Microscopy and microanalysis study of the indium (In) behavior in the intestinal mucosa, the liver, the kidney and the testicle.

Several studies have demonstrated that In used in medicine has several impacts on organs like spleen and lungs after its systemic administration. In the present study, ultrastructural and microanalytical methods were used to investigate the impact of the presence of this element in the intestinal mucosa, the liver, the kidney and the testicle after its administration in two ways. After intraperitoneal administration, In was selectively concentrated in the lysosomes of hepatocytes, of tubular proximal convoluted cells and of Sertoli and Leydig cells. After intragastric administration, ultrastructural study showed that this element was concentrated in the lysosomes of duodenal enterocytes. Microanalytical methods showed that In was precipitated in those organelles in the form of insoluble phosphate salts. Similarly to other studies, it seemed that since In is a foreign element for the organism, it was precipitated in lysosomes, very probably due to the activity of an intralysosomal enzyme the acid phosphatase, to avoid its invasion to organism via the blood. This mechanism of precipitation of the mineral elements is of great interest in the process of defensive reaction of the organism against intoxication by foreign elements.

[Role of the duodenal and hepatic cells lysosomes in the phenomenon of gadolinium accumulation]. / Rôle des lysosomes des cellules duodénales et hépatiques dans le phénomène d'accumulation du gadolinium.

The behaviour of the intestinal mucosa and of the liver after an administration of a gadolinium salt has been studied in the Wistar rat using transmission electron microscopy, ion mass spectrometry, and electron probe microanalysis. Six hours after parenteral administration, gadolinium is concentrated with phosphorus in the lysosomes of hepatocytes and Küppfer cells. Six hours after its oral administration, gadolinium is detected in the duodenal enterocytes lysosomes, but never in those of the liver cells. It is suggested that this mechanism of local concentration limits the diffusion through the digestive barrier of foreign elements, some of them being toxic and none of them having a physiological function.

Secondary ion mass spectrometry as a tool for investigating radiopharmaceutical distribution at the cellular level: the example of I-BZA and (14)C-I-BZA.

UNLABELLED: Further development of nuclear medicine for imaging and internal radiotherapy demands a precise knowledge of the tissue and cellular distribution of radiopharmaceuticals. Ion microscopy (secondary ion mass spectrometry [SIMS]) may be particularly useful in this respect. We used SIMS to study the biodistribution of the melanoma-targeting molecule N-(2-diethylaminoethyl)-4-iodobenzamide (I-BZA), both in its native state and radiolabeled with (14)C. METHODS: C57BL6/J1/co mice bearing pulmonary colonies of B16 melanoma cells were injected with I-BZA or (14)C-I-BZA. Appropriate tissues were fixed and included in epoxy embedding resin for SIMS studies. The distribution of unlabeled I-BZA was studied by detecting its stable iodine atom ((127)I). (14)C-I-BZA distribution was studied by dual detection of (127)I and (14)C. The time course of I-BZA concentrations at sites of tissue fixation was studied by measuring the signal ratio of (14)C and the naturally occurring isotope (13)C. RESULTS: SIMS showed that I-BZA concentrated in the cytoplasm of tumoral melanocytes (melanoma cells) and in the cytoplasm of tumor-infiltrating macrophages (melanophages). I-BZA was also detected in the cytoplasm of normal melanocytes in the pigmented structures of skin and eye. Interpretation of I-BZA distribution by using electron micrographs of adjacent sections showed that the intracytoplasmic melanin-rich organelles (melanosomes) were responsible for I-BZA retention. The distributions of (127)I and (14)C after (14)C-I-BZA injection were identical, even when I-BZA was separately labeled with (14)C at 2 different positions, indicating the stability of the amide bond of I-BZA. The time course of the (14)C/(13)C ratio in the melanosomes of melanoma cells suggested a retention half-life of about 38 h. CONCLUSION: Contrary to previous suggestions that I-BZA fixes principally to sigma-1 membrane receptors, our results strongly indicate that I-BZA associates with intracytoplasmic melanin pigments. Early I-BZA accumulation, in both melanocytes and melanophages, suggests that this compound fixes to preformed melanin rather than being incorporated during de novo melanin synthesis. These quantitative and qualitative data obtained with I-BZA illustrate the excellent potential of SIMS for studying the biologic fate of radiopharmaceuticals.

[Meteorological data and risk assessment in France after the Chernobyl accident (26 April 1986). Historical update]. / Données métrologiques et évaluation des risques en France lors de l'accident de Tchernobyl (26 avril 1986). Mise au point historique.

The authors indicate the origin of the data used by the French Public Health Authority in 1986 to estimate the risk of the radioactive fall out following the Chernobyl accident. The technical means developed in order to establish this data, and the precedent experience gained, are described. The principal results are given. The terms of the 28 May 1986 note to the Academy of Sciences by R. Latarjet, which concluded that the low level of this fallout did not justify any countermeasure, except the control of the imported food, are confirmed. Rational dispositions are required in order to improve the information of the population, referring to the Swedish model, which involves the intervention of the medical staff specialized in radiotoxicology, radiopathology, nuclear medicine, and especially trained.

