U.S./U.S.S.R. joint research in space biology and medicine on Cosmos biosatellites
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Cardiovascular variables such as heart rate, arterial blood pressure, stroke volume and the shape of electrocardiographic complexes all fluctuate on a beat to beat basis. These fluctuations have traditionally been ignored or, at best, treated as noise to be averaged out. The variability in cardiovascular signals reflects the homeodynamic interplay between perturbations to cardiovascular function and the dynamic response of the cardiovascular regulatory systems. Modern signal processing techniques provide a means of analyzing beat to beat fluctuations in cardiovascular signals, so as to permit a quantitative, noninvasive or minimally invasive method of assessing closed loop hemodynamic regulation and cardiac electrical stability. This method promises to provide a new approach to the clinical diagnosis and management of alterations in cardiovascular regulation and stability.
In this second article in the two-part series on pharmacology in space, Claire Lathers and colleagues discuss the pharmacology of drugs used to control motion sickness in space and note that the pharmacology of the 'ideal' agent has yet to be worked out. That motion sickness may impair the pharmacological action of a drug by interfering with its absorption and distribution because of alteration of physiology is a problem unique to pharmacology in space. The authors comment on the problem of designing suitable ground-based studies to evaluate the pharmacological effect of drugs to be used in space and discuss the use of salivary samples collected during space flight to allow pharmacokinetic evaluations necessary for non-invasive clinical drug monitoring.
This brief review concerns acute and chronic metabolic responses to resistive-type exercise (RTE) (i.e., Olympic/power weight lifting and bodybuilding). Performance of RTE presents power output substantially greater (10-15-fold) than that evident with endurance-type exercise. Accordingly, RTE relies heavily on the anaerobic enzyme machinery of skeletal muscle for energy supply, with alterations in the rate of aerobic metabolism being modest. Hydrolysis of high energy phosphate compounds (PC, ATP), glycogenolysis, and glycolysis are evident during an acute bout of RTE as indicated by metabolic markers in mixed fiber type skeletal muscle samples. The type of RTE probably influences the magnitude of these responses since the increase in blood lactate is much greater during a typical "bodybuilding" than "power lifting" session. The influence of RTE training on acute metabolic responses to RTE has received little attention. An individual's inherent metabolic characteristics are apparently sufficient to meet the energy demands of RTE as training of this type does not increase VO2max or substantially alter the content of marker enzymes in mixed fiber type skeletal muscle. Analyses of pools of fast- vs slow-twitch fibers, however, indicate that RTE-induced changes may be fiber type specific. Future studies should better delineate the metabolic responses to RTE and determine whether these are related to the enhanced performance associated with such training.
Studies on animal models demonstrate that platelet products contribute to vascular spasm in ischemic syndromes and that this is reversible with administration of ketanserin and thromboxane synthesis inhibitors. Laboratory animals (dogs, rabbits, and rats) that had femoral artery ligations exhibited supersensitivity to serotonin within days in their collateral blood vessels. This supersensitivity lasted at least 6 months. The response to serotonin was reversed by ketanserin, but not by 5HT-1 antagonists. Supersensitivity does not extend to norepinephrine, and alpha blockers do not influence the response to serotonin. It appears that platelet activation by endothelial injury contributes to ischemia through blood vessel occlusion and vascular spasm. When platelet activation occurs in vivo, blood vessel occlusion and vascular spasm are reversible in part by using ketanserin or agents that block thromboxane synthesis or its action. Combining both classes of agents reverses spasm completely. These findings support existing evidence that platelet products contribute to vascular disease, and provide an approach to improved management with currently available pharmacologic agents.
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Studies from space flights over the past two decades have demonstrated that there are basic physiological changes in humans during space flight. These changes include cephalad fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known but the general approach has been to investigate systemic and hormonal changes. However, data from the 1973-1974 Skylabs, Spacelab 3 (SL-3), Spacelab D-I (SL-DI), and now the new SLS-1 missions support a more basic biological response to microgravity that may occur at the tissue, cellular, and molecular level. This report summarizes ground-based and SLS-1 experiments that examined the mechanism of loss of red blood cell mass in humans, the loss of bone mass and lowered osteoblast growth under space flight conditions, and loss of immune function in microgravity.
