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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.

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At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats

We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

NASA Discipline Regulatory Physiology↗
NASA NTRS2002

Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats

The mammalian Per1 gene is an important component of the core cellular clock mechanism responsible for circadian rhythms. The rodent liver and other tissues rhythmically express Per1 in vitro but typically damp out within a few cycles. In the liver, the peak of this rhythm occurs in the late subjective night in an ad lib-fed rat, but will show a large phase advance in response to restricted availability of food during the day. The relationship between this shift in the liver clock and food-anticipatory activity (FAA), the circadian behavior entrained by daily feeding, is currently unknown. Insulin is released during feeding in mammals and could serve as an entraining signal to the liver. To test the role of insulin in the shift in liver Per1 expression and the generation of FAA, per-luciferase transgenic rats were made diabetic with a single injection of streptozotocine. Following 1 week of restricted feeding and locomotor activity monitoring, liver was collected for per-luc recording. In two separate experiments, FAA emerged and liver Per1 phase-shifted in response to daytime 8-h food restriction. The results rule out insulin as a necessary component of this system.

NASA Discipline Space Human Factors↗
NASA NTRS2012

New Therapeutic Window of Regenerative Opportunity in Diabetic Retinopathy by VESGEN Analysis

Vascular pattern may serve as a useful new biomarker principle of complex, multi-scale signaling in pathological, physiological angiogenesis and microvascular remodeling. Each angiogenesis stimulator or inhibitor we have analyzed, including VEGF, bFGF, TGF-beta1, angiostatin and triamcinolone acetonide, has induced a novel "fingerprint" or "signature" biomarker vascular pattern that is spatio-temporally unique. Remodeling vasculature thereby provides an informative read-out of dominant molecular signaling, when analyzed by innovative, fractal-based VESsel GENeration (VESGEN) Analysis software. Using VESGEN to analyze ophthalmic clinical vascular images, we recently introduced a potential paradigm shift to the understanding of early-stage progression that suggests new regenerative opportunities for human diabetic retinopathy (DR), the major blinding disease for working-aged adults. In a pilot study, we discovered that angiogenesis oscillates as a surprising, homeostatic-like regeneration of retinal vessels during early progression of DR (IOVS 51(1):498). Results suggest that the term non-proliferative DR may be a misnomer. In new studies, normalization of the vasculature will be determined from the response of vascular pattern to therapeutic monitoring and treatment. We have mapped and quantified in vivo experimental models of angiogenesis, lymphangiogenesis and intravital blood flow from cellular/molecular to higher systems levels that include a murine model of infant retinopathy of prematurity (ROP); developing and pathological coronary and placental-like vessel models; progressive intestinal inflammation, growing murine tumors, and other pathological, physiological and therapeutically treated tissues of transgenic mice and avian embryos. Vascular Alterations, Visual Impairments (VIIP) & Increased Intracranial Pressure (ICP), Immunosuppression & Bone Loss: NASA-defined risk categories for human space exploration and ISS Utilization

Parsons-Wingert, Patricia A.↗
NASA NTRS2016

Bone Turnover Does Not Reflect Skeletal Aging in Older Hispanic Men with Type 2 Diabetes

The paradox of fragility fracture in the presence of non-osteoporotic bone mineral density in older patients with type 2 diabetes mellitus (DM2) makes it difficult to clinically predict fracture in this vulnerable group. Serum osteocalcin (OC), a marker of bone turnover, increases with normal skeletal aging indicating risk of fracture. However, OC has been reported to be lower in patients with DM2. An inverse association between higher glycated hemoglobin levels (HbA1c) and lower serum OC in older DM2 patients triggered discussions encouraging further investigation. A key question to be answered is whether changes in glucose metabolism is responsible for bone metabolic changes, ultimately leading to increased risk of fragility fractures in DM2 patients. While these studies were conducted among Caucasian and Asian populations, this has not been studied in Hispanic populations who suffer from a higher prevalence of DM2. The Cameron County Hispanic Cohort (CCHC) in Texas is a homogeneous Hispanic cohort known to have high prevalence of DM2 (30%). Our preliminary data from this cohort reported OC levels lower than the suggested threshold for fragility fracture in post-menopausal women. We further investigated whether bone turnover in older CCHC adults with DM2 show a normal pattern of skeletal aging. Samples and data were obtained from a nested cohort of 68 (21 men and 47 women) Hispanic older adults (≥50 years) who had a diagnosis of DM2. Given high prevalence of uncontrolled DM2 in this cohort, we divided population into two groups: i) poor DM2 control with HbA1c level ≥8 (48% men and 38% women) and ii) good DM2 control with HbA1c level <8). A crosssectional analysis documented associations between serum OC and age adjusted HbA1c levels. There was no direct association between age and OC concentrations in our study. Higher HbA1c was associated with lower serum OC in men (odds ratio -6.5, 95% confidence interval -12.7 to - 0.3, p < 0.04). No significant associations were identified in women. Bone turnover in older Hispanic men with DM2 in our study does not reflect normal pattern of skeletal aging. It is unclear why similar results were not identified in women. We will continue to follow this cohort to investigate longitudinal trend of changes of bone turnover and its relationship with HbA1c in both men and women of this cohort.

