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1.
Prev Med ; 153: 106725, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34271076

RESUMO

Behavioral theories inform the development of lifestyle interventions to address low participation in physical activity (PA); however, relatively little is known about the value of self-determination theory (SDT) for explaining screen time (ST) behaviors or in extending SDT into a dyadic context. Actor-partner (i.e., parent-adolescent) interdependence models (APIMs) allow for examination of these interpersonal relationships. The purpose of this study was to examine PA and ST among parent-adolescent dyads using the cross-sectional Family Life, Activity, Sun, Health, and Eating (FLASHE) Study. Parent-adolescent dyads provided responses to online surveys addressing PA (n = 1177 dyads) and ST (n = 1489 dyads) behaviors. We examined the influence of SDT-based constructs (perceived competence and motivation) on PA and ST behaviors. Structural equations were used to estimate APIMs in STATA 15.1. Full models provided a good fit to the data. For both PA and ST, perceived competence was more strongly associated with motivation among adolescents compared with parents (PA: ß = 0.72 vs. 0.58, ST: ß = 0.34 vs. 0.22, p's < 0.001). Parental motivation was associated with parental PA and both adolescent motivation for PA and ST (p's < 0.001). Parental motivation was not associated with adolescent ST-behavior. Adolescent motivation was only associated with parent motivation for PA. In the FLASHE study, SDT constructs extend acceptably to the dyadic setting, with PA models providing a slightly better fit to the data than ST models. Longitudinal studies that target perceived competence and the self-regulation of motivation in parents and their adolescents are a next logical step to understanding both PA and ST behaviors.


Assuntos
Motivação , Tempo de Tela , Adolescente , Estudos Transversais , Exercício Físico , Humanos , Relações Pais-Filho , Pais
2.
J Pediatr Adolesc Gynecol ; 34(6): 832-838, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34271198

RESUMO

STUDY OBJECTIVE: Adolescent pregnancy contributes to accelerated trajectories of adiposity and cardiometabolic diseases. Two potentially low-cost prevention strategies include promoting physical activity (PA) and limiting television (TV) viewing. Few studies have explored these behavior patterns in perinatal adolescents. This study sought to characterize PA and TV viewing in a socioeconomically disadvantaged perinatal adolescent population. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: A cross-sectional, retrospective, 10-item survey was used to explore behavior patterns in 79 predominantly Black (86%) postpartum adolescents. MAIN OUTCOME MEASURES: Outcomes included self-reported changes in PA from pre-pregnancy through pregnancy, and 7-day recall of PA and TV viewing in postpartum. RESULTS: The majority of adolescents (66%) reported being active on ≥3 days/week in pre-pregnancy; however, many reported low PA (≤2 days/wk) in their first (59%), second (66%), and third (54%) trimesters. Adolescents who reported being active on ≥5 days/wk in pre-pregnancy (19%) experienced first trimester PA decline, which subsequently plateaued. This group remained the most active throughout pregnancy. In postpartum, over half (54%) of all adolescents reported low PA and irrespective of PA, spent considerable time watching TV (median = 1680.0 minutes, inerquartile range = 2940). CONCLUSION: Interventions promoting PA coupled with reducing TV viewing during pregnancy and in postpartum may benefit perinatal adolescents. The findings from this study suggest that PA history is a predictor of gestational PA, and low PA and high TV viewing in postpartum underscore the need for behavioral intervention. Conducting a brief assessment of PA history in early gestation may offer important insight.


Assuntos
Televisão , Populações Vulneráveis , Adolescente , Estudos Transversais , Exercício Físico , Feminino , Humanos , Período Pós-Parto , Gravidez , Estudos Retrospectivos
3.
Artigo em Inglês | MEDLINE | ID: mdl-32514369

