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Introduction: Low-energy proximal femur fractures in elderly patients result from factors, like osteoporosis and falls. These fractures impose high rates of economic and social costs. In this study, we aimed to build predictive models by applying machine learning (ML) methods on radiomics features to predict low-energy proximal femur fractures. Methods: Computed tomography scans of 40 patients (mean ± standard deviation of age = 71 ± 6) with low-energy proximal femur fractures (before a fracture occurs) and 40 individuals (mean ± standard deviation of age = 73 ± 7) as a control group were included. The regions of interest, including neck, trochanteric, and intertrochanteric, were drawn manually. The combinations of 25 classification methods and 8 feature selection methods were applied to radiomics features extracted from ROIs. Accuracy and the area under the receiver operator characteristic curve (AUC) were used to assess ML models' performance. Results: AUC and accuracy values ranged from 0.408 to 1 and 0.697 to 1, respectively. Three classification methods, including multilayer perceptron (MLP), sequential minimal optimization (SMO), and stochastic gradient descent (SGD), in combination with the feature selection method, SVM attribute evaluation (SAE), exhibited the highest performance in the neck (AUC = 0.999, 0.971 and 0.971, respectively; accuracy = 0.988, 0.988, and 0.988, respectively) and the trochanteric (AUC = 1, 1 and 1, respectively; accuracy = 1, 1 and 1, respectively) regions. The same methods demonstrated the highest performance for the combination of the 3 ROIs’ features (AUC = 1, 1 and 1, respectively; accuracy =1, 1 and 1, respectively). In the intertrochanteric region, the combination methods, MLP + SAE, SMO + SAE, and SGD + SAE, as well as the combination of the SAE method and logistic regression (LR) classification method exhibited the highest performance (AUC = 1, 1, 1 and 1, respectively; accuracy= 1, 1, 1 and 1, respectively). Conclusion: Applying machine learning methods to radiomics features is a powerful tool to predict low-energy proximal femur fractures. The results of this study can be verified by conducting more research on bigger datasets.

Glucosamine is widely prescribed as a dietary supplement used to treat arthritis. In this study, the radioprotective ability of glucosamine was evaluated against radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Blood samples were collected from five healthy male donors and were divided into four groups. Isolated lymphocytes and blood samples were treated with 10 µM of glucosamine for 2 h before exposure to 2 Gy radiation. The radioprotective potential of glucosamine was assessed by micronucleus assay, reactive oxygen species (ROS) level analysis, and flow cytometry. Irradiation significantly increased the micronuclei frequency as compared to the control group. Contrary to that pretreatment with glucosamine before irradiation significantly reduced the frequency of micronuclei. Furthermore, pretreatment with glucosamine significantly prevented the percentage of apoptotic lymphocytes. Also, glucosamine pretreatment significantly reduced the production of ROS in irradiated lymphocytes. This study shows glucosamine to be a potent radioprotector against radiation that induces DNA damage and apoptosis in human lymphocytes. Several additional in vivo and in vitro studies are needed before glucosamine can be considered as a radioprotective candidate in patients undergoing radiation therapy.

Background and Objective: Cancer incidence is 24% higher in children and young adults exposed to Computed Tomography (CT) scans than those unexposed. Non-repairing of ionizing radiation-induced DNA Double-Strand Breaks (DSBs) can initiate carcinogenesis. In the present study, we aimed to investigate the radioprotective potential of melatonin against DSBs in peripheral blood lymphocytes of patients undergoing abdomen-pelvis CT examinations. Methods: This double-blind, placebo-controlled clinical trial was conducted on thirty patients. These patients were divided into two groups; group one (control) patients who have undergone the CT examination received a single oral dose of placebo, while in group two, patients received a single oral dose of 100mg melatonin. In both the groups, blood samples were collected 5-10min before and 30 minutes after the CT examination. The lymphocytes from these samples were isolated and DSBs were analyzed using γH2AX immunofluorescence microscopy. Results: Compared to the control group, the use of melatonin 1h before the CT examination caused a significant reduction in γH2AX-foci, indicating a reduction in DSBs. In addition, no side effect was observed in patients following 100mg melatonin administration. Conclusion: For the first time, this study has shown that melatonin has protective effects against radiationinduced genotoxicity in peripheral blood lymphocytes of patients undergoing abdomen-pelvis CT examinations. Therefore, melatonin can be considered as a promising candidate for reducing DSBs in patients undergoing abdomen-pelvis CT examinations.

Background: Radiation-induced enteritis and proctitis are common side effects of abdominopelvic cancers among patients that undergo radiotherapy for prostate, colorectal or urinary cancers. Exposure of these tissues to high doses of radiation leads to damage to villous, inflammation, pain, ulcer and bleeding, which may cause malabsorption and gastrointestinal disorders. To date, several procedures such as pharmaceutical treatment have been proposed for protection and mitigation of gastrointestinal toxicity following radiotherapy. Aims: In the current study, we aimed to investigate the possible radioprotection of ileum and colon in rats using a combination of melatonin and metformin. Methods: In this experimental study, 30 male Wistar rats were randomly assigned to six groups: control, melatonin (100 mg/kg) treatment, melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment, radiation (10 Gy to whole body) group, radiation + melatonin (100 mg/kg) treatment, and radiation + melatonin (100 mg/kg) plus metformin (100 mg/kg) treatment. After 3.5 days, rats were sacrificed and their ileum and colon tissues carefully removed. Histopathological evaluations were conducted on these tissue samples. Results: Histological evaluations reported moderate to severe damages to ileum and colon following whole body irradiation. Melatonin administration was able to protect the ileum remarkably, while the combination of melatonin and metformin was less effective. Interestingly, for the colon, melatonin was less effective while its combination with metformin was able to protect against radiation toxicity completely. Conclusion: For the ileum, melatonin was a more effective radioprotector compared to its combination with metformin. However, the combination of melatonin and metformin can be proposed as an ideal radioprotector for the colon.

