The efficacy of DFO-HOPO, DTPA-DX and DTPA for enhancing the excretion of plutonium and ameriicum from the rat.

A hydroxypridinone derivative of desferrioxamine (Na-DFO-HOPO), a dihydroxamic derivative of diethylenetriaminepenta-acetic acid (ZnNa-DTPA-DX), and DTPA (CaNa3- and ZnNa3-DTPA) were tested at dosages of 30 mumol kg-1 for their ability to remove 238Pu or 241Am from rats after their intravenous injection as citrate or inhalation as nitrate. The most effective treatment regimen for injected Pu was the repeated administration of DFO-HOPO; by 7 days the body content was reduced to 8% of that in untreated animals. Repeated dosages of 3 mumol kg-1 DFO-HOPO were as effective as those of 30 mumol kg-1 DTPA. After inhalation of Pu nitrate, repeated treatment with DTPA, DTPA-DX or DFO-HOPO reduced the body content by 7 days to, respectively, 10, 15 and 31% of those in untreated animals. After inhalation of Am, DTPA-DX and DTPA were equally effective, the body contents being reduced to 7% of control values with repeated treatment. Injection of DFO-HOPO was ineffective for enhancing the elimination of inhaled or injected Am. The results confirm the strategy of examining the use of siderophore analogues for the decorporation of Pu or Am. However, at present DTPA should remain the agent of choice, particularly after inhalation.     

The efficacies of 3,4,3-LIHOPO and DTPA for enhancing the excretion of plutonium and americium from the rat: comparison with other siderophore analogues.

With DTPA as a comparison, the siderophore analogue code named 3,4,3-LIHOPO has been tested for its ability to remove 238Pu and 241Am from rats after their inhalation or intravenous injection as nitrate. The most effective treatment regimen for inhaled Pu was the repeated administration of 30 mumol kg-1 3,4,3-LIHOPO. By 7 days after exposure, the Pu contents of the lungs and total body were reduced respectively to 2 and 4% of those in untreated animals. These values were six and three times less than when DTPA was administered using the same protocol. For inhaled Am, 3,4,3-LIHOPO and DTPA were considered equally effective, the lung and total body contents being reduced respectively to 13 and 10% of those in controls. Some animals showed slight degenerative changes in the liver and proximal tubules of the kidneys after the repeated administration of 30 mumol kg-1 of 3,4,3-LIHOPO; however these changes were less marked than after DTPA treatment. After the intravenous injection of Pu, the most effective regimen was the single administration of 3 mumol kg-1 3,4,3-LIHOPO. The body content at 7 days was reduced to 7% controls compared with 19% after the repeated administration of 30 mumol kg-1 DTPA. At a dosage of 30 mumol kg-1, 3,4,3-LIHOPO was less effective owing to the higher retention of Pu in the liver. With repeated dosages of 30 mumol kg-1 3,4,3-LIHOPO was more effective than DTPA for the decorporation of Am; the body contents were 16 and 31% of those in controls respectively. Importantly, the body content was still reduced to 28% of control after a single administration of 3 mumol kg-1. The ligand 3,4,3-LIHOPO, which is also superior to other siderophore analogues, could represent a most significant development in the decorporation of Pu and Am.     

Efficacy and Toxicity of NN′N″N‴-tetra(2,3,4-trihydroxybenzoyl)-spermine for Decorporation of 239Pu from Mice