RESUMO

BACKGROUND: Children from low-income families experience accelerated BMI gain and learning loss during summer. Healthy Summer Learners (HSL) addresses accelerated BMI gain and academic learning loss during summer by providing academic- and health-focused programming. This manuscript reports the effects of HSL on underlying obesogenic behaviors (i.e., physical activity, screen time, sleep, diet) that lead to accelerated summer BMI gain, a necessary first step to informing a future randomized controlled trial of HSL. METHODS: In the summer of 2018 and 2019 using a quasi-experimental study design, 180 children (90 per summer, 7.9 years [SD = 1.0], 94% non-Hispanic Black, 40% male) at two schools (i.e., one per summer) who were struggling academically (25-75% on a standardized reading test) were provided a free, school-based 6-week health- and academic-focused summer program (i.e., HSL, n = 60), a 4- to 6-week academic-focused summer program (i.e., 21st Century Summer Learning program (21C), n = 60), or no summer program (n = 60). Children wore the Fitbit Charge 2™ over a 10-week period during the summers (June-Aug) of 2018-2019. Differences within (within child days attend vs. not attend) and between (differences between groups attend vs. not attend) were evaluated using mixed effects linear regression. RESULTS: Regression estimates indicated that, on days attending, HSL children experienced a greater reduction in sedentary minutes (- 58.6 [95% CI = - 92.7, - 24.4]) and a greater increase in moderate-to-vigorous physical activity (MVPA) (36.2 [95% CI = 25.1, 47.3]) and steps (2799.2 [95% CI = 2114.2, 3484.2]) compared to 21C children. However, both HSL and 21C children were more active (i.e., greater MVPA, total steps) and less sedentary (i.e., less sedentary minutes and total screen time) and displayed better sleeping patterns (i.e., earlier and less variability in sleep onset and offset) on days they attended than children in the control. CONCLUSIONS: HSL produced greater changes in physical activity than 21C. However, attendance at either HSL or 21C leads to more healthy obesogenic behaviors. Based on the behavioral data in this pilot study, a larger trial may be warranted. These results must be considered along with the pending primary outcomes (i.e., academics and BMI z-score) of the HSL pilot to determine if a full-scale trial is warranted. TRIAL REGISTRATION: NIH-NCT03321071. Registered 25 October 2017.

4.
J Frailty Aging ; 9(3): 165-171, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32588032

RESUMO

BACKGROUND: Walking interventions improve physical function, reduce fall risk, and prevent mobility disability-even in those with compromised walking ability. However, most prior studies have been conducted in controlled research settings, with no dissemination of an evidence-based walking program for older adults who have mobility limitations and/or are socially isolated. OBJECTIVES: This study reports data on the feasibility and acceptability of a community-based walking program (Walk On!) for older adults who are functionally limited, and assesses changes in physical function among attendees. The program sessions focused on long-distance walking, and took place for one-hour, for two days/week, and for 12 weeks at a time. DESIGN: Pilot implementation study. SETTING: Local church in Winston-Salem, NC. PARTICIPANTS: 49 program participants; Measurements: Physical function battery and satisfaction survey data, as well as formative evaluation data from six attendees of a focus group, are reported. RESULTS: The majority of the participants were >75 years (71%), female (65%), and presented with low levels of physical function (usual gait speed=0.79±0.16; 30.6% used an assistive device). Satisfaction with the program was high (100% would recommend it to others) and focus group results were overwhelmingly positive. Mean attendance to scheduled sessions was 77%±21%, and 63% of participants attended at least 75% of scheduled sessions (n=8 attended 100%). On average, participants improved their 6-min walk distance by 8.9%, their SPPB score by 15.4%, their timed-up-go time by 9.0%, and their usual gait speed by 11.4%. CONCLUSION: The results of the initial evaluation of Walk On! show high feasibility and acceptability of the program, as well as efficacy for improving physical function. Further research is needed to evaluate a delivery method for wider implementation of the program and to definitively test its effectiveness for improving function and other health benefits.


Assuntos
Serviços de Saúde Comunitária/organização & administração , Promoção da Saúde/organização & administração , Limitação da Mobilidade , Desenvolvimento de Programas , Caminhada , Idoso , Estudos de Viabilidade , Feminino , Grupos Focais , Humanos , Masculino , Projetos Piloto , Avaliação de Programas e Projetos de Saúde , Caminhada/fisiologia
5.
Pediatr Obes ; 13(7): 433-441, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29761652

