IN VIVO public monitoring in emergency exposure scenarios by means of spectrometric and non-spetrometric devices.

In a nuclear or radiological accident scenario, when potentially members of the public can undergo internal contamination by anthropogenic radionuclides released in the atmosphere, effective methods that can be used directly in the field to perform a fast scan for internal contamination on a large number of individuals can play a major role to undertake appropriate countermeasures. Specific attention should be paid to the individual monitoring of children since they constitute the sensitive population group with the highest risk of developing cancer. At the ENEA Casaccia Research Center in Rome (Italy), monitoring procedures based on a portable HPGe detector and ratemeters were tested in the field. A total of 170 acquisitions of uncontaminated volunteers for the blank measurements were collected, 105 acquisitions on adult and 65 acquisitions on 10-y/o children. The detection limit calculation, in terms of activity taken up (Bq), was carried out according to the Standard ISO's 11929 and 28218, whereas the corresponding 'minimum effective dose' (mSv) was calculated based on international commission on radiological protection (ICRP) Publications 134, 137 and 141. Results and evaluations of the measurement campaign are presented and discussed in respect to the aspects reported in the current literature.

Large-scale individual monitoring of internal contamination by gamma-emitting radionuclides in nuclear accident scenarios.

The results obtained in a measurement campaign concerning internal contamination by the gamma-emitting radionuclides of a large number of individuals are presented in this work. The aim is to assess the effectiveness of the spectrometric method in an emergency response following a nuclear power plant accident or a spread of radionuclides in the atmosphere due to an act of terrorism. An HPGe portable spectrometer, deployed in a collective protection apparatus, was used for both whole-body and thyroid measurements. An adult bottle mannequin absorption (BOMAB) and thyroid phantoms were used to evaluate the detector performance. The BOMAB phantom was provided by the Italian Institute of Ionizing Radiation Metrology (INMRI) for the ENEA intercomparison exercise. Thyroid phantoms were provided by the Belgian Nuclear Research Centre for the 'Child and Adult Thyroid Monitoring After Reactor Accident' European intercomparison exercise. The instrument performance was further evaluated by collecting spectral data from healthy volunteers, using acquisition times of 180 s and 100 s, respectively, for the whole-body and thyroid measurements. The detector showed good accuracy in quantifying radionuclide activities in the adult BOMAB and in the thyroids of persons of all ages. The proposed method allows us to detect in vivo activity leading to a committed effective dose E(50) and committed thyroid equivalent doses H T greater than 2 mSv due to all gamma-emitting fission products, if the scan is performed within five days after intake. Assuming, for instance, an acute inhalation of 137Cs and 131I, the obtained detection limit values for adults lead to a E(50) value equal to 0.08 mSv and an H T value of 0.27 mSv. The E(50) and H T values show that the proposed method can be successfully used when the dose assessment must be rapidly performed for a large number of individuals in the eventuality of the scenarios previously mentioned.

Large-scale individual thyroid monitoring following nuclear accidents by means of non-spectrometric devices.

In order to properly respond to an emergency caused by an accident in a nuclear power plant with a spread of radionuclides in the atmosphere, we propose a field procedure to perform a large-scale individual thyroid monitoring of internal contamination due to inhalation of 131I, by means of non-spectrometric equipment, in particular dose rate meters. Specific attention is paid to the individual monitoring of children, because of the very high radiosensitivity of the child's thyroid to the carcinogenic effects of ionising radiation. The device performance was evaluated by measuring mock iodine sources provided in the Child and Adult Thyroid Monitoring After Reactor Accident (CAThyMARA) intercomparison and, just for a scintillator dose rate meter, by means of 60 s acquisitions of healthy volunteers' thyroids. All the devices showed a remarkable accuracy in quantification of equivalent 131I activity in the thyroids of persons of all ages. The selected scintillator dose rate meter showed detection limit values resulting in a maximum committed equivalent dose to thyroid HT, assuming an acute 131I inhalation occurred five days before the measurement, equal to 10 mSv (related to five-year-old children). Considering the level of HT values associated with the calculated detection limit activities, the proposed procedure has a significant sensitivity to be used for fast internally thyroid monitoring in nuclear or radiological emergencies, allowing daily monitoring a large amount of individuals.

