Search NASA⌕ Search

SEARCH · Search NASA

Results for “Pathological effect”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8

Minimal microwave anisotrophy from perturbations induced at late times

Aside from primordial gravitational instability of the cosmological fluid, various mechanisms have been proposed to generate large-scale structure at relatively late times, including, e.g., 'late-time' cosmological phase transitions. In these scenarios, it is envisioned that the universe is nearly homogeneous at the times of last scattering and that perturbations grow rapidly sometimes after the primordial plasma recombines. On this basis, it was suggested that large inhomogeneities could be generated while leaving relatively little imprint on the cosmic microwave background (MBR) anisotropy. In this paper, we calculate the minimal anisotropies possible in any 'late-time' scenario for structure formation, given the level of inhomogeneity observed at present. Since the growth of the inhomogeneity involves time-varying gravitational fields, these scenarios inevitably generate significant MBR anisotropy via the Sachs-Wolfe effect. Moreover, we show that the large-angle MBR anisotropy produced by the rapid post-recombination growth of inhomogeneity is generally greater than that produced by the same inhomogeneity growth via gravitational instability. In 'realistic' scenarios one can decrease the anisotropy compared to models with primordial adiabatic fluctuations, but only on very small angular scales. The value of any particular measure of the anisotropy can be made small in late-time models, but only by making the time-dependence of the gravitational field sufficiently 'pathological'.

Jaffe, Andrew H.↗

Physiological response of rats to delivery of helium and xenon: implications for hyperpolarized noble gas imaging

The physiological effects of various hyperpolarized helium and xenon MRI-compatible breathing protocols were investigated in 17 Sprague-Dawley rats, by continuous monitoring of blood oxygen saturation, heart rate, EKG, temperature and endotracheal pressure. The protocols included alternating breaths of pure noble gas and oxygen, continuous breaths of pure noble gas, breath-holds of pure noble gas for varying durations, and helium breath-holds preceded by two helium rinses. Alternate-breath protocols up to 128 breaths caused a decrease in oxygen saturation level of less than 5% for either helium or xenon, whereas 16 continuous-breaths caused a 31.5% +/- 2.3% decrease in oxygen saturation for helium and a 30.7% +/- 1. 3% decrease for xenon. Breath-hold protocols up to 25 s did not cause the oxygen saturation to fall below 90% for either of the noble gases. Oxygen saturation values below 90% are considered pathological. At 30 s of breath-hold, the blood oxygen saturation dropped precipitously to 82% +/- 0.6% for helium, and to 76.5% +/- 7. 4% for xenon. Breath-holds longer than 10 s preceded by pre-rinses caused oxygen saturation to drop below 90%. These findings demonstrate the need for standardized noble gas inhalation procedures that have been carefully tested, and for continuous physiological monitoring to ensure the safety of the subject. We find short breath-hold and alternate-breath protocols to be safe procedures for use in hyperpolarized noble gas MRI experiments. Copyright 2000 John Wiley & Sons, Ltd.

NASA Discipline Life Sciences Technologies↗

Determinants of diastolic myocardial tissue Doppler velocities: influences of relaxation and preload

Myocardial tissue Doppler echocardiography (TDE) has been proposed as a tool for the assessment of diastolic function. Controversy exists regarding whether TDE measurements are influenced by preload. In this study, left ventricular volume and high-fidelity pressures were obtained in eight closed-chest dogs during intermittent caval occlusion. The time constant of isovolumic ventricular relaxation (tau) was altered with varying doses of dobutamine and esmolol. Peak early diastolic myocardial (E(m)) and transmitral (E) velocities were measured before and after preload reduction. The relative effects of changes in preload and relaxation were determined for E(m) and compared with their effects on E. The following results were observed: caval occlusion significantly decreased E (DeltaE = 16.4 +/- 3.3 cm/s, 36.6 +/- 13.7%, P < 0.01) and E(m) (DeltaE(m) = 1. 3 +/- 0.4 cm/s, 32.5 +/- 26.1%, P < 0.01) under baseline conditions. However, preload reduction was similar for E under all lusitropic conditions (P = not significant), but these effects on E(m) decreased with worsening relaxation. At tau < 50 ms, changes in E(m) with preload reduction were significantly greater (DeltaE(m) = 2.8 +/- 0.6 cm/s) than at tau = 50-65 ms (DeltaE(m) = 1.2 +/- 0.2 cm/s) and at tau >65 ms (DeltaE(m) = 0.5 +/- 0.1 cm/s, P < 0.05). We concluded that TDE E(m) is preload dependent. However, this effect decreases with worsening relaxation.

