WorldWideScience

Sample records for vivo radioprotection studies

  1. Targeting DNA Repair through Podophyllotoxin and Rutin Formulation in Hematopoietic Radioprotection: An in Silico, in Vitro, and in Vivo Study

    Directory of Open Access Journals (Sweden)

    M. H. Yashavarddhan

    2017-10-01

    Full Text Available Drug discovery field has tremendously progressed during last few decades, however, an effective radiation countermeasure agent for the safe administration to the victims of radiation exposure is still unavailable. This multi-model study is aimed at elucidating the mechanistic aspects of a novel podophyllotoxin and rutin combination (henceforth referred as G-003M in the hematopoietic radioprotection and its involvement in the DNA damage and repair signaling pathways. Using in silico study, we identified the binding sites and structural components of G-003M and validated in vitro. We further studied various in vivo endpoints related to the DNA repair and cell death pathways in mice pre-administered with G-003M, irradiated and subsequently euthanized to collect blood and bone marrow cells. In silico study showed the binding of podophyllotoxin to β-tubulin and presence of a functional hydroxyl group in the rutin, suggested their involvement in G2/M arrest and the free radical scavenging respectively. This experimentation was further validated through in vitro studies. In vivo mice studies confirmed that G-003M pre-administration attenuated DNA damage and enhanced repair after whole body exposure. We further noticed a decrease in the levels of γH2AX, p53BP1, and ATM kinase and an increase in the levels of DNA pk, Ku 80, Ligase IV, Mre 11, Rad 50 and NBS 1 in the blood and bone marrow cells of the G-003M pre-administered and irradiated mice. We noticed an overall increase in the pro-survival factors in the G-003M pre-treated and irradiated groups establishing the radioprotective efficacy of this formulation. The lead obtained from this study will certainly help in developing this formulation as a safe and effective radioprotector which could be used for humans against any planned or emergency exposure of radiation.

  2. Novel approach to in vivo screening for radioprotective activity in whole mice. In vivo electron spin resonance study probing the redox reaction of nitroxyl

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Yuri; Anzai, Kazunori; Ueda, Jun-ichi; Ozawa, Toshihiko [National Inst. of Radiological Sciences, Chiba (Japan)

    2000-06-01

    Previously, we reported that X-irradiation enhanced the signal decay of a spin probe injected into whole mice measured by in vivo ESR, and that the observed enhancement was suppressed by the preadministration of cysteamine, a radioprotector [Miura, Y., Anzai, K., Urano, S. and Ozawa, T. (1997) Free Rad. Biol. Med. 23: 533-540]. In the present study, the suppression activity of the X-ray-induced increase in the ESR signal decay rate (termed suppression index, SI) was measured for several radioprotectors: 5-hydroxytryptamine (5-HT), S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721), 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (TEMPOL), cimetidine, interleukin-1{beta} (IL-1{beta}) and stem cell factor (SCF). The enhancement of the ESR signal decay of carbamoyl-PROXYL due to X-irradiation was suppressed by a treatment with all of the radioprotectors examined, showing positive SI values. However, a dose-dependency of 5-HT or WR-2721 was not observed, suggesting that several mechanisms exist for radioprotection and a modification of the signal decay rate. Although the in vivo ESR system cannot be used in place of the 30-day survival method for the assessment of radioprotectors, this system might be applicable to in vivo, non-invasive screening prior to using the 30 day survival method. (author)

  3. In vivo radioprotective activity of Panax ginseng and diethyldithiocarbamate.

    Science.gov (United States)

    Kim, S H; Cho, C K; Yoo, S Y; Koh, K H; Yun, H G; Kim, T H

    1993-01-01

    Studies were performed to determine whether the water fraction and the alkaloid fraction of Panax ginseng protect against radiation damage to jejunal crypts of N:GP(s) mice and induction of micronuclei (MN) in cytokinesis-blocked (CB) lymphocytes of C57BL/6 mice after in vivo irradiation with 60Co gamma-rays. The radioprotective effect of ginseng was compared with the effect of diethyldithiocarbamate (DDC). Jejunum was protected by the water fraction (2 mg/ml of drinking water) (P ginseng (P ginseng may reduce cell damage caused by gamma-rays, especially damage to DNA molecules, and play a role in the repair or regeneration process of damaged cells.

  4. Radioprotection of mouse CNS endothelial cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lyubimova, N.; Coultas, P.; Martin, R. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)

    1996-12-31

    Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy {gamma}-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

  5. Radioprotection of mouse CNS endothelial cells in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lyubimova, N.; Coultas, P.; Martin, R. [Peter MacCallum Cancer institute, Melbourne, Victoria (Australia)

    1997-03-01

    After treatments with monoamine oxidase inhibitors and L-DOPA, the blood brain barrier causes a build-up of dopamine in brain capillary endothelial cells. Conversion of the dopamine to a fluorophore provides a marker which can be used to measure endothelial cell density by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed loss within 24 hours of a sub-population of about 15 % of the endothelial cells. As a first step, rather than use the later endpoints of radionecrosis it was decided to examine directly whether Hoechst 33342 could protect against this rapid initial endothelial cell loss. Ten minutes after intravenous injection of Joechst 33342, in mouse brain the ligand was confined to endothelial cells and, for irradiation at this time, there was protection against endothelial cell loss over the first 24 hours after after exposure. Ablation of the sensitive subpopulation in unprotected mice took place over a dose range of 1 to 3 Gy {gamma}-rays but doses between 12 to 20 Gy were required in the presence of the ligand. This protection equated to a high dose modification factor of approximately 7 and may reflect suppression of apoptosis in this sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole, and how the observed protection affects late CNS necrosis development, has yet to be determined. However these results suggest a potential use of DNA-binding radioprotectors with limited penetration in investigations of the relative significance of endothelial and parenchymal damage in normal tissue responses to ionising radiation. (authors)

  6. Radioprotective properties of apple polyphenols: an in vitro study.

    Science.gov (United States)

    Chaudhary, Pankaj; Shukla, Sandeep Kumar; Kumar, I Prem; Namita, I; Afrin, Farhat; Sharma, Rakesh Kumar

    2006-08-01

    Present study was undertaken to evaluate the radioprotective ability of total polyphenols extracted from edible portion (epicarp and mesocarp) of apple. Prior administration of apple polyphenols to murine thymocytes significantly countered radiation induced DNA damage (evaluated by alkaline halo assay) and cell death (trypan blue exclusion method) in a dose dependent manner maximally at a concentration of 2 and 0.2 mg/ml respectively. Apple polyphenols in a dose dependent fashion inhibited both radiation or Fenton reaction mediated 2-deoxyribose (2-DR) degradation indicating its ability to scavenge hydroxyl radicals and this activity was found to be unaltered in presence of simulated gastric juice. Similarly apple polyphenols in a dose dependent fashion scavenged DPPH radicals (maximum 69% at 1 mg/ml), superoxide anions (maximum 88% at 2 mg/ml), reduced Fe(3 +) to Fe(2 +) (maximum at 1 mg/ml) and inhibited Fenton reaction mediated lipid peroxidation (maximum 66% at 1.5 mg/ml) further establishing its antioxidative properties. Studies carried out with plasmid DNA revealed the ability of apple polyphenols to inhibit radiation induced single as well as double strand breaks. The results clearly indicate that apple polyphenols have significant potential to protect cellular system from radiation induced damage and ability to scavenge free radicals might be playing an important role in its radioprotective manifestation.

  7. Study on induction of radioprotection using antioxidant combinations

    Energy Technology Data Exchange (ETDEWEB)

    Lim, J. S.; Choe, Y. K.; Lee, H. G.; Kim, K. D. [Korea Research Institute of Bioscience and Biotechnology, Taejeon (Korea)

    2000-04-01

    Antioxidants are applied in tumor patients during chemo- or radiotherapy due to its cytoprotective effects. Therefore, aim of our study was to evaluate the effect of exposure with a variety of antioxidants on primary bone marrow cells after {gamma}-irradiation. We studied the radiation-induced cell death in comparison to mouse bone marrow cells after single-dose irradiation with 1, 2, 3 or 6 Gy and controls without irradiation. Cells cultured in vitro had been exposed to different concentrations of antioxidants prior to {gamma}-irradiation. The effect was evaluated 6, 8, 17 or 24 h after radiation exposure by propium iodide staining. While sodium selenite and N-acetylcyseine could achieve significant inhibition of radiation-induced cell death, aminoguanidine and alpha-lipoic acid were not shown to inhibit it. Furthermore, the combination of N-acetylcysteine with some mild antioxidants such as BHA, propyl gallate, quercetin or trolox induced the significant inhibition of radiation-induced cell death. However, these effect was different depending on the duration of radiation exposure and the concentration of antioxidants added in culture. Although the radioprotective effect of antioxidants should be compared with the effect on tumor itself, our results indicate that the use of antioxidants in combination can efficiently modulate the radiation-induced cell damage like apoptosis and can be applied in tumor patients during radiotherapy. 26 refs., 7 figs., 7 tabs. (Author)

  8. An experimental study of radioprotective effect of ginseng alkaloid fraction on cellular damage

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Seong Yul; Cho, Chul Koo; Kim, Mi Sook; Yoo, Hyung Jun; Kim, Seong Ho; Kim, Tae Hwan [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1997-09-01

    This paper is to assess the effect of Adaptagen as a radioprotector in which main component is alkaloid fraction of ginseng. Evaluation was made in vitro and in vivo study with NIGP(S) mouse by the measurement of regeneration of jejunal crypt cell and micronucleus assay to analyze radioprotective effect of ginseng alkaloid fraction in comparison with that of water fraction after whole body irradiation. The results were as follows, 1. The degree of radiation damage of mouse jejunal crypt cell was diminished in both of alkaloid and water fraction groups compared to control group but more in alkaloid fraction group than water fraction group. 2. Regeneration of mouse jejunal crypt cell was higher both in alkaloid and water fraction groups than control group. 3. In vitro study, frequency of micronucleus was diminished in tendency for the treated groups than control group but statistically insignificant. 4. In vitro study, frequency of micronucleus was diminished in both alkaloid and water fraction groups compared to control group but more in alkaloid fraction group than water fraction group.

  9. Study of radioprotective effect of the resveratrol;Estudo do efeito radioprotetor do resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Carolina dos Santos

    2009-07-01

    Resveratrol (3,4,5 trihydroxystilbene), a phenolic phytoalexin occurring naturally in a wide variety of plants, such as grapevines, in response to injury as fungal infections and exposure to ultraviolet light. In the wines this compound is present at high levels and is considered one of the highest antioxidant constituents. This high capacity to scavenge the free radicals generated by several biologic processes by resveratrol can provide a prevention of human cardiovascular diseases and several types of cancer. The main objective of this study was to determine the in vitro radioprotective effect of resveratrol in cell culture with the aid of the tests of cytotoxicity of resveratrol (IC50%) and lethal dose 50% of gamma radiation (LD50). Studies of the level of resveratrol toxicity, found by cytotoxicity test performed by neutral red uptake assay, and lethal dose 50% (LD50) of gamma radiation from source of Cobalt-60 (Co-60) was performed in cell culture NCTC Clone 929 from ATCC. The IC50% of resveratrol was about 50 M/L. The DL50 of gamma radiation showed a value of about 354 Gy. On the basis of these biological results, it was performed studies of radioprotective effect of resveratrol on the same experimental conditions, verifying that the resveratrol in concentrations between 12.5 M/L and 25 M/L showed a more pronounced radioprotective effect. (author)

  10. Representative parameter of immunostimulatory ginseng polysaccharide to predict radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Son, Hyeog Jin; Shim, Ji Young; Ahn, Ji Yeon; Yun, Yeon Sook; Song, Jie Young [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2008-09-15

    According to the increase in the use of radiotherapy to cancer patients, many approaches have been tried to develop new agents for the protection of surrounding normal tissues. However, it is still few applied in the clinic as a radioprotector. We aim to find a representative parameter for radioprotection to easily predict the activity of in vivo experiment from the results of in vitro screening. The polysaccharide extracted from Panax ginseng was used in this study because the immunostimulator has been regarded as one of the radioprotective agent category and was already reported having a promising radioprotective activity through the increase of hematopoietic cells and the production of several cytokines. Mitogenic activity, AK cells activity and nitric oxide production were monitored for the in vitro immunological assay, and endogenous Colony-Forming Unit (e-CFU) was measured as in vivo radioprotective parameter. The immunological activity was increased by the galactose contents of ginseng polysaccharide dependently. The result of this study suggests that mitogenic activity of splenocytes demonstrated a good correlation with in vivo radioprotective effect, and may be used as a representative parameter to screen the candidates for radioprotector.

  11. Radioprotective Agents

    Directory of Open Access Journals (Sweden)

    Ilker Kelle

    2008-01-01

    Full Text Available Since1949, a great deal of research has been carried out on the radioprotective activity of various chemical substances. Thiol compounds, compounds which contain –SH radical, different classes of pharmacological agents and other compounds such as vitamine C and WR-2721 have been shown to reduce mortality when administered prior to exposure to a lethal dose of radiation. Recently, honey bee venom as well as that of its components melittin and histamine have shown to be valuable in reduction of radiation-induced damage and also provide prophylactic alternative treatment for serious side effects related with radiotherapy. It has been suggested that the radioprotective activity of bee venom components is related with the stimulation of the hematopoetic system.

  12. Radioprotection: mechanism and radioprotective agents including honeybee venom

    Energy Technology Data Exchange (ETDEWEB)

    Varanda, E.A.; Tavares, D.C. [UNESP, Araraquara, SP (Brazil). Escola de Ciencias Farmaceuticas. Dept. de Ciencias Biologicas

    1998-07-01

    Since 1949, a great deal of research has been carried on the radioprotective action of chemical substances. These substances have shown to reduce mortality when administered to animals prior to exposure to a lethal dose of radiation. This fact is of considerable importance since it permits reduction of radiation-induced damage and provides prophylactic treatment for the damaging effects produced by radiotherapy. The following radioprotection mechanisms were proposed: free radical scavenger, repair by hydrogen donation to target molecules formation of mixed disulfides, delay of cellular division and induction of hypoxia in the tissues. Radioprotective agents have been divided into four major groups: the thiol compounds, other sulfur compounds, pharmacological agents (anesthetic drugs, analgesics, tranquilizers, etc.) and other radioprotective agents (WR-1065, WR-2721, vitamins C and E, glutathione, etc.). Several studies revealed the radioprotective action of Apis mellifera honeybee venom as well as that of its components mellitin and histamine. Radioprotective activity of bee venom involves mainly the stimulation of the hematopoietic system. In addition, release of histamine and reduction in oxygen tension also contribute to the radioprotective action of bee venom. (author)

  13. Workstations studies and radiation protection; Etudes de postes et radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Lahaye, T. [Direction des relations du travail, 75 - Paris (France); Donadille, L.; Rehel, J.L.; Paquet, F. [Institut de Radioprotection et de Surete Nucleaire, 92 - Fontenay-aux-Roses (France); Beneli, C. [Paris-5 Univ., 75 (France); Cordoliani, Y.S. [Societe Francaise de Radioprotection, 92 - Fontenay-aux-Roses (France); Vrigneaud, J.M. [Assistance Publique - Hopitaux de Paris, 75 (France); Gauron, C. [Institut National de Recherche et de Securite, 75 - Paris (France); Petrequin, A.; Frison, D. [Association des Medecins du Travail des Salaries du Nucleaire (France); Jeannin, B. [Electricite de France (EDF), 75 - Paris (France); Charles, D. [Polinorsud (France); Carballeda, G. [cabinet Indigo Ergonomie, 33 - Merignac (France); Crouail, P. [Centre d' Etude sur l' Evaluation de la Protection dans le Domaine Nucleaire, 92 - Fontenay-aux-Roses (France); Valot, C. [IMASSA, 91 - Bretigny-sur-Orge (France)

    2006-07-01

    This day on the workstations studies for the workers follow-up, was organised by the research and health section. Devoted to the company doctors, for the competent persons in radiation protection, for the engineers of safety, it presented examples of methodologies and applications in the medical, industrial domain and the research, so contributing to a better understanding and an application of regulatory measures. The analysis of the workstation has to allow a reduction of the exposures and the risks and lead to the optimization of the medical follow-up. The agenda of this day included the different subjects as follow: evolution of the regulation in matter of demarcation of the regulated zones where the measures of workers protection are strengthened; presentation of the I.R.S.N. guide of help to the realization of a workstation study; implementation of a workstation study: case of radiology; the workstation studies in the research area; Is it necessary to impose the operational dosimetry in the services of radiodiagnostic? The experience feedback of a competent person in radiation protection (P.C.R.) in a hospital environment; radiation protection: elaboration of a good practices guide in medical field; the activities file in nuclear power plant: an evaluation tool of risks for the prevention. Methodological presentation and examples; insulated workstation study; the experience feedback of a provider; Contribution of the ergonomics to the determiners characterization in the ionizing radiation exposure situations;The workstations studies for the internal contamination in the fuel cycle facilities and the consideration of the results in the medical follow-up; R.E.L.I.R. necessity of workstation studies; the consideration of the human factor. (N.C.)

  14. Radioprotection by metals: Selenium

    Science.gov (United States)

    Weiss, J. F.; Srinivasan, V.; Kumar, K. S.; Landauer, M. R.

    The need exists for compounds that will protect individuals from high-dose acute radiation exposure in space and for agents that might be less protective but less toxic and longer acting. Metals and metal derivatives provide a small degree of radioprotection (dose reduction factor animal survival after whole-body irradiation). Emphasis is placed here on the radioprotective potential of selenium (Se). Both the inorganic salt, sodium selenite, and the organic Se compound, selenomethionine, enhance the survival of irradiated mice (60Co, 0.2 Gy/min) when injected IP either before (-24 hr and -1 hr) or shortly after (+15 min) radiation exposure. When administered at equitoxic doses (one-fourth LD10; selenomethionine = 4.0 mg/kg Se, sodium selenite = 0.8 mg/kg Se), both drugs enhanced the 30-day survival of mice irradiated at 9 Gy. Survival after 10-Gy exposure was significantly increased only after selenomethionine treatment. An advantage of selenomethionine is lower lethal and behavioral toxicity (locomotor activity depression) compared to sodium selenite, when they are administered at equivalent doses of Se. Sodium selenite administered in combination with WR-2721, S-2-(3-aminopropylamino)ethylphosphorothioic acid, enhances the radioprotective effect and reduces the lethal toxicity, but not the behavioral toxicity, of WR-2721. Other studies on radioprotection and protection against chemical carcinogens by different forms of Se are reviewed. As additional animal data and results from human chemoprevention trials become available, consideration also can be given to prolonged administration of Se compounds for protection against long-term radiation effects in space.

  15. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: An FTIR microspectroscopic imaging study

    Energy Technology Data Exchange (ETDEWEB)

    Cakmak G.; Miller L.; Zorlu, F.; Severcan, F.

    2012-03-03

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH{sub 2} groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH{sub 3} groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems.

  16. Amifostine, a radioprotectant agent, protects rat brain tissue lipids against ionizing radiation induced damage: an FTIR microspectroscopic imaging study.

    Science.gov (United States)

    Cakmak, Gulgun; Miller, Lisa M; Zorlu, Faruk; Severcan, Feride

    2012-04-15

    Amifostine is the only approved radioprotective agent by FDA for reducing the damaging effects of radiation on healthy tissues. In this study, the protective effect of amifostine against the damaging effects of ionizing radiation on the white matter (WM) and grey matter (GM) regions of the rat brain were investigated at molecular level. Sprague-Dawley rats, which were administered amifostine or not, were whole-body irradiated at a single dose of 800 cGy, decapitated after 24 h and the brain tissues of these rats were analyzed using Fourier transform infrared microspectroscopy (FTIRM). The results revealed that the total lipid content and CH(2) groups of lipids decreased significantly and the carbonyl esters, olefinic=CH and CH(3) groups of lipids increased significantly in the WM and GM after exposure to ionizing radiation, which could be interpreted as a result of lipid peroxidation. These changes were more prominent in the WM of the brain. The administration of amifostine before ionizing radiation inhibited the radiation-induced lipid peroxidation in the brain. In addition, this study indicated that FTIRM provides a novel approach for monitoring ionizing radiation induced-lipid peroxidation and obtaining different molecular ratio images can be used as biomarkers to detect lipid peroxidation in biological systems. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Hydrogen as a New Class of Radioprotective Agent

    Science.gov (United States)

    Qian, Liren; Shen, Jianliang; Chuai, Yunhai; Cai, Jianming

    2013-01-01

    It is well known that most of the ionizing radiation-induced damage is caused by hydroxyl radicals (·OH) follows radiolysis of H2O. Molecular hydrogen (H2) has antioxidant activities by selectively reducing ·OH and peroxynitrite(ONOO-). We firstly hypothesized and demonstrated the radioprotective effect of H2 in vitro and in vivo, which was also repeated on different experimental animal models by different departments. A randomized, placebo-controlled study showed that consumption of hydrogen-rich water reduces the biological reaction to radiation-induced oxidative stress without compromising anti-tumor effects. These encouraging results suggested that H2 represents a potentially novel preventative strategy for radiation-induced oxidative injuries. H2 is explosive. Therefore, administration of hydrogen-rich solution (physiological saline/pure water/other solutions saturated with H2) may be more practical in daily life and more suitable for daily consumption. This review focuses on major scientific and clinical advances of hydrogen-rich solution/H2 as a new class of radioprotective agent. PMID:24155664

  18. Quality control and radioprotection in dental cone beam computed tomography - case study

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Ligiane C.N.; Ferreira, Nadya M.P.D., E-mail: lnadya@ime.eb.br [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil)

    2011-07-01

    The radiological protection in medical and odontologic radiology follows The Order (Portaria) 453/98 of the Ministry of Health, which presents the minimum set of tests for the constancy X-ray equipment. These tests follow the procedures set forth in the Resolution no. 64, the National Agency for Sanitary Vigilance. This work aims to show a study on dental cone beam computed tomography (CBCT), evaluating the physical parameters that influence the performance and image quality and presenting the appropriate tests to this new system. The authors analyzed the tests specific for computed tomography (CT) of the Resolution no. 64, feasibility assessment of them and if their interpretations are compatible with CBCT. Once determined if testing is feasible, compare with those presented in the manual provided by the equipment manufacturer. The CT scanner used was the Mini-Cat Tomography Scanner Xoran Technologies of KAVO. In the study it was verified that four tests could be reproduced in CBCT: noise, accuracy and uniformity in the number of CT of water and spatial resolution. Considering experimental data, the methodology and tolerance of manufacturer for the first two tests were more appropriate. For the uniformity test of the CT number, we recommend using the phantom quality control. Three new tests were suggested to be made in the quality control of the Cone Beam: linearity, artifacts and alignment of the beam. (author)

  19. Study on radioprotection of alliin and damage mechanism in hepatocyte after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Tae Jeong; Kim, Won Tae [Dept, of Radiological Science, Kaya University, Kimhae (Korea, Republic of)

    2016-12-15

    Liver tissue damage by a radiation exposure caused a jaundice and ascitic fluid e form harden atrophy. The reason for this lies in morphological damage of a liver cells. This study tried that observe damage mechanism of the cell organelles. It was especially observed mitochondria, endoplasmic reticulum and nuclear membrane associated with energy metabolizable. also, This study had with a radio-protector development research at the same time. Radio-protector was used to alliin that has an blood flow increase. Cell observation make used of transmission electron microscope(TEM). The result of an experiment, 7Gy of whole body irradiation was caused an inflammation in cell organelles and hypertrophy of the nucleus membrane. After 20 days, The hepatocyte has been observed in a damaged membrane on peroxisome, mitochondria and vacuole of the cell organelles. After 30 days, The hepatocyte has been observed in disconnected ribosomes on a rough endoplasmic reticulum. There was looked a giant lipoblast. There was clearly normal observed a mitochondria and nucleus membrane in the hepatocyte after alliin injection. aslo, It was no damaged the nucleus membrane. Therefore, It was identified portion a radio-protector effect from alliin.

  20. Study on radioprotection effects of clinoptilolite on sub-acute radiation-injured mice

    Directory of Open Access Journals (Sweden)

    Na LI

    2016-03-01

    Full Text Available Objective  To study the protection effect of clinoptilolite (Cp against radiation injury. Methods  Fortyeight male BALB/c mice were randomly divided into 6 groups, namely normal control group (distilled water + sham irradiation, radiation control group (distilled water + irradiation, 300mg/kg 523 group (200mg/kg nilestriol 24h before irradiation and 100mg/ kg nilestriol 4h after irradiation, 56mg/kg Cp group (56mg/kg Cp + irradiation, 167mg/kg Cp group (167mg/kg Cp + irradiation and 500mg/kg Cp group (500mg/kg Cp + irradiation. Seven days after the administration of the drug, all the mice but those from the normal control group were irradiated with γ-ray irradiation of 137Cs in the dose of 4.0Gy, at the rate of 0.75Gy/min. All the mice were given the drug for 14 days after irradiation. RBC, WBC and PLT counts in peripheral blood, superoxide dismutases (SOD activity, malondialdehyde (MDA level, glutathione peroxidase (GSH-Px level in blood serum, the content of deoxyribonucleic acid (DNA and hematopoietic stem cells in bone marrow were determined. Results  Compared with radiation control group, on 10th day after irradiation, RBC counts in peripheral blood of 56mg/kg Cp group and 167mg/kg Cp group were significantly higher (P<0.05, P<0.01, and WBC counts in peripheral blood of 56mg/kg Cp group and 500mg/kg Cp group were significantly higher (P<0.01. On 14th day after irradiation, compared with radiation control group, the SOD activities in blood serum of three Cp groups were elevated (P<0.05, P<0.01, the GSH-Px levels were elevated in blood serum of 167mg/kg Cp group and 500mg/kg Cp group (P<0.01, the DNA contents were significantly higher in 56mg/kg Cp group and 500mg/kg Cp group (P<0.05, P<0.01, the hematopoietic stem cells were significantly increased in number in bone marrow of three Cp groups (P<0.01. Conclusion  The clinoptilolite possesses protective effect against injury induced by 137Cs γ-irradiation in mice. DOI: 10.11855/j

  1. Radioprotective potential of mint: A brief review

    Directory of Open Access Journals (Sweden)

    Baliga Manjeshwar

    2010-01-01

    Full Text Available Radiation is an important modality in cancer treatment and estimates are that between one third and one half of all patients will require ionizing irradiation therapy during some point in their clinical management. However, the radiation-induced damage to the normal tissues restricts the therapeutic doses of radiation that can be delivered to tumors and thereby limits the effectiveness of the treatment. The use of chemical compounds (radioprotectors represents an obvious strategy to improve the therapeutic index in radiotherapy. However, most of the synthetic radioprotective compounds studied have shown inadequate clinical application owing to their inherent toxicity and high cost. These observations necessitated a search for alternative agents that are less toxic and highly effective. Studies in the recent past have shown that some medicinal plants possess radioprotective effects. Two species of the commonly used aromatic herb mint, Mentha piperita and M. arvensis protected mice against the γ-radiation-induced sickness and mortality. Detail investigations have also shown that the aqueous extract of M. piperita protected the vital radiosensitive organs: the testis, gastrointestinal and hemopoetic systems in mice. The radioprotective effects are possibly due to free radical scavenging, antioxidant, metal chelating, anti-inflammatory, antimutagenic, and enhancement of the DNA repair processes. This review for the first time summarizes the observations and elucidates the possible mechanisms responsible for the beneficial effects. The lacunae in the existing knowledge and directions for future research are also addressed.

  2. The evaluation of the radioprotective effect of chyavanaprasha (an ayurvedic rasayana drug) in mice exposed to lethal dose of gamma-radiation: a preliminary study.

    Science.gov (United States)

    Jagetia, Ganesh Chandra; Baliga, Manjeshwar Shrinath

    2004-01-01

    The effect of various doses of 50% ethanolic extract of chyavanaprasha (an Ayurvedic rejuvenating herbal preparation) was studied on the survival of mice exposed to 10 Gy of gamma-radiation. Treatment with chyavanaprasha, consecutively for fi ve days before irradiation, delayed symptoms of radiation sickness and onset of mortality when compared with the non-drug treated irradiated controls. All doses of chyavanaprasha provided a significant protection against gastrointestinal (GI) death (death of animals within 10 days after exposure to radiation), however, highest protection against GI death was observed for 15 mg/kg chyavanaprasha. Chyavanaprasha also provided a significant protection against the bone marrow death after 10 to 40 mg/kg. However, the best protection was seen for 15 mg/kg, where the highest number of survivors was observed at the end of 30 days post-irradiation. The drug was non-toxic up to a dose of 6 g/kg b. wt., the highest drug dose that could be tested. Our study demonstrates that chyavanaprasha can provide good radioprotection at a very low non-toxic dose. Copyright 2004 John Wiley & Sons, Ltd.

  3. Attitudes des prescripteurs de scanner en matiere de radioprotection ...

    African Journals Online (AJOL)

    Objectif: Evaluer les attitudes des prescripteurs de scanner en matière de radioprotection des patients à Lomé au Togo. Méthodologie: Etude transversale descriptive ... Objective: Estimate the attitudes of CT scan prescribers regarding radiation protection of the patients in Lome. Methods: Cross-sectional study performed ...

  4. Radioprotection provides functional mechanics but delays healing of irradiated tendon allografts after ACL reconstruction in sheep.

    Science.gov (United States)

    Seto, Aaron U; Culp, Brian M; Gatt, Charles J; Dunn, Michael

    2013-12-01

    Successful protection of tissue properties against ionizing radiation effects could allow its use for terminal sterilization of musculoskeletal allografts. In this study we functionally evaluate Achilles tendon allografts processed with a previously developed radioprotective treatment based on (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) crosslinking and free radical scavenging using ascorbate and riboflavin, for ovine anterior cruciate ligament reconstruction. Arthroscopic anterior cruciate ligament (ACL) reconstruction was performed using double looped allografts, while comparing radioprotected irradiated and fresh frozen allografts after 12 and 24 weeks post-implantation, and to control irradiated grafts after 12 weeks. Radioprotection was successful at preserving early subfailure mechanical properties comparable to fresh frozen allografts. Twelve week graft stiffness and anterior-tibial (A-T) translation for radioprotected and fresh frozen allografts were comparable at 30 % of native stiffness, and 4.6 and 5 times native A-T translation, respectively. Fresh frozen allograft possessed the greatest 24 week peak load at 840 N and stiffness at 177 N/mm. Histological evidence suggested a delay in tendon to bone healing for radioprotected allografts, which was reflected in mechanical properties. There was no evidence that radioprotective treatment inhibited intra-articular graft healing. This specific radioprotective method cannot be recommended for ACL reconstruction allografts, and data suggest that future efforts to improve allograft sterilization procedures should focus on modifying or eliminating the pre-crosslinking procedure.

  5. Radioprotection against DNA damage by an extract of Indian green mussel, Perna viridis (L.)

    Digital Repository Service at National Institute of Oceanography (India)

    Kumaran, S.P.; Kutty, B.C.; Chatterji, A.; Parameswaran, P.S.; Mishra, K.P.

    This study describes the radioprotective ability of a hydrolysate prepared using an enzymeacid hydrolysis method from the green mussel Perna viridis in terms of its ability to prevent radiation-induced damage in plasmid DNA, cell death, reactive...

  6. Interventional techniques in medicine and radioprotection; Les techniques interventionnelles en medecine et radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Le Guen, B.; Bar, O.; Benderitter, M.; Bourguignon, M.; Chevillard, S.; Gauron, Ch.; Lallemand, J.; Lombard, J.; Maccia, C.; Sapoval, M.; Bernier, M.O.; Pirard, Ph.; Jacob, S.; Donadille, L.; Aubert, B.; Clairand, I.; Mozziconacci, J.G.; Brot, A.M.; Jarrige, V.; Huet, Ch.; Marchal, C.; Martin, M.; Bar, O.; Degrange, J.P.; Livarek, B.; Menechal, Ph.; Sapoval, M.; Pellerin, O.

    2009-07-01

    This document gathers the slides of the available presentations given during this conference day. Nineteen presentations are assembled in the document and deal with: 1 - Interventional radiology: why is it developing? (M. Sapoval); 2 - exposure particularities in interventional radiology (O. Bar); 3 - doses received by organs in interventional cardiology (C. Maccia); 4 - Patients exposure: description of cumulated exposure of patients treated in interventional cardiology (M.O. Bernier); 5 - 2004 inquiry to dermatologists about post-interventional radiology radio-dermatitis (P. Pirard); 6 - exposure and risks to operators (S. Jacob); 7 - dosimetric evaluation techniques and results about interventional imaging operators' extremities (L. Donadille and F. Merat); 8 - bibliographic study of doses received by operators with non-protected organs (B. Aubert); 9 - ORAMED European project: optimization of operational dosimeter uses in interventional radiology (I. Clairand); 10 - reference levels and dosimetric evaluation of patients (C. Maccia); 11 - optimization in coronary angioplasty (J.G. Mozziconacci, A.M. Brot and V. Jarrige); 12 - dosimetry in medical over-exposure situation (C. Huet); 13 - significant radioprotection events in interventional radiology declared to the Nuclear Safety Authority (ASN) - status and experience feedback (C. Marchal); 14 - interventional radiology and unwanted effects (M. Benderitter); 15 - global analyses and new exposure indicators in human epidermis cells (M. Martin); 16 - radioprotection regulations and training (O. Bar); 17 - zoning and workplace analysis in interventional cardiology (J.P. Degrange); 18 - guide of good clinical practices: example of interventional cardiology (B. Livarek); 19 - how to encourage the radioprotection optimization in interventional radiology: the ASN's point of view (P. Menechal). (J.S.)

  7. Analysis of Minocycline as a Radioprotectant

    Science.gov (United States)

    Mehrotra, Shalini

    Exposure to radiation is increasing in a variety of settings including space exploration, diagnostic medical procedures and radiotherapy. Cells of the hematopoietic system, such as white blood cells (WBC), are especially sensitive to radiation and their decline can result in Acute Radiation Syndrome (ARS). Radiotherapy is often used for cancers of the central nervous system (CNS), but includes the risk for normal tissue damage, often leading to cognitive impairment. The literature suggests that tetracyclines can be radioprotectors of the hematopoietic system with potential utility in radiation emergencies and anticancer radiotherapy. Minocycline, a semisynthetic tetracycline derivative, has anti-inflammatory, free radical scavenging, anti-apoptotic and anti-angiogenic properties with exceptional penetration into the CNS. These qualities make it a viable candidate for use in combination with radiotherapy for CNS tumors as a normal tissue radioprotectant and for hematopoietoc recovery following whole-body irradiation. This study was undertaken to determine the potential of minocycline as a radioprotective agent of the hematopoietic system and CNS in response to whole-body irradiation with 1, 2 and 3 Gy (γ-rays). C57BL/6 mice were injected with minocycline, 5 times beginning immediately before irradiation. Spleen, blood and brain were collected on days 4 and 32 post-irradiation. WBC and other cell populations were determined in the blood and spleen while cytokines were quantified in CD3-activated splenocytes and homogenized brain supernatants. We also evaluated the impact of minocycline on DNA synthesis and viability of human glioblastoma cells versus astrocytes and microglia. Minocycline increased counts and percentages of splenic macrophages, granulocytes, natural killer (NK), T and CD8 + T cells on day 4 and B cells on day 32. Minocycline up-regulated interleukin-1α (IL-1α)which is radioprotective, as well as granulocyte-macrophage colony stimulating factor (GM

  8. Evaluation of the radioprotective efficacy of rifaximin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Won Woo; Kim, Mi Sook; Jeong, Jae Hoon; Kim, Hee Jong [Dept. of Radiation Treatment Research, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-04-15

    Radiation exposure causes severe intestinal damage, and intestinal injury has been shown to plays a pivotal role in survival. The non-systemic antibiotic, rifaximin, is used in the treatment of traveler's diarrhea due to bacterial enteropathogens and has an anti-biotic and an anti-inflammatory effect with low gastrointestinal absorption of < 0.4%. Rifaximin also has been used for treatment of irritable bowel syndrome, small bowel bacterial overgrowth, pouchitis. Jahraus et al. reported that rifaximin diminishes neutropenia following potentially lethalmwhole-body radiation. The purpose of this study was to evaluate the radioprotective effect of rifaximin on ionizing radiation-induced intestinal injury. Rifaximin showed increased survival rate as well as decreased weight loss between pre treatment and post treatment. Fortunately rifaximin seems to involveincreased number of crypt cells and length of villus. These findings suggest that rifaximin can be a strategy by protecting intestinal injury.

  9. In vitro screening of radioprotective properties in the novel glucosylated flavonoids.

    Science.gov (United States)

    Yu, Hao; Haskins, Jeremy S; Su, Cathy; Allum, Allison; Haskins, Alexis H; Salinas, Victoria A; Sunada, Shigeaki; Inoue, Taisuke; Aizawa, Yasushi; Uesaka, Mitsuru; Kato, Takamitsu A

    2016-11-01

    Novel glucosyl flavonoids are developed by the addition of glucose to naturally occurring flavonoids. Flavonoids are known antioxidants that possess radioprotective properties. In order to investigate the radioprotective properties of novel glucosyl flavonoids, in vitro DNA double-strand breaks (DSBs) analysis was carried out. In the present study, Quercetin, Naringenin, and Hesperetin groups of flavonoids included in the natural and novel glucosyl 13 flavonoids were investigated. Flavonoids were mixed with Lambda DNA, and subsequently exposed to gamma‑rays. Furthermore, DNA DSB yields were visualized by gel electrophoresis. Quercetin derivatives displayed reduced DNA DSB formation at 10 µM. At a high concentration, the majority of flavonoids displayed radioprotective properties as a reduction of DSB yields. Suppression of DSB formation was confirmed via the molecular combing assay for Quercetin, and three monoglucosyl flavonoids. Glucosylation showed positive effects for radioprotection and monoglucosyl-Rutin showed superior radioprotective properties when compared to monoglucosyl-Naringin and Hesperidin. In addition, Quercetin derivatives had greater total antioxidant capacities and DPPH radical scavenging ability than other flavonoid groups. Since Quercetin, Isoquercetin, and Rutin display poor water solubility, monoglucosyl-Rutin, maltooligosyl-Isoquercetin, and maltooligosyl-Rutin may be better radioprotective agents and easily bioavailable with increased water solubility.

  10. RADIOPROTECTION CAMPAIGN AND CARD: EDUCATIONAL STRATEGIES THAT REDUCE CHILDREN'S EXCESSIVE EXPOSURE TO RADIOLOGICAL EXAMS.

    Science.gov (United States)

    Bernardo, Mônica Oliveira; Almeida, Fernando Antonio de; Morgado, Flavio

    2017-01-01

    To analyze the results of an initiative aimed at improving the reasonable use of radiological examinations, ensuring their technical quality, implementing a radioprotection campaign that includes training of the professional team, and introducing the radioprotection card for children under 12 years old as a tool for parents and doctors to control children's exposure to radiation. The study was held in a health care insurance system covering 140,000 people. A radioprotection campaign was implemented according to Image Gently • protocols, ensuring the lowest dose of radiation and the quality of examinations, and the radioprotection card was implemented. To assess the effectiveness of these actions, the number of radiological examinations performed at the pediatric emergency room in a period of one year preceding the campaign was compared with the number of radiological examinations performed one year after the campaign. The campaign was well accepted by all professionals, families, and patients involved. In the year following the implementation of radioprotection strategies, there was a 22% reduction of radiological examinations performed at the pediatric emergency room. There was also a 29% reduction in the request of two or more radiological examinations for the same child or examinations with two or more incidences. The campaign and the radioprotection card for children under 12 years old proved to be feasible strategies and correlated with a reduction in radiological examinations requested and performed at the pediatric emergency room.

  11. Therapeutic Nanoparticles Based on Curcumin and Bamboo Charcoal Nanoparticles for Chemo-Photothermal Synergistic Treatment of Cancer and Radioprotection of Normal Cells.

    Science.gov (United States)

    Xie, Jiani; Yong, Yuan; Dong, Xinghua; Du, Jiangfeng; Guo, Zhao; Gong, Linji; Zhu, Shuang; Tian, Gan; Yu, Shicang; Gu, Zhanjun; Zhao, Yuliang

    2017-04-26

    Low water solubility, extensive metabolism, and drug resistance are the existing unavoidable disadvantages of the insoluble drug curcumin in biomedical applications. Herein, we employed d-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-functionalized near-infrared (NIR)-triggered photothermal mesoporous nanocarriers with bamboo charcoal nanoparticles (TPGS-BCNPs) to load and deliver curcumin for improving its bioavailability. This system could considerably increase the accumulation of curcumin in cancer cells for enhanced curcumin bioavailability via simultaneously promoting the cellular internalization of the as-synthesized composite (TPGS-BCNPs@curcumin) by the size effect of NPs and considerably triggering controlled curcumin release from TPGS-BCNPs@curcumin by NIR stimulation and reducing efflux of curcumin by the P-glycoprotein (P-gp) inhibition of TPGS, so as to enhance the therapeutic effect of curcumin and realize a better chemo-photothermal synergetic therapy in vitro and in vivo. Besides cancer therapy, studies indicated that curcumin and some carbon materials could be used as radical scavengers that play an important role in the radioprotection of normal cells. Hence, we also investigated the free-radical-scavenging ability of the TPGS-BCNPs@curcumin composite in vitro to preliminarily evaluate its radioprotection ability for healthy tissues. Therefore, our work provides a multifunctional delivery system for curcumin bioavailability enhancement, chemo-photothermal synergetic therapy of cancer, and radioprotection of healthy tissues.

  12. Radioprotective effects of antioxidative plant flavonoids in mice

    Energy Technology Data Exchange (ETDEWEB)

    Shimoi, Kayoko; Masuda, Shuichi; Shen, Bingrong; Furugori, Michiyo; Kinae, Naohide [Laboratory of Food Hygiene, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka (Japan)

    1996-01-19

    Radioprotective effects of tea infusions and plant flavonoids were investigated by using the micronucleus test for anticlastogenic activity and the thiobarbituric acid assay for antioxidative activity. A single gastric intubation of rooibos tea (Aspalathus linearis) infusion at 1 ml per mouse 2 h prior to {gamma}-ray irradiation (1.5 Gy) reduced the frequency of micronucleated reticulocytes (MNRETs). After the fractionation of rooibos tea infusion, the flavonoid fraction was found to be most anticlastogenic and antioxidative. From this fraction, luteolin was isolated as an effective component. Then, anticlastogenic effects of 12 flavonoids containing luteolin and their antioxidative activities against lipid peroxidation by Fenton`s reagent were examined. A good correlation (r=0.717) was observed between both activities. Luteolin showed the most effective potency. A gastric intubation of luteolin (10 {mu}mol/kg) 2 h prior to {gamma}-ray irradiation (6 Gy) suppressed lipid peroxidation in mouse bone marrow and spleen and a trend of protective effect of luteolin against the decrease of endogenous ascorbic acid in mouse bone marrow after {gamma}-ray irradiation (3 Gy) was observed. These results suggest that plant flavonoids, which show antioxidative potency in vitro, work as antioxidants in vivo and their radioprotective effects may be attributed to their scavenging potency towards free radicals such as hydroxyl radicals. Therefore, the flavonoids contained in tea, vegetables and fruits seem to be important as antioxidants in the human diet.

  13. Radioprotection calculations for the TRADE experiment

    CERN Document Server

    Zanini, L; Herrera-Martínez, A; Kadi, Y; Rubbia, Carlo; Burgio, N; Carta, M; Santagata, A; Cinotti, L

    2002-01-01

    The TRADE project is based on the coupling of, in a sub-critical configuration, of a 115 MeV, 2 mA proton cyclotron with a TRIGA research reactor at the ENEA Casaccia centre (Rome). Detailed radioprotection calculations using the FLUKA and EA-MC Monte Carlo codes were performed during the feasibility study. The study concentrated on dose rates due to beam losses in normal operating conditions and in the calculation of activation in the most sensitive components of the experiment. Results show that a shielding of 1.4 m of barytes concrete around the beam line will be sufficient to maintain the effective doses below the level of 10 Mu Sv/h, provided that the beam losses are at the level of 10 nA/m. The activation level around the beam line and in the water will be negligible, while the spallation target will reach an activation level comparable to the one of a fuel element at maximum burnup.

  14. Radioprotective activity in some medicinal herbs

    Energy Technology Data Exchange (ETDEWEB)

    Yonezawa, Morio (Osaka Prefectural Univ., Sakai (Japan). Research Center for Radioisotopes)

    1993-09-01

    Water-soluble, ethanol-insoluble extracts prepared from several medicinal herbs of the Araliaceae and other families were tested for their radioprotective activity by either measuring 30 days survival rates (a commonly applied method) or counting the thrombocytes 14 days after irradiation (an improved method) in mice. The extracts were i.p. injected once within 4 min after the whole body X-ray irradiation. Of 12 materials examined, Aralia elata, Angelica acutiloba and Morus bombysis seemed to be good starting materials for preparing radioprotective substance(s) because of their relatively high specific activity and high yields of the extracts. (author).

  15. Assay for the antioxidant and radioprotectant activity of extracts form endemic plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Kim, Ji Hyang; Woo, Hyun Jung [KAERI, Taejeon (Korea, Republic of); Plewa, Michael J. [University of Illinois, Illinosi (United States)

    2004-07-01

    Since radiation damage and oxygen poisoning occur through the formation of reactive oxygen species, it is a challenging task to develop agents with high antioxidant and radioprotectant activities from plant species. In this study, several species of Korean endemic plants were chosen as experimental candidates. Water-and ethanol extracts were made from the candidates and tested for their antioxidant and radioprotectant activities. In vitro antioxidant assay of the aqueous-organic extracts was carried out using the free radical 2,2-diphenyl-1-picryl-hydrazyl scavenging method. Radioprotective effects were tested by means of experimental on irradiated cell cultures and animals. Among others, the water-extract of Ixeris dentata leaves showed a marked effect on the viability of B16 melanoma cells and provided a radioprotective effect on the number of the leukocytes in the irradiated rodents. DNA damage in the lymphocytes after {gamma}-irradiation decreased in the extract administered animals. Many of the extracts tested in this study showed a slightly lower activity in free radical scavenging than the well-known chemical antiozidants such as ascorbic acid, butylated hydroxytuluene, and glutathione. However, some extracts showed an antioxidant activity similar to that of {alpha}-tocopherol acetate and caffeine. These results support the optimistic view for developing radioprotective agents from the Korean endemic plants that showed a strong antioxidant activity.

  16. Evaluation of qualification and radioprotection knowledge of dentists in Rio de Janeiro, Brazil; Capacitacao e formacao do odontologo em radioprotecao no Estado do Rio de Janeiro

    Energy Technology Data Exchange (ETDEWEB)

    Padilha Filho, L.G.; Borges, J.C. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia

    1996-12-31

    The status and implications of the actual radioprotection knowledge of people studying dentistry is evaluated. A brief research of the current situation in Brazil is presented. The inclusion of a discipline - or the remaking of existing ones - in the curricula of Brazilian dentistry schools, covering subjects from radioprotection to images quality control is suggested 6 refs., 2 figs.

  17. Human Keratinocytes Radioprotection with Mentha Longifolia

    Science.gov (United States)

    Rizzo, Angela Maria; Berselli, P.; Zava, S.; Negroni, M.; Corsetto, P.; Montorfano, G.; Bertolotti, A.; Ranza, E.; Ottolenghi, A.; Berra, B.

    Antioxidants are suggested to act as radioprotectors, and dietary supplements based on antiox-idants have been proposed for astronauts involved in long-term space missions. Plant extracts with antioxidant properties may be used in dietetic supplements for astronauts; in fact recent nutritional guidelines suggest that "fruits and vegetables may become as important on space-going vessels as limes were on the sea-going vessels of old". Mint presents a large variety of biological properties, such as antiallergenic, antibacterial, anti-inflammatory, antitumor, an-tiviral, gastrointestinal protective, hepatoprotective, chemopreventive activities, most of which are attributable to its antioxidant activity. The aim of the present study is to evaluate the antioxidant properties and protective bio-efficacy of a phenol enriched Mentha longifolia ex-tract on gamma rays stressed human keratinocytes (NCTC2544). We assessed first the in vitro antioxidant activity (ABTS and DPPH), and then evaluated different stress markers in order to investigate various oxidative stress targets: cell viability (MTT); retained proliferating ca-pability (CA); DNA damage (histone H2AX) and protein damage (HSP70 induction). Results indicate that this Mint extract has a higher antioxidant activity respect to fresh extracts, that could be responsible of its really interesting radio-protective effects.

  18. Radioprotective Effects of Heat-Killed Mycobacterium Tuberculosis in Cultured Cells and Radiosensitive Tissues

    Directory of Open Access Journals (Sweden)

    Yuanyuan Chen

    2016-11-01

    Full Text Available Background: Exposure to ionizing radiation (IR often causes severe damage to radiosensitive tissues, which limits the use of radiotherapy in cancer patients. Novel safe and effective radioprotectant is urgently required. It has been reported toll like receptor 2 (TLR2 plays a critical role in radioresistance. In this study, we demonstrated the protective effects of Heat-Killed Mycobacterium tuberculosis (HKMT, a potent TLR2 agonist, against IR. Methods: Cell survival and apoptosis were determined by CCK-8 assay and Annexin V assay, respectively. An immunofluorescence staining assay was used to detect the translocation of nuclear faktor-kappa beta (NF-kB p65. Tissue damage was evaluated by Haematoxilin-Eosin (HE staining assay. We also used a flow cytometry assay to measure the number of nucleated cells and CD34+ hemopoietic stem cells in bone marrow. A western blot assay was used to detect the changes of proteins involving TLR signaling pathway. Results: We found that HKMT increased cell viability and inhibited cell apoptosis after irradiation. HKMT induced NF-kB translocation and activated Erk1/2, p38 signaling pathway. HKMT also protected bone marrow and testis from destruction. Radiation-induced decreases of nucleated cells and CD34+ hemopoietic stem cells in bone marrow were also inhibited by HKMT treatment. We found that radiation caused increase of inflammatory cytokines was also suppressed by HKMT. Conclusion: Our data showed that HKMT exhibited radioprotective effects in vivo and in vitro through activating NF-kB and MAPK signaling pathway, suggesting a potential of HKMT as novel radioprotector.

  19. Rasayana drugs from the Ayurvedic system of medicine as possible radioprotective agents in cancer treatment.

    Science.gov (United States)

    Baliga, Manjeshwar Shrinath; Meera, Sharake; Vaishnav, Lalit Kumar; Rao, Suresh; Palatty, Princy Louis

    2013-11-01

    The use of ionizing radiation, which is the cornerstone of cancer treatment, is compromised by the radiosensitivity of normal tissues. A chemical that can give selective benefit to the normal cells against the deleterious effects of ionizing radiation has been a long-sought goal. However, most of the compounds studied have shown inadequate clinical application owing to their inherent toxicity, undesirable side effects, and high cost. Studies carried out in the past 2 decades have shown that some of the classical Indian Ayurvedic drugs (Amritaprasham, Ashwagandha Rasayana, Brahma Rasayana, Chyavanprasha, Narasimha Rasayana, and Triphala Churna) possess radioprotective effects. In the current review, an attempt is made to summarize the radioprotective observations of these Ayurvedic drugs and the mechanisms responsible for the radioprotective effects.

  20. Radioprotection of targeted and bystander cells by methylproamine

    Energy Technology Data Exchange (ETDEWEB)

    Burdak-Rothkamm, Susanne [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom); Oxford University Hospitals, Cellular Pathology, Oxford (United Kingdom); Smith, Andrea; Lobachevsky, Pavel; Martin, Roger [Peter MacCallum Cancer Centre, Molecular Radiation Biology Laboratory, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Prise, Kevin M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast (United Kingdom)

    2014-09-23

    Radioprotective agents are of interest for application in radiotherapy for cancer and in public health medicine in the context of accidental radiation exposure. Methylproamine is the lead compound of a class of radioprotectors which act as DNA binding anti-oxidants, enabling the repair of transient radiation-induced oxidative DNA lesions. This study tested methylproamine for the radioprotection of both directly targeted and bystander cells. T98G glioma cells were treated with 15 μM methylproamine and exposed to {sup 137}Cs γ-ray/X-ray irradiation and He{sup 2+} microbeam irradiation. Radioprotection of directly targeted cells and bystander cells was measured by clonogenic survival or γH2AX assay. Radioprotection of directly targeted T98G cells by methylproamine was observed for {sup 137}Cs γ-rays and X-rays but not for He{sup 2+} charged particle irradiation. The effect of methylproamine on the bystander cell population was tested for both X-ray irradiation and He{sup 2+} ion microbeam irradiation. The X-ray bystander experiments were carried out by medium transfer from irradiated to non-irradiated cultures and three experimental designs were tested. Radioprotection was only observed when recipient cells were pretreated with the drug prior to exposure to the conditioned medium. In microbeam bystander experiments targeted and nontargeted cells were co-cultured with continuous methylproamine treatment during irradiation and postradiation incubation; radioprotection of bystander cells was observed. Methylproamine protected targeted cells from DNA damage caused by γ-ray or X-ray radiation but not He{sup 2+} ion radiation. Protection of bystander cells was independent of the type of radiation which the donor population received. (orig.) [German] Radioprotektive Agenzien sind sowohl in der Strahlentherapie von Krebserkrankungen als auch im Strahlenschutz im Zusammenhang mit akzidenteller Exposition von Bedeutung. Methylproamine ist die Leitsubstanz einer Klasse von

  1. Restoration of Radiation Injury by Ginseng. II. Some Properties of the Radioprotective Substances

    OpenAIRE

    米沢, 司郎; 加藤, 智雄; 武田, 篤彦; M., YONEZAWA; N., KATOH; A., TAKEDA; 大阪府立放射線中央研究所第4部; 大阪府立放射線中央研究所第4部; 大阪府立放射線中央研究所第4部; Department of Medicine and Hygiene, Radiation Center of Osaka Prefecture; Department of Medicine and Hygiene, Radiation Center of Osaka Prefecture; Department of Medicine and Hygiene, Radiation Center of Osaka Prefecture

    1981-01-01

    Some properties of the radioprotective substances in a ginseng extract that increased the 30-day survival ratio in irradiated mice were studied. Methanol-soluble fraction of the extract did not protect the irradiated animals. Acid or alkali (0.12 N) inactivated the extract at 60℃. But the radioprotective activity was stable after heating the ginseng extract in physiological saline at pH 7 in a boiling-water bath for 15 min. The ginseng extract was separated into two fractions by CM-cellulose ...

  2. Radioprotective Effects of Hairy Roots of Ginseng

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Hyun Jung; Kim, Jin Kyu [Korea Atomic research Institute, Jeongeup (Korea, Republic of); Kim, Eun Young; Yang, Deok Cho [Chungbuk National Univ., Cheongju (Korea, Republic of)

    2005-07-01

    Panax ginseng is an important medicinal plant in Korea, which has broad efficacious effects against hypertension, diabetes, nociception and cancer. And it improves weakness. The native ginseng is a slow growing plant taking 5-7 years from seed planting to mature root harvesting, during which time much care is needed since its growth is susceptible to many environmental factors such as soil, shade, climate, pathogens and pests. Nowadays, a wild ginseng has become extremely scarce and the ginseng supply depends almost exclusively on field cultivation, which is a time-consuming and labor-intensive process. To meet the demand for the plant in the international market, a bioreactor technology is a useful tool for production of root biomass on a large scale. Therefore, suspension culture of ginseng roots in bioreactors is viewed as a primary alternative method for large-scale production and recently our laboratory has developed a protocol for the in vitro culture of P. ginseng. About 60-70% of cellular DNA damage produced by ionizing radiation is caused by OH, formed from the radiolysis of water. Oxidative stress occurs when there is an excessive free radical production and/or low antioxidant defense, and results in the chemical alterations of biomolecules causing structural and functional modifications. The generation of the reactive oxygen metabolites plays an important role in the pathogenesis of the irradiation-induced tissue injury. An extensive literature review implicates cellular DNA as the primary target for the biological and lethal effects of ionizing radiation. Besides DNA, lipids and proteins are also attacked by free radicals. The purpose of this study, aimed at investigating the possible radioprotective effect of the hairy roots of P. ginseng on irradiation-induced damage by the comet assay.

  3. In vitro and in vivo study of endothelial cells radio-induced death modulation by Sphingosine-1-Phosphate; Etude in vitro et in vivo de la regulation de la mort radioinduite des cellules endotheliales par la Sphingosine-1-Phosphate

    Energy Technology Data Exchange (ETDEWEB)

    Bonnaud, St

    2007-01-15

    Protecting the vasculature from radiation-induced death is a major concern in tissue radioprotection. Developing a model of endothelial cells radiosensitivity, we proved that HMEC-1 undergo 2 waves of death after exposure to 15 Gy: an early pre mitotic apoptosis dependent of ceramide generation and a delayed DNA damage-induced mitotic death. Sphingosine-1-Phosphate (S1P), a ceramide antagonist, protects HMEC-1 only from early apoptosis, but not from mitotic death. We confirmed in vivo the S1P radioprotection from ceramide-mediated radio-induced apoptosis, and that S1P radioprotection is partially mediated by S1Ps receptors. Segregation between these 2 types of death may give the opportunity to define a new class of radioprotectors for normal tissue where quiescent endothelium represent the most sensitive target, while excluding malignant tumor containing pro-proliferating angiogenic endothelial cells, sensitive to mitotic death. (author)

  4. 2-Mercaptopropionyiglycine Affords Enhanced Radioprotection After a Liposome Encapsulation

    OpenAIRE

    R.N., SHARAN; A., ALAM; SANGHAMITRA, CHAKRABORTY; JYOTI R., SAIKIA; P.N., SRIVASTAVA; lmmunology Laboratory, Department of Biochemistry, School of Life Sciences North-Eastern Hill University; Radiation &Molecular Biology Unit, Department of Biochemistry, School of Life Sciences North-Eastern Hill University; Nuclear Science Center, JNU Campus

    1995-01-01

    Use of radioprotective drugs in radiotherapy is desirable to protect normal tissues. 2-mercaptopropionyiglycine (MPG) has shown promising results in experimental radioprotection. In this report, a liposome drug delivery system for MPG has been used in Swiss albino mice exposed to 1 to 8 Gy whole body Gamma-irradiation to test whether or not this modality enhances the MPG afforded radio-protection. A statistically significant, dose dependent enhancement of protection by liposome encapsulated M...

  5. Radiobiological study of the radioprotective activity of a natural Iranian compound, ''Shir-Khecht''; Etude radiobiologique de l'activite radioprotectrice d'un compose naturel Iranien: le ''Shir-Khecht''

    Energy Technology Data Exchange (ETDEWEB)

    Rouhanizadeh, N. [Commissariat a l' Energie Atomique, 92 - Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1968-01-01

    After reviewing the primary mechanisms of the action of ionizing radiation, the possible mechanisms of the action of radioprotective substances, the various chemical structures having a protective effect and the methods for studying chemical radioprotection, the author presents the results he has obtained with natural Iranian product: ''Shir-Khecht''. Tests with this product at lethal and sublethal doses have been carried out on the rat using various means of introduction. The effect of radiation, both with and without protection, has been studied using histological and biochemical methods. The product examined has, in effect, a protective action; it is, furthermore, non-toxic and active when taken orally. (author) [French] Apres avoir rappele les mecanismes primaires de l'action des rayonnements ionisants, les mecanismes possibles de l'action des substances radioprotectrices, les diverses structures chimiques possedant un effet protecteur et les methodes d'etude de la radioprotection chimique, l'auteur presente les resultats qu'il a obtenus en utilisant un compose naturel iranien: le ''Shir-Khecht''. Des essais de ce produit, chez le rat, par diverses voies d'introduction, a dose letale et subletale ont ete effectues. L'effet des radiations, avec et sans protection, a ete etudie a l'aide de methodes histologiques et biochimiques. Le compose essaye possede un pouvoir protecteur; il est, de plus, non toxique et actif par voie orale. (auteur)

  6. Radioprotection rayonnements, dosimétrie, protection

    CERN Document Server

    Marey, Gérard

    2014-01-01

    Pour tous les travailleurs du nucléaire comme pour les étudiants des licences professionnelles et des BTS Environnement nucléaire et BTS radioprotection, l'ouvrage rassemble de façon progressive, claire et précise toutes les informations scientifiques et pratiques qui leur sont indispensables. Une première partie résume les données de base relatives à la structure de la matière, la stabilité des noyaux, les différents rayonnements, leur énergie et la décroissance radioactive. La deuxième partie constitue une approche progressive de la radioprotection s'appuyant sur l'influence des rayonnement sur la matière pour définir les notions de dose et aborder le dimensionnement des protections biologiques et des éléments de ventilation. Enfin, la dernière partie traite de la mise en oeuvre pratique de la radioprotection sur le terrain et de la gestion des déchets nucléaires en application de la technologie actuelle, de la réglementation et des directives imposées par l'exploitant qu'est EDF. De...

  7. Effect of radioprotective sulphydryl compounds on the oxygen tension in the spleen of mice

    NARCIS (Netherlands)

    Meer, C. van der; Valkenburg, P.W.; Remmelts, M.

    1961-01-01

    In a previous paper the mechanism of the radioprotective action of the biologically active amines histamine, epinephrine, tryptamine and β-phenylethylamine was investigated. In studying the effect of these compounds on the oxygen tension in the spleen and bone marrow of unanæsthetized mice strong

  8. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  9. Radioprotective Effect of Lidocaine on Function and Ultrastructure of Salivary Glands Receiving Fractionated Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Hakim, Samer George, E-mail: samer.hakim@mkg-chir.mu-luebeck.de [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Benedek, Geza Attila [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Su Yuxiong [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Department of Oral and Maxillofacial Surgery, Sun Yat-Sen University, Guanghua School of Stomatology, Guanghua (China); Jacobsen, Hans Christian [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany); Klinger, Matthias [Institute of Anatomy, University of Luebeck, Luebeck (Germany); Dendorfer, Andreas [Institute of Experimental and Clinical Pharmacology and Toxicology, University of Luebeck, Luebeck (Germany); Hemmelmann, Claudia [Institute of Medical Biometry and Statistics, University of Luebeck, Luebeck (Germany); Meller, Birgit [Department of Radiology and Nuclear Medicine, University of Luebeck, Luebeck (Germany); Nadrowitz, Roger; Rades, Dirk [Department of Radiation Oncology, University of Luebeck, Luebeck (Germany); Sieg, Peter [Department of Oral and Maxillofacial Surgery, University of Luebeck, Luebeck (Germany)

    2012-03-15

    Purpose: Radiation-induced xerostomia still represents a common side effect after radiotherapy for head-and-neck malignancies. The aim of the present study was to examine the radioprotective effect of lidocaine hydrochloride during fractionated radiation in an experimental animal model. Methods and Materials: To evaluate the influence of different radiation doses on salivary gland function and the radioprotective effect of lidocaine, rabbits were irradiated with 15, 25, 30, and 35 Gy (equivalent doses in 2-Gy fractions equivalent to 24, 40, 48, and 56 Gy, respectively). Lidocaine hydrochloride (10 and 12 mg/kg) was administered before every radiation fraction in the treatment groups. Salivary gland function was assessed by flow sialometry and sialoscintigraphy, and the morphologic changes were evaluated using transmission electron microscopy. Results: Functional impairment was first observed after 35 Gy and pretreatment with lidocaine improved radiation tolerance of both parotid and submandibular glands. The use of 12 mg/kg lidocaine was superior and displayed significant radioprotection with regard to flow sialometry and sialoscintigraphy. The ultrastructure was largely preserved after pretreatment with both lidocaine doses. Conclusions: Lidocaine represents an effective radioprotective agent and a promising approach for clinical application to avoid radiation-induced functional impairment of salivary glands.

  10. Genetic predisposition and implications for radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Streffer, Christian [University Clinics, Essen, Essen (Germany)

    2000-05-01

    Treatments of cancer patients with ionizing radiation have shown in some cases severe acute radiation effects after radiation doses which are very well tolerated by most patients. Skin fibroblasts of these patients studied after in vitro irradiation also showed a high radiosensitivity frequently. It was found that these effects are based on genetic predisposition which was usually inherited from their parents. During recent years quite a number of these syndromes have been described in humans and often the responsible genes have been characterized: Ataxia telangiectasia, Bloom's syndrome, Fanconi anemia, Li Fraumeni syndrome, Nevoid basal cell carcinoma syndrome, Neurofibromatosis, Nijmegen breakage syndrome, Retinoblastoma. In most cases it was found that the regulation processes of DNA repair processes and of the cell cycle for cell proliferation are disturbed. Frequently these processes cannot be separated from each other. Quite a number of these syndromes also show genomic instability which can also be induced by radiation exposures. These Phenomena have mainly been studied by determining the rate of chromosomal aberrations many cell generations after the exposure took place. Genomic instability apparently plays an important role for the development of stochastic late effects for which multistep events are necessary. This is especially for carcinogenesis the case. In mice it has been shown that radiation-induced genomic instability can be transmitted to the next mouse generation. In mouse models and also with radiotherapy patients it has been shown that genetic predisposition not only increases radiosensitivity with respect to cell survival and chromosomal damage but also to carcinogenesis. This has been observed cf. with p53-knock out mice and with children after radiotherapy cf. treatment of retinoblastoma. In the children with a genetic predisposition for retinoblastoma secondary tumours occurred to a much higher rate than in those children with

  11. Note from the radioprotection group's shipping service

    CERN Multimedia

    2006-01-01

    Le service SHIPPING du groupe de radioprotection souhaite vous rappeler qu'avant toute expédition de matériel susceptible d'être radioactif, une demande de transport doit être établie par EDH en cochant la case appropriée (danger radioactif). Merci de bien vouloir prendre note des informations figurant dans le site Web: http://cern.ch/service-rp-shipping Toute demande non conforme ne sera pas prise en compte. Radioactive Shipping Service http://cern.ch/service-rp-shippingTél: 73171Fax: 69200

  12. Radioprotective effects of dragon's blood and its extracts on radiation-induced myelosuppressive mice.

    Science.gov (United States)

    Ran, Yuanyuan; Wang, Ran; Hasan, Murtaza; Jia, Qiutian; Tang, Bo; Shan, Shuangquan; Deng, Yulin; Qing, Hong

    2014-07-03

    Dragon׳s blood, a traditional Chinese herb, has been used to "panacea of blood activating" and its major biological activity appears to be from phenolic compounds. In this study, our research aims to examine the effects of Dragon׳s blood (DB) and its extracts (DBE) on radiation-induced myelosuppressive mice. Adult BALB/C mice were exposed to the whole body irradiation with 4 Gy (60)Co γ-rays. DB and DBE were respectively administered orally for 5 constitutive days prior to irradiation treatment. The radioprotective effects and relevant mechanisms of DB and DBE in radiation-induced bone marrow injury were investigated by ex vivo examination. We found that the administration of DB and DBE significantly increased the numbers of peripheral blood cells and colony forming unit of bone marrow-derived stem/progenitor cells. Interestingly, compared with the irradiation group, the administration of DB and DBE significantly decreased the levels of the inflammatory cytokines such as IL-6, TNF-α and IFN-γ and oxidative stress injury such as SOD, CAT, GSH, MDA in serum of mice. Furthermore, DBE markedly improved the morphology of bone marrow histopathology. Our data suggest that DB and DBE effectively attenuate radiation-induced damage in bone marrow, which is likely associated with the anti-oxidative and anti-inflammatory properties of DB and DBE. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. The effect of radiofrequency ablation on different organs: Ex vivo and in vivo comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul, E-mail: rhimhc@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Choi, Dongil; Kim, Young-sun; Lee, Min Woo; Chang, Ilsoo; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Objective: The purposes of this study are to evaluate the ex vivo and in vivo efficacy of radiofrequency ablation (RFA) on different porcine tissues by the ablation of three different sites simultaneously. Materials and methods: A multichannel RFA system, enables three separate tumors to be ablated simultaneously, was used. RFA procedures were applied to normal porcine liver, kidney, and muscle together ex vivo (n = 12) and in vivo (n = 17). Pre-impedances, defined as baseline systemic impedances of tissues before beginning RFA, and the areas of ablation zones were measured and compared. Results: The areas of ablation zones among three organs had a significant difference in decreasing order as follows: liver, muscle, and kidney in the ex vivo study (p = 0.001); muscle, liver, and kidney in the in vivo study (p < 0.0001). The areas of ablation zones between ex vivo and in vivo had a significant difference in the liver and muscle (each p < 0.05). There was no significant correlation between the areas of ablation zones and pre-impedances in both studies. Conclusions: Renal RFA produced the smallest ablation zone in both in vivo and ex vivo studies. Muscular RFA demonstrated the largest ablation zone in the in vivo study, and hepatic RFA showed the largest ablation zone in the ex vivo study. This variability in the tissues should be considered for performing an optimized RFA for each organ site.

