scholarly journals Modeling cell survival and change in amount of DNA during protracted irradiation

2016 ◽  
Vol 58 (3) ◽  
pp. 302-312 ◽  
Author(s):  
Yusuke Matsuya ◽  
Kaori Tsutsumi ◽  
Kohei Sasaki ◽  
Yuji Yoshii ◽  
Takaaki Kimura ◽  
...  
Keyword(s):  
Low Dose ◽  
Dose Range ◽  
Flow Cytometric Analysis ◽  
Chinese Hamster ◽  
Clonogenic Survival ◽  
High Dose ◽  
X Rays ◽  
Theoretical Evaluation ◽  
Flow Cytometric ◽  
M Phase

Abstract Hyper-radiosensitivity (HRS) is a well-known bioresponse under low-dose or low-dose-rate exposures. Although disorder of the DNA repair function, non-targeted effects and accumulation of cells in G2 have been experimentally observed, the mechanism for inducing HRS by long-term irradiation is still unclear. On the basis of biological experiments and a theoretical study, we have shown that change in the amount of DNA associated with accumulation of cells in G2 enhances radiosensitivity. To demonstrate continuous irradiation with 250 kVp X-rays, we adopted a fractionated regimen of 0.186 or 1.00 Gy per fraction at intervals of 1 h (i.e. 0.186 Gy/h, 1.00 Gy/h on average) to Chinese Hamster Ovary (CHO)-K1 cells. The change in the amount of DNA during irradiation was quantified by flow cytometric analysis with propidium iodide (PI). Concurrently, we attempted a theoretical evaluation of the DNA damage by using a microdosimetric-kinetic (MK) model that was modified to incorporate the change in the amount of DNA. Our experimental results showed that the fraction of the cells in G2/M phase increased by 6.7% with 0.186 Gy/h and by 22.1% with 1.00 Gy/h after the 12th irradiation. The MK model considering the change in amount of DNA during the irradiation exhibited a higher radiosensitivity at a high dose range, which could account for the experimental clonogenic survival. The theoretical results suggest that HRS in the high dose range is associated with an increase in the total amount of DNA during irradiation.

scholarly journals Skin regeneration is accelerated by a lower dose of multipotent mesenchymal stromal/stem cells—a paradigm change

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Gertraud Eylert ◽  
Reinhard Dolp ◽  
Alexandra Parousis ◽  
Richard Cheng ◽  
Christopher Auger ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Low Dose ◽  
Dose Range ◽  
High Dose ◽  
Full Thickness ◽  
Burn Wound ◽  
Dermal Regeneration Template ◽  
Yorkshire Pigs ◽  
Stromal Stem Cells

Abstract Background Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®. Methods We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm2 of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin. Result We found that the low dose range between 200 and 40,000 cells/cm2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm2 and a high dose of 2,000,000 cells/cm2. The low dose of 40,000 cells/cm2 accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control. Conclusion This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.

A study of the effect of X-rays on the electrical properties of mammalian nerve and muscle

1963 ◽  
Vol 157 (969) ◽  
pp. 536-561 ◽  
Keyword(s):  
Dose Rate ◽  
Action Potentials ◽  
Time Course ◽  
Low Dose ◽  
High Dose ◽  
X Rays ◽  
Low Dose Rate ◽  
End Plate ◽  
Small Doses ◽  
Motor End Plate

Resting potentials, action potentials, and miniature end-plate potentials have been re­corded from isolated phrenic-diaphragm preparations of the rat during and after irradiation with X-rays. Relatively small doses of a few thousand roentgens have no obvious effect on the preparation for many hours but larger doses, of the order of 70 to 150 kr irreversibly block neuromuscular transmission. The block is not accompanied by any change in the size of action potentials, resting potentials, membrane constants or miniature potentials recorded in the muscle with intracellular electrodes, or in the size of action potentials recorded in the nerve. Records made at the motor end-plate show that the cause of the block is a ‘pre-synaptic ’ failure of impulse propagation in the intramuscular part of the nerve. The time course of the failure depends largely on the rate at which X-rays are delivered to the pre­paration: at a high dose-rate (70kr/min) the block develops rapidly and is accompanied by an increase in the frequency of miniature potentials; at a low dose-rate (7 kr/min) larger doses are required, the latency is longer and the miniature potentials continue at a normal frequency. The sequence in which different parts of the muscle become blocked, the abrupt nature of the failure at an individual motor end-plate, and the increase in frequency of the miniature potentials together suggest that the action of X-rays is to block conduction in the nerve near its terminals, possibly by depolarizing points where the axons branch and the safety factor for the propagation of impulses is low. The results reported in this paper do not support the hypotheses that small doses of X-rays at a high or a low dose-rate lead to an initial 'enhancement' of function or that they produce immediate and reversible changes in the permeability of excitable membranes to ions.