NASA Discipline Cardiopulmonary↗

[Role of membrane lipids in myocardial cytoprotection]

The cardiomyocyte capacity to regulate ATP production to face any change in energy demand is a major determinant of cardiac function. This process is based on a balanced fatty acid (FA) metabolism, because FA is the main fuel of the heart, although the most expensive one in oxygen. The pathway is, however, weakly controlled by the cardiac myocyte which can well regulate FA mitochondrial entry but not cell FA uptake. For this reason, several pathological situations often result from either harmful accumulation of FA and derivatives or excess FA-oxidation. Control of the FA/glucose balance by decreased energy production from FA would thus offer an alternative strategy in the treatment of ischaemia, providing the cardiomyocytes weak ability in handling the non-metabolised FA is controlled. The initiation and the regulation of cardiac contraction both result from membrane activity; the other major role of lipids in the heart is their contribution to membrane homeostasis through phospholipid synthesis pathways and phospholipases. The anti-anginal activity of Trimetazidine, reported as a cytoprotective effect without a haemo-dynamic component; is associated with reduced use of FA for energy. However, accumulation of FA and derivatives has never been observed. Trimetazidine is reported to increase significantly the synthesis of phospholipids without influencing the other lipid classes, thus increasing the incorporation of FA in membrane structures. This cytoprotection appears to be based on the redirection of the use of FA to phospholipid synthesis, which would decrease their availability for energy production. This class of compounds, with the same properties as Trimetazidine, offers a metabolic approach to the treatment of ischaemia.

Cytoprotection/physiology↗

Eosinophilia of dystrophin-deficient muscle is promoted by perforin-mediated cytotoxicity by T cell effectors

Previous investigations have shown that cytotoxic T lymphocytes (CTLs) contribute to muscle pathology in the dystrophin-null mutant mouse (mdx) model of Duchenne muscular dystrophy through perforin-dependent and perforin-independent mechanisms. We have assessed whether the CTL-mediated pathology includes the promotion of eosinophilia in dystrophic muscle, and thereby provides a secondary mechanism through which CTLs contribute to muscular dystrophy. Quantitative immunohistochemistry confirmed that eosinophilia is a component of the mdx dystrophy. In addition, electron microscopic observations show that eosinophils traverse the basement membrane of mdx muscle fibers and display sites of close apposition of eosinophil and muscle membranes. The close membrane apposition is characterized by impingement of eosinophilic rods of major basic protein into the muscle cell membrane. Transfer of mdx splenocytes and mdx muscle extracts to irradiated C57 mice by intraperitoneal injection resulted in muscle eosinophilia in the recipient mice. Double-mutant mice lacking dystrophin and perforin showed less eosinophilia than was displayed by mdx mice that expressed perforin. Finally, administration of prednisolone, which has been shown previously to reduce the concentration of CTLs in dystrophic muscle, produced a significant reduction in eosinophilia. These findings indicate that eosinophilia is a component of the mdx pathology that is promoted by perforin-dependent cytotoxicity of effector T cells. However, some eosinophilia of mdx muscle is independent of perforin-mediated processes.

