims of this study are to examine in children: (i) obesity-related alterations in satiety factors such as leptin, ghrelin, and obestatin; (ii) the link between satiety factors and cardiometabolic risk factors; and (iii) the impact of a physical activity-based lifestyle intervention on the levels of these satiety factors in the obese. We studied a total of 21 adolescents (BMI percentile, 99.0 +/- 0.6 for 15 obese and 56.2 +/- 1.1 for 6 lean). The obese subjects underwent a 3-month randomized controlled physical activity-based lifestyle intervention. Leptin, soluble leptin receptor (sOB-R), ghrelin, and obestatin levels were determined as the primary outcome measures. Other markers of cardiometabolic disease such as inflammation and insulin resistance were also determined. Body composition was measured by dual-energy X-ray absorptiometry. The concentrations of ghrelin, obestatin, and sOB-R were significantly lower in the obese children compared to the lean controls, whereas that of leptin was higher (all P < 0.05). Although intervention led to a net increase in obestatin (P < 0.01) and no change in ghrelin levels, the balance between ghrelin and obestatin (ratio of ghrelin to obestatin, G/O) decreased (P < 0.02). Intervention reduced leptin and increased sOB-R (P < 0.01 for both). Significant associations between satiety factors and other cardiometabolic risk factors were also observed. Taken together, alterations in the levels of satiety factors are evident early in the clinical course of obesity, but physical activity-based lifestyle intervention either prevented their continued increase or normalized their levels. These beneficial effects appear to aid in the maintenance of body weight and reduction in cardiovascular risk.
Asunto(s)
Ejercicio Físico/fisiología , Ghrelina/sangre , Leptina/sangre , Obesidad/sangre , Receptores de Leptina/sangre , Saciedad , Adolescente , Biomarcadores/sangre , Peso Corporal , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Inflamación , Resistencia a la Insulina , Estilo de Vida , Masculino , Actividad Motora , Obesidad/terapiaRESUMEN
Genes involved in the regulation of catecholamine function may be important in obesity because of the role catecholamines play in energy expenditure and lipolysis. To determine if common single nucleotide polymorphisms (SNPs) in beta(1)-adrenergic receptor (ADRB1), beta(2)-adrenergic receptor (ADRB2), beta(3)-adrenergic receptor (ADRB3), and alpha(2)-adrenergic receptor (ADRA2A) genes associate with obesity and metabolic alterations, we recruited 74 healthy African American and 161 white men and women (age, 18-49 years) to participate in this case-control genetic association study. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism. Associations between genotype and body mass index (BMI), percentage of body fat (by measuring skinfold thickness in 7 different sites), fasting (12-hour) plasma glucose, insulin, potassium concentrations, glycated hemoglobin, and insulin resistance (homeostasis model assessment [HOMA(IR)] score) were performed. Among whites, the ADRB1 Arg389-->Gly variant associated with insulin concentrations and HOMA(IR): mean +/- SD values for insulin and HOMA(IR) in Arg389 homozygotes and carriers of the Gly were 10 +/- 7.0 and 12 +/- 9.4 micro IU/mL (P = .02) and 2.1 +/- 1.7 and 2.6 +/- 2.2 (P = .057), respectively. Systolic blood pressure was higher in whites for carriers of the ADBR1 Ser49 compared to Gly49 homozygotes (124 +/- 12.6 vs 119 +/- 11.3 mm Hg, respectively; P = .02). Subsequent analysis revealed that these associations were attributable to a higher BMI among obese participants. The ADRA2A G1780A SNP associated with BMI and percentage of body fat in African Americans (P = .05). Interactions were detected between ADRA2A C-1291G and ADRB2 Gln27-->Glu variants for obesity in African Americans and between ADRA2A C-1291G SNP and ADBR1 haplotype for obesity in whites. We conclude that common SNPs in adrenergic receptor genes may be important susceptibility loci for obesity and related alterations. Because of the limited size of our populations, our results should be interpreted with caution and should be replicated in larger populations.
