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PubMedDate not supplied

[Study of the radioprotective effect of the NO-synthase inhibitor L-NAME in Chinese hamster cell culture].

A radioprotective effect of L-NAME was estimated by the yield of the aberrant anaphases after exposure of Chinese hamster cells to different doses of gamma-rays and beta-particles. It was shown that cell treatment with L-NAME before irradiation only decreased the frequency of radiation-induced chromosome aberrations. The equal yield of the aberrant anaphases was found in the cells treated with L-NAME and irradiated with 6 Gy gamma-rays later and in the cells non-treated with L-NAME and irradiated with 3 Gy gamma-rays. The treatment of cells with L-NAME just before and immediately after irradiation did not modify the radiation-induced frequency of the chromosome aberrations. The treatment of cells with L-NAME decreased the level of SH-groups (as estimated by UV-spectrophotometer) and increased the chromatin condensation (as estimated by flow cytometry). It was suggested that radioprotective effect of L-NAVE may be connected with its cooperation with DNA. Condensation of L-NAME on the surface of DNA resulted in increasing of probability of the chemical repair of DNA-radicals after irradiation. Thus, these results indicate the involvement of NO-dependent mechanism of the realization of the radiation-induced damage to the hereditary cell structure and optimal conditions for the realization as well as the conceivable mechanism of radioprotective effect one of the most inhibitors of NO-synthase--L-NAME.

Animals↗
PubMed2001

Dosimetric effect of source centering and residual plaque for beta-emitting catheter based intravascular brachytherapy sources.

Catheter-based radiation delivery systems employing both beta-particle and gamma-ray emitters are currently being investigated for their efficacy in addressing restenosis following percutaneous coronary intervention (PCI). The dosimetric consequences of source centering within the arterial lumen and presence of residual plaque are potentially important issues for the uniform delivery of dose to the arterial tissue. In this study, we have examined the effect of source centering on the resulting dose to the arterial wall from clinical intravascular brachytherapy sources containing 32P and 90Sr/Y90. Monte Carlo simulations using the MCNP code were performed for these catheter-based sources with offsets of 0.5 mm and 1 mm from the center of the arterial lumen in homogenous water medium as well as in the presence of residual plaque. Three different positions were modeled and the resulting dose values were analyzed to assess their impact on the resulting dose distribution. The results indicate a variation ranging from -40% to +70% for 32P source and -30% to +50% for 90Sr/90Y at a radial distance of 2 mm from the center of the coronary artery, relative to the dose from a centered source, for a 0.5 mm offset. The variation for a 1 mm offset ranges from -65% to +182% for 32P source and to -50% to +140% for 90Sr/90Y. A concentric residual plaque layer was also modeled so as to assess the combined influence of offset and residual plaque on the dosimetry. Finally the effect of cardiac motion and its potential impact on catheter position and hence the dose distribution is also examined by considering two separate cases of catheter displacement. The results indicate that dose variations range between -28% to +91% when it is assumed that cardiac motion causes catheter movement during coronary lesion irradiation.

Beta Particles↗
PubMed1996

Glycosomes--the organelles of glycogen metabolism.

This article reviews the data concerning the electron microscopical interpretation of glycogen. It demonstrates that glycogen in the cell is associated with the enzymes involved in its metabolism and that the glycogen-protein complex forms morphologically distinct cell organelles called glycosomes. Glycogen can be visualized in the electron microscope (EM) by histochemical procedures, or by negative staining, but it does not react with heavy metals such as uranium and lead. The protein component of glycosomes, stainable by heavy metals, appears in EM as 20-30 nm granules. While biochemical findings have long indicated the association of glycogen and protein in the cell, morphological interpretation traditionally defined the protein component of glycosomes as particles of glycogen. Accordingly, the term alpha or beta particles, introduced to define particles of glycogen, became subsequently applied to the protein component visible in sections stained by heavy metals. The history of microscopic research reveals the conditions which led to such interpretation. Morphological analysis of the reaction of glycosomes to the acids shows that glycosomes deposited free in the cytosol (lyoglycosomes) are acid labile, whereas the others (desmoglycosomes), intimately associated with different cellular structures, are acid-resistant. These 2 groups correspond to lyo- and desmoglycogen distinguished in early biochemical studies on the basis of their different resistance to the cold trichloroacetic acid. The theory of glycosomes provides a new paradigm which clarifies numerous unexplained data in the microscopic literature on glycogen, and opens a vast field for the research on the cellular metabolism of glycogen, with the use of modern molecular and cellular biology techniques.

