Radium - 226 retention in placenta and whole body of rat

The 226Ra retention in the placenta of rat during 3 successive pregnancies (92-213 days after injection) was about 4-5 x 10(-3)% of the injected dose (ID) constituting nearly 0.009% of the whole body 226Ra content (45-55% ID) in each pregnancy. Thus a uniform relationship was being displayed between the two contents to a reasonable extent. The implication of this observation is discussed vis-a-vis the determination of Ra body burden.     

Sympathetic nerve activity and whole body heat stress in humans

We and others have shown that moderate passive whole body heating (i.e., increased internal temperature ～0.7°C) increases muscle (MSNA) and skin sympathetic nerve activity (SSNA). It is unknown, however, if MSNA and/or SSNA continue to increase with more severe passive whole body heating or whether these responses plateau following moderate heating. The aim of this investigation was to test the hypothesis that MSNA and SSNA continue to increase from a moderate to a more severe heat stress. Thirteen subjects, dressed in a water-perfused suit, underwent at least one passive heat stress that increased internal temperature ～1.3°C, while either MSNA (n = 8) or SSNA (n = 8) was continuously recorded. Heat stress significantly increased mean skin temperature (Δ～5°C, P < 0.001), internal temperature (Δ～1.3°C, P < 0.001), mean body temperature (Δ～2.0°C, P < 0.001), heart rate (Δ～40 beats/min, P < 0.001), and cutaneous vascular conductance [Δ～1.1 arbitrary units (AU)/mmHg, P < 0.001]. Mean arterial blood pressure was well maintained (P = 0.52). Relative to baseline, MSNA increased midway through heat stress (Δ core temperature 0.63 ± 0.01°C) when expressed as burst frequency (26 ± 14 to 45 ± 16 bursts/min, P = 0.001), burst incidence (39 ± 13 to 48 ± 14 bursts/100 cardiac cyles, P = 0.03), or total activity (317 ± 170 to 489 ± 150 units/min, P = 0.02) and continued to increase until the end of heat stress (burst frequency: 61 ± 15 bursts/min, P = 0.01; burst incidence: 56 ± 11 bursts/100 cardiac cyles, P = 0.04; total activity: 648 ± 158 units/min, P = 0.01) relative to the mid-heating stage. Similarly, SSNA (total activity) increased midway through the heat stress (normothermia; 1,486 ± 472 to mid heat stress 6,467 ± 5,256 units/min, P = 0.03) and continued to increase until the end of heat stress (11,217 ± 6,684 units/min, P = 0.002 vs. mid-heat stress). These results indicate that both MSNA and SSNA continue to increase as internal temperature is elevated above previously reported values.     

Carbohydrate ingestion augments L-carnitine retention in humans.

Maintaining hyperinsulinemia (approximately 150 mU/l) during steady-state hypercarnitinemia (approximately 550 micromol/l) increases skeletal muscle total carnitine (TC) content by approximately 15% within 5 h. The present study aimed to investigate whether an increase in whole body carnitine retention can be achieved through L-carnitine feeding in conjunction with a dietary-induced elevation in circulating insulin. On two randomized visits (study A), eight men ingested 3 g/day L-carnitine followed by 4 x 500-ml solutions, each containing flavored water (Con) or 94 g simple sugars (glucose syrup; CHO). In addition, 14 men ingested 3 g/day L-carnitine followed by 2 x 500 ml of either Con or CHO for 2 wk (study B). Carbohydrate ingestion in study A resulted in a fourfold greater serum insulin area under the curve when compared with Con (P < 0.001) and in a lower plasma TC concentration throughout the CHO visit (P < 0.05). Twenty-four-hour urinary TC excretion in the CHO visit was lower than in the Con visit in study A (155.0 +/- 10.7 vs. 212.1 +/- 17.2 mg; P < 0.05). In study B, daily urinary TC excretion increased after 3 days (65.9 +/- 18.0 to 281.0 +/- 35.0 mg; P < 0.001) and remained elevated throughout the Con trial. During the CHO trial, daily urinary TC excretion increased from a similar basal value of 53.8 +/- 9.2 to 166.8 +/- 17.3 mg after 3 days (P < 0.01), which was less than during the Con trial (P < 0.01), and it remained lower over the course of the study (P < 0.001). The difference in plasma TC concentration in study A and 24-h urinary TC excretion in both studies suggests that insulin augmented the retention of carnitine in the CHO trials.     

Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.     

A refined method for assessing 99mTc-MDP whole body retention in prostate cancer patients

Whole body retention (WBR) of ^99mTc labeled methylene diphosphonate (MDP) has been shown to significantly differentiate various clinical stages of prostate cancer. Whole body measurements, when performed at 5 min and 24 h after i.v. administration of ^99mTc-MDP, allows for the calculations of percentage whole body retention (% WBR) after one day. The latter can be expressed relative to either the anterior or posterior projection, or in combination as the geometric mean value.In an attempt to better describe the clinical course of prostate cancer patients with bone metastases we have refined the % WBR calculations to include a normalization factor. The latter consists of the mean 24-h value of WBR's as obtained from 10 prostate cancer patients without bony métastases as determined by bone scintigram. These values were determined for each projection to be: anterior = 26.5 ± 4.7%, posterior = 37.5 ± 7.4%, and geometric mean = 31.5 ± 5.7%. The % WBR is then divided by the normalization factor of choice and expressed as (% WBR)^N.These data are used to better express ^99mTc MDP 24-h whole body retentions when following the clinical course of patients with metastatic carcinoma of the prostate. Caution should be exercised when interpreting these data when metabolic bone pathology is present. A false negative (% WBR)^N value will result if an infiltration of the ^99mTc-MDP occurs during administration.     

Opposite actions of caffeine and creatine on muscle relaxation time in humans.

The effect of creatine and caffeine supplementation on muscle torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (T(max)), contraction time (CT) from 0.25 to 0.75 of T(max), and relaxation time (RT) from 0.75 to 0.25 of T(max) were measured during an exercise test consisting of 30 intermittent contractions of musculus quadriceps (2 s stimulation, 2 s rest) that were induced by electrical stimulation. According to a double-blind randomized crossover design, subjects (n = 10) performed the exercise test before (pretest) and after (posttest) creatine supplementation (Cr, 4 x 5 g/day, 4 days), short-term caffeine intake (Caf, 5 mg x kg(-1) x day(-1), 3 days), creatine supplementation + short-term caffeine intake (Cr+Caf), acute caffeine intake (ACaf, 5 mg/kg) or placebo. Compared with placebo, Cr shortened RT by approximately 5% (P < 0.05). Conversely, Caf increased RT (+ approximately 10%, P < 0.05), in particular as RT increased because of fatigue. RT was not significantly changed by either Cr+Caf or ACaf. T(max) and CT were similar during all experimental conditions. Initial T(max) was approximately 20% of voluntary maximal isometric contraction force, which was not different between treatments. It is concluded that Caf intake (3 days) prolongs muscle RT and by this action overrides the shortening of RT due to creatine supplementation.     

A convenient six-point blood sampling schedule for determining whole body cholesterol kinetics in humans

Parameters of total body cholesterol metabolism in humans can be determined by using a three-pool model to analyze the turnover of plasma cholesterol following the injection of radiolabeled cholesterol. In the past this required a rigorous schedule of approximately 36 blood samples over a 10-month period. We have developed a convenient sampling schedule involving only six large samples, each analyzed in sextuplicate. Such a reduction in the frequency of samples is possible only when considerable confidence in the model is available. In general, the simplified sampling strategy depends upon considerable prior experience with the model, only moderate biological error, and estimatable subject to subject variation in model parameters. Because the timing of the samples is critical and because the optimal times will differ for different subjects, the six-point strategy involves using the first three samples (drawn at days 1, 7, and 24 or, for hypercholesterolemic subjects, at days 1, 8, and 28) in conjunction with results from previous studies to set the time for the next sample; the process is reiterated for the last two points. In this study, we have compared parameter estimates obtained by the new six-point schedule with those obtained simultaneously (in the same, single turnover study) by the old 36-point schedule in the same 26 subjects. Both schedules gave comparable values. In particular, the coefficients of variation between values obtained by the two methods for each of the four parameters for which we have developed predictive equations were quite low: PR 1.5%, M1 4.1%, M3min 13%, Mtot min 4.3%. The simplified six-point schedule makes it feasible to study long-term cholesterol turnover in substantial numbers of patients.     