NASA Discipline Musculoskeletal↗

Rat limb unloading - Soleus histochemistry, ultrastructure, and electromyography

The effects of hindlimb unloading on rat-soleus histochemisty, ultrastructure, and electromyogram (EMG) activity were investigated. It was found that, after 14 days of tail suspension, the area of type I and type IIa muscle fibers decreased by 63 and 47 percent, respectively, mainly due to the degradation of subsarcolemmal mitochondria and myofibrils. After 10 days, 3 percent of type IIa fibers exhibited segmental necrosis. After four days, video monitoring revealed abnormal plantar flexion of the hindfeet, which shortened the soleus working range. The EMG activity shifted from tonic to phasic, and aggregate activity decreased drastically after only seven days. The results indictate that the pathological changes in the soleus resulted from unloaded contractions, reduced use, compromised blood flow, and shortened working length.

Riley, D. A.↗

Preflight studies on tolerance of pocket mice to oxygen and heat. IV - Observations on the brain

Experiments designed to ascertain the effects of oxygen at 8, 10, and 12 psi partial pressure on the brains of pocket mice (Perognathus longimembris) were carried out at room temperature (24 C, 75 F) and at 32 C (90 F). The animals exposed to 8-12 psi at 32 C had been in earlier KO2 oxygen tests. Five animals exposed either to 10 or 12 psi (517 mm or 620 mm Hg) O2 partial pressure at 32 C died during the course of the tests, possibly as a consequence of injury sustained by the earlier O2 partial pressure testing. Autopsy was not carried out. In the other 36 exposed animals, no pathological changes were observed in the brain. It is thus highly probable that oxygen pressures at the hyperbaric levels to which the pocket mice would be exposed during the Apollo XVII mission would not result in any lesions in the brain.

Bailey, O. T.↗

Ultrasound in space

Physiology of the human body in space has been a major concern for space-faring nations since the beginning of the space era. Ultrasound (US) is one of the most cost effective and versatile forms of medical imaging. As such, its use in characterizing microgravity-induced changes in physiology is being realized. In addition to the use of US in related ground-based studies, equipment has also been modified to fly in space. This involves alteration to handle the stresses of launch and different power and cooling requirements. Study protocols also have been altered to accommodate the microgravity environment. Ultrasound studies to date have shown a pattern of adaptation to microgravity that includes changes in cardiac chamber sizes and vertebral spacing. Ultrasound has been and will continue to be an important component in the investigation of physiological and, possibly, pathologic changes occurring in space or as a result of spaceflight.

Review, Tutorial↗

Neuro-behavioral Consequences of Low Dose Radiation Social Isolation and Sex Differences in the Longevity MCAT Mouse Model

The physiological responses to spaceflight elicit wide-ranging consequences and resemble aspects of aging on Earth. Previous studies have shown that oxidative damage via reactive oxygen species (ROS), contributes to aging-related pathologies. Our study uses 1-year old C57BL/6NJ male and female mice (astronaut-relevant age) that underwent exposure to 0.5 gray of gamma radiation together with social isolation and were euthanized 12 weeks after. We used the longevity MCAT mouse model in which human catalase is overexpressed in the mitochondria, for ROS quenching. We aimed to determine whether in older mice quenching ROS, will mitigate the neuro-behavioral consequences of low dose ionizing radiation and/or social isolation and whether the outcomes will differ in males and females. We have performed five mission relevant behavioral tests which focused on performance, memory, physical stance, and stress. We have detected both sex and radiation effects; the older females look physically better are faster and perform better almost in all behavioral tests compared to their male counterparts. On the other hand, they are more sensitive to low dose radiation in many cases, in some cases this effect was indeed mitigated in the MCAT mice, pointing out to the importance of ROS in response to radiation stress and social isolation. We have measured plasma (7- and 90-days post radiation), cytokines, corticosterone and hippocampal cytokine and microglial activation at the end of the experiment. We saw significant changes in the plasma markers due to radiation, sex, and genotype in both short and long post radiation period and detected long term sex and radiation effects in the brain. Our focus is now on applying advanced statistical modeling to corelate the behavioral tests with our recent molecular findings to look for specific biomarkers that could predict behavioral deficits.

radiation↗

The effect of head-down tilt and water immersion on intracranial pressure in nonhuman primates

