scholarly journals Idiorrhythmic dose-rate variability in dietary zinc intake generates a different response pattern of zinc metabolism than conventional dose–response feeding

1997 ◽  
Vol 78 (1) ◽  
pp. 173-191 ◽  
Author(s):  
Berislav MomČilović ◽  
Philip G. Reeves ◽  
Michael J. Blake
Keyword(s):  
Dose Rate ◽  
Dose Response ◽  
Male Rats ◽  
Metabolic Efficiency ◽  
Zinc Metabolism ◽  
Deficient Diet ◽  
Zinc Intake ◽  
Conventional Dose ◽  
Zn Concentration ◽  
Different Response

We compared the effects of idiorrhythmic dose-rate feeding and conventional dose-response on the induction of intestinal metallothionein (IMT), expression of aortal heat-shock protein mRNA (HSP70mRNA) induced by restraint stress, and accumulation of Zn in the femur and incisor of young growing male rats. An idiorrhythmic approach requires that the average dietary Zn concentration (modulo, M) over the whole experiment (epoch, E) is kept constant across different groups. This is done by adjusting the Zn concentration of the supplemented diet supplied to compensate for the reduction in the number of days on which Zn-supplemented diet is fed, the latter being spread evenly over the experiment. Idiorrhythms involve offering the diet with n times theoverall Zn concentration (M) only every nth day with Zn-deficient diet offered on other days. Idiorrythmic Zn dose-rate feeding changed Zn accumulation in the femur and incisor in a complexbi-modal fashion, indicating that metabolic efficiency of dietary Zn is not constant but depends on Zn dose-rate. In contrast to feeding Zn in the conventional dose-response scheme, iMT and HSP7OmRNA were not affected by idiorrhythmic dose-rate feeding. Idiorrhythmic cycling in dietary Zn load posed no risk of a biochemical overload nor caused the animals to be stressed. Idiorrhythmic dose-rate feeding brings the dimension of time to the conventional dose-response

scholarly journals Magnesium and calcium deficiencies additively increase zinc concentrations and metallothionein expression in the rat liver

2012 ◽  
Vol 109 (3) ◽  
pp. 425-432 ◽  
Author(s):  
Megumi Kotani ◽  
Ki Hyun Kim ◽  
Natsumi Ishizaki ◽  
Masayuki Funaba ◽  
Tohru Matsui
Keyword(s):  
Rat Liver ◽  
Control Diet ◽  
Mrna Level ◽  
Male Rats ◽  
Mrna Levels ◽  
Deficient Diet ◽  
Mg Deficiency ◽  
Ca Deficiency ◽  
Zn Concentration ◽  
Dietary Treatments

Mg deficiency increases the concentration of Zn in the liver. We investigated the effect of Mg deficiency on the expression of Zn-regulating factors such as Zn transporters and metallothionein (MT) in the rat liver. Because Ca deficiency alleviates some of the effects of Mg deficiency, we also investigated the interactions associated with Ca and Mg deficiencies. Growing male rats were given a control diet, a Mg-deficient diet, a Ca-deficient diet and a Mg- and Ca-deficient diet for 3 weeks. Mg and Ca deficiencies additively increased the mRNA levels of MT-1 and MT-2, the MT protein concentration and the concentration of Zn in the liver. The hepatic mRNA level of Zip14 increased with Mg deficiency but not with Ca deficiency. The dietary treatments did not affect the mRNA levels of other Zn transporters such as Zip1, Zip5, ZnT1, ZnT5 and ZnT6 in the liver. Ca deficiency was found to decrease the amount of femoral Zn and increase serum Zn concentration. This did not occur in the case of Mg deficiency. These results suggest that Mg deficiency enhances hepatic Zn uptake by the up-regulation of Zip14 expression and increases hepatic Zn concentration, leading to the enhancement of MT expression. Ca deficiency causes a transfer of Zn from the bone to the liver, which increases hepatic Zn concentration and, in turn, up-regulates the expression of MT. Because Mg and Ca deficiencies increase hepatic Zn concentration and increase MT expression by different mechanisms, their effects are additive.

scholarly journals The effect of various levels of fructose in a copper-deficient diet on Cu deficiency in male rats

1990 ◽  
Vol 63 (2) ◽  
pp. 387-395 ◽  
Author(s):  
Charles G. Lewis ◽  
Meira Fields ◽  
Todd Beal
Keyword(s):  
Dose Response ◽  
Plasma Cholesterol ◽  
Male Rats ◽  
Deficient Diet ◽  
Cu Deficiency ◽  
Erythrocyte Superoxide Dismutase ◽  
Dietary Fructose ◽  
Nitrogen Concentrations ◽  
Inverse Response ◽  
Starch Diet

