scholarly journals Hyperacetylation of Cardiac Mitochondrial Proteins Is Associated with Metabolic Impairment and Sirtuin Downregulation after Chronic Total Body Irradiation of ApoE -/- Mice

2019 ◽  
Vol 20 (20) ◽  
pp. 5239 ◽  
Author(s):  
Zarko Barjaktarovic ◽  
Juliane Merl-Pham ◽  
Ignacia Braga-Tanaka ◽  
Satoshi Tanaka ◽  
Stefanie M. Hauck ◽  
...  
Keyword(s):  
Low Dose ◽  
Great Majority ◽  
Tca Cycle ◽  
Heart Mitochondria ◽  
Acid Oxidation ◽  
Cardiac Damage ◽  
Heart Metabolism ◽  
Increased Risk ◽  
Radiation Induced ◽  
Total Body

Chronic exposure to low-dose ionizing radiation is associated with an increased risk of cardiovascular disease. Alteration in energy metabolism has been suggested to contribute to radiation-induced heart pathology, mitochondrial dysfunction being a hallmark of this disease. The goal of this study was to investigate the regulatory role of acetylation in heart mitochondria in the long-term response to chronic radiation. ApoE-deficient C57Bl/6J mice were exposed to low-dose-rate (20 mGy/day) gamma radiation for 300 days, resulting in a cumulative total body dose of 6.0 Gy. Heart mitochondria were isolated and analyzed using quantitative proteomics. Radiation-induced proteome and acetylome alterations were further validated using immunoblotting, enzyme activity assays, and ELISA. In total, 71 proteins showed peptides with a changed acetylation status following irradiation. The great majority (94%) of the hyperacetylated proteins were involved in the TCA cycle, fatty acid oxidation, oxidative stress response and sirtuin pathway. The elevated acetylation patterns coincided with reduced activity of mitochondrial sirtuins, increased the level of Acetyl-CoA, and were accompanied by inactivation of major cardiac metabolic regulators PGC-1 alpha and PPAR alpha. These observations suggest that the changes in mitochondrial acetylation after irradiation is associated with impairment of heart metabolism. We propose a novel mechanism involved in the development of late cardiac damage following chronic irradiation.

scholarly journals Very Large Amounts of Radiation are Required to Produce Cancer

Dose-Response ◽  
2007 ◽  
Vol 5 (4) ◽  
pp. dose-response.0 ◽  
Author(s):  
Antone L. Brooks ◽  
T. Edmond Hui ◽  
Lezlie A. Couch
Keyword(s):  
Cancer Risk ◽  
Low Dose ◽  
Theoretical Calculations ◽  
Low Doses ◽  
Biological Organization ◽  
The Public ◽  
Increased Risk ◽  
Large Populations ◽  
Radiation Induced Cancer ◽  
Radiation Induced

The public fear of radiation is in part driven by the Linear No Threshold Hypothesis (LNTH), or the concept that each and every ionization increases the risk for cancer. Even if this were true, it is important to recognize that the increased risk is very small at low doses and cannot be detected. This paper demonstrates the large number of assumptions and extrapolations needed when using the LNTH to estimate low-dose cancer risk. The manuscript provides information at every level of biological organization suggesting that many of these linear assumptions do not hold. While the initial damage may be produced linearly with dose, the processing of that damage is very non-linear. Finally, the paper provides the unique prospective on radiation-induced cancer, demonstrating that it takes large amounts (total energy) of radiation delivered to large populations to detect an increase in cancer frequency. These observations are supported by both theoretical calculations and examples based on past human radiation exposure.

scholarly journals Radiation-induced ovarian follicle loss occurs without overt stromal changes

Reproduction ◽  
2018 ◽  
Vol 155 (6) ◽  
pp. 553-562 ◽  
Author(s):  
Bruce F Kimler ◽  
Shawn M Briley ◽  
Brian W Johnson ◽  
Austin G Armstrong ◽  
Susmita Jasti ◽  
...  
Keyword(s):  
Low Dose ◽  
Ovarian Tissue ◽  
Ovarian Follicle ◽  
Ovarian Follicles ◽  
Specific Protein ◽  
Reproductive Aging ◽  
Ovarian Stroma ◽  
Cesium 137 ◽  
Radiation Induced ◽  
Total Body

Radiation damage due to total body irradiation (TBI) or targeted abdominal radiation can deplete ovarian follicles and accelerate reproductive aging. We characterized a mouse model of low-dose TBI to investigate how radiation affects the follicular and stromal compartments of the ovary. A single TBI dose of either 0.1 Gy or 1 Gy (Cesium-137 γ) was delivered to reproductively adult CD1 female mice, and sham-treated mice served as controls. Mice were euthanized either 2 weeks or 5 weeks post exposure, and ovarian tissue was harvested. To assess the ovarian reserve, we classified and counted the number of morphologically normal follicles in ovarian histologic sections for all experimental cohorts using an objective method based on immunohistochemistry for an oocyte-specific protein (MSY2). 0.1 Gy did not affect that total number of ovarian follicles, whereas 1 Gy resulted in a dramatic loss. At two weeks, there was a significant reduction in all preantral follicles, but early antral and antral follicles were still present. By five weeks, there was complete depletion of all follicle classes. We examined stromal quality using histologic stains to visualize ovarian architecture and fibrosis and by immunohistochemistry and quantitative microscopy to assess cell proliferation, cell death and vasculature. There were no differences in the ovarian stroma across cohorts with respect to these markers, indicating that this compartment is more radio-resistant relative to the germ cells. These findings have implications for reproductive health and the field of fertility preservation because the radiation doses we examined mimic scatter doses experienced in typical therapeutic regimens.

