Cell Renewal Systems Research Articles

The Impact of Sleep on Haematological Parameters in Firefighters.

Sleep is a vital process that impacts biological functions such as cell renewal, bone regeneration, and immune system support. Disrupted sleep can interrupt erythropoiesis, leading to fewer red blood cells, reduced haemoglobin concentration, and decreased haematocrit levels, potentially contributing to haematological disorders. This is particularly concerning for shift workers for example firefighters. While previous studies have explored sleep's adverse effects on various professions, research specific to firefighters is limited. This study investigates the relationship between sleep quality and haematological parameters among firefighters in Northeast Portugal. From a sample of 201 firefighters, variations in red blood cells, haemoglobin, and haematocrit values were linked to sleep quality. The study utilised non-parametric tests (Wilcoxon-Mann-Whitney, Spearman's correlation) to explore the connection between sleep quality and haematological profile. The impact of covariates on haematological parameters was assessed using non-parametric ANCOVA (Quade's). A multiple regression analysis was employed to further understand how sleep quality and various confounding variables impact haematological levels. Findings suggest a negative link between sleep quality and haematological levels, meaning that as sleep quality deteriorates, there is a tendency for haematological levels to decrease, as indicated by Spearman's correlation (rRBC = -0.157, pRBC = 0.026; rHb = -0.158, pHb = 0.025; rHCT = -0.175, pHCT = 0.013). As observed in scientific literature, the correlation found suggests a possible inhibition of erythropoiesis, the process responsible for red blood cell production. Despite firefighters presenting a haematological profile within the reference range (RBC: 5.1 × 106/mm3 (SD ± 0.4), Hb: 15.6 g/dL (SD ± 1.3), 47% (SD ± 1.0), there is already an observable trend towards lower levels. The analysis of co-variables did not reveal a significant impact of sleep quality on haematological levels. In conclusion, this study underscores the importance of sleep quality in determining haematological parameters among firefighters. Future research should investigate the underlying mechanisms and long-term implications of poor sleep quality on firefighter health. Exploring interventions to enhance sleep quality is vital for evidence-based strategies promoting firefighter well-being.

Missing pieces of the pituitary puzzle: participation of extra-adenohypophyseal placode-lineage cells in the adult pituitary gland.

The pituitary gland is a major endocrine tissue composing of two distinct entities, the adenohypophysis (anterior pituitary, cranial placode origin) and the neurohypophysis (posterior pituitary, neural ectoderm origin), and plays important roles in maintaining vital homeostasis. This tissue is maintained by a slow, consistent cell-renewal system of adult stem/progenitor cells. Recent accumulating evidence shows that neural crest-, head mesenchyme-, and endoderm lineage cells invade during pituitary development and contribute to the maintenance of the adult pituitary gland. Based on these novel observations, this article discusses whether these lineage cells are involved in pituitary organogenesis, maintenance, regeneration, dysplasia, or tumors.

Plasma Rich in Growth Factors Promotes Autophagy in ARPE19 Cells in Response to Oxidative Stress Induced by Blue Light.

Age-related macular degeneration (AMD) causes the degeneration of photoreceptors and retinal cells leading to vision loss in older subjects. Among possible exogenous risk factors, it has been recently proposed that long-term exposure to blue light could aggravate the course of AMD. In the search for therapeutic options, plasma rich in growth factors (PRGF) has been shown to enhance cell antioxidant pathways and protect photoreceptors against the harm produced by blue light, although its mechanism of action remains unknown. One possible mechanism, autophagy, is one of the most conservative cell renewal systems used in eukaryotes to destroy cellular components that have been damaged by some kind of insult. The oxidative stress of exposure to blue light is known to induce cell autophagy. In this study, we examined the combined effects on autophagy of blue light and PRGF in a retinal cell line, ARPE19. In response to treatment with both PRGF and blue light, we detected the modulated expression of autophagy markers such as NF-kB, p62/sqstm1, Atg5, LC3 and Beclin1, and inflammatory markers such as IL1B and IL18. Our findings suggest that PRGF promotes cell autophagy in response to exposure to blue light.

