STATE OF COGNITIVE FUNCTIONS IN CHILDREN WITH PATHOLOGY OF DIGESTIVE ORGANS, WHO LIVE AT RADIOACTIVE CONTAMINATED TERRITORIES OF UKRAINE. / STAN KOGNITYVNYKh FUNKTsIY̆ U DITEY̆ Z PATOLOGIIeIu ORGANIV TRAVLENNIa, IaKI PROZhYVAIuT' NA RADIOAKTYVNO ZABRUDNENYKh TERYTORIIaKh UKRAÏNY.

OBJECTIVE: to study the state of cognitive functions in children who were born and permanently live at radioactive contaminated territories (RCT) with pathology of the upper digestive tract, using pathopsychological testing; to increase the effectiveness of treatment and prophylactic measures aimed at preserving and restoring the health of RCT residents. DESIGN, PATIENTS AND METHODS: A randomized blind controlled clinical trial was conducted. There were examined, a total of 90 persons aged 6 to 17 years (35 boys and 55 girls) who were divided into two groups: the control group (I) included 30 persons of the conventional «clean¼ territories, and the main group (II) - 60 patients with patho- logy of the digestive organs who were born and live at the RCT. The study program included: the collection of anam- nesis, complaints; clinical and instrumental examinations. The following tests were applied by us: «What things are hidden in the drawings¼, Toulouse-Pieron, Raven, and Luria testing. For detecting the anxiety level, and the subjec- tive signs of autonomic dysfunctions were used the Spilberg-Hanin self-diagnosis and the Wein questionnaire, respectively. RESULTS: It was shown that in children aged 6-11 years, according to the results of the Toulouse-Pieron test, speed of cognitive information-processing was significantly decreased by 7.17 conventional units, while on the back- ground of the etiopathogenetic treatment of the digestive tract - by 10.24 conventional units relative to the va- lues of the control group. The long-term memory was statistically significantly decreased in the examined children of senior school age (from 12 to 17 years). A significant increase in reactive anxiety and a reverse correlation between the personal anxiety (PA) and speed of cognitive information-processing (r = -0.331) were recorded in patients aged 6-11 years. In older patients, PA was increased.Сonclusions. The obtained results indicate that the state of cognitive functions was characterized by a decrease in speed of cognitive information-processing, long-term memory and a high level of anxiety in children aged from 6 to 17 years residents of RСT with pathology of digestive organs, according to the used testing.

The Influence of Aerosol Density and Shape Factor on the Assessment of Internal Exposure to 239Pu.

Internal exposure due to inhalation of aerosols depends on the ratio of aerodynamic shape factor (χ) to aerosol mass density (ρ). Inhaled aerosol parameters may differ from the default ρ and χ values provided by the International Commission on Radiological Protection, which are adopted for the assessment of internal exposures. This paper focuses on the influences of χ/ρ on the assessment of internal exposure to Pu for reference workers. Regional deposition fractions are found to decrease with increasing χ/ρ, and larger decreases are observed with smaller activity median aerodynamic diameter aerosols, while the slow clearance fractions (fs) in the tracheobronchial region are more sensitive for larger activity median aerodynamic diameter aerosols. Results from biokinetics calculations reveal that both the time-dependent content (excretion) and cumulative activities are determined mainly for particles initially deposited in the alveolar-interstitial region, while fs affects the local cumulative activities in the tracheobronchial region. χ/ρ is proven to have different influences for aerosols with different activity median aerodynamic diameters. The default χ/ρ values can be used when activity median aerodynamic diameters are greater than 1 µm, while one should pay attention to the value of χ/ρ when activity median aerodynamic diameters are less than 1 µm, where significant influence may be anticipated.

Internal Dose Assessment after 131I-Iodide Misadministration in a Patient With Incompletely Blocked Thyroid Uptake: Personalized Internal Dose Assessment by Estimating Individual-Specific Biokinetics.