scholarly journals SUN-042 Low Dose Cyproterone Acetate for the Treatment of Transgender Women - a Retrospective Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Naomi Even-Zohar ◽  
Yael Sofer ◽  
Iris Yaish ◽  
Merav Serebro ◽  
Karen Tordjman ◽  
...  
Keyword(s):  
Cyproterone Acetate ◽  
Dose Group ◽  
Low Dose ◽  
Dose Range ◽  
Hormonal Treatment ◽  
Transgender Women ◽  
High Dose ◽  
Historical Cohort ◽  
Treatment Groups ◽  
First Time

Abstract Introduction : Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (<20 mg/day), compared with high dose (>50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.

Flow cytometric analysis of marrow cell kinetics in children treated with high-dose MTX and CF rescue

1986 ◽  
Vol 16 (3) ◽  
pp. 277-281 ◽  
Author(s):  
Masahito Tsurusawa ◽  
Kuniaki Sasaki ◽  
Hatsufumi Matsuoka ◽  
Yoshifumi Yamamoto ◽  
Naoyuki Katano ◽  
...  
Keyword(s):  
Cell Kinetics ◽  
Marrow Cell ◽  
Flow Cytometric Analysis ◽  
High Dose ◽  
Flow Cytometric

scholarly journals Flow cytometric analysis of bromodeoxyuridine-substituted cells stained with 33258 Hoechst.

1977 ◽  
Vol 25 (7) ◽  
pp. 927-934 ◽  
Author(s):  
S A Latt ◽  
Y S George ◽  
J W Gray
Keyword(s):  
Flow Cytometry ◽  
Cell Growth ◽  
Deoxyribonucleic Acid ◽  
Flow Cytometric Analysis ◽  
Chinese Hamster ◽  
Acid Synthesis ◽  
Whole Cells ◽  
Flow Cytometric ◽  
Deoxyribonucleic Acid Synthesis ◽  
Average Fluorescence

This paper describes a flow-cytometric application of the quenching of fluorescence from 33258 Hoechst stained Chinese hamster ovary-line cells due to the incorporation of 5-bromo-deoxyuridine (BrdU) into the cellular deoxyribonucleic acid. Cells were grown for 24 hr in medium containing BrdU in concentrations ranging from 1 x 10(-8) to 1 x 10(-4) M. For each concentration we measured the average fluorescence as determined by flow cytometry, the extent of BrdU substitution and the effect of the BrdU on cell growth. We determined that a BrdU concentration of 1 x 10(-5) M resulted in sufficient substitution to quench the fluorescence from 33258 Hoechst by a factor of 4, allowing discrimination between cycling and noncycling cells. The extent of BrdU substitution after growth for 24 hr in this concentration of BrdU was 64%. These data indicate the feasibility of detecting deoxyribonucleic acid synthesis in whole cells using the 33258 Hoechst-BrdU methodology.

Also High Dose of Aspirin Prolongs Bleeding Time, But Later After Ingestion

1979 ◽  
Author(s):  
E. Waiter ◽  
R. Siess ◽  
R. Zimmermann ◽  
E. Weber
Keyword(s):  
Low Dose ◽  
Bleeding Time ◽  
Dose Range ◽  
Blood Levels ◽  
High Dose ◽  
Antithrombotic Agent ◽  
Double Blind ◽  
Significant Prolongation ◽  
Small Doses ◽  
Induced Aggregation

O’Grady and Moncada (Lancet, 1978, ii, 780) found after ingestion of 0.3 g but not after 3.9g of aspirin a significant prolongation of the bleeding time, measured 2h after ingestion. This confirmed their unpublished findings in cats and rabbits, and also their suggestion, that aspirin as an antithrombotic agent should be used in small doses. We decided to test a intermediate dose of 1.5g in comparison to 0.3 and 4.0. Young healthy volunteers received in a double blind trial at random with 14 days interval the three doses. Bleeding time was measured and blood taken for collagen induced aggregation and blood levels of ASA and SA before, 2, 4 and 5.5 after ingestion of ASA. Bleeding time increased significantly 2 h after 0.3g ASA from 213 to 380 sec.(n=8,p <0.01), and from 181 to 408 after 1. g. The high dose of 4g led to a smaller prolongation from 224 to 342 after 2 h, but reached the low dose range after 4 h, 440 sec. (p < 0.01). Collagen-induced aggregation (1 μg/m 1 and 5 μg/ml) was independent from the digese of ASA reduced, beginning after two hours. Our findings do not confirm the result of O’Grady and Moncada. The slower increase of bleeding time after the high dose of ASA must be discussed in relation to ASA and SA blood-levels and reversible inhibition of cyclooxygenase in endothelial cells

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