Rianon, N.↗
NASA NTRS2011

Fractal-Based Oscillation of Macular Arteriogenesis and Dropout During Progressive Diabetic Retinopathy

By both fractal (D1) and branching (Lv) analysis, macular arterial density oscillated with progression from mild NPDR to PDR. Results are consistent with out study reported recently for the entire arterial and venous branching trees within 50 degree FAs by VESGEN generational branching analysis. Current and previous results are important for advances in early-stage regenerative DR therapies, for which reversal of DR progression to a normal vessel density may be possible. For example, potential use of regenerative angiogenesis stimulators to reverse vascular dropout during mild and severe NPDR is not indicated for treatment of moderate NPDR.

Radharkrishnan, Krishnan↗
NASA NTRS2004

Calibration Experiments Conducted for Noninvasive Blood Glucose Sensing Through the Eye

There are more than 16 million diabetics in the United States and more than 100 million worldwide. Diabetes can lead to severe complications over time such as blindness, renal and cardiovascular diseases, and peripheral neuropathy in the limbs. Poor blood circulation in diabetics can lead to gangrene and the subsequent amputation of extremities. In addition, this pathology is the fourth leading cause of death in the United States. The most effective way to manage diabetes is frequent blood glucose monitoring performed by the patients themselves. However, because of pain, inconvenience, and the fear of developing infections from finger-prick blood tests or implants, many patients monitor their blood glucose levels less frequently than is recommended by their physicians. Therefore, a noninvasive, painless, and convenient method to monitor blood glucose would greatly benefit diabetics. Likewise, detecting, preventing, and treating the untoward effects of prolonged space travel (e.g., a human mission to Mars) in real-time requires the development of noninvasive diagnostic technologies that are compact and powerful. As a "window to the body," the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and to help develop preventative and therapeutic countermeasures early. The noninvasive feature of these technologies permits frequent repetition of tests, enabling an evaluation of the response to therapy.

Ansari, Rafat R.↗
NASA NTRS1999

Novel Approaches to Cellular Transplantation from the US Space Program

Research in the treatment of type I diabetes is entering a new era that takes advantage of our knowledge in an ever increasing variety of scientific disciplines. Some may originate from very diverse sources, one of which is the Space Program at National Aeronautics and Space Administration (NASA). The Space Program contributes to diabetes-related research in several treatment modalities. As an ongoing effort for medical monitoring of personnel involved in space exploration activities NASA and the extramural scientific community investigate strategies for noninvasive estimation of blood glucose levels. Part of the effort in the space protein crystal growth program is high-resolution structural analysis insulin as a means to better understand the interaction with its receptor and with host immune components and as a basis for rational design of a "better" insulin molecule. The Space Program is also developing laser technology for potential early cataract detection as well as a noninvasive analyses for addressing preclinical diabetic retinopathy. Finally, NASA developed an exciting cell culture system that affords some unique advantages in the propagation and maintenance of mammalian cells in vitro. The cell culture system was originally designed to maintain cell suspensions with a minimum of hydrodynamic and mechanical sheer while awaiting launch into microgravity. Currently the commercially available NASA bioreactor (Synthecon, Inc., Houston, TX) is used as a research tool in basic and applied cell biology. In recent years there is continued strong interest in cellular transplantation as treatment for type I diabetes. The advantages are the potential for successful long-term amelioration and a minimum risk for morbidity in the event of rejection of the transplanted cells. The pathway to successful application of this strategy is accompanied by several substantial hurdles: (1) isolation and propagation of a suitable uniform donor cell population; (2) management of host immune rejection; (3) protection from the autoimmune component of the disease; and (4) anatomic placement of the engrafted cells that permits timely response to blood sugar levels as well as effective release and deployment of insulin. Bioreactor technology may provide some critical advances for surmounting some of these scientific hurdles. The NASA bioreactor is a horizontally rotating cylinder that is completely filled with culture medium. Gaseous exchange is maintained by a concentric cylinder of permeable silicon. In slow rotation (15-25 rpm) particles of small mass such as cells and tissue aggregates remain suspended in the rotating body of fluid. This novel approach suspends cells without stirring thus, allowing objects of different size mass to colocate and interact in a very low shear environment. In fact, analysis of the forces acting on individual cells in the rotating bioreactor reveals that the cells are continuously falling through the fluid medium. The conditions in the bioreactor permit assembly of cells into aggregates. three-dimensional tissue growth, synthesis of intercellular matrix,10 differentiation, and some sinusoid formations that may serve as a surrogate vasculature for larger tissue segments.