Summary

Male SAS/4 mice were injected i.v. with 6·6 kBq ²³⁹Pu-citrate. After 1 or 24 h a single i.p. injection of 15 or 30 μmol kg^?1 or repeated (three or four) daily injections of 30 μmol kg^?1 of tetra-THB-spermine were given, and at 4 or 7 days Pu retention was measured in liver, kidneys and femur. Besides tetra-THB-spermine, equimolar doses of tetra-DHB-spermine were injected for comparison, or equimolar doses of diethylene triamine-pentaacetic acid (DPTA) as a reference compound. Histological changes in kidneys and liver were examined after i.p. injections of 30 μmol kg^?1 or at 2–13 times higher doses of tetra-THB-spermine. The results show that: (1) Introduction of an additional hydroxy group into the aromatic moieties of tetra-DHB-spermine results in increased hydrophilicity, lower toxicity and a lower renal retention of Pu. (2) Tetra-THB-spermine and tetra-DHB-spermine are similarly effective in removing plutonium from liver and bone. Their efficacies in removing Pu from bone are approximately similar to those of DTPA but for whole-body removal they are generally inferior. (3) Multiple (30 μmol kg^?1) of tetra-THB-spermine were no more effective than a single injection at mobilizing Pu from the liver. (4) Four injections of tetra-THB-spermine induced cloudy swelling and fatty degeneration in epithelial cells of the proximal convoluted tubules. At levels of 400 μmol kg^?1 tetra-THB-spermine produced severe degenerative glomerular lesions, foci of liver necrosis and thromboses of the portal vein branch.     

The efficacies of pure LICAM(C) and DTPA on the retention of plutonium-238 and americium-241 in rats after their inhalation as nitrate and intravenous injection as citrate

The pure carboxylated catechoyl amide LICAM(C) and the calcium and zinc salts of diethylenetriaminepenta-acetic acid (DTPA), were tested for efficacy for removing 238Pu and 241Am from rats after inhalation of the nitrate or intravenous injection of the citrate. The results were compared with the efficacy of methylated LICAM(C) used in previous experiments. It was shown that: (1) after inhalation of 238Pu nitrate, DTPA was far superior to pure LICAM(C); (2) after intravenous injection of 238Pu citrate, the infusion of DTPA plus LICAM(C) was only marginally more effective than DTPA alone; and (3) after inhalation or intravenous injection of 238Pu plus 241Am, the efficacy of pure LICAM(C) was only marginally more effective than the methylated form and neither form was effective for the decorporation of 241Am. It was concluded that DTPA, at present, remains the chelating agent of choice for treating persons accidentally contaminated with transportable forms of Pu and Am.     

Efficacy of 3,4,3-LIHOPO for Enhancing the Excretion of Plutonium from Rat after Simulated Wound Contamination as a Tributyl-n-phosphate Complex

The siderophone analogue 3,4,3-LIHOPO, referred to hereafter as LIHOPO, has been examined for its ability to remove ²³⁸Pu in a tributyl-n-phosphate (TBP) complex from rat after intramuscular (i.m.) or subcutaneous (s.c.) contamination. The chelating agent was administered at a dosage of 30 µmol.kg^?1, 30 min after the contamination, either by intravenous (i.v.) or local injection. By day 7 after exposure, local (i.m.) administration of LIHOPO reduced the amounts of i.m.-injected ²³⁸Pu in the wound site, skeleton and liver to 75, 20 and 25% respectively of those in untreated animals. At the i.m. Pu wound site, local treatment was superior to i.v. treatment; both ligands were equally effective. At the s.c. Pu wound site, local and systemic treatments were equally effective and LIHOPO was superior to DTPA. After translocation, LIHOPO was the most effective treatment for enhancing Pu excretion, whatever the route of contamination and treatment: the administration of LIHOPO and DTPA reduced whole-body Pu retention by a factor 1·8 and 1·4 respectively. All these results are encouraging for the use of LIHOPO in the future but more studies are needed, concerning both the toxicity of the compound and its use in man.     

Orally administered DTPA di-ethyl ester for decorporation of 241Am in dogs: Assessment of safety and efficacy in an inhalation-contamination model

Abstract

Purpose: Currently two injectable products of diethylenetriaminepentaacetic acid (DTPA) are U.S. Food and Drug Administration (FDA)-approved for decorporation of ²⁴¹Am; however, an oral product is considered more amenable in a mass casualty situation. The di-ethyl ester of DTPA, named C2E2, is being developed as an oral drug for treatment of internal radionuclide contamination.