scholarly journals Upper GI Bleeding Secondary to Radiation Gastritis in a Patient with Preexisting Portal Hypertensive Gastropathy

2021 ◽  
pp. 513-518
Author(s):  
Samragnyi Madala ◽  
Abhishek Polavarapu ◽  
Dhineshreddy Gurala ◽  
Vivek Gumaste
Keyword(s):  
Radiation Therapy ◽  
Gastrointestinal Bleeding ◽  
Argon Plasma Coagulation ◽  
Argon Plasma ◽  
Laser Coagulation ◽  
Portal Hypertensive Gastropathy ◽  
Gastrointestinal Malignancy ◽  
Nonalcoholic Fatty Liver ◽  
Increased Risk ◽  
Radiation Induced

We commonly see patients presenting with either portal hypertensive gastropathy (PHG) or radiation gastritis. Radiation-induced hemorrhagic gastritis is an unusual lethal complication postradiation. Patients with preexisting PHG have very friable mucosa that can easily bleed after radiation for cancer treatment. There is an increased risk of bleeding with both entities present together. Our aim is to focus on treatment and possible prevention of gastrointestinal bleeding in patients with preexisting PHG undergoing radiation therapy for newly diagnosed cancer. Several therapies like prednisolone, argon plasma coagulation, laser coagulation have been proposed. There are no set guidelines for treatment. In these patients, if radiation therapy is indicated either for hepatic or gastrointestinal malignancy, it is suggested to premedicate with proton pump inhibitors or sucralfate. We describe a case of 73-year-old female who presented with upper gastrointestinal bleeding. She had liver cirrhosis secondary to nonalcoholic fatty liver disease and diagnosed with pancreatic cancer, for which she received chemoradiation. She was found to have both radiation gastritis and PHG with diffuse erythematous, edematous, congested mucosa with diffuse oozing blood in the antrum making it very challenging to treat.

scholarly journals Cumulative incidence and risk factors for radiation induced leukoencephalopathy in high grade glioma long term survivors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Robert Terziev ◽  
Dimitri Psimaras ◽  
Yannick Marie ◽  
Loic Feuvret ◽  
Giulia Berzero ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cumulative Incidence ◽  
High Grade Glioma ◽  
High Grade ◽  
Nucleotide Polymorphisms ◽  
Increased Risk ◽  
Radiation Induced ◽  
Long Term Survivors

AbstractThe incidence and risk factors associated with radiation-induced leukoencephalopathy (RIL) in long-term survivors of high-grade glioma (HGG) are still poorly investigated. We performed a retrospective research in our institutional database for patients with supratentorial HGG treated with focal radiotherapy, having a progression-free overall survival > 30 months and available germline DNA. We reviewed MRI scans for signs of leukoencephalopathy on T2/FLAIR sequences, and medical records for information on cerebrovascular risk factors and neurological symptoms. We investigated a panel of candidate single nucleotide polymorphisms (SNPs) to assess genetic risk. Eighty-one HGG patients (18 grade IV and 63 grade III, 50M/31F) were included in the study. The median age at the time of radiotherapy was 48 years old (range 18–69). The median follow-up after the completion of radiotherapy was 79 months. A total of 44 patients (44/81, 54.3%) developed RIL during follow-up. Twenty-nine of the 44 patients developed consistent symptoms such as subcortical dementia (n = 28), gait disturbances (n = 12), and urinary incontinence (n = 9). The cumulative incidence of RIL was 21% at 12 months, 42% at 36 months, and 48% at 60 months. Age > 60 years, smoking, and the germline SNP rs2120825 (PPARg locus) were associated with an increased risk of RIL. Our study identified potential risk factors for the development of RIL (age, smoking, and the germline SNP rs2120825) and established the rationale for testing PPARg agonists in the prevention and management of late-delayed radiation-induced neurotoxicity.

scholarly journals Myocardial infarctions, subtypes and coronary atherosclerosis in SLE: a case–control study

2021 ◽  
Vol 8 (1) ◽  
pp. e000515
Author(s):  
Isak Samuelsson ◽  
Ioannis Parodis ◽  
Iva Gunnarsson ◽  
Agneta Zickert ◽  
Claes Hofman-Bang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Coronary Atherosclerosis ◽  
Great Majority ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Medical File ◽  
Similar Frequency ◽  
Ventricular Ejection Fraction ◽  
Increased Risk