  14. Radioprotective effects of aronia on radiation irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Mun, Hwan Sik; Lee, Jun Haeng [Dept. of Radiology, Nambu University, Gwangju (Korea, Republic of)

    2017-09-15

    The present study was intended to orally administer aronia to rats, irradiate radiation once to the whole bodies of the rats, and conduct blood tests to observe, compare, and analyze changes in blood cells, such as leukocytes, erythrocytes, and platelets, in order to examine the radioprotective effects of aronia. As experimental animals, 15 male Sprague-Dawley (SD) rats aged six weeks weighing 200∼250 g were taken and divided into the normal group (A) of five rats, the 5 Gy control group (B) of five rats, and the 5 Gy experimental group (C) of five rats. The normal group (A) was not irradiated at all, the control group (B) was administered with general diets and irradiated, and the experimental group(C) was orally administered with 50 mg/kg/day of aronia two times per day to achieve a distilled water oral dose of 100 mg/kg/day and irradiated thereafter (5 Gy at 500 cGy/min) for 14 days. After the experiment, differences in leukocytes, erythrocytes, and platelets among the normal group (A), the control group (B), and the experimental group (C) were examined by comparing the counts of the blood cells and the results showed no statistically significant differences. However, on a detailed review, the normal group (A) showed statistically higher mean values for all of lymphocytes, hemoglobin, and mean corpuscular hemoglobin as compared to the control group (B) and the experimental group (C). Statistically significant differences in the counts of lymphocytes were shown between the normal group (A) and the control group (B), and between the normal group (A) and the experimental group (C); furthermore, statistically significant differences in mean corpuscular hemoglobin were shown between the normal group (A) and the experimental group (C). Given the results of the present study, in irradiated rats, aronia was generally considered as having no radioprotective effect on leukocyte, erythrocyte, and platelet while having statistically significant radioprotective effects on

  15. Free radical scavenging and radioprotective effects of carnosine and anserine

    Energy Technology Data Exchange (ETDEWEB)

    Fu Haiying [Nuclear Professional School, School of Engineering, University of Tokyo, 2-22 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1188 (Japan); Katsumura, Yosuke [Nuclear Professional School, School of Engineering, University of Tokyo, 2-22 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1188 (Japan); Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1195 (Japan); Department of Nuclear Engineering and Management, School of Engineering, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8656 (Japan)], E-mail: katsu@n.t.u-tokyo.ac.jp; Lin Mingzhang [Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1195 (Japan); Muroya, Yusa; Hata, Kuniki [Nuclear Professional School, School of Engineering, University of Tokyo, 2-22 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1188 (Japan); Fujii, Kentaro; Yokoya, Akinari; Hatano, Yoshihiko [Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakata shirane, Tokaimura, Nakagun, Ibaraki 319-1195 (Japan)

    2009-12-15

    Two histidine-containing natural dipeptides, carnosine and anserine ({beta}-alanyl-1-methyl-L-histidine), have been examined for their antioxidant and radioprotective abilities. Pulse radiolysis studies indicated the antioxidative properties of carnosine and anserine aqueous solutions at different pH. The rate constants for the reaction OH radical with carnosine at neutral pH were determined to be 5.3x10{sup 9} M{sup -1} s{sup -1} at 300 nm, and 4.1x10{sup 9} M{sup -1} s{sup -1} at 400 nm, respectively. Carnosine and anserine also protected plasmid pUC18 DNA from X-ray radiation-induced strand breaks as evidenced from the studies by agarose gel electrophoresis. Carnosine showed higher protective efficiency under the experimental conditions. Our data demonstrated that carnosine and anserine may play an important role in the maintenance of the antioxidant system.

  16. Oral antioxidants for radioprotection during medical imaging examinations

    Science.gov (United States)

    Velauthapillai, Nivethan

    The oncogenic effect of ionizing radiation (IR) is clearly established and occurs in response to DNA damage. Many diagnostic imaging exams make use of IR and the oncogenic risk of IR-based imaging has been calculated. We hypothesized that the DNA damage sustained from IR exposure during medical imaging exams could be reduced by pre-medicating patients with antioxidants. First, we tested and validated a method for measuring DNA double-strand breaks (DSBs) in peripheral blood mononuclear cells (PBMCs) exposed to low doses of ionizing radiation. Afterwards, we conducted a pilot clinical study in which we administered oral antioxidants to patients undergoing bone scans, prior to radiotracer injection. We showed that oral antioxidant pre-medication reduced the number of DSBs in PBMCs induced by radiotracer injection. Our study shows proof-of-principle for this simple and inexpensive approach to radioprotection in the clinical setting.

  17. Utility of DF-1 for Radioprotection in Lymphocytes

    Science.gov (United States)

    Reynolds, Julia; Casey, Rachael; Wu, Honglu; Huff, Janice; Emami, Kamal; Moore, Valerie; Jeevarajan, Antony

    2007-01-01

    The development of degenerative changes in the vasculature, such as atherosclerosis, is a known consequence of exposure to ionizing radiation, and is thus a concern for astronaut health following long duration space flight. Cellular damage caused by radiation is due to free radical generation and DNA damage. The goal of this project was to assess the ability of a C60-derivative, DF-1, to mitigate cellular damage resulting from radiation exposure in primary human lymphocytes. DF-1 is a water-soluble C60 fullerene encapsulated in dendrimeric functional groups that is proposed to exhibit antioxidant properties. Human lymphocytes are radiosensitive and travel throughout the body potentially causing bystander effects in any tissues they contact. These cells were subjected to varying doses of gamma radiation in the presence or absence of DF-1. Cells were collected at 48 hours post-irradiation for chromosomal aberration studies and at 72 hours post-irradiation for micronuclei studies. These studies showed that the irradiated cells contained more chromosomal aberrations and micronuclei than the control cells. Addition of the DF-1 reduced the amount of observed DNA damage in the irradiated cells. Growth curves were measured for the lymphocytes exposed to 0 and 4 Gray gamma irradiations, and we observed less growth in the cells irradiated at 4 Gy. 2,7-dichlorofluorescein diacetate was used to detect reactive oxygen species production, and increased production of ROS was observed in the irradiated lymphocytes. Human lymphocytes were subjected to varying doses of gamma or photon radiation in the presence and absence of DF-1 and a known radioprotectant, amifostine. After irradiation, the production of reactive oxygen species, growth curves and cell viability were measured. These cells were also collected to quantify chromosomal aberrations and micronuclei formation. We predict that irradiated cells will show the most damage and that DF-1 will provide protective effects similar

  18. Radioprotective potential of histamine on rat small intestine and uterus

    Science.gov (United States)

    Carabajal, E.; Massari, N.; Croci, M.; Martinel Lamas, D.; Prestifilippo, J.P.; Ciraolo, P.; Bergoc, R.M.; Rivera, E.S.; Medina, V.A.

    2012-01-01

    The aim of this study was to improve knowledge about histamine radioprotective potential investigating its effect on reducing ionising radiation-induced injury and genotoxic damage on the rat small intestine and uterus. Forty 10-week-old male and 40 female Sprague-Dawley rats were divided into 4 groups. Histamine and histamine-5Gy groups received a daily subcutaneous histamine injection (0.1 mg/kg) starting 24 h before irradiation. Histamine-5Gy and untreated-5Gy groups were irradiated with a dose of whole-body Cesium-137 irradiation. Three days after irradiation animals were sacrificed and tissues were removed, fixed, and stained with haematoxylin and eosin, and histological characteristics were evaluated. Proliferation, apoptosis and oxidative DNA markers were studied by immunohistochemistry, while micronucleus assay was performed to evaluate chromosomal damage. Histamine treatment reduced radiation-induced mucosal atrophy, oedema and vascular damage produced by ionising radiation, increasing the number of crypts per circumference (239±12 vs 160±10; Phistamine decreased the frequency of micronuclei formation and also significantly attenuated 8-OHdG immunoreactivity, a marker of DNA oxidative damage. Furthermore, radiation induced flattening of the endometrial surface, depletion of deep glands and reduced mitosis, effects that were completely blocked by histamine treatment. The expression of a proliferation marker in uterine luminal and glandular cells was markedly stimulated in histamine treated and irradiated rats. The obtained evidences indicate that histamine is a potential candidate as a safe radio-protective agent that might increase the therapeutic index of radiotherapy for intra-abdominal and pelvic cancers. However, its efficacy needs to be carefully investigated in prospective clinical trials. PMID:23361244

  19. Morphological study of the radioprotective effect of vitamin E (dl-alpha-tocopheryl) in tissue reparation in rats; Estudo morfologico do efeito radioprotetor da vitamina E (dl-alfa-tocoferil) na reparacao tecidual em ratos

    Energy Technology Data Exchange (ETDEWEB)

    Manzi, Flavio Ricardo [Pontificia Univ. Catolica de Minas Gerais, Belo Horizonte, MG (Brazil). Raduilogia Odontologica]. E-mail: manzi@pucminas.br; Boscolo, Frab Norberto; Almeida, Solange Maria de [Universidade Estadual de Campinas, Piracicaba, SP (Brazil). Faculdade de Odontologia. Radiologia Odontologica; Tuji, Fabricio Mesquita [Para Univ., Belem, PA (Brazil). Radiologia Odontologica

    2003-12-01

    The purpose of this work was to evaluate the action of the vitamin E as a radioprotective agent in the process of tissue reparation in rats submitted to a surgical procedure, which consisted of a wound done in the fore dorsal area. The animals were divided into five groups: group C (controls) - wound; group VE - previous treatment with vitamin E (90 UI); group IR - wound and irradiation of the borders three days after surgery; group VEIR - previous treatment with 90 UI of the vitamin E and irradiation of the borders three days after the surgery; group OIR - previous treatment with olive oil and irradiation of the borders three days after surgery. The radioprotective effect of the vitamin E was evaluated using hematoxylin-eosin stained specimens in order to identify granulation tissue, at 4, 7, 14 and 21 days after the surgical procedures. The results showed that 6 Gy of electron irradiation with a beam of 6 MeV caused retardation of the tissue repairing process and that vitamin E was effective as a radioprotective agent. (author)

  20. Hibernation for space travel: Impact on radioprotection.

    Science.gov (United States)

    Cerri, Matteo; Tinganelli, Walter; Negrini, Matteo; Helm, Alexander; Scifoni, Emanuele; Tommasino, Francesco; Sioli, Maximiliano; Zoccoli, Antonio; Durante, Marco

    2016-11-01

    Hibernation is a state of reduced metabolic activity used by some animals to survive in harsh environmental conditions. The idea of exploiting hibernation for space exploration has been proposed many years ago, but in recent years it is becoming more realistic, thanks to the introduction of specific methods to induce hibernation-like conditions (synthetic torpor) in non-hibernating animals. In addition to the expected advantages in long-term exploratory-class missions in terms of resource consumptions, aging, and psychology, hibernation may provide protection from cosmic radiation damage to the crew. Data from over half century ago in animal models suggest indeed that radiation effects are reduced during hibernation. We will review the mechanisms of increased radioprotection in hibernation, and discuss possible impact on human space exploration. Copyright © 2016 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  1. Hibernation for space travel: Impact on radioprotection

    Science.gov (United States)

    Cerri, Matteo; Tinganelli, Walter; Negrini, Matteo; Helm, Alexander; Scifoni, Emanuele; Tommasino, Francesco; Sioli, Maximiliano; Zoccoli, Antonio; Durante, Marco

    2016-11-01

    Hibernation is a state of reduced metabolic activity used by some animals to survive in harsh environmental conditions. The idea of exploiting hibernation for space exploration has been proposed many years ago, but in recent years it is becoming more realistic, thanks to the introduction of specific methods to induce hibernation-like conditions (synthetic torpor) in non-hibernating animals. In addition to the expected advantages in long-term exploratory-class missions in terms of resource consumptions, aging, and psychology, hibernation may provide protection from cosmic radiation damage to the crew. Data from over half century ago in animal models suggest indeed that radiation effects are reduced during hibernation. We will review the mechanisms of increased radioprotection in hibernation, and discuss possible impact on human space exploration.

  2. Radio-protective role of antioxidant agents

    Directory of Open Access Journals (Sweden)

    Alireza Shirazi

    2012-10-01

    Full Text Available Ionizing radiation interacts with biological systems to produce reactive oxygen species and reactive nitrogen species which attack various cellular components. Radio-protectors act as prophylactic agents to shield healthy cells and tissues from the harmful effects of radiation. Past research on synthetic radio-protectors has brought little success, primarily due to the various toxicity-related problems. Results of experimental research show that antioxidant nutrients, such as vitamin E and herbal products and melatonin, are protective against the damaging effects of radiation, with less toxicity and side effects. Therefore, we propose that in the future, antioxidant radio-protective agents may improve the therapeutic index in radiation oncology treatments.

  3. Radioprotective effects of Cordyceps sinensis extracts on {gamma}-irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Beong Gyu [Wongwang Health Science College, Iri (Korea, Republic of); Kim, On Joong; Kim, Jae Young [Dongguk University, Seoul (Korea, Republic of)

    1999-06-01

    Effect of single intraperitoneal administration of Cordyceps sinensis (Cs) extract at 24 hour before whole-body {gamma} - irradiation on the survival ratio, body weight, organ weight changes and serum metabolites in the irradiated mice were investigated. The single pre-administration of Cs extract increased the 40-day survival ration of irradiated mice from 66.7 percent to 83.4 percent. The administration of Cs extract completely prevented weight reductions of spleen and thymus produced by {gamma} - irradiation (P < 0.05, P < 0.01). Similar but somewhat less radioprotective effect was also found in the testis of the Cs treated mice. The administration of Cs inhibited the serum hyperglycemia produced by irradiation on the day 7th(P < 0.01). However, it did not influence the serum cholesterol and protein levels on the days examined. The present study is the first report regarding Cs which was tested and found to be radioprotective. (Author)

  4. Assessment of the Radioprotection Efficacy of Antioxidant Substances in Foods in regard to Clonogenic Cell Survival

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyosung; Lee, Minho; Kim, Eunhee [Seoul National Univ., Seoul (Korea, Republic of)

    2014-05-15

    Radiation is perceived as a hazard in spite of its diverse uses. The public are more sensitive than ever to the activities from the nuclear power plant industry since Fukushima accident and the consequential environment contamination. The never-dissolved fear from the public of the nuclear energy costs the nuclear industry too much for safety measures not to mention brings the public uneasy life. Beta carotene, oltipraz and luteolin, which are easily taken from various foods, are substances that may protect cells from damage caused by unstable molecules known as free radicals. The purpose of this study is to inform people of accessible radiation protection measures in everyday lives. Three antioxidant substances were investigated regarding their radioprotection effects counted in terms of clonogenic cell surviving fraction in vitro. The radioprotection efficacy was observed with those substances at concentrations below certain levels. At concentrations beyond those levels, the efficacy was canceled out by their inherent cytotoxicity.

  5. In vivo and ex vivo confocal endomicroscopy of pancreatic cystic lesions: A prospective study.

    Science.gov (United States)

    Krishna, Somashekar G; Modi, Rohan M; Kamboj, Amrit K; Swanson, Benjamin J; Hart, Phil A; Dillhoff, Mary E; Manilchuk, Andrei; Schmidt, Carl R; Conwell, Darwin L

    2017-05-14

    To investigate the reproducibility of the in vivo endoscopic ultrasound (EUS) - guided needle based confocal endomicroscopy (nCLE) image patterns in an ex vivo setting and compare these to surgical histopathology for characterizing pancreatic cystic lesions (PCLs). In a prospective study evaluating EUS-nCLE for evaluation of PCLs, 10 subjects underwent an in vivo nCLE (AQ-Flex nCLE miniprobe; Cellvizio, MaunaKea, Paris, France) during EUS and ex vivo probe based CLE (pCLE) of the PCL (Gastroflex ultrahigh definition probe, Cellvizio) after surgical resection. Biopsies were obtained from ex vivo CLE-imaged areas for comparative histopathology. All subjects received intravenous fluorescein prior to EUS and pancreatic surgery for in vivo and ex vivo CLE imaging respectively. A total of 10 subjects (mean age 53 ± 12 years; 5 female) with a mean PCL size of 34.8 ± 14.3 mm were enrolled. Surgical histopathology confirmed 2 intraductal papillary mucinous neoplasms (IPMNs), 3 mucinous cystic neoplasms (MCNs), 2 cystic neuroendocrine tumors (cystic-NETs), 1 serous cystadenoma (SCA), and 2 squamous lined PCLs. Characteristic in vivo nCLE image patterns included papillary projections for IPMNs, horizon-type epithelial bands for MCNs, nests and trabeculae of cells for cystic-NETs, and a "fern pattern" of vascularity for SCA. Identical image patterns were observed during ex vivo pCLE imaging of the surgically resected PCLs. Both in vivo and ex vivo CLE imaging findings correlated with surgical histopathology. In vivo nCLE patterns are reproducible in ex vivo pCLE for all major neoplastic PCLs. These findings add further support the application of EUS-nCLE as an imaging biomarker in the diagnosis of PCLs.

  6. Radiation exposure and radioprotection of physicians, technologists and nurses during their contact with patients who are or were subjected to studies with ionizing radiation

    OpenAIRE

    Charilaos Koutis; Athanasios Kotsalos; Eirini Kotsalou

    2013-01-01

    The applications of emission x- g- and b- rays in Medicine give solution to everyday diagnostic and therapeutic problems, but expose the Medical staff in radiation risk and its consequences. Aim: The purpose of this article was the review of literature relating to the risk of radiation exposure and radiation protection instructions for doctors, technologists and nurses during their contact with patients who have or had performed studies using ionizing radiation. Method and Material: The metho...

  7. Production and Radioprotective Effects of Pyrroloquinoline Quinone

    Directory of Open Access Journals (Sweden)

    De-Xuan Yang

    2011-12-01

    Full Text Available Pyrroloquinoline quinone (PQQ was produced by fermentation of the Methylovorus sp. MP688 strain and purified by ion-exchange chromatography, crystallization and recrystallization. The yield of PQQ reached approximately 125 mg/L and highly pure PQQ was obtained. To determine the optimum dose of PQQ for radioprotection, three doses (2 mg/kg, 4 mg/kg, 8 mg/kg of PQQ were orally administrated to the experimental animals subjected to a lethal dose of 8.0 Gy in survival test. Survival of mice in the irradiation + PQQ (4 mg/kg group was found to be significantly higher in comparison with the irradiation and irradiation + nilestriol (10 mg/kg groups. The numbers of hematocytes and bone marrow cells were measured for 21 days after sublethal 4 Gy gamma-ray irradiation with per os of 4 mg/kg of PQQ. The recovery of white blood cells, reticulocytes and bone marrow cells in the irradiation + PQQ group was faster than that in the irradiation group. Furthermore, the recovery of bone marrow cell in the irradiation + PQQ group was superior to that in irradiation + nilestriol group. Our results clearly indicate favourable effects on survival under higher lethal radiation doses and the ability of pyrroloquinoline quinine to enhance haemopoietic recovery after sublethal radiation exposure.

  8. Radioprotective agents to prevent cellular damage due to ionizing radiation.

    Science.gov (United States)

    Smith, Tyler A; Kirkpatrick, Daniel R; Smith, Sean; Smith, Trevor K; Pearson, Tate; Kailasam, Aparna; Herrmann, Kortney Z; Schubert, Johanna; Agrawal, Devendra K

    2017-11-09

    Medical imaging has become a central component of patient care to ensure early and accurate diagnosis. Unfortunately, many imaging modalities use ionizing radiation to generate images. Ionizing radiation even in low doses can cause direct DNA damage and generate reactive oxygen species and free radicals, leading to DNA, protein, and lipid membrane damage. This cell damage can lead to apoptosis, necrosis, teratogenesis, or carcinogenesis. As many as 2% of cancers (and an associated 15,000 deaths annually) can be linked to computed tomography exposure alone. Radioprotective agents have been investigated using various models including cells, animals, and recently humans. The data suggest that radioprotective agents working through a variety of mechanisms have the potential to decrease free radical damage produced by ionizing radiation. Radioprotective agents may be useful as an adjunct to medical imaging to reduced patient morbidity and mortality due to ionizing radiation exposure. Some radioprotective agents can be found in high quantities in antioxidant rich foods, suggesting that a specific diet recommendation could be beneficial in radioprotection.

  9. Radioprotective role in lung of the flaxseed lignan complex enriched in the phenolic secoisolariciresinol diglucoside (SDG).

    Science.gov (United States)

    Christofidou-Solomidou, Melpo; Tyagi, Sonia; Pietrofesa, Ralph; Dukes, Floyd; Arguiri, Evguenia; Turowski, Jason; Grieshaber, Philip A; Solomides, Charalambos C; Cengel, Keith A

    2012-12-01

    While dietary wholegrain Flaxseed (FS) has potent anti-inflammatory, anti-fibrotic and antioxidant properties in murine models of acute and chronic lung injury, the main bioactive ingredient that contributes to these protective effects remains unknown. This study evaluated the lignan complex of FS (FLC) enriched in secoisolariciresinol diglucoside with respect to lung radioprotective and tumor radiosensitizing efficacy using a mouse model of thoracic radiation-induced pneumonopathy. C57/Bl6 mice were fed 0% FS, 10% FS, 10% FLC or 20% FLC for 3 weeks, then irradiated with a single fraction (13.5 Gy) of X-ray radiation treatment (XRT). Mouse survival was monitored for 4 months after irradiation and inflammatory lung parameters were evaluated in bronchoalveolar lavage (BAL) fluid. Gene and protein levels of protective antioxidant and phase II enzymes were evaluated in lung tissue using qPCR and protein levels were verified by immunoblotting. Prolonged administration of the FLC diet was well tolerated and was not associated with any toxicity. Importantly, comparable to the whole grain 10% FS diet, irradiated mice fed 10% and 20% FLC diets displayed improved survival. Improved hemodynamic measurements were also recorded in irradiated mice fed 10% FS or 10% FLC diet compared to irradiated 0% FS fed mice. Flaxseed lignan complex diet also attenuated polymorphonuclear infiltration and overall lung inflammation to levels comparable to those in nonirradiated mice. Flaxseed lignan complex, similarly to FS, up-regulated gene expression as well as protein levels of protective antioxidant enzymes such as heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO1). Dietary FLC induced radiosensitizing effects in our murine model of metastatic lung cancer. Importantly, protection of normal tissue does not thwart tumor cell death by radiation treatment. The dietary lignan complex of FS, mainly consisting of the phenolic secoisolariciresinol, is protective against radiation

  10. Studies on environmental radioactivity radioprotection in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Ieda I.L.; Figueira, Rubens C.L.; Fabra, Edson Luiz

    1995-12-31

    This work presents the results of the continuous environmental survey programmes carried out by the Radio-Ecological Coastal Laboratory (LARELI) of the Sao Paulo State Agency for the Coordination of Special Projects (COPESP). Artificial radionuclides in marine samples were routinely monitored through the laboratory`s research monitoring programme since 1990. Some examples of analysis carried out in our laboratory are discussed, mainly as large samples volumes are required. Marine samples (seawater, fish) are collected monthly of the Brazilian coast between the State of Rio Grande do Sul (latitude 32{sup 0} 11`S) and the state of Para (latitude 00{sup 0} 26`S), evaluating the artificial radionuclide concentration. Data are used to describe the radio-ecological situation along the Brazilian coast to obtain radionuclide reference levels, as well as data for estimating the exposure of our population to fallout radionuclides. This information is used as a base for detecting any future contamination. The main origin of the radionuclides detected are nuclear device test in the atmosphere and accidents (like Chernobyl) in the northern hemisphere. (author). 6 refs., 1 fig., 3 tabs.

  11. Assessment in vitro of radioprotective efficacy of curcumin and resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Sebastia, Natividad, E-mail: natividad.sebastia@uv.es [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain); Montoro, Alegria [Servicio de Proteccion Radiologica, Hospital Universitario La Fe, 46009, Valencia (Spain); Montoro, Amparo [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain); Almonacid, Miguel; Villaescusa, Juan Ignacio [Servicio de Proteccion Radiologica, Hospital Universitario La Fe, 46009, Valencia (Spain); Cervera, Jose; Such, Esperanza; Silla, Ma Angeles [Servicio de Hematologia, Hospital Universitario La Fe, 46009, Valencia (Spain); Soriano, Jose Miguel [Area de Nutricion y Bromatologia, Facultat de Farmacia, Universitat de Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot (Spain)

    2011-09-15

    Many natural substances have been studied in recent past to be used as radioprotectors to mitigate ionizing radiation-induced damage in mammalian systems due to its effectiveness given both pre- and post-irradiation and for long time with out drug-related toxicity. Curcumin and trans-resveratrol are both natural occurring polyphenols, obtained from the root of Curcuma longa and from grapes and other berries, respectively. These compounds have shown antioxidant, anti-inflammatory, immunostimulant and anti-carcinogenic properties. Our aim was to evaluate the radioprotective efficacy, in vitro, of curcumin and trans-resveratrol separately against radiation-induced chromosomal aberrations. The study was carried out by the pre-treatment of human blood lymphocytes at concentrations from 0 to 500 {mu}g mL{sup -1} and from 0 to 50 {mu}g mL{sup -1} for curcumin and trans-resveratrol, respectively. The results showed that all concentrations tested reduced radiation-induced chromosomal damage. Maximum damage protection was observed at the concentration of 5 {mu}g mL{sup -1} for curcumin and 0.5 {mu}g mL{sup -1} for trans-resveratrol. Thus, our results show that curcumin and trans-resveratrol pre-treatment significantly protect normal lymphocytes against {gamma}-radiation-induced cellular damage.

  12. Radioprotection of tendon tissue via crosslinking and free radical scavenging.

    Science.gov (United States)

    Seto, Aaron; Gatt, Charles J; Dunn, Michael G

    2008-08-01

    Ionizing radiation could supplement tissue bank screening to further reduce the probability of diseases transmitted by allografts if denaturation effects can be minimized. It is important, however, such sterilization procedures be nondetrimental to tissues. We compared crosslinking and free radical scavenging potential methods to accomplish this task in tendon tissue. In addition, two forms of ionizing irradiation, gamma and electron beam (e-beam), were also compared. Crosslinkers included 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glucose, which were used to add exogenous crosslinks to collagen. Free radical scavengers included mannitol, ascorbate, and riboflavin. Radioprotective effects were assessed through tensile testing and collagenase resistance testing after irradiation at 25 kGy and 50 kGy. Gamma and e-beam irradiation produced similar degenerative effects. Crosslinkers had the highest strength at 50 kGy, EDC treated tendons had 54% and 49% higher strength than untreated, for gamma and e-beam irradiation respectively. Free radical scavengers showed protective effects up to 25 kGy, especially for ascorbate and riboflavin. Crosslinked samples had higher resistance to collagenase and over a wider dose range than scavenger-treated. Of the options studied, the data suggest EDC precrosslinking or glucose treatment provides the best maintenance of native tendon properties after exposure to ionizing irradiation.

  13. Synthesis and Radioprotective Activity of Mitochondria Targeted Dihydropyridines In Vitro

    Directory of Open Access Journals (Sweden)

    Yurui Zhang

    2017-10-01

    Full Text Available The radiation-induced damage to mitochondrial oxidative respiratory chain could lead to generating of superoxide anions (O2− and secondary reactive oxygen species (ROS, which are the major resources of continuous ROS production after radiation. Scavenging radiation-induced ROS effectively can help mitochondria to maintain their physiological function and relief cells from oxidative stress. Dihydropyridines (DHPs are biomimetic hydrogen sources that could protect cells against radiation damage. In this study, we designed and synthetized three novel mitochondrial-targeted dihydropyridines (Mito-DHPs that utilize the mitochondrial membrane potential to enter the organelle and scavenge ROS. MitoTracker confirmed Mito-DHPs accumulation in mitochondria, and the DCFH-DA assay demonstrated effective ROS scavenging activity. In addition, the γ-H2AX and comet assay demonstrated the ability of Mito-DHPs to protect against both radiation and ROS-induced DNA strand breaks. Furthermore, Mito-DHP1 proved to be non-toxic and displayed significant radioprotection activity (p < 0.05 in vitro. Mito-DHPs are therefore promising antioxidants that could penetrate the membrane of mitochondria, scavenge excessive ROS, and protect cells against radiation-induced oxidative damage.

  14. In vivo toxicity study of Lantana camara

    OpenAIRE

    Badakhshan Mahdi Pour; Sreenivasan Sasidharan

    2011-01-01

    Objective: To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. Methods: The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. Results: All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Conclusions: Methanolic...

  15. Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies.

    Science.gov (United States)

    Zhu, Hong; Kochevar, Irene E; Behlau, Irmgard; Zhao, Jie; Wang, Fenghua; Wang, Yucheng; Sun, Xiaodong; Hamblin, Michael R; Dai, Tianhong

    2017-01-01

    To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colony-forming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log10) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted.

  16. Digital Radiography for Determination of Primary Tooth Length: In Vivo and Ex Vivo Studies

    Directory of Open Access Journals (Sweden)

    Maria D. Basso

    2015-01-01

    Full Text Available Background. Methods for determining the root canal length of the primary tooth should yield accurate and reproducible results. In vitro studies show some limitations, which do not allow their findings to be directly transferred to a clinical situation. Aim. To compare the accuracy of radiographic tooth length obtained from in vivo digital radiograph with that obtained from ex vivo digital radiograph. Method. Direct digital radiographs of 20 upper primary incisors were performed in teeth (2/3 radicular resorption that were radiographed by an intraoral sensor, according to the long-cone technique. Teeth were extracted, measured, and mounted in a resin block, and then radiographic template was used to standardise the sensor-target distance (30 cm. The apparent tooth length (APTL was obtained from the computer screen by means of an electronic ruler accompanying the digital radiography software (CDR 2.0, whereas the actual tooth length (ACTL was obtained by means of a digital calliper following extraction. Data were compared to the ACTL by variance analysis and Pearson’s correlation test. Results. The values for APTL obtained from in vivo radiography were slightly underestimated, whereas those values obtained from ex vivo were slightly overestimated. No significance was observed (P≤0.48 between APTL and ACTL. Conclusion. The length of primary teeth estimated by in vivo and ex vivo comparisons using digital radiography was found to be similar to the actual tooth length.

  17. Radioprotection et ingénierie nucléaire

    CERN Document Server

    2006-01-01

    Le développement de l'énergie nucléaire repose sur deux piliers essentiels : la sûreté nucléaire, qui concerne la machine, et la radioprotection, qui se préoccupe des hommes. Construit de manière fiable, un réacteur nucléaire se doit d'irradier le moins possible ses opérateurs et conduire à un impact très faible pour les populations avoisinantes. Tout cela est soumis à des règles strictes, élaborées au niveau international, et qui ne tolèrent aucun écart. Les ingénieurs qui ont à concevoir, construire et conduire ces machines doivent maîtriser les règles de protection : cet ouvrage leur est destiné. La radioprotection, si elle se fonde principalement sur des bases scientifiques, intègre également une dimension sociétale exigeante. Ces activités sont en effet sous le regard critique et permanent de nos concitoyens, qui exigent des acteurs de cette industrie une maîtrise totale de la radioprotection ; un ingénieur qui ne connaîtrait pas la genèse de la radioprotection, ses règle...

  18. Radioprotective effect of chlorpromazine on the survival of mice

    Energy Technology Data Exchange (ETDEWEB)

    Kale, R.K.; Chandra, D. [Jawaharlal Nehru Univ., New Dalhi (India). School of Life Sciences

    2000-05-01

    Importance of radiomodification by phenothiazines like chlorpromazine (CPZ) in improving the radiation therapy of cancer has recently been suggested. To achieve a greater application and wide acceptance, the radioprotective potential of CPZ is examined in terms of survival of animals. Swiss albino mice were administered CPZ intraperitonially and irradiated with different doses of g-rays at the dose rate of 1.38 Gy/min. The death profile, median survival time and temporal survival pattern was determined. Administration of CPZ prior to irradiation resulted in decrease of death rate, enhancement of median survival time and significant delay in early decline in survival of animals. Radioprotective ability of CPZ was clearly visible from the temporal survival pattern. CPZ shifted the survival curves towards the right side. The protective action of CPZ against radiation effect was reversed in presence of ferrous (Fe2+) ions and on the other hand, the protective effect of CPZ was enhanced considerably in presence of ferric (Fe3+) ions. CPZ provided considerable protection to mice irradiated with g-rays. Radioprotective effectiveness of CPZ could be attributed to multiple mechanisms of action. The enhanced radioprotection in presence of Fe3+ ions and radiosensitization in presence of Fe2+ ions by CPZ were an important observations and probably be ascribed to the altered redox activity of Fe3+ and Fe2+ ions by CPZ or vice-versa. Since, CPZ is in regular chemical use, these findings might be significant for the improvement radiation therapy of cancer. (author)

  19. In vivo toxicity study of Lantana camara.

    Science.gov (United States)

    Pour, Badakhshan Mahdi; Sasidharan, Sreenivasan

    2011-06-01

    To investigate the toxicity of methanol extract of various parts (Root, Stem, Leaf, Flower and Fruit) of Lantana camara (L. Camara) in Artemia salina. The methanol extracts of L. camara were tested for in vivo brine shrimp lethality assay. All the tested extract exhibited very low toxicity on brine shrimp larva. The results showed that the root extract was the most toxic part of L. camara and may have potential as anticancer agent. Methanolic extract of L. camara is relatively safe on short-term exposure.

  20. Development of Orally Administered γ-Tocotrienol (GT3) Nanoemulsion for Radioprotection.

    Science.gov (United States)

    Ledet, Grace A; Biswas, Shukla; Kumar, Vidya P; Graves, Richard A; Mitchner, Demaurian M; Parker, Taylor M; Bostanian, Levon A; Ghosh, Sanchita P; Mandal, Tarun K

    2016-12-24

    The purpose of this study was two-fold: (1) to formulate γ-tocotrienol (GT3) in a nanoemulsion formulation as a prophylactic orally administered radioprotective agent; and (2) to optimize the storage conditions to preserve the structural integrity of both the formulation and the compound. γ-tocotrienol was incorporated into a nanoemulsion and lyophilized with lactose. Ultra performance liquid chromatography-mass spectroscopy (UPLC-MS) was used to monitor the chemical stability of GT3 over time, the particle size and ζ potential, and scanning electron microscopy (SEM) were used to study the physical stability of the nanoemulsion. Radioprotective and toxicity studies were performed in mice. The liquid formulation exhibited GT3 degradation at all storage temperatures. Lyophilization, in the presence of lactose, significantly reduced GT3 degradation. Both the liquid and lyophilized nanoemulsions had stable particle size and ζ potential when stored at 4 °C. Toxicity studies of the nanoemulsion resulted in no observable toxicity in mice at an oral dose of 600 mg/kg GT3. The nano-formulated GT3 (300 mg/kg) demonstrated enhanced survival efficacy compared to GT3 alone (200 and 400 mg/kg) in CD2F1 mice exposed to total body gamma radiation. The optimal long-term storage of formulated GT3 is as a powder at -20 °C to preserve drug and formulation integrity. Formulation of GT3 as a nanoemulsion for oral delivery as a prophylactic radioprotectant shows promise and warrants further investigation.

  1. Radioprotective effect of novel disubstituted thioureas on pea (Pisum sativum L.) development.

    Science.gov (United States)

    Mehandjiev, A; Kosturkova, G; Vassilev, G; Noveva, S

    2002-01-01

    The review presents our research on the influence of novel thiourea compounds on the biological and genetic effect of gamma-rays using in vivo and in vitro systems of pea. Some novel disubstituted thioureas: o-allylthioureidobenzoic acid (ATB); o-phenylthioureidobenzoic acid (PTB); N-allyl-N'-2-pyridylthiourea (A-2-PTU); N-phenyl-N'-2-pyridylthiourea (P-2-PTU) and 1,4-allylthioureidosalicylic acid (ATUS) were examined. Pea (Pisum sativum L.) seeds from five varieties were used. Experiments in vivo and in vitro were carried under laboratory, greenhouse and field conditions. The data revealed the PTB radioprotective effect demonstrated by: reduction of chromosome aberrations by 2 folds; 50% increase of germinating and surviving plants in M1; twice higher frequency of induced mutations in M2 generation relative to irradiation without PTB treatment; decreasing the level of induced radiation suppression leading to favorable effect on the initial stem and root development of pea. ATB radioprotective effect was demonstrated in vitro by: 25-35% stimulation of organogenesis; by 20-50% increase in bud formation; by 25% stimulation of growth. The effect of A-2-PTU and P-2-PTU depended on the irradiation dose. The protective effect of A-2-PTU is more pronounced at lower irradiation dose, while the effect of P-2-PTU is more pronounced at higher irradiation dose. ATUS, opposite to the other compounds, revealed radiosensibilizing effect by: 16-27% increase in lethality caused by gamma-rays leading to lower number of germinating and surviving plants in M1; 50% decrease in the number of induced mutations in M2 generation; limiting the types of induced mutations at the higher irradiation dose. As a result of the experiments useful mutation forms were obtained, characterized with: earliness, lodging and disease resistance; higher productivity.

  2. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    Energy Technology Data Exchange (ETDEWEB)

    Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  3. Radioprotection shielding for neutrons induced by the reaction (2H (40 MeV), 12C)

    Science.gov (United States)

    Fadil, M.

    2017-09-01

    In the framework of design studies for SPIRAL2, the simulation of the neutron flux generated by 40 MeV deuterons on a thick 12C target was performed and compared to experimental data. The calculation of the dose rate of these neutrons allowed to compare four materials being considered for radioprotection shielding: barites, gypsum, ordinary concrete and heavy concrete. The simulated map of the neutron dose rate in the production building shows a very high dose rate around the neutron source and in the environment of some of the accelerator equipment.

  4. Radioprotection shielding for neutrons induced by the reaction (2H (40 MeV, 12C

    Directory of Open Access Journals (Sweden)

    Fadil M.

    2017-01-01

    Full Text Available In the framework of design studies for SPIRAL2, the simulation of the neutron flux generated by 40 MeV deuterons on a thick 12C target was performed and compared to experimental data. The calculation of the dose rate of these neutrons allowed to compare four materials being considered for radioprotection shielding: barites, gypsum, ordinary concrete and heavy concrete. The simulated map of the neutron dose rate in the production building shows a very high dose rate around the neutron source and in the environment of some of the accelerator equipment.

  5. Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies.

    Science.gov (United States)

    Abdelbary, Ghada A; Amin, Maha M; Zakaria, Mohamed Y

    2017-11-01

    Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance. Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis. The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed. In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile. Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.

  6. In Vivo Cytogenetic Studies on Aspartame

    Directory of Open Access Journals (Sweden)

    Entissar S. AlSuhaibani

    2010-01-01

    Full Text Available Aspartame (a-Laspartyl-L-phenylalanine 1-methylester is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol was investigated in vivo using chromosomal aberration (CA test and sister chromatid exchange (SCE test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight. Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI. However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.

  7. Radioprotective activities of beer administration for radiation-induced acute toxicity in mice.

    Science.gov (United States)

    Monobe, Manami; Koike, Sachiko; Uzawa, Akiko; Aoki, Mizuho; Takai, Nobuhiko; Fukawa, Takeshi; Furusawa, Yoshiya; Ando, Koich

    2004-12-01

    We previously found that drinking beer reduces chromosome aberrations in blood lymphocytes that were collected and irradiated in vitro. In this study, we investigated the radioprotective activities of beer-administration for bone marrow and intestine in mice. C3H/He female mice received an oral administration of beer, ethanol or saline at a dose of 1 ml/mouse 30 min before whole body irradiation with 137Cs gamma rays or LET 50 keV/microm carbon ions. Radioprotective activities were estimated using a LD(50/30) (The dose required to kill 50% of the mice within 30 days) and a microcolony technique for intestine. The LD(50/30) for the beer-administered mice was significantly increased in comparison with saline administered mice. The LD(50/30) of gamma-ray was 7.8 Gy (p beer-, ethanol- and saline-administered group, respectively. The LD(50/30) of carbon ions was 6.6 Gy (p beer-, ethanol- and saline-administered groups, respectively. The crypt survivals that were semi-logarithmically plotted against dose were well fitted to a linear regression line. The dose reduction factor (DRF) (D10) of beer- and ethanol-administered mice for gamma rays was 1.09 and 1.08, respectively. The DRF (D10) of beer- and ethanol-administered mice for carbon ions was 1.08 and 1.07, respectively. The radioprotection by beer-administration is due to not only OH radical-scavenge action by the ethanol contained in beer.

  8. Radioprotection in the infirmary praxis in service of hemodynamic; Radioprotecao na praxis da enfermagem em servico de hemodinamica

    Energy Technology Data Exchange (ETDEWEB)

    Flor, Rita de Cassia, E-mail: flor@ifsc.edu.br; Gelbcke, Francine Lima, E-mail: fgelbcke@ccs.ufsc.b [Universidade Federal de Santa Catarinha (CCS/UFSC), Florianopolis, SC (Brazil). Secretaria do Programa de Pos-Graduacao em Enfermagem

    2011-10-26

    Qualitative study made in a hemodynamic service at Santa Catarina, Brazil, viewing to analyse the attitude of workers in infirmary related to the use of radioprotection measurements in interventionist procedures. A methodology of Labor Psycho dynamics was used through the observations, collective interviews and the document analysis. Totally it was realized 36 encounters, completed a total of 54 observation hours. The results have shown that the workers used defense strategies for justification the not use of some radioprotection measurements. Yet, become evident that the measurements related to the distance from the radiation source and the exposure time have not used sometimes, perhaps due to negligence. Finally, it was concluded that, some attitudes adopted by the workers referred to the lack of a continued educational program

  9. Evaluation of radioprotective effect of aloe vera and zinc/copper compounds against salivary dysfunction in irradiated rats.

    Science.gov (United States)

    Nejaim, Yuri; I V Silva, Amaro; V Vasconcelos, Taruska; J N L Silva, Emmanuel; M de Almeida, Solange

    2014-09-01

    The aim of this study was to evaluate the radioprotective and reparative effects of compounds based on aloe vera, zinc, and copper against salivary gland dysfunction in Wistar rats. A total of 150 Wistar rats were randomly divided into 12 groups, in which the animals received aloe vera and/or zinc and copper. In eight of these groups the animals were also subjected to irradiation before or after administration of the substances. After 27 days, sialometry tests were performed. Data were analyzed using ANOVA and the Tukey test (P aloe vera before or after irradiation showed a significantly higher salivary flow rate than rats that had been simply irradiated. When both substances were administered, a statistically significant difference in the salivary flow rate was observed in comparison with the irradiation alone group seven days after irradiation. The present results suggest that aloe vera exerts positive protective and reparative effects, and can be considered a potential radioprotective substance.

  10. The radioprotective effect of a new aminothiol (20-PRA

    Directory of Open Access Journals (Sweden)

    M.F. Dolabela

    1998-08-01

    Full Text Available We examined the radioprotective effect of aminothiol 2-N-propylamine-cyclo-hexanethiol (20-PRA on a human leukemic cell line (K562 following various radiation doses (5, 7.5 and 20 Gy using a source of 60Co g-rays. At 5 Gy and 1 nM 20-PRA, a substantial protective effect (58% was seen 24 h after irradiation, followed by a decrease at 48 h (11%. At the high radiation dose (20 Gy a low protective effect was also seen (35%. In addition, the antitumorigenic potential of 10 nM 20-PRA was shown by the inhibition of crown gall formation induced by Agrobacterium tumefaciens. The radioprotective potency of 20-PRA is 105-106 times higher than that of the aminothiol WR-1065 (N-(2-mercaptoethyl-1,3-diaminopropane whose protective effect is in the 0.1 to 1.0 mM range.

  11. Innate Immune Pathways Associated with Lung Radioprotection by Soy Isoflavones

    OpenAIRE

    Abernathy, Lisa M.; Fountain, Matthew D.; JOINER, Michael C.; Hillman, Gilda G.

    2017-01-01

    Introduction Radiation therapy for lung cancer causes pneumonitis and fibrosis. Soy isoflavones protect against radiation-induced lung injury, but the mediators of radioprotection remain unclear. We investigated the effect of radiation on myeloid-derived suppressor cells (MDSCs) in the lung and their modulation by soy isoflavones for a potential role in protection from radiation-induced lung injury. Methods BALB/c mice (5–6 weeks old) received a single 10 Gy dose of thoracic irradi...

  12. Evaluation de la mise en oeuvre des mesures de radioprotection ...

    African Journals Online (AJOL)

    Seulement 08.1% des services faisaient une surveillance médicale de leur personnel. Conclusion : Le niveau de mise en oeuvre des mesures de radioprotection des travailleurs dans les services de radiologie reste à améliorer et la création d'une autorité de réglementation est souhaitable pour une meilleure protection ...

  13. Proton irradiation of stem cells: Radiation damage and chemical radioprotection

    Science.gov (United States)

    Riley, R. C.; Montour, J. L.; Gurney, C. W.

    1972-01-01

    Effects of high energy protons on erythropoietic stem cells and radioprotection by chemicals were investigated in NASA Space Radiation Effects Laboratory. The effects of a parallel beam of 600 MeV protons. The fluence, when converted to dose, were referenced to the synchrocyclotron beam monitors which were then used to administer radiation exposures. Mice were given graded doses to 300 rads to determine dose-response curve. Other mice received saline, AET, or 5-hydroxytryptamine 10 to 15 minutes before exposure.

  14. Selected recent in vivo studies on chemical measurements in invertebrates.

    Science.gov (United States)

    Majdi, S; Ren, L; Fathali, H; Li, X; Ewing, A G

    2015-06-07

    In vivo measurements of neurotransmitters and related compounds have provided a better understanding of the chemical interactions that are a major part in functioning of brains. In addition, a great deal of technology has been developed to measure chemical species in other areas of living organisms. A key part of this work has been sampling technologies as well as direct measurements in vivo. This is extremely important when sampling from the smallest animal systems. Yet, very small invertebrate systems are excellent models and often have better defined and more easily manipulated genetics. This review focuses on in vivo measurements, electrochemical methods, fluorescence techniques, and sampling and is further narrowed to work over approximately the last three years. Rapid developments of in vivo studies in these model systems should aid in finding solutions to biological and bioanalytical challenges related to human physiological functions and neurodegenerative diseases.

  15. A method to study in vivo stability of DNA nanostructures.

    Science.gov (United States)

    Surana, Sunaina; Bhatia, Dhiraj; Krishnan, Yamuna

    2013-11-01

    DNA nanostructures are rationally designed, synthetic, nanoscale assemblies obtained from one or more DNA sequences by their self-assembly. Due to the molecularly programmable as well as modular nature of DNA, such designer DNA architectures have great potential for in cellulo and in vivo applications. However, demonstrations of functionality in living systems necessitates a method to assess the in vivo stability of the relevant nanostructures. Here, we outline a method to quantitatively assay the stability and lifetime of various DNA nanostructures in vivo. This exploits the property of intact DNA nanostructures being uptaken by the coelomocytes of the multicellular model organism Caenorhabditis elegans. These studies reveal that the present fluorescence based assay in coelomocytes of C. elegans is an useful in vivo test bed for measuring DNA nanostructure stability. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Antioxidant, anticlastogenic and radioprotective effect of Coleus aromaticus on Chinese hamster fibroblast cells (V79) exposed to gamma radiation.

    Science.gov (United States)

    Rao, B S Satish; Shanbhoge, R; Upadhya, D; Jagetia, G C; Adiga, S K; Kumar, P; Guruprasad, K; Gayathri, P

    2006-07-01

    Coleus aromaticus (Benth, Family: Laminaceae), Indian Oregano native to India and Mediterranean, is well known for its medicinal properties. A preliminary study was undertaken to elucidate in vitro free radical scavenging potential and inhibition of lipid peroxidation by C.aromaticus hydroalcoholic extract (CAE). Anti-clastogenic and radioprotective potential of CAE were studied using micronucleus assay after irradiating Chinese hamster fibroblast (V79) cells. CAE at 10, 20, 40, 60, 80, 100 and 120 mug/ml resulted in a dose-dependent increase in radical scavenging ability against various free radicals viz., 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide anion (O(2)(*-)), hydroxyl (OH(*)) and nitric oxide (NO(*)) generated in vitro. A maximum scavenging potential was noticed at 100 mug/ml and a saturation point was reached thereafter with the increasing doses of CAE. The free radical scavenging potential of the extract was in the order of DPPH > ABTS > Superoxide > Hydroxyl > Nitric oxide. CAE also exhibited a moderate inhibition of lipid peroxidation in vitro, with a maximum inhibition at 60 mug/ml (33%), attaining saturation at higher doses. The extract also rendered protection against radiation induced DNA damage, as evidenced by the significant (P < 0.05) decrease in the percentage of radiation-induced micronucleated cells (MN) and frequency of micronuclei (total). A maximum anticlastogneic effect/ radioprotection was noticed at a very low concentration i.e., 5 mug/ml of CAE, treated 1 h prior to 2 Gy of gamma radiation. A significant (P < 0.0001) anticlastogenic/radioprotective effect was also observed when the cells were treated with an optimum dose of CAE (5 mug/ml) 1 h prior to 0.5, 1, 2 and 4 Gy of gamma radiation compared with the respective radiation control groups. Overall, our results established an efficient antioxidant, anticlastogenic and radioprotective potential of CAE, which may be of

  17. Fifth meeting of persons competent in radiation protection; Cinquiemes rencontres des personnes competentes en radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2007-07-01

    During this meeting will successively be approached: the statutory frame, the practical guide for the realization of the dosimetry studies of work stations presenting a risk of exposure to ionizing radiations, a study of post in conventional and interventional radiology, study of post in interventional cardiology, the roles and the missions of the P.C.R. (person competent in radiation protection) in a subcontractor company in I.N.B. (base nuclear installation), the application of the zoning order for the activities of industrial radiography, the evolution of the statutory measures in protection of the workers against the dangers of ionizing radiations, all which concerns the P.C.R. (training, missions, certification, educational role), the controls of radioprotection, the external controls of radioprotection, the surveillance of working zones, surveillance of effluents,management of the radioactive waste and effluents, classification of the personnel and the surveillance of the exposure, dosimetry by radio photo luminescence, the systeme S.I.S.E.R.I.. (N.C.)

  18. Haematopoiesis radioprotection in Balb/c mice by an aqueous mycelium extract from the Basidiomycete Pleurotus ostreatus mushroom.

    Science.gov (United States)

    Llauradó, G; Morris, H J; Tamayo, V; Lebeque, Y; Beltrán, Y; Marcos, J; Moukha, S; Creppy, E E; Bermúdez, R C

    2015-01-01

    The study examined the radioprotective activity of an aqueous extract from Pleurotus ostreatus mycelium administered to Balb/c mice. Male mice were whole-body irradiated on day 0 ((60)Co, at 0.43 Gy/min) and divided into two groups. The extract was administered intraperitoneally to one group (100 mg/kg) on days - 10 to - 6 and - 2 to +1 with respect to the irradiation. The irradiated-control group was injected with saline solution; non-irradiated mice were used as negative controls. The radioprotective effect was evident by increases in bone marrow cellularity (5.1 × 10(6)/femur vs. 1.1 × 10(6)/femur in saline-control mice, p < 0.05), leucocyte counts (10.5 × 10(9)/L vs. 4.5 × 10(9)/L, p < 0.05), and spleen cellularity (11.2 × 10(7)/spleen vs. 6.2 × 10(7)/spleen, p < 0.05). The extract stimulated macrophage phagocytic activity as judged by a faster rate of carbon clearance in terms of absorbance ratios (1.62 vs. 2.01, p < 0.05). Therefore, this extract may be a candidate therapeutic agent with radioprotective activity for haematopoiesis damage, particularly to cells involved in immune function.

  19. Radioprotective effect of the extract of Ziziphus joazeiro and Anacardium occidentale on embryos of Biomphalaria glabrata submitted to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Williams N.; Silva, Luanna R.S.; Silva, Edvane B. [Universidade Federal de Pernambuco (DEN/UFPE), Recife, PE (Brazil). Dept. de Energia Nuclear. Grupo de Estudos em Radioprotecao e Radioecologia; Silva, Ronaldo C. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica; Lacerda, Laila B.N.; Silva, Hianna A.M.F.; Santos, Mariana L.O.; Sa, Jose L.F.; Melo, Ana M.M.A. [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de de Biofisica e Radiobiologia. Lab. de Radiobiologia

    2011-07-01

    Electromagnetic radiations are energies that can be classified as non-ionizing and ionizing. This type of energy is propagated by a material medium and the vacuum. The important characteristic of ionizing radiation is the localized release of large amounts of energy. The biological effects of radiation result principally from damage to DNA, which is the critical target. Given these harmful effects caused by radiation highlights the importance of acquiring knowledge about the radioprotective substance, because they act to protect the living tissue, decreasing the damage he caused by the effects of radiation. In this study we investigated the radioprotective effect of extract hydroalcoholic of Ziziphus joazeiro and Anacardium occidentale on embryos of Biomphalaria glabrata. The embryos of Biomphalaria glabrata pigmented were divided into 18 groups of 100 specimens. The experimental groups were exposed to the extracts at a concentration of 200 ppm and then irradiated. For irradiation, we used a source of {sup 60}Co (Gammacell of Radionics Labs. Dose rate = 4.359 Gy/h). The viability of the embryos was examined using a stereoscopic microscope and statistical analysis was performed using the test Student-Newman-Keuls and {chi}{sup 2}. Our results showed that the extracts of hydroalcoholic Ziziphus joazeiro showed radioprotective effect and that the aqueous extract of the bark of Anacardium occidentale exhibited a reduction in its embryotoxic effect. (author)

  20. Vasoactive and radioprotective properties of isothiourea derivatives having NOS-inhibitory activity

    Energy Technology Data Exchange (ETDEWEB)

    Filimonova, Marina V.; Shevchenko, Ludmila I.; Ulyanenko, Stepan E.; Makarchuk, Victorya M.; Kuznetsova, Mary N.; Shevchuk, Aza S.; Lushnikova, Galina A.; Chesnakova, Ekaterina A. [Medical Radiological Research Center Health Ministry of Russia, 4, Korolev street, Obninsk, 249036, Kaluga region (Russian Federation)

    2014-07-01

    We studied vasoactive and radioprotective properties of new original N-acyl, S-alkyl isothiourea derivatives which are potent inhibitors of nitric oxide synthases (preferably eNOS and iNOS). These compounds have a moderate toxicity (LD50 - 400-550 mg/kg), and are stable in aqueous solutions. In hemodynamic studies, these compounds exhibited high vasotropic activity. The use of these compounds in doses of 5-15 mg/kg (0,01-0,03 LD{sub 50}) in the experimental animals in a state of the severe hemorrhagic or endo-toxic shock causes a potent vasopressor effect, accompanied by a significant and continuous rise in blood pressure. The increasing of vascular tone developed over 2-5 min after injection and persisted for at least 60-90 minutes, excelling at least 3-5 times the duration of α1-adreno-mimetic vasopressor action. The rapid increase in vascular tone under the influence of these compounds in normo-tonic animals caused protective baroreflex to prevent high blood pressure. At doses of 10-15 mg/kg the reflex reaction was mild, but at higher doses (30-40 mg/kg) the reaction was fierce and prolonged, and was accompanied by severe bradycardia, decreasing of the cardiac output and a significant weakening of the peripheral blood flow. In all cases, the hemodynamic response was reflexive and easily eliminated by atropine. The ability of these compounds to induce circulatory hypoxia was the basis for the study of their radioprotective properties. The study of radioprotective effect on the survival of animals exposed to lethal doses of γ-radiation (10 Gy) and on the survival of hematopoietic clonogenic cells showed that these compounds in doses of 80-150 mg/kg (0,2-0,3 LD50) have considerable radioprotective action, which is comparable with the protective effect of the maximum tolerated dose of cystamine. The factor of change in dose for γ-radiation, estimated by the LD{sub 50}, was 1,42-1,58. We also investigated the ability of the test compounds, due to their hypoxic

  1. Radioprotective effect of vitamin E in parotid glands: a morphometric analysis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Carolina Cintra; Boscolo, Frab Norberto; Almeida, Solange Maria de [Universidade Estadual de Campinas (UNICAMP), Piracicaba, SP (Brazil). Dept. de Diagnostico Oral; Ramos-Perez, Flavia Maria de Moraes; Perez, Danyel Elias da Cruz, E-mail: flavia.ramosperez@ufpe.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Clinica e Odontologia Preventiva; Novaes, Pedro Duarte [Universidade Estadual de Campinas (UNICAMP), Piracicaba, SP (Brazil). Escola de Odontologia. Dept. de Morfologia

    2013-11-01

    The aim of this study was to evaluate the radioprotective effect of vitamin E on rat parotid glands by morphometric analysis. Sixty male rats were divided into 5 groups (n=6): control, in which animals received olive oil solution; olive oil/irradiated, in which animals received olive oil and were irradiated with a dose of 15 Gy of gamma radiation; irradiated, in which animals were irradiated with a dose of 15 Gy gamma radiation; vitamin E, which received {alpha}-tocopherol acetate solution; vitamin E/irradiated, which received {alpha}-tocopherol acetate solution before irradiation with a dose of 15 Gy gamma rays. Half of the animals were euthanized at 8 h, and the remaining at 30 days after irradiation. Both parotid glands were surgically removed and morphometric analysis of acinar cells was performed. Data were subjected to two-way ANOVA and Tukey's test ({alpha}=0.05). Morphometric analysis showed a significant reduction in the number of parotid acinar cells at 30 days in olive oil/irradiated and irradiated groups. In groups evaluated over time a significant reduction was shown at 30 days in olive oil/irradiated and irradiated groups, indicating that ionizing radiation caused tissue damage. The vitamin E/irradiated group presented more acinar cells than the irradiated group, but no statistically significant difference was observed (p>0.05). In conclusion, vitamin E seems to have failed as a radioprotective agent on acinar cells in rat parotid glands. (author)

  2. Restoration of radiation injury by ginseng, 2. Some properties of the radioprotective substances

    Energy Technology Data Exchange (ETDEWEB)

    Yonezawa, M.; Katoh, N.; Takeda, A. (Radiation Center of Osaka Prefecture, Sakai (Japan))

    1981-09-01

    Some properties of the radioprotective substances in a ginseng extract that increased the 30-day survival ratio in irradiated mice were studied. Methanol-soluble fraction of the extract did not protect the irradiated animals. Acid or alkali (0.12 N) inactivated the extract at 60/sup 0/C. But the radioprotective activity was stable after heating the ginseng extract in physiological saline at pH 7 in a boiling-water bath for 15 min. The ginseng extract was separated into two fractions by CM-cellulose column chromatography. One of them (CM-A) was significantly efficacious at 5% level, and the other (CM-B) at 0.1% level with the doses proportional to their yields. CM-B, not containing saponin, was subjected to further purification, UV spectrum and a biuret test suggested the presence of protein in this fraction. The supernatant obtained after heating CM-B solution at pH 7 was separated into three fractions, namely G-I, G-II and G-III, by gel-chromatography with a Sephadex G-75 column. Both G-I (0.44 mg per animal) and G-III (0.84 mg, calculated dose) were significantly efficacious, but G-II (0.47 mg) was not.

  3. Radioprotective and Apoptotic Properties of a Combination of α-Tocopherol Acetate and Ascorbic Acid.

    Science.gov (United States)

    Vasil'eva, I N; Bespalov, V G; Baranenko, D A

    2016-06-01

    We studied radioprotective and apoptotic properties of a combination of α-tocopherol acetate and ascorbic acid. α-Tocopherol acetate (10 mg/kg body weight) or ascorbic acid (20 mg/kg) or combination of these agents in the same doses was orally administered to male rats at various terms before and after single whole-body exposure to γ-irradiation in the doses of 2 and 8 Gy. Irradiation increased the frequency of chromosome aberrations in bone marrow cells and plasma level of low-molecular-weight DNA. Vitamin combination administered before or after irradiation significantly reduced the frequency of chromosome aberrations by 2-2.5 times. Administration of this combination 10 min before irradiation 1.5-fold increased the content of low-molecular-weight DNA in blood plasma in comparison with the control animals exposed to radiation. The combination of α-tocopherol acetate and ascorbic acid produced radioprotective effects and enhanced apoptosis in irradiated cells.

  4. Combined Modality Radioprotection: The Use of Glucan and Selenium with WR-2721

    Science.gov (United States)

    1990-05-01

    hemopoietic ef- agents when used in combination. Radioprotection fol- fects of these combinations as well as those of the single 1074 i. J. Radiation...radioprotective combination eval- tiveness of these cocktails. REFERENCES 1. Ainsworth, E. J.; IrekM, R *,."M., Whell , F>:ASTaylor, characteristics

  5. Radioprotection, biological effects of the radiations and security in the handling of radioactive material

    CERN Document Server

    Teran, M

    2000-01-01

    The development of the philosophy of the radioprotection is dependent on the understanding of the effects of the radiation in the man. Behind the fact that the radiation is able to produce biological damages there are certain factors with regard to the biological effects of the radiations that determine the boarding of the radioprotection topics.

  6. Molecular targets for radioprotection by low dose radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hang Rhan; Lee, Yoon Jin; Cho, Chul Koo; Lee, Su Jae; Bae, Sang woo; Lee, Yun Sil [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2004-07-01

    Adaptive response is a reduced effect from a higher challenging dose of a stressor after a smaller inducing dose had been applied a few hrs earlier. Radiation induced fibrosarcoma (RIF) cells did not show such an adaptive response, i.e. a reduced effect from a higher challenging dose (2 Gy) of a radiation after a priming dose (1 cGy) had been applied 4 or 7 hrs earlier, but its thermoresistant clone (TR) did. Since inducible HSP70 and HSP25 expressions were different between these two cell lines, the role of inducible HSP70 and HSP25 in adaptive response was examined. When inducible hsp70 or hsp25 genes were transfected to RIF cells, radioresistance in clonogenic survival and reduction of apoptosis was detected. The adaptive response was also acquired in these two cell lines, and inducible hsp70 transfectant showed more pronounced adaptive response than hsp25 transfectant. From these results, inducible HSP70 and HSP25 are at least partly responsible for the induction of adaptive response in these cells. Moreover, when inducible HSP70 or HSP25 genes were transfected to RIF cells, coregulation of each gene was detected and heat shock factor (HSF) was found to be responsible for these phenomena. In continuation of our earlier study on the involvement of heat shock protein (HSP) 25 and HSP70 in the induction of adaptive response, we have now examined the involvement of these proteins in the induction of the adaptive response, using an animal model system. C57BL6 mice were irradiated with 5 cGy of gamma radiation 3 times for a week (total of 15cGy) and a high challenge dose (6Gy) was given on the day following the last low dose irradiation. Survival rate of the low dose pre-irradiated mice was increased to 30%. Moreover, high dose-mediated induction of apoptosis was also reduced by low dose pre-irradiation. To elucidate any link existing between HSP and induction of the adaptive response, reverse transcriptase (RT)-polymerase chain reaction (PCR) analysis was performed

  7. Persistence of DNA studied in different ex vivo and in vivo rat models simulating the human gut situation

    NARCIS (Netherlands)

    Wilcks, A.; Hoek, van A.H.A.M.; Joosten, R.G.; Jacobsen, B.B.L.; Aarts, H.J.M.

    2004-01-01

    This study aimed to evaluate the possibility of DNA sequences from genetically modified plants to persist in the gastrointestinal (GI) tract. PCR analysis and transformation assays were used to study DNA persistence and integrity in various ex vivo and in vivo systems using gnotobiotic rats. DNA

  8. Coagulation Management in Jersey Calves: An ex vivo Study.

    Science.gov (United States)

    Gröning, Sabine; Maas, Judith; van Geul, Svenja; Rossaint, Rolf; Steinseifer, Ulrich; Grottke, Oliver

    2017-01-01

    Jersey calves are frequently used as an experimental animal model for in vivo testing of cardiac assist devices or orthopedic implants. In this ex vivo study, we analyzed the coagulation system of the Jersey calves and the potential of human-based coagulation management to circumvent perioperative bleeding complications during surgery. Experimental Procedure: Blood from 7 Jersey calves was subjected to standard laboratory tests and thromboelastometry analysis. An ex vivo model of dilutional coagulopathy was used to study the effects of fibrinogen or prothrombin complex concentrate supplementation. Fibrinolysis was induced with tissue plasminogen activator to identify potential therapeutic strategies involving tranexamic acid or aprotinin. Furthermore, anticoagulation strategies were evaluated by incubating the blood samples with dabigatran or rivaroxaban. Baseline values for thromboelastometry and standard laboratory parameters, including prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin III, and D-dimers, were established. Fifty percent diluted blood showed a statistically significant impairment of hemostasis. The parameters significantly improved after the administration of fibrinogen or prothrombin complex concentrate. Tranexamic acid and aprotinin ameliorated tissue plasminogen activator-induced fibrinolysis. Both dabigatran and rivaroxaban significantly prolonged the coagulation parameters. In this ex vivo study, coagulation factors, factor concentrate, antifibrinolytic reagents, and anticoagulants regularly used in the clinic positively impacted coagulation parameters in Jersey calf blood. © 2017 S. Karger AG, Basel.

  9. In vivo study of human skin using pulsed terahertz radiation

    Energy Technology Data Exchange (ETDEWEB)

    Pickwell, E [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Cole, B E [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Fitzgerald, A J [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom); Pepper, M [Semiconductor Physics Group, Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE (United Kingdom); Wallace, V P [TeraView Ltd, Unit 302/4 Cambridge Science Park, Cambridge CB4 0WG (United Kingdom)

    2004-05-07

    Studies in terahertz (THz) imaging have revealed a significant difference between skin cancer (basal cell carcinoma) and healthy tissue. Since water has strong absorptions at THz frequencies and tumours tend to have different water content from normal tissue, a likely contrast mechanism is variation in water content. Thus, we have previously devised a finite difference time-domain (FDTD) model which is able to closely simulate the interaction of THz radiation with water. In this work we investigate the interaction of THz radiation with normal human skin on the forearm and palm of the hand in vivo. We conduct the first ever systematic in vivo study of the response of THz radiation to normal skin. We take in vivo reflection measurements of normal skin on the forearm and palm of the hand of 20 volunteers. We compare individual examples of THz responses with the mean response for the areas of skin under investigation. Using the in vivo data, we demonstrate that the FDTD model can be applied to biological tissue. In particular, we successfully simulate the interaction of THz radiation with the volar forearm. Understanding the interaction of THz radiation with normal skin will form a step towards developing improved imaging algorithms for diagnostic detection of skin cancer and other tissue disorders using THz radiation.

  10. Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency.

    Science.gov (United States)

    Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai

    Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine

  11. Radioprotective effects of CBLB502 on γ-radiated Rhesus monkey

    Directory of Open Access Journals (Sweden)

    Xing SHEN

    2015-06-01

    Full Text Available Objective A Rhesus monkey model was employed to study the radioprotective effects of a Toll-like receptor 5 agonist, CBLB502, against 7.0Gy whole-body irradiation of 60Co gamma-rays. Methods Thirty animals were assigned to a placebo treatment group, a WR-2721 positive control group, and three CBLB502 treatment groups (n=6 animals/group. Each animal was irradiated with 7.0Gy 60Co γ and given CBLB502 at 2.5, 10 and 40μg/kg, respectively in treatment groups, or WR-2721 at 30mg/kg, or physiological saline 0.3ml/kg for the placebo treatment group. The treatment was given once by intramuscular injection 30 min before irradiation. All irradiated animals received symptomatic treatment based on same guidelines. General observation, peripheral blood tests, hemopoietic progenitor cell colony-counting, and histopathological examination were performed. Results We found that 10 or 40μg/kg CBLB502 treatment resulted in 100% survival, while the survival rate was 33% in placebo treatment group. Hematopoietic recovery in the WR-2721 treatment group was marginally superior to the irradiation control group. Nadirs of peripheral white cell and platelet counts of animals treated with 40μg/kg of CBLB502 were significantly higher than those of the placebo treatment group (P<0.05. CBLB502 at 40μg/kg also gave a shortened duration of low platelet count, earlier recovery time, reduced the amount of blood transfusion and damage to the bone marrow and intestine. Conclusion All Rhesus monkeys irradiated with 7.0Gy 60Co γ-rays would suffer from severe acute radiation sickness of hematopoietic system. CBLB502 at 40μg/kg is radioprotective in this model and a single intramuscular injection of CBLB502 in a dose of 40μg/kg 30min before irradiation gives better radioprotective effects than WR-2721. DOI: 10.11855/j.issn.0577-7402.2015.04.07

  12. Radioprotection and Shielding Aspects of the nTOF Spallation Source

    CERN Document Server

    Vlachoudis, V; Buono, S; Cennini, P; Dahlfors, M; Ferrari, A; Kadi, Y; Herrera-Martínez, A; Lacoste, V; Radermacher, E; Rubbia, Carlo; Zanini, L

    2002-01-01

    The neutron Time of Flight (nTOF) facility at CERN is a high flux neutron source obtained by the spallation of 20 GeV/c protons onto a solid lead target. The first experimental measurements performed in Apr. 2001 have revealed an important neutron background, 50 to 100 times higher than expected, along with some secondary effects like air activation, with a strong presence of 7Be and 41Ar. In a subsequent study this neutron background was accounted to the strong presence of charged particles and especially negative muons, resulting from the interaction of the high-energy proton beam with the lead target. The present paper reports the study and solutions to the radioprotection and shielding aspects related to the nTOF spallation source.