Asunto(s)
Obesidad/genética , Polimorfismo de Nucleótido Simple , Receptores Adrenérgicos/genética , Adulto , Negro o Afroamericano , Glucemia/análisis , Índice de Masa Corporal , Femenino , Genotipo , Haplotipos , Humanos , Resistencia a la Insulina , Masculino , Población BlancaRESUMEN
The main objectives of this paper were to test the hypothesis that polymorphisms in NOS1 and NOS3 genes associate with ACS in SCD patients and to characterize the association between physician-diagnosed asthma and acute chest syndrome (ACS). Case-control study of sickle cell disease patients >or=5 years old with ACS (cases; n=86) and those without ACS (controls; n=48) was carried out. Associations between ACS and the AAT repeat in intron 13 (formerly intron 20) of the NOS1, and with NOS3 T-786C polymorphism were explored. Physician-diagnosed asthma was determined by chart review, patient- or parent (guardian)-reported asthma, and drug use. Eighty five percent of participants with asthma had at least one episode of ACS compared to 14.6% of controls: adjusted odds ratio (OR) (95%CI) 5.46 (2.20,13.5), P= or<0.0001. Asthma correlated with the number of episodes of ACS (P<0.001). NOS1 AAT repeat polymorphism associated with the risk of ACS (P=0.001) in patients without physician-diagnosed asthma. No associations were found between the genotype of the NOS3 T-786C SNP and ACS. Physician-diagnosed asthma is a major risk factor for ACS. NOS1 AAT repeat polymorphism may contribute to physician-diagnosed asthma.
Asunto(s)
Anemia de Células Falciformes/complicaciones , Dolor en el Pecho/etiología , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo I/genética , Polimorfismo Genético , Enfermedad Aguda , Adolescente , Asma/diagnóstico , Población Negra , Estudios de Casos y Controles , Niño , Femenino , Frecuencia de los Genes , Humanos , Intrones , Masculino , SíndromeRESUMEN
Our goal was to explore associations between ss2 adrenergic receptor polymorphisms and markers of asthma severity in African American and Caucasian patients with asthma. Polymorphisms at loci -1023, -654, -47, 46, 79, 491, and 523 were genotyped and haplotypes were imputed in 143 African Americans and 336 Caucasians. C523A genotype associated with percentage of African Americans (but not of Caucasians) having an asthma exacerbation: AA, AC, and CC genotypes were 17, 29, and 40%, respectively (p = 0.018). Symptom scores, pulmonary function, and rescue inhaler use paralleled exacerbation prevalence. We conclude the 523 A allele modifies asthma severity in African Americans.
Asunto(s)
Asma/genética , Negro o Afroamericano , Polimorfismo de Nucleótido Simple , Receptores Adrenérgicos beta 2/genética , Adulto , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Estudios Multicéntricos como Asunto , Obesidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función Respiratoria , Factores Sexuales , Fumar , Población BlancaRESUMEN
beta 2 adrenergic receptors ( beta 2 ARs) are important mediators of lipolysis. The beta 2 AR gene is highly polymorphic. To determine the contribution of beta 2 AR polymorphisms to variability in whole body lipolysis, we compared basal and terbutaline-stimulated lipolytic rates (Ra) using tracer techniques in 14 healthy, non-obese males (n=7) and females (n=7) who were homozygous for Cys-19/Arg16/Gln27 or Arg-19/Gly16/Glu27 haplotypes. Fasting (overnight) Ra values were higher in females compared to males. Mean+/-SD Ra, Ra/body weight, Ra/fat free mass, Ra/fat, and Ra/energy expenditure rates in males and females were 155+/-46 vs 311+/-111 micromol/min (P=.007); 2.0+/-0.61 vs 5.2+/-2.3 micromol/(min kg) (P=.006); 2.5+/-0.75 vs 7.8+/-3.4 micromol/(min kg) (P=.003); 10+/-3.7 vs 17+/-7.4 micromol/(min kg) (P=.09); and 144+/-45.5 vs 392+/-111 micromol/d (P=.0001), respectively. Mean+/-SD basal glycerol concentrations were higher in females compared to males: 62+/-5.6 vs 36+/-17 micromol/L (P=.003). Basal glycerol concentrations and Ra values were similar by beta2 AR haplotype. Basal glucose and insulin concentrations tended to be higher in males compared to females and were similar by haplotype. Terbutaline-stimulated changes in glycerol concentrations were variable and are not related to either sex or haplotype. We conclude that compared to haplotype, sex is a more important determinant of basal lipolysis after a 12-hour fast in healthy, non-obese individuals.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Haplotipos , Lipólisis/genética , Receptores Adrenérgicos beta 2/genética , Caracteres Sexuales , Terbutalina/farmacología , Adulto , Glucemia/análisis , Metabolismo Energético , Femenino , Glicerol/sangre , Humanos , Insulina/sangre , Cinética , Peroxidación de Lípido , Lipólisis/efectos de los fármacos , Masculino , Persona de Mediana Edad , Valores de Referencia , Terbutalina/sangre , Terbutalina/farmacocinéticaRESUMEN