Intracranial pressure (ICP) is investigated in primates during and after -6-deg head-down tilt (HDT) and immersion in water to examine the effects of the headward fluid shift related to spaceflight. Following the HDT the primates are subjected to head-out thermoneutral water immersion, and the ICP is subsequently measured. ICP is found to increase from 3.8 +/- 1.1 to 5.3 +/- 1.3 mm Hg during the horizontal control period. ICP stabilizes at -6.3 +/- 1.3 mm Hg and then increases to -2.2 +/- 1.9 mm Hg during partial immersion, and ICP subsequently returns to preimmersion levels after immersion. These data indicate that exposure to HDT or water immersion lead to an early sharp increase in ICP, and water immersion alone leads to higher ICP levels. A significant conclusion of the work is that the ICP did not approach pathological levels, and this finding is relevant to human spaceflight research.

Keil, Lanny C.↗

The effect of increased gravitational stress on bone

A group of 34 adult male chickens were chronically accelerated over an 18-week period; for the last 4 weeks the surviving animals were subjected to a 3-g field. Males of a similar weight and age were used as static controls. The objective was to evaluate the effects of an altered gravitational state on the physical properties of the tibia bone tested for torsional fracture. Of the 34 initial animals, 15 survived for the entire period and were subjected to analysis. The results suggest that the altered morphology produced by increased gravitational fields does not materially affect bone strength, at least in torsion. Decreased bone diameters were accompanied by increased cortical thickness without change in the bone resistance to torsion. The findings of increased cortical thickness with decreased bone diameter suggest reversal of the usual cellular dynamics of adult bone. Data on bone ash and density failed to reveal any substantial changes in bone mineral or organic content. Histological examination of the cortical bone did not disclose any evidence of pathology.

Riggins, R. S.↗

Statistical performance of the intensified charged coupled device

The first analysis of the statistical performance of the intensified charge coupled device (CCD) is presented. The Poisson statistics of the arriving photons, the exponential pulse height distribution of the microchannel plate in the image intensifier, and the effects of discrete digitization of the charge in reading the CCD are included. A range of intensifier gains from the high levels that permit pulse counting to the low levels that can be used with the accumulation of charge on the CCD is considered. As a tool for this analysis, an analytical model of the performance of the detector system that is generally useful for predicting many aspects of system performance under a wide range of conditions is developed. The statistical penalty for operating the intensified CCD in the charge accumulation mode is not severe, and in some applications it may be desirable to accept this penalty to gain the advantages of increased dynamic range through charge accumulation. This investigation has revealed no pathological aspects of the operation of the detector system.

Sandel, B. R.↗

Ionizing Radiation Affects Gene Expression in Mouse Skin and Bone

Future long-duration space exploration beyond low earth orbit will increase human exposure to space radiation and microgravity conditions as well as associated risks to skeletal health. In animal studies, radiation exposure (greater than 1 Gy) is associated with pathological changes in bone structure, enhanced bone resorption, reduced bone formation and decreased bone mineral density, which can lead to skeletal fragility. Definitive measurements and detection of bone loss typically require large and specialized equipment which can make their application to long duration space missions logistically challenging. Towards the goal of developing non-invasive and less complicated monitoring methods to predict astronauts' health during spaceflight, we examined whether radiation induced gene expression changes in skin may be predictive of the responses of skeletal tissue to radiation exposure. We examined oxidative stress and growth arrest pathways in mouse skin and long bones by measuring gene expression levels via quantitative polymerase chain reaction (qPCR) after exposure to total body irradiation (IR). To investigate the effects of irradiation on gene expression, we used skin and femora (cortical shaft) from the following treatment groups: control (normally loaded, sham-irradiated), and IR (0.5 Gy 56Fe 600 MeV/n and 0.5 Gy 1H 150 MeV/n), euthanized at one and 11 days post-irradiation (IR). To determine the extent of bone loss, tibiae were harvested and cancellous microarchitecture in the proximal tibia quantified ex vivo using microcomputed tomography (microCT). Statistical analysis was performed using Student's t-test. At one day post-IR, expression of FGF18 in skin was significantly greater (3.8X) than sham-irradiated controls, but did not differ at 11 days post IR. Expression levels of other genes associated with antioxidant response (Nfe2l2, FoxO3 and Sod1) and the cell cycle (Trp53, Cdkn1a, Gadd45g) did not significantly differ between the control and IR groups at either time point. Radiation exposure resulted in a 27.0% increase in FGF18-positive hair follicles at one day post-IR and returned to basal levels at 11 days post-IR. A similar trend was observed from FGF18 gene expression analysis of skin. In bone (femora), there was an increase in the expression of the pro-osteoclastogenic cytokine, MCP-1, one day after IR compared to non-irradiated controls. FGF18 expression in skin and MCP- 1 expression in bone were found to be positively correlated (P less than 0.002, r=0.8779). Further, microcomputed tomography analysis of tibia from these animals showed reduced cancellous bone volume (-9.9%) at 11 days post- IR. These results suggest that measurements of early radiation induced changes in FGF18 gene expression in skin may have value for predicting subsequent loss of cancellous bone mass. Further research may lead to the development of a relatively simple diagnostic tool for bone loss, with the advantage that hair follicles and skin are relatively easy to acquire from human subjects.