Environmental radioactivity analyses in Italy following the Fukushima Dai-ichi nuclear accident.

Following the Fukushima power plants accident on the 11th March 2011, the radioactivity monitoring programme at the Italian ENEA research centres was activated in order to detect the possible new input of radionuclides through atmospheric transport and precipitation. Measurements of (131)I and (134,137)Cs were carried out on atmospheric particulate, atmospheric deposition, seawater and mussels and sheep milk. In the daily samples of air particulate, (131)I was detectable between March 28 and April 12, with extremely low concentrations (<1 mBq m(-3); the detection limit for (131)I was ~0.2 mBq m(-3)) while Cs isotopes were always below the detection limit (<0.2 mBq m(-3)). The two main episodes of (131)I atmospheric deposition were registered in La Spezia research centre, around March 28 and April 15, reaching values of 17.8 ± 1.1 and 8.0 ± 2.5 Bq m(-2) respectively; maximum values of (134)Cs and (137)Cs were 0.11 ± 0.03 and 0.17 ± 0.02 Bq m(-2), respectively, detected in Brasimone research centre in April (reference date April 15). Mussels and seawater were collected in the Gulf of La Spezia: only mussels after the main (131)I deposition, on March 28, contained a measurable, although very small, amount of (131)I (0.18 ± 0.05 Bq kg(-1), detection limit (131)I = 0.03 Bq kg(-1) wet weight - soft parts). The (131)I was also detected in sheep milk in Rome (Casaccia research centre) until May 5, showing a maximum concentration of 4.9 ± 0.4 Bq L(-1). As for other European Countries for which data are available, activity levels remain of no concern for public health.

Internal dosimetry: towards harmonisation and coordination of research.

The CONRAD Project is a Coordinated Network for Radiation Dosimetry funded by the European Commission 6th Framework Programme. The activities developed within CONRAD Work Package 5 ('Coordination of Research on Internal Dosimetry') have contributed to improve the harmonisation and reliability in the assessment of internal doses. The tasks carried out included a study of uncertainties and the refinement of the IDEAS Guidelines associated with the evaluation of doses after intakes of radionuclides. The implementation and quality assurance of new biokinetic models for dose assessment and the first attempt to develop a generic dosimetric model for DTPA therapy are important WP5 achievements. Applications of voxel phantoms and Monte Carlo simulations for the assessment of intakes from in vivo measurements were also considered. A Nuclear Emergency Monitoring Network (EUREMON) has been established for the interpretation of monitoring data after accidental or deliberate releases of radionuclides. Finally, WP5 group has worked on the update of the existing IDEAS bibliographic, internal contamination and case evaluation databases. A summary of CONRAD WP5 objectives and results is presented here.

Coordination of research on internal dosimetry in Europe: the CONRAD project.

The EUropean RAdiation DOSimetry Group (EURADOS) initiated in 2005 the CONRAD Project, a Coordinated Network for Radiation Dosimetry funded by the European Commission (EC), within the 6th Framework Programme (FP). The main purpose of CONRAD is to generate a European Network in the field of Radiation Dosimetry and to promote both research activities and dissemination of knowledge. The objective of CONRAD Work Package 5 (WP5) is the coordination of research on assessment and evaluation of internal exposures. Nineteen institutes from 14 countries participate in this action. Some of the activities to be developed are continuations of former European projects supported by the EC in the 5th FP (OMINEX and IDEAS). Other tasks are linked with ICRP activities, and there are new actions never considered before. A collaboration is established with CONRAD Work Package 4, dealing with Computational Dosimetry, to organise an intercomparison on Monte Carlo modelling for in vivo measurements of (241)Am deposited in a knee phantom. Preliminary results associated with CONRAD WP5 tasks are presented here.

Cushing's syndrome patient who exhibited congestive heart failure.