Background: Nephrotoxicity is a prevalent consequence of cancer treatment using radiotherapy and chemotherapy or their combination. There are two methods; histological and biochemical, to assess the kidney damage caused by toxic agents in animal studies. Although these methods are used for the try-out of renoprotective factors, these methods are invasive and time-consuming, and also, lack the necessary sensitivity for primary diagnosis. Quantitative renal 99mTc-DMSA scintigraphy is a noninvasive, precise and sensitive radionuclide technique which is used to assess the extent of kidney damage, so that the extent of injury to the kidney will be indicated by the renal uptake rate of 99mTc-DMSA in the kidney. In addition, this scintigraphy evaluates the effect of the toxic agents by quantifying the alterations in the biodistribution of the radiopharmaceutical. Conclusion: In this review, the recent findings about the renoprotective agents were evaluated and screened with respect to the use of 99mTc-DMSA , which is preclinically and clinically used for animal cases and cancer patients under the treatment by radiotherapy and chemotherapy.

Background:Melatonin is a natural body product that has shown potent antioxidant property against various toxic agents. For more than two decades, the abilities of melatonin as a potent radioprotector against toxic effects of ionizing radiation (IR) have been proved. However, in the recent years, several studies have been conducted to illustrate how melatonin protects normal cells against IR. Studies proposed that melatonin is able to directly neutralize free radicals produced by IR, leading to the production of some low toxic products.Discussion:Moreover, melatonin affects several signaling pathways, such as inflammatory responses, antioxidant defense, DNA repair response enzymes, pro-oxidant enzymes etc. Animal studies have confirmed that melatonin is able to alleviate radiation-induced cell death via inhibiting pro-apoptosis and upregulation of anti-apoptosis genes. These properties are very interesting for clinical radiotherapy applications, as well as mitigation of radiation injury in a possible radiation disaster. An interesting property of melatonin is mitochondrial ROS targeting that has been proposed as a strategy for mitigating effects in radiosensitive organs, such as bone marrow, gastrointestinal system and lungs. However, there is a need to prove the mitigatory effects of melatonin in experimental studies.Conclusion:In this review, we aim to clarify the molecular mechanisms of radioprotective effects of melatonin, as well as possible applications as a radiation countermeasure in accidental exposure or nuclear/radiological disasters.

Purpose: Lung tissue is one of the most sensitive organs to ionizing radiation (IR). Early and late side effects of exposure to IR can limit the radiation doses delivered to tumors that are within or adjacent to this organ. Pneumonitis and fibrosis are the main side effects of radiotherapy for this organ. IL-4 and IL-13 have a key role in the development of pneumonitis and fibrosis. Metformin is a potent anti-fibrosis and redox modulatory agent that has shown radioprotective effects. In this study, we aimed to evaluate possible upregulation of these cytokines and subsequent cascades such as IL4-R1, IL-13R1, Dual oxidase 1 (DUOX1) and DUOX2. In addition, we examined the potential protective effect of metformin in these cytokines and genes, as well as histopathological changes in rat’s lung tissues. Methods: 20 rats were divided into 4 groups: control; metformin treated; radiation + metformin; and radiation. Irradiation was performed with a 60Co source delivering 15 Gray (Gy) to the chest area. After 10 weeks, rats were sacrificed and their lung tissues were removed for histopathological, real-time PCR and ELISA assays. Results: Irradiation of lung was associated with an increase in IL-4 cytokine level, as well as the expression of IL-4 receptor-a1 (IL4ra1) and DUOX2 genes. However, there was no change in the level of IL-13 and its downstream gene including IL-13 receptor-a2 (IL13ra2). Moreover, histopathological evaluations showed significant infiltration of lymphocytes and macrophages, fibrosis, as well as vascular and alveolar damages. Treatment with metformin caused suppression of upregulated genes and IL-4 cytokine level, associated with amelioration of pathological changes. Conclusion: Results of this study showed remarkable pathological damages, an increase in the levels of IL-4, IL4Ra1 and Duox2, while that of IL-13 decreased. Treatment with metformin showed ability to attenuate upregulation of IL-4–DUOX2 pathway and other pathological damages to the lung after exposure to a high dose of IR.

Background: Nowadays, ionizing radiations are used for various medical and terroristic aims. These purposes involve exposure to ionizing radiations. Hence, people are at risk for acute or late effects. Annually, millions of cancer patients undergo radiotherapy during their course of treatment. Also, some radiological or nuclear events in recent years pose a threat to people, hence the need for radiation mitigation strategies. Amifostine, the first FDA approved radioprotector, has shown some toxicities that limit its usage and efficiency. Due to these side effects, scientists have researched for other agents with less toxicity for better radioprotection and possible mitigation of the lethal effects of ionizing radiations after an accidental exposure. Flavonoids have shown promising results for radioprotection and can be administered in higher doses with less toxicity. Studies for mitigation of ionizing radiation-induced toxicities have concentrated on natural antioxidants. Detoxification of free radicals, management of inflammatory responses and attenuation of apoptosis signaling pathways in radiosensitive organs are the main mechanisms for radiation protection and mitigation with flavonoids and natural antioxidants. However, several studies have proposed that a combination in the form of some antioxidants may alleviate radiation toxicities more effectively in comparison to a single form of antioxidants. Conclusion: In this review, we focus on recent findings about natural radioprotectors and mitigators which are clinically applicable for radiotherapy patients, as well as injured people in possible radiation accidents. © 2018 Bentham Science Publishers.