OBJECTIVE: Our objective was to determine whether beta(2)-adrenergic receptor polymorphisms influence terbutaline-stimulated changes in glucose, insulin, and potassium concentrations in healthy adults. METHODS: Seven healthy adults homozygous for the Arg-19/Gly16/Glu27 haplotype (RGE) and seven homozygous for the Cys-19/Arg16/Gln27 haplotype (CRQ) volunteered to receive a 1-hour infusion of terbutaline (0.01 mg/kg). A 2-compartment pharmacokinetic model was fitted to the terbutaline concentrations. Concentrations of glucose and insulin were fitted simultaneously by use of a coupled feedback indirect response model. An indirect response model was also fitted to the plasma potassium concentration versus time data. The -2 log-likelihood ratio test was used to determine whether estimates of the covariates of diplotype and sex improved the model fittings. RESULTS: Demographic variables, anthropometric characteristics, and pharmacokinetics did not differ by diplotype. The coupled feedback model fitted the glucose and insulin concentration data well with excellent precision. Terbutaline stimulated production of glucose (S(1)) to a greater extent in RGE compared with CRQ diplotypes, as follows: S(1) = 0.039 +/- 0.007 (mean +/- SD) versus 0.0276 +/- 0.01, respectively (P <.05, -2 log-likelihood criterion). The baseline values, disposition rate constants for glucose (k(out1)) and insulin (k(out2)), production rate of insulin (S(2)), feedback effect of insulin on glucose (S(3)), and pharmacodynamic parameters for potassium did not differ by diplotype or sex. CONCLUSIONS: The beta(2) receptor diplotype influences receptor-stimulated glucose production in healthy, nonobese individuals, which is consistent with beta(2) receptor-mediated hepatic glycogenolysis. Future metabolic studies of this system should consider beta(2) receptor genetic variants.
Asunto(s)
Receptores Adrenérgicos beta 2/genética , Terbutalina/farmacología , Adolescente , Adulto , Glucemia/análisis , Relación Dosis-Respuesta a Droga , Femenino , Haplotipos , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad , Modelos Biológicos , Terbutalina/farmacocinéticaRESUMEN
Linear growth occurs as the result of growth plate chondrocytes undergoing proliferative and hypertrophic phases. Paracrine feedback loops that regulate the entry of chondrocytes into the hypertrophic phase have been shown and similar pathways likely exist for the proliferative phase. Human long-bone growth plate chondrocytes were cultured in vitro. The proliferative effects of a variety of factors were determined by [3H]thymidine uptake and the gene expression profile of these cells was determined by DNA microarray analysis. Serum, insulin-like growth factor (IGF)-I and -II, transforming growth factor-beta (TGF-beta, fibroblast growth factor (FGF)-1, -2, and -18, and platelet-derived growth factor (PDGF)-BB were potent stimulators of proliferation. FGF-10, testosterone, and bone morphogenetic proteins (BMP)-2, -4, and -6 inhibited proliferation. Microarray analysis showed that the genes for multiple members of the IGF-I, TGF-beta, FGF, and BMP pathways were expressed, suggesting the presence of autocrine/paracrine pathways that regulate the proliferative phase of growth plate-mediated growth.
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Condrocitos/citología , Placa de Crecimiento/citología , Sustancias de Crecimiento/farmacología , Proteínas Tirosina Quinasas , Adolescente , Animales , Bovinos , División Celular/efectos de los fármacos , Células Cultivadas , Niño , Condrocitos/metabolismo , Colágeno/biosíntesis , Colágeno/genética , Relación Dosis-Respuesta a Droga , Matriz Extracelular/metabolismo , Femenino , Sangre Fetal , Perfilación de la Expresión Génica , Sustancias de Crecimiento/metabolismo , Hormonas/farmacología , Humanos , Masculino , ARN Mensajero/biosíntesis , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos , Receptores de Factores de Crecimiento de Fibroblastos/biosíntesis , Timidina/metabolismoRESUMEN
Most of the energy requirement for cell growth, differentiation, and development is met by the mitochondria in the form of ATP produced by the process of oxidative phosphorylation. Human mitochondrial DNA encodes a total of 13 proteins, all of which are essential for oxidative phosphorylation. The mRNAs for these proteins are translated on mitochondrial ribosomes. Recently, the genes for human mitochondrial ribosomal proteins (MRPs) have been identified. In this review, we summarize their refined chromosomal location. It is well known that mutations in the mitochondrial translation system, i.e., ribosomal RNA and transfer RNA cause various pathologies. In this review, we suggest possible associations between clinical conditions and MRPs based on coincidence of genetic map data and chromosomal location. These MRPs may be candidate genes for the clinical condition or may act as modifiers of existing known gene mutations (mt-tRNA, mt-rRNA, etc.).
