Nicole Colas-Linhart

Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C.

OBJECTIVE Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy.

Aggression and the Three Opioid Families (Endorphins, Enkephalins, and Dynorphins) in Mice

Previous studies suggest that brain opioid activity decreases aggression in animal models. The main objective of the current study was to examine the possible genetic relationship between intermale aggression and brain levels of enkephalins, endorphins, and dynorphins in 11 inbred strains of mice. Pursuit, rattling, and attack behaviors were observed in a dyadic encounter with a standard opponent. It appeared that, as expected, enkephalins and endorphins were always negatively correlated with aggression scores. The findings indicate that brain Met5 -enkephalin levels were significantly and highly positively correlated with attack latency. Brain adrenocorticotrophic hormone (ACTH) and β-endorphin levels were significantly and negatively correlated with the number of rattlings, which is consistent with the hypothesis that rattling is a stress-related behavior. In contrast with Met5-enkephalin, ACTH and β-endorphin, the correlations between dynorphin A and aggression scores were nonsignificant and very low. These preliminary results suggest that common genetic sources of variation contribute to differences between the 11 inbred strains in both endogenous opioidergic systems and intermale aggression. Further studies are required to confirm the genetic relationship between offensive aggression and brain enkephalins and endorphins and to better understand the mechanisms underlying the role of endogenous opioids in offensive aggression with regard to opioid receptor activity.

Incidence of Dysthyroidism during Interferon Therapy in Chronic Hepatitis C

Seventy-nine patients (40 males, 39 females) were enrolled in a prospective study of lymphoblastoid interferon-alpha (IFN), 3-5 MU three times weekly. They were randomly assigned to receive either 12 months of IFN therapy, or to 6 months of observation followed by 6 months of IFN therapy. The thyroid functional and immunological status was checked every other month during and after treatment. Before treatment, antithyroid antibodies were found in 6 patients (7.5%). Two were hypothyroid and were excluded from the study before starting IFN therapy. Seventy-seven patients received IFN therapy. Of these, thyroid abnormalities appeared in 6 (7.5%). Hyperthyroidism was observed in 3 patients. Two recovered within a few months, but 1 developed subsequent hypothyroidism. Hypothyroidism was observed in 2 patients. TSH blood values were persistently abnormal, but thyroid antibody levels remained increased and fluctuating. Thyroid function usually recovered within a few months; but 2 patients required hormonal therapy and 1 was treated with carbimazole. In 1 patient, a small thyroid papillary carcinoma was observed, but no evidence of relationship with the liver disease or with IFN therapy was found. In a patient with chronic hepatitis C, systematic thyroid assessment should be performed before initiating IFN therapy, including clinical examination, and measurement of TSH and anti-thyroperoxidase antibodies (TPO Ab). During treatment, a TSH assay every other month appears to be necessary and sufficient.

Non-medical exposure to radioiodines and thyroid cancer

Abstract. The Chernobyl accident, which occurred 32 years after the accidental exposure of Marshall islanders, resulted in the exposure of neighbouring populations to a mixture of iodine isotopes and in an increased incidence of thyroid cancer. The highest thyroid doses were received by the youngest age groups. This review describes the existing evidence, and examines factors that may have increased the risk. It also stresses problems with contemporary thyroid measurements, and the lack of information on the sensitivity of the thyroid to short-lived iodine isotopes and iodine-131. Practical considerations for nuclear physicians, epidemiologists and thyroidologists are discussed in the light of this major accident.

Induction of unstable and stable chromosomal aberrations by 99mTc : in-vitro and in-vivo studies

BackgroundBiological dosimetry, which determines the dose of acquired radiation by measuring radiation-induced variation of biological parameters, can help assess radiation damage in an individual. Evaluation of radiation exposure requires setting up reference curves for each type of radiation. AimTo evaluate the potential induction of chromosome aberrations by a clinical diagnostic dose of 99mTc. MethodsDicentrics, rings, excess fragments, complete reciprocal translocations and incomplete reciprocal translocations were scored in peripheral blood lymphocytes from patients exposed to a 99mTc bone scintigraphy. A specific relationship between the radiation dose delivered by 99mTc and the frequency of stable and unstable chromosomal aberrations was established in vitro to estimate whole-body dose. Chromosome analysis using fluorescence plus Giemsa and fluorescence in-situ hybridization was undertaken on six patients before and after a 99mTc bone scintigraphy. Dicentrics, rings, excess fragments, and translocations were scored in blood lymphocytes after in vitro 99mTc external irradiation in order to construct dose calibration curves. ResultsAnalysis of the in-vitro data shows that the number of both unstable and stable aberrations has a quadratic linear relationship to the dose. Our in-vivo irradiation studies showed that activities of 99mTc-hexamethylene diphosphonate (99mTc-HDP) used for bone investigations do not induce any additional unstable chromosome aberrations and translocations. The frequencies obtained did not differ significantly from background values. Conclusions99mTc can produce unstable and stable chromosomal aberrations in vitro. 99mTc-HDP administration does not induce supplementary chromosomal aberrations. The dose–response curves will allow a more accurate evaluation of the risk related to in-vivo administration of 99mTc labelled radiopharmaceuticals, and they can be used to assess the safe upper limit of injected activity in humans.

Thyroid cell irradiation by radioiodines: a new Monte Carlo electron track-structure code

The most significant impact of the Chernobyl accident is the increased incidence of thyroid cancer among children who were exposed to short-lived radioiodines and 131-iodine. In order to accurately estimate the radiation dose provided by these radioiodines, it is necessary to know where iodine is incorporated. To do that, the distribution at the cellular level of newly organified iodine in the immature rat thyroid was performed using secondary ion mass microscopy (NanoSIMS50). Actual dosimetric models take only into account the averaged energy and range of beta particles of the radio-elements and may, therefore, imperfectly describe the real distribution of dose deposit at the microscopic level around the point sources. Our approach is radically different since based on a track-structure Monte Carlo code allowing following-up of electrons down to low energies (» 10eV) what permits a nanometric description of the irradiation physics. The numerical simulations were then performed by modelling the complete disintegrations of the short-lived iodine isotopes as well as of 131I in new born rat thyroids in order to take into account accurate histological and biological data for the thyroid gland.