In the present studies, aspects of some disease activity measures in rheumatoid arthritis (RA) have been investigated, including the effect of glucocorticoids on this activity. In RA, serum interleukin(IL)-6 levels were elevated and were shown to have a circadian rhythm, with peak levels in the morning, declining towards low or normal levels in the afternoon and evening. In contrast, serum levels of tumour necrosis factor(TNF) alpha were low and stable. In other connective tissue diseases, serum TNF alpha levels were elevated but without circadian variation, while IL-6 levels were low and stable. Nocturnal administration (at 2:00 a.m.) of low-dose prednisolone a few hours before the early morning peak of IL-6 was shown to be significantly more effective in reducing clinical symptoms of disease activity and serum IL-6 levels than the traditional morning administration (at 7:30 a.m.) of the same dose of prednisolone. Circulating monocytes are activated in RA, expressing receptors related to adhesion and phagocytosis. Treatment with glucocorticoids suppressed the expression of these receptors on monocytes, and this may be one mechanism of the beneficial effect of glucocorticoids in RA. Endogenous levels of cortisol seem to play a minor role in expression of monocyte receptors. The different acute phase markers used to assess disease activity in RA showed good corrrelations with each other and with serum IL-6 levels. There were especially strong corrrelations between C-reactive protein (CRP) and Serum amyloid protein A (SAA), and between fibrinogen and erythrocyte sedimentation rate (ESR). Fibrinogen and CRP showed stronger correlation than ESR with the Modified Health Assessment Questionnaire (MHAQ) score and with the neutrophil count. Four simple objective function tests were each compared with the HAQ score a with a radiological joint damage score (Larsen score). The objective function tests correlated with the MHAQ score, and each of these two methods of assessing physical disability correlated with pain, CRP and ESR. In addition, most of the objective function tests correlated significantly with radiological joint damage, while the MHAQ score did not.

Chlamydomonas reinhardtii, a unicellular eukaryotic green alga, serves as a model organism to study the circadian clock in plants and animals. Rhodopsins are blue/green-light photoreceptors also found in C. reinhardtii. Chlamyrhodopsin (COP), the most abundant eyespot protein, was reported to have no role in the phototactic and photophobic responses in C. reinhardtii. Its function is yet unknown. In the present study, we hypothesized that the function of COP is to mediate entrainment of the circadian clock by light. In order to test this hypothesis, a C. reinhardtii selection marker conferring resistance to the antibiotic paromomycin was cloned into a COP RNAi construct obtained from another lab. Firstly, the COP RNAi construct was restriction digested to linearize it. The linearized plasmid was then blunt ended with T4 DNA polymerase and dephosphorylated with phosphatase. The linearized fragment was ligated with the paromomycin resistance marker obtained by restriction digestion of the plasmid containing it and transformed into E.coli. The recombinant clones obtained were confirmed by restriction digests. Fusion regions and the orientation of the insert in the recombinant plasmid were confirmed by sequencing. An attempt was made to transform C. reinhardtii with the construct, but this was not successful. Future studies will be required to optimize the C. reinhardtii transformation method. Transformants with reduced COP amounts can then be tested for defects in resetting the clock after light pulses. This will determine whether chlamyrhodopsin is involved in the circadian input pathway or not. The results of the complete project are expected to contribute to our understanding of the circadian clock of many other organisms including humans.

