scholarly journals Cancer and Low Dose Responses in vivo: Implications for Radiation Protection

Dose-Response ◽  
2007 ◽  
Vol 5 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
R. E. J. Mitchel
Keyword(s):  
Radiation Protection ◽  
Radiation Risk ◽  
Large Body ◽  
Epidemiological Data ◽  
Tissue Type ◽  
Human Populations ◽  
Low Doses ◽  
Dose Limits ◽  
High Doses

The Linear No Threshold (LNT) hypothesis states that ionizing radiation risk is directly proportional to dose, without a threshold. This hypothesis, along with a number of additional derived or auxiliary concepts such as radiation and tissue type weighting factors, and dose rate reduction factors, are used to calculate radiation risk estimates for humans, and are therefore fundamental for radiation protection practices. This system is based mainly on epidemiological data of cancer risk in human populations exposed to relatively high doses (above 100 mSv), with the results linearly extrapolated back to the low doses typical of current exposures. The system therefore uses dose as a surrogate for risk. There is now a large body of information indicating that, at low doses, the LNT hypothesis, along with most of the derived and auxiliary concepts, is incorrect. The use of dose as a predictor of risk needs to be re-examined and the use of dose limits, as a means of limiting risk needs to be re-evaluated. This re-evaluation could lead to large changes in radiation protection practices.

scholarly journals Radiation Risk Prediction and Genetics: The Influence of the TP53 Gene in vivo

Dose-Response ◽  
2005 ◽  
Vol 3 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
R. E. J. Mitchel
Keyword(s):  
Risk Prediction ◽  
Radiation Risk ◽  
Tp53 Gene ◽  
Cell Cycle Checkpoints ◽  
Low Doses ◽  
Regulatory Pathways ◽  
Dose Limits ◽  
Changes In Risk ◽  
Qualitative Changes

Risk prediction and dose limits for human radiation exposure are based on the assumption that risk is proportional to total dose. However, there is concern about the appropriateness of those limits for people who may be genetically cancer prone. The TP53 gene product functions in regulatory pathways for DNA repair, cell cycle checkpoints and apoptosis, processes critical in determining ionizing radiation risk for both carcinogenesis and teratogenesis. Mice that are deficient in TP53 function are cancer prone. This review examines the influence of variations in TP53 gene activity on cancer and teratogenic risk in mice exposed to radiation in vivo, and compares those observations to the assumptions and predictions of radiation risk inherent in the existing system of radiation protection. Current assumptions concerning a linear response with dose, dose additivity, lack of thresholds and dose rate reduction factors all appear incorrect at low doses. TP53 functional variations can further modify radiation risk from either high or low doses, or risk from radiation exposures combined with other stresses, and those modifications can result in both quantitative and qualitative changes in risk.

Seizures in Rats Associated with Divalent Cation Inhibition of Na+–K+-ATP'ase

1971 ◽  
Vol 49 (11) ◽  
pp. 1217-1224 ◽  
Author(s):  
J. Donaldson ◽  
T. St-Pierre ◽  
J. Minnich ◽  
A. Barbeau
Keyword(s):  
Divalent Cation ◽  
Regional Analysis ◽  
Intraventricular Injection ◽  
Specific Inhibition ◽  
Low Doses ◽  
High Doses ◽  
Very High

In vitro determination of rat brain microsomal ATP'ase activity revealed specific inhibition of the Na+–K+-ATP'ase by cations in the order Zn2+ > Cu2+ > Fe2+ > Mn2+. Intraventricular injection of the same cations or of ouabain resulted in convulsions. Regional analysis of ATP'ase from brains of rats after convulsions showed inhibited Na+–K+-ATP'ase activity in hippocampus and hypothalamus. Hippocampus and hypothalamus were found to have the highest Na+–K+-ATP'ase activity in the rat brain.The potent inhibitors of Na+–K+-ATP'ase in vitro (ouabain, Zn2+, and Cu2+) were similarly effective in vivo (hippocampus and hypothalamus), while the inhibitors relatively ineffective in vitro (Fe2+ and Mn2+) were similarly of low potency in vivo. The potent inhibitors of Na+–K+-ATP'ase caused convulsions at low doses; the ineffective inhibitors caused convulsions only at very high doses.

