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

BACKGROUND: Biological 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. AIM: To evaluate the potential induction of chromosome aberrations by a clinical diagnostic dose of 99mTc. METHODS: Dicentrics, 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. RESULTS: Analysis 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. CONCLUSIONS: 99mTc 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.     

Estimating the 5-Percentile of the Species Sensitivity Distributions Without Any Assumptions about the Distribution

A non-parametric method is described to estimate the hazardeous concentration for p% of the species, the HCp, and the confidence limits for this value, the HCp(). For this method, all observed sensitivities are ordered from high to low sensitivity. The HC5 is the k-th observation were k is the largest integer below 0.05×(n+1). It is described how the HCp() can be calculated. A table is presented for easy calculation of several conservative confidence limits for the HC5. For the HC5(0.05), a second table is presented which can be used to interpolate between the conservative estimate of the HC5(0.05) and the next higher observed concentration. The non-parametric HC5 and HC5(0.05) estimation is illustrated with an example of sensitivity data on malathion. For this data set, the log-normal HC5 and HC5(0.05) estimations appear to be conservative compared with the non-parametric estimate. It is stressed that HC5 and HC5(0.05) estimates will often be much more affected by the non-randomness of the species set for which sensitivity data are available than by the choice of the statistical method.     

Isoprenoids of the soft coral Sarcophyton glaucum: Nyalolide, a new biscembranoid, and other terpenoids

The chemical content of Sarcophyton glaucum, one of the more abundant soft corals on many coral reefs, collected from many seas, was thoroughly explored, resulting in the discovery of a large number of cembranoids, biscembranoids, sterols, and other secondary metabolites. The presently investigated Kenyan specimens of S. glaucum yielded three new metabolites, i.e., nyalolide (15), a biscembranoid, 16-oxosarcoglaucol acetate (16), a cembranoid, and the sesquiterpene guaiacophine (17). Nyalolide was also isolated from the Kenyan soft coral Sarcophyton elegans. The structures of the new compounds were elucidated by interpretation of their MS and 1D and 2D NMR experiments and, in the case of nyalolide, possessing 11 chiral centers, secured by X-ray diffraction analysis.     

Digestion rate of legume carbohydrates and glycemic index of legume-based meals

A study was performed to examine the rate of digestion of available carbohydrate in legumes and its mixtures with cereals, prepared as commonly eaten. The legumes and cereals studied were lentil (Lens sculenta), pea (Pisum sativum), bean (Phaseolus vulgaris, var tortola), rice (Oryza sativa) and spaghetti. Foods were purchased at the city market. Total starch content and the carbohydrate digestion rates were determined using the enzymatic method proposed by Englyst et al. Total starch levels ranged from 7.78 g/100 g in cooked flour bean to 20.6 g/100 g in a bean-spaghetti dish, and dietary fiber contents ranged from 2.4 g/100 g in a cooked 70:30 lentil-rice mixture to 5.26 g/100 g in a cooked whole bean. The rapid digestion rate carbohydrates showed values from 4.8 in the bean soup to 8.9 in the bean-spaghetti combination. The same results show, expressed as rapid available glucose (RAG), the amount of rapid carbohydrate/100 g food or meal as eaten, and as the starch digestion index (SDI), the percentage of rapid carbohydrate digestion rate in relation to the total amount of carbohydrate. The RAG values ranged between 5.0 for cooked beans and 10 for cooked beans and spaghetti, and the SDI ranged between 40 for cooked pea flour and 62 for cooked bean flour. Legumes prepared as soup showed a higher rapid digestion rate than legumes prepared as whole grain. The bean-spaghetti based-meal and the lentil-based meal showed glycemic index mean and standard deviation values of 76.8 +/- 43.4 and 49.3 +/- 29.5, RAG values of 7.0 and 6.0, and SDI values of 57 and 54, respectively. The knowledge of the importance of the carbohydrate digestion rates in human health in increasing, and probably will soon be used in the development of the food pyramid. The foods with a moderate fraction of rapid digestion rate, such as legumes, should be included in the base of the pyramid.     

Nongranulomatous anterior uveitis associated with alendronate therapy

We describe a case of acute nongranulomatous anterior uveitis associated with alendronate therapy, in an adult woman, without medical history of previous diseases, except for intercurrent problems of osteoporosis. The symptoms disappeared abruptly after anti-inflammatory therapy and discontinuation of alendronate. Side effects associated with ocular inflammation have been recently documented in 3 patients under alendronate therapy. Clinical and laboratory diagnosis of ocular inflammation syndromes are also reviewed.     

