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At least 19 records

Angiotensin converting enzyme inhibition and the kidney

Angiotensin II (Ang II) induces a marked reduction in renal blood flow at doses well below those required to induce a pressor response, and as blood flow falls there is a decline in glomerular filtration rate and sodium excretion. This striking sensitivity of the renal blood supply led many workers to consider the possibility that angiotensin functions as a local renal hormone. As angiotensin converting enzyme (ACE) was found in particular abundance in the lung, it seemed reasonable to suspect that most of the conversion occurred there, and that the function of Ang II would be primarily systemic, rather than intrarenal. In this review, I will explore the evidence that has accumulated on these two possibilities, since they have important implications for our current understanding of normal kidney function and derangements of kidney function in disease.

NASA Program Biomedical Research↗

Circadian and sleep-dependent regulation of hormone release in humans

Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian rhythm sleep disorders, including the dyssomnia of shift work and visual impairment. Yet to be fully investigated are the interactions of these factors with age and gender. Characterization of the factors governing hormone secretion is critical to understanding the temporal regulation of endocrine systems and presents many exciting areas for future research.

Non-NASA Center↗

Simian virus 40, poliovirus vaccines, and human cancer: research progress versus media and public interests

From 1955 through early 1963, millions of people were inadvertently exposed to simian virus 40 (SV40) as a contaminant of poliovirus vaccines; the virus had been present in the monkey kidney cultures used to prepare the vaccines and had escaped detection. SV40 was discovered in 1960 and subsequently eliminated from poliovirus vaccines. This article reviews current knowledge about SV40 and considers public responses to reports in the media. SV40 is a potent tumour virus with broad tissue tropism that induces tumours in rodents and transforms cultured cells from many species. It is also an important laboratory model for basic studies of molecular processes in eukaryotic cells and mechanisms of neoplastic transformation. SV40 neutralizing antibodies have been detected in individuals not exposed to contaminated poliovirus vaccines. There have been many reports of detection of SV40 DNA in human tumours, especially mesotheliomas, brain tumours and osteosarcomas; and DNA sequence analyses have ruled out the possibility that the viral DNA in tumours was due to laboratory contamination or that the virus had been misidentified. However, additional studies are necessary to prove that SV40 is the cause of certain human cancers. A recently published review article evaluated the status of the field and received much media attention. The public response emphasized that there is great interest in the possibility of health risks today from vaccinations received in the past.

Review, Tutorial↗

Common endocrine control of body weight, reproduction, and bone mass

Bone mass is maintained constant between puberty and menopause by the balance between osteoblast and osteoclast activity. The existence of a hormonal control of osteoblast activity has been speculated for years by analogy to osteoclast biology. Through the search for such humoral signal(s) regulating bone formation, leptin has been identified as a strong inhibitor of bone formation. Furthermore, intracerebroventricular infusion of leptin has shown that the effect of this adipocyte-derived hormone on bone is mediated via a brain relay. Subsequent studies have led to the identification of hypothalamic groups of neurons involved in leptin's antiosteogenic function. In addition, those neurons or neuronal pathways are distinct from neurons responsible for the regulation of energy metabolism. Finally, the peripheral mediator of leptin's antiosteogenic function has been identified as the sympathetic nervous system. Sympathomimetics administered to mice decreased bone formation and bone mass. Conversely, beta-blockers increased bone formation and bone mass and blunted the bone loss induced by ovariectomy.

NASA Discipline Regulatory Physiology↗

Space flight nutrition research: platforms and analogs

Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

NASA Discipline Regulatory Physiology↗

Sodium sensitive hypertension: renal and adrenal non-modulation in its pathogenesis

The thrust of this essay will be to organize a growing body of evidence which indicates that an abnormality of the kidney, and the adrenal, involving disordered regulation through the renin-angiotensin system, is responsible for the pathogenesis in about 45% of patients--a discrete subgroup that may be most common cause of hypertension. That fundamental abnormality leads to disordered renal sodium handling and sodium-sensitive hypertension, abnormalities in the renal vascular response to changes in sodium intake and to angiotensin II, blunted decrements of renin release in response to saline or angiotensin II, and an accentuated renal vasodilator response to angiotensin converting enzyme (ACE) inhibition. ACE inhibition not only increases renal blood flow substantially more in these patients than it does in normal subjects, ACE inhibition also restores to normal the renal vascular and adrenal response to angiotensin II, renin release in response to angiotensin II, renal sodium handling--and ultimately blood pressure. Finally, and perhaps most intriguing, similar abnormalities have been found in 50% of the normotensive offspring of patients with essential hypertension and evidence is accruing to indicate that the abnormality is inherited as a Mendelian dominant.