Mechanisms of dorsal-ventral patterning in noggin-induced neural tissue

Development ◽  
1997 ◽  
Vol 124 (12) ◽  
pp. 2477-2488 ◽  
Author(s):  
A.K. Knecht ◽  
R.M. Harland
Keyword(s):  
Neural Tissue ◽  
Bmp Signaling ◽  
Cell Interactions ◽  
Dependent Manner ◽  
Low Doses ◽  
Morphogenetic Protein ◽  
High Doses ◽  
Dose Dependent ◽  
Cell Cell

We have investigated mechanisms of dorsal-ventral patterning of neural tissue, using Xenopus ectoderm neuralized by noggin protein. This tissue appears to be patterned dorsoventrally; cp1-1, a gene expressed in the dorsal brain, and etr-1, a gene largely excluded from the dorsal brain, are expressed in separate territories in noggin-treated explants (Knecht, A. K., Good, P. J., Dawid, I. B. and Harland, R. M. (1995) Development 121, 1927–1936). Here we show further evidence that this pattern represents a partial dorsal-ventral organization. Additionally, we test two mechanisms that could account for this pattern: a dose-dependent response to a gradient of noggin protein within the explant, and regulative cell-cell interactions. We show that noggin exhibits concentration-dependent effects, inducing cp1-1 at low doses but repressing it at high doses. Since noggin acts by antagonizing Bone Morphogenetic Protein (BMP) signaling, this result suggests that BMPs also may act in a dose-dependent manner in vivo. However, in the absence of a noggin gradient, regulative cell-cell interactions can also pattern the tissue. Such regulation is facilitated by increased motility of noggin-treated cells. Finally, the response of cells to both of these patterning mechanisms is ultimately controlled by a third process, the changing competence of the responding tissue.

CYCLOOXYGENASE INDIPENDENT PLATELET AGGREGATION:RELATION WITH ASPI RIN CONCENTRATION

1987 ◽  
Author(s):  
C Cordova ◽  
F Violi ◽  
D Praticò ◽  
A Ghiselli ◽  
C Alessandri ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Low Doses ◽  
Dose Dependent Fashion ◽  
Threshold Doses ◽  
High Doses ◽  
Dose Dependent

Low doses of aspirin (20 mg/day) were previously reported to be uneffective in preventing platelet aggregation (PA) induced by pairs of aggregating agents such as PAF and adrenalin.This was in part attributed to the inability of such treatment to inhibit lipo oxygenase-dependent PA.The latter can be observed in vitro in"aspl rinated"platelets stimulated with high quantities of aggregating -agents.The aim of this study was to evaluate if the lipooxygenase-dependent PA was influenced by aspirin in a dose-dependent fashion. PA was studied in platelet rich plasma (PRP)(Born's method) by using threshold doses of aggregating agents (TDA) such as PAF(4-75 nM),epinephrine(0.6-2 μM) and collagen(2-4 μg/ml).PA performed in PRP pretrated with 100μM aspirin was fully prevented;in the same samples thromboxane (Tx) A2 evaluated by its metabolite Tx B2 was almost absent.Increasing amount of PAF(20 fold TDA),epinephrine(20 fold TDA) and collagen (36 fold TDA) do aggregate"aspirinated"pla telets;similarly"aspirinated"platelets aggregate when stimulated-with a pair of aggregating agents (TDA of PAF+epinephrine).This phenomenon was not detected if platelets were incubated with higher amounts of aspirin (250-500 μM).The study suggests that aspirin could influence lipooxygenase-dependent PA.This hypothesis is sup ported by a research showing the aspirin inhibits dose-dependently platelet HETE formation.A further study is now in progress to eva luate the influence of high doses of aspirin on cyclooxygenase-i"n dependent PA in vivo.

scholarly journals Effect of Ionizing Radiation on Human Health

2019 ◽  
Vol 5 (03) ◽  
pp. 200-205
Author(s):  
Ashish Chaturvedi ◽  
Vinod Jain
Keyword(s):  
Ionizing Radiation ◽  
Radiation Protection ◽  
Radiation Effects ◽  
Radiation Risk ◽  
X Rays ◽  
Medical Benefits ◽  
Radiation Induced Cancer ◽  
Precautionary Measures ◽  
High Doses ◽  
Effects Of Radiation

The effects of radiation was first recognized in the use of X-rays for medical diagnosis. The rush in exploiting the medical benefits led fairly to the recognition of the risks and induced harm associated with it. In the early days, the most obvious harm resulting from high doses of radiation, such as radiation burns were observed and protection efforts were focused on their prevention, mainly for practitioners rather than patients. Although the issue was narrow, this lead to the origin of radiation protection as a discipline. Subsequently, it was gradually recognized that there were other, less obvious, harmful radiation effects such as radiation-induced cancer, for which there is a certain risk even at low doses of radiation. This risk cannot be completely prevented but can only be minimized. Therefore, the balancing of benefits from nuclear and radiation practices against radiation risk and efforts to reduce the residual risk has become a major feature of radiation protection. In this paper, we shall be looking at the precautionary measures for protecting life, properties and environment against ionizing radiation.

scholarly journals Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Elena Alcalde-Estévez ◽  
Patricia Sosa ◽  
Ana Asenjo-Bueno ◽  
Patricia Plaza ◽  
Gemma Olmos ◽  
...  
Keyword(s):  
Myogenic Differentiation ◽  
Adipogenic Differentiation ◽  
Horse Serum ◽  
Annexin V ◽  
Skeletal Muscle Regeneration ◽  
Regeneration Process ◽  
Low Doses ◽  
High Doses ◽  
Muscular Regeneration

AbstractUraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C2C12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.

