Background: We aimed to evaluate osteoporosis, bone mineral density, and fracture risk in irradiated patients by computerized tomography derived Hounsfield Units (HUs) calculated from radiation treatment planning system.

PurposeDuring head and neck cancer treatment, the radiation response of the oral mucosa represents a frequent early side effect. Besides radiation-induced inhibition of proliferation, various other cellular responses occur. The radiation response of adherens and tight junction proteins was so far mostly investigated with large single-dose irradiation protocols, in vivo and in vitro. Therefore, the current study was initiated to investigate the impact of daily fractionated irradiation on the expression of adherens and tight junction proteins in vivo.Materials and methodsFractionation with 5 × 3 Gy/week (days 0–4, 7–11) was given to the snouts of mice. Groups of 5 animals per day were euthanized every second day between day 0 (unirradiated controls) and day 14, and their tongues subjected to histological processing. Adherens junction marker (β-catenin and E‑cadherin) and tight junction marker (claudin-1 and occludin) expression was analysed in the oral mucosa of unirradiated controls and during two weeks of fractionated irradiation.ResultsAdherens as well as tight junction marker proteins were rapidly and consistently upregulated in both the germinal as well as the functional layer of the oral mucosa. This represents a previously unknown parameter of the epithelial radiation response to clinically relevant fractionation protocols.ConclusionFractionated irradiation significantly enhanced the expression of all proteins investigated. This study revealed a new parameter of the epithelial radiation response to fractionated irradiation.Electronic supplementary materialThe online version of this article (10.1007/s00066-018-1302-6) contains supplementary material, which is available to authorized users.

Purpose During head and neck cancer radiotherapy, oral mucositis is the most frequent early side effect. Systemic dermatan sulfate (DS) administration has been shown to significantly decrease oral mucosal radiation reactions during daily fractionated irradiation (IR) in an established mouse model. The aim of this study was to investigate the mechanism of the oral epithelial differentiation process, during IR alone and in combination with DS treatment in the same mouse model. Methods Fractionated IR 5 × 3 Gy/week was given to the snouts of mice over two weeks, either alone (IR) or in combination with daily DS treatment of 4 mg/kg (IR + DS). Groups of mice (n = 3) were sacrificed every second day over the course of 14 days in both experimental arms. Their tongue was excised and subjected to immunohistochemical processing. Results In the p16 analysis as a proliferation marker, the difference between IR alone and IR + DS in the germinal (proliferation) layer was not significant, not stimulating the proliferation process. For the p21 analysis as a differentiation marker on the functional (differentiation) layer, the difference between IR alone and IR + DS arms was significant, indicating that DS inhibited the differentiation process. In the cytokeratin (CK) analysis as the indicator of cellular skeletal integrity, the percentage of antibody-positive cells was above the normal level in both experimental arms and significantly superior in the IR + DS arm. Conclusion The mucosal protective activity of DS, instead of stimulating proliferation, is based on prevention of cell loss by a combination of effects leading to the inhibition of cellular differentiation and an increase in the expression of epithelial mechanical strength between intercellular mechanical junctions.

Oral mucositis is the most frequently occurring early side effect of head-and-neck cancer radiotherapy. Systemic dermatan sulfate (DS) treatment revealed a significant radioprotective potential in a preclinical model of oral mucositis. This study was initiated to elucidate the mechanistic effects of DS in the same model. Irradiation comprised daily fractionated irradiation (5 × 3 Gy/week) over two weeks, either alone (IR) or in combination with daily dermatan sulfate treatment of 4 mg/kg (IR + DS). Groups of mice (n = 5) were sacrificed every second day over the course of 14 days in both experimental arms, their tongues excised and evaluated. The response to irradiation with and without DS was analyzed on a morphological (cell numbers, epithelial thickness) as well as on a functional (proliferation and expression of inflammation, hypoxia and epithelial junction markers) level. The mucoprotective activity of DS can be attributed to a combination of various effects, comprising increased expression of epithelial junctions, reduced inflammation and reduced hypoxia. No DS-mediated effect on proliferation was observed. DS demonstrated a significant mucositis-ameliorating activity and could provide a promising strategy for mucositis treatment, based on targeting specific, radiation-induced, mucositis-associated signaling without stimulating proliferation.

Background: Radiation-induced brain injury is an evident side effect of brain irradiation (IR). Often leads to severe and debilitating cognitive dysfunction and neuronal damage. Ionizing radiation results in oxidative and inflammatory processes. Radiation-induced cognitive impairments are also associated with alterations in glutamate composition. Increased release or decreased uptake of glutamate results in dysregulation of neuronal homeostasis, leading to oxidative stress, mitochondrial dysfunctions, and neuroinflammation. Materials and Methods: Twenty-one rats were taken in the study, and 14 of underwent whole brain IR with a 20 Gray single dose. Ceftriaxone (CTX) treatment was applied in addition to the IR, for 15 days. Animals were divided into three groups. Group1:Normal control; Group2:Placebo(IR-only), Group3:IR+CTX. The one-way ANOVA statistical test was used to compare groups. The value of p<0.05 was accepted as statistically significant. Results: In addition to the IR applied CTX treatment exhibited a positive impact on the results of the three-chamber sociability test, open field test and passive avoidance learning test, hippocampal CA1, CA3, and Purkinje neuron counts, brain levels of brain-derived neurotrophic factor, Glutamate transporter-1 and Superoxide dismutases activity. As well, CTX decreased the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde and tumor necrosis factor-alpha. Conclusion: Ceftriaxone represented a promising effectiveness on radiation-induced neurocognitive impairments and degradation of social-memory capacity by reducing neuronal loss, oxidative stress, and neuroinflammation in the brain. Also, CTX application induces scavenging of glutamate from the synapses helps to prevent glutamate excitotoxicity, and protects neurons from excitotoxic cell death.