Animals↗
PubMed1976

A special pattern of the smooth endoplasmic reticulum in the kidney of the snail Cryptomphalus aspersa.

A special structural pattern of the smooth endoplasmic reticulum (SER) has been observed in the kidney of the snail Cryptomphalus aspersa. Two types of cells (clear and dark) cover the foldings of the renal sac; the dark cells are by far the most numerous. A cisterna of SER enveloping the nucleus appears invariably in both types of cells, with no disruptions, or small ones (from 50 to 90 nm) along its profile. The layer of cytoplasm lodged between the external nuclear membrane and this cisterna is found invariably to be from 0-20 to 0-25 mum in width. Glycogen is abundant in the cytoplasm as alpha particles, and also in the nucleus, but as beta particles. It is noteworthy that absolutely no glycogen is present in the layer of cytoplasm lodged between the nuclear membrane and the surrounding SER envelope. Long profiles of SER are also observed closely approaching and parallel to the plasma membrane of the dark cells. Considering the role of SER in glycogen metabolism in the kidney of the snail, the possible function of these cisternae as a support system ofr enzymes involved in the metabolism of glucides is discussed.

Animals↗
PubMed2006

Effects of different sizes of beta-tricalcium phosphate particles on bone augmentation within a titanium cap in rabbit calvarium.

This study evaluated the effects of different sizes of beta-TCP particles on bone augmentation within a titanium cap. In 20 rabbits, the calvarium was exposed and a circular groove was prepared. After marrow penetration, a standardized hemispherical titanium cap was placed in the circular grove. The cap was filled with small-sized (100-250 microm) or medium-sized (250-500 microm) beta-TCP particles for the experimental site and without beta-TCP for the control site. After one and three months of healing, the animals were euthanized and examined histologically. There was a statistically significant difference in the amount of mineralized bone generated between the experimental and control groups in the three-month specimens. Furthermore, the medium-sized particles showed significantly more mineralized bone than did the small-sized particles. Based on these findings, we suggested that beta-TCP might be effective for bone formation and that medium-sized particles are more useful than small-sized particles in bone maturation.

Animals↗
PubMed1976

The appearance and degradation of specific hepatocellular cytoplasmic inclusion bodies in rat liver due to D-galactosamine. I. The relation between the amount of liver glycogen and the appearance of the atypical dense bodies in the liver cell.

One of the most sensitive and specific signs of the galactosamine effect upon the rat liver cell is the appearance of PAS-positive and diastase-resistant granules within the cytoplasm of hepatocytes. Light-microscopic, histochemical, biochemical, and electron-microscopic findings reveal that the appearance of these ADB (= atypical dense bodies) depends upon a working glycogen metabolism at the time of GalN treatment. The ADB are composed of particles resembling, due to shape and size, ribosomes and beta particles of glycogen. Most of them are surrounded by the rER, but they are never enclosed by a limiting membrane. Due to sequential changes they can be generally classified into three types; the early, the intermediate, and the late type. In seven experiments it can be shown, that the appearance of the ADB depends upon the time and dosage after GalN treatment. They occur even if an additional treatment with galactose or uridine prevents the liver from the features of a hepatitis, as also shown in the livers of newborn animals up to 3 weeks of age. The histochemical response against various glucosidases, hexosaminidases, pronase, and RNAse as well as against various fixatives indicates that ADB are composed of, at least, two different constituents, the former RNAse-sensitive and visible with routine light-microscopic staining procedures, the latter RNA-resistant, PAS-positive, and invisible after staining with H & E or toluidine blue. The latter is diastase-resistant, suggesting that this portion of ADB does not represent the usual glycoproteins but some abnormal metabolite of glycogen. The ADB can be detected with maximal accumulation in the cytoplasm of hepatocytes at that time when the glycogen content determined in the liver homogenate by biochemical methods is greatly reduced.

