Alleviation of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma-ray on male reproductive endocrine damages induced by subsequent high-dose irradiation

Irradiation has been widely reported to damage organisms by attacking on proteins, nucleic acid and lipids in cells. However, radiation hormesis after low-dose irradiation has become the focus of research in radiobiology in recent years. To investigate the effects of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma (gamma)-ray on male reproductive endocrine capacity induced by subsequent high-dose irradiation, the brains of the B6C3F(1) hybrid strain male mice were irradiated with 0.05 Gy of C-12(6+) ion or Co-60 gamma-ray as the pre-exposure dose, and were then irradiated with 2 Gy as challenging irradiation dose at 4 h after pre-exposure. Serum pituitary gonadotropin hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), testosterone, testis weight, sperm count and shape were measured on the 35th day after irradiation. The results showed that there was a significant reduction in the levels of serum FSH, LH, testosterone, testis weight and sperm count, and a significant increase in sperm abnormalities by irradiation of the mouse brain with 2 Gy of C-12(6+) ion or Co-60 gamma-ray. Moreover, the effects were more obvious in the group irradiated by C-12(6+) ion than in that irradiated by Co-60 gamma-ray. Pre-exposure with low-dose C-12(6+) ion or Co-60 gamma-ray significantly alleviated the harmful effects induced by a subsequent high-dose irradiation.

Induction of cytogenetic adaptive response in spermatogonia and spermatocytes by pre-exposure of mouse testis to low-dose C-12(6+) ions

To investigate the effects of pre-exposure of mouse testis to low-dose C-12(6+) ions on cytogenetics of spermatogonia and spermatocytes induced by subsequent high-dose irradiation. the testes of outbred Kun-Ming strain mice were irradiated with 0.05 Gy of C-12(6+) ions as the pre-exposure dose, and then irradiated with 2 Gy as challenging dose at 4 h after per-exposure. Poly(ADP-ribose) polymerase (PARPs) activity and PARP-1 protein expression were respectively measured by using the enzymatic and Western blot assays at 4 h after irradiation; chromosomal aberrations in spermatogonia and spermatocytes were analyzed by the air-drying method at 8 h after irradiation. The results showed that there was a significant increase in the frequency of chromosomal aberrations and significant reductions of PARP activity and PARP-1 expression level in the mouse testes irradiated with 2 Gy of C-12(6+) ions. However, pre-exposure of mouse testes to a low dose of C-12(6+) ions significantly increased PARPs activity and PARP-1 expression and alleviated the harmful effects induced by a subsequent high-dose irradiation. PARP activity inhibitor 3-aminobenzamide (3-AB) treatment blocked the effects of PARP-1 on cytogenetic adaptive response induced by low-dose C-12(6+) ion irradiation. The data suggest that pre-exposure of testes to a low dose of heavy ions can induce cytogenetic adaptive response to subsequent high-dose irradiation. The increase of PARP-1 protein induced by the low-dose ionizing irradiation may be involved in the mechanism of these observations. (C) 2008 Elsevier B.V. All rights reserved.

Study on the apoptosis and Bcl-2/Bax expression of human hepatoma SMMC-7721 cells after exposure to heavy-ion and X-ray irradiations

This study is aimed at observing the apoptosis and Bcl-2/Bax gene expression of mammalian cells following heavy-ion and X-ray irradiations. Exponentially growing human hepatoma SMMC-7721 cells cultured in vitro were irradiated with a C-12 ion beam of 50 MeV/u (corresponding to a LET value of 44.56 keV/mu m) from Heavy Ion Research Facility in Lanzhou (HIRFL) at doses varying from 0 to 3 Gy. The X-ray irradiation (8 MV) was performed in the therapy unit of the General Hospital of the Lanzhou Military Area. Survival fractions of irradiated cells at various doses were measured by means of MTT assay. Apoptotic cells after irradiation were analyzed with fluorescence microscope and flow cytometer (FCM). Immuno-histological assay were applied to detect the expression of Bcl-2/Bax genes in the irradiated cells. The survival fraction of SMMC-7721 cells decreased gradually (vs. control p<0.05) with increasing the dose of the carbon ion beam more obviously than X-ray irradiation, and the carbon ion irradiation efficiently induced cell apoptosis and significantly promoted the expression of Bax gene while Bcl-2 gene expression was restrained. High-LET heavy ion beam would induce cell apoptosis effectively than low-LET X-ray, and the apoptosis rate is correlated with the transcription of Bcl-2/Bax and the ratio of Bcl-2/Bax in human hepatoma SMMC-7721 cells after irradiation to heavy ion beam.

