Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects / Efectos Protectores y Mecanismos de la Decocción de Huangqi Contra los Efectos Secundarios Inducidos por la Radiación

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.

La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.

Leptomeningeal malignancy of childhood: sharing learning between childhood leukaemia and brain tumour trials.

Leptomeningeal malignancy complicates childhood cancers, including leukaemias, brain tumours, and solid tumours. In leukaemia, such malignancy is thought to invade leptomeninges via the vascular route. In brain tumours, dissemination from the primary tumour, before or after surgery, via CSF pathways is assumed; however, evidence exists to support the vascular route of dissemination. Success in treating leptomeningeal malignancy represents a rate-limiting step to cure, which has been successfully overcome in leukaemia with intensified systemic therapy combined with intra-CSF therapy, which replaced cranial radiotherapy for many patients. This de-escalated CNS-directed therapy is still associated with some neurotoxicity. The balanced benefit justifies exploration of ways to further de-escalate CNS-directed therapy. For primary brain tumours, standard therapy is craniospinal radiotherapy, but attendant risk of acute and delayed brain injury and endocrine deficiencies compounds post-radiation impairment of spinal growth. Alternative ways of treating leptomeninges by intensifying drug therapy delivered to CSF are being investigated-preliminary evidence suggests improved outcomes. This Review seeks to describe methods of intra-CSF drug delivery and drugs in use, and consider how the technique could be modified and additional drugs might be selected for this route of administration.

Intensity dependent disruptive effects of light at night on activation of the HPG axis of tree sparrows (Passer montanus).

Artificial light at night (ALAN) has become increasingly recognized as a disruptor of the reproductive endocrine process and behavior of wild birds. However, there is no evidence that ALAN directly disrupt the hypothalamus-pituitary-gonadal (HPG) axis, and no information on the effects of different ALAN intensities on birds. We experimentally tested whether ALAN affects reproductive endocrine activation in the HPG axis of birds, and whether this effect is related to the intensity of ALAN, in wild tree sparrows (Passer montanus). Forty-eight adult female birds were randomly assigned to four groups. They were first exposed to a short light photoperiod (8 h light and 16 h dark per day) for 20 days, then exposed to a long light photoperiod (16 h light and 8 h dark per day) to initiate the reproductive endocrine process. During these two kinds of photoperiod treatments, the four groups of birds were exposed to 0, 85, 150, and 300 lux light in the dark phase (night) respectively. The expression of the reproductive endocrine activation related TSH-ß, Dio2 and GnRH-I gene was significantly higher in birds exposed to 85 lux light at night, and significantly lower in birds exposed to 150 and 300 lux, relative to the 0 lux control. The birds exposed to 85 lux had higher peak values of plasma LH and estradiol concentration and reached the peak earlier than birds exposed to 0, 150, or 300 lux did. The lower gene expression of birds exposed to 150 and 300 lux reduced their peak LH and estradiol values, but did not delay the timing of these peaks compared to the control group. These results reveal that low intensity ALAN accelerates the activation of the reproductive endocrine process in the HPG axis, whereas high intensity ALAN retards it.

Effects of green light on the growth of spotted halibut, Verasper variegatus, and Japanese flounder, Paralichthys olivaceus, and on the endocrine system of spotted halibut at different water temperatures.

We have previously shown that the somatic growth of barfin flounder, Verasper moseri, was promoted by green light. The present study was undertaken to elucidate whether growth-promoting effect of green light can be observed in other flatfishes and to understand the roles of endocrine systems in green light-induced growth. Herein, we demonstrated facilitation of growth by green light in the spotted halibut, Verasper variegatus, and Japanese flounder, Paralichthys olivaceus. Blue and blue-green light showed potencies that were similar to that of green light, while the potencies of red and white light were equivalent to that of ambient light (control). We also examined the effects of green light on growth and endocrine systems of V. variegatus at various water temperatures. Growth of the fish was facilitated by green light at four different water temperatures examined; the fish were reared for 31 days at 12 and 21 °C, and 30 days at 15 and 18 °C. Increase in condition factor was observed at 15 and 18 °C. Among the genes encoding hypothalamic hormones, expression levels of melanin-concentrating hormone 1 (mch1) were enhanced by green light at the four water temperatures. Expression levels of other genes including mch2 increased at certain water temperatures. No difference was observed in the expression levels of pituitary hormone genes, including those of growth hormone and members of proopiomelanocortin family, and in plasma levels of members of the insulin family. The results suggest that green light may generally stimulate growth of flatfishes. Moreover, it is conceivable that MCH, production of which is stimulated by green light, is a key hormone; it augments food intake, which is intimately coupled with somatic growth.