Comparison of the intracellular behavior of gold (Au) and indium (In) in testicle after their parenteral administration.

The subcellular behavior of several mineral elements was studied using modern techniques of observation like transmission electron microscopy and analysis like electron probe microanalysis and secondary ion mass spectrometry. In the present ultrastructural and analytical investigations, we undertake to compare the intracellular behavior of a heavy metal, gold, and a III-A group element, indium, on rat testicular tissues after their parenteral administrations. Our ultrastructural results showed that while gold was found only in the lysosomes of Leydig cells under electron dense needles, indium was observed as electron-dense deposits in the lysosomes of both Leydig and Sertoli cells. No ultrastructural modifications were observed in the testicular tissues of the control rats. The microanalytical study showed that gold was concentrated in lysosomes with sulfur as a sulfate crystalline structure whereas indium was concentrated in the same organelle as insoluble phosphate salt. These results demonstrated that testicular Leydig and Sertoli cells have the ability to selectively concentrate indium but gold was concentrated only in the first kind of cells. The mechanism implicated in this concentration phenomenon is a biochemical one involving intralysosomal hydrolytic enzymes, the acid phosphatase and the arylsulfatase. This mechanism occurs in order to protect the organism and to avoid the presence of toxic metals under soluble and free form.

In nephrotic syndromes podocytes synthesize and excrete proteins into the tubular fluid: an electron and ion microscopic study.

Described here are the findings of an electron and ion microscopic study of renal biopsies of young children, with a particular attention to the intracytoplasmic and intranuclear changes observed in the podocytes of the proteinuric patients. In the cytoplasm, there is a considerable development of the ergastoplasm, associated with a dilatation of the endoplasmic reticulum and with the formation of large vacuoles containing nitrogen and sulfur. These changes are characteristics of cells synthesizing and excreting proteins. In the nuclei of many podocytes, the most striking change is a complete or quasi-complete disappearance of condensed chromatin, suggesting an intense transcription activity of the corresponding cells. The amount of the proteins excreted from the podocytes must be considered as significant, even if a quantitative evaluation was not possible.

The use of secondary ion mass spectrometry (SIMS) to evaluate internal contamination.

Secondary ion mass spectrometry (SIMS) permits the detection of stable and radioactive elements in microvolume. Based on the ablation of specimens by ion bombardment, this mass spectrometry method allows a rapid assessment of trace elements in biological samples and enables accurate isotopic ratio determination. In this work, an application of SIMS in studies involving element microdistribution is illustrated on the basis of analyses of duodenal tissue sections from rats contaminated with either cerium or thorium. For this purpose, tests are performed with SIMS to analyze tissue sections obtained 12, 24 and 48 hr after contamination. In this report, strengths and limitations of SIMS are pointed out as an important tool in biological research.

Histological changes in rat duodenum mucosa after whole-body gamma irradiation.

In order to understand the mechanisms of intestinal injuries due to ionizing radiation, various groups of rats have been whole-body irradiated by gamma-rays at two dose rates (1 Gy/min and 1 Gy/hr), three doses (1, 2 and 4 Gy) and two post-irradiation times (24 and 48 hr). Duodenum samples of the animals were prepared for light microscopy, according to classical methods for histology and TUNEL reaction. A small number of morphological differences were observed within the mucosa between the two dose rates used. The extent and the number of lesions were more important at the slower dose rate (1 Gy/hr) and increased with the total dose. Clear cavities were seen inside the lamina propria which appeared like capillaries free of blood cells. The mitotic index calculated from crypt cells showed a regular decrease with the dose, which was exacerbated at 48 hr post-irradiation. On the other hand, the apoptotic index increased with the dose and the postirradiation time. Our results lead to hypothesize another mechanism of intestinal mucosa renewal allowing to explain mucosa denudations observed after radiotherapy. Thus we propose a new concept in which the duodenal mucosa renewal may occur by whole villi shedding into the duodenal lumen.

Non-medical exposure to radioiodines and thyroid cancer.

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.

Bioquímica da esquistossomose mansônica: envolvimento dos siderossomos nos processos inflamatórios hepáticos / Biochemistry of schistosomiasis mansoni: involvement of siderosomes in hepatic inflammatory processes

Os processos inflamatórios que se desenvolvem durante as etapas avançadas da esquistossomose mansônica foram relacionados, com o acúmulo de siderossomos, a capacidade dos ions ferrosos/férricos de desencadearem a formaçäo de radicais livres e a peroxidaçäo de lipídios membranáceos, assim como à diminuiçäo da estabilidade das membranas dos diversos componentes do comportamento lisossômico hepático. Os lisossomos isolados de figados de camundongos infectados por 100 cercárias, com 80 e 100 dias de infecçäo, foram respectivamente, 2,5 e quase 4 vezes mais frágeis que os controles, isolados de figados de camundongos näo infectados. A presença de siderossomos em grande quantidade foi demonstrada por espectrometria aos raios-X