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Journal articles on the topic 'Lungs Radiation injuries'
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1
Saburova, A. S., M. V. Filimonova, V. V. Yuzhakov, L. I. Shevchenko, N. D. Yakovleva, L. N. Bandurko, A. E. Koretskaya, N. K. Fomina, V. O. Saburov, and A. S. Filimonov. "The influence of nitric oxide synthases inhibitor Т1023 on the development of radiation pneumofibrosis in rats." Radiatsionnaya Gygiena = Radiation Hygiene 13, no. 1 (March 31, 2020): 60–67. http://dx.doi.org/10.21514/1998-426x-2020-13-1-60-67.
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The purpose of the work was to study the ability of the NOS inhibitor T1023 to prevent late radiation injuries. Methods: the effects of T1023 (75 mg / kg, once i.p. 30 minutes before the irradiation) on the development of post-radiation pulmonitis and pneumofibrosis in rats with thoracic exposure to g-radiation at a dose of 12.5 Gy were studied histopathologically and morphometrically. The results of the studies showed that there wasn’t a significant objective effect of T1023 on the development of early radiation-induced lung injuries (9 weeks after irradiation). But it prevented late radiation induced lung injuaries (26 weeks after irradiation) – there were a significant lesser pathomorphological manifestations of post-radiation pulmonitis, proliferation of connective tissue and the development of fibrotic changes in the lung parenchyma. At this stage, the action of T1023 clearly contributed to the preservation of the normal histostructure of the lungs, reducing by 40% the content of compaction zones in the parenchyma. The ability of the NOS inhibitor T1023 to significantly limit the development of lungs late radiation reaction confirms the promise of further development of this compound as a means for prevention radiation therapy complications.
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DiCarlo, Andrea L. "Scientific research and product development in the United States to address injuries from a radiation public health emergency." Journal of Radiation Research 62, no. 5 (July 24, 2021): 752–63. http://dx.doi.org/10.1093/jrr/rrab064.
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Abstract The USA has experienced one large-scale nuclear incident in its history. Lessons learned during the Three-Mile Island nuclear accident provided government planners with insight into property damage resulting from a low-level release of radiation, and an awareness concerning how to prepare for future occurrences. However, if there is an incident resulting from detonation of an improvised nuclear device or state-sponsored device/weapon, resulting casualties and the need for medical treatment could overwhelm the nation’s public health system. After the Cold War ended, government investments in radiation preparedness declined; however, the attacks on 9/11 led to re-establishment of research programs to plan for the possibility of a nuclear incident. Funding began in earnest in 2004, to address unmet research needs for radiation biomarkers, devices and products to triage and treat potentially large numbers of injured civilians. There are many biodosimetry approaches and medical countermeasures (MCMs) under study and in advanced development, including those to address radiation-induced injuries to organ systems including bone marrow, the gastrointestinal (GI) tract, lungs, skin, vasculature and kidneys. Biomarkers of interest in determining level of radiation exposure and susceptibility of injury include cytogenetic changes, ‘omics’ technologies and other approaches. Four drugs have been approved by the US Food and Drug Administration (FDA) for the treatment of acute radiation syndrome (ARS), with other licensures being sought; however, there are still no cleared devices to identify radiation-exposed individuals in need of treatment. Although many breakthroughs have been made in the efforts to expand availability of medical products, there is still work to be done.
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Nudnov, N. V., V. M. Sotnikov, and V. V. Ledenev. "A new Method of Quantitative Estimation of Radiation-Induced Lung Damage in Oncological Patients on the CT in Dynamics." Medical Visualization, no. 5 (October 28, 2017): 56–65. http://dx.doi.org/10.24835/1607-0763-2017-5-56-65.
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Objective: to develop a methodology for quantitative assessment of changes in density parameters of pulmonary tissue on the basis of dynamic CT data, which makes it possible to assess the presence of the dependence of changes in lung tissue on the time elapsed after radiation therapy (RT), the dose and volume of irradiated pulmonary tissue.Materials and methods. Using the data collected by 11 patients with malignant lymphomas, we developed a new diagnostic technique for quantitative analysis, which is based on the analysis of the density of pulmonary tissue before and after RT in areas with a selected range of doses throughout the lung volume. All selected patients received LT in the chest region, using 3D-planning, fractions of 2Gy and total focal doses of 13–56 Gy. Also, each patient had at least two CT examinations (a total of 25 studies in the Dicom- format). The first CT scan was performed before LT, repeated – within 2–7 months after the end of RT.Results. In 6 patients, control CT examinations were performed 2.1–2.8 months after RT. As a result, a quantitative increase in the density indices in the range from +12 to +62 HU in regions of the lungs irradiated at a dose of more than 19 Gy was noted, different from the control areas. The volume of these areas of the lungs was from 16% to 30% of the total lung volume, and the volume of regions with the maximum values of density growth – from 7% to 14%. These changes in density are below the “visual” threshold. In control areas, the density change varied from −15 HU (increased airiness) to + 8 HU. According to the data of other CT studies performed later than 3 months after RT, the reverse development of changes characterizing the early radiation reaction was observed.Conclusions. A series of CT studies performed before and at various intervals after RT allows quantitative assessment of the dynamics of the indices of the density of irradiated pulmonary tissue, which is necessary for an objective assessment of the severity of early radiation-induced injuries of pulmonary tissue sites, depending on the dose. A study of the dynamics of these changes in pulmonary tissue density over time with RT and the connection of this indicator with the baseline data may allow one to predict radiation-induced damage to the lungs on the one hand, and on the other, to evaluate individual radiosensitivity.
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Khomutova, E. Y., P. V. Novikov, and A. S. Shatalov. "Possibilities of low-dose radiation therapy in the treatment of intrapulmonary injuries caused by COVID-19 infection." Medical Visualization 25, no. 1 (March 24, 2021): 27–34. http://dx.doi.org/10.24835/1607-0763-991.
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This paper examines the relevance of the use of a single irradiation of lungs in treatment of pneumonia caused by a new coronavirus infection. Clinical observations are presented that demonstrate perspectives in the treatment of this disease. Patients with severe pneumonia who were prescribed LD-RT (low-dose radiation therapy) at a dose of 0.5–1.5 Gy showed shorter recovery times and no complications. This method of treatment has shown its effectiveness in a number of studies from different countries, predicting success and economic benefits in its further use and study. A literature search containing information on relevant studies was carried out in PubMed, EMBASE, Web of Science and Google Scholar systems. Attention was focused on full-text articles given their general availability in a pandemic.
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Eckersley, Martyn, Carla Goncalves, Dalip Kumar, and Saman Perera. "A case of a mobile intrathoracic foreign object." Trauma 22, no. 1 (October 15, 2019): 70–73. http://dx.doi.org/10.1177/1460408619880140.
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Penetrating chest trauma to children is rare in the UK, making up 0.8% of wounds to children. When it does occur, it often results in damage to mediastinal structures including but not limited to the heart, lungs and great vessels. Rarely foreign objects can be intrapericardial. We present the case of a 14-year-old boy who presented haemodynamically stable following pellet gun wound to the chest. Multi-modality imaging revealed the bullet to be in the pericardium without associated cardiothoracic injuries, confirmed following surgery. Although a multi-modality imaging approach was used in diagnosing the precise location of the gun pellet, including imaging involving ionising radiation, we argue that early localisation can potentially be achieved with initial imaging and basic anatomical correlation, reducing the time to diagnosis. Using all the images available, including CT scout images, can assist in localisation and identifying important negatives.
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Ubysz, Dorota, Wojciech Giermaziak, and Aurelia Ostrowska. "Adverse Events During Hyperbaric Oxygen Therapy – Literature Review." Polish Hyperbaric Research 76, no. 3 (September 1, 2021): 45–66. http://dx.doi.org/10.2478/phr-2021-0016.
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Abstract As any other therapy method, hiperbaric oxygen therapy is connected with the risk of complications. The article is a review of the results of research on adverse events of hyperbaric oxygen therapy. The most common are: borotrauma of the middle ear, paranasal sinuses or lungs, oxygen toxicity can be pulmonary, ocular in extreme cases leading to cataracts, claustrophobia, pulmonary edema or hypoglycaemia. Research has shown that these events occur in the presence of high oxygen concentration or high pressure. Depending on the severity of complications, they are short-term not causing discontinuation of therapy or long-term excluding continuation of treatment. However adverse events connected with oxygen therapy are not common and are usually mild. This confirms that HBOT is an effective and safe method of treating decompression sickness, carbon monoxide poisoning, and the treatment of chronic wounds, delayed radiation injuries or necrotic soft tissue infections.
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Li, Bailong, Cheng Li, Mo Zhu, Youjun Zhang, Jicong Du, Yang Xu, Bin Liu, et al. "Hypoxia-Induced Mesenchymal Stromal Cells Exhibit an Enhanced Therapeutic Effect on Radiation-Induced Lung Injury in Mice due to an Increased Proliferation Potential and Enhanced Antioxidant Ability." Cellular Physiology and Biochemistry 44, no. 4 (2017): 1295–310. http://dx.doi.org/10.1159/000485490.
