Thesis--M. Phil., University of Hong Kong, 1982.

published_or_final_version / Physiology / Master / Master of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

No description available.

The effect of melatonin, a hormone that triggers biological rhythms, was examined in relation to food intake and macronutrient selection. Wistar rats (n = 48) of both sexes were divided into 3 groups and offered a simultaneous choice of 2 diets: a carbohydrate-rich diet and a protein-rich diet, with a different type of carbohydrate and protein in each of the groups. Increased short- (4h post-injection) and long-term (12h post-injection) nocturnal total food intake was found following intraperitoneal administration of melatonin (10 000 and 15 000 pg/ml blood) at dark onset. Melatonin increased short-term carbohydrate-rich diet intake similarly across sensory contrasting diets (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and genders. However, melatonin caused an inconsistent increase in protein-rich diet intake across the various diets (casein, soy isolate, and egg protein) and genders. In conclusion, melatonin favors carbohydrate intake at the beginning of the activity period, and may act as a time indicator that provides a night signal.

Thesis (Ph. D.)--University of Hong Kong, 1996. / Includes bibliographical references (leaf 72-104).

Thesis (M.S.)--University of Wyoming, 2009. / Title from PDF title page (viewed on July 22, 2010). Includes bibliographical references (p. 74-91).

Orientadora: Isabel Cristina Cherici Camargo / Coorientador: Luiz Gustavo de Almeida Chuffa / Banca: Telma Goncalves Carneiro Spera de Andrade / Banca: Ana Paula Alves Favareto / Resumo: Os esteroides anabólicos androgênicos são prescritos para o tratamento de várias doenças, porém apresentam efeitos colaterais mesmo em dosagens terapêuticas. Entre eles, destaca-se o decanoato de nandrolona (DN), o qual age sobre receptores de andrógenos (AR) e estrógenos (ERα e ERβ). Paralelamente, a melatonina (MLT) tem despertado a atenção na área da saúde devido às suas propriedades antioxidantes e profiláticas, com o intuito de reduzir ou suprimir os efeitos colaterais promovidos por fármacos. Então, o presente estudo teve por objetivo avaliar o ciclo estral, a estrutura histológica e a imunomarcação para AR, ERα e ERβ em ovários de ratas androgenizadas submetidas ao tratamento com MLT. Ratas Wistar (n = 8/grupo) receberam óleo mineral (Controle), DN (7,5 mg/kg; via subcutânea, 15 dias) e o tratamento com MLT (10 mg/kg; via intraperitoneal, 7 dias) isoladamente, previamente ou concomitantemente ao esteroide. O ciclo estral foi monitorado. Os ovários foram coletados e preparados para a avaliação do tecido. Nas ratas androgenizadas, a MLT recuperou o peso e o tecido ovariano, mas não restabeleceu o ciclo estral. O número e área dos corpos lúteos dos animais que receberam MLT, previamente ou concomitantemente ao DN, foram similares ao controle, e apenas o tratamento prévio restabeleceu a quantidade de folículos saudáveis e atrésicos. Nos folículos, a MLT promoveu uma fraca expressão do ERα e ERβ, e nos corpos lúteos inibiu a diminuição na expressão de ERβ induzido pelo DN. O tratamento prévio com MLT atenuou o aumento na expressão do AR promovido pelo DN em folículos atrésicos e corpos lúteos. Em conclusão, a MLT apresentou efeito benéfico nos ovários androgenizados através da recuperação da foliculogênese e da luteogênese. O tratamento prévio com melatonina foi mais eficaz em relação ao tratamento concomitante / Abstract: Androgenic anabolic steroids are prescribed as treatment to several diseases, however, they present side effects even in therapeutic dosages. Among them, we highlight the nandrolone decanoate (ND) which acts on androgen receptors (AR) and estrogen receptors (ERα e ERβ). At the same time, melatonin (MLT) has raised attention in health area due to its antioxidant and prophylactic properties intending reduction or surpassing side effects caused by medicine. Thus, the present study aimed assess the estrous cycle, histological structure and AR, ERα and ERβ immunolocalization in androgenized rats ovaries undergone treatment with MLT. Wistar rats (n= 8/group) received mineral oil (Control), ND (7,5 mg/kg; subcutaneously, 15 days) and treatment with MLT (10 mg/kg; intraperitoneally, 7 days) singly, previously or concomitantly to steroid. Estrous cycle was monitored. The ovaries were collected and prepared for tissue assessment. In androgenized rats, MLT recovered weight and ovarian tissue, but it did not reestablish the estrous cycle. The number and area of corpus luteum of animals which received MLT, previously or concomitantly to ND, were similar to control, and only previous treatment reestablished the quantity of healthy and atretic follicles. In follicles, MLT promoted a weak expression of the ERα and ERβ, and in corpora lutea, it inhibited the decrease in the ERβ expression induced by ND. Previous treatment with MLT mitigated the increase in AR expression promoted by ND in atretic follicles and corporea lutea. In conclusion, melatonin presented a beneficial effect on the androgenized ovaries through the recovery of the folliculogenesis and luteogenesis. The previous treatment was the most effective / Mestre