Cushing's Syndrome (CS) may sometimes lead to dilated cardiomyopathy, even though this condition can be partially or completely reversed after treatment. In this article we report the case of a 28-yr-old woman with CS secondary to adrenal adenoma who exhibited congestive heart failure as an initial symptom. Two weeks before being admitted to our hospital, the patient started complaining of shortness of breath, orthopnea, paroxysmal nocturnal dyspnea and generalized edema. A physical examination did not reveal signs of hypercortisolism. Chest auscultation revealed bilateral diffused crepitation; blood pressure was 180/120 mmHg with heart rate of 90 beats/min. A chest X-ray showed a cardiac shade enlargement due to congestive heart failure. Transthoracic echocardiography demonstrated a dilated left ventricle and an impaired left ventricular systolic function. The patient's urinary cortisol excretion was elevated and circadian rhythm of cortisol was absent. ACTH level was low. In addition, plasma cortisol failed to decrease after administration of dexamethasone. An abdominal magnetic resonance imaging scan showed a 7-cm right adrenal mass. The patient was administered oxygen, spironolactone, ACE-inhibitor and the signs and symptoms of heart failure gradually improved. A laparoscopic right adrenalectomy was performed and pathological examination of the gland showed a benign adrenocortical adenoma. After the adrenalectomy the patient was started on hydrocortisone therapy and 5 months later the wall thickness of the left ventricle was within normal range and the patient's blood pressure was 130/80 mmHg. In conclusion we report the case of heart failure as the main clinical symptom in CS secondary to adrenal adenoma.

Assessment of total body potassium in healthy Italian men.

BACKGROUND: Whole-body (40)K counting is a valuable tool for assessing cellular changes in body composition with ageing. AIM: The objectives of this study were to assess total body potassium (TBK) and body cell mass (BCM) differences with age, and to compare TBK and BCM between individuals with a body mass index (BMI) < 25 kg m(-2) versus > 25 kg m(-2). SUBJECTS AND METHODS: Body composition of 840 healthy Italian men, 18-70 years of age, was measured by whole-body counting of (40)K. BCM (kg) was calculated as 0.00833 x TBK (mmol). RESULTS: Body weight did not differ among groups. TBK, TBK/height, TBK/body weight, and BCM were significantly lower for the 51-70-year-old group compared with all other groups. The 51-70-year-old group with a BMI < 25 kg m(-2) had significantly lower TBK, TBK/height, and BCM than all other decades with a BMI < 25 kg m(-2); whereas TBK/body weight was significantly lower than the 18-30 and 31-40-year-old groups. The 51-70-year-old group with a BMI > 25 kg m(-2) had significantly lower TBK, TBK/height, TBK/body weight, and BCM than all other decades with a BMI > 25 kg m(-2). CONCLUSION: TBK and BCM decrease significantly with ageing, which could result in decreased functional capacity in older adults.

Two dimerization domains in the trans-activation response RNA-binding protein (TRBP) individually reverse the protein kinase R inhibition of HIV-1 long terminal repeat expression.

Trans-activation response (TAR) RNA-binding protein (TRBP) is a cellular protein that binds to the human immunodeficiency virus-1 (HIV-1) TAR element RNA. It has two double-stranded RNA binding domains (dsRBDs), but only one is functional for TAR binding. TRBP interacts with the interferon-induced protein kinase R (PKR) and inhibits its activity. We used the yeast two-hybrid assay to map the interaction sites between the two proteins. We show that TRBP and PKR-N (178 first amino acids of PKR) interact with PKR wild type and inhibit the PKR-induced yeast growth defect in this assay. We characterized two independent PKR-binding sites in TRBP. These sites are located in each dsRBD in TRBP, indicating that PKR-TRBP interaction does not require the RNA binding activity present only in dsRBD2. TRBP and its fragments that interact with PKR reverse the PKR-induced suppression of HIV-1 long terminal repeat expression. In addition, TRBP activates the HIV-1 long terminal repeat expression to a larger extent than the addition of each domain. These data suggest that TRBP activates gene expression in PKR-dependent and PKR-independent manners.