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Background/Aims: Radiation therapy is an important treatment for thoracic cancer; however, side effects accompanied with radiotherapy lead to limited tumor control and a decline in patient quality of life. Among these side effects, radiation-induced lung injury (RILI) is the most serious and common. Hence, an effective remedy for RILI is needed. Mesenchymal stromal cells (MSCs) are multipotent adult stem cells that have been demonstrated to be an effective treatment in some disease caused by tissue damage. However, unlike other injuries, RILI received limited therapeutic effects from implanted MSCs due to local hypoxia and extensive reactive oxygen species (ROS) in irradiated lungs. Since the poor survival of MSCs is primarily due to hypoxia and ROS generation, we hypothesize that persistent and adaptive hypoxia treatment induces enhanced resistance to hypoxic stress in implanted MSC. The aim of this study is to investigate whether persistent and adaptive hypoxia treatment of bmMSCs prior to their transplantation in injured mice enhanced survival and improved curative effects in RILI. Methods: Primary bmMSCs were obtained from the marrow of six-week-old male C57BL6/J mice and were cultured either under normoxic conditions (21% O2) or hypoxic conditions (2.5% O2). Mice were injected with normoxia/hypoxia MSCs after thoracic irradiation (20 Gy). The therapeutic effects of MSCs on RILI were assessed by pathological examinations that included H&E staining, Masson staining and α-SMA staining; meanwhile, inflammatory factors were measured using an ELISA. The morphology of MSCs in vitro was recorded using a microscope and identified by flow cytometry, cell viability was measured using the CCK-8 assay, the potential for proliferation was detected by the EdU assay, and ROS levels were measured using a ROS fluorogenic probe. In addition, HIF-1α and several survival pathway proteins (Akt, p-Akt, Caspase-3) were also detected by western blotting. Results: Implanted MSCs alleviated both early radiation-induced pneumonia and late pulmonary fibrosis. However, hypoxia MSCs displayed a more pronounced therapeutic effect compared to normoxia MSCs. Compared to normoxia MSCs, the hypoxia MSCs demonstrated greater cell viability, an enhanced proliferation potential, decreased ROS levels and increased resistance to hypoxia and ROS stress. In addition, hypoxia MSCs achieved higher activation levels of HIF-1α and Akt, and HIF-1α played a critical role in the development of resistance. Conclusion: Hypoxia enhances the therapeutic effect of mesenchymal stromal cells on radiation-induced lung injury by promoting MSC proliferation and improving their antioxidant ability, mediated by HIF-1α.
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Burgess, Matthew, Franklin Valdera, David Varon, Esko Kankuri, and Kristo Nuutila. "The Immune and Regenerative Response to Burn Injury." Cells 11, no. 19 (September 29, 2022): 3073. http://dx.doi.org/10.3390/cells11193073.
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Burn are diverse and complex injuries that not only have local effects but also serious systemic consequences through severe and prolonged inflammatory response. They are caused by heat, electricity, friction, chemicals, or radiation and are commonly divided into superficial, superficial partial-, deep partial- and full-thickness injuries. The severity of the burn depends mainly on the size and depth of the injury but also on location, age, and underlying systemic diseases. A prolonged and strong immune response makes major burns even worse by causing multiple systemic effects including damage to the heart, lungs, blood vessels, kidneys, and other organs. Burns that do not require surgical excision, superficial and superficial partial-thickness, follow the known progression of wound healing (inflammation, proliferation, remodeling), whilst deep partial- and full thickness injuries requiring excision and grafting do not. For these burns, intervention is required for optimal coverage, function, and cosmesis. Annually millions of people worldwide suffer from burns associated with high morbidity and mortality. Fortunately, over the past decades, burn care has significantly improved. The improvement in understanding the pathophysiology of burn injury and burn wound progression has led to developments in skin grafting, fluid resuscitation, infection control and nutrition This review article focuses on the immune and regenerative responses following burn injury. In the Introduction, we describe the epidemiology of burns and burn pathophysiology. The focus of the following chapter is on systemic responses to burn injury. Next, we define the immune response to burns introducing all the different cell types involved. Subsequently, we discuss the regenerative cell response to burns as well as some of the emerging novel treatments in the battle against burns.
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Davydkin, V. I. "PROFESSOR IVAN NIKIFOROVICH PIKSIN (to the 85th anniversary of the birth)." Grekov's Bulletin of Surgery 178, no. 6 (March 18, 2020): 80–82. http://dx.doi.org/10.24884/0042-4625-2019-178-6-80-82.
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The article is dedicated to the 85th birthday of the famous scientist, honored worker of science of the Russian Federation, honored worker of science of the Republic of Mordovia, honored doctor of the Republic of Mordovia, laureate of State prize, head of the scientific-pedagogical surgical school, doctor of medical Sciences professor Piksin Ivan Nikiforovich. I. N. Piksin is the author of fundamental studies of the biomedical effects of quantum radiation at the molecular, cellular and organismal levels in patients with acute destructive diseases of the lungs, purulent-septic diseases, lactational mastitis and other pathologies. The team of the scientific-pedagogical school led by I. N. Piksin explores the problems of diagnosis and treatment of gastroduodenal bleeding, mechanical jaundice, pancreatitis, suppurative diseases of the lung and pleura, surgical diseases of the heart, blood vessels, prevention of complications of limb injuries, diabetes and diabetic foot care, pediatric orthopedics. Under the leadership of I. N. Piksin, new minimally invasive technologies have introduced: transthoracic drainage and rehabilitation therapy of purulent cavities of the lung and pleura, percutaneous and transhepatic cholecystocholangiography, diagnostic and treatment interventions in space-occupying lesions of the abdomen and thyroid gland, ultrasound techniques of diabetes in acute destructive pancreatitis and others. He is considered as one of organizers of higher medical education system in the region. The professor is actively working on improvement in training of medical and scientific personnel for various regions of the Russian Federation.
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Vasil’ev, A. Yu, and I. S. Obelchak. "Multidetector computed tomography in the diagnosis of lesions of the main vessels for gunshot injury of the chest." Regional blood circulation and microcirculation 18, no. 1 (May 3, 2019): 31–38. http://dx.doi.org/10.24884/1682-6655-2019-18-1-31-38.
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Purpose – examine the possibilities of multislice computed tomangiography (MSCTA) in case of suspected damage to the great vessels in a chest gunshot fghting injury.Material and methods. A radiation survey of 130 wounded with gunshot injuries of the chest to assess the nature, diagnosis of gunshot injuries of the vascular bed.Results. Of the 130 wounded with gunshot wounds to the chest, 41 (31.5 %) of the injured had gunshot wounds to the chest were nonpenetrating, and 89 (68.5 %) had penetrating injuries. In 76 (58.4 %) patients with gunshot chest injuries, the nature of the wound was fragmentation, in 54 (41.6 %), wounds were bullet wounds. In the algorithm of radiation examination of patients with gunshot wounds of the chest to identify the nature of damage to the organs of the mediastinum and vascular structures, the main method of visualization was MSCT with contrast enhancement. Damage to the bone skeleton of the chest (ribs, collarbone, sternum, scapula) by MSCT was observed in 23 (17.6 %) patients. Almost half – 66 (50.1 %) of the wounded with gunshot injuries during MSCT examination, traumatic injury (pulmonitis) of the lung was observed. In 2 (1.5 %) cases, damage to the heart was detected that was not recognized at the stage of skilled surgical care. False posttraumatic aneurysm of the thoracic aorta was diagnosed in two wounded. Accuracy, sensitivity, specifcity of MSCT angiography in imaging of the vascular bed and diagnosis of damage to the great vessels of the chest cavity was 98, 97 and 97 %, respectively.Conclusions. MSCT made it possible to reliably assess the nature of the gunshot injuries of the chest, identify timely damage to the great vessels of the mediastinum, determine the localization of the foreign injuring bodies near the vascular structures, and determine the surgical tactics.
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Orlov, Yurii P., Sergey V. Sviridov, and Evgeny N. Kakulya. "Pathophysiological aspects of oxygen, hypoxia and free radical oxidation in critical conditions." Clinical nutrition and metabolism 2, no. 2 (April 15, 2021): 66–79. http://dx.doi.org/10.17816/clinutr88951.
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Oxygen is the main regulator of metabolic processes in the body not only in the context of normal physiology, but also in the development of various critical conditions.
In recent years, the problem of pathogenesis of a number organs' and systems' diseases has been enriched by knowledge of the mechanism of damage to cellular structures. Oxygen turned out to be the main factor of damage the very oxygen, due to the lack of which cell death occurs. It turned out that the so-called reactive oxygen species having an unpaired electron have a biological effect, which, depending on the concentration, can be regulatory or, conversely, toxic. Accordingly, interest has also been aroused in compounds that normally prevent the toxic effect of reactive oxygen species antioxidants. Today it is generally recognized that oxidative stress plays an important and possibly a key role in the pathogenesis of critical conditions. Thus, on the one side, excessive production of free radicals is considered as one of the manifestations of the body's protective reaction to the effects of various environmental factors and living conditions (infections, injuries, toxins, ionizing radiation, physical stress, hypothermia, hypoxia, various types of stress), on the other ― increased production of free radicals quickly leads to irreversible damage: destruction of the erythrocytes' membranes with subsequent hemolysis, transformation of hemoglobin into methemoglobin, DNA damage, desensitization of plasma membrane receptors, inactivation of various hormones and enzymes, including antiradical and antiperoxide protection enzymes.
The problem of using oxygen in critical conditions is currently widely discussed in the periodical literature with an emphasis on the oxygen concentrations used in patients, both in operating rooms and in intensive care units. Oxygen used in the intensive care of acute respiratory failure and hypoxia should have a certain concentration range. The toxic effects of oxygen can occur with its prolonged use in high concentrations, which causes not only its direct toxic effect on the lungs, but also in the potentiation of the activation of free radical oxidation and excessive production of reactive oxygen species.