Pellis, Neal R.↗
NASA NTRS1998

Antiproliferative effect of elevated glucose in human microvascular endothelial cells

Diabetic microangiopathy has been implicated as a fundamental feature of the pathological complications of diabetes including retinopathy, neuropathy, and diabetic foot ulceration. However, previous studies devoted to examining the deleterious effects of elevated glucose on the endothelium have been performed largely in primary cultured cells of macrovessel origin. Difficulty in the harvesting and maintenance of microvascular endothelial cells in culture have hindered the study of this relevant population. Therefore, the objective of this study was to characterize the effect of elevated glucose on the proliferation and involved signaling pathways of an immortalized human dermal microvascular endothelial cell line (HMEC-1) that possess similar characteristics to their in vivo counterparts. Human dermal microvascular endothelial cells (HMEC-1) were grown in the presence of normal (5 mM) or high D-glucose (20 mM) for 14 days. The proliferative response of HMEC-1 was compared under these conditions as well as the cAMP and PKC pathways by in vitro assays. Elevated glucose significantly inhibited (P < 0.05) HMEC-1 proliferation after 7, 10, and 14 days. This effect was not mimicked by 20 mM mannitol. The antiproliferative effect was more pronounced with longer exposure (1-14 days) to elevated glucose and was irreversible 4 days after a 10-day exposure. The antiproliferative effect was partially reversed in the presence of a PKA inhibitor, Rp-cAMP (10-50 microM), and/or a PKC inhibitor, Calphostin C (10 nM). HMEC-1 exposed to elevated glucose (20 mM) for 14 days caused an increase in cyclic AMP accumulation, PKA, and PKC activity but was not associated with the activation of downstream events such as CRE and AP-1 binding activity. These data support the hypothesis that HMEC-1 is a suitable model to study the deleterious effects of elevated glucose on microvascular endothelial cells. Continued studies with HMEC-1 may prove advantageous in delineation of the molecular pathophysiology associated with diabetic microangiopathy.

NASA Discipline Cell Biology↗
NASA NTRS2017

Association Between Vascular Density and Loss of Protective RAS During Early NPDR by Fractal Dimension

Purpose: Our hypothesis predicts that blood vessels within the retina increase in density during early-stage nonproliferative diabetic retinopathy (NPDR), based on previous results of a small retrospective study. For the current prospective study, the remodeling of arteries and veins during progression of early NPDR is assessed by a repertoire of parameters that includes the fractal dimension (D(sub f) ). In complex structures such as branching vascular trees, D(sub f) is a sensitive measure of space-filing capacity. The renin-angiotensin system (RAS) is implicated in DR pathogenesis and the function of circulating angiogenic cells (CACs), a critical bone marrow-derived population instrumental in vascular repair. Methods: Arterial and venous branching patterns were extracted from images of 6 normal controls and 3 early NPDR subjects (2 moderate, 1 mild) acquired by Heidelberg Spectralis (Registered Trademark) OCT following fluorescein angiography (FA). The vascular branching patterns were analyzed by NASAs VESsel GENeration Analysis (VESGEN) software, in which skeletonized representations were generated automatically to yield D(sub f) by the box-counting method. For binary 2D images, D(sub f) varies between limiting Euclidean dimensions of 1 and 2. Peripheral blood of diabetics and controls was collected for CD34+ CAC isolation. The gene expression of RAS in CACs was assessed by qPCR for Mas receptor to Ang-(1-7). The vasoreparative function of the CACs was measured by migration ability toward CXCL12 (SDF-1). Results: By D(sub f), venous and arterial densities were 1.370 +/- 0.006 and 1.329 +/- 0.016 for early NPDR, compared to 1.318 +/- 0.012 and 1.320 +/- 0.036 for control. The space filling capacity in early NPDR measured by D(sub f), a sensitive parameter, therefore demonstrated a pronounced increase for veins, but not for arteries. Mas receptor mRNA in CACs was increased in diabetics without DR but reduced with onset of NPDR, indicating possible loss of compensation of protective RAS during early DR. Migratory dysfunction of CD34+ cells was further associated with DR. Conclusions: As assessed by the fractal dimension in our preliminary study, the space-filling capacity of veins, but not arteries, was greater in early NPDR than in control. Larger patient populations will be examined as we complete our ongoing longitudinal study. Results further suggest the protective RAS axis within diabetic CACs is lost early in DR and is associated with increased vascular remodeling as evidenced by VESGEN analysis.

