scholarly journals THE COMPARATIVE EFFECTS OF NEUTRONS AND X-RAYS ON THE WHOLE BODY

1937 ◽  
Vol 66 (6) ◽  
pp. 667-688 ◽  
Author(s):  
John H. Lawrence ◽  
Robert Tennant
Keyword(s):  
Normal Tissue ◽  
Whole Body ◽  
X Rays ◽  
Average Daily Dose ◽  
Tissue Destruction ◽  
Delayed Effects ◽  
Long Period ◽  
Tolerance Dose ◽  
Daily Dose ◽  
Small Doses

Irradiation of the whole bodies of mice with neutron rays in sufficient quantities, leads to a clinical, bacteriological and anatomical picture similar to that following Roentgen irradiation. The mucosa of the small intestine and the lymphoid and hemapoietic tissues are the most radiosensitive. The mechanism of death after both forms of radiation seems to be a combination of tissue destruction and enterogenous infection, the former predominating in the acute deaths after large doses. Aside from any possible delayed effects from exposure to small doses over a long period of time, concerning which we have no information, these changes after relatively large doses make it imperative that workers in laboratories generating neutrons protect themselves from exposure by screening. For the same amount of ionization measured by a small bakelite-walled thimble chamber, neutrons are more biologically destructive than x-rays. The average daily dose to those working with neutrons should not exceed one-fourth of the tolerance dose accepted for x-rays. Whether daily doses of this magnitude, over a long period of time, will result in damage is not known. Also, if neutrons are tried therapeutically normal tissue must be protected from undue irradiation.

scholarly journals Analysis of lncRNA-miRNA-mRNA Expression Pattern in Heart Tissue After Total Body Irradiation in a Mouse Model

2020 ◽  
Author(s):  
Molykutty J. Aryankalayil ◽  
Shannon Martello ◽  
Michelle Bylicky ◽  
Jared M. May ◽  
Sunita Chopra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Normal Tissue ◽  
Heart Tissue ◽  
Whole Body ◽  
Mouse Heart ◽  
Heart Cells ◽  
Rna Expression ◽  
Messenger Rnas ◽  
Delayed Effects ◽  
Radiation Induced

Abstract Background: Radiation therapy is integral to effective thoracic cancer treatments, but its application is limited by sensitivity of critical organs such as the heart. The impacts of acute radiation-induced damage and its chronic effects on normal heart cells are highly relevant in radiotherapy with increasing lifespans of patients. Biomarkers for normal tissue damage after radiation exposure, whether accidental or therapeutic, are being studied as indicators of both acute and delayed effects. Recent research has highlighted the potential importance of RNAs, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as biomarkers to assess radiation damage. Understanding changes in mRNA and non-coding RNA expression will elucidate biological pathway changes after radiation. Methods: To identify significant expression changes in mRNAs, lncRNAs, and miRNAs, we performed whole transcriptome microarray analysis of mouse heart tissue at 48h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray (Gy). We also validated changes in specific lncRNAs through RT-qPCR. Ingenuity Pathway Analysis (IPA) was used to identify pathways associated with gene expression changes. Results: We observed sustained increases in lncRNAs and mRNAs, across all doses of radiation. Alas2, Aplnr, and Cxc3r1 were the most significantly downregulated mRNAs across all doses. Among the significantly upregulated mRNAs were cell-cycle arrest biomarkers Gdf15, Cdkn1a, and Ckap2. Additionally, IPA identified significant changes in gene expression relevant to senescence, apoptosis, hemoglobin synthesis, inflammation, and metabolism. LncRNAs Abhd11os, Pvt1, Trp53cor1, and Dino showed increased expression with increasing doses of radiation. We did not observe any miRNAs with sustained up- or downregulation across all doses, but miR-149-3p, miR-6538, miR-8101, miR-7118-5p, miR-211-3p, and miR-3960 were significantly upregulated after 12 Gy. Conclusions: Radiation-induced RNA expression changes may be predictive of normal tissue toxicities and may indicate targetable pathways for radiation countermeasure development and improved radiotherapy treatment plans.