Characterization of TRBP1 and TRBP2. Stable stem-loop structure at the 5' end of TRBP2 mRNA resembles HIV-1 TAR and is not found in its processed pseudogene.

TRBP1 and TRBP2 cDNAs have been isolated based on the ability of the protein that they encode to bind HIV-1 TAR RNA. The two cDNAs have different 5' end-termini resulting in 21 additional amino acids for TRBP2 protein compared to TRBP1. The corresponding gene is conserved in mammalian species. By PCR amplification of a human library, we have isolated an additional 22 nucleotides in the 5' end of TRBP2 cDNA. Based on the addition of these 22 new nucleotides, the first 87 nucleotides of TRBP2 mRNA can fold into a stable stem-loop structure that resembles TAR RNA. We have also isolated the DNA sequence that represents the TRBP processed pseudogene. The absence of full alignment between TRBP2 full-length cDNA and this sequence suggests that the stem-loop structure could have prevented a complete reverse transcription during pseudogene formation. Using different antibodies, three forms of TRBP can be identified in primate cells at 40, 43 and 50 kD, suggesting a differential expression from the cDNAs and post-translational modifications. Both TRBP1 and TRBP2 activate the basal and the Tat-activated level of the HIV-1 LTR in human and murine cells. Our data indicate that TRBP proteins act at a level prior to Tat function. TRBP could contribute to improved HIV expression in murine models.

Development and characterisation of a head calibration phantom for in vivo measurements of actinides.

The investigation of actinides' internal contamination in human body makes use of a variety of techniques. In large scale screening the technique of "in vivo" evaluation of bone 241Am burden via the determination of the nuclide activity in the skull is often used. For this purpose, adequate calibration procedures and standard phantoms are needed. The present paper summarises the studies and technical procedures followed for the development of a calibration phantom based on a commercial Alderson angiographic head in which a set of 24 241Am point sources were embedded. A theoretical study was first carried out, at the ENEA Institute for Radiation Protection, using the MCNP4-B Monte Carlo code to determine the point source distribution that closely approximates a homogeneous bone contamination. The numerical models were also used to evaluate the resulting degree of approximation. The point sources were prepared at the ENEA National Metrology Institute for ionising radiation quantities and were traceable to the Italian national standard of radionuclide activity. The sources were prepared by quantitatively dispensing a liquid solution onto a plastic disc. The activity of each source was checked by gamma-ray spectrometry and the reproducibility of the activity values was determined. Each source was then placed in the optimum position in the skull, given by the Monte Carlo modelling, by a precision mechanical device. The phantom was finally used to calibrate a whole body counter operating at the ENEA Institute for Radiation Protection. The paper reports the main theoretical and experimental aspects of this work, and also discusses the results of the first calibrations.

Radiation dose to the testes after 131I therapy for ablation of postsurgical thyroid remnants in patients with differentiated thyroid cancer.

UNLABELLED: Radioiodine-131 is used in differentiated thyroid cancer (DTC) for ablation of postsurgical thyroid remnants and destruction of metastases. The question may be raised of whether 131I treatment of DTC in male patients may give an irradiation dose to the testes that could impair fertility. Few data in the literature concern the dose absorbed by the testes after 1311 therapy for DTC. Because 131I kinetics may be altered by the hypothyroid condition commonly present at the time of treatment and by the radioiodinated iodoproteins released by the damaged thyroid tissue, the dose values reported in the International Commission on Radiological Protection (ICRP) tables for euthyroid men may not be appropriate. To clarify this problem, three male subjects undergoing 131I therapy for ablation of thyroid remnants shortly after thyroidectomy for DTC were studied. METHODS: The mean administered activity was 1256 MBq, and the duration of the study was 2 wk. The gamma dose was measured by thermoluminescent dosimeters (TLDs) applied to the lower poles of the testes. Correction factors were calculated for the distance of the TLD from the center of the testes and for attenuation by the testes of the gamma rays reaching the TLD. After correction, the gamma dose to the testes ranged from 21 to 29 mGy. The gamma dose calculated by the Medical Internal Radiation Dose (MIRD) method from blood and urine samples was similar (18-20 mGy) to that measured by TLDs. The beta dose was estimated by the MIRD method from blood activity and testicular volume and ranged between 14 and 31 mGy. RESULTS: The total (beta and gamma) doses to testes were 30, 33 and 43 microGy/MBq in the three subjects. CONCLUSION: These values are close to those derived from the ICRP tables (26-37 microGy/MBq 131I) for euthyroid subjects. The present data indicate that significant irradiation is delivered to the testes after the administration of the 131I ablative dose to thyroidectomized patients. The relevance of the radiation absorbed by testes on fertility remains to be established.

