[Show abstract][Hide abstract] ABSTRACT: Ionizing radiation induces altered brain tissue homeostasis and can lead to morphological and functional deficits. The aim of the present study was to investigate the short-term and long-term effect of ionizing radiation on cell population resides adult rat hippocampus.
Adult male Wistar rats received whole- brain irradiation with fractionated doses of gamma rays (a total dose of 20 Gy) and were investigated 30 and 100 days later. A combination of Fluoro-Jade C histochemistry for visualization of degenerating neurons, immunohistochemistry for detection of astrocytes and confocal microscopy were used to quantify the neurodegenerative changes in the hippocampal dentate gyrus and CA1 subfield.
A significant increase of Fluoro-Jade C labelled neurons was seen in both of investigated areas through the whole experiment, predominantly 30 days after irradiation. Non- significant decrease of GFAP- immunoreactive astrocytes was found in the hippocampal dentate gyrus and CA1 subfield until 100 days after irradiation.
Our recent results showed that radiation response of cell types resides the adult hippocampus may play contributory role in the development of adverse radiation-induced late effects.Key words: radiation dosage - dose fractionation - rat - hippocampus - Fluoro-Jade C - GFAP.
Full-text · Article · Jun 2015 · Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti
[Show abstract][Hide abstract] ABSTRACT: Ionizing radiation induces altered brain tissue homeostasis and can lead to morphological and functional deficits. In this study, adult male Wistar rats received whole-body exposure with fractionated doses of gamma rays (a total dose of 5 Gy) and were investigated 30 and 60 days later. Immunohistochemistry and confocal microscopy were used to determine proliferation rate of cells residing or derived from the forebrain anterior subventricular zone (SVZa) and microglia distributed along and/or adjacent to subventricular zone-olfactory bulb axis. Cell counting was performed in four anatomical parts along the well-defined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. Different spatiotemporal distribution pattern of cell proliferation was seen up to 60 days after irradiation through the migratory pathway. A population of neuroblasts underwent less evident changes up to 60 days after treatment. Fractionated exposure led to decline or loss of resting as well as reactive forms of microglia until 60 days after irradiation. Results showed that altered expression of the SVZa derived cells and ultimative decrease of microglia may contribute to development of radiation-induced late effects.
Full-text · Article · Dec 2014 · Neurochemical Research
[Show abstract][Hide abstract] ABSTRACT: Background:
The aim of our study was to investigate radiationinduced shortterm effects on the rat forebrain.
Material and methods:
Adult male Wistar rats received whole body exposure with fractionated doses of gamma rays (a total dose of 3 Gy) and were investigated seven and 14 days later. Immunohistochemistry and confocal microscopy were used to determine proliferating cells derived from anterior subventricular zone (SVZa) and distributed along the subventricular zone olfactory bulb axis (SVZ OB axis). Cell counting was performed in four anatomical parts along the welldefined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm.
Different rate of cell overdistribution was found in all counted parts through the entire experiment, mostly detectable in the elbow and horizontal arm.
Results suggested that radiation response of proliferating cells resides the SVZa may a play contributory role in the development of more adverse radiationinduced: late effects.
Full-text · Article · Oct 2013 · Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti
[Show abstract][Hide abstract] ABSTRACT: Ionizing radiation can induce significant injury to normal brain structures. To assess radiation-induced late effects, adult male Wistar rats received whole-body exposure with fractionated doses of gamma rays (a total dose of 4Gy) and were investigated thirty, sixty and ninety days later. Immunohistochemistry and confocal microscopy were used to determine the density of neuroblasts derived from the anterior subventricular zone (SVZa) and brain resident microglia distributed along and/or adjacent to subventricular zone-olfactory bulb axis (SVZ-OB axis). Cell counting was performed in four anatomical parts along the well defined pathway, known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. Strong overdistribution of neuroblasts was seen in the SVZa thirty and sixty days after irradiation replaced by a steep decline in the following parts of the RMS and the highest decrease ninety days after radiation treatment along the entire SVZ-OB axis. Radiation treatment led to a decline or loss of microglia in almost all counted parts through the entire experiment. Results showed that ultimate decline of the SVZa descendants and loss of microglia suggests a contributory role of reduced neurogenesis in the development of radiation-induced late effects.