Syfte och frågeställningar Syftet med studien var att få en uppfattning om hur kosten och måltidsmönstret påverkas av en oregelbunden dygnsrytm hos skiftarbetande poliser. Syftet var också att skapa en bild av hur och vilka metoder som används för att skapa goda kost- och sömnrutiner i vardagen. Specifika frågeställningar var hur poliser upplever att deras kostvanor och måltidsmönster påverkas av skiftarbete med en oregelbunden dygnsrytm samt vilka livsstrategier som används för att hantera kost- och sömnvanor som skiftarbetande polis. Metod Datainsamlingen är baserad på intervjuer med fyra poliser, två kvinnliga och två manliga i åldrarna 26 till 37 år, som arbetar i en närförort till Stockholm. Respondenterna valdes ut med hjälp av bekvämlighetsurval via en bekant inom polisen. Samtliga deltagare kontaktades via telefon för att bli informerade om studiens syfte, frågeställningar, genomförande, för att boka in tid för intervju och blev dessutom upplysta om att de har full anonymitet i studien. Veckan innan intervjuerna ägde rum gjordes en pilotintervju med kontaktpersonen. Dagen innan deltagarna intervjuades mejlades frågorna ut. Samtliga intervjuer, förutom den sista, hölls på polisstationen i ett avskilt rum. Den sista intervjun var en telefonintervju. De tre första intervjuerna spelades in med hjälp av en diktafon, för att sedan ordagrant kunna transkriberas, bearbetas och analyseras. Den fjärde intervjun spelades in med hjälp av en mobil, varefter filen överfördes till dator. Resultat och slutsats Respondenternas svar visade individuella skillnader i upplevelsen av hur kosten påverkas av skiftarbete och en oregelbunden dygnsrytm. Regelbundenheten i måltidsmönstret verkar vara mest lidande av detta. Det finns en tendens till att måltiderna förskjuts och att poliserna missar framförallt lunchen, ifall de har arbetat nattskift. I stället äts någon form av frukost två gånger per dag. Livsstrategierna som används skulle kunna förbättras, för att ytterligare skapa bättre regelbundenhet i vardagen. / Aim The aim of this study was to gain insight into how the diet and meal pattern of shift working police officers is affected by an irregular daily routine. The purpose was also to illustrate how and what methods are used to create healthy eating and sleeping routines in everyday life. More specifically, the research questions were how police officers experience that their eating habits and meal patterns are affected by shift work with irregular daily routines and what life strategies are used to handle diet and sleeping habits as a shift working police officer. Method The data collection is based on interviews with four police officers, of whom two are female and two male between the ages of 26 and 37 years and work at a police station in the Stockholm area. The respondents were selected on the basis of convenience sample through an acquaintance within the police. All participants were contacted via telephone and were informed of the study’s purpose, research questions and method before an interview was booked. They were also informed of the fact that they would remain anonymous. A pilot interview was held with the contact person one week prior to the interviews. The participants received the interview questions by e-mail the day before the interview. All interviews, apart from the final one, were conducted at the police station in a private room. The last interview was held over the phone. The first three interviews were recorded with a dictaphone and were later transcribed, revised and analyzed. The fourth interview was recorded with a cellphone, after which the sound file was transferred to a computer. Results and conclusions The results highlighted individual differences in the experience of how the diet is affected by shift work and an irregular daily routine. The regularity of the meal pattern appears to suffer the most. There is a tendency that the meals are displaced and that the police officers primarily miss out on lunch in case they have worked a night shift. Instead they eat some form of breakfast twice per day. The life strategies that are used could be enhanced in order to create better regularity in the police officers’ everyday lives.

In mammals, circadian rhythms are generated by transcriptional-translational feedback loops consisting of a set of clock genes and their protein products. Among them, Bmal1 is a critical clock gene in generating and maintaining circadian rhythms. Moreover, orphan nuclear receptors REV-ERBs and RORs were known to respectively repress and activate Bmal1 transcription. In our study, we further demonstrated that: (1) REV-ERBalpha might be the main regulator in maintaining Bmal1 oscillation in thymus. (2) Rorgamma mRNA is constant in muscle and testis, and rhythmic in liver, while Rorgammat mRNA is only expressed in thymus, at constant levels. Moreover, the expressions of these two Rorgamma isoforms are affected in Clock mutant mice in a distinct way. (3) RORgamma and RORgammat can activate Bmal1 transcription at a similar level. (4) Rorgamma is a clock-controlled gene. Altogether, our results suggest that the crucial role of REV-ERBs and RORs in peripheral clocks. Furthermore, our work highlights functional differences among mammalian peripheral clocks, which provides important insights into the complexity of the circadian system.

We present a model of coupled transcriptional-translational ultradian oscillators (TTOs) as a possible mechanism for the circadian rhythm observed at the cellular level. It includes nonstationary Poisson interactions between the transcriptional proteins and their affined gene sites. The associated reaction-rate equations are nonlinear ordinary differential equations of stochastic switching type. We compute the deterministic limit of this system, or the limit as the number of gene-proteins interactions per unit of time becomes large. In this limit, the random variables of the model are simply replaced by their limiting expected value. We derive the Kolmogorov equations — a set of partial differential equations —, and we obtain the associated moment equations for a simple instance of the model. In the stationary case, the Kolmogorov equations are linear and the moment equations are a closed set of equations. In the nonstationary case, the Kolmogorov equations are nonlinear and the moment equations are an open-ended set of equations. In both cases, the deterministic limit of the moment equations is in agreement with the deterministic state equations.