Asunto(s)
ADN Mitocondrial/genética , Mitocondrias/genética , Enfermedades Mitocondriales/genética , Proteínas Ribosómicas/genética , Mapeo Cromosómico , Orden Génico , Enfermedades Genéticas Congénitas/genética , Humanos , Enfermedades Mitocondriales/terapiaRESUMEN
Leukotrienes (LT) mediate inflammation in asthma. The fraction of exhaled nitric oxide (FE(NO)) is thought to be a sensitive and reproducible method for assessing airway inflammation in asthmatics and the anti-inflammatory effects of drugs. A number of factors are known to contribute to intrapatient variation in FE(NO) which can confound interpretation. The aims of this study were to characterize the time-course of FE(NO), determine the effect of montelukast on the time-course of FE(NO), and evaluate the influence of the LTC(4) synthase A(-444)C polymorphism on montelukast-evoked changes in FE(NO). Following a 2-week run-in, 7 males and 5 females with asthma, 10-16 years old, received 5 or 10 mg of montelukast or an identical placebo at bedtime for 7 days in double-blind, crossover fashion, followed by a 7-day washout. FE(NO)was quantified every 30 min for 3 or 6 hr at baseline and on days 1, 2, 3, and 7 of treatment. A time-averaged value for FE(NO) was calculated (FE(NO)*), and % changes in FE(NO)* relative to baseline vs. time following placebo and montelukast were compared. The genotype of the A(-444)C polymorphism was determined by PCR and RFLP. FE(NO) varied markedly as a function of time in each patient. Time-averaged values of FE(NO) (FE(NO)*) during placebo and montelukast treatment were similar. Montelukast significantly reduced the slope of the % change in FE(NO)* vs. time curve in heterozygotes (n = 4), but not in A/A homozygotes (n = 8). These data suggest that heterozygotes respond better to montelukast compared to A/A homozygotes, at least with respect to changes in FE(NO). We conclude that assessment of inflammation or the anti-inflammatory effects of drugs in asthma based on single determinations of FE(NO) can be misleading. We further conclude that the A(-444)C polymorphism in the LTC(4) synthase gene probably contributes to interpatient variability in montelukast-evoked changes in FE(NO)* and warrants further study.
Asunto(s)
Acetatos/farmacología , Antiasmáticos/farmacología , Asma/tratamiento farmacológico , Asma/enzimología , Pruebas Respiratorias , Glutatión Transferasa/genética , Óxido Nítrico/análisis , Quinolinas/farmacología , Adolescente , Niño , Estudios Cruzados , Ciclopropanos , Método Doble Ciego , Femenino , Humanos , Masculino , Farmacogenética , Polimorfismo Genético , Espirometría , Sulfuros , Factores de TiempoRESUMEN
The most common cause of congenital adrenal hyperplasia is steroid 21-hydroxylase deficiency. The molecular genetics of this disease are such that genotyping is a potentially useful tool in its diagnosis. An assay was developed using real-time, quantitative PCR to detect deletions of the steroid 21-hydroxylase gene (CYP21A2). This assay was able to detect heterozygous gene deletions with an alpha error rate of less than 5%, with a power greater than 95%. When combined with allele-specific PCR, genotyping for the nine most common mutations can be completed within hours of blood sampling. This technique was used to study subjects with 21-hydroxylase deficiency in North Florida. Twenty-eight subjects with congenital adrenal hyperplasia, seven first-degree relatives and thirteen normal subjects, were characterized. Of 96 chromosomes, 69 abnormal alleles were identified. Among unrelated abnormal alleles, the frequency of specific mutations was 28% for a gene deletion, 24% for the intron 2 splice mutation, 10% for ile172asn, 8% each for val281leu and the exon 6 cluster, and 6% for gln318x mutations. These frequencies, as well as the genotype/phenotype correlation, were similar to those found in comparable populations. The utility of genotyping in the diagnosis of 21-hydroxylase deficiency is increased by the rapidity of the analysis. With quantitative PCR, the need for more expensive and time consuming Southern blot analysis is reduced and limited to the clarification of certain genotypes. Faster results will allow for more timely initiation of appropriate therapy and limit the exposure of potentially unnecessary therapy.