Structure-Function Correlations in the Mechanism of Action of Key Antiperspirant Agents Containing Al(III) and ZAG Salts.

Aluminum hydrolysis chemistry is an important part of modern society because of the dominance of Al(III) as a highly effective antiperspirant active. However, the century-old chemistry centered on aluminum chloride (ACL) is not comprehensive enough to address all of the in vivo events associated with current commercial antiperspirants and their mechanism of action. The present study aims to address the knowledge gap among extensively studied benchmark ACL, its modified version aluminum chlorohydrate (ACH), and a more complex but less explored group of aluminum zirconium chlorohydrate glycine complexes (ZAG salts) toward understanding the mechanism of action under consumer-relevant conditions. ACH, which is the Al source used in the manufacture of ZAG salts, provides a bridge between ACL and ZAG chemistry. High viscosity and gel formation driven by pH and a specific Al(III) salt upon hydrolysis are considered the criteria for building an in vivo occlusive mass to retard or stop the flow of sweat to the skin surface, thus providing an antiperspirant effect. Rheological studies indicated that ACL and aluminum zirconium tetrachlorohydrex glycine (TETRA) were the most efficacious salt actives. Spectroscopic studies, diffraction studies, and elemental analysis suggested that small metal oxide and hydroxide species with coparticipating glycine as well as various polynuclear and oligomeric species are the key to gel formation. At a given pH, the key ingredients (NaCl, urea, bovine serum albumin, and lactic acid) in artificial sweat were found to have little influence on Al(III) salt hydrolysis. The effects of the sweat components were mostly limited to local complex formation and kinetic modification. The in vitro comparative experiments with various Al(III) and ZAG salt systems offer unprecedented insights into the chemistry of different salt types, thus paving the way for engineering more efficacious antiperspirant systems.

Quantifying the Deposition of Airborne Particulate Matter Pollution on Skin Using Elemental Markers.

Airborne particulate matter (PM) pollution is an environmental and health concern. The health impact of PM pollution has typically focused on the respiratory system. The impact of PM pollution on skin has been largely understudied due to the lack of a quantitative method to measure the deposition on skin. This manuscript presents a method to quantify PM pollution on skin using elemental markers as a proxy for PM. Skin tape strips were collected from forehead and buttock of 100 outdoor workers in Beijing, China. Skin samples were analyzed for 19 elemental markers using inductively coupled plasma mass spectrometry. To determine the specific elemental signature of PM for the region, air samples were collected over 7 days for PM < 2.5 µm (PM2.5) and analyzed for the same 19 elements as the skin samples. An enrichment factor was calculated for each element and the potential source was evaluated. Using the elemental markers unique to PM pollution for the region, the PM concentration deposited on skin was determined to be 0.621-2.53 µg PM2.5 /cm2. This method can be re-applied in different regions and the PM concentration on skin can inform future studies on the health impact of air pollution on skin.

High dietary iron increases oxidative stress and radiosensitivity in the rat retina and vasculature after exposure to fractionated gamma radiation.

Radiation exposure in combination with other space environmental factors including microgravity, nutritional status, and deconditioning is a concern for long-duration space exploration missions. Astronauts experience altered iron homeostasis due to adaptations to microgravity and an iron-rich food system. Iron intake reaches three to six times the recommended daily allowance due to the use of fortified foods on the International Space Station. Iron is associated with certain optic neuropathies and can potentiate oxidative stress. This study examined the response of eye and vascular tissue to gamma radiation exposure (3 Gy fractionated at 37.5 cGy per day every other day for 8 fractions) in rats fed an adequate-iron diet or a high-iron diet. Twelve-week-old Sprague-Dawley rats were assigned to one of four experimental groups: adequate-iron diet/no radiation (CON), high-iron diet/no radiation (IRON), adequate-iron diet/radiation (RAD), and high-iron diet/radiation (IRON+RAD). Animals were maintained on the corresponding iron diet for 2 weeks before radiation exposure. As previously published, the high-iron diet resulted in elevated blood and liver iron levels. Dietary iron overload altered the radiation response observed in serum analytes, as evidenced by a significant increase in catalase levels and smaller decrease in glutathione peroxidase and total antioxidant capacity levels. 8-OHdG immunostaining, showed increased intensity in the retina after radiation exposure. Gene expression profiles of retinal and aortic vascular samples suggested an interaction between the response to radiation and high dietary iron. This study suggests that the combination of gamma radiation and high dietary iron has deleterious effects on retinal and vascular health and physiology.