  13. Persistence of DNA studied in different ex vivo and in vivo rat models simulating the human gut situation

    DEFF Research Database (Denmark)

    Wilcks, Andrea; van Hoek, A.H.A.M.; Joosten, R.G.

    2004-01-01

    This study aimed to evaluate the possibility of DNA sequences from genetically modified plants to persist in the gastrointestinal (GI) tract. PCR analysis and transformation assays were used to study DNA persistence and integrity in various ex vivo and in vivo systems using gnotobiotic rats. DNA...... studied was either plasmid DNA, naked plant DNA or plant DNA embedded in maize flour. Ex vivo experiments performed by incubating plant DNA in intestinal samples, showed that DNA is rapidly degraded in the upper part of the GI tract whereas degradation is less severe in the lower part. In contrast...

  14. Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

    Science.gov (United States)

    Al-Oran, Sawsan Atallah; Hassuneh, Mona Rushdie; Al-Qaralleh, Haitham Naief; Rayyan, Walid Abu; Al-Thunibat, Osama Yosef; Mallah, Eyad; Abu-Rayyan, Ahmed; Salem, Shadi

    2017-01-01

    This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional) assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional), we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/106 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg. PMID:29204086

  15. Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

    Directory of Open Access Journals (Sweden)

    Ibrahim Salameh Al-Majali

    2017-10-01

    Full Text Available This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional, we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/10 6 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg.

  16. Combined effect of hormones and radioprotective substances in case of animal exposure to ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Benke, D.; Bodo-Sekejchidinch, K.; Ehanta, A.

    1982-02-01

    The effect of anabolic and other relative preparations used in the national therapy in combination with radioprotective compounds tested earlier in experiments with animals was studied. The investigations were carried out on albino male mice of CFLP line. X-ray exposure was carried out with the help of a TNH-250 type unit for deep irradiation (630 R and 800 R doses). For gamma irradiation, a /sup 60/Co facility was utilized. AET radioprotective compounds (S/sub 2/-beta-aminoethylisothiouronium-bromide-hydrobromide) and ixeprin (bis-alfa-propinyl-glycyl-sodium disulfide) were used. Nerobolyl (norandrostenolon-phenylpropionate) and retabolyl (norandrostenolon-decanoat) were studied among anabolic hormones. Experiments were also conducted using retandrolom (testosteron-phenylpropionate) which did not belong to anabolics but was used in oncology as a supporting agent. Three days prior to the irradiation, intraperitoneal intections of nerobolyl (10 mg/kg) dissolved in oil for intections, ratabolyl (50 mg/kg) and retandrol (25 mg/kg) began to be made to groups of animals, 15 mice in each. Control groups received intraperitoneally only 0.5 ml of oil. In another series of experiments hormones were used even after the irradiation. Radioprotectors were introduced, as a rule, 20 min. prior to the radiation exposure. Ixeprin, as an effective radioprotector, was introduced 3 hours after the irradiation. When evaluating the results of the experiments, the number of animals which survived during 30 days after the irradiation and the rate of mortality were taken into consideration, gain in weight was also taken into account. A single introduction of an anabolic in combination with a radioprotector (AET or ixeprin) usually did not contribute to an increase of the survival rate of irradiated animals.

  17. In Vivo Assessment of Muscle Contractility in Animal Studies.

    Science.gov (United States)

    Iyer, Shama R; Valencia, Ana P; Hernández-Ochoa, Erick O; Lovering, Richard M

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a "direct measure" of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive measure of the overall health of the muscle is assessment of its primary function, which is to produce contractile force. The majority of animal models testing contractile force have been limited to the muscle groups moving the ankle, with advantages and disadvantages depending on the equipment. Here, we describe in vivo methods to measure torque, to produce a reliable muscle injury, and to follow muscle function within the same animal over time. We also describe in vivo methods to measure tension in the leg and thigh muscles.

  18. Study on advancement of in vivo counting using mathematical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Kinase, Sakae [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2003-05-01

    To obtain an assessment of the committed effective dose, individual monitoring for the estimation of intakes of radionuclides is required. For individual monitoring of exposure to intakes of radionuclides, direct measurement of radionuclides in the body - in vivo counting- is very useful. To advance in a precision in vivo counting which fulfills the requirements of ICRP 1990 recommendations, some problems, such as the investigation of uncertainties in estimates of body burdens by in vivo counting, and the selection of the way to improve the precision, have been studied. In the present study, a calibration technique for in vivo counting application using Monte Carlo simulation was developed. The advantage of the technique is that counting efficiency can be obtained for various shapes and sizes that are very difficult to change for phantoms. To validate the calibration technique, the response functions and counting efficiencies of a whole-body counter installed in JAERI were evaluated using the simulation and measurements. Consequently, the calculations are in good agreement with the measurements. The method for the determination of counting efficiency curves as a function of energy was developed using the present technique and a physiques correction equation was derived from the relationship between parameters of correction factor and counting efficiencies of the JAERI whole-body counter. The uncertainties in body burdens of {sup 137}Cs estimated with the JAERI whole-body counter were also investigated using the Monte Carlo simulation and measurements. It was found that the uncertainties of body burdens estimated with the whole-body counter are strongly dependent on various sources of uncertainty such as radioactivity distribution within the body and counting statistics. Furthermore, the evaluation method of the peak efficiencies of a Ge semi-conductor detector was developed by Monte Carlo simulation for optimum arrangement of Ge semi-conductor detectors for

  19. Cerebral radioprotection by pentobarbital: Dose-response characteristics and association with GABA agonist activity

    Energy Technology Data Exchange (ETDEWEB)

    Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H. (National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD (USA))

    1990-05-01

    Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time.

  20. Enzymeaticial analysis and soluble proteins assays on radioprotective effects of cordyceps militaris

    Energy Technology Data Exchange (ETDEWEB)

    Yoo, Beong Gyu [Wonkwang Health Science College, Iksan (Korea, Republic of); Park, Joon Chul [Ansan 1 College, Ansan (Korea, Republic of)

    2001-06-01

    Effect of single pre-administration of Cordyceps militaries (Cm) extract on the survival ratio, body weight and organ weight changes and blood cell counts after whole-body {gamma}-irradiation were investigated. The single pre-administration of Cm extract at 24 hrs before {gamma}-irradiation increased the 40-day survival ration of irradiated mice from 60.1% to 71/4%. The administration of Cm extract completely prevented weight reductions of spleen and thymus produced by {gamma}-irradiation (P<0.01, P<0.05). Similar but somewhat less radioprotective effect was also found in the testis of the Cm treated mice. The administration of Cm extract retarded the reduction of both leukocyte and lymphocyte counts occured during the first 7 days and accelerated the recovery of the counts thereafter. The extract also accelerated the recovery of the erythrocyte counts occurred after the day 21th. SDS-polyacrylamide gel electrophoresis of the soluble proteins extracted from various organs did not reveal differences to any extent in all groups except in the levers of the irradiated and extract treated groups, in which some proteins were missing or less present. Also, the result of general intra and extra mycelial enzyme assays with Cm, extramycelial enzyme activity was relatively higher than the intramycelial enzyme. Cm appeared to indicate that {alpha}-amylase was the highest among the enzymes and gluosidase and chitinase were followed. Since the spleen, thymus and testis have been well known as radiosensitive organs, the protective action of Cm extract on irradiated mice may be responsible for its enhancing recovery of these organs. Although the exact mechanism in protective effect of Cm extract on irradiated mice is not clear yet, the present study is the first report regarding the Cm which was tested and found to be a potential radioprotective agent.

  1. Comparison of radioprotective effects of caffeine and ascorbic acid in male mice

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Kyu; Kim, Ji Hyang; Lee, Byoung Hun [KAERI, Taejon (Korea, Republic of); Yoon, Yong Dal [Hanyang Univ., Seoul (Korea, Republic of)

    2003-04-01

    The oxygen effect in radiation biology is well known. Since oxygen enhances radiation-induced biological damage, antioxidants should be radioprotectors. Ascorbic acid (vitamin C) or caffeine is an essential component in the diet of humans and a small range of other mammals. Radioprotective effects of vitamin C have been demonstrated in certain cells and animals, which would result from scavenging free radicals. Caffeine is the main psychoactive ingredient of coffee, tea, even coke with a high frequency of concurrent use in humans. Caffeine has been recently reported as a scavenger of hydroxyl radical in millimolar levels and a potently radioprotector in a chronically exposed rodent. This study investigates functional radioprotection of caffeine and ascorbic acid against gamma irradiation in male mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with 80 mg/kg body weight by i.p injection, a single exposure 1 hour before irradiation. Ascorbic acid was administered 330 mg/liter in drinking water through all the experimental period. The remaining mice were kept as sham controls. After collecting a serum from the experimental mice 6 hr after irradiation, qualitative analysis of testosterone was performed by means of radioimmunoassay (RIA). For histological investigation, testes were removed 1 week after irradiation and fixed in NBF. Fixed testes were processed for paraffin sections and stained by H-E. The circulating testosterone significantly decreased in all irradiated groups. The harmful effect of radiation on the body and organ weight and the appearance of semiferous tubules were significantly improved in the caffeine - or ascorbic acid-treated group. In conclusion, caffeine and ascorbic acid protected spermatogenesis from impairment against gamma radiation, acting as a radioprotector.

  2. Radioprotective Effects of Sulfurcontaining Mineral Water of Ramsar Hot Spring with High Natural Background Radiation on Mouse Bone Marrow Cells

    Directory of Open Access Journals (Sweden)

    Heidari A. H.

    2017-12-01

    Full Text Available Background: We intend to study the inhibitory effect of sulfur compound in Ramsar hot spring mineral on tumor-genesis ability of high natural background radiation. Objective: The radioprotective effect of sulfur compounds was previously shown on radiation-induced chromosomal aberration, micronuclei in mouse bone marrow cells and human peripheral lymphocyte. Ramsar is known for having the highest level of natural background radiation on Earth. This study was performed to show the radioprotective effect of sulfur-containing Ramsar mineral water on mouse bone marrow cells. Method: Mice were fed three types of water (drinking water, Ramsar radioactive water containing sulfur and Ramsar radioactive water whose sulfur was removed. Ten days after feeding, mice were irradiated by gamma rays (0, 2 and 4 Gy. 48 and 72 hours after irradiating, mice were killed and femurs were removed. Frequency of micronuclei was determined in bone marrow erythrocytes. Results: A significant reduction was shown in the rate of micronuclei polychromatic erythrocyte in sulfur-containing hot spring water compared to sulfur-free water in hot spring mineral water. Gamma irradiation induced significant increases in micronuclei polychromatic erythrocyte (MNPCE and decreases in polychromatic erythrocyte/polychromatic erythrocyte + normochromatic erythrocyte ratio (PCEs/ PCEs+NCEs (P < 0.001 in sulfur-containing hot spring water compared to sulfur-free hot spring mineral water. Also, apparently there was a significant difference between drinking water and sulfur-containing hot spring water in micronuclei polychromatic erythrocyte and polychromatic erythrocyte/polychromatic erythrocyte+ normochromatic erythrocyte ratio. Conclusion: The results indicate that sulfur-containing mineral water could result in a significant reduction in radiation-induced micronuclei representing the radioprotective effect of sulfur compounds.

  3. The functions of laminins: lessons from in vivo studies

    DEFF Research Database (Denmark)

    Ryan, M C; Christiano, A M; Engvall, E

    1996-01-01

    here. Instead, I will focus on the recent evidence gathered from gene knock out experiments in mice and from naturally occurring human and mouse gene mutations. The most obvious lesson from the above studies--other than demonstrating the importance of laminins in general--is that the structural......, through interactions with various receptors. It is interesting that the in vivo studies summarized above support both activities. In the case of laminin 5 mutations, the phenotypic consequence appears to be due primarily to the loss of an important structural link between the epithelial cytokeratins...

  4. Meta-analysis of dragon’s blood resin extract as radio-protective agent

    Directory of Open Access Journals (Sweden)

    Subaika Mahmood

    2017-09-01

    Full Text Available In health sciences, much efforts had been made in past years to explore the radio-protective agents from natural resources due to rapid exposure of radiations to environment such as space traveling, radiotherapy and largely growing telecommunication industry. It becomes crucial to find natural sources for radio-protection. In correspondence, dragon’s blood (DB is a traditional Chinese medicinal plant that possesses great medicinal values due to the presence of several phenolic compounds. For a long time, DB has been used in treatment of blood stasis, inflammation, oxidative stress, immune suppression and tumors, but recently it has been extensively used as radio-protective agent. There is no comprehensive review on radio- protective characterization of DB resin extract in literature. In our review, an attempt has been made to highlight unique and inherent radio-protection in liver, brain, kidney, lung, spleen and cerebrum. This review will help people in exploring the radioactive protectants from natural resources.

  5. The use of radioprotective indicators in medicine; Indicadores em protecao radiologica: emprego na pratica medica

    Energy Technology Data Exchange (ETDEWEB)

    Tilly Junior, Joao G.; Schmidt, Margot F.S. [Secretaria de Estado da Saude, Curitiba, PR (Brazil)

    1996-12-31

    Radioprotection indicators are proposed as per the World Health Organization guide-lines, in order to establish policies as well as to show the development and identified new operational strategic in radiological protection 4 refs., 1 tab.

  6. Comparative Pharmaceutical Evaluation of Candesartan and Candesartan Cilexetil: Physicochemical Properties, In Vitro Dissolution and Ex Vivo In Vivo Studies.

    Science.gov (United States)

    Amer, Ahmed M; Allam, Ahmed N; Abdallah, Ossama Y

    2017-09-25

    The aim of the present work is to answer the question is it possible to replace the ester prodrug candesartan cilexetil (CC) by its active metabolite candesartan (C) to bypass the in vivo variable effect of esterase enzymes. A comparative physicochemical evaluation was conducted through solubility, dissolution, and stability studies; additionally, ex vivo permeation and in vivo studies were assessed. C demonstrated higher solubility over CC at alkaline pH. Moreover, dissolution testing using the pharmacopeial method showed better release profile of C even in the absence of surfactant in the testing medium. Both drugs demonstrated a slight degradation in acidic pH after short-term stability. Instead, shifting to alkaline pH of 6.5 and 7.4 showed superiority of C solution stability compared to CC solution. The ex vivo permeation results demonstrated that the parent compound C has a significant (P candesartan for clinical use similarly to azilsartan and its prodrug.

  7. Mechanism of radioprotection by dihydroxy-1-selenolane (DHS): Effect of fatty acid conjugation and role of glutathione peroxidase (GPx).

    Science.gov (United States)

    Verma, Prachi; Kunwar, Amit; Arai, Kenta; Iwaoka, Michio; Priyadarsini, K Indira

    2017-10-30

    Dihydroxy-1-selenolane (DHS) previously reported to exhibit radioprotective activity was investigated to understand its mechanism of action in CHO cells of epithelial origin. DHS pre-treatment at 25 μM for 16 h significantly protected CHO cells from radiation (4-11 Gy)-induced delayed mitotic cell death. Further to examine, how increased cellular uptake can influence this mechanism, studies have been performed with DHS-C6, a lipophilic conjugate of DHS. Accordingly CHO cells pre-treated with DHS-C6, showed increased survival against radiation exposure. Notably treatment with both DHS and DHS-C6 significantly increased glutathione peroxidase (GPx) activity in cells by ∼ 2.5 fold. Additionally, the compound DHS or DHS-C6 led to faster repair of DNA in irradiated cells and subsequently inhibited the G2/M arrest. Anticipating the role of GPx in radioprotection, our investigations revealed that addition of mercaptosuccinic acid, a pharmacological inhibitor of GPx reversed all the above effects of DHS or DHS-C6. Further inhibitors of check point kinase 1 (CHK1) and DNA-protein kinase (DNA-PK) although abrogated the radioprotective effect of DHS or DHS-C6 separately, did not show additive effect in combination with GPx inhibitor, suggesting their cross talk. In contrast to these results, both DHS and DHS-C6 treatment did not protect spleen lymphocytes from the radiation-induced apoptosis. Thus results confirmed that both DHS and DHS-C6 protected cells from radiation-induced mitotic death by augmenting DNA repair in a GPx dependant manner. Copyright © 2017. Published by Elsevier B.V.

  8. How to promote the optimization of radioprotection in interventional radiology: the ASN's point of view; Comment favoriser l'optimisation de la radioprotection en radiologie interventionnelle: le point de vue de l'ASN

    Energy Technology Data Exchange (ETDEWEB)

    Menechal, Ph. [Autorite de Surete Nucleaire, Division de Bordeaux, 75 - Paris (France); Valero, M.; Godet, J.L [Autorite de Surete Nucleaire, Direction des rayonnements ionisants et de la sante, 75 - Paris (France)

    2009-07-01

    Within a context of development of interventional imagery practices, radioprotection in interventional radiology and in operating theatre suite where ionizing radiation are used has become a matter of concern. Before the publication of a work group created at the initiative of the ASN (the French nuclear safety authority) with a professional group (the GPMED, the permanent group of radioprotection experts for medical and forensics applications of ionizing radiations), the authors, members of the ASN, based on declared events and radioprotection inspection reports, give an overview of the faced challenges and problems and of progresses to be made in terms of radioprotection, dosimetry, procedures, and personnel qualification. They make a distinction between the patient radioprotection issue and the worker radioprotection issue

  9. Meta-analysis of dragon’s blood resin extract as radio-protective agent

    OpenAIRE

    Subaika Mahmood; Toseef Fatima; Hina Zulfaqar; Romana Saher; Muhammad Rafiq; Abdul Rehman; Rongji Dai; Muhammad Ashfaq; Murtaza Hasan

    2017-01-01

    In health sciences, much efforts had been made in past years to explore the radio-protective agents from natural resources due to rapid exposure of radiations to environment such as space traveling, radiotherapy and largely growing telecommunication industry. It becomes crucial to find natural sources for radio-protection. In correspondence, dragon’s blood (DB) is a traditional Chinese medicinal plant that possesses great medicinal values due to the presence of several phe...

  10. An ex vivo culture system to study thyroid development.

    Science.gov (United States)

    Delmarcelle, Anne-Sophie; Villacorte, Mylah; Hick, Anne-Christine; Pierreux, Christophe E

    2014-06-06

    The thyroid is a bilobated endocrine gland localized at the base of the neck, producing the thyroid hormones T3, T4, and calcitonin. T3 and T4 are produced by differentiated thyrocytes, organized in closed spheres called follicles, while calcitonin is synthesized by C-cells, interspersed in between the follicles and a dense network of blood capillaries. Although adult thyroid architecture and functions have been extensively described and studied, the formation of the "angio-follicular" units, the distribution of C-cells in the parenchyma and the paracrine communications between epithelial and endothelial cells is far from being understood. This method describes the sequential steps of mouse embryonic thyroid anlagen dissection and its culture on semiporous filters or on microscopy plastic slides. Within a period of four days, this culture system faithfully recapitulates in vivo thyroid development. Indeed, (i) bilobation of the organ occurs (for e12.5 explants), (ii) thyrocytes precursors organize into follicles and polarize, (iii) thyrocytes and C-cells differentiate, and (iv) endothelial cells present in the microdissected tissue proliferate, migrate into the thyroid lobes, and closely associate with the epithelial cells, as they do in vivo. Thyroid tissues can be obtained from wild type, knockout or fluorescent transgenic embryos. Moreover, explants culture can be manipulated by addition of inhibitors, blocking antibodies, growth factors, or even cells or conditioned medium. Ex vivo development can be analyzed in real-time, or at any time of the culture by immunostaining and RT-qPCR. In conclusion, thyroid explant culture combined with downstream whole-mount or on sections imaging and gene expression profiling provides a powerful system for manipulating and studying morphogenetic and differentiation events of thyroid organogenesis.

  11. Free radicals induced by sunlight in different spectral regions - in vivo versus ex vivo study.

    Science.gov (United States)

    Lohan, Silke B; Müller, Robert; Albrecht, Stephanie; Mink, Kathrin; Tscherch, Kathrin; Ismaeel, Fakher; Lademann, Jürgen; Rohn, Sascha; Meinke, Martina C

    2016-05-01

    Sunlight represents an exogenous factor stimulating formation of free radicals which can induce cell damage. To assess the effect of the different spectral solar regions on the development of free radicals in skin, in vivo electron paramagnetic resonance (EPR) investigations with human volunteers and ex vivo studies on excised human and porcine skin were carried out. For all skin probes, the ultraviolet (UV) spectral region stimulates the most intensive radical formation, followed by the visible (VIS) and the near infrared (NIR) regions. A comparison between the different skin models shows that for UV light, the fastest and highest production of free radicals could be detected in vivo, followed by excised porcine and human skin. The same distribution pattern was found for the VIS/NIR spectral regions, whereby the differences in radical formation between in vivo and ex vivo were less pronounced. An analysis of lipid composition in vivo before and after exposure to UV light clearly showed modifications in several skin lipid components; a decrease of ceramide subclass [AP2] and an increase of ceramide subclass [NP2], sodium cholesterol sulphate and squalene (SQ) were detectable. In contrast, VIS/NIR irradiation led to an increase of ceramides [AP2] and SCS, and a decrease of SQ. These results, which are largely comparable for the different skin models investigated in vivo and ex vivo, indicate that radiation exposure in different spectral regions strongly influences radical production in skin and also results in changes in skin lipid composition, which is essential for barrier function. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Fiducial markers for MR histological correlation in ex vivo or short-term in vivo animal experiments: a screening study.

    Science.gov (United States)

    Rouvière, Olivier; Reynolds, Carol; Le, Yuan; Lai, Jinping; Roberts, Lewis R; Felmlee, Joel P; Ehman, Richard L

    2006-01-01

    To test injectable fiducial markers for magnetic resonance (MR) histological correlation in ex vivo or in vivo animal experiments. A total of 35 potential markers were tested ex vivo in pork muscle. The end-points were: 1) visibility, size, and shape on MR images and at macroscopic examination; 2) 24-hour stability; and 3) microscopic appearance. Selected markers were injected in vivo (rabbit's muscle and breast tumor tissue) to test their three-hour in vivo stability and their potential toxicity. Finally, different dilutions of the two best markers were assessed again through the same screening tests to determine whether their size on MR images could be customized by dilution. Two fluid acrylic paints containing inorganic pigments were found to be potentially interesting markers. On MR images, they created well-defined susceptibility artifacts. The markers made with iridescent bronze paint (iron oxide coated mica particles) were readily visible on microscopy and their size on MR images could be customized by dilution. The iridescent stainless steel paint (iron, chromium, nickel) created ex vivo the smallest markers in tissue but needed colloidal iron staining to be visible on microscopy and could not be easily diluted. Fluid acrylic paints are potentially interesting markers for MR histological correlation. Further studies are needed to assess their long-term properties.

  13. Photoacoustic analysis of thyroid cancer in vivo: a pilot study

    Science.gov (United States)

    Kim, Jeesu; Kim, Min-Hee; Jo, Kwanhoon; Ha, Jeonghoon; Kim, Yongmin; Lim, Dong-Jun; Kim, Chulhong

    2017-03-01

    Thyroid cancer is one of the most prevalent cancers. About 3-8% of the people in the United States have thyroid nodules, and 5-15% of these nodules are malignant. Fine-needle aspiration biopsy (FNAB) is a standard procedure to diagnose malignity of nodules. However, about 10-20% of FNABs produce indeterminable results, which leads to repeat biopsies and unnecessary surgical operations. We have explored photoacoustic (PA) imaging as a new method to identify cancerous nodules. In a pilot study to test its feasibility, we recruited patients with thyroid nodules (currently 36 cases with 21 malignant and 15 benign nodules), acquired in vivo PA and ultrasound (US) images of the nodules in real time using a recently-developed clinical PA/US imaging system, and analyzed the acquired data offline. The preliminary results show that malignant and benign nodules could be differentiated by utilizing their PA amplitudes at different excitation wavelengths. This is the first in vivo PA analysis of thyroid nodules. Although a larger-scale study is needed for statistical significance, the preliminary results show the good potential of PA imaging as a non-invasive tool for triaging thyroid cancer.

  14. Comparative In vivo, Ex vivo, and In vitro Toxicity Studies of Engineered Nanomaterials

    Science.gov (United States)

    Efforts to reduce the number of animals in engineered nanomaterials (ENM) toxicity testing have resulted in the development of numerous alternative toxicity testing methods, but in vivo and in vitro results are still evolving and variable. This inconsistency could be due to the f...

  15. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

    Directory of Open Access Journals (Sweden)

    Gabriella Lopes DE REZENDE BARBOSA

    2016-01-01

    Full Text Available Abstract The purpose of this study was to perform a microcomputed tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a microcomputed tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey’s post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05. The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues.

  16. Micro-CT evaluation of the radioprotective effect of resveratrol on the mandibular incisors of irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Rezende Barbosa, Gabriella Lopes de; Almeida, Solange Maria de, E-mail: gabriellalopes@live.com [Universidade de Campinas (UNICAMP), Piracicaba, SP (Brazil). Escola de Odontologia. Departmento de Diagnostico Oral; Pimenta, Luiz Andre [University of North Carolina at Chapel Hill, School of Dentistry, Department of Dental Ecology, Chapel Hill, NC (United States)

    2016-05-01

    The purpose of this study was to perform a micro computerized tomographic evaluation of the radioprotective effect of resveratrol on the volume of mandibular incisors of irradiated rats. A second aim was to make a quantitative assessment of the effect of x-ray exposure on these dental tissues. Twenty adult male rats were divided into four groups: control, irradiated control, resveratrol, and irradiated resveratrol. The resveratrol groups received 100 mg/kg of resveratrol, whereas the irradiated groups were exposed to 15 Gy of irradiation. The animals were sacrificed 30 days after the irradiation procedure, and their mandibles were removed and scanned in a micro computerized tomography unit. The images were loaded into Mimics software to allow segmentation of the mandibular incisor and assessment of its volume. The results were compared by One-way ANOVA and Tukey's post hoc test, considering a 5% significance level. The irradiated groups showed significantly diminished volumes of the evaluated teeth, as compared with the control group (p < 0.05). The resveratrol group presented higher values than those of the irradiated groups, and volumes similar to those of the control group. High radiation doses significantly affected tooth formation, resulting in alterations in the dental structure, and thus lower volumes. Moreover, resveratrol showed no effective radioprotective impact on dental tissues. Future studies are needed to evaluate different concentrations of this substance, in an endeavor to verify its potential as a radioprotector for these dental tissues. (author)

  17. Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue

    Directory of Open Access Journals (Sweden)

    Abolhasan Rezaeyan

    2016-01-01

    Full Text Available This study was carried out to evaluate radioprotective effects of hesperidin (HES administration before the irradiation on the cardiac oxidative stress and histopathological changes in an experimental rat model. The cardiovascular complications of radiation exposure cause morbidity and mortality in patients who received radiotherapy. HES, an antioxidant flavonoid found in citrus fruits, suggests the protection against the tissue damage. Fifty-eight rats were divided into four groups: Group 1 received phosphate buffered saline (PBS and sham radiation; Group 2, HES and sham radiation; Group 3, PBS and radiation; and Group 4, HES and radiation. The rats were exposed to single dose of 18 Gy of 6 MV X-ray. One hundred milligrams per kilogram doses of HES was administered for 7 days before irradiation. The estimation of superoxide dismutase (SOD, malondialdehyde (MDA, and histopathological analyses was performed at 24 h and 8 weeks after radiation exposure. The irradiation of chest area resulted in an elevated MDA level and decreased SOD activity. Moreover, long-term pathological lesions of radiation were inflammation, fibrosis, the increased number of mast cells and macrophages, and development of plaque, vascular leakage, myocardial degeneration, and myocyte necrosis. Although the administration of HES decreases inflammation, fibrosis, mast cell and macrophage numbers, and myocyte necrosis, it did not result in reduced thrombus, myocardium degeneration, and vascular leakage. In conclusion, these results suggest that HES can perform a radioprotection action. The protective effect of HES may be attributable to its immunomodulatory effects and free radical-scavenging properties.

  18. Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature.

    Science.gov (United States)

    Kalman, Noah S; Zhao, Sherry S; Anscher, Mitchell S; Urdaneta, Alfredo I

    2017-07-01

    As more cancer patients survive their disease, concerns about radiation therapy-induced side effects have increased. The concept of radioprotection and radiation injury mitigation and treatment offers the possibility to enhance the therapeutic ratio of radiation therapy by limiting radiation therapy-induced normal tissue injury without compromising its antitumor effect. Advances in the understanding of the underlying mechanisms of radiation toxicity have stimulated radiation oncologists to target these pathways across different organ systems. These generalized radiation injury mechanisms include production of free radicals such as superoxides, activation of inflammatory pathways, and vascular endothelial dysfunction leading to tissue hypoxia. There is a significant body of literature evaluating the effectiveness of various treatments in preventing, mitigating, or treating radiation-induced normal tissue injury. Whereas some reviews have focused on a specific disease site or agent, this critical review focuses on a mechanistic classification of activity and assesses multiple agents across different disease sites. The classification of agents used herein further offers a useful framework to organize the multitude of treatments that have been studied. Many commonly available treatments have demonstrated benefit in prevention, mitigation, and/or treatment of radiation toxicity and warrant further investigation. These drug-based approaches to radioprotection and radiation injury mitigation and treatment represent an important method of making radiation therapy safer. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The Beneficial Radioprotective Effect of Tomato Seed Oil Against Gamma Radiation-Induced Damage in Male Rats.

    Science.gov (United States)

    Ezz, Magda K; Ibrahim, Nashwa K; Said, Mahmoud M; Farrag, Mostafa A

    2018-01-16

    Radiation protection research receives intense focus due to its significant impact on human health. The present study was undertaken to investigate the protective effect of pretreatment with tomato seed oil (TSO) against gamma radiation-induced damage in rats. Male Wistar rats were divided into four groups: (1) untreated control; (2) TSO-supplemented; (3) gamma-irradiated; (4) TSO-pretreated and gamma-irradiated. Acute exposure of animals to a single gamma radiation dose (6 Gy) induced oxidative stress in major body organs, altered serum lipid homeostasis, significantly increased serum testosterone and sorbitol dehydrogenase levels, and elicited a systemic inflammation as manifested by the induction of serum vascular cell adhesion molecule-1. Oral pretreatment with TSO (1 ml/kg; 3 times/week for 8 weeks) before exposure to gamma radiation protected rats against ionizing radiation-induced oxidative stress, restored lipid homeostasis, and suppressed systemic inflammation. Histological findings of target tissues verified biochemical data. The radioprotective ability of TSO was attributed to its content of phytosterols, policosanol, and antioxidants, including lycopene, β-carotene, lutein, and tocopherols. TSO is considered a promising radioprotective agent that can be effectively used to protect the body from the damaging effects of harmful radiation.

  20. In vitro and in vivo studies on biodegradable magnesium alloy

    Directory of Open Access Journals (Sweden)

    Lida Hou

    2014-10-01

    Full Text Available The microstructure, mechanical property, electrochemical behavior and biocompatibility of magnesium alloy (BioDe MSM™ were studied in the present work. The experimental results demonstrated that grain refining induced by extrusion improves the alloy strength significantly from 162 MPa for the as-cast alloy to 241 MPa for the as-extruded one. The anticorrosion properties of the as-extruded alloy also increased. Furthermore, the hemolysis ratio was decreased from 4.7% for the as-cast alloy to 2.9% for the as-extruded one, both below 5%. BioDe MSM™ alloy shows good biocompatibility after being implanted into the dorsal muscle and the femoral shaft of the New Zealand rabbit, respectively, and there are no abnormalities after short-term implantation. In vivo observation indicated that the corrosion rate of this alloy varies with different implantation positions, with higher degradation rate in the femur than in the muscle.

  1. Radiation protection textbook; Manuel pratique de radioprotection (3. Ed.)

    Energy Technology Data Exchange (ETDEWEB)

    Gambini, D.J.; Granier, R

    2007-07-01

    This textbook of radiation protection presents the scientific bases, legal and statutory measures and technical means of implementation of the radioprotection in the medical and industrial sectors, research and nuclear installations. It collects the practical information (organization, analysis of post, prevention, evaluation and risks management, the controls, the training and the information) usually scattered and the theoretical knowledge allowing every person using ionizing radiation: To analyze jobs in controlled areas, to watch the respect for the current regulations, to participate in the training and in the information of the staffs exposed to intervene in accidental situation. This third edition is widely updated and enriched by the most recent scientific and legal data concerning, notably, the human exposure, the dosimetry, the optimization of the radiation protection and the epidemiological inquiries. The contents is as follows: physics of ionizing radiation, ionizing radiation: origin and interaction with matter, dosimetry and protection against ionizing radiation, detection and measurement of ionizing radiation, radiobiology, legal measures relative to radiation protection, human exposure of natural origin, human exposure of artificial origin, medical, dental and veterinarian radiology, radiotherapy, utilization of unsealed sources in medicine and research, electronuclear industry, non nuclear industrial and aeronautical activities exposing to ionizing radiation, accidental exposures. (N.C.)

  2. Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

    Science.gov (United States)

    Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

    2012-09-01

    P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

  3. Training in radioprotection at undergraduate and postgraduate level at the school of pharmacy and biochemistry, Buenos Aires University

    Energy Technology Data Exchange (ETDEWEB)

    Bergoc, R.; Caro, R.A.; Rivera, E.S. [Buenos Aires University, School of Pharmacy and Biochemistry, Radioisotopes Laboratory, Buenos Aires (Argentina); Menossi, C. [Nuclear Regulatory Authority (Argentina)

    2000-05-01

    The advancement of knowledge in physics studies, medicine, pharmacology, cell biology and other disciplines that take place during the last 60 years is principally due to radioisotopes techniques. For this reason, the importance to teach radioisotopes methodologies at undergraduate and postgraduate levels kept growing. At the same time it was necessary to harmonize the use of these methodologies with environmental preservation. The School of Pharmacy and Biochemistry of the University of Buenos Aires offers four different Courses on Methodology of Radioisotopes in which the Radiological Protection is focalized under different aspects: 1) A Course for students in the Biochemistry Cycle; 2) A Course for post-Graduate in Medicine, Biochemistry, Biology, Chemists or other disciplines related to the health. 3) Another one for professionals wishing to up-date their knowledge; and finally, 4) one for Technicians in Nuclear Medicine and/or Biomedicine. The aims for teaching Radiological Protection are different for the four levels; in 1), the subject was done from 1960, (optional or mandatory) and with a arrived number of students. In some aspects the teaching of radioprotection is formative and in others informative, because the approval of the a signature does not habitable to ask from the Nuclear Regulatory Authority the authorization to work with radioactive material; in 2), the Course begun in 1962 and 1520 professionals have approved it. In this case the training in radioprotection aspects is theoretical and practical and very intensive, encompassing: dosimetric magnitudes and units, internal and external dosimetry of {sup 125}I, {sup 131}I, {sup 201}Tl, {sup 99M}Tc, {sup 60}Co and other isotopes, qualification of area, working conditions, contamination barriers, shielding; justification, optimization and dose limits; radioactive wastes; legal aspects; national and international legislation. The intensity of the training is in accord with that required by each

  4. The Efficiency of Methionine as a Radioprotectant of Bacillus anthracis for Cell Viability and Outgrowth Time after UVC and Gamma Irradiation

    Science.gov (United States)

    2015-03-01

    4. TITLE AND SUBTITLE The Efficiency of Methionine as a Radioprotectant of Bacillus anthracis for Cell Viability and Outgrowth Time after UVC and...THE EFFICIENCY OF METHIONINE AS A RADIOPROTECTANT OF BACILLUS ANTHRACIS FOR CELL VIABILITY AND...subject to copyright protection in the United States. AFIT-ENP-MS-15-M-105 THE EFFICIENCY OF METHIONINE AS A RADIOPROTECTANT OF BACILLUS

  5. Antinociceptive properties of shikonin: in vitro and in vivo studies.

    Science.gov (United States)

    Gupta, Bhawana; Chakraborty, Sabyasachi; Saha, Soumya; Chandel, Sunita Gulabsingh; Baranwal, Atul Kumar; Banerjee, Manish; Chatterjee, Mousumi; Chaudhury, Ashok

    2016-07-01

    Shikonin possess a diverse spectrum of pharmacological properties in multiple therapeutic areas. However, the nociceptive effect of shikonin is not largely known. To investigate the antinociceptive potential of shikonin, panel of GPCRs, ion channels, and enzymes involved in pain pathogenesis were studied. To evaluate the translation of shikonin efficacy in vivo, it was tested in 3 established rat pain models. Our study reveals that shikonin has significant inhibitory effect on pan sodium channel/N1E115 and NaV1.7 channel with half maximal inhibitory concentration (IC50) value of 7.6 μmol/L and 6.4 μmol/L, respectively, in a cell-based assay. Shikonin exerted significant dose dependent antinociceptive activity at doses of 0.08%, 0.05%, and 0.02% w/v in pinch pain model. In mechanical hyperalgesia model, dose of 10 and 3 mg/kg (intraperitoneal) produced dose-dependent analgesia and showed 67% and 35% reversal of hyperalgesia respectively at 0.5 h. Following oral administration, it showed 39% reversal at 30 mg/kg dose. When tested in first phase of formalin induced pain, shikonin at 10 mg/kg dose inhibited paw flinching by ∼71%. In all studied preclinical models, analgesic effect was similar or better than standard analgesic drugs. The present study unveils the mechanistic role of shikonin on pain modulation, predominantly via sodium channel modulation, suggesting that shikonin could be developed as a potential pain blocker.

  6. Electron microscopy methods for studying in vivo DNA replication intermediates.

    Science.gov (United States)

    Lopes, Massimo

    2009-01-01

    The detailed understanding of the DNA replication process requires structural insight. The combination of psoralen crosslinking and electron microscopy has been extensively exploited to reveal the fine architecture of in vivo DNA replication intermediates. This approach proved instrumental to uncover the basic mechanisms of DNA duplication, as well as the perturbation of this process by genotoxic treatments. The replication structures need to the stabilized in vivo (by psoralen crosslinking) prior to extraction and enrichment procedures, finally leading to the visualization at the transmission electron microscope. This chapter outlines the procedures required to visualize in vivo replication intermediates of genomic DNA, extracted from budding yeast or cultured mammalian cells.

  7. Mood Disorders Are Glial Disorders: Evidence from In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Matthias L. Schroeter

    2010-01-01

    Full Text Available It has recently been suggested that mood disorders can be characterized by glial pathology as indicated by histopathological postmortem findings. Here, we review studies investigating the glial marker S100B in serum of patients with mood disorders. This protein might act as a growth and differentiation factor. It is located in, and may actively be released by, astro- and oligodendrocytes. Studies consistently show that S100B is elevated in mood disorders; more strongly in major depressive than bipolar disorder. Successful antidepressive treatment reduces S100B in major depression whereas there is no evidence of treatment effects in mania. In contrast to the glial marker S100B, the neuronal marker protein neuron-specific enolase is unaltered. By indicating glial alterations without neuronal changes, serum S100B studies confirm specific glial pathology in mood disorders in vivo. S100B can be regarded as a potential diagnostic biomarker for mood disorders and as a biomarker for successful antidepressive treatment.

  8. Placental glucose transfer: a human in vivo study.

    Directory of Open Access Journals (Sweden)

    Ane M Holme

    Full Text Available The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply determines the fetal venous-arterial glucose difference (reflecting fetal consumption.Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein and outgoing vessels (uterine vein and umbilical artery.There were significant mean (SD uteroplacental arterio-venous 0.29 (0.23 mmol/L and fetal venous-arterial 0.38 (0.31 mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42 mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001, but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001 and the glucose concentration in the umbilical artery (r = -0.45, p = 0.004. Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001, but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values.We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly

  9. In vivo localization studies in the stramenopile alga Nannochloropsis oceanica.

    Science.gov (United States)

    Moog, Daniel; Stork, Simone; Reislöhner, Sven; Grosche, Christopher; Maier, Uwe-G

    2015-02-01

    The tiny eustigmatophyte Nannochloropsis sp. recently emerged as a promising model organism for biotechnology as it possesses a considerably high cellular oil content interesting for biodiesel production. Furthermore, the alga was shown to be genetically well accessible providing powerful tools for biotechnological engineering as well as basic research. Nannochloropsis sp. can be transformed very efficiently taking advantage of homologous recombination, however, so far it remained unclear whether these organisms are also suitable model systems for in vivo protein localization studies due to their small cell size. Here we present, to our knowledge, the first protein localization studies based on the expression of chimeric fluorescent fusion proteins in the genus Nannochloropsis using N. oceanica CCMP1779 as a model organism. Besides expressing a cytosolic green fluorescent protein (GFP), the reporter could be directed into subcellular structures such as the mitochondria, the endoplasmic reticulum and secretory pathway as well as the complex plastid including the periplastidal compartment and the stroma via fusion of specific N-terminal targeting sequences. These results expand the potential of N. oceanica as a model system in biotechnology as well as cellular biology for which now an almost complete molecular tool set exists. Copyright © 2015 Elsevier GmbH. All rights reserved.

  10. Biochemical and molecular genetic approaches on the radioprotective mechanism of natural products

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hee; Lee, Eun Ju; Sung, Woo Kyung; Piao, Wen Hua [Kyunghee University, Seoul (Korea)

    1999-04-01

    We reported the radio-protective effect of DTT. The treatment of DTT increased cell survival after gamma-irradiation, decreased in the frequencies of micronucleus, and reduction in DNA fragmentation and apoptotic cells. Induction of apoptosis after UV-C irradiation was revealed by the changes in the relative cell death, increase in the relative amount of apoptotic cells, and the induction of DNA fragmentation. About 100 medicinal plants were purchased and methanol extract samples were prepared. Radio-protective and radio-sensitizing activities of these samples were screened. Seven samples showed above 20% radio-protective activities: Salvia miltiorrhiza, Areca catechu, Cornus officinalis, Alpiniae officinari rhizoma, Meliae fructus, Alpiniae katsumadaii semen, Betulae cortex. Acanthopanax sessiliflous showed the highest radio-sensitizing effect and 10 other samples revealed moderate activities: Melia japonica, Agastache rugosa, Platycodon gradiflorum, Broussonetia bazinoki, Angelica gigas, Inula helenium, Chelidonium majus, Pulsatilla koreana, Oldenlandia diffusa, Dioscorea batatas. (author). 49 refs., 9 figs., 7 tabs.

  11. Laser welding and syncristallization techniques comparison: "Ex vivo" study.

    Science.gov (United States)

    Fornaini, Carlo; Meleti, Marco; Vescovi, Paolo; Merigo, Elisabetta; Rocca, Jean-Paul

    2013-12-30

    Stabilization of implant abutments through electric impulses at high voltage for a very short time (electrowelding) was developed in the Eighties. In 2009, the same procedure was performed through the use of laser (laser welding) The aim of this study is to compare electrowelding and laser welding for intra-oral implant abutments stabilization on "ex vivo models" (pig jaws). Six bars were welded with two different devices (Nd:YAG laser and Electrowelder) to eighteen titanium implant abutment inserted in three pig jaws. During the welding process, thermal increase was recorded, through the use of k-thermocouples, in the bone close to the implants. The strength of the welded joints was evaluated by a traction test after the removal of the implants. For temperature measurements a descriptive analysis and for traction test "values unpaired t test with Welch's correction" were performed: the significance level was set at Pwelding gives a lower thermal increase than Electrowelding at the bone close to implants (Mean: 1.97 and 5.27); the strength of laser welded joints was higher than that of Electrowelding even if nor statistically significant. (Mean: 184.75 and 168.29) CONCLUSION: Electrowelding seems to have no advantages, in term of thermal elevation and strength, while laser welding may be employed to connect titanium implants for immediate load without risks of thermal damage at surrounding tissues.

  12. In vivo studies of biotin absorption in distal rat intestine

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, B.B.; Rosenberg, I.H.

    1986-03-01

    The authors have extended their previous studies of biotin absorption in rat proximal jejunum (PJ) to examine biotin absorptive capacity of rat ileum (I) and proximal colon (PC) using in vivo intestinal loop technique. Intestinal loops (2.5 cm) were filled with 0.3 ml of solution containing (/sup 3/H)-biotin and (/sup 14/C)-inulin in phosphate buffer, pH 6.5. Biotin absorption was determined on the basis of luminal biotin disappearance after correction for inulin recovery and averaged (pmol/loop-10 min; X +/- SEM). In related experiments, 5-cm loops of PJ, distal I (DI), or PC were filled with 0.5 ml of solution of similar composition (1.0 ..mu..M biotin). The abdominal cavity was closed and the rats were allowed to recover from anesthesia, then sacrificed 3 hr after injection. Biotin absorption averaged 96.2% (PJ), 93.2% (DI), and 25.8% (PC) of the dose administered. These differences were reflected in the radioactive biotin content of plasma and intestinal loop, kidney, and liver. These data demonstrate significant biotin absorption in rat DI and PC, as required if the intestinal microflora are to be considered as a source of biotin for the host.

  13. In Vivo Toxicity Studies of Europium Hydroxide Nanorods in Mice

    Science.gov (United States)

    Patra, Chitta Ranjan; Abdel Moneim, Soha S.; Wang, Enfeng; Dutta, Shamit; Patra, Sujata; Eshed, Michal; Mukherjee, Priyabrata; Gedanken, Aharon; Shah, Vijay H; Mukhopadhyay, Debabrata

    2009-01-01

    Lanthanide nanoparticles and nanorods have been widely used for diagnostic and therapeutic applications in biomedical nanotechnology due to their fluorescence properties and pro-angiogenic to endothelial cells, respectively. Recently, we have demonstrated that europium (III) hydroxide [EuIII(OH)3] nanorods, synthesized by the microwave technique and characterized by several physico-chemical techniques, can be used as pro-angiogenic agents which introduce future therapeutic treatment strategies for severe ischemic heart/limb disease, and peripheral ischemic disease. The toxicity of these inorganic nanorods to endothelial cells was supported by several in vitro assays. To determine the in vivo toxicity, these nanorods were administered to mice through intraperitoneal injection (IP) everyday over a period of seven days in a dose dependent (1.25 to 125 mgKg−1day−1) and time dependent manner (8–60 days). Bio-distribution of europium elements in different organs was analyzed by inductively coupled plasma mass spectrometry (ICPMS). Short-term (S-T) and long-term (L-T) toxicity studies (mice sacrificed on day 8 and 60 for S-T and L-T, respectively) show normal blood hematology and serum clinical chemistry with the exception of a slight elevation of liver enzymes. Histological examination of nanorod treated vital organs (liver, kidney, spleen and lungs) showed no or only mild histological changes that indicate mild toxicity at the higher dose of nanorods. PMID:19616569

  14. Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies

    Science.gov (United States)

    Cogoli, A.

    1996-01-01

    The study of the function of immune cells in microgravity has been studied for more than 20 years in several laboratories. It is clear today that the immune system is depressed in more than 50% of the astronauts during and after space flight and that the activation of T lymphocytes by mitogens in vitro changes dramatically. This article gives an overview of the gravitational studies conducted by our laboratory in Spacelab, in MIR station, in sounding rockets and on the ground in the clinostat and the centrifuge. Three experimental approaches are followed in our work: (i) Ex vivo studies are performed with blood samples drawn from astronauts; (ii) in vivo studies are based on the application of seven antigens to the skin of the astronauts; (iii) in vitro studies are carried out with immune cells purified from the blood of healthy donors (not astronauts). The data from our in vivo and ex vivo studies are in agreement with those of other laboratories and show that the immunological function is depressed in the majority of astronauts as a consequence of the stress of space flight rather than by a direct influence of gravity on the cell. Immune depression may become a critical hazard on long duration flights on space stations or to other planets. In vitro experiments show that cultures of free-floating lymphocytes and monocytes undergo a dramatic depression of activation by the mitogen concanavalin A, while activation is more than doubled when the cells are attached to microcarrier beads. Such effects may be attributed to both direct and indirect effects of gravitational unloading on basic biological mechanisms of the cell. While the in vitro data are very important to clarify certain aspects of the biological mechanism of T cells activation, they are not descriptive of the changes of the immunological function of the astronauts.

  15. Physical and biological dosimetry for risk perception in radioprotection

    Directory of Open Access Journals (Sweden)

    Ademir Amaral

    2005-10-01

    Full Text Available The increase in ionizing radiation (IR applications, especially nuclear, has been followed by the growth of public concern for the potential associated risks. The public’s perception of such risks is often based on the philosophy that IR is harmful at any exposure level. On the other hand, although radiation workers have knowledge about the nature of IR and its potential health effects, the relationship between absorbed dose and risk is not well understood, principally for low doses. This report presents an overview of physical and biological dosimetry as complementary methodologies, as well as their possible contribution for improving risk perception in radioprotection.O crescente aumento das aplicações das radiações ionizantes, em particular as radiações de origem nuclear, tem sido acompanhado pelo aumento do interesse público em relação aos riscos associados a essas aplicações. A percepção de tais riscos por parte da população é freqüentemente baseada na filosofia que a radiação ionizante é perigosa independentemente dos níveis de exposição. Por outro lado, apesar dos trabalhadores ocupacionalmente expostos terem conhecimento da natureza da IR e seus possíveis efeitos á saúde, a relação entre dose absorvida e risco não é bem entendida por estes, em particular para baixos valores de dose. Este artigo resume aspectos da dosimetria física e biológica como metodologias complementares na melhoria da percepção dos riscos em radioproteção.

  16. Ex vivo and in vivo topographic studies of bladder by optical coherence tomography (Invited Paper)

    Science.gov (United States)

    Daniltchenko, Dmitri; Sachs, Markus D.; Lankenau, Eva; Koenig, Frank; Burkhardt, Mick; Huettmann, Gereon; Kristiansen, Glen; Schnorr, Dietmar; Al-Shukri, Salman; Loening, Stefan A.

    2005-06-01

    Conventional imaging modalities like CT or ultrasonography have a spatial resolution of 70-1000 rim. OCT is a new method by which light of a certain wavelength is introduced into a fiberglass optic to measure tissue structures of up to 2.5 mm depth with a spatial resolution of up to 10-15 μm. We utilized the Tomograph Sirius 713, developed at the Medical Laser Centre in cooperation with 4-Optics AG, Lubeck, Germany. This apparatus uses a special Super- Luminescence-Diode (SLD) that produces light within the near infrared wavelength, with a central wavelength of 1300 nm. The coherence length is reduced to 15 μm. The light is introduced into a fiberglass optic which is several meters long and is easy to handle. To measure the depth of invasion and position of urothelial bladder tumors, the fiberglass optic is attached to a regular endoscope (Wolf, Knittlingen, Germany) via an OCT adapter. That way, in parallel to the regular endoscopic view of the bladder mucosa with or without pathologic findings, an OCT picture of the superficial as well as the deeper muscle layers is visible online. OCT was used to obtain 945 images from the bladder in vivo und ex vivo of 65 patients. OCT of normal bladder mucosa allows to image a cross section of up to 2.5 mm. It is possible to distinguish transitional epithelium, lamina propria, smooth muscles and capillaries. In cystitis, the thickness of the mucosa is constant, but the distinction between the different layers is blurred. In squamous metaplasia there is thickening of the epithelial layer, with preservation of lamination of the lower layers. In transitional cell carcinoma there is a complete loss of the regular layered structure. It is easily possible to distinguish the border between tumour and normal bladder tissue. OCT is a new high-resolution imaging procedure. It has the potential to improve the diagnostics of the urothelium and its lesions. In conjunction with a highly sensitive orientating procedure like fluorescence

  17. In and ex vivo breast disease study by Raman spectroscopy

    DEFF Research Database (Denmark)

    Raniero, L.; Canevari, R. A.; Ramalho, L. N. Z.

    2011-01-01

    In this work, Raman spectra in the 900-1,800 cm(-1) wavenumber region of in vivo and ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured. In the case of the in vivo tissues, the Raman spectra were collected for both transcutaneous...... (with skin) and skin-removed tissues. To identify the spectral differences between normal and cancer breast tissue, the paired t-test was carried out for each wavenumber using the whole spectral range from both groups. Quadratic discriminate analysis based on principal component analysis (PCA) was also...... used to determine and evaluate differences in the Raman spectra for the various samples as a basis for diagnostic purposes. The differences in the Raman spectra of the samples were due to biochemical changes at the molecular, cellular and tissue levels. The sensitivity and specificity...

  18. Radioprotection to the Gonads in Pediatric Pelvic Radiography: Effectiveness of Developed Bismuth Shield

    Directory of Open Access Journals (Sweden)

    Vahid Karami

    2017-06-01

    Full Text Available Background: The use and effectiveness of traditional lead gonad shields in pediatric pelvic radiography has been challenged by several literatures over the past two decades. The aim of this study was to develop a new radioprotective gonad shields to be use in pediatric pelvic radiography. Materials and Methods: The commercially available 0.06 mm lead equivalent bismuth garment has cropped squarely and used as ovarian shield to cover the entire region of pelvis. In order to prevent deterioration of image quality due to beam hardening artifacts, a 1-cm foam as spacer was located between the shield and patients pelvis. Moreover, we added a lead piece at the cranial position of the bismuth garment to absorb the scatter radiations to the radiosensitive organs. In girls, 49 radiographs with shield and 46 radiographs without shield was taken. The radiation dose was measured using thermoluminescent dosimeters (TLDs. Image quality assessments were performed using the European guidelines. For boys, the lead testicular shields was developed using 2 cm bismuth garment, added to the sides. The prevalence and efficacy of testicular shields was assessed in clinical practice fromFebruary 2016 to June 2016. Results: Without increasing the dose to the breast, thyroid and the lens of the eyes, the use of bismuth shield has reduced the entrance skin dose(ESD of the pelvis and radiation dose to the ovaries by 62.2% and 61.7%, respectively (P

  19. Radioprotective Effect of Thymol Against Salivary Glands Dysfunction Induced by Ionizing Radiation in Rats.

    Science.gov (United States)

    Abedi, Seyed Mohammad; Yarmand, Fateme; Motallebnejad, Mina; Seyedmajidi, Maryam; Moslemi, Dariush; Bijani, Ali; Hosseinimehr, Seyed Jalal

    2016-01-01

    The aim of this study was to investigate the radioprotective effect of thymol as a natural product against salivary glands dysfunction induced by ionizing radiation in rats. The rats were treated with thymol at dose of 50 mg/Kg before exposure to ionizing radiation at dose 15 Gy. Salivary gland function was evaluated with radioisotope scintigraphy and then salivary gland to background counts ratio was calculated. Ionizing radiation caused significant salivary glands dysfunction at the 3th and the 70th days with reduction in radioactivity uptake in salivary glands. Ratios of salivary gland to background radioactivities were 2.0 ± 0.05, 1.58 ± 0.62 and 1.99 ± 0.07 at 3th days for control, radiation, and thymol plus radiation groups, respectively. Thymol significantly protected acute and chronic salivary gland dysfunction induced by ionizing radiation in the rats.This finding may have been a promising application of thymol for the protection of salivary glands dysfunction induced by ionizing irradiation in patients exposed to radiation in head and neck cancer therapy.

  20. Radioprotective effect of sodium selenite on bone repair in the tibia of ovariectomized rats

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, Deborah Queiroz de; Neves, Ellen Gaby; Boscolo, Frab Norberto; Almeida, Solange Maria de [University of Campinas (UNICAMP), Piracicaba, SP (Brazil). Piracicaba Dental School. Department of Oral Diagnosis. Oral Radiology Area; Ramos-Perez, Flavia Maria de Moraes [Federal University of Pernambuco, Recife, PE (Brazil). Department of Clinical and Preventive Dentistry; Marques, Marcelo Rocha [University of Campinas (UNICAMP), Piracicaba, SP (Brazil). Piracicaba Dental School. Division of Histology. Department of Morphology

    2012-07-01

    This study evaluated protection by selenium (Se) in the bone repair process in ovariectomized rats after irradiation. For such purpose, 80 ovariectomized female Wistar rats were randomly divided into 4 experimental groups: ovariectomized (Ov), Ov/Se, Ov/irradiated (Irr) and Ov/ Se/Irr. A bone defect was created on the tibia of all animals 40 days after ovariectomy. Two days after surgery, only the Ov/Se and Ov/Se/Irr rats received 0.8 mg Se/kg. Three days after surgery, only the Ov/Irr and Ov/Se/Irr rats received 10 Gy of x-rays on the lower limb region. The animals were euthanized at 7, 14, 21 and 28 days after surgery to assess the repair process, which was evaluated by analysis of trabecular bone number (Masson Trichrome) and birefringence analysis (Picrosirius). It was possible to observe a delay in the bone repair process in the ovariectomized/irradiated group and similarity between the ovariectomized, Ov/Se and Ov/Se/Irr groups. In conclusion, sodium selenite exerted a radioprotective effect in the bone repair of tibia of ovariectomized rats without toxicity. (author)

  1. Qualichem In Vivo: A Tool for Assessing the Quality of In Vivo Studies and Its Application for Bisphenol A

    Science.gov (United States)

    Maxim, Laura; van der Sluijs, Jeroen P.

    2014-01-01

    In regulatory toxicology, quality assessment of in vivo studies is a critical step for assessing chemical risks. It is crucial for preserving public health studies that are considered suitable for regulating chemicals are robust. Current procedures for conducting quality assessments in safety agencies are not structured, clear or consistent. This leaves room for criticism about lack of transparency, subjective influence and the potential for insufficient protection provided by resulting safety standards. We propose a tool called “Qualichem in vivo” that is designed to systematically and transparently assess the quality of in vivo studies used in chemical health risk assessment. We demonstrate its use here with 12 experts, using two controversial studies on Bisphenol A (BPA) that played an important role in BPA regulation in Europe. The results obtained with Qualichem contradict the quality assessments conducted by expert committees in safety agencies for both of these studies. Furthermore, they show that reliance on standardized guidelines to ensure scientific quality is only partially justified. Qualichem allows experts with different disciplinary backgrounds and professional experiences to express their individual and sometimes divergent views—an improvement over the current way of dealing with minority opinions. It provides a transparent framework for expressing an aggregated, multi-expert level of confidence in a study, and allows a simple graphical representation of how well the study integrates the best available scientific knowledge. Qualichem can be used to compare assessments of the same study by different health agencies, increasing transparency and trust in the work of expert committees. In addition, it may be used in systematic evaluation of in vivo studies submitted by industry in the dossiers that are required for compliance with the REACH Regulation. Qualichem provides a balanced, common framework for assessing the quality of studies that may

  2. Radioprotective effect of calcium given with feed on exposure to tritium oxide

    Energy Technology Data Exchange (ETDEWEB)

    Kazbekova, D.A.; Kalistratova, V.S.; Kulyamin, V.A.

    1979-12-01

    A 1.5-fold increase in calcium content of the rat diet attenuates the symptoms of radiation sickness induced by tritium and prolongs survival time. Elevation of blood serum nonspecific cholinesterase level and stimulation of lymphopoiesis were observed. The possible mechanisms of radioprotective action of calcium are discussed.

  3. Per-operative X-ray radiotherapy: personnel radiation protection in the operating theatre suite; Radiotherapie peroperatoire par rayons X: radioprotection du personnel au bloc operatoire

    Energy Technology Data Exchange (ETDEWEB)

    Lisbona, A.; Josset-Gaudaire, S.; Brunet, G.; Delpon, G. [ICO Centre Rene-Gauducheau, Saint-Herblain (France)

    2011-10-15

    The authors report the radioprotection study required in the exploitation authorization file associated with the putting into service of the Zeiss Meditec Intrabeam system. After having evoked the characteristics of this equipment (power, dose rate, treatment duration) and some characteristics of the building, they report the results of the zoning and workstation study. Two situations have assessed: the operator is present in the operating theatre suite behind a leaded screens, or stands outside of the operating theatre suite. The received dose is assessed on a basis of 50 treatments a year. Dose rate levels comply with personnel radiation protection requirements. Short communication

  4. Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

    Directory of Open Access Journals (Sweden)

    Anastasia Velalopoulou

    2017-11-01

    Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS, pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

  5. Robust rat pulmonary radioprotection by a lipophilic Mn N-alkylpyridylporphyrin, MnTnHex-2-PyP5+

    Directory of Open Access Journals (Sweden)

    Benjamin Gauter-Fleckenstein

    2014-01-01

    Full Text Available With the goal to enhance the distribution of cationic Mn porphyrins within mitochondria, the lipophilic Mn(IIImeso-tetrakis(N-n-hexylpyridinium-2-ylporphyrin, MnTnHex-2-PyP5+ has been synthesized and tested in several different model of diseases, where it shows remarkable efficacy at as low as 50 µg/kg single or multiple doses. Yet, in a rat lung radioprotection study, at higher 0.6–1 mg/kg doses, due to its high accumulation and micellar character, it became toxic. To avoid the toxicity, herein the pulmonary radioprotection of MnTnHex-2-PyP5+ was assessed at 50 µg/kg. Fischer rats were irradiated to their right hemithorax (28 Gy and treated with 0.05 mg/kg/day of MnTnHex-2-PyP5+ for 2 weeks by subcutaneously-implanted osmotic pumps, starting at 2 h post-radiation. The body weights and breathing frequencies were followed for 10 weeks post-radiation, when the histopathology and immunohistochemistry were assessed. Impact of MnTnHex-2-PyP5+ on macrophage recruitment (ED-1, DNA oxidative damage (8-OHdG, TGF-β1, VEGF(A and HIF-1α were measured. MnTnHex-2-PyP5+ significantly decreased radiation-induced lung histopathological (H&E staining and functional damage (breathing frequencies, suppressed oxidative stress directly (8-OHdG, or indirectly, affecting TGF-β1, VEGF (A and HIF-1α pathways. The magnitude of the therapeutic effects is similar to the effects demonstrated under same experimental conditions with 120-fold higher dose of ~5000-fold less lipophilic Mn(IIImeso-tetrakis(N-ethylpyridinium-2-ylporphyrin, MnTE-2-PyP5+.

  6. DMA, a bisbenzimidazole, offers radioprotection by promoting NFκB transactivation through NIK/IKK in human glioma cells.

    Directory of Open Access Journals (Sweden)

    Navrinder Kaur

    Full Text Available BACKGROUND: Ionizing radiation (IR exposure often occurs for human beings through occupational, medical, environmental, accidental and/or other sources. Thus, the role of radioprotector is essential to overcome the complex series of overlapping responses to radiation induced DNA damage. METHODS AND RESULTS: Treatment of human glioma U87 cells with DMA (5- {4-methylpiperazin-1-yl}-2-[2'-(3, 4-dimethoxyphenyl-5'-benzimidazolyl] in the presence or absence of radiation uncovered differential regulation of an array of genes and proteins using microarray and 2D PAGE techniques. Pathway construction followed by relative quantitation of gene expression of the identified proteins and their interacting partners led to the identification of MAP3K14 (NFκB inducing kinase, NIK as the candidate gene affected in response to DMA. Subsequently, over expression and knock down of NIK suggested that DMA affects NFκB inducing kinase mediated phosphorylation of IKKα and IKKβ both alone and in the presence of ionizing radiation (IR. The TNF-α induced NFκB dependent luciferase reporter assay demonstrated 1.65, 2.26 and 3.62 fold increase in NFκB activation at 10, 25 and 50 µM DMA concentrations respectively, compared to control cells. This activation was further increased by 5.8 fold in drug + radiation (50 µM +8.5 Gy treated cells in comparison to control. We observed 51% radioprotection in control siRNA transfected cells that attenuated to 15% in siRNA NIK treated U87 cells, irradiated in presence of DMA at 24 h. CONCLUSIONS: Our studies show that NIK/IKK mediated NFκB activation is more intensified in cells over expressing NIK and treated with DMA, alone or in combination with ionizing radiation, indicating that DMA promotes NIK mediated NFκB signaling. This subsequently leads to the radioprotective effect exhibited by DMA.

  7. Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates.

    Directory of Open Access Journals (Sweden)

    Sitara S R Ajjampur

    Full Text Available Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic protists that inhabit the gastrointestinal tract. Although Blastocystis spp. have been associated with gastrointestinal symptoms, irritable bowel syndrome and urticaria, their clinical significance has remained controversial. We established an ex vivo mouse explant model to characterize adhesion in the context of tissue architecture and presence of the mucin layer. Using confocal microscopy with tissue whole mounts and two axenic isolates of Blastocystis spp., subtype 7 with notable differences in adhesion to intestinal epithelial cells (IEC, isolate B (ST7-B and isolate H (more adhesive, ST7-H, we showed that adhesion is both isolate dependent and tissue trophic. The more adhesive isolate, ST7-H was found to bind preferentially to the colon tissue than caecum and terminal ileum. Both isolates were also found to have mucinolytic effects. We then adapted a DSS colitis mouse model as a susceptible model to study colonization and acute infection by intra-caecal inoculation of trophic Blastocystis spp.cells. We found that the more adhesive isolate ST7-H was also a better colonizer with more mice shedding parasites and for a longer duration than ST7-B. Adhesion and colonization was also associated with increased virulence as ST7-H infected mice showed greater tissue damage than ST7-B. Both the ex vivo and in vivo models used in this study showed that Blastocystis spp. remain luminal and predominantly associated with mucin. This was further confirmed using colonic loop experiments. We were also successfully able to re-infect a second batch of mice with ST7-H isolates obtained from fecal cultures and demonstrated similar histopathological findings and tissue damage thereby coming closer to proving Koch's postulates for this parasite.

  8. Ex Vivo and In Vivo Mice Models to Study Blastocystis spp. Adhesion, Colonization and Pathology: Closer to Proving Koch's Postulates.

    Science.gov (United States)

    Ajjampur, Sitara S R; Png, Chin Wen; Chia, Wan Ni; Zhang, Yongliang; Tan, Kevin S W

    2016-01-01

    Blastocystis spp. are widely prevalent extra cellular, non-motile anerobic protists that inhabit the gastrointestinal tract. Although Blastocystis spp. have been associated with gastrointestinal symptoms, irritable bowel syndrome and urticaria, their clinical significance has remained controversial. We established an ex vivo mouse explant model to characterize adhesion in the context of tissue architecture and presence of the mucin layer. Using confocal microscopy with tissue whole mounts and two axenic isolates of Blastocystis spp., subtype 7 with notable differences in adhesion to intestinal epithelial cells (IEC), isolate B (ST7-B) and isolate H (more adhesive, ST7-H), we showed that adhesion is both isolate dependent and tissue trophic. The more adhesive isolate, ST7-H was found to bind preferentially to the colon tissue than caecum and terminal ileum. Both isolates were also found to have mucinolytic effects. We then adapted a DSS colitis mouse model as a susceptible model to study colonization and acute infection by intra-caecal inoculation of trophic Blastocystis spp.cells. We found that the more adhesive isolate ST7-H was also a better colonizer with more mice shedding parasites and for a longer duration than ST7-B. Adhesion and colonization was also associated with increased virulence as ST7-H infected mice showed greater tissue damage than ST7-B. Both the ex vivo and in vivo models used in this study showed that Blastocystis spp. remain luminal and predominantly associated with mucin. This was further confirmed using colonic loop experiments. We were also successfully able to re-infect a second batch of mice with ST7-H isolates obtained from fecal cultures and demonstrated similar histopathological findings and tissue damage thereby coming closer to proving Koch's postulates for this parasite.

  9. Laser welding to assist penetrating keratoplasty: in vivo studies

    Science.gov (United States)

    Menabuoni, Luca; Mincione, F.; Mincione, G. P.; Pini, Roberto

    1998-01-01

    Laser-induced corneal welding has been tested in vivo to perform experimental trials of penetrating keratoplasty (corneal transplantation). Twenty rabbits of 2500 - 3500 g in weight were selected to undergo laser-assisted corneal transplantation and then subjected to follow up on 2 - 15 postoperative days. Good sealing along the entire cut length was obtained soon after the surgical operation. Histology examinations evidenced that the laser-assisted surgical procedure provides a satisfactory healing process of corneal tissue in times that are substantially shorter than those of the conventional procedure.

  10. Web application for the control and management of radioprotection equipment in the Cadarache centre; Application WEB pour le controle et la gestion des appareils de radioprotection sur le centre de Cadarache

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2010-07-01

    The author describes a web 2-type application which has been developed for the periodic calibration controls of radioprotection equipment in Cadarache. This application aims at offering an easy and immediate and even remote access to information, at selecting information with respect to uses (radioprotection department, administrator, and so on), at securing and safeguarding homogeneous data, at editing control statistics. The different functionalities are briefly presented with their displayed interface

  11. Radioprotective effect of N-acetyl-L-cysteine free radical scavenger on compressive mechanical properties of the gamma sterilized cortical bone of bovine femur.