The review presents current data on the physiological role of oxygen, its participation in metabolic processes against the background of inflammation, hypoxia and under conditions of activation of free radical oxidation processes. The recent approach to oxygen therapy and the research data presented in the review urge to relate to oxygen as a drug in order to avoid manifestations of its toxic effects.
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Fliss, H., and M. Menard. "Rapid neutrophil accumulation and protein oxidation in irradiated rat lungs." Journal of Applied Physiology 77, no. 6 (December 1, 1994): 2727–33. http://dx.doi.org/10.1152/jappl.1994.77.6.2727.
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Exposure of lungs to high doses of ionizing radiation can initiate an injurious acute inflammatory response. We show that neutrophil content in the lungs of rats exposed to 10 Gy whole body gamma radiation increased threefold 4.5 h after irradiation and returned to normal by 24 h. Oxidized methionine in the proteins of the lungs, heart, liver, kidney, and jejunum increased significantly in 2 h. Treatment with the antioxidant dithiothreitol immediately after irradiation prevented methionine oxidation. Methionine oxidation was also observed after intrabronchial instillation of phorbol myristate acetate, a model of neutrophil oxidant-mediated pulmonary injury, as well as in isolated lungs perfused with hypochlorous acid, confirming the ability of neutrophil oxidants to cause protein oxidation in lungs. No change in glutathione or protein sulfhydryl content was detected in irradiated lungs 4.5 h after irradiation, possibly as a result of protection by the observed increase in pulmonary glutathione reductase. We therefore show that the acute pulmonary inflammatory response to radiation involves rapid neutrophil accumulation, oxidant production, and protein oxidation.
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Redaelli, Paola, Amando Gamba, Antonello Stefano Martino, and Michele Triggiani. "Unexpected Radiation-Induced Aortic Wall Thickening Requiring Composite Graft Technique during Off-Pump Coronary Artery Bypass Grafting." Case Reports in Surgery 2017 (2017): 1–2. http://dx.doi.org/10.1155/2017/3831749.
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Mediastinal radiation is commonly used to treat Hodgkin’s and non-Hodgkin’s lymphoma, lung and breast cancer. Cardiac complications after radiation therapy are well described, although rare. A large spectrum of injuries can occur, causing long term morbidity among survivors. We describe a case of post-actinic ascending aortic wall thickening that prevented saphenous vein proximal anastomosis and was successfully managed with aortic no-touch off-pump coronary artery bypass grafting (OPCAB), 25 years after radiation therapy for Hodgkin’s lymphoma.
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Wang, Bao-Zhong, Li-Ping Wang, Hui Han, Fang-Li Cao, Guang-Yao Li, Jun-Long Xu, Xiu-Wen Wang, and Le-Xin Wang. "Interleukin-17A antagonist attenuates radiation-induced lung injuries in mice." Experimental Lung Research 40, no. 2 (January 21, 2014): 77–85. http://dx.doi.org/10.3109/01902148.2013.872210.
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Wang, R., J. Rahimian, M. R. Girvigian, M. J. Miller, and L. Mariscal. "Quantitative Analysis of Stereotactic Body Radiation Therapy (SBRT)-Induced Lung Injuries." International Journal of Radiation Oncology*Biology*Physics 96, no. 2 (October 2016): E674. http://dx.doi.org/10.1016/j.ijrobp.2016.06.2315.
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Dykan, Iryna. "Radiation diagnostics of thoracic gunshot wounds." Radiation Diagnostics, Radiation Therapy, no. 2 (2020): 70–80. http://dx.doi.org/10.37336/2707-0700-2020-2-6.
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The frequency of thoracic injuries in the general structure of combat surgical trauma remains at the level of 7-12 % and unchanged from the time of the Second World War to the current armed conflicts. The overwhelming majority of them (up to 72 %) are shrapnel gunshot wounds. The formation of a gunshot wound occurs due to the action of a shock wave; a wounding projectile; energy of side impact and vortex wake. The shape, size, features of the wound canal are determined by the kinetic energy of the wounding agent and the physical properties of the damaged tissues. The lung parenchyma is loose and elastic, so small-caliber bullets with low energy cause minimal damage. The wound canal is well differentiated on CT-slices. Its cavity is filled with blood, fragments of destroyed tissue, air bubbles. On the periphery, the contusion zone is determined (area of increased attenuation in the lung-ground-glass opacity). Shrapnel wounds can be accompanied by ruptures of the pulmonary parenchyma with hemorrhages, bilateral pulmonary contusion, damage to the bone frame and soft tissues of the chest. Vascular injury with massive hemorrhage into the pleural cavity and tense hemopneumothorax are one of the main causes of mortality in penetrating wounds. Transmediastinal gunshot wounds, armor trauma and bullet embolism require special attention during radiation examination of victims. The purpose of radiation diagnostics of modern combat trauma is to identify and fully characterize injuries and their complications. The amount of diagnostic information is determined by the level of medical care. Key words: gunshot wounds, chest cavity organs, radiation diagnostics.
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Chen, Zhiyuan, Bin Wang, Jiali Dong, Yuan Li, Shuqin Zhang, Xiaozhou Zeng, Huiwen Xiao, Saijun Fan, and Ming Cui. "Gut Microbiota-Derived l-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury." International Journal of Molecular Sciences 22, no. 21 (October 23, 2021): 11436. http://dx.doi.org/10.3390/ijms222111436.
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Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.
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Yadav, Marshleen, Sagar Bhayana, Joseph Liu, Lanchun Lu, Jason Huang, Ya Ma, Zahida Qamri, et al. "Two-miRNA–based finger-stick assay for estimation of absorbed ionizing radiation dose." Science Translational Medicine 12, no. 552 (July 15, 2020): eaaw5831. http://dx.doi.org/10.1126/scitranslmed.aaw5831.
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Nuclear radiation and radioactive fallouts resulting from a nuclear weapon detonation or reactor accidents could result in injuries affecting multiple sensitive organs, defined as acute radiation syndrome (ARS). Rapid and early estimation of injuries to sensitive organs using markers of radiation response is critical for identifying individuals who could potentially exhibit ARS; however, there are currently no biodosimetry assays approved for human use. We developed a sensitive microRNA (miRNA)–based blood test for radiation dose reconstruction with ±0.5 Gy resolution at critical dose range. Radiation dose–dependent changes in miR-150-5p in blood were internally normalized by a miRNA, miR-23a-3p, that was nonresponsive to radiation. miR-23a-3p was not highly expressed in blood cells but was abundant in circulation and was released primarily from the lung. Our assay showed the capability for dose estimation within hours to 1 week after exposure using a drop of blood from mice. We tested this biodosimetry assay for estimation of absorbed ionizing radiation dose in mice of varying ages and after exposure to both improvised nuclear device (IND)–spectrum neutrons and gamma rays. Leukemia specimens from patients exposed to fractionated radiation showed depletion of miR-150-5p in blood. We bridged the exposure of these patients to fractionated radiation by comparing responses after fractionated versus single acute exposure in mice. Although validation in nonhuman primates is needed, this proof-of-concept study suggests the potential utility of this assay in radiation disaster management and clinical applications.
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Maznyk, N. O., T. S. Sypko, V. P. Starenkyi, I. M. Hukova, S. V. Artiukh, and L. V. Cherkasko. "Features of cytogenetic effects in oncological patients during radiotherapy with prior radiation exposure." Український радіологічний та онкологічний журнал 29, no. 4 (December 23, 2021): 48–64. http://dx.doi.org/10.46879/ukroj.4.2021.48-64.
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Background. Radiotherapy can be used numerous times for treating oncological patients as one of the most effective ways of fighting against cancer. However, there is limited data on the effect of prior radiation exposure on the further development of cytogenetic alterations under the influence of radiological factors. Primary radiation treatment, as well as the second one, is an example of a complex scenario of fractionated irradiation, examination of which is of fundamental and practical importance for understanding complex processes of formation and elimination of cytogenetic markers of radiation exposure for further improvement of biodosimetry system and development of personalised radiotherapy. Purpose. To determine the nature of changes of radiation-induced cytogenetic alterations and genomic disorders in patients with lung, head and neck cancer during radiotherapy on the background of prior radiation exposure. during radiotherapy with prior radiation exposure. Materials and methods. 29 oncological patients with lung, head and neck cancer were examined. 16 of them received radiotherapy for the first time, and 13 – for the second. We studied chromosome aberration frequency and genomic disorders during external beam radiation therapy by cytogenetic test. Results. In the patients pre-irradiation level of cytogenetic injuries exceeded spontaneous level. In addition, chromosome aberration frequency in the patients, who had received prior radiation exposure, was significantly higher than those who had not been treated with radiotherapy. It depended on the period between radiotherapy treatment courses. The increase in level of radiation-induced cytogenetic injuries during the whole radiotherapy treatment course of patients was observed, regardless of prior therapeutic exposure. Under quite a high level of chromosome damage in the group of secondary patients at the beginning of the treatment, chromosome aberration increase rates were higher than in the group of the primary patients. The distribution of markers of radiation exposure over cells during radiotherapy was overdispersed according to Poisson statistics in both of the groups. The changes in the frequency of genomic disorders were mostly of fluctuating nature. Conclusions. In the secondary patients, the level of cytogenetic indexes before radiotherapy exceeded the indexes of the primary patients. The level of chromosome damage increased during the radiotherapy treatment course in both primary and secondary patients, but at different rates. The additional genotoxic effect of reirradiation manifested itself only in a greater maximum quantity of aberrations per aberrant cell in the secondary patients. In terms of increased rates of cytogenetic injuries, a more significant genotoxic effect from the second radiotherapy on the background of prior radiation exposure was not detected.