Biodosimetry estimate for high-LET irradiation

The purpose of this paper is to prepare for an easy and reliable biodosimeter protocol for radiation accidents involving high-linear energy transfer (LET) exposure. Human peripheral blood lymphocytes were irradiated using carbon ions (LET: 34.6 keV mu m(-1)), and the chromosome aberrations induced were analyzed using both a conventional colcemid block method and a calyculin A induced premature chromosome condensation (PCC) method. At a lower dose range (0-4 Gy), the measured dicentric (dics) and centric ring chromosomes (cRings) provided reasonable dose information. At higher doses (8 Gy), however, the frequency of dics and cRings was not suitable for dose estimation. Instead, we found that the number of Giemsa-stained drug-induced G2 prematurely condensed chromosomes (G2-PCC) can be used for dose estimation, since the total chromosome number (including fragments) was linearly correlated with radiation dose (r = 0.99). The ratio of the longest and the shortest chromosome length of the drug-induced G2-PCCs increased with radiation dose in a linear-quadratic manner (r = 0.96), which indicates that this ratio can also be used to estimate radiation doses. Obviously, it is easier to establish the dose response curve using the PCC technique than using the conventional metaphase chromosome method. It is assumed that combining the ratio of the longest and the shortest chromosome length with analysis of the total chromosome number might be a valuable tool for rapid and precise dose estimation for victims of radiation accidents.

Adaptive hormetic response of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma-ray on growth hormone (GH) and body weight induced by subsequent high-dose irradiation

The brain of the Kun-Ming strain mice were irradiated with 0.05 Gy of C-12(6+) ion or Co-60 gamma-ray as the pre-exposure dose, and were then irradiated with 2 Gy of 12C6+ ion or Co-60 gamma-ray as challenging irradiation dose at 4 h after per-exposure. Body weight and serum growth hormone (GH) concentration were measured at 35th day after irradiation. The results showed that irradiation of mouse brain with 2 Gy of C-12(6+) ion or Co-60 gamma-ray significantly diminished mouse body weight and level of serum GH. The relative biological effectiveness values of a 2 Gy dose of C-12(6+) ion calculated with respect to Co-60 gamma-ray were 1.47 and 1.34 for body weight and serum GH concentration, respectively. Pre-exposure with a low-dose (0.05 Gy) of C-12(6+) ion or Co-60 gamma-ray significantly alleviated reductions of mouse body weight and level of serum GH induced by a subsequent high-dose (2 Gy) irradiation. The data suggested that low-dose ionizing irradiation can induce adaptive hormetic responses to the harmful effects of pituitary by subsequent high-dose exposure.

Separation of drug enantiomers by capillary electrophoresis in the presence of neutral cyclodextrins

This is a selected review, highlighting our results obtained in an extended screening program ("The German-Chinese Drug Screening Program"), with a focus on a set of original data obtained with heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin(TM-beta-CD) as the chiral solvating agent (CSA). The enantioseparation of 86 drugs by capillary zone electrophoresis in the presence of this CSA was successful for 47 drugs. The migration separation factors (alpha(m)) and the migration retardation factors (R-m) were compared with those found for native beta-cyclodextrin (beta-CD). The patterns thus obtained were also compared with those observed for hexakis(2,3,6-tri-O-methyl)-alpha-CD (TM-alpha-CD) and octakis(2,3,6-tri-O-methyl)-gamma-CD (TM-gamma-CD), respectively. From the statistical data, it can be concluded that there is a remarkable influence of the analyte structure on the electrophoretic data. A substructure 4H was found in the analyte structure that has a significant influence on the analytes' behaviour. Thus, analytes bearing the substructure 4H do not only have a strong affinity to the CDs but also a high rate of success of chiral separation in all systems reviewed. In light of this, the different ring sizes of native cyclodextrins (alpha-, beta- and gamma-CD) readily explain their behaviour towards a limited test set of chiral drugs. Sterical considerations point to the significance of side-on-binding versus inclusion in the cavity of the host. In addition to the findings from the screening program, numerous references to the Literature are given. (C) 2000 Elsevier Science B.V. All rights reserved.