    Science.gov (United States)

    Allaveisi, Farzaneh; Hashemi, Bijan; Mortazavi, Seyed Mohammad Javad

    2015-03-01

    Gamma sterilization of bone allografts is used as a gold standard method to provide safety against disease transmission. However, it is well documented that high dose levels of ionizing radiation can degrade bone mechanical properties. This effect, which is attributed to the formation of free radicals through radiolysis of the water content of collagen, can lead to post-implantation difficulties such as pre-failure and/or secondary fractures of bone allografts. Recently, treatment of irradiated allografts with free radical scavengers is used to protect them against radiation-induced damages. This study aimed to investigate the radioprotective role of N-acetyl-L-cysteine (NAC) during the gamma sterilization of the cortical bone of bovine femurs using the compressive test. Totally, 195 cubic specimens with a dimension of 5 × 5 × 3 cubic mm were divided into 13 groups including a control and 12 experimental groups exposed to 18, 36, and 70 kGy at three different NAC concentrations (1.25, 12.5, and 25 mM for 18 kGy; 5, 50, and 100 mM for 36 kGy; 10, 100, and 200 mM for 70 kGy). The mechanical behavior of the sterilized specimens was studied using the uniaxial compressive test. The results indicated a concentration-dependent radioprotection effect of NAC on the plastic properties of the cortical bones. The concentration dependency of NAC was in turn related to radiation dose levels. In conclusion, treatment of bone specimens with a characteristic concentration of NAC during exposure to specific radiation dose levels can provide an efficient radioprotection window for preserving the mechanical stability of gamma sterilized allografts.

  12. Podophyllum hexandrum Offers Radioprotection by Modulating Free Radical Flux: Role of Aryl-Tetralin Lignans

    Directory of Open Access Journals (Sweden)

    Raman Chawla

    2006-01-01

    Full Text Available We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1 and chloroform fractions (S2], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1 and 41% (S2] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05 antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 μg ml−1. S1 exhibited 58.40 ± 0.8% inhibition (at 0.025 μg ml−1 of the formation of reactive nitrite radicals, comparable to S2 (52.45 ± 0.825%, and also showed 45.01% site-specific activity (1000 μg ml−1, along with significant (P < 0.05 electron donation potential (50–2000 μg ml−1 compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05 higher levels of podophyllotoxin β-d-glucopyranoside (16.5 times and demethyl podophyllotoxin glucoside (2.9 times compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.

  13. Development of Antioxidant COX-2 Inhibitors as Radioprotective Agents for Radiation Therapy—A Hypothesis-Driven Review

    Directory of Open Access Journals (Sweden)

    Markus Laube

    2016-04-01

    Full Text Available Radiation therapy (RT evolved to be a primary treatment modality for cancer patients. Unfortunately, the cure or relief of symptoms is still accompanied by radiation-induced side effects with severe acute and late pathophysiological consequences. Inhibitors of cyclooxygenase-2 (COX-2 are potentially useful in this regard because radioprotection of normal tissue and/or radiosensitizing effects on tumor tissue have been described for several compounds of this structurally diverse class. This review aims to substantiate the hypothesis that antioxidant COX-2 inhibitors are promising radioprotectants because of intercepting radiation-induced oxidative stress and inflammation in normal tissue, especially the vascular system. For this, literature reporting on COX inhibitors exerting radioprotective and/or radiosensitizing action as well as on antioxidant COX inhibitors will be reviewed comprehensively with the aim to find cross-points of both and, by that, stimulate further research in the field of radioprotective agents.

  14. Experimental Design and Data Analysis of In Vivo Fluorescence Imaging Studies.

    Science.gov (United States)

    Ding, Ying; Lin, Hui-Min

    2016-01-01

    The objective of this chapter is to provide researchers who conduct in vivo fluorescence imaging studies with guidance in statistical aspects in the experimental design and data analysis of such studies. In the first half of this chapter, we introduce the key statistical components for designing a sound in vivo experiment. Particular emphasis is placed on the issues and designs that pertain to fluorescence imaging studies. Examples representing several popular types of fluorescence imaging experiments are provided as case studies to demonstrate how to appropriately design such studies. In the second half of this chapter, we explain the fundamental statistical concepts and methods used in the data analysis of typical in vivo experiments. We also provide specific examples in in vivo imaging studies to illustrate the key steps of analysis procedure.

  15. Lipid nanoparticles for transdermal delivery of flurbiprofen: formulation, in vitro, ex vivo and in vivo studies

    Directory of Open Access Journals (Sweden)

    Venkateswarlu Vobalaboina

    2009-02-01

    Full Text Available Abstract The aim of the study is to prepare aqueous dispersions of lipid nanoparticles – flurbiprofen solid lipid nanoparticles (FLUSLN and flurbiprofen nanostructured lipid carriers (FLUNLC by hot homogenization followed by sonication technique and then incorporated into the freshly prepared hydrogels for transdermal delivery. They are characterized for particle size, for all the formulations, more than 50% of the particles were below 300 nm after 90 days of storage at RT. DSC analyses were performed to characterize the state of drug and lipid modification. Shape and surface morphology were determined by TEM which revealed fairly spherical shape of the formulations. Further they were evaluated for in vitro drug release characteristics, rheological behaviour, pharmacokinetic and pharmacodynamic studies. The pharmacokinetics of flurbiprofen in rats following application of SLN gel (A1 and NLC gel (B1 for 24 h were evaluated. The Cmax of the B1 formulation was 38.67 ± 2.77 μg/ml, which was significantly higher than the A1 formulation (Cmax = 21.79 ± 2.96 μg/ml. The Cmax and AUC of the B1 formulation were 1.8 and 2.5 times higher than the A1 gel formulation respectively. The bioavailability of flurbiprofen with reference to oral administration was found to increase by 4.4 times when gel formulations were applied. Anti-inflammatory effect in the Carrageenan-induced paw edema in rat was significantly higher for B1 and A1 formulation than the orally administered flurbiprofen. Both the SLN and NLC dispersions and gels enriched with SLN and NLC possessed a sustained drug release over period of 24 h but the sustained effect was more pronounced with the SLN and NLC gel

  16. CD47 deficiency confers cell and tissue radioprotection by activation of autophagy

    Science.gov (United States)

    Soto-Pantoja, David R.; Miller, Thomas W.; Pendrak, Michael L.; DeGraff, William G.; Sullivan, Camille; Ridnour, Lisa A.; Abu-Asab, Mones; Wink, David A.; Tsokos, Maria; Roberts, David D.

    2012-01-01

    Accidental or therapeutic exposure to ionizing radiation has severe physiological consequences and can result in cell death. We previously demonstrated that deficiency or blockade of the ubiquitously expressed receptor CD47 results in remarkable cell and tissue protection against ischemic and radiation stress. Antagonists of CD47 or its ligand THBS1/thrombospondin 1 enhance cell survival and preserve their proliferative capacity. However the signaling pathways that mediate this cell-autonomous radioprotection are unclear. We now report a marked increase in autophagy in irradiated T-cells and endothelial cells lacking CD47. Irradiated T cells lacking CD47 exhibit significant increases in formation of autophagosomes comprising double-membrane vesicles visualized by electron microscopy and numbers of MAP1LC3A/B+ puncta. Moreover, we observed significant increases in BECN1, ATG5, ATG7 and a reduction in SQSTM1/p62 expression relative to irradiated wild-type T cells. We observed similar increases in autophagy gene expression in mice resulting from blockade of CD47 in combination with total body radiation. Pharmacological or siRNA-mediated inhibition of autophagy selectively sensitized CD47-deficient cells to radiation, indicating that enhanced autophagy is necessary for the prosurvival response to CD47 blockade. Moreover, re-expression of CD47 in CD47-deficient T cells sensitized these cells to death by ionizing radiation and reversed the increase in autophagic flux associated with survival. This study indicates that CD47 deficiency confers cell survival through the activation of autophagic flux and identifies CD47 blockade as a pharmacological route to modulate autophagy for protecting tissue from radiation injury. PMID:22874555

  17. Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies.

    Science.gov (United States)

    Tjandrawinata, Raymond R; Trisina, Jessica; Rahayu, Puji; Prasetya, Lorentius Agung; Hanafiah, Aang; Rachmawati, Heni

    2014-01-01

    DLBS1033 is a bioactive protein fraction isolated from Lumbricus rubellus that tends to be unstable when exposed to the gastrointestinal environment. Accordingly, appropriate pharmaceutical development is needed to maximize absorption of the protein fraction in the gastrointestinal tract. In vitro, ex vivo, and in vivo stability assays were performed to study the stability of the bioactive protein fraction in gastric conditions. The bioactive protein fraction DLBS1033 was found to be unstable at low pH and in gastric fluid. The "enteric coating" formulation showed no leakage in gastric fluid-like medium and possessed a good release profile in simulated intestinal medium. DLBS1033 was absorbed through the small intestine in an intact protein form, confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) analysis. This result confirmed that an enteric coating formula using methacrylic acid copolymer could protect DLBS1033 from the acidic condition of the stomach by preventing the release of DLBS1033 in the stomach, while promoting its release when reaching the intestine. From the blood concentration-versus-time curve, (99m)Tc-DLBS1033 showed a circulation half-life of 70 minutes. This relatively long biological half-life supports its function as a thrombolytic protein. Thus, an enteric delivery system is considered the best approach for DLBS1033 as an oral thrombolytic agent.

  18. International symposium on in vivo body composition studies: Program and abstracts

    Energy Technology Data Exchange (ETDEWEB)

    1986-01-01

    This booklet contains the program and individual abstracts for papers presented at the International symposium on in vivo body composition studies. The presentations were divided into five sessions. Individual abstracts were indexed for the Energy Data Base. (DT)

  19. The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

    Science.gov (United States)

    Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

    2017-08-02

    The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

  20. Qualification and certification in radioprotection of odontology students in the State of Rio de Janeiro; Capacitacao e formacao em radioprotecao dos alunos de odontologia no Estado do Rio de Janeiro

    Energy Technology Data Exchange (ETDEWEB)

    Padilha Filho, Lucas Gomes [Hospital Universitario Clementino Fraga Filho, Rio de Janeiro, RJ (Brazil); Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Dept. de Radiologia; Borges, Jose Carlos [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Programa de Engenharia Nuclear

    2000-08-01

    The main aim of this study was to conduct a critical survey on the qualification and certification in radioprotection of odontology students from all dental schools in the State of Rio de Janeiro and some dental schools in the State of Sao Paulo, Brazil. The methodology involved the use of questionnaires applied to radiology professors and supervisors and former students. The questionnaires consisted of open and closed questions, which allowed an analysis of both qualitative and quantitative aspects. A critical analysis of the answers revealed that the students' knowledge of radioprotection is very poor, particularly with regard to the new guidelines of the Brazilian Ministry for Health. Consequently, we suggest that dental schools should reform the contents of radiology teaching, thus permitting upcoming students to be better prepared for the challenge of professional quality. (author)

  1. Evaluation of bioaccumulation using in vivo laboratory and field studies.

    Science.gov (United States)

    Weisbrod, Annie V; Woodburn, Kent B; Koelmans, Albert A; Parkerton, Thomas F; McElroy, Anne E; Borgå, Katrine

    2009-10-01

    A primary consideration in the evaluation of chemicals is the potential for substances to be absorbed and retained in an organism's tissues (i.e., bioaccumulated) at concentrations sufficient to pose health concerns. Substances that exhibit properties that enable biomagnification in the food chain (i.e., amplification of tissue concentrations at successive trophic levels) are of particular concern due to the elevated long-term exposures these substances pose to higher trophic organisms, including humans. Historically, biomarkers of in vivo chemical exposure (e.g., eggshell thinning, bill deformities) retrospectively led to the identification of such compounds, which were later categorized as persistent organic pollutants. Today, multiple bioaccumulation metrics are available to quantitatively assess the bioaccumulation potential of new and existing chemicals and identify substances that, upon or before environmental release, may be characterized as persistent organic pollutants. This paper reviews the various in vivo measurement approaches that can be used to assess the bioaccumulation of chemicals in aquatic or terrestrial species using laboratory-exposed, field-deployed, or collected organisms. Important issues associated with laboratory measurements of bioaccumulation include appropriate test species selection, test chemical dosing methods, exposure duration, and chemical and statistical analyses. Measuring bioaccumulation at a particular field site requires consideration of which test species to use and whether to examine natural populations or to use field-deployed populations. Both laboratory and field methods also require reliable determination of chemical concentrations in exposure media of interest (i.e., water, sediment, food or prey, etc.), accumulated body residues, or both. The advantages and disadvantages of various laboratory and field bioaccumulation metrics for assessing biomagnification potential in aquatic or terrestrial food chains are discussed

  2. Fluorescence Lifetime Imaging System for in Vivo Studies

    Directory of Open Access Journals (Sweden)

    Moinuddin Hassan

    2007-07-01

    Full Text Available In this article, a fluorescence lifetime imaging system for small animals is presented. Data were collected by scanning a region of interest with a measurement head, a linear fiber array with fixed separations between a single source fiber and several detection fibers. The goal was to localize tumors and monitor their progression using specific fluorescent markers. We chose a near-infrared contrast agent, Alexa Fluor 750 (Invitrogen Corp., Carlsbad, CA. Preliminary results show that the fluorescence lifetime for this dye was sensitive to the immediate environment of the fluorophore (in particular, pH, making it a promising candidate for reporting physiologic changes around a fluorophore. To quantify the intrinsic lifetime of deeply embedded fluorophores, we performed phantom experiments to investigate the contribution of photon migration effects on observed lifetime by calculating the fluorescence intensity decay time. A previously proposed theoretical model of migration, based on random walk theory, is also substantiated by new experimental data. The developed experimental system has been used for in vivo mouse imaging with Alexa Fluor 750 contrast agent conjugated to tumor-specific antibodies (trastuzumab [Herceptin]. Three-dimensional mapping of the fluorescence lifetime indicates lower lifetime values in superficial breast cancer tumors in mice.

  3. Development of enhanced radioprotectors - Biochemical and molecular genetical approaches on the radioprotective mechanism of natural products

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Hee; Lee, Eun Ju; Hong, Jung A [Kyunghee University, Seoul (Korea)

    2000-04-01

    To identify radio-protective agent candidate among medicinal plants and to elucidate the mechanism of action of the candidate material by using modern biochemical and molecular biological methods, we screened radio-protective activity among 48 medicinal plants. Seven samples showed above 20% protective activities against oxidative cell damage: Euryale ferox, Glycyrrhiza uralensis, Salvia miltiorrhiza, Eucomia ulmoides, Paeonia suffruticosa, Spirodela polyrrhiza, and Nelumbo nucifera. We also screened for oxidative stress sensitizing activity among other 51 medicinal plants. Among those samples, 11 samples showed good sensitizing effect; Melia azedarach, Agastache rugosa, Catalpa ovata, Prunus persica, Sinomenium acutum, Pulsatilla koreana, Oldenlandia diffusa, Anthriscus sylvestris, Schizandra chinensis, Gleditsia sinensis, and Cridium officinale. We also reported the radio-protective effect of DTT. The treatment of DTT increased cell survival after gamma-irradiation, decreased in the frequencies of micronucleus, and reduction in DNA fragmentation and apoptotic cells. Induction of apoptosis after UV-C irradiation was revealed by the changes in the relative cell death, increase in the relative amount of apoptotic cells, and the induction of DNA fragmentation. 165 refs., 9 figs., 8 tabs. (Author)

  4. Radioprotective effects of Dragon's blood and its extract against gamma irradiation in mouse bone marrow cells.

    Science.gov (United States)

    Ran, Yuanyuan; Wang, Ran; Lin, Fankai; Hasan, Murtaza; Jia, Qiutian; Tang, Bo; Xia, Yu; Shan, Shuangquan; Wang, Xiao; Li, Qiang; Deng, Yulin; Qing, Hong

    2014-06-01

    The radioprotective effects of Dragon's blood (DB) and its extracts (DBE) were investigated using the chromosomal aberrant test, micronucleus and oxidative stress assay for anti-clastogenic and anti-oxidative activity. Adult BALB/C mice were exposed to the whole body irradiation with 4 Gy (60)Co γ-rays. DB and DBE were administered orally once a day from 5 days prior to irradiation treatment to 1 day after irradiation. The mice were sacrificed on 24 h after irradiation. The cells of bone marrow were measured by counting different types of chromosomal aberrations and the frequency of micronuclei. Oxidative stress response was carried out by analysis of serum from blood. DB and DBE significantly decreased the number of bone marrow cells with chromosome aberrations after irradiation with respect to irradiated alone group. The administration of DB and DBE also significantly reduced the frequencies of micronucleated polychromatic erythrocytes (MPCE) and micronucleated normochromatic erythrocytes (MNCE). In addition, DB and DBE markedly increased the activity of antioxidant enzymes and the level of antioxidant molecular. Malondialdehyde (MDA) and nitric oxide (NO) levels in serum were significantly reduced by DB and DBE treatment. Our data suggested that DB and DBE have potential radioprotective properties in mouse bone marrow after (60)Co γ-ray exposure, which support their candidature as a potential radioprotective agent. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  5. EXPERIMENTAL STUDIES ON INFLAMMATION : II. EXPERIMENTAL CHEMICAL INFLAMMATION IN VIVO.

    Science.gov (United States)

    Wolf, E P

    1923-03-31

    1. None of the salts tested produce a marked inflammation in vivo in concentrations under 10 per cent. Potassium salts and the different citrates produced atypical inflammatory reactions in mice, but not in frogs. There was no true inflammation, however, characterized by blood vessel changes, migration of polymorphonuclear leucocytes and erythrocytes, and fluid exudation. 2. Synergistic action occurs when equal parts of strontium and magnesium salts are employed. There is a change in the appearance of the mesentery without a true inflammation, and this change does not occur with either salt alone. 3. Amino-acids and amines as a class do not produce inflammation, but histamine produces a marked inflammatory reaction in frogs and mice. 4. Tyramine does not cause an inflammatory reaction but has other marked effects; agglutination thrombi occur within the smaller blood vessels, both veins and arteries; in frogs there is a rapid clumping of the white blood cells followed by a true coagulation with strands of fibrin and entanglement of erythrocytes. This is very widespread and often kills the animal within an hour after injection. In mice it is the erythrocytes that clump and coagulation occurs very much later, usually at the end of 24 hours; still later there is complete absorption of the coagulated masses and the mesenteric circulation returns to normal. None of the mice died during the stage of clumping, and the clots never extended up the larger vessels as they did in the frogs. These effects are similar to the phenomena observed in the in vitro work, in which clumping of the cells appeared constantly. 5. Cantharidinum, histamine, and turpentine produced the most rapid and marked inflammation of any substances tried. These substances are all strongly positively chemotactic in vitro. The differences occurring when these substances are used in different species is a quantitative rather than a qualitative one, the body temperature being of some importance. Papain acted

  6. Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin

    Energy Technology Data Exchange (ETDEWEB)

    Cenedella, R.J.; Fleschner, C.R. (Kirksville College of Osteopathic Medicine, MO (USA))

    1990-10-01

    The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea.

  7. Stratum corneum damage and ex vivo porcine skin water absorption - a pilot study

    DEFF Research Database (Denmark)

    Duch Lynggaard, C; Bang Knudsen, D; Jemec, G B E

    2009-01-01

    A simple ex vivo screening technique would be of interest for mass screening of substances for potential barrier disruptive qualities. Ex vivo water absorption as a marker of skin barrier integrity was studied on pig ear skin. Skin water absorption was quantified by weighing and weight changes were...... found to reflect prehydration barrier damage. It is suggested that this simple model may be elaborated to provide a rapid, economical screening tool for potential skin irritants....

  8. Radiation protection measures of agents exposed to OctreoTher: product using {sup 90}Y; Radioprotection du personnel lors de traitements par OctreoTher: produit utilisant l'yttrium-90

    Energy Technology Data Exchange (ETDEWEB)

    Bramoulle, C.; Prunier, C.; Mantzarides, M.; Guilloteau, D.; Baulieu, J.L.; Besnard, J.C. [Centre Hospitalier Universitaire de Tours Bretonneau, Service de Medecine Nucleaire, 37 - Tours (France); Bastie, A.M. [Novartis Pharma S.A., 92 - Rueil-Malmaison (France); Lavocat-Discherl, C. [Mallinckrodt France, 91 - Les Ulis (France)

    2003-09-01

    In nuclear department of Tours, dosimetry surveillance is passive with counting of monthly dose, but we do not study radiation exposure along time of medical and paramedical agents. In this study we wanted to study the real radiation exposure of two categories of agents working in the therapeutic protocol of neuroendocrine tumours with somatostatin analogue radiolabeled with 90-yttrium (OctreoTher - Novartis). Thus we used operational dosimeter and we identified moments when exposure was maximum. Then we could take measures to limit the radioactive exposure of agents. In the in vitro nuclear department laboratory, storage of empty bottles of OctreoTher and treatment of radioactive waste were the optimum radioactive exposure moments for these agents. We then used Plexiglas boxes to reduce this skin equivalent dose from 240 {mu}Sv to 15 {mu}Sv. For the nurses who took in charge the treatment with {sup 90}Y octreotide (OctreoTher), optimum radioactive exposure was perfusion manipulations and removal. We used plumb parapets near the patient and Plexiglas boxes to put perfusion and empty bottles of OctreoTher. We reduced skin equivalent dose from 1300 {mu}Sv to 150 {mu}Sv. Operational dosimeter allowed us to identify radioactive exposure of agents of in vitro and in vivo nuclear departments during {sup 90}Y-OctreoTher treatment of neuroendocrine tumours. During this study we took radioprotection measures to reduce significantly the received equivalent dose, essentially with Plexiglas boxes and plumb parapets during the perfusion of {sup 90}Y-OctreoTher and radioactive waste treatment. (authors)

  9. Radioprotection of patients and workers in interventional and operating block radiology; La radioprotection des patients et des travailleurs en radiologie interventionnelle et au bloc operatoire

    Energy Technology Data Exchange (ETDEWEB)

    Menechal, P. [Autorite de Surete Nucleaire, Div. de Bordeaux, 33 (France); Valero, M.; Megnigbeto, C.; Marchal, C.; Godet, J.L. [Autorite de surete nucleaire, Dir. des rayonnements ionisants et de la sante, 75 - Paris (France)

    2011-03-15

    Over the last ten years or so, extensive development in radiological and implantable equipment has generated significant growth in radio-guided procedures. The real benefit of these practices to patients explains their development. These procedures can be undertaken using not only dedicated, specific fixed installations and computed tomography scanners, but also mobile installations in facilities not designed for radiography, such as operating blocks. The complexity of these procedures and the times spent implementing the required radiation can lead to major detrimental effects on personnel and patients, if they are not fully controlled. Many specialist medical disciplines now perform invasive procedures guided by images. Optimisation of patient doses mainly depends on the training level of medical teams, the intrinsic performance characteristics of the equipment used, adjustment of the technical parameters and the presence or absence of qualified personnel. Optimisation of professional personnel exposure is complex and depends on the performance conditions of procedures, which can expose workers extensively and non-uniformly. Designation of personnel competent in radioprotection, assessment of risks and definition of controlled areas, analysis of workstations and dosimetric monitoring of operators (especially of body extremities) are difficult to implement. Use of collective and personal protective equipment must be improved. The general manager of the French nuclear safety authority (ASN) has referred the matter to the permanent group of radioprotection experts (GPMED) to ensure that recommendations are drawn up in the short term. (authors)

  10. Bioactive protein fraction DLBS1033 containing lumbrokinase isolated from Lumbricus rubellus: ex vivo, in vivo, and pharmaceutic studies

    Directory of Open Access Journals (Sweden)

    Tjandrawinata RR

    2014-09-01

    Full Text Available Raymond R Tjandrawinata,1 Jessica Trisina,1 Puji Rahayu,1 Lorentius Agung Prasetya,1 Aang Hanafiah,2 Heni Rachmawati3 1Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, Indonesia; 2National Nuclear Energy Agency, Bandung, Indonesia; 3School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia Abstract: DLBS1033 is a bioactive protein fraction isolated from Lumbricus rubellus that tends to be unstable when exposed to the gastrointestinal environment. Accordingly, appropriate pharmaceutical development is needed to maximize absorption of the protein fraction in the gastrointestinal tract. In vitro, ex vivo, and in vivo stability assays were performed to study the stability of the bioactive protein fraction in gastric conditions. The bioactive protein fraction DLBS1033 was found to be unstable at low pH and in gastric fluid. The “enteric coating” formulation showed no leakage in gastric fluid–like medium and possessed a good release profile in simulated intestinal medium. DLBS1033 was absorbed through the small intestine in an intact protein form, confirmed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE analysis. This result confirmed that an enteric coating formula using methacrylic acid copolymer could protect DLBS1033 from the acidic condition of the stomach by preventing the release of DLBS1033 in the stomach, while promoting its release when reaching the intestine. From the blood concentration–versus-time curve, 99mTc-DLBS1033 showed a circulation half-life of 70 minutes. This relatively long biological half-life supports its function as a thrombolytic protein. Thus, an enteric delivery system is considered the best approach for DLBS1033 as an oral thrombolytic agent. Keywords: bioactive protein fraction, enteric coated tablet, pharmacodynamic

  11. A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies.

    Science.gov (United States)

    Huber, K; Aichler, M; Sun, N; Buck, A; Li, Z; Fernandez, I E; Hauck, S M; Zitzelsberger, H; Eickelberg, O; Janssen, K P; Keller, U; Walch, A

    2014-10-01

    The aim of this study was to establish an ex vivo model for a faster optimisation of sample preparation procedures, for example matrix choice, in matrix-assisted laser desorption/ionisation (MALDI) drug imaging studies. The ionisation properties of four drugs, afatinib, erlotinib, irinotecan and pirfenidone, were determined in an ex vivo tissue experiment by spotting decreasing dilution series onto liver sections. Hereby, the drug signals were distinctly detectable using different matrix compounds, which allowed the selection of the optimal matrix for each drug. The analysis of afatinib and erlotinib yielded high drug signals with α-cyano-4-hydroxycinnamic acid matrix, whereas 2,3-dihydroxybenzoic acid was identified as optimal matrix for irinotecan and pirfenidone detection. Our method was validated by a MALDI drug imaging approach of in vivo treated mouse tissue resulting in corresponding findings, indicating the spotting method as an appropriate approach to determine the matrix of choice. The present study shows the accordance between the detection of ex vivo spotted drugs and in vivo administered drugs by MALDI-TOF and MALDI-FT-ICR imaging, which has not been demonstrated so far. Our data suggest the ex vivo tissue spotting method as an easy and reliable model to optimise MALDI imaging measurements and to predict drug detection in tissue sections derived from treated mice prior to the recruitment of laboratory animals, which helps to save animals, time and costs.

  12. In vitro and in vivo study of commercial calcium phosphate cement HydroSet™.

    Science.gov (United States)

    Kent, Niall W; Blunn, Gordon; Karpukhina, Natalia; Davis, Graham; de Godoy, Roberta Ferro; Wilson, Rory M; Coathup, Melanie; Onwordi, Lyris; Quak, Wen Yu; Hill, Robert

    2018-01-01

    The commercial calcium phosphate cement, HydroSet™, was investigated in vitro, studying phase formation, compressive strength and setting time, followed by an ovine in vivo study to measure osseointegration, bone apposition and bone-to-graft contact. The X-ray diffraction and 31 P Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) results showed the initial formation of octacalcium phosphate and hydroxyapatite at one hour. Over 7 days the octacalcium phosphate transformed to apatite, which was the only crystalline phase of the cement at 28 days. This apatite phase is thought to be a calcium deficient apatite. In the scanning electron microscopy, histological images of 12-week ovine in vivo results showed a high degree of osseointegration, 92.5%. Compressive strength comparisons between in vitro and in vivo measurements showed a dramatic difference between the in vitro measurements (highest 25.4 MPa) and in vivo (95 MPa), attributed to bone ingrowth into the cement in vivo. To the best of our knowledge this is the first time phase evolution of HydroSet™ and the properties studied in vitro complement the in vivo evaluation of the cement in a publication. The significance of the new finding of initial formation of octacalcium phosphate in this cement is discussed. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 21-30, 2018. © 2016 Wiley Periodicals, Inc.

  13. In vivo toxicity studies of fusarium mycotoxins in the last decade: a review.

    Science.gov (United States)

    Escrivá, L; Font, G; Manyes, L

    2015-04-01

    This review summarizes the information regarding the in vivo studies of Fusarium mycotoxins in the last decade. The most common studies are classified as subacute toxicity, subchronic toxicity, acute toxicity, toxicokinetic studies and teratogenicity in order of importance. The most used animals in in vivo studies are pigs, rats, chickens and mice. Fumonisin B1, deoxynivalenol, zearalenone, nivalenol and T-2 toxin are the most studied fusarotoxins. Studies with combinations of mycotoxins are also frequent, deoxynivalenol generally being one of them. The predominant route of administration is oral, administered mostly in the form of naturally contaminated feed. Other administration routes also used are intraperitoneal, intravenous and subcutaneous. In vivo research on Fusarium mycotoxins has increased since 2010 highlighting the need for such studies in the field of food and feed safety. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. A novel antithrombotic effect of sulforaphane via activation of platelet adenylate cyclase: ex vivo and in vivo studies.

    Science.gov (United States)

    Jayakumar, Thanasekaran; Chen, Wei-Fan; Lu, Wan-Jung; Chou, Duen-Suey; Hsiao, George; Hsu, Chung-Yi; Sheu, Joen-Rong; Hsieh, Cheng-Ying

    2013-06-01

    Sulforaphane is a naturally occurring isothiocyanate, which can be found in cruciferous vegetables such as broccoli and cabbage. Sulforaphane was found to have very potent inhibitory effects on tumor growth through regulation of diverse mechanisms. However, no data are available concerning the effects of sulforaphane on platelet activation and its relative issues. Activation of platelets caused by arterial thrombosis is relevant to a variety of cardiovascular diseases. Hence, the aim of this study was to examine the in vivo antithrombotic effects of sulforaphane and its possible mechanisms in platelet activation. Sulforaphane (0.125 and 0.25 mg/kg) was effective in reducing the mortality of ADP-induced acute pulmonary thromboembolism in mice. Other in vivo studies also revealed that sulforaphane (0.25 mg/kg) significantly prolonged platelet plug formation in mice. In addition, sulforaphane (15-75 μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen. Sulforaphane inhibited platelet activation accompanied by inhibiting relative Ca(2+) mobilization; phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs) and Akt; and hydroxyl radical (OH(●)) formation. Sulforaphane markedly increased cyclic (c)AMP, but not cyclic (c)GMP levels, and stimulated vasodilator-stimulated phosphoprotein (VASP) phosphorylation. SQ22536, an inhibitor of adenylate cyclase, but not ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxal in-1-one), an inhibitor of guanylate cyclase, obviously reversed the sulforaphane-mediated effects on platelet aggregation; PKC activation, p38 MAPK, Akt and VASP phosphorylation; and OH(●) formation. Furthermore, a PI3-kinase inhibitor (LY294002) and a p38 MAPK inhibitor (SB203580) both significantly diminished PKC activation and p38 MAPK and Akt phosphorylation; in contrast, a PKC inhibitor (RO318220) did not diminish p38 MAPK or Akt phosphorylation stimulated by collagen. This

  15. A radiotracer for In vivo studies of acetylcholinesterase: p-[{sup 18}F]fluorodonepezil

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S. Y.; Choi, Y. S.; Choi, Y.; Kim, S. E.; Lee, K. H.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of); Lee, J. W. [Seoul National Univ., Seoul (Korea, Republic of)

    1999-05-01

    Alzheimer's disease (AD) is one of senile dementia caused by lack of acetylcholine in central nervous system, and in vivo studies of acetylcholinesterase (AChE) have been carried out using many radiolabeled AChE inhibitors (donepezil, tacrine, physostigmine, CP-126,998, etc). Donepezil, a FDA approved drug for AD is now in clinical use. Therefore, we synthesized and evaluated p-[{sup 18}F]fluorodonepezil in mice. Biodistribution studies demonstrated that p-[{sup 18}F]fluorodonepezil binds non-specifically in vivo and does not suffer from metabolism in mouse brain. This study suggests that radioligands with higher binding affinity may be required to visualize AChE in vivo and further studies are needed to develop better radiotracers.

  16. Imaging of Small Vessels Using Photoacoustics: An In Vivo Study

    NARCIS (Netherlands)

    Siphanto, Ronald I.; Kolkman, R.G.M.; Huisjes, A.; Pilatou, M.H.; de Mul, F.F.M.; Steenbergen, Wiendelt; van Adrichem, Leon N.A.

    2004-01-01

    Background and Objectives The ability to correctly visualize the architectural arrangement of microvasculature is valuable to many diverse fields in medicine. In this study, we applied photoacoustics (PA) to obtain high-resolution images of submillimeter blood vessels. - Study Design/Materials and

  17. Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies.

    Science.gov (United States)

    Thomas, Lydia; Zakir, Foziyah; Mirza, Mohd Aamir; Anwer, Md Khalid; Ahmad, Farhan Jalees; Iqbal, Zeenat

    2017-08-01

    In the present study, various nanoemulsions were prepared using Labrafac PG+Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032±0.023nm, viscosity 78.23±22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1-3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88μg/cm2/h as compared to NE2 (76.05μg/cm2/h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75±88μg) is significantly higher than NE2 (771.25±67μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Renal denervation by intravascular ultrasound: Preliminary in vivo study

    Science.gov (United States)

    Sinelnikov, Yegor; McClain, Steve; Zou, Yong; Smith, David; Warnking, Reinhard

    2012-10-01

    Ultrasound denervation has recently become a subject of intense research in connection with the treatment of complex medical conditions including neurological conditions, development of pain management, reproduction of skin sensation, neuropathic pain and spasticity. The objective of this study is to investigate the use of intravascular ultrasound to produce nerve damage in renal sympathetic nerves without significant injury to the renal artery. This technique may potentially be used to treat various medical conditions, such as hypertension. The study was approved by the Institutional Animal Care and Use Committee. Ultrasound was applied to renal nerves of the swine model for histopathological evaluation. Therapeutic ultrasound energy was delivered circumferentially by an intravascular catheter maneuvered into the renal arteries. Fluoroscopic imaging was conducted pre-and post-ultrasound treatment. Animals were recovered and euthanized up to 30 hours post procedure, followed by necropsy and tissue sample collection. Histopathological examination showed evidence of extensive damage to renal nerves, characterized by nuclear pyknosis, hyalinization of stroma and multifocal hemorrhages, with little or no damage to renal arteries. This study demonstrates the feasibility of intravascular ultrasound as a minimally invasive renal denervation technique. Further studies are necessary to evaluate the long-term safety and efficacy of this technique and its related clinical significance.

  19. In vivo studies of peritendinous tissue in exercise

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, Henning; Skovgaard, D

    2000-01-01

    Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods...

  20. Impact of Environmental Enrichment Devices on NTP In Vivo Studies.

    Science.gov (United States)

    Churchill, Sheba R; Morgan, Daniel L; Kissling, Grace E; Travlos, Gregory S; King-Herbert, Angela P

    2016-02-01

    The goal of this study was to determine whether the use of nesting material or polycarbonate shelters as enrichment devices would have an impact on end points commonly measured during the conduct of the National Toxicology Program (NTP) 13-week studies. The study design was consistent with the NTP 13-week toxicity studies. Harlan Sprague-Dawley (HSD) rats and their offspring and B6C3F1/N mice were assigned to control (unenriched) and enriched experimental groups. Body weight, food and water consumption, behavioral observations, fecal content, clinical pathology, gross pathology, organ weights, and histopathology were evaluated. Enriched male mice and male and female rats exhibited decreased feed intake without a subsequent decrease in body weight; this may have been the result of the nesting material reducing the effect of cold stress, thereby allowing for more efficient use of feed. There were statistical differences in some hematological parameters; however, these were not considered physiologically relevant since all values were within the normal range. Gross pathology and histopathological findings were background changes and were not considered enrichment-related. Nesting material and shelters were used frequently and consistently and allowed animals to display species-typical behavior. There was no significant impact on commonly measured end points in HSD rats and B6C3F1/N mice given enrichment devices. © The Author(s) 2016.

  1. Do Carbamazepine, Gabapentin, or Other Anticonvulsants Exert Sufficient Radioprotective Effects to Alter Responses From Trigeminal Neuralgia Radiosurgery?

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, John C. [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); College of Arts and Sciences, University of Pittsburgh, Pittsburgh, PA (United States); Kim, Hyun [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Kano, Hideyuki [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Greenberger, Joel S.; Arai, Yoshio [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Niranjan, Ajay [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Lunsford, L. Dade; Kondziolka, Douglas [Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Flickinger, John C., E-mail: flickingerjc@upmc.edu [Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Pittsburgh Cancer Institute, Pittsburgh, PA (United States); Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA (United States)

    2012-07-15

    Purpose: Laboratory studies have documented radioprotective effects with carbamazepine. We sought to determine whether carbamazepine or other anticonvulsant/neuroleptic drugs would show significant radioprotective effects in patients undergoing high-dose small-volume radiosurgery for trigeminal neuralgia. Methods and Materials: We conducted a retrospective review of 200 patients undergoing Gamma Knife (Elekta Instrument AB, Stockholm, Sweden) stereotactic radiosurgery for trigeminal neuralgia between February 1995 and May 2008. We selected patients treated with a maximum dose of 80 Gy with 4-mm diameter collimators, with no previous microvascular decompression, and follow-up {>=}6 months (median, 24 months; range, 6-153 months). At the time of radiosurgery, 28 patients were taking no anticonvulsants, 62 only carbamazepine, 35 only gabapentin, 21 carbamazepine plus gabapentin, 17 carbamazepine plus other anticonvulsants, and 9 gabapentin plus other anticonvulsants, and 28 were taking other anticonvulsants or combinations. Results: Pain improvement developed post-radiosurgery in 187 of 200 patients (93.5%). Initial complete pain relief developed in 84 of 200 patients (42%). Post-radiosurgery trigeminal neuropathy developed in 27 of 200 patients (13.5%). We could not significantly correlate pain improvement or initial complete pain relief with use of carbamazepine, gabapentin, or use of any anticonvulsants/neuroleptic drugs or other factors in univariate or multivariate analysis. Post-radiosurgery numbness/paresthesias correlated with the use of gabapentin (1 of 36 patients with gabapentin vs. 7 of 28 without, p = 0.017). In multivariate analysis, decreasing age, purely typical pain, and use of gabapentin correlated (p = 0.008, p = 0.005, and p = 0.021) with lower risks of developing post-radiosurgery trigeminal neuropathy. New post-radiosurgery numbness/paresthesias developed in 3% (1 of 36), 5% (4 of 81), and 13% (23 of 187) of patients on gabapentin alone, with age

  2. MTR and In-vivo 1H-MRS studies on mouse brain with parkinson's disease

    Science.gov (United States)

    Yoon, Moon-Hyun; Kim, Hyeon-Jin; Chung, Jin-Yeung; Doo, Ah-Reum; Park, Hi-Joon; Kim, Seung-Nam; Choe, Bo-Young

    2012-12-01

    The aim of this study was to investigate whether the changes in the magnetization transfer ratio (MTR) histogram are related to specific characteristics of Parkinson's disease (PD) and to investigate whether the MTR histogram parameters are associated with neurochemical dysfunction by performing in vivo proton magnetic resonance spectroscopy (1H-MRS). MTR and in vivo 1H-MRS studies were performed on control mice (n = 10) and 1-methyl-1,2,3,6-tetrahydropyridine intoxicated mice (n = 10). All the MTR and in vivo 1H-MRS experiments were performed on a 9.4 T MRI/MRS system (Bruker Biospin, Germany) using a standard head coil. The protondensity fast spin echo (FSE) images and the T2-weighted spin echo (SE) images were acquired with no gap. Outer volume suppression (OVS), combined with the ultra-short echo-time stimulated echo acquisition mode (STEAM), was used for the localized in-vivo 1H-MRS. The quantitative analysis of metabolites was performed from the 1H spectra obtained in vivo on the striatum (ST) by using jMRUI (Lyon, France). The peak height of the MTR histograms in the PD model group was significantly lower than that in the control group (p early phase of neuronal dysfunction of neurotransmitters.

  3. Large scale in vivo recordings to study neuronal biophysics.

    Science.gov (United States)

    Giocomo, Lisa M

    2015-06-01

    Over the last several years, technological advances have enabled researchers to more readily observe single-cell membrane biophysics in awake, behaving animals. Studies utilizing these technologies have provided important insights into the mechanisms generating functional neural codes in both sensory and non-sensory cortical circuits. Crucial for a deeper understanding of how membrane biophysics control circuit dynamics however, is a continued effort to move toward large scale studies of membrane biophysics, in terms of the numbers of neurons and ion channels examined. Future work faces a number of theoretical and technical challenges on this front but recent technological developments hold great promise for a larger scale understanding of how membrane biophysics contribute to circuit coding and computation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. In Vivo Assessment of Muscle Contractility in Animal Studies

    OpenAIRE

    Iyer, Shama R.; Valencia, Ana P.; Hern?ndez-Ochoa, Erick O.; Richard M Lovering

    2016-01-01

    In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Animal models provide unmitigated access to histological samples, which provide a ?direct measure? of damage. However, even with unconstrained access to tissue morphology and biochemistry assays, the findings typically do not account for loss of muscle function. Thus, the most comprehensive meas...

  5. In vivo studies of peritendinous tissue in exercise

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, Henning; Skovgaard, D

    2000-01-01

    Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods...... exercise. This coincides with a surprisingly marked drop in tissue pressure during contraction. With regards to both circulation, metabolism and collagen formation, peritendinous tissue represents a dynamic, responsive region that adapts markedly to acute muscular activity....

  6. Photodynamic activity of tetraazachlorin derivate studied in vivo

    Directory of Open Access Journals (Sweden)

    V. I. Ivanova-Radkevich

    2013-01-01

    Full Text Available The results of investigation for photodynamic activity of new tetraazachlorin derivate – tetramethyltribenzotetraazachlorin, synthesized in Research Institute of Organic Intermediates and Dyes. The study was performed on female mice of СВА line. The tumor model was transferred solid ascetic sarcoma S-37. The samples of photosensitizer, previously solubilized in 10% aqueou s solution ofCremophor EL, injected to mice intravenously on the 7th day of tumor growth in dose of 1–2 mg/kg. Two hours later the irradiation of sensitized tumor using light emitting diode device in a maximal wavelength of 755 nm (light power density – 50 mW/cm2, maximal total light dose – 300 J/cm2 was performed. The efficacy of photodynamic therapy was assessed by growth inhibition rates in the study group comparing with control group. The study showed that photodynamic therapy with investigated sample in dose of 2 mg/kg and light dose of 300 J/cm2 significantly inhibited the tumor growth (inhibition rate of 70–80% within 20 days, indicating prospectivity of subsequent investigations of tetraazachlorin as photosensitizer for photodynamic therapy of malignant tumors. 

  7. Critical considerations when planning experimental in vivo studies in dental traumatology

    DEFF Research Database (Denmark)

    Andreasen, Jens O; Andersson, Lars

    2011-01-01

    In vivo studies are sometimes needed to understand healing processes after trauma. For several reasons, not the least ethical, such studies have to be carefully planned and important considerations have to be taken into account about suitability of the experimental model, sample size and optimizing...

  8. Image enhancement based on in vivo hyperspectral gastroscopic images: a case study.

    Science.gov (United States)

    Gu, Xiaozhou; Han, Zhimin; Yao, Liqing; Zhong, Yunshi; Shi, Qiang; Fu, Ye; Liu, Changsheng; Wang, Xiguang; Xie, Tianyu

    2016-10-01

    Hyperspectral imaging (HSI) has been recognized as a powerful tool for noninvasive disease detection in the gastrointestinal field. However, most of the studies on HSI in this field have involved ex vivo biopsies or resected tissues. We proposed an image enhancement method based on in vivo hyperspectral gastroscopic images. First, we developed a flexible gastroscopy system capable of obtaining in vivo hyperspectral images of different types of stomach disease mucosa. Then, depending on a specific object, an appropriate band selection algorithm based on dependence of information was employed to determine a subset of spectral bands that would yield useful spatial information. Finally, these bands were assigned to be the color components of an enhanced image of the object. A gastric ulcer case study demonstrated that our method yields higher color tone contrast, which enhanced the displays of the gastric ulcer regions, and that it will be valuable in clinical applications.

  9. Image enhancement based on in vivo hyperspectral gastroscopic images: a case study

    Science.gov (United States)

    Gu, Xiaozhou; Han, Zhimin; Yao, Liqing; Zhong, Yunshi; Shi, Qiang; Fu, Ye; Liu, Changsheng; Wang, Xiguang; Xie, Tianyu

    2016-10-01

    Hyperspectral imaging (HSI) has been recognized as a powerful tool for noninvasive disease detection in the gastrointestinal field. However, most of the studies on HSI in this field have involved ex vivo biopsies or resected tissues. We proposed an image enhancement method based on in vivo hyperspectral gastroscopic images. First, we developed a flexible gastroscopy system capable of obtaining in vivo hyperspectral images of different types of stomach disease mucosa. Then, depending on a specific object, an appropriate band selection algorithm based on dependence of information was employed to determine a subset of spectral bands that would yield useful spatial information. Finally, these bands were assigned to be the color components of an enhanced image of the object. A gastric ulcer case study demonstrated that our method yields higher color tone contrast, which enhanced the displays of the gastric ulcer regions, and that it will be valuable in clinical applications.

  10. Study of cultured fibroblasts in vivo using NMR

    Energy Technology Data Exchange (ETDEWEB)

    Karczmar, G.S.

    1984-01-01

    The goal of this thesis was to study the compartmentation of phosphorylated glycolytic intermediates in intact Chicken Embryo Fibroblasts (CEFs) using /sup 31/P NMR at 109 MHz. Because glycolysis is regulated differently in normal and virally transformed CEFs, NMR experiments were performed on both types of cells. A technique for maintaining functional cells at high densities in an NMR magnet is described. Signals were detected from cytoplasmic inorganic phosphate (P/sub i/), ATP, NAD, NADH, phosphorylcholine and phosphorylethanolamine. The effect of external glucose on cytoplasmic pools of phosphates was studied. However, experiments with /sup 32/P labelled P/sub i/ showed that as the concentration of glucose in the medium was increased, the amount of phosphate sequestered in the cells increased. They conclude that there is a pool of P/sub i/ which is not detected by high resolution of NMR and that the size of this pool increases as the rate of glycolysis increases. These effects were found only in cultured cells; the data for transformed and normal cells were similar. Longitudinal relaxation times of intracellular phosphates in normal, transformed, and primary CEFs were measured.

  11. Study of cultured fibroblasts in vivo using NMR

    Energy Technology Data Exchange (ETDEWEB)

    Karczmar, G.S.

    1984-08-01

    The goal was to study the compartmentation of phosphorylated glycolytic intermediates in intact Chicken Embryo Fibroblasts (CEFs) using /sup 31/P NMR at 109 MHz. A technique for maintaining functional cells at high densities in an NMR magnet is described. Signals were detected from cytoplasmic inorganic phosphate (P/sub i/), ATP, NAD, NADH, phosphorylcholine and phosphorylethanolamine. The effect of external glucose on cytoplasmic pools of phosphates was studied. When cells were perfused with glucose-free medium the rate of glycolysis decreased, the amplitudes of the ATP resonances decreased, and the P/sub i/ intensity increased. The quantity of NMR-detectable P/sub i/ produced was significantly greater than the quantity of NMR-detectable ATP which was lost. Experiments with /sup 32/P labeled P/sub i/ showed that as the concentration of glucose in the medium was increase, the amount of phosphate sequestered in the cells increased. We conclude that there is a pool of P/sub i/ which is not detected by high resolution NMR and that the size of this pool increases as the rate of glycolysis increase. Longtitudinal relaxation times of intracellular phosphates in normal, transformed, and primary CEFs were measured. The results demonstrate that relaxation times of phosphates are sensitive to structural and metabolic changes which occur when cells are grown in culture. 59 references. 31 figures.

  12. Studies of DNA supercoiling in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Cook, David Nelson [Univ. of California, Berkeley, CA (United States)

    1990-10-01

    This thesis describes a number of diverse experiments whose common theme is to elaborate some aspect of DNA supercoiling. The torsion elastic constant of DNA is measure as a function of superhelix density using the technique of picosecond Time Resolved Fluorescence Polarization Anisotropy (FPA) of intercalated ethidium bromide. The results agree with theories which predict that the anisotropy decay should vary with the square root of the relative viscosity. This experiment furthermore demonstrates a sensitivity of FPA to a change in torsion elastic constant of less than 10%. A number of covalently closed DNA samples, ranging in superhelix density from = -0.123 to +0.042, are then examined. A novel method for measuring changes in local supercoiling on a large PNA molecule which is sensitive to changes in supercoiling of regions of chromosomal DNA as short as 1 kilobase in length is presented. Study of chromosomal supercoiling regulating anaerobic gene expression in the facultative photosynthetic bacterium, Rhodobacter capsulatus showed that no stable change in chromosomal supercoiling upon a shift from aerobic respiratory growth to anaerobic photosynthetic conditions. Studies to detect transient changes in DNA supercoiling indicate that DNA downstream from heavily transcribed genes for the photosynthetic reaction center are relaxed or perhaps overwound upon the induction of photosynthetic metabolism. These results are interpreted in terms of the twin domain model of transcriptional supercoiling.

  13. Studies of DNA supercoiling in vivo and in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Cook, D.N.

    1990-10-01

    This thesis describes a number of diverse experiments whose common theme is to elaborate some aspect of DNA supercoiling. The torsion elastic constant of DNA is measure as a function of superhelix density using the technique of picosecond Time Resolved Fluorescence Polarization Anisotropy (FPA) of intercalated ethidium bromide. The results agree with theories which predict that the anisotropy decay should vary with the square root of the relative viscosity. This experiment furthermore demonstrates a sensitivity of FPA to a change in torsion elastic constant of less than 10%. A number of covalently closed DNA samples, ranging in superhelix density from = [minus]0.123 to [plus]0.042, are then examined. A novel method for measuring changes in local supercoiling on a large PNA molecule which is sensitive to changes in supercoiling of regions of chromosomal DNA as short as 1 kilobase in length is presented. Study of chromosomal supercoiling regulating anaerobic gene expression in the facultative photosynthetic bacterium, Rhodobacter capsulatus showed that no stable change in chromosomal supercoiling upon a shift from aerobic respiratory growth to anaerobic photosynthetic conditions. Studies to detect transient changes in DNA supercoiling indicate that DNA downstream from heavily transcribed genes for the photosynthetic reaction center are relaxed or perhaps overwound upon the induction of photosynthetic metabolism. These results are interpreted in terms of the twin domain model of transcriptional supercoiling.

  14. Studying Kinetochores In Vivo Using FLIM-FRET.

    Science.gov (United States)

    Yoo, Tae Yeon; Needleman, Daniel J

    2016-01-01

    Kinetochores play essential roles in coordinating mitosis, as a mechanical connector between chromosome and microtubule and as a source of numerous biochemical signals. These mechanical and biochemical behaviors of kinetochores change dynamically in cells during mitosis. Therefore, understanding kinetochore function requires an imaging tool that quantifies the protein-protein interactions or biochemical changes with high spatiotemporal resolution. FRET has previously been used in combination with biosensors to probe protein-protein interactions and biochemical activity. In this chapter, we introduce FLIM-FRET, a lifetime-based method that quantifies FRET, and describe the use of FLIM-FRET as a method for studying dynamic kinetochore behavior in cells with high spatiotemporal resolution.

  15. Ac magnetic susceptibility study of in vivo nanoparticle biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Gutierrez, L; Veintemillas-Verdaguer, S; Serna, C J; Morales, M P [Instituto de Ciencia de Materiales de Madrid, ICMM-CSIC, Sor Juana Ines de la Cruz 3, Cantoblanco 28049, Madrid (Spain); MejIas, R; Barber, D F [Centro Nacional de BiotecnologIa, CNB-CSIC, Darwin 3, Cantoblanco 28049, Madrid (Spain); Lazaro, F J, E-mail: lucia@icmm.csic.es [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, Maria de Luna 3, 50018, Zaragoza (Spain)

    2011-06-29

    We analysed magnetic nanoparticle biodistribution, before and after cytokine conjugation, in a mouse model by ac susceptibility measurements of the corresponding resected tissues. Mice received repeated intravenous injections of nanoparticle suspension for two weeks and they were euthanized 1 h after the last injection. In general, only 10% of the total injected nanoparticles after multiple exposures were found in tissues. The rest of the particles may probably be metabolized or excreted by the organism. Our findings indicate that the adsorption of interferon to DMSA-coated magnetic nanoparticles changes their biodistribution, reducing the presence of nanoparticles in lungs and therefore their possible toxicity. The specific targeting of the particles to tumour tissues by the use of an external magnetic field has also been studied. Magnetic nanoparticles were observed by transmission electron microscopy in the targeted tissue and quantified by ac magnetic susceptibility.

  16. Intravital microscopy to study leukocyte recruitment in vivo.

    Science.gov (United States)

    Pinho, Vanessa; Coelho, Fernanda Matos; Menezes, Gustavo Batista; Cara, Denise Carmona

    2011-01-01

    The intravital microscopy is a valuable tool to capture images of cells in living organisms and to make studies of molecular determinants of leukocyte trafficking easier. Using this technique, we can directly visualize and measure each step of the leukocyte recruitment paradigm, including leukocyte rolling flux, rolling velocity, adhesion, and emigration. Thus, it is possible to understand the process involved in leukocyte homing as well as the cell recruitment to inflammatory tissues. Nowadays, two types of intravital microscopy are used routinely. The light microscopy is used to assess migration of intravascular cells in thin, tissues which must be sufficiently translucent. Epifluorescence microscopy allows the visualization of the microcirculation while permitting the distinction of leukocyte subpopulations in solid organs.

  17. Novel instrumentation to determine peel force in vivo and preliminary studies with adhesive skin barriers.

    Science.gov (United States)

    Krueger, Evan M; Cullum, Malford E; Nichols, Thom R; Taylor, Michael G; Sexton, William L; Murahata, Richard I

    2013-11-01

    Adhesive barriers secure medical devices to skin. Laboratory adhesion models are not predictive of in vivo performance. The objectives of these studies were to validate a novel peel force device, and to investigate relationships between barrier formulations, barrier width, subjective discomfort during barrier removal, and substrates. Three hydrocolloid barrier formulations in three widths were adhered to ethylene/methyl acrylate film (EMA), VITRO-SKIN(®) and human abdominal skin. Peel force was measured using a MTS Insight™ and a cyberDERM Inc. Mini Peel Tester (CMPT). Subjects reported their discomfort. Peel forces were highly correlated between devices and highly dependent on substrate. Data suggested a weak direct association between peel force in vivo and discomfort. The 0.5″-wide barriers had the most precise peel forces measurements in vivo. A weak negative relationship between normalized peel force and barrier width on human skin was found. There was a strong positive relationship between peel force in vivo and on EMA, whereas no correlation was observed with VITRO-SKIN(®). The CMPT correlates with a standard instrument and can advantageously investigate adhesion in vivo. Barrier width and substrate impact the reliability and predictability of peel force measurements. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. High-resolution ex vivo magnetic resonance angiography: a feasibility study on biological and medical tissues

    Directory of Open Access Journals (Sweden)

    Boel Lene WT

    2010-03-01

    Full Text Available Abstract Background In biomedical sciences, ex vivo angiography is a practical mean to elucidate vascular structures three-dimensionally with simultaneous estimation of intravascular volume. The objectives of this study were to develop a magnetic resonance (MR method for ex vivo angiography and to compare the findings with computed tomography (CT. To demonstrate the usefulness of this method, examples are provided from four different tissues and species: the human placenta, a rice field eel, a porcine heart and a turtle. Results The optimal solution for ex vivo MR angiography (MRA was a compound containing gelatine (0.05 g/mL, the CT contrast agent barium sulphate (0.43 mol/L and the MR contrast agent gadoteric acid (2.5 mmol/L. It was possible to perform angiography on all specimens. We found that ex vivo MRA could only be performed on fresh tissue because formalin fixation makes the blood vessels permeable to the MR contrast agent. Conclusions Ex vivo MRA provides high-resolution images of fresh tissue and delineates fine structures that we were unable to visualise by CT. We found that MRA provided detailed information similar to or better than conventional CTA in its ability to visualize vessel configuration while avoiding interfering signals from adjacent bones. Interestingly, we found that vascular tissue becomes leaky when formalin-fixed, leading to increased permeability and extravascular leakage of MR contrast agent.

  19. In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography.

    Science.gov (United States)

    Mele, Antonietta; Fonzino, Adriano; Rana, Francesco; Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Giustino, Arcangela; Conte Camerino, Diana; Desaphy, Jean-François

    2016-02-01

    Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultrasonographic volume determined in vivo with either method was linearly correlated to the volume determined ex-vivo from excised muscles as muscle weight-to-density ratio. For both soleus and gastrocnemius muscles, a strong linear correlation was obtained between the ultrasonographic volume and the muscle fiber cross-sectional area determined ex-vivo on muscle cryosections. Thus ultrasonography allowed the longitudinal in vivo evaluation of muscle atrophy progression during hindlimb unloading. This study validates ultrasonography as a powerful method for the evaluation of rodent muscle atrophy in vivo, which would prove useful in disease models and therapeutic trials.

  20. Numerical Model Study of In Vivo Magnetic Nanoparticle Tumor Heating.

    Science.gov (United States)

    Pearce, John A; Petryk, Alicia A; Hoopes, P Jack

    2017-12-01

    Iron oxide nanoparticles are currently under investigation as heating agents for hyperthermic treatment of tumors. Major determinants of effective heating include the biodistribution and minimum iron oxide loading required to achieve adequate heating at practically achievable magnetic field strengths. These inter-related criteria ultimately determine the practicality of this approach to tumor treatment. Further, in our experience the currently used treatment assessment criterion for hyperthermia treatment-cumulative equivalent minutes at 43 °C, CEM43 -provides an inadequate description of the expected treatment effectiveness. Couple numerical models to experimental measurements to study the relative heating effectiveness described by cell death predictions. FEM numerical models were applied to increase the understanding of a carefully calibrated series of experiments in mouse mammary adenocarcinoma. The numerical model results indicate that minimum tumor loadings between approximately 1.3 to 1.8 mg of Fe per cm3 of tumor tissue are required to achieve the experimentally observed temperatures in magnetic field strengths of 32 kA/m (rms) at 162 kHz. We show that including multiple cell death processes operating in parallel within the numerical models provides valuable perspective on the likelihood of successful treatment. We show and believe that these assessment methods are more accurate than a single assessment figure of merit based only on the comparison of thermal histories, such as the CEM method.

  1. Clindamycin and tetracycline as immunomodulating agents: an in vivo study.

    Science.gov (United States)

    Corrales, I; Suarez, A; Lima, A; Ballestero, S; Gómez-Lus, M L; Prieto, J

    1989-01-01

    The present study was undertaken to determine the effects of clindamycin and tetracycline, both intravenously administered, on antibody response to thymus-dependent antigen (PC-KLH) in BALB/c mice. The immunological parameters evaluated were: DPFC/spleen (direct plaque forming-cells), antibody secretion median rate (PC50), heterogeneity index (Hi), number of total splenic lymphocytes and cellular viability. The results showed that clindamycin (i.v.) increased the humoral response; 28 mg/kg was the dose that showed the greatest enhancement (+73%). The PC50 was not affected by clindamycin but Hi decreased at 28 mg/kg and increased at 2.8 mg/kg doses, although neither result was statistically significant. When tetracycline was given i.v., a slight decrease in the anti-PC DPFC number was observed. Although the PC50 was greater at 10 mg/kg (p less than 0.05), Hi was smaller at the 1 mg/kg dose (p less than 0.05).

  2. In vivo cerebral blood flow autoregulation studies using rheoencephalography

    Science.gov (United States)

    Bodo, M.; Pearce, F.; Garcia, A.; Van Albert, S.; Settle, T.; Szebeni, J.; Baranyi, L.; Hartings, J.; Armonda, R.

    2010-04-01

    Acute management of patients with traumatic brain/blast injury is a challenge. To minimize secondary injury and improve outcome, it is critical to detect neurological deterioration early, when it is potentially reversible. One potential monitoring method is cerebral electrical impedance (rheoencephalography-REG) because of its non-invasiveness and good time resolution. Reported here are the results of cerebral blood flow (CBF) manipulations comparing electroencephalogram (EEG) with REG (both intra-cerebral) and measuring with surface and skull REG electrodes. Our hypothesis was that REG would reflect spreading depression and CBF autoregulation. Animal experiments were performed using one rat (four trials with intracerebral electrodes), monkeys (n=8, with surface electrodes) and pigs (n = 24 pigs with skull electrodes; 57 trials, 19 types of liposomes). Challenges included intracranial pressure (ICP) elevation, liposome infusion, and hemorrhage. Data were stored on a PC and evaluated off line. CBF autoregulation was evaluated both by visual inspection and by a Matlab script. These studies confirmed that REG reflects CBF autoregulation and that REG is useful for detecting spreading depression (SD), vasospasm and the lower limit of CBF autoregulation. These findings have clinical relevance for use in noninvasive neuro-monitoring in the neurosurgery intensive care and during transportation of patients with brain injury.

  3. In vivo study of myocardial elastography under graded ischemia conditions

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Wei-Ning; Provost, Jean; Konofagou, Elisa E [Department of Biomedical Engineering, Columbia University, New York, NY (United States); Fujikura, Kana [Department of Radiology, Columbia University, New York, NY (United States); Wang Jie, E-mail: ek2191@columbia.edu [Department of Medicine, Columbia University, New York, NY (United States)

    2011-02-21

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  4. In vivo study of myocardial elastography under graded ischemia conditions

    Science.gov (United States)

    Lee, Wei-Ning; Provost, Jean; Fujikura, Kana; Wang, Jie; Konofagou, Elisa E.

    2011-02-01

    The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction

  5. Radioprotection and Cell Cycle Arrest of Intestinal Epithelial Cells by Darinaparsin, a Tumor Radiosensitizer

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Junqiang; Doi, Hiroshi [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Saar, Matthias; Santos, Jennifer [Department of Urology, School of Medicine, Stanford University, Stanford, California (United States); Li, Xuejun; Peehl, Donna M. [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States); Knox, Susan J., E-mail: sknox@stanford.edu [Department of Radiation Oncology, School of Medicine, Stanford University, Stanford, California (United States)

    2013-12-01

    Purpose: It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. Methods and Materials: The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. Results: In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. Conclusions: DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy.

  6. Radioprotection and cell cycle arrest of intestinal epithelial cells by darinaparsin, a tumor radiosensitizer.

    Science.gov (United States)

    Tian, Junqiang; Doi, Hiroshi; Saar, Matthias; Santos, Jennifer; Li, Xuejun; Peehl, Donna M; Knox, Susan J

    2013-12-01

    It was recently reported that the organic arsenic compound darinaparsin (DPS) is a cytotoxin and radiosensitizer of tumor cells in vitro and in subcutaneous xenograft tumors. Surprisingly, it was also found that DPS protects normal intestinal crypt epithelial cells (CECs) from clonogenic death after ionizing radiation (IR). Here we tested the DPS radiosensitizing effect in a clinically relevant model of prostate cancer and explored the radioprotective effect and mechanism of DPS on CECs. The radiation modification effect of DPS was tested in a mouse model of orthotopic xenograft prostate cancer and of IR-induced acute gastrointestinal syndrome. The effect of DPS on CEC DNA damage and DNA damage responses was determined by immunohistochemistry. In the mouse model of IR-induced gastrointestinal syndrome, DPS treatment before IR accelerated recovery from body weight loss and increased animal survival. DPS decreased post-IR DNA damage and cell death, suggesting that the radioprotective effect was mediated by enhanced DNA damage repair. Shortly after DPS injection, significant cell cycle arrest was observed in CECs at both G1/S and G2/M checkpoints, which was accompanied by the activation of cell cycle inhibitors p21 and growth arrest and DNA-damage-inducible protein 45 alpha (GADD45A). Further investigation revealed that DPS activated ataxia telangiectasia mutated (ATM), an important inducer of DNA damage repair and cell cycle arrest. DPS selectively radioprotected normal intestinal CECs and sensitized prostate cancer cells in a clinically relevant model. This effect may be, at least in part, mediated by DNA damage response activation and has the potential to significantly increase the therapeutic index of radiation therapy. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. An in vivo study on bone formation behavior of microporous granular calcium phosphate.

    Science.gov (United States)

    Dalmônico, G M L; Franczak, P F; Levandowski, N; Camargo, N H A; Dallabrida, A L; da Costa, B D; Gil, O García; Cambra-Moo, O; Rodríguez, M A; Canillas, M

    2017-06-27

    This study was developed based on in vivo investigation of microporous granular biomaterials based on calcium phosphates, involving matrices of β-tricalcium phosphate (β-TCP), hydroxyapatite (HA), biphasic compositions of both phases and a control group. The physicochemical characterization of materials was carried out by X-Ray diffraction (DRX) and mercury porosimetry. Biodegradability, bioactivity and neoformation processes were investigated by Raman spectroscopy, scanning electron microscopy (SEM) and polarized light conducted on biopsies obtained from in vivo tests for periods of 90 and 180 days. These were performed to evaluate the behavior of granular microporous compositions in relation to bone neoformation. Through the performance obtained from in vivo assays, excellent osseointegration and bone tissue neoformation were observed. The results are encouraging and show that the microporous granular biomaterials of HA, β-TCP and biphasic compositions show similar results with perfect osseointegration. Architectures simulating a bone structure can make the difference between biomaterials for bone tissue replacement and repair.

  8. Glycation of wood frog (Rana sylvatica) hemoglobin and blood proteins: in vivo and in vitro studies

    Science.gov (United States)

    MacDonald, Justin A.; Degenhardt, Thorsten; Baynes, John W.; Storey, Kenneth B.

    2010-01-01

    The effects of in vivo freezing and glucose cryoprotectant on protein glycation were investigated in the wood frog, Rana sylvatica. Our studies revealed no difference in the fructoselysine content of blood plasma sampled from control, 27 h frozen and 18 h thawed wood frogs. Glycated hemoglobin (GHb) decreased slightly with 48 h freezing exposure and was below control levels after 7 d recovery, while glycated serum albumin was unchanged by 48 h freezing but did increase after 7 d of recovery. In vitro exposure of blood lysates to glucose revealed that the GHb production in wood frogs was similar to that of the rat but was lower than in leopard frogs. We conclude that wood frog hemoglobin was glycated in vitro; however, GHb production was not apparent during freezing and recovery when in vivo glucose is highly elevated. It is possible that wood frog blood proteins have different in vivo susceptibilities to glycation. PMID:19540217

  9. Revisiting optical clearing with dimethyl sulfoxide (DMSO): in vitro and in vivo studies

    Science.gov (United States)

    McClure, R. Anthony; Stoianovici, Charles; Karma, Sanjeev; Choi, Bernard

    2009-02-01

    Functional optical characterization of disease progression and response to therapy suffers from loss of spatial resolution and imaging depth due to scattering, impacting the ability of researchers to localize and quantify molecular processes. Here we report on the ability of dimethyl sulfoxide (DMSO) to reduce temporarily the optical scattering of skin. Data collected from in vitro phantom images and in vivo fluorescence images demonstrate the potential of this simple method to mitigate the blurring effects of scattering with topical application, which we expect will improve the accuracy and localization of in vivo molecular imaging studies.

  10. Applicability of handmade expanded polytetrafluoroethylene trileaflet-valved conduits for pulmonary valve reconstruction: An ex vivo and in vivo study.

    Science.gov (United States)

    Kan, Chung-Dann; Wang, Jieh-Neng; Chen, Wei-Ling; Lu, Pong-Jeu; Chan, Ming-Yao; Lin, Chia-Hung; Hsieh, Wan-Chin

    2017-09-20

    The handmade expanded polytetrafluoroethylene (ePTFE) trileaflet-valved conduit could potentially be used as a substitute pulmonary valve replacement material, especially in children. The current study investigated (1) the function of the ePTFE trileaflet-valved conduits in an ex vivo experimental system and (2) the short-term performance of the conduit in a porcine model to verify its clinical applicability. The competency of the ePTFE trileaflet-valved conduits was estimated through ex vivo (using a pulmonary mock circulation loop) and in vivo (in a porcine model with a damaged pulmonary valve) experiments. Explants were examined by gross morphology and histopathologic examination. In the ex vivo experiment, the ePTFE trileaflet-valved conduits were determined to effectively increase mean pulmonary pressure from 10.2 to 14.4 mm Hg compared with defective silicon-valved conduits. In addition, the regurgitation fraction value of ePTFE trileaflet-valved conduits was 15.9% to 18.1%, which was significantly better than the defective valve conduits (regurgitation fraction = 73.5%-85.7%). In the in vivo experiment, the valved conduits were confirmed to be with good valve position maintenance, and the valve and leaflets showed no signs of thickening or peeling after a short-term implantation period. There were also no significant signs of inflammation reaction on histopathologic examination. The ePTFE trileaflet-valved conduits for pulmonary valve reconstruction showed acceptable performance and outcomes in the ex vivo and in vivo experiments. The ePTFE trileaflet-valved conduit may be clinically useful, although additional studies in animals should be conducted to determine its long-term outcomes. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  11. Radioprotective effect of vitamin E on salivary glands after radioiodine therapy for differentiated thyroid cancer: a randomized-controlled trial.