Materials and methods: Single-dose decorporation efficacy of C2E2 administered 24-h post contamination was determined in beagle dogs using a ²⁴¹Am nitrate inhalation contamination model. Single and multiple dose toxicity studies in beagle dogs were performed as part of an initial safety assessment program. In addition, the genotoxic potential of C2E2 was evaluated by the in vitro bacterial reverse mutation Ames test, mammalian cell chromosome aberration cytogenetic assay and an in vivo micronucleus test.

Results: Oral administration of C2E2 significantly increased ²⁴¹Am elimination over untreated controls and significantly reduced the retention of ²⁴¹Am in tissues, especially liver, kidney, lung and bone. Daily dosing of 200 mg/kg/day for 10 days was well tolerated in dogs. C2E2 was found to be neither mutagenic or clastogenic.

Conclusions: The di-ethyl ester of DTPA (C2E2) was shown to effectively enhance the elimination of ²⁴¹Am after oral administration in a dog inhalation-contamination model and was well tolerated in toxicity studies.     

The Response of the International Commission on Radiological Protection to Calls for a Reduction in the Dose Limits for Radiation Workers and Members of the Public

Summary

The removal of ²³⁸Pu and ²⁴¹Am by five chelating agents prepared in China was compared in pilot experiments with removal by Ca-DTPA and LICAM(C). The most promising substance is quinamic acid (a methyliminodiacetic poly-quinoline derivative, code name 811 or 703-73), especially in combination with Ca-DTPA. However, the best over-all reduction of both ²³⁸Pu and ²⁴¹Am in all the organs studied was achieved by Ca-DTPA administered at a ten-fold human equivalent dosage.     

Dietary habits and energy balance in an under 21 male international soccer team

Soccer presents a metabolic challenge which is not necessarily matched by players’ habitual dietary intake. To examine the effects of a bespoke diet, 22 players completed the Ball Sport Endurance and Sprint Test (BEAST_90mod) protocol, followed by 4 days of regulated nutritional intake. The diet consisted of 10 g?kg^?1 body mass (BM) and 1.7 g?kg^?1 BM of carbohydrate and protein, respectively. On day 5, players followed a prematch nutritional strategy of 7 g?kg^?1 BM of carbohydrate and 1 g?kg^?1 BM of protein divided into three meals and then repeated the BEAST_90mod. The players’ pre-intervention intake consisted of 49 ± 7.1% or 3.5 g ± 1.0 g?kg^?1 BM for carbohydrate and 19 ± 3.8% of total daily energy intake or 1.3 g ± 0.5 g?kg^?1 BM for protein. Following the tailor-made dietary intervention, players ran an additional 887 ± 233 m (8.1%; d = 2.4). An acute dietary intervention provided a positive effect on a valid simulated soccer match play test.     

Increased retention of americium in kidneys as compared with plutonium in an actinide wound contamination model in the rat

Abstract

Purpose: Americium-241 (²⁴¹Am) presents a potential risk for nuclear industry workers associated with reactor decommissioning and aging combustible materials. The purpose of this study was to investigate Am renal retention after actinide contamination by wounding in the rat.

Materials and methods: Anesthetized rats were contaminated with Mixed Oxide (MOX) (7.1% Plutonium [Pu] by mass and containing 27% Am as % total alpha activity), Pu or Am nitrate following an incision wound of the hind leg. Times of euthanasia ranged from 2 hours to 5 months after contamination. Pu and Am levels were quantified following radiochemistry and alpha-spectrophotometry.

Results: Initial data show that over the experimental period the proportion of Am in kidneys as a fraction of total kidney alpha activity was elevated as compared to MOX powder indicating a specific retention in this organ. The percentage of Pu was similar to the powder. After MOX contamination, kidney to liver ratios appeared to increase more markedly for Am (from 0.2 at 7 days to 0.6 at 90 days) as compared with Pu (0.1 at 7 days to 0.2 at 90 days). In accordance with tissue actinide retention the dose from Am to the kidney increases with time. For comparison, the ratio of estimated equivalent doses due to Am to kidney is 1.5-fold greater than for Pu (around 90 versus 60 mSv).