Background: It has been proposed that increased levels of pro-inflammatory and pro-fibrotic cytokines play a key role in radiation-induced lung injury. Interleukin-4 (IL-4) and IL-13 are two pro-fibrotic cytokines that promote the production of free radicals through stimulation of Duox1 and Duox2. In this experimental study, we aimed to evaluate the expression of IL4Ra1, Duox1, IL13Ra2, and Duox2 genes following rat’s lung irradiation. Objectives: Also, we detected the modulatory effect of a combination of curcumin and L-selenomethionine on the expression of these genes. Methods: Twenty male rats were divided into four groups as G1: control (no treatment or radiation); G2: treatment with a combination of curcumin and L-selenomethionine; G3: radiation; G4: radiation plus a combination of curcumin and L-selenomethionine. sixty-seven days after irradiation, rats were killed for detecting the expression of IL4Ra1, IL13Ra2, Duox1, and Duox2. Results: The results showed no detectable expression for IL13Ra2, while the expression of IL4Ra1, Duox1, and Duox2 was increased. Treatment with a combination of curcumin and L-selenomethionine could attenuate the expression of these genes. Conclusions: This study proposes that upregulation of Duox1 and Duox2 may be involved in radiation-induced lung injury. Treatment with a combination of curcumin and L-selenomethionine may be useful for the mitigation of lung injury through modulation of these genes.

Radiation-induced hematopoietic suppression and myelotoxicity can occur due to the nuclear accidents, occupational irradiation and therapeutic interventions. Bone marrow dysfunction has always been one of the most important causes of morbidity and mortality after ionizing irradiation.This study aims to investigate the protective effect of telmisartan against radiation-induced bone marrow injuries in a Balb/c mouse model.In this experimental study, male Balb/c mice were divided into four groups as follow: group 1: mice received phosphate buffered saline (PBS) without irradiation, group 2: mice received a solution of telmisartan in PBS without irradiation, group 3: mice received PBS with irradiation, and group 4: mice received a solution of telmisartan in PBS with irradiation. A solution of telmisartan was prepared and administered orally at 12 mg/kg body weight for seven consecutive days prior to whole body exposing to a single sub-lethal dose of 5 Gy X-rays. Protection of bone marrow against radiation induced damage was investigated by Hematoxylin-Eosin (HE) staining assay at 3, 9, 15 and 30 days after irradiation.Histopathological analysis indicated that administration of telmisartan reduced X-radiation-induced damage and improved bone marrow histology. The number of different cell types in bone marrow, including polymorphonuclear /mononuclear cells and megakaryocytes significantly increased in telmisartan treated group compared to the only irradiated group at all-time points.The results of the present study demonstrated an efficient radioprotective effect of telmisartan in mouse bone marrow against sub-lethal X-irradiation.

Herniarin is a member of simple coumarins, which are a group of common secondary metabolites in plants. The aim of the present study was to investigate the effects of herniarin on genotoxicity and apoptosis induced by cisplatin in rat bone marrow cells. The experimental rats were treated with four different doses of herniarin (50, 100, 200, and 400 mg/kg.) for seven consecutive days. The cisplatin (5 mg/kg, i.p.) was injected into mice 1 h after the last oral herniarin administration on the seventh day. The protective effects of herniarin were investigated by hematological test, flow cytometry, micronucleus assay, and reactive oxygen species (ROS) level analysis. Herniarin caused a marked reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after exposure to cisplatin at doses of 200 and 400 mg/kg. Furthermore, herniarin significantly increased the levels of both red and white blood cells in peripheral blood. Treatment of rats with herniarin before cisplatin, significantly decreased the percentage of apoptotic and necrotic cells and the ROS level in bone marrow cells. This study indicated that herniarin can be introduced as a new chemoprotective agent against cisplatin-induced genotoxicity in the future.

Background Testis is one of the most sensitive organs against the toxic effect of ionizing radiation. Exposure to even a low dose of radiation during radiotherapy, diagnostic radiology, or a radiological event could pose a threat to spermatogenesis. This may lead to temporary or permanent infertility or even transfer of genomic instability to the next generations. Objective In this study, we evaluated the protective effect of treatment with three natural antioxidants; resveratrol, alpha lipoic acid, and coenzyme Q10 on radiation-induced spermatogenesis injury. Materials and Methods 30 NMRI mice (6-8 wk, 30 ± 5 gr) were randomly divided into six groups (n = 5/each) as 1) control; 2) radiation; 3) radiation + resveratrol; 4) radiation + alpha lipoic acid; 5) radiation + resveratrol + alpha lipoic acid; and 6) radiation+ Q10. Mice were treated with 100 mg/kg resveratrol or 200 mg/kg alpha lipoic acid or a combination of these drugs. Also, Q10 was administered at 200 mg/kg. All treatments were performed daily from two days before to 30 min before irradiation. Afterward, mice were exposed to 2 Gy 60 Co gamma rays; 37 days after irradiation, the testicular samples were collected and evaluated for histopathological parameters. Results Results showed that these agents are able to alleviate some toxicological parameters such as basal lamina and epididymis decreased sperm density. Also, all agents were able to increase Johnsen score. However, they could not protect against radiation-induced edema, atrophy of seminiferous tubules, and hyperplasia in Leydig cells. Conclusion This study indicates that resveratrol, alpha-lipoic acid, and Q10 have the potential to reduce some of the side effects of radiation on mice spermatogenesis. However, they cannot protect Leydig cells as a source of testosterone and seminiferous tubules as the location of sperm maturation.