Cerebral energetic effects of creatine supplementation in humans

There has been considerable interest in the use of creatine (Cr) supplementation to treat neurological disorders. However, in contrast to muscle physiology, there are relatively few studies of creatine supplementation in the brain. In this report, we use high-field MR (31)P and (1)H spectroscopic imaging of human brain with a 7-day protocol of oral Cr supplementation to examine its effects on cerebral energetics (phosphocreatine, PCr; ATP) and mitochondrial metabolism (N-acetyl aspartate, NAA; and Cr). We find an increased ratio of PCr/ATP (day 0, 0.80 +/- 0.10; day 7, 0.85 +/- 09), with this change largely due to decreased ATP, from 2.7 +/- 0.3 mM to 2.5 +/- 0.3 mM. The ratio of NAA/Cr also decreased (day 0, 1.32 +/- 0.17; day 7 1.18 +/- 0.13), primarily from increased Cr (9.6 +/- 1.9 to 10.1 +/- 2.0 mM). The Cr-induced changes significantly correlated with the basal state, with the fractional increase in PCr/ATP negatively correlating with the basal PCr/ATP value (R = -0.74, P < 0.001). As NAA is a measure of mitochondrial function, there was also a significant negative correlation between basal NAA concentrations with the fractional change in PCr and ATP. Thus healthy human brain energetics is malleable and shifts with 7 days of Cr supplementation, with the regions of initially low PCr showing the largest increments in PCr. Overall, Cr supplementation appears to improve high-energy phosphate turnover in healthy brain and can result in either a decrease or an increase in high-energy phosphate concentrations.     

Responses of whole body protein synthesis, nitrogen retention and glucose kinetics to supplemental starch in goats

An isotope dilution experiment was conducted to determine the effect of metabolizable energy intake (MEI) as starch on whole body protein synthesis (WBPS), nitrogen (N) retention and glucose irreversible loss rate (ILR) in four adult goats (Capra hircus). The goats were fed isonitrogenous diets containing three different metabolizable energy (1.0, 1.5 and 2.0 times maintenance) twice daily. Energy above maintenance was supplemented with cornstarch. The WBPS and glucose ILR during 5 to 7 h after feeding were measured by a primed-continuous infusion of [2H5]phenylalanine, [2H2]tyrosine, [2H4]tyrosine and [13C6]glucose for 4 h, with measurements of plasma concentrations of metabolites and insulin. Ruminal characteristics were also determined. Increasing MEI improved N retention, despite decreased digestible N. Increasing MEI decreased ruminal pH and ammonia nitrogen. In plasma, decreased urea N, increased total amino N and tyrosine, and trends for increases in phenylalanine and insulin resulted from increasing MEI. Increasing MEI increased ILR of glucose, phenylalanine and tyrosine, and hydroxylation rate of phenylalanine and WBPS. We conclude that in goats increasing MEI as starch enhances WBPS in the absorptive state and N retention, despite a decrease in digestible N. These changes are probably associated with both decreased ammonia absorption and increased amino acid absorption.     

Natriuresis and carbohydrate-induced antinatriuresis in fasted, hydrated hypertensives.

After an overnight fast and oral hydration with water, hypertensive subjects developed a significant natriuresis (mean urine sodium excretions increased from 130 to 291 mueq/min. The incidence of a natriuresis (greater than 200 mueq sodium excreted per minute) was 75% in the hypertensive group (16 subjects) compared to 27% in a previously studied normotensive group (22 subjects). The incidence of a carbohydrate-induced antinatriuresis (greater than 30% decrease in urinary sodium excretion) was 62% in the hypertensive group compared to 41% in the normotensive group. No decrease in plasma volume (131I-labeled albumin concentration) due to a shift of solute and water intracellularly could be documented to explain the antinatriuretic effect of glucose. An incidental observation was a significant decrease in plasma zinc concentrations after glucose ingestion.     

The role of baseline in the cutaneous vasoconstrictor responses during combined local and whole body cooling in humans

