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[Kinetics of lipid peroxidation induced by UV beta rays in human keratinocyte and fibroblast cultures].

Lipid peroxidation has been implicated in skin damage by ultraviolet radiation. The aim of the study was to determine the kinetic of lipid peroxidation induced by ultraviolet beta (UVB) in adult keratinocytes and fibroblasts in culture. The keratinocytes were obtained from a single primary culture and the fibroblasts were in the same subculture (4 to 10 transfers). For UVB irradiation, the cells were maintained in a small volume of Hanks balanced salt solution and were irradiated (0.75, 1.5, 3 and 4.5 Jcm-2). Then cells were cultured for 3 to 48 hours. Lipid peroxidation was estimated by free MDA determination in both extracellular medium and cells using a size exclusion chromatography coupled to an HPLC procedure. In addition, LDH release in culture media was evaluated as in indice of cytotoxicity. An increase of total free MDA was observed 3 hours after cell irradiation which was dose-dependent from 0.75 to 3 Jcm-2 for keratinocytes and fibroblasts. MDA was detected both in cells and in culture media. As soon as 3 hours after irradiation 90% in total MDA was present in the culture media. Kinetic of lipid peroxidation: for 0.75 Jcm-2, an elevation of MDA was observed 12 hours after irradiation in both cultures. A further increase in MDA was noted 24 hours after fibroblasts irradiation but not in irradiated keratinocytes. LDH release in culture media increased with post irradiation time until 48 hours. The cytotoxic effect of UVB irradiation on keratinocytes and fibroblasts cultures was shown by an enhancement of lipid peroxidation which was detectable during 48 hours after irradiation. An increase of LDH release was observed simultaneously.

Adult↗

[The irradiation levels of the participants in the cleanup of the aftermath of the Chernobyl accident in 1986-1987 and the verification of the dosimetric data].

It is considered the organization of individual dosimetric monitoring (IDM) within 30-km zone around Chernobyl nuclear power plant (CNPP) in 1986 for different contingents of recovery workers: the CNPP personnel, Management for Construction 605 (MC-605), military recovery workers, persons assigned to 30-km zone. It is concluded that the quality of IDM had decreased in the following series: the MC-605 personnel, the CNPP personnel, the assigned persons, and military units. The method of dosimetric data verification for recovery workers in 1986 is presented which is based on the analyses of the dependency H(delta)/In delta from delta, where delta is a step of the histogram of distribution, and H(delta) is delta-entropy of distribution. The results obtained by this method correspond to the results of the experts' estimation. It was shown that 60% of registered individual doses for the whole contingent of the recovery workers differ from the real exposure doses. Using the theory of hybrid lognormal distribution it was obtained, in our opinion, real external dose distribution for all the recovery workers. It was estimated that 7% of recovery workers received doses more than 0.25 Gy. Also, the data on values of mean and collective doses for different contingents, as well as for all persons involved in recovery operations is presented.

Absorption↗

The kinetics of repair of sublethal radiation-induced damage in pig skin: studies with multiple interfraction intervals.

The kinetics of the repair of radiation-induced sublethal damage (SLD) was studied for the epidermis of the pig. A total of either 7 or 14 interfraction intervals with incomplete repair was achieved by giving 28 fractions either as 7 x 2 fractions/day plus a top-up dose of 17 Gy (half tolerance) or as 14 x 2 fractions/day. The dose per fraction ranged from 1.96-4.82 Gy. A total of 9 intervals ranging from 0.17 h up to 8 h between fractions was used. The incidence of moist desquamation, as an estimate of acute epidermal response, was used as an end point to establish dose-effect relationships. The data were analyzed using either the incomplete repair model of Thames, assuming mono-exponential repair kinetics, or a modified version of the incomplete repair model, assuming bi-exponential repair of sublethal damage. Both methods of analysis allowed for the longer overnight interval between fractions. Analysis assuming mono-exponential repair gave a T1/2 of 0.74 h for the combined data, although there was a trend toward a longer half-time when only the longer interfraction intervals ( > 1.0 h) were used in the analysis. A further analysis using the modified version of an incomplete repair model gave a fast and a slow component of repair with significantly different half-times of 0.09 and 4.5 h, respectively. Varying the number of incomplete repair intervals by replacing half the number of fractions with a single half-tolerance top-up dose did not modify the kinetics of repair significantly, in terms of either the repair half-times or the proportion of repair associated with a fast and slow component. Reanalysis of data published previously for 3 and 4 fractions using the modified incomplete repair model again resulted in two components of repair, represented by the significantly different half-times of 0.17 and 3.0 h. These values were similar to those obtained from the multiple-fraction experiment. These data clearly demonstrate that an acutely responding tissue is associated with a long T1/2 for the repair of SLD which is independent of the dose per fraction. For accelerated fractionation schedules in the clinic, using multiple fractions per day, these results suggest a need to control the intervals between fractions carefully and when appropriate to reduce the total dose to avoid serious normal-tissue complications.