In July 2017, a medical accident occurred in South Korea, in which I-iodide solution was misadministered to the wrong patient. Although the International Commission on Radiological Protection provided internal dose coefficients for iodine for blocked thyroid, they were not reliable enough for determining the dose to the patient (whose thyroid uptake was incompletely blocked) due to a discrepancy in biokinetics. Therefore, a personalized dose assessment was performed to derive the individual-specific dose coefficients for the patient. Initially, the thyroid biokinetics of the patient were statistically clarified by fitting bioassay monitoring results and the corresponding predicted bioassay values, which were calculated repeatedly for varying iodine transfer rates in an iodine biokinetic model. After determining the transfer rate for the patient, the individual-specific dose coefficients were then calculated in accordance with latest recommendations of the International Commission on Radiological Protection. According to the individual-specific biokinetics, the 24 h thyroid uptake fraction of iodine was estimated as 0.52%. The thyroid absorbed dose of the patient was evaluated as 21.2 Gy, which differed greatly (by about 9 Gy) from the dose evaluated simply using the reference data for blocked thyroid uptake. The personalized dose assessment carried out for the patient not only reduced considerable uncertainties in the internal dose calculation, but also improved the reliability of the calculated internal dose by adopting the latest dosimetric data, including specific absorbed fraction values based on voxel phantoms. Through the dose assessment of the patient, the methodology of personalized dose assessment considering individual-specific biokinetics was developed.

Early Toxicity of a Phase 2 Trial of Combined Salvage Radiation Therapy and Hormone Therapy in Oligometastatic Pelvic Node Relapses of Prostate Cancer (OLIGOPELVIS GETUG P07).

PURPOSE: Limited pelvic nodal relapse of prostatic cancer is a paramount challenge for locoregional salvage treatments. Salvage whole pelvis radiation therapy as considered in the BLINDED trial is an attractive option, but there are concerns about its toxicity. This article describes early toxicity with the technique. METHODS AND MATERIALS: BLINDED was a prospective multicenter phase 2 trial investigating high-dose salvage pelvic irradiation with an additional dose to the fluorocholine-based positron emission tomography-positive pelvic lymph nodes, combined with 6-month androgen blockade. The prescribed dose was 54 Gy in 1.8 Gy fractions with up to 66 Gy in 2.2 Gy fractions to the pathologic pelvic lymph nodes. Early toxicity was defined as toxicity until 1 year after radiation therapy. Patients quality of life was assessed using the European Organisation for Research and Treatment of Cancer questionnaires (QLQ-C30 and QLQ-PR25). RESULTS: Seventy-four patients were recruited in 15 French radiation oncology departments between August 2014 and July 2016. Seven were excluded before treatment because of violation of the inclusion criteria. The intention-to-treat analysis therefore included 67 patients. Half had received prior prostatic irradiation. Median age was 67.7 ± 6.5 years. Grade 2 acute urinary toxicity was observed in 9 of 67 patients (13.4%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Three patients (4.4%) had grade 3 urinary toxicity. Grade 2 acute digestive toxicity was observed in 10 of 67 patients (14.9%), and grade 2 1-year toxicity occurred in 4 of 67 patients (6%). Patients with prior prostate bed irradiation did not exhibit increased urinary or digestive toxicity. The European Organisation for Research and Treatment of Cancer questionnaire scores at 1 year did not worsen significantly. CONCLUSIONS: The acute and 1-year toxicity of the BLINDED protocol was satisfactory, even in patients with a history of prostatic irradiation.