    Science.gov (United States)

    Upadhyaya, Arun; Zhou, Pingping; Meng, Zhaowei; Wang, Peng; Zhang, Guizhi; Jia, Qiang; Tan, Jian; Li, Xue; Hu, Tianpeng; Liu, Na; Wang, Sen; Liu, Xiaoxia; Wang, Huiying; Zhang, Chunmei; Zhao, Fengxiao; Yan, Ziyu; Wang, Xiaoran; Zhang, Xuemeng; Zhang, Wan

    2017-11-01

    This study aimed to examine the radioprotective effect of vitamin E on salivary glands after radioactive iodine (I) therapy in patients with differentiated thyroid cancer. Eighty-two patients with differentiated thyroid cancer were enrolled in this study. They were divided randomly into four groups (control group: 22 cases, group A: 23 cases, group B: 22 cases, and group C: 15 cases) before postsurgical ablation therapy with 100 mCi I. The patients in groups A, B, and C received vitamin E 100, 200, and 300 mg/day orally, respectively, for a duration of 1 week before to 4 weeks after I therapy. Salivary gland function was assessed using salivary gland scintigraphy immediately before and 6 months after I therapy. Uptake fraction (UF), uptake index (UI), excretion fraction (EF), and excretion ratio (ER) of each salivary gland were measured and compared. On comparison between before and after I therapy in the control group, there was a significant decrease in UF of both right and left parotid glands (all Pgland (Pgland (Pgland and both submandibular glands (all Pgland (Pgland (Pglands (all Psalivary scintigraphy parameters among the four groups, there was a significant difference in ΔUI of the right parotid gland (Pglands (all Pgland (Pgland (Pglands after I therapy.

  12. The radioprotective effects of Origanum vulgare extract against genotoxicity induced by (131)I in human blood lymphocyte.

    Science.gov (United States)

    Arami, Sanam; Ahmadi, Amirhossein; Haeri, S Abolghasem

    2013-04-01

    Radioiodine ((131)I) has been widely used for the treatment of patients with thyroid diseases. However, there is a persisting concern about the induction of second tumor and genetic damage after (131)I therapy. The purpose of this study was to investigate the radioprotective effects of Origanum vulgare extract against genotoxicity induced by (131)I in human lymphocytes. Whole blood samples from human volunteers were incubated with origanum extract at doses of 12.5, 25, 50 and 100 μg/mL. After 1 hour of incubation, the lymphocytes were incubated with (131)I (20 μCi/mL) for 1 hour. The lymphocytes were then cultured with a mitogenic stimulant to evaluate micronucleus formation in cytokinesis-blocked binucleated cells. Incubation of lymphocytes with (131)I induced additional genotoxicity and shown by increases in micronuclei (MN) frequency in human lymphocytes. Origanum at three last doses significantly reduced the MN frequency in cultured lymphocytes. The maximum protective effect and the maximum decrease in the frequency of MN were observed at 100 μg/mL of origanum, which caused a reduction of 70% (pOriganum extract also exhibited an excellent and dose-dependent radical-scavenging activity against 1,1-diphenyl-2-picrylhydrazyl-free radicals. This study has important implications for patients undergoing nuclear medicine procedures. The results indicate a protective role for origanum extract against the genetic damage induced by radiopharmaceutical administration.

  13. Radioprotection of mice by a single subcutaneous injection of heat-killed Lactobacillus casei after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Nomoto, K.; Yokokura, T.; Tsuneoka, K.; Shikita, M. (Yakult Central Institute for Microbiological Research, Tokyo (Japan))

    1991-03-01

    Treatment of whole-body gamma-irradiated mice with a preparation of Lactobacillus casei (LC 9018) immediately after irradiation caused a sustained increase in serum colony-stimulating activity which was followed by an enhanced repopulation of granulocyte-macrophage colony-forming cells in the femoral marrow and spleen. Numbers of blood leukocytes, erythrocytes, and platelets were increased earlier in the treated mice than in the controls, and the survival rate was elevated significantly. The radioprotective effect was dependent on the dose of LC 9018 as well as on the dose of radiation. These results demonstrate the value of LC 9018 for the treatment of myelosuppression after radiotherapy or radiation accidents.

  14. [Cellular radioprotective mechanisms to the action of cadmium ions on pea seedlings].

    Science.gov (United States)

    Mikhieiev, O M; Hushcha, M I; Shylina, Iu V

    2003-01-01

    The reaction of pea (Pisum sativum L.) seedlings on the test--action (gamma-radiation) depending on a phase of seedling reaction on modifying action of cadmium ions was investigated. The existence of correlation between growth rate of the seedling main root and proliferative activity of root apex meristem and the type of radiomodificating effect was established. Radioprotective (radioadaptation) effect was observed at the 5 Gy dose irradiation of the seedlings at the final moment of hypercompensatory phase of the growth reaction on the action of 0.625 MkM CdSO4.

  15. Response and Monte Carlo evaluation of a reference ionization chamber for radioprotection level at calibration laboratories

    Science.gov (United States)

    Neves, Lucio P.; Vivolo, Vitor; Perini, Ana P.; Caldas, Linda V. E.

    2015-07-01

    A special parallel plate ionization chamber, inserted in a slab phantom for the personal dose equivalent Hp(10) determination, was developed and characterized in this work. This ionization chamber has collecting electrodes and window made of graphite, and the walls and phantom made of PMMA. The tests comprise experimental evaluation following international standards and Monte Carlo simulations, employing the PENELOPE code to evaluate the design of this new dosimeter. The experimental tests were conducted employing the radioprotection level quality N-60 established at the IPEN, and all results were within the recommended standards.

  16. Light-dependent pigment migration in blowfly photoreceptors studied by in vivo CLSM

    NARCIS (Netherlands)

    Stavenga, DG; Leertouwer, HL; Smits, RP

    The light-dependent migration of pigment granules in the soma of fly photoreceptors has been studied in vivo with a fast confocal laser scanning microscope. Images as well as photometric measurements were obtained in the reflection and fluorescence modes. Measurements at the single cell level were

  17. GABAERGIC MODULATION OF STRIATAL CHOLINERGIC INTERNEURONS - AN IN-VIVO MICRODIALYSIS STUDY

    NARCIS (Netherlands)

    DEBOER, P; WESTERINK, BHC

    Striatal cholinergic interneurons have been shown to receive input from striatal gamma-aminobutyric acid (GABA)-containing cell elements. GABA is known to act on two different types of receptors, the GABA(A) and the GABA(B) receptor. Using in vivo microdialysis, we have studied the effect of

  18. An experimental model to study isolated effects of thrombin in vivo.

    NARCIS (Netherlands)

    Siller-Matula, J.M.; Bayer, G.; Bergmeister, H.; Quehenberger, P.; Petzelbauer, P.; Friedl, P.H.A.; Mesteri, I.; Jilma, B.

    2010-01-01

    BACKGROUND: In addition to a recognized role in the coagulation cascade and haemostasis, thrombin is known to have multiple functions. We hypothesized that protracted intravenous infusion of thrombin at steady state will allow to study isolated thrombin effects in vivo. METHODS: Thrombin

  19. Small animal positron emission tomography imaging and in vivo studies of atherosclerosis

    DEFF Research Database (Denmark)

    Hag, Anne Mette Fisker; Ripa, Rasmus Sejersten; Pedersen, Sune Folke

    2013-01-01

    Atherosclerosis is a growing health challenge globally, and despite our knowledge of the disease has increased over the last couple of decades, many unanswered questions remain. As molecular imaging can be used to visualize, characterize and measure biological processes at the molecular and cellu...... knowledge obtained from in vivo positron emission tomography studies of atherosclerosis performed in small animals....

  20. Real-Time Amperometric Recording of Extracellular H2O2 in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study

    Science.gov (United States)

    Reid, Caroline H.; Finnerty, Niall J.

    2017-01-01

    We detail an extensive characterisation study on a previously described dual amperometric H2O2 biosensor consisting of H2O2 detection (blank) and degradation (catalase) electrodes. In vitro investigations demonstrated excellent H2O2 sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo studies were performed to mimic physiological conditions prior to in vivo deployment. Exposure to brain tissue homogenate identified reliable sensitivity and selectivity recordings up to seven days for both blank and catalase electrodes. Furthermore, there was no compromise in pre- and post-implanted catalase electrode sensitivity in ex vivo mouse brain. In vivo investigations performed in anaesthetised mice confirmed the ability of the H2O2 biosensor to detect increases in amperometric current following locally perfused/infused H2O2 and antioxidant inhibitors mercaptosuccinic acid and sodium azide. Subsequent recordings in freely moving mice identified negligible effects of control saline and sodium ascorbate interference injections on amperometric H2O2 current. Furthermore, the stability of the amperometric current was confirmed over a five-day period and analysis of 24-h signal recordings identified the absence of diurnal variations in amperometric current. Collectively, these findings confirm the biosensor current responds in vivo to increasing exogenous and endogenous H2O2 and tentatively supports measurement of H2O2 dynamics in freely moving NOD SCID mice. PMID:28698470

  1. Real-Time Amperometric Recording of Extracellular H₂O₂ in the Brain of Immunocompromised Mice: An In Vitro, Ex Vivo and In Vivo Characterisation Study.

    Science.gov (United States)

    Reid, Caroline H; Finnerty, Niall J

    2017-07-08

    We detail an extensive characterisation study on a previously described dual amperometric H₂O₂ biosensor consisting of H₂O₂ detection (blank) and degradation (catalase) electrodes. In vitro investigations demonstrated excellent H₂O₂ sensitivity and selectivity against the interferent, ascorbic acid. Ex vivo studies were performed to mimic physiological conditions prior to in vivo deployment. Exposure to brain tissue homogenate identified reliable sensitivity and selectivity recordings up to seven days for both blank and catalase electrodes. Furthermore, there was no compromise in pre- and post-implanted catalase electrode sensitivity in ex vivo mouse brain. In vivo investigations performed in anaesthetised mice confirmed the ability of the H₂O₂ biosensor to detect increases in amperometric current following locally perfused/infused H₂O₂ and antioxidant inhibitors mercaptosuccinic acid and sodium azide. Subsequent recordings in freely moving mice identified negligible effects of control saline and sodium ascorbate interference injections on amperometric H₂O₂ current. Furthermore, the stability of the amperometric current was confirmed over a five-day period and analysis of 24-h signal recordings identified the absence of diurnal variations in amperometric current. Collectively, these findings confirm the biosensor current responds in vivo to increasing exogenous and endogenous H₂O₂ and tentatively supports measurement of H₂O₂ dynamics in freely moving NOD SCID mice.

  2. Biocompatibility assessment of modified Portland cement in comparison with MTA® : In vivo and in vitro studies

    Directory of Open Access Journals (Sweden)

    I Khalil

    2012-01-01

    Full Text Available Aim: The aim of our study is to elaborate a new cement based on Portland cement (PC, Modified Portland Cement (MPC with modified chemical and physical properties that allow easier clinical manipulation and faster setting time than MTA® and then to evaluate its cytotoxicity in vitro and its biocompatibility in vivo in comparison with MTA® . Materials and Methods: Elaboration of MPC: Portland cement powder slenderly grinded to homogenize the particles, mixed with a radiopaque element and a setting time accelerator. A comparative in vitro study (MTS test of the toxic effect of MTA® and MPC with culture isolated from the calvaria of 18-day-old fetal Swiss OF1 mice are done. A comparative in vivo study of the biocompatibility of MTA® and MPC: Under general anaesthesia, three holes (2.5 mm were made in both the left and right femurs of six White New Zealand rabbits. In the first hole MPC is placed, in the second MTA® and the third one is left empty (negative control group. Three weeks after implantation, two rabbits are sacrificed, then two other rabbits over six weeks and the last two after twelve weeks. The neck of the femur is trimmed and prepared for undecalcified histological studies. Mann-Whitney test was used to analyze the results. Results: The cell viability test according to the morphological observations suggested the biocompatibility of the two biomaterials tested. The in vivo test showed similar biocompatibility between MTA® and MPC. Bone healing and minimal inflammatory response adjacent to MTA® and MPC implants were observed at all experimental periods (3, 6 and 12 weeks, suggesting that both materials are well tolerated. Conclusion: This pilot comparative study of MTA® and MPC showed no or very limited toxic effects of both cements in vitro and similar biocompatibility in vivo. However, additional in vivo and clinical studies should be done on MPC before it can be introduced in our clinical practice.

  3. Nigrosome-1 on Susceptibility Weighted Imaging to Differentiate Parkinson's Disease From Atypical Parkinsonism: An In Vivo and Ex Vivo Pilot Study

    NARCIS (Netherlands)

    Meijer, F.J.A.; Steens, S.C.A.; Rumund, A. van; Cappellen van Walsum, A.M. van; Kusters, B.; Esselink, R.A.J.; Verbeek, M.M.; Bloem, B.R.; Góraj, B.M.

    2016-01-01

    BACKGROUND: Previous case-control studies have suggested that the absence of a swallow-tail appearance in the substantia nigra on high-resolution SWI, representing nigrosome-1, has high accuracy to identify Parkinson's disease (PD). The first goal of our study was to evaluate nigrosome-1 ex vivo

  4. Does amifostine have radioprotective effects on salivary glands in high-dose radioactive iodine-treated differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Chao; Wang, Guoming; Zuo, Shuyao [Qingdao University, Department of Nuclear Medicine, Affiliated Hospital, Medical College, Qingdao, Shandong Province (China); Xie, Jiawei [Qingdao University, Medical College, Qingdao (China); Jiang, Zhongxin [Qingdao University, Affiliated Hospital, Medical College, Qingdao (China)

    2010-09-15

    To assess the effects of amifostine on salivary glands in radioactive iodine-treated differentiated thyroid cancer. We searched the MEDLINE, EMBASE and the Cochrane Library for randomized controlled clinical trials which compared the effects of amifostine with those of placebo or acid-stimulating agents. Two randomized controlled clinical trials with a total of 130 patients were included. Both studies had a low risk of bias. There were no statistically significant differences between the effects of amifostine and acid-stimulating agents on the incidence of xerostomia (RR 0.24, 95% CI 0.01 to 9.52), the decrease of scintigraphically measured uptake of {sup 99m}Tc by the parotid (RR 0.30, 95% CI -2.28 to 2.88) or submandibular glands (RR 1.90, 95% CI -1.46 to 5.26) at 12 months, or the reduction in blood pressure (RR 5.00, 95% CI 0.25 to 99.16). Neither of the included trials investigated death from any cause, morbidity, health-related quality of life or costs. The results of two randomized controlled clinical trials suggest that amifostine has no significant radioprotective effects on salivary glands in radioactive iodine treatment of differentiated thyroid cancer. The use of acid-stimulating agents to increase salivation should remain the first choice during radioactive iodine treatment of differentiated thyroid cancer. Patients should also be well informed of the importance of hydration and acid stimulation. (orig.)

  5. Effect of chronic treatment with Rosiglitazone on Leydig cell steroidogenesis in rats: In vivo and ex vivo studies

    Directory of Open Access Journals (Sweden)

    Lima Maria C

    2010-02-01

    Full Text Available Abstract Background The present study was designed to examine the effect of chronic treatment with rosiglitazone - thiazolidinedione used in the treatment of type 2 diabetes mellitus for its insulin sensitizing effects - on the Leydig cell steroidogenic capacity and expression of the steroidogenic acute regulatory protein (StAR and cholesterol side-chain cleavage enzyme (P450scc in normal adult rats. Methods Twelve adult male Wistar rats were treated with rosiglitazone (5 mg/kg administered by gavage for 15 days. Twelve control animals were treated with the vehicle. The ability of rosiglitazone to directly affect the production of testosterone by Leydig cells ex vivo was evaluated using isolated Leydig cells from rosiglitazone-treated rats. Testosterone production was induced either by activators of the cAMP/PKA pathway (hCG and dbcAMP or substrates of steroidogenesis [22(R-hydroxy-cholesterol (22(R-OH-C, which is a substrate for the P450scc enzyme, and pregnenolone, which is the product of the P450scc-catalyzed step]. Testosterone in plasma and in incubation medium was measured by radioimmunoassay. The StAR and P450scc expression was detected by immunocytochemistry. Results The levels of total circulating testosterone were not altered by rosiglitazone treatment. A decrease in basal or induced testosterone production occurred in the Leydig cells of rosiglitazone-treated rats. The ultrastructural and immunocytochemical analysis of Leydig cells from rosiglitazone-treated rats revealed cells with characteristics of increased activity as well as increased StAR and P450scc expression, which are key proteins in androgen biosynthesis. However, a number of rosiglitazone-treated cells exhibited significant mitochondrial damage. Conclusion The results revealed that the Leydig cells from rosiglitazone-treated rats showed significant reduction in testosterone production under basal, hCG/dbcAMP- or 22 (R-OH-C/pregnenolone-induced conditions, although

  6. Black pepper constituent piperine: genotoxicity studies in vitro and in vivo.

    Science.gov (United States)

    Thiel, Anette; Buskens, Carin; Woehrle, Tina; Etheve, Stéphane; Schoenmakers, Ankie; Fehr, Markus; Beilstein, Paul

    2014-04-01

    Piperine is responsible for the hot taste of black pepper. Publications on genotoxicity of piperine are reported: negative Ames Tests and one in vitro micronucleus test (MNT). In vivo tests were mainly negative. In the majority of the data the administered dose levels did not follow the dose selection requirements of regulatory guidelines of having dose levels up to the maximum tolerated dose (MTD). The only oral high dose studies were a positive in vivo MNT in mice in contrast to a negative in vivo chromosome aberration test in rats. Thus, conflicting results in genotoxicity testing are published. To investigate this further, we administered piperine to mice up to the MTD and determined micronuclei-frequency. Piperine reduces core body temperature and interferes with blood cells both being known to result in irrelevant positive in vivo MNTs. Therefore we added mechanistic endpoints: core body temperature, haematology, erythropoietin level, and organ weights. Additionally an in vitro MNT in Chinese hamster ovary cells was performed. Piperine was negative in the in vitro MNT. It caused significant reduction of core body temperature, decrease of white blood cells and spleen weights but no increase in the micronucleus-frequency. Thus, in our studies piperine was not genotoxic. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Timing in administration of a heat-killed Lactobacillus casei preparation for radioprotection in mice

    Energy Technology Data Exchange (ETDEWEB)

    Tsuneoka, Kazuko; Ishihara, Hiroshi; Dimchev, A.B.; Shikita, Mikio (National Inst. of Radiological Sciences, Chiba (Japan)); Nomoto, Koji; Yokokura, Teruo

    1994-09-01

    A single subcutaneous injection of a preparation of heat-killed Lactobacillus casei (LC 9018), given before or after irradiation, significantly increased the survival rate of mice that had received 8.5-Gy [sup 137]Cs whole-body [gamma]-irradiation. A similar radioprotective effect was observed when LC 9018 was administered within the period from 2 days before irradiation to 9 h after irradiation, the pre-irradiation treatment being slightly better than the post-irradiation treatment. Increases in the weight of the spleen and in the number of endogenous spleen colonies on days 8 and 12 after irradiation suggested that the radioprotective effect was based on enhanced recovery of hematopoietic tissues. The activity of macrophage colony-stimulating factor (M-CSF) in serum was rapidly increased by the treatment and was maintained at the elevated level for 13 days. At the same time, an increased level of M-CSF mRNA was detected in the livers of the treated mice. However, LC 9018 failed to save the lives of mice when administered 3 days after irradiation, although it increased serum M-CSF as effectively as noted above. The small advantage of the pre-irradiation over the post-irradiation treatment was not explained by the increases of metallothionein in the hematopoietic tissues of the treated mice. (author).

  8. Radioprotection of {beta}-carotene evaluated on mouse somatic and germ cells

    Energy Technology Data Exchange (ETDEWEB)

    Salvadori, Daisy M.F.; Ribeiro, Lucia R. [Departamento de Patologia, Faculdade de Medicina, Universidade Estadual Paulista-UNESP, Botucatu-SP (Brazil); Xiao, Yun; Boei, Jan J.; Natarajan, A.T. [MGC Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratory, State University of Leiden, Leiden (Netherlands)

    1996-09-23

    In the present paper, the protective effect of {beta}-carotene was evaluated after whole body exposure of mice to 2 Gy of X-rays. Splenocytes, reticulocytes, bone marrow cells and spermatids were evaluated for the frequency of micronuclei (MN) induced by X-rays. Mice were treated (gavage) with {beta}-carotene (10, 25 and 50 mg/kg b.w.) for 5 consecutive days and, 4 h after the last treatment, the animals were irradiated. The results obtained showed different frequencies of X-ray-induced-MN between different cell populations analysed and also different response of these cells to the {beta}-carotene treatment. The radioprotective effect of {beta}-carotene was observed in splenocytes, reticulocytes, and spermatids but not in bone marrow cells. No dose-response relationship for {beta}-carotene was detected. The time of sampling, the sensitivity of the cells as well as the antioxidant activity of {beta}-carotene are discussed as important factors for the radioprotective action of this provitamin.

  9. Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.

    Directory of Open Access Journals (Sweden)

    Xinhua Chen

    Full Text Available BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.

  10. In vitro and in vivo haemolytic studies of tentacle-only extract from jellyfish Cyanea capillata.

    Science.gov (United States)

    Xiao, Liang; Zhang, Jing; Wang, Qian-qian; He, Qian; Liu, Si-hua; Li, Yue; Zhang, Li-ming

    2010-06-01

    To approach the real haemolytic process of jellyfish toxins, both in vitro and in vivo haemolysis of tentacle-only extract (TOE) from jellyfish Cyanea capillata has been studied. Dose-response curves of the haemolytic activity of TOE in vitro were sigmoid shaped in both erythrocyte suspension and diluted whole blood, with the former more sensitive to TOE. The in vivo haemolysis increased sharply in the first 10 min and was followed by a gradual increase in the following 3h, with increasing blood potassium and lactic acid accordingly. SC5b-9 complexes were significantly up-regulated in vitro, but not in vivo. These results showed that the haemolysis of TOE in diluted whole blood and in vivo is not totally consistent with that in the erythrocyte suspension, and blood plasma might play a protective role against haemolysis. Thus we suggested that erythrocyte suspension can be used to test the damage of toxin on erythrocyte membrane, while the diluted whole blood may be more suitable to test the haemolysis of toxins. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Studying liver cancer metastasis by in vivo imaging and flow cytometer

    Science.gov (United States)

    Wang, Chen; Gu, Zhengqin; Guo, Jin; Li, Yan; Liu, Guangda; Wei, Xunbin

    2009-11-01

    Primary liver cancer (hepatocellular carcinoma, or HCC) is associated with liver cirrhosis 60-80% of the time. Liver cancer is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. About 80% of people with primary liver cancer are male. Although two-thirds of people have advanced liver disease when they seek medical help, one third of the patients have cancer that has not progressed beyond the liver. HCC may metastasize to the lung, bones, kidney, and many other organs. Surgical resection, liver transplantation, chemotherapy and radiation therapy are the foundation of current HCC therapies. However the outcomes are poor: the survival rate is almost zero for metastatic HCC patients. Molecular mechanisms of HCC metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of HCC cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern liver tumor cell spread through the microenvironment in vivo with real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess liver tumor cell spreading and the circulation kinetics of liver tumor cells. A real- time quantitative monitoring of circulating liver tumor cells by the in vivo flow cytometer will be useful to assess the effectiveness of the potential therapeutic interventions.

  12. A Critical Analysis of the Available In Vitro and Ex Vivo Methods to Study Retinal Angiogenesis

    Directory of Open Access Journals (Sweden)

    A. F. Moleiro

    2017-01-01

    Full Text Available Angiogenesis is a biological process with a central role in retinal diseases. The choice of the ideal method to study angiogenesis, particularly in the retina, remains a problem. Angiogenesis can be assessed through in vitro and in vivo studies. In spite of inherent limitations, in vitro studies are faster, easier to perform and quantify, and typically less expensive and allow the study of isolated angiogenesis steps. We performed a systematic review of PubMed searching for original articles that applied in vitro or ex vivo angiogenic retinal assays until May 2017, presenting the available assays and discussing their applicability, advantages, and disadvantages. Most of the studies evaluated migration, proliferation, and tube formation of endothelial cells in response to inhibitory or stimulatory compounds. Other aspects of angiogenesis were studied by assessing cell permeability, adhesion, or apoptosis, as well as by implementing organotypic models of the retina. Emphasis is placed on how the methods are applied and how they can contribute to retinal angiogenesis comprehension. We also discuss how to choose the best cell culture to implement these methods. When applied together, in vitro and ex vivo studies constitute a powerful tool to improve retinal angiogenesis knowledge. This review provides support for researchers to better select the most suitable protocols in this field.

  13. Protection of bone marrow and gastrointestinal tract used as a criterion for comparative evaluation of effectiveness of different radioprotective agents

    Energy Technology Data Exchange (ETDEWEB)

    Pyatovskaya, N.N.; Brumberg, I.E. (Voenno-Meditsinskaya Akademiya, Leningrad (USSR))

    It has been shown on mice that unlike cystamine, 4-aminobenzo- 2,1,3-thiadiazol exerts a radioprotective effect on the haemopoietic tissue and fails to protect the gastrointestinal tract. In the bone marrow, this preparation is only effective in relation to stem cells.

  14. Precision-cut hamster liver slices as an ex vivo model to study amoebic liver abscess.

    Science.gov (United States)

    Carranza-Rosales, Pilar; Santiago-Mauricio, María Guadalupe; Guzmán-Delgado, Nancy Elena; Vargas-Villarreal, Javier; Lozano-Garza, Gerardo; Ventura-Juárez, Javier; Balderas-Rentería, Isaías; Morán-Martínez, Javier; Gandolfi, A Jay

    2010-10-01

    Entamoeba histolytica is the etiological agent of amoebiasis, the second cause of global morbidity and mortality due to parasitic diseases in humans. In approximately 1% of the cases, amoebas penetrate the intestinal mucosa and spread to other organs, producing extra-intestinal lesions, among which amoebic liver abscess (ALA) is the most common. To study ALA, in vivo and in vitro models are used. However, animal models may pose ethical issues, and are time-consuming and costly; and cell cultures represent isolated cellular lineages. The present study reports the infection of precision-cut hamster liver slices with Entamoeba histolytica trophozoites. The infection time-course, including tissue damage, parallels findings previously reported in the animal model. At the same time amoebic virulence factors were detected in the infected slices. This new model to study ALA is simple and reproducible, and employs less than 1/3 of the hamsters required for in vivo analyses. Copyright 2010 Elsevier Inc. All rights reserved.

  15. Design, development and in vitro-in vivo study of tramadol-paracetamol inlay tablets.

    Science.gov (United States)

    Kotta, Sabna; Bijumol, C; Anitha, Y; Dileep, K J; Valsala, Kumari

    2014-02-01

    The objective of this work is to formulate, optimize and evaluate in-lay tablets of tramadol-paracetamol. This study investigated the effect of hydrophobic, plastic and hydrophilic types of polymers and their content level on release profile of a highly water-soluble drug tramadol hydrochloride. A 3(2) full factorial design was employed for the optimization of the sustained release (SR) formula of tramadol hydrochloride using ethyl cellulose, eudragit and carbopol. CP9 (66% carbopol and compression load of 6 ton) with a percentage drug release of 89.03 after 12 hours were found to be most comparable to the marketed product in terms of similarity factor and most appropriately fits to zero-order kinetics. Hence, it was selected for in vivo study. Statistical analysis of in vivo studies showed that the plasma drug level after oral administration from the prepared formulation is almost comparable to the marketed product (p 971).

  16. A nanoparticle dispersion method for in vitro and in vivo nanotoxicity study.

    Science.gov (United States)

    Kim, Seong C; Chen, Da-Ren; Qi, Chaolong; Gelein, Robert M; Finkelstein, Jacob N; Elder, Alison; Bentley, Karen; Oberdörster, Günter; Pui, David Y H

    2010-03-01

    The dispersion in air of nanoparticles of different sizes, materials and morphologies with controlled agglomeration involving aerosol delivery for in vivo and in vitro studies is one of the most difficult challenges in the field of nanoparticle toxicology. We describe here a nanoparticle dispersion system using an electrospray method to deliver airborne nanoparticles (approximately 10-100 nm) with spatial uniformity and controllable particle concentration for in vitro and in vivo studies. With the dispersion method, single nanoparticles (polystyrene latex particles, TiO(2), Au, Mn, quantum dots, and carbon nanotubes) can be delivered to cells and animals via the air. The degree of agglomeration can be controlled by changing the suspension feeding rate to simulate realistic conditions for exposure studies.

  17. Radioprotective Effect of Propolis on the Blood Corpuscle of a Mouse by SEM after X-irradiation on the Whole Body

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Tae Jeong [Dept. of Radiological Science, Kaya University, Kimhae (Korea, Republic of)

    2008-03-15

    After x-ray 5 Gy radiation on the whole body of a mouse using a linear accelerator, its leucocyte, erythrocyte, and platelet were observed by SEM. Also, after injecting propolis into the abdominal cavity, the radio-protective effect of blood corpuscles was studied. The observation of micromorphology in blood corpuscles revealed that the number of leukocyte, erythrocyte, and thrombocyte decreased in the experimental group and the lump got together in blood corpuscles after 10 and 20 days. In RBC, crack or break on the surface and poikilosperocytes were observed. In the irradiation group, the size of leucocytes was smaller than that in control group and the number of villus at the verge substantially decreased. The blood corpuscles in the propolis group, however, had the similar results to control group.

  18. Radioprotective and In-Vitro Cytotoxic Sapogenin from Euphorbia ...

    African Journals Online (AJOL)

    Purpose: Euphorbia neriifolia Linn. (Euphorbiaceae) plant is traditionally used in the treatment of abdominal troubles, bronchitis, tumours, leucoderma, piles, inflammation, and enlargement of spleen. The objective of this study was to evaluate the antioxidant and anticancer activities of a sapogenin isolate of this plant.

  19. In vivo functional genomic studies of sterol carrier protein-2 gene in the yellow fever mosquito.

    Directory of Open Access Journals (Sweden)

    Rong Peng

    Full Text Available A simple and efficient DNA delivery method to introduce extrachromosomal DNA into mosquito embryos would significantly aid functional genomic studies. The conventional method for delivery of DNA into insects is to inject the DNA directly into the embryos. Taking advantage of the unique aspects of mosquito reproductive physiology during vitellogenesis and an in vivo transfection reagent that mediates DNA uptake in cells via endocytosis, we have developed a new method to introduce DNA into mosquito embryos vertically via microinjection of DNA vectors in vitellogenic females without directly manipulating the embryos. Our method was able to introduce inducible gene expression vectors transiently into F0 mosquitoes to perform functional studies in vivo without transgenic lines. The high efficiency of expression knockdown was reproducible with more than 70% of the F0 individuals showed sufficient gene expression suppression (<30% of the controls' levels. At the cohort level, AeSCP-2 expression knockdown in early instar larvae resulted in detectable phenotypes of the expression deficiency such as high mortality, lowered fertility, and distorted sex ratio after induction of AeSCP-2 siRNA expression in vivo. The results further confirmed the important role of AeSCP-2 in the development and reproduction of A. aegypti. In this study, we proved that extrachromosomal transient expression of an inducible gene from a DNA vector vertically delivered via vitellogenic females can be used to manipulate gene expression in F0 generation. This new method will be a simple and efficient tool for in vivo functional genomic studies in mosquitoes.

  20. Chitosan-alginate capsules as oral delivery system for insulin: studies in vitro and in vivo

    OpenAIRE

    Rodrigues, C.A.; R. M. LUCINDA-SILVA; P. CLASEN; S. MAFFEZZOLLI; Bürger, C

    2009-01-01

    The aim of this study was to assess chitosan:alginate capsules as gastric resistant systems for oral administration of insulin. Chitosan:alginate capsules of insulin were tested in simulated gastric and intestinal media and in vivo. The capsules released only about 20% of the insulin after 60 minutes of incubation in simulated gastric medium. On the other hand, almost all the encapsulated insulin was released after being incubated for 90 min in simulated intestinal medium. When capsules conta...

  1. Antitumor effects of Osthol from Cnidium monnieri: an in vitro and in vivo study.

    Science.gov (United States)

    Chou, Szu-Yuan; Hsu, Chun-Sen; Wang, Kun-Teng; Wang, Min-Chieh; Wang, Ching-Chiung

    2007-03-01

    Cnidium monnieri (L.) Cusson is a Chinese medicine which is used widely by traditional medicine doctors. Osthol is a major bio-activity compound of the herb. In this study, osthol was isolated from C. monnieri and its in vitro and in vivo antitumor effects studied. The results of the in vitro study showed: that osthol inhibited the growth of HeLa, in a time- and concentration-dependent manner, with IC(50) values of 77.96 and 64.94 microm for 24 and 48 h, respectively; that osthol had lower cytotoxic effects in primary cultured normal cervical fibroblasts; and that increased DNA fragmentation and activated PARP in HeLa after treatment with osthol which could induce apoptosis. The results of the in vivo model showed that the survival days of the P-388 D1 tumor-bearing CDF(1) mice were prolonged (ILS% = 37) after osthol (30 mg/kg) was given once a day for 9 days. Based on these results, it is suggested that osthol could inhibit P-388 D1 cells in vivo and induce apoptosis in HeLa cells in vitro, and that osthol is good lead compound for developing antitumor drugs. However, C. formosanum Yabe of Taiwan's endemic plants contained little osthol, with no imperatorin, and its major components were different from that of C. monnieri. Therefore, it is suggested that C. formosanum also may possess economic worth.

  2. Improving In Vitro to In Vivo Extrapolation by Incorporating Toxicokinetic Measurements: A Case Study of Lindane-Induced Neurotoxicity

    Science.gov (United States)

    Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicit...

  3. Descemet Membrane Thickening as a Sign for the Diagnosis of Corneal Graft Rejection: An Ex Vivo Study.

    Science.gov (United States)

    VanDenBerg, Ryan; Diakonis, Vasilios F; Bozung, Alison; Gameiro, Gustavo Rosa; Fischer, Oliver; El Dakkak, Ahmed; Ulloa-Padilla, Jan Paul; Anagnostopoulos, Apostolos; Dubovy, Sander; Abou Shousha, Mohamed

    2017-12-01

    To disclose, using an ex vivo study, the histopathological mechanism behind in vivo thickening of the endothelium/Descemet membrane complex (En/DM) observed in rejected corneal grafts (RCGs). Descemet membrane (DM), endothelium, and retrocorneal membranes make up the total En/DM thickness. These layers are not differentiable by high-definition optical coherence tomography; therefore, the source of thickening is unclear from an in vivo perspective. A retrospective ex vivo study (from September 2015 to December 2015) was conducted to measure the thicknesses of DM, endothelium, and retrocorneal membrane in 54 corneal specimens (31 RCGs and 23 controls) using light microscopy. Controls were globes with posterior melanoma without corneal involvement. There were 54 corneas examined ex vivo with mean age 58.1 ± 12.2 in controls and 51.7 ± 27.9 years in RCGs. The ex vivo study uncovered the histopathological mechanism of En/DM thickening to be secondary to significant thickening (P vivo study shows that DM is responsible for thickening of the En/DM in RCGs observed in vivo by high-definition optical coherence tomography and not the endothelium or retrocorneal membrane.

  4. Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

    Science.gov (United States)

    Biegon, Anat; Kim, Sung-Won; Logan, Jean; Hooker, Jacob M.; Muench, Lisa; Fowler, Joanna S.

    2010-01-01

    Background Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Methods Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [11C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Results Nicotine administration produced significant, dose-dependent reductions in [11C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Conclusions Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior. PMID:20188349

  5. Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Biegon, A.; Kim, S.-W.; Logan, J.; Hooker, J.M.; Muench, L.; Fowler, J.S.

    2010-01-12

    Cigarette smoking and nicotine have complex effects on human physiology and behavior, including some effects similar to those elicited by inhibition of aromatase, the last enzyme in estrogen biosynthesis. We report the first in vivo primate study to determine whether there is a direct effect of nicotine administration on brain aromatase. Brain aromatase availability was examined with positron emission tomography and the selective aromatase inhibitor [{sup 11}C]vorozole in six baboons before and after exposure to IV nicotine at .015 and .03 mg/kg. Nicotine administration produced significant, dose-dependent reductions in [{sup 11}C]vorozole binding. The amygdala and preoptic area showed the largest reductions. Plasma levels of nicotine and its major metabolite cotinine were similar to those found in cigarette smokers. Nicotine interacts in vivo with primate brain aromatase in regions involved in mood, aggression, and sexual behavior.

  6. Anxiety reactivity and anxiety perseveration represent independent dimensions of anxiety vulnerability: an in vivo study.

    Science.gov (United States)

    Rudaizky, Daniel; MacLeod, Colin

    2014-01-01

    Trait anxiety is a relatively stable disposition reflecting an individual's tendency to experience anxious symptomatology, typically measured using questionnaires such as the Spielberger Trait Anxiety Inventory (STAI-T). While trait anxiety commonly is considered a unitary construct, recent questionnaire research suggests that two different dimensions of anxiety vulnerability account for independent variance in trait anxiety scores. These dimensions are anxiety reactivity (AR), reflecting the intensity of anxiety reactions to stressors, and anxiety perseveration (AP), reflecting the persistence of anxiety symptoms. This study investigated whether in vivo measures of these two facets independently contribute to anxiety vulnerability. Seventy-two participants were exposed to a novel stress task designed to yield measures of AR and AP. Regression analysis determined that these in vivo measures were unrelated to each other, and each accounted for independent variance in trait anxiety scores. The implications of these findings for the assessment and understanding of anxiety vulnerability are discussed.

  7. In Vivo Imaging Study of Angiogenesis in a Channelized Porous Scaffold

    Directory of Open Access Journals (Sweden)

    Margherita Tamplenizza

    2015-05-01

    Full Text Available The main scientific issue hindering the development of tissue engineering technologies is the lack of proper vascularization. Among the various approaches developed for boosting vascularization, scaffold design has attracted increasing interest over the last few years. The aim of this article is to illustrate a scaffold design strategy for enhancing vascularization based on sacrificial microfabrication of embedded microchannels. This approach was combined with an innovative poly(ether urethane urea (PEUtU porous scaffold to provide an alternative graft substitute material for the treatment of tissue defects. Fluorescent and chemiluminescent imaging combined with computed tomography were used to study the behavior of the scaffold composition within living subjects by analyzing angiogenesis and inflammation processes and observing the variation in x-ray absorption, respectively. For this purpose, an IntegriSense 680 probe was used in vivo for the localization and quantification of integrin αvβ3, due to its critical involvement in angiogenesis, and a XenoLight RediJect Inflammation Probe for the study of the decline in inflammation progression during healing. Overall, the collected data suggest the advantages of embedding a synthetic vascular network into a PEUtU porous matrix to enhance in vivo tissue integration, maturation, and regeneration. Moreover, our imaging approach proved to be an efficient and versatile tool for scaffold in vivo testing.

  8. Hepatoprotective activity of Sapindus mukorossi and Rheum emodi extracts: in vitro and in vivo studies.

    Science.gov (United States)

    Ibrahim, Mohammed; Khaja, Mohammed Nane; Aara, Anjum; Khan, Aleem Ahmed; Habeeb, Mohammed Aejaz; Devi, Yalavarthy Prameela; Narasu, Mangamoori Lakshmi; Habibullah, Chitoor Mohammed

    2008-04-28

    To study the hepatoprotective capacity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi) extracts in CCl(4) treated male rats. The dried powder of S. mukorossi and R. emodi was extracted successively with petroleum ether, benzene, chloroform, and ethanol and concentrated in vacuum. Primary rat hepatocyte monolayer cultures were used for in vitro studies. In vivo, the hepatoprotective capacity of the extract of the fruit pericarp of S. mukorossi and the rhizomes of R. emodi was analyzed in liver injured CCl(4)-treated male rats. In vitro: primary hepatocytes monolayer cultures were treated with CCl(4) and extracts of S. mukorossi & R. emodi. A protective activity could be demonstrated in the CCl(4) damaged primary monolayer culture. In vivo: extracts of the fruit pericarp of S. mukorossi (2.5 mg/mL) and rhizomes of R. emodi (3.0 mg/mL) were found to have protective properties in rats with CCl(4) induced liver damage as judged from serum marker enzyme activities. The extracts of S. mukorossi and R. emodi do have a protective capacity both in vitro on primary hepatocytes cultures and in in vivo in a rat model of CCl(4) mediated liver injury.

  9. Efficacy of biogenic selenium nanoparticles against Leishmania major: in vitro and in vivo studies.

    Science.gov (United States)

    Beheshti, Nasibeh; Soflaei, Saied; Shakibaie, Mojtaba; Yazdi, Mohammad Hossein; Ghaffarifar, Fatemeh; Dalimi, Abdolhossein; Shahverdi, Ahmad Reza

    2013-07-01

    This study investigated the in vitro and in vivo effectiveness of biogenic selenium nanoparticles (Se NPs), biosynthesized by Bacillus sp. MSh-1, against Leishmania major (MRHO/IR/75/ER). The 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay was used to evaluate the cytotoxicity effects of the biogenic Se NPs against both promastigote and amastigote forms of L. major. In a separate in vivo experiment, we also determined the preventive and therapeutic effects of biogenic Se NPs in BALB/c mice following subcutaneous infected with L. major. The MTT assays showed that the highest toxicity occurred after 72 h against both promastigote and amastigote forms of L. major. The cytotoxicity of Se NPs was higher at all incubation times (24, 48, and 72 h) against the promastigote than the amastigote form (pdoses of biogenic Se NPs delayed the development of localized cutaneous lesions. Moreover, daily administration of Se NPs (5 or 10 mg kg(-1) day(-1)) in similarly infected BALB/c mice that had not received prophylactic doses of Se NPs also abolished the localized lesions after 14 days. Based on these in vitro and in vivo studies, biogenic Se NPs can be considered as a novel therapeutic agent for treatment of the localized lesions typical of cutaneous leishmaniasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

  10. Crystallization Study and Comparative in Vitro–in Vivo Hydrolysis of PLA Reinforcement Ligament

    Science.gov (United States)

    Beslikas, Theodore; Gigis, Ioannis; Goulios, Vasilios; Christoforides, John; Papageorgiou, George Z.; Bikiaris, Dimitrios N.

    2011-01-01

    In the present work, the crystallization behavior and in vitro–in vivo hydrolysis rates of PLA absorbable reinforcement ligaments used in orthopaedics for the repair and reinforcement of articulation instabilities were studied. Tensile strength tests showed that this reinforcement ligament has similar mechanical properties to Fascia Latta, which is an allograft sourced from the ilio-tibial band of the human body. The PLA reinforcement ligament is a semicrystalline material with a glass transition temperature around 61 °C and a melting point of ~178 °C. Dynamic crystallization revealed that, although the crystallization rates of the material are slow, they are faster than the often-reported PLA crystallization rates. Mass loss and molecular weight reduction measurements showed that in vitro hydrolysis at 50 °C initially takes place at a slow rate, which gets progressively higher after 30–40 days. As found from SEM micrographs, deterioration of the PLA fibers begins during this time. Furthermore, as found from in vivo hydrolysis in the human body, the PLA reinforcement ligament is fully biocompatible and after 6 months of implantation is completely covered with flesh. However, the observed hydrolysis rate from in vivo studies was slow due to high molecular weight and degree of crystallinity. PMID:22072906

  11. The role of chloride channels in rat corpus cavernosum: in vivo study.

    Science.gov (United States)

    Chung, Shiu-Dong; Kuo, Yuh-Chen; Liu, Shih-Ping; Chang, Hong-Chiang; Yu, Hong-Jeng; Hsieh, Ju-Ton

    2009-03-01

    Recent studies have identified the existence of outward, depolarizing chloride currents in isolated rat, rabbit, and human corpus cavernosum muscle cells. However, few articles have demonstrated the functional role of chloride channels in vivo in corpus cavernosum smooth muscle. Aim. To investigate the role of calcium-dependent chloride channels in erectile function of rat corpus cavernosum smooth muscle. Adult male Wistar rats were used to perform an in vivo study in a rat model of erection. Both crura of the rats were isolated to in order to record intracavernosal pressure (ICP) during basal conditions and electrical stimulation of erection, with and without intracorporeal injection of norepinephrine, chloride transport inhibitors, and chloride channel blockers. ICP. ICP increased as the amplitude of electrical stimulation increased, and decreased in a dose-dependent manner (during electrical stimulation) as norepinephrine injection strength increased. Injection into the corpus cavernosum of the Cl(-) channel blockers, niflumic acid, anthracene-9-carboxylic acid, and 4,4'-diisothiocyano-2,2'-stilbene-disulfonic acid increased ICP. Injection into the corpus cavernosum of the Cl(-) channel transport inhibitors bumetanide, ethacrynic acid, and HCO(3)-free 4-(2-hydroxyethyl )-1-1- piperazine ethanesulphonic acid buffer, and also increase the ICP. The effects of both Cl(-) channel blockers and Cl(-) channel transport inhibitors on ICP were concentration-dependent. Our findings suggest that chloride channels play an important role in the regulation of corpus cavernous smooth muscle tone in vivo.

  12. Synthetic trehalose dicorynomycolate (S-TDCM). Behavioral effects and radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Landauer, M.R.; Mcchesney, D.G.; Ledney, G.D. [Armed Forces Radiobiology Research Inst., Bethesda, MD (United States)

    1997-03-01

    This study evaluated synthetic trehalose dicorynomycolate (S-TDCM), an immunomodulator, for its survival enhancing capacity and behavioral toxicity in B6D2F1 female mice. In survival experiments, mice were administered S-TDCM (25-400 {mu}g/mouse i.p.) 20-24 hr before 5.6 Gy mixed-field fission-neutron irradiation (n) and {gamma}-photon irradiation. The 30-day survival rates for mice treated with 100-400 {mu}g/mouse S-TDCM were significantly enhanced compared to controls. Toxicity of S-TDCM was measured in nonirradiated mice by locomotor activity, food intake, water consumption, and alterations in body weight. A dose-dependent decrease was noted in all behavioral measures in mice treated with S-TDCM. Doses of 100 and 200 {mu}g/mouse S-TDCM significantly reduced motor activity beginning 12 hr postinjection with recovery by 24 hr. A dose of 400 {mu}g/mouse significantly decreased activity within the first 4 hr after administration and returned to control levels by 32 hr following injection. Food and water intake were significantly depressed at doses of 200 and 400 {mu}g/mouse on the day following drug administration, and were recovered in 24 hr. Body weight was significantly decreased in the 200 {mu}g/mouse group for 2 days and in the 400 {mu}g/mouse group for 4 days following injection. A dose of 100 {mu}g/mouse effectively enhanced survival after fission-neutron irradiation with no adverse effect on food consumption, water intake, or body weight and a minimal, short-term effect on locomotor activity. (author)

  13. Drosophila melanogaster as an animal model for the study of Pseudomonas aeruginosa biofilm infections in vivo.

    Directory of Open Access Journals (Sweden)

    Heidi Mulcahy

    2011-10-01

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen capable of causing both acute and chronic infections in susceptible hosts. Chronic P. aeruginosa infections are thought to be caused by bacterial biofilms. Biofilms are highly structured, multicellular, microbial communities encased in an extracellular matrix that enable long-term survival in the host. The aim of this research was to develop an animal model that would allow an in vivo study of P. aeruginosa biofilm infections in a Drosophila melanogaster host. At 24 h post oral infection of Drosophila, P. aeruginosa biofilms localized to and were visualized in dissected Drosophila crops. These biofilms had a characteristic aggregate structure and an extracellular matrix composed of DNA and exopolysaccharide. P. aeruginosa cells recovered from in vivo grown biofilms had increased antibiotic resistance relative to planktonically grown cells. In vivo, biofilm formation was dependent on expression of the pel exopolysaccharide genes, as a pelB::lux mutant failed to form biofilms. The pelB::lux mutant was significantly more virulent than PAO1, while a hyperbiofilm strain (PAZHI3 demonstrated significantly less virulence than PAO1, as indicated by survival of infected flies at day 14 postinfection. Biofilm formation, by strains PAO1 and PAZHI3, in the crop was associated with induction of diptericin, cecropin A1 and drosomycin antimicrobial peptide gene expression 24 h postinfection. In contrast, infection with the non-biofilm forming strain pelB::lux resulted in decreased AMP gene expression in the fly. In summary, these results provide novel insights into host-pathogen interactions during P. aeruginosa oral infection of Drosophila and highlight the use of Drosophila as an infection model that permits the study of P. aeruginosa biofilms in vivo.

  14. Cannabinoid antagonist in nanostructured lipid carriers (NLCs): design, characterization and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Esposito, Elisabetta; Ravani, Laura [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Drechsler, Markus [BIMF/Soft Matter Electron Microscopy, University of Bayreuth (Germany); Mariani, Paolo [Department of Life and Environmental Sciences and CNISM, Università Politecnica delle Marche, I-60100 Ancona (Italy); Contado, Catia [Department of Chemical and Pharmaceutical Sciences, University of Ferrara, I-44121 Ferrara (Italy); Ruokolainen, Janne [Department of Applied Physics, Aalto University, 00076 Aalto (Finland); Ratano, Patrizia; Campolongo, Patrizia [Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Roma (Italy); Trezza, Viviana [Department of Science, Roma Tre University, 00146 Roma (Italy); Nastruzzi, Claudio, E-mail: nas@unife.it [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy); Cortesi, Rita [Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara (Italy)

    2015-03-01

    This study describes the preparation, characterization, and in vivo evaluation in rats of nanostructured lipid carriers (NLCs) encapsulating rimonabant (RMN) as prototypical cannabinoid antagonist. A study was conducted in order to optimize NLC production by melt and ultrasonication method. NLCs were prepared by alternatively adding the lipid phase into the aqueous one (direct protocol) or the aqueous phase into the lipid one (reverse protocol). RMN-NLCs have been characterized by cryogenic transmission electron microscopy (cryo-TEM), X-ray, photon correlation spectroscopy (PCS) and sedimentation field flow fractionation (SdFFF). Reverse NLCs were treated with polysorbate 80. RMN release kinetics have been determined in vitro by dialysis method. In vivo RMN biodistribution in rats was evaluated after intranasal (i.n.) administration of reverse RMN-NLC. The reverse protocol enabled to prevent the lost of lipid phase and to achieve higher RMN encapsulation efficacy (EE) with respect to the direct protocol (98% w/w versus 67% w/w). The use of different protocols did not affect NLC morphology and dimensional distribution. An in vitro dissolutive release rate of RMN was calculated. The in vivo data indicate that i.n. administration of RMN by reverse NLC treated with polysorbate 80 increased RMN concentration in the brain with respect to the drug in solution. The nanoencapsulation protocol presented here appears as an optimal strategy to improve the low solubility of cannabinoid compounds in an aqueous system suitable for in vivo administration. - Highlights: • Rimonabant (RMN) can be encapsulated in nanostructured lipid carriers (NLCs). • Nanoencapsulation improves RMN solubility in a stable physiologic aqueous formulation. • RMN is released in vitro from NLC by a controlled dissolutive release modality. • I.n. administration leads to higher RMN concentration in the brain with respect to plasma. • NLC increases RMN concentration in the brain with respect to

  15. Botulinum Toxin Confers Radioprotection in Murine Salivary Glands

    Energy Technology Data Exchange (ETDEWEB)

    Zeidan, Youssef H., E-mail: zeidan@miami.edu [Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, Florida (United States); Xiao, Nan; Cao, Hongbin [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Kong, Christina [Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, California (United States); Department of Pathology, Stanford University School of Medicine, Stanford, California (United States); Le, Quynh-Thu; Sirjani, Davud [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States)

    2016-04-01

    Purpose: Xerostomia is a common radiation sequela, which has a negative impact on the quality of life of patients with head and neck cancer. Current treatment strategies offer only partial relief. Botulinum toxins (BTX) have been successfully used in treating a variety of radiation sequelae such as cystitis, proctitis, fibrosis, and facial pain. The purpose of this study was to evaluate the effect of BTX on radiation-induced salivary gland damage. Methods and Materials: We used a previously established model for murine salivary gland irradiation (IR). The submandibular glands (SMGs) of C5BL/6 mice (n=6/group) were injected with saline or BTX 72 hours before receiving 15 Gy of focal irradiation. Saliva flow was measured 3, 7, and 28 days after treatment. The SMGs were collected for immunohistochemistry, confocal microscopy, and Western blotting. A cytokine array consisting of 40 different mouse cytokines was used to evaluate cytokine profiles after radiation treatment. Results: Irradiated mice showed a 50% reduction in saliva flow after 3 days, whereas mice preinjected with BTX had 25% reduction in saliva flow (P<.05). Cell death detected by TUNEL staining was similar in SMG sections of both groups. However, neutrophil infiltrate, detected by myeloperoxidase staining, was 3-fold lower for the BTX treated mice. A cytokine array showed a 2-fold upregulation of LPS-induced chemokine (LIX/CXCL5) 3 days after IR. BTX pretreatment reduced LIX levels by 40%. At 4 weeks after IR, the saline (control) group showed a 40% reduction in basal SMG weight, compared with 20% in the BTX group. Histologically, BTX-pretreated glands showed relative preservation of acinar structures after radiation. Conclusions: These data suggest that BTX pretreatment ameliorates radiation-induced saliva dysfunction. Moreover, we demonstrate a novel role for CXCL5 in the acute phase of salivary gland damage after radiation. These results carry important clinical implications for the treatment of

  16. Effect of renal perfusion and structural heterogeneity on shear wave elastography of the kidney: an in vivo and ex vivo study.

    Science.gov (United States)

    Liu, Xiaona; Li, Na; Xu, Tao; Sun, Fang; Li, Rui; Gao, Qimin; Chen, Lianxiang; Wen, Chaoyang

    2017-08-08

    To evaluate the effect of perfusion status on elasticity measurements of different compartments in the kidney using shear wave elastography (SWE) both in vivo and ex vivo. Thirty-two rabbit kidneys were used to observe the elasticity variation caused by renal artery stenosis and vein ligation in vivo, and six beagle kidneys were studied ex vivo to explore the effect of renal perfusion on elasticity. Supersonic SWE was applied to quantify the elasticity values of different renal compartments (cortex, medulla and sinus). Additionally, histopathological examination was performed to explore the possible mechanisms. The elasticity of the cortex was higher than that of the medulla, and the elasticity of the sinus was lowest among the compartments in native kidneys. The Young's modulus (YM) of the cortex, medulla and sinus increased gradually as the duration of renal vein ligation increased, from 16.34 ± 1.01 kPa to 55.06 ± 5.61 kPa, 13.71 ± 1.16 kPa to 39.63 ± 2.91 kPa, and 12.61 ± 0.84 kPa to 29.30 ± 2.04 kPa, respectively. In contrast, the YM of the three compartments respectively decreased with progressive artery stenosis, from 16.34 ± 1.83 kPa to 11.21 ± 1.79 kPa, 13.31 ± 1.67 kPa to 8.07 ± 1.37 kPa, and 12.78 ± 2.66 kPa to 6.72 ± 0.95 kPa. Artery perfusion was the main factor influencing elasticity in ex vivo. The cortical elasticity was more prone to change with renal perfusion both in vivo and ex vivo. Histopathological examination showed progressive changes in the structure and content of the three compartments, consistent with the elasticity variation. Both the complex structure/anisotropy and the perfusion of the kidney obviously influence the evaluation of renal elasticity. The measurement of SWE should be performed at a specific location along a certain angle or direction, and renal perfusion status should also be taken into account to ensure reproducible detection.

  17. Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges.

    Science.gov (United States)

    Chapman, Kathryn; Adjei, Akosua; Baldrick, Paul; da Silva, Antonio; De Smet, Karen; DiCicco, Richard; Hong, Seung Suh; Jones, David; Leach, Michael W; McBlane, James; Ragan, Ian; Reddy, Praveen; Stewart, Donald I H; Suitters, Amanda; Sims, Jennifer

    2016-01-01

    Biosimilars are biological medicinal products that contain a version of the active substance of an already authorised original biological medicinal product (the innovator or reference product). The first approved biosimilar medicines were small proteins, and more recently biosimilar versions of innovator monoclonal antibody (mAb) drugs have entered development as patents on these more complex proteins expire. In September 2013, the first biosimilar mAb, infliximab, was authorised in Europe. In March 2015, the first biosimilar (Zarxio™, filgrastim-sndz, Sandoz) was approved by the US Food and Drug Administration; however, to date no mAb biosimilars have been approved in the US. There are currently major differences between how biosimilars are regulated in different parts of the world, leading to substantial variability in the amount of in vivo nonclinical toxicity testing required to support clinical development and marketing of biosimilars. There are approximately 30 national and international guidelines on biosimilar development and this number is growing. The European Union's guidance describes an approach that enables biosimilars to enter clinical trials based on robust in vitro data alone; in contrast, the World Health Organization's guidance is interpreted globally to mean in vivo toxicity studies are mandatory. We reviewed our own experience working in the global regulatory environment, surveyed current practice, determined drivers for nonclinical in vivo studies with biosimilar mAbs and shared data on practice and study design for 25 marketed and as yet unmarketed biosimilar mAbs that have been in development in the past 5y. These data showed a variety of nonclinical in vivo approaches, and also demonstrated the practical challenges faced in obtaining regulatory approval for clinical trials based on in vitro data alone. The majority of reasons for carrying out nonclinical in vivo studies were not based on scientific rationale, and therefore the authors

  18. Crystal and molecular structure of N-(thioacetyl)tryptamine. A radioprotective indole compound

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, T.; Shimizu, S.; Inoue, M. (Osaka Coll. of Pharmacy, Matsubara (Japan)); Kitamura, K.; Wakahara, A.; Tomita, K.; Shinoda, M.

    1981-04-01

    The crystal structure of N-(thioacetyl)tryptamine, a radioprotective agent, has been determined by the X-ray method. The crystal is monoclinic, space, group P2/sub 1//c with the unit cell dimensions: a = 23.761 (5), b = 5.553 (1), c = 8.889 (2) A, and ..beta.. = 94.04 (4)/sup 0/. The structure was solved by the direct method and succesive Fourier syntheses, and refined by the block-diagonal least-squares method to give a final R-value of 0.072. In the crystal, the molecules are held together with van der Waals contacts between the nonpolar groups of adjacent molecules, and an intermolecular hydrogen bond between the sulfur and nitrogen atoms of the side chain (N-H ... S = 3.322 A). The folded conformation observed in this compound could be related to the protection of DNA against irradiation.

  19. Safety and radioprotection issues with post-accelerated high intensity ribs

    Science.gov (United States)

    Moscatello, Marie-Hélène

    2008-10-01

    Radioactive ion beams have been produced with the ISOL method for more than 35 years in several laboratories all over the world. The intensities and the variety of nuclei have been always growing, and while the ISOL beams were first used at ion source extraction energy, post-accelerated RIBs became available following the pioneering work at Louvain-la-Neuve. Meanwhile, a powerful production method was developed with the use of fission products extracted from fissile targets, and is nowadays used at several places. The next facilities, under construction and those of next generation, will use fission as one of the main production methods for RIBs and will offer orders of magnitude higher intensities. The post-acceleration of such high intensity and long lived RIBs implies many new constraints. This paper presents these constraints for the facilities under construction and those of next generation, focusing on the safety and radioprotection issues.

  20. Ex vivo comparative study on three sinus lift tools for transcrestal detaching maxillary sinus mucosa.

    Science.gov (United States)

    Li, Yanfeng; Hu, Pin; Han, Yishi; Fan, Jiadong; Dong, Xinming; Ren, Huan; Yang, Chunhao; Shi, Tingting; Xia, Dong

    2017-07-04

    The objective of this study was to comparatively evaluate 3 different sinus lift tools, namely umbrella-shaped sinus lift curette YSL-04, our recently designed probe-improved sinus lift curettes, and our newly invented elevator 014, using our previous developed goat ex vivo models for direct visualizing the effectiveness of detaching sinus mucosa in real time. Goat ex vivo models for direct visualizing the effectiveness of detaching sinus mucosa in real time were generated according to our previously developed protocol. The effectiveness for each tool was evaluated through the length of sinus mucosa detached in mesial and distal directions or buccal and palatal directions, and the space volume created by detaching maxillary sinus mucosa in mesial, distal, buccal and palatal directions. The results showed that all 3 sinus lift tools could transcrestally detach the maxillary sinus mucosa and create extra space under the elevated sinus floor on the goat ex vivo sinus models. Moreover, our newly invented elevator 014 had advantages over the other 2 in term of the capability to detach the sinus mucosa. Our newly invented elevator 014 might be a promising tool for detaching maxillary sinus mucosa in transcrestal maxillary sinus floor elevation.

  1. Studying circulating prostate cancer cells by in-vivo flow cytometer

    Science.gov (United States)

    Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2012-03-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

  2. Studies on the in vivo biotransformation of the tobacco alkaloid beta-nicotyrine.

    Science.gov (United States)

    Liu, X; Castagnoli, K; Van Der Schyf, C J; Castagnoli, N

    2000-05-01

    This paper reports the results of studies on the in vivo metabolic fate of the tobacco alkaloid 1-methyl-2-(3-pyridinyl)pyrrole (beta-nicotyrine) in New Zealand white rabbits. Two previously characterized metabolites, 5-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (5-hydroxycotinine) and 2-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one, were present in low concentrations in the urine of the treated animals. The major urinary metabolite of beta-nicotyrine was identified as cis-3'-hydroxy-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone (cis-3'-hydroxycotinine), the diastereoisomer of the major urinary metabolite of (S)-nicotine. The pathway leading to cis-3'-hydroxycotinine is proposed to proceed via autoxidation of 2-hydroxy-1-methyl-5-(3-pyridinyl)pyrrole, a postulated cytochrome P450-generated metabolite of beta-nicotyrine, followed by reduction of the carbon-carbon double bond present in the resulting 3-hydroxy-3-pyrrolin-2-one species. This proposal is supported by the in vivo biotransformation of 2-acetoxy-1-methyl-5-(3-pyridinyl)pyrrole, a latent form of the putative hydroxypyrrole intermediate, to cis-3'-hydroxycotinine. The in vivo conversion of 5-hydroxy-1-methyl-5-(3-pyridinyl)-3-pyrrolin-2-one to 5-hydroxycotinine is offered as evidence that supports the proposed reduction step.

  3. In vivo neutron activation analysis: body composition studies in health and disease

    Energy Technology Data Exchange (ETDEWEB)

    Ellis, K.J.; Cohn, S.H.

    1984-01-01

    In vivo analysis of body elements by neutron activation is an important tool in medical research. It has provided a direct quantitative measure of body composition of human beings in vivo. Basic physiological differences related to age, sex, race, and body size have been assessed by this noninvasive technique. The diagnosis and management of patients with various metabolic disorders and diseases has also been demonstrated. Two major facilities at Brookhaven are being utilized exclusively for in vivo neutron activation analysis (IVNAA) of calcium, phosphorus, sodium, chlorine, nitrogen, hydrogen, and potassium. These elements serve as the basis for a four compartment model of body composition: protein, water, mineral ash, and fat. Variations in these compartments are demonstrated in clinical research programs investigating obesity, anorexia, cancer, renal failure, osteoporosis, and normal aging. IVNAA continues to provide a unique approach to the evaluation of clinical diagnosis, efficacy of therapeutic regimens, and monitoring of the aging process. Classical balance studies usually require the patient to be admitted to a hospital for extended periods of confinement. IVNAA, however, allows for clinical management of the patient on an out-patient basis, an important aspect for treatment of chronic diseases. 25 references, 3 figures, 5 tables.

  4. The radioprotection challenges associated with the dismantling of nuclear facilities; Les enjeux de radioprotection associes au demantelement des installations nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2011-01-15

    This document proposes an overview of the different studies performed by the CEPN (the French Centre of investigation on protection assessment in the nuclear sector) to develop principles and good practices in the field of radiation protection in the case of dismantling activities. These issues are addressed with respect to the characteristics of these dismantling activities, i.e. the evolution of radiological conditions under which workers are intervening, the production and handling of very important volumes of radioactive and conventional wastes, and the possible existence of a site rehabilitation project

  5. Antiangiogenic Effects of VH02, a Novel Urea Derivative: In Vitro and in Vivo Studies

    Directory of Open Access Journals (Sweden)

    Suwadee Phowichit

    2016-09-01

    Full Text Available Vascular endothelial growth factor receptor 2 (VEGFR2 is a vital target for therapeutic intervention in cancer. We have recently described a computer-based drug design for a small molecule VEGFR2 inhibitor named VH02 (1-((1-(1H-indazol-6-yl-1H-1,2,3-triazol-4-ylmethyl-3-(3-chloromethylphenylurea. This study aimed to further explore the anti-angiogenic activity of VH02 both in vitro and in vivo. The in vitro assays include cell viability, capillary-like tube formation, MMP activity, and western blot analyses of signaling through VEGFR2 while the in vivo anti-angiogenic response were performed to evaluate the effect on vascularization in Matrigel plug applied in C57BL/6L mice. VH02 reduced angiogenesis behavior of EA.hy926 including cell viability, migration, adhesion, capillary-like tube formation, and MMP-2 activity induced by VEGF. Furthermore, VH02 regulated angiogenesis by directly inhibiting VEGFR2 on Tyr1175 signaling pathway leading to the inhibition of Akt-mediated cell survival and migration. Disruption of phosphorylation at VEGFR2-Tyr1175 by VH02 abolished FAK-Tyr397 signaling but not phosphorylation of p38 MAPK. This suggests that blockade of FAK by VH02 apparently associated with reduction of endothelial cell motility. Actin cytoskeleton rearrangement was diminished by VH02 in human endothelial cells. The anti-angiogenic effect of VH02 was confirmed in the in vivo model, revealing the reduction of vascular density in Matrigel plug after VH02 treatment. Additionally, the pericyte-like cells surrounding blood vessels in the plugs were significantly reduced as well as vascular density and p-Akt intensity. Our findings indicate that VH02 successfully inhibits VEGF-induced angiogenesis both in vitro and in vivo models. The compound could be further developed as an antiangiogenesis agent for cancer therapy.

  6. In vivo thermoluminescent dosimetry in studies of helicoid computed tomography and excretory urogram; Dosimetria termoluminiscente In vivo en estudios de tomografia computada helicoidal y urograma excretor

    Energy Technology Data Exchange (ETDEWEB)

    Cruz C, D.; Azorin N, J. [UAM-I, 09340 Mexico D.F. (Mexico); Saucedo A, V.M.; Barajas O, J.L. [Unidad de Especialidades Medicas, Secretaria de la Defensa Nacional, 11500 Mexico D.F. (Mexico)

    2005-07-01

    The dosimetry is the field of measurement of the ionizing radiations. It final objective is to determine the 'absorbed dose' for people. The dosimetry is vital in the radiotherapy, the radiological protection and the treatment technologies by irradiation. Presently work, we develop 'In vivo' dosimetry, in exposed patients to studies of helical computed tomography and excretory urogram. The dosimetry 'in vivo' was carried out in 20 patients selected aleatorily, for each medical study. The absorbed dose was measured in points of interest located in crystalline, thyroid, chest and abdomen of each patient, by means of thermoluminescent dosemeters (TLD) LiF: Mg,Cu,P + Ptfe of national fabrication. Also it was quantified the dose in the working area. (Author)

  7. Modeling gastrointestinal drug absorption requires more in vivo biopharmaceutical data: experience from in vivo dissolution and permeability studies in humans.

    Science.gov (United States)

    Lennernäs, Hans

    2007-10-01

    The majority (84%) of the 50 most-sold pharmaceutical products in the US and European markets are given orally. The dominating role of this route in drug therapy is a consequence of it being safe, efficient and easily accessible with minimal discomfort to the patient in comparison with other routes of drug administration. A successful drug discovery and development of oral pharmaceutical products require an in-depth understanding of multiple biochemical and physiological processes that determine the dissolution rate, intestinal permeability, gastrointestinal transit, first-pass extraction and systemic exposure-time profiles of drugs. It is crucial to realize that these basic biopharmaceutic and pharmacokinetic properties are crucial to focus on to allow successful drug development. Identification of the rate-limiting step(s) in order to overcome these barriers and understanding of the sources of variability are important in the selection of suitable candidate molecules in drug development. Several reports based on in vitro investigations in various cell models have suggested that carrier-mediated intestinal efflux may be a major reason for incomplete absorption and variable bioavailability of drugs, as well being a site for drug-drug and specific food-drug interactions. However, many drugs which were initially suggested to undergo significant efflux in vitro were later shown to be completely absorbed in vivo. This apparent discrepancy between in vitro and in vivo results may be due to several factors that will be discussed in this review. Novel data on solubility and dissolution in human gastrointestinal derived fluids will be reviewed. The effect of food intake on solubility and dissolution rate of a range of drugs including felodipine, danazol, griseofulvin, cyclosporine, probucol and ubiquinone in simulated and real intestinal fluids is discussed. The biopharmaceutic and physicochemical data discussed here can potentially be used as a benchmark set for

  8. Effects of gamma rays on rat testis tissue according to the morphological parameters and immunohistochemistry: radioprotective role of silymarin

    Science.gov (United States)

    Marzban, Mohsen; Anjamshoa, Maryam; Jafari, Parnia; Masoumi, Hossien; Ahadi, Reza; Fatehi, Daryoush

    2017-01-01

    Objective To determine the radioprotective effects of Silymarin in adult male Sprague-Dawley rats irradiated with γ-rays. Methods The present experimental study was performed in Tehran University of Medical Sciences, Tehran, Iran from December 2009 to March 2010. The study was performed on 40 rats, which were randomly and equally divided into four groups: 1) control group: neither received Silymarin nor irradiated with γ-rays; 2) γ-irradiation group: testis region exposed to 2Gy of γ-rays; 3) Silymarin & γ-irradiation: rats received 100 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays; 4) Silymarin & γ-irradiation: rats received 200 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays. After animal experiments and preparing the tissue sections, different histological and histomorphological parameters of seminiferous tubules and the biological characteristics of Leydig cells were evaluated applying quantitative assessment, Johnson scoring, and Leydig cell apoptosis assay by TUNEL method. The data were analyzed applying ANOVA and Tukey’s post hoc test, using SPSS software (V.19). Results Irradiation of 2 Gy γ-rays to the testis of the rats significantly affected the frequency of spermatogonia, primary spermatocyte, round spermatid, spermatozoa, seminiferous tube and lumen diameters, thickness of the epithelium, Leydig cell nuclear diameter and volume, epithelium height, and apoptotic cells (p<0.05). However, administration of Silymarin improved the mentioned parameters specifically in 200 mg/kg of dosage. Conclusion Silymarin could act as a potent radioprotector and it can be used in modulation as well as improvement to radiation therapy to prevent male reproductive function, specifically seminiferous tubules in an animal model; however, its molecular mechanism is still not clear and needs more molecular researches. PMID:28848626

  9. Effects of gamma rays on rat testis tissue according to the morphological parameters and immunohistochemistry: radioprotective role of silymarin.