We present a model of coupled transcriptional-translational ultradian oscillators (TTOs) as a possible mechanism for the circadian rhythm observed at the cellular level. It includes nonstationary Poisson interactions between the transcriptional proteins and their affined gene sites. The associated reaction-rate equations are nonlinear ordinary differential equations of stochastic switching type. We compute the deterministic limit of this system, or the limit as the number of gene-proteins interactions per unit of time becomes large. In this limit, the random variables of the model are simply replaced by their limiting expected value. We derive the Kolmogorov equations — a set of partial differential equations —, and we obtain the associated moment equations for a simple instance of the model. In the stationary case, the Kolmogorov equations are linear and the moment equations are a closed set of equations. In the nonstationary case, the Kolmogorov equations are nonlinear and the moment equations are an open-ended set of equations. In both cases, the deterministic limit of the moment equations is in agreement with the deterministic state equations.

Objetivo: Avaliar a relação do turno escolar e o ritmo circadiano de crianças e adolescentes sob a expressão de sintomas comportamentais e de níveis de cortisol e melatonina. Métodos: Estudo transversal envolvendo 639 estudantes do ensino fundamental e médio (idade média de 13,03 anos, variando de 8–18; 58,5% meninas) recrutados em cidades localizadas na região do Vale do Taquari, Rio Grande do Sul, Brasil. Na segunda fase, 80 participantes foram selecionados aleatoriamente para coleta de saliva para análise de melatonina e cortisol. Os parâmetros circadianos do sono foram acessados pelo auto-relato de duração do sono nos dias de semana e fins de semana, diferenças no horário de acordar e dormir, déficit de sono, ponto médio do sono nos dias de semana e fins de semana, jetlag social e pela versão em português do Morningness-Eveningness Questionnaire (MEQ) para avaliação do cronotipo. Os desfechos, níveis de melatonina e cortisol salivares, foram medidos através de amostras de saliva pela manhã, tarde e noite, e problemas de comportamento (sintomas psiquiátricos), foram avaliados usando a Lista de verificação comportamental para crianças e adolescentes (em inglês, Child Behavior Checklist, CBCL). O estudo foi realizado de acordo com as diretrizes éticas internacionais (número de aprovação no comitê de ética: 12-0386 GPPG/HCPA). Resultados: No primeiro artigo, estudantes do turno da manhã eram significativamente mais velhos, apresentavam maior diferença entre os horários de acordar e dormir, maior déficit de sono e jetlag social. O déficit de sono apresentado por meninas foi maior do que o observado em meninos da mesma idade. regressão multivariada, utilizando o método passo-a-passo, identificou jetlag social, diferença nos horários de acordar nos dias de semana e fins de semana e ponto médio nos fins de semana como preditores significativos de déficit de sono. O segundo artigo demonstrou que o turno escolar influenciou a secreção de melatonina, a qual se correlacionou com os parâmetros do sono circadianos, diferentemente para o grupo não-clínico e clínico. Os níveis de melatonina foram positivamente correlacionados com ponto médio do sono em estudantes do turno da manhã, e negativamente correlacionados com ponto médio do sono em estudantes do turno da tarde. No terceiro artigo, identificou-se idade, horário de início da escola, ponto médio de sono e duração do sono nos dias de semana como preditores de sintomas psiquiátricos, avaliados pelo CBCL. Os estudantes do turno da manhã, classificados como cronotipo do tipo vespertino, apresentaram menor duração do sono durante a semana e maior jetlag social do que estudantes do tipo matutino. Além disso, os alunos do turno da manhã com sintomas psiquiátricos apresentaram menor duração do sono e padrão circadiano de sono mais cedo. Conclusões: Os achados do presente estudo mostram que o turno escolar influencia os parâmetros circadianos de sono, fatores fisiológicos e sintomas psiquiátricos em crianças e adolescentes. Nossos resultados reforçam a importância de redirecionar crianças e adolescentes para um turno escolar que contemple as preferências individuais de sono, prevenindo as consequências negativas à saúde, tanto no sono quanto em sintomas psiquiátricos. / Objective: To evaluate the relationship of the school schedules and the circadian rhythm of children and adolescents under the expression of behavioral symptoms and cortisol and melatonin levels. Methods: This cross-sectional study involved 639 elementary and high