RESUMO

BACKGROUND: Vitamin D deficiency has been associated with non-alcoholic fatty liver disease (NAFLD). However, the role of polymorphisms determining vitamin D status remains unknown. OBJECTIVES: The objectives of this study were to determine in UK children with biopsy-proven NAFLD (i) their vitamin D status throughout a 12-month period and (ii) interactions between key vitamin D-related genetic variants (nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7, vitamin D receptor, group-specific component, CYP2R1) and disease severity. METHODS: In 103 paediatric patients with NAFLD, serum 25-hydroxyvitamin D (25OHD) levels and genotypes were determined contemporaneously to liver biopsy and examined in relation to NAFLD activity score and fibrosis stage. RESULTS: Only 19.2% of children had adequate vitamin D status; most had mean 25OHD levels considered deficient (<25 nmol·L-1 , 25.5%) or insufficient (<50 nmol·L-1 , 55.3%). Patients had significantly lower 25OHD levels in winter months (95% CI: 22.7-31.2 nmol·L-1 ) when compared with spring (30.5-42.1 nmol·L-1 ; P = 0.0089), summer (36.3-47.2 nmol·L-1 ; P < 0.0001) and autumn (34.2-47.5 nmol·L-1 ; P = 0.0003). Polymorphisms in the nicotinamide adenine dinucleotide synthase-1/dehydrocholesterol reductase-7 (rs3829251, rs12785878) and vitamin D receptor (rs2228570) genes were independently associated with increased steatosis; while a group-specific component variant (rs4588) was associated with increased inflammation in liver biopsies. CONCLUSIONS: Children with NAFLD in the UK have particularly low winter vitamin D status, with vitamin D insufficiency prevalent throughout the year. Polymorphisms in the vitamin D metabolic pathway are associated with histological severity of paediatric NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica/genética , Polimorfismo Genético , Vitamina D/análogos & derivados , Amida Sintases/genética , Criança , Colestanotriol 26-Mono-Oxigenase/genética , Estudos de Coortes , Família 2 do Citocromo P450/genética , Feminino , Humanos , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Receptores de Calcitriol/genética , Estações do Ano , Vitamina D/sangue
6.
Clin Obes ; 8(1): 68-79, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29224232

RESUMO

Targeting physical inactivity in children is pertinent to aiding in the decrease of childhood obesity rates. Only 33% of adolescents are obtaining the recommended goal of at least 60 min of physical activity per day. The objectives of this review are to summarize professional recommendations for physical activity and exercise in children and adolescents, and identify family-centred strategies that can be implemented by weight management clinicians. Clinically oriented recommendations and policy statements from professional organizations were identified through literature and internet searches, summarized using rubrics of aerobic, muscle strengthening and bone strengthening exercise, then examined for details on family-based focus, inclusion of child developmental stage and age, and application to the prevention and treatment of obesity. Current recommendations give guidelines for the amount of physical activity that children should acquire and how many days a week activities should occur. However, available guidelines need an improved approach to addressing the role of the parents and caregivers in targeting physical activity and weight management in youth. Efforts must be taken in order to make sure that the types of physical activity offered are both suitable and enjoyable. Sports, games, free play and other age appropriate activities are adequate ways to increase moderate to vigorous physical activity in children. Differentiating physical activities types in accordance with developmental stage, level of enjoyment, and family characteristics is needed to establish sustainable habits. One paediatric obesity program has developed approaches to teaching families fun and engaging ways to be active together.


Assuntos
Comportamento do Adolescente , Comportamento Infantil , Exercício Físico , Comportamentos Relacionados com a Saúde , Estilo de Vida Saudável , Pais/psicologia , Obesidade Infantil/terapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Conhecimentos, Atitudes e Prática em Saúde , Promoção da Saúde , Humanos , Relações Pais-Filho , Poder Familiar , Obesidade Infantil/diagnóstico , Obesidade Infantil/fisiopatologia , Obesidade Infantil/psicologia , Fatores de Tempo , Resultado do Tratamento , Redução de Peso
7.
Osteoporos Int ; 26(4): 1311-8, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25572045