scholarly journals Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Molykutty J. Aryankalayil ◽  
Shannon Martello ◽  
Michelle A. Bylicky ◽  
Sunita Chopra ◽  
Jared M. May ◽  
...  
Keyword(s):  
Gene Expression ◽  
Normal Tissue ◽  
Heart Tissue ◽  
Whole Body ◽  
Mouse Heart ◽  
Heart Cells ◽  
Rna Expression ◽  
Messenger Rnas ◽  
Delayed Effects ◽  
Radiation Induced

Abstract Background Radiation therapy is integral to effective thoracic cancer treatments, but its application is limited by sensitivity of critical organs such as the heart. The impacts of acute radiation-induced damage and its chronic effects on normal heart cells are highly relevant in radiotherapy with increasing lifespans of patients. Biomarkers for normal tissue damage after radiation exposure, whether accidental or therapeutic, are being studied as indicators of both acute and delayed effects. Recent research has highlighted the potential importance of RNAs, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) as biomarkers to assess radiation damage. Understanding changes in mRNA and non-coding RNA expression will elucidate biological pathway changes after radiation. Methods To identify significant expression changes in mRNAs, lncRNAs, and miRNAs, we performed whole transcriptome microarray analysis of mouse heart tissue at 48 h after whole-body irradiation with 1, 2, 4, 8, and 12 Gray (Gy). We also validated changes in specific lncRNAs through RT-qPCR. Ingenuity Pathway Analysis (IPA) was used to identify pathways associated with gene expression changes. Results We observed sustained increases in lncRNAs and mRNAs, across all doses of radiation. Alas2, Aplnr, and Cxc3r1 were the most significantly downregulated mRNAs across all doses. Among the significantly upregulated mRNAs were cell-cycle arrest biomarkers Gdf15, Cdkn1a, and Ckap2. Additionally, IPA identified significant changes in gene expression relevant to senescence, apoptosis, hemoglobin synthesis, inflammation, and metabolism. LncRNAs Abhd11os, Pvt1, Trp53cor1, and Dino showed increased expression with increasing doses of radiation. We did not observe any miRNAs with sustained up- or downregulation across all doses, but miR-149-3p, miR-6538, miR-8101, miR-7118-5p, miR-211-3p, and miR-3960 were significantly upregulated after 12 Gy. Conclusions Radiation-induced RNA expression changes may be predictive of normal tissue toxicities and may indicate targetable pathways for radiation countermeasure development and improved radiotherapy treatment plans.

scholarly journals AB0474 THE USE OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) IN WOMEN WITH ANKYLOSING SPONDYLITIS (AS) DURING PREGNANCY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1264.2-1265
Author(s):  
O. Krichevskaya ◽  
T. Dubinina ◽  
E. Ilinykh ◽  
S. Glukhova ◽  
A. Demina
Keyword(s):  
New York ◽  
Back Pain ◽  
Nsaid Therapy ◽  
International Studies ◽  
Average Daily Dose ◽  
Time Data ◽  
The Third ◽  
Increased Risk ◽  
Daily Dose ◽  
Adherence To Therapy