school students (mean age 13.03 years, range 8–18, 58.5% female) recruited from the cities located in the Vale do Taquari region, Rio Grande do Sul, Brazil. In the second phase, 80 participants were randomly selected for saliva collection to analyze melatonin and cortisol. Circadian sleep parameters were assessed by self-reported sleep duration on weekdays and weekends, bedtime and wake time differences, sleep deficit, midpoint of sleep on weekdays and weekends, social jetlag, and the Portuguese version of Morningness-Eveningness Questionnaire (MEQ) for assessment of chronotype. The outcomes, salivary melatonin and cortisol levels, were measured in morning, afternoon, and night saliva samples, and behavior problems (psychiatric symptoms) were assessed using the Child Behavior Checklist (CBCL). This study was performed according to international ethical guidelines (ethics committee approval number: 12–0386 GPPG/HCPA). Results: In the first article, the morning-school-time students presented significantly higher age, bedtime and wake up differences, sleep deficits, and social jetlag. The sleep deficit presented by girls was greater than that observed in boys of the same age. A step-by-step multivariate logistic regression identified social jetlag, the difference between waking times on weekdays and weekends, and the mid-point of sleep on weekends as significant predictors of sleep deficit. In the second article, school start time influenced the melatonin secretion, which correlated with circadian sleep parameters, although differently for non-clinical and clinical groups. Melatonin levels were positively correlated with sleep midpoint in morning students, and negatively correlated with sleep midpoint in afternoon students. In the third article, we identified age, school start time, midpoint of sleep on weekdays, and sleep duration on weekdays as predictors of psychiatric symptoms, as evaluated by the CBCL. Students with a morning school start time whose chronotype was classified as evening had shorter sleep duration on weekdays and higher social jetlag than morning-type participants. Moreover, students with a morning school start time and psychiatric symptoms had shorter duration of sleep and earlier circadian sleep patterns. Conclusion: The findings of the present study showed that school start time influences on the circadian sleep patterns, physiological factors and psychiatric symptoms in children and adolescents. Our findings emphasize the importance to redirect children and adolescents for a school start time that includes the individual preferences of sleep, preventing the negative health consequences, both in sleep and in psychiatric symptoms.

Dentro de cada ser há um “relógio” interno que regula os ciclos diários da alimentação, sono, vigília, e até mesmo humor. É assim que ocorre: quando sentimos fome devemos comer e quando sentimos sono devemos dormir. As atividades diárias, a imposição de um horário, seja de trabalho ou escolar, afetam de maneira distinta cada pessoa, sendo que para algumas estas determinações atendem em “cheio” a suas preferências e para outras exigem um enorme esforço; muitas vezes, essa adaptação é impossível. Assim sendo, há horas do dia em que cada aluno está mais disposto a fazer determinadas tarefas, como as escolares entre outras. Neste contexto, identificaram-se os grupos de alunos quanto à alocação do ciclo vigília/sono: estudo de suas características e de suas relações com o processo de ensino aprendizagem, validando a Escala Matutino/Vespertino (que resultou no primeiro artigo citado nessa tese). Validada a Escala, o principal objetivo desta tese é relacionar os grupos de alunos de ambos os cronotipos (matutino/vespertino) com o turno escolar e o rendimento escolar, assim como algumas atividades que gosta de realizar fora da sala de aula, com alunos de uma escola pública de Ensino Médio e com alunos de cinco escolas públicas de Ensino Fundamental do Município de Farroupilha/RS. Observando que os resultados apresentados do Ensino Médio e Fundamental não foram os mesmos, foi analisado ao longo das idades da amostra, dos 11 aos 17 anos, foram relacionadas às variáveis: idade, cronotipo (matutino/vespertino), turno escolar, rendimento escolar e a taxa de reprovação. Os resultados levaram a conclusão que alunos matutinos do Ensino Fundamental (dos 11 aos 14 anos de idade) apresentam significativamente um rendimento escolar superior aos demais grupos de alunos no turno da manhã, consequentemente, menor taxa de reprovação. No Ensino Médio (15 aos 17 anos de idade) o grupo que apresentou rendimento significativamente superior aos demais grupos foi o dos alunos matutinos que estudam