vascular↗
NASA NTRS2002

Insulin secretion and sensitivity in space flight: diabetogenic effects

Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of "other" causes of diabetes, including, but not restricted to, genetic beta-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-alpha production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the "disposition index" as an essential model to be used in the clinical management of space flight-induced muscle loss.

Review↗
NASA NTRS2001

Evidence of Stratosphere-to-Troposphere Transport Within a Mesoscale Model and Total Ozone Mapping Spectrometer Total Ozone

We evaluate evidence for stratospheric mass transport into, and mass remaining in, the troposphere during an intense midlatitude cyclone. Mesoscale forecast model analysis fields from the Mesoscale Analysis and Prediction System were matched with total ozone observations from the Total Ozone Measurement Spectrometer. Combined with parcel back trajectory calculations, the analyses imply that two mechanisms contributed to the mass exchange: (1) An area of dynamically induced exchange was observed on the cyclone's southern edge. Parcels originally in the stratosphere crossed the jet core and were diluted through turbulent mixing with tropospheric air; (2) Diabetic effects reduced parcel potential vorticity (PC) for trajectories traversing precipitation regions, creating a 'PV hole' signature in the center of the cyclone. Air with characteristics of ozone and water vapor found in the lower stratosphere remained in the troposphere. The strength of the latter process may be unusual. Combined with other research, these results suggest that precipitation-induced diabetic effects can significantly modify (either decreasing or increasing) parcel potential vorticity, depending on parcel trajectory configuration with respect to maximum heating regions and jet core. The diabetic heating effect on stratosphere-troposphere exchange (STE) is more important to tropopause erosion than to altering parcel trajectories. In addition, these results underline the importance of using not only PC but also chemical constituents for diagnoses of STE.

Olsen, Mark A.↗
NASA NTRS1998

Autonomic neuropathies

A limited autonomic neuropathy may underlie some unusual clinical syndromes, including the postural tachycardia syndrome, pseudo-obstruction syndrome, heat intolerance, and perhaps chronic fatigue syndrome. Antibodies to autonomic structures are common in diabetes, but their specificity is unknown. The presence of autonomic failure worsens prognosis in the diabetic state. Some autonomic neuropathies are treatable. Familial amyloid polyneuropathy may respond to liver transplantation. There are anecdotal reports of acute panautonomic neuropathy responding to intravenous gamma globulin. Orthostatic hypotension may respond to erythropoietin or midodrine.

Non-NASA Center↗
NASA NTRS2016

Association Between Increased Vascular Density and Loss of Protective RAS in Early-Stage NPDR

Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The prevailing paradigm of NPDR progression is that vessels drop out prior to abnormal, vision-impairing regrowth at late-stage proliferative diabetic retinopathy (DR). However, surprising results for our previous preliminary study 1 with NASA's VESsel GENeration Analysis (VESGEN) software showed that vessels proliferated considerably during moderate NPDR compared to drop out at both mild and severe NPDR. Validation of our hypothesis will support development of successful early-stage regenerative therapies such as vascular repair by circulating angiogenic cells (CACs). The renin-angiotensin system (RAS)is implicated in the pathogenesis of DR and in the function of CACs, a critical bone marrow-derived population that is instrumental in vascular repair.

Fractal↗
NASA NTRS1984

Computer Analysis of Eye Blood-Vessel Images

Technique rapidly diagnoses diabetes mellitus. Photographs of "whites" of patients' eyes scanned by computerized image analyzer programmed to quantify density of small blood vessels in conjuctiva. Comparison with data base of known normal and diabetic patients facilitates rapid diagnosis.

Wall, R. J.↗