Background:NSAIDs remain the first-line drugs in treatment of AS. During pregnancy, COX-2 non-selective NSAIDs are allowed for intake up to 32 weeks, but the question of the dose-dependent effect of NSAIDs on fetal organogenesis in the 1st trimester and on fetal kidney function and the increased risk of bleeding in childbirth when taken in the second half of pregnancy continues to be discussed. At the same time, data on the effectiveness of NSAIDs, including their low and medium doses, during pregnancy are extremely small.Objectives:to describe the frequency of using NSAIDs during pregnancy, to determine relationship between the dose of NSAIDs, adherence to therapy with the activity of AS.Methods:50 pregnancies were followed in 49 pregnant women with confirmed AS (modified New York criteria, 1984). The average age of the pts was 31.6 ± 4.9 years, the duration of the disease was 134.4 ± 85.8 months. The visits were conducted at 10-11, 20-21, and 31-32 weeks of pregnancy. The BASDAI in the month of conception and in the trimesters (trim.) of pregnancy was: 1,4[0,6; 3,3]; 2,3[1,2; 4,4]; 2,8[1,4; 4,2] and 2,2[1,6; 4,0], respectively. The level of nocturnal back pain according to the NRS in the first, second and third trim. was: 3.2±2.0; 5.4±2.5 and 5.2±2.6, respectively. The drug of choice was ibuprofen at a maximum daily dose of 1200 mg, its withdrawal - no later than 32 weeks of pregnancy.Adherence to NSAID therapy was defined as the ratio of the actual dose taken to the prescribed dose; an indicator of less than 80% was regarded as non-adherence to therapy. The total dose of NSAIDs was determined by the NSAID intake index (M. Dougados, 2001). The” actual daily dose” of ibuprofen was the sum of the doses of ibuprofen taken, divided by the number of actual days of taking the drug. The “average daily dose” was defined as the sum of the ibuprofen doses taken, divided by the number of days in the trimester.Results:At the time of conception and in the first, second and third trim. of pregnancy, NSAIDs were taken 23 (46%), 20 (40%), 30 (60%) and 21 (43.8%) women, respectively. The NSAID intake index, the actual and average daily dose of ibuprofen are shown in the Table 1.month of conceptiontrim. 1trim. 2trim. 3the actual daily dose, mg-700[425; 800]800[400; 1000]750[400; 1200]the average daily dose, mg-158[87,9; 307,7]355,1[138,5; 685,7]580[320; 1200]NSAIDs intake index28,6 [16,7; 50]5,8 [2,9; 11,8]15,5 [4,7; 30,9]24,4 [9,5; 50]The index of NSAID intake in the first trim. was lower than before pregnancy and in the second half of gestation (p<0.05 compared to the month of conception, II and III trim.). The average daily dose of ibuprofen was also lower in the first trim. than in the second and third trim. (p<0.05), while the actual daily dose in the second trim. was higher than in the first and third trim. (p<0.05 in all cases).There was no correlation between BASDAI AS activity, the level of nocturnal pain and the ibuprofen intake index, likewise the fact of NSAID withdrawal throughout pregnancy. In addition, there were no differences in BASDAI levels and back pain in women with a subjective need for NSAIDs, who did and did’t take ibuprofen.50% of women were committed to NSAID therapy in the first trim., 43.5% in the second trim., and 67.4% in the third trim. In pts with non-adherence to NSAID therapy, the BASDAI level was higher than in those who followed the recommendations of the rheumatologist throughout pregnancy: in the first trim. – 3.8[3.4; 4.7] and 1.7[0.8; 2.2]; in the second trim. - 3[2.3; 4.6] and 1.4[0.8; 2.7]; in the third trim. - 3.1[2.1; 4.0] and 1.7[1.1; 4.0], p<0.05 in all cases. However, women with adherence > 80% were initially less active and NSAIDs were prescribed “on demand”, which increased their compliance.Conclusion:intake of ibuprofen in low doses does not affect the activity of AS. Due to the ongoing discussion about the effect of NSAIDs on neonatal outcomes, further international studies are required for development an optimal treatment regimen during pregnancy with a possible extension of the indications for the appointment of TNF inhibitors (BASDAI<4).Disclosure of Interests:None declared.

Letters to the Editor

PEDIATRICS ◽  
1973 ◽  
Vol 52 (3) ◽  
pp. 469-469
Author(s):  
Daniel Safer ◽  
Richard P. Allen
Keyword(s):  
Significant Relationship ◽  
Dose Range ◽  
Growth Suppression ◽  
Average Daily Dose ◽  
Letters To The Editor ◽  
Daily Dose

You are quite correct; the dose of dextroamphetamine was not included in the paper.1 The daily dose range for dextroamphetamine was 5 to 40 mg. The average daily dose was 12.4 mg. Fifty-four percent of the children received this medication during the summer, and 10% received the medication three times daily. There was no significant relationship between the dose of dextroamphetamine and growth suppression, a finding presented in Table IV of the paper. We do not know if doses less than 5 mg daily are nonsuppressive of growth.