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Wan, Xinlong, Xuan Shi, Mengke Li, Qing Chen, Chang Xue, Guanghui Li, Yeke Huang, et al. "The Protective Effects and Mechanism of Doxepin on Radiation–Induced Lung Injury in Rats." Dose-Response 20, no. 2 (April 2022): 155932582211071. http://dx.doi.org/10.1177/15593258221107193.
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Radiation-induced lung injuries (RILI) is one of the serious complications of radiotherapy posed by the damage of alveolar cells and inflammation over-reaction. We aimed to investigate the potential protective effects of doxepin on RILI (20 Gy total dose at 3 Gy/min of X-ray irradiation), as well as its underlying mechanism. For animal experiments, such parameters as Immunohistochemistry and hematoxylin and eosin (H&E) staining, WBC (white blood cell), CRP (C-reactive protein), Western blot, and q-PCR were detected. The results indicated that both survival status and weight increase of irradiated rats treated by doxepin (3 mg/kg/day, rat) were higher than those of treated with irradiation alone (Dosing started the day before irradiation). Further, histological examinations showed doxepin could tenuate the radiation injury, as indicated as alveolar inflammatory exudation and there was only mild interstitial inflammation infiltration. Western blotting and q-PCR showed that expression of NF-κβ in X group were higher than that in XMD group. For the first time, we reported doxepin functioned as a radioprotectant candidate, which provide a promising application of doxepin for protecting radiotherapy injuries.
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Wang, Kai-Xuan, Wen-Wen Cui, Xu Yang, Ai-Bin Tao, Ting Lan, Tao-Sheng Li, and Lan Luo. "Mesenchymal Stem Cells for Mitigating Radiotherapy Side Effects." Cells 10, no. 2 (February 1, 2021): 294. http://dx.doi.org/10.3390/cells10020294.
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Radiation therapy for cancers also damages healthy cells and causes side effects. Depending on the dosage and exposure region, radiotherapy may induce severe and irreversible injuries to various tissues or organs, especially the skin, intestine, brain, lung, liver, and heart. Therefore, promising treatment strategies to mitigate radiation injury is in pressing need. Recently, stem cell-based therapy generates great attention in clinical care. Among these, mesenchymal stem cells are extensively applied because it is easy to access and capable of mesodermal differentiation, immunomodulation, and paracrine secretion. Here, we summarize the current attempts and discuss the future perspectives about mesenchymal stem cells (MSCs) for mitigating radiotherapy side effects.
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Chapel, Alain, Alexandra Semont, Sabine Francois, Moubarack Mouiseddine, and Dominique Thierry. "Human Mesenchymal Stem Cells (MSC) Home at Injured Sites after Local Irradiation and Contribute To Reduce Radiation-Induced Intestinal Lesion." Blood 106, no. 11 (November 16, 2005): 1691. http://dx.doi.org/10.1182/blood.v106.11.1691.1691.
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Abstract Some patients who undergo radiotherapy may develop side effects that can be life threatening. Tissue complications can result in functional alterations of organs caused by radiation-induced stem cell depletion. Stem cell therapy is a promising approach to improve radiotherapy-enhanced tissue complications. The multipotential of Mesenchymal Stem Cells (MSC), their easy isolation and high ex vivo expansive capacity make these cells good candidates for replenishment of the depleted stem cell compartment during radiotherapy. In this study, we make the assumption that radiation-induced normal tissue injuries might play a role in the recruitment of MSC for tissue repair. We isolated MSC from the human bone marrow (hMSC) and transplanted them via the systemic route into immunotolerent NOD/SCID mice. Using two models of radiation-induced lesion (total body irradiation: TBI, total abdominal irradiation: TAI), we have studied the link between tissue damage and hMSC implantation. Tissue alterations were studied by histological analysis. hMSC in tissues of transplant was quantified by real-time PCR assay 14 days after their injection. In unirradiated NOD/SCID mice, hMSC homed significantly in lung (0.06% of total lung cells), muscle (0.07%) and bone marrow (0.14%). Following TBI of NOD/SCID mice at a sublethal dose (3.2 Gy), we observed an increase of engraftment in brain (0.07%), heart (0.05%), liver (0.11%), muscle (0.12%) and bone marrow (0.37%) compared to unirradiated mice. TAI (8 Gy) induced a significant increase of hMSC engraftment levels in kidney (0.10%), stomach (0.12%), liver (0.44%), spleen (0.94%), and small intestine (0.17%) compared to TBI mice. Histological study show that MSC reduce radiation-induced intestinal lesion: following AI, MSC accelerate the renewal of small intestine in participating to their regenerative process. From 3 days after radiation exposure, when hMSC are injected, the integrity of small intestine is already regained. The villus length is significantly increased (1.7 fold compared with control). We also observe many proliferating zone). 15 days after irradiation, the villus length remains elevated and is significantly increased in comparison with uninjected or unirradiated group. We then demonstrated that hMSC could accelerate and favour small intestinal regeneration after radiation-induced their damages. We conclude that mainly MSC implantation takes place in radiation-injured organs of exposed areas. We demonstrate the capacity of hMSC to improve the spontaneous renewal of NOD/SCID mice small intestine. The characterization of the capacity of MSC in intestinal functional recover is under progress in our laboratory.
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Kahn, Johannes, David Kaul, Georg Böning, Roman Rotzinger, Patrick Freyhardt, Philipp Schwabe, Martin Maurer, Diane Renz, and Florian Streitparth. "Quality and Dose Optimized CT Trauma Protocol – Recommendation from a University Level-I Trauma Center." RöFo - Fortschritte auf dem Gebiet der Röntgenstrahlen und der bildgebenden Verfahren 189, no. 09 (June 26, 2017): 844–54. http://dx.doi.org/10.1055/s-0043-108996.
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Purpose As a supra-regional level-I trauma center, we evaluated computed tomography (CT) acquisitions of polytraumatized patients for quality and dose optimization purposes. Adapted statistical iterative reconstruction [(AS)IR] levels, tube voltage reduction as well as a split-bolus contrast agent (CA) protocol were applied. Materials and Methods 61 patients were split into 3 different groups that differed with respect to tube voltage (120 – 140 kVp) and level of applied ASIR reconstruction (ASIR 20 – 50 %). The CT protocol included a native acquisition of the head followed by a single contrast-enhanced acquisition of the whole body (64-MSCT). CA (350 mg/ml iodine) was administered as a split bolus injection of 100 ml (2 ml/s), 20 ml NaCl (1 ml/s), 60 ml (4 ml/s), 40 ml NaCl (4 ml/s) with a scan delay of 85 s to detect injuries of both the arterial system and parenchymal organs in a single acquisition. Both the quantitative (SNR/CNR) and qualitative (5-point Likert scale) image quality was evaluated in parenchymal organs that are often injured in trauma patients. Radiation exposure was assessed. Results The use of IR combined with a reduction of tube voltage resulted in good qualitative and quantitative image quality and a significant reduction in radiation exposure of more than 40 % (DLP 1087 vs. 647 mGyxcm). Image quality could be improved due to a dedicated protocol that included different levels of IR adapted to different slice thicknesses, kernels and the examined area for the evaluation of head, lung, body and bone injury patterns. In synopsis of our results, we recommend the implementation of a polytrauma protocol with a tube voltage of 120 kVp and the following IR levels: cCT 5mm: ASIR 20; cCT 0.625 mm: ASIR 40; lung 2.5 mm: ASIR 30, body 5 mm: ASIR 40; body 1.25 mm: ASIR 50; body 0.625 mm: ASIR 0. Conclusion A dedicated adaptation of the CT trauma protocol (level of reduction of tube voltage and of IR) according to the examined body region (head, lung, body, bone) combined with a split bolus CA injection protocol allows for a high-quality CT examination and a relevant reduction of radiation exposure in the examination of polytraumatized patients Key Points Citation Format
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Manouchehr Aghajanzadeh, Ali Alasvand Lahbar, Mohammad Reza Asgari, Ramin Ebrahimian, Ali Alavi Fomani, Azita Tangestaninejad, and Yousha Pooramadi. "Comparative study of the need for re-intervention after chest tube remove in two groups with and without chest x-ray in Patients Admitted into Razi and Poursina hospital in Rasht city." International Journal of Biological and Pharmaceutical Sciences Archive 2, no. 1 (September 30, 2021): 157–63. http://dx.doi.org/10.53771/ijbpsa.2021.2.1.0050.