No preview · Article · Sep 2013 · Acta histochemica
[Show abstract][Hide abstract] ABSTRACT: We investigated radiation-induced delayed alterations of proliferating population, cells undergoing apoptosis and glial cells housed rat brain neurogenic region. Adult male Wistar rats were investigated 30, 60 or 90 days after whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Using immunohistochemistry for detection of cell proliferation marker Ki-67, caspase3 as apoptotic marker and GFAP for mature astrocytes we have been performed quantitative analysis in different forebrain's areas along the SVZ-OB axis, i.e. in the anterior subvetricular zone (SVZa), vertical arm, elbow and horizontal arm. In animals that survived thirty days after radiation treatment initial decrease of the Ki-67-positive cells was seen in regions along the SVZ-OB axis. The highest increase was observed in vertical arm on the 60th day followed by the most striking decline on the 90th day after irradiation. Cells undergoing apoptosis didn't showed expressive increase during entire experiment except of horizontal arm. The most striking changes of GFAP-positive cells were seen 30 and 60 days after irradiation in vertical arm and elbow. Results suggested that radiation response of proliferating cells and astrocytes resides the SVZa may play contributory role in development of more adverse radiation-induced late effects.
Full-text · Article · Mar 2013 · General Physiology and Biophysics
[Show abstract][Hide abstract] ABSTRACT: Ionizing radiation as one of the strongest cytogenetic factors can induce significant injury to the adult brain. In the present study, adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (a total dose of 3Gy). Seven, 14 and 21 days after irradiation the cell types located in the neurogenic anterior subventricular zone (SVZa) were labeled using immunohistochemistry for SVZa-derived young neurons and astrocytes. Cell counting was performed in four anatomical parts along the pathway known as the rostral migratory stream (RMS) represented by the SVZa, vertical arm, elbow and horizontal arm of the RMS. A considerable increase was seen in the number of neuroblasts in the SVZa, vertical arm and elbow on day 7 after irradiation. Until days 14 and 21 there was a marked decline in the density of young neurons, mostly in the horizontal arm of the RMS. In contrast, the number of astrocytes gradually increased in the caudal parts of the RMS until day 14 after irradiation. Strong enhancement was replaced by a steep decline within the RMS up to 21 days after treatment. Our results showed that the radiation response of proliferating cells originating from the SVZa may play a contributory role in the development of more adverse late radiation-induced effects.
Full-text · Article · Oct 2012 · Acta histochemica
[Show abstract][Hide abstract] ABSTRACT: Increasing prevalence of non-malignant thyroid disorders in women with breast cancer has been known for several decades; it is said to be associated with a better prognosis of the cancerous disease. The aim of this work was to analyse associations between thyropathies found in women with breast cancer and particular prognostic factors.
A group of 110 women with breast cancer were tested for autoimmune thyroiditis (AIT) and functional changes of the thyroid gland. Presence of thyroid-peroxidase autoantibodies (TPOAb), serum levels of thyroid-stimulating hormone (TSH) and free thyroxine (FT3, FT4) were determined after the surgery but before adjuvant cancer treatment (radiotherapy, chemotherapy or hormone therapy) initiation. Conventionally evaluated prognostic factors of breast cancer, including histological grading and molecular predictive factors (i.e. the status of the hormone receptors and the human epidermal growth factor receptor) were assessed - these were divided into four basic categories.
The incidence of AIT and subclinical hypothyroidism in the study group was 37.3% and 20%, respectively, i.e. higher than in the general population. The only correlation found was between thyropathies and the specific prognostic factors was that with G1 breast cancer grading.
No preview · Article · Jan 2012 · Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti
[Show abstract][Hide abstract] ABSTRACT: The aim of the present study was to investigate the effect of ionizing radiation on the cell population that co-forms hippocampal formation in an adult rat brain.