Using natural, stable calcium isotopes of human blood to detect and monitor changes in bone mineral balance.

We are exploring variations in the Ca isotope composition of blood and urine as a new tool for early diagnosis and monitoring of changes in bone mineral balance for patients suffering from metabolic bone disease, cancers that originate in or metastasize to bone, and for astronauts who spend time in low gravity environments. Blood samples are often collected instead of, or in addition to, urine in clinical settings, so it is useful to know if variations in the Ca isotope composition of blood carry the same information as variations in urine. We found that the Ca isotope composition of blood shifts in the same direction and to the same magnitude (~2 parts per ten thousand--pptt) as that of urine in response to skeletal unloading during bed rest. However, the Ca isotope composition of blood is lighter than that of urine by 12 ± 2 pptt. This offset between blood and urine may result from Ca isotope fractionation occurring in the kidneys. This is the first study to confirm the suspected offset between the Ca isotope composition of blood and urine in humans, to directly quantify its magnitude, and to establish that either blood or urine can be used to detect and quantify bone loss.

Body mass changes during long-duration spaceflight.

BACKGROUND: During early spaceflights, many crewmembers did not meet their caloric requirements and consequently lost body mass during flight, as assessed by a decrease in postflight body mass. Maintaining body mass during spaceflight is crucial for maintaining crew health and monitoring body mass is thus important to medical operations as well as being a key component of human research. Determining body mass becomes difficult in a microgravity environment. METHODS: We report data from two mass measurement devices on the International Space Station (ISS): the Russian body mass measuring device (BMMD), which uses spring oscillation physics, and NASA's Space Linear Acceleration Mass Measurement Device (SLAMMD), which uses Newton's second law of motion (F = ma). RESULTS: For 25 crewmembers whose body mass was measured on both devices, significant body mass loss occurred compared to preflight (gravimetric scale) and averaged -4.4% as assessed by BMMD and -2.8% as assessed by SLAMMD. After an initial loss in the first 30 d of flight, body mass remained constant through the rest of the mission, as determined using either device. The mean difference between the two devices was 1.1 kg when the closest SLAMMD and BMMD measurements were compared (6.9 ± 6.2 d apart). Dietary intake during flight is approximately 80% of the World Health Organization estimated requirement and the decrease in body mass follows in-flight energy intake closely on average. CONCLUSION: Body mass monitoring is important for monitoring crew health during a mission and to help ensure that crewmembers consume adequate energy intake to mitigate the risks of spaceflight.

Sex-specific responses of bone metabolism and renal stone risk during bed rest.

The purpose of this study was to directly assess sex differences in bone loss, bone biochemistry, and renal stone risk in bed rest. Bed rest simulates some spaceflight effects on human physiology and can be used to address the potential existence of sex-specific effects on bone metabolism and renal stone risk in space. We combined data from the control subjects in five head-down-tilt bed rest studies (combined n = 50 men, 24 women) of differing durations (14-90 days). All subjects were healthy volunteers. Mean age was 35 ± 9 years for women and 33 ± 8 years for men. The main outcome measures were bone density and biochemistry, and renal stone risk chemistry. Before bed rest began, men had higher bone mineral density and content (P < 0.001), and excreted more biomarkers of bone resorption and calcium per day than did women (P < 0.05). These differences remained during bed rest. A number of urine chemistry analytes increased (e.g., calcium) or decreased (e.g., sodium, citrate, and urine volume) significantly for men and women during bed rest. These changes may predispose men to higher stone risk. Men and women do not have substantially different responses to the skeletal unloading of bed rest.

Increased dietary iron and radiation in rats promote oxidative stress, induce localized and systemic immune system responses, and alter colon mucosal environment.

Astronauts are exposed to increased body iron stores and radiation, both of which can cause oxidative damage leading to negative health effects. The purpose of this study was to investigate combined effects of high dietary iron (650 mg/kg diet) and radiation exposure (0.375 Gy cesium-137 every other day for 16 d) on markers of oxidative stress, immune system function, and colon mucosal environment in male Sprague-Dawley rats (n=8/group). Control rats consumed adequate iron (45 mg/kg diet) and were not irradiated. Combined treatments increased liver glutathione peroxidase, serum catalase, and colon myeloperoxidase while decreasing total fecal short-chain fatty acid concentrations. The high-iron diet alone increased leukocyte count. Radiation decreased the T-cell CD4:CD8 ratio. Plasma iron was negatively correlated with cytokine production in activated monocytes. Genes involved in colon microbial signaling, immune response, and injury repair were altered by radiation. Genes involved with injury repair and pathogen recognition changed with dietary iron. These data demonstrate that dietary iron and radiation, alone and combined, contribute to oxidative stress that is related to immune system alterations in circulation and the colon. The model presented may help us better understand the changes to these systems that have been identified among astronauts.