Proton therapy for hepatocellular carcinoma: Current knowledges and future perspectives.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, as few patients can be treated with currently available curative local modalities. In patients with HCC where curative modalities are not feasible, radiation therapy (RT) has emerged as an alternative or combination therapy. With the development of various technologies, RT has been increasingly used for the management of HCC. Among these advances, proton beam therapy (PBT) has several unique physical properties that give it a finite range in a distal direction, and thus no exit dose along the beam path. Therefore, PBT has dosimetric advantages compared with X-ray therapy for the treatment of HCC. Indeed, various reports in the literature have described the favorable clinical outcomes and improved safety of PBT for HCC patients compared with X-ray therapy. However, there are some technical issues regarding the use of PBT in HCC, including uncertainty of organ motion and inaccuracy during calculation of tissue density and beam range, all of which may reduce the robustness of a PBT treatment plan. In this review, we discuss the physical properties, current clinical data, technical issues, and future perspectives on PBT for the treatment of HCC.

Management and survival analysis of elderly patients with a cancer in the digestive system who refused to receive anticancer treatments.

Treatment and management of cancers in elderly patients require some special considerations. A better understanding of how cancers progress in those elderly patients who have not received any anticancer treatments could better help us in treating these patients and in making end-of-life decisions. Over the past years, we had encountered 57 elderly patients, aged 75 to 94 years (87.6 on average), with a cancer in the digestive system, who refused to accept anticancer treatment but who did receive the best available supportive and palliative care. Clinicopathological data of these patients were analyzed. Of these 57 cases, 49 were at an advanced or late stage, while the remaining eight were at an early stage at the time of diagnosis. The median overall survival time of all the patients was 11 months, and almost the entire cohort manifested multiple-organ impairments. The average number of malfunctioning organs per patient was 3.68. After carefully predicting, and then preventing or managing complications, only 54.4% of the patients eventually died of multiple-organ functional failure. Nearly 18% of the single organ dysfunctions were finally well-controlled. Our data provide the first statistical information on the survival time and the direct cause of death of the elderly patients with a cancer in the digestive system not treated with chemotherapy or other direct anticancer interventions, but who did receive the best available supportive and palliative cares. During their struggle with cancer, elderly patients clearly could benefit from prophylactic interventions on organ dysfunction.

Inclusion of thin target and source regions in alimentary and respiratory tract systems of mesh-type ICRP adult reference phantoms.

It is not feasible to define very small or complex organs and tissues in the current voxel-type adult reference computational phantoms of the International Commission on Radiological Protection (ICRP), which limit dose coefficients for weakly penetrating radiations. To address the problem, the ICRP is converting the voxel-type reference phantoms into mesh-type phantoms. In the present study, as a part of the conversion project, the micrometer-thick target and source regions in the alimentary and respiratory tract systems as described in ICRP Publications 100 and 66 were included in the mesh-type ICRP reference adult male and female phantoms. In addition, realistic lung airway models were simulated to represent the bronchial (BB) and bronchiolar (bb) regions. The electron specific absorbed fraction (SAF) values for the alimentary and respiratory tract systems were then calculated and compared with the values calculated with the stylized models of ICRP Publications 100 and 66. The comparisons show generally good agreement for the oral cavity, oesophagus, and BB, whereas for the stomach, small intestine, large intestine, extrathoracic region, and bb, there are some differences (e.g. up to ~9 times in the large intestine). The difference is mainly due to anatomical difference in these organs between the realistic mesh-type phantoms and the simplified stylized models. The new alimentary and respiratory tract models in the mesh-type ICRP reference phantoms preserve the topology and dimensions of the voxel-type ICRP phantoms and provide more reliable SAF values than the simplified models adopted in previous ICRP Publications.

[Towards an improvement of the quality of life after radiotherapy in children]. / Vers une amélioration de la qualité de vie après une radiothérapie réalisée dans l'enfance.

Pediatric radiotherapy did not differ technically from adult radiotherapy but its characteristics, its difficulties and challenges are specific. Thanks in part to this treatment, overall survival of French children with cancer is around 80%. It is therefore important to integrate in the elaboration of the treatment planning potential side long-term effects. Indeed, whatever the technique is, even the most sophisticated, it is usually inevitable that healthy nearby organs receive a dose of radiation. Dose limits on organs at risk come from adult data and are adapted for children. After the treatment, it is important to graduate the potential risks of side effects to propose a personalized monitoring protocol avoiding excessive medicalization. This article presents the medical thinking concerning radiotherapy in different anatomical areas (brain, head and neck, chest, abdomen) including concepts of dose level corresponding to side effects usually described. In parallel, we present follow-up recommendations with the aim to preserve an optimal quality of life for the adults cured of a childhood cancer, currently called survivors.