RADIATION HAZARDS IN THE FIELD OF PEDIATRICS

PEDIATRICS ◽  
1957 ◽  
Vol 20 (5) ◽  
pp. 921-940
Author(s):  
Meinhard Robinow ◽  
Frederic N. Silverman
Keyword(s):  
Radiation Injury ◽  
Radiation Safety ◽  
The United States ◽  
Point Of View ◽  
Public Understanding ◽  
X Rays ◽  
Tissue Destruction ◽  
Radiation Hazards ◽  
External Sources ◽  
Radiation Induced

The different types of injury from external sources of ionizing radiation are briefly described and the manifestations of radiation injury in the fetus, the infant and the child are reviewed. If radiation therapy for malignant disease is excluded from consideration, it is found that x-ray damage to skin, other tissue destruction, and growth impairment are relatively minor radiation hazards compared to the dangers of leukemia and other malignancy and of radiation-induced genetic damage. Consideration is given to somatic radiation injury as largely an individual problem and genetic injury as a population problem. This point of view is reflected in the differing recommendations concerning "permissible doses" for individuals and for populations. Medical radiation represents a major and presumably growing source of exposure to individuals and to the population in the United States. Various ways are shown in which excessive diagnostic exposure to x-rays, especially in children, can be reduced without interference with requirements of diagnosis. Control of avoidable radiation can be accomplished by combined attack from different fronts. The more important approaches to radiation safety are discussed. They include attention to technical detail, personnel monitoring, maintenance of radiation records, radiation safety through legislative control and public education. The responsibility of the physician in promoting public understanding of radiation hazards is emphasized.

Abstract 187: Loop Diuretic Therapy in Acute Decompensated Heart Failure among Premier Hospitals

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Behnood Bikdeli ◽  
Kelly Strait ◽  
Kumar Dharmarajan ◽  
Chohreh Partovian ◽  
Nancy Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Loop Diuretic ◽  
Acute Decompensated Heart Failure ◽  
Diuretic Therapy ◽  
Loop Diuretics ◽  
High Rate ◽  
Average Daily Dose ◽  
Duration Of Therapy ◽  
Daily Dose ◽  
Hospital Use

Background: Although loop diuretics are frequently used for patients with heart failure (HF), little is known about the variation in patterns of diuretic therapy in US hospitals. We sought to describe such treatment patterns among a diverse group of hospitals. Methods: We studied HF hospitalizations occurring during 2009-10 in Premier Inc. hospitals participating in a collaborative project to pool administrative and charge data, which includes information about drug types, average daily dose, and duration of therapy. We excluded hospitals with less than 25 HF hospitalizations. For ease of comparison, all diuretic doses were converted to bioequivalent doses of intravenous (IV) furosemide: 40mg IV furosemide ∼ 80mg oral furosemide ∼ 20mg (oral or IV) torsemide ∼ 1mg (oral or IV) bumetanide. Summary statistics were calculated. Results: Among 366 studied hospitals (264,675 HF hospitalizations), use of any loop diuretic had an interquartile range (IQR) from 92% to 96% (median: 94%). At the hospital level, the average daily dose IQR varied from 45mg to 64 mg (median: 55 mg) and the median duration of therapy was 4 days (IQR: 4 to 4; median: 4), as was the median length of stay. The IQR for use of furosemide varied from 89% to 94% (median: 92%), and its median average daily dose had an IQR from 40mg to 60 mg (median: 53 mg). Hospital use of bumetanide had an IQR from 2% to 11%, and hospital use of torsemide had an IQR from 0% to 4% (medians of 5% and 1%, respectively). The variation in median average daily dose for bumetanide and torsemide was greater than for furosemide (bumetanide IQR: 79mg to 127 mg, with median of 89 mg; torsemide IQR: 53mg to 120 mg, with median of 80 mg). Use of IV diuretics on the last day before home discharge had an IQR from 16% to 33% (median: 24%) across hospitals. Conclusion: US hospitals administer loop diuretics, particularly furosemide, to the vast majority of HF inpatients. The duration and daily dosage of therapy was similar across most hospitals. In contrast, a minority of hospitals used bumetanide and torsemide for several patients. The daily dosage of these agents showed more marked variation. We observed a high rate of intravenous diuretic use on the last day of hospitalization, with considerable variation across hospitals.

scholarly journals Optimal LDR to Protect the Kidney From Diabetes: Whole-Body Exposure to 25 mGy X-rays Weekly for 8 Weeks Efficiently Attenuates Renal Damage in Diabetic Mice