RESUMO

UNLABELLED: The role of acid-base metabolism in bone health is controversial. In this meta-analysis, potassium bicarbonate and potassium citrate lowered urinary calcium and acid excretion and reduced the excretion of the bone resorption marker NTX. These salts may thus be beneficial to bone health by conserving bone mineral. INTRODUCTION: The role of acid-base homeostasis as a determinant of bone health and the contribution of supplemental alkali in promoting skeletal integrity remain a subject of debate. The objective of this study was, therefore, to conduct a meta-analysis to assess the effects of supplemental potassium bicarbonate (KHCO3) and potassium citrate (KCitr) on urinary calcium and acid excretion, markers of bone turnover and bone mineral density (BMD) and to compare their effects with that of potassium chloride (KCl). METHODS: A total of 14 studies of the effect of alkaline potassium salts on calcium metabolism and bone health, identified by a systematic literature search, were analysed with Review Manager (Version 5; The Cochrane Collaboration) using a random-effects model. Authors were contacted to provide missing data as required. Results are presented as the standardised (SMD) or unstandardized mean difference (MD) (95 % confidence intervals). RESULTS: Urinary calcium excretion was lowered by intervention with both KHCO3 (P = 0.04) and KCitr (P = 0.01), as was net acid excretion (NAE) (P = 0.002 for KHCO3 and P = 0.0008 for KCitr). Both salts significantly lowered the bone resorption marker NTX (P < 0.00001). There was no effect on bone formation markers or BMD. KHCO3 and KCitr lowered calcium excretion to a greater extent than did KCl. CONCLUSIONS: This meta-analysis confirms that supplementation with alkaline potassium salts leads to significant reduction in renal calcium excretion and acid excretion, compatible with the concept of increased buffering of hydrogen ions by raised circulating bicarbonate. The observed reduction in bone resorption indicates a potential benefit to bone health.


Assuntos
Bicarbonatos/farmacologia , Conservadores da Densidade Óssea/farmacologia , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Citrato de Potássio/farmacologia , Compostos de Potássio/farmacologia , Bicarbonatos/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Reabsorção Óssea/prevenção & controle , Cálcio/urina , Humanos , Compostos de Potássio/uso terapêutico
8.
Int J Obes (Lond) ; 29 Suppl 2: S40-5, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16385751

RESUMO

OBJECTIVE: To investigate the relations of attendance of children in an after-school physical activity (PA) program to changes in body composition and cardiovascular fitness (CVF). DESIGN: Eight-month after-school PA-based intervention. SUBJECTS: In all, 278 third-grade boys and girls from nine elementary schools (age, 8.7 y (s.d. = 0.6 y), body mass index (BMI) 19.1 kg/m2 (s.d. = 4.4) and percent body fat (%BF) 26.0 (s.d. = 9.0)). MEASUREMENTS: Body composition (from dual-energy X-ray absorptiometry), BMI (from height and weight), waist circumference (WC) and CVF (from the YMCA submaximal bench-stepping test). RESULTS: There was a significant negative linear trend between level of attendance in the after-school program and change in %BF and fat mass; there was also a significant positive linear trend between program attendance and change in CVF. There was a marginally significant linear trend between program attendance and fat-free mass. Greater increases in bone mineral density were observed with higher program attendance. Changes in BMI and WC were not influenced by program attendance. CONCLUSION: Understanding the dose-response effect of PA on health outcomes, particularly body composition, in children is crucial in our effort to prevent overweight and its health consequences. Since there is limited data available to base PA dose recommendations for youths, findings from this study are relevant, and suggest that greater health benefits can be obtained in young children with more frequent participation in PA.


Assuntos
Terapia por Exercício/métodos , Cooperação do Paciente , Aptidão Física/fisiologia , Composição Corporal , Densidade Óssea , Doenças Cardiovasculares/prevenção & controle , Criança , Feminino , Seguimentos , Humanos , Análise dos Mínimos Quadrados , Masculino , Fatores de Risco
9.
Horm Metab Res ; 37(6): 369-74, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16001329

RESUMO

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis.


