Photorespiration Regulates Carbon-Nitrogen Metabolism by Magnesium Chelatase D Subunit in Rice.

The growth and development of plants are dependent on the interaction between carbon and nitrogen metabolism. Essential information about the metabolic regulation of carbon-nitrogen metabolism is still lacking, such as possible interactions among nitrogen metabolism, photosynthesis, and photorespiration. This study shows that higher photorespiration consumes more CO2 fixed by photosynthesis, making the high photosynthetic efficiency mutant fail to increase production. In order to clarify the effects of photosynthesis and photorespiration on carbon and nitrogen metabolism in high photosynthetic efficiency mutant, a yellow-green leaf mutant (ygl53) was isolated from rice (Oryza sativa L.). Its chlorophyll (Chl) content decreased, but chloroplast development was not affected. Genetic analysis demonstrated that YGL53 encodes the magnesium chelatase D subunit (ChlD). The ygl53 mutant showed an increased net assimilation rate (An) and electron transport flux efficiency and catalase (CAT) activity, and it also had a higher photorespiration rate (Pr), lower H2O2, and reduced nitrogen uptake efficiency (NUpE); however, there was no loss in yield. The higher activities of glutamate synthase (GOGAT) and glutamine synthetase (GS) ensure the α-ketoglutaric acid (2-OG) and ammonia (NH3) availabilities, which are produced from photorespiration in the ygl53 mutant. These have an important function for carbon and nitrogen metabolism homeostasis in ygl53. Further analysis indicated that the energy and substances derived from carbon metabolism supplemented nitrogen metabolism in the form of photorespiration to ensure its normal development when the An of photosynthesis was increased in the ygl53 mutant with reduced NUpE.

Simulating the approximate irregular field dose distribution in radiotherapy using an ultrasound tracking technique.

PURPOSE: This study used an ultrasound image tracking algorithm (UITA) in combination with a proposed simulation program for the approximate irregular field dose distribution (SPAD) to assess the feasibility of performing dose distribution simulations for two-dimensional radiotherapy. METHODS: This study created five different types of multileaf collimator openings, and applied a SPAD to analyze the matrix position parameters for each regular field to generate a static program-simulation dose distribution map (PDDM), whose similarity was then compared with a static radiochromic film experimental-measurement dose distribution map (EDDM). A two-dimensional respiration motion simulation system (RMSS) was used to reproduce the respiration motion, and the UITA was used to capture the respiration signals. Respiration signals were input to the SPAD to generate two dynamic PDDMs, which were compared for similarity with the dynamic EDDM. RESULTS: In order to verify the dose distribution between different dose measurement techniques, the gamma passing rate with 2%/2 mm criterion was used for the EDDM and PDDM, the passing rates were between 94.31% and 99.71% in the static field analyses, and between 84.45% and 96.09% for simulations with the UITA signal input and between 89.35% and 97.78% for simulations with the original signal input in the dynamic field analyses. CONCLUSIONS: Static and dynamic dose distribution maps can be simulated based on the proposed matrix position parameters of various fields and by using the UITA to track respiration signals during radiation therapy. The present findings indicate that it is possible to develop a reusable and time-saving dose distribution measurement tool.

FUNCTION OF EXTERNAL RESPIRATION AND MARKERS OF OXIDATIVE STRESS IN CHILDREN-RESIDENTS OF RADIOACTIVELY CONTAMINATED TERRITORIES. / FUNKTsIIa ZOVNIShN'OGO DYKhANNIa I MARKERY OKSYDATYVNOGO STRESU U DITEY̆ ­ MEShKANTsIV RADIOAKTYVNO ZABRUDNENYKh TERYTORIY̆.

