Rate of loss of radioiron from mouse and man

1960 ◽  
Vol 198 (4) ◽  
pp. 784-786 ◽  
Author(s):  
John D. Bonnet ◽  
Alan L. Orvis ◽  
Albert B. Hagedorn ◽  
Charles A. Owen

Forty-two male and female mice, 8 weeks old, were given radioiron (Fe59) in doses of 0.006–0.1 µc, containing 0.013–0.17 µg of iron, by intraperitoneal or intravenous routes. Assays of the radioactivity of the whole body revealed an initial rapid loss of Fe59 (15–20%) lasting about 6 days. Thereafter the Fe59 left the mice at a steady rate of 0.39%/day (half-life 180 days). One 34-year-old normal man was given 10.6 µc of Fe59, containing 8.2 µg of iron, intravenously. Based on counts from the entire body, the biologic rate of loss of the Fe59 was about 0.14%/day (half-life 500 days), and there was little or no initial loss such as occurred in the mouse. The Fe59 in the circulating erythrocytes was essentially unchanged for the first 3 months. It then fell to a new level of about 90% of the previous one; the mid-point of the fall was about 120 days after the administration of the radioiron. The difference in the rates of loss of radioiron from mice and man seems to be related primarily to the life span of the circulating red cells.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Shailendra B Patel

Hypothesis: Xenosterol excretion by the mammalian body is wholly dependent on Abcg5/Abcg8 function. Methods: To test our hypothesis, we loaded Abcg8-/- mice with dietary plant sterols until they manifested biochemical (elevated plant sterols) and pathological changes (poor body weight, macrothrombocytopenia). All dietary xenosterols were eliminated from the diet and kinetics of xenosterol loss monitored over the ensuing 16 days, monitoring plasma, bile, and stool losses, as well as whole body sterol determinations. Results: After loading Abcg8-/- mice with plant sterols, plasma sitosterol levels in both male and female mice averaged 80mg/dL. Surprisingly, there was rapid loss of xenosterols from blood as well as tissues (liver, whole body), with losses of xenosterols detected in bile and feces. By day 16, stool xenosterols were almost undetectable and reflected the dramatic loss of whole body xenosterols. Conclusions: Our data refute our hypothesis. Although loss of sterolin function leads to severe xenosterolemia in both humans and mice, at least in mice, there appears to be a pathway(s) for elimination via the biliary/intestinal route. Characterization of the transporters involved may shed further light on sterol trafficking.


2016 ◽  
Vol 310 (5) ◽  
pp. E332-E345 ◽  
Author(s):  
Risa M. Wolf ◽  
Xia Lei ◽  
Zhi-Chun Yang ◽  
Maeva Nyandjo ◽  
Stefanie Y. Tan ◽  
...  

C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity.


1988 ◽  
Vol 254 (2) ◽  
pp. 367-372 ◽  
Author(s):  
Y Murakami ◽  
M Marumo ◽  
S I Hayashi

Antizyme, a protein inhibitor of ornithine decarboxylase (ODC), was shown to be induced in mouse kidney by repeated injection of putrescine. Antizyme was also present as a complex with ODC in the kidney of untreated mouse. The amount of the renal ODC-antizyme complex was 3-fold higher in male mice than in female mice. On the contrary, the proportion of ODC present as a complex with antizyme was 24-fold higher in females than in males, and the decay of renal ODC activity after cycloheximide treatment was about 5-fold more rapid in females than in males. Administration of testosterone to female mice, a procedure known to prolong the half-life of renal ODC, increased both ODC activity and the content of ODC-antizyme complex, but decreased the antizyme/ODC ratio in the kidney. These results are consistent with the previous observation in HTC cells that the decay rate of ODC activity in the presence of cycloheximide correlated well with the proportion of ODC present as a complex with antizyme, suggesting the ubiquitous role of antizyme in ODC degradation.


PEDIATRICS ◽  
1966 ◽  
Vol 38 (6) ◽  
pp. 1047-1056
Author(s):  
Marta S. Billings ◽  
James N. Yamazaki ◽  
Leslie R. Bennett ◽  
Baldwin G. Lamson

1. Four-day-old male and female Long-Evans x Sprague-Dawley F1 hybrid rats were exposed to a single total body x-ray dose of 125, 25, 5, and 0 r and then were observed during their entire lifespan for weight changes, signs of morbidity and age at death. 2. There was a 10% reduction of life span in the 125 r exposed female rats. None of the male groups showed significant shortening of longevity. 3. Mean body weights were consistently lower in both male and female groups exposed to 125 r total body irradiation. 4. Female rats exposed to 25 and 125 r attained their maximum weights at a younger age than their non-irradiated controls. 5. External tumors appeared earlier in female rats. Tumor incidence was not increased by irradiation in either sex. 6. Male parentage influenced the length of life span of progeny to a greater degree than the irradiation exposure at the employed dose-level. The influence of female parentage upon longevity cannot be evaluated in this study. 7. Low dose radiation life shortening can only be demonstrated in long-lived strains. Hereditary and radiation life shortening effects are not cumulative under conditions of this study.