Assuntos
Regulação Neoplásica da Expressão Gênica , Neoplasia Endócrina Múltipla Tipo 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Núcleo Celular/metabolismo , Proteínas do Citoesqueleto/metabolismo , DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasia Endócrina Múltipla Tipo 1/genética , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , Fatores de Transcrição/metabolismo , Transcrição Gênica
10.
Ann Hum Biol ; 31(6): 647-59, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15799232

RESUMO

BACKGROUND: Few studies have examined growth data from adolescent girls in Latin America and almost none have been conducted in Nicaragua. Thus this study examines growth data from Nicaraguan adolescent girls. AIM: This study describes cross-sectional growth data from a sample of Nicaraguan girls. These data are compared with data from Mexican-US and Guatemalan girls. It is hypothesized that (a) Mexican-US and Guatemalan wealthy ladina girls will show better indicators of nutritional status when compared with the Nicaraguan girls, and (b) the Nicaraguan girls will show similar anthropometric indicators when compared with poor Guatemalan girls. SUBJECTS AND METHODS: Anthropometric and age at menarche data were collected from a sample of 154 adolescent girls ages 10-17 years living in Managua, Nicaragua. RESULTS: The findings revealed that these girls are significantly shorter and lighter than US, Mexican-US and wealthy Guatemalan adolescent girls. These girls are also significantly taller and heavier than their poor Guatemalan counterparts. CONCLUSION: This study reveals that the Nicaraguan girls are undernourished when compared with other Latin American girls living in an improved overall environment. The data also reveal that the Nicaraguan girls have better indicators of nutritional status when compared with a cohort of poor Guatemalan girls.


Assuntos
Desenvolvimento do Adolescente/fisiologia , Tamanho Corporal , Estado Nutricional/fisiologia , Adolescente , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Guatemala , Humanos , Americanos Mexicanos , Nicarágua , Pobreza , População Urbana
11.
Int J Sports Med ; 24(8): 588-92, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14598195

RESUMO

Electronic pedometers are accurate for assessing steps taken while walking in normal weight adults but the accuracy of these devices has not been tested in overweight and obese men and women. The primary purpose of this study was to assess the accuracy of an electronic pedometer for measuring steps taken at various walking speeds in groups of adults with variations in body mass index (BMI). The secondary purpose was to determine if the manufacturer recommended position is the best placement position for overweight and obese adults. Participants were categorized into one of three BMI categories identified by the World Health Organization: normal (N = 25; < 25 kg x m(-2)), overweight (N = 24; 25 - 29.9 kg x m(-2)), or obese (N = 17; > or = 30 kg x m(-2)). Participants walked on a treadmill for 3 min at 54, 67, 80, 94, and 107 m x min(-1) for a total of 15 min. During the treadmill walking, three electronic pedometers tallied steps taken. The pedometers were placed at the waist level, one on the anterior mid-line of the thigh (front; manufacturer recommended placement), one on the mid-axillary line (side), and one on the posterior mid-line of the thigh (back). Concurrently, a researcher counted steps using a hand-tally counter. Category of BMI did not affect the accuracy of the pedometer at any walking speed (54 m x min(-1), p = 0.991; 67 m x min(-1), p = 0.556; 80 m x min(-1), p = 0.591; 94 m x min(-1), p = 0.426; 107 m x min(-1), p = 0.869). At 54 m x min(-1), the front, side, and back pedometers significantly underestimated hand-tally counted steps by 20 % (p < 0.001), 33 % (p < 0.001), and 26 % (p < 0.001), respectively. At 67 m x min(-1) the front, side, and back pedometers significantly underestimated hand-tally counted steps by 7 % (p = 0.027), 13 % (p < 0.001), 11 % (p = 0.002), respectively. The steps recorded by the electronic pedometers placed at the front, side and back of the waist were not significantly different than steps counted by the hand-tally counter at speeds of 80 m x min(-1) and higher for all subjects combined. An electronic pedometer accurately quantified steps walked at speeds of 80 m x min(-1) or faster in persons with a normal BMI and those classified as overweight or obese. The placement of the pedometer on the front, side or back of the waistband did not affect accuracy of the pedometer for counting steps.