    Science.gov (United States)

    Marzban, Mohsen; Anjamshoa, Maryam; Jafari, Parnia; Masoumi, Hossien; Ahadi, Reza; Fatehi, Daryoush

    2017-06-01

    To determine the radioprotective effects of Silymarin in adult male Sprague-Dawley rats irradiated with γ-rays. The present experimental study was performed in Tehran University of Medical Sciences, Tehran, Iran from December 2009 to March 2010. The study was performed on 40 rats, which were randomly and equally divided into four groups: 1) control group: neither received Silymarin nor irradiated with γ-rays; 2) γ-irradiation group: testis region exposed to 2Gy of γ-rays; 3) Silymarin & γ-irradiation: rats received 100 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays; 4) Silymarin & γ-irradiation: rats received 200 mg/kg of Silymarin 24hrs before exposure to 2Gy of γ-rays. After animal experiments and preparing the tissue sections, different histological and histomorphological parameters of seminiferous tubules and the biological characteristics of Leydig cells were evaluated applying quantitative assessment, Johnson scoring, and Leydig cell apoptosis assay by TUNEL method. The data were analyzed applying ANOVA and Tukey's post hoc test, using SPSS software (V.19). Irradiation of 2 Gy γ-rays to the testis of the rats significantly affected the frequency of spermatogonia, primary spermatocyte, round spermatid, spermatozoa, seminiferous tube and lumen diameters, thickness of the epithelium, Leydig cell nuclear diameter and volume, epithelium height, and apoptotic cells (p<0.05). However, administration of Silymarin improved the mentioned parameters specifically in 200 mg/kg of dosage. Silymarin could act as a potent radioprotector and it can be used in modulation as well as improvement to radiation therapy to prevent male reproductive function, specifically seminiferous tubules in an animal model; however, its molecular mechanism is still not clear and needs more molecular researches.

  10. Effects of single injection of local anesthetic agents on intervertebral disc degeneration: ex vivo and long-term in vivo experimental study.

    Directory of Open Access Journals (Sweden)

    Koji Iwasaki

    Full Text Available Analgesic discography (discoblock can be used to diagnose or treat discogenic low back pain by injecting a small amount of local anesthetics. However, recent in vitro studies have revealed cytotoxic effects of local anesthetics on intervertebral disc (IVD cells. Here we aimed to investigate the deteriorative effects of lidocaine and bupivacaine on rabbit IVDs using an organotypic culture model and an in vivo long-term follow-up model.For the organotypic culture model, rabbit IVDs were harvested and cultured for 3 or 7 days after intradiscal injection of local anesthetics (1% lidocaine or 0.5% bupivacaine. Nucleus pulposus (NP cell death was measured using confocal microscopy. Histological and TUNEL assays were performed. For in vivo study, each local anesthetic was injected into rabbit lumbar IVDs under a fluoroscope. Six or 12 months after the injection, each IVD was prepared for magnetic resonance imaging (MRI and histological analysis.In the organotypic culture model, both anesthetic agents induced time-dependent NP cell death; when compared with injected saline solution, significant effects were detected within 7 days. Compared with the saline group, TUNEL-positive NP cells were significantly increased in the bupivacaine group. In the in vivo study, MRI analysis did not show any significant difference. Histological analysis revealed that IVD degeneration occurred to a significantly level in the saline- and local anesthetics-injected groups compared with the untreated control or puncture-only groups. However, there was no significant difference between the saline and anesthetic agents groups.In the in vivo model using healthy IVDs, there was no strong evidence to suggest that discoblock with local anesthetics has the potential of inducing IVD degeneration other than the initial mechanical damage of the pressurized injection. Further studies should be performed to investigate the deteriorative effects of the local injection of analgesic agents

  11. An ex vivo approach to botanical-drug interactions: a proof of concept study.

    Science.gov (United States)

    Wang, Xinwen; Zhu, Hao-Jie; Munoz, Juliana; Gurley, Bill J; Markowitz, John S

    2015-04-02

    Botanical medicines are frequently used in combination with therapeutic drugs, imposing a risk for harmful botanical-drug interactions (BDIs). Among the existing BDI evaluation methods, clinical studies are the most desirable, but due to their expense and protracted time-line for completion, conventional in vitro methodologies remain the most frequently used BDI assessment tools. However, many predictions generated from in vitro studies are inconsistent with clinical findings. Accordingly, the present study aimed to develop a novel ex vivo approach for BDI assessment and expand the safety evaluation methodology in applied ethnopharmacological research. This approach differs from conventional in vitro methods in that rather than botanical extracts or individual phytochemicals being prepared in artificial buffers, human plasma/serum collected from a limited number of subjects administered botanical supplements was utilized to assess BDIs. To validate the methodology, human plasma/serum samples collected from healthy subjects administered either milk thistle or goldenseal extracts were utilized in incubation studies to determine their potential inhibitory effects on CYP2C9 and CYP3A4/5, respectively. Silybin A and B, two principal milk thistle phytochemicals, and hydrastine and berberine, the purported active constituents in goldenseal, were evaluated in both phosphate buffer and human plasma based in vitro incubation systems. Ex vivo study results were consistent with formal clinical study findings for the effect of milk thistle on the disposition of tolbutamide, a CYP2C9 substrate, and for goldenseal׳s influence on the pharmacokinetics of midazolam, a widely accepted CYP3A4/5 substrate. Compared to conventional in vitro BDI methodologies of assessment, the introduction of human plasma into the in vitro study model changed the observed inhibitory effect of silybin A, silybin B and hydrastine and berberine on CYP2C9 and CYP3A4/5, respectively, results which more

  12. [In vivo dosimetry study of semi-conductors EPD-20 in total body irradiation technique].

    Science.gov (United States)

    Besbes, M; Mahjoubi, H; Kochbati, L; Ben Abdennabi, A; Farhat, L; Abdessaied, S; Salem, L; Frikha, H; Nasr Ben Ammar, C; Hentati, D; Gargouri, W; Messai, T; Benna, F; Maalej, M

    2010-01-01

    The objective of this work was the study of in vivo dosimetry performed in a series of 54 patients receiving total body irradiation (TBI) at the Salah-Azaiz Institute of Tunis since 2004. In vivo dosimetry measurements were compared to analytically calculated doses from monitor units delivered. The irradiation was conducted by a linear accelerator (Clinac 1800, Varian, Palo Alto, USA) using nominal X-rays energies of 6 MV and 18 MV, depending on the thickness of the patient at the abdomen. The dose was measured by semi-conductors p-type EPD-20. These diodes were calibrated in advance with an ionization chamber "PTW Farmer" type of 0.6cm(3) and were placed on the surface of plexiglas phantom in the same TBI conditions. A study of dosimetric characteristics of semi-conductors EPD-20 was carried out as a function of beam direction and temperature. Afterwards, we conducted a comparative analysis of doses measured using these detectors during irradiation to those calculated retrospectively from monitor units delivered to each patient conditioned by TBI. Experience showed that semi-conductors are sensitive to the angle of beam radiation (0-90 degrees ) and the temperature (22-40 degrees C). The maximum variation is respectively 5 and 7%, but in our irradiation conditions these correction factors are less than 1%. The analysis of the results of the in vivo dosimetry had shown that the ratio of the average measured doses and analytically calculated doses at the abdomen, mediastina, right lung and head are 1.005, 1.007, 1.0135 and 1.008 with a standard deviation "type A" respectively of 3.04, 2.37, 7.09 et 4.15%. In vivo dosimetry by semi-conductors is in perfect agreement with dosimetry by calculation. However, in vivo dosimetry using semiconductors is the only technique that can reflect the dose actually received instantly by the patient during TBI given the many factors that calculation can not take into account: patient and organs motions and the heterogeneity of the

  13. Nanomedicine for Inner Ear Diseases: A Review of Recent In Vivo Studies

    Directory of Open Access Journals (Sweden)

    Dong-Kee Kim

    2017-01-01

    Full Text Available Nanoparticles are promising therapeutic options for inner ear disease. In this report, we review in vivo animal studies in the otologic field using nanoparticles over the past 5 years. Many studies have used nanoparticles to deliver drugs, genes, and growth factors, and functional and morphological changes have been observed. The constituents of nanoparticles are also diversifying into various biocompatible materials, including poly(lactic-co-glycolic acid (PLGA. The safe and effective delivery of drugs or genes in the inner ear will be a breakthrough for the treatment of inner ear diseases, including age-related hearing loss.

  14. Effect of implanted brachytherapy seeds on optical fluence distribution: preliminary ex vivo study

    Science.gov (United States)

    Hetzel, Fred W.; Chen, Qun; Ding, Meisong; Newman, Francis; Dole, Kenneth C.; Huang, Zheng; Blanc, Dominique

    2007-02-01

    Photodynamic therapy (PDT) has gradually found its place in the treatment of malignant and non-malignant human diseases. Currently, interstitial PDT is being explored as an alternative modality for newly diagnosed and recurrent organ-confined prostate cancer. The interstitial PDT for the treatment of prostate cancer might be considered to treat prostates with permanent radioactive seeds implantation. However, the effect of implanted brachytherapy seeds on the optical fluence distribution of PDT light has not been studied before. This study investigated, for the first time, the effect of brachytherapy seed on the optical fluence distribution of 760 nm light in ex vivo models (meat and canine prostate).

  15. VEGF-releasing suture material for enhancement of vascularization: development, in vitro and in vivo study.

    Science.gov (United States)

    Bigalke, Christian; Luderer, Frank; Wulf, Katharina; Storm, Thilo; Löbler, Marian; Arbeiter, Daniela; Rau, Bettina M; Nizze, Horst; Vollmar, Brigitte; Schmitz, Klaus-Peter; Klar, Ernst; Sternberg, Katrin

    2014-12-01

    As it has been demonstrated that bioactive substances can be delivered locally using coated surgical suture materials, the authors developed a vascular endothelial growth factor (VEGF)-releasing suture material that should promote vascularization and potentially wound healing. In this context, the study focused on the characterization of the developed suture material and the verification of its biological activity, as well as establishing a coating process that allows reproducible and stable coating of a commercially available polydioxanone suture material with poly(l-lactide) (PLLA) and 0.1μg and 1.0μg VEGF. The in vitro VEGF release kinetics was studied using a Sandwich ELISA. The biological activity of the released VEGF was investigated in vitro using human umbilical vein endothelial cells. The potential of the VEGF-releasing suture material was also studied in vivo 5days after implantation in the hind limb of Wistar rats, when the histological findings were analyzed. The essential results, enhanced cell viability in vitro as well as significantly increased vascularization in vivo, were achieved using PLLA/1.0μg VEGF-coated suture material. Furthermore, ELISA measurements revealed a high reproducibility of the VEGF release behavior. Based on the results achieved regarding the dose-effect relationship of VEGF, the stability during its processing and the release behavior, it can be predicted that a bioactive suture material would be successful in later in vivo studies. Therefore, this knowledge could be the basis for future studies, where bioactive substances with different modes of action are combined for targeted, overall enhancement of wound healing. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Effects of high-dose gamma irradiation on tensile properties of human cortical bone: Comparison of different radioprotective treatment methods.

    Science.gov (United States)

    Allaveisi, Farzaneh; Mirzaei, Majid

    2016-08-01

    There are growing interests in the radioprotective methods that can reduce the damaging effects of ionizing radiation on sterilized bone allografts. The aim of this study was to investigate the effects of 50kGy (single dose, and fractionated) gamma irradiation, in presence and absence of l-Cysteine (LC) free radical scavenger, on tensile properties of human femoral cortical bone. A total of 48 standard tensile test specimens was prepared from diaphysis of femurs of three male cadavers (age: 52, 52, and 54 years). The specimens were assigned to six groups (n=8) according to different irradiation schemes, i.e.; Control (Non-irradiated), LC-treated control, a single dose of 50kGy (sole irradiation), a single dose of 50kGy in presence of LC, 10 fractions of 5kGy (sole irradiation), and 10 fractions of 5kGy in presence of LC. Uniaxial tensile tests were carried out to evaluate the variations in tensile properties of the specimens. Fractographic analysis was performed to examine the microstructural features of the fracture surfaces. The results of multivariate analysis showed that fractionation of the radiation dose, as well as the LC treatment of the 50kGy irradiated specimens, significantly reduced the radiation-induced impairment of the tensile properties of the specimens (Psterilization on tensile properties of human cortical bone can be substantially reduced by free radical scavenger treatment, dose fractionation, and the combined treatment of these two methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Radioprotective effects of Bmi-1 involve epigenetic silencing of oxidase genes and enhanced DNA repair in normal human keratinocytes.

    Science.gov (United States)

    Dong, Qinghua; Oh, Ju-Eun; Chen, Wei; Kim, Roy; Kim, Reuben H; Shin, Ki-Hyuk; McBride, William H; Park, No-Hee; Kang, Mo K

    2011-06-01

    Normal human keratinocytes (NHKs) undergo premature senescence following exposure to ionizing radiation (IR). This study investigates the effect of Bmi-1, a polycomb group protein, on radiation-induced senescence response. When exposed to IR, NHK transduced with Bmi-1 (NHK/Bmi-1) showed reduced senescent phenotype and enhanced proliferation compared with control cells (NHK/B0). To investigate the underlying mechanism, we determined the production of reactive oxygen species (ROS), expression of ROS-generating enzymes, and DNA repair activities in cells. ROS level was increased upon irradiation but notably reduced by Bmi-1 transduction. Irradiation led to strong induction of oxidase genes, e.g., Lpo (lactoperoxidase), p22-phox, p47-phox, and Gp91, in NHK/B0 but their expression was almost completely silenced in NHK/Bmi-1. Induction of oxidase genes upon irradiation was linked with loss of trimethylated histone 3 at lysine 27 (H3K27Me3), but NHK/Bmi-1 expressed a higher level of H3K27Me3 compared with NHK/B0. Bmi-1 transduction suppressed IR-associated induction of jumanji domain containing 3 while enhancing the expression of EZH2, thereby preventing the loss of H3K27Me3 in the irradiated cells. Furthermore, NHK/Bmi-1 demonstrated increased repair of IR-induced DNA damage compared with NHK/B0. These results indicate that Bmi-1 elicits radioprotective effects on NHK by mitigating the genotoxicity of IR through epigenetic mechanisms.

  18. CRISPR/Cas9 Promotes Functional Study of Testis Specific X-Linked Gene In Vivo.

    Directory of Open Access Journals (Sweden)

    Minyan Li

    Full Text Available Mammalian spermatogenesis is a highly regulated multistage process of sperm generation. It is hard to uncover the real function of a testis specific gene in vitro since the in vitro model is not yet mature. With the development of the CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated 9 system, we can now rapidly generate knockout mouse models of testis specific genes to study the process of spermatogenesis in vivo. SYCP3-like X-linked 2 (SLX2 is a germ cell specific component, which contains a Cor1 domain and belongs to the XLR (X-linked, lymphocyte regulated family. Previous studies suggested that SLX2 might play an important role in mouse spermatogenesis based on its subcellular localization and interacting proteins. However, the function of SLX2 in vivo is still elusive. Here, to investigate the functions of SLX2 in spermatogenesis, we disrupted the Slx2 gene by using the CRISPR/Cas9 system. Since Slx2 is a testis specific X-linked gene, we obtained knockout male mice in the first generation and accelerated the study process. Compared with wild-type mice, Slx2 knockout mice have normal testis and epididymis. Histological observation of testes sections showed that Slx2 knockout affected none of the three main stages of spermatogenesis: mitosis, meiosis and spermiogenesis. In addition, we further confirmed that disruption of Slx2 did not affect the number of spermatogonial stem cells, meiosis progression or XY body formation by immunofluorescence analysis. As spermatogenesis was normal in Slx2 knockout mice, these mice were fertile. Taken together, we showed that Slx2 itself is not an essential gene for mouse spermatogenesis and CRISPR/Cas9 technique could speed up the functional study of testis specific X-linked gene in vivo.

  19. Radio-protection problems presented by iodine isotopes in nuclear fuel chemical treatment plants (1962); Les problemes de radioprotection poses par les isotopes de l'iode dans les installations de traitement chimique des combustibles (1962)

    Energy Technology Data Exchange (ETDEWEB)

    Bouzigues, H.; Scheidhauer, J.; Messainguiral, L. [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

    1962-07-01

    The origin of radio-iodine and the conditions in which it is liberated are given. The authors review the question of the risks associated with the presence of this radioelement In the atmosphere. Finally a method is proposed for the trapping and rapid measuring of the iodine in the vapour form, applicable to radioprotection. (authors) [French] L'origine et les conditions de liberation du radioiode sont exposees. Les auteurs font le point de la question des risques associes a la presence de ce radioelement dans l'atmosphere. Enfin, une methode de piegeage et de mesure rapide de l'iode a l'etat de vapeur applicable a la radioprotection, est proposee. (auteurs)

  20. AN IN VIVO STUDY OF THE EFFECTS OF IONIZING RADIATION ON TISSUES BY LASER FLUORESCENCE SPECTROSCOPY

    Directory of Open Access Journals (Sweden)

    I. A. Guseva

    2016-01-01

    Full Text Available Background: Laser fluorescence spectroscopy (LFS is widely used in various medical areas, oncology being the most known of them. In general, the LFS is used for in vivo diagnostics of tumors. Recent studies have shown that this method could be used for diagnostics of local inflammation, induced by thermal or mechanical injury. It is of interest if LFS could be used for assessment of soft biological tissue injury caused by radiation exposure. Aim: To study fluorescence of an exogenous photosensitizer and its changes over time in the radiation injury area by LFS method in vivo. Materials and methods: The experiment was done in 12 outbred SHK mice whose right hind limbs were irradiated using a gamma-therapy device ROKUS-AM (source, 60Co, at dose of 15 Gy. Before irradiation, the photosensitizer Photosens was administered to all animals intraperitoneally at dose of 2.5 mg/kg. For 21 days fluorescence was assessed in vivo with a laser diagnostic system LAKK-M in the “fluorescence” operation mode, with an excitation wavelength of 635 nm. At days 7 and 21, tissue samples from the irradiated areas of the model animals were studied histologically and differential blood cell counts were assessed simultaneously. Results: The LFS method showed an increase in the accumulation of the photosensitizer in the affected area, compared to an intact contralateral area, with higher signal intensity from the irradiated limb. The changes in the fluorescence signal from the affected over time had two characteristic peaks at days 3 and 14, probably reflecting the stage of local radiation injury. Conclusion: The use of LFS with an exogenous photosensitizer has a potential for a personalized assessment of radiation reactions in radiology.

  1. In Vivo Quantification of the Nonlinear Shear Modulus in Breast Lesions: Feasibility Study.

    Science.gov (United States)

    Bernal, Miguel; Chamming's, Foucauld; Couade, Mathieu; Bercoff, Jeremy; Tanter, Mickaël; Gennisson, Jean-Luc

    2016-01-01

    Breast cancer detection in the early stages is of great importance since the prognosis, and the treatment depends more on this. Multiple techniques relying on the mechanical properties of soft tissues have been developed to help in early detection. In this study, we implemented a technique that measures the nonlinear shear modulus (NLSM) (μ(NL)) in vivo and showed its utility to detect breast lesions from healthy tissue. The technique relies on the acoustoelasticity theory in quasi-incompressible media. In order to recover μ(NL), static elastography and supersonic shear imaging are combined to subsequently register strain maps and shear modulus maps while the medium is compressed. Then, μ(NL) can be recovered from the relationship between the stress, deduced from strain maps, and the shear modulus. For this study, a series of five nonlinear phantoms were built using biological tissue (pork liver) inclusions immersed in an agar-gelatin gel. Furthermore, 11 in vivo acquisitions were performed to characterize the NLSM of breast tissue. The phantom results showed a very good differentiation of the liver inclusions when measuring μ(NL) with a mean value of -114.1 kPa compared to -34.7 kPa for the gelatin. Meanwhile, values for the shear modulus for the liver and the gelatin were very similar, 3.7 and 3.4 kPa, respectively. In vivo NLSM mean value for the healthy breast tissue was of -95 kPa, while mean values of the benign and the malignant lesions were -619 and -806 kPa with a strong v ariability, respectively. This study shows the potential of the acoustoelasticity theory in quasi-incompressible medium to bring a new parameter for breast cancer diagnosis.

  2. A Compton imager for in-vivo dosimetry of proton beams-A design study

    Energy Technology Data Exchange (ETDEWEB)

    Kormoll, T., E-mail: thomas.kormoll@physik.tu-dresden.d [Technische Universitaet Dresden, OncoRay-Center for Radiation Research in Oncology, Fetscherstr. 74, 01307 Dresden (Germany); Fiedler, F.; Schoene, S. [Forschungszentrum Dresden-Rossendorf, Institute for Radiation Research, Bautzner Landstr. 400, 01328 Dresden (Germany); Wuestemann, J. [Technische Universitaet Dresden, OncoRay-Center for Radiation Research in Oncology, Fetscherstr. 74, 01307 Dresden (Germany); Zuber, K. [Technische Universitaet Dresden, Institute for Nuclear and Particle Physics, Zellescher Weg 19, 01069 Dresden (Germany); Enghardt, W. [Technische Universitaet Dresden, OncoRay-Center for Radiation Research in Oncology, Fetscherstr. 74, 01307 Dresden (Germany); Forschungszentrum Dresden-Rossendorf, Institute for Radiation Research, Bautzner Landstr. 400, 01328 Dresden (Germany)

    2011-01-21

    In-beam SPECT during therapeutic proton beam irradiation is a novel method for three dimensional in-vivo dose verification. For this purpose a Compton camera design is evaluated with respect to the special requirements and conditions that arise from this application. Different concepts are studied by means of simulation concerning the angular resolution and efficiency. It was found that a cadmium zinc telluride system can perform sufficiently well. For further evaluation the construction of a semiconductor scintillator hybrid system is under way.

  3. In vivo studies of aquaporins 3 and 10 in human stratum corneum

    DEFF Research Database (Denmark)

    Jungersted, Jakob Mutanu; Bomholt, Julie; Bajraktari, Niada

    2013-01-01

    Aquaporins (AQPs) constitute one family of transmembrane proteins facilitating transport of water across cell membranes. Due to their specificity, AQPs have a broad spectrum of physiological functions, and for keratinocytes there are indications that these channel proteins are involved in cell...... by AQP3 and AQP10 antibodies. In conclusion, identification of AQP3 and AQP10 protein in SC in an in vivo model is new. Together with the new “minimal-invasive” method for SC collection presented, this opens for new possibilities to study the role of AQPs in relation to function of the skin barrier....

  4. An in vivo model to study the anti-malaric capacity of plant extracts

    Directory of Open Access Journals (Sweden)

    Misael Chinchilla

    1998-03-01

    Full Text Available An in vivo model to study the antimalaric effect of plant extracts is described. White mice (25-30g body weight are treated subcutaneously with 0.6ml of the diluted extract starting seven days before P. berghei infection; treatment continues until death or for 30 days. Simultaneously 0.2ml of the extract are applied per os starting three days before infection. In a test of the model, treated and non-treated animals differed in body weight, survival time, haematocrite, parasitemia development, and spleen or liver weight of recent dead or killed mice.

  5. In vivo absorption studies of insulin from an oral delivery system.

    Science.gov (United States)

    Jerry, N; Anitha, Y; Sharma, C P; Sony, P

    2001-01-01

    Alginate microspheres prepared by an emulsion-based process were loaded with insulin by a remote loading process. We observed that the time of exposure, pH of the remote loading medium, and beta-cyclodextrin complexation of insulin influenced drug loading. In vivo absorption studies of insulin from optimized microspheres were carried out in diabetic albino rats. Serum sugar levels on administration of multiple oral doses of the microspheres and a radioimmunoassay for serum insulin indicated absorption of insulin from the gastrointestinal region. This process could be utilized for the development of an oral insulin delivery system.

  6. Evaluation of the Doxycycline Release from AH26 Sealer-Doxycycline Combination: An ex vivo Study

    OpenAIRE

    Ashofteh Yazdi, Kazem; Shokouhinejad, Noushin; Moazeni, Esmaeil; Mirzayi Rad, Sina

    2011-01-01

    INTRODUCTION The purpose of this ex vivo study was to determine the releasing characteristics and doxycycline dentinal diffusion of AH26 sealer-doxycycline combination from apical 3mm of tooth root and apical foramen. MATERIALS AND METHODS One-hundred and two recently extracted single-rooted human teeth were decoronated and prepared with #3 and #4 Gates-Glidden drills and rotary Mtwo files. Smear layer was removed; all surfaces except for apical 3mm of each root were sealed with two coats of ...

  7. Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study

    Directory of Open Access Journals (Sweden)

    El-Moukhtar Aliouat

    2013-07-01

    Full Text Available Some compounds articulated around a piperazine or an ethylenediamine linker have been evaluated in vitro to determine their activity in the presence of a 3T6 fibroblast cell line and an axenic culture of Pneumocystis carinii, respectively. The most efficient antifungal derivatives, namely N,N′-bis(benzamidine-4-ylethane-1,2-diamine (compound 6, a diamidine and N-(benzamidine-4-yl-N′-phenylethane-1,2-diamine (compound 7, a monoamidine, exhibited no cytotoxicity and were evaluated in vivo in a rat model. Only the diamidine 6 emerged as a promising hit for further studies.

  8. Detection of pre-charring optical behavior at a laser catheter-tip in blood: ex vivo and in vivo study

    Science.gov (United States)

    Takahashi, Mei; Ito, Arisa; Kajihara, Takuro; Arai, Tsunenori

    2011-03-01

    We studied a pre-charring optical behavior of blood at a laser catheter-tip during a red laser irradiation (663 nm, CW) with around 50 W/cm2 in blood to prevent charring at the laser catheter-tip. The laser irradiated red-blood-cell shape changes were microscopically observed. A round formation, aggregation, and hemolysis were found until blood charring (ex vivo). A time-history of diffuse-reflected light power and transmitted light power from a thin blood layer which was irradiated by the red laser were measured with microscope optics to investigate the charring process. The diffusereflected light power decreased following a gentle peak before the charring. This decrease indicated the pre-charring behavior which might be induced by scattering and absorption changes due to red-blood-cell degenerations described above. Using the laser catheter located in porcine heart, we successfully detected the pre-charring behavior by a backscattering light power (in vivo). We demonstrated charring prevention availability with the laser power control (ex vivo). We think that the backscattering light power measurement and laser power control via the laser catheter might be useful to detect pre-charring behavior, and to prevent the charring for therapeutic laser irradiation in blood under catheterization such as arrhythmia treatment with photodynamic therapy.

  9. Ocular Surface Epithelialization Pattern After Simple Limbal Epithelial Transplantation: An In Vivo Observational Study.

    Science.gov (United States)

    Mittal, Vikas; Jain, Rajat; Mittal, Ruchi

    2015-10-01

    To study the in vivo pattern of ocular surface epithelialization after simple limbal epithelial transplantation (SLET). A retrospective interventional case series was performed at a cornea and anterior segment services of a referral tertiary care center between June 2012 and March 2015. Patients with unilateral limbal stem cell deficiency who underwent SLET and whose medical records had serial and detailed photographic documentation of ocular surface healing were reviewed. The outcome measures consisted of the pattern of ocular surface epithelialization, time taken for complete ocular surface epithelialization, and assessment of the possible variations in the explants' characteristics in vivo. Five patients fulfilled the inclusion criteria. Mean age was 30.8 years, the male:female ratio was 4:1. Mean follow-up after the SLET period was 10.8 months. A 2-line improvement in visual acuity was seen in 3 of 5 patients. The mean number of explants was 11.4 (range, 5-19). The first clinical evidence of proliferation of the corneal epithelium from the limbal explants was seen on the second day in all patients, and ocular surface epithelialization was complete in all cases within 14 days. The explants disappeared within 1 to 2 months in all but 1 case (24 weeks). Variations were seen in explant activity with the size and age of the explants. The in vivo pattern of ocular surface epithelialization after SLET appears to be similar to in vitro epithelialization observed after CLET. The observations in this study provide a lead for performing further laboratory and clinical research in SLET.

  10. In Vivo Bioluminescence Imaging for the Study of Intestinal Colonization by Escherichia coli in Mice▿

    Science.gov (United States)

    Foucault, M.-L.; Thomas, L.; Goussard, S.; Branchini, B. R.; Grillot-Courvalin, C.

    2010-01-01

    Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2 = 0.98) or transcutaneously in the abdominal region of whole animals (R2 = 0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2ΩPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization. PMID:19880653

  11. In vivo bioluminescence imaging for the study of intestinal colonization by Escherichia coli in mice.

    Science.gov (United States)

    Foucault, M-L; Thomas, L; Goussard, S; Branchini, B R; Grillot-Courvalin, C

    2010-01-01

    Bioluminescence imaging (BLI) is emerging as a powerful tool for real-time monitoring of infections in living animals. However, since luciferases are oxygenases, it has been suggested that the requirement for oxygen may limit the use of BLI in anaerobic environments, such as the lumen of the gut. Strains of Escherichia coli harboring the genes for either the bacterial luciferase from Photorhabdus luminescens or the PpyRE-TS and PpyGR-TS firefly luciferase mutants of Photinus pyralis (red and green thermostable P. pyralis luciferase mutants, respectively) have been engineered and used to monitor intestinal colonization in the streptomycin-treated mouse model. There was excellent correlation between the bioluminescence signal measured in the feces (R2=0.98) or transcutaneously in the abdominal region of whole animals (R2=0.99) and the CFU counts in the feces of bacteria harboring the luxABCDE operon. Stability in vivo of the bioluminescence signal was achieved by constructing plasmid pAT881(pGB2OmegaPamiluxABCDE), which allowed long-term monitoring of intestinal colonization without the need for antibiotic selection for plasmid maintenance. Levels of intestinal colonization by various strains of E. coli could be compared directly by simple recording of the bioluminescence signal in living animals. The difference in spectra of light emission of the PpyRE-TS and PpyGR-TS firefly luciferase mutants and dual bioluminescence detection allowed direct in vitro and in vivo quantification of two bacterial populations by measurement of red and green emitted signals and thus monitoring of the two populations simultaneously. This system offers a simple and direct method to study in vitro and in vivo competition between mutants and the parental strain. BLI is a useful tool to study intestinal colonization.

  12. A feasibility study of in vivo applications of single beam acoustic tweezers

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ying, E-mail: yli582@usc.edu; Lee, Changyang; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk [NIH Transducer Resource Center and Department of Biomedical Engineering, University of Southern California, Los Angeles, California 90089-1111 (United States)

    2014-10-27

    Tools that are capable of manipulating micro-sized objects have been widely used in such fields as physics, chemistry, biology, and medicine. Several devices, including optical tweezers, atomic force microscope, micro-pipette aspirator, and standing surface wave type acoustic tweezers have been studied to satisfy this need. However, none of them has been demonstrated to be suitable for in vivo and clinical studies. Single beam acoustic tweezers (SBAT) is a technology that uses highly focused acoustic beam to trap particles toward the beam focus. Its feasibility was first theoretically and experimentally demonstrated by Lee and Shung several years ago. Since then, much effort has been devoted to improving this technology. At present, the tool is capable of trapping a microparticle as small as 1 μm, as well as a single red blood cell. Although in comparing to other microparticles manipulating technologies, SBAT has advantages of providing stronger trapping force and deeper penetration depth in tissues, and producing less tissue damage, its potential for in vivo applications has yet been explored. It is worth noting that ultrasound has been used as a diagnostic tool for over 50 years and no known major adverse effects have been observed at the diagnostic energy level. This paper reports the results of an initial attempt to assess the feasibility of single beam acoustic tweezers to trap microparticles in vivo inside of a blood vessel. The acoustic intensity of SBAT under the trapping conditions that were utilized was measured. The mechanical index and thermal index at the focus of acoustic beam were found to be 0.48 and 0.044, respectively, which meet the standard of commercial diagnostic ultrasound system.

  13. A feasibility study of in vivo applications of single beam acoustic tweezers

    Science.gov (United States)

    Li, Ying; Lee, Changyang; Chen, Ruimin; Zhou, Qifa; Shung, K. Kirk

    2014-10-01

    Tools that are capable of manipulating micro-sized objects have been widely used in such fields as physics, chemistry, biology, and medicine. Several devices, including optical tweezers, atomic force microscope, micro-pipette aspirator, and standing surface wave type acoustic tweezers have been studied to satisfy this need. However, none of them has been demonstrated to be suitable for in vivo and clinical studies. Single beam acoustic tweezers (SBAT) is a technology that uses highly focused acoustic beam to trap particles toward the beam focus. Its feasibility was first theoretically and experimentally demonstrated by Lee and Shung several years ago. Since then, much effort has been devoted to improving this technology. At present, the tool is capable of trapping a microparticle as small as 1 μm, as well as a single red blood cell. Although in comparing to other microparticles manipulating technologies, SBAT has advantages of providing stronger trapping force and deeper penetration depth in tissues, and producing less tissue damage, its potential for in vivo applications has yet been explored. It is worth noting that ultrasound has been used as a diagnostic tool for over 50 years and no known major adverse effects have been observed at the diagnostic energy level. This paper reports the results of an initial attempt to assess the feasibility of single beam acoustic tweezers to trap microparticles in vivo inside of a blood vessel. The acoustic intensity of SBAT under the trapping conditions that were utilized was measured. The mechanical index and thermal index at the focus of acoustic beam were found to be 0.48 and 0.044, respectively, which meet the standard of commercial diagnostic ultrasound system.

  14. The Antimicrobial efficacy of Elaeis guineensis: characterization, in vitro and in vivo studies.

    Science.gov (United States)

    Vijayarathna, Soundararajan; Zakaria, Zuraini; Chen, Yeng; Latha, Lachimanan Yoga; Kanwar, Jagat R; Sasidharan, Sreenivasan

    2012-04-26

    The urgent need to treat multi-drug resistant pathogenic microorganisms in chronically infected patients has given rise to the development of new antimicrobials from natural resources. We have tested Elaeis guineensis Jacq (Arecaceae) methanol extract against a variety of bacterial, fungal and yeast strains associated with infections. Our studies have demonstrated that E. guineensis exhibits excellent antimicrobial activity in vitro and in vivo against the bacterial and fungal strains tested. A marked inhibitory effect of the E. guineensis extracts was observed against C. albicans whereby E. guineensis extract at ½, 1, or 2 times the MIC significantly inhibited C. albicans growth with a noticeable drop in optical density (OD) of the bacterial culture. This finding confirmed the anticandidal activity of the extract on C. albicans. Imaging using scanning (SEM) and transmission (TEM) electron microscopy was done to determine the major alterations in the microstructure of the extract-treated C. albicans. The main abnormalities noted via SEM and TEM studies were the alteration in morphology of the yeast cells. In vivo antimicrobial activity was studies in mice that had been inoculated with C. albicans and exhibited good anticandidal activity. The authors conclude that the extract may be used as a candidate for the development of anticandidal agent.

  15. Carbon-11 labeling of CP-126,998*: A radiotracer for in vivo studies of acetylcholinesterase

    Energy Technology Data Exchange (ETDEWEB)

    Musachio, J.L.; Flesher, J.E.; Scheffel, U. [Johns Hopkins Medical Institutions, Baltimore, MD (United States)] [and others

    1996-05-01

    The study of acetylcholinesterase (AChE) via PET is of interest as reduced activity of this enzyme has been observed in Alzheimer`s disease. Our efforts to develop a radiotracer for mapping of AChE have focused on the N-benzylpiperidine benzisoxazole, CP-126,998, a highly potent (IC{sub 50}=0.48 nm) and selective inhibitor of AChE. High specific activity [C-11] CP-126,998 was synthesized (14 - 24% radiochemical yield, non-decay corrected) by treatment of the desmethyl precursor, CP-118,954, with [C-11] methyl iodide and tetrabutylammonium hydroxide in DMF. In vivo studies with [C-11] CP-126,998 in mice show that this radiotracer displays highest uptake in striatum (6.2 %ID/g), a brain region known to be rich in AChE. The (striatum-cerebellum)/cerebellar radioactivity ratio reached a maximum of 4.3 at 30 min postinjection, and this ratio decreased to 2.4 at 120 min. .Radiotracer binding was saturable in vivo by pretreatment with CP-118,954. Pretreatment of mice with diisopropylfluorophosphate (4 mg/kg i.p.), a known AChE inhibitor, significantly inhibited binding in striatum in a dose-dependent manner. Initial results suggest that [C-11] CP-126,998 may prove useful as a marker for the study of AChE in humans via PET.

  16. Remineralization of early enamel lesions using casein phosphopeptide amorphous calcium Phosphate: An ex-vivo study

    Directory of Open Access Journals (Sweden)

    Ruchi Vashisht

    2010-01-01

    Full Text Available Objective: This study aimed at qualitatively evaluating the remineralization potential of casein phosphopeptide amorphous calcium phosphate on artificial early enamel lesions in an ex-vivo scenario by observing the treated tooth surface using a scanning electron microscope (SEM. Materials and Methods: This randomized study was conducted on 10 subjects undergoing orthodontic treatment with premolar extraction as part of their treatment. Artificial white lesions were created with the application of 37% phosphoric acid for 20 mins. Teeth were then divided into two groups: one experimental and the other control. Customised orthodontic band with a window was luted with intermediate restorative material in the experimental group whereas in the control group, band without a window was luted. The casein phosphopeptide amorphous calcium phosphate (GC TOOTH MOUSSE paste was then applied on the window region of the experimental group for 3 mins thrice daily after meals for 14 days, whereas no paste was applied in the control group. After 14 days, teeth were extracted and viewed under an SEM. Results: The study groups showed remineralization of the lesions as compared with the control group in most of the samples. Conclusion: Casein phophopeptide could significantly remineralize the artificial enamel lesions in vivo.

  17. In vivo field dependence of proton relaxation times in human brain, liver and skeletal muscle: a multicenter study

    DEFF Research Database (Denmark)

    Henriksen, O; de Certaines, J D; Spisni, A

    1993-01-01

    and MRS, the in vivo field dispersion of T1 and T2 has been measured in order to evaluate whether ex vivo data are representative for the in vivo situation. Brain, skeletal muscle, and liver of healthy human volunteers were studied. Fifteen MR units with a field strength ranging from 0.08 T to 1.5 T took......T1 and T2 relaxation times are fundamental parameters for signal contrast behaviour in MRI. A number of ex vivo relaxometry studies have dealt with the magnetic field dispersion of T1. By means of multicenter study within the frame of the COMAC BME Concerted Action on Tissue Characterization by MRI...... part in the trial, which comprised 218 volunteers. All the MR systems were tested for measurement accuracy using the Eurospin TO5 test object. The measured relaxation data were subsequently corrected according to the obtained calibration curves. The results showed a clear field dispersion of T1...

  18. Comparative study of skin autofluorescence expression in atopic dermatitis and psoriasis: A prospective in vivo study.

    Science.gov (United States)

    Yim, J H; Jeong, K H; Shin, M K

    2017-05-01

    Treatment of atopic dermatitis (AD) and psoriasis requires their differentiation from other eczematoid dermatitis and a determination of disease severity. However, both can be clinically difficult and the findings subjectively interpreted. We investigated the utility of in vivo autofluorescence (AF) measurements for diagnosis of both diseases, and determination of severity. Thirty patients with AD and 30 with psoriasis were recruited, together with sex- and age-matched patients with healthy skin. AF intensity was measured using the EcoSkin® fluorescence video dermatoscope. In AD and psoriasis patients, AF in non-sun-exposed lesional and non-lesional skin was measured. To identify the locations that reflect characteristics of AD, AF was also measured at the other sites in the patients with AD. AD was associated with lower AF and psoriasis with higher AF intensity peaking around 620 nm. In addition, skin AF intensity of each disease was associated with severity of lesion. Non-invasive measurement of skin AF in vivo can aid in diagnosis of AD and psoriasis as well as in treatment monitoring. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Sustained-release microspheres of amifostine for improved radio-protection, patient compliance, and reduced side effects.

    Science.gov (United States)

    Wu, Hong-Yu; Hu, Zhen-Hua; Jin, Tuo

    2016-11-01

    A biweekly administration of sustained-release microsphere dosage form of amifostine, a radioprotective drug used in radiotherapy, was performed to examine the feasibility to minimize injection frequency and blood concentration-associated side effects. Model animal trials indicated that this subcutaneously injecting microspheres, 50-100 μm in diameter, achieved bi-weekly prolonged radio-protective efficacy and, at the same time, significantly reduced skin irritation than the solution form of amifostine given by the same administration route. In addition, the hypertension associated with blood concentration of amifostine was not observed in the drug-treated rats. The animals given the amifostine microspheres and amifostine showed significantly differences in white blood cell, red blood cell, hematocrit, hemoglobin and spleen tissue histopathology after exposed under a cobalt-60 γ-radiation at a dose rate of 1.0 Gy/min for 6 min. The in vitro release profile of amifostine from the micropsheres showed a minor initial burst (less than 20% of total drug loading in the first day of administration), consisting with the side effects observations. The results suggest that amifostine encapsulated in sustained-release microspheres may be an ideal dosage form for prolonged radio-protective efficacy and improved patient compliance.

  20. Study of in vivo catheter biofilm infections using pediatric central venous catheter implanted in rat.

    Science.gov (United States)

    Chauhan, Ashwini; Ghigo, Jean-Marc; Beloin, Christophe

    2016-03-01

    Venous access catheters used in clinics are prone to biofilm contamination, contributing to chronic and nosocomial infections. Although several animal models for studying device-associated biofilms were previously described, only a few detailed protocols are currently available. Here we provide a protocol using totally implantable venous access ports (TIVAPs) implanted in rats. This model recapitulates all phenomena observed in the clinic, and it allows bacterial biofilm development and physiology to be studied. After TIVAP implantation and inoculation with luminescent pathogens, in vivo biofilm formation can be monitored in situ, and biofilm biomass can be recovered from contaminated TIVAP and organs. We used this protocol to study host responses to biofilm infection, to evaluate preventive and curative antibiofilm strategies and to study fundamental biofilm properties. For this procedure, one should expect ∼3 h of hands-on time, including the implantation in one rat followed by in situ luminescence monitoring and bacterial load estimation.

  1. An immunohistological study of anhydrous topical ascorbic acid compositions on ex vivo human skin.

    Science.gov (United States)

    Heber, Geoffrey K; Markovic, Boban; Hayes, Amanda

    2006-06-01

    Ascorbic acid has numerous essential and beneficial functions in normal and photoaged skin. Ionisation of ascorbic acid in aqueous topical formulations leads to oxidative degradation. Ascorbic acid in an anhydrous vehicle would inherently have greater stability. The objective of this study was to observe the effects of two anhydrous formulations containing microfine particles of ascorbic acid on neocollagenesis and cytokeratin production in ex vivo human skin. Vitamin C preparations were applied topically onto the surface of freshly excised human abdominal skin. Following an exposure time of 48 h with appropriate controls, skin discs were cut into sections, placed on slides and assessed using immunohistochemical (antibodies: collagen type I, III, cytokeratin) staining. Analysis was performed using microscopy and descriptive rating. Both formulations resulted in increased production of collagen types I and III and cytokeratin. The application of anhydrous formulations containing microfine particles of ascorbic acid to ex vivo human skin in this study resulted in neocollagenesis and increased production of cytokeratin. This approach appears to enable biological effects of ascorbic acid in the skin using a vehicle which would provide it greater stability than an aqueous vehicle.

  2. In vivo study effect of particulate Bioglass in the prevention of infection in open fracture fixation.

    Science.gov (United States)

    Xie, Zong-Ping; Zhang, Chang-Qing; Yi, Cheng-Qing; Qiu, Jian-Jun; Wang, Jian-Qiang; Zhou, Juan

    2009-07-01

    There are many in vitro experiments showing that particulate bioactive glasses have a broad and certain antibacterial effect, but there is no report about this antibacterial effect in vivo so far. The aim of this study is to examine the efficacy of particulate Bioglass in reducing the rate of infection with Staphylococcus aureus after the fixation of open tibial fractures in rabbits. The test in vivo was carried out with male rabbits split into two groups infected with Staphylococcus aureus at the right tibial fracture sites fixed with plate and screw, either with or without bioactive glass respectively. Culture results show that six of ten rabbits from the control group had a positive culture for the strain of Staphylococcus aureus ATCC25923, compared with six of the nine rabbits from the Bioglass group. The median radiographic score is 4.5 points for the rabbits from the control group and 4 points for the rabbits from the Bioglass group. The median histopathological score was 2.5 points for the rabbits in the control group and 3 points for the rabbits in the Bioglass group. In conclusion, this study showed no significant difference between the rates of infection of two groups. Particulate Bioglass did not reduce the rate of infection with Staphylococcus aureus after the fixation of open tibial fractures in rabbits. (c) 2008 Wiley Periodicals, Inc.

  3. Ex vivo rabbit cornea diffusion studies with a soluble insert of moxifloxacin.

    Science.gov (United States)

    Sebastián-Morelló, María; Calatayud-Pascual, María Aracely; Rodilla, Vicent; Balaguer-Fernández, Cristina; López-Castellano, Alicia

    2018-02-01

    The objective of this research was to develop and evaluate an ocular insert for the controlled drug delivery of moxifloxacin which could perhaps be used in the treatment of corneal keratitis or even bacterial endophthalmitis. We have evaluated the ex vivo ocular diffusion of moxifloxacin through rabbit cornea, both fresh and preserved under different conditions. Histological studies were also carried out. Subsequently, drug matrix inserts were prepared using bioadhesive polymers. The inserts were evaluated for their physicochemical parameters. Ophthalmic ex vivo permeation of moxifloxacin was carried out with the most promising insert. The formulate insert was thin and provided higher ocular diffusion than commercial formulations. Ocular diffusion studies revealed significant differences between fresh and frozen corneas. Histological examinations also showed differences in the thickness of stroma between fresh and frozen corneas. The ophthalmic insert we have developed allows a larger quantity of moxifloxacin to permeate through the cornea than existing commercial formulations of the drug. Ocular delivery of moxifloxacin with this insert could be a new approach for the treatment of eye diseases.

  4. Laser system for optical biopsy and in-vivo study of the human skin

    Science.gov (United States)

    Borisova, Ekaterina G.; Avramov, Lachezar A.

    2001-04-01

    The aim of this study was to perform a preliminary evaluation of the diagnostic potential of noninvasive laser-induced autofluorescence spectroscopy (LIAFS) for human skin in vivo. The autofluorescence characterization of tissue relies on different spectral properties of tissue. It was demonstrated a differentiation between normal skin and skin with vitaligo. In our experimental investigation of the autofluorescence spectrum of human skin in vivo a nitrogen laser with excitation wavelength 337 nm was used. Two fluorescence bands were observed at 440 and 490 nm, these were attributed to reduced nicotinamide adenine dinucleotide (NADH) and collagen. The intensity of the NADH emission band was markedly reduced in the skin with vitaligo compared with the normal skin, which could indicate different redox conditions in skin with vitaligo. The autofluorescence spectrum of human skin depends on the main internal absorbers, which are blood and melanin. In this study was described the effect caused by melanin content on the shape of the autofluorescence spectrum of human skin. Human skin fluorescence spectrum might provide dermatologists with important information and such investigations are successfully used now in skin disease diagnostics, in investigation of the environmental factor impact or for evaluation of treatment efficiency. The goal of this work is optimization of detection and diagnosis of hollow organs and skin.

  5. A review of in vivo animal studies in retinal prosthesis research.

    Science.gov (United States)

    Bertschinger, Dimiter R; Beknazar, Evgueny; Simonutti, Manuel; Safran, Avinoam B; Sahel, José A; Rosolen, Serge G; Picaud, Serge; Salzmann, Joel

    2008-11-01

    The development of a functional retinal prosthesis for acquired blindness is a great challenge. Rapid progress in the field over the last 15 years would not have been possible without extensive animal experimentation pertaining to device design and fabrication, biocompatibility, stimulation parameters and functional responses. This paper presents an overview of in vivo animal research related to retinal prosthetics, and aims to summarize the relevant studies. A Pubmed search of the English language literature was performed. The key search terms were: retinal implant, retinal prosthesis, artificial vision, rat, rabbit, cat, dog, sheep, pig, minipig. In addition a manual search was performed based on references quoted in the articles retrieved through Pubmed. We identified 50 articles relevant to in vivo animal experimentation directly related to the development of a retinal implant. The highest number of publications related to the cat (n = 18). The contribution of animal models to the development of retinal prosthetic devices has been enormous, and has led to human feasibility studies. Grey areas remain regarding long-term tissue-implant interactions, biomaterials, prosthesis design and neural adaptation. Animals will continue to play a key role in this rapidly evolving field.

  6. Preliminary study of synthetic aperture tissue harmonic imaging on in-vivo data

    Science.gov (United States)

    Rasmussen, Joachim H.; Hemmsen, Martin C.; Madsen, Signe S.; Hansen, Peter M.; Nielsen, Michael B.; Jensen, Jørgen A.

    2013-03-01

    A method for synthetic aperture tissue harmonic imaging is investigated. It combines synthetic aperture sequen- tial beamforming (SASB) with tissue harmonic imaging (THI) to produce an increased and more uniform spatial resolution and improved side lobe reduction compared to conventional B-mode imaging. Synthetic aperture sequential beamforming tissue harmonic imaging (SASB-THI) was implemented on a commercially available BK 2202 Pro Focus UltraView ultrasound system and compared to dynamic receive focused tissue harmonic imag- ing (DRF-THI) in clinical scans. The scan sequence that was implemented on the UltraView system acquires both SASB-THI and DRF-THI simultaneously. Twenty-four simultaneously acquired video sequences of in-vivo abdominal SASB-THI and DRF-THI scans on 3 volunteers of 4 different sections of liver and kidney tissues were created. Videos of the in-vivo scans were presented in double blinded studies to two radiologists for image quality performance scoring. Limitations to the systems transmit stage prevented user defined transmit apodization to be applied. Field II simulations showed that side lobes in SASB could be improved by using Hanning transmit apodization. Results from the image quality study show, that in the current configuration on the UltraView system, where no transmit apodization was applied, SASB-THI and DRF-THI produced equally good images. It is expected that given the use of transmit apodization, SASB-THI could be further improved.

  7. Improvement of thymol properties by complexation with cyclodextrins: in vitro and in vivo studies.

    Science.gov (United States)

    Nieddu, Maria; Rassu, Giovanna; Boatto, Gianpiero; Bosi, Paolo; Trevisi, Paolo; Giunchedi, Paolo; Carta, Antonio; Gavini, Elisabetta

    2014-02-15

    Thymol, an effective agent for microbial diseases, has a low aqueous solubility and a strong bitter/irritating taste. These physicochemical characteristics need to be improved to develop pharmaceutical preparations. This study evaluates whether β-cyclodextrin and a copolymer based on dimethylaminoethyl methacrylate (DMAEMA) interact with thymol in order to control powderization, solubilization, and taste-masking properties. The thymol-β-cyclodextrin complex was prepared by co-precipitation and sealed-heating methods. The DMAEMA copolymer was mixed with the complex using a new approach, instead of spray coating, to decrease thymol volatility. In vivo studies were performed. Sealed-heating is a suitable method for including thymol in β-cyclodextrin with a good loading efficiency; thymol volatility control is achieved by mixing the complex with the DMAEMA copolymer. β-Cyclodextrin accelerates the in vivo thymol absorption rate compared with the free drug; the thymol half-life is still long. Therefore, a low number of administrations per day are required. Although bioavailability is unchanged with respect to free thymol, high doses could be administered of a selected formulation without compromising the compliance. Furthermore, thymol that is not absorbed is held along the intestine, where it can useful in the treatment and/or prevention of intestinal bacterial diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Hydroxytyrosol inhibits cholangiocarcinoma tumor growth: an in vivo and in vitro study.

    Science.gov (United States)

    Li, Shuai; Han, Zhiyang; Ma, Yong; Song, Ruipeng; Pei, Tiemin; Zheng, Tongsen; Wang, Jiabei; Xu, Dongsheng; Fang, Xiang; Jiang, Hongchi; Liu, Lianxin

    2014-01-01

    Cholangiocarcinoma (CCA) is a type of digestive tumor that is associated with a high rate of mortality due to the difficulty of early diagnosis and the resistance of this tumor type to chemotherapy. Hydroxytyrosol (HT), which is derived from virgin olive oil (VOO), has recently been reported to inhibit the proliferation of various types of human cancer cells. In the present study, we investigated the effect of HT on CCA. The antiproliferative and proapoptotic effects of HT on CCA were evaluated in the human CCA cell lines TFK-1 and KMBC and the human gallbladder cancer cell line GBS-SD. We also assessed this effect in vivo. We found that 75 µM HT inhibited the proliferation of the TFK-1, KMBC and GBS-SD cell lines. However, 200 µM HT treatment did not affect the proliferation of the human bile duct cell line HIBEpiC. More importantly, HT (250 and 500 mg/kg/day) markedly inhibited the growth of CCA xenografts in mice. G2/M phase cell cycle arrest and apoptosis were observed using flow cytometry and western blotting, and we also noted a time- and dose-dependent inhibition of phospho-ERK, with no changes in total-ERK, during treatment with HT. The present study showed that HT induces cell cycle arrest and apoptosis in vitro and in vivo. These data suggest that HT, which possesses excellent biocompatibility and few side-effects, could be developed as a novel agent against CCA.

  9. In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals.

    Science.gov (United States)

    Pinto, Suyene Rocha; Sarcinelle, Michelle Alvares; de Souza Albernaz, Marta; da Silva, Franciana Maria Rosa; Seabra, Sergio Henrique; Almeida do Nascimento, Patricia; Carvalho, Cosme Leonardo Gomes; Santos-Oliveira, Ralph

    2014-10-01

    The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Controlled release of dutasteride from biodegradable microspheres: in vitro and in vivo studies.

    Directory of Open Access Journals (Sweden)

    Xiangyang Xie

    Full Text Available The aim of the present work was to study the in vitro/in vivo characteristics of dutasteride loaded biodegradable microspheres designed for sustained release of dutasteride over four weeks. An O/W emulsion-solvent evaporation method was used to incorporate dutasteride, which is of interest in the treatment of benign prostatic hyperplasia (BPH, into poly(lactide-co-glycolide (PLGA. A response surface method (RSM with central composite design (CCD was employed to optimize the formulation variables. A prolonged in vitro drug release profile was observed, with a complete release of the entrapped drug within 28 days. The pharmacokinetics study showed sustained plasma drug concentration-time profile of dutasteride loaded microspheres after subcutaneous injection into rats. The in vitro drug release in rats correlated well with the in vivo pharmacokinetics profile. The pharmacodynamics evaluated by determination of the BPH inhibition in the rat models also showed a prolonged pharmacological response. These results suggest the potential use of dutasteride loaded biodegradable microspheres for the management of BPH over long periods.

  11. The strain behavior of the anterior cruciate ligament during stair climbing: an in vivo study.

    Science.gov (United States)

    Fleming, B C; Beynnon, B D; Renstrom, P A; Johnson, R J; Nichols, C E; Peura, G D; Uh, B S

    1999-03-01

    Stair climbing is a closed kinetic chain exercise that is thought to be useful for knee rehabilitation following anterior cruciate ligament (ACL) reconstruction while protecting the graft from excessive strain. The objectives of this study were to measure the strain produced in the anteromedial band (AMB) of the normal ACL during stair climbing in vivo. We have previously shown that the normal AMB strain pattern during knee passive flexion-extension motion is similar to that of an ACL graft immediately after graft fixation. We successfully tested five subjects with normal ACLs, who were candidates for arthroscopic meniscectomy under local anesthesia. AMB strain was measured in vivo using the Differential Variable Reluctance Transducer (MicroStrain, Burlington, VT). The stair climbing activities were performed on a StairMaster 4000PT (Randall Sports Medicine, Kirkland, WA). Two different climbing cadences were evaluated; 80 and 112 steps per minute. Consistent with our previous studies of ACL biomechanics, strain values increased as the knee was moved from a flexed to an extended position. The mean peak AMB strain values for the 80 and 112 steps per minute conditions were 2.69% (+/-2.89&) and 2.76% (+/-2.68%), respectively. These values were not significantly different. Compared with other rehabilitation activities previously tested in the same manner, the AMB strain values produced during stair climbing were highly variable across subjects. High strain values were observed in some patients but not in others.

  12. Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

    Science.gov (United States)

    Salem, Heba F; Ahmed, Sayed M; Hassaballah, Ashraf E; Omar, Mahmoud M

    2015-01-01

    Background The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results The size of glutathione-modulated nanoliposomes was glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections. PMID:26229435

  13. Diagnostic accuracy of proximal caries by digital radiographs: an in vivo and in vitro comparative study.

    Science.gov (United States)

    Li, Gang; Qu, Xin-min; Chen, Yan; Zhang, Jie; Zhang, Zu-yan; Ma, Xu-chen

    2010-03-01

    The aim of this study was to evaluate if the diagnostic accuracy of proximal dental caries in digital radiographs was similar when obtained in in vivo and in vitro conditions. Thirty-nine noncavitated teeth were collected from 11 subjects who had part of upper or lower jaws excised owing to cyst or neoplasm. Before operation, radiographs of the teeth involved were taken with the digital imaging system Digora Optime (Soredex, Helsinki, Finland), and after operation, the same extracted teeth were mounted in plaster blocks and exposed with the same digital imaging system. The teeth were subsequently sectioned for histologic validation of the lesions. Six observers evaluated all of the radiographs according to a 5-category scale. Receiver operating characteristic analysis was performed. Repeated-measure analysis of variance was used for the statistical analysis. There were no significant differences between digital radiographs taken in in vivo and in vitro conditions for diagnosis of proximal dental caries (P = .286). Detection accuracy of proximal dental caries obtained from an in vitro study can be considered to be representative of diagnostic accuracy of proximal dental caries obtained in the real clinical situation. Copyright 2010 Mosby, Inc. All rights reserved.

  14. Surface modification minimizes the toxicity of silver nanoparticles: an in vitro and in vivo study.

    Science.gov (United States)

    Das, Balaram; Tripathy, Satyajit; Adhikary, Jaydeep; Chattopadhyay, Sourav; Mandal, Debasis; Dash, Sandeep Kumar; Das, Sabyasachi; Dey, Aditi; Dey, Sankar Kumar; Das, Debasis; Roy, Somenath

    2017-08-01

    Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system. Ag-NPs released excess Ag+ ions leads to activation of NADPH oxidase and helps in generating the reactive oxygen species (ROS). Silver nanoparticles elicit the production of excess amount of ROS results activation of TNF-α. Ag-NPs activates caspase-3 and 9 which are the signature of mitochondrial pathway. Ag-NPs are responsible to decrease the antioxidant enzymes and imbalance the oxidative status into the cells but functionalization with BSA and PEG helps to protect the adverse effect of Ag-NPs on the cells. This study suggested that Ag-NPs are toxic to normal cells which directly lead with human health. Surface functionalization may open the gateway for further use of Ag-NPs in different area such as antimicrobial and anticancer therapy, industrial use or in biomedical sciences.

  15. In vivo study of experimental pneumococcal meningitis using magnetic resonance imaging

    DEFF Research Database (Denmark)

    Brandt, C.T.; Simonsen, H.; Liptrot, Matthew George

    2008-01-01

    Background: Magnetic Resonance Imaging (MRI) methods were evaluated as a tool for the study of experimental meningitis. The identification and characterisation of pathophysiological parameters that vary during the course of the disease could be used as markers for future studies of new treatment......-vivo with MRI. Increasing BBB-breakdown and ventricle size was observed in rats with meningitis whereas changes in brain water distribution were heterogeneous. MRI will be a valuable technique for future studies aiming at evaluating or optimizing adjunctive treatments. © 2008 Brandt et al; licensee Bio......-rat variation as the disease progressed, but without overall differences compared to uninfected rats (P > 0.05). Areas of well-'perfused' muscle decreased with the progression of infection indicative of septicaemia (P = 0.05). Conclusion: The evolution of bacterial meningitis was successfully followed in...

  16. Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals.

    Science.gov (United States)

    Vasin, Mikhail V; Ushakov, Igor B

    2015-01-01

    This review gives a comparative evaluation of the radioprotective properties and the therapeutic index (TI) of radioprotectors from various pharmacological group in experiments on both small and large animals. It presents a hypothesis explaining the decrease in the TI of cystamine and 5-methoxytryptamine (mexamine), and the retention of that of α1-adrenomimetic indralin, and also compares the effects on large and small animals. The considerable differences in the therapeutic indices of catecholamines, serotonin and cystamine are a consequence of specific features of their mechanisms of radioprotective action. Radioprotectors acting via receptor mediation tend to provide a more expanded window of protection. The reduction in the TI of cystamine in larger animals, such as dogs, may be caused by the greater increase in toxicity of aminothiols in relation to the decrease in their optimal doses for radioprotective effect in going from mice to dogs, which is a consequence of the slower metabolic processes in larger animals. The somatogenic phase of intoxication by cystamine is significantly longer than the duration of its radioprotective effect, and increases with irradiation. The decrease in the radioprotective effect and the TI of mexamine in experiments with dogs may be caused by their lower sensitivity to the acute hypoxia induced by the mexamine. This is because of lower gradient in oxygen tension between tissue cells and blood capillaries under acute hypoxia that is determined by lower initial oxygen consumption in a large animal as compared with a small animal. Indralin likely provides optimal radioprotective effects and a higher TI for large animals via the increased specificity of its adrenergic effect on tissue respiration, which supports the development of acute hypoxia in the radiosensitive tissues of large animals. The stimulatory effect of indralin on early post-irradiation haematopoietic recovery cannot provide a high level of radioprotective action for

  17. Comparative efficacy and the window of radioprotection for adrenergic and serotoninergic agents and aminothiols in experiments with small and large animals

    Science.gov (United States)

    Vasin, Mikhail V.; Ushakov, Igor B.

    2015-01-01

    This review gives a comparative evaluation of the radioprotective properties and the therapeutic index (TI) of radioprotectors from various pharmacological group in experiments on both small and large animals. It presents a hypothesis explaining the decrease in the TI of cystamine and 5-methoxytryptamine (mexamine), and the retention of that of α1-adrenomimetic indralin, and also compares the effects on large and small animals. The considerable differences in the therapeutic indices of catecholamines, serotonin and cystamine are a consequence of specific features of their mechanisms of radioprotective action. Radioprotectors acting via receptor mediation tend to provide a more expanded window of protection. The reduction in the TI of cystamine in larger animals, such as dogs, may be caused by the greater increase in toxicity of aminothiols in relation to the decrease in their optimal doses for radioprotective effect in going from mice to dogs, which is a consequence of the slower metabolic processes in larger animals. The somatogenic phase of intoxication by cystamine is significantly longer than the duration of its radioprotective effect, and increases with irradiation. The decrease in the radioprotective effect and the TI of mexamine in experiments with dogs may be caused by their lower sensitivity to the acute hypoxia induced by the mexamine. This is because of lower gradient in oxygen tension between tissue cells and blood capillaries under acute hypoxia that is determined by lower initial oxygen consumption in a large animal as compared with a small animal. Indralin likely provides optimal radioprotective effects and a higher TI for large animals via the increased specificity of its adrenergic effect on tissue respiration, which supports the development of acute hypoxia in the radiosensitive tissues of large animals. The stimulatory effect of indralin on early post-irradiation haematopoietic recovery cannot provide a high level of radioprotective action for

  18. In vivo nuclear magnetic resonance studies of hepatic methoxyflurane metabolism. I. Verification and quantitation of methoxydifluoroacetate.

    Science.gov (United States)

    Selinsky, B S; Perlman, M E; London, R E

    1988-05-01

    The elimination and metabolism of the fluorinated inhalation anesthetic methoxyflurane (2,2-dichloro-1,1-difluoroethyl methyl ether) in rats has been monitored using in vivo 19F nuclear magnetic resonance at 8.45 T. The elimination of methoxyflurane from rat liver as measured using a surface coil is a first order process when measured beginning 2-3 hr after the end of methoxyflurane anesthesia over a period of 12 hr. The rate constant for hepatic methoxyflurane elimination is dependent upon the duration of anesthesia, varying from 0.24 hr-1 for 15 min of anesthesia to 0.07 hr-1 for 1 hr of anesthesia. Methoxyflurane was shown to be metabolized in the liver to methoxydifluoroacetate using the surface coil method. No resonance for hepatic fluoride ion could be observed in vivo. Pure sodium methoxydifluoroacetate was synthesized in order to confirm the identity of the resonances in liver and urine. 19F NMR spectra of urine collected from anesthetized rats contain resonances for two methoxyflurane metabolites, methoxydifluoroacetate and inorganic fluoride. Studies with liver homogenates imply that fluoride is quickly cleared from the liver and eliminated from the body through the urine, explaining the inability to observe hepatic fluoride using a surface coil. The 19F NMR resonance for inorganic fluoride in urine was found to be broadened by interaction with metal ions, since the broadening could be eliminated by treatment with chelating resin.

  19. Acoustic hemostasis of porcine superficial femoral artery: Simulation and in-vivo experimental studies

    Science.gov (United States)

    Zeng, Xiaozheng; Mitchell, Stuart; Miller, Matthew; Barnes, Stephen; Hopple, Jerry; Kook, John; Moreau-Gobard, Romain; Hsu, Stephen; Ahiekpor-Dravi, Alexis; Crum, Lawrence A.; Eaton, John; Wong, Keith; Sekins, K. Michael

    2012-10-01

    In-vivo focused ultrasound studies were computationally simulated and conducted experimentally with the aim of occluding porcine superficial femoral arteries (SFA) via thermal coagulation. A multi-array HIFU applicator was used which electronically scanned multiple beam foci around the target point. The spatio-temporally averaged acoustic and temperature fields were simulated in a fluid dynamics and acousto-thermal finite element model with representative tissue fields, including muscle, vessel and blood. Simulations showed that with an acoustic power of 200W and a dose time of 60s, perivascular tissue reached 91°C; and yet blood reached a maximum 59°C, below the coagulation objective for this dose regime (75°C). Per simulations, acoustic-streaming induced velocity in blood reached 6.1cm/s. In in-vivo experiments, several arteries were treated. As simulated, thermal lesions were observed in muscle surrounding SFA in all cases. In dosing limited to 30 to 60 seconds, it required 257W to provide occlusion (one complete and one partial occlusion). Angiography and histology showed evidence of thrombogenesis and collagen shrinkage-based vessel constriction at these doses.

  20. [In vitro and in vivo study of electromagnetic compatibility of cellular phones and pacemakers].

    Science.gov (United States)

    Gellér, L; Thuróczy, G; Merkely, B

    2001-09-09

    Electromagnetic compatibility (EMC) of cellular phones and pacemakers (PM) was examined in four different cellular phone system (NMT, GSM, RLL, DCS 1800 MHz) and in fifteen different PM type in-vitro and in-vivo in humans. After more than 1100 in-vitro and 130 in-vivo tests we concluded, that the electromagnetic immunity of the PMs which are implanted in Hungary is suitable with only few exceptions. The highest rate of EMC problems was observed with NMT 450 MHz cellular phones (10.5%-63%). There was no EMC disturbance observed with GSM and DCS 1800 MHz cellular phones. There was only one case when clinically significant symptom was noticed with only one PM type and with NMT system cellular phone when the distance of cellular phone was 3-4 cms, and the power was maximal. There was not any EMC disturbance observed with none of the cellular phone systems during normal talking and when the distance of the PM and cellular phone was more than 20 cms. Our study supports guidelines which suggest that PM patients should contact their physicians when using cellular phones and cellular phones and PMs should not get closer than 20 cms.