Conclusion: After actinide contamination of wounds, Am is concentrated in the kidneys as compared to Pu leading to potential exposure of renal tissue to both alpha particles and gamma radiation.     

Sampling and measurement of transuranic elements in interstitial waters of sediments

The construction and installation of porous cup soil solution samplers and their operation in a saltmarsh is described. Levels of transuranic contamination in the saltmarsh sediments are relatively high (up to 930 kBq m⁻² for ²⁴¹Am and 500 kBq m⁻² for ^239,240Pu), but levels in the interstitial, or sediment-pore, waters are low, generally in the range 1 to 50 mBqL⁻¹. Both ²⁴¹Am/^239,240Pu ratios and concentrations of dissolved transuranic elements are affected by the degree of inundation of the sampling site. These parameters also vary over time in an apparently unpredictable manner. The K_d values (solid/solution distribution coefficients) for Pu and Am are comparable with those measured by other workers at this site.     

Delayed contrast‐enhanced MRI of cartilage: Comparison of nonionic and ionic contrast agents

The objective of this study was to evaluate if cartilage fixed charge density is the only factor determining the distribution of the measured delayed gadolinium‐enhanced magnetic resonance imaging of cartilage index, T₁(Gd‐DTPA^2?), across cartilage in the clinical delayed gadolinium‐enhanced magnetic resonance imaging of cartilage protocol. Nineteen subjects with osteoarthritis and 14 controls were included. Cartilage T₁(Gd) was measured following administration of 0.2 mmol kg^?1 of nonionic (Gd‐DTPA‐BMA) and, at a different date, anionic (Gd‐DTPA^2?). T₁(Gd‐DTPA‐BMA) was plotted against T₁(Gd‐DTPA^2?); a slope of 0 would indicate domination by charge effects; a nonzero slope would suggest that other factors influence T₁(Gd‐DTPA‐BMA), and hence potentially T₁(Gd‐DTPA^2?). The low slope of the curve found in osteoarthritis subjects (0.31) indicates that Gd‐DTPA‐BMA penetrated most osteoarthritis cartilage to the same extent, and T₁(Gd‐DTPA‐BMA) did not differentiate cartilages, which were differentiated by T₁(Gd‐DTPA^2?). The higher slopes in control subjects (0.88) are possibly due to inhibited transport of contrast agent into healthier cartilage, potentially exaggerated by the fast body clearance of the nonionic contrast agent. Overall, the use of anionic Gd‐DTPA^2? for delayed gadolinium‐enhanced magnetic resonance imaging of cartilage is indicated for better discrimination of the health status of cartilage. Future studies could be designed to use contrast‐enhanced dynamics to understand the transport properties of tissues in the joint and to evaluate the concentration of tissue constituents. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

An investigation of the effects of TETRA RF fields on intracellular calcium in neurones and cardiac myocytes

Purpose:?This study aimed to determine whether Terrestrial Trunked Radio (TETRA) fields can affect intracellular calcium signalling in excitable cells.

Materials and methods:?Intracellular calcium concentration ([Ca^{2 +} ]_i) was measured in cultured rat cerebellar granule cells and cardiac myocytes during exposure to TETRA fields (380.8875 MHz pulse modulated at 17.6 Hz, 25% duty cycle). [Ca^{2 +} ]_i was measured as fura-PE3, fluo-3 or fluo-4 fluorescence by digital image analysis.