Circadian rhythms are known to be entrained to the 24 hour day through interactions between endogenous mechanisms and a number exogenous factors that include the light-dark cycle and social interaction. Intensive care patients are thought to be prone to disturbances in their circadian rhythms due to isolation from environmental changes and sensory deprivation as a result of sedation and sleep disturbance. The main aim of this thesis was to determine whether circadian rhythms in critically ill patients are desynchronised from the environment in comparison with those observed in healthy individuals, using urinary aMT6s excretion, plasma melatonin and core body temperature as markers of the endogenous clock. Patients in the Intensive Care Unit (ICU) at the Royal Free Hospital, London, who were stable, inotrope-free, not undergoing haemodiafiltration and with an ICU stay of more than three days were studied. Cosinor analysis of retrospective core body temperature data taken from nursing charts showed that a statistically significant rhythm with a period of 24h was present in 49.5% of the patient days studied. The position of acrophase showed abnormalities within individuals and between individuals. Prospective core body temperature studies confirmed the findings of abnormal circadian rhythmicity but suggested that the rhythms were influenced by fever associated with infection. Urinary 6-sulphatoxymelatonin (aMT6s) excretion data detected rhythmic activity and allowed for the identification of four patterns of excretion rate over 24h: normal rhythmicity, phase shifted rhythms, abnormal with frequent fluctuations and abnormal but arrhythmic. Urinary aMT6s excretion rate measured on two or three occasions at weekly intervals identified changes associated with the normalisation of circadian rhythmicity, namely an increase in the amplitude in some patients and the development of significant diurnal changes from grossly abnormal patterns of urinary aMT6s excretion in others. This trend was seen in patients that were improving clinically, but could not be associated with disease severity as determined by APACHE II scoring. Studies on the circadian rhythms of urine volume and creatinine clearance suggested that renal function in the absence of acute renal failure was still impaired or possibly influenced by treatment medication and could modify urinary aMT6s excretion. Measurements of plasma melatonin identified circadian rhythmicity in 7 out of 9 patients of which 5 were significant by cosinor analysis. These 5 patients had plasma melatonin rhythms that were either normal or phase shifted. The circadian rhythms of plasma cortisol, plasma prolactin and plasma TSH in most ICU patients were also abnormal and showed poor correlations with plasma melatonin. Overall this thesis provides evidence of abnormal circadian rhythmicity in critically ill patients and identifies this group of patients as one that might benefit from light or melatonin treatment to help resynchronise rhythms.