Adult male Wistar rats were exposed to whole-body irradiation with fractionated doses of gamma rays (the total dose of 4 Gy). Thirty, 60 and 90 days after irradiation the cell-specific types housed in the CA1, CA3 subregions and adjacent layers were labelled using immunohistochemistry for specific cell phenotypes; Ki-67 marker was used for proliferating cells and GFAP for detection of astrocytes.
During the 30th day post-exposure, a considerable increase in the numbers of Ki-67-positive cells was seen. Moreover, significant decline in the density of neurons, mostly in the CA1 subregion, was observed on the 60th day. Slight overaccumulation of Ki-67-positive cells was seen in CA1 area 90 days after radiation treatment. Temporary decrease of GFAP-positive astrocytes was seen thirty days after irradiation, followed by their subsequent increase 60 days after exposure. Secondary decrease of GFAP-positive cells in both of regions was found in the group surviving 90 days post-irradiation.
Results showed that radiation response of neurons and astrocytes that form the adult hippocampus may play contributory role in the development of prognostically unfavourable adverse radiation-induced late effect.
Full-text · Article · Jan 2012 · Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti
[Show abstract][Hide abstract] ABSTRACT: Ionizing radiation commonly used in the radiotherapy of brain tumours can cause adverse side effects to surrounding normal
brain tissue. The most significant response of adult brain to radiation damage is induction of apoptosis. The adult mammalian
subventricular zone (SVZ) of the brain lateral ventricles (LV) and their subsequent lateral ventricular extension, the rostral
migratory stream (RMS), is one of the few areas, which retains the ability to generate new neurons and glial cells throughout
life. Taking into account the fact, that ionizing radiation is one of the strongest exogenous factors affecting cell proliferation,
the aim of the present study was to investigate the occurrence of radiation-induced apoptosis in this neurogenic region. Adult
male Wistar rats were investigated 1, 5 or 10 days after single whole-body gamma irradiation with the dose of 3 Gy. Apoptotic
cell death was determined by in situ labelling of DNA nick ends (TUNEL) and fluorescence microscopy evaluation of TUNEL-positive
cells. Considerable increase of apoptotic TUNEL-positive cells was observed 24 hrs after irradiation in caudal parts of RMS;
i.e. in the vertical arm and elbow of RMS. Initial increase was followed by strong reduction of apoptosis in the RMS and by
secondary over-accumulation of apoptotic cells in the animals that survived ten days after exposure. Results showed, that
the proliferating population of cells, arisen in SVZ are highly sensitive to radiation-induced apoptosis. This observation
should have implications for clinical radiotherapy to avoid complications in therapeutic brain irradiation.
Key wordsionizing radiation–rat brain–rostral migratory stream–apoptosis–TUNEL
[Show abstract][Hide abstract] ABSTRACT: Aim: The aim was to assess the role of percutaneous endoscopic gastrostomy (PEG) in the treatment of patients with advanced head & neck tumors. Methods: Patients with malignant tumors of the head and neck region are often in locally advanced stage and suffer from various degrees of malnutrition at the time of diagnosis. Toxicity of chemoradiotherapy worsens the unfavorable nutritional status and often leads to treatment gaps or even premature treatment termination. PEG was applied prophylactically to retain the nutritional status of treated patients and to mitigate the adverse reactions to radiotherapy. In the retrospective analysis we assessed the importance of percutaneous endoscopic gastrostomy that was implanted prophylactically in the treatment of 83 patients with advanced head & neck tumors. The time interval from the date of diagnosis to the start of radiotherapy treatment, the treatment gaps caused by radiotoxicity; and the loss of body weight during the treatment in the two groups of patients - with prophylactic PEG and without PEG was analyzed. At the same time we assessed the influence of these factors on the overall survival. Results: The time interval between the diagnosis of malignant head & neck tumor and the start of chemoradiotherapy treatment was on average 39.2 days for patients diagnosed and treated in Martin University Hospital compared to 51.7 days for patients diagnosed in different hospitals. The toxicity of concomitant chemoradiotherapy in the treatment of patients