space radiation↗

A Study of Aberrant Glycosylation in Simulated Microgravity Using Laser Induced AutoFluorescence and Flow Cytometry

A number of pathologies and cellular dysfunctions including neoplasms have been correlated with autofluorescence. The complications of aging and diabetes have been associated with the accumulation of non-enzymatic glycosylations of tissue macromolecules. These products are known as the Advanced Glycosylated End Products (AGEs). A physical property associated with AGEs is the emission of 570 mn or 630 nm light energy (autofluorescence) following the absorption of 448 mm energy associated with the argon laser. This investigation sought to assess the induction of argon-laser induced autofluorescence in a variety of in vitro culture systems. Different fluorescence intensities distinguished tumor lines from normal cell populations. Laser-stimulated autofluorescence discriminated primary cultures of lymphocytes grown in the presence of excess glucose as opposed to normal glucose concentrations. The effects of deglycosylating agents upon laser-induced autofluorescence were also assessed. The studies included studies of cell cycle analysis using Propidium Iodide stained DNA of cells grown in simulated microgravity using NASA Bioreactor Vessels in media of normal and elevated glucose concentrations.

Lawless, B. DeSales↗

Realtime Multichannel System for Beat to Beat QT Interval Variability

The measurement of beat-to-beat QT interval variability (QTV) shows clinical promise for identifying several types of cardiac pathology. However, until now, there has been no device capable of displaying, in real time on a beattobeat basis, changes in QTV in all 12 conventional leads in a continuously monitored patient. While several software programs have been designed to analyze QTV, heretofore, such programs have all involved only a few channels (at most) and/or have required laborious user interaction or offline calculations and postprocessing, limiting their clinical utility. This paper describes a PC-based ECG software program that in real time, acquires, analyzes and displays QTV and also PQ interval variability (PQV) in each of the eight independent channels that constitute the 12lead conventional ECG. The system also processes certain related signals that are derived from singular value decomposition and that help to reduce the overall effects of noise on the realtime QTV and PQV results.

Starc, Vito↗

Noninvasive Diagnosis of Coronary Artery Disease Using 12-Lead High-Frequency Electrocardiograms