The topic of pharmacology in space, i.e. the administration of drugs during space flight and the subsequent pharmacokinetic handling of the pharmaceuticals, is a new field about which little is known. In a two-part series, Claire Lathers and colleagues highlight some of the current questions in this field. In this first article the physiological and biochemical changes associated with weightlessness in space are discussed. These changes induce adaptive alterations which may influence the pharmacokinetic properties of drugs. The cardiovascular system is of particular relevance here. Also discussed are the classes of pharmacological agent that are most likely to be used during space flight for medical problems and thus, by necessity, will become drugs to be examined in space to determine whether their pharmacokinetic and pharmacodynamic properties are altered. Therapy of the most common spaceflight ailment-motion sickness-will be considered next month in Part 2.
1. Organisms may be affected by many environmental factors during space flight, e.g., acceleration, weightlessness, decreased pressure, changes in oxygen tension, radiofrequency radiation and vibration. 2. Previous studies of change in body temperature--one response to these environmental factors--are reviewed. 3. Conditions leading to heat stress and hypothermia are discussed.
The etiology, clinical presentation, and management of hypophosphatemia are reviewed. Phosphorus is a major intracellular anion and plays an important role in many biochemical pathways relating to normal physiologic functions. Approximately 60 to 90% of the 1 to 1.5 g of daily dietary phosphorus intake is absorbed, and of that amount, about two thirds is excreted in the urine. The overall incidence of hypophosphatemia is about 2 to 3% of all hospitalized patients. Factors associated with hypophosphatemia include phosphate-binding antacid therapy, nasogastric suction, liver disease, sepsis, alcoholism, and acidosis associated with diabetic ketoacidosis. Patients receiving parenteral nutrient solutions were also at higher risk for hypophosphatemia before the routine supplementation of these formulations with phosphate. Patients with hypophosphatemia may be asymptomatic or may experience weakness, malaise, anorexia, bone pain, and respiratory arrest. The major systems involved include the neuromuscular, hematologic, and skeletal systems. Phosphorus-containing products used to treat hypophosphatemia are a combination of monobasic and dibasic phosphate salts. Therefore, it is essential to calculate doses in millimoles rather than milligrams or milliequivalents to more accurately reflect the phosphorus concentration and to avoid potentially serious dosage errors. Normal daily requirements are readily maintained by dietary sources of phosphorus such as milk products or may be supplemented by phosphate-containing products administered orally or intravenously. Since phosphorus is a key factor in many organ systems, it is essential to monitor serum phosphorus concentrations in patients at risk for hypophosphatemia.
The use of magnetic fluids and magnetic particles in combinatorial hyperthermia therapy for cancer treatment is reviewed. The investigation approach adopted for producing thermoregulating particles and tissue model studies for studying particle retention and heating characteristics is discussed.
Air passenger miles will likely double by year 2020. The altered and restrictive environment in an airliner cabin can influence haematological homeostasis in passengers and crew. Flight-related deep venous thromboemboli (DVT) have been associated with at least 577 deaths on 42 of 120 airlines from 1977 to 1984 (25 deaths/million departures), whereas many such cases go unreported. However, there are four major factors that could influence formation of possible flight-induced DVT: sleeping accommodations (via sitting immobilisation); travellers' medical history (via tissue injury); cabin environmental factors (via lower partial pressure of oxygen and lower relative humidity); and the more encompassing chair-rest deconditioning (C-RD) syndrome. There is ample evidence that recent injury and surgery (especially in deconditioned hospitalised patients) facilitate thrombophlebitis and formation of DVT that may be exacerbated by the immobilisation of prolonged air travel.In the healthy flying population, immobilisation factors associated with prolonged (>5 hours) C-RD such as total body dehydration, hypovolaemia and increased blood viscosity, and reduced venous blood flow (pooling) in the legs may facilitate formation of DVT. However, data from at least four case-controlled epidemiological studies did not confirm a direct causative relationship between air travel and DVT, but factors such as a history of vascular thromboemboli, venous insufficiency, chronic heart failure, obesity, immobile standing position, more than three pregnancies, infectious disease, long-distance travel, muscular trauma and violent physical effort were significantly more frequent in DVT patients than in controls. Thus, there is no clear, direct evidence yet that prolonged sitting in airliner seats, or prolonged experimental chair-rest or bed-rest deconditioning treatments cause DVT in healthy people.