no turno da tarde. Os resultados contribuem para uma melhor compreensão entre o ritmo biológico/rendimento escolar/turno escolar em distintos níveis escolares e desta forma ajudar pais, escolas e políticas educacionais no sentido de aprimorar o processo de ensino-aprendizagem. O relato de caso aqui apresentado sugere uma interferência do ritmo circadiano no rendimento escolar. Entretanto, estudos com amostragens maiores e mais diversificados são necessários para propor este parâmetro como integrante de políticas públicas a serem adotadas evitando o efeito negativo do ciclo vigília/sono individual sobre o rendimento escolar. / Within each one there is a "clock" that regulates the internal dailycycles of eating, sleeping, waking, and even humor. So it happens: when we feel hungry we eat and when we feel sleepy we sleep. The daily activities, the setting of a time, affects each person differently, whether at work or school, and to some person these determinations is"perfect" to their preferences, and others determinations requires ahuge effort, and often, this adaptation is impossible. Thus, there are times of day that each student is more willing to do certain tasks, such as homework and others. In this context, we identified groups ofstudents by the allocation of the sleep / wake cycle, by studying their characteristics and their relationships with the teaching and learning process and validating the scale Morning / Evening, which resulted inthe first article of this thesis. With the validated scale, the main objective of this thesis is to associate groups of students from both chronotype (morning/afternoon) with school hours and school performance, at first with students from a public high school and later with students from five public schools in elementary school, in thecity of Farroupilha- RS. Noting that the results of the elementary school and high school were not the same, we analyzed the influence of the age of students: from 11 to 17 years. Related variables were: age, chronotype (morning / afternoon), school hours, school performance andfailure rate. The results showed that morning of elementary school students (from 11 to 14 years old) had a significantly higheracademic achievement to other groups of students on the morning shiftand a lower failure rate. In high school (15 to 17 years old), the morning group studying in the afternoon showed significantly higher yield than the other students. With this information, the schools, parents and the Departments of Education might rethink the best school hours to attend school and get better returns. Even the case report presented here suggest a circadian rhythm interference with school performance studies with a larger with sample is needed to indicate it as public politics to be adopted to avoid the negative effect of the sleep / wake cycle on individual school performance.

Introdução: O ciclo sono-vigília, a alimentação e o metabolismo de lipídios e de glicose estão sujeitos à regulação circadiana a qual visa sincronizar a energia disponível e o gasto necessário para mudanças no meio externo de acordo com a fase claro-escuro. O desajuste do ritmo circadiano pode ser fator causal para uma relação positiva entre o trabalho noturno e obesidade. A exposição ao estresse crônico devido à liberação de glicocorticóides provoca distribuição anômala de gordura, principalmente em região abdominal que está associada à resistência a insulina, hipertrigliceridemia, e hipertensão arterial. A exposição ao estresse crônico é considerado um dessincronizador de ritmos biológicos, induz liberação de glicocorticoides esta associada a distúrbios alimentares que podem levar a obesidade. Objetivos: Este estudo objetiva avaliar o efeito da associação de modelos experimentais de estresse crônico e de obesidade sobre parâmetros bioquímicos, ponderais, nociceptivos e comportamentais. Adicionalmente, à avaliação do padrão temporal de glicose, insulina, grelina e corticosterona. Métodos: Foram utilizados 96 ratos Wistar machos com 60 dias de idade divididos em 4 grupos: dieta padrão (C), Dieta hipercalórica (dieta de cafeteria) (D), estresse crônico (estresse crônico por restrição 1h/dia/5 dias por semana, entre às 9h e às 12h) associado a dieta padrão (E), estresse crônico associado a dieta hipercalórica (DE). Após 80 dias de experimento os animais foram avaliados no campo aberto (atividade locomotora e exploratória), labirinto em cruz elevado (comportamento do tipo ansioso) e testes de formalina e tail-flick (comportamento da resposta nociceptiva). Após os animais foram mortos em 3 períodos do dia (7h -ZT0, 19h - ZT12 e 1h - ZT18) para avaliação dos níveis plasmáticos de