Results:?Granule cells exposed at specific absorption rates (SARs) of 5, 10, 20, 50 or 400 mW · kg^?1 showed no significant changes in resting [Ca^{2 +} ]_i. Increases in [Ca^{2 +} ]_i in response to potassium-induced depolarization were significantly different from sham controls in TETRA-exposed cells, but the majority of the difference was attributable to initial biological variation between cell cultures. No difference was found between fura-PE3 (UV excitation) and fluo-3 (visible light excitation) measurements in these cells. Exposure to TETRA (50 or 400 mW · kg^?1) had no significant effect on either the rate or amplitude of spontaneous Ca^{2 +} transients in cardiac myocytes. The cells showed normal responses to salbutamol (50 μM) and acetylcholine (10 μM).

Conclusions:?Overall, these results showed no evidence of any consistent or biologically relevant effect of TETRA fields on [Ca^{2 +} ]_i in granule cells and cardiac myocytes at any of the SAR tested.     

Translocation of Plutonium from Rat and Monkey Lung after Inhalation of Industrial Plutonium Oxide and Mixed Uranium and Plutonium Oxide

This study was designed to compare the translocation from lung of the Pu contained in the pure and mixed industrial oxides PuO₂ and (U,Pu)O₂. The latter had a Pu content of 20% w/w. For this purpose, young adult male rats and male and female baboons were exposed to a single inhalation of these oxides. Two baboons were exposed to the reference PuO₂, i.e. ²³⁹PuO₂. Rats were killed under anaesthesia 1, 15, 30, 90 and 180 days after exposure, and baboons, also under anaesthesia, 1 year thereafter. The results indicate that lung retention of Pu was independent of the oxide inhaled, but was smaller in rat (12–15% of the initial pulmonary burden, 6 months after exposure) than in baboon (56–80% of this burden, 1 year after exposure). In rat, Pu translocation kinetics were similar for the two industrial oxides, but as from day 15 after inhalation until 6 months thereafter, measurement of Pu deposits in the liver and skeleton showed that translocation of Pu from the mixed oxide was 2–3 times greater than that from the industrial Pu oxide. In baboon, the largest amounts of Pu were retained in the lung and thoracic lymph nodes for the three oxides inhaled. Pu translocation to the liver, skeleton and kidneys, and also urinary Pu excretion, were greater after inhalation of the mixed oxide than after inhalation of the industrial and reference Pu oxides. Nevertheless, the amount of mixed oxide Pu translocated to these sites and excreted in urine remained under 3% of the initial pulmonary burden.     

Separation techniques for low-level determination of actinides in soil samples

The separation methods for soil samples applied at PSI are based on extraction chromatography and ion exchange. After sample leaching, the actinides are pre-concentrated via precipitation using oxalic acid. Besides the classical separation methods applying the extraction chromatographic resins U/TEVA™ (for U, Th), TRU™ (Pu, Am), new methods were recently implemented to increase the radiochemical recovery of particularly trivalent Am and Cm. These methods do not require initial reduction of Pu(IV) to Pu(III) but stabilize Pu on the tetravalent oxidation state using a mixture of NaNO₂/H₂O₂ in strong acidic medium. The Pu-fraction is then fixed along with Th onto Dowex AG 1-X2 anion exchanger resin. Th is eluted via complexation with 10 M HCl, Pu via reduction with HI. The fractions of Am+Cm and U are loaded onto DGA™ resin. This resin shows extraordinary high distribution coefficients (k′-values) exceeding 10⁴ (for Am) in strong nitric acid medium. The separation between U and Am is obtained quantitatively by decreasing the HNO₃ concentration from 3 to 0.25 M (stripping of the U-fraction) while Am can be easily eluted thereafter using 0.25 M HCl as complexation compound.     