  1. In Vivo and Cadaver Studies of the Canalicular/Lacrimal Sac Mucosal Folds

    Directory of Open Access Journals (Sweden)

    Yongsheng You

    2016-01-01

    Full Text Available Purpose. The study aimed to investigate canalicular/lacrimal sac mucosal folds (CLS-MFs in vivo and in cadavers in order to explore their functional roles in the lacrimal drainage system. Method. The observations of CLS-MFs in vivo were performed on 16 patients with chronic dacryocystitis after undergoing an endonasal endoscopic dacryocystorhinostomy (EE-DCR. The lacrimal sacs and common canaliculi of 19 adult cadavers were dissected. The opening/closing of an orifice and mucosal fold was recorded. All of the specimens were subjected to a histological examination. Results. The upper and lower lacrimal canaliculi in all of the samples united to form a common canaliculus that opened to the lacrimal sac. CLS-MFs were observed in 10 of the 16 patients (62.5% and 9 of the 19 cadavers (47.4%. The orifices or mucosal folds could be opened or closed when related muscles contracted or relaxed. Histological sections showed a mucosal fold at one side of an orifice. Conclusion. Common canaliculus is the most common type that the canaliculus opens to lacrimal sac. CLS-MFs exist in a certain ratio that can be opened/closed with the movement of the orifices. They may be involved in the drainage of tears or the pathogenesis of acute dacryocystitis or lacrimal sac mucocele.

  2. Scapholunate ligament injury adversely alters in vivo wrist joint mechanics: an MRI-based modeling study.

    Science.gov (United States)

    Johnson, Joshua E; Lee, Phil; McIff, Terence E; Toby, E Bruce; Fischer, Kenneth J

    2013-09-01

    We investigated the effects of scapholunate ligament injury on in vivo radiocarpal joint mechanics using image-based surface contact modeling. Magnetic resonance images of 10 injured and contralateral normal wrists were acquired at high resolution (hand relaxed) and during functional grasp. Three-dimensional surface models of the radioscaphoid and radiolunate articulations were constructed from the relaxed images, and image registration between the relaxed and grasp images provided kinematics. The displacement driven models were implemented in contact modeling software. Contact parameters were determined from interpenetration of interacting bodies and a linear contact rule. Peak and mean contact pressures, contact forces and contact areas were compared between the normal and injured wrists. Also measured were effective (direct) contact areas and intercentroid distances from the grasp images. Means of the model contact areas were within 10 mm(2) of the direct contact areas for both articulations. With injury, all contact parameters significantly increased in the radioscaphoid articulation, while only peak contact pressure and contact force significantly increased in the radiolunate articulation. Intercentroid distances also increased significantly with injury. This study provides novel in vivo contact mechanics data from scapholunate ligament injury and confirms detrimental alterations as a result of injury. Copyright © 2013 Orthopaedic Research Society.

  3. Multigram Synthesis and in Vivo Efficacy Studies of a Novel Multitarget Anti-Alzheimer’s Compound

    Directory of Open Access Journals (Sweden)

    Irene Sola

    2015-03-01

    Full Text Available We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer’s disease (AD. Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.

  4. IN VIVO STUDY OF PHENOLIC COMPOUNDS ROLE ON ANTIHYPERCHOLESTEROL ACTIVITY OF VIRGIN COCONUT OIL

    Directory of Open Access Journals (Sweden)

    Tri Joko Raharjo

    2010-06-01

    Full Text Available The role of phenolic compounds on antihypercholeserol activity of Virgin Coconut Oil (VCO has been investigated. The in vivo studies ware carried out by treatment of two groups of Wistar white mouse (Ratus norvegicus using high phenolic VCO and low phenolic VCO respectively, followed by analysis of lipid profile in blood and liver serum of the mouse. In addition a group of hypercholesterol mouse was treated with low phenolic VCO and the blood serum lipid profile was compared with untreated hypercholesterol mouse. The results show that phenolic compound play an important role on antihypercholesterol of VCO. Group of mouse treated with high phenolic VCO have better lipid profile (blood serum: total cholesterol: 70 mg/dL, triglyceride: 76 mg/dL, HDL: 20 mg/dL, LDL: 35 mg/dL; liver serum: total cholesterol:7 mg/dL, triglyceride: 19 mg/dL compared with the group treated with low phenolic VCO (blood serum: total cholesterol: 82 mg/dL, triglyceride: 100 mg/dL, HDL: 21 mg/dL, LDL: 41 mg/dL; liver serum: total cholesterol: 9 mg/dL, triglyceride: 34 mg/dL. Hypercholesterol mouse tests shown that low phenolic VCO treatment result in decreasing of blood serum cholesterol level by 52.10% which was not significantly different compared to untreated mouses (decreasing of blood serum cholesterol level by 48.61%.   Keywords: antihypercholesterol, phenolic compound, VCO, in vivo

  5. Initial study on in vivo conductivity mapping of breast cancer using MRI.

    Science.gov (United States)

    Shin, Jaewook; Kim, Min Jung; Lee, Joonsung; Nam, Yoonho; Kim, Min-Oh; Choi, Narae; Kim, Sooyeon; Kim, Dong-Hyun

    2015-08-01

    To develop and apply a method to measure in vivo electrical conductivity values using magnetic resonance imaging (MRI) in subjects with breast cancer. A recently developed technique named MREPT (MR electrical properties tomography) together with a novel coil combination process was used to quantify the conductivity values. The overall technique was validated using a phantom study. In addition, 90 subjects were imaged (50 subjects with previously biopsy-confirmed breast tumor and 40 normal subjects), which was approved by our institutional review board (IRB). A routine clinical protocol, specifically a T2 -weighted FSE (fast spin echo) imaging data, was used for reconstruction of conductivity. By employing the coil combination, the relative error in the conductivity map was reduced from ~70% to 10%. The average conductivity values in breast cancers regions (0.89 ± 0.33S/m) was higher compared to parenchymal tissue (0.43 S/m, P conductivity compared to benign cases (0.56 S/m, n = 5) (P conductivity compared to in situ cancers (0.57 S/m) (P conductivity mapping of breast cancers is feasible using a noninvasive in vivo MREPT technique combined with a coil combination process. The method may provide a tool in the MR diagnosis of breast cancer. © 2014 Wiley Periodicals, Inc.

  6. [X-ray bone densitometry. Study of in vitro and in vivo reproducibility].

    Science.gov (United States)

    Luisetto, G; Zangari, M; Ridolfi, P; Tizian, L; Ziliotto, D

    1991-01-01

    We studied the reproducibility in vitro and in vivo of a new bone densitometer (HOLOGIC QDR-1000, software version 4.03) which uses an x-ray source at two different levels of energy. Short and long term coefficient of variation (c.v.) in vitro is less than 0.5%. In vivo c.v. is less than 1% in normal body weight subjects and less than 3% in obese subjects. The ingestion of 500 mg of calcium element did not modify bone mineral density (BMD), while 1000 mg determined an increase of BMD equal to 2.6% and 1.5% in the two subjects examined. The increase of water thickness on a three femoral heads phantom caused a progressive reduction of bone mineral content (BMC) and BMD until 12.1% less than basal value and an increase of c.v. from 0.1% to 1%. The addition of oil to water at different percentages determined a slight increase of both BMC and BMD, till 3.5% with 66% of oil in water, if compared with the values obtained with water alone. The reduction of soft tissue around the bone determined a progressive decrease of BMD reaching 3.4% less than basal value when the reduction was 30%.

  7. An ex vivo porcine nasal mucosa explants model to study MRSA colonization.

    Directory of Open Access Journals (Sweden)

    Pawel Tulinski

    Full Text Available Staphylococcus aureus is an opportunistic pathogen able to colonize the upper respiratory tract and skin surfaces in mammals. Methicillin-resistant S. aureus ST398 is prevalent in pigs in Europe and North America. However, the mechanism of successful pig colonization by MRSA ST398 is poorly understood. To study MRSA colonization in pigs, an ex vivo model consisting of porcine nasal mucosa explants cultured at an air-liquid interface was evaluated. In cultured mucosa explants from the surfaces of the ventral turbinates and septum of the pig nose no changes in cell morphology and viability were observed up to 72 h. MRSA colonization on the explants was evaluated followed for three MRSA ST398 isolates for 180 minutes. The explants were incubated with 3×10(8 CFU/ml in PBS for 2 h to allow bacteria to adhere to the explants surface. Next the explants were washed and in the first 30 minutes post adhering time, a decline in the number of CFU was observed for all MRSA. Subsequently, the isolates showed either: bacterial growth, no growth, or a further reduction in bacterial numbers. The MRSA were either localized as clusters between the cilia or as single bacteria on the cilia surface. No morphological changes in the epithelium layer were observed during the incubation with MRSA. We conclude that porcine nasal mucosa explants are a valuable ex vivo model to unravel the interaction of MRSA with nasal tissue.

  8. An ex vivo spinal cord injury model to study ependymal cells in adult mouse tissue.

    Science.gov (United States)

    Fernandez-Zafra, Teresa; Codeluppi, Simone; Uhlén, Per

    2017-08-15

    Traumatic spinal cord injury is characterized by an initial cell loss that is followed by a concerted cellular response in an attempt to restore the damaged tissue. Nevertheless, little is known about the signaling mechanisms governing the cellular response to injury. Here, we have established an adult ex vivo system that exhibits multiple hallmarks of spinal cord injury and allows the study of complex processes that are difficult to address using animal models. We have characterized the ependymal cell response to injury in this model system and found that ependymal cells can become activated, proliferate, migrate out of the central canal lining and differentiate in a manner resembling the in vivo situation. Moreover, we show that these cells respond to external adenosine triphosphate and exhibit spontaneous Ca(2+) activity, processes that may play a significant role in the regulation of their response to spinal cord injury. This model provides an attractive tool to deepen our understanding of the ependymal cell response after spinal cord injury, which may contribute to the development of new treatment options for spinal cord injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Botulinum neurotoxin serotype D is poorly effective in humans: an in vivo electrophysiological study.

    Science.gov (United States)

    Eleopra, Roberto; Montecucco, Cesare; Devigili, Grazia; Lettieri, Christian; Rinaldo, Sara; Verriello, Lorenzo; Pirazzini, Marco; Caccin, Paola; Rossetto, Ornella

    2013-05-01

    Botulinum neurotoxins act on nerve endings and block neurotransmitter release. Their potency is due to their enzymatic activity and high affinity binding to neurons. Botulinum toxin type A is used in the treatment of human diseases characterized by hyperactivity of peripheral cholinergic nerve terminals, but some patients are or become resistant to it. This can be overcome by using other botulinum toxins, and studies have been performed with different toxin serotypes. Botulinum neurotoxin type D has never been tested in humans in vivo, and, therefore, we investigated the action of this toxin in mouse and human muscles. Botulinum toxin type D potency was determined on mouse hemidiaphragm and on rat neuronal cultures. From these experiments, doses to be injected in human volunteers were decided. The compound muscle action potential of toxin-injected Extensor Digitorum Brevis muscle was measured at different times points after injection in human volunteers. Botulinum toxin type D is poorly effective in inducing human skeletal muscle paralysis. Botulinum toxin type D is very potent in mice and almost ineffective in humans in vivo. The results shed new light on the mechanism of toxin type D binding to the neuronal surface receptors. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Bioequivalence study of paracetamol tablets: in vitro-in vivo correlation.

    Science.gov (United States)

    Domínguez, A; Medina, R; Hurtado, M

    2000-08-01

    The bioequivalence of three chemically equivalent paracetamol generic Mexican products (500 mg tablets) was evaluated in 12 healthy volunteers using the American innovator product (Tylenol, McNeil, Fort Washington, PA), as the reference. Single oral doses of each product were administered at 1-week intervals using a 4 x 4 Latin square design balanced for the first residual effect. The total amount of paracetamol excreted in urine in 24 hr was taken as a measure of bioavailability. In addition, moment analysis was used to estimate in vitro mean dissolution time (MDT) from dissolution profiles obtained following the USP 23 dissolution test specified for paracetamol tablets and to estimate in vivo mean residence time (MRT) from urinary excretion data. Significant differences in the dissolution performance and in the cumulative amount of paracetamol excreted in urine up to 24 hr were observed when the data were analyzed by analysis of variance (ANOVA) (p paracetamol products studied can be considered equivalent to the reference product Tylenol. A linear correlation between in vitro MDT and in vivo MRT was found.

  11. Development of highly potent melanogenesis inhibitor by in vitro, in vivo and computational studies

    Directory of Open Access Journals (Sweden)

    Abbas Q

    2017-07-01

    Full Text Available Qamar Abbas,1 Zaman Ashraf,2 Mubashir Hassan,1 Humaira Nadeem,3 Muhammad Latif,4 Samina Afzal,5 Sung-Yum Seo1 1Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Republic of Korea; 2Department of Chemistry, Allama Iqbal Open University, Islamabad, 3Riphah Institute of Pharmaceutical Sciences, Riphah International University, Islamabad, Pakistan; 4Center for Genetics and Inherited Diseases, Taibah University, Almadinah Almunawwarah, Kingdom of Saudi Arabia; 5Faculty of Pharmacy, Bahauddin Zakria University, Multan, Pakistan Abstract: The present work describes the synthesis of few hydroxylated amide derivatives as melanogenesis inhibitors. In vitro, in vivo and computational studies proved that compound 6d is a highly potent melanogenesis inhibitor compared to standard kojic acid. The title amides 4a–e and 6a–e were synthesized following simple reaction routes with excellent yields. Most of the synthesized compounds exhibited good mushroom tyrosinase inhibitory activity, but compound 6d showed excellent activity (IC50 0.15 µM compared to standard kojic acid (IC50 16.69 µM. Lineweaver–Burk plots were used for the determination of kinetic mechanism, and it was found that compounds 4c and 6d showed non-competitive inhibition while 6a and 6b showed mixed-type inhibition. The kinetic mechanism further revealed that compound 6d formed irreversible complex with the target enzyme tyrosinase. The Ki values determined for compounds 4c, 6a, 6b and 6d are 0.188, 0.84, 2.20 and 0.217 µM respectively. Results of human tyrosinase inhibitory activity in A375 human melanoma cells showed that compound 6d exhibited 91.9% inhibitory activity at a concentration of 50 µg/mL. In vivo cytotoxicity evaluation of compound 6d in zebrafish embryos showed that it is non-toxic to zebrafish. Melanin depigmentation assay performed in zebrafish indicated that compound 6d possessed greater potential in decreasing melanin contents

  12. A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study.

    Science.gov (United States)

    Candiota, Ana Paula; Acosta, Milena; Simões, Rui Vasco; Delgado-Goñi, Teresa; Lope-Piedrafita, Silvia; Irure, Ainhoa; Marradi, Marco; Bomati-Miguel, Oscar; Miguel-Sancho, Nuria; Abasolo, Ibane; Schwartz, Simó; Santamaria, Jesús; Penadés, Soledad; Arús, Carles

    2014-04-05

    Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs. The post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP. We have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments

  13. Development of aceclofenac nanovesicular system using biomaterial for transdermal delivery: physical characterization, ex vivo, in vivo, and anti-inflammatory studies.

    Science.gov (United States)

    Gaur, Praveen Kumar; Purohit, Suresh; Mishra, Shikha

    2013-01-01

    Aceclofenac is an important NSAID; however, it causes GI disturbances whereas employing transdermal route would require permeation enhancer for systemic application, thereby causing skin damage. Ceramide 2 is a natural lipid having an important role in the maintenance of skin. Aceclofenac-loaded nanovesicles of ceramide-2, cholesterol, palmitic acid, and cholesteryl sulfate were formulated and analyzed for physical and biological properties. Film hydration method was used to prepare the vesicles and physical parameters, in vitro drug release and stability were evaluated. Then, they were formulated into gel and evaluated against a commercial formulation (CF) and gel-containing plain drug (CPG) for ex vivo, in vivo drug permeation, and anti-inflammatory activity. The developed formulations showed best physical profile and ACV-1 gave 92.89% drug release in in vitro studies. Ex vivo studies showed drug permeation between 15.32-31.12 μg/cm(2), whereas CPG and CF released 0.47 and 2.81 μg/cm(2), respectively. ACVG-1 and CF showed Cmax of 8.1 and 1.2 μg/ml at 8 and 4 h, respectively. ACVG-1 showed 11.6 times AUC than CF. ACVG-1 inhibited edema by 44% in first hour itself. Ceramide 2 and palmitic acid played an important role in the formulation and promotes the drug permeation through stratum corneum and dermis. Ceramide content of the formulation also contributes towards stability and skin protection. The composition of the vesicle formulation performs an important role in physical properties and drug permeation, thereby producing an optimum formulation.

  14. Placental transport of large molecules –a study using human ex vivo placental perfusion

    DEFF Research Database (Denmark)

    Mathiesen, Line

    2011-01-01

    and extrapolation to the in vivo situation critical. In my PhD study I have focused on validation and studies with placental perfusion of substances with a high molecular weight, which require transport or carrier molecules to be transported from the maternal to the fetal side, and longer perfusion time demanding...... nutrients, gas and waste transport between the maternal blood and the developing fetus and maintaining pregnancy by producing hormones. The placenta consists of cells of both maternal and fetal origin and forms a complex barrier between the maternal and fetal blood that allows for passage of different...... within two hours of perfusion with a fetal flow rate of 3 mL/min. Negative controls are added to ensure that substance transfer is not due to leakage, e.g. high molecular weight substances that only pass the placental barrier with bulk flow through a leakage in the fetal system. Dextran (40kD) can...

  15. In vivo fluorescence studies of whole blood after chitosan bio-functionalized gold nanorods administration

    Energy Technology Data Exchange (ETDEWEB)

    Garabagiu, Sorina [National Institute for Research and Development of Isotopic and Molecular Technologies, 65-103 Donath, 400293 Cluj-Napoca (Romania); Pestean, Cosmin [University of Agricultural Science and Veterinary Medicine, Cluj-Napoca (Romania); Stefan, Razvan, E-mail: rstefan@usamvcluj.ro [University of Agricultural Science and Veterinary Medicine, Cluj-Napoca (Romania)

    2013-11-15

    Gold nanorods (GNR) have been prepared by a seed mediated method and then functionalized with chitosan, in order to increase their biocompatibility. The interaction of GNR with whole blood has been assessed by means of fluorescence spectroscopy. The whole blood gives rise to a fluorescence emission peak with the maximum centered at 475 nm when a 410 nm excitation wavelength has been used. In vivo assessment of the existence of nanorods in the bloodstream is proven by the increase of the whole blood fluorescence due to metal enhanced fluorescence phenomenon, which leads to an increase of fluorescence emission in the close vicinity of noble metal anisotropic nanostructures. -- Highlights: • Gold nanorods have been synthesized and bio-functionalized with chitosan. • Chitosan–gold nanorods interaction was studied by UV–vis and FTIR spectroscopy. • Bio-functionalized gold nanorods solution was injected to a rabbit. • Fluorescence studies of whole blood in the presence of gold nanorods were performed.

  16. In-vitro and in-vivo study of indomethacin loaded gelatin nanoparticles.

    Science.gov (United States)

    Kumar, Rakesh; Nagarwal, Ramesh C; Dhanawat, Meenakshi; Pandit, Jayanta Kumar

    2011-06-01

    The present research work deals with fabrication of indomethacin loaded gelatin nanoparticles prepared by double desolvation method for controlled drug delivery. Submicron polymeric particles with size 20% in 1 hr) followed by controlled release (> 75% in 12 hr). Among the kinetic models employed, the Higuchi model showed a better fit (R2 > 0.9) with n IDM) was studied by rat paw model and IGNP significantly (P IDM. Pharmacokinetic study showed significant enhancement (P IDM. Cmax of IGNP had higher value (110.81 +/- 8.53 microg/mL) compared to that of IDM (51.66 +/- 7.5 microg/mL). AUC0-12 was 1009.78 +/- 80.24 and 194.33 +/- 46.76/microg x h/mL in IGNP and IDM respectively (relative bioavailability 500%). Further, a good in vitro-in vivo correlation established the formulation for future trials.

  17. Preparation oral levofloxacin colon-specific microspheres delivery: in vitro and in vivo studies.

    Science.gov (United States)

    Jin, Lei; Ding, Yicun; Feng, Mingli; Cao, Qin

    2016-01-01

    The aim of this study was to prepare levofloxacin-loaded chitosan microspheres and to evaluate their in vitro and in vivo characteristics. Glutaraldehyde-crosslinked microspheres were prepared using a spray-drying method, and characterized in terms of the morphological examination, particle size distribution, entrapment efficiency, drug loading and in vitro release. Pharmacokinetics and colon biodistribution studies were used to evaluate that microspheres have more advantage than the conventional formulations. The surface morphology of the freeze-dried microspheres were smooth, discrete with a regular spherical to near-spherical shape. Size of the microspheres after freeze-drying was 4.96 ± 0.76 μm and well-distributed. The zeta potential of microspheres was -29.3 ± 2.1 mV. An average drug loading of 9.3 ± 0.4% and encapsulation efficiency of 81.1 ± 4.7% of levofloxacin microspheres were obtained with the optimized preparation parameters. The cumulative release rate of levofloxacin microspheres was followed by a sustained release and fitted for classic Higuchi kinetic model. In vivo studies showed that chitosan microspheres are thought to have the potential to maintain levofloxacin concentration within target ranges for a long time, decreasing side effects caused by concentration fluctuation, ensuring the efficiency of treatment and improving patient compliance by reducing dosing frequency. It also does not cause any harmful or toxic effect in colon and rectum as evaluated by histopathologic studies.

  18. Minibeam radiotherapy with small animal irradiators; in vitro and in vivo feasibility studies

    Science.gov (United States)

    Bazyar, Soha; Inscoe, Christina R.; O’Brian, E. Timothy; Zhou, Otto; Lee, Yueh Z.

    2017-12-01

    Minibeam radiation therapy (MBRT) delivers an ultrahigh dose of x-ray (⩾100 Gy) in 200–1000 µm beams (peaks), separated by wider non-irradiated regions (valleys) usually as a single temporal fraction. Preclinical studies performed at synchrotron facilities revealed that MBRT is able to ablate tumors while maintaining normal tissue integrity. The main purpose of the present study was to develop an efficient and accessible method to perform MBRT using a conventional x-ray irradiator. We then tested this new method both in vitro and in vivo. Using commercially available lead ribbon and polyethylene sheets, we constructed a collimator that converted the cone beam of an industrial irradiator to 44 identical beams (collimator size  ≈  4  ×  10 cm). The dosimetry characteristics of the generated beams were evaluated using two different radiochromic films (beam FWHM  =  246  ±  32 µm center-to-center  =  926  ±  23 µm peak-to-valley dose ratio  =  24.35  ±  2.10 collimator relative output factor  =  0.84  ±  0.04). Clonogenic assays demonstrated the ability of our method to induce radiobiological cell death in two radioresistant murine tumor cell lines (TRP  =  glioblastoma B16-F10  =  melanoma). A radiobiological equivalent dose (RBE) was calculated by evaluating the acute skin response to graded doses of MBRT and conventional radiotherapy (CRT). Normal mouse skin demonstrated resistance to doses up to 150 Gy on peak. MBRT significantly extended the survival of mice with flank melanoma tumors compared to CRT when RBE were applied (overall p  <  0.001). Loss of spatial resolution deep in the tissue has been a major concern. The beams generated using our collimator maintained their resolution in vivo (mouse brain tissue) and up to 10 cm deep in the radiochromic film. In conclusion, the initial dosimetric, in vitro and in vivo evaluations confirmed the

  19. Characterizing physical properties and in vivo OCT imaging study of Cu-Sn-S nanocrystals

    Directory of Open Access Journals (Sweden)

    Yaotian Liang

    2017-01-01

    Full Text Available Highly yield Cu2SnS3 nanocrystals (CTS NCs have been attracted more attentions in these years, the CTS NCs with strong absorption in near-infrared (NIR region which can serve as the contrast agent of Optical Coherence Tomography (OCT imaging. These NCs can be synthesized by facile method, and exhibit a Localized Surface Plasmon Resonance (LSPR peak in NIR region. The LSPR peak position of the CTS NCs depends on the ratio of copper to tin in the synthesis process. The highest intensity of LSPR at 1380nm when Cu:Sn ratio reach to 9:1. The TEM analysis and X-ray diffraction pattern reveals the formation of CTS NCs with an average size of 6nm and the structure is kesterite crystal phase. In order to apply the NCs in vivo and in vitro study, we used PEGylated phospholipid (DSPE-PEG to modified NCs, and the colloidal stability and cell viability of DSPE-PEG CTS NCs are very suitable for the in vivo OCT imaging study. To quantitatively analyze the contrast effect of DSPE-PEG CTS NCs, the contrast agent was injected from the tail vein of ICR mice, then applied the SD-OCT system monitor the vein of the mouse pinna for 30 minutes. The results indicated that the DSPE-PEG CTS NCs created an obvious signal in the OCT imaging process, which provide the basis for the application of CTS NCs as the contrast agent for the bioimaging study.

  20. Evaluation of the effect of photodynamic antimicrobial therapy in dentin caries: a pilot in vivo study

    Science.gov (United States)

    Borges, F. M. C.; de-Melo, M. A. S.; Lima, J. M. P.; Zanin, I. C. J.; Rodrigues, L. K. A.; Nobre-dos-Santos, M.

    2010-02-01

    In vitro and in situ studies have demonstrated that the photodynamic antimicrobial therapy (PACT) is effective in reducing Streptococcus mutans population in artificially carious dentin. This pilot in vivo study evaluated the antimicrobial effect of PACT using toluidine blue O (TBO) and a light-emitting diode (LED) in carious dentin lesions. Five healthy adult volunteers (19-36 yr), with at least 4 active carious cavities each, participated in this study. Teeth of each volunteer were randomly divided into four groups: (1) without TBO and without light (Control); (2) with TBO alone (TBO); (3) with LED at 94/J cm2 alone (LED); and (4) with TBO plus LED at 94 J/cm2 (PACT). Each cavity was divided into two halves. The baseline carious dentin sample was collected from half of each cavity. Following, the treatments were performed using a random distribution of tooth into treatments. Then, the second collection of carious dentin samples was performed. Before and after treatments, dentin samples were analyzed with regard to the counts of total viable microorganisms, total streptococci, mutans streptococci, and lactobacilli. The data were statistically analyzed by Kruskal-Wallis and Student-Newman-Keuls tests (α=5%). Log reductions ranged from -0.12 to 2.68 and significant reductions were observed for PACT (group 4) when compared to the other groups (1, 2, and 3) for total streptococci and mutans streptococci. Concluding, PACT was effective in killing oral microorganisms present in in vivo carious dentin lesions and may be a promising technique for eliminating bacteria from dentin before restoration.

  1. Uptake of Gold Nanoparticles in Several Rat Organs after Intraperitoneal Administration In Vivo: A Fluorescence Study

    Directory of Open Access Journals (Sweden)

    Mohamed Anwar K. Abdelhalim

    2013-01-01

    Full Text Available Background. The gold nanoparticles (GNPs have potential applications in cancer diagnosis and therapy. In an attempt to characterise the potential toxicity or hazards of GNPs as a therapeutic or diagnostic tool, the fluorescence spectra in several rat organs in vivo were measured after intraperitoneal administration of GNPs. Methods. The experimental rats were divided into control and six groups (G1A, G1B, G2A, G2B, G3A, and G3B; G1: 20 nm; G2: 10 nm; G3: 50 nm; A: infusion of GNPs for 3 days; B: infusion of GNPs for 7 days. The fluorescence measurements were investigated in the liver, kidney, heart, and lung organs of rats after intraperitoneal administration of GNPs for periods of 3 and 7 days in vivo. Results. The 10 and 20 nm GNPs exhibited spherical morphology shape, while the 50 nm GNPs exhibited hexagonal shape. A sharp decrease in the fluorescence intensity induced with the larger 50 nm GNPs in the liver, kidney, heart, and lung organs of rats at the exposure duration of 3 and 7 days in vivo compared with the smaller 10 and 20 nm GNPs was observed. Conclusions. The decrease in fluorescence intensity may be attributed to occurrence of strong quenching, decrease in number and surface area of GNPs, and high clearance of GNPs via urine and bile. Moreover, decreasing size may lead to an exponential increase in surface area relative to volume, thus making GNPs surface more reactive on aggregation and to its surrounding biological components. The size, shape, surface area, number, and clearance of GNPs play a key role in toxicity and accumulation in the different rat organs. This study demonstrates that fluorescence peak intensity is particle size and exposure duration dependent. This study suggests that fluorescence intensity can be used as a useful tool for pointing to bioaccumulation and toxicity induced by GNPs in the different rat organs.

  2. Transscleral diffusion of carboplatin: an in vitro and in vivo study.

    Science.gov (United States)

    Simpson, Amanda E; Gilbert, Jake A; Rudnick, David E; Geroski, Dayle H; Aaberg, Thomas M; Edelhauser, Henry F

    2002-08-01

    To compare the in vitro scleral permeability of carboplatin using either a fibrin sealant or a balanced salt solution (BSS) vehicle and to measure in vivo ocular tissue levels following subconjunctival injection of carboplatin in fibrin sealant or BSS. The permeability of carboplatin in fibrin sealant or BSS through human eye bank sclera was tested using an in vitro perfusion apparatus. Levels of carboplatin permeating the sclera were measured every hour for 24 hours using atomic absorption spectrometry. In vivo studies were performed in Dutch Belted rabbits injected subconjunctivally with carboplatin in either fibrin sealant or BSS; eyes were enucleated at 1(1/2) hours, 48 hours, and 2 weeks after injection, and levels of carboplatin were measured in various tissues. In vitro carboplatin in fibrin sealant had a peak permeability constant of 13.7 +/- 2.3 x 10(-6) cm/s; carboplatin in BSS, 27.0 +/- 1.7 x 10(-6) cm/s. After 24 hours, 33.2% +/- 1.8% of the carboplatin was retained in the fibrin sealant, while 5.5% +/- 1.0% was retained in the BSS. In vivo subconjunctival injection of carboplatin in fibrin sealant vehicle achieved 11.83 +/- 5.16 microg/mL in the vitreous at 1(1/2) hours and 0.03 +/- 0.06 microg/mL in the vitreous at 2 weeks. The fibrin sealant also attained 396.59 +/- 177.84 microg/mg in the choroid and retina at 1(1/2) hours and 3.38 +/- 1.97 microg/mg in the choroid and retina at 2 weeks. (Data are given as mean +/- SEM.) Fibrin sealant provided a more controlled and localized release of carboplatin and delivered carboplatin to the ocular tissues for up to 2 weeks. This study reports the use of fibrin sealant as a subconjunctival delivery vehicle for carboplatin, and quantifies ocular drug levels achieved in an animal model.

  3. Improved extrinsic polymer optical fiber sensors for gamma-ray monitoring in radioprotection applications

    Science.gov (United States)

    de Andrés, A. I.; Esteban, Ó.; Embid, M.

    2017-08-01

    Gamma radiation detection in the range of 662 keV, the reference for environmental protection, is done through extrinsic optical fiber sensors. The fluorescence rendered by an inorganic scintillator when irradiated with such gamma rays is gathered by a modified polymer optical fiber tip. This modification increases the recorded signal when compared with plain unaltered fiber. Two fiber tip modification are then compared in terms of light gathering capability. A chemically etched fiber, in which the cladding and part of the core are removed, and a tapered fiber in which the core-cladding structure is kept. Both structures are comparable in length and final diameter, and show linear response in the tested range up to 2 Gy/h air Kerma rate. The etched fiber shows a higher slope than the tapered one, although both improve the signal gathered by a plain fiber tip. The easy fabrication and handling of the reported transducers, together with the improved signal gathering, allow to reduce the overall system budget with the use of low-cost optoelectronics in the detection stage. This offers a significant improvement for surveillance systems in radioprotection applications, in which presence of gamma radiation coming out accidental leakage or spurious sources activity is the main target.

  4. The effects of selenium on glutathione peroxidase activity and radioprotection in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Diamond, A.M.; Murray, J.L.; Dale, P.; Tritz, R.; Grdina, D.J.

    1995-09-05

    The media of representative mammalian cell lines were supplemented with low levels of selenium in the form of sodium selenite in order to investigate the effects of selenium on mammalian cells. Following incubation in 30 nM sodium selenite, these cells were assayed for changes in glutathione peroxidase (GPx) activity. The cells examined included NIH 3T3 mouse fibroblasts, PC12 rat sympathetic precursor cells, SupT-1 human lymphocytes, MCF-7{sup adr} human breast carcinoma cells and AA8 Chinese hamster ovary cells. Selenium supplementation resulted in a marginal increase in GPx activity for the NIH 3T3, MCF-7{sup adr} and Supt-1 cells but stimulated GPx activity approximately 5-fold in PC12 and AA8 cells. AA8 cells were selected to evaluate whether selenium supplementation was radioprotective against {sup 60}cobalt gamma irradiation. Protection against radiation-induced mutation was measured by evaluating mutation frequency at the hprt locus. In this assay, preincubation of AA8 CHO cells significantly protected these cells from exposure to 8 Gy.

  5. Physique appliquée à l’exposition externe dosimétrie et radioprotection

    CERN Document Server

    Antoni, Rodolphe

    2013-01-01

    Cet ouvrage fait la synthèse de nombreuses années d'expériences en dosimétrie et techniques de protection contre l’exposition externe, aussi bien dans le domaine industriel que médical. Il rappelle les concepts physiques de base puis propose un certain nombre d'outils d’évaluation des nuisances radiologiques, et les moyens de s'en prémunir, en détaillant notamment les techniques de calcul pour des blindages appropriés. Le premier chapitre traite de la définition des grandeurs radiométriques et dosimétriques fondamentales. Il permet d’aborder au chapitre 2 la question de l'interaction rayonnement-matière sous un angle dédié au dépôt de la dose dans les tissus biologiques. Le troisième chapitre définit quant à lui les grandeurs de protection et les grandeurs opérationnelles liées à la radioprotection. Dans les deux chapitres suivants, l’accent a été mis sur la définition des risques et contre-mesures associées (i.e. protections biologiques) inhérents aux sources de rayonnemen...

  6. Radioprotective Action of Low-Intensity Light into the Red Absorption Band of Endogenous Molecular Oxygen

    Science.gov (United States)

    Ivanov, A. V.; Mashalov, A. A.; Zakharov, S. D.

    2016-08-01

    Application of ionizing radiation in oncology (radiation therapy) is a widespread way to eliminate malignant tumors. Normal tissues are inevitable included in any radiation field, and their reliable protection is actual till now. All attempts to solve the problem are based on search of effective radioprotectors, i.e. chemical compounds of various classes, which should be entered into the patient. To date about 50,000 compounds with some radioprotection properties had been tested, but the most effective of them have been simultaneously the most toxic. Here the preliminary results of researches devoted to development of an optical technique on basis of the light-oxygen effect for the protection of women with breast cancer from side effects of the radiation therapy are presented. A low intensity emission of the semiconductor laser in a red spectral interval was used to excite a very small quantity of endogenous molecular oxygen in O2(1Δg) state. It is shown, that application of the method at occurrence of earliest signs of radiation injury allows notably reducing dangerous breaks in radiation therapy course.

  7. Nitroxides as antioxidants – possibilities of their application in chemoprevention and radioprotection

    Directory of Open Access Journals (Sweden)

    Sabina Tabaczar

    2011-01-01

    Full Text Available Nitroxides as stabile organic radicals were used initially as spin labels in spectroscopy of electron paramagnetic resonance (EPR with respect to parameters such as pH of an intercellular environment, oxygenation of cells and tissues, fluidity of biological membranes, conformational state and topography of proteins. Nitroxides have also been used in biology and medicine as contrast agents in magnetic resonance imaging (MRI. When their antioxidant activities were discovered, an era of research on the potential utility of these agents began. Nitroxides can modulate the redox state of the cell by participation in oxidation/reduction reactions. Therefore, they are extensively examined in various models of oxidative stress. The antioxidant effect of nitroxides is a result of their ability to catalyze dismutation of superoxide radical (superoxide dismutase-like activity, inhibit lipid peroxidation, prevent Fenton and Haber-Weiss reactions by oxidation of transition metal ions to a higher oxidative state, and confer catalase-like activity on heme proteins. In the present paper the antioxidative mechanisms of nitroxides are presented. The relation between structure, function and the rate of nitroxide reduction inside cells and tissues is also presented. The application of nitroxides in chemoprevention and radioprotection is discussed.

  8. Radioprotective effect of Ganoderma lucidum (Leyss. ex. Fr. ) Karst after X-ray irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, H.Y.; Lian, S.L.; Lin, C.C. (Kaohsiung Medical College (Taiwan))

    1990-01-01

    Six to seven week old male mice of ICR strain were exposed to 500 or 650 cGy of X-ray during experiments to determine if Ganoderma lucidum could be a factor in modification of radiation damage. Continuous intraperitoneal injection of the extract from Ganoderma lucidum before or after irradiation of 500 and 650 cGy of X-ray was found to improve the 30-day survival fractions of ICR mice, but wasn't significant by statistical analysis. The administration also enhanced the recoveries of the body weights and increased the recovery of hemograms of irradiated mice from radiation damage by injecting before or after radiation exposure, especially for the treatment of 500 cGy irradiation. The 10-day CFUs was significantly higher for Ganoderma lucidum treated groups than for untreated groups. However, the differences of radioprotective effect between the X-ray irradiated groups with Ganoderma lucidum pretreated and post-treated were not significant (p greater than 0.05).

  9. In vivo (31)P MRS study of skeletal muscle metabolism in patients with postpolio residual paralysis.

    Science.gov (United States)

    Sharma, Uma; Kumar, Virendra; Wadhwa, Sanjay; Jagannathan, Naranamangalan R

    2007-02-01

    The muscle metabolism of at-rest patients with varying degrees of postpolio residual paralysis (PPRP) was studied and compared with that of controls using in vivo phosphorus magnetic resonance spectroscopy. The phosphocreatine (PCr)/inorganic phosphate (Pi) and PCr/adenosine triphosphate ratios were lower in patients than in controls. Reduction in PCr/Pi suggests abnormalities in oxidative phosphorylation. A significant increase was observed in the phosphomonoester/PCr ratio in patients, indicating the accumulation of intermediary compounds of the glycolytic pathway. Furthermore, the phosphodiester/PCr ratio was also significantly increased in patients. In general, the observed changes in metabolite ratios were found to be related to the degree of residual paralysis, suggesting that metabolic changes are secondary to chronic neurogenic processes. These metabolic alterations appear to be the possible cause of energy deficit and underlying muscle fatigue in PPRP patients. The present results provide an insight into the metabolic impairment and degree of muscle damage in patients with PPRP.

  10. In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt(1)-DALDA Analogues

    DEFF Research Database (Denmark)

    Ballet, Steven; Betti, Cecilia; Novoa, Alexandre

    2014-01-01

    In this study the μ opioid receptor (MOR) ligands DALDA (Tyr-d-Arg-Phe-Lys-NH2) and Dmt(1)-DALDA (Dmt-d-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast......-brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt(1)-DALDA 1, compounds 4-7 are mixed MOR/DOR agonists, expected to produce reduced...

  11. Chitosan-alginate capsules as oral delivery system for insulin: studies in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    C. A. RODRIGUES

    2009-05-01

    Full Text Available The aim of this study was to assess chitosan:alginate capsules as gastric resistant systems for oral administration of insulin. Chitosan:alginate capsules of insulin were tested in simulated gastric and intestinal media and in vivo. The capsules released only about 20% of the insulin after 60 minutes of incubation in simulated gastric medium. On the other hand, almost all the encapsulated insulin was released after being incubated for 90 min in simulated intestinal medium. When capsules containing 20 IU and 40 IU insulin were given to rats by gavage, signifi cantly reduced plasma glucose levels were observed (33.7 % and 51.7%, respectively two hours after the treatment, which returned to normal after six hours. These results indicate that chitosan:alginate capsules are potential carriers for oral protein delivery. Keywords: chitosan:alginate capsules; insulin; oral administration.

  12. Impact of ceftibuten on intestinal microflora: in vitro and in vivo studies.

    Science.gov (United States)

    Gismondo, M R; Drago, L; Lombardi, A; Fassina, C

    1994-01-01

    The present study examines the possible interference of ceftibuten on intestinal microflora. In 60 germ-free mice, an intestinal microflora similar to the human one was implanted. The mice were then treated with a single dose and twice the therapeutic dose of ceftibuten. In another experiment, ten human volunteers were given ceftibuten in doses equivalent to 400 mg/day for 7 days in order to evaluate the ceftibuten faecal concentration, the possible interference on microflora and the quantity of indacan (as a measure of the bacterial metabolism in the gut) excreted in one day. The results obtained in vivo and in vitro have shown that ceftibuten in therapeutic doses does not alter the equilibrium of normal intestinal microflora.

  13. Radiographic diagnosis of incipient proximal caries: an ex-vivo study.

    Science.gov (United States)

    da Silva Neto, José Moreira; dos Santos, Rosenês Lima; Sampaio, Maria Carmeli Correia; Sampaio, Fábio Correia; Passos, Isabela Albuquerque

    2008-01-01

    The aim of this ex vivo study was to compare visual clinical and radiographic examinations to the histological analysis for proximal caries diagnosis in extracted permanent molars and premolars. The relationship between clinical aspects and carious lesions was also evaluated. Eighty-eight proximal surfaces (44 freshly extracted teeth) were longitudinally sectioned with a 370-microm diamond disk, thinned with wet silicon carbide paper and observed with a stereomicroscope at x40 magnification. Sensitivity and specificity were 65.6% and 83.3% for clinical examination and 29.7% and 95.8% for radiographic examination, respectively. Kappa values ranged from 0.64 to 0.91. The white spots corresponded to lesions restricted to enamel, while the dark spots corresponded to lesions that reached the dentinoenamel junction. In most cases, cavitation corresponded to dentin lesions. It may be concluded that interproximal radiographic examination is not a reliable method for detection of incipient proximal carious lesions.

  14. Adapalene pretreatment increases follicular penetration of clindamycin: In vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Jain Gaurav

    2007-01-01

    Full Text Available Background: Topical retinoids normalize desquamation, reduce comedogenesis and may enhance the penetration of other topicals providing more effective treatment of acne. Aim: We evaluated the effect of adapalene on skin penetration of clindamycin phosphate when it is applied concomitantly or after various time durations following adapalene application. Methods: The in vitro studies were carried out using excised rat skin, whereas the in vivo studies were conducted on healthy human volunteers. Radioactive clindamycin phosphate (1% gel was applied to rat skin sections and to the hands of human volunteers concomitantly and after the pretreatment of the skin for 3, 5 and 10 min with 10 mg of adapalene (0.1% gel. Quantification of clindamycin phosphate was performed by liquid scintillation. Results: In vitro skin penetration and distribution of clindamycin phosphate was affected by the pretreatment time. Significantly higher skin concentration of clindamycin phosphate (15.5% with largest proportion in viable skin layer (9.4% of applied dose was found when clindamycin phosphate gel was applied after the pretreatment of the skin with adapalene gel for 5 min. Further increase in pretreatment time has no additive influence on the penetration of clindamycin phosphate. In vivo results were in corroboration with the in vitro results and demonstrate significantly higher concentration of clindamycin phosphate (19% in the skin following pretreatment with adapalene gel for 5 min. Adapalene acts as a penetration enhancer and increases the penetration of topical clindamycin phosphate. Conclusion: Application of clindamycin phosphate gel after the pretreatment of skin with adapalene gel for 5 min may contribute significantly to the increased efficacy of therapy.

  15. Generic sustained release tablets of trimetazidine hydrochloride: Preparation and in vitro–in vivo correlation studies

    Directory of Open Access Journals (Sweden)

    Longmei Wang

    2016-06-01

    Full Text Available The aim of the current work was to develop generic sustained-release tablets containing 35 mg trimetazidine dihydrochloride and to establish an in vitro–in vivo correlation that could predict the bioavailability. The marketed sustained release tablet (Vastarel MR used as reference, a sustained-release matrix tablet was prepared using hydroxypropyl methylcellulose (HPMC as matrix by wet granulation and the in vitro dissolution profiles of the self-made tablets were determined in four different dissolution media (0.1 M HCl, pH 4.5 PBS, pH 6.8 PBS and water. A higher similarity between prepared tablets and Vastarel MR was established, with similarity factor (f2 ranging from 60 to 75 in the four media. The in vivo pharmacokinetics was studied in six healthy beagles. Compared with Vastarel MR, the Cmax of self-made tablets was slightly decreased, while the Tmax and MRT0–t were slightly prolonged, but with no significant difference (P > 0.05. The average of relative bioavailability (F was 102.52% based on AUC0–t. For log-transformed AUC0–t and Cmax, the upper confidence limit on the appropriate criterion is <0, indicating these two formulations were population bioequivalent. The in vivo–in vitro correlation coefficient obtained from point-to-point analysis of self-made tablets was 0.9720. In conclusion, the prepared tablets were bioequivalent to the marketed tablets, according to both the in vitro release rate and extent of absorption, and a good in vivo–in vitro correlation was established for the self-made tablets that indicated in vitro dissolution tests could be used as a surrogate for bioavailability studies.

  16. Stryphnodendron adstringens and purified tannin on Pythium insidiosum: in vitro and in vivo studies.

    Science.gov (United States)

    Trolezi, Rodrigo; Azanha, Juliana Maziero; Paschoal, Natália Rodrigues; Chechi, Jéssica Luana; Dias Silva, Marcelo José; Fabris, Viciany Eric; Vilegas, Wagner; Kaneno, Ramon; Fernandes Junior, Ary; Bosco, Sandra de Moraes Gimenes

    2017-02-23

    Pythium insidiosum is the etiological agent of pythiosis, an emerging life-threatening infectious disease in tropical and subtropical regions. The pathogen is a fungus-like organism resistant to antifungal therapy, for this reason, most cases need extensive surgical debridments as treatment, but depending on the size and anatomical region of the lesion, such approach is unfeasible. We investigate the fungicidal effect and toxicity of crude bark extract of Stryphnodendron adstringens and commercially available tannin on Pythium insidiosum both in vitro and in vivo. Standardized fragments of mycelia of fifteen isolates of P. insidiosum were tested with different concentrations of bark extract (10 to 30% v/v) and tannin (0.5, 1.0 and 1.5 mg/mL). For in vivo study, fifteen rabbits were experimentally infected with zoospores of P. insidiosum and treated by oral and intralesional applications of bark extract and tannin. Acute toxicity tests with both substances were also performed in rats. In vitro studies showed fungicidal effect for both substances at different concentrations and the SEM showed alteration on the cell wall surface of the pathogen. All infected rabbits developed a firm nodular mass that reached around 90 mm2 ninety days after inoculation, but neither the intralesional inoculation of tannin, nor the oral administration of crude extract and tannin were able to promote remission of the lesions. Lesions developed by rabbits presented an encapsulated abscess being quite different of naturally acquired pythiosis, which is characterized by ulcerated lesions. Since no toxicity was observed in rats or rabbits inoculated with these products, while in vitro experiments showed direct antifungal effect, therapeutic activity of S. adstringens and tannin should be clinically tested as an alternative for healing wounds in naturally acquired pythiosis.

  17. Direct detection and quantification of abasic sites for in vivo studies of DNA damage and repair

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanming [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States)], E-mail: yanming.wang@case.edu; Liu Lili [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Wu Chunying [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Bulgar, Alina [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States); Somoza, Eduardo; Zhu Wenxia [Division of Radiopharmaceutical Science, Case Center for Imaging Research, Department of Radiology, Case Western Reserve University, Cleveland, OH 44122 (United States); Gerson, Stanton L. [Department of Hematology and Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44122 (United States)

    2009-11-15

    Use of chemotherapeutic agents to induce cytotoxic DNA damage and programmed cell death is a key strategy in cancer treatments. However, the efficacy of DNA-targeted agents such as temozolomide is often compromised by intrinsic cellular responses such as DNA base excision repair (BER). Previous studies have shown that BER pathway resulted in formation of abasic or apurinic/apyrimidinic (AP) sites, and blockage of AP sites led to a significant enhancement of drug sensitivity due to reduction of DNA base excision repair. Since a number of chemotherapeutic agents also induce formation of AP sites, monitoring of these sites as a clinical correlate of drug effect will provide a useful tool in the development of DNA-targeted chemotherapies aimed at blocking abasic sites from repair. Here we report an imaging technique based on positron emission tomography (PET) that allows for direct quantification of AP sites in vivo. For this purpose, positron-emitting carbon-11 has been incorporated into methoxyamine ([{sup 11}C]MX) that binds covalently to AP sites with high specificity. The binding specificity of [{sup 11}C]MX for AP sites was demonstrated by in vivo blocking experiments. Using [{sup 11}C]MX as a radiotracer, animal PET studies have been conducted in melanoma and glioma xenografts for quantification of AP sites. Following induction of AP sites by temozolomide, both tumor models showed significant increase of [{sup 11}C]MX uptake in tumor regions in terms of radioactivity concentration as a function of time, which correlates well with conventional aldehyde reactive probe (ARP)-based bioassays for AP sites.

  18. Formulation Study of Topically Applied Lotion: In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Syed Nisar Hussain Shah

    2013-01-01

    Full Text Available ntroduction: This article presents the development and evaluation of a new topical formulation of diclofenac diethylamine (DDA as a locally applied analgesic lotion. Methods: To this end, the lotion formulations were formulated with equal volume of varying concentrations (1%, 2%, 3%, 4%; v/v of permeation enhancers, namely propylene glycol (PG and turpentine oil (TO. These lotions were subjected to physical studies (pH, viscosity, spreadability, homogeneity, and accelerated stability, in vitro permeation, in vivo animal studies and sensatory perception testing. In vitro permeation of DDA from lotion formulations was evaluated across polydimethylsiloxane membrane and rabbit skin using Franz cells. Results: It was found that PG and TO content influenced the permeation of DDA across model membranes with the lotion containing 4% v/v PG and TO content showed maximum permeation enhancement of DDA. The flux values for L4 were 1.20±0.02 μg.cm-2.min-1 and 0.67 ± 0.02 μg.cm-2.min-1 for polydimethylsiloxane and rabbit skin, respectively. Flux values were significantly different (p < 0.05 from that of the control. The flux enhancement ratio of DDA from L4 was 31.6-fold and 4.8-fold for polydimethylsiloxane and rabbit skin, respectively. In the in vivo animal testing, lotion with 4% v/v enhancer content showed maximum anti-inflammatory and analgesic effect without inducing any irritation. Sensatory perception tests involving healthy volunteers rated the formulations between 3 and 4 (values ranging between -4 to +4, indicating a range of very bad to excellent, respectively. Conclusion: It was concluded that the DDA lotion containing 4% v/v PG and TO exhibit the best performance overall and that this specific formulation should be the basis for further clinical investigations.

  19. Tri-layered composite plug for the repair of osteochondral defects: in vivo study in sheep

    Directory of Open Access Journals (Sweden)

    Altug Yucekul

    2017-04-01

    Full Text Available Cartilage defects are a source of pain, immobility, and reduced quality of life for patients who have acquired these defects through injury, wear, or disease. The avascular nature of cartilage tissue adds to the complexity of cartilage tissue repair or regeneration efforts. The known limitations of using autografts, allografts, or xenografts further add to this complexity. Autologous chondrocyte implantation or matrix-assisted chondrocyte implantation techniques attempt to introduce cultured cartilage cells to defect areas in the patient, but clinical success with these are impeded by the avascularity of cartilage tissue. Biodegradable, synthetic scaffolds capable of supporting local cells and overcoming the issue of poor vascularization would bypass the issues of current cartilage treatment options. In this study, we propose a biodegradable, tri-layered (poly(glycolic acid mesh/poly(l-lactic acid-colorant tidemark layer/collagen Type I and ceramic microparticle-coated poly(l-lactic acid-poly(ϵ-caprolactone monolith osteochondral plug indicated for the repair of cartilage defects. The porous plug allows the continual transport of bone marrow constituents from the subchondral layer to the cartilage defect site for a more effective repair of the area. Assessment of the in vivo performance of the implant was conducted in an ovine model (n = 13. In addition to a control group (no implant, one group received the implant alone (Group A, while another group was supplemented with hyaluronic acid (0.8 mL at 10 mg/mL solution; Group B. Analyses performed on specimens from the in vivo study revealed that the implant achieves cartilage formation within 6 months. No adverse tissue reactions or other complications were reported. Our findings indicate that the porous biocompatible implant seems to be a promising treatment option for the cartilage repair.

  20. In vivo Study of the Accuracy of Dual-arch Impressions.

    Science.gov (United States)

    de Lima, Luciana Martinelli Santayana; Borges, Gilberto Antonio; Junior, Luiz Henrique Burnett; Spohr, Ana Maria

    2014-06-01

    This study evaluated in vivo the accuracy of metal (Smart®) and plastic (Triple Tray®) dual-arch trays used with vinyl polysiloxane (Flexitime®), in the putty/wash viscosity, as well as polyether (Impregum Soft®) in the regular viscosity. In one patient, an implant-level transfer was screwed on an implant in the mandibular right first molar, serving as a pattern. Ten impressions were made with each tray and impression material. The impressions were poured with Type IV gypsum. The width and height of the pattern and casts were measured in a profile projector (Nikon). The results were submitted to Student's t-test for one sample (α = 0.05). For the width distance, the plastic dual-arch trays with vinyl polysiloxane (4.513 mm) and with polyether (4.531 mm) were statistically wider than the pattern (4.489 mm). The metal dual-arch tray with vinyl polysiloxane (4.504 mm) and with polyether (4.500 mm) did not differ statistically from the pattern. For the height distance, only the metal dual-arch tray with polyether (2.253 mm) differed statistically from the pattern (2.310 mm). The metal dual-arch tray with vinyl polysiloxane, in the putty/wash viscosities, reproduced casts with less distortion in comparison with the same technique with the plastic dual-arch tray. The plastic or metal dual-arch trays with polyether reproduced cast with greater distortion. How to cite the article: Santayana de Lima LM, Borges GA, Burnett LH Jr, Spohr AM. In vivo study of the accuracy of dual-arch impressions. J Int Oral Health 2014;6(3):50-5.

  1. Effect of epicatechin against radiation-induced oral mucositis: in vitro and in vivo study.

    Directory of Open Access Journals (Sweden)

    Yoo Seob Shin

    Full Text Available PURPOSE: Radiation-induced oral mucositis limits the delivery of high-dose radiation to head and neck cancer. This study investigated the effectiveness of epicatechin (EC, a component of green tea extracts, on radiation-induced oral mucositis in vitro and in vivo. EXPERIMENTAL DESIGN: The effect of EC on radiation-induced cytotoxicity was analyzed in the human keratinocyte line HaCaT. Radiation-induced apoptosis, change in mitochondrial membrane potential (MMP, reactive oxygen species (ROS generation and changes in the signaling pathway were investigated. In vivo therapeutic effects of EC for oral mucositis were explored in a rat model. Rats were monitored by daily inspections of the oral cavity, amount of oral intake, weight change and survival rate. For histopathologic evaluation, hematoxylin-eosin staining and TUNEL staining were performed. RESULTS: EC significantly inhibited radiation-induced apoptosis, change of MMP, and intracellular ROS generation in HaCaT cells. EC treatment markedly attenuated the expression of p-JNK, p-38, and cleaved caspase-3 after irradiation in the HaCaT cells. Rats with radiation-induced oral mucositis showed decreased oral intake, weight and survival rate, but oral administration of EC significantly restored all three parameters. Histopathologic changes were significantly decreased in the EC-treated irradiated rats. TUNEL staining of rat oral mucosa revealed that EC treatment significantly decreased radiation-induced apoptotic cells. CONCLUSIONS: This study suggests that EC significantly inhibited radiation-induced apoptosis in keratinocytes and rat oral mucosa and may be a safe and effective candidate treatment for the prevention of radiation-induced mucositis.

  2. The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

    Science.gov (United States)

    Glynn, Nigel; Kenny, Helena; Quisenberry, Leah; Halsall, David J; Cook, Paul; Kyaw Tun, Tommy; McDermott, John H; Smith, Diarmuid; Thompson, Christopher J; O'Gorman, Donal J; Boelen, Anita; Lado-Abeal, Joaquin; Agha, Amar

    2017-05-01

    Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle. © 2016 John Wiley & Sons Ltd.

  3. In-vivo corneal pulsation in relation to in-vivo intraocular pressure and corneal biomechanics assessed in-vitro. An animal pilot study.

    Science.gov (United States)

    Rogala, Maja M; Danielewska, Monika E; Antończyk, Agnieszka; Kiełbowicz, Zdzisław; Rogowska, Marta E; Kozuń, Marta; Detyna, Jerzy; Iskander, D Robert

    2017-09-01

    The aim was to ascertain whether the characteristics of the corneal pulse (CP) measured in-vivo in a rabbit eye change after short-term artificial increase of intraocular pressure (IOP) and whether they correlate with corneal biomechanics assessed in-vitro. Eight New Zealand white rabbits were included in this study and were anesthetized. In-vivo experiments included simultaneous measurements of the CP signal, registered with a non-contact method, IOP, intra-arterial blood pressure, and blood pulse (BPL), at the baseline and short-term elevated IOP. Afterwards, thickness of post-mortem corneas was determined and then uniaxial tensile tests were conducted leading to estimates of their Young's modulus (E). At the baseline IOP, backward stepwise regression analyses were performed in which successively the ocular biomechanical, biometric and cardiovascular predictors were separately taken into account. Results of the analysis revealed that the 3rd CP harmonic can be statistically significantly predicted by E and central corneal thickness (Models: R2 = 0.662, p biomechanics in-vitro was confirmed. In particular, spectral analysis revealed that higher amplitude and power of the 3rd CP harmonic indicates higher corneal stiffness, while the 1st CP harmonic correlates positively with the corresponding harmonic of the BPL signal. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. In vivo human time-exposure study of orally dosed commercial silver nanoparticles.

    Science.gov (United States)

    Munger, Mark A; Radwanski, Przemyslaw; Hadlock, Greg C; Stoddard, Greg; Shaaban, Akram; Falconer, Jonathan; Grainger, David W; Deering-Rice, Cassandra E

    2014-01-01

    Human biodistribution, bioprocessing and possible toxicity of nanoscale silver receive increasing health assessment. We prospectively studied commercial 10- and 32-ppm nanoscale silver particle solutions in a single-blind, controlled, cross-over, intent-to-treat, design. Healthy subjects (n=60) underwent metabolic, blood counts, urinalysis, sputum induction, and chest and abdomen magnetic resonance imaging. Silver serum and urine content were determined. No clinically important changes in metabolic, hematologic, or urinalysis measures were identified. No morphological changes were detected in the lungs, heart or abdominal organs. No significant changes were noted in pulmonary reactive oxygen species or pro-inflammatory cytokine generation. In vivo oral exposure to these commercial nanoscale silver particle solutions does not prompt clinically important changes in human metabolic, hematologic, urine, physical findings or imaging morphology. Further study of increasing time exposure and dosing of silver nanoparticulate silver, and observation of additional organ systems are warranted to assert human toxicity thresholds. In this study, the effects of commercially available nanoparticles were studied in healthy volunteers, concluding no detectable toxicity with the utilized comprehensive assays and tests. As the authors rightfully state, further studies are definitely warranted. Studies like this are much needed for the more widespread application of nanomedicine. © 2014.

  5. In vivo studies of radiation potentiaton by iodoacetamide and observations on tumor transplantation immunity

    Energy Technology Data Exchange (ETDEWEB)

    Richards, W. Robert [Univ. of California, Berkeley, CA (United States); Kelly, Lola S. [Univ. of California, Berkeley, CA (United States)

    1970-10-01

    Iodoacetamide has been shown by others to be a radiation sensitizer for bacteria and for certain mammalian cells tested in vitro. This work describes an examination of the effectiveness of iodoacetamide used in vivo. Survival of ascites tumor cells maintained in the peritoneal cavity of mice was used as an indicator of sensitization. Survival was assessed using TD50 and total tumor cell population determination methods. A comparison of results obtained by these methods is made. The effects of oxygen tension and radiation dose rate upon results was examined. Iodoacetamide was found to be effective as a radiation sensitizer under all conditions although to a lesser degree than that reported by others for in vitro experiments with bacteria. Radioactive tracer studies indicate that iodoacetamide has rapid and total access to most if not all tissues of the body. This fact coupled with the observation of a sensitization in an in vivo system where the anoxia so prevalent in well developed tumors was present, suggests the possibility of clinical usefulness of iodoacetamide in cancer radiation therapy. Certain observations are reported on the effect of various cell and host treatment procedures upon cell population growth kinetics seen subsequent to inoculation of hosts with the cells. A hypothesis is presented which can account for the observations made by the author and also for those made by some others who report that large inocula, i.e., greater than 10 cells, are required to give rise to a lethal tumor in isologous hosts of the strain of tumor origin. The hypothesis may also account for what is known in the literature as the 'Hybrid Effect.'

  6. Spheroid-plug model as a tool to study tumor development, angiogenesis, and heterogeneity in vivo.

    Science.gov (United States)

    Szade, Krzysztof; Zukowska, Monika; Szade, Agata; Collet, Guillaume; Kloska, Damian; Kieda, Claudine; Jozkowicz, Alicja; Dulak, Jozef

    2016-02-01

    Subcutaneous injection of the tumor cell suspension is a simple and commonly used tool for studying tumor development in vivo. However, subcutaneous models poorly resemble tumor complexity due to the fast growth not reflecting the natural course. Here, we describe an application of the new spheroid-plug model to combine the simplicity of subcutaneous injection with improved resemblance to natural tumor progression. Spheroid-plug model relies on in vitro formation of tumor spheroids, followed by injection of single tumor spheroid subcutaneously in Matrigel matrix. In spheroid-plug model, tumors grow slower in comparison to tumors formed by injection of cell suspension as assessed by 3D ultrasonography (USG) and in vivo bioluminescence measurements. The slower tumor growth rate in spheroid-plug model is accompanied by reduced necrosis. The spheroid-plug model ensures increased and more stable vascularization of tumor than classical subcutaneous tumor model as demonstrated by 3D USG Power Doppler examination. Flow cytometry analysis showed that tumors formed from spheroids have enhanced infiltration of endothelial cells as well as hematopoietic and progenitor cells with stem cell phenotype (c-Kit(+) and Sca-1(+)). They also contain more tumor cells expressing cancer stem cell marker CXCR4. Here, we show that spheroid-plug model allows investigating efficiency of anticancer drugs. Treatment of spheroid-plug tumors with known antiangiogenic agent axitinib decreased their size and viability. The antiangiogenic activity of axitinib was higher in spheroid-plug model than in classical model. Our results indicate that spheroid-plug model imitates natural tumor growth and can become a valuable tool for cancer research.

  7. CMD-05, a novel promising clinical anti-diabetic drug candidate, in vivo and vitro studies.

    Science.gov (United States)

    Ma, Jie; Li, Huan; Hu, Xiangnan; Yang, Lu; Chen, Qi; Hu, Congli; Chen, Zhihao; Tian, Xiaoyan; Yang, Yang; Luo, Ying; Gan, Run; Yang, Junqing

    2017-04-13

    Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC 50 of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma. Long-term administration of CMD-05 decreased HbA1c and TG levels and improved the islet function without significantly effect on body weight. Furthermore, CMD-05 reduced INS-1 cell apoptosis and increased GLP-1 secretion in NCI-H716. After oral administration, CMD-05 reached peak concentration at 30 min with half-life of 288 minutes and the inhibitory rate of DPP-IV greater than 50% lasted for 15 h. In fasted normal rats, CMD-05 didn't cause significant hypoglycemia. CMD-05 had a lower cytotoxicity than vildagliptin in vitro and its maximum tolerance dose in mice is beyond 2000 mg/kg. These results indicated that CMD-05 has similar activity with vildagliptin in vivo and has a much longer half-life and lower cytotoxicity than vildagliptin.

  8. Mechanical properties and in vivo study of modified-hydroxyapatite/polyetheretherketone biocomposites.

    Science.gov (United States)

    Ma, Rui; Li, Qiankuan; Wang, Lin; Zhang, Xianghua; Fang, Lin; Luo, Zhongkuan; Xue, Bai; Ma, Lei

    2017-04-01

    Polyether ether ketone (PEEK) has received much attention for its excellent mechanical properties and biocompatibility. Here, the silane coupling agent KH560 [γ-(2,3-epoxypropoxy)propyltrimethoxysilane] is used for graft modification of bioactive HA (hydroxyapatite) particles and for preparing HA/PEEK composites via a hot-press molding method. The prepared HA/PEEK composites were tested for their mechanical properties with SEM (scanning electron microscopy), infrared spectroscopy, and thermo-analysis. The results show that silane coupling KH-560 modifies HA successfully and that the tensile strengths of HA/PEEK and m-HA/PEEK composites indicate an increasing and then a decreasing tendency with increasing HA contents. The non-modified HA/PEEK composites display the same trend as the modified specimens with lower tensile strength and consist of sharp points. When the HA content is 5wt.%, the tensile strength of m-HA/PEEK composite reaches its maximum, which is 23% higher than that of pure PEEK specimens. The in vivo experiments of m-HA/PEEK used a biomechanical push-out test, SEM, optical microscopy, and an Image-Pro Express C image analysis system. The growth of the bone tissues around the m-HA/PEEK composites with an HA content of 5wt.% is better than that of specimens with different HA contents. This finding shows the nano-scale effect of the bioactive filler HA in PEEK substrates, which obviously contributes to the growth of the surrounding bone issues in vivo. This study could provide theoretical support for the further promotion and application of high-performance engineering plastics such as PEEK in biomedical fields. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Aberrant response to commensal Bacteroides thetaiotaomicron in Crohn's disease: an ex vivo human organ culture study.

    Science.gov (United States)

    Edwards, L A; Lucas, M; Edwards, E A; Torrente, F; Heuschkel, R B; Klein, N J; Murch, S H; Bajaj-Elliott, M; Phillips, A D

    2011-05-01

    Human ex vivo evidence indicating that an inappropriate immune response(s) to nonpathogenic bacteria contributes to disease pathogenesis in pediatric Crohn's disease (CD) is limited. The aim of the present study was to compare and contrast the early innate immune response of pediatric "healthy" versus CD mucosa to pathogenic, probiotic, and commensal bacteria. "Healthy control" and CD pediatric mucosal biopsies (terminal ileum and transverse colon) were cocultured for 8 hours with E. coli O42, Lactobacillus GG (LGG), Bacteroidesthetaiotaomicron (B. theta), or stimulated with interleukin (IL)-1β (positive control). Matched nonstimulated biopsies served as experimental controls. IL-8 was the immune marker of choice. IL-8 mRNA and protein levels were quantified by quantitative polymerase chain reaction and sandwich enzyme-linked immunosorbent assay, respectively. IL-8 secretion was observed when control, ileal biopsies were exposed to pathogenic O42 and probiotic LGG, with no response noted to commensal B. theta. In comparison, Crohn's ileal biopsies showed impaired ability to induce IL-8 in response to O42 and LGG. Control colonic tissue showed a limited response to O42 or B. theta and LGG significantly reduced IL-8 secretion. Unlike control tissue, however, Crohn's ileal and colonic tissue did respond to B. theta, with more enhanced expression in the colon. We provide the first ex vivo data to support the notion that aberrant mucosal recognition of commensal bacteria may contribute to pediatric CD. While IL-8 responses to O42 and LGG varied with disease status and anatomical location, B. theta consistently induced significant IL-8 both in ileal and colonic CD tissue, which was not seen in control, healthy tissue. Copyright © 2010 Crohn's & Colitis Foundation of America, Inc.

  10. Computed Tomography Angiography With High Flow Rates: An In Vitro and In Vivo Feasibility Study.

    Science.gov (United States)

    Mihl, Casper; Kok, Madeleine; Wildberger, Joachim E; Turek, Jakub; Muehlenbruch, Georg; Das, Marco

    2015-07-01

    The aims of this study were to test high-flow application of contrast media (CM) using novel high-flow needles and to assess injection- and flow-related parameters in a circulation phantom and in an in vivo population. A circulation phantom simulating physiological parameters was used. Preheated CM (300 mg/mL) was injected at flow rates varying between 5 and 15 mL/s through a novel 18-gauge high-flow intravenous injection needle. In addition, feasibility of these high-flow needles was tested with administration of flow rates of 9 mL/s in 20 patients referred for pre-transcatheter aortic valve implantation assessment. Injection parameters (eg, peak pressures, peak flow rates) in both phantom and in vivo setup were continuously monitored by a data acquisition program. Attenuation at predefined levels of the aorta (eg, aortic root to common femoral arteries) was measured in all patients to determine clinical applicability. In the phantom setup, injection rates up to 15 mL/s were feasible. An enhancement plateau was reached at 11 mL/s (464 [20] HU). In patients, no pressure- or flow-related complications (eg, extravasation) were recorded (mean [SD] peak pressure, 154 [8] psi; mean [SD] peak flow rate, 9.2 [0.1 mL/s; range, 9.1-9.6]). Diagnostic attenuation values were reached at all predefined levels of the aorta (330.8 [113.1] HU to 622.9 [81.5] HU). These results indicate that injections with 9 mL/s using high-flow injection needles are safe. The pressure limit of 325 psi was not reached, and the injections resulted in diagnostic attenuation values. Using this dedicated needle, high flow rates should not be considered a drawback for CM application in routine CT angiography examinations.