Identification of motor neurons and a mechanosensitive sensory neuron in the defecation circuitry of Drosophila larvae.

Defecation allows the body to eliminate waste, an essential step in food processing for animal survival. In contrast to the extensive studies of feeding, its obligate counterpart, defecation, has received much less attention until recently. In this study, we report our characterizations of the defecation behavior of Drosophila larvae and its neural basis. Drosophila larvae display defecation cycles of stereotypic frequency, involving sequential contraction of hindgut and anal sphincter. The defecation behavior requires two groups of motor neurons that innervate hindgut and anal sphincter, respectively, and can excite gut muscles directly. These two groups of motor neurons fire sequentially with the same periodicity as the defecation behavior, as revealed by in vivo Ca(2+) imaging. Moreover, we identified a single mechanosensitive sensory neuron that innervates the anal slit and senses the opening of the intestine terminus. This anus sensory neuron relies on the TRP channel NOMPC but not on INACTIVE, NANCHUNG, or PIEZO for mechanotransduction.

An internal radiation dosimetry computer program, IDAC 2.0, for estimation of patient doses from radiopharmaceuticals.

The internal dosimetry computer program internal dose assessment by computer (IDAC) for calculations of absorbed doses to organs and tissues as well as effective doses to patients from examinations with radiopharmaceuticals has been developed. The new version, IDAC2.0, incorporates the International Commission on Radiation Protection (ICRP)/ICRU computational adult male and female voxel phantoms and decay data from the ICRP publication 107. Instead of only 25 source and target regions, calculation can now be made with 63 source regions to 73 target regions. The major advantage of having the new phantom is that the calculations of the effective doses can be made with the latest tissue weighting factors of ICRP publication 103. IDAC2.0 uses the ICRP human alimentary tract (HAT) model for orally administrated activity and for excretion through the gastrointestinal tract and effective doses have been recalculated for radiopharmaceuticals that are orally administered. The results of the program are consistent with published data using the same specific absorption fractions and also compared with published data from the same computational phantoms but with segmentation of organs leading to another set of specific absorption fractions. The effective dose is recalculated for all the 34 radiopharmaceuticals that are administered orally and has been published by the ICRP. Using the new HAT model, new tissue weighting factors and the new adult computational voxel phantoms lead to an average effective dose of half of its earlier estimated value. The reduction mainly depends on electron transport simulations to walled organs and the transition from the stylised phantom with unrealistic interorgan distances to more realistic voxel phantoms.

Assessing the reliability of dose coefficients for ingestion and inhalation of 226Ra and 90Sr by members of the public.

Assessments of risk to a population group resulting from internal exposure to a particular radionuclide can be used to assess the reliability of the appropriate International Commission on Radiological Protection (ICRP) dose coefficient, E(50), used as a radiation protection device for the specified exposure pathway. An estimate of the uncertainty on the risk is important for informing judgements on reliability. This paper describes the application of parameter uncertainty analysis to quantify uncertainties resulting from internal exposures to radioisotopes of the alkaline earth metals, (90)Sr and (226)Ra, by members of the UK public. The study derives uncertainties in biokinetic model parameter values to calculate the distributions of the effective dose per unit intake using the ICRP Publication 60 formalism. The distributions are used to infer the uncertainty on the mean effective dose per unit intake to inform the derivation of uncertainty factors (UF) for the appropriate ICRP Publication 72 dose coefficients. Here, a UF indicates a 95 % probability that the best estimate of risk per unit intake is within a factor, UF, of the nominal risk associated with the appropriate ICRP dose coefficient, E(50), with respect to uncertainties in the biokinetic model parameter values. Ingestion: it is assumed that exposure occurs through the ingestion of radionuclides present in food and water. The results for both radionuclides suggest a UF of within 3 for all age groups, with median values close to the ICRP values. Inhalation: it is assumed that environmental exposure to radium occurs primarily due to insoluble forms present in fly ash discharged from coal-fired power stations; for strontium, exposure is assumed to occur due to residual aerosols produced as a result of atmospheric nuclear testing and nuclear reactor accidents. The results suggest a UF of around 3 and 6 for inhalation of (90)Sr and (226)Ra, respectively, by members of the public.

