Dynamics of Uptake and Metabolism of Small Molecules in Cellular Response Systems

BACKGROUND: Proper cellular function requires uptake of small molecules from the environment. In response to changes in extracellular conditions cells alter the import and utilization of small molecules. For a wide variety of small molecules the cellular response is regulated by a network motif that combines two feedback loops, one which regulates the transport and the other which regulates the subsequent metabolism. RESULTS: We analyze the dynamic behavior of two widespread but logically distinct two-loop motifs. These motifs differ in the logic of the feedback loop regulating the uptake of the small molecule. Our aim is to examine the qualitative features of the dynamics of these two classes of feedback motifs. We find that the negative feedback to transport is accompanied by overshoot in the intracellular amount of small molecules, whereas a positive feedback to transport removes overshoot by boosting the final steady state level. On the other hand, the negative feedback allows for a rapid initial response, whereas the positive feedback is slower. We also illustrate how the dynamical deficiencies of one feedback motif can be mitigated by an additional loop, while maintaining the original steady-state properties. CONCLUSIONS: Our analysis emphasizes the core of the regulation found in many motifs at the interface between the metabolic network and the environment of the cell. By simplifying the regulation into uptake and the first metabolic step, we provide a basis for elaborate studies of more realistic network structures. Particularly, this theoretical analysis predicts that FeS cluster formation plays an important role in the dynamics of iron homeostasis

Stimulant Reduction Intervention using Dosed Exercise (STRIDE) - CTN 0037: Study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is a need for novel approaches to the treatment of stimulant abuse and dependence. Clinical data examining the use of exercise as a treatment for the abuse of nicotine, alcohol, and other substances suggest that exercise may be a beneficial treatment for stimulant abuse, with direct effects on decreased use and craving. In addition, exercise has the potential to improve other health domains that may be adversely affected by stimulant use or its treatment, such as sleep disturbance, cognitive function, mood, weight gain, quality of life, and anhedonia, since it has been shown to improve many of these domains in a number of other clinical disorders. Furthermore, neurobiological evidence provides plausible mechanisms by which exercise could positively affect treatment outcomes. The current manuscript presents the rationale, design considerations, and study design of the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) CTN-0037 Stimulant Reduction Intervention using Dosed Exercise (STRIDE) study.</p> <p>Methods/Design</p> <p>STRIDE is a multisite randomized clinical trial that compares exercise to health education as potential treatments for stimulant abuse or dependence. This study will evaluate individuals diagnosed with stimulant abuse or dependence who are receiving treatment in a residential setting. Three hundred and thirty eligible and interested participants who provide informed consent will be randomized to one of two treatment arms: Vigorous Intensity High Dose Exercise Augmentation (DEI) or Health Education Intervention Augmentation (HEI). Both groups will receive TAU (i.e., usual care). The treatment arms are structured such that the quantity of visits is similar to allow for equivalent contact between groups. In both arms, participants will begin with supervised sessions 3 times per week during the 12-week acute phase of the study. Supervised sessions will be conducted as one-on-one (i.e., individual) sessions, although other participants may be exercising at the same time. Following the 12-week acute phase, participants will begin a 6-month continuation phase during which time they will attend one weekly supervised DEI or HEI session.</p> <p>Clinical Trials Registry</p> <p>ClinicalTrials.gov, <a href="http://www.clinicaltrials.gov/ct2/show/NCT01141608">NCT01141608</a></p> <p><url>http://clinicaltrials.gov/ct2/show/NCT01141608?term=Stimulant+Reduction+Intervention+using+Dosed+Exercise&rank=1</url></p

O exercício físico no tratamento da depressão em idosos: revisão sistemática Physical exercise in the treatment of depression in the elderly: a systematic review

OBJETIVOS: Revisar a literatura quanto (I) ao possível efeito protetor do exercício físico sobre a incidência de depressão e (II) à eficácia do exercício físico como intervenção no tratamento da depressão. MÉTODO: Revisão sistemática de artigos em inglês e português nas bases ISI, PubMed, SciELO e LILACS de janeiro de 1993 a maio de 2006, utilizando conjuntamente os termos "depressão", "idosos" e "exercício". Artigos que avaliaram o efeito do exercício em idosos com doenças clínicas ou que utilizaram escalas para depressão somente para um diagnóstico inicial foram excluídos. RESULTADOS: Do total de 155 artigos, 22 atenderam aos critérios de inclusão, e oito foram acrescentados com busca manual. Os artigos de corte transversal (n = 8) utilizaram somente questionários de auto-avaliação para medir os níveis de atividade física. Os artigos longitudinais (n = 22) utilizaram também pedômetro digital, consumo direto de oxigênio e o exercício físico como intervenção metodológica. Os estudos que atenderam ao objetivo I apontaram para uma relação inversamente proporcional entre atividade física e alterações nos níveis de depressão. Os trabalhos que utilizaram o exercício como intervenção terapêutica na depressão encontraram resultados divergentes e apontaram para a interferência de fatores fisiológicos e psicológicos nessa relação. CONCLUSÃO: O papel do exercício e da atividade física no tratamento da depressão direciona-se para duas vertentes: a depressão promove redução da prática de atividades físicas; a atividade física pode ser um coadjuvante na prevenção e no tratamento da depressão no idoso.<br>OBJECTIVES: To review the literature on the (I) possible protective effect of physical activity on the incidence of depression, and (II) on the efficacy of physical exercise as a therapeutic intervention in depression. METHODS: Systematic review of ISI, PubMed, LILACS and SciELO articles in English and Portuguese from January 1993 to May 2005 using the keywords "depression," "elderly," and "exercise." Articles assessing the effect of physical exercise in the elderly with clinical diseases or that used depression scales only for initial diagnosis were excluded. RESULTS: We found 155 articles, 22 of which met the inclusion criteria. Other eight studies were included after a manual search. Cross-sectional studies (n = 8) used only self-evaluation questionnaires to measure the levels of physical activity. Longitudinal studies (n = 22) also used digital pedometer, direct measurements of oxygen consumption and physical exercise as methodological intervention. The studies meeting the first objective pointed to an inverse relationship between physical activity and changes in levels of depression. The studies that used physical activity as a therapeutic intervention in depression found divergent results and pointed to the interference of physiological and psychological factors on this relation. CONCLUSION: There are two aspects involved in the role of physical activity and exercise in the treatment of depression. Depression decreases the practice of physical activities; physical activity may be useful in the treatment and prevention of depression in the elderly