glicose, insulina, corticosterona, e grelina. Resultados: Nossos resultados indicam que os animais que consumiram dieta hipercalórica apresentaram aumento na locomoção. Além disso, mostraram alterações comportamentais em relação ao comportamento do tipo ansioso em animais estressados. Adicionalmente, os ratos estressados que consumiram a dieta hipercalórica não diferiram do grupo controle em delta de peso, peso relativo das adrenais e nos níveis de corticosterona, indicando que o estabelecimento da obesidade é influenciado pela ativação crônica do eixo HHA indexada pela hipertrofia das adrenais observada no grupo de animais submetidos a estresse crônico. No entanto em animais estressados que consumiram a dieta hipercalórica não apresentaram hipertrofia das adrenais. Também confirmamos o padrão temporal dos hormônios corticosterona e insulina, porém, nos horários avaliados não foi possível detectar a existência do padrão temporal da grelina e da glicose. Adicionalmente, os níveis de corticosterona sofreram efeito do estresse crônico e interação entre obesidade e do horário do dia. Por outro lado, o padrão temporal da insulina sofreu efeito apenas da dieta. No entanto, os níveis glicêmicos sofreram os efeitos do consumo da dieta e interação entre dieta e estresse. Conclusão: Os resultados desta dissertação sugerem que a exposição ao estresse crônico e à obesidade influencia o padrão temporal de biomarcadores periféricos que podem ter impactos comportamentais e repercussões metabólicas. / Introduction: The sleep-wake cycle, feeding and metabolism of lipids and glucose are subject to circadian regulation, which aims to synchronize the available energy and expense required for changes in the external environment according to the light/dark phase. Such rhythms are coordinated by circadian clocks. Alterations in the circadian rhythm may be a causal factor for a positive relationship between shift work and obesity. Exposure of chronic stress due to release of glucocorticoids cause abnormal fat distribution, especially in the abdominal region that is associated with insulin resistance, hypertriglyceridemia, and hypertension. Exposure to chronic stress, which is related to biological rhythms desynchronized and induces release of glucocorticoids associated with eating disorders that can lead to obesity. Objectives: Since chronic stress is an important component of modern life often associated with binge eating and obesity this study aims to evaluate the effect of the combination of experimental models of chronic stress and obesity on weight, behavior and biochemical parameters, associated to evaluation of the temporal pattern of peripheral markers (glucose, insulin, ghrelin and corticosterone). Methods: Was used 96 male Wistar rats at 60 days old were divided into 4 groups: diet standard (C), hypercaloric diet (cafeteria diet) (HD), chronic stress (chronic stress by restricting 1h/day/5 days a week between 9am and 12pm for 80 days) associated with the standard diet (S), chronic stress associated with hypercaloric diet (SHD). After 80 days of experiment the animals were evaluated in the open field (locomotor and exploratory activities), elevated plus maze (anxiety-like behavior) and formalin tests and tail-flick (nociceptive response). After 24h the animals were killed in three periods of the day (ZT0-7h, ZT12-19h - and ZT18-1h) to evaluate plasma levels of glucose, insulin, corticosterone, and ghrelin. Results: Our results indicate that HD group increase in locomotion. Also, shows behavioral changes elevated plus maze test, such as anxiety. Additionally, SHD group did not differ from control group on delta weight, relative weight of the adrenals and corticosterone levels, indicating that the establishment of obesity is influenced by chronic HPA axis activation, which is indexed by adrenal hypertrophy observed in the group of animals subjected to chronic stress. However in stressed animals who consumed the high calorie diet showed no adrenal hypertrophy.We also demonstrated the temporal pattern of plasmatic levels corticosterone and insulin; however, it was not possible to detect the temporal pattern of ghrelin and glucose levels at the times analyzed. Additionally, corticosterone levels suffered effects of obesity, chronic stress and the time of day. Furthermore, the temporal pattern of insulin was affected only by obesity. However, glucose levels suffered the effects of obesity and interaction between obesity and chronic stress. Conclusion: The results of this work suggest that exposure to chronic stress and hypercaloric diet may influence the temporal pattern of peripheral biomarkers that which may impact on behavior and metabolism.