[Five-year results of IMRT for prostate cancer - toxicity]. / Petileté výsledky IMRT karcinomu prostaty - toxicita.

BACKGROUND: Intensity modulated radiotherapy (IMRT) plays a crucial role in the treatment of prostate cancer thanks to its capacity for healthy tissue sparing. This work reports on the acute and late toxicity rates among 233 patients treated with high-dose IMRT. MATERIAL AND METHODS: From June 2003 to December 2007, 233 men with clinically localized prostate cancer underwent radical radiotherapy. One hundred sixty patients were treated with IMRT to the prostate and the base of seminal vesicles to 78 Gy in 39 fractions, 73 patients underwent simultaneous integrated boost. Prescribed doses were 82 Gy and 73,8 Gy in 41 fractions to the prostate and seminal vesicles, respectively. Late toxicity was evaluated prospectively using a RTOG/FC-LENT score. RESULTS: Thirty patients (12.8%) experienced acute Grade 2 gastrointestinal (GI) toxicity. No acute Grade 3 or 4 GI toxicity developed. Forty two patients (18.1%) experienced acute Grade 2 genitourinary toxicity and 23 patients (9.9%) had Grade 3 GU toxicity. Grade 4 Genitourinary toxicity was observed in nine (3.8%) patients, due to a need of short-term urinary catheterization. With a median follow-up of 49.2 months, the estimated 5-year cumulative incidence of Grade 2 gastrointestinal toxicity was 22.4%. The estimated 5-year cumulative incidence of Grade 2 genitourinary toxicity was 17.7%. CONCLUSION: Intensity modulated radiotherapy enables dose escalation to 78-82 Gy with an acceptable toxicity.

Virus, protozoa and organic compounds decay in depurated oysters.

AIMS: (1) Evaluate the dynamic of the depuration process of Crassostrea gigas oysters using different ultraviolet doses with different amounts of contaminants (virus, protozoa and organic contaminants) and (2) investigate the morphological changes in the oysters' tissues produced by the depuration procedures. METHODS: The oysters were allocated in sites with different degrees of contamination and analyzed after 14 days. Some animals were used as positive controls by artificial bioaccumulation with HAdV2 and MNV1 and subjected to depuration assays using UV lamps (18 or 36 W) for 168 h. The following pollutants were researched in the naturally contaminated oysters, oysters after 14 days in sites and oysters during the depuration processes: virus (HAdV, HAV, HuNoV GI/GII and JCPyV), by (RT) qPCR; protozoa (Cryptosporidium and Giardia species), by immunomagnetic separation and immunofluorescence; and organic compounds (AHs, PAHs, LABs, PCBs and organochlorine pesticides-OCs), by chromatography. Changes in the oysters' tissues produced by the depuration processes were also evaluated using histochemical analysis by light microscopy. In the artificially bioaccumulated oysters, only HAdV2 and MNV1 were investigated by (RT) qPCR before the depuration procedures and after 96 and 168 h of these procedures. RESULTS: At 14 days post-allocation, HAdV was found in all the sites (6.2 × 105 to 4.4 × 107 GC g(-1)), and Giardia species in only one site. Levels of PCBs and OCs in the oyster's tissues were below the detection limit for all samples. AHs (3.5 to 4.4 µg g(-1)), PAHs (11 to 191 ng g(-1)) and LABs (57 to 751 ng g(-1)) were detected in the samples from 3 sites. During the depuration assays, we found HAdV, Giardia and Cryptosporidium species until 168 h, independent of UV treatment. AHs, PAHs and LABs were found also after 168 h of depuration (36 W and without UV lamp). The depuration procedures did not produce changes in the oysters' tissues. In the artificially contaminated and depurated oysters, we detected HAdV until 168 h and MNV1 until 96 h of depuration. CONCLUSION: The applied depuration treatments were unable to eliminate the protozoa or to degrade the HAdV genomes but were able to degrade the MNV1 genomes. Similarly, the UV water treatment was not efficient for aliphatic hydrocarbons, PAHs and LABs, as their concentrations were equivalent or higher to the concentrations of the control samples and samples from depuration tanks without UV treatment.