Background: Although radiotherapy is a common choice for cancer therapy, various types of toxicities in irradiated normal tissues limit the received dose by tumor cells. The gastrointestinal tract is one of the most sensitive organs to the detrimental effects of radiation. As a result of a high dose of ionizing radiation, acute morphological changes to the intestine are observed within days to weeks. Objectives: In this study, we aimed to evaluate the protective effects of metformin against radiation-induced small intestine injury. Methods: In this experimental study, we used 20 male Wistar albino rats in four groups including control, 10 Gy irradiation, metformin alone, and metformin with radiation. Metformin was orally administered 24 hours before irradiation for three days. Afterward, the rats were sacrificed 3.5 days after radiation exposure. The duodenum and jejunum were removed and fixed in 10% formalin. For light microscopic studies, duodenum and jejunum specimens were embedded in paraffin and then, 5 µm sections were obtained and stained with hematoxylin and eosin. Results: Irradiation led to a significant shortening of villi and mucosal atrophy, edema and inflammation in villi, and epithelial degeneration. When rats were treated with metformin, these damages were ameliorated in both duodenum and jejunum. Conclusions: In this study, we showed that metformin can be proposed for the radioprotection of the small intestine. This property is very obvious, especially for damages to the villous and epithelium. Although further studies are needed for exploring the protective mechanisms of metformin in this organ, it is possible that suppressing the production of free radicals via mitochondria or inflammatory responses plays a role.

Background Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressor's interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remains to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence. The non-targeted effect in radiobiology refers to a dynamic complex response in non-irradiated tissues caused by the release of presumably of clastogenic factors from irradiated cells. Although, most of these responses in non-targeted tissues have marked similarities to irradiated tissues, other studies have shown some differences. Also, the non-targeted effect has shown sex and tissue specificity that are seen in irradiated tissues too. So far, several studies have been conducted to depict mechanisms that may be involved in this phenomenon. Epigenetic dysfunctions, DNA damage and cell death are responsible for initiation of several signaling pathways that finally result in secretion of clastogenic factors. Moreover, studies have shown that damage to both nucleus and mitochondrial DNA, membrane and some organelles is involved. Oxidized DNA associated with other cell death factors stimulates secretion of inflammatory as well as some anti-inflammatory cytokines from irradiated area. Additionally, oxidative stress that results in damage to cellular structures to include cell membranes can affect secretion of exosomes and miRNAs. These bystander effect exogenous mediators migrate to distant tissues and stimulate various signaling pathways which can lead to changes in immune responses, epigenetic modulations and radiation carcinogenesis. Conclusion In this review, we focus on descriptive and hierarchical events with emphasis on the molecular and functional interactions of ionizing radiation with cells to the mechanisms involved in cancer induction in non-targeted tissues.

BACKGROUND Para-18F-fluorohippuric acid (18F-PFH) and ortho-124I-iodohippuric acid (124IOIH) were recently identified as potential radiotracers suitable for conducting renography using positron emission tomography (PET). The aim of this work was to estimate preliminary human-equivalent internal radiation dose of 18F-PFH and 124I-OIH using the biodistribution data reported in healthy rats. The results were compared with the absorbed dose data of technetium-99m-mercaptoacetyltriglycine (99mTc- MAG3) as documented in the International Commission on Radiological Protection (ICRP) publication 80. METHODS The medical internal radiation dose (MIRD) formula was applied to extrapolate data from rats to human and to project the absorbed radiation dose for various organs in humans. S factor was calculated by Monte-Carlo N-particle (MCNP) simulation. RESULTS Our dose prediction shows that an injection of 18F-PFH or 124I-OIH in humans would result in an estimated effective absorbed dose of 0.09 or 0.17 µSv/MBq respectively for whole body, which is about 135 or 73 times respectively lower than that obtained with an injection of 99mTc-MAG3. All organs except kidneys would receive an estimated effective absorbed dose of

Metformin is a widely prescribed drug used in the treatment of patients with type 2 diabetes. In this study, the radioprotective effect of metformin was investigated against cytotoxicity and genotoxicity induced by ionizing radiation (IR) in human peripheral blood lymphocytes. Human lymphocytes were treated with metformin at concentrations 10 and 50 μM for 2 h and irradiated with 6 MV X-rays. The radiation antagonistic potential of metformin was assessed by MTT [3-(4,5-dimethyl-2-thiaozolyl)-2,5-diphenyl-2H tetrazolium bromide] assay, chromosomal aberration (CA) analysis, cytokinesis blocked micronucleus (CBMN) assay, and flow cytometry. Observations demonstrated a radiation-dose-dependent decrease in the percentage of cell viability after 24 h. It was found that pretreatment with metformin (10 and 50 μM) increased the percentage of cell viability. A highly significant dose modifying factor (DMF) 1.35 and 1.42 was observed for 10 and 50 μM metformin, respectively. Metformin (10 and 50 μM) pretreatment significantly decreased the frequency of dicentrics (DCs), acentric fragments (AFs), rings (RIs), micronuclei (MN), and nucleoplasmic bridges (NPBs) in irradiated human peripheral blood lymphocytes. Also, treatment with metformin (10 and 50 μM) without irradiation did not increase the number of MN, NPBs, DCs, AFs, RIs, and did not show a cytostatic effect in the human peripheral blood lymphocytes. On the other hand, metformin treatment (10 and 50 μM) 2 h prior to irradiation significantly reduced X-radiation-induced apoptotic incidence in human lymphocytes. The present study demonstrates metformin to be an effective radioprotector against DNA damage and apoptosis induced by IR in human lymphocytes. These data have an important application for the protection of lymphocytes from the genetic damage and side-effects induced by radiotherapy in cancer patients.