OBJECTIVE: to evaluate the influence of processes of lipid peroxidation, and antioxidant protection on the function of external respiration in children-residents of radioactive contaminated territories. MATERIALS AND METHODS: There were examined children of school age, inhabitants of radioactive contaminated ter- ritories (RCT) without respiratory and pulmonary pathology, and patients with bronchial asthma (BA). Examination of the ventilation lung function was performed by the method of pneumotachography according to the analysis of the «flow-volume¼ loop. End products of lipid peroxidation (LPO), reacting with thiobarbituric acid (malondialde- hyde), enzymes-antioxidants - catalase, superoxide dismutase, glutathione peroxidase, glutathione transferase were studied to determine the signs of oxidative stress. RESULTS: Examinations of ventilation lung function in children-residents of RCT without respiratory and pulmonary pathology showed no significant deviations of its parameters beyond the limits of physiological fluctuations; a decrease in bronchial patency at different levels of the bronchial tree was established in children with BA. An increased incidence of bronchial hyperreactivity was noted in both the patients with BA and those who did not have bronchopulmonary pathology. The absence of an increase in the content of LPO products (malondialdehyde) in blood serum of children-residents of RCT with increased activity of catalase and group of glutathione enzymes indi- cates the sufficiency of compensatory possibilities of antioxidant protection. CONCLUSIONS: Studies of correlation between the function of external respiration and markers of oxidative stress determined that the indices of bronchial patency directly correlate with the activity of enzymes-antioxidants of the glutathione group and inversely - with the content of the LPO products in children-residents of RCT. The frequency of bronchospasm inversely correlated with the activity of glutathione group antioxidants. There are inverse correla- tion of 137Cs content in the body with the activity of glutathione transferase and glutathione peroxidase.

M4-muscarinic acetylcholine receptor into the pedunculopontine tegmental nucleus mediates respiratory modulation of conscious rats.

The pedunculopontine tegmental nucleus (PPTg) has been shown to have important functions relevant to the regulation of behavioral states and various motor control systems, including breathing control. The PPTg is considered an important nucleus in the mesopontine region with considerably cholinergic input to the ventral respiratory column. In addition, recent studies indicate that cholinergic innervation of the ventral respiratory column may play an important role in modulation of breathing. Here, we investigated the cholinergic stimulation of the PPTg and the changes in breathing output in conscious rats. Male Wistar rats (280-350 g, N = 5-12/group) with unilateral stainless steel cannula implanted into the PPTg were used. Respiratory parameters (tidal volume (VT), respiratory frequency (fR) and ventilation (VE)) were analyzed by whole body plethysmography. In unrestrained awake rats, unilateral injection of the cholinergic muscarinic agonist carbachol (10 mM-100 nL) in the PPTg decreased fR, and increase VT, without changing VE. The changes in fR and VT elicited by carbachol into the PPTg are abolished by previous blockade of the M4 muscarinic cholinergic receptors tropicamide into the PPTg. No significant changes in fR and VT elicited by carbachol were observed after blockade of the M1 and/or M3 muscarinic cholinergic receptors pirenzepine or 4-DAMP into the PPTg. Our data suggest that the changes in fR and VT produced by muscarinic cholinergic stimulation of PPTg is presumably mediated through a Gi-coupled M4 muscarinic receptors.

The temporal sequence of improved mitochondrial function on the dynamics of respiration, mobility, and cognition in aged Drosophila.

Aging is associated with mitochondrial decline and reduced adenosine triphosphate (ATP) production leading to cellular dysfunction, but this is improved by long-wavelength light absorbed by cytochrome c oxidase, increasing cytochrome c oxidase activity, ATP production and improving metabolism, sensory motor function, and cognition. Yet, the sequence of these events is unknown. We give old flies a single 90-minute 670-nm pulse and measure temporal sequences of changes in respiration, ATP, motor, and cognitive ability. Respiration increased significantly 20 minutes after light initiation and remained elevated for 4 days. Measurable ATP increased at 1 hour, peaking at 3 hours, and then declined rapidly. Respiration improved before ATP increased, which indicates an early ATP sink. Flies explore environments stereotypically, which is lost with aging but is reestablished for 7 hours after light exposure. However, again, there are improvements before there are peaks in ATP production. Improved mobility and cognitive function persist after ATP levels return to normal. Hence, elevated ATP in age may initiate independent signaling mechanisms that result in improvements in aged metabolism and function.

IPW-5371 Proves Effective as a Radiation Countermeasure by Mitigating Radiation-Induced Late Effects.