In vivo cell lineage analysis in cyproterone acetate-treated rat liver using genetic labeling of hepatocytes

Genetic labeling using recombinant retroviruses is a powerful strategy for the study of cell lineage in the liver. However, this type of vector is only able to infect dividing cells. The synthetic steroid cyproterone acetate (CPA) is mitogenic and carcinogenic in the adult rat liver. In this study, we used retroviral vectors carrying the nuclear targeted beta-galactosidase gene to selectively label and follow the fate of hepatocytes dividing on administration of CPA. Labeled cells as well as those in mitosis were preferentially located around the portal tract, whereas apoptotic bodies were predominant in the pericentral area. Labeled hepatocytes did not disappear after apoptosis, suggesting a preferential elimination of nontransduced cells. The presence of labeled binucleated hepatocytes showed the persistence of a binucleation process. Finally, we performed long-term analysis of labeled cells in transgenic animals tolerant for beta-galactosidase and treated with 2-acetylaminofluorene (2-AAF) to promote the growth of CPA-initiated hepatocytes. The presence of beta-galactosidase-positive hepatocyte clones showed that hepatocytes divided during treatment with 2-AAF. Only 3% of beta-galactosidase clones were positive for the placental form of glutathione S-transferase (GSTp), indicating the absence of a preferential appearance of preneoplastic foci in the population of beta-galactosidase-labeled hepatocytes. In conclusion, our results show that the mitogenic and tumor-initiating activities of CPA are directed toward different hepatocyte populations.     

Follicle-stimulating hormone activates mitogen-activated protein kinase in preneoplastic and neoplastic ovarian surface epithelial cells

To investigate the role of FSH in ovarian cancer development, the present study examined the expression of FSH receptor (FSH-R) and the effect of FSH on proliferation of normal, preneoplastic, and neoplastic ovarian surface epithelium (OSE) cells. Recently, immortalized OSE (IOSE) cell lines, including IOSE-29 (preneoplastic) and IOSE-29EC (neoplastic), were used. Our results indicated that FSH-R mRNA was expressed and that FSH exerted a growth stimulatory effect in normal, preneoplastic, and neoplastic OSE cells. To investigate the mechanism of the growth stimulatory effect, the activation of MAPKs by FSH was examined in preneoplastic and neoplastic OSE cells. Treatment with FSH resulted in MAPK activation of IOSE-29 and IOSE-29EC cells, whereas the stimulatory effect of FSH on cellular proliferation and MAPK activation was completely abolished in the presence of PD98059, a MAPK kinase inhibitor, suggesting that the growth stimulatory effect of FSH is mediated through MAPK activation in these OSE cells. In a time-dependent study, FSH significantly increased MAPK activity at 5-10 min in IOSE-29 cells. The activated MAPK declined to the control level after 20 min in these cells. Similarly, treatment with FSH significantly induced MAPK activation after 5 min and sustained it for 60 min in IOSE-29EC cells. In addition, treatment with FSH resulted in substantial phosphorylation of Elk-1, confirming that FSH action is mediated via activation of MAPK. In conclusion, we have demonstrated that FSH-R was expressed, and FSH induced growth stimulation in normal, preneoplastic, and neoplastic OSE cells. Furthermore, treatment with FSH stimulated activation of the MAPK cascade and phosphorylated Elk-1 in neoplastic OSE cells. These results suggest that the MAPK cascade may be involved in cellular functions such as growth stimulation in response to FSH in preneoplastic and neoplastic OSE cells.     

Translation and validation of the Amsterdam preoperative anxiety and information scale (APAIS) for use in Japan

Preoperative anxiety is a very common phenomenon that adversely affects a patient's physical and psychological outcome. To evaluate subjective complaints such as anxiety, use of a validated psychological instrument is essential. In this study, we translated, culturally adapted and validated the Amsterdam preoperative anxiety and information scale (APAIS) for use in Japan. One hundred and twenty-six preoperative patients participated in this cross-sectional study. The psychometric properties of the APAIS evaluated by factor analysis, correlation with the state-trait anxiety inventory (STAI) and Cronbach's were very similar to those of the original Dutch and English versions. Female gender and a high information requirement were associated with high preoperative anxiety. In conclusion, the Japanese version of the APAIS is a valid and reliable instrument for screening Japanese patients for preoperative anxiety and information requirements. Female gender and high information requirement may be associated with high preoperative anxiety.