Biomedical subjects

Theodore B Vanitallie

Publications and source records attributed to Theodore B Vanitallie.

4 recordsLinked to original sources

PubMed2006

Sleep and energy balance: Interactive homeostatic systems.

For early humans, acquisition of food by hunting and/or gathering was a hunger-driven process requiring vigilance and (often) strenuous physical effort during daylight hours. To sustain such activities, hunter-gatherers also needed periodic rest and sleep-pursuits most effectively undertaken at night. In recent years, research has given us new insights into the physiologic underpinnings of these behaviors. Specifically, evidence has been uncovered indicating that the homeostatic regulation of food intake on the one hand and that of sleep on the other hand, are intertwined. Thus, carefully performed studies of eating behavior in rats indicate that duration of sleep after ingestion of a meal is closely correlated to the meal's energy content. In 1999, it was discovered that mice and dogs functionally deficient in the appetite-stimulating hormone, hypocretin-1, become narcoleptic, suggesting the existence of a "hard-wired" connection between regulation of hunger and satiety and regulation of sleep. Administered into the nucleus accumbens shell, hypocretin-1 induces feeding and locomotor activity in Sprague-Dawley rats. Hypocretin neurons in the hypothalamus are responsive to metabolic cues capable of signaling nutritional status. The suprachiasmatic nucleus, the body's principal circadian clock, exchanges information with the hypocretin system about the light/dark cycle and the body's metabolic condition. Circadian Clock mutant mice exhibit an attenuated diurnal feeding rhythm and become hyperphagic and obese. Both disruption of the circadian cycle and sleep deprivation can affect energy balance and, over time, may bring about substantial changes in body composition. Although there is growing evidence that interleukin-6 and several other proinflammatory cytokines are "sleep factors" that also affect energy balance, any possible role they might have in coordinating sleep/wakefulness with food-motivated behavior awaits clarification. Yet, the evidence is increasingly strong that the neurophysiologic and metabolic mechanisms responsible for the control of food-seeking behavior and the control of sleep and wakefulness are coordinated so that hunger and vigilance are paired during the daylight hours, and satiety and sleep are paired during darkness. The hypothalamic neuronal system that links these mechanisms is predominantly, but not exclusively, hypocretinergic, and is responsive to the suprachiasmatic nucleus circadian pacemaker and to certain metabolic signals of depletion and repletion.

Animals↗

PubMed2005

Ancel Keys: a tribute.

Ancel Keys, Ph.D., who died in November, 2004, at the age of 100, was among the first scientists to recognize that human atherosclerosis is not an inevitable consequence of aging, and that a high-fat diet can be a major risk factor for coronary heart disease. During World War II, he and a group of talented co-workers at the University of Minnesota conducted a large-scale study of experimentally-induced human starvation. The data generated by this study - which was immediately recognized to be a classic - continue to be of inestimable value to nutrition scientists. In his later years, Keys spent more time at his home in Naples, Italy, where he had the opportunity to continue his personal study of the beneficial effects on health and longevity of a Mediterranean diet.

Editorial↗

PubMed2003

Frailty in the elderly: contributions of sarcopenia and visceral protein depletion.

In any given population of free-living individuals 65 years of age and older, a substantial proportion (in the range of 6% to 25%) suffers from many of the elements of the syndrome of frailty. Although the syndrome is complex and still lacks a standard definition, there is a growing consensus about the signs and symptoms as well as the pattern of biological correlates that characterize this disorder. Patients who are afflicted with frailty typically exhibit loss of muscle strength, fatigue easily, are physically inactive, and have a slow-and often unsteady-gait, with an increased risk (and fear) of falling. They are likely to have a poor appetite and to have undergone a recent, unintentional loss of weight. Frail individuals are more likely than the nonfrail to experience impaired cognition and depression. They die sooner. Frailty, of course, is frequently complicated by a variety of coexistent illnesses. Among the biological correlates of frailty are sarcopenia (now readily measurable by dual-energy x-ray absorptiometry [DXA]), osteopenia (with an increased susceptibility to fracture), and activation of the inflammatory and coagulation systems, with a rise in inflammatory cytokines and several markers of coagulopathy. Age-dependent changes in a number of hormones also appear to promote the development of frailty in the elderly, particularly via their effects on muscle mass and strength, bone density, and by contributing to activation of the catabolic cytokines. In particular, serum levels of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) decline progressively during aging, and an association between reduction in the levels of these hormones and the involution of advancing age has been proposed. It is not yet known whether, in comparison with their nonfrail counterparts, frail individuals consistently manifest larger reductions in GH and IGF-1 (and other anabolic hormones). More research is needed before it will be known whether the benefits of administering GH to the frail elderly will outweigh the disadvantages. The poor appetite and weight loss that occur in many frail individuals are likely to be accompanied by a degree of visceral protein depletion (with its attendant morbidity), which can be estimated by making serial measurements of indicators of visceral protein status such as transthyretin (TTR), retinol-binding protein (RBP), and albumin. One characteristic of the frailty syndrome that distinguishes it from the effects of aging per se is the potential reversibility of many of its features. Progressive resistance training is feasible for many elderly individuals-even the oldest old-and, by increasing muscle mass and strength, can ameliorate or reverse important aspects of physical frailty. To the extent that visceral protein depletion has been caused by an inadequate intake of calories and protein, consumption of a more adequate diet can result in betterment of the frail patient's nutritional status, as determined by clinical improvement and favorable changes in TTR, RBP, and albumin.

Aged↗

PubMed2002

Stress: a risk factor for serious illness.

The body's principal adaptive responses to stress stimuli are mediated by an intricate stress system, which includes the hypothalamic-pituitary-adrenocortical (HPA) axis and the sympathoadrenal system (SAS). Dysregulation of the system, caused by the cumulative burden of repetitive or chronic environmental stress challenges (allostatic load) contributes to the development of a variety of illnesses including hypertension, atherosclerosis, and the insulin-resistance-dyslipidemia syndrome, as well as certain disorders of immune function. The brain's limbic system, particularly the hippocampus and amygdala, is also intimately involved in the stress response. Chronically elevated corticosteroid levels induced by persisting stress may adversely affect hippocampal structure and function, producing deficits of both memory and cognition. The ability of stress to cause illness in humans is most clearly exemplified by post-traumatic stress disorder (PTSD), which consists of a predictable constellation of distressing behavioral symptoms and physiological features. An appreciable proportion of the observed variance in vulnerability to PTSD is attributable to genetic factors. The relationship of this disorder to its precipitating cause-a recent, severely traumatic event-is unambiguous. The neuroendocrinology of PTSD is noteworthy, being characterized in many adult victims by enhanced negative feedback sensitivity of glucocorticoid receptors in the stress response system, and lower than normal urinary and plasma cortisol levels. Adult patients with PTSD also have been shown to exhibit exaggerated catecholamine responses to trauma-related stimuli. On the other hand, severely maltreated prepubertal children with PTSD continue to excrete greater than normal urinary cortisol, catecholamines, and dopamine years after disclosure of the causative abuse.

Animals↗