Animals↗
PubMed1999

Biokinetics and dosimetry of titanium tritide particles in the lung.

Doses of internal radiation from inhalation of metal tritide aerosols are potentially a major radiation protection problem encountered by nuclear industry workers. Based on results of experiments with rats intratracheally instilled with titanium tritide particles and on a self-absorption factor of beta particles determined by a numerical method, a biokinetic model was developed for inhaled particles of titanium tritide. Results showed that lung burdens of the tritide are well represented by a two-component exponential equation; biological half-lives derived for the retention of 3H in lung were 0.81 d and 66 d. The tritium clearance rate via urine or feces was described by bi-phase exponential components. At 121 d after instillation, 82% of the initial lung burden of 3H had been eliminated, of which 37% was excreted in urine, 29% via feces, and 16% through exhaled air. Based on simulation results of the biokinetic model, the cumulative absorbed dose and committed effective dose were calculated as well as the annual limit of intake (ALI) and derived air concentration (DAC). The ALI and DAC values for titanium tritide were a factor of 5 lower than values for tritiated water. This information will be useful in developing new guidelines for radiation protection purposes.

Administration, Inhalation↗
PubMed2003

Dose assessment for inhaling hafnium particles based on laboratory rats study.

Internal radiation from inhalation of hafnium tritide aerosols may be a significant radiation protection problem encountered by nuclear facility workers. Based on experimental results of the rat intratracheally instilled with hafnium tritide particles and on a self-absorption factor of beta particles determined by a numerical method, a biokinetic model was developed for inhaled particles of hafnium tritide. Results show that lung burdens of the tritide are well represented by a two-component exponential equation; biological half-lives derived for the retention of 3H in lung were 4.9 d and 1,257 d for the short- and long-term clearance, respectively. The tritium clearance rate via urine or feces was described by bi-phase exponential components. At the end of the experiment (180 d after instillation), only approximately 30% of the initial lung burden of 3H had been eliminated, of which approximately 98% was excreted via feces and 2% in urine, but none through exhaled air. Results also showed that a large percentage (70%) of the hafnium tritide initially present in lung still remained in the organ 6 mo after the exposure. The calculation of the radiation dose indicates that the cumulative dose to the lung directly from the tritide particles was approximately 10(6) times the lung dose from the dissolved tritium in the lung region. The committed effective dose to the lung was estimated to be 5.41 x 10(-10) Sv Bq(-1), which is over 99% of that to the whole body. The dose to the liver was 6.00 x 10(-15) Sv Bq(-1). This information will be useful in developing new guidelines for radiation protection purposes.

Administration, Inhalation↗
PubMed1998

Ultracytochemical demonstration of glycogen in cone, but not in rod, photoreceptor cells in the rat retina.

The presence of native glycogen in photoreceptor cells of the rat retina has not been identified in the literature. We have studied this ultracytochemically. After perfusion with glutaraldehyde fixative, the eyes were enucleated, and the retinal tissues, postfixed with OsO4, were embedded in epoxy resin. Some tissues were treated with saliva before postfixation. Ultrathin sections, stained by the periodic acid-thiocarbohydrazide-silver proteinate (PA-TCH-SP) method or with uranyl acetate and lead citrate, were examined by electron microscopy. On routinely stained sections, glycogen particles seemed to be absent in the cytoplasmic matrix of the photoreceptor cells because they were indistinguishable from the numerous ribosomes. This was due to a similarity in size and electron density. After PA-TCH-SP staining, fine electron-dense reaction products appeared on small cytoplasmic particles (but not on ribosomes) in the inner segments, perikarya and synaptic terminals of a subpopulation of photoreceptor cells. These particles, 15-25 nm in diameter, were identified as beta-particles of glycogen because of their susceptibility to enzyme digestion. The glycogen-rich photoreceptor cells were thought to be cone cells by reasons of their morphological features, such as synaptic terminals, nuclei and outer segments. These results suggest that the cone, but not the rod, photoreceptor cells in the rat contain abundant glycogen.