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Introduction: The most common types of injuries following blunt or sharp trauma of lungs and the pleural space are pneumothorax, hemothorax and hemopneumothorax, which in most cases are resolved through supportive care and thoracostomy (use of chest tubes). Removal of the CT (chest tube) can result in complication such as pneumothorax and accumulation of fluid in the pleural space. Despite the lack of a standard guideline regarding the management of patients post CT removal, it is advised to procure a CXR as a means of a conservative approach. However, most of the findings acquired from the post CT removal CXR are not clinically significant and in the case of patients requiring intervention, there are almost always clinical signs and symptoms present. Considering the prior statements, the lack of a standard guideline even in the general and thoracic surgery references, show cases the importance of this study. This study is set upon proving that, the omission of post CT removal CXR in asymptomatic patients will not have an impact on the clinical outcome of the case and will reduce the costs as well as the patients' exposure to radiation and hospital stay. Methods: This study is designed as cross-sectional study with a sample size of 200 patients who were hospitalized for CT insertion in the Surgery clinic of Razi and Poursina Hospitals in Rasht between 21/4/2019 and 20/4/2020 and matched our entry criteria. The patients were divided into 2 groups of 100, with one group being monitored without CXR and the other with the use of CXR. Some forms were designed as checklists for the task of data collection. The data analysis was done through Fisher's exact test, Chi square test and Mann Whitney U test. In addition, the Significance level was set at 0.05 (p value ≤ 0.05). Result: Out of the 200 patients included in our study, 120 were male (60%) and the rest (40%) were female. The most common underlying disease in both groups (with and without CXR) of our study was Hip fracture. In both groups, The most frequent reason for CT insertion was pleural effusion (36% and 43% in with CXR and without CXR groups respectively), but the difference between the 2 groups was not statistically significant (p = 0.597). In most of the cases, 1 CT was inserted and there was no statistically significant difference between the 2 groups. The difference between the 2 groups regarding the need for intervention (11 cases in the CXR group and 6 cases in the Non CXR group) was also statistically insignificant. The duration of hospital stay did not show a statistically significant difference between the 2 groups (p = 0.644). Conclusion: Our study suggests that whether a post CT removal CXR is obtained or not, will not make a statistically significant difference in the number of interventions, the cause of intervention, and the number of inserted CTs and the duration of hospital stay. Therefore, it can be suggested that the need for reintervention in post CT removal patients can be determined through clinical signs, symptoms and the surgeon's judgment, without the need for a routine CXR.
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Yue, Weisheng, Guilin Zhang, Ping Liu, Jianqi Sun, Yeukuang Hwu, Jung Ho Je, Mingguang Tan, and Yan Li. "Aerosol-induced lung injuries observed by synchrotron radiation X-ray phase-contrast imaging technique." Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 262, no. 2 (September 2007): 304–12. http://dx.doi.org/10.1016/j.nimb.2007.05.032.
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Kadivar, Fatemeh, Gholamhassan Haddadi, Mohammad Amin Mosleh-Shirazi, Fatemeh Khajeh, and Alireza Tavasoli. "Protection effect of cerium oxide nanoparticles against radiation-induced acute lung injuries in rats." Reports of Practical Oncology & Radiotherapy 25, no. 2 (March 2020): 206–11. http://dx.doi.org/10.1016/j.rpor.2019.12.023.
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Popova, I. E., L. T. Khamidova, I. E. Goncharova, V. M. Abuchin, R. Sh Muslimov, T. G. Barmina, E. A. Tarabrin, I. E. Selina, M. K. Nanoyan, and O. A. Chernysheva. "Radiation diagnostics of injuries and complications with a blind penetrating wound of the chest received from a construction and installation gun." Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH), no. 1 (February 3, 2022): 99–110. http://dx.doi.org/10.20340/vmi-rvz.2022.1.case.4.
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On the example of a clinical case, the possibilities of radiation diagnosis of a rare type of injury received from a construction and installation gun are shown. The modern possibilities of radiation diagnostics in the detection of injuries and complications in a gunshot wound of the chest are shown. Ultrasound data on the presence of intrapleural contents allowed us to determine the penetrating nature of the wound. The data obtained by polypositional chest radiography gave an idea of the localization and size of the foreign body. During chest CT, an accurate anatomical characteristic of the wound canal was given, the exact localization of the foreign body was indicated, an intrapulmonary hematoma, a lung contusion were identified, the exact nature and volume of the intrapleural contents were determined. In the postoperative period, CT revealed PE and infarct pneumonia, and scintigraphy assessed the total deficit of lung perfusion, which affected the treatment tactics. In the diagnosis of complications of breast injury such as intrapulmonary hematoma, infarction pneumonia, inflammatory changes in the soft tissues of the chest wall, ultrasound diagnostic data are comparable with CT results.
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Kubo, K., T. Kimura, H. Sakaguchi, N. Imano, H. Kawabata, Y. Takeuchi, Y. Doi, et al. "Computed Tomographic Appearance of Radiation Injuries in Lung After Two Prescribed Dose of 48Gy With Stereotactic Body Radiation Therapy." International Journal of Radiation Oncology*Biology*Physics 93, no. 3 (November 2015): E421. http://dx.doi.org/10.1016/j.ijrobp.2015.07.1620.
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Cogno, Nicolò, Roman Bauer, and Marco Durante. "An Agent-Based Model of Radiation-Induced Lung Fibrosis." International Journal of Molecular Sciences 23, no. 22 (November 11, 2022): 13920. http://dx.doi.org/10.3390/ijms232213920.
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Early- and late-phase radiation-induced lung injuries, namely pneumonitis and lung fibrosis (RILF), severely constrain the maximum dose and irradiated volume in thoracic radiotherapy. As the most radiosensitive targets, epithelial cells respond to radiation either by undergoing apoptosis or switching to a senescent phenotype that triggers the immune system and damages surrounding healthy cells. Unresolved inflammation stimulates mesenchymal cells’ proliferation and extracellular matrix (ECM) secretion, which irreversibly stiffens the alveolar walls and leads to respiratory failure. Although a thorough understanding is lacking, RILF and idiopathic pulmonary fibrosis share multiple pathways and would mutually benefit from further insights into disease progression. Furthermore, current normal tissue complication probability (NTCP) models rely on clinical experience to set tolerance doses for organs at risk and leave aside mechanistic interpretations of the undergoing processes. To these aims, we implemented a 3D agent-based model (ABM) of an alveolar duct that simulates cell dynamics and substance diffusion following radiation injury. Emphasis was placed on cell repopulation, senescent clearance, and intra/inter-alveolar bystander senescence while tracking ECM deposition. Our ABM successfully replicates early and late fibrotic response patterns reported in the literature along with the ECM sigmoidal dose-response curve. Moreover, surrogate measures of RILF severity via a custom indicator show qualitative agreement with published fibrosis indices. Finally, our ABM provides a fully mechanistic alveolar survival curve highlighting the need to include bystander damage in lung NTCP models.
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Lierova, Anna, Jitka Kasparova, Alzbeta Filipova, Jana Cizkova, Lenka Pekarova, Lucie Korecka, Nikola Mannova, Zuzana Bilkova, and Zuzana Sinkorova. "Hyaluronic Acid: Known for Almost a Century, but Still in Vogue." Pharmaceutics 14, no. 4 (April 11, 2022): 838. http://dx.doi.org/10.3390/pharmaceutics14040838.
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Hyaluronic acid (HA) has a special position among glycosaminoglycans. As a major component of the extracellular matrix (ECM). This simple, unbranched polysaccharide is involved in the regulation of various biological cell processes, whether under physiological conditions or in cases of cell damage. This review summarizes the history of this molecule’s study, its distinctive metabolic pathway in the body, its unique properties, and current information regarding its interaction partners. Our main goal, however, is to intensively investigate whether this relatively simple polymer may find applications in protecting against ionizing radiation (IR) or for therapy in cases of radiation-induced damage. After exposure to IR, acute and belated damage develops in each tissue depending upon the dose received and the cellular composition of a given organ. A common feature of all organ damage is a distinct change in composition and structure of the ECM. In particular, the important role of HA was shown in lung tissue and the variability of this flexible molecule in the complex mechanism of radiation-induced lung injuries. Moreover, HA is also involved in intermediating cell behavior during morphogenesis and in tissue repair during inflammation, injury, and would healing. The possibility of using the HA polymer to affect or treat radiation tissue damage may point to the missing gaps in the responsible mechanisms in the onset of this disease. Therefore, in this article, we will also focus on obtaining answers from current knowledge and the results of studies as to whether hyaluronic acid can also find application in radiation science.
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Zhang, Chunyang, Yan Zhu, Ji Wang, Lisheng Hou, Wei Li, and Huaijie An. "CXCR4-Overexpressing Umbilical Cord Mesenchymal Stem Cells Enhance Protection against Radiation-Induced Lung Injury." Stem Cells International 2019 (February 5, 2019): 1–12. http://dx.doi.org/10.1155/2019/2457082.
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Less quantity of transplanted mesenchymal stem cells (MSCs) influences the therapeutic effects on radiation-induced lung injury (RILI). Previous studies have demonstrated that MSCs overexpressing Chemokine (C-X-C motif) receptor 4 (CXCR4) could increase the quantity of transplanted cells to local tissues. In the present study, we conducted overexpressing CXCR4 human umbilical cord mesenchymal stem cell (HUMSC) therapy for RILI. C57BL mice received single dose of thoracic irradiation with 13 Gy of X-rays and then were administered saline, control HUMSCs, or CXCR4-overexpressing HUMSCs via tail vein. Transfection with CXCR4 enhanced the quantity of transplanted HUMSCs in the radiation-induced injured lung tissues. CXCR4-overexpressing HUMSCs not only improved histopathological changes but also decreased the radiation-induced expression of SDF-1, TGF-β1, α-SMA, and collagen I and inhibited the radiation-induced decreased expression of E-cadherin. Transplanted CXCR4-overexpressing HUMSCs also could express pro-SP-C, indicated adopting the feature of ATII. These finding suggests that CXCR4-overexpressing HUMSCs enhance the protection against RILI and may be a promising strategy for RILI treatment.
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Sagindikova, G. E., E. A. Kogan, and T. E. Shakhanov. "Mortality and morbidity of chronic lung disease and its morphological features in population of Semipalatinsk region." PULMONOLOGIYA, no. 3 (June 28, 2007): 87–92. http://dx.doi.org/10.18093/0869-0189-2007-0-3-87-92.