There is an ongoing and significant need for radiation countermeasures to reduce morbidities and mortalities associated with exposure of the heart and lungs from a radiological or nuclear incidents. Radiation-induced late effects occur months to years after exposure, stemming from significant tissue damage and remodeling, resulting in fibrosis and loss of function. TGF-ß is reported to play a role in both pulmonary and cardiac fibrosis. We investigated the ability of a small molecule TGF-ß receptor 1 inhibitor, IPW-5371, to mitigate the effects of thoracic irradiation in C57L/J mice, a murine model that most closely resembles that observed in humans in the induction of fibrosis and dose response. To simulate a radiological event, radiation was administered in two doses: 5 Gy total-body irradiation (eliciting a whole-body response) and immediately after that, a thoracic "top-up" of 6.5 Gy irradiation, for a total dose of 11.5 Gy to the thorax. IPW-5371 was administered once daily, orally, starting 24 h postirradiation for 6 or 20 weeks at a dose of 10 mg/kg or 30 mg/kg. Animals were monitored for a period of 180 days for survival, and cardiopulmonary injury was assessed by echocardiography, breathing rate and arterial oxygen saturation. Exposure of the thorax (11.5 Gy) induced both pulmonary and cardiac injury, resulting in a reduced life span with median survival of 135 days. IPW-5371 treatment for 6 weeks, at both 10 mg/kg and 30 mg/kg, delayed disease onset and mortality, with median survival of 165 days. Twenty weeks of IPW-5371 treatment at 30 mg/kg preserved arterial O2 saturation and cardiac contractile reserve and resulted in significant decreases in breathing frequency and cardiac and pulmonary fibrosis. This led to dramatic improvement in survival compared to the irradiated, vehicle-treated group (P < 0.001), and was statistically insignificant from the nonirradiated group. We observed that IPW-5371 treatment resulted in decreased pSmad3 tissue levels, confirming the effect of IPW-5371 on TGF-ß signaling. These results demonstrate that IPW-5371 represents a potentially promising radiation countermeasure for the treatment of radiation-induced late effects.

Cerium Oxide Nanoparticles: A Potential Medical Countermeasure to Mitigate Radiation-Induced Lung Injury in CBA/J Mice.

Cerium oxide nanoparticles (CNPs) have a unique surface regenerative property and can efficiently control reactive oxygen/nitrogen species. To determine whether treatment with CNPs can mitigate the delayed effects of lung injury after acute radiation exposure, CBA/J mice were exposed to 15 Gy whole-thorax radiation. The animals were either treated with nanoparticles, CNP-18 and CNP-ME, delivered by intraperitoneal injection twice weekly for 4 weeks starting 2 h postirradiation or received radiation treatment alone. At the study's end point of 160 days, 90% of the irradiated mice treated with high-dose (10 µM) CNP-18 survived, compared to 10% of mice in the radiation-alone (P < 0.0001) and 30% in the low-dose (100 nM) CNP-18. Both low- and high-dose CNP-ME-treated irradiated mice showed increased survival rates of 40% compared to 10% in the radiation-alone group. Multiple lung functional parameters recorded by flow-ventilated whole-body plethysmography demonstrated that high-dose CNP-18 treatment had a significant radioprotective effect on lethal dose radiation-induced lung injury. Lung histology revealed a significant decrease (P < 0.0001) in structural damage and collagen deposition in mice treated with high-dose CNP-18 compared to the irradiated-alone mice. In addition, significant reductions in inflammatory response (P < 0.01) and vascular damage (P < 0.01) were observed in the high-dose CNP-18-treated group compared to irradiated-alone mice. Together, the findings from this preclinical efficacy study clearly demonstrate that CNPs have both clinically and histologically significant mitigating and protective effects on lethal dose radiation-induced lung injury.

Analysis of Long-Term 4-Dimensional Computed Tomography Regional Ventilation After Radiation Therapy.

PURPOSE: To determine whether regional ventilation, as measured using 4-dimensional computed tomography (4D-CT), declines after radiation therapy (RT). METHODS AND MATERIALS: We analyzed pretreatment 4D-CT scans associated with 2 RT courses. We quantified regional pulmonary function over equivalent dose in 2 Gy (EQD2α/ß=3) intervals of 0 to 5 Gy, 5 to 20 Gy, 20 to 40 Gy, and >40 Gy using percentile-normalized intensity-based (VentInt) and Jacobian-based (VentJac) ventilation metrics. We modeled the impact of dose on mean ventilation (Vent¯) and regional tidal volume (rTV: tidal volume [TV] within a dose interval normalized to total lung TV). We also identified clinical and dosimetric factors that affected regional ventilation changes (ΔVent¯ and ΔrTV) after RT for the >20 Gy dose interval. RESULTS: After RT, Vent¯Int exhibited statistically significant dose-dependent declines within the 20 to 40 Gy (-5.0%; P=.03) and >40 Gy (-6.8%; P<.01) intervals. Vent¯Jac exhibited a declining trend after RT only for the >40 Gy interval (-4.6%; P=.07). Factors associated with ΔVent¯Int for the >20 Gy dose interval included airway stenosis progression (P=.03) and gross tumor volume (P=.09). Both rTVInt and rTVJac were associated with small (<2%) but significant declines after RT for 20 to 40 Gy and >40 Gy intervals. Factors associated with declining rTVInt (P<.05) for the >20 Gy dose interval included airway stenosis progression, greater V20 (volume of lung receiving >20 Gy), and smaller fraction of emphysema in V20. The association between the absence of chronic obstructive pulmonary disease and declining rTV trended toward significance (P=.09). CONCLUSIONS: Regional ventilation, as measured using 4D-CT, demonstrates a dose-dependent decline after RT. Our results support the use of 4D-CT ventilation imaging for monitoring regional pulmonary function change after RT.