Background: Radiation toxicity is one of the major concerns for patients with gastrointestinal cancers that undergo radiotherapy. Duodenum is one of the most radiosensitive parts of gastrointestinal system that may be exposed to a high dose of radiation during radiotherapy for some cancers. The development or identification of appropriate radioprotectors with less toxicity is an interesting aim in radiobiology for clinical radiotherapy applications. In the present study, we aimed to evaluate the radioprotective effect of melatonin and metformin combination in rat's duodenum. In addition, we compared our results with the radioprotective effect of melatonin, when administered alone. Materials and Methods: Thirty male rats were divided into six groups: control, melatonin treatment, melatonin plus metformin treatment, whole-body irradiation, irradiation with melatonin treatment, and irradiation with melatonin plus metformin treatment. Irradiation was performed with 10 Gy cobalt-60 gamma rays, while 100 mg/kg of melatonin and metformin were administered 24 h before to 72 h after irradiation. After 3.5 days, their duodenum tissues were removed for histopathological evaluation. Results: Irradiation of rats led to mild-to-moderate mucositis signs, infiltration of inflammatory cells, necrosis, and damage to Brunner's glands and reduction of goblet cells. Melatonin was able to alleviate these damages, while melatonin plus metformin could reduce some radiation toxicity signs. Conclusion: Administration of melatonin plus metformin could reduce mucositis in duodenum. However, the administration of melatonin is more effective for mitigation of duodenal injury compared with melatonin plus metformin.

Introduction Producing appropriate diagnostic images along with patient radiation protection is the goal of radiography. Due to the advancements of radiography, concerns about observing the principles of radiation protection exist. Therefore, this study aimed to evaluate the observance of the principles of radiation protection in radiographic examinations with emphasis on field size collimation, suitability of exposure factors and the use of protective equipment for the patients and their companions. Methods Using a cross‐sectional study design, two radiography students on their final year of study observed 100 radiographic examinations from the imaging departments of five educational hospitals. The SPSS version 24 software was used to analyse the results. Results The radiation field collimation was obtained in 46% of the studied radiographs. Patients had companions present during the examination in 26% of the studies; however, protective equipment was only used for 4% of the patients’ companions, and no protective equipment was applied for patients. The observance rate of the various principles of radiation protection including field size restriction, the use of protective equipment for the patients and their companions, and suitability of the selected exposure factors was on average 44.6%. Conclusion The observance rate of the principles of radiation protection was insufficient in the studied educational hospitals, specifically in field size collimation and the use of protective equipment for the patients and their companions. Therefore, emphasis on the strict implementation of the radiation protection guidelines and continuous training of radiographers are required., This study aimed to evaluate the observance of the principles of radiation protection in radiographic examinations. Field size collimation, suitability of exposure factors and the use of protective equipment for the patients and their companions were done on average 44.6% in the reviewed examinations.

Metformin is widely used as an oral hypoglycemic drug in the management of type 2 diabetes mellitus. This study evaluated the possible protective effects of metformin against cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells. Two different doses of metformin (50 and 100 mg/kg b.w.) were administered orally to experimental animals for seven consecutive days. On the seventh day, the rats were exposed to cisplatin (5 mg/kg, i.p.) 1 h after the last oral metformin administration. Rats in the control group were treated orally with 10 ml/kg PBS for 7 consecutive days and a single intraperitoneal injection of saline (0.9%) on the 7th day. The antagonistic effects of metformin against cisplatin were evaluated using micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis, and flow cytometry. Treatment with 50 and 100 mg/kg metformin before cisplatin injection produced a significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after cisplatin treatment with a corresponding increase in the PCE/(PCE + NCE) ratio. Moreover, metformin markedly elevated the levels of both red and white blood cells in peripheral blood and decreased the percentage of apoptotic cells and the ROS level in bone marrow cells of rats treated with cisplatin. The data suggest that metformin has potential chemoprotective properties in rat bone marrow after cisplatin treatment, which support its candidature as a potential chemoprotective agent for cancer patients undergoing chemotherapy.

Background and Objective: Glucosamine is a widely prescribed dietary supplement used in the treatment of osteoarthritis. In the present study, the chemoprotectant ability of glucosamine was evaluated against cisplatin-induced genotoxicity and cytotoxicity in rat bone marrow cells. Methods: Glucosamine was orally administrated to rats at doses of 75 and 150 mg/kg body weight for seven consecutive days. On the seventh day, the rats were treated with a single injection of cisplatin (5 mg/kg, i.p.) at 1h after the last oral administration. The cisplatin antagonistic potential of glucosamine was assessed by micronucleus assay, Reactive Oxygen Species (ROS) level analysis, hematological analysis, and flow cytometry. Results: Glucosamine administration to cisplatin-treated rats significantly decreased the frequencies of Micronucleated Polychromatic Erythrocytes (MnPCEs) and Micronucleated Normchromatic Erythrocytes (MnNCEs), and also increased PCE/(PCE+NCE) ratio in bone marrow cells. Furthermore, treatment of rats with glucosamine before cisplatin significantly inhibited apoptosis, necrosis and ROS generation in bone marrow cells, and also increased red blood cells count in peripheral blood. Conclusion: This study shows glucosamine to be a new effective chemoprotector against cisplatin-induced DNA damage and apoptosis in rat bone marrow cells. The results of this study may be helpful in reducing the harmful effects of cisplatin-based chemotherapy in the future.

Genotoxicity in lymphocytes of cancer patients undergoing radiotherapy can lead to lymphocytopenia. Lymphocytopenia induced by radiotherapy is one of the most unfavorable prognostic biological markers in cancer patients, since it has been accepted to be associated with poor prognosis in terms of both survival time and response to cancer therapy. Therefore, reduction in lymphocytopenia may increase treatment efficiency. Research endeavors with synthetic radioprotectors in the past have met with little success primarily due to toxicity-related problems. These disadvantages have led to interest on the use of some plants and phytochemicals as radioprotector. The aim of this paper is to review protective role of some plants and phytochemicals against genotoxicity-induced by ionizing radiation in human blood lymphocytes. Therefore, current review may help the future researches to decrease lymphocytopenia in radiotherapeutic clinical trials.