Assuntos
Índice de Massa Corporal , Ergometria/instrumentação , Ergometria/normas , Monitorização Ambulatorial/instrumentação , Monitorização Ambulatorial/normas , Obesidade/fisiopatologia , Caminhada/fisiologia , Adulto , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
12.
J Nutr ; 131(12): 3189-96, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11739864

RESUMO

The detrimental sequelae of severe zinc deficiency on the thymus and T-lymphocyte compartment of the mammalian immune system have been established, but underlying mechanisms remain unknown. Hypothesizing that the alterations in T-lymphocyte number and function observed during zinc deficiency may result from changes in gene expression, we sought to compare thymic mRNA expression profiles of zinc-deficient and zinc-normal mice utilizing cDNA arrays. For our murine model described herein, 3 wk of dietary zinc deficiency did not perturb food intake or growth rate in young adult, outbred mice, but significantly depressed multiple parameters of zinc status. Furthermore, fluorescence-activated cell sorting (FACS) analysis demonstrated no changes in thymocyte populations expressing the cell surface markers CD3, CD4 or CD8, establishing that observed changes in mRNA abundances were not attributable to different thymocyte populations. Yet notably, at this moderate level of zinc deficiency, cDNA array analysis identified four potentially zinc-regulated mRNAs whose modulation was confirmed independently, twice, using both semiquantitative and real-time quantitative reverse transcription-polymerase chain reaction. Expression of one of these genes (myeloid cell leukemia sequence-1) was depressed, whereas the others [DNA damage repair and recombination protein 23B, the mouse laminin receptor and the lymphocyte-specific protein tyrosine kinase (LCK)] were elevated in the zinc-deficient mice. Further Western analysis demonstrated that the zinc binding protein LCK was elevated in these zinc-deficient mice. Results demonstrate that 3 wk of dietary zinc insufficiency can alter specific thymic mRNA and protein abundances before alterations occur in thymocyte development as detectable by FACS analysis.


Assuntos
Contagem de Linfócitos , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Tirosina Quinases/genética , Linfócitos T , Timo/enzimologia , Zinco/deficiência , Animais , Western Blotting , Dieta , Citometria de Fluxo , Regulação Enzimológica da Expressão Gênica , Masculino , Camundongos , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Zinco/administração & dosagem
13.
Proc Natl Acad Sci U S A ; 98(24): 13507-13, 2001 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-11717422

RESUMO

Mammalian nutritional status affects the homeostatic balance of multiple physiological processes and their associated gene expression. Although DNA array analysis can monitor large numbers of genes, there are no reports of expression profiling of a micronutrient deficiency in an intact animal system. In this report, we have tested the feasibility of using cDNA arrays to compare the global changes in expression of genes of known function that occur in the early stages of rodent zinc deficiency. The gene-modulating effects of this deficiency were demonstrated by real-time quantitative PCR measurements of altered mRNA levels for metallothionein 1, zinc transporter 2, and uroguanylin, all of which have been previously documented as zinc-regulated genes. As a result of the low level of inherent noise within this model system and application of a recently reported statistical tool for statistical analysis of microarrays [Tusher, V.G., Tibshirani, R. & Chu, G. (2001) Proc. Natl. Acad. Sci. USA 98, 5116-5121], we demonstrate the ability to reproducibly identify the modest changes in mRNA abundance produced by this single micronutrient deficiency. Among the genes identified by this array profile are intestinal genes that influence signaling pathways, growth, transcription, redox, and energy utilization. Additionally, the influence of dietary zinc supply on the expression of some of these genes was confirmed by real-time quantitative PCR. Overall, these data support the effectiveness of cDNA array expression profiling to investigate the pleiotropic effects of specific nutrients and may provide an approach to establishing markers for assessment of nutritional status.


Assuntos
Regulação da Expressão Gênica , Mucosa Intestinal/metabolismo , Zinco/deficiência , Animais , Suplementos Nutricionais , Perfilação da Expressão Gênica , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Ratos , Ratos Sprague-Dawley
14.
Drug Des Discov ; 17(3): 243-51, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11469754

RESUMO

A first-in-class non-peptide antagonist of the motilin receptor was identified through electronic screening of our corporate database against a 3D pharmacophore. The pharmacophore was developed from the motilin 22 residue endogenous peptide using NMR structural data, principles of peptide folding, and peptide structure activity relationships. The NMR data supported helical content within the peptide, and both the hydrophobic staple and N-capping box motifs were identified in the motilin sequence. The conformational features of these motifs were imposed on the peptide structure, providing a constrained conformer as a starting point for database searching. A trisubstituted cyclopentene lead was identified directly from the electronic search. Compounds in this series inhibit the binding of 125I-motilin to human antral smooth muscle membrane and antagonize motilin-induced intracellular calcium mobilization in cells expressing the human motilin receptor. A potent compound developed through optimization, RWJ 68023, is active in binding and cell-based functional assays and is also effective in inhibiting motilin-induced contractility in segments of rabbit duodenum. This orally active compound is currently undergoing clinical evaluation for the treatment of gastrointestinal disorders associated with altered motility.