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This work was aimed to study prevalence, morbidity, mortality and morphological features of chronic respiratory pathology (CRP) in population living for a long time at Semipalatinsk region contaminated with radioactive products. We analyzed healthcare reports on prevalence, mortality and morbidity of CRP in population of Semipalatinsk region from 1969 to 2003 and questioned 7 274 residents of Semipalatinsk region using a special ly developed screening questionnaire. The latter considered the radiation related route and clinical status of the person. We have also analysed 631 autopsy reports of died patients with CRP and archive autopsy, biopsy and resected samples from 300 patients with CRP living near the experimental range from their childhood to 2003. The resected and autopsy samples of 22 patients with CRP living at the territories with normal radiation level was the control group. The results showed a tendency to increase in morbidity and mortality of CRP in proportion of the radiation dose and neighbourhood of the living place to the experimental range. The morbidity and mortality of CPR tended to decrease in 1992–2003 when nuclear experiments were stopped. Besides of well known morphological features of CRP we found severe sclerosis of the bronchial walls and interstitial tissue, vascular injuries and haemosiderosis, neuroendocrine cell hyperplasia, dysplasia of bronchial, bronchiolar and alveolar epithelium. These facts suppose the role of radiation as etiological and pathogenic factor of CRP.
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Fan, Ming, Lawrence B. Marks, Donna Hollis, Gunilla G. Bentel, Mitchell S. Anscher, Gregory Sibley, R. Edward Coleman, Ronald J. Jaszczak, and Michael T. Munley. "Can We Predict Radiation-Induced Changes in Pulmonary Function Based on the Sum of Predicted Regional Dysfunction?" Journal of Clinical Oncology 19, no. 2 (January 15, 2001): 543–50. http://dx.doi.org/10.1200/jco.2001.19.2.543.
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PURPOSE: To determine whether changes in whole-lung pulmonary function test (PFT) values are related to the sum of predicted radiation therapy (RT)-induced changes in regional lung perfusion. PATIENTS AND METHODS: Between 1991 and 1998, 96 patients (61% with lung cancer) who were receiving incidental partial lung irradiation were studied prospectively. The patients were assessed with pre- and post-RT PFTs (forced expiratory volume in one second [FEV1] and diffusion capacity for carbon monoxide [DLCO]) for at least a 6-month follow-up period, and patients were excluded if it was determined that intrathoracic recurrence had an impact on lung function. The maximal declines in PFT values were noted. A dose-response model based on RT-induced reduction in regional perfusion (function) was used to predict regional dysfunction. The predicted decline in pulmonary function was calculated as the weighted sum of the predicted regional injuries: equation [Formula: see text] where Vd is the volume of lung irradiated to dose d, and Rd is the reduction in regional perfusion anticipated at dose d. RESULTS: The relationship between the predicted and measured reduction in PFT values was significant for uncorrected DLCO (P = .005) and borderline significant for DLCO (P = .06) and FEV1 (P = .08). However, the correlation coefficients were small (range, .18 to .30). In patients with lung cancer, the correlation coefficients improved as the number of follow-up evaluations increased (range, .43 to .60), especially when patients with hypoperfusion in the lung adjacent to a central mediastinal/hilar thoracic mass were excluded (range, .59 to .91). CONCLUSION: The sum of predicted RT-induced changes in regional perfusion is related to RT-induced changes in pulmonary function. In many patients, however, the percentage of variation explained is small, which renders accurate predictions difficult.
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Mansour, Somya Z., Fatma S. M. Moawed, Monda M. M. Badawy, and Hebatallah E. Mohamed. "Boswellic Acid Synergizes With Low-Level Ionizing Radiation to Modulate Bisphenol Induced-Lung Toxicity in Rats by Inhibiting JNK/ERK/c-Fos Pathway." Dose-Response 18, no. 4 (October 1, 2020): 155932582096959. http://dx.doi.org/10.1177/1559325820969597.
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Bisphenol A (BPA) is a low molecular weight chemical compound that has a deleterious effect on the endocrine system. It was used in plastics manufacturing with injurious effects on different body systems. Occupational exposure to low-level ionizing radiation (<1 Gy) is shown to attenuate an established inflammatory process and therefore enhance cell protection. Therefore, the objective of this study was to investigate the protective effect of boswellic acid (BA) accompanied by whole-body low-dose gamma radiation (γ-R) against BPA-induced lung toxicity in male albino rats. BPA intoxication induced with 500 mg/kg BW. Rats received 50 mg BA/kg BW by gastric gavage concomitant with 0.5 Gy γ-R over 4 weeks. The immunoblotting and biochemical results revealed that BA and/or γ-R inhibited BPA-induced lung toxicity by reducing oxidative damage biomolecules; (MDA and NADPH oxidase gene expression), inflammatory indices (MPO, TNF-α, IL-6, and gene expression of CXCR-4). Moreover, BA and or/γ-R ameliorated the lung inflammation via regulation of the JNK/ERK/c-Fos and Nrf2/ HO-1 signaling pathways. Interestingly, our data demonstrated that BA in synergistic interaction with γ-R is efficacious control against BPA-induced lung injury via anti-oxidant mediated anti-inflammatory activities.
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Kursova, L. V., A. G. Konoplyannikov, V. V. Pasov, I. N. Ivanova, M. V. Poluektova, and O. A. Konoplyannikova. "Possibilities for the Use of Autologous Mesenchymal Stem Cells in the Therapy of Radiation-Induced Lung Injuries." Bulletin of Experimental Biology and Medicine 147, no. 4 (April 2009): 542–46. http://dx.doi.org/10.1007/s10517-009-0538-7.
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Fleming, Robert E., and Michael Kasper. "ALVEOLAR EPITHELIAL REPAIR BY TYPE II PNEUMOCYTES IN THE RADIATION-INJURED RAT LUNG. † 2297." Pediatric Research 39 (April 1996): 386. http://dx.doi.org/10.1203/00006450-199604001-02322.
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OGASAWARA, NOBUHIKO, KAZUYOSHI SUGA, YUICHI KARINO, and NAOFUMI MATSUNAGA. "Perfusion Characteristics of Radiation-Injured Lung on Gd-DTPA-Enhanced Dynamic Magnetic Resonance Imaging." Investigative Radiology 37, no. 8 (August 2002): 448–57. http://dx.doi.org/10.1097/00004424-200208000-00006.
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Velazquez, M., and D. P. Schuster. "Effect of regional pulmonary blood flow on extravascular lung water measurements with PET." Journal of Applied Physiology 65, no. 3 (September 1, 1988): 1267–73. http://dx.doi.org/10.1152/jappl.1988.65.3.1267.
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We examined the effect of regional pulmonary blood flow (PBF) on lung water measurements made with a blood-borne label (15O-water) and positron emission tomography (PET) in five dogs. The total lung water (TLW) content of a lung region obtained at equilibrium after intravenous injection of 15O-water (TLW-water) was compared with calculations made from lung density measurements (TLW-density) also obtained with PET. These latter measurements are proportional to the tissue attenuation of radioactivity originating from an external source encircling the animal and are independent of PBF. Comparisons were made before and 60 min after oleic acid-induced injury confined to the left caudal lobe (LCL). PBF fell 61% in regions from the dorsal half of the LCL after lung injury and was unchanged on the right side. Both before and after injury, TLW-density was 10-15% higher than TLW-water. This systematic difference is probably due to overestimates of TLW-density resulting from partial volume and scattered radiation effects. When TLW-water and TLW-density were compared in 151 3-ml regions from both normal and injured lung, the disparity between the two methods of calculating TLW increased in regions with a PBF less than 0.5 ml.min-1.ml lung-1 (less than 20% of base line). However, this represented only 22% of the injured regions analyzed. Thus lung water measurements made with PET and 15O-water are accurate until regional PBF is severely reduced. With PET, such areas can be eliminated from analysis or regions can be made sufficiently large so the overall effect on the TLW measurement is minimized.
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Tatomir, Jovanka. "Procedure zdravstvene nege pacijenta sa opekotinskom traumom / Procedures health care of the patient with burns trauma." SESTRINSKI ŽURNAL 3, no. 1 (November 1, 2016): 48. http://dx.doi.org/10.7251/sez0116048t.
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The burns are tissue damage caused under the influence of pathogenic amounts of heat, chemicals, electricity or radiation of different bodies.Etiological factors generally can be divided into four groups: thermal, chemical, electrical and radiation burns.Tissue damage is directly related to high temperature and length of exposure to harmful agents. The higher the temperature and longer works, the damage was more severe. Etiologic agents can cause minor injuries in the form of erythema of the skin, and severe destruction of body parts or the whole organism. System changes occur and are particularly pronounced in severely burned patients. These are patients with more than 25% body surface area burned, regardless of the depth, electrical burns, subdermal burns over 10% of body surface area burned with associated lung injuries, fractures, contusions, wounds, diseases previously. The burns are the most serious violations of the organism due to the involvement of almost all organs and systems. Extensive burns are therefore called and burns disease.The treatment of burned patients conducted team with a multidisciplinary approach. The nurse is an integral part of the team. The treatment of burns consists of first aid, general medical and surgical treatment. Prophylactic antibiotic therapy is applied in extensive burns. The main aim of local treatment of the disposal of burned area.Nursing care of the patient with burns trauma is of particular importance for the outcome of the treatment and prevention of complications. Nursing process involves numerous and complex medical-technical intervention, such as: continuous monitoring of vital functions; daily dressing wounds, with the absolute application of the principles of aseptic techniques; taking laboratory analysis; placement of a urinary catheter connected to a closed drainage system, to be followed hour diuresis; placement central venous catheter, peripheral venous catheters; taking blood cultures and urine culture with the aim of diagnosis of septic states.