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878984 ◽  
Author(s):  
Jie Cheng ◽  
Fengsheng Li ◽  
Guanjun Wang ◽  
Weiying Guo ◽  
Shan Huang ◽  
...  
Keyword(s):  
Low Dose ◽  
Collagen Iv ◽  
Whole Body ◽  
Detectable Effect ◽  
X Rays ◽  
Diabetic Mice ◽  
Low Dose Radiation ◽  
Functional Changes ◽  
Renal Expression

To explore an optimal frequency of whole-body low-dose radiation (LDR) to protect the kidney from diabetes, type 1 diabetic mice were induced with multiple injections of low-dose streptozotocin in male C57BL/6J mice. Diabetic or age-matched normal mice received whole-body exposure to 12.5 or 25 mGy either every other day or weekly for 4 or 8 weeks. Diabetes decreased the urinary creatinine and increased the microalbumin in urine, renal accumulation of 3-nitrotyrosine and 4-hydroxynonenal, and renal expression of collagen IV and fibronectin. All these renal pathological and functional changes in diabetic mice were significantly attenuated by exposure to LDR at all regimens. However, whole-body exposure of diabetic mice to 25 mGy weekly and to 12.5 mGy every other day for 8 weeks provided a better prevention of diabetic nephropathy than other LDR regimens. Furthermore, whole-body exposure to 25 mGy weekly for 8 weeks showed no detectable effect on the kidney of normal mice, but whole-body exposure to normal mice at 12.5 mGy every other day for 8 weeks increased urinary microalbumin and renal expression of collagen IV and fibronectin. These results suggest that whole-body exposure to LDR at 25 mGy weekly is the optimal condition of LDR to protect the kidney from diabetes.

scholarly journals Plain Radiography May Be Safely Omitted for Selected Major Trauma Patients Undergoing Whole Body CT: Database Study

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Sarah Hudson ◽  
Adrian Boyle ◽  
Stephanie Wiltshire ◽  
Lisa McGerty ◽  
Sara Upponi
Keyword(s):  
Major Trauma ◽  
Research Network ◽  
Whole Body ◽  
Trauma Patients ◽  
X Rays ◽  
Database Study ◽  
Primary Survey ◽  
Whole Body Ct ◽  
Plain Films ◽  
Body Ct

Introduction. Whole body CT is being used increasingly in the primary survey of major trauma patients. We evaluated whether omitting plain films of the chest and pelvis in the primary survey was safe. We compared the probability of survival of patients and time to CT who had plain X-rays to those who did not.Method. We performed a database study on major trauma patients admitted between 2008 and 2010 using data from Trauma, Audit and Research Network (TARN) and our PACS system. We included adult major trauma patients who has an ISS of greater than 15 and underwent whole body CT.Results. 245 patients were included in the study. 44 (17.9%) did not undergo plain films. The median time to whole body CT from the time of admission was longer (47 minutes) in patients having plain films, than those who did not have plain films performed (30 minutes),P<0.005. Mortality was increased in the group who received plain films, 9.5% compared to 4.5%, but this was not statistically significant (P=0.77).Conclusion. We conclude that plain films may be safely omitted during the primary survey of selected major trauma patients.

scholarly journals Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and emphysema in a predictive mouse model not via CB1 receptor activation

2017 ◽  
Vol 313 (2) ◽  
pp. L267-L277 ◽  
Author(s):  
Z. Helyes ◽  
Á. Kemény ◽  
K. Csekő ◽  
É. Szőke ◽  
K. Elekes ◽  
...  
Keyword(s):  
Tobacco Smoke ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Cannabinoid Receptor ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Whole Body ◽  
Myeloperoxidase Activity ◽  
Tissue Destruction ◽  
Cell Hyperplasia

Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations with light microscopy. Daily marijuana inhalation evoked severe bronchial hyperreactivity after a week. Characteristic perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis, emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4 mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated with these changes. Airway hyperresponsiveness and inflammation were not altered in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke induced hyperresponsiveness after 2 mo and significantly later caused inflammatory cell infiltration/activation with only mild emphysema. We provide the first systematic and comparative experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and emphysema, which are not mediated by the CB1 receptor.

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.

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