Assuntos
Receptores dos Hormônios Gastrointestinais/antagonistas & inibidores , Receptores de Neuropeptídeos/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Duodeno/efeitos dos fármacos , Duodeno/fisiologia , Motilidade Gastrointestinal/efeitos dos fármacos , Humanos , Conformação Molecular , Dados de Sequência Molecular , Motilina/metabolismo , Coelhos
15.
Pharmacogenomics ; 2(2): 95-106, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11368749

RESUMO

The attempt to develop novel antibiotics, active against organisms resistant to current therapies, has led researchers to seek and explore new drug targets. The rapid sequencing and analysis of entire microbial genomes has identified large numbers of genes that may be sufficiently different from their human counterparts to be exploited as targets for antimicrobial treatment. As a first step, the importance of the various putative targets for microbial growth and survival must be assessed. Emerging validation technologies are becoming increasingly sophisticated and, in certain cases, allow prioritisation of the best targets. In this paper, genetically assisted target evaluation (GATE) is introduced as a versatile target validation technology. GATE concomitantly manipulates both synthesis and stability of the targeted protein using copper ions as an effector. This technology allows rapid quantitation of the lethal consequences of inactivation of targeted gene products in Saccharomyces cerevisiae. Additional tools can then be applied to extend these results into pathogenic organisms, such as Candida albicans.


Assuntos
Anti-Infecciosos/administração & dosagem , Regulação da Expressão Gênica/fisiologia , Marcação de Genes/métodos , Proteínas/química , Proteínas/genética , Animais , Sistemas de Liberação de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos
16.
Infect Immun ; 68(5): 2728-34, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10768966

RESUMO

Earlier studies showed that mice primed for a few hours with the trans-sialidase (TS) of Trypanosoma cruzi, the agent of Chagas' disease, become highly susceptible to trypanosomal infection. These studies suggest that TS affects parasite virulence independent of antigenic stimulation. Potentially, TS could enhance or reduce the virulence of heterologous microbes depending on the mechanism of TS action and on the type of immune response elicited by the particular parasite. We tested this hypothesis by expressing heterologous TS in Leishmania major, a protozoan parasite that causes cutaneous leishmaniasis and lacks TS and the TS product alpha2-3-linked sialic acid. Leishmania cells transfected with a T. cruzi TS expression construct made high levels of active enzyme, which was present in the promastigotes and shed into the extracellular milieu. TS expression did not affect L. major binding to and entry into cultured macrophages or its tropism for macrophage infection in vivo. However, TS-expressing L. major exhibited elevated virulence in BALB/c mice, as determined by lesion progression, parasite numbers, and macro- and microscopic examination of cutaneous lesions. Several genetic tests proved that the enhanced virulence was directly attributable to TS expression. The results are consistent with TS functioning to sabotage the mouse immune system to confer a growth advantage on T. cruzi and transgenic L. major. These data suggest that heterologous expression of T. cruzi virulence factors in Leishmania may provide a new approach for dissecting their function in vivo.


Assuntos
Glicoproteínas/fisiologia , Leishmania major/patogenicidade , Leishmaniose Cutânea/parasitologia , Neuraminidase/fisiologia , Trypanosoma cruzi/enzimologia , Animais , Modelos Animais de Doenças , Feminino , Expressão Gênica , Glicoproteínas/genética , Leishmaniose Cutânea/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Neuraminidase/genética , Virulência
17.
Nurs Sci Q ; 13(2): 137-42, 2000 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11847698

RESUMO

The purpose of this review was to examine published research on basic conditioning factors described in Orem's self-care deficit theory of nursing, in order to identify operational definitions, measurement strategies, and the results of the analyses. Thirty-five research articles published between 1987 and 1997 met the criteria for inclusion in the review. Consensus or lack of consensus in operational definitions for specific factors was determined and successful measurement methods were identified. Recommendations are made for revising conceptual and operational definitions. Suggested measurement strategies for the factors are discussed.