Respiratory Motion, Anterior Heart Displacement and Heart Dosimetry: Comparison Between Prone (Pr) and Supine (Su) Whole Breast Irradiation.

To analyze respiratory motion of surgical clips, chest wall (CW) and the anterior displacement of the heart and its impact on heart dosimetry between prone (Pr) and supine (Su) positions during whole breast radiotherapy after breast conserving surgery. Sixteen patients underwent 4D-CT for radiotherapy planning in Pr and Su positions. Maximum inhale and maximum exhale phases were analyzed. Mean 3D vectorial displacements ± standard deviations (SD) of the surgical clips were measured. Volumetric changes of the CW were recorded and compared. Cardiac displacement was assessed by a volume between the inner surface of CW and the myocardium of the heart (CW/H-V). For left-sided cases, comparative dosimetry was performed in each position simulating no- (Pr-noC, Su-noC) versus daily correction protocols (Pr-C, Su-C). The movements of 81 surgical clips were analyzed. Prone positioning significantly reduced both the mean 3D vectorial displacements (1.1 ± 0.6 (Pr) vs. 2.0 ± 0.9 mm (Su), p < 0.01) and their variability (0.3 ± 0.2 vs. 0.5 ± 0.3 mm, p = 0.01). Respiration-induced volumetric changes of CW were also significantly lower in Pr (2.3 ± 4.9 vs. 9.6 ± 7.1 cm(3), p < 0.01). The CW/H-V was significantly smaller in Pr than in Su (39.9 ± 14.6 vs. 64.3 ± 28.2 cm(3), p < 0.01). Besides identical target coverage heart, left-anterior-descending coronary artery (LADCA) and ipsilateral lung dose parameters were lowered with Pr-C compared to Pr-noC, Su-C and Su-noC. Prone position significantly reduced respiration-related surgical clip movements, their variability as well as CW movements. Significant anterior heart displacement was observed in Pr. Prone position with daily online correction could maximize the heart and LADCA protection.

Light respiratory processes and gross photosynthesis in two scleractinian corals.

The light dependency of respiratory activity of two scleractinian corals was examined using O2 microsensors and CO2 exchange measurements. Light respiration increased strongly but asymptotically with elevated irradiance in both species. Light respiration in Pocillopora damicornis was higher than in Pavona decussata under low irradiance, indicating species-specific differences in light-dependent metabolic processes. Overall, the coral P. decussata exhibited higher CO2 uptake rates than P. damicornis over the experimental irradiance range. P. decussata also harboured twice as many algal symbionts and higher total protein biomass compared to P. damicornis, possibly resulting in self-shading of the symbionts and/or changes in host tissue specific light distribution. Differences in light respiration and CO2 availability could be due to host-specific characteristics that modulate the symbiont microenvironment, its photosynthesis, and hence the overall performance of the coral holobiont.

Effects of short-term radiation emitted by WCDMA mobile phones on teenagers and adults.