Animals↗

Mortality from leukemia after irradiation in infancy for skin hemangioma.

From 1920 through 1959, 14,624 infants were exposed to ionizing radiation for skin hemangioma at Radiumhemmet. They were all less than 18 months old (mean 6 months) at the time of first exposure. The irradiated hemangiomas were located all over the body. The weighted bone marrow dose was on average 0.13 Gy (range < 0.01-4.6 Gy). During the period 1920-1986, 20 deaths from leukemia (11 childhood and 9 adult) were observed in the cohort compared with 17 expected during the same period. There were no significant associations between childhood leukemia and radiation dose. Despite the relatively large number of infants studied, the low average dose to bone marrow limited the possibility of detecting a small radiation risk as might be predicted from other radiation studies.

Adult↗

[100 years of roentgen rays. The contribution of Austrian scientists to discovery and applications].

In January 1896 experiments were made around the world with cathode-tubes to test Röntgen's paper "a new kind of rays". Mostly hands without pathological variations were X-rayed. At the same time in Vienna the clinical applications of X-rays were investigated. Two patients were successfully operated on after X-ray-examination. Remarkable for that time was an X-ray of an arteriogram of the arm of a dead person. It was made on 17th January 1896. The experiments with Lenard's cathode-tube were important for the discovery of X-rays. His experimentation was the inspiration for Röntgen's discovery of X-rays.

Angiography↗

[The need to account for beta radiation in determining the total radiation exposure of those working in cleanup].

The role of external beta-radiation as one of the major radiation factors effected persons involved in recovery operations (liquidators) after the accident at the Chernobyl nuclear power plant is considered. The paper uses the data of discriminate individual dosimetric monitoring of beta- and gamma-radiation for different groups of liquidators and experimentally received dose distribution in tissue equivalent material in the places of carrying out work. The results obtained by calculation were also used. It was established that experimentally determined ratios of beta-radiation doses to gamma-radiation doses have a good correlation with estimates resulted by calculation. It allowed the authors to use these estimates and individual gamma-radiation dose distribution for drawing histograms of individual beta-radiation dose distribution for open parts of skin, for lens, and gonads in cases of liquidators involved in building "sarcophagus". The obtained estimates of individual doses in the near surface tissue and organs exceeds significantly exposure levels for the whole body. This fact should draw the special attention to the rise in the number of radiation-induced cancer and cataracts.

Absorption↗

Potential advantages of treatment of transplanted saphenous vein aorto-coronary artery bypass grafts with beta irradiation to prevent graft occlusion.

Intimal proliferation or Neointimal hyperplasia (NIH) is a vascular lesion that often arises in arteries after balloon angioplasty or other vessel wall injuries. FIH is a vascular lesion that develops in autologous saphenous vein grafts (SVG) after transplantation into the aorto-coronary circulation or the peripheral vascular circulation. FIH shares elements of smooth muscle migration, proliferation and fibrous tissue deposition in common with nibrointimal proliferation (NIH). Either NIH of a coronary artery or FIH of a SVG obstruct the vascular lumen and result in myocardial dysfunction. Local radiotherapy has been used for several decades to reduce the post-operative recurrence of the fibrovascular proliferations of pterygia and keloids. Similarly, in animal and human experiments, endovascular radiotherapy has been shown to reduce arterial smooth muscle proliferation. Consideration of the similarities of vascular smooth muscle cell proliferation in NIH and FIH leads one to suggest that endovascular beta irradiation can reduce FIH as well as it reduces NIH. The goal of such treatment is to achieve a clinically significant decrease in the morbidity and mortality resulting from SVG occlusions. The potential for large reduction of the consequences of SVG occlusion, the very large number of patients at risk, and the simplicity of the proposed intervention encourages prompt scientific evaluation of this technique.

Beta Particles↗

[The build up of absorbed doses in the critical organs of cereal grains in a contaminated area after the accident at the Chernobyl Atomic Electric Power Station].