Iron status and its relations with oxidative damage and bone loss during long-duration space flight on the International Space Station.

BACKGROUND: Increases in stored iron and dietary intake of iron during space flight have raised concern about the risk of excess iron and oxidative damage, particularly in bone. OBJECTIVES: The objectives of this study were to perform a comprehensive assessment of iron status in men and women before, during, and after long-duration space flight and to quantify the association of iron status with oxidative damage and bone loss. DESIGN: Fasting blood and 24-h urine samples were collected from 23 crew members before, during, and after missions lasting 50 to 247 d to the International Space Station. RESULTS: Serum ferritin and body iron increased early in flight, and transferrin and transferrin receptors decreased later, which indicated that early increases in body iron stores occurred through the mobilization of iron to storage tissues. Acute phase proteins indicated no evidence of an inflammatory response during flight. Serum ferritin was positively correlated with the oxidative damage markers 8-hydroxy-2'-deoxyguanosine (r = 0.53, P < 0.001) and prostaglandin F2α (r = 0.26, P < 0.001), and the greater the area under the curve for ferritin during flight, the greater the decrease in bone mineral density in the total hip (P = 0.031), trochanter (P = 0.006), hip neck (P = 0.044), and pelvis (P = 0.049) after flight. CONCLUSION: Increased iron stores may be a risk factor for oxidative damage and bone resorption.

Bioavailability of nanoparticulate hematite to Arabidopsis thaliana.

The environmental effects and bioavailability of nanoparticulate iron (Fe) to plants are currently unknown. Here, plant bioavailability of synthesized hematite Fe nanoparticles was evaluated using Arabidopsis thaliana (A. thaliana) as a model. Over 56-days of growing wild-type A. thaliana, the nanoparticle-Fe and no-Fe treatments had lower plant biomass, lower chlorophyll concentrations, and lower internal Fe concentrations than the Fe-treatment. Results for the no-Fe and nanoparticle-Fe treatments were consistently similar throughout the experiment. These results suggest that nanoparticles (mean diameter 40.9 nm, range 22.3-67.0 nm) were not taken up and therefore not bioavailable to A. thaliana. Over 14-days growing wild-type and transgenic (Type I/II proton pump overexpression) A. thaliana, the Type I plant grew more than the wild-type in the nanoparticle-Fe treatment, suggesting Type I plants cope better with Fe limitation; however, the nanoparticle-Fe and no-Fe treatments had similar growth for all plant types.

Space flight calcium: implications for astronaut health, spacecraft operations, and Earth.

The space flight environment is known to induce bone loss and, subsequently, calcium loss. The longer the mission, generally the more bone and calcium are lost. This review provides a history of bone and calcium studies related to space flight and highlights issues related to calcium excretion that the space program must consider so that urine can be recycled. It also discusses a novel technique using natural stable isotopes of calcium that will be helpful in the future to determine calcium and bone balance during space flight.

Bone metabolism and nutritional status during 30-day head-down-tilt bed rest.

Bed rest studies provide an important tool for modeling physiological changes that occur during spaceflight. Markers of bone metabolism and nutritional status were evaluated in 12 subjects (8 men, 4 women; ages 25-49 yr) who participated in a 30-day -6° head-down-tilt diet-controlled bed rest study. Blood and urine samples were collected twice before, once a week during, and twice after bed rest. Data were analyzed using a mixed-effects linear regression with a priori contrasts comparing all days to the second week of the pre-bed rest acclimation period. During bed rest, all urinary markers of bone resorption increased ~20% (P < 0.001), and serum parathyroid hormone decreased ~25% (P < 0.001). Unlike longer (>60 days) bed rest studies, neither markers of oxidative damage nor iron status indexes changed over the 30 days of bed rest. Urinary oxalate excretion decreased ~20% during bed rest (P < 0.001) and correlated inversely with urinary calcium (R = -0.18, P < 0.02). These data provide a broad overview of the biochemistry associated with short-duration bed rest studies and provide an impetus for using shorter studies to save time and costs wherever possible. For some effects related to bone biochemistry, short-duration bed rest will fulfill the scientific requirements to simulate spaceflight, but other effects (antioxidants/oxidative damage, iron status) do not manifest until subjects are in bed longer, in which case longer studies or other analogs may be needed. Regardless, maximizing research funding and opportunities will be critical to enable the next steps in space exploration.