ObjectivePatients with SLE have increased risk of myocardial infarction (MI). Few studies have investigated the characteristics of SLE-related MIs. We compared characteristics of and risk factors for MI between SLE patients with MI (MI-SLE), MI patients without SLE (MI-non-SLE) and SLE patients without MI (non-MI-SLE) to understand underlying mechanisms.MethodsWe identified patients with a first-time MI in the Karolinska SLE cohort. These patients were individually matched for age and gender with MI-non-SLE and non-MI-SLE controls in a ratio of 1:1:1. Retrospective medical file review was performed. Paired statistics were used as appropriate.ResultsThirty-four MI-SLE patients (88% females) with a median age of 61 years were included. These patients had increased number of coronary arteries involved (p=0.04), and ≥50% coronary atherosclerosis/occlusion was numerically more common compared with MI-non-SLE controls (88% vs 66%; p=0.07). The left anterior descending artery was most commonly involved (73% vs 59%; p=0.11) and decreased (<50%) left ventricular ejection fraction occurred with similar frequency in MI-SLE and MI-non-SLE patients (45% vs 36%; p=0.79). Cardiovascular disease (44%, 5.9%, 12%; p<0.001) and coronary artery disease (32%, 2.9%, 0%; p<0.001), excluding MI, preceded MI/inclusion more commonly in MI-SLE than in MI-non-SLE and non-MI-SLE patients, respectively. MI-SLE patients had lower plasma albumin levels than non-MI-SLE patients (35 (29–37) vs 40 (37–42) g/L; p=0.002).ConclusionIn the great majority of cases, MIs in SLE are associated with coronary atherosclerosis. Furthermore, MIs in SLE are commonly preceded by symptomatic vascular disease, calling for attentive surveillance of cardiovascular disease and its risk factors and early atheroprotective treatment.

scholarly journals Effect of low-dose total-body radiotherapy on immune microenvironment

2021 ◽  
Vol 14 (8) ◽  
pp. 101118
Author(s):  
Zhuo Chen ◽  
Zhouxue Wu ◽  
Tobias Achu Muluh ◽  
Shaozhi Fu ◽  
Jingbo Wu
Keyword(s):  
Low Dose ◽  
Immune Microenvironment ◽  
Total Body

scholarly journals P125: Low dose intravenous ketorolac in renal colic, a pilot randomized controlled trial

CJEM ◽  
2020 ◽  
Vol 22 (S1) ◽  
pp. S109-S110
Author(s):  
J. Chao ◽  
P. Brasher ◽  
K. Cheung ◽  
R. Sharma ◽  
K. Badke ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Renal Colic ◽  
Standard Dose ◽  
Controlled Trial ◽  
Pain Reduction ◽  
Primary Objective ◽  
Recruitment Rate ◽  
Convenience Sample ◽  
Increased Risk

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are first-line analgesics for emergency department (ED) patients with renal colic. Lower doses of intravenous (IV) ketorolac may provide similar pain relief to standard dosing in patients with acute pain. Patients with renal colic may be at increased risk of acute kidney injury; exposing them to lower doses of NSAIDs may put them at lower risk while providing equally effective analgesia. We conducted a pilot study to determine the feasibility of a randomized trial comparing the effectiveness and safety of low with standard ketorolac dosing in ED patients with suspected renal colic. The primary objective was to demonstrate the ability to achieve an enrolment target of 2 patients per week. Methods: We enrolled a convenience sample of adults presenting to an academic urban ED with unilateral flank pain suspected to be renal colic. We randomized patients to 10 mg (low dose, intervention) or 30 mg (standard dose, control). Participants, treating physicians and nurses, and researchers were blinded to treatment allocation. Our main feasibility outcome was the recruitment rate. Secondary outcomes were changes in pain scores (0-10) at 30 and 120 minutes post-ketorolac administration, vital signs, adverse events and ED length of stay. Results: We approached 82 patients, of whom 47 (57.3%) were eligible. Of these, 36 consented to participating and 30 were randomized. The proportion of screened patients who were enrolled was 36.6% (30/82). We completed enrolment over a 21-week period, with an average recruitment rate of 1.5 patients/week (range 0-4). The average baseline pain score for all participants was 6.9 (SD = 2.1). At 30 minutes post-ketorolac administration, the low dose group had a mean pain reduction of 2.0 points compared to a pain reduction of 1.7 in standard dose group (difference = 0.3, 90% CI: -0.7 to 1.4). Conclusion: These preliminary results support the possibility that low dose ketorolac may be efficacious in this patient population. We did not meet our target recruitment of 2 patients per week as this was primarily due to restricted recruitment hours. To successfully conduct a larger trial, we would need to expand both recruitment hours and the number of sites.

Low-Dose Total Body Irradiation in Non-Hodgkin Lymphoma

1990 ◽  
Vol 13 (4) ◽  
pp. 280-284 ◽  
Author(s):  
W. J. De Neve ◽  
M. L. M. Lybeert ◽  
J. H. Meerwaldt
Keyword(s):  
Hodgkin Lymphoma ◽  
Total Body Irradiation ◽  
Low Dose ◽  
Non Hodgkin Lymphoma ◽  
Total Body
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