Animals↗
PubMed1994

Effectiveness of radon relative to acute 60Co gamma-rays for induction of micronuclei in vitro and in vivo.

Because radon and its progeny (referred to collectively here as radon) emit alpha particles with a wide range of energies, as well as beta particles and gamma-rays, it is important to quantitate the relationship between initial damage induced by radon and that by acute low-LET radiation. We have evaluated dose-response relationships for induction of micronuclei both in vivo and in vitro following exposure to radon or 60Co. To determine if isolation procedures altered the cells' responsiveness to 60Co gamma-ray exposures, animals were exposed before cell isolation, or cells were isolated and then exposed. The data were described by linear dose-response functions and were not significantly different when the radiation exposure was in vivo or in vitro (respectively micronuclei/1000 binucleated cells = 1.6 +/- 6.5 + 62 +/- 2.7 D; micronuclei/1000 binucleated cells = 15.4 +/- 26.0 + 54.6 +/- 11.4 D, where D is in Gy). Primary rat lung fibroblasts (RLF) or Chinese hamster ovary (CHO-K1) cells were exposed in vitro to either radon or 60Co gamma-rays. Radon was 10.9 +/- 2.6 and 12.5 +/- 2.4 times as effective per Gy of radiation dose in producing micronuclei as was 60Co in RLF and CHO-K1 cells respectively. To determine the relative biological effectiveness of in vivo radon exposure, animals were exposed to either radon or 60Co, and lung fibroblasts were isolated and evaluated for radiation-induced micronuclei. In vivo radon exposure was 10.6 +/- 1.0 times as effective as acute whole-body 60Co exposure in producing micronuclei in lung fibroblasts. Different cell lines and exposure conditions resulted in similar effectiveness factors. Such ratios help evaluate the biological damage, hazard and risk associated with radon inhalation.

Animals↗
PubMed1993

A model of cell inactivation by alpha-particle internal emitters.

Tumor-associated antibodies labeled with 131I and 90Y have been used in the treatment of malignant disease with some success. The use of alpha-particle-emitting radionuclides as radiolabels offers potential advantages over beta-particle sources. The short range in tissue (< 100 microns) and the high linear energy transfer associated with alpha-particle emitters will result in a more concentrated deposition of energy at the site of radionuclide decay. Thus, if radiolabeled antibodies can be bound to malignant cells specifically, a high differential cell killing can be achieved between the malignant and the normal cells. However, the energy deposition pattern will be strongly dependent upon the configuration of alpha-particle sources relative to the cells, and will consequently impact upon the dose-response characteristics. The purpose of this paper is to study distributions of energy deposition from alpha-particle-emitting radioimmunoconjugates distributed uniformly and nonuniformly around cells through theoretical modeling. Energy deposition spectra for cell nuclei are calculated and used to estimate the survival fraction by a simple biological model. We show that survival curves resulting from nonuniform distributions of alpha-particle-emitting radiolabeled antibodies can depart significantly from the classical exponential survival model applied to external alpha-particle beams. The survival curves may have initial slopes much steeper than those produced by a uniform distribution of sources, and they may also depart from linearity. Furthermore, the results of the modelling indicate how survival curves are dependent on the cell and radiolabel spacing. The results from our model compare reasonably well with published experimental data and can be used to facilitate the design and interpretation of radiobiological experiments.

Alpha Particles↗
PubMed2006

The effect of varying the particle size of beta tricalcium phosphate carrier of recombinant human bone morphogenetic protein-4 on bone formation in rat calvarial defects.