Different types of lasers are now routinely used to prepare single-walled carbon nanotubes. The original method developed by researchers at Rice University used a "double-pulse laser oven" process. Several researchers have used variations of the lasers to include one-laser pulse (green or infrared), different pulse widths (ns to micros as well as continuous wave), and different laser wavelengths (e.g., CO2, or free electron lasers in the near to far infrared). Some of these variations are tried with different combinations and concentrations of metal catalysts, buffer gases (e.g., helium), oven temperatures, flow conditions, and even different porosities of the graphite targets. This article is an attempt to cover all these variations and their relative merits. Possible growth mechanisms under these different conditions will also be discussed.
The latest process for producing large quantities of single-walled carbon nanotubes (SWNTs) to emerge from the Rice University, dubbed HiPco, is living up to its promise. The current production rates approach 450 mg/h (or 10 g/day), and nanotubes typically have no more than 7 mol % of iron impurities. Second-generation HiPco apparatus can run continuously for 7-10 days at a time. In the HiPco process nanotubes grow in high-pressure, high-temperature flowing CO on catalytic clusters of iron. Catalyst is formed in situ by thermal decomposition of iron pentacarbonyl, which is delivered intact within a cold CO flow and then rapidly mixed with hot CO in the reaction zone. Upon heating, the Fe(CO)5 decomposes into atoms that condense into larger clusters. SWNTs nucleate and grow on these particles in the gas phase via CO disproportionation: CO + CO --> CO2 + C (SWNT), catalyzed by the Fe surface. The concentration of CO2 produced in this reaction is equal to that of carbon and can therefore serve as a useful real-time feedback parameter. It was used to study and optimize SWNT production as a function of temperature, pressure, and Fe(CO)5 concentration. The results of the parametric study are in agreement with current understanding of the nanotube formation mechanism.
Microbial adaptation to environmental stimuli is essential for survival. While several of these stimuli have been studied in detail, recent studies have demonstrated an important role for a novel environmental parameter in which microgravity and the low fluid shear dynamics associated with microgravity globally regulate microbial gene expression, physiology, and pathogenesis. In addition to analyzing fundamental questions about microbial responses to spaceflight, these studies have demonstrated important applications for microbial responses to a ground-based, low-shear stress environment similar to that encountered during spaceflight. Moreover, the low-shear growth environment sensed by microbes during microgravity of spaceflight and during ground-based microgravity analogue culture is relevant to those encountered during their natural life cycles on Earth. While no mechanism has been clearly defined to explain how the mechanical force of fluid shear transmits intracellular signals to microbial cells at the molecular level, the fact that cross talk exists between microbial signal transduction systems holds intriguing possibilities that future studies might reveal common mechanotransduction themes between these systems and those used to sense and respond to low-shear stress and changes in gravitation forces. The study of microbial mechanotransduction may identify common conserved mechanisms used by cells to perceive changes in mechanical and/or physical forces, and it has the potential to provide valuable insight for understanding mechanosensing mechanisms in higher organisms. This review summarizes recent and future research trends aimed at understanding the dynamic effects of changes in the mechanical forces that occur in microgravity and other low-shear environments on a wide variety of important microbial parameters.
Extension of human habitation into space requires that humans carry with them many of the microorganisms with which they coexist on Earth. The ubiquity of microorganisms in close association with all living things and biogeochemical processes on Earth predicates that they must also play a critical role in maintaining the viability of human life in space. Even though bacterial populations exist as locally adapted ecotypes, the abundance of individuals in microbial species is so large that dispersal is unlikely to be limited by geographical barriers on Earth (i.e., for most environments "everything is everywhere" given enough time). This will not be true for microbial communities in space where local species richness will be relatively low because of sterilization protocols prior to launch and physical barriers between Earth and spacecraft after launch. Although community diversity will be sufficient to sustain ecosystem function at the onset, richness and evenness may decline over time such that biological systems either lose functional potential (e.g., bioreactors may fail to reduce BOD or nitrogen load) or become susceptible to invasion by human-associated microorganisms (pathogens) over time. Research at the John F. Kennedy Space Center has evaluated fundamental properties of microbial diversity and community assembly in prototype bioregenerative systems for NASA Advanced Life Support. Successional trends related to increased niche specialization, including an apparent increase in the proportion of nonculturable types of organisms, have been consistently observed. In addition, the stability of the microbial communities, as defined by their resistance to invasion by human-associated microorganisms, has been correlated to their diversity. Overall, these results reflect the significant challenges ahead for the assembly of stable, functional communities using gnotobiotic approaches, and the need to better define the basic biological principles that define ecosystem processes in the space environment. Copyright 2004 Springer-Verlag.