Protracted Treatment of C57B1 Mice with Zn-DTPA after 241Am Injection Reduces the Long-term Radiation Effects

Summary

Repeated intraperitoneal injections of ZnNa₃-diethylenetriaminepenta-acetate (ZnDTPA), once a week, during 8 successive weeks, and starting 4 days after injection of 58 and 373 kBq ²⁴¹Am/kg to C57B1 mice, were an effective protection against long-term radiation damage. At both dose levels of ²⁴¹Am, Zn-DTPA reduced the ²⁴¹Am concentration in bones by between 33% and 45%, and in the liver by 97%. Mean survival with ²⁴¹Am was shortened in Zn-DTPA-treated mice, by 17% at the lower dose level and by 70% at the higher dose level. After treatment with DTPA at the lower ²⁴¹Am level, survival became equal to that of control mice without ²⁴¹Am, while at the higher level life span was still shortened. After the lower ²⁴¹Am dose the incidence of bone tumours, liver carcinomas and the total number of all malignant tumours were significantly reduced by chelation therapy. The decrease in bone tumour incidence was proportional to the decrease in ²⁴¹Am concentration and reduction in cumulative radiation dose in bone after chelation therapy. The incidence of liver carcinomas was reduced to that in non-²⁴¹Am-injected mice and the reduction was thus proportional to the 97% reduction in ²⁴¹Am concentration of the liver at the end of chelation therapy. After the higher ²⁴¹Am dose no tumours showed up in sham-treated mice, probably due to the overkill effect on the cells at risk. In the corresponding Zn-DTPA-treated mice, bone tumours and a few other malignant tumours were observed.     

Aerobic Requirements for Moving Handweights Through Various Ranges of Motion While Walking

In brief: This study compared the aerobic metabolic requirements of normal walking (without handweights and with normal arm motions) with requirements of walking while pumping 1-,2-, or 3-lb handweights through Various ranges of motion. Nine male subjects Walked with and without handweights at speeds of 1.12 to 1.79 m· sec^?1. Adding hand-Weighted arm movements significantly increased the oxygen consumption (V O₂) of normal walking by 2.1 to 25.5 ml· kg^?1· min^?1. The V O₂ for handweighted walking ranged from 17 to 43 ml· kg^?1· min^?1, or 113% to 255% of normal walking requirements at any given speed. These results indicate that walking while moving handweights through large ranges of motion provides a combined upper and lower body aerobic stimulus that is sufficient for endurance training for persons with poor to excellent levels of aerobic fitness.     

α-Particle and γ-ray spectrometry of a plutonium solution for impurity determination

A highly enriched ²⁴⁰Pu solution was measured by α-particle and γ-ray spectrometry to determine other radionuclides present in the material as impurities. Low activities of ²³⁸Pu, ²⁴¹Am, ²⁴³Cm and ²⁴⁴Cm were determined by measuring thin sources, made from the original solution, in a high-resolution alpha-particle spectrometer. The sources were prepared by evaporating the plutonium solution on quartz plates in a vacuum chamber. From the ingrowth of ²⁴¹Am in the original solution, the amount of ²⁴¹Pu could be calculated. After radiochemical separation of ²⁴¹Am, the plutonium was measured by high-efficiency alpha-particle spectrometry to determine the amount of ²³⁸Pu. The enriched ²⁴⁰Pu material was also measured by high-resolution gamma-ray spectrometry, using two different HPGe detectors to determine the impurities of ²³⁹Pu and ²⁴¹Am. The preparation of the sources and the measurement methods are described and discussed. The measured impurities, given in % of the ²⁴⁰Pu activity, are compared with the values on the certificate.     

Aerobic exercise capacity at sea level and at altitude in Kenyan boys, junior and senior runners compared with Scandinavian runners