Hormonally mediated effects of artificial light at night on behavior and fitness: linking endocrine mechanisms with function.

Alternation between day and night is a predictable environmental fluctuation that organisms use to time their activities. Since the invention of artificial lighting, this predictability has been disrupted and continues to change in a unidirectional fashion with increasing urbanization. As hormones mediate individual responses to changing environments, endocrine systems might be one of the first systems affected, as well as being the first line of defense to ameliorate any negative health impacts. In this Review, we first highlight how light can influence endocrine function in vertebrates. We then focus on four endocrine axes that might be affected by artificial light at night (ALAN): pineal, reproductive, adrenal and thyroid. Throughout, we highlight key findings, rather than performing an exhaustive review, in order to emphasize knowledge gaps that are hindering progress on proposing impactful and concrete plans to ameliorate the negative effects of ALAN. We discuss these findings with respect to impacts on human and animal health, with a focus on the consequences of anthropogenic modification of the night-time environment for non-human organisms. Lastly, we stress the need for the integration of field and lab experiments as well as the need for long-term integrative eco-physiological studies in the rapidly expanding field of light pollution.

Biological effects and mechanisms of shortwave radiation: a review.

With the increasing knowledge of shortwave radiation, it is widely used in wireless communications, radar observations, industrial manufacturing, and medical treatments. Despite of the benefits from shortwave, these wide applications expose humans to the risk of shortwave electromagnetic radiation, which is alleged to cause potential damage to biological systems. This review focused on the exposure to shortwave electromagnetic radiation, considering in vitro, in vivo and epidemiological results that have provided insight into the biological effects and mechanisms of shortwave. Additionally, some protective measures and suggestions are discussed here in the hope of obtaining more benefits from shortwave with fewer health risks.

Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma.

BACKGROUND: Endocrine dysfunction is a common sequela of craniospinal irradiation (CSI). Dosimetric data suggest that proton radiotherapy (PRT) may reduce radiation-associated endocrine dysfunction but clinical data are limited. METHODS: Seventy-seven children were treated with chemotherapy and proton (n = 40) or photon (n = 37) radiation between 2000 and 2009 with ≥3 years of endocrine screening. The incidence of multiple endocrinopathies among the proton and photon cohorts is compared. Multivariable analysis and propensity score adjusted analysis are performed to estimate the effect of radiotherapy type while adjusting for other variables. RESULTS: The median age at diagnosis was 6.2 and 8.3 years for the proton and photon cohorts, respectively (P = .010). Cohorts were similar with respect to gender, histology, CSI dose, and total radiotherapy dose and whether the radiotherapy boost was delivered to the posterior fossa or tumor bed. The median follow-up time was 5.8 years for proton patients and 7.0 years for photon patients (P = .010). PRT was associated with a reduced risk of hypothyroidism (23% vs 69%, P < .001), sex hormone deficiency (3% vs 19%, P = .025), requirement for any endocrine replacement therapy (55% vs 78%, P = .030), and a greater height standard deviation score (mean (± SD) -1.19 (± 1.22) vs -2 (± 1.35), P = .020) on both univariate and multivariate and propensity score adjusted analysis. There was no significant difference in the incidence of growth hormone deficiency (53% vs 57%), adrenal insufficiency (5% vs 8%), or precocious puberty (18% vs 16%). CONCLUSIONS: Proton radiotherapy may reduce the risk of some, but not all, radiation-associated late endocrine abnormalities.

Medical consequences of Chernobyl with focus on the endocrine system: Part 1.

In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information on effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.

Medical Consequences of Chernobyl with Focus on the Endocrine System - Part 2.

In the last 70 years, atomic disasters have occurred several times. The nuclear power plant accident at Chernobyl in 1986 in North-Central Ukraine was a unique experience in population exposures to radiation by all ages, and ongoing studies have brought a large amount of information effects of radiation on human organism. Concerning the deteriorating global security situation and the strong rhetoric of some of the world leaders, the knowledge on the biological effects of ionizing radiation and the preventive measures designed to decrease the detrimental effects of radiation gains a new dimension, and involves all of us. This review focuses on the long-term effects of Chernobyl catastrophe especially on the endocrine system in children and in adults, and includes a summary of preventive measures in case of an atomic disaster.

Update on endocrine and metabolic therapy-related late effects observed in survivors of childhood neoplasia.