A noninvasive, sensitive method of diagnosing certain pathological conditions of the human heart involves computational processing of digitized electrocardiographic (ECG) signals acquired from a patient at all 12 conventional ECG electrode positions. In the processing, attention is focused on low-amplitude, high-frequency components of those portions of the ECG signals known in the art as QRS complexes. The unique contribution of this method lies in the utilization of signal features and combinations of signal features from various combinations of electrode positions, not reported previously, that have been found to be helpful in diagnosing coronary artery disease and such related pathological conditions as myocardial ischemia, myocardial infarction, and congestive heart failure. The electronic hardware and software used to acquire the QRS complexes and perform some preliminary analyses of their high-frequency components were summarized in Real-Time, High-Frequency QRS Electrocardiograph (MSC- 23154), NASA Tech Briefs, Vol. 27, No. 7 (July 2003), pp. 26-28. To recapitulate, signals from standard electrocardiograph electrodes are preamplified, then digitized at a sampling rate of 1,000 Hz, then analyzed by the software that detects R waves and QRS complexes and analyzes them from several perspectives. The software includes provisions for averaging signals over multiple beats and for special-purpose nonrecursive digital filters with specific low- and high-frequency cutoffs. These filters, applied to the averaged signal, effect a band-pass operation in the frequency range from 150 to 250 Hz. The output of the bandpass filter is the desired high-frequency QRS signal. Further processing is then performed in real time to obtain the beat-to-beat root mean square (RMS) voltage amplitude of the filtered signal, certain variations of the RMS voltage, and such standard measures as the heart rate and R-R interval at any given time. A key signal feature analyzed in the present method is the presence versus the absence of reduced-amplitude zones (RAZs). In terms that must be simplified for the sake of brevity, an RAZ comprises several cycles of a high-frequency QRS signal during which the amplitude of the high-frequency oscillation in a portion of the signal is abnormally low (see figure). A given signal sample exhibiting an interval of reduced amplitude may or may not be classified as an RAZ, depending on quantitative criteria regarding peaks and troughs within the reduced-amplitude portion of the high-frequency QRS signal. This analysis is performed in all 12 leads in real time.

Schlegel, Todd T.↗

Examining the Effects of 4He Exposure on the Gut-Brain Axis

Beyond low earth orbit, space radiation poses significant risks to astronaut health. Previous studies have shown that the microbial composition of the gastrointestinal (GI) microbiome changes upon exposure to high linear energy transfer radiation. Interestingly, radiation-induced shifts in GI microbiota composition are linked to various neuropsychological disorders. Herein, we aimed to study changes in GI microbiota and behaviors of rats exposed to whole-body radiation (0, 5, or 25 cGy 4 He, 250 MeV/n) at approximately 6 months of age. Fecal samples were collected 24 hours prior to 4 He radiation and 24 hours and 7 days post-exposure for quantitative PCR analyses to assess fecal levels of spore-forming bacteria (SFB), Bifidobacterium, Lactobacillus, and Akkermansia. Rats were also tested in the social odor recognition memory (SORM) test at 7 days following 4 He exposure. A subset of rats was euthanized 90 minutes following completion of the SORM test, and GI tissue from small intestine to colon were prepared for examining overall histological changes and immunohistochemical staining for serotonin (5-HT). No notable pathological changes were observed in GI tissues. Akkermansia spp. and SFB were significantly decreased the 25 cGy group at 24 hours and 7 days post-exposure compared to pre-exposure, respectively. Bifidobacterium and Lactobacillus spp. showed no significant changes. 5-HT production was significantly higher in the proximal small intestine and the cecum in the 25 cGy group compared to the sham group. The 25 cGy group exhibited deficits in recognition in SORM testing at 7 days post-exposure. Taken together, these results suggest a connection between GI microbiome 3 composition, serotonin production, and neurobehavioral performance, and that this connection may be disrupted upon exposure to 25 cGy of 4 He ions

Carli B Jones↗

Coping with the diagnostic complexities of the compartment syndrome

This review recognizes that, given the various complexities associated with the condition, no pat answers can be given to fit every patient with the compartment syndrome. The authors first give a definition of the syndrome, together with a brief account of how this self-perpetuating pathologic cycle is triggered. Next, they delineate specific anatomical features of compartments that are likely to be involved, and follow this with an inventory of symptoms and signs to look for in suspected cases. After sorting out the entities that can mimic the compartment syndrome, the authors describe three essential techniques of measuring tissue pressure, which can prove invaluable in diagnosing the compartment syndrome.

NASA Program Biomedical Research↗