Engineering topics

Heer, M.

Publications and source records attributed to Heer, M..

8 records

NASA NTRS2016

Risk of Visual Impairment and Intracranial Hypertension After Space Flight: Evaluation of the Role of Polymorphism of Enzymes Involved in One-Carbon Metabolism

Data from the Nutritional Status Assessment protocol provided biochemical evidence that the one-carbon metabolic pathway may be altered in individuals experiencing vision-related issues during and after space flight (1, 2). Briefly, serum concentrations of homocysteine, cystathionine, 2-methylcitric acid, and methylmalonic acid were significantly (P<0.001) higher (25-45%) in astronauts with ophthalmic changes than in those without such changes (1). These differences existed before, during, and after flight. Serum folate was lower (P<0.01) during flight in individuals with ophthalmic changes. Preflight serum concentrations of cystathionine and 2-methylcitric acid, and mean in-flight serum folate, were significantly (P<0.05) correlated with postflight changes in refraction (1). A follow-up study was conducted to evaluate a small number of known polymorphisms of enzymes in the one-carbon pathway, and to evaluate how these relate to vision and other medical aspects of the eye. Specifically, we investigated 5 polymorphisms in MTRR, MTHFR, SHMT, and CBS genes and their association with ophthalmic changes after flight in 49 astronauts. The number of G alleles of MTRR 66 and C alleles of SHMT1 1420 both contributed to the odds of visual disturbances (3). Block regression showed that B-vitamin status at landing and genetics were significant predictors for many of the ophthalmic outcomes studied (3). In conclusion, we document an association between MTRR 66 and SHMT1 1420 polymorphisms and space flightinduced vision changes. These data document that individuals with an altered 1-carbon metabolic pathway may be predisposed to anatomic and/or physiologic changes that render them susceptible to ophthalmic damage during space flight.

Smith, S. M.↗

NASA NTRS2015

Fibroblast Growth Factor 23 in Long-Duration Spaceflight

Bokhari, R.↗

NASA NTRS2014

Fibroblast Growth Factor-23 in Bed Rest and Spaceflight

Many nutritional factors influence bone, from the basics of calcium and vitamin D, to factors which influence bone through acid/base balance, including protein, sodium, and more. Fibroblast growth factor 23 (FGF23) is a recently identified factor, secreted from osteocytes, which is involved in classic (albeit complex) feedback loops controlling phosphorus homeostasis through both vitamin D and parathyroid hormone (PTH) (1, 2). As osteocytes are gravity sensing cells, it is important to determine if there are changes in FGF23 during spaceflight. In extreme cases, such as chronic kidney disease, FGF23 levels are highly elevated. FGF23 imbalances, secondary to dietary influences, may contribute to skeletal demineralization and kidney stone risk during spaceflight. Presented with an imbalanced dietary phosphorus to calcium ratio, increased secretion of FGF23 will inhibit renal phosphorus reabsorption, resulting in increased excretion and reduced circulating phosphorus. Increased intake and excretion of phosphorus is associated with increased kidney stone risk in both the terrestrial and microgravity environments. Highly processed foods and carbonated beverages are associated with higher phosphorus content. Ideally, the dietary calcium to phosphorus ratio should be at minimum 1:1. Nutritional requirements for spaceflight suggest that this ratio not be less than 0.67 (3), while the International Space Station (ISS) menu provides 1020 mg Ca and 1856 mg P, for a ratio of 0.55 (3). Subjects in NASA's bed rest studies, by design, have consumed intake ratios much closer to 1.0 (4). FGF23 also has an inhibitory influence on PTH secretion and 1(alpha)-hydroxylase, both of which are required for activating vitamin D with the conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Decreased 1,25-dihydroxyvitamin D will result in decreased intestinal phosphorus absorption, and increased urinary phosphorus excretion (via decreased renal reabsorption). Should a decrease in 1,25- dihydroxyvitamin D be necessary to reduce intestinal phosphorus absorption, calcium absorption will also proportionally be reduced, potentially leading to skeletal demineralization. Demineralization of bone can increase kidney stone risk, a medical issue that could prove detrimental to mission success. Given the interrelationships described above, we sought to determine circulating FGF23 concentrations in spaceflight and ground analog studies to better understand the potential effects of dietary phosphorus on bone and calcium metabolism. We analyzed serum from ISS astronauts participating in studies of bone biochemistry, including the Nutrition SMO and Pro K experiments, and we also evaluated FGF23 during extended-duration bed rest. Serum intact FGF23 levels were determined using an ELISA kit from Kainos laboratories in Japan. While initial evaluation of the data showed no changes over time during flight or bed rest, evaluation continues of FGF23 data in light of dietary factors, PTH, vitamin D status, and other biochemical and endocrine factors.