The present study was designed to examine the effects of various levels of fructose in a copper-deficient diet on some of the signs of Cu deficiency in the rat. Weanling male rats were randomly assigned to one of five diets which contained 0.6 μg Cu/g diet and 627 g carbohydrate/kg which was (g/kg): 627 fructose (diet 100); 470 fructose, 157 starch (diet 75); 313.5 fructose, 313.5 starch (diet 50); 157 fructose, 470 starch (diet 25); or 627 starch (diet 0). Rats ate their respective diets for either 2 or 5 weeks. There was a significant linear inverse response of body-weight (P< 0.0001), packed cell volume (p< 0.0001) and erythrocyte superoxide dismutase (EC1.15.1.1) activity (P< 0.008) to increasing levels of dietary fructose and a direct linear response of plasma cholesterol (P< 0.05) and blood urea nitrogen concentrations (P< 0.001) to increasing levels of dietary fructose. Liver, kidney and pancreatic Cu concentrations decreased in a dose-response manner as the level of dietary fructose increased. In general, if fructose was included in the diet the signs of Cu deficiency were exacerbated in a dose-response manner.

Ultrahigh dose-rate FLASH irradiation increases the differential response between normal and tumor tissue in mice

2014 ◽  
Vol 6 (245) ◽  
pp. 245ra93-245ra93 ◽  
Author(s):  
Vincent Favaudon ◽  
Laura Caplier ◽  
Virginie Monceau ◽  
Frédéric Pouzoulet ◽  
Mano Sayarath ◽  
...  
Keyword(s):  
Dose Rate ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Lung Tumors ◽  
Late Complications ◽  
Short Pulses ◽  
Conventional Dose ◽  
Induced Apoptosis ◽  
Factor Α

In vitro studies suggested that sub-millisecond pulses of radiation elicit less genomic instability than continuous, protracted irradiation at the same total dose. To determine the potential of ultrahigh dose-rate irradiation in radiotherapy, we investigated lung fibrogenesis in C57BL/6J mice exposed either to short pulses (≤500 ms) of radiation delivered at ultrahigh dose rate (≥40 Gy/s, FLASH) or to conventional dose-rate irradiation (≤0.03 Gy/s, CONV) in single doses. The growth of human HBCx-12A and HEp-2 tumor xenografts in nude mice and syngeneic TC-1 Luc+ orthotopic lung tumors in C57BL/6J mice was monitored under similar radiation conditions. CONV (15 Gy) triggered lung fibrosis associated with activation of the TGF-β (transforming growth factor–β) cascade, whereas no complications developed after doses of FLASH below 20 Gy for more than 36 weeks after irradiation. FLASH irradiation also spared normal smooth muscle and epithelial cells from acute radiation-induced apoptosis, which could be reinduced by administration of systemic TNF-α (tumor necrosis factor–α) before irradiation. In contrast, FLASH was as efficient as CONV in the repression of tumor growth. Together, these results suggest that FLASH radiotherapy might allow complete eradication of lung tumors and reduce the occurrence and severity of early and late complications affecting normal tissue.

Cholangiocarcinoma: The impact of endobiliary high-dose-rate (HDR) brachytherapy dose response on survival

Brachytherapy ◽  
2006 ◽  
Vol 5 (2) ◽  
pp. 91
Author(s):  
Matthew Biagioli ◽  
B-Chen Wen ◽  
Brandon Patton ◽  
Caroline Hoffman ◽  
Mark Harvey
Keyword(s):  
Dose Rate ◽  
Dose Response ◽  
High Dose Rate ◽  
High Dose ◽  
Hdr Brachytherapy ◽  
The Impact

Kinetics of DNA Repair Under Chronic Irradiation at Low and Medium Dose Rates in Repair Proficient and Repair Compromised Normal Fibroblasts

2021 ◽  
Author(s):  
Elena K. Zaharieva ◽  
Megumi Sasatani ◽  
Kenji Kamiya
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Dose Rate ◽  
Dose Response ◽  
Chronic Irradiation ◽  
Dose Rates ◽  
Chronic Radiation ◽  
Damage Repair ◽  
Kinetics Of ◽  
Medium Dose