Objective: The objective of this study is to observe the effect of 100-mg melatonin in reducing the levels of double-strand breaks (DSB) induced by 10 mGy and 100 mGy X-ray in peripheral lymphocyte applying H2AX immunofluorescence microscopy and comparing the different efficacies of melatonin ingestion 1 and 2 h before irradiation. Materials and Methods: Informed consent was obtained from five healthy males, nonathlete, and nonsmoking human volunteers aged between 25 and 35 years. Each volunteer was given a single oral dose of 100 mg melatonin at 9 a.m. Blood samples were collected in vacutainer tubes (without any preservative to separate the serum, and with heparin as an anticoagulant for separating leukocytes for in vitro exposure to gamma radiation) 5–10 min before then 1 and 2 h after melatonin ingestion. Afterward, each sample was subdivided into nonirradiated and irradiated groups (10 mGy and 100 mGy). After irradiation, lymphocytes of samples were separated. The isolated lymphocytes in each group were permeabilized for DSB assessment and stained against the phosphorylated histone variant γH2AX. Results: Melatonin ingestion 1 and 2 h before irradiation caused a significant reduction in γH2AX foci. Results further indicate that the change in ingestion of melatonin from 1 to 2 h before exposure had no significant effect. In addition, melatonin administration showed no side effects. Conclusion: The present study showed that melatonin will prove effective in radioprotection against ionizing radiation (IR)-induced DNA damage in human lymphocytes. Our results suggest ingestion of 100-mg melatonin by patients before exposure to IR in radiology.

Background: Radiosensitization using nanoparticles is proposed as a novel strategy for treatment of different cancers. Superparamagnetic iron oxide nanoparticles (SPIONs) have been reported to enhance effects of radiotherapy in several researches. Objective: The objective of this research is to investigate the radiosensitization properties of polyglycerol coated SPIONs (PG-SPIONs) on U87-MG cancer cells. Material and Methods: In this experimental study, polyglycerol coated SPIONs were synthesized by thermal decomposition method and characterized by FTIR, TEM and VSM analysis. Cellular uptake of nanoparticles by cells was examined via AAS. Cytotoxicity and radiosensitization of nanoparticles in combination with radiation were evaluated by MTT and colony assay, respectively. Results: Mean size of nanoparticles was 17.9±2.85 nm. FTIR verified SPIONs coating by Polyglycerol and VSM showed that they have superparamagnetic behaviour. Viability significantly (P < 0.001) decreased at concentrations above 100µg/ml for SPIONs but not for PG-SPIONs (P > 0.05). Dose verification results by TLD for doses of 2 and 4 Gy were 2±0.19 and 4±0.12 Gy respectively. The combination index for all situations was less than 1 and the effect is antagonism. Conclusion: However, PG-SPIONs combination with 6 MV X-ray reduced survival of U87-MG cells compared to radiation alone but the effect is antagonism.

Currently, ionizing radiation (IR) plays a key role in the agricultural and medical industry, while accidental exposure resulting from leakage of radioactive sources or radiological terrorism is a serious concern. Exposure to IR has various detrimental effects on normal tissues. Although an increased risk of carcinogenesis is the best-known long-term consequence of IR, evidence has shown that other diseases, particularly diseases related to inflammation, are common disorders among irradiated people. Autoimmune disorders are among the various types of immune diseases that have been investigated among exposed people. Thyroid diseases and diabetes are two autoimmune diseases potentially induced by IR. However, the precise mechanisms of IR-induced thyroid diseases and diabetes remain to be elucidated, and several studies have shown that chronic increased levels of inflammatory cytokines after exposure play a pivotal role. Thus, cytokines, including interleukin-1(IL-1), tumor necrosis factor (TNF-α) and interferon gamma (IFN-γ), play a key role in chronic oxidative damage following exposure to IR. Additionally, these cytokines change the secretion of insulin and thyroid-stimulating hormone(TSH). It is likely that the management of inflammation and oxidative damage is one of the best strategies for the amelioration of these diseases after a radiological or nuclear disaster. In the present study, we reviewed the evidence of radiation-induced diabetes and thyroid diseases, as well as the potential roles of inflammatory responses. In addition, we proposed that the mitigation of inflammatory and oxidative damage markers after exposure to IR may reduce the incidence of these diseases among individuals exposed to radiation.

Para-18F-fluorohippuric acid (18F-PFH) and ortho-124I-iodohippuric acid (124IOIH) were recently identified as potential radiotracers suitable for conducting renography using positron emission tomography (PET). The aim of this work was to estimate preliminary human-equivalent internal radiation dose of 18F-PFH and 124I-OIH using the biodistribution data reported in healthy rats. The results were compared with the absorbed dose data of technetium-99m-mercaptoacetyltriglycine (99mTc- MAG3) as documented in the International Commission on Radiological Protection (ICRP) publication 80.The medical internal radiation dose (MIRD) formula was applied to extrapolate data from rats to human and to project the absorbed radiation dose for various organs in humans. S factor was calculated by Monte-Carlo N-particle (MCNP) simulation.Our dose prediction shows that an injection of 18F-PFH or 124I-OIH in humans would result in an estimated effective absorbed dose of 0.09 or 0.17 µSv/MBq respectively for whole body, which is about 135 or 73 times respectively lower than that obtained with an injection of 99mTc-MAG3. All organs except kidneys would receive an estimated effective absorbed dose of0.1 µSv/MBq for 18F-PFH or 124I-OIH. Kidneys would receive a dose of 0.83 or 0.77 µSv/MBq respectively for 18F-PFH or 124I-OIH.Our results indicate that 18F-PFH and 124I-OIH would deliver much safer levels and lower radiation doses to the patients compared to 99mTc-MAG3 and warrants a clinical trial to estimate the radiation doses more accurately.