Biokinetic analysis code development and applications to visualise the distribution of intake activity.

Measurements for internal dose assessment are required to be conducted based on the distribution of radionuclides in the body, which may change depending on the lapsed time. In this study, a biokinetic analysis code, which can be used in practical radiation control is developed, and the results of (60)Co and (137)Cs biokinetics are visualised as examples by drawing the depositions for each organ and tissue in a figure of the body as a function of lapsed time. In addition, based on visualised biokinetics, precautions for in vivo measurements are also discussed. These discussions led to the conclusion that the information of visualised biokinetics is useful for actual measurements in practical radiation control.

Complications of oncologic therapy in the abdomen and pelvis: a review.

Cancer therapy has significantly improved in the past few decades with development of various newer classes of cytotoxic chemotherapy as well as novel, molecularly targeted chemotherapy. Similar to chemotherapy, radiotherapy is another important therapeutic option used in the curative and palliative management of various abdominal malignancies. However, both these treatments affect the tumor as well as the normal tissues, leading to significant toxicity. These side effects range from mild to life threatening, and may involve multiple organs. Imaging plays an important role in the early identification of such complications, which may allow more effective patient management. The aim of this article is to discuss and illustrate the wide spectrum of chemotherapy and radiotherapy induced complications in the abdomen and pelvis.

Proton beam therapy for hepatocellular carcinoma located adjacent to the alimentary tract.

PURPOSE: To evaluate the safety and effectiveness of proton beam therapy for hepatocellular carcinoma (HCC) located adjacent to the alimentary tract. PATIENTS AND METHODS: Forty-seven patients (median age, 69 years; range, 43-82 years) who had HCC located within 2 cm of the alimentary tract underwent proton beam therapy. Liver damage according to the Child-Pugh classification was Class A in 35 patients, Class B in 9, and Class C in 3. Treatment protocols of the early 16 patients and the late 31 patients were 72.6 GyE in 22 fractions and 77 GyE in 35 fractions, respectively. RESULTS: During the median follow-up period of 23 months, 24 patients died; the remaining 23 patients were alive until September 2008. The median overall survival was 33.9 months (95% confidence interval [CI], 10.8-57.0 months). Actuarial overall and local progression-free survival rates at 3 years were 50.0% and 88.1%, respectively. Grade 2 and 3 alimentary tract hemorrhage was observed in 3 (6.4%) and 1 (2.1%) patients, respectively. CONCLUSIONS: Our proton beam therapy strategy for HCC located adjacent to the alimentary tract seems to be effective but should be performed with caution.

Impact of UV-B radiation on the digestive enzymes and immune system of larvae of Indian major carp Catla catla.