Commentary on ‘Resveratrol commonly displays hormesis: Occurrence and biomedical significance’

2010 ◽  
Vol 29 (12) ◽  
pp. 1024-1025 ◽  
Author(s):  
David G Lindsay
Keyword(s):  
Dose Response ◽  
Low Doses ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Beneficial Effects ◽  
In Vitro Systems ◽  
High Doses

Many phenolics found naturally in food have the capacity to show beneficial effects at low doses and toxicity at high doses in in vitro systems. Resveratrol is no exception. Nonetheless, in the nutritional context, the evidence that resveratrol shows hormetic effects is very limited and is of questionable relevance given its rapid metabolism in the stomach. Hormesis can only be confirmed if evidence for a J- or U-shaped dose-response relationship is found in in vivo doses that are relevant to human intakes.

Amplifying Effect of Sumatriptan on Noradrenaline Venoconstriction in Migraine Patients

Cephalalgia ◽  
1993 ◽  
Vol 13 (6) ◽  
pp. 383-388 ◽  
Author(s):  
Alessandro Panconesi ◽  
Giancarlo Franchi ◽  
Bruno Anselmi ◽  
Carlo Curradi ◽  
Brunetto Tarquini
Keyword(s):  
Low Doses ◽  
Therapeutic Action ◽  
Hand Vein ◽  
Subcutaneous Sumatriptan ◽  
Amplifying Effect ◽  
High Doses ◽  
A Minor ◽  
Cranial Arteries

The venoconstrictive activity of sumatriptan and its interaction with noradrenaline (NA)- and 5-hydroxy-tryptamine (5HT) venoconstriction was studied in vivo in the hand vein of migraineurs. Sumatriptan, injected at increasing doses into the vein, caused local venoconstriction after a 500 mg dose, comparable to that induced by 0.5–1 mg of 5HT. This venoconstriction was completely inhibited by low doses of ketanserin (5 mg). Subcutaneous sumatriptan (6 mg) provoked a minor increase in vein tone, lasting less than 30 min. Non-venoconstrictive doses of sumatriptan (10–100 mg), injected in the hand vein, produced an amplification of NA-venoconstriction but not of 5HT-induced venoconstriction. A similar increased effect was displayed by subcutaneous sumatriptan (6 mg) for at least 1 h. Sumatriptan appears to cause peripheral venoconstriction only at high doses locally applied (in the hand vein), by acting on 5HT2 receptors. Clinical subcutaneous doses (6 mg) do not show significant venoconstrictive effects. The amplifying effect on NA venoconstriction, also caused by 5HT, ergotamine and dihydroergotamine in human cranial arteries, may be important in explaining the therapeutic action of sumatriptan in migraine attacks.

scholarly journals Peripheral 5-HT1Aand 5-HT7Serotonergic Receptors Modulate Parasympathetic Neurotransmission in Long-Term Diabetic Rats

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Beatriz Restrepo ◽  
María Luisa Martín ◽  
Luis San Román ◽  
Asunción Morán
Keyword(s):  
Inhibitory Action ◽  
Vagal Stimulation ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
Low Doses ◽  
Dual Effect ◽  
High Doses

We analyzed the modulation of serotonin on the bradycardia inducedin vivoby vagal electrical stimulation in alloxan-induced long-term diabetic rats. Bolus intravenous administration of serotonin had a dual effect on the bradycardia induced either by vagal stimulation or exogenous Ach, increasing it at low doses and decreasing it at high doses of 5-hydroxytryptamine (5-HT), effect reproduced by 5-carboxamidotryptamine maleate (5-CT), a 5-HT1/7agonist. The enhancement of the bradycardia at low doses of 5-CT was reproduced by 5-HT1Aagonist 8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) and abolished by WAY-100,635, 5-HT1Aantagonist. Pretreatment with 5-HT1antagonist methiothepin blocked the stimulatory and inhibitory effect of 5-CT, whereas pimozide, 5-HT7antagonist, only abolished 5-CT inhibitory action. In conclusion, long-term diabetes elicits changes in the subtype of the 5-HT receptor involved in modulation of vagally induced bradycardia. Activation of the 5-HT1Areceptors induces enhancement, whereas attenuation is due to 5-HT7receptor activation. This 5-HT dual effect occurs at pre- and postjunctional levels.

Sign in / Sign up

Export Citation Format

Share Document