Bokhari, R.↗

NASA NTRS2009

Nutritional Status Assessment (SMO 016E)

Until 2006, it was not been possible to assess nutritional status of crewmembers on the ISS during flight because blood and urine could not be collected during ISS missions. Postflight observations of alterations in status of several nutrients are troubling, and we require the ability to monitor the status of these nutrients during flight to determine if there is a specific impetus or timeframe for these changes. In addition to the monitoring of crew nutritional status during flight, in-flight sample collection would allow better assessment of countermeasure effectiveness. Collecting samples during flight is one of the objectives of SMO 016E, and it is also designed to expand the current medical requirement for nutritional assessment (MR016L) to include additional normative markers for assessing crew health and countermeasure effectiveness. Additional markers of bone metabolism will be measured to better monitor bone health and the effectiveness of countermeasures to prevent bone resorption. New markers of oxidative damage will be measured to better assess the type of oxidative insults that occur during space flight. The array of nutritional assessment variables will be expanded to include ones that will allow us to better understand changes in folate, vitamin K, and vitamin B6 status, as well as risk factors for cardiovascular and oxidative damage during and after flight. Stress hormones and hormones that affect bone and muscle metabolism will also be measured. Measuring these additional variables will allow us to better monitor the health of crewmembers and make more accurate recommendations for their rehabilitation. Several nutritional assessment variables are altered at landing, but it is not known how long these changes persist. We extended the original protocol to include an additional postflight blood and urine sample collection 30 days after landing. Data are being collected before, during, and after flight. These data will provide a complete survey of how nutritional status and related systems are affected by space flight. Analyzing the data will help us to define nutritional requirements for long-duration missions. This expanded set of measurements will also aid in the identification of nutritional countermeasures to counteract, for example, the deleterious effects of microgravity on bone and muscle and the effects of space radiation.

Smith, S. M.↗

NASA NTRS2009

Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism during Spaceflight and Recovery (Pro K)

Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

Smith, Scott M.↗

NASA NTRS2007

Artificial Gravity: Effects on Bone Turnover

The impact of microgravity on the human body is a significant concern for space travelers. Since mechanical loading is a main reason for bone loss, artificial gravity might be an effective countermeasure to the effects of microgravity. In a 21-day 6 head-down tilt bed rest (HDBR) pilot study carried out by NASA, USA, the utility of artificial gravity (AG) as a countermeasure to immobilization-induced bone loss was tested. Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density was determined by DXA and pQCT before and after bed rest. Urinary excretion of bone resorption markers (n-telopeptide and helical peptide) were increased from pre-bed rest, but there was no difference between the control and the AG group. The same was true for serum c-telopeptide measurements. Bone formation markers were affected by bed rest and artificial gravity. While bone-specific alkaline phosphatase tended to be lower in the AG group during bed rest (p = 0.08), PINP, another bone formation marker, was significantly lower in AG subjects than CN before and during bed rest. PINP was lower during bed rest in both groups. For comparison, artificial gravity combined with ergometric exercise was tested in a 14-day HDBR study carried out in Japan (Iwase et al. J Grav Physiol 2004). In that study, an exercise regime combined with AG was able to significantly mitigate the bed rest-induced increase in the bone resorption marker deoxypyridinoline. While further study is required to more clearly differentiate bone and muscle effects, these initial data demonstrate the potential effectiveness of short-radius, intermittent AG as a countermeasure to the bone deconditioning that occurs during bed rest and spaceflight. Future studies will need to optimize not only the AG prescription (intensity and duration), but will likely need to include the use of exercise or other combined treatments.

Heer, M.↗

NASA NTRS2007

Nutritional Status Assessment (SMO 016E)

It has not been possible to assess nutritional status of crew members on the ISS during flight because blood and urine could not be collected during ISS missions. Postflight observations of alterations in nutritional status for several nutrients are troubling, and we require the ability to monitor the status of these nutrients during flight to determine if there is a specific impetus or timeframe for these changes. In addition to the monitoring of crew nutritional status during flight, in-flight sample collection would allow better assessment of countermeasure effectiveness. SMO 016E is also designed to expand the current medical requirement for nutritional assessment (MR016L) to include additional normative markers for assessing crew health and countermeasure effectiveness. Additional markers of bone metabolism will be measured to better monitor bone health and the effectiveness of countermeasures to prevent bone resorption. New markers of oxidative damage will be measured to better assess the type of oxidative insults that occur during space flight. The array of nutritional assessment parameters will be expanded to include parameters that will allow us to better understand changes in folate and vitamin B6 status, and related cardiovascular risk factors during and after flight. Additionally, stress hormones and hormones that affect bone and muscle metabolism will also be measured. This additional assessment will allow us to better monitor the health of crew members and make more accurate recommendations for their rehabilitation. Several nutritional assessment parameters are altered at landing, but it is not known how long these changes persist. We extended the current protocol to include an additional postflight blood and urine sample collection 30 days after landing. Data are being collected before, during, and after flight. These data will provide a complete survey of how nutritional status and related systems are affected by space flight. Analyzing the data will help us to define nutritional requirements for long-duration missions. This expanded set of measurements will also aid in the identification of nutritional countermeasures to counteract, for example, the deleterious effects of microgravity on bone and muscle and the effects of space radiation.

Smith, S. M.↗

NASA NTRS1991

Effects of 10 days 6 degrees head-down tilt on the responses to fluid loading and lower body negative pressure

In an international collaborative project six normal male subjects were studied before, during and after 10 days 6 degrees HDT. Fluid intake was controlled at 40 ml/(kgbw day). Urine volume and body weight were determined daily. Fluid loading and LBNP were performed in all three phases of the study. Body weight diminished by 2.6% because of fluid loss. Blood volume diminished by 13%. The responses to fluid loading were similar in the three phases of the study. Sixty minutes after end of infusion only 5.5% of the infused saline remained in the intravascular compartment. Excess interstitial fluid was eliminated in the next 24 hs but a negative balance was recorded also in the following day. The compliance of the lower limbs expressed as the rate of limb volume change/unit LBNP change was increased at the end of the HDT phase and during the post HDT phase. The set point of intravascular volume was defended, as shown by the response to FL. HDT increased the compliance of the lower limbs.

Non-NASA Center↗