Stress in wild and captive snakes : quantification, effects and the importance of management

As in other animals, distress and impaired welfare have a deleterious effect on the mental, physical and behavioral health of snakes in the wild and in captivity. Besides anthropogenic disturbance, the availability of food and shelter, the presence of predators, and environmental factors, such as seasonality and climatological changes, are important factors that affect the stress level and subsequent welfare in wild snake populations. In captive snakes, inappropriate management is the most prominent cause of chronic stress and impaired welfare. Chronic stress can be assumed by looking at the snake's behavior, but there is need for a standardized quantification method to pin-point more accurately (chronic) stress levels. The biomarker suitable in this framework is the level of corticosterone in plasma, feces and shed skin

Single and fractionated ionizing radiation induce alterations in endothelial connexin expression and channel function

Radiotherapy is an effective treatment for most tumor types. However, emerging evidence indicates an increased risk for atherosclerosis after ionizing radiation exposure, initiated by endothelial cell dysfunction. Interestingly, endothelial cells express connexin (Cx) proteins that are reported to exert proatherogenic as well as atheroprotective effects. Furthermore, Cxs form channels, gap junctions and hemichannels, that are involved in bystander signaling that leads to indirect radiation effects in non-exposed cells. We here aimed to investigate the consequences of endothelial cell irradiation on Cx expression and channel function. Telomerase immortalized human Coronary Artery/Microvascular Endothelial cells were exposed to single and fractionated X-rays. Several biological endpoints were investigated at different time points after exposure: Cx gene and protein expression, gap junctional dye coupling and hemichannel function. We demonstrate that single and fractionated irradiation induce upregulation of proatherogenic Cx43 and downregulation of atheroprotective Cx40 gene and protein levels in a dose-dependent manner. Single and fractionated irradiation furthermore increased gap junctional communication and induced hemichannel opening. Our findings indicate alterations in Cx expression that are typically observed in endothelial cells covering atherosclerotic plaques. The observed radiation-induced increase in Cx channel function may promote bystander signaling thereby exacerbating endothelial cell damage and atherogenesis

Gold nanoparticles meet medical radionuclides

Thanks to their unique optical and physicochemical properties, gold nanoparticles have gained increased interest as radiosensitizing, photothermal therapy and optical imaging agents to enhance the effectiveness of cancer detection and therapy. Furthermore, their ability to carry multiple medically relevant radionuclides broadens their use to nuclear medicine SPECT and PET imaging as well as targeted radionuclide therapy. In this review, we discuss the radiolabeling process of gold nanoparticles and their use in (multimodal) nuclear medicine imaging to better understand their specific distribution, uptake and retention in different in vivo cancer models. In addition, radiolabeled gold nanoparticles enable image-guided therapy is reviewed aswell as the enhancement of targeted radionuclide therapy and nanobrachytherapy through an increased dose deposition and radiosensitization, as demonstrated by multiple Monte Carlo studies and experimental in vitro and in vivo studies. (C) 2021 The Authors. Published by Elsevier Inc

Cardiovascular diseases related to ionizing radiation : the risk of low-dose exposure (Review)

Traditionally, non-cancer diseases are not considered as health risks following exposure to low doses of ionizing radiation. Indeed, non-cancer diseases are classified as deterministic tissue reactions, which are characterized by a threshold dose. It is judged that below an absorbed dose of 100 mGy, no clinically relevant tissue damage occurs, forming the basis for the current radiation protection system concerning non-cancer effects. Recent epidemiological findings point, however, to an excess risk of non-cancer diseases following exposure to lower doses of ionizing radiation than was previously thought. The evidence is the most sound for cardiovascular disease (CVD) and cataract. Due to limited statistical power, the dose-risk relationship is undetermined below 0.5 Gy; however, if this relationship proves to be without a threshold, it may have considerable impact on current low‑dose health risk estimates. In this review, we describe the CVD risk related to low doses of ionizing radiation, the clinical manifestation and the pathology of radiation-induced CVD, as well as the importance of the endothelium models in CVD research as a way forward to complement the epidemiological data with the underlying biological and molecular mechanisms

Selected Endothelial Responses after Ionizing Radiation Exposure

Along with the development of novel chemotherapeutic agents, radiation therapy has revolutionized the prognosis of patients with various cancers. However, with a longer life expectancy, radiation treatment-related comorbidity, like cardiovascular diseases (CVDs), becomes an issue for cancer survivors. In addition, exposure to X-rays for medical diagnostics is dramatically increasing at the present times. A pressing question is whether or not exposure to these very low doses can cause health damage. Below 0.5 gray (Gy), an increased risk cannot be evidenced by epidemiology alone, and in vitro and in vivo mechanistic studies focused on the elucidation of molecular signaling pathways are needed. Given the critical role of the endothelium in normal vascular functions, a complete understanding of radiation-induced endothelial dysfunction is crucial. In this way, the current radiation protection system could be refined if needed, making it possible to more accurately assess the cardiovascular risk in the low-dose region. Finally, radiation-induced CVD, like CVD in general, is a progressive disorder that may take years to decades to manifest. Therefore, experimental studies are warranted to fulfill the urgent need to identify noninvasive biomarkers for an early detection and potential interventions—together with a healthy lifestyle—that may prevent or mitigate these adverse effects

Daily allergy burden and heart rate characteristics in adults with allergic rhinitis based on a wearable telemonitoring system

Background: Allergic rhinitis includes a certain degree of autonomic imbalance. However, no information is available on how daily changes in allergy burden affect autonomic imbalance. We aimed to estimate associations between daily allergy burden (allergy symptoms and mood) and daily heart rate characteristics (resting heart rate and sample entropy, both biomarkers of autonomic balance) of adults with allergic rhinitis, based on real-world measurements with a wearable telemonitoring system. Methods: Adults with a tree pollen allergy used a smartphone application to self-report daily allergy symptoms (score 0–44) and mood (score 0–4), and a Mio Alpha 2 wristwatch to collect heart rate characteristics during two pollen seasons of hazel, alder and birch in Belgium. Associations between daily allergy burden and heart rate characteristics were estimated using linear mixed effects distributed lag models with a random intercept for individuals and adjusted for potential confounders. Results: Analyses included 2497 participant-days of 72 participants. A one-point increase in allergy symptom score was associated with an increase in next-day resting heart rate of 0.08 (95% CI: 0.02–0.15) beats per minute. A one-point increase in mood score was associated with an increase in same-day sample entropy of 0.80 (95% CI: 0.34–1.26) × 10−2. No associations were found between allergy symptoms and heart rate sample entropy, nor between mood and resting heart rate. Conclusion: Daily repeated measurements with a wearable telemonitoring system revealed that the daily allergy burden of adults with allergic rhinitis has systemic effects beyond merely the respiratory system.</p

Modulation of gene expression in endothelial cells in response to high LET nickel ion irradiation

Ionizing radiation can elicit harmful effects on the cardiovascular system at high doses. Endothelial cells are critical targets in radiation-induced cardiovascular damage. Astronauts performing a long-term deep space mission are exposed to consistently higher fluences of ionizing radiation that may accumulate to reach high effective doses. In addition, cosmic radiation contains high linear energy transfer (LET) radiation that is known to produce high values of relative biological effectiveness (RBE). The aim of this study was to broaden the understanding of the molecular response to high LET radiation by investigating the changes in gene expression in endothelial cells. For this purpose, a human endothelial cell line (EA.hy926) was irradiated with accelerated nickel ions (Ni) (LET, 183 keV/mu m) at doses of 0.5, 2 and 5 Gy. DNA damage was measured 2 and 24 h following irradiation by gamma-H2AX foci detection by fluorescence microscopy and gene expression changes were measured by microarrays at 8 and 24 h following irradiation. We found that exposure to accelerated nickel particles induced a persistent DNA damage response up to 24 h after treatment. This was accompanied by a downregulation in the expression of a multitude of genes involved in the regulation of the cell cycle and an upregulation in the expression of genes involved in cell cycle checkpoints. In addition, genes involved in DNA damage response, oxidative stress, apoptosis and cell-cell signaling (cytokines) were found to be upregulated. An in silico analysis of the involved genes suggested that the transcription factors, E2F and nuclear factor (NF)-kappa B, may be involved in these cellular responses

Differential response to acute low dose radiation in primary and immortalized endothelial cells

Purpose : The low dose radiation response of primary human umbilical vein endothelial cells (HUVEC) and its immortalized derivative, the EA.hy926 cell line, was evaluated and compared. Material and methods: DNA damage and repair, cell cycle progression, apoptosis and cellular morphology in HUVEC and EA.hy926 were evaluated after exposure to low (0.05-0.5 Gy) and high doses (2 and 5 Gy) of acute X-rays. Results : Subtle, but significant increases in DNA double-strand breaks (DSB) were observed in HUVEC and EA.hy926 30 min after low dose irradiation (0.05 Gy). Compared to high dose irradiation (2 Gy), relatively more DSB/Gy were formed after low dose irradiation. Also, we observed a dose-dependent increase in apoptotic cells, down to 0.5 Gy in HUVEC and 0.1 Gy in EA.hy926 cells. Furthermore, radiation induced significantly more apoptosis in EA.hy926 compared to HUVEC. Conclusions : We demonstrated for the first time that acute low doses of X-rays induce DNA damage and apoptosis in endothelial cells. Our results point to a non-linear dose-response relationship for DSB formation in endothelial cells. Furthermore, the observed difference in radiation-induced apoptosis points to a higher radiosensitivity of EA.hy926 compared to HUVEC, which should be taken into account when using these cells as models for studying the endothelium radiation response