Rapidly assessing changes in bone mineral balance using natural stable calcium isotopes.

The ability to rapidly detect changes in bone mineral balance (BMB) would be of great value in the early diagnosis and evaluation of therapies for metabolic bone diseases such as osteoporosis and some cancers. However, measurements of BMB are hampered by difficulties with using biochemical markers to quantify the relative rates of bone resorption and formation and the need to wait months to years for altered BMB to produce changes in bone mineral density large enough to resolve by X-ray densitometry. We show here that, in humans, the natural abundances of Ca isotopes in urine change rapidly in response to changes in BMB. In a bed rest experiment, use of high-precision isotope ratio MS allowed the onset of bone loss to be detected in Ca isotope data after about 1 wk, long before bone mineral density has changed enough to be detectable with densitometry. The physiological basis of the relationship between Ca isotopes and BMB is sufficiently understood to allow quantitative translation of changes in Ca isotope abundances to changes in bone mineral density using a simple model. The rate of change of bone mineral density inferred from Ca isotopes is consistent with the rate observed by densitometry in long-term bed rest studies. Ca isotopic analysis provides a powerful way to monitor bone loss, potentially making it possible to diagnose metabolic bone disease and track the impact of treatments more effectively than is currently possible.

High-precision measurement of variations in calcium isotope ratios in urine by multiple collector inductively coupled plasma mass spectrometry.

We describe a new chemical separation method to isolate Ca from other matrix elements in biological samples, developed with the long-term goal of making high-precision measurement of natural stable Ca isotope variations a clinically applicable tool to assess bone mineral balance. A new two-column procedure utilizing HBr achieves the purity required to accurately and precisely measure two Ca isotope ratios ((44)Ca/(42)Ca and (44)Ca/(43)Ca) on a Neptune multiple collector inductively coupled plasma mass spectrometer (MC-ICPMS) in urine. Purification requirements for Sr, Ti, and K (Ca/Sr > 10 000; Ca/Ti > 10 000 000; and Ca/K > 10) were determined by addition of these elements to Ca standards of known isotopic composition. Accuracy was determined by (1) comparing Ca isotope results for samples and standards to published data obtained using thermal ionization mass spectrometry (TIMS), (2) adding a Ca standard of known isotopic composition to a urine sample purified of Ca, and (3) analyzing mixtures of urine samples and standards in varying proportions. The accuracy and precision of δ(44/42)Ca measurements of purified samples containing 25 µg of Ca can be determined with typical errors less than ±0.2‰ (2σ).

Fe isotope fractionation during equilibration of Fe-organic complexes.

Despite the importance of Fe-organic complexes in the environment, few studies have investigated Fe isotope effects driven by changes in Fe coordination that involve organic ligands. Previous experimental (Dideriksen et al., 2008, Earth Planet Sci. Lett. 269:280-290) and theoretical (Domagal-Goldman et al., 2009, Geochim. Cosmochim. Acta 73:1-12) studies disagreed on the sense of fractionation between Fe-desferrioxamine B (Fe-DFOB) and Fe(H(2)O)(6)(3+). Using a new experimental technique that employs a dialysis membrane to separate equilibrated Fe-ligand pools, we measured the equilibrium isotope fractionations between Fe-DFOB and (1) Fe bound to ethylenediaminetetraacetic acid (EDTA) and (2) Fe bound to oxalate. We observed no significant isotope fractionation between Fe-DFOB and Fe-EDTA (Delta(56/54)Fe(Fe-DFOB/Fe-EDTA) approximately 0.02 +/- 0.11 per thousand) and a small but significant fractionation between Fe-DFOB and Fe-oxalate (Delta(56/54)Fe(Fe-DFOB/Fe-Ox(3)) = 0.20 +/- 0.11 per thousand). Taken together, our results and those of Dideriksen et al. (2008) reveal a strong positive correlation between measured fractionation factors and the Fe-binding affinity of the ligands. This correlation supports the experimental results of Dideriksen et al. (2008). Further, it provides a simple empirical tool that may be used to predict fractionation factors for Fe-ligand complexes not yet studied experimentally.