BACKGROUND: With the rapid increasing use of third generation (3 G) mobile phones, social concerns have arisen concerning the possible health effects of radio frequency-electromagnetic fields (RF-EMFs) emitted by wideband code division multiple access (WCDMA) mobile phones in humans. The number of people, who complain of various symptoms such as headache, dizziness, and fatigue, has also increased. Recently, the importance of researches on teenagers has been on the rise. However, very few provocation studies have examined the health effects of WCDMA mobile phone radiation on teenagers. METHODS: In this double-blind study, two volunteer groups of 26 adults and 26 teenagers were simultaneously investigated by measuring physiological changes in heart rate, respiration rate, and heart rate variability for autonomic nervous system (ANS), eight subjective symptoms, and perception of RF-EMFs during sham and real exposure sessions to verify its effects on adults and teenagers. Experiments were conducted using a dummy phone containing a WCDMA module (average power, 250 mW at 1950 MHz; specific absorption rate, 1.57 W/kg) within a headset placed on the head for 32 min. RESULTS: Short-term WCDMA RF-EMFs generated no significant changes in ANS, subjective symptoms or the percentages of those who believed they were being exposed in either group. CONCLUSIONS: Considering the analyzed physiological data, the subjective symptoms surveyed, and the percentages of those who believed they were being exposed, 32 min of RF radiation emitted by WCDMA mobile phones demonstrated no effects in either adult or teenager subjects.

The delayed pulmonary syndrome following acute high-dose irradiation: a rhesus macaque model.

Several radiation dose- and time-dependent tissue sequelae develop following acute high-dose radiation exposure. One of the recognized delayed effects of such exposures is lung injury, characterized by respiratory failure as a result of pneumonitis that may subsequently develop into lung fibrosis. Since this pulmonary subsyndrome may be associated with high morbidity and mortality, comprehensive treatment following high-dose irradiation will ideally include treatments that mitigate both the acute hematologic and gastrointestinal subsyndromes as well as the delayed pulmonary syndrome. Currently, there are no drugs approved by the Food and Drug Administration to counteract the effects of acute radiation exposure. Moreover, there are no relevant large animal models of radiation-induced lung injury that permit efficacy testing of new generation medical countermeasures in combination with medical management protocols under the FDA animal rule criteria. Herein is described a nonhuman primate model of delayed lung injury resulting from whole thorax lung irradiation. Rhesus macaques were exposed to 6 MV photon radiation over a dose range of 9.0-12.0 Gy and medical management administered according to a standardized treatment protocol. The primary endpoint was all-cause mortality at 180 d. A comparative multiparameter analysis is provided, focusing on the lethal dose response relationship characterized by a lethal dose50/180 of 10.27 Gy [9.88, 10.66] and slope of 1.112 probits per linear dose. Latency, incidence, and severity of lung injury were evaluated through clinical and radiographic parameters including respiratory rate, saturation of peripheral oxygen, corticosteroid requirements, and serial computed tomography. Gross anatomical and histological analyses were performed to assess radiation-induced injury. The model defines the dose response relationship and time course of the delayed pulmonary sequelae and consequent morbidity and mortality. Therefore, it may provide an effective platform for the efficacy testing of candidate medical countermeasures against the delayed pulmonary syndrome.

A pilot study in rhesus macaques to assess the treatment efficacy of a small molecular weight catalytic metalloporphyrin antioxidant (AEOL 10150) in mitigating radiation-induced lung damage.

The objective of this pilot study was to explore whether administration of a catalytic antioxidant, AEOL 10150 (C48H56C15MnN12), could reduce radiation-induced lung injury and improve overall survival when administered after 11.5 Gy of whole thorax lung irradiation in a non-human primate model. Thirteen animals were irradiated with a single exposure of 11.5 Gy, prescribed to midplane, and delivered with 6 MV photons at a dose rate of 0.8 Gy min. Beginning at 24 h post irradiation, the AEOL 10150 cohort (n = 7) received daily subcutaneous injections of the catalytic antioxidant at a concentration of 5 mg kg for a total of 4 wk. All animals received medical management, including dexamethasone, based on clinical signs during the planned 180-d in-life phase of the study. All decedent study animals were euthanized for failure to maintain saturation of peripheral oxygen > 88% on room air. Exposure of the whole thorax to 11.5 Gy resulted in radiation-induced lung injury in all animals. AEOL 10150, as administered in this pilot study, demonstrated potential efficacy as a mitigator against fatal radiation-induced lung injury. Treatment with the drug resulted in 28.6% survival following exposure to a radiation dose that proved to be 100% fatal in the control cohort (n = 6). Computed tomography scans demonstrated less quantitative radiographic injury (pneumonitis, fibrosis, effusions) in the AEOL 10150-treated cohort at day 60 post-exposure, and AEOL 10150-treated animals required less dexamethasone support during the in-life phase of the study. Analysis of serial plasma samples suggested that AEOL 10150 treatment led to lower relative transforming growth factor-Beta-1 levels when compared with the control animals. The results of this pilot study demonstrate that treatment with AEOL 10150 results in reduced clinical, radiographic, anatomic, and molecular evidence of radiation-induced lung injury and merits further study as a medical countermeasure against radiation-induced pulmonary injury.