Techno-economic analysis of a hybrid power system based on the cost-effective hydrogen production method for rural electrification, a case study in Iran

Rural electrification challenges in Iran are the most important obstacle to achieve electricity access for the entire population. The current study focuses on finding an optimal renewable energy system to meet the load of a small village by renewable resources. This village faces frequent power outages, common in many far-off villages in Iran. A hybrid photovoltaics/wind turbine/biogas generator/fuel cell renewable energy system is proposed and analyzed for both stand-alone and on-grid application. Fuel cells are used alongside a hydrogen tank, batteries, and a reformer or an electrolyzer, to act as storage devices and backup component. The main goal is to find an optimal configuration that can meet the electricity demand and be satisfactory from both an economic and environmental point of view. The results indicated that using solar, wind and biogas is the most affordable method and that adding fuel cell to this configuration would increase costs by 33–37%, but also improve system flexibility. Using a reformer is more efficient and about 6% less costly, but also creates more pollution. The cost of energy for a stand-alone system with reformer was calculated to be 0.164 to 0.233 $/kWh, while the on-grid system cost of energy was 0.096–0.125 $/kWh.

Gastrointestinal disorders and diet

The gastrointestinal tract is affected directly and indirectly by nutrition, as the diet supplies energy to the intestinal cells and affects the gut microbiome, motility, cell renewal, metabolite production and immune system. Nutritional management is critical for the treatment of many gastrointestinal disorders. There is a wide variety of diet types for different disorders, including diets that are highly digestible, low in fat, contain novel proteins uncommon in most pet foods, those with hydrolysed proteins, and diets high in fibre sources. Specific nutrients and supplements may also be used in gastrointestinal disorders, including cobalamin and other vitamins, omega-3 fatty acids, glutamine, and pre- and probiotics. This paper will discuss the nutritional management of acute vomiting and diarrhoea; chronic enteropathy including inflammatory bowel disease; protein losing enteropathy; and feline constipation.

Techno-economic feasibility analysis of hydrogen fuel cell and solar photovoltaic hybrid renewable energy system for academic research building

A hydrogen fuel cell (HFC) and solar photovoltaic (SPV) hybrid renewable energy system (HRES) for stand-alone applications is proposed. This system arrangement of a hydrogen tank, battery, and an electrolyzer are used as like the energy storage. The economic viability of using HRES power to supply the electrical load demand of academic research building located at 23°12′N latitude and 77°24′E longitudes, India is examined. The fuzzy logic program computes the optimum value of capital and replacement cost of the components, which is then utilized in HOMER pro software to calculate the optimum performance of HRES. The results shows the HFC and battery bank are the most significant modules of the HRES to meet load demand at late night and early morning hours. The AC primary load consuming 20712.63kWh/year out of total power generation of HRES which is 24570.72kWh/year. The excess of electricity produced by HRES is 791.7709kWh/year with the optimized cost of energy, unmet electrical load and capacity shortage of 0%.

A DNA hypermethylation module for the stem/progenitor cell signature of cancer

Many DNA-hypermethylated cancer genes are occupied by the Polycomb (PcG) repressor complex in embryonic stem cells (ESCs). Their prevalence in the full spectrum of cancers, the exact context of chromatin involved, and their status in adult cell renewal systems are unknown. Using a genome-wide analysis, we demonstrate that ∼75% of hypermethylated genes are marked by PcG in the context of bivalent chromatin in both ESCs and adult stem/progenitor cells. A large number of these genes are key developmental regulators, and a subset, which we call the “DNA hypermethylation module,” comprises a portion of the PcG target genes that are down-regulated in cancer. Genes with bivalent chromatin have a low, poised gene transcription state that has been shown to maintain stemness and self-renewal in normal stem cells. However, when DNA-hypermethylated in tumors, we find that these genes are further repressed. We also show that the methylation status of these genes can cluster important subtypes of colon and breast cancers. By evaluating the subsets of genes that are methylated in different cancers with consideration of their chromatin status in ESCs, we provide evidence that DNA hypermethylation preferentially targets the subset of PcG genes that are developmental regulators, and this may contribute to the stem-like state of cancer. Additionally, the capacity for global methylation profiling to cluster tumors by phenotype may have important implications for further refining tumor behavior patterns that may ultimately aid therapeutic interventions.

The Analysis of the Expression of a Novel Gene,Xenopus Polka Dots, which was Expressed in the Embryonic and Larval Epidermis during Early Development

The epidermis serves as a barrier protecting organs and tissues from the environment, and comprises many types of cells. A cell renewal system is established in epidermis: old epithelial cells are replaced by newly differentiated cells, which are derived from epidermal stem cells located near basement membrane. In order to examine the mechanism of epidermal development, we isolated a novel gene expressed in Xenopus epidermis and named the gene Xenopus polka dots (Xpod) from its polka dot-like expression pattern throughout larval periods. Several immunohistochemical examinations showed that the Xpod-expressing cell type is neither p63-positive epidermal stem cells, nor the α-tubulin-positive ciliated cells, but a subset of the foxi1e-positive ionocytes. The forced gene expression of foxi1e caused the suppression of Xpod expression, while Xpod showed no effect on foxi1e expression. In a comparison of several osmotic conditions, we found that hypertonic culture caused the increase in number of the Xpod-expressing cell, whereas number of the foxi1e-expressing cells was reduced under the hypertonic condition. These results show the possibility that Xpod is involved in the establishment of a certain subpopulation of ionocytes under hypertonic conditions.

Abstract LB-174: A DNA hypermethylation module for the stem/progenitor cell signature of cancer

Abstract It has been firmly established that cancer gene expression partly mimics the gene expression signature in embryonic stem cells (ESC). Since most cancers arise in adult stem or progenitor cells, rather than ESC, we now compare cancer chromatin to both embryonic and adult cell renewal systems to understand the relationships between DNA hypermethylation, gene expression, and chromatin states. DNA hypermethylation at CpG island promoters of hundreds of genes, including classic tumor suppressors, is a major modulator of gene expression in human cancers. Past studies suggest ∼ 50% of these are frequently marked by polycomb complex (PcG) transcriptional repressors, but not DNA methylation, in embryonic stem cells (ESC). In ESC, PcG occupancy is predominantly in the context of “bivalent chromatin”, wherein the active transcription mark H3K4me3 and the repressive PcG mark H3K27me3 are simultaneously present. Genes so marked are in a low, but poised, transcription state important for stemness and self-renewal, characteristics shared with tumor cells. Using whole genome ChIP-seq and DNA methylation arrays, we find between 70 to 80% of genes with DNA hypermethylation in cancer have bivalent chromatin not only in ESC, but also in adult stem cells. For these genes, there appears to be an epigenetic switch in cancer wherein bivalent chromatin is replaced by DNA hypermethylation resulting in tighter repression of gene expression. Many of these DNA methylated cancer genes are constituents of the recently proposed “PRC module” of the “ESC cancer signature.” Our data suggest a “DNA methylation module” that recapitulates the “stem cell signature” and that DNA hypermethylation may be a key mechanism that confers cell-renewal and stemness to tumor cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-174. doi:10.1158/1538-7445.AM2011-LB-174

Stress and the epigenetic landscape: a link to the pathobiology of human diseases?

Accumulating evidence points to a major role for chronic stress of cell renewal systems in the pathogenesis of important human diseases, including cancer, atherosclerosis and diabetes. Here we discuss emerging evidence that epigenetic abnormalities may make substantial contributions to these stress-induced pathologies. Although the mechanisms remain to be fully elucidated, we suggest that chronic stress can elicit heritable changes in the chromatin landscape that 'lock' cells in abnormal states, which then lead to disease. We emphasize the need to investigate epigenetic states in disease and links to stress and to consider how the knowledge gained through these studies may foster new means of disease prevention and management.

A fuzzy logic controller for a hybrid PV/FC green power system

Design and utilisation of a fuzzy logic controller (FLC) for a hybrid photovoltaic (PV) and proton exchange membrane fuel cell (PEMFC) renewable power system is studied in this paper. The FLC is designed and utilised to compensate load changing effects as well as to establish a sustainable energy source by eliminating the effects of the changes on the source side. As well known, the output power of the PV source is directly affected from the sunlight. Therefore, changing solar irradiation levels of sunlight must be compensated as well not to affect the load side power balance. A DC/AC converter is used to control the power flow from the hybrid PV-PEMFC source to the load side by maintaining a sustainable source of power. All of the system components are modelled in Matlab/Simulink environment and combined with the FLC model, which is also developed in Matlab/Simulink environment by using functional blocks of the Simulink.

Intestinal cellular localization of PCNA protein and CYP1A mRNA in Atlantic salmon Salmo salar L. exposed to a model toxicant

BackgroundThe aim of the study was to examine the intestinal cellular localization of proliferating cell nuclear antigen (PCNA) and cytochrome P450 A1 (CYP1A) expression in Atlantic salmon Salmo salar L. exposed to a model toxicant. The stress response was induced by intraperitoneal injection of four salmon with a single dose (50 mg/kg) of the CYP1A inducer β-naphthoflavone (BNF) and intestinal tissue (mid and distal intestine; MI and DI) was sampled seven days later. Samples for histology and gene transcription analysis were collected from four exposed fish and four control fish. PCNA was assessed by immunohistochemistry, CYP1A mRNA was studied by in situ hybridization (ISH) and finally the transcription of five genes was quantified by real-time quantitative RT-PCR (real-time RT-PCR); two detoxifying genes (CYP1A and glutathione S-transferase; GST), a stress marker gene (heat shock protein 70; HSP70), PCNA and a gene marker of apoptosis (caspase 6A).ResultsPCNA protein and CYP1A mRNA were successfully localized in the intestinal cells (MI) of both experimental groups. At the cellular level, BNF significantly lowered intestinal cell proliferation and increased the CYP1A mRNA levels compared to the control group. The real-time RT-PCR data, which showed an increased mRNA expression both in the MI and DI of 139- and 62-fold, respectively, confirmed the increased cellular CYP1A mRNA levels detected using ISH. HSP70 expression was also up-regulated in the exposed fish. The other examined genes did not show any differential regulation in the experimental fish group.ConclusionThis study showed that CYP1A mRNA had a specific intestinal cellular transcription pattern in Atlantic salmon exposed to BNF. At the cellular level CYP1A mRNA expression was always observed at or around the cell nucleus close to the basolateral cell membrane and at the tissue level CYP1A mRNA expression was most frequently observed in the basal and apex area of the intestinal folds. Taken together, a link between the intestinal detoxification system (CYP1A) and cell renewal system (PCNA) is indicated with these two processes being inversely correlated in BNF exposed fish.

Radioprotective Effects of Aloe Vera Leaf Extract on Swiss Albino Mice against Whole-Body Gamma Irradiation

The skin, being a cell-renewal system, is one of the first organs to be affected in total-body irradiation during radiotherapy. An attempt has been made in the present study to explore radiation-induced biochemical alterations caused by whole-body gamma irradiation and their modulation in Swiss albino mice by Aloe vera leaf extract (AVE). Mice were selected for this study from an inbreed colony and divided into four different groups: I (double-distilled water-treated group): considered as normal; II (Aloe vera-treated group): the animals were administered 1 g/kg body-wt/day Aloe vera leaf extract; III (radiation-treated group): the animals were exposed to 6 Gy gamma radiation at the dose rate of 0.96 Gy/min; and IV (combination group): animals were administered Aloe vera leaf extract continuously for 15 consecutive days, and on the 15th day they were irradiated to 6 Gy gamma radiation after 30 minutes of extract administration. The animals from the above groups were autopsied after 6 hours, 24 hours, and at 3, 7, 14, and 21 days of radiation. Biochemical estimations of DNA, lipid peroxidation, glutathione, catalase, and superoxide-dismutase were made. Total DNA, catalase, superoxide dismutase (SOD) activity in the skin, and glutathione (GSH) in the liver and blood significantly decreased compared to normal, but lipid peroxidation (LPO) in the liver and blood increased in the irradiated control group. In contrast, in experimental animals, DNA, catalase, and SOD in the skin and GSH in the liver and blood increased significantly, whereas LPO in the liver and blood decreased in comparison to irradiated control animals. Thus, Aloe vera leaf extract is found to have damage-resistant properties against radiation-induced biochemical alterations in Swiss albino mice.

Thyroid hormone regulation of stem cell development during intestinal remodeling

During amphibian metamorphosis the small intestine is remodeled from larval to adult form, analogous to the mammalian intestine. The larval epithelium mostly undergoes apoptosis, while a small number of stem cells appear, actively proliferate, and differentiate into the adult epithelium possessing a cell-renewal system. Because amphibian intestinal remodeling is completely controlled by thyroid hormone (T3) through T3 receptors (TRs), it serves as an excellent model for studying the molecular mechanism of the mammalian intestinal development. TRs bind T3 response elements in target genes and have dual functions by interacting with coactivators or corepressors in a T3-dependent manner. A number of T3 response genes have been isolated from the Xenopus laevis intestine. They include signaling molecules, matrix metalloproteinases, and transcription factors. Functional studies have been carried out on many such genes in vitro and in vivo by using transgenic and culture technologies. Here we will review recent findings from such studies with a special emphasis on the adult intestinal stem cells, and discuss the evolutionarily conserved roles of T3 in the epithelial cell-renewal in the vertebrate intestine.

Stem-Cell Biology and Cancer Therapy: The More Things Change…

Stem-Cell Biology and Cancer Therapy: The More Things Change…

Radioautographic study of the seasonal distribution of leukocytes in turtles Phrynops hilarii (Chelonia Chelidae)

The aim of this study was to present a morphological description of the leukocytes of Phrynops hilarii turtles according to the seasonal distribution of these cells and to show their replacement in the blood circulation using a radioautographic method. Five animals of both sexes weighing 600–1200 g were used. The animal's blood was aspirated, smeared on glass slides, and stained with the Romanowsky stain, and 500 cells of each animal were counted during each season. The results obtained were analyzed statistically by analysis of variance followed by the Bonferroni test (NCSS), with the level of significance set at p < 0.05. The radioautographic analysis of turtle blood exposed to 1000 μCi of 3H-thymidine and developed after 30 days showed a large number of silver grains incorporated into the cells, except for basophils, with cell renewal occurring every seven days. Quantitative data demonstrated a seasonal influence on the distribution of some leukocyte types, with the following “ p” values: heterophils ( p = 0.0007), basophils ( p = 0.0002), monocytes ( p = 0.0016), eosinophils ( p = 0.0073). However, using this statistical method, it was not possible to detect a significant difference related to seasonal influence on lymphocytes ( p = 0.16295) or thrombocytes ( p = 0.1046). Using this experimental animal model, a seasonal influence on the distribution of some leukocyte types was observed, and the radioautographic method revealed a cell renewal system occurring every seven days, except for basophils.

Hematopoietic cell renewal systems: mechanisms of coping and failing after chronic exposure to ionizing radiation

On the occasion of the first international workshop on systems radiation biology we review the role of cell renewal systems in maintaining the integrity of the mammalian organism after irradiation. First, 11 radiation emergencies characterized by chronic or protracted exposure of the human beings to ionizing irradiation were "revisited". The data provide evidence to suggest that at a daily exposure of about 10-100 mSv, humans are capable of coping with the excess cell loss for weeks or even many months without hematopoietic organ failure. Below 10 mSv/day, the organisms show some cellular or subcellular indicators of response. At dose rates above 100 mSv/day, a progressive shortening of the life span of the irradiated organism is observed. To elucidate the mechanisms relevant to tolerance or failure, the Megakaryocyte-thrombocyte cell renewal system was investigated. A biomathematical model of this system was developed to simulate the development of thrombocyte concentration as a function of time after onset of chronic radiation exposure. The hematological data were taken from experimental chronic irradiation studies with dogs at the Argonne National Laboratory, USA. The results of thrombocyte response patterns are compatible with the notion of an "excess cell loss" (compared to the steady-state) in all proliferative cell compartments, including the stem cell pool. The "excess cell loss" is a function of the daily irradiation dose rate. Once the stem cell pool is approaching an exhaustion level, a "turbulence region" is reached. Then it takes a very little additional stress for the system to fail. We conclude that in mammalian radiation biology (including radiation medicine), it is important to understand the physiology and pathophysiology of cell renewal systems in order to allow predicting the development of radiation induced lesions.

Ageing and activity: their effects on the functional reserve capacities of the heart and vascular smooth and skeletal muscles

During perinatal life striated muscles grow through the acquisition of more contractile cells (myocytes or fibres) followed by their postnatal enlargement (i.e. hypertrophy). In the ageing adult these events are reversed, with a progressive loss of myocytes that cannot be fully compensated despite the presence of cell renewal systems or reactive myocyte hypertrophy. Hence the functional reserve capacities of the heart and skeletal muscles decline with age. This is probably a consequence of physiological ageing and diminished levels of physical activity. As a result daily tasks once taken for granted become progressively more difficult, and eventually impossible, to perform. For example, sufficient coordinated absolute muscle force is required for an individual to rise from a chair or climb stairs, and the reserve capacity of the heart is a major determinant of an individual's ability to remain active and cope with daily stresses and illnesses. Long-term participation in endurance-based activities helps to preserve cardiac reserve, and has both direct and indirect beneficial effects on vascular smooth muscle and health preservation within the cardiovascular system. In contrast, this type of activity does little to protect skeletal muscles against the age-related losses of fast-twitch fibres, small motor units, overall muscle mass and power output. While resistance exercise promotes fibre hypertrophy in skeletal muscles, and to a lesser extent in myocytes of the heart, the explosive power of muscles still declines with age. Hence, while physical activity is important in attenuating age-related changes in muscle function and its reserve capacity, it delays rather than prevents the deleterious effects of ageing per se. Despite this, in a culture where inactivity has become an accepted part of life we still need to explore in greater detail the benefits of habitual physical activity, and use this information as a community-based educational tool to help prevent or delay cardiovascular disease, obesity, arthritis and the frailty associated with old age.

Prolactin: Fishy Tales of Its Primary Regulator and Function

Prolactin (PRL) is an important regulator of multiple biological functions, and the control of PRL expression integrates a wide spectrum of molecules throughout vertebrates. PRL-releasing peptide (PrRP) seems to be an essential stimulator of PRL transcription and secretion in teleost pituitary and peripheral organs. In the amphibious euryhaline mudskipper, the localization of mRNA levels of PrRP and PRL as well as their regulation during acclimation to different environments are closely related. The presence of PrRP-PRL axes in the peripheral organs might suggest an ancient history of this axis prior to the evolution of the hypothalamus-pituitary, and it is possible that the PrRP is an original and primary regulator of PRL. In the euryhaline fishes, the permeability of gut of seawater-acclimated fish is generally greater than that of the freshwater (FW)-acclimated fish. The modification in the epithelial cell renewal system may play an important role in regulation of the permeability. PRL induces the cell proliferation during FW acclimation, whereas cortisol stimulates both cell proliferation and apoptosis. Indeed, a large proportion of the various actions of PRL seem to be associated directly or indirectly with cell proliferation and/or apoptosis, which might be a primary function of PRL.

Multi-organ involvement as a pathogenetic principle of the radiation syndromes: a study involving 110 case histories documented in SEARCH and classified as the bases of haematopoietic indicators of effect

The purpose of this contribution is to analyse the extent and severity of radiation-induced multi-organ involvement (MOI) and multi-organ failure (MOF) following whole body exposure to ionising radiation in 110 patients who were involved in different radiation accidents that occurred between 1945 and 2000. The clinical case histories were documented systematically in SEARCH (System for Evaluation and Archiving of Radiation Accidents based on Case Histories), which was established by our group in collaboration with international experts. The consequences of radiation-induced MOI in these patients were examined for two severity-of-response categories. On the basis of early (days 1–10 following exposure) haematological signs and symptoms, 45 of the patients could be assigned to response category (RC) 4; 65 patients presented early haematological changes characteristic for RC 3. All patients assigned to RC 4 died within 60 days, whilst the patients in RC 3 survived the first 100 days owing to an autologous haematopoietic recovery as well as necessary recovery of other organ systems. All of the 45 patients assigned to RC 4 suffered from the consequences of haematological, gastrointestinal, skin and neurovascular involvement. Regarding other organ systems in these 45 patients in RC 4, 20 patients showed evidence of cardiovascular involvement, 32 showed respiratory involvement, 25 showed liver involvement and 32 showed urogenital involvement. The patients assigned to RC 3 also displayed MOI, but at a significantly lower level. All of them showed signs and symptoms of involvement of haematopoiesis, the gastrointestinal system, skin and the neurovascular system. However, in contrast to the RC 4 patients, the RC 3 patients were reported to have less severe impairments of the cardiovascular, respiratory, metabolic and urogenital systems. It also became clear that the symptomatology of organ system involvement could be traced not only to the pathophysiology of the rapidly turning over cell renewal systems but — of equal or more importance — to the vascular system and specifically, to the endothelial components. Thus, it will be a challenge of further research to consider the cellular and molecular mechanisms involved in radiation-induced MOI and MOF. Necessary therapeutic measures should be determined on an improved pathophysiological basis.