Identification of limiting steps for efficient trans-activation of HIV-1 promoter by Tat in Saccharomyces cerevisiae.

Cellular context is an important determinant for the activity of Tat, the trans-activator of human immunodeficiency virus (HIV). We have investigated HIV-1 promoter expression and trans-activation in Saccharomyces cerevisiae to provide clues about the limiting steps for Tat activity in this organism. A minimal 43-nucleotide HIV promoter (HIV43) has the activity of a weak yeast promoter in the presence or absence of various enhancer binding sites (bs), whereas the entire long terminal repeat is not expressed. None of these constructs could be trans-activated by Tat. Fusion proteins Gal4 binding domain (BD)-Tat48 and Gal4BD-Tat72 are active with different efficiencies on various yeast promoters that have Gal4 bs. They have 70 and 50% of Gal4 wild type activity on hybrid HIV promoters fused to Gal4 bs only in the presence of AP1 bs. This study shows that trans-activation of the HIV-1 promoter by Tat occurs in yeast when Tat is targeted to the promoter and a functional enhancer activity is present. Sp1 function and Tat transfer from the RNA to the promoter are two major elements for in vivo trans-activation of HIV-1 that are defective in S. cerevisiae but can be replaced by functional equivalents.

Twenty-four-hour pattern of hunger sensation in obesity complicated by type 2 diabetes mellitus: a pattern recognition by spectral analysis.

Hunger sensation (HS) in humans physiologically shows intraday (circadian) and within-day (ultradian) recursivity. This intrinsic periodicity was investigated by applying the cosinor method and spectral analysis to the 24-hour profile of HS (orexigram) derived by a self-rating score (from 1 to 10 hunger units [HU]) recorded every half-hour. The study of circadian and ultradian recursivity on the orexigram was performed in 30 diabetic obese patients ([DOPs], 14 men and 16 women aged 22 to 62 years; body weight, 77 to 130 kg; body mass index, 31-47). The control group consisted of 30 clinically healthy subjects ([CHS], 15 men and 15 women aged 21 to 60 years; body weight, 65 to 72 kg; body mass index, 23 to 25). DOPs showed two types of orexigrams in which hunger was felt with limitation to the diurnal part of the day or with extension to the night, respectively. The type 1 orexigram was characterized by a normal spectrum and circadian rhythm. The type 2 orexigram was characterized by subsidiary ultradian components associated with an abnormal elevation of the circadian mesor and a significant delay of the circadian phase, as the spectral analysis was indicative of a structural difference in the frequencies that sustain the intraday and within-day recursivity of the HS. Accordingly, DOPs can be recognized by their orexigram as "eurectic" or "hyperrectic" to indicate subjects with a normal or an exaggerated HS, respectively, during the 24-hour span.

Chronobiometric identification of disorders of hunger sensation in essential obesity: therapeutic effects of dexfenfluramine.