A systematic study has been made of the reduction of life span in mice exposed to a single whole-body dose of 15 MeV X-rays. 4604 mice of an inbred A substrain were used, all of the same age, 30 days, when irradiated. Nine dose groups, from 50 to 780 r, were used, with a large number of control mice, which were kept to the end of their lives under the same conditions as the irradiated animals. An analysis of the survival curves has revealed two effects of radiation: a reduction in the median age and an increase in standard deviation of the distribution of ages at death. The latter was found to be a quadratic function of dose and it is suggested that the increase is the result of the larger spread in the ages of onset of diseases in irradiated animals. The reduction of life span was found to be proportional to dose, with no threshold. It amounts to 5∙66 ± 0∙18 weeks per 100 r, or to 38 % of the median life span for a dose equal to the LD 50 (698 r). The difference between the life-shortening in males and females was not statistically significant. The data have also been analyzed in terms of Gompertz plots and it was found that they cannot be represented by straight lines, although the displacement of the curves caused by radiation is roughly proportional to dose. The fact that after correcting for the change in standard deviation, all survival curves are parallel to each other, suggests that the effect of exposure is to ‘age' the animal, by the removal of a few weeks of its early life.


2016 ◽  
Vol 121 (3) ◽  
pp. 781-791 ◽  
Author(s):  
Ryma Boukari ◽  
Orlane Rossignol ◽  
Cécile Baldy ◽  
François Marcouiller ◽  
Aida Bairam ◽  
...  

We tested the hypothesis that membrane progesterone receptors (mPR) contribute to respiratory control in adult male and female mice. Mice were implanted with osmotic minipumps for continuous infusion of small interfering RNA (siRNA) directed against mPRα, mPRβ, or a control solution in the fourth ventricle (to target brain stem respiratory areas) for 14 days. We then performed respiratory and metabolic recordings by whole body plethysmography at rest and in response to hypoxia (12% O2) or hypercapnia (5% CO2, 5 min each). For each treatment, we have verified with immunohistochemistry that the staining intensity of mPRα or mPRβ in the brain stem is decreased. At rest, the siRNA against mPRα and mPRβ increased respiratory frequency in males only. The siRNA against mPRβ almost tripled the frequency of apneas in male and in female mice, while the siRNA against mPRα had no effect. Regarding respiratory chemoreflex, the siRNA against mPRβ suppressed the response to hypoxia in male and female mice and reduced by ∼50% the response to hypercapnia, while the siRNA against mPRα had more limited effects. Interestingly, control females had higher ventilatory response to hypoxia and hypercapnia than males, and these sex-specific effects were suppressed by the siRNA against mPRβ, whereas they were still present after treatment with the siRNA against mPRα. We conclude that mPRβ reduces apnea frequency in male and female mice and establishes sex-specific ventilatory chemoreflex.


2015 ◽  
Vol 118 (11) ◽  
pp. 1386-1395 ◽  
Author(s):  
Orlane Ballot ◽  
Vincent Joseph ◽  
Jorge Soliz

We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency ( fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (−25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (−37% in males, −59% in females) and VT (−38% in males, −47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia.


Author(s):  
V. C. Wynne-Edwards

SUMMARYFrom two series of samples of different populations of herrings from the neighbourhood of the Isle of Man, data were obtained of the lengths, weights, gonad-weights, and ages of 396 mature fishes. The growths of the whole body and of the gonads were represented by the upper portions of S-shaped curves. The male and female body-weights are nearly the same at any age over the range considered, but the testes of the male are always heavier than the ovaries of the female in such comparable fishes. The females attain a greater size than the males.The weight of the gonads bears a linear relationship (as a first approximation) to the total weight of the fish over the range of size considered. The regression functions evaluated for the two sexes arewhere y is the gonad-weight and x the total weight of the fish, both in grams. The difference between the weights of testes and ovaries in male and female fishes of the same size is therefore about 4·7 gm., which is shown to be significant. It cannot be due to specific gravity of growthrate differences, since the regression coefficient (0·26) is the same for both sexes.It is suggested that the reproductive organs start to develop in the summer following the laying down of the first winter ring on the scales; and that the initial handicap in female gonad-weight may be due to the males being smaller than the females at this time.Confirmation of the conclusions drawn from the Calf herring is given by a similar analysis of the Low herring samples.


Reproduction ◽  
2009 ◽  
Vol 137 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Hossein Mozdarani ◽  
Elmina Nazari

Cytogenetic damage expressed as micronuclei (MN) in 4–8-cell embryos generated after irradiation of male or male and female mice in the absence and presence of vitamin C was investigated. Male NMRI mice were whole body exposed to 4 Gy γ-rays and mated with non-irradiated superovulated female mice in 6 successive weeks after irradiation in a weekly interval. In experiments involving irradiation of both male and female mice, irradiated male mice for 6 weeks post irradiation were mated with female mice irradiated after induction of superovulation. Effect of 100 mg/kg vitamin C (ascorbic acid) on the frequency of MN was also studied. Pregnant animals were euthanized and embryos flushed from the oviducts and fixed on slides. The rate of MN observed in embryos generated from irradiated male compared with control group dramatically increased (P<0.01). Frequency of MN in this group decreased dramatically after vitamin C treatment (P<0.01). Frequency of MN in embryos generated by mating both male and female irradiated mice was higher than that observed for those embryos generated by irradiated male mice alone. However, a considerable modifying effect of vitamin C was observed for this group too (P<0.05). Results indicate that irradiation of gonads during spermatogenesis and preovulatory stage oocytes may lead to unstable chromosomal aberrations and probably stable chromosomal abnormalities affecting pairing and disjunction of chromosomes in successive preimplantation embryos expressed as MN. The way vitamin C reduces clastogenic effects of radiation on germ cells leading to reduced frequency of MN in pre-embryos might be due to its antioxidation and radical scavenging properties.


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