Disturbed sleep is common in asthma and impairs quality of life in these patients. Melatonin has sleep-inducing activity and reportedly affects smooth muscle tone and inflammation. The aim of this study was to evaluate the effect of melatonin on sleep in female patients with stable mild and moderate asthma. Twenty consecutive patients were recruited into the study. After a two-week run-in period, they were randomized to receive melatonin 3 mg (n= 10) or placebo for four weeks. Sleep quality and daytime somnolence were assessed by the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale, respectively. Pulmonary function was assessed by spirometry. Use of relief medication, asthma symptoms and morning and evening peak expiratory flow rate (PEFR) were recorded daily. Melatonin treatment, but not placebo, significantly improved subjective quality of sleep (p = 0,034), sleep latency (p = 0.031), sleep duration (p = 0,034), sleep disturbances (p = 0,034), daytime dysfunction (p = 0,025) and subjective daytime somnolence (p = 0,028). No significant difference in asthma symptoms, use of relief medication and daily PEFR was found between the two groups. We conclude that melatonin can improve sleep in patients with asthma without significantly affecting pulmonary function or asthma symptoms. Further studies looking into long-term effects of melatonin on airway inflammation and bronchial hyperresponsiveness are needed before melatonin can be safely recommended in asthmatic patients. / AlteraÃÃes do sono sÃo comuns na asma, dificultando o manuseio desta condiÃÃo e reduzindo a qualidade de vida dos seus portadores. A melatonina (MLT) possui aÃÃo indutora do sono e apresenta baixa incidÃncia de efeitos adversos. Existem relatos de que a MLT tambÃm possui aÃÃo sobre o tÃnus da musculatura lisa e exerce atividade imunomoduladora, potencialmente Ãteis no tratamento da asma. O objetivo principal deste estudo foi avaliar os efeitos da administraÃÃo noturna da MLT sobre o sono e a funÃÃo pulmonar de pacientes com asma persistente leve e moderada. O estudo foi um ensaio clÃnico randomizado, duplo-cego, controlado por placebo e duraÃÃo total de seis semanas. Vinte pacientes do sexo feminino foram submetidas a um perÃodo de prÃ-tratamento de duas semanas com beclometasona na dose de 1000 mcg/dia e salbutamol quando necessÃrio, ambos por via inalatÃria. ApÃs esse perÃodo, foram randomizadas para receber MLT na dose de 3 mg (n= 10) ou placebo (n= 10) duas horas antes do horÃrio habitual de sono, por quatro semanas. A qualidade do sono e a sonolÃncia diurna foram avaliadas pelo Ãndice de Qualidade de Sono de Pittsburgh (IQSP) e pela Escala de SonolÃncia de Epworth (ESE) respectivamente, enquanto a funÃÃo pulmonar foi avaliada por espirometria. Foram realizadas medidas domiciliares diurnas e noturnas do pico de fluxo expiratÃrio. Um registro diÃrio de sintomas de asma e de uso de broncodilatador inalatÃrio foi mantido durante todo o perÃodo. ApÃs a fase de tratamento, a qualidade do sono, a sonolÃncia diurna e a funÃÃo pulmonar foram reavaliadas. Os resultados demonstram que o grupo que utilizou a MLT, ao contrÃrio do grupo placebo, apresentou melhora da qualidade subjetiva do sono (p= 0,034), da latÃncia do sono (p= 0,031), da duraÃÃo do sono (p= 0,034), dos distÃrbios do sono (p= 0,034), das disfunÃÃes diurnas (p= 0,025) e do grau de sonolÃncia diurna subjetiva (p= 0,028). Nenhuma diferenÃa estatisticamente significante foi observada nos sintomas de asma, no uso de broncodilatador para alÃvio de sintomas e nas medidas diÃrias de PFE entre os grupos MLT e placebo. Em conclusÃo, a MLT melhora a qualidade do sono e reduz a sonolÃncia diurna em pacientes com asma persistente leve e moderada, sem produzir efeitos detectÃveis sobre sintomas ou sobre a funÃÃo pulmonar. Estudos adicionais sobre os efeitos a longo prazo da MLT na inflamaÃÃo das vias aÃreas e na hiper-responsividade brÃnquica, sÃo necessÃrios antes que esta substÃncia possa ser recomendada com seguranÃa em pacientes asmÃticos.