with malignancies in the head & neck region is manifested by severe odynophagia, dysphagia, xerostomia, dysgeusia and malnutrition; and it is associated with a high risk of treatment interruptions and early termination of radiotherapy. In the group of patients who had PEG during the treatment, the treatment gaps caused by acute radiotoxicity were on average 3.6 days shorter compared to patients without PEG. The weight loss was on average 4.3 kg for patients with PEG, compared to 6.9 kg in the control group of patients without PEG. The evaluation of prognostic factors - gender, age, stage, treatments gaps caused by treatment toxicity and chemoradiotherapy with prophylactic PEG implantation - showed that treatment interruptions lasting more than 5 days and chemoradiotherapy treatment without preventive PEG were significant risk factors of 3-year survival. Conclusion: The results confirm that PEG implanted before the start of radiotherapy treatment reduces undesired interruptions of concomitant chemoradiotherapy in patients with advanced head & neck tumors and improves the overall survival. Percutaneous gastrostomy ensures enteral nutrition and hydratation of patients during manifestation of radiochemotherapy toxicity, it reduces the body weight loss during the treatment, positively influences morbidity of patients, it decreases the need of parenteral support treatment and it allows the majority of patients to take the ambulant treatment and to retain the adequate quality of life.
No preview · Article · Jan 2011 · Otorinolaryngologie a Foniatrie
[Show abstract][Hide abstract] ABSTRACT: To evaluate the analgesic effect of low-dose radiotherapy in the treatment of plantar fasciitis and to analyse prognostic factors.
Retrospective analysis was used in the assessment of the analgesic effect after the 1st and 2nd series of low-dose radiotherapy. The treatment regime of 273 patients included total dose of 4.0 Gy, with fraction dose 1.0 Gy, received 2-3 times a week. Recommended follow-up was 3 months. In 323 cases of plantar fasciitis, prognostic factors (age, sex and pain duration before treatment) were evaluated.
Analgesic effect of total dose of 4.0 Gy was 55.7% after the 1st series and 74.8% after the 2nd series. The results are comparable to published results. Pain duration before treatment shorter than 6 months had a significant effect on the treatment. Age was also a significant prognostic factor, with benefits in the group of patients younger than 50 years.
Results confirm the advantageous analgesic effect of the dose regime received by our group of 273 patients. Analysis of prognostic factors shows greater benefit of treatment in the acute stage of plantar fasciitis. When treating young patients, however, the possible risks of radiotherapy should be considered compared to other treatment modalities.
No preview · Article · Jan 2010 · Klinická onkologie: casopis Ceské a Slovenské onkologické spolecnosti
[Show abstract][Hide abstract] ABSTRACT: Radiotherapy of tumors in the chest and neck regions may have serious pulmonary side effects. It is well known that inflammation is an essential manifestation of radiation-induced injury. This can heal spontaneously, by specific treatment, or it may progress to more intensive inflammation up to irreversible pulmonary fibrosis. To prevent such complications, it would be useful to have a simple non-invasive and sensitive method for monitoring the course of airway and lung post-irradiation inflammation. This study is devoted to search for such a method. We supposed that cough response intensity (CRI) could be one of the methods, which we are looking for. Guinea pigs (Trik strain, n=32) were used in the study. Animals were divided into two subgroups. Animals of a non-untreated (NT) group (n=14; M=7, F=7) were submitted to sham chest irradiation. The animals of a treated (XRT) group (n=18; M=9, F=9) were exposed to a single dose of gamma rays. Cough was provoked by exposure of animals to citric acid aerosol (CA) in gradually increasing concentrations (0.05-1.6M). CRI testing was performed two days before sham/real chest irradiation, than on 1st, 3rd, 10th, 15th, 21st, and 28th days following the day of irradiation. CRI was quantified in each animal by counting the number of coughs induced by all used concentration of CA. We found a significant increase of CRI in the animals of XRT group on 10th and 21st day compared with the NT animals. An increase of CRI also was found inside the XRT group on the 10th day after irradiation compared with the pre-irradiation value of CRI.