Review, Tutorial↗

Regulatory physiology discipline science plan

The focus of the Regulatory Physiology discipline of the Space Physiology and Countermeasures Program is twofold. First, to determine and study how microgravity and associated factors of space flight affect the regulatory mechanisms by which humans adapt and achieve homeostasis and thereby regulate their ability to respond to internal and external signals; and, second, to study selected physiological systems that have been demonstrated to be influenced by gravity. The Regulatory Physiology discipline, as defined here, is composed of seven subdisciplines: (1) Circadian Rhythms, (2) Endocrinology, (3) Fluid and Electrolyte Regulation, (4) Hematology, (5) Immunology, (6) Metabolism and Nutrition, and (7) Temperature Regulation. The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the area of regulatory physiology. It covers the research areas critical to NASA's programmatic requirements for the Extended-Duration Orbiter, Space Station Freedom, and exploration mission science activities. These science activities include ground-based and flight; basic, applied, and operational; and animal and human research and development. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, identifies science priorities, and defines critical questions in regulatory physiology. It contains a general plan that will be used by both NASA Headquarters Program Offices and the field centers to review and plan basic, applied, and operational intramural and extramural research and development activities in this area.

Source record↗

Viral carcinogenesis: revelation of molecular mechanisms and etiology of human disease

The RNA and DNA tumor viruses have made fundamental contributions to two major areas of cancer research. Viruses were vital, first, to the discovery and analysis of cellular growth control pathways and the synthesis of current concepts of cancer biology and, second, to the recognition of the etiology of some human cancers. Transforming retroviruses carry oncogenes derived from cellular genes that are involved in mitogenic signalling and growth control. DNA tumor viruses encode oncogenes of viral origin that are essential for viral replication and cell transformation; viral oncoproteins complex with cellular proteins to stimulate cell cycle progression and led to the discovery of tumor suppressors. Viral systems support the concept that cancer development occurs by the accumulation of multiple cooperating events. Viruses are now accepted as bona fide etiologic factors of human cancer; these include hepatitis B virus, Epstein-Barr virus, human papillomaviruses, human T-cell leukemia virus type I and hepatitis C virus, plus several candidate human cancer viruses. It is estimated that 15% of all human tumors worldwide are caused by viruses. The infectious nature of viruses distinguishes them from all other cancer-causing factors; tumor viruses establish long-term persistent infections in humans, with cancer an accidental side effect of viral replication strategies. Viruses are usually not complete carcinogens, and the known human cancer viruses display different roles in transformation. Many years may pass between initial infection and tumor appearance and most infected individuals do not develop cancer, although immunocompromised individuals are at elevated risk of viral-associated cancers. Variable factors that influence viral carcinogenesis are reviewed, including possible synergy between viruses and environmental cofactors. The difficulties in establishing an etiologic role for a virus in human cancer are discussed, as well as the different approaches that proved viral links to cancer. Future directions for tumor virus studies are considered.

NASA Program Biomedical Research and Countermeasur↗

Idiopathic orthostatic intolerance and postural tachycardia syndromes

Upright posture imposes a substantial gravitational stress on the body, for which we are able to compensate, in large part because of the autonomic nervous system. Alteration in autonomic function, therefore, may lead to orthostatic intolerance. On one extreme, patients with autonomic failure caused by degenerative loss of autonomic function are severely disabled by orthostatic hypotension and may faint whenever they stand up. Fortunately, such patients are relatively rare. On the other hand, disabling orthostatic intolerance can develop in otherwise normal young people. These patients can be severely impaired by symptoms of fatigue, tachycardia, and shortness of breath when they stand up. The actual incidence of this disorder is unknown, but these patients make up the largest group of patients referred to centers that specialize in autonomic disorders. We will review recent advances made in the understanding of this condition, potential pathophysiological mechanisms that contribute to orthostatic intolerance, therapeutic alternatives currently available for the management of these patients, and areas in which more research is needed.