Early Embryonic Exposure to Polychlorinated Biphenyls Disrupts Heat-Shock Protein 70 Cognate Expression in Zebrafish

Polychlorinated biphenyls (PCBs) are persistent environmental contaminants that have documented neurological effects in children exposed in utero. To better define neuronally linked molecular targets during early development, zebrafish embryos were exposed to Aroclor 1254, a mixture of PCB congeners that are common environmental contaminants. Microarray analysis of the zebrafish genome revealed consistent significant changes in 38 genes. Of these genes, 55% (21) are neuronally related. One gene that showed a consistent 50% reduction in expression in PCB-treated embryos was heat-shock protein 70 cognate (Hsc70). The reduction in Hsc70 expression was confirmed by real-time polymerase chain reaction (PCR), revealing a consistent 30% reduction in expression in PCB-treated embryos. Early embryonic exposure to PCBs also induced structural changes in the ventro-rostral cluster as detected by immunocytochemistry. In addition, there was a significant reduction in dorso-rostral neurite outgrowth emanating from the RoL1 cell cluster following PCB exposure. The serotonergic neurons in the developing diencephalon showed a 34% reduction in fluorescence when labeled with a serotonin antibody following PCB exposure, corresponding to a reduction in serotonin concentration in the neurons. The total size of the labeled neurons was not significantly different between treated and control embryos, indicating that the development of the neurons was not affected, only the production of serotonin within the neurons. The structural and biochemical changes in the developing central nervous system following early embryonic exposure to Aroclor 1254 may lead to alterations in the function of the affected regions.

Bioactive, Luminescent and Mesoporous Europium-doped Hydroxyapatite as a Drug Carrier

Bioactive, luminescent and mesoporous europium-doped hydroxyapatite (Eu:HAp) was successfully prepared through a simple one-step route using cationic surfactant as template. The obtained multifunctional hydroxyapatite was performed as a drug delivery carrier to investigate the drug storage/release properties using ibuprofen (IBU) as a model drug

Fabrication, characterization of spherical CaWO4:Ln@MCM-41(Ln=Eu3+, Dy3+, Sm3+, Er3+) composites and their applications as drug release systems

Spherical MCM-41 particles with a diameter of about 150 nm have been successfully coated with CaWO4:Ln (Ln = Eu3+, Dy3+, Sm3+, Er3+) phosphor layers through a simple Pechini sol-gel process. The obtained CaWO4:Ln@MCM-41 composites, which kept the mesoporous structure of MCM-41 and the luminescent properties of phosphors, were investigated as a drug delivery system using aspirin (ASPL) as a model drug.

On the chemical synthesis and drug delivery response of folate receptor-activated, polyethylene glycol-functionalized magnetite nanoparticles

We describe here the chemical synthesis and in vitro drug delivery response of polyethylene glycol (PEG)-functionalized magnetite (Fe3O4) nanoparticles, which were activated with a stable ligand, folic acid, and conjugated with an anticancer drug, doxorubicin. The functionalization and conjugation steps in the chemical synthesis were confirmed using Fourier transform infrared spectroscopy. The drug-release behavior of PEG-functionalized and folic acid-doxorubicin-conjugated magnetic nanoparticles was characterized by two stages involving an initial rapid release, followed by a controlled release. (C) 2007 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Preparation and Characterization of Interpenetration Polymer Network Films Based on Poly(vinyl alcohol) and Poly(acrylic acid) for Drug Delivery

A series of full interpenetrating polymer network (full-IPN) films of poly(acrylic acid) (PAA)/poly (vinyl alcohol) (PVA) were prepared by radical solution polymerization and sequential IPN technology. Attenuated total reflectance-Fourier transform infrared spectroscopy, swelling properties, mechanical properties, morphology, and glass transition temperature of the films were investigated. FTIR spectra analysis showed that new interaction hydrogen bonds between PVA and PAA were formed. Swelling property of the films in distilled water and different pH buffer solution was studied. Swelling ratio increased with increasing PAA content of IPN films in all media, and swelling ratio decreased with increasing PVA crosslink degree. Tensile strength and elongation at break related not only to the constitution of IPNs but also to the swelling ratio of IPNs.

Luminescence functionalization of mesoporous silica with different morphologies and applications as drug delivery systems

Ordered mesoporous silica (MCM-41) particles with different morphologies were synthesized through a simple hydrothermal process. Then these silica particles were functionalized with luminescent YVO4:EU3+ layers via the Pechini sol-gel process. The obtained YVO4:Eu3+ and MCM-41 composites, which maintained the mesoporous structure of MCM-41 and the red luminescence property of YVO4:Eu3+ were investigated as drug delivery systems using ibuprofen (IBU) as model drug. The physicochemical properties of the samples were characterized by X-ray diffraction (XRD), Fourier transform-infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), N-2 adsorption, and photoluminescence (PL) spectra, respectively.