Background Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. Discussion Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted interests for both aims. COX-2 activity is associated with ROS production and inflammatory signs in normal tissues. These effects further amplify radiation toxicity in irradiated cells as well as adjacent cells through a phenomenon known as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues causes oxidative DNA damage and elevated cancer risk. Moreover, in tumors, the activation of this enzyme can increase resistance of malignant cells to radiotherapy. Hence, the inhibition of COX-2 has been proposed for better therapeutic response and amelioration of normal tissues. Celecoxib is one of the most studied COX-2 inhibitor for radiosensitization and radioprotection, while some other inhibitors have shown interesting results. Conclusion In this review, we describe the role of COX-2 in radiation normal tissue injury as well as irradiated bystander and non-targeted cells. In addition, mechanisms of COX-2 induced tumor resistance to radiotherapy and the potential role of COX-2 inhibition are discussed.

In this study, we tried to estimate human absorbed dose ofThe medical internal radiation dose (MIRD) formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. S factor calculated by Monte-Carlo N-particle (MCNP) simulation and also this factor has been taken from the tables presented in MIRD pamphlet No.11. Hence, two radiation absorbed dose were calculated for organs.Our dose prediction shows that an 185MBq injection of gallium-68-1,4,7-triazacyclononane-1-γ-glutamylglycine-4,7-diacetic acid (The results showed that

Every year, millions of cancer patients undergo radiation therapy for treating and destroying abnormal cell growths within normal cell environmental conditions. Thus, ionizing radiation can have positive therapeutic effects on cancer cells as well as post-detrimental effects on surrounding normal tissues. Previous studies in the past years have proposed that the reduction and oxidation metabolism in cells changes in response to ionizing radiation and has a key role in radiation toxicity to normal tissue. Free radicals generated from ionizing radiation result in upregulation of cyclooxygenases (COXs), nitric oxide synthase (NOSs), lipoxygenases (LOXs) as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase), and their effected changes in mitochondrial functions are markedly noticeable. Each of these enzymes is diversely expressed in multiple cells, tissues and organs in a specific manner. Overproduction of reactive oxygen radicals (ROS), reactive hydroxyl radical (ROH) and reactive nitrogen radicals (RNS) in multiple cellular environments in the affected nucleus, cell membranes, cytosol and mitochondria, and other organelles, can specifically affect the sensitive and modifying enzymes of the redox system and repair proteins that play a pivotal role in both early and late effects of radiation. In recent years, ionizing radiation has been known to affect the redox functions and metabolism of NADPH oxidases (NOXs) as well as having destabilizing and detrimental effects on directly and indirectly affected cells, tissues and organs. More noteworthy, chronic free radical production may continue for years, increasing the risk of carcinogenesis and other oxidative stress-driven degenerative diseases as well as pathologies, in addition to late effect complications of organ fibrosis. Hence, knowledge about the mechanisms of chronic oxidative damage and injury in affected cells, tissues and organs following exposure to ionizing radiation may help in the development of treatment and management strategies of complications associated with radiotherapy (RT) or radiation accident victims. Thus, this medically relevant phenomenon may lead to the discovery of potential antioxidants and inhibitors with promising results in targeting and modulating the ROS/NO-sensitive enzymes in irradiated tissues and organ injury systems.

In a previous article, we showed that metformin (MET) can reduce ionizing radiation (IR) induced apoptosis in human peripheral blood mononuclear cells. However, the anti-apoptotic mechanism of MET against IR remains unclear. The present study attempts to investigate the mechanism of action of MET in limiting X-ray induced apoptosis in human peripheral blood mononuclear cells.Mononuclear cells were treated with MET for 2 hours and irradiated with 6 MV X-rays. The gene expression levels of BAX, CASP3 and BCL2 were determined 24 hours post irradiation using real time quantitative polymerase chain reaction (qPCR) technique. Furthermore, the protein levels of BAX, CASP3 and BCL2 were analyzed by Western blotting assay.Radiation exposure increased the expressions of BAX and CASP3 genes, and decreased the expression of BCL2 gene in mononuclear cells. Conversely, an increase in BCL2 gene expression along with a decrease in BAX and CASP3 genes expression was observed in MET plus irradiated mononuclear cells. It was found that radiation increased BAX/BCL2 ratio, while MET pretreatment reduced these ratios. Also, treatment with MET without irradiation did not change the expressions of BAX, CASP3 and BCL2 genes. On the other hand, downregulated expression of BCL2 protein and upregulated expressions of BAX and CASP3 proteins were found in 2 Gy irradiated mononuclear cells, while pretreatment with MET significantly reversed this tendency.These results suggest that MET can protect mononuclear cells against apoptosis induced by IR through induction of cellular anti-apoptotic signaling.Key words: ionizing radiation - metformin - apoptosis - genes - proteins - blood cells.

Stem cell therapy opens a new window in medicine to overcome several diseases that remain incurable. It appears such diseases as cardiovascular disorders, brain injury, multiple sclerosis, urinary system diseases, cartilage lesions and diabetes are curable with stem cell transplantation. However, some questions related to stem cell therapy have remained unanswered. Stem cell imaging allows approval of appropriated strategies such as selection of the type and dose of stem cell, and also mode of cell delivery before being tested in clinical trials. MRI as a non-invasive imaging modality provides proper conditions for this aim. So far, different contrast agents such as superparamagnetic or paramagnetic nanoparticles, ultrasmall superparamagnetic nanoparticles, fluorine, gadolinium and some types of reporter genes have been used for imaging of stem cells. The core subject of these studies is to investigate the survival and differentiation of stem cells, contrast agent’s toxicity and long term following of transplanted cells. The promising results of in vivo and some clinical trial studies may raise hope for clinical stem cells imaging with MRI.

Background: Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Discussion: Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect. Inflammation in both irradiated and non-irradiated cells can trigger genomic instability, leading to increased risk of carcinogenesis. Targeting the inflammatory mediators has been an interesting idea for improving the therapeutic ratio throughout the reduction of normal tissue injury as well as an increase in tumor response to radiotherapy. Conclusion: So far, various targets have been proposed for the amelioration of radiation toxicity in radiotherapy. Of different targets, NF-IoB, COX-2, some of NADPH Oxidase subfamilies, TGF-I², p38 and the renin-angiotensin system have shown promising results. Interestingly, inhibition of these targets can help sensitize the tumor cells to the radiation treatment with some mechanisms such as suppression of angiogenesis and tumor growth as well as induction of apoptosis. In this review, we focus on recent advances on promising studies for targeting the inflammatory mediators in radiotherapy. © 2018 Bentham Science Publishers.