Previous work showed that local cooling (LC) attenuates the vasoconstrictor response to whole body cooling (WBC). We tested the extent to which this attenuation was due to the decreased baseline skin blood flow following LC. In eight subjects, skin blood flow was assessed using laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was expressed as LDF divided by blood pressure. Subjects were dressed in water-perfused suits to control WBC. Four forearm sites were prepared with microdialysis fibers, local heating/cooling probe holders, and laser-Doppler probes. Three sites were locally cooled from 34 to 28 degrees C, reducing CVC to 45.9 +/- 3.9, 42 +/- 3.9, and 44.5 +/- 4.8% of baseline (P < 0.05 vs. baseline; P > 0.05 among sites). At two sites, CVC was restored to precooling baseline levels with sodium nitroprusside (SNP) or isoproterenol (Iso), increasing CVC to 106.4 +/- 12.4 and 98.9 +/- 10.1% of baseline, respectively (P > 0.05 vs. precooling). Whole body skin temperature, apart from the area of blood flow measurement, was reduced from 34 to 31 degrees C. Relative to the original baseline, CVC decreased (P < 0.05) by 44.9 +/- 2.8 (control), 11.3 +/- 2.4 (LC only), 29 +/- 3.7 (SNP), and 45.8 +/- 8.7% (Iso). The reductions at LC only and SNP sites were less than at control or Iso sites (P < 0.05); the responses at those latter sites were not different (P > 0.05), suggesting that the baseline change in CVC with LC is important in the attenuation of reflex vasoconstrictor responses to WBC.     

Effect of a short-term moderate whole body hyperthermia of healthy humans on their peripheral lymphocytes

A short (75-110 min) mild (39.5 degrees C) whole body hyperthermia of humans does not alter the absolute amount of peripheral lymphocytes immediately after heating, but significantly reduces their relative amount due to neutrophil increase. Body heating does not induce lymphocyte degeneration: their potential viability does not reduce. The total level of lymphocyte oxidative metabolism remains unaltered, while SDG and LDG activities are seen reduced and increased, respectively. Lymphocytes adapt to body heating by inducing thermotolerant state and activating anaerobic metabolism.     

Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans

We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41°C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ODQ, 15 ± 3% maximum CVC (CVC(max)); DMSO, 14 ± 3% CVC(max); Ringer, 17 ± 6% CVC(max); P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVC(max); DMSO, 64 ± 4% CVC(max); Ringer, 63 ± 4% CVC(max); P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34°C local temperature, CVC did not differ among sites (ODQ, 17 ± 2% CVC(max); DMSO, 18 ± 4% CVC(max); Ringer, 18 ± 3% CVC(max); P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVC(max); DMSO, 86 ± 4% CVC(max); Ringer, 90 ± 2% CVC(max); P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming.     

Plasma guanidino compounds are altered by oral creatine supplementation in healthy humans.

Although creatine is one of the most widely used nutritional supplements for athletes as well as for patients with neuromuscular disorders, the effects of oral creatine supplementation on endogenous creatine synthesis in humans remains largely unexplored. The aim of the present study was to investigate the metabolic consequences of a frequently used, long-term creatine ingestion protocol on the circulating creatine synthesis precursor molecules, guanidinoacetate and arginine, and their related guanidino compounds. For this purpose, 16 healthy young volunteers were randomly divided to ingest in a double-blind fashion either creatine monohydrate or placebo (maltodextrine) at a dosage of 20 g/day for the first week (loading phase) and 5 g/day for 19 subsequent wk (maintenance phase). Fasting plasma samples were taken at baseline and at 1, 10, and 20 wk of supplementation, and guanidino compounds were determined. Plasma guanidinoacetate levels were reduced by 50% after creatine loading and remained approximately 30% reduced throughout the maintenance phase. Several circulating guanidino compound levels were significantly altered after creatine loading but not during the maintenance phase: homoarginine (+35%), alpha-keto-delta-guanidinovaleric acid (+45%), and argininic acid (+75%) were increased, whereas guanidinosuccinate was reduced (-25%). The decrease in circulating guanidinoacetate levels suggests that exogenous supply of creatine chronically inhibits endogenous synthesis at the transamidinase step in humans, supporting earlier animal studies showing a powerful repressive effect of creatine on l-arginine:glycine amidinotransferase. Furthermore, these data suggest that this leads to enhanced utilization of arginine as a substrate for secondary pathways.     

Effect of 60Co-Gamma whole body irradiation and treatment with radioprotector on the retention of 144Ce, in mice

In animal experiments the effects of 7.5 Gy whole-body irradiation (LD50/30) and/or of radioprotecting compound (WR-2721) on the retention and elimination of 144Ce were investigated. It was stated that in the first three days there was an increase in the deposition of 144Ce after whole-body irradiation and upon treatment with radioprotective compound WR-2721.     

Glucocorticoids and melanocortins in the regulation of body weight in humans.