BACKGROUND: Beta tricalcium phosphate (beta-TCP) has been developed as one of the carriers of recombinant human bone morphogenetic protein (rhBMP). However, it is not known whether the particle size of beta-TCP is related to its resorption rate and the degree of bone formation. The purpose of this study was to evaluate the effect of using beta-TCP with different particle sizes on the ability of rhBMP-4 to enhance bone formation in the rat calvarial defect model. METHODS: Calvarial, 8-mm-diameter, critical-size defects were created in 100 male Sprague-Dawley rats. Five groups of 20 animals each received either rhBMP-4 (2.5 microg) using beta-TCP with a particle size of 50 to 150 microm, rhBMP-4 (2.5 microg) using beta-TCP with a particle size of 150 to 500 microm, a beta-TCP control with a particle size of 50 to 150 microm, a beta-TCP control with a particle size of 150 to 500 microm, or a sham-surgery control, respectively, and were evaluated by measuring their histologic and histometric parameters following a 2- and 8-week healing interval. RESULTS: There were no significant differences in the defect closure, new bone area, or augmented area between either the two rhBMP-4/beta-TCP groups or between the two beta-TCP control groups at 2 and 8 weeks. CONCLUSIONS: rhBMP-4 combined with either small- or large-particle beta-TCP had a significant effect on the induction of bone formation compared to either a small- or large-particle beta-TCP control or a sham-surgery control. Within the parameters of this study, varying the particle size of beta-TCP did not seem to have a significant effect on bone formation.

Animals↗
PubMed1977

Hydrodynamic properties of 2-mercaptoethanol-modified glycogen.

Treatment of glycogen with 2-mercaptoethanol and iodoacetamide gives rise to a modified glycogen which resembles the original glycogen in its hydrodynamic behaviour but has a pronounced tendency to aggregate. The modified glycogen can be distinguished easily, by its diffusion coefficient, from glycogen degraded by more traditional methods of extraction. The 'fundamental' glycogen particle appears to be composed of two or three glycogen beta-particles linked by a single protein chain.

Animals↗
PubMed2005

The promise of targeted {alpha}-particle therapy.

The use of monoclonal antibodies to deliver radioisotopes directly to tumor cells has become a promising strategy to enhance the antitumor effects of native antibodies. Since the alpha- and beta-particles emitted during the decay of radioisotopes differ in significant ways, proper selection of isotope and antibody combinations is crucial to making radioimmunotherapy a standard therapeutic modality. Because of the short pathlength (50-80 microm) and high linear energy transfer ( approximately 100 keV/microm) of alpha-emitting radioisotopes, targeted alpha-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissues than beta-emitters. These properties make targeted alpha-particle therapy ideal for the elimination of minimal residual or micrometastatic disease. Radioimmunotherapy using alpha-emitters such as (213)Bi, (211)At, and (225)Ac has shown activity in several in vitro and in vivo experimental models. Clinical trials have demonstrated the safety, feasibility, and activity of targeted alpha-particle therapy in the treatment of small-volume and cytoreduced disease. Further advances will require investigation of more potent isotopes, new sources and methods of isotope production, improved chelation techniques, better methods for pharmacokinetic and dosimetric modeling, and new methods of isotope delivery such as pretargeting. Treatment of patients with less-advanced disease and, ultimately, randomized trials comparing targeted alpha-particle therapy with standard approaches will be required to determine the clinical utility of this approach.

Alpha Particles↗
PubMed2004

Radioimmunotherapy with alpha-particle emitting radionuclides.

An important consideration in the development of effective strategies for radioimmunotherapy is the nature of the radiation emitted by the radionuclide. Radionuclides decaying by the emission of alpha-particles offer the possibility of matching the cell specific reactivity of monoclonal antibodies with radiation with a range of only a few cell diameters. Furthermore, alpha-particles have important biological advantages compared with external beam radiation and beta-particles including a higher biological effectiveness, which is nearly independent of oxygen concentration, dose rate and cell cycle position. In this review, the clinical settings most likely to benefit from alpha-particle radioimmunotherapy will be discussed. The current status of preclinical and clinical research with antibodies labeled with 3 promising alpha-particle emitting radionuclides - (213)Bi, (225)Ac, and (211)At - also will be summarized.

Actinium↗
PubMedDate not supplied

Efficiency curve of the ionization chamber of the SIR.