Review↗

Nutrition and muscle loss in humans during spaceflight

The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.

NASA Program Biomedical Research and Countermeasur↗

The Research Plan: Closing the ExMC Med02 "Pharmacy" Gap

HRP Human Research Roadmap: Risk and Gap Risk of Adverse Health Outcomes and Decrements in Performance due to Inflight Medical Conditions. Med02 "Pharmacy" Gap: We do not have the capability to provide a safe and effective medication formulary for exploration missions delivering a recommendation for a chemically stable, safe, and effective medication formulary that will support the operational needs of exploration space missions research strategy evidence-based formulary and models innovative analytical tools and methodologies novel treatments and preventive measures Planned review by a panel of experts from the pharmaceutical industry, regulatory, and academic scientific communities Formulary Selection Formulary Potency and Shelf life Formulary Safety and Toxicity Novel Technology Proof-of-Concept Portable real-time chemical analysis Innovative drug development / design

Daniels, Vernie↗

Immune function during space flight

It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.

manned↗

Wallops and its role in depressed metabolism

Facilities and organization at the Wallops station are reviewed and some current research work is described that pertains to noise abatement studies as well as some testing phases on V/STOL aircraft. Radiation biology results of various space flights are reviewed and some efforts for the Regulatory Biology Program, involving depressed metabolism aspects of space travel are detailed.

Holton, E. M.↗

NASA Workshop on Biological Adaptation

A workshop was convened to review the current program in Space Biology Biological Adaptation Research and its objectives and to identify future research directions. Two research areas emerged from these deliberations: gravitational effects on structures and biomineralization and gravity affected regulatory mechanisms. The participants also recommended that research concentrate on rapidly growing animals, since gravity effects may be more pronounced during growth and development. Both research areas were defined and future research directions were identified. The recommendations of the workshop will assist the Life Sciences Division of NASA in it assessment and long-range planning of these areas of space biology. Equally important, the workshop was intended to stimulate thought and research among those attending so that they would, in turn, interest, excite, and involve other members of the academic community in research efforts relevant to these programs.

Morey-Holton, Emily↗

Nutrition in space

The authors review studies conducted to define nutritional requirements for astronauts during space flight and to assess nutrition before, during, and after space flight. Topics include space food systems, research and limitations on spacecraft, physiological adaptation to weightlessness, energy requirements, dietary intake during space flight, bone demineralization, gastrointestinal function, blood volume, and nutrition requirements for space flight. Benefits of space-related nutrition research are highlighted.

Review↗

Food and nutrition in space: application to human health

The National Aeronautics and Space Administration begins the new millennium with the hope of expanding human space exploration beyond Earth's orbit. These extended-duration missions (3-5 years) require an in-depth assessment of the critical risks (referred to as "show stoppers") to humans when exposed to the remote environment and reduced gravity conditions for such long periods of time. Food, and the nutrition it provides, is paramount to crew health. For short-duration spaceflight (30 days), the nutrient requirements pertaining to physiological adaptations are likely to be satisfied without significant impact on crew performance or health. However, prolonged exposure to reduced gravity, or microgravity, and isolation may alter human nutrient requirements as well as increase the psychosocial role of food/meals in daily activities. An outline of critical questions and related research needs in the area of food and nutrition has been drafted (1) at NASA JSC with the help of the National Space Biomedical Research Institute (http://www.nsbri.org). The research areas outlined in this plan will directly impact the success of extended-duration human space missions. Findings from this research will have direct applications to human health issues faced here on Earth.

NASA Discipline Regulatory Physiology↗

Water and Energy Dietary Requirements and Endocrinology of Human Space Flight

Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

short duration↗