[Morphologic changes in mice trachea, bronchi and lungs after prolonged combined radiation and inhaled chemical exposure].

Investigations of morphology and morphometry of the breathing organs (trachea, bronchi and lungs) and immunogenesis of mice subject to a combined sequential exposure to fractionated external γ-irradiation by the total dose of 350 cGy and a mix of acetone, ethanol and acetaldehyde in MPCs for piloted spacecrafts simulating the estimated levels in crewed exploration missions were conducted. Morphologic changes in the breathing organs of animals after space missions point to immunogenesis activation and appearance of a "structural trace" as a chronic inflammation with the growth of fibrous connective tissue in tracheal, bronchial and lung walls, increase in volume fractions of glands and vessels and reduction in loose fibrous connective tissue. Formation of the fibrous connective tissue was particularly noticeable in respiratory parts of the breathing organs suggesting a high risk of long-term adverse effects.

Reduced lung dose and improved inspiration level reproducibility in visually guided DIBH compared to audio coached EIG radiotherapy for breast cancer patients.

INTRODUCTION: Patients with left-sided breast cancer with lymph node involvement have routinely been treated with enhanced inspiration gating (EIG) for a decade at our institution. In a transition from EIG to deep inspiration breath hold (DIBH) we compared the two techniques with focus on target coverage, dose to organs at risk and reproducibility of the inspiration level (IL). MATERIAL AND METHODS: Twenty-four patients were computed tomography (CT) scanned with EIG and DIBH. For DIBH we used visual feedback and for EIG audio coaching, both during scan and treatment. Treatment plans for 50 Gy over 25 fractions were calculated. Seventeen of the patients were included in the analysis of reproducibility. They were audio coached for one minute before beam-on in DIBH at nine treatment sessions. These respiration curves were analysed with average maximum IL and standard deviation (SD) for the EIG part of the respiratory signal, and mean IL and SD for the DIBH. Comparison of dosimetric and respiration parameters were performed with the Wilcoxon signed rank-sum test. RESULTS: In DIBH, the ipsilateral lung volume increased further compared to EIG (p < 0.0004, mean increase 11%). This lead to a 9% mean reduction (p = 0.002) of the ipsilateral lung volume receiving 20 Gy (V20 Gy). We found no other significant dosimetric differences between the two methods. The reproducibility of the IL was better with the DIBH method, observed as a significantly smaller SD in most patients (p < 0.04 for 16 of 17 patients). CONCLUSION: The DIBH method resulted in a significantly larger lung volume and lower ipsilateral lung V20 Gy compared to EIG. The IL for visually guided DIBH was more reproducible than audio-coached EIG. Based on these findings, the DIBH technique is our new breathing adaptation standard for radiotherapy of patients with left-sided breast cancer with lymph node involvement.

Does low intensity laser therapy reduce pain and change orofacial myofunctional conditions?

Due to its multifactorial pain aspects, combined therapies are required for the the comprehensive management of temporomandibular joint disorders (TMD). Interdisciplinary forms of therapies, such as laser therapy, and health care or medical professionals, such as speech therapists, have been proposed for this comprehensive management. The aims of this study were the following: 1. verify whether low-intensity laser therapy would promote significant pain remission; 2. evaluate whether this changes orofacial myofunctional conditions in the sample, as tested, using the Orofacial Myofunctional Evaluation with Scores (OMES); and 3. evaluate whether or not the pain improvement would remain stable after a 30-day follow-up for pain conditions. The study included 12 female volunteers diagnosed with myofascial pain and ages ranging from 18 to 60 years old, with or without intra-articular TMD, according to axis I of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Participants were assessed for pain on palpation, using a visual analogue scale (VAS), before treatment (A1), immediately after 30 days of intervention, i.e, after eight sessions of Low Intensity Laser Therapy (LILT) (A2), and 30 days after the end of the treatment with LILT (A3) (follow-up). Comparing the three evaluation times, it was observed that there was a significant decrease in the values of subjective pain to palpation (p < 0.05). The initial pain (A1) differed significantly from the A2, but did not differ significantly from A3.