The efficiency of the SIR ionization chamber versus photon energy has been obtained by an iterative method, starting from a few monoenergetic gamma-ray emitters. The relative standard uncertainty on the efficiency curve obtained is lower than 10(-2) above 65 keV. An efficiency curve for beta particles has been deduced in a similar manner, from measurements of (quasi-) pure beta emitters. The possible uses of the efficiency curve to identify inconsistent SIR data or discrepant decay scheme data are discussed.

Journal Article↗
PubMed1998

1H NMR spectroscopy study of the dynamic properties of glycogen in solution by steady-state magnetisation measurement with off-resonance irradiation.

The dynamics of size-selected fractions of glycogen in solution have been investigated by proton NMR spectroscopy, using a recently described relaxation study method which relies on strong offresonance irradiation. The dependence of the steady-state magnetisation on angle and intensity of the effective radio-frequency field was measured and compared to theoretical curves derived from different models of motion. Absence or presence of contributions to relaxation from molecular motions on the microsecond time scale can be tested with this method, without having to resort to models. We found that glycogen dipolar relaxation did not result from isotropic Brownian rotation, and despite some contribution from slow motion (> 1 microsecond) to relaxation in glycogen alpha-particles extracted from rat liver, bulk movement of the molecules did not appear to participate in averaging the dipolar term to zero. Whereas hepatic glycogen rat beta-particles and commercial oyster glycogen displayed very similar relaxation properties, alpha-particles showed significantly different behaviour. However, all results were compatible with a diversity of movements within the molecule, ranging from freely rotating pyranoside rings through collective chain motion and possibly to bulk movement of the beta sub-units within the alpha-particle.

Animals↗
PubMed1991

Therapeutic radionuclides: production and decay property considerations.

The development of effective therapeutic radiopharmaceuticals requires careful consideration in the selection of the radionuclide. The in vivo targeting and clearance properties of the carrier molecule must be balanced with the decay properties of the attached radionuclide. Radionuclides for therapeutic applications fall into three general categories: beta-particle emitters, alpha-particle emitters, and Auger and Coster-Kronig-electron emitters following electron capture. Alpha particles and Auger electrons deposit their energy over short distances with a high LET that limits the ability of cells to repair damage to DNA. Despite their high levels of cytotoxicity, the relatively short range of alpha particles requires binding of the carrier molecule to most cancer cells within a tumor in order to be effective. Because of the extremely short range of Auger electrons, the radionuclide must be carried directly into the nucleus to elicit high radiotoxicity, making it necessary to deliver the radionuclide to every cell within a tumor cell population. These characteristics impose rigid restrictions on the nature of the carrier molecules for these types of particle emitters but successful targeting of these types of radionuclides could result in high therapeutic ratios. Most beta-emitting radionuclides are produced in nuclear rectors via neutron capture reactions; however, a few are produced in charged-particle accelerators. For radionuclides produced by direct neutron activation, the quantities and specific activities that can be produced are determined in large part by the cross-section of the target isotope and the flux of the reactor. Many applications (e.g., therapeutic bone agents, radiolabeled microspheres, radiocolloids) do not require high-specific activities and can therefore utilize the wide range of radionuclides that can be produced in sufficient quantity by direct neutron activation. Other applications (e.g., MAb labeling) require high-specific activity radionuclides in order to deliver a sufficient number of radionuclide atoms to the target site without saturating the target or compromising the integrity of the carrier molecule. Most radionuclides, produced at NCA levels in reactors, are produced via indirect reactions. High-specific activity beta emitters can also be obtained from radionuclide generator systems where the longer-lived parent radionuclide may be obtained from direct neutron activation, as a fission product, or from charged-particle accelerators. It is essential that the half-life of a radionuclide used in RNT be compatible with the rates of localization in target tissues and clearance of the carrier molecule from normal tissues. This consideration is especially important for the various MAbs and their fragments that are currently under investigation as carrier molecules to RIT.(ABSTRACT TRUNCATED AT 400 WORDS)

Half-Life↗