Introdução: O reconhecimento da importância da nutrição enteral em pacientes hospitalizados gerou novos métodos de administração, o que leva a muitas perguntas: quais são os efeitos cronobiológicos da terapia nutricional contínua ou intermitente? Objetivo: O objetivo deste estudo foi avaliar o efeito do horário de administração da nutrição enteral como Zeitgeber do ritmo biológico no gasto energético e consumo de oxigênio, mensurados por calorimetria indireta. Métodos: Ensaio clínico randomizado, realizado de dezembro de 2009 a novembro de 2010, em 34 pacientes com doença neurológica, com idade entre 52 e 80 anos, alimentados através de uma sonda nasoenteral, 15 através de infusão contínua por 24 horas/dia e 19 em quantidades comparáveis de forma intermitente, a cada 4 horas, dás 8 às 20 horas. Foram realizadas 4 medidas de calorimetria indireta nas 24 horas (A: 07:30 h, B: 10:30 h, C: 14:30 h e D :21:30 horas), durante 3 dias, para cada paciente. Resultados: A idade média foi de 69,5±8,50% eram do sexo masculino, IMC 22 ±3,9 kg/m²(homens) e 25±5,6 kg/m²(mulheres). O gasto energético e o consumo de oxigênio mostrou diferença significativa entre os grupos contínuo e intermitente: 1478±817 kcal/24h, (IC: 1249 – 1706), 1782±862 kcal/24h (IC: 1579 – 1984) (p=0.05); 212±117 ml/min (IC: 179 – 245); 257±125 ml/min (IC: 227 – 286) (p=0.048), respectivamente. No gasto energético e consumo de oxigênio diferenças estatisticamente significativas foram encontradas entre as mensurações A, B, C e D em ambos os grupos. Comparando o gasto energético e consumo de oxigênio entre os grupos por Mann-Whitney, houve uma diferença estatisticamente significativa em tempo B e C (p = < 0,01). Conclusão: Foi observado neste estudo uma variação circadiana do gasto energético e consumo de oxigênio nos dois métodos de administração da nutrição enteral, sugerindo que apenas uma medida de calorimetria indireta no dia não é capaz de mostrar a verdadeira necessidade do paciente. Observamos também que o gasto energético foi mais elevado à noite nos dois métodos de administração da alimentação. Além disso, o gasto energético e o consumo de oxigênio foi maior no método de administração intermitente em todos os tempos. / Introduction: The importance of enteral nutrition has grown in recognition resulting in new methods of administration. That leads to many questions such as: what are the chronobiologic effects of continuous or intermittent nutrition therapy? Objectives: The aim of this study was to evaluate the use of enteral nutrition as a Zeitgeber of biological rhythm. Energy expenditure and oxygen consumption were measured by indirect calorimetry in continuous or intermittent nutrition patterns. Methods: A randomized clinical trial was conducted from December 2009 to November 2010. Thirty four neurological patients received through the same kind of calibrated nasogastric tube the standard protein and energy intakes calculated for each subject, 15 through continuous infusion for 24 hours/day and 19 intermittently in comparable quantities, every 4 hours, from 8:00 to 20:00 h. Four indirect calorimetry measures were carried out during the 24 hours (A: 07:30h, B: 10:30h, C: 14:30h and D: 21:30h), for 3 days, for each patient. Results: The mean age was 69.5±8, 50% were male; BMI 22±3.9kg/m² (men), 25±5.6 kg/m² (women). Energy expenditure end oxygen consumption presented a significant difference between the continuous and intermittent groups (1478±817 kcal/24h, (CI: 1249 – 1706), 1782±862kcal/24h (CI: 1579 – 1984) (p=0.05); 212±117 ml/min (CI: 179 – 245); 257±125 ml/min (CI: 227 – 286) (p= 0.048), respectively). In the energy expenditure and oxygen consumption, statistically significant differences were found between the A, B, C and D measures in both groups. By comparing the energy expenditure and the oxygen consumption between the groups by the Mann-Whitney test a statistically significant difference was observed for times B and C (p=< 0.01). Conclusion: A circadian variation of energy expenditure and oxygen consumption was observed in both enteral nutrition administration methods used in this work, suggesting that only one indirect calorimetry measure per day is not able to show the patient’s true needs. It was also observed that the energy expenditure was higher at night in both food administration methods. Moreover, the energy expenditure and oxygen consumption was higher in the intermittent administration method in all times.