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Circadian (daily) regulation of metabolic pathways implies that food may be metabolized differentially over the daily cycle. To test that hypothesis, we monitored the metabolism of older subjects in a whole-room respiratory chamber over two separate 56-h sessions in a random crossover design. In one session, one of the 3 daily meals was presented as breakfast, whereas in the other session, a nutritionally equivalent meal was presented as a late-evening snack. The duration of the overnight fast was the same for both sessions. Whereas the two sessions did not differ in overall energy expenditure, the respiratory exchange ratio (RER) was different during sleep between the two sessions. Unexpectedly, this difference in RER due to daily meal timing was not due to daily differences in physical activity, sleep disruption, or core body temperature (CBT). Rather, we found that the daily timing of nutrient availability coupled with daily/circadian control of metabolism drives a switch in substrate preference such that the late-evening Snack Session resulted in significantly lower lipid oxidation (LO) compared to the Breakfast Session. Therefore, the timing of meals during the day/night cycle affects how ingested food is oxidized or stored in humans, with important implications for optimal eating habits.

Studies in humans and animal models indicate a key contribution of angiotensin II to the pathogenesis of glomerular diseases. To examine the role of type 1 angiotensin ([AT.sub.1]) receptors in glomerular inflammation associated with autoimmune disease, we generated [MRL-Fas.sup.lpr/lpr] (lpr) mice lacking the major murine type 1 angiotensin receptor ([AT.sub.1A]); lpr mice develop a generalized autoimmune disease with glomerulonephritis that resembles SLE. Surprisingly, [AT.sub.1A] deficiency was not protective against disease but instead substantially accelerated mortality, proteinuria, and kidney pathology. Increased disease severity was not a direct effect of immune cells, since transplantation of [AT.sub.1A]-deficient bone marrow did not affect survival. Moreover, autoimmune injury in extrarenal tissues, including skin, heart, and joints, was unaffected by [AT.sub.1A] deficiency. In murine systems, there is a second type 1 angiotensin receptor isoform, [AT.sub.1B], and its expression is especially prominent in the renal glomerulus within podocytes. Further, expression of renin was enhanced in kidneys of [AT.sub.1A]-deficient lpr mice, and they showed evidence of exaggerated [AT.sub.1B] receptor activation, including substantially increased podocyte injury and expression of inflammatory mediators. Administration of losartan, which blocks all type 1 angiotensin receptors, reduced markers of kidney disease, including proteinuria, glomerular pathology, and cytokine mRNA expression. Since [AT.sub.1A]-deficient lpr mice had low blood pressure, these findings suggest that activation of type 1 angiotensin receptors in the glomerulus is sufficient to accelerate renal injury and inflammation in the absence of hypertension., Introduction The renin-angiotensin system (RAS) has profound effects on blood pressure and vascular reactivity (1). Angiotensin II, acting through type 1 angiotensin ([AT.sub.1]) receptors, contributes to the pathophysiology of diverse [...]

Components of the renin-angiotensin system (RAS) are expressed in a number of areas in the brain involved in cardiovascular control. However, it has been difficult to link RAS actions in [...]

Prostacyclin is one of a number of lipid mediators elaborated from the metabolism of arachidonic acid by the cyclooxygenase (COX) enzymes. This prostanoid is a potent inhibitor of platelet aggregation, and its production by endothelial cells and protective role in the vasculature are well established. In contrast, much less is known regarding the function of this prostanoid in other disease processes. We show here that COX-2-dependent production of prostacyclin plays an important role in the development of fibrotic lung disease, limiting both the development of fibrosis and the consequential alterations in lung mechanics. In stark contrast, loss of prostaglandin E2 synthesis and signaling through the [G.sub.s]-coupled EP2 and EP4 receptors had no effect on the development of disease. These findings suggest that prostacyclin analogs will protect against bleomycin-induced pulmonary fibrosis in COX-[2.sup.-/-] mice. If such protection is observed, investigation of these agents as a novel therapeutic approach to pulmonary fibrosis in humans may be warranted. prostaglandin; IP; lung mechanics; EP2; microsomal prostaglandin [E.sub.2] synthase 1 doi:10.1152/ajplung.00492.2005

The mouse has become the most important model organism for the study of human physiology and disease. However, until the recent generation of mice lacking the enzyme gulanolactone oxidase (Gulo), the final enzyme in the astorbic acid biosynthesis pathway, examination of the role of ascorbic acid in various biochemical processes using this model organism has not been possible. In the mouse, similar to most mammals but unlike humans who carry a mutant copy of this gene, Gulo produces ascorbic acid from glucose. We report here that, although ascorbic acid is essential for survival, its absence does not lead to measurable changes in proline hydroxylation. Vitamin C deficiency had no significant effect on the hydroxylation of proline and collagen production during tumor growth or in angiogenesis associated with minor or mammary gland growth. This suggests that factors other than ascorbic acid can support proline hydroxylation and collagen synthesis in vivo. Furthermore, the failure of [Gulo.sup-/-] mice to thrive on a vitamin C-deficient diet therefore suggests that ascorbic acid plays a critical role in survival other than the maintenance of the vasculature. ascorbic acid; collagen: angiogenesis: prolyl hydroxylase

Objectives: The prevalence of Alzheimer's disease and associated disorders is increasing. Rural residents in the United States have less access to memory care specialists and educational and community resources than in other areas of the country. Over a decade ago, we initiated an interdisciplinary rural caregiving telemedicine program to reach Kentucky residents in areas of the state where resources for supporting individuals with dementia are limited. Telemedicine programs involve a short informational presentation followed by a question and answer session; programs are offered 4 times a year. The purpose of this study was to explore questions asked over 1 year of the rural caregiving telemedicine program—encompassing 5 programs—to identify the scope of dementia‐related knowledge gaps among attendees. Methods: Questions from the 5 programs were recorded and content analyzed to identify areas of frequent informational requests. Results: There were a total of 69 questions over the 5 sessions. For each program, questions ended due to time constraints rather than exhausting all inquiries. The most common topical areas of questions related to risk factors, behavioral management, diagnosis, and medications. Discussion and Implications: This study highlights that rural caregivers in Kentucky have diverse dementia educational needs. Rural communities may benefit from additional, targeted resources addressing these common areas of unmet informational needs. [ABSTRACT FROM AUTHOR]

Background and Objectives Recruitment and retention of research participant serve as a significant challenge in the search for ways to slow or prevent Alzheimer's disease. While barriers to participation are well documented, less is known about motivations for Alzheimer's disease clinical research participation. The purpose of this study was to explore what motivates individuals—who ultimately develop an ongoing connection to research and frequently participate—to engage and stay involved in Alzheimer's disease research. Research Design and Methods Individuals who had participated in multiple Alzheimer's disease-related clinical trials, or their study partners, were interviewed about their decisions to engage and remain in research. Findings Interviews were completed with 33 individuals, 28 research participants, and 5 study partners. All interviews were audio-recorded and transcribed verbatim for analysis. Respondents indicated learning about research opportunities through the media, community events, doctors, and other research participants. While many were initially motivated by a family history or knowing someone with Alzheimer's disease, others had no personal exposure. Individuals in prevention studies were generally proactive and viewed research as a constructive way to address memory concerns. While several individuals acknowledged personal benefits of research participation, most indicated an understanding of the importance of research and being motivated to help others in the future, frequently referencing a sense of social responsibility or moral obligation to help. Positive relationships with personnel at the site encouraged continued involvement. Discussion and Implications These findings suggest that efforts to identify research participants should highlight the value of research and help illuminate how participation may contribute to well-being of future generations. [ABSTRACT FROM AUTHOR]