The diabetes drug metformin can mitigate the genotoxic effects of cytotoxic agents and has been proposed to prevent or even cure certain cancers. Metformin reduces DNA damage by mechanisms that are only incompletely understood. Metformin scavenges free radicals, including reactive oxygen species and nitric oxide, which are produced by genotoxicants such as ionizing or non-ionizing radiation, heavy metals, and chemotherapeutic agents. The drug may also increase the activities of antioxidant enzymes and inhibit NADPH oxidase, cyclooxygenase-2, and inducible nitric oxide synthase, thereby limiting macrophage recruitment and inflammatory responses. Metformin stimulates the DNA damage response (DDR) in the homologous end-joining, homologous recombination, and nucleotide excision repair pathways. This review focuses on the protective properties of metformin against genomic instability.

a b s t r a c t Background: There is no general consensus on the optimal criteria for the application of bone scintigraphy in screening of bone metastasis in patients with prostate cancer. Our study was conducted to assess the value of bone scan for pre-treatment staging of asymptomatic treatment-naive patients with prostate cancer. Methods: A total of 203 consecutive asymptomatic and treatment-naive patients with prostate cancer (age: 67.6 ± 6.4 years) who were referred to our department for whole body bone scintigraphy were enrolled in the study. Three hours after intravenous injection of 20 mCi 99m Tc-MDP, all patients underwent whole body bone scanning using a single head gamma camera. The planar images were supplemented with SPECT as needed for questionable abnormalities or those having uncertain location on planar images. Results: The mean serum PSA levels, serum alkaline phosphatase (ALP) and Gleason score (GS) were 42.41 ± 37.1 ng/ml, 223.9 ± 129.9 IU/L and 6.7 ± 1.1, respectively. A total of 55 cases (27.1%) out of 203 patients had bone metastases. The univariate analysis showed that serum PSA levels, GS and ALP were all significant predictors of bone metastases. However, only serum PSA and ALP levels were found to be independent predictors of bone metastasis in the multivariate logistic regression analysis. The combination of PSA and ALP (in which patients with either elevated PSA (>20 ng/ml) or elevated ALP were considered as positive) had the best screening value, with 98.2% sensitivity and 48.6% specificity. Conclusion: Serum ALP screening can be employed as a tool to detect the subgroup of patients who are at high risk of bone metastases, while having a PSA of

The purpose of this study was to compare estimation of radiation absorbed doses to patients following bone scans with technetium-99m-labeled methylene diphosphonate (MDP) with the estimates given in MIRDose software. In this study, each patient was injected 25 mCi of (99m)Tc-MDP. Whole-body images from thirty patients were acquired by gamma camera at 10, 60, 90, 180 minutes after (99m)Tc-MDP injection. To determine the amount of activity in each organ, conjugate view method was applied on images. MIRD equation was then used to estimate absorbed doses in different organs of patients. At the end, absorbed dose values obtained in this study were compared with the data of MIRDose software. The absorbed doses per unit of injected activity (mGy/MBq × 10(-4)) for liver, kidneys, bladder wall and spleen were 3.86 ± 1.1, 38.73 ± 4.7, 4.16 ± 1.8 and 3.91 ± 1.3, respectively. The results of this study may be useful to estimate the amount of activity that can be administered to the patient and also showed that methods used in the study for absorbed dose calculation is in good agreement with the data of MIRDose software and it is possible to use by a clinician.

The diagnostic accuracy of nuclear medicine reporting can be improved by awareness of these instrument-related artifacts. Both awareness and experience are also important when it comes to detecting and identifying normal (and abnormal) variants. We present a case of hot spot on the upper right chest in the region of right subclavicular region resulting from injection of radiotracer from central subclavian line. A 52-year-old woman with a history of left breast cancer and recent bone pain was referred to our nuclear medicine department for skeletal survey. Anterior views of chest show a focus of increased radiotracer uptake corresponding to anterior arch of one of the right second rib. The nuclear physician reported it as a focal rib bony lesion and recommended radiological evaluation. As technician later explained, physicians realized that injection site was a central subclavian line on the right side and hot spot on that region is due to injection site. The appearance of both skeletal and soft-tissue uptake depends heavily on imaging technique (such as the route of radiotracer administration) and the interpreting physicians should be aware of the impact of technical factors on image quality.

INTRODUCTION: The purpose of this study was to compare estimation of radiation absorbed doses to patients following bone scans with technetium-99m-labeled methylene diphosphonate (MDP) with the estimates given in MIRDose software. METHODS: In this study, each patient was injected 25 mCi of 99m Tc-MDP. Whole-body images from thirty patients were acquired by gamma camera at 10, 60, 90, 180 minutes after 99m Tc-MDP injection. To determine the amount of activity in each organ, conjugate view method was applied on images. MIRD equation was then used to estimate absorbed doses in different organs of patients. At the end, absorbed dose values obtained in this study were compared with the data of MIRDose software. Results: The absorbed doses per unit of injected activity (mGy/MBq A— 10 -4 ) for liver, kidneys, bladder wall and spleen were 3.86 ± 1.1, 38.73 ± 4.7, 4.16 ± 1.8 and 3.91 ± 1.3, respectively. CONCLUSIONS: The results of this study may be useful to estimate the amount of activity that can be administered to the patient and also showed that methods used in the study for absorbed dose calculation is in good agreement with the data of MIRDose software and it is possible to use by a clinician.