The calculation method for absorbed doses of ionizing radiations in critical organs of cereals during the first vegetation period after the ChNPP accident is presented. Calculation of radiation burden on plants nearly 5 settlements in the 30 km zone of ChNPP accident are carried out. gamma-radiation of radionuclide fallouts is demonstrated to give the main contribution into absorbed dose and dose ratio beta- to gamma-radiation varied within the range from 5 to 10 depending on radionuclide composition of fallouts.

Absorption↗

Results of contact beta-irradiation of choroidal melanomas.

Between the end of 1986 and the end of October 1996 81 patients suffering from choroidal melanoma were irradiated at the Department of Ophthalmology University Medical School of Debrecen. The irradiations were performed with Ruthenium-106 beta ray emitting scleral plaques (ophthalmic applicators). The radioactive plaques were implanted surgically, fixed by episcleral sutures onto the sclera covering the base of the tumour, and removed by another operation when sufficient time for irradiation had elapsed. For the treatment of tumours in the vicinity of the optic nerve special plaques were used with a notch for the nerve. Precise localisation of the tumours was established by intraoperative ultrasonography and transillumination. The mean follow up period was 3.5 years after the irradiation. Tumour regression was recorded by fluorescein angiography, ultrasonography and fundus photography. In 75 cases (92.5%) the treatment was successful. Additional laser photocoagulation was performed after irradiation in 26 cases. The irradiation by Ruthenium-106 scleral plaques of choroidal melanomas proved to be an effective treatment in cases of small and medium sized choroidal melanomas in our practice and the results are similar to those of the largest radiotherapy centers of Europe.

Beta Particles↗

Dosimetry of beta emitting radionuclides for use in balloon angioplasty.

The dose at varying distances from the surface of an infinite cylinder containing 90Y, 32P and 188Re respectively is calculated using published scaled point dose kernels for these three radionuclides. It is shown that all are suitable radionuclides for use in the irradiation of arteries subsequent to balloon angioplasty. All three may be used as a radioactive liquid in the angioplasty balloon, thereby simplifying the procedure and enabling a uniform radiation dose to be given to the arterial wall. It is however shown that there is a rapid reduction in dose with distance from the arterial wall which demands careful specification of the prescribed radiation dose. A similar rapid reduction with distance is also found with a central radioactive wire or with a radioactive stent containing the same radionuclides.

Angioplasty, Balloon↗

Radioimmunotherapy targeting of HER2/neu oncoprotein on ovarian tumor using lead-212-DOTA-AE1.

UNLABELLED: The specificity, toxicity and efficacy of lead (212Pb) radioimmunotherapy were evaluated in nude mice bearing the SK-OV-3 human ovarian tumor cell line expressing the HER2/neu proto-oncogene. METHODS: The therapeutic agent used was the tumor-specific anti-HER2/neu monoclonal antibody AE1 conjugated to 212Pb, 212Bi being the daughter and thus the source of the alpha-particle and beta emissions. A bifunctional derivative of tetraazacyclododecanetetraacetic acid (p-SCN-Bz-DOTA) was used to couple 212Pb to the anti-HER2/neu monoclonal antibody AE1. The chelating agent did not alter the binding affinity to its antigenic target or the pharmacokinetics and tissue distribution of the AE1 antibody. Toxicity and therapeutic efficacy of 212Pb-AE1 were evaluated in nude mouse ascites or solid tumor models, wherein SK-OV-3 cells were administered i.p. or s.c., respectively. RESULTS: The dose-limiting acute toxicity after i.v. administration of 212Pb-AE1 was bone marrow suppression, which was observed at doses above 25 microCi. Therefore, doses of 10 and 20 microCi were used in efficacy trials. The i.p. administration of 212Pb-AE1 3 days after i.p. tumor inoculation led to a significant (P2 = 0.015) prolongation of tumor-free survival. In a second model, i.v. treatment with 212Pb-AE1 3 days after s.c. tumor inoculation prevented subsequent tumor development in all animals treated with 10 or 20 microCi of 212Pb-AE1 (P2 = 0.002 compared to control groups). This efficacy in the adjuvant setting was antibody specific because treatments with equivalently labeled control antibody or unlabeled AE1 antibody or no treatment were less effective. The rate of growth of small (mean tumor volume, 15 mm3) SK-OV-3 tumors was modestly inhibited. However, tumor growth was not inhibited in mice bearing larger (mean tumor volume, 146 mm3) SK-OV-3 tumors by the administration of a single dose of 10 or 20 microCi of 212Pb-AE1. CONCLUSION: Lead-212-AE1 as an intact radiolabeled monoclonal antibody may be of only modest value in the therapy of bulky solid tumors due to the short physical half-life of 212Pb and time required to achieve a useful tumor-to-normal tissue ratio of radionuclide after administration. However, the radiolabeled monoclonal antibody may be useful in therapy of tumors in the adjuvant setting. Furthermore, 212Pb may be of value in select situations, including treatment of leukemia, intercavitary therapy or strategies that target vascular endothelial cells of tumors.