We present time and dose dependencies for the formation of 53BP1 and γH2AX DNA damage repair foci after chronic radiation exposure at dose rates of 140, 250 and 450 mGy/day from 3 to 96 h, in human and mouse repair proficient and ATM or DNA-PK deficient repair compromised cell models. We describe the time/dose-response curves using a mathematical equation which contains a linear component for the induction of DNA damage repair foci after irradiation, and an exponential component for their resolution. We show that under conditions of chronic irradiation at low and medium dose rates, the processes of DNA double-strand breaks (DSBs) induction and repair establish an equilibrium, which in repair proficient cells manifests as a plateau-shaped dose-response where the plateau is reached within the first 24 h postirradiation, and its height is proportionate to the radiation dose rate. In contrast, in repair compromised cells, where the rate of repair may be exceeded by the DSB induction rate, DNA damage accumulates with time of exposure and total absorbed dose. In addition, we discuss the biological meaning of the observed dependencies by presenting the frequency of micronuclei formation under the same irradiation conditions as a marker of radiation-induced genomic instability. We believe that the data and analysis presented here shed light on the kinetics of DNA repair under chronic radiation and are useful for future studies in the low-to-medium dose rate range.

scholarly journals A comparison of the short-term kinetics of zinc metabolism in women during fasting and following a breakfast meal

1998 ◽  
Vol 80 (4) ◽  
pp. 363-370 ◽  
Author(s):  
Nicola M. Lowe ◽  
Leslie R. Woodhouse ◽  
Janet C. King
Keyword(s):  
Energy Content ◽  
Compartment Model ◽  
Zinc Metabolism ◽  
Short Term ◽  
Compartment System ◽  
Breakfast Meal ◽  
Physiological Importance ◽  
Two Compartment Model ◽  
Zn Concentration ◽  
Kinetics Of

The physiological importance and mechanism of the postprandial fall in plasma Zn concentration is not well understood. In order to gain further information on this apparent redistribution of plasma Zn, a stable isotope, 70Zn, was used to study the effect of a breakfast meal on plasma Zn kinetics. Nine women participated in two trials, a fasting trial and a breakfast-meal trial; five of the women participated in a third trial in which the energy content of the breakfast meal was doubled. At each trial, 0.1mg of 70Zn was infused intravenously, and the plasma disappearance of the isotope was analysed using a two-compartment model of Zn kinetics. Plasma Zn concentration fell significantly following the two trials in which the subjects were given meals, reaching low points that were 13 and 19 %, respectively, below concentrations at comparable times during the fasting trial. Kinetic analysis revealed that after the doubled breakfast meal there was a significant fall (P < 0.007) in the size of the most rapidly turning over Zn pool (pool (a)) from 2.90 (se 0.13)mg in the fasting state to 2.47 (se 0.14) mg postprandially. The fractional turnover rate of pool (a) to other extravascular Zn pools, i.e. outside the two-compartment system, was also significantly elevated after the doubled breakfast meal (P < 0.05). These results suggest that the decline in plasma Zn concentration following a meal is due to a redistribution of Zn from the plasma to other more slowly turning over extravascular pools that may be involved in the assimilation and metabolism of fuels following food intake.

Kinetic analysis of zinc metabolism and its regulation in normal humans

1986 ◽  
Vol 251 (2) ◽  
pp. R398-R408 ◽  
Author(s):  
M. E. Wastney ◽  
R. L. Aamodt ◽  
W. F. Rumble ◽  
R. I. Henkin
Keyword(s):  
Compartmental Model ◽  
Additional Data ◽  
Normal Subjects ◽  
The Body ◽  
Whole Body ◽  
Zinc Metabolism ◽  
Zinc Intake ◽  
Normal Humans ◽  
Taste And Smell ◽  
Oral Supplement

Zinc metabolism was studied in 32 normal volunteers after oral (n = 25) or intravenous (n = 7) administration of 65Zn. Data were collected from the blood, urine, feces, whole body, and over the liver and thigh regions for 9 mo while the subjects consumed their regular diets (containing 10 mg Zn ion/day) and for an additional 9 mo while the subjects received an exogenous oral supplement of 100 mg Zn ion/day. Data from each subject were fitted by a compartmental model for zinc metabolism that was developed previously for patients with taste and smell dysfunction. These data from normal subjects were used to determine the absorption, distribution, and excretion of zinc and the mass of zinc in erythrocytes, liver, thigh, and whole body. By use of additional data obtained from the present study, the model was refined further such that a large compartment, which was previously determined to contain 90% of the body zinc, was subdivided into two compartments to represent zinc in muscle and bone. When oral zinc intake was increased 11-fold three new sites of regulation of zinc metabolism were identified in addition to the two sites previously defined in patients with taste and smell dysfunction (absorption of zinc from gut and excretion of zinc in urine). The three new sites are exchange of zinc with erythrocytes, release of zinc by muscle, and secretion of zinc into gut. Regulation at these five sites appears to maintain some tissue concentrations of zinc when dietary zinc increases.

Fentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet

2021 ◽  
Author(s):  
Emilie Laboureyras ◽  
Meric Ben Boujema ◽  
Annie Mauborgne ◽  
John Simmers ◽  
Michel Pohl ◽  
...  
Keyword(s):  
Male Rats ◽  
Deficient Diet ◽  
Analgesic Tolerance ◽  
Underlying Mechanisms

scholarly journals Syngeneic and allogeneic bone marrow engraftment after total body irradiation: dependence on dose, dose rate, and fractionation

Blood ◽  
1991 ◽  
Vol 77 (3) ◽  
pp. 661-669 ◽  
Author(s):  
JD Down ◽  
NJ Tarbell ◽  
HD Thames ◽  
PM Mauch
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Radiation Dose ◽  
Dose Rate ◽  
Dose Response ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Allogeneic Bone ◽  
Low Dose Rate ◽  
Total Body

Abstract Murine bone marrow chimera models were used to assess the efficacy of host total body irradiation (TBI) given at different doses, dose rates, and fractionation schemes in providing for engraftment of syngeneic and allogeneic bone marrow. B6-Hbbd congenic and LP mice, respectively, were used as donors (10(7) bone marrow cells) for syngeneic and allogenic (H-2 compatible) transplantation in standard B6 recipients. Stable marrow chimerism was determined from host and donor stem cell- derived hemoglobin phenotypes (Hbbs and Hbbd) on gel electrophoresis at 3 months posttransplant. Partial engraftment of syngeneic marrow was seen at single doses as low as 2 Gy, with the donor component increasing steadily with increasing TBI dose to a level of 100% at 7 Gy. Immunologic resistance of the host appeared to prevent allogeneic engraftment until 5.5 Gy. A very steep radiation dose response was then observed so that the level of chimerism with 6 Gy and above became comparable with syngeneic engraftment. Low dose rate (5 cGy minute-1) and fractionated TBI required higher total doses for equivalent engraftment (radiation dose-sparing) in both syngeneic and allogenic bone marrow transplantation. This displacement in the dose-response curve on fractionation was seen with interfraction intervals of 3 and 6 hours. A further dose-sparing effect was observed on extending the interval to 18 and 24 hours, but only for allogeneic transplantation, and may therefore be related to recovery of immune-mediated graft resistance. The involvement of multiple target cell populations in determining allogenic engraftment rendered the application of the linear-quadratic model for radiation cell survival problematic in this case. The recovery in dose when low dose rate and 6-hour interfraction intervals were applied in either syngeneic or allogeneic BMT is consistent with appreciable sub-lethal damage repair in the primitive self-renewing stem cell population of the host marrow. These results contrast with the poor repair capacity of the 11-day spleen colony- forming units (CFUs) population after fractionated irradiation and support the notion that ablation of early stem cells in the pre-CFUs compartment is essential for long-term marrow engraftment.

scholarly journals The effect of protein-deficient isoenergetic diets on the growth of rat jejunal mucosa

1982 ◽  
Vol 48 (1) ◽  
pp. 25-36 ◽  
Author(s):  
Gabrielle Syme
Keyword(s):  
Surface Area ◽  
G Protein ◽  
Protein Deficiency ◽  
Male Rats ◽  
Jejunal Mucosa ◽  
Metaphase Arrest ◽  
Villus Height ◽  
Deficient Diet ◽  
Protein Deficient Diet ◽  
Delayed Maturation

1. Newly weaned 21-d-old male rats were given isoenergetic diets containing 200, 100 and 50 g protein/kg for 7, 14, 28 or 70 d. The mid-jejunum was removed from the rats and a micrometric analysis of the mucosa was made. The following measurements were made: number of villi/mm2, vilius dimensions, villus surface area, crypt depth, crypt: villus, the number of cells/crypt in metaphase arrest per h.2. Comparisons were made between animals of the same age but on different diets, and animals on the same diet but of different ages. The latter comparison gave information on the effect of protein deficiency on the pattern of maturation of each feature of The villus or crypt studied.3. The effect of protein deficiency was not consistent at each stage of maturation. For instance villus height was decreased when compared with the controls following 28 d on a protein-deficient diet but not after 7 or 70 d.4. The only measurement to be unaffected by protein deficiency was the number of villi per unit area.5. In general the 50 g protein/kg diet had a more pronounced effect than the 100 g protein/kg diet. Protein deficiency delayed maturation by either slowing or inhibiting changes seen in normal maturation.6. In rats given 50 g protein/kg diet, although the villus surface area did not increase as the rats matured there were increases in epithelial cell production rate and number of crypts per villus.

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