Assuntos
Coleta de Dados/métodos , Interpretação Estatística de Dados , Pesquisa em Enfermagem/métodos , Teoria de Enfermagem , Autocuidado , Atitude Frente a Saúde , Características Culturais , Coleta de Dados/normas , Família/psicologia , Nível de Saúde , Humanos , Avaliação das Necessidades , Pesquisa em Enfermagem/normas , Projetos de Pesquisa , Fatores de Risco , Teoria de Sistemas
18.
Neurosci Lett ; 242(3): 177-9, 1998 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-9530934

RESUMO

Neuropeptide Y (NPY) and catecholamines are synthesized in response to stress. Adrenal NPY mRNA and tyrosine hydroxylase (TH) mRNA were measured by Northern analysis 2 h after a single 20 min bout of shaker stress in exercised and sedentary male Sprague-Dawley rats. Long-term exercise (18 weeks of voluntary wheel running) alone did not significantly alter adrenal NPY mRNA or TH mRNA levels. However, increases in stress-induced NPY and TH mRNA abundances were significantly enhanced by long-term exercise (P < 0.01). These results suggest that long-term physical activity may enhance the ability to synthesize NPY and catecholamines under conditions of stress.


Assuntos
Medula Suprarrenal/fisiologia , Neuropeptídeo Y/genética , Condicionamento Físico Animal/fisiologia , Estresse Fisiológico/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Animais , Northern Blotting , Catecolaminas/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Masculino , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Fisiológico/genética
19.
Nurs Sci Q ; 11(3): 116-22, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9923327

RESUMO

The purposes of this descriptive study were to examine the relationships between self-concept and (a) self-care, (b) dependent-care, and (c) basic conditioning factors for children with cancer, and to compare the self-concept of children on- and off-therapy. The theoretical framework was Orem's self-care deficit theory of nursing. The sample consisted of 74 children with cancer and their mothers. Results showed small but significant correlations between variables, providing some evidence that if children had higher self-concept scores they performed more self-care activities and received more dependent-care from their mothers. The self-concept scores of the on- and off-therapy groups were not significantly different. This study supports Orem's theory and reinforces the need to promote positive self-concept.


Assuntos
Neoplasias/psicologia , Psicologia do Adolescente , Psicologia da Criança , Autocuidado/métodos , Autocuidado/psicologia , Autoimagem , Adolescente , Criança , Dependência Psicológica , Feminino , Humanos , Masculino , Neoplasias/terapia , Pesquisa Metodológica em Enfermagem , Teoria de Enfermagem , Enfermagem Pediátrica/métodos , Inquéritos e Questionários
20.
Drug Des Discov ; 15(3): 135-48, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9689497

RESUMO

A series of cyclic sulfone dihydropyridines ranging in sulfone ring size from five to nine membered have been evaluated for calcium antagonist activity. Increasing the sulfone ring size from 5 to 8 membered resulted in a two orders of magnitude in vitro potency increase. Aromatic substitution which favored tracheal effects over aortic effects was found to be 2-NO2 and 2-Cl, 6-F. The ester side chain which was found to maximize in vivo activity was the N-benzyl-N-methyl aminoethyl moiety. Combination of all these structural features resulted in RWJ 22108, a bronchoselective calcium channel blocker which preclinically exhibits an antiasthmatic profile.


Assuntos
Antiasmáticos/farmacologia , Brônquios/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Piridinas/farmacologia , Animais , Antiasmáticos/química , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/metabolismo , Ligação Competitiva/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/química , Bloqueadores dos Canais de Cálcio/farmacocinética , Fenômenos Químicos , Físico-Química , Cães , Desenho de Fármacos , Feminino , Técnicas In Vitro , Modelos Moleculares , Nitrendipino/farmacocinética , Especificidade de Órgãos , Piridinas/química , Coelhos , Relação Estrutura-Atividade , Traqueia/efeitos dos fármacos , Traqueia/metabolismo
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