Animals↗

Irradiation and stenting.

Intravascular irradiation by both gamma and beta sources has been shown to prevent neointimal proliferation after balloon injury in the overstretch pig coronary model. A number of clinical studies are underway that involve brachytherapy from gamma sources in vessels that have been stented. The purpose of this review is to analyse the physical nature of the interaction of various forms of radiation with stent materials and to summarize the available experimental information for relevant clinical correlates of these effects. The ultimate use of vascular radiation in the presence of metallic stents will require knowledge of the possible dose alterations, and where possible, techniques to compensate for these effects.

Animals↗

Response to radiation therapy in animal restenosis models.

Intracoronary radiation therapy for prevention of restenosis is a new emerging technology which is tested nowadays in clinical trials. Several methods of radiation and a variety of isotopes have been tested in different animal models in order to prove the concept and to find a friendly user system for this application. Using the same treatment doses both gamma and beta emitters demonstrated similar results despite differences in isotope characteristics: penetration, activity, dose rate and treatment time. In addition, intracoronary radiation delivered via a catheter-based system prior to coronary stenting showed reduction of neointimal hyperplasia in the porcine coronary stent model and may further reduce restenosis coupled to stent implantation. The value of radioactive stents is also considered especially in large vessels with regard to their low activity and their proximity to the vessel wall. Adventitial labeling and immunostaining suggested the mechanism by which radiation reduces smooth muscle cell proliferation at the adventitia and affects on favorable vessel remodeling. These studies which were pioneered in this new field and have facilitated the clinical trials of using radiotherapy for prevention of restenosis are reviewed and discussed in this paper.

Animals↗

Apolipoprotein E2 (Arg136 --> Cys) mutation in the receptor binding domain of apoE is not associated with dominant type III hyperlipoproteinemia.

Using apoE phenotyping by immunoblotting and apoE genotyping we identified four heterozygous carriers of a rare apolipoprotein (apo) E2 variant, apoE2 (Arg136 --> Cys). ApoE2 (Arg136 --> Cys) was not distinct from apoE2 (Arg158 --> Cys) by phenotyping, but produced a unique pattern of bands on CfoI restriction typing of a 244 bp apoE gene fragment. Two of the four apoE2 (Arg136 --> Cys)/3 heterozygotes had elevated triglycerides, two were normolipidemic. The composition of very low density lipoproteins (VLDL) was normal in each of the four apoE2 (Arg136 --> Cys) carriers, regardless of the triglyceride concentrations. None of the apoE2 (Arg136 --> Cys) carriers displayed a broad beta-band and none revealed beta-migrating particles in the VLDL. The two hypertriglyceridemic carriers of apoE2 (Arg136 --> Cys) were, therefore, classified as having type IV rather than type III hyperlipoproteinemia. LDL receptor binding activities were studied using recombinant apoE loaded to dimyristoylphosphatidylcholine (DMPC) vesicles and to VLDL and from an apoE-deficient individual. LDL receptor binding of apoE2 (Arg136 --> Cys) was 14% of apoE3 and was thus higher than that of apoE2 (Arg158 --> Cys). Both apoE2 (Arg136 --> Cys) and apoE2 (Arg158 --> Cys) displayed substantial heparin binding (61 and 53% of apoE3, respectively). As the dominant apoE variants known so far are characterized by more pronounced reductions of heparin binding, we suggest that apoE2 (Arg136 --> Cys) is not associated with dominant expression of type III hyperlipoproteinemia. These findings lend support to the concept that apoE variants predisposing to dominant type III hyperlipoproteinemia differ from recessive mutations by a more severe defect in heparin binding.

Adult↗

[Biological and medical applications of the cathodoluminescence in the scanning electron microscope (author's transl)].

The light emission according to the excitation of solids and molecules by electrons--named cathodoluminescence--extends the analytical field of applications of the scanning electron microscope. This method can be applied in biological and medical research. It can be used for the investigation of marked specimens similar to the fluorescence microscopy. The autoluminescence of some substances can also be used for special applications. The cathodoluminescence in the scanning electron microscope has the advantage that more sensitive detector-systems can be used than with the fluorescence microscope. Moreover, in the scanning microscope it is possible to combine the cathodoluminescence mode with other imaging or analytical equipments.

Beta Particles↗

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