In human beings, hunger is a proprioceptive signal that shows intraday (circadian components) and within-day (ultradian components) recursivity. Both periodic components can be investigated by chronobiometric procedures by combining the Cosinor method with spectral analysis. A 24-hour profile of hunger sensation (HS) can be plotted on a 1-to-10 scale of intensity using self-rated scores performed every half-hour of the day. Circadian and ultradian components were studied in 60 patients affected by essential obesity (20 men and 40 women; mean age, 38.4 years; mean body weight, 101 kg) before and after treatment with dexfenfluramine (Isomeride; Servier, Orléans, France) 15 mg orally twice daily, for 30 days. The control group consisted of 30 clinically healthy subjects (15 men and 15 women; mean age, 37.5 years; mean body weight, 69 kg). Chronobiometric analysis shows three patterns in obese patients, which suggests that HS may be normal (eurectic obesity), exaggerated (hyperrectic obesity), or diminished (hyporectic obesity). After dexfenfluramine administration, HS was showed a substantial decrease in the daily mean level. The spectrum of resolution in circadian and ultradian components was found to be maintained in eurectic obesity and partially readjusted in hyperrectic and hyporectic obesities. This demonstrates that dexfenfluramine acts not only as an anorectic but also as a chronizer by interfering with the recursive components of HS. The anorectic and chronizing effects suggest that dexfenfluramine is a "chronoanorectic drug" that interacts with the chronobiologic properties of the serotoninergic system.

Blood pressure 24-hour pattern in two industrialized countries (Italy and Japan) with a different culture in salt intake.

This study investigates the blood pressure (BP) 24-hour pattern in representative samples of 2 industrialized countries, Italy and Japan, showing different cultures in salt intake. BP was monitored by means of a noninvasive ambulatory device whose readings were analyzed by means of chronobiometric procedures. The results show that the 24-hour BP pattern is not substantially different in Italian and Japanese subjects. In particular, the expected lower BP in the Italians was not detected despite their lower salt intake. Because the 24-hour mean BP value was seen not to be proportional to salt intake, the hypothesis is formulated that maintenance of the pressure regimen within a given range of variability is a principle of human physiology. To comply with this rule the Japanese people are supposed to have ethnically developed a certain resistance to dietary salt for which their cardiovascular apparatus is protected (phyletic escape to dietary sodium excess).

Thyroid hypofunction related with the progression of human immunodeficiency virus infection.

Thyroid function was evaluated in 119 human immunodeficiency virus (HIV) infected patients at different stages of infection, compared with euthyroid normal subjects and hepatitis C virus infected blood donors as control groups. The low T3 state, well documented in severe nonthyroidal illnesses, was not found in these HIV infected patients. They showed lower FT4 levels and higher TSH and TBG values than euthyroid normal controls. These findings suggested a thyroid hypofunction becoming more evident with the progression of the infection as also supported by the presence of antithyroid autoantibodies mainly found in the symptomatic stages of the infection.

A chronobiological approach to circulating levels of renin, angiotensin-converting enzyme, aldosterone, ACTH, and cortisol in Addison's disease.

This study deals with a chronobiological approach to the circadian rhythm of the renin-angiotensin-aldosterone system (RAAS) and the ACTH-cortisol axis (ACA) in patients with Addison's disease (PAD). The aim is to explore the mechanism(s) for which the circadian rhythmicity of the RAAS and ACA takes place. The study has shown that both the RAAS and ACA are devoid of a circadian rhythm in PAD. The lack of rhythmicity for renin and ACTH provides indirect evidence that their rhythmic secretion is in some way related to the circadian oscillation of aldosterone and cortisol. This implies a new concept: a positive feedback may be included among the mechanisms which chronoregulate the RAAS and ACA.

Circadian rhythm of cardiac output, peripheral vascular resistance, and related variables by a beat-to-beat monitoring.

This study aimed to explore the 24-h patterns of stroke volume, cardiac output, and peripheral vascular resistance along with other correlated variables, such as left ventricular ejection time, ejection velocity index, thoracic fluid index, heart rate, and blood pressure. The study was performed on 12 clinically healthy subjects by means of a noninvasive beat-to-beat monitoring using the thoracic electric bioimpedance technique associated with the automated sphygmomanometric recording. Time data series were analyzed by means of chronobiological procedures. The results documented the occurrence of a circadian rhythm for all the variables investigated, giving relevance to the beat-to-beat bioperiodicity of cardiac output and peripheral vascular resistance. Temporal quantification of the investigated variables may be useful for a better insight of the chronophysiology of the cardiovascular apparatus.