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AL-Suhbani, Musherah, Saif Serag, Nor El Houda Baghous, and Chakir El Mahjoub. "Evaluation the Impact of Changing Patient Thickness on Treatment Dose Amount Given to Injured Area." Open Access Macedonian Journal of Medical Sciences 10, B (September 27, 2022): 2118–23. http://dx.doi.org/10.3889/oamjms.2022.10760.
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Radiation therapy provides an appropriate radiation dose to tumors. The proportion of this dose varies according to the injured part and its location. Targeting the part affected by the tumor with an appropriate radiation dose requires high accuracy in measuring from the radiation source to the patient and the amount of dose. This treatment was applied using digital linear accelerators and computers to treat the tumor with radiation. In most cases, it is used chemotherapy, one of the standard cancer treatments. However, those doses affect the patient as it leads to loss of appetite, which negatively affects the patient's weight. The patient loses weight during treatment, and the affected area's thickness changes during a Computed Tomography (CT) scan of the body for treatment planning. This led to changes in dose distribution to the target area and adjacent organs (organs at risk). This study examines the impact of changes in the patient's treatment area thickness on both dose and Source Surface Distance (SSD). In this study, we apply five different parts of cancer (lung, prostate, uterus, rectum, and vulva) that were treated by the traditional method using a linear accelerator and using a one-dimensional beam. Furthermore, CT takes images of the affected area to locate the tumor and plan treatment. Also, XIO device is used to track the patient's thickness during treatment and take a three-dimensional (3D) image of the patient during daily treatment sessions. The obtained results showed that the changing in treatment area thickness between 0.5 - 2.3cm, led to a change in the distance from the source to the patient's body, where the percentage of change was from 0.43 to 2.67%. Furthermore, the results showed that the dose increase of the planning target volume (PTV) by 1.54%, prostate 0.13%, rectum 0.38%, and bladder 0.83%, when the treatment area decreased thickness to 1.47 cm for prostate cancer. Moreover, the clinical target volume (CTV) dose by 0.40%, PTV 3.65%, rectum 3.84%, and bladder 3.19% decrease when the treatment area thickness increase by 3.16 cm in cervical cancer. Thus, the dose changed for the affected organ significantly more than the reference dose.
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Zheng, Yijun, and Duming Zhu. "Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis." Oxidative Medicine and Cellular Longevity 2016 (2016): 1–6. http://dx.doi.org/10.1155/2016/5806057.
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Since it was proposed in 2007, molecular hydrogen therapy has been widely concerned and researched. Many animal experiments were carried out in a variety of disease fields, such as cerebral infarction, ischemia reperfusion injury, Parkinson syndrome, type 2 diabetes mellitus, metabolic syndrome, chronic kidney disease, radiation injury, chronic hepatitis, rheumatoid arthritis, stress ulcer, acute sports injuries, mitochondrial and inflammatory disease, and acute erythema skin disease and other pathological processes or diseases. Molecular hydrogen therapy is pointed out as there is protective effect for sepsis patients, too. The impact of molecular hydrogen therapy against sepsis is shown from the aspects of basic vital signs, organ functions (brain, lung, liver, kidney, small intestine, etc.), survival rate, and so forth. Molecular hydrogen therapy is able to significantly reduce the release of inflammatory factors and oxidative stress injury. Thereby it can reduce damage of various organ functions from sepsis and improve survival rate. Molecular hydrogen therapy is a prospective method against sepsis.
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Saini, Rashmi, Savita Verma, Abhinav Singh, and Manju Lata Gupta. "Role of Active Principles of Podophyllum hexandrum in Amelioration of Radiation Mediated Lung Injuries by Reactive Oxygen/Nitrogen Species Reduction." CellBio 02, no. 03 (2013): 105–16. http://dx.doi.org/10.4236/cellbio.2013.23012.
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Wen, Sicheng, Mark Dooner, Elaine Papa, Michael Del Tatto, Mandy Pereira, Theodor Borgovan, Yan Cheng, et al. "Biodistribution of Mesenchymal Stem Cell-Derived Extracellular Vesicles in a Radiation Injury Bone Marrow Murine Model." International Journal of Molecular Sciences 20, no. 21 (November 2, 2019): 5468. http://dx.doi.org/10.3390/ijms20215468.
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We have previously shown that injury induced by irradiation to murine marrow can be partially or completely reversed by exposure to human or murine mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Investigation of the biodistribution of EVs in vivo is essential for understanding EV biology. In this study, we evaluated the DiD lipid dye labeled MSC-EV biodistribution in mice under different conditions, including different MSC-EV doses and injection schedules, time post MSC-EV injection, and doses of radiation. DiD-labeled MSC-EVs appeared highest in the liver and spleen; lower in bone marrow of the tibia, femur, and spine; and were undetectable in the heart, kidney and lung, while a predominant EV accumulation was detected in the lung of mice infused with human lung fibroblast cell derived EVs. There was significantly increased MSC-EV accumulation in the spleen and bone marrow (tibia and femur) post radiation appearing with an increase of MSC-EV uptake by CD11b+ and F4/80+ cells, but not by B220 cells, compared to those organs from non-irradiated mice. We further demonstrated that increasing levels of irradiation caused a selective increase in vesicle homing to marrow. This accumulation of MSC-EVs at the site of injured bone marrow could be detected as early as 1 h after MSC- EV injection and was not significantly different between 2 and 24 h post MSC-EV injection. Our study indicates that irradiation damage to hematopoietic tissue in the spleen and marrow targets MSC-EVs to these tissues.
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Hong, Zhen-Yu, Sung Ho Eun, Kwangwoo Park, Won Hoon Choi, Jung Il Lee, Eun-Jung Lee, Ji Min Lee, Michael D. Story, and Jaeho Cho. "Development of a small animal model to simulate clinical stereotactic body radiotherapy-induced central and peripheral lung injuries." Journal of Radiation Research 55, no. 4 (February 20, 2014): 648–57. http://dx.doi.org/10.1093/jrr/rrt234.
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Liu, Daming, Fanxuan Kong, Yong Yuan, Prem Seth, Weidong Xu, Hao Wang, Fengjun Xiao, et al. "Decorin-Modified Umbilical Cord Mesenchymal Stem Cells (MSCs) Attenuate Radiation-Induced Lung Injuries via Regulating Inflammation, Fibrotic Factors, and Immune Responses." International Journal of Radiation Oncology*Biology*Physics 101, no. 4 (July 2018): 945–56. http://dx.doi.org/10.1016/j.ijrobp.2018.04.007.
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Feng, Mingxiang, Miao Lin, Haining Zhou, Yunhe Zhu, Baishen Chen, Xin Ye, Chuoji Huang, Juncheng Zhang, and Chunxue Bai. "Clinical utility of circulating genetically abnormal cells within low-dose computed tomography lung cancer screening: A correlative MCPND trial study." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e15536-e15536. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e15536.
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e15536 Background: Recent screening trial results using low-dose computed tomography (LDCT) have been shown to reduce lung cancer mortality in high-risk patients. However, high false-positive rates, inter-grader variability, and radiation injuries are challenging, and therefor highlight the necessity for complementary biomarkers. The diagnostic performance of circulating genetically abnormal cells (CACs) was respectively evaluated in samples collected from patients with pulmonary nodules before and after lung lobectomy within the Multicenter Chinese Pulmonary Nodule Detection (MCPND) trial. We also propose a deep learning that detects related genetically abnormal cells in excisions of symptomatic lesions to identify the source of CACs. Methods: 269 plasma samples (n = 179, before surgery; n = 90, after surgery) from 179 participants, including 125 patients with lung cancer and 54 donors with benign nodular lesions, were analyzed by using a FISH–based assay for 3p22.1, 3q29, 10q22_3 and CEP10. Diagnostic performance of CAC was evaluated in a blinded validation group. 109 paraffin-embedded specimens (45 benign nodular lesions, 64 malignancies) obtained from participants were tested in the same way to identify the genetically abnormal cells. Results: The diagnostic performance of CACs for lung cancer detection was 91% for sensitivity and 81% for specificity. For all participants, CACs had a positive predictive value of 92% and 80% for negative predictive value, respectively. Area under the ROC curve was 0.89 (P < 0.01; 95%CI (0.82, 0.96)). 90 plasma samples were drawn from patients within 10 days after surgery. Of these samples, 58 participants’ CACs level reduced and 25 of them remained stable. Moreover, of 64 malignant specimens, genetically abnormal cells were detected in 60 specimens. However, only 4 specimens were detected having genetically abnormal cells in 45 benign nodular lesions. Conclusions: This validation study indicated that the number of genetically abnormal cells in circulation decreased after surgical resection, which suggested CACs could be released from lung cancer. CACs have diagnostic and prognostic value and could assist to improve the diagnostic accuracy in early stage lung cancer after low-dose computed tomography. Clinical trial information: ChiCTR1900026233.
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Aliotta, Jason M., Mandy Pereira, and Peter J. Quesenberry. "Tissue-Specific Gene Expression of Marrow Cells Co-Cultured with Various Murine Organs." Blood 112, no. 11 (November 16, 2008): 388. http://dx.doi.org/10.1182/blood.v112.11.388.388.