PURPOSE: Ultraviolet radiation is a potent threat to the aquatic animals. Exposure to such stressor affects metabolic and immunological processes. The present investigation aims to study the effect of UV-B radiation on digestive enzymes and immunity of larvae of Catla catla. MATERIALS AND METHODS: Larvae were exposed to ultraviolet-B (UV-B, 280-320 nm) radiation (145 microW/cm(2)) for three different exposure times of 5, 10 and 15 min on every other day. After 55 days, important digestive enzymes were assayed. For immunological study, lysozyme, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were measured. Then the fish were kept for one month without radiation and lysozyme level was measured. RESULTS: Protein concentration varied directly with the duration of exposure and was highest among fish that had received the 15 min UV-B irradiation. Significantly higher amylase, protease, trypsin and chymotrypsin activities were found in 5 min exposed fish compared to others. Lysozyme level was significantly higher in control group compared to the UV-B treated fish. The lysozyme level decreased with the increasing duration of UV-B radiation. When fish were kept without UV-B radiation for one month, lysozyme level was brought to the normal level in all treatments, except 15 min exposed fish. The GOT and GPT levels were significantly higher in the 15 min exposed group than others. CONCLUSIONS: The effects of UV-B radiation on the digestive physiology and immune system of catla have been clearly observed in the present study. The decreased enzyme activities in UV-B radiated fish results into improper digestion and poor growth.

Suspended C60 nanoparticles protect against short-term UV and fluoranthene photo-induced toxicity, but cause long-term cellular damage in Daphnia magna.

The increased production of nanotechnology materials is a potential source of nano-sized particles (NSPs) in aquatic ecosystems. Meanwhile, polycyclic aromatic hydrocarbons (PAHs), in the presence of ecologically relevant levels of ultraviolet radiation (UV), can be acutely toxic to aquatic species including fish and invertebrates. Considering that suspended carbon-based NSPs (e.g., C60 fullerenes) may act in similar ways as dissolved organic matter (DOM) by altering the bioavailability of PAHs, the objective of this research was to determine the effect of suspended C60 on the photo-induced toxicity of fluoranthene. Transmission electron microscopy indicated that the presence of C60 protected cellular components (e.g., mitochondria, microvilli, and basal infoldings) in organisms exposed to UV and fluoranthene phototoxicity in short-term exposures. However, we found that long-term exposure (21d) of low-level C60 caused significant cellular damage in the Daphnia magna alimentary canal. This paper highlights the importance of examining the interactions between existing stressors and nanoparticles in the aquatic environment.

A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-kappaB, COX-1, and COX-2.

Radiation-induced mucositis is a common and serious side effect of radiotherapy. Molecular mechanisms of mucosal injury, however, are still poorly understood and extremely difficult to study in humans. A novel Dark Agouti rat model using fractionated radiotherapy to induce mucositis has been developed to investigate the occurrence of alimentary mucosal injury. Twenty-four Dark Agouti rats were randomly assigned to receive either fractionated radiotherapy or no radiotherapy. The irradiated rats received a fractionated course of abdominal radiotherapy at 45 Gy/18 fractions/6 weeks treating thrice weekly (i.e., at a radiation dose of 2.5 Gy per fraction). After each week of radiation, a group of irradiated rats was killed. Histomorphology and mucin distribution in the alimentary tract was investigated. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay was used to examine apoptosis in the colon and jejunum, and intestinal morphometry was used to assess villus length, crypt length, and mitotic crypt count. Immunohistochemistry of p53, nuclear factor-kappaB, cyclooxygenase (COX)-1, and COX-2 was also done. The fractionated radiotherapy course induced alimentary mucositis from week 1, with more severe injury seen in the small intestine. The hallmark appearance of apoptosis was present in the crypts of the small and large intestine. In the jejunum and colon, goblet cell disorganization and degeneration was obvious and crypt mitotic counts were severely depleted throughout the treatment. Expression of p53, nuclear factor-kappaB, COX-1, and COX-2 was increased in the irradiated intestinal sections. Fractionated radiation-induced alimentary mucositis has been effectively documented in the Dark Agouti rat for the first time. Further studies investigating the molecular mechanisms underlying radiation-induced mucositis are planned to ultimately achieve anti-mucotoxic-targeted therapies.