PURPOSE OF REVIEW: To provide a summary of the most recent research pertaining to the endocrine and metabolic complications observed in childhood cancer survivors. RECENT FINDINGS: Data on prevalence and risk associations are increasingly available from large cohorts of childhood cancer survivors. New directions in research include novel risk-prediction strategies and the study of genetic predisposition. SUMMARY: Endocrine complications are observed in more than 50% of adult childhood cancer survivors. Some continue to develop decades following cancer treatment exposures. The present review provides a summary of the most recent outcomes research pertaining to growth, thyroid, gonadal-reproductive, bone and body composition with emphasis on new directions and challenges in each area.

Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats.

Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method.

Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: a review.

BACKGROUND Since childhood cancer survival has increased, long-term effects of treatment have gained interest. Childhood Hodgkin's lymphoma has been treated successfully for decades now. We provide an overview of the literature on long-term endocrine side effects, such as gonadal dysfunction and growth retardation, as a result of childhood Hodgkin's lymphoma treatment. METHODS A comprehensive search of the Pubmed database was performed. RESULTS We identified 16 studies (10 studies: 298 male survivors and 6 studies: 230 female survivors) about gonadal dysfunction. In survivors treated with alkylating agents or pelvic radiotherapy, severe gonadal damage is described. Recovery was rarely described. Seven studies (481 survivors) about bone mineral density (BMD) and growth were identified. The effects on BMD appear to be small. Data on growth are scarce, but show that radiotherapy in a dose of >30 Gy including the spine, especially in pre-pubertal children, results in reduced height. We included 10 studies (4012 survivors) about thyroid complications. Hypothyroidism is the most common thyroid disorder after radiotherapy. There is also a significant incidence in thyroid carcinoma after low-dose radiation. In survivors treated with chemotherapy only, hypothyroidism and thyroid cancer have not been reported. CONCLUSIONS The severity of endocrine toxicity after childhood Hodgkin's lymphoma depends on the type of treatment. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy. The knowledge obtained in specific follow-up programmes for paediatric cancer survivors will help to find the optimal balance between curability and long-term side effects.

Endocrine late effects after total body irradiation in patients who received hematopoietic cell transplantation during childhood: a retrospective study from a single institution.

PURPOSE: To evaluate the effects of total body irradiation (TBI) on the endocrine system in adults treated with hematopoietic cell transplantation (HCT) during childhood. METHODS: We studied 40 patients who underwent HCT between 1988 and 2004, mainly for childhood cancer. In 23 patients, the conditioning regimen consisted of high-dose chemotherapy and TBI (TBI+). In the other 17 patients, who did not receive TBI (TBI-), HCT was performed after high-dose chemotherapy alone. RESULTS: Overall, 34% of patients in the TBI+ group showed growth hormone deficiency, compared with none of the patients in the TBI- group (P < 0.05). Leydig cell failure was found in 23% of patients in the TBI+ group and in 0% of the patients in the TBI- group. Elevated FSH levels, suggesting spermatogenesis damage, were found in all the patients receiving TBI and in 36% of the patients in the TBI- group (P < 0.001). Also, primary hypothyroidism was more common in TBI+ (34%) than in TBI- (5.8%) patients (P < 0.05). CONCLUSIONS: Our data indicate that endocrine late effects after HCT are more frequent in patients who received TBI, an observation that should be considered, even if the choice of the conditioning regimen is determined by the underlying condition in most cases.

[Effect of radio-ecological conditions in the ChNPP exclusion zone on morphofunctional state and responsiveness of organs and tissues of laboratory animals].

The state of hematopoietic, reproductive and endocrine systems of the organisms of male rats and their offspring in generations (F0-F1-F2) was studied, and the sensitivity of an organism to the action of carcinogen (Af mice) after a stay in the ChNPP exclusion zone was analyzed. It was ascertained that the most significant changes of the morphofunctional state of the animals were observed in the II generation (F2), which remained for a long period under the conditions of radioactive contamination. We have revealed an increased number of leukocytes, neutrophils, lymphocytes, and, especially, monocytes as against while the decrease in the number of erythrocytes and haemoglobin content; the decrease of thyroid function and cortical layer of the adrenals as opposed to while the increase in the relative weight of testes and their epididymides and the decrease in the number of spermatocytes and spermatozoa in the testis tissue. The exposure of Af mice in the exclusion zone increases the processes of mutagenesis and carcinogenesis, and changes the organism response to standardized action of chemical carcinogen. The increase in the exposure time of animals intensifies metabolic processes in a cell and increases their sensitivity to the action of xenobiotics.

Clinical outcomes of adult patients with primary intracranial germinomas treated with low-dose craniospinal radiotherapy and local boost.