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Abstract We have previously demonstrated that murine bone marrow cells co-cultured with lung opposite a cell-impermeable membrane express high levels of lung cell-specific genes (Aliotta et al, Stem Cells, 2007;25(9):2245–56). Greater changes in gene expression were noted in marrow cells co-cultured with radiation-injured lung. A factor smaller than the pore size of the cell-impermeable membrane (0.4μm) is responsible for these changes as cell-free conditioned media (CM) had a similar effect on co-cultured marrow cells. Lung-derived microvesicles were found to enter marrow cells in culture and may be among the factors responsible for these phenotypic changes. We wished to determine if these observations could be generalized to co-cultures using other murine organs and whether these changes in gene expression are tissue-specific. Whole bone marrow (WBM) cells were isolated from C57BL/6 mice and co-cultured with lung, liver, heart and WBM cells from C57BL/6 mice exposed to 1200 centigrey (cGy) of total body irradiation (TBI) or no radiation. Control WBM cells were co-cultured with no tissue (control). Co-cultured WBM cells were analyzed 7 or 14 days later by Real Time RT-PCR and fold difference in target gene expression was determined (relative to control cells). In addition, cell-free CM made from the same organs was co-cultured for 7 or 14 days with WBM cells which were then analyzed by RT-PCR. Alternatively, CM was analyzed for the presence of microvesicles by electron microscopy (EM) of ultracentrifuged (UCF) pelleted material. WBM co-cultured only with lung had increased gene expression of surfactant proteins A (Sp-A) and C (Sp-C, 89 and 334-fold increase vs. control, respectively) whereas WBM co-cultured only with brain had increased gene expression of Glial Fibrillary Acidic Protein (GFAP, 4.6-fold increase vs. control). Slight increases in Albumin expression were seen in all co-culture groups but expression was markedly elevated in WBM co-cultured with liver (162,657-fold increase vs. control). Expression of heart-specific markers, including Troponin I and T2, was seen in WBM co-cultured with heart but these levels were not significantly different from those of other co-culture groups. Radiation injury augmented expression of certain genes in co-cultured WBM, including Sp-A (1019 vs. 89-fold increase) in lung co-cultures and GFAP (24 vs. 4.6-fold increase) in brain co-cultures. WBM co-cultured with CM from all organs demonstrated similar changes in gene expression. In addition, pelleted material from UCF CM contained RNA that was specific to the tissue from which the CM was made. EM of UCF CM demonstrated numerous membranebound particles 50–200nm in size that were typical of microvesicles in appearance. These data suggest that changes seen in gene expression of co-cultured WBM are largely tissue-specific, depending on the tissue they are co-cultured with. Microvesicles released by various tissues in co-culture may be among the mediators responsible for the changes seen in WBM gene expression.
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Magnuson-Osborn, Teresia A., Claes Dahlgren, John H. Hartwig, and Thomas P. Stossel. "Human Plasma Gelsolin Inhibits Cellular Responses to Platelet Activating Factor (PAF)." Blood 106, no. 11 (November 16, 2005): 3568. http://dx.doi.org/10.1182/blood.v106.11.3568.3568.
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Abstract Gelsolin is a highly conserved intracellular actin-binding protein with an extracellular isoform named plasma gelsolin (pGSN). Relatively high (250 mg /L) blood concentrations of pGSN decrease in response to trauma, major surgery, sepsis, burns, ionizing radiation, and hyperoxia. Depletion of pGSN to a critical (~20%) level precedes and predicts complications of primary injuries such as lung permeability changes, ARDS, assisted ventilation and death. Administration of recombinant pGSN ameliorates such complications and reduces mortality in animal models. A proposed mechanism for pGSN’s protective effects is that it inhibits inflammatory mediators generated during primary injuries, since pGSN binds bioactive mediators, including lysophospatidic acid (LPA) and endotoxin in vitro. Because of its structural similarity we hypothesized that plasma gelsolin binds also to the potent lipid mediator platelet activating factor (PAF) and report here on the inhibition of PAF-induced cellular activation. Recombinant pGSN inhibited PAF-induced P-selectin up-regulation by human platelets as measured by flow cytometry. A ten- to 40-fold molar excess (0.5–20 μM) of pGSN over PAF inhibits P-selectin expression by 40 to 80%. The concentrations of plasma gelsolin used approximate the ~2–3 μM concentrations in plasma, and the molar excess of pGSN over PAF is probably greater in biological systems, where PAF has nanomolar affinity for its receptor. pGSN also inhibited PAF-induced superoxide anion (O2-) production (measured by chemiluminescence) of human neutrophils (PMN) in a concentration-dependent manner. The inhibition was up to 80% at a concentration of 10 μM (tenfold molar excess over PAF). A phospholipid-binding peptide derived from pGSN (QRLFQVKGRR) also inhibited PAF-mediated O2- generation by PMN. The inhibition was 65% at a 1:1 molar ratio (1 μM). In conclusion pGSN interferes with PAF-induced cellular activation in vitro, suggesting a mechanism for the protective role of plasma gelsolin that has been observed in vivo.
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Moss, Nelson S., Brandon S. Imber, Kavya Prasad, Bae P. Chu, Arun Goel, David Aramburu-Nunez, Michael Bellamy, et al. "69. PERMANENT INTRACAVITARY Cs131 BRACHYTHERAPY FOR PREVIOUSLY-IRRADIATED RECURRENT BRAIN METASTASES: INITIAL CLINICAL AND RADIATION SAFETY EXPERIENCE." Neuro-Oncology Advances 2, Supplement_2 (August 2020): ii14. http://dx.doi.org/10.1093/noajnl/vdaa073.056.
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Abstract OBJECTIVE Recurrence of previously-irradiated brain metastases (BrM) presents a significant challenge. We describe our initial experience using salvage resection with Cs131 brachytherapy in previously-irradiated BrM. METHODS Between September 2019 and April 2020, 9 patients with recurrent BrM underwent maximally-safe metastatectomy. Following pathological confirmation of viable recurrence, cavities were implanted with permanent Cs131 brachytherapy (GammaTile, GT Medical Technologies). Prescribed dose was 60Gy at 5mm from the cavity. Postimplant dosimetry (V100) was calculated on postoperative day 1 fused CT/MRI. Intraoperative team exposure was recorded using intraoperative ring dosimetry, and patient dose-rates measured postoperatively informed patient, family and medical-staff exposure modeling. RESULTS Nine patients (55% female, median age 54) underwent 10 implantations (6 supratentorial, 4 infratentorial). Median preoperative maximum diameter was 3.5cm (2.3–6.3) and histologies included breast, gastrointestinal, lung, kidney and oral cavity squamous cell carcinomas. Five had undergone prior resection or laser ablation. All lesions received >/=1 prior course of stereotactic irradiation a median of 10.1 months (3.7–15.9) earlier. Eight lesions were gross-totally resected. Median number of implanted Cs131 seeds was 16 (12–28) with median seed strength of 61.8U (42.4–98.0). Median postoperative cavity size was well-correlated with the number of implanted seeds (Pearson R=0.75, p=0.03). Median V100 dose coverage of the cavities and uniform 5mm expansion of the cavities were 99% (79–100%) and 79% (51–95%), respectively. Median measured exposure rates were 90mR/hr (28–152) on contact, 9.15mR/hr (2.7–13.9) at 30cm and 1.4mR/hr (0.6–2.3) at 1 meter from the patient. Mean ring dose was 6.83mrem (0–18) for the radiation oncologist and 9.17mrem (0–15) for the neurosurgeon. Modeled lifetime family-member and visitor exposure was 116mrem (52-193mrem), and healthcare worker exposure was 39mrem (17-64mrem), all well below regulatory limits. There were no immediate wound complications or unanticipated neurologic injuries. CONCLUSION In our early experience, salvage interstitial Cs131 implantation was safely employed for recurrent brain metastases.
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Roper, Jason M., Sean C. Gehen, Rhonda J. Staversky, M. Christine Hollander, Albert J. Fornace, and Michael A. O'Reilly. "Loss of Gadd45a does not modify the pulmonary response to oxidative stress." American Journal of Physiology-Lung Cellular and Molecular Physiology 288, no. 4 (April 2005): L663—L671. http://dx.doi.org/10.1152/ajplung.00355.2004.
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It is well established that exposure to high levels of oxygen (hyperoxia) injures and kills microvascular endothelial and alveolar type I epithelial cells. In contrast, significant death of airway and type II epithelial cells is not observed at mortality, suggesting that these cell types may express genes that protect against oxidative stress and damage. During a search for genes induced by hyperoxia, we previously reported that airway and alveolar type II epithelial cells uniquely express the growth arrest and DNA damage ( Gadd) 45a gene. Because Gadd45a has been implicated in protection against genotoxic stress, adult Gadd45a (+/+) and Gadd45a (−/−) mice were exposed to hyperoxia to investigate whether it protected epithelial cells against oxidative stress. During hyperoxia, Gadd45a deficiency did not affect loss of airway epithelial expression of Clara cell secretory protein or type II epithelial cell expression of pro-surfactant protein C. Likewise, Gadd45a deficiency did not alter recruitment of inflammatory cells, edema, or overall mortality. Consistent with Gadd45a not affecting the oxidative stress response, p21Cip1/WAF1 and heme oxygenase-1 were comparably induced in Gadd45a (+/+) and Gadd45a (−/−) mice. Additionally, Gadd45a deficiency did not affect oxidative DNA damage or apoptosis as assessed by oxidized guanine and terminal deoxyneucleotidyl transferase-mediated dUTP nick-end labeling staining. Overexpression of Gadd45a in human lung adenocarcinoma cells did not affect viability or survival during exposure, whereas it was protective against UV-radiation. We conclude that increased tolerance of airway and type II epithelial cells to hyperoxia is not attributed solely to expression of Gadd45a.