The aim of this study was to characterize Kenyan runners in regard to their oxygen uptake and blood and ammonia responses when running. Untrained Kenyan boys (14.2±0.2 years) and Scandinavian runners were included for comparison. The studies were performed at altitude (～2.000 m.a.s.l.) and, for several Kenyan and Scandinavian runners, at sea level as well. At altitude sedentary adolescent Kenyan boys had a mean maximal oxygen uptake (Vo_2max) of 47 (44–51) ml · kg^?1· min^?1, whereas similarly aged boys regularly walking or running but not training for competition reached above 62 (58–71) ml · kg^?1· min^?1 in Vo^2max. Kenyan runners in active training had 68±1.4 ml · kg^?1· min^?1 at altitude and 79.9±1.4 ml · kg^?1· min^?1 at sea level, with individuals reaching 85 ml · kg^?1· min^?1. The best Scandinavian runners were not significantly different from the Kenyan runners in Vo_2max both at altitude and at sea level, but none of the Scandinavians reached as high individual values as observed for some Kenyan runners. The running efficiency, determined as the oxygen cost at a given running speed, was less in the Kenyan runners, and the difference became more pronounced when body weight was expressed in ml · kg^?0.75 min^?1. Blood lactate concentration was in general lower in the Kenyan than in the Scandinavian runners, and the Kenyans also had extremely low ammonia accumulation in the blood even at very high exercise intensities. It is concluded that it is the physical activity during childhood, combined with intense training as teenagers that brings about the high Vo_2max observed in some Kenyan runners. Their high aerobic capacity, as well as their good running economy, makes them such superior runners. In addition, their low blood lactate and ammonia accumulation in blood when running may also be contributing factors.     

Synthesis and preliminary evaluation of MP-2269: A novel,nonaromatic small-molecule blood-pool MR contrast agent

A nonaromatic, small-molecule, gadolinium(3+)-chelate code named MP-2269 was synthesized and evaluated in animals as a potential MR contrast agent for blood pool. The ligand of MP-2269 was prepared by conjugating a lipophilic, albumin-binding moiety, 4-pentylbicyclo[2.2.2]octane-1-carboxylic acid, to an amino-functionalized DTPA derivative by means of a diaspartic acid linker. Proton relaxometry studies in vitro yielded spin-lattice relaxivities (R₁) for MP-2269 of 6.2, 20.0 and 26.1 mM^?1 sec^?1 in water, rabbit blood, and human blood, respectively. The enhanced relaxivities in blood indicate sig nificant binding of the agent to blood proteins. At a dose of 45 μmol/kg, MP-2269 showed a biphasic rabbit blood clearance profile with half-lives of 4.7 and 142 minutes, respectively, for the fast and slow components. In rats, the agent is cleared predominantly through the hepatobiliary pathway (～70% in 24 h by this mode). The LD₅₀ value of MP-2269 is ～3.0 mmol/kg in mice. Preliminary MR angiograms obtained in the rabbit showed excellent enhancement of blood vessels. Hence, MP-2269 has potential for future exploitation as a contrast agent for MR angiography.     

High dose Nitrate ingestion does not improve 40 km cycling time trial performance in trained cyclists

ABSTRACT

This study evaluated the chronic effects of nitrate (NO₃^?) ingestion over three days, on 40 km TT performance in 11trained cyclists (VO_2max: 60.8 ± 7.4 ml.kg^?1.min^?1; age: 36 ± 9 years; height: 1.80 ± 0.06 m; body mass: 87.2 ± 12.0 kg). Utilising a double-blind randomised cross-over design, participants completed three 40 km TT on a Velotron® ergometer following the ingestion of either a 140 ml of “BEET It sport®” NO₃^? shot containing 12.8 mmol or 800 mg of NO₃^?, a placebo drink or nothing (control). Performance, oxygen consumption (VO₂), blood bicarbonate (HCO3-), pH and lactate (BLa) and ratings of perceived exertion (RPE) were measured every 10 km throughout the TT. The present findings show that NO₃^? ingestion had no effect on TT performance (NO₃^?: 4098.0 ± 209.8 vs. Placebo: 4161.9 ± 263.3 s, p = 0.296, ES = 0.11), or VO₂ (p = 0.253, ES = 0.13). Similarly, blood lactate and RPE were also unaffected by the experimental conditions (p = 0.522, ES = 0.06; p = 0.085, ES = 0.30) respectively. Therefore, these results suggest that a high dose of NO₃^? over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists.