Radiation of bilateral adrenal metastases is associated with a high risk of primary adrenal insufficiency.

BACKGROUND: Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Radiotherapy (RT) is one option available to treat adrenal metastases. The risk of primary adrenal insufficiency (PAI) after adrenal RT is unclear. OBJECTIVE: Determine the incidence and the timeline of PAI in patients undergoing adrenal RT. DESIGN, SETTING AND PARTICIPANTS: Single-centre longitudinal retrospective cohort study of adult patients with adrenal metastases treated with RT between 2010 and 2021. RESULTS: Of 56 patients with adrenal metastases treated with adrenal RT, eight (14.3%) patients developed PAI at a median of 6.1 months (interquartile range [IQR]: 3.9-13.8) after RT All patients developing PAI had either unilateral RT in the setting of contralateral adrenalectomy or bilateral adrenal RT. Patients who developed PAI received a median RT dose of 50 Gy (IQR: 44-50 Gy), administered in a median of five fractions (IQR: 5-6). Treated metastases decreased in size and/or metabolic activity on positron emission tomography in seven patients (87.5%). Patients were initiated on hydrocortisone (median daily dose of 20 mg, IQR: 18-40) and fludrocortisone (median daily dose of 0.05 mg, IQR: 0.05-0.05 mg). At the end of the study period, five patients died, all due to extra-adrenal malignancy, at a median time of 19.7 months (IQR: 16-21.1 months) since RT and median time of 7.7 months (IQR: 2.9-12.5 months) since the diagnosis of PAI. CONCLUSION: Patients receiving unilateral adrenal RT with two intact adrenal glands have a low risk of PAI. Patients receiving bilateral adrenal RT have a high risk of PAI and require close monitoring.

The protective effect of N-acetyl cysteine against selenium toxicity and gamma irradiation in rats.

N-acetyl cysteine (NAC) is a nutritional supplement and greatly applied as an antioxidant in vivo and in vitro. Therefore, this study aimed to assess the metabolic and antioxidant protective effect of NAC against selenium (Se) toxicity and gamma irradiation in rats by measuring biochemical and molecular parameters. This study was conducted on sixty rats divided into six equal different groups; control, NAC, Rad, Se, Rad + NAC, and Se + NAC groups. Oxidative/nitrosative makers (LPO, NO, and NOS), antioxidants status markers (GSH, GPx, and SOD), liver metabolic markers (LDH, SDH, and ATP), and plasma metabolic markers (Glucose, total cholesterol, and total proteins) were measured using commercial colorimetric kits while plasma corticosterone concentration was measured using commercial ELISA kit. Also, Levels of NR3C1 and Glut-2 genes expression using reverse transcription-quantitative polymerase chain reaction were done. Our results revealed that Se toxicity and gamma irradiation induced significant increases in oxidative/nitrosative stress markers and a significant decrease in antioxidant status markers in the liver and adrenal tissues. Moreover, metabolic disorders were recorded as manifested by elevation of plasma ALT, Albumin, glucose and cholesterol, and decrease in protein levels associated with a significant increase in corticosterone concentration. This was also accompanied by a significant decrease in SDH activity and ATP production in the hepatic tissue. Molecular analysis showed a marked increase in NR3C1 mRNA and decrease in Glut-2 mRNA in liver tissue. However, NAC supplementation attenuated the changes induced by these toxins. Finally, we could conclude that, oral supplementation of NAC can modulate the metabolic disturbances and has protective effects in rats exposed to Se toxicity and gamma irradiation.

Single-institutional outcome-analysis of low-dose stereotactic body radiation therapy (SBRT) of adrenal gland metastases.

BACKGROUND: Adrenal gland metastases are a common diagnostic finding in various tumor diseases. Due to the increased use of imaging methods, they are diagnosed more frequently, especially in asymptomatic patients. SBRT has emerged as a new, alternative treatment option in the field of radiation oncology. In the past, it was often used for treating inoperable lung, liver, prostate, and brain tumors. Meanwhile, it is also an established keystone in the treatment of oligometastatic diseases. This retrospective study aims to evaluate the effect of low-dose SBRT in patients with adrenal metastases. METHODS: We analyzed a group of 31 patients with 34 adrenal gland lesions treated with low-dose SBRT between July 2006 and July 2019. Treatment-planning was performed through contrast-enhanced CT, followed by image-guided stereotactic radiotherapy using cone-beam CT. The applied cumulative median dose was 35 Gy; the median single dose was 7 Gy. We focused on local control (LC), progression-free survival (PFS), overall survival (OS), as well as acute and late toxicity. RESULTS: Seven adrenal gland metastases (20.6%) experienced local failure, 80.6% of the patients faced a distant progression. Fourteen patients were still alive. Median follow-up for all patients was 9.8 months and for patients alive 14.4 months. No treatment-related side-effects >grade 2 occurred. Of all, 48.4% suffered from acute gastrointestinal disorders; 32.3% reported acute fatigue, throbbing pain in the renal area, and mild adrenal insufficiency. Altogether, 19.4% of the patients faced late-toxicities, which were as follows: Grade 1: 12.9% gastrointestinal disorders, 3.2% fatigue, Grade 2: 9.7% fatigue, 6.5% headache, 3.2% loss of weight. The 1-year OS and probability of LF were 64 and 25.9%, respectively. CONCLUSION: Low-dose SBRT has proven as an effective and safe method with promising outcomes for treating adrenal metastases. There appeared no high-grade toxicities >grade 2, and 79.4% of treated metastases were progression-free. Thus, SBRT should be considered as a therapy option for adrenal metastases as an individual therapeutic concept in the interdisciplinary discussion as an alternative to surgical or systemic treatment.

[Metabolic and ultrastructural adaptation mechanisms during the primary prophylactic action of low-intensity electromagnetic radiation under normal and radiation conditions]. / Metabolicheskie i ul'trastrukturnye mekhanizmy adaptatsii pri pervichno-profilakticheskom deistvii nizkointensivnogo élektromagnitnogo izlucheniia v usloviiakh normy i radiatsii.

BACKGROUND: Experimental studies have established that that low-intensity ultrahigh frequency (UHF) electromagnetic radiation (EMR) has a preventive effect under the action of radiation and other pathogenic factors, which manifests itself in the accelerated development of adaptation, in the predominance of anabolic reactions over catabolic ones, and in the strengthening of the body' structural reserves. At the same time, from the standpoint of studying the mechanisms of primary prevention, it is very important not only to identify the overall adaptation effect, but also to have an idea on the specific contribution of a physical factor used in the development of adaptation. AIM: To identify metabolic and ultrastructural adaption parameters under the action of low-intensity UHF EMR on healthy animals and to determine their stability (safety), by using a model of radiation exposure. MATERIAL AND METHODS: The experiments were carried on 42 mature male rats weighing 180-200g. All the rats were divided into 5 groups: 2 experimental groups of 8 animals each for the comparative study of the specific features of adaptation developed under the preliminary action of UHF EMR in healthy animals and under radiation; 2 control groups of 8 animals each, and one intact group of 10 animals. The lumbar region (the area of the projection of the adrenal glands) was exposed to UHF EMP for 2 min daily (a cycle of 10 sessions). The animals were once irradiated at 2 Gy 60Co gamma ray doses, by using an Agat-R apparatus. The investigation objects were the liver, adrenal glands, testes, and thymus. The investigators used biochemical assays (the levels of RNA and DNA, antioxidant activity, specific activity in the thymocyte genome), transmission electron microscopy of adrenocorticocytes in the adrenal bundle zone and Sertoli cells in the testis. Mitochondria (number, average and total area, number of cristae) were morphometrically analyzed. RESULTS: The metabolic and ultrastructural adaption changes induced by UHF EMR in healthy animals were ascertained to be able to withstand the pathogenic effect of radiation and at the same time showed both stability (safety) and certain variability (plasticity) in their reactions. In this case, there were increases in the synthesis of nucleic acids and in the activity of the antioxidant system; there was also mitochondrial structural stability that was more manifested in the adrenocorticocytes in the adrenal bundle zone. At the same time, there was also a decrease in the intensity (magnitude) of a number of adaptive indicators, although by and large they were significantly higher than the level of control (the effect of radiation). DISCUSSION: Thus, the effect of UHF EMR on healthy animals contributed to the development of adaptive rearrangements in the organs studied. The essence of these changes was mainly the enhancement of synthetic reactions, as indicated by a larger amount of RNA and DNA, the activation of cellular and intracellular regeneration with the increased processes of hyperplasia of the mitochondrial cristae and the higher levels of ribosomes and polysomes. In addition, it can be assumed that the use of UHF EMR has laid the physicochemical foundations of its antioxidant action as conformational rearrangements in the membranes, which increased their structural stability. The findings are indicative of the increased level of morphofunctional reserves in the studied cells and tissues due to their increased bioenergetic and plastic potential. CONCLUSION: This study has provided new data that expand our understanding of the features of the development of adaptive mechanisms and the formation of the body's structural and functional reserves under the primary prophylactic action of low-intensity UHF EMR, by using the model of radiation exposure.

[PHYTOCORRECTION OF IMMUNOLOGICAL AND BIOCHEMICAL CHANGES IN THE COMBINED IMPACT OF COAL DUST AND HIGH DOSE OF RADIATION].

The objective of this researsh is to study the effects of Eminium Regelii phytopreparation (ERP) on immune status and free radical oxidation in the tissues of the adrenal glands and immunocompetent organs after combined exposure to 6 Gy dose of gamma irradiation and coal dust (remote period). The study was realized on 30 white laboratory male rats of the Wistar line, weighing 240±20g, that were divided into equal 3 groups: I group - intact, ІІ group - were exposured to combined effects of coal dust and gamma irradiation, III group - were exposured to combined effects and in parallel taking phytopreparation Eminium Regel. The animals of II and III groups were irradiated 90 days prior to the study at the TERAGAM 60Co radiotherapy unit ("ISOTREND spol. S.r.o.", Czech Republic) in dose of 6 Gy once. Experimental animals received phytopreparation of ER 2.5 mg/kg per day on calculate of body mass for 14 days. The results of the conducted studies showed that in the long-term period after the actions of the sublethal dose of gamma radiation and coal dust, significant changes were revealed that were characterized by a decrease in immunological reactivity, increased lipoperoxidation and inhibition of antioxidant defense activity of the organism. After exposure to ER, oxidative stress was alleviated, sufficient restoration of antioxidant protection and immune system indices, which were disrupted by the combined effects of a single high dose of radiation and a prolonged three-month inhalation of coal dust.

Radiotherapy for adrenal gland metastases from hepatocellular carcinoma

Background. Several studies have found benefits of radiotherapy for adrenal metastasis from hepatocellular carcinoma (HCC). However, the efficacy, safety and outcome issues have not yet been fully addressed. Therefore, we performed this study to further elucidate the feasibility and outcome of radiotherapy in treating adrenal metastasis from HCC. Methods. We retrospectively analyzed 81 patients with adrenal metastasis from HCC between 2001 and 2015. Eighteen patients received helical tomotherapy and 63 patients received conventional radiotherapy, including two-dimensional (2-D) or three-dimensional conformal radiotherapy (3-D CRT). The median radiation dose was 50 Gy (range 26-64 Gy) with median fraction size of 2.0 Gy (range 2.0-5.0 Gy). Tumor responses, adverse effects, patient outcomes and prognostic factors were analyzed. Results. An objective response (complete and partial response) was achieved in 55.6% patients. The helical tomotherapy group showed higher objective response rate than the conventional radiotherapy group (P = 0.031). The major adverse effects were anorexia (51.8%), nausea (41.9%), and fatigue (35.8%). Similar toxicity profile occurred in the 2-D, 3-D CRT and helical tomotherapy groups. The overall survival (OS) rate at 1, 2 and 5 years was 59.9, 35.0, and 12.9%, respectively, with a median survival of 15 months. Patients who received helical tomotherapy achieved a better OS compared to the conventional radiotherapy group (P = 0.047). However, multivariate analysis indicated that radiotherapy technique was not an independent prognostic factor for patient outcome. Conclusion. These results suggest that radiotherapy offers a noninvasive approach in controlling adrenal metastasis from HCC with promising local control and acceptable tolerability (AU)

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An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse.

INTRODUCTION: Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. METHODS: A multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours. RESULTS: The BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk. CONCLUSION: This is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.

Radiation dose in cardiac SPECT/CT: An estimation of SSDE and effective dose.

AIMS: The dose levels for Computed Tomography (CT) localization and attenuation correction of Single Photon Emission Computed Tomography (SPECT) are limited and reported as Volume Computed Tomography Dose Index (CTDIvol) and Dose-Length Product (DLP). This work presents CT dose estimation from Cardiac SPECT/CT based on new American Association of Physicists in Medicine (AAPM) Size Specific Dose Estimation (SSDE) parameter, effective dose, organ doses and also emission dose from nuclear issue. MATERIAL AND METHODS: Myocardial perfusion SPECT/CT for 509 patients was included in the study. SSDE, effective dose and organ dose were calculated using AAPM guideline and Impact-Dose software. Data were analyzed using R and SPSS statistical software. Spearman-Pearson correlation test and linear regression models were used for finding correlations and relationships among parameters. RESULTS: The mean CTDIvol was 1.34 mGy±0.19 and the mean SSDE was 1.7 mGy±0.16. The mean±SD of effective dose from emission, CT and total dose were 11.5±1.4, 0.49±0.11 and 12.67±1.73 (mSv) respectively. The mean±SD of effective dose from emission, CT and total dose were 11.5±1.4, 0.49±0.11 and 12.67±1.73 (mSv) respectively. The spearman test showed that correlation between body size and organ doses is significant except thyroid and red bone marrow. CTDIvol was strongly dependent on patient size, but SSDE was not. Emission dose was strongly dependent on patient weight, but its dependency was lower to effective diameter. CONCLUSION: The dose parameters including CTDIvol, DLP, SSDE, effective dose values reported here are very low and below the reference level. This data suggest that appropriate CT acquisition parameters in SPECT/CT localization and attenuation correction are very beneficial for patients and lowering cancer risks.

Stress-associated radiation effects in pygmy wood mouse Apodemus uralensis (Muridae, Rodentia) populations from the East-Urals Radioactive Trace.

This work is based on the comparative analysis of data obtained in the course of monitoring pygmy wood mouse populations (Apodemus uralensis Pallas, 1811) in the East-Urals Radioactive Trace (EURT) area and background territories. The effect of population size and its interaction with the radioactivity on biochemical parameters in the spleen and adrenal glands was studied. The concentrations of total lipids, proteins, DNA and RNA, activity of glucose-6-phosphate isomerase and catalase as well as the level of lipid peroxidation (LPO) were evaluated. The functional-metabolic shifts seen with large population sizes were characterized by delipidisation of adrenocortical cells, increased LPO as the main mechanism for steroidogenesis, growth of the protein components of the adrenal glands to maintain their hyperfunction, as well as immunosuppression associated with the restriction of carbohydrates providing splenocytes, reduction of DNA synthesis, and the development of a pro-/antioxidant imbalance. Reactivity of the neuroendocrine and hematopoietic systems of animals experiencing a high population density was higher in the EURT zone compared with the reference group. This difference can be explained by the additional stress from the chronic radiation exposure. The level of LPO, catalase activity, and DNA/protein ratio in the spleen and the total protein content in the adrenal glands were the most sensitive to the interaction of population size and radiation exposure. The harmful effect (distress) of the interaction of non-radiation and radiation factors can manifest when there is a population abundance above 30 ind./100 trap-day and a radiation burden which exceeds the lower boundary of the Derived Consideration Reference Levels, which is above 0.1 mGy/day.

Estimation of organ doses to patients undergoing hepatic chemoembolization procedures.

The aim of this study is to evaluate organ and tissue absorbed doses to patients undergoing hepatic chemoembolization procedures performed in two hospitals in the city of Recife, Brazil. Forty eight patients undergoing fifty hepatic chemoembolization procedures were investigated. For the 20 cases with PA projection only, organs and tissues dose to KAP conversion coefficients were calculated using the mesh-based anthropometric phantom series FASH and MASH coupled to the EGSnrc Monte Carlo code. Clinical, dosimetric and irradiations parameters were registered for all patients. The maximum organ absorbed doses found were 2.4 Gy, 0.85 Gy, 0.76 Gy and 0.44 Gy for skin, kidneys, adrenals and liver, respectively.

Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas.

The circadian clock of man and mammals shows a hierarchic organization. The master clock, located in the suprachiasmatic nuclei (SCN), controls peripheral oscillators distributed throughout the body. Rhythm generation depends on molecular clockworks based on transcriptional/translational interaction of clock genes. Numerous studies have shown that the clockwork in peripheral oscillators is capable to maintain circadian rhythms for several cycles in vitro, i.e. in the absence of signals from the SCN. The aim of the present study is to analyze the effects of irradiation with X-rays on the clockwork of liver, adrenal and pancreas. To this end organotypic slice cultures of liver (OLSC) and organotypic explant cultures of adrenal glands (OAEC) and pancreas (OPEC) were prepared from transgenic mPer2(luc) mice which express luciferase under the control of the promoter of an important clock gene, Per2, and allow to study the dynamics of the molecular clockwork by bioluminometry. The preparations were cultured in a membrane-based liquid-air interface culturing system and irradiated with X-rays at doses of 10 Gy and 50 Gy or left untreated. Bioluminometric real-time recordings show a stable oscillation of all OLSC, OAEC and OPEC for up to 12 days in vitro. Oscillations persist after irradiation with X-rays. However, a dose of 50 Gy caused a phase advance in the rhythm of the OLSC by 5 h, in the OPEC by 7 h and in the OAEC by 6 h. Our study shows that X-rays affect the molecular clockwork in liver, pancreas and adrenal leading to phase advances. Our results confirm and extend previous studies showing a phase-advancing effect of X-rays at the level of the whole animal and single cells.

UV laser radiation alters the embryonic protein profile of adrenal-kidney-gonadal complex and gonadal differentiation in the lizard, Calotes Versicolor.

PURPOSE: To examine the impact of ultraviolet (UV) laser radiation on the embryos of Calotes versicolor in terms of its effects on the protein profile of the adrenal-kidney-gonadal complex (AKG), sex determination and differentiation, embryonic development and hatching synchrony. MATERIALS AND METHODS: The eggs of C. versicolor, during thermo-sensitive period (TSP), were exposed to third harmonic laser pulses at 355 nm from a Q-switched Nd:YAG laser for 180 sec. Subsequent to the exposure they were incubated at the male-producing temperature (MPT) of 25.5 ± 0.5°C. The AKG of hatchlings was subjected to protein analysis by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and to histology. RESULTS: The UV laser radiation altered the expression of the protein banding pattern in the AKG complex of hatchlings and it also affected the gonadal sex differentiation. SDS-PAGE of AKG of one-day-old hatchlings revealed a total of nine protein bands in the control group whereas UV laser irradiated hatchlings expressed a total of seven protein bands only one of which had the same Rf as a control band. The UV laser treated hatchlings have an ovotestes kind of gonad exhibiting a tendency towards femaleness instead of the typical testes. CONCLUSIONS: It is inferred that 355 nm UV laser radiation during TSP induces changes in the expression of proteins as well as their secretions. UV laser radiation had an impact on the gonadal differentiation pathway but no morphological anomalies were noticed.

Effects and safety of ¹³¹I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry.

Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (¹³¹I-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of ¹³¹I-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical ¹³¹I-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the ¹³¹I-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 ¹³¹I-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD-were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1±8.2 to 129.5±13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through ¹³¹I-MIBG radiotherapy. This indicated that most of the ¹³¹I-MIBG radiotherapy was performed safely without significant side effects.

Light stimulates the mouse adrenal through a retinohypothalamic pathway independent of an effect on the clock in the suprachiasmatic nucleus.

The brain's master circadian pacemaker resides within the hypothalamic suprachiasmatic nucleus (SCN). SCN clock neurons are entrained to the day/night cycle via the retinohypothalamic tract and the SCN provides temporal information to the central nervous system and to peripheral organs that function as secondary oscillators. The SCN clock-cell network is thought to be the hypothalamic link between the retina and descending autonomic circuits to peripheral organs such as the adrenal gland, thereby entraining those organs to the day/night cycle. However, there are at least three different routes or mechanisms by which retinal signals transmitted to the hypothalamus may be conveyed to peripheral organs: 1) via retinal input to SCN clock neurons; 2) via retinal input to non-clock neurons in the SCN; or 3) via retinal input to hypothalamic regions neighboring the SCN. It is very well documented that light-induced responses of the SCN clock (i.e., clock gene expression, neural activity, and behavioral phase shifts) occur primarily during the subjective night. Thus to determine the role of the SCN clock in transmitting photic signals to descending autonomic circuits, we compared the phase dependency of light-evoked responses in the SCN and a peripheral oscillator, the adrenal gland. We observed light-evoked clock gene expression in the mouse adrenal throughout the subjective day and subjective night. Light also induced adrenal corticosterone secretion during both the subjective day and subjective night. The irradiance threshold for light-evoked adrenal responses was greater during the subjective day compared to the subjective night. These results suggest that retinohypothalamic signals may be relayed to the adrenal clock during the subjective day by a retinal pathway or cellular mechanism that is independent of an effect of light on the SCN neural clock network and thus may be important for the temporal integration of physiology and metabolism.

Immunorehabilitating effect of ultrahigh frequency electromagnetic fields in immunocompromised animals.

We observed immunorehabilitation effects of ultrahigh frequency electromagnetic fields (microwaves) in immunocompromised animals. It was shown that microwave irradiation of the thyroid gland area could abolish actinomycin D- and colchicine-induced immunosuppression and did not affect immunosuppression caused by 5-fluorouracil. These findings suggest that changes in the hormonal profile of the organism during microwave exposure can stimulate the processes of transcription and mitotic activity of lymphoid cells.

Free radical oxidation in rats in the delayed period after combined exposure to dust and radiation.

We studied the intensity of free radical processes in organs (liver, spleen, thymus, lymph nodes of the small intestine, and adrenal glands) and cells (lymphocytes) in the delayed period after combined exposure to a sublethal dose of γ-radiation (6 Gy) and asbestos dust particles. Combined exposure was followed by accumulation of LPO metabolites (diene conjugates and malonic dialdehyde) in homogenates of the studied organs and resulted in antioxidant defense failure in experimental animals. Ionizing radiation have a pivotal role in these processes.

Changes in activity of stress-realizing body systems as a result of terahertz irradiation at nitric oxide frequencies in albino rats under conditions of acute stress.

We studied the effects of irradiation with teraherz electromagnetic waves at frequencies corresponding to nitric oxide emission and absorption molecular spectrum (150,176-150,664 GHz) on activity of the sympathoadrenal and pituitary-adrenal axes of the stress response in albino male rats under conditions of acute immobilization stress. It was shown that terahertz waves exert stress-limiting effect and are capable of reducing the levels of catecholamines, corticotropin, and corticosterone in male rats exposed to acute stress.

Chronic exposure to an extremely low-frequency magnetic field induces depression-like behavior and corticosterone secretion without enhancement of the hypothalamic-pituitary-adrenal axis in mice.

An extremely low-frequency magnetic field (ELF-MF) is generated by power lines and household electrical devices. Many studies have suggested an association between chronic ELF-MF exposure and anxiety and/or depression. The mechanism of these effects is assumed to be a stress response induced by ELF-MF exposure. However, this mechanism remains controversial. In the present study, we investigated whether chronic ELF-MF exposure (intensity, 1.5 mT; [corrected] total exposure, 200 h) affected emotional behavior and corticosterone synthesis in mice. ELF-MF-treated mice showed a significant increase in total immobility time in a forced swim test and showed latency to enter the light box in a light-dark transition test, compared with sham-treated (control) mice. Corticosterone secretion was significantly high in the ELF-MF-exposed mice; however, no changes were observed in the amount of the adrenocorticotropic hormone and the expression of genes related to stress response. Quantification of the mRNA levels of adrenal corticosteroid synthesis enzymes revealed a significant reduction in Cyp17a1 mRNA in the ELF-MF-exposed mice. Our findings suggest the possibility that high intensity and chronic exposure to ELF-MF induces an increase in corticosterone secretion, along with depression- and/or anxiety-like behavior, without enhancement of the hypothalamic-pituitary-adrenal axis.

Timed maternal melatonin treatment reverses circadian disruption of the fetal adrenal clock imposed by exposure to constant light.

Surprisingly, in our modern 24/7 society, there is scant information on the impact of developmental chronodisruption like the one experienced by shift worker pregnant women on fetal and postnatal physiology. There are important differences between the maternal and fetal circadian systems; for instance, the suprachiasmatic nucleus is the master clock in the mother but not in the fetus. Despite this, several tissues/organs display circadian oscillations in the fetus. Our hypothesis is that the maternal plasma melatonin rhythm drives the fetal circadian system, which in turn relies this information to other fetal tissues through corticosterone rhythmic signaling. The present data show that suppression of the maternal plasma melatonin circadian rhythm, secondary to exposure of pregnant rats to constant light along the second half of gestation, had several effects on fetal development. First, it induced intrauterine growth retardation. Second, in the fetal adrenal in vivo it markedly affected the mRNA expression level of clock genes and clock-controlled genes as well as it lowered the content and precluded the rhythm of corticosterone. Third, an altered in vitro fetal adrenal response to ACTH of both, corticosterone production and relative expression of clock genes and steroidogenic genes was observed. All these changes were reversed when the mother received a daily dose of melatonin during the subjective night; supporting a role of melatonin on overall fetal development and pointing to it as a 'time giver' for the fetal adrenal gland. Thus, the present results collectively support that the maternal circadian rhythm of melatonin is a key signal for the generation and/or synchronization of the circadian rhythms in the fetal adrenal gland. In turn, low levels and lack of a circadian rhythm of fetal corticosterone may be responsible of fetal growth restriction; potentially inducing long term effects in the offspring, possibility that warrants further research.