The last decade witnessed a dramatic increase in knowledge concerning regulation of body weight and obesity. According to recent concepts constancy of body weight is a side product of regulatory events which ensure constant glucose fluxes to the brain. Within these control systems glucocorticoids and melanocortins play a fundamental role at several sites. The melanocortin neurons in the arcuate nucleus are important mediators of the feedback effects of leptin and insulin. Glucocorticoid and mineralocorticoid receptors in hippocampal neurons are crucial as they define the balance between glucose allocation processes and food intake. Thereby, the hippocampal structures determine the setpoint for bodyweight regulation. Novel approaches to treatment of obesity must aim at manipulating these brain structures.     

The effect of age on heat tolerance in cattle as determined by the whole body40K and nitrogen retention

Eleven non-lactating Holstein cows of 8–10 years of age and 12 female Holstein calves of 5–6 months of age were maintained, during winter season, in the climatic laboratory for 3 days at thermoneutral climate (18.3°C, 50% RH) followed by 3 days at hot climate (32.2°C, 50% RH). Feed and water were provided ad libitum. Whole body⁴⁰K counting, nitrogen balance, body weight and rectal temperature were taken on the third day on each animal at the climatic exposures mentioned above. Body potassium decreased significantly in cows (p < 0.01) but not in calves. Nitrogen retention decreased with heat exposure in cows and calves (p < 0.01) and the balance was negative in cows but positive in calves. In cows, body weight decreased with heat exposure 1.81%, significantly (p < 0.05), but it did not change significantly in calves. The final rise in body temperature under hot climate was significant in cows and calves (p < 0.01), being 0.82°C and 1.07°C, respectively. The heat-induced changes, except the rise in body temperature, were significantly different in cows from those in calves. These results indicate that calves are more heat tolerant than cows on the basis of catabolic reactions but not on rectal temperature rise.

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Zusammenfassung Während des Winters wurden 11 nicht laktierende Holstein Kühe im Alter von 8–10 Jahren und 12 Holstein Kälber im Alter von 5–6 Monaten 3 Tage lang zunächst in thermoneutralem Klima (18,3°C, 50% RF) und danach 3 Tage in der Hitze bei 32,2°C und 50% RF gehalten. In der Hitze fiel das Körper-Kalium bei den Kühen signifikant (p < 0,01) ab, nicht aber bei den Kälbern. Bei beiden fiel die Stickstoffretention signifikant (p < 0,01) ab, und die Bilanz wurde bei den Kühen negativ, nicht aber bei den Kälbern. Das Körpergewicht der Kühe fiel 1,81% (p < 0,05), das der Kälber blieb unbeeinflusst. Die Körpertemperatur war am Ende bei den Kühen 0,82°C und bei den Kälbern 1,07°C höher (p < 0,01). Dies spricht dafür, dass die Kälber in Hinsicht auf die katabolischen Reaktionen eine höhere Hitzetoleranz haben als die Kühe.

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Resume 11 vaches de race Holstein âgées de 8 à 10 ans, mais hors de lactation et 12 génisses de 5 à 6 mois de la même race ont été placées, durant l'hiver, en atmosphère contrôlée. Elles ont passé tout d'abord 3 jours en climat neutre (18,3°C et 50% d'humidité relative), puis 3 jours dans une atmosphère chaude (32,2°C et 40% h.r.). On leur a donné à manger et à boire ad libitum. A la fin de chacune de ces périodes, on a mesuré pour chaque animal la teneur en⁴⁰K, le bilan d'azote, le poids et la température rectale. Le taux de potasse a diminué de façon significative chez les vaches (p < 0,01), mais pas chez les génisses. La rétention d'azote décrofît avec le chaud tant chez les vaches que chez les génisses (p <0,01) et son bilan est négatif chez les vaches, positif chez les génisses. Le poids des vaches a diminué de 1,81% (significatif à p < 0,05), mais ne s'est pas modifié de façon significative chez les génisses. La température s'est élevée de 0,82°C chez les vaches et de 1,07°C chez les génisses (significatif tous les deux à p < 0,01). Toutes les répercussions d'une exposition au chaud on été significatives entre vaches et génisses, à l'exception de la température du corps. Ceci montre que les génisses offrent une plus grande tolérance à la chaleur que les vaches si l'on se base sur leurs réactions cataboliques, mais pas selon la température rectale.

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Contribution from the Missouri Agricultural Experiment Station, Journal Series No. 6037.

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On a leave at the University of Missouri.