The authors document the long term follow up of adult patients with histologically proven primary intracranial germinoma treated with radiotherapy alone using a craniospinal with local boost technique. A retrospective review was conducted on adults diagnosed with intracranial germinoma who received radiotherapy at the Princess Margaret Hospital, Toronto from 1990 to 2007. The study group consisted of 10 males with a median age of 24.1 years. All patients received radiotherapy alone using craniospinal radiotherapy and local boost. There were 10 patients (all male) with a median follow up of 10.9 years (range 2.2-18.9 years). At date of last follow up all patients were still alive, none with relapsed disease. Seven of ten patients (70%) had panhypopituitarianism prior to commencing radiotherapy and hormonal function was not affected in those with an intact pituitary axis. There was no reported cognitive decline in the treated cohort. For adult intracranial germinomas, with long term follow up, low-dose craniospinal radiotherapy with in field boost is highly effective with minimal morbidity.

Dark-phase light contamination disrupts circadian rhythms in plasma measures of endocrine physiology and metabolism in rats.

Dark-phase light contamination can significantly disrupt chronobiologic rhythms, thereby potentially altering the endocrine physiology and metabolism of experimental animals and influencing the outcome of scientific investigations. We sought to determine whether exposure to low-level light contamination during the dark phase influenced the normally entrained circadian rhythms of various substances in plasma. Male Sprague-Dawley rats (n = 6 per group) were housed in photobiologic light-exposure chambers configured to create 1) a 12:12-h light:dark cycle without dark-phase light contamination (control condition; 123 µW/cm(2), lights on at 0600), 2) experimental exposure to a low level of light during the 12-h dark phase (with 0.02, 0.05, 0.06, or 0.08 µW/cm(2) light at night), or 3) constant bright light (123 µW/cm(2)). Dietary and water intakes were recorded daily. After 2 wk, rats underwent 6 low-volume blood draws at 4-h intervals (beginning at 0400) during both the light and dark phases. Circadian rhythms in dietary and water intake and levels of plasma total fatty acids and lipid fractions remained entrained during exposure to either control conditions or low-intensity light during the dark phase. However, these patterns were disrupted in rats exposed to constant bright light. Circadian patterns of plasma melatonin, glucose, lactic acid, and corticosterone were maintained in all rats except those exposed to constant bright light or the highest level of light during the dark phase. Therefore even minimal light contamination during the dark phase can disrupt normal circadian rhythms of endocrine metabolism and physiology and may alter the outcome of scientific investigations.

Endocrine consequences of childhood malignancies.

Advances in cancer therapy over the last years have resulted in improved survival rates for pediatric cancer patients. However, new treatments are associated with short and long-term morbidity. The endocrine system is particularly sensitive to cancer therapies. Long-term survivors of childhood cancer are at risk for hypothalamic pituitary dysfunction, gonadal failure or disorders relating to pubertal progress, thyroid disease, obesity, disorders of lipid metabolism and disorders of bone and mineral metabolism. Long-term follow-up is indicated, as these disorders may not become apparent until adulthood.

Study on endocronological effects of radon speleotherapy on respiratory diseases.

BACKGROUND: Radon, as a radioactive noble gas of natural origin, is generally present in the atmosphere of caves during the speleotherapeutic treatment of different diseases. However, the role of radon in the therapeutic effect is not fully clarified yet. Endocrine parameter levels may be influenced by radon-like endocrine levels in balneotherapeutic treatments (bath treatment). For this reason changes of these parameters were examined in this study. PATIENTS AND METHOD: A total of 81 speleotherapy patients were involved in the survey. They spent four hours daily in Tapolca Cave, five days a week, for two weeks. In this study, the thyreoiedea stimulating hormone, free triiodine-tironin, free thyroxine, prolactine, cortisol, dehydroepiandrosterone sulphate, adrenocorticotropic hormone, and beta endorphine levels of the body were examined before and after the treatment. RESULTS: After statistical analysis of the data a significant decrease of cortisol levels of patients was found, which was not directly correlated with radon concentration. In the case of thyroid hormones, there were no significantly detectable changes of the hormone levels except for low radon concentration levels a significant decrease in the free thyroxine and the thyreoiedea stimulating hormone level of male patients was observed. CONCLUSION: Speleotherapy has an effect on the level of endocrine hormones; however, no direct correlation with differences in radon level was found. For patients whose endocrine levels fell outside the normal endocrine parameter values, more striking changes in endocrine hormone levels were seen, but changes of these parameters could not be statistically analyzed due to the small number of cases.