Full-text · Article · Dec 2007 · Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
[Show abstract][Hide abstract] ABSTRACT: Thoracic irradiation may cause an acute lymphocytic alveolitis or hypersensitivity pneumonitis. It is well known that cough reflex is sensitized by a number of inflammatory mediators. The purpose of the present study was to investigate the effect of the thoracic irradiation on the cough response in awake guinea pigs. Guinea pigs (Trik strain) were exposed to sham irradiation (n=16), a single irradiation dose of 10 Gy (n=12), and a fractionated irradiation dose (in five fractions) of 15 Gy (n=12) delivered to the thorax. Cough was induced by citric acid aerosol inhalation in gradually increasing concentrations (0.05-1.6 M) during the first week after thoracic irradiation. The cough response was expressed as a total number of coughs induced during all citric acid challenges. Irradiated animals with single dose of 10 Gy exhibited a time- dependent significant increase of citric acid-induced cough in the 6th day after irradiation compared with control animals (P=0.005), whereas cough was not altered significantly in irradiated animals with fractionated dose of 15 Gy. This study demonstrates that the increased cough response may be a determinant of the functional changes of airway nerve-endings mediating cough in the early phase after thoracic irradiation.
Full-text · Article · Oct 2006 · Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
[Show abstract][Hide abstract] ABSTRACT: It is reasonable to suppose that airway mucosa can be damaged by irradiation applied to chest and neck regions. The inflammatory process is a consequence of an injury. Airway inflammation is one mechanism responsible for cough induction. So, one can suppose that radiotherapy (RT) focused on the patients' chest or neck may injure airway mucosa, which might change sensitivity of the nerve-endings mediating the cough reflex. The purpose of this study was to examine cough reflex sensitivity (CRS) in patients who underwent RT in the chest and neck regions. CRS test using capsaicin was performed in patients with breast cancer (Group A, n=19), and with lung or neck cancer in (Group B, n=14) who underwent RT. Capsaicin aerosol in doubled concentrations (0.49-1000 microM) was inhaled by a single breath. CRS was defined as the lowest capsaicin concentration that evoked 2 or more coughs (C2). Radiation doses ranged from 40 to 70 Gy. Capsaicin cough challenge was performed before and then in the 2(nd) and 5(th) week of RT. We observed a significantly reduced value of C2, i.e., increased cough reflex sensitivity, in Group B in the 2(nd) week of RT (P= 0.04). We conclude that CRS in the lung or neck cancer patients undergoing RT is significantly enhanced, which could result from injury to the nerve endings in airway mucosa.
Full-text · Article · Oct 2006 · Journal of physiology and pharmacology: an official journal of the Polish Physiological Society
[Show abstract][Hide abstract] ABSTRACT: Primary tumours of the brain represent about 1,5% of all cancers. Patients presenting with malignant glioma will undergo local excision and/or external radiation therapy. Despite this therapy, nearly all tumours will recur. Moreover, it has been shown that 90% of recurrences occur within 2 cm of the initial tumour. This is mainly due to the poor radiosensitivity of gliomas, and to the fragility of normal brain tissue. Brachytherapy may represent an interesting therapeutic alternative, since its rapid dose fall-off offers an opportunity to spare normal brain tissue.
[Show abstract][Hide abstract] ABSTRACT: A case of multiple, cutaneous metastases as the first sign of lung cancer in a patient with well-differentiated, papillary, transitional cell carcinoma of the urinary bladder is presented. In the left clavicular region were two, sharply demarcated, dark red tumors measuring 3 and 2 cm in diameter with a history of rapid growth and intermittent spontaneous bleeding. Thorough examination of the patient revealed 16 additional skin lesions, which were dark red macules and papules, 2-3 mm in diameter, situated on the left side of the chest. The skin biopsy material (tumors, macular and papular lesions) was studied using histological and immunohistochemical techniques and showed intact epidermis and massive dermal and subcutaneous metastatic involvement by a small cell carcinoma with neuroendocrine differentiation most likely originating in the lung.
No preview · Article · Jan 1999 · European journal of dermatology: EJD