Dose-dependent histological alterations in the rat lung following intravenous application of Re-188-labeled microspheres.

PURPOSE: The objective of this study was to determine the dose-effect correlation of pneumopathy after application of Rhenium-188 microspheres (Re-188 MS) in an animal model using histological changes as an end-point. METHODS AND MATERIALS: Wistar rats received an intravenous injection of Re-188 MS yielding doses that ranged from ˜ 2 to ˜ 55 Gy. Lungs were removed after ˜ 25 weeks and prepared for histology. Sections were evaluated using a semi-quantitative 5-tiered score. Dose groups of 10 Gy intervals were statistically analyzed using the Chi-square test with respect to grade and extent of connective tissue accumulation, thickness of vessel walls and accumulation of alveolar macrophages (AM). RESULTS: There was a statistically significant increase in connective tissue content and extent in all dose groups compared to control lungs and at least between each other dose group. The steepest increase in connective tissue was at doses higher than 40 Gy. Starting from that dose, a statistically significant increase of AM accumulation and vessel wall thickness occurred. CONCLUSIONS: There was a clear dose-effect correlation between radiation dose and histological changes. These findings allow an estimation of potential normal tissue damage especially during tumor treatments of liver lesions with radioactive particles in patients with significant liver-to-lung shunts.

Determination and maintenance of DE minimis risk for migration of residual tritium (3H) from the 1969 Project Rulison nuclear test to nearby hydraulically fractured natural gas wells.

The Project Rulison underground nuclear test was a proof-of-concept experiment that was conducted under the Plowshare Program in 1969 in the Williams Fork Formation of the Piceance Basin in west-central Colorado. Today, commercial production of natural gas is possible from low permeability, natural gas bearing formations like that of the Williams Fork Formation using modern hydraulic fracturing techniques. With natural gas exploration and production active in the Project Rulison area, this human health risk assessment was performed in order to add a human health perspective for site stewardship. Tritium (H) is the radionuclide of concern with respect to potential induced migration from the test cavity leading to subsequent exposure during gas-flaring activities. This analysis assumes gas flaring would occur for up to 30 d and produce atmospheric H activity concentrations either as low as 2.2 × 10 Bq m (6 × 10 pCi m) from the minimum detectable activity concentration in produced water or as high as 20.7 Bq m (560 pCi m), which equals the highest atmospheric measurement reported during gas-flaring operations conducted at the time of Project Rulison. The lifetime morbidity (fatal and nonfatal) cancer risks calculated for adults (residents and workers) and children (residents) from inhalation and dermal exposures to such activity concentrations are all below 1 × 10 and considered de minimis. The implications for monitoring production water for conforming health-protective, risk-based action levels also are examined.

Mitigation of radiation-induced lung injury with EUK-207 and genistein: effects in adolescent rats.

Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50-100%), levels of TGF-ß1 expression (75-100%), activated macrophages (20-60%) and fibrosis (60-80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (∼37% in adolescents vs. ∼10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater.

Dose-modifying factor for captopril for mitigation of radiation injury to normal lung.

Our goal is to develop countermeasures for pulmonary injury following unpredictable events such as radiological terrorism or nuclear accidents. We have previously demonstrated that captopril, an angiotensin converting enzyme (ACE) inhibitor, is more effective than losartan, an angiotensin type-1 receptor blocker, in mitigating radiation-pneumopathy in a relevant rodent model. In the current study we determined the dose modifying factors (DMFs) of captopril for mitigation of parameters of radiation pneumonitis. We used a whole animal model, irradiating 9-10-week-old female rats derived from a Wistar strain (WAG/RijCmcr) with a single dose of irradiation to the thorax of 11, 12, 13, 14 or 15 Gy. Our study develops methodology to measure DMFs for morbidity (survival) as well as physiological endpoints such as lung function, taking into account attrition due to lethal radiation-induced pneumonitis. Captopril delivered in drinking water (140-180 mg/m(2)/day, comparable with that given clinically) and started one week after irradiation has a DMF of 1.07-1.17 for morbidity up to 80 days (survival) and 1.21-1.35 for tachypnea at 42 days (at the peak of pneumonitis) after a single dose of ionizing radiation (X-rays). These encouraging results advance our goals, since DMF measurements are essential for drug labeling and comparison with other mitigators.