  11. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    Directory of Open Access Journals (Sweden)

    Wenjia Guo

    2015-10-01

    Full Text Available The purpose of this study was to develop a PLGA microspheres-based donepezil (DP formulation which was expected to sustain release of DP for one week with high encapsulation efficiency (EE. DP derived from donepezil hydrochloride was encapsulated in PLGA microspheres by the O/W emulsion-solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared successfully with average diameter of 30 µm, drug loading of 15.92 ± 0.31% and EE up to 78.79 ± 2.56%. Scanning electron microscope image showed it has integrated spherical shape with no drug crystal and porous on its surface. Differential scanning calorimetry and X-ray diffraction results suggested DP was in amorphous state or molecularly dispersed in microspheres. The Tg of PLGA was increased with the addition of DP. The release profile in vitro was characterized with slow but continuous release that lasted for about one week and fitted well with first-order model, which suggested the diffusion governing release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained. The results suggest the potential use of DP microspheres for treatment of Alzheimer's disease over long periods.

  12. Biocompatibility of Four Common Orthopedic Biomaterials Following a High-Salt Diet: An In Vivo Study

    Directory of Open Access Journals (Sweden)

    Mathieu Lecocq

    2017-07-01

    Full Text Available Nowadays, salt consumption appears to be drastically above the recommended level in industrialized countries. The health consequences of this overconsumption are heavy since high-salt intake induces cardiovascular disease, kidney dysfunction, and stroke. Moreover, harmful interaction may also occur with orthopaedic devices because overconsumption of salt reinforces the corrosive aspect of biological tissues and favors bone resorption process. In the present study, we aimed to assess the in vivo effect of three weeks of a high-salt diet, associated (or not with two weeks of the neuro-myoelectrostimulation (NMES rehabilitation program on the biocompatibility of four biomaterials used in the manufacture of arthroplasty implants. Thus, two non-metallic (PEEK and Al2O3 and two metallic (Ti6Al4V and CrCo compounds were implanted in the rat tibial crest, and the implant-to-bone adhesion and cell viability of two surrounded muscles, the Flexor Digitorum (FD and Tibialis Anterior (TA, were assessed at the end of the experiment. Results indicated lower adhesion strength for the PEEK implant compared to other biomaterials. An effect of NMES and a high-salt diet was only identified for Al2O3 and Ti6Al4V implants, respectively. Moreover, compared to a normal diet, a high-salt diet induced a higher number of dead cells on both muscles for all biomaterials, which was further increased for PEEK, Al2O3, and CrCo materials with NMES application. Finally, except for Ti6Al4V, NMES induced a higher number of dead cells in the directly stimulated muscle (FD compared to the indirectly stimulated one (TA. This in vivo experiment highlights the potential harmful effect of a high-salt diet for people who have undergone arthroplasty, and a rehabilitation program based on NMES.

  13. In vivo and in vitro studies of borate based glass micro-fibers for dermal repairing.

    Science.gov (United States)

    Zhou, Jie; Wang, Hui; Zhao, Shichang; Zhou, Nai; Li, Le; Huang, Wenhai; Wang, Deping; Zhang, Changqing

    2016-03-01

    Full-thickness skin defects represent urgent clinical problem nowadays. Wound dressing materials are hotly needed to induce dermal reconstruction or to treat serious skin defects. In this study, the borate bioactive glass (BG) micro-fibers were fabricated and compared with the traditional material 45S5 Bioglass(®) (SiG) micro-fibers. The morphology, biodegradation and bioactivity of BG and SiG micro-fibers were investigated in vitro. The wound size reduction and angiogenic effects of BG and SiG micro-fibers were evaluated by the rat full-thickness skin defect model and Microfil technique in vivo. Results indicated that the BG micro-fibers showed thinner fiber diameter (1 μm) and better bioactivity than the SiG micro-fibers did. The ionic extracts of BG and SiG micro-fibers were not toxic to human umbilical vein endothelial cells (HUVECs). In vivo, the BG micro-fiber wound dressings obviously enhanced the formation of blood vessel, and resulted in a much faster wound size reduction than the SiG micro-fibers, or than the control groups, after 9 days application. The good skin defect reconstruction ability of BG micro-fibers contributed to the B element in the composition, which results in the better bioactivity and angiogenesis. As shown above, the novel bioactive borate glass micro-fibers are expected to provide a promising therapeutic alternative for dermal reconstruction or skin defect repair. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. In vitro–in vivo studies of the quantitative effect of calcium, multivitamins and milk on single dose ciprofloxacin bioavailability

    Directory of Open Access Journals (Sweden)

    Baishakhi Dey

    2015-12-01

    Full Text Available Ciprofloxacin, commonly used in India as an anti-microbial for prolonged use in chronic and non-specific indications, may affect the bioavailability of the drug. The drug prescribed is commonly taken with multivitamins, calcium and milk. A simple and reliable analytical methodology obtaining a correlation with in vivo urinary excretion studies using UV and HPLC and in vitro dissolution studies (IVIVC has shown a significant increase in elimination rate of ciprofloxacin co-administered with multivitamins, calcium and milk. Appreciable IVIVC results proved that dissolution studies could serve as an alternative to in vivo bioavailability and also support bio-waivers.

  15. The use of planarians as in vivo animal model to study laser biomodulation effects

    Science.gov (United States)

    Munin, Egberto; Garcia, Neila Maria Rocha; Braz, Allison Gustavo; de Souza, Sandra Cristina; Alves, Leandro Procópio; Salgado, Miguel Angel Castillo; Pilla, Viviane

    2007-02-01

    A variety of effects is attributed to the photo stimulation of tissues, such as improved healing of ulcers, analgesic and anti-inflammatory effects, stimulation of the proliferation of cells of different origins and stimulation of bone repair. Some investigations that make qualitative evaluations, like wound healing and evaluation of pain and edema, can be conducted in human subjects. However, deeper investigations on the mechanisms of action of the light stimulus and other quantitative works that requires biopsies or destructive analysis has to be carried out in animal models or in cell cultures. In this work, we propose the use of planarians as a model to study laser-tissue interaction. Contrasting with cell cultures and unicellular organisms, planarians are among the simplest organism having tissue layers, central nerve system, digestive and excretory system that might have been platforms for the evolution of the complex and highly organized tissues and organs found in higher organisms. For the present study, 685 nm laser radiation was employed. Planarians were cut transversally, in a plane posterior to the auricles. The body fragments were left to regenerate and the proliferation dynamics of stem cells was studied by using histological analysis. Maximum cell count was obtained for the laser treated group at the 4 th experimental day. At that experimental time, we also had the largest difference between the irradiated and the non-irradiated control group. We concluded that the studied flatworm could be an interesting animal model for in vivo studies of laser-tissue interactions.

  16. A new approach for cerumenolytic treatment in children: In vivo and in vitro study.

    Science.gov (United States)

    Soy, F K; Ozbay, C; Kulduk, E; Dundar, R; Yazıcı, H; Sakarya, E U

    2015-07-01

    To demonstrate the effects of various cerumenolytic solutions in vivo and in vitro and to measure the change in pain following treatment. The study was done as a single-centre, prospective and double-blind study. Among 1243 paediatric patients with total or nearly total occlusive plug in 4 years period, those who accepted endoscopic ear examination and cleaning via aspiration after a follow-up period of at least 10 days following treatment were included in the study. Day of total TM visualisation was noted and removal co-efficient was calculated. The pre and post-treatment pain levels of the patients were assessed using analogue chromatic continuous scale (ACCS). In the in vitro part, cerumen samples collected at equal amounts from 20 patients were treated at 36-400°C in 6 different tubes with the same solutions and their dissolution degrees were assessed over a period of 5 days (Hour 6, Hour 12, Hour 48, Hour 72, Hour 92, Hour 120). Additionally, the degree of resolution in the tube treated with distilled water was considered to be the control reference. In the in vivo part of the study, total TM visualisation was observed in Group 1 at 50.2% (Day 3), in Group at 57.1%, in Group at 62.3%, in Group at 44.3% and in Group 5 at 73.5%. The group with the lowest removal co-efficient was Group 5 (removal co-efficient=1.623). In reference to the ACCS pain scores of the patients, the intra-group change pre-post treatment was found statistically significant for all groups (p=0.008; p=0.0222; p=0.005; p=0.026; p=0.018). After statistical analysis between the groups the difference between Group 5 and other groups was found statistically significant (p=0.002; p=0.026; p=0.044; p=0.034). In the in vitro part of the study, the best dissolution was observed in Group 2. In our study, the best cerumenolytic solutions were identified to be glycerine 10cc+3% hydrogen peroxide 10cc+10% sodium bicarbonate 10cc+distilled water 10cc. Especially the use of this mixture ease in terms of

  17. Electrochemical properties of titanium nitride nerve stimulation electrodes: an in vitro and in vivo study.

    Science.gov (United States)

    Meijs, Suzan; Fjorback, Morten; Jensen, Carina; Sørensen, Søren; Rechendorff, Kristian; Rijkhoff, Nico J M

    2015-01-01

    The in vivo electrochemical behavior of titanium nitride (TiN) nerve stimulation electrodes was compared to their in vitro behavior for a period of 90 days. Ten electrodes were implanted in two Göttingen minipigs. Four of these were used for electrical stimulation and electrochemical measurements. Five electrodes were kept in Ringer's solution at 37.5°C, of which four were used for electrical stimulation and electrochemical measurements. The voltage transients measured in vivo were 13 times greater than in vitro at implantation and they continued to increase with time. The electrochemical properties in vivo and the tissue resistance (Rtissue) followed a similar trend with time. There was no consistent significant difference between the electrochemical properties of the in vivo and in vitro electrodes after the implanted period. The differences between the in vivo and in vitro electrodes during the implanted period show that the evaluation of electrochemical performance of implantable stimulation electrodes cannot be substituted with in vitro measurements. After the implanted period, however, the performance of the in vivo and in vitro electrodes in saline was similar. In addition, the changes observed over time during the post-implantation period regarding the electrochemical properties of the in vivo electrodes and Rtissue were similar, which indicates that these changes are due to the foreign body response to implantation.

  18. Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

    Science.gov (United States)

    Jones, Kate; Morton, Jackie; Smith, Ian; Jurkschat, Kerstin; Harding, Anne-Helen; Evans, Gareth

    2015-03-04

    The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Antimicrobial photodynamic therapy with fulleropyrrolidine: photoinactivation mechanism of Staphylococcus aureus, in vitro and in vivo studies.

    Science.gov (United States)

    Grinholc, Mariusz; Nakonieczna, Joanna; Fila, Grzegorz; Taraszkiewicz, Aleksandra; Kawiak, Anna; Szewczyk, Grzegorz; Sarna, Tadeusz; Lilge, Lothar; Bielawski, Krzysztof P

    2015-05-01

    A family of N-methylpyrrolidinium fullerene iodide salts has been intensively studied to determine their applicability in antimicrobial photodynamic therapy (APDT). This study examined in vitro the efficacy of a C60 fullerene functionalized with one methylpyrrolidinium group to kill upon irradiation with white light gram-negative and gram-positive bacteria, as well as fungal cells, and the corresponding mechanism of the fullerene bactericidal action. The in vitro studies revealed that the high antistaphylococcal efficacy of functionalized fullerene could be linked to their ability to photogenerate singlet oxygen and superoxide anion. Following Staphylococcus aureus photoinactivation, no modifications of its genomic DNA were detected. In contrast, photodamage of the cell envelope seemed to be a dominant mechanism of bactericidal action. In in vivo studies, a 2 log10 reduction in the average bioluminescent radiance between treated and non-treated mice was reached. One day post APDT treatment, moist and abundant growth of bacteria could be observed on wounds of non-fulleropyrrolidine and dark control mice. APDT-treated wounds stayed visibly clear up to the third day. Moreover, cytotoxicity test on human dermal keratinocytes revealed great safety of using the sensitizer toward eukaryotic cells. These data indicate potential application of functionalized fullerene as antistaphylococcal sensitizer for superficial infections.

  20. Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

    Science.gov (United States)

    Asic, Adna; Kurtovic-Kozaric, Amina; Besic, Larisa; Mehinovic, Lejla; Hasic, Azra; Kozaric, Mirza; Hukic, Mirsada; Marjanovic, Damir

    2017-07-01

    The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Corneal Re-innervation and Sensation Recovery in Patients with Herpes Zoster Ophthalmicus: An In Vivo and Ex Vivo Study of Corneal Nerves

    Science.gov (United States)

    Cruzat, Andrea; Hamrah, Pedram; Cavalcanti, Bernardo M.; Zheng, Lixin; Colby, Kathryn; Pavan-Langston, Deborah

    2016-01-01

    Purpose To study corneal reinnervation and sensation recovery in Herpes zoster Ophthalmicus (HZO). Methods Two patients with HZO were studied over time with serial corneal esthesiometry and laser in vivo confocal microscopy (IVCM). A Boston keratoprosthesis (B-KPro) type 1 was implanted and the explanted corneal tissues were examined by immunofluorescence histochemistry for βIII-tubulin to stain for corneal nerves. Results The initial central corneal IVCM performed in each patient, showed a complete lack of the subbasal nerve plexus, which was in accordance with severe loss of sensation (0 of 6 cm) measured by esthesiometry. When IVCM was repeated 2 years later prior to undergoing surgery, Case 1 showed a persistent lack of central subbasal nerves and sensation (0 of 6). In contrast, Case 2 showed regeneration of the central subbasal nerves (4,786 µm/mm2) with partial recovery of corneal sensation (2.5 of 6 cm). Immunostaining of the explanted corneal button in Case 1 showed no corneal nerves while Case 2, showed central and peripheral corneal nerves. Eight months after surgery, IVCM was again repeated in the donor tissue around the B-KPro in both patients, to study innervation of the corneal transplant. Case 1 showed no nerves, while Case 2 showed new nerves growing from the periphery into the corneal graft. Conclusions We demonstrate that regaining corneal innervation and function is possible in patients with HZO as shown by corneal sensation, IVCM, and ex-vivo immunostaining, indicating zoster neural damage is not always permanent and it may recover over an extended period of time. PMID:26989956

  2. Surface Changes of PathFile after Glide Path Preparation: An Ex Vivo and In Vivo Study.

    Science.gov (United States)

    Kim, Yul; Love, Robert; George, Roy

    2017-10-01

    The aim of this study was to evaluate the changes in the surface profile of rotary nickel-titanium (NiTi) files designed to prepare a glide path and conventional stainless steel (SS) hand files when used in extremely narrow canals both in clinical and experimental conditions. This ex vivo/in vivo study used either SS #10 K hand files or the PathFile system (Dentsply Maillefer, Ballaigues, Switzerland) to establish a glide path in maxillary molars with narrow root canals (defined as canals that bound a #8 K-file at the working length). After treatment, all files were cleaned and scanned using a noncontact laser profilometer. Changes to the surface profile (Ra cutting edge waviness = RaCEW) and roughness (Ra cutting edge roughness = RaCER) of the cutting edges and the surface roughness of the flute area (Sa flute roughness = SaFR) were analyzed. #10 K-files had significant increases in all types of measurements (RaCEW, RaCEW, and SaFR) after the preparation of second mesiobuccal canals compared with the control group (P flute (SaFR) (P flute and cutting edge) values across all PathFile sizes compared with control values. This study showed that PathFiles had significantly less surface defects compared with SS files after the preparation of narrow canals, indicating their possible benefits when establishing a glide path in extremely narrow canals. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  3. Bioequivalence Methodologies for Topical Drug Products: In Vitro and Ex Vivo Studies with a Corticosteroid and an Anti-Fungal Drug.

    Science.gov (United States)

    Leal, Leila Bastos; Cordery, Sarah F; Delgado-Charro, M Begoña; Bunge, Annette L; Guy, Richard H

    2017-04-01

    To examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental approaches can be reliably and reproducibly used to establish (in)equivalence between formulations for skin application. In vitro drug release through artificial membranes, and drug penetration into porcine skin ex vivo, were compared with published human in vivo studies. Two betamethasone valerate (BMV) formulations, and three marketed econazole nitrate (EN) creams were assessed. For BMV, the stratum corneum (SC) uptake of drug in 6 h closely matched data observed in vivo in humans, and distinguished between inequivalent formulations. SC uptake of EN from the 3 creams mirrored the in vivo equivalence in man (both clinically and via similar tape-stripping experiments). However, EN clearance from SC ex vivo did not parallel that in vivo, presumably due to the absence of a functioning microcirculation. In vitro release of BMV from the different formulations did not overlap with either ex vivo or in vivo tape-stripping data whereas, for EN, a good correlation was observed. No measurable permeation of either BMV or EN was detected in a 6-h in vitro skin penetration experiment. In vitro and ex vivo methods for topical bioequivalence determination can show correlation with in vivo outcomes. However, these surrogates have understandable limitations. A "one-size-fits-all" approach for topical bioequivalence evaluation may not always be successful, therefore, and the judicious use of complementary methods may prove a more effective and reliable strategy.

  4. Synthesis and evaluation of 4-[F-18]fluoro thalidomide for the in vivo studies of angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D. H.; Choi, Y. S.; Jeong, K. H.; Lee, K. H.; Choi, Y.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of)

    2005-07-01

    Thalidomide has been recently rediscovered for its possible utility as an antitumor agent, although it was marketed as a sedative in the 1950s and later found to be a potent teratogen. In this study, therefore, F-18 labeled thalidomide was synthesized and evaluated for the in vivo studies of angiogenesis. 4-[F-18]Fluoro thalidomide ([F-18]1) was prepared by labeling of 4-trimethylammonium thalidomide triflate with TBA[F-18]F in DMSO (90 .deg. C, 10 min) and purified by HPLC. The triflate salt was prepared from 3-fluoro phthalic anhydride in 3 steps. [F-18]1 was incubated with HUVEC cells at 37 .deg. C for 15, 30, 60, and 120 min, respectively. Dynamic PET images of [F-18]1 was obtained in mice implanted with LLC cells. In vitro metabolism study of [F-18]1 was carried out using mouse, rabbit, or human liver microsomes in the presence of NADPH, and the metabolites obtained from the mouse liver microsomal incubation of 1 were analyzed using LC-MS. Radiochemical yield of [F-18]1 was 50-60%, and the specific activity was 42-120 GBq/imol. The HUVEC cell uptake of [F-18]1 increased with time (100% at 15 min and 241% at 120 min). PET images showed that the radioactivity was accumulated in the liver, the kidneys and the bladder of the mice, and brain uptake was shown from 40 min postinjection. However, there was low level of radioactivity uptake in tumor. [F-18]1 was not metabolized by mouse, rabbit, or human liver microsomes but was hydrolyzed significantly at physiological pH. The hydrolyzed product was further analyzed by LC-MS, showing a mass peak corresponding to that of 4-fluoro-N-(o-carboxybenzoyl)glutamic acid imide. This result suggests that [F-18]1 is easily hydrolyzed at physiological pH and thus may not be suitable for the in vivo studies of tumor angiogenesis at least in rodents, although it was reported that the hydrolysis product of thalidomide may be responsible for its angiogenesis activity in humans.

  5. In Vivo Consumption of Cranberry Exerts ex Vivo Antiadhesive Activity against FimH-Dominated Uropathogenic Escherichia coli: A Combined in Vivo, ex Vivo, and in Vitro Study of an Extract from Vaccinium macrocarpon.

    Science.gov (United States)

    Rafsanjany, Nasli; Senker, Jandirk; Brandt, Simone; Dobrindt, Ulrich; Hensel, Andreas

    2015-10-14

    For investigation of the molecular interaction of cranberry extract with adhesins of uropathogenic Escherichia coli (UPEC), urine from four volunteers consuming standardized cranberry extract (proanthocyanidin content = 1.24%) was analyzed within ex vivo experiments, indicating time-dependent significant inhibition of 40-50% of bacterial adhesion of UPEC strain NU14 to human T24 bladder cells. Under in vitro conditions a dose-dependent increase in bacterial adhesion was observed with proanthocyanidin-enriched cranberry Vaccinium macrocarpon extract (proanthocyanidin content = 21%). Confocal laser scanning microscopy and scanning electron microscopy proved that V.m. extract led to the formation of bacterial clusters on the outer plasma membrane of the host cells without subsequent internalization. This agglomerating activity was not observed when a PAC-depleted extract (V.m. extract(≠PAC)) was used, which showed significant inhibition of bacterial adhesion in cases where type 1 fimbriae dominated and mannose-sensitive UPEC strain NU14 was used. V.m. extract(≠PAC) had no inhibitory activity against P- and F1C-fimbriae dominated strain 2980. Quantitative gene expression analysis indicated that PAC-containing as well as PAC-depleted cranberry extracts increased the fimH expression in NU14 as part of a feedback mechanism after blocking FimH. For strain 2980 the PAC-containing extract led to up-regulation of P- and F1C-fimbriae, whereas the PAC-depleted extract had no influence on gene expression. V.m. and V.m. extract(≠PAC) did not influence biofilm and curli formation in UPEC strains NU14 and 2980. These data lead to the conclusion that also proanthocyanidin-free cranberry extracts exert antiadhesive activity by interaction with mannose-sensitive type 1 fimbriae of UPEC.

  6. Comparison of ultrasound, digital, and conventional radiography in differentiating periapical lesions: An in vivo study

    Directory of Open Access Journals (Sweden)

    Purnachandrarao Naik Nunsavathu

    2015-01-01

    Full Text Available Aims and Objectives: To evaluate in vivo the efficacy of ultrasound, digital and conventional radiography in identifying periapical lesions. To compare the results of the above imaging modalities with histopathology, which is considered to be the gold standard for diagnosis. Materials and Methods: Thirty patients aged between 15 and 45 years with periapical lesions associated with maxillary or mandibular anterior teeth indicated for endodontic surgery or extraction were selected for the study. Pre-operatively, conventional, digital periapical radiography and ultrasonography were done and interpreted. Endodontic surgery or extraction was performed including curettage of apical tissue to enable histopathological investigation, which provided the gold standard diagnosis. All measurements and findings were compared and statistically analyzed. Results: In conventional and digital radiography, the periapical lesions were readily identified but observers were unable to differentiate granuloma from cyst using these modalities only. But ultrasonography was able to give the true nature of the periapical pathology. All the cases diagnosed by ultrasound were confirmed with histopathology, and maximal number of cases diagnosed by ultrasound correlated with the histopathological diagnosis. Conclusion: The present study confirms that ultrasound is a promising and reliable imaging technique for differentiating periapical lesions i.e., periapical cysts and granulomas. Based on the echo texture of their contents and the presence of vascularity using color Doppler, periapical cyst and granulomas can be readily identified. The present study is further applicable for the evaluation of periapical lesions of the posterior teeth and evaluation of other jaw lesions.

  7. Effect of metal fragments in brain on electrical monitoring: In vitro and in vivo rat studies

    Science.gov (United States)

    Ahmed, A.; Bodo, M.; Armonda, R. A.

    2010-04-01

    Preliminary results showed, measurements by rheoencephalography (REG) very promising as a practical, noninvasive continuous monitoring modality of traumatic brain/blast injuries. As the impact of metal fragments on the REG signal is unknown, we report here results of our study .The in vitro study confirmed that impedance pulse amplitude waves do not change in the presence of metal (needles) placed between electrodes. In vivo studies: rats under anesthesia (10 rats, 101 trials) were measured after implantation of EEG and REG electrodes in the brain. Metal fragments were represented by 18 g needles inserted and removed between EEG and REG electrodes. Data were stored in a PC. EEG recording typically showed amplitude decrease; REG showed transitory amplitude increase after placement of a needle into either hemisphere. Removal of needles caused a decrease in REG amplitude after a transitory increase. The change in REG amplitude statistically was non-significant. Cerebral blood flow (CBF) autoregulation(AR) persisted following placement of metal fragments in rat brain.

  8. Gnotobiotic rodents: an in vivo model to study microbe-microbe interactions

    Directory of Open Access Journals (Sweden)

    Rebeca eMartin

    2016-03-01

    Full Text Available Germ-free rodents have no microorganisms living in or on them, allowing researchers to specifically control an animal’s microbiota through the direct inoculation of bacteria of interest. This strategy has been widely used to decipher host-microbe interactions as well as the role of microorganisms in both i the development and function of the gut barrier (mainly the intestinal epithelium and ii homeostasis and its effects on human health and disease. However, this in vivo model also offers a more realistic environment than an assay tube in which to study microbe-microbe interactions, without most of the confounding interactions present in the intestinal microbiota of conventionally raised mice. This review highlights the usefulness of controlled-microbiota mice in studying microbe-microbe interactions. To this end, we summarize current knowledge on germ-free animals as an experimental model for the study of the ecology and metabolism of intestinal bacteria as well as of microbe-microbe interactions.

  9. The isolated perfused equine distal limb as an ex vivo model for pharmacokinetic studies.

    Science.gov (United States)

    Friebe, M; Stahl, J; Kietzmann, M

    2013-06-01

    Even though intra-articular injections play an important role in the treatment of joint-related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, an ex vivo model for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments (n = 11), which also included histological examinations of the joint capsule. As the model's first implementation, the articular efflux rate of betamethasone (BM), administered as BM disodium phosphate intra-articularly to the fetlock joint (4 mg BM/joint), was investigated. The concentration of BM in the venous perfusate of the radial vein was measured by means of high-performance liquid chromatography. The average BM efflux rate per minute was calculated to be 5.1 μg/min with values ranging from 9 μg/min to 2.9 μg/min. 7.5 h after i.a. application, 2.3 mg BM had left the joint via the radial vein. Using this inexpensive setup, the presented model allows studying a variety of pharmacological topics without the ethical limitations of animal studies. © 2012 Blackwell Publishing Ltd.

  10. Preliminary Study of In Vivo Formed Dental Plaque Using Confocal Microscopy and Scanning Electron Microscopy

    Directory of Open Access Journals (Sweden)

    KA. Al-Salihi

    2009-12-01

    Full Text Available Objective: Confocal laser scanning microscopy (CLSM is relatively a new light microscopical imaging technique with a wide range of applications in biological sciences. The primary value of CLSM for the biologist is its ability to provide optical sections from athree-dimensional specimen. The present study was designed to assess the thickness and content of in vivo accumulated dental plaque using CLSM and scanning electron microscopy (SEM.Materials and Methods: Acroflat lower arch splints (acrylic appliance were worn by five participants for three days without any disturbance. The formed plaques were assessed using CLSM combined with vital fluorescence technique and SEM.Results: In this study accumulated dental plaque revealed varied plaque microflora vitality and thickness according to participant’s oral hygiene. The thickness of plaque smears ranged from 40.32 to 140.72 μm and 65.00 to 128.88 μm for live (vital and dead accumulated microorganisms, respectively. Meanwhile, the thickness of plaque on the appliance ranged from 101 μm to 653 μm. CLSM revealed both dead and vital bacteria on the surface of the dental plaque. In addition, SEM revealed layers of various bacterial aggregations in all dental plaques.Conclusion: This study offers a potent non-invasive tool to evaluate and assess the dental plaque biofilm, which is a very important factor in the development of dental caries.

  11. Application of tetra-isopalmitoyl ascorbic acid in cosmetic formulations: stability studies and in vivo efficacy.

    Science.gov (United States)

    Maia Campos, Patrícia M B G; Gianeti, Mirela D; Camargo, Flávio B; Gaspar, Lorena R

    2012-11-01

    Liposoluble vitamin C derivatives, such as tetra-isopalmitoyl ascorbic acid (IPAA), are often used in dermocosmetic products due to their higher stability than vitamin C free form as well as its proposed effects in skin; however, there are no studies analyzing IPAA stability or its in vivo effects when present in dermocosmetic formulations. Thus, this study aimed to evaluate chemical stability and pre-clinical and clinical efficacy of dermocosmetic formulations containing IPAA in skin hydration and microrelief. Chemical stability of the formulations added with 1% IPAA was evaluated by heat stress during 35 days by HPLC. For pre-clinical evaluation, experimental formulations were topically applied on hairless skin mice during 5 days and animal skins were analyzed by non-invasive biophysic techniques (water content of stratum corneum, TEWL, viscoelasticity, and microrelief) and by histopathological studies. For clinical efficacy tests, the formulations were topically applied to the forearm and face of human volunteers, and 3h and 15 days after applications, the skins were evaluated by the same non-invasive techniques mentioned before. Results showed that formulations containing IPAA had medium stability and had pronounced moisturizing effects on stratum corneum and on viable epidermis. These formulations also improved skin microrelief especially in relation to skin smoothness and roughness. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. RGD-targeted paramagnetic liposomes for early detection of tumor: In vitro and in vivo studies

    Energy Technology Data Exchange (ETDEWEB)

    Li Wei; Su Bo; Meng Shuyan; Ju Lixia; Yan Linghua; Ding Yongmei; Song Yin; Zhou Wei; Li Heyan; Tang Liang; Zhao Yinmin [Research Institute of Oncology, Tongji University Medical School, 507 Zhenmin Road, Shanghai 200433 (China); Zhou Caicun, E-mail: caicunzhou@yahoo.com.cn [Research Institute of Oncology, Tongji University Medical School, 507 Zhenmin Road, Shanghai 200433 (China)

    2011-11-15

    Magnetic resonance molecular imaging has emerged as a potential approach for tumor diagnosis in the last few decades. This approach consists of the delivery of MR contrast agents to the tumor by specific targeted carriers. For this purpose, a lipopeptide was constructed by using a cyclic RGD peptide headgroup coupled to palmitic acid anchors via a KGG tripeptide spacer. Targeted paramagnetic liposomes were then prepared by the incorporation of RGD-coupled-lipopeptides into lipid bilayers for specific bounding to tumor. In vitro, study demonstrated that RGD-targeted liposomes exhibited a better binding affinity to targeted cells than non-targeted liposomes. MR imaging of mice bearing A549 tumors with the RGD-targeted paramagnetic liposomes also resulted in a greater signal enhancement of tumor compared to non-targeted liposomes and pure contrast agents groups. In addition, biodistribution study also showed specific tumor targeting of RGD-targeted paramagnetic liposomes in vivo. Therefore, RGD-targeted paramagnetic liposomes prepared in the present study may be a more promising method for early tumor diagnosis.

  13. The potential of isotopically enriched magnesium to study bone implant degradation in vivo.

    Science.gov (United States)

    Draxler, Johannes; Martinelli, Elisabeth; Weinberg, Annelie M; Zitek, Andreas; Irrgeher, Johanna; Meischel, Martin; Stanzl-Tschegg, Stefanie E; Mingler, Bernhard; Prohaska, Thomas

    2017-03-15

    This pilot study highlights the substantial potential of using isotopically enriched (non-radioactive) metals to study the fate of biodegradable metal implants. It was possible to show that magnesium (Mg) release can be observed by combining isotopic mass spectrometry and isotopic pattern deconvolution for data reduction, even at low amounts of Mg released a from slowly degrading (26)Mg enriched (>99%) Mg metal. Following implantation into rats, structural in vivo changes were monitored by μCT. Results showed that the applied Mg had an average degradation rate of 16±5μmyear(-1), which corresponds with the degradation rate of pure Mg. Bone and tissue extraction was performed 4, 24, and 52weeks after implantation. Bone cross sections were analyzed by laser ablation inductively coupled plasma mass spectrometry (ICP-MS) to determine the lateral (26)Mg distribution. The (26)Mg/(24)Mg ratios in digested tissue and excretion samples were analyzed by multi collector ICP-MS. Isotope pattern deconvolution in combination with ICP-MS enabled detection of Mg pin material in amounts as low as 200ppm in bone tissues and 20ppm in tissues up to two fold increased Mg levels with a contribution of pin-derived Mg of up to 75% (4weeks) and 30% (24weeks) were found adjacent to the implant. After complete degradation, no visual bone disturbance or residual pin-Mg could be detected in cortical bone. In organs, increased Δ(26)Mg/(24)Mg values up to 16‰ were determined compared to control samples. Increased Δ(26)Mg/(24)Mg values were detected in serum samples at a constant total Mg level. In contrast to urine, feces did not show a shift in the (26)Mg/(24)Mg ratios. This investigation showed that the organism is capable of handling excess Mg well and that bones fully recover after degradation. Magnesium alloys as bone implants have faced increasing attention over the past years. In vivo degradation and metabolism studies of these implant materials have shown the promising application

  14. An In Vivo Study on Load Distribution in Different Implant Configurations for Supporting Fixed Partial Dentures.

    Science.gov (United States)

    Kobari, Hiromori; Yoda, Nobuhiro; Chen, Junning; Kawata, Tetsuo; Sasaki, Keiichi

    2016-01-01

    The aims of this study were to develop a device for in vivo measurement of three-dimensional (3D) loads on implants and to investigate the effects of implant configuration on the load distribution under a three-unit fixed partial denture (FPD). A 67-year-old female patient with three implants (in the mandibular left second premolar, first molar, and second molar regions) was recruited. Four implant configurations for a three-unit FPD depending on the number and position of the implants were considered in this study. They included a three-implant prosthesis and three types of two-implant prosthesis: a central pontic, posterior cantilever, and anterior cantilever, with the same superstructure (splinted three crowns) for the same occlusal contact. Customized abutments and 3D piezoelectric force transducers were fixed to the implants of the four configurations with the superstructure. The loads on the implants were recorded during maximum voluntary clenching (MVC-test) and when chewing a piece of chewing gum (GUMtest). The occlusal forces on the dental arch during MVC-test with the four implant configurations did not exhibit significant differences. In the three-implant prosthesis, there were no significant differences in the mean maximum resultant load on each implant in both tests. In the central pontic, the load on the second premolar was significantly greater than that on the second molar in the MVC-test but there were no significant differences in the GUM-test. High loads were detected on the first molar in both the posterior cantilever and anterior cantilever. The highest load was detected on the first molar in the posterior cantilever during the GUMtest. The in vivo 3D load-measuring device using the piezoelectric force transducers enabled the measurement of the functional load on implants supporting a FPD. The results suggested, within the limitations of this study, that a three-implant prosthesis and central pontic provide biomechanically beneficial designs

  15. Evaluation of the Doxycycline Release from AH26 Sealer-Doxycycline Combination: An ex vivo Study.

    Science.gov (United States)

    Ashofteh Yazdi, Kazem; Shokouhinejad, Noushin; Moazeni, Esmaeil; Mirzayi Rad, Sina

    2011-01-01

    The purpose of this ex vivo study was to determine the releasing characteristics and doxycycline dentinal diffusion of AH26 sealer-doxycycline combination from apical 3mm of tooth root and apical foramen. One-hundred and two recently extracted single-rooted human teeth were decoronated and prepared with #3 and #4 Gates-Glidden drills and rotary Mtwo files. Smear layer was removed; all surfaces except for apical 3mm of each root were sealed with two coats of nail polish. To quantify the release and diffusion of the doxycycline at different time intervals (30 min, 48 and 72 h) after root canal obturation, the samples were randomly divided into three groups (n=30; 0.5 h, 48 h, 72 h). To evaluate the release of doxycycline from AH26 sealer-doxycycline combination at six concentrations of antibiotic including 0.5%, 1%, 2%, 5%, 10% and 20%; each experimental group was divided into six equal subgroups (n=5). Root canals were filled with gutta-percha and AH26-doxycycline combinations and then were placed in vials containing 1.25mL of phosphate buffer saline solution (PBS). After 30 min, 48 and 72 h, the amount of doxycycline released from specimens into PBS were determined by measuring the absorbance values using UV spectrophotometry at λ(max)=350 nm. Data were analyzed using two-way ANOVA. The findings of this study revealed that AH26 sealer-doxycycline combination released variable measures of antibiotic at each time interval and in the various concentrations. At 30 min, no statistically significant differences were obtained between the results of subgroups, but at 48 and 72 h these differences were significant (P<0.001). The results also showed that differences between 0.5 h, 48 h and 72 h were significant within subgroups (P<0.01). Under the conditions of this ex vivo study, doxycycline can be released from AH26 sealer-antibiotic combination through 3mm of apical root and apical foramen at 30 min, 48 and 72 h after mixing the sealer with doxycycline at concentrations

  16. Crystallization study and comparative in vitro-in vivo hydrolysis of PLA reinforcement ligament

    National Research Council Canada - National Science Library

    Beslikas, Theodore; Gigis, Ioannis; Goulios, Vasilios; Christoforides, John; Papageorgiou, George Z; Bikiaris, Dimitrios N

    2011-01-01

    In the present work, the crystallization behavior and in vitro-in vivo hydrolysis rates of PLA absorbable reinforcement ligaments used in orthopaedics for the repair and reinforcement of articulation...

  17. Biocompatibility of nanosilver-coated orthodontic brackets: an in vivo study

    Directory of Open Access Journals (Sweden)

    Gamze Metin-Gürsoy

    2016-12-01

    Full Text Available Abstract Background Nanosilver particles of which antibacterial and antifungal properties have been shown in various in vitro and in vivo studies are used in many medical and dental fields for the prevention of infection. In this study, it is intended to evaluate the biocompatibility of nanosilver-coated brackets. Methods Nanosilver coating process was applied to the standard orthodontic brackets by a physical vapor deposition system. Brackets were coated with nanosilver particles of 1 μ thickness. A total of 12 Wistar Albino rats were included in the study (six and control (six groups. For the study and control groups, four nanosilver-coated and four standard brackets were aseptically implanted subcutaneously in the dorsal region of each rat. The brackets were removed with the surrounding tissues on days 7, 14, 30, and 60. The specimens were evaluated for inflammatory response. Results No significant difference was found in terms of tissue reaction between the study and control groups. On day 7, randomly distributed brown-black granules were seen in the granulation tissue adjacent to the bracket in the study group. These foreign particles continued along the bracket cavity in a few samples, but the inflammatory response was insignificant between the groups. Mast cell count was found to be significantly smaller only on day 7 in the study group than in the control group. Conclusions Nanosilver-coated orthodontic brackets were found to be similar with the standard type concerning inflammation. Further researches are needed with regard to the assessment of the brown-black granules, especially on the deposition of the vessel walls.

  18. MASM, a Matrine Derivative, Offers Radioprotection by Modulating Lethal Total-Body Irradiation-Induced Multiple Signaling Pathways in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Jianzhong Li

    2016-05-01

    Full Text Available Matrine is an alkaloid extracted from Sophora flavescens Ait and has many biological activities, such as anti-inflammatory, antitumor, anti-fibrosis, and immunosuppressive properties. In our previous studies, the matrine derivative MASM was synthesized and exhibited potent inhibitory activity against liver fibrosis. In this study, we mainly investigated its protection against lethal total-body irradiation (TBI in rats. Administration of MASM reduced the radiation sickness characteristics and increased the 30-day survival of rats before or after lethal TBI. Ultrastructural observation illustrated that pretreatment of rats with MASM significantly attenuated the TBI-induced morphological changes in the different organs of irradiated rats. Gene expression profiles revealed that pretreatment with MASM had a dramatic effect on gene expression changes caused by TBI. Pretreatment with MASM prevented differential expression of 53% (765 genes of 1445 differentially expressed genes induced by TBI. Pathway enrichment analysis indicated that these genes were mainly involved in a total of 21 pathways, such as metabolic pathways, pathways in cancer, and mitogen-activated protein kinase (MAPK pathways. Our data indicated that pretreatment of rats with MASM modulated these pathways induced by TBI, suggesting that the pretreatment with MASM might provide the protective effects on lethal TBI mainly or partially through the modulation of these pathways, such as multiple MAPK pathways. Therefore, MASM has the potential to be used as an effective therapeutic or radioprotective agent to minimize irradiation damages and in combination with radiotherapy to improve the efficacy of cancer therapy.

  19. In vivo experimental study of anterior cervical fusion using bioactive polyetheretherketone in a canine model.

    Science.gov (United States)

    Shimizu, Takayoshi; Fujibayashi, Shunsuke; Yamaguchi, Seiji; Otsuki, Bungo; Okuzu, Yaichiro; Matsushita, Tomiharu; Kokubo, Tadashi; Matsuda, Shuichi

    2017-01-01

    Polyetheretherketone (PEEK) is a widely accepted biomaterial, especially in the field of spinal surgery. However, PEEK is not able to directly integrate with bone tissue, due to its bioinertness. To overcome this drawback, various studies have described surface coating approaches aimed at increasing the bioactivity of PEEK surfaces. Among those, it has been shown that the recently developed sol-gel TiO2 coating could provide PEEK with the ability to bond with bone tissue in vivo without the use of a bone graft. This in vivo experimental study using a canine model determined the efficacy of bioactive TiO2-coated PEEK for anterior cervical fusion. Sol-gel-derived TiO2 coating, which involves sandblasting and acid treatment, was used to give PEEK bone-bonding ability. The cervical interbody spacer, which was designed to fit the disc space of a beagle, was fabricated using bioactive TiO2-coated PEEK. Both uncoated PEEK (control) and TiO2-coated PEEK spacers were implanted into the cervical intervertebral space of beagles (n = 5 for each type). After the 3-month survival period, interbody fusion success was evaluated based on μ-CT imaging, histology, and manual palpation analyses. Manual palpation analyses indicated a 60% (3/5 cases) fusion (no gap between bone and implants) rate for the TiO2-coated PEEK group, indicating clear advantage over the 0% (0/5 cases) fusion rate for the uncoated PEEK group. The bony fusion rate of the TiO2-coated PEEK group was 40% according to μCT imaging; however, it was 0% of for the uncoated PEEK group. Additionally, the bone-implant contact ratio calculated using histomorphometry demonstrated a better contact ratio for the TiO2-coated PEEK group than for the uncoated PEEK group (mean, 32.6% vs 3.2%; p = 0.017). The TiO2-coated bioactive PEEK implant demonstrated better fusion rates and bone-bonding ability than did the uncoated PEEK implant in the canine anterior cervical fusion model. Bioactive PEEK, which has bone-bonding ability

  20. Radioprotective effects of flavonoids against to chromosomal damage: relation between the structure and activity

    Energy Technology Data Exchange (ETDEWEB)

    Alcaraz, M.; Acevedo, C.; Benavente-Garcia, O.; Castillo, J.; Vicente, V.; Canteras, M.

    2004-07-01

    Protective effects of grape (Vitis vinifera) seed (GSE), Citrus spp. fruits (CE) and olive Olea europaea L) leaf (OL) extracts, the flavonoids diosmin and rutin, widely used as pharmaceuticals, and diemthyl sulphoxide (DMSO) against chromosomal damage induced by X-rays and g radiation were determined by using two different micronucleus test for anti genotoxic activity. The quantitative distribution of several flavones-3-ols was determined using HPLC in a grape (Vitis vinifera), seed extract (GSE) and Olea european (OL) of four cultivars grown in the region of Murcia. Polymer>C4 units made up the largest group of procyanidins in the GSE (90,92%, expressed as HPLC% area). The antioxidant activity of GSE and other reference compounds was investigated by measuring theirs ability to scavenge the ABTS+ radical cation (TEAC). The most effective compounds were in order: GSE >rutin>(+)-catechin>OL>diosmina>ascorbic acid. The radioprotective effects of GSE and other reference compounds were determined by using the micronucleus test for anticlastogenic activity, any reduction of the frequency of micronucleated polychromatic erythrocytes (mnOCEs) being evaluated in the bone marrow of mouse exposed to X rays; and evaluating the reduction in the frequency of micronuclei in citokinesis-blocked cells of human lymphocytes exposed to g-rays. The most effective compounds were, in order: GSE>rutin>dimetylsufoxide (DMSO)>ascorbic acid>OL>6-n-propyl-2-thiouracil-6c (PTU)>disomin. The higher ABTS scavenging capacity and antigenotoxic activity of GSE can be explained, structurally, by the high number of conjugated structures between the catechol groups in the B-rings ant the 3-OH free groups of the polymeric polyphenolic skeleton and, in addition, by the stability of the aroxyl flavonoide radical generated in the above processes. (Author)

  1. In vivo sup 1 sup 3 C MRS studies of carbohydrate metabolism

    CERN Document Server

    Halliday, J

    2003-01-01

    The work described in this thesis was performed by the except where indicated, within the Magnetic Resonance Centre at the University of Nottingham during the period between October 1999 and October 2002. Although much is known about the major pathways of carbohydrate metabolism, there is still much to be learnt about the exact mechanisms of many of these pathways. Of particular interest is how these pathways are modified under different physiological conditions and in diseased states. sup 1 sup 3 C NMR spectroscopy provides a non-invasive means for studying carbohydrate metabolism in vivo, and the work presented within this thesis gives two such examples of this in human subjects. Natural abundance sup 1 sup 3 C NMR spectroscopy was used to measure glycogen levels in gastrocnemius muscle. The diurnal changes in response to mixed meals were measured in both type 2 diabetic subjects and age and weight matched controls. Metabolic studies were performed to complement the NMR measurements. The data obtained in th...

  2. Ozone therapy as an adjuvant for endondontic protocols: microbiological - ex vivo study and citotoxicity analyses.

    Science.gov (United States)

    Nogales, Carlos Goes; Ferreira, Marina Beloti; Montemor, Antonio Fernando; Rodrigues, Maria Filomena de Andrade; Lage-Marques, José Luiz; Antoniazzi, João Humberto

    2016-01-01

    This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I - control; Group II - standard protocol; Group III - standard protocol + ozone gas at 40 µg/mL; and Group IV - standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) - broth medium; Group II - aqueous ozone at 2 µg/mL; Group III - aqueous ozone at 5 µg/mL; and Group IV - aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results.

  3. Prognostic significance of vascularity in cutaneous melanoma: pilot study using in vivo confocal scanning laser microscopy.

    Science.gov (United States)

    Humphrey, Shannon; Walsh, Noreen M; Delaney, Laura; Propperova, Iva; Langley, Richard G B

    2006-01-01

    Tumor vascularity may be of strong prognostic significance in cutaneous melanoma. We are the first to use a novel, noninvasive, in vivo confocal scanning laser microscope (CSLM) to evaluate vascularity in cutaneous melanoma. Our purpose was to apply a CSLM to assess vascularity in melanoma and to evaluate the prognostic significance of these findings. Patients with a suspicious pigmented lesion were prospectively recruited to undergo CSLM prior to skin biopsy, and those diagnosed with melanoma were included in this study. A blinded observer graded tumor vascularity from still digital CSLM images. The CSLM vascularity grading was correlated to tumor thickness and ulceration as a proxy for clinical prognosis. Sixty-six patients and 67 lesions underwent imaging with CSLM. Eleven patients were diagnosed with melanoma, including six in situ and five invasive melanomas. Prominent vascularity was observed in all advanced melanomas. There was an overall increase in mean tumor thickness between the absent (x = 0.315 mm) to prominent (x = 1.51 mm) categories. In this pilot study, vascularity was readily detected in cutaneous melanomas using CSLM. Prominent vascularity was observed in patients with advanced cutaneous melanomas. Our preliminary results are encouraging and indicate potential for the use of CSLM to assess vascularity in cutaneous melanoma, with potential prognostic and therapeutic implications.

  4. Inter- and intra-operator variability associated with extracapsular suture tensioning: an ex vivo study.

    Science.gov (United States)

    Dunn, A L; Buffa, E A; Marchevsky, A M; Heller, J; Moores, A P; Farrell, M

    2012-01-01

    To determine inter- and intra- operator variability associated with extracapsular suture tensioning as performed during lateral fabello-tibial suture placement. Ex vivo study. Fifteen Greyhound cadaveric pelvic limbs were prepared by cutting the cranial cruciate ligament and placing an extracapsular fabello-tibial suture. On two occasions, three surgeons tensioned the extracapsular suture of each stifle. Stifles were returned to 135 degrees of flexion and the suture tension was measured using a commercially available suture tensioner with inbuilt tensiometer. Intra-operator and inter-operator agreement were assessed using the limits of agreement method. A linear mixed effects model was specified to assess the effect of operator, repeated estimates and stifle order on tension applied. The mean difference within the three operators ranged from 0 to 14.7N. With 95% limits of agreement, on most occasions for all three operators, the difference was between -31.7 and 41.0 N. The mean difference between the three operators ranged from 6.0 to 30.7 N. With 95% limits of agreement, on most occasions the difference between operators was between -25.6 and 62.5 N. Marked variation exists in the tension applied during fabello-tibial suture application, both within and between surgeons. This variation may lead to inconsistent clinical outcomes. Further studies are required to determine the clinical consequences of this marked variation in extracapsular suture tensioning.

  5. Comparative evaluation of bond strength of three contemporary self-etch adhesives: An ex vivo study

    Directory of Open Access Journals (Sweden)

    Vineeta Nikhil

    2011-01-01

    Full Text Available Aim: This study evaluated the effect of 2-hydroxymethyl methacrylate (HEMA and the type of solvent on the tensile bond strength of the following three self-etch adhesives: Adper easy one (HEMA-rich adhesive which contained ethanol, G-Bond (HEMA-free adhesive which contained acetone, and Xeno V (HEMA-free adhesive which contained butanol as a solvent. Material and Methods: Intact mandibular molars were mounted in self-cured resin and the occlusal surfaces were ground with # 600 SiC paper. Adhesives were applied on the prepared dentinal surfaces and the resin composite was condensed in the split brass mold (5 × 3 mm placed over the adhesive surface. The specimens were stored in normal saline and placed in incubator at 37°C. After 24 hours, the specimens were tested in tensile mode at a crosshead speed of 1 mm/min. Statistical analysis was done using One way ANOVA and Tukey′s HSD test. Results: The mean bond strengths of Adper easy one, G-Bond, and Xeno V were 12.41 MPa, 10.09 MPa, and 8.67 MPa, respectively. Conclusions: Comparison of contemporary adhesives in this ex vivo study revealed that the ethanol-based HEMA-rich self-etch adhesive is better than HEMA-free self-etch adhesive that contained acetone and butanol as the solvents, when compared in terms of bond strength.

  6. Comparative evaluation of bond strength of three contemporary self-etch adhesives: An ex vivo study.

    Science.gov (United States)

    Nikhil, Vineeta; Singh, Vijay; Chaudhry, Suruchi

    2011-04-01

    This study evaluated the effect of 2-hydroxymethyl methacrylate (HEMA) and the type of solvent on the tensile bond strength of the following three self-etch adhesives: Adper easy one (HEMA-rich adhesive) which contained ethanol, G-Bond (HEMA-free adhesive) which contained acetone, and Xeno V (HEMA-free adhesive) which contained butanol as a solvent. Intact mandibular molars were mounted in self-cured resin and the occlusal surfaces were ground with # 600 SiC paper. Adhesives were applied on the prepared dentinal surfaces and the resin composite was condensed in the split brass mold (5 × 3 mm) placed over the adhesive surface. The specimens were stored in normal saline and placed in incubator at 37°C. After 24 hours, the specimens were tested in tensile mode at a crosshead speed of 1 mm/min. Statistical analysis was done using One way ANOVA and Tukey's HSD test. The mean bond strengths of Adper easy one, G-Bond, and Xeno V were 12.41 MPa, 10.09 MPa, and 8.67 MPa, respectively. Comparison of contemporary adhesives in this ex vivo study revealed that the ethanol-based HEMA-rich self-etch adhesive is better than HEMA-free self-etch adhesive that contained acetone and butanol as the solvents, when compared in terms of bond strength.

  7. Loxosceles gaucho venom-induced acute kidney injury--in vivo and in vitro studies.

    Directory of Open Access Journals (Sweden)

    Rui V Lucato

    Full Text Available BACKGROUND: Accidents caused by Loxosceles spider may cause severe systemic reactions, including acute kidney injury (AKI. There are few experimental studies assessing Loxosceles venom effects on kidney function in vivo. METHODOLOGY/PRINCIPAL FINDINGS: In order to test Loxosceles gaucho venom (LV nephrotoxicity and to assess some of the possible mechanisms of renal injury, rats were studied up to 60 minutes after LV 0.24 mg/kg or saline IV injection (control. LV caused a sharp and significant drop in glomerular filtration rate, renal blood flow and urinary output and increased renal vascular resistance, without changing blood pressure. Venom infusion increased significantly serum creatine kinase and aspartate aminotransferase. In the LV group renal histology analysis found acute epithelial tubular cells degenerative changes, presence of cell debris and detached epithelial cells in tubular lumen without glomerular or vascular changes. Immunohistochemistry disclosed renal deposition of myoglobin and hemoglobin. LV did not cause injury to a suspension of fresh proximal tubules isolated from rats. CONCLUSIONS/SIGNIFICANCE: Loxosceles gaucho venom injection caused early AKI, which occurred without blood pressure variation. Changes in glomerular function occurred likely due to renal vasoconstriction and rhabdomyolysis. Direct nephrotoxicity could not be demonstrated in vitro. The development of a consistent model of Loxosceles venom-induced AKI and a better understanding of the mechanisms involved in the renal injury may allow more efficient ways to prevent or attenuate the systemic injury after Loxosceles bite.

  8. Pulse release of doxazosin from hydroxyethylcellulose compression coated tablet: mechanistic and in vivo study.

    Science.gov (United States)

    Biswas, Nikhil; Guha, Arijit; Sahoo, Ranjan Kumar; Kuotsu, Ketousetuo

    2015-01-01

    Chronotherapeutically programmed hydroxyethylcellulose (HEC) based compression coated doxazosin tablets were prepared and the influence of disintegrants croscarmellose sodium, L-hydroxypropylcellulose (L-HPC), gellan gum on drug release and in vivo performance were investigated. Infrared spectroscopy and differential scanning calorimetric studies did not indicate any excipient incompatibility in the tablets. The disintegrants induced a continuous water influx resulting in a rapid expansion of the membrane. The subsequent formation of fractures into the coats leads to a fast drug release after an initial lag time. Release rates indicated that croscarmellose sodium and L-HPC were directly proportional to their concentration in the formulations. In vitro optimized croscarmellose sodium-HEC matrix showed significantly faster (p 0.99). The mechanism involved in release was anomalous transport and super case II transport with matrix swelling. The pulsatile tablets showed no changes either in physicochemical appearance, drug content or in dissolution pattern during its accelerated stability studies. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Ozone therapy as an adjuvant for endondontic protocols: microbiological – ex vivo study and citotoxicity analyses

    Science.gov (United States)

    NOGALES, Carlos Goes; FERREIRA, Marina Beloti; MONTEMOR, Antonio Fernando; RODRIGUES, Maria Filomena de Andrade; Lage-MARQUES, José Luiz; ANTONIAZZI, João Humberto

    2016-01-01

    ABSTRACT Objectives This study evaluated the antimicrobial efficacy of ozone therapy in teeth contaminated with Pseudomonas aeruginosa, Enterococcus faecalis, and Staphylococcus aureus using a mono-species biofilm model. Parallel to this, the study aimed to evaluate the cytotoxicity of ozone for human gingival fibroblasts. Material and Methods: One hundred and eighty single-root teeth were contaminated with a mono-species biofilm of Enterococcus faecalis, Pseudomonas aeruginosa, and Staphylococcus aureus. Groups were formed: Group I – control; Group II – standard protocol; Group III – standard protocol + ozone gas at 40 µg/mL; and Group IV – standard protocol + aqueous ozone at 8 µg/mL. In parallel, human gingival fibroblasts were submitted to the MTT test. Cells were plated, then ozone was applied as follows: Group I (control) – broth medium; Group II – aqueous ozone at 2 µg/mL; Group III – aqueous ozone at 5 µg/mL; and Group IV – aqueous ozone at 8 µg/mL. Data were submitted to the Kruskal Wallis test and Bonferroni post hoc analyses to assess microbiology and cytotoxicity, respectively (pozone therapy improved the decontamination of the root canal ex vivo. Ozone was toxic to the cells on first contact, but cell viability was recovered. Thus, these findings suggest that ozone might be useful to improve root canal results. PMID:28076466

  10. In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA

    Directory of Open Access Journals (Sweden)

    Saiful Azmi Johari

    2017-01-01

    Full Text Available Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50 value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50 of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.

  11. In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA

    Science.gov (United States)

    Mohtar, Mastura; Syed Mohamad, Sharifah Aminah; Mohammat, Mohd Fazli; Sahdan, Rohana; Mohamed, Azman; Mohamad Ridhwan, Mohamad Jemain

    2017-01-01

    Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates. PMID:28536702

  12. A split luciferase complementation assay for studying in vivo protein-protein interactions in filamentous ascomycetes.

    Science.gov (United States)

    Kim, Hee-Kyoung; Cho, Eun Ji; Jo, Seong mi; Sung, Bo Reum; Lee, Seunghoon; Yun, Sung-Hwan

    2012-06-01

    Protein-protein interactions play important roles in controlling many cellular events. To date, several techniques have been developed for detection of protein-protein interactions in living cells, among which split luciferase complementation has been applied in animal and plant cells. Here, we examined whether the split luciferase assay could be used in filamentous ascomycetes, such as Gibberella zeae and Cochliobolus heterostrophus. The coding sequences of two strongly interacting proteins (the F-box protein, FBP1, and its partner SKP1) in G. zeae, under the control of the cryparin promoter from Cryphonectria parasitica, were translationally fused to the C- and N-terminal fragments of firefly luciferase (luc), respectively. Each fusion product inserted into a fungal transforming vector carrying the gene for resistance to either geneticin or hygromycin B, was transformed into both fungi. We detected complementation of split luciferase proteins driven by interaction of the two fungal proteins with a high luminescence intensity-to-background ratio only in the fungal transformants expressing both N-luc and C-luc fusion constructs. Using this system, we also confirmed a novel protein interaction between transcription factors, GzMCM1 and FST12 in G. zeae, which could hardly be proven by the yeast two-hybrid method. This is the first study demonstrating that monitoring of split luciferase complementation is a sensitive and efficient method of studying in vivo protein-protein interactions in filamentous ascomycetes.

  13. In vitro and in vivo pathogenicity studies of Pasteurella multocida strains harbouring different ompA.

    Science.gov (United States)

    Katoch, Shailja; Sharma, Mandeep; Patil, R D; Kumar, Sandeep; Verma, Subhash

    2014-09-01

    Pasteurella multocida is a pathogenic, Gram-negative bacterium that is commonly found as normal flora in nasopharynx of variety of wild and domestic animals. Numerous virulence factors have been described for P. multocida isolates which include adherence and colonization factors, iron-regulated and acquisition proteins, extracellular enzymes such as neuraminidase, lipopolysaccharide (LPS), capsule and a variety of outer membrane proteins (Omp). OmpA has a significant role in stabilizing the cell envelope structure by providing physical linkage between the outer membrane & peptidoglycan. It has been shown to mediate P. multocida -host cells interaction via heparin and/or fibronectin binding and therefore act as an important invasive molecule which could determine the final outcome of initial infection. Comparative nucleotide sequence analysis of ompA gene of P. multocida has revealed that despite extensive genetic diversity in ompA of P. multocida, most sequences could be classified into two major allele classes namely ompA allele (I) and allele (II). The P. multocida recovered from nasal cavity of bovine and belonging to two ompA classes were tested for their differential virulence. In vitro pathogenicity studies on Madin Darby Bovine Kidney (MDBK) cell line employing adhesion and invasion assays indicated that P. multocida strain with ompA (I) is more invasive than P. multocida strain with ompA (II). In vivo studies in mice further reiterated that the isolates harbouring ompA(I) were comparatively more virulent to isolates harbouring ompA (II).

  14. In Vivo Human Skin Penetration Study of Sunscreens by Confocal Raman Spectroscopy.

    Science.gov (United States)

    Tippavajhala, Vamshi Krishna; de Oliveira Mendes, Thiago; Martin, Airton Abrahão

    2017-10-05

    This research work mainly deals with the application of confocal Raman spectroscopic technique to study in vivo human skin penetration of sunscreen products, as there are a lot of controversies associated with their skin penetration. Healthy human volunteers were tested for penetration of two commercial sunscreen products into their volar forearm skin for a period of 2 h. Measurements were taken before and after application of these sunscreen products. All the confocal Raman spectra were pre-processed and then subjected to multivariate two-dimensional principal component analysis and classical least squares analysis to determine the skin penetration of these sunscreens in comparison to the "sunscreen product spectrum" which was considered as the control. Score plots of principal component analysis of confocal Raman spectra indicated clear separation between the spectra before and after application of sunscreen products. Loading plots showed the maximum differences in the spectral region from 1590 to 1626 cm(-1) where the characteristic peak of the pure sunscreen products was observed. Classical least squares analysis has shown a significant penetration to a depth of 10 μm in the volar forearm skin of healthy human volunteers for both these sunscreen products. The results confirm that the penetration of these tested sunscreen products was restricted to stratum corneum and also prove that confocal Raman spectroscopy is a simple, fast, nondestructive, and noninvasive semi-quantitative analytical technique for these studies.

  15. Multicomponent solid forms of felodipine: preparation, characterisation, physicochemical and in-vivo studies.

    Science.gov (United States)

    Chadha, Renu; Sharma, Mohit; Haneef, Jamshed

    2017-03-01

    This study aimed to improve biopharmaceutical parameters of the poorly soluble antihypertensive drug, felodipine, by preparing multicomponent solid forms using three coformers, viz. imidazole, nicotinamide and malonic acid. The multicomponent solid forms were prepared by mechanochemical synthesis and characterised by various analytical techniques. These solid forms were further assessed for their physicochemical parameters. Pharmacokinetic and in-vivo antihypertensive activity was performed in rats. Felodipine (FEL) was found to be cocrystallised with imidazole (FEL-IM) while it formed eutectic with nicotinamide (FEL-NCT) and malonic acid (FEL-MA). Cocrystal was sustained by NH…N and NH….O hydrogen-bonded network. Solubility and intrinsic dissolution studies in 0.1 N HCl (pH 1.2) revealed that eutectics exhibited higher solubility and release rate than cocrystal vis-a-vis pure drug and were found to be stable under accelerated storage condition. Significant enhancement of bioavailability was observed in eutectics (3.5- to twofold) and cocrystal (1.3-fold) compared with the pure drug. Antihypertensive activity of new solid forms in an animal model showed a marked decrease in systolic blood pressure. Mechanochemical approach was successful to prepare multicomponent solid forms that have the potential to improve biopharmaceutical parameters of the poorly soluble drug, FEL. © 2017 Royal Pharmaceutical Society.

  16. Morpho-anatomical study of Stevia rebaudiana roots grown in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Rafael V. Reis

    Full Text Available ABSTRACT Stevia rebaudiana (Bertoni Bertoni, Asteraceae, is used as a food additive because its leaves are a source of steviol glycosides. There are examples of tissue culture based on micropropagation and phytochemical production of S. rebaudiana leaves but there are few studies on adventitious root culture of S. rebaudiana. More than 90% of the plants used in industry are harvested indiscriminately. In order to overcome this situation, the development of methodologies that employ biotechnology, such as root culture, provides suitable alternatives for the sustainable use of plants. The aim of this study was to compare morpho-anatomical transverse sections of S. rebaudiana roots grown in vitro and in vivo. The in vitro system used to maintain root cultures consisted of a gyratory shaker under dark and light conditions and a roller bottle system. Transverse sections of S. rebaudiana roots grown in vitro were structurally and morphologically different when compared to the control plant; roots artificially maintained in culture media can have their development affected by the degree of media aeration, sugar concentration, and light. GC–MS and TLC confirmed that S. rebaudiana roots grown in vitro have the ability to produce metabolites, which can be similar to those produced by wild plants.

  17. An In Vivo Study of Self-Regulated Study Sequencing in Introductory Psychology Courses

    Science.gov (United States)

    de Leeuw, Joshua R.; Motz, Benjamin A.; Goldstone, Robert L.

    2016-01-01

    Study sequence can have a profound influence on learning. In this study we investigated how students decide to sequence their study in a naturalistic context and whether their choices result in improved learning. In the study reported here, 2061 undergraduate students enrolled in an Introductory Psychology course completed an online homework tutorial on measures of central tendency, a topic relevant to an exam that counted towards their grades. One group of students was enabled to choose their own study sequence during the tutorial (Self-Regulated group), while the other group of students studied the same materials in sequences chosen by other students (Yoked group). Students who chose their sequence of study showed a clear tendency to block their study by concept, and this tendency was positively associated with subsequent exam performance. In the Yoked group, study sequence had no effect on exam performance. These results suggest that despite findings that blocked study is maladaptive when assigned by an experimenter, it may actually be adaptive when chosen by the learner in a naturalistic context. PMID:27003164

  18. The scientific bases of radiation protection; Les fondements scientifiques de la radioprotection

    Energy Technology Data Exchange (ETDEWEB)

    Cosset, J.M. [Institut Curie, 75 - Paris (France); Boissiere, A.; Eschenbrenner, A. [Groupe de Physique des Solides, Universite Paris-6-7, CNRS UMR 75-88, 75 - Paris (France)] [and others

    2003-07-01

    Six articles constitute this chapter about radiation protection. Double strand breaks induced by K events on DNA, effects of dose rate on double strand breaks make the object of two first articles. The study of speciation can give information in the field of internal dosimetry, it is the subject of the third article. The fourth article relates the work about the distribution profiles of iodine 127 and iodine 129 among thyroid of young rats born of mother deprived in steady iodine but contaminated by iodine 129 in a period varying from 489 hours (new born) to 21 days (adolescents) after the birth. The fifth article studies the interest of the expansion in vivo of haematopoietic cells for the treatment of radioinduced aplastic anemia. The last text is devoted to the genotoxic effects of radio frequencies. (N.C.)

  19. Perfusion estimation using contrast-enhanced 3-dimensional subharmonic ultrasound imaging: an in vivo study.

    Science.gov (United States)

    Sridharan, Anush; Eisenbrey, John R; Liu, Ji-Bin; Machado, Priscilla; Halldorsdottir, Valgerdur G; Dave, Jaydev K; Zhao, Hongjia; He, Yu; Park, Suhyun; Dianis, Scott; Wallace, Kirk; Thomenius, Kai E; Forsberg, Flemming

    2013-09-01

    and improved visualization of the UCA flow. Microsphere perfusion data were available for 4 canines (1 was excluded because of an error with the reference blood sample) and showed a mean (SD) perfusion of 9.30 (6.60) and 5.15 (3.42) mL/min per gram before and after the ligation, respectively. The reference standard showed significant correlation with the overall 3D HI perfusion estimates (r = 0.38; P = 0.007), but it correlated more strongly with 3D SHI (r = 0.62; P < 0.001). In addition, these results showed an improvement over the quasi-2D HI and SHI perfusion estimates (r = -0.05 and r = 0.14) and 2D SHI perfusion estimates previously reported by our group (r = 0.57). In this preliminary study, 3D contrast-enhanced nonlinear ultrasound was able to quantify perfusion in vivo. Three-dimensional SHI resulted in better overall agreement with the reference standard than 3D HI did and was superior to previously reported 2D SHI results. Three-dimensional SHI outperforms the other methods for estimating blood perfusion because of the improved visualization of the complete perfused vascular networks.

  20. Perfusion estimation using contrast enhanced three-dimensional subharmonic ultrasound imaging: an in vivo study

    Science.gov (United States)

    Sridharan, Anush; Eisenbrey, John R.; Liu, Ji-Bin; Machado, Priscilla; Halldorsdottir, Valgerdur G.; Dave, Jaydev K.; Zhao, Hongjia; He, Yu; Park, Suhyun; Dianis, Scott; Wallace, Kirk; Thomenius, Kai E.; Forsberg, Flemming

    2013-01-01

    suppression and improved visualization of UCA flow. Microsphere perfusion data were available for 4 canines (1 was excluded because of an error with the reference blood sample) and showed an average perfusion of 9.30 ± 6.60 and 5.15 ± 3.42 mL/min/g pre and post ligation, respectively. The reference standard showed significant correlation with overall 3D HI perfusion estimates (r=0.38; P=0.007), but correlated more strongly with 3D SHI (r=0.62; P<0.001). Additionally, these results showed an improvement over the quasi-2D HI and SHI perfusion estimates (r=−0.05 and r=0.14) and 2D SHI perfusion estimates previously reported by our group (r=0.57) Conclusions In this preliminary study, 3D contrast-enhanced nonlinear ultrasound was able to quantify perfusion in vivo. 3D SHI resulted in better overall agreement with the reference standard than 3D HI and was superior to previously reported 2D SHI results. 3D SHI outperforms the other methods for estimating blood perfusion, due to the improved visualization of the complete perfused vascular networks. PMID:23695085

  1. In vivo Biotinylation Based Method for the Study of Protein-Protein Proximity in Eukaryotic Cells

    Directory of Open Access Journals (Sweden)

    Arman Kulyyassov

    2014-01-01

    Full Text Available Introduction: The spatiotemporal order plays an important role in cell functioning and is affected in many pathologies such as cancer and neurodegenerative diseases. One of the ultimate goals of molecular biology is reconstruction of the spatiotemporal structure of a living cell at the molecular level. This task includes determination of proximities between different molecular components in the cell and monitoring their time- and physiological state-dependent changes. In many cases, proximity between macromolecules arises due to their interactions; however, the contribution of dynamic self-organization in generation of spatiotemporal order is emerging as another viable possibility. Specifically, in proteomics, this implies that the detection of protein-protein proximity is a more general task than gaining information about physical interactions between proteins, as it could detail aspects of spatial order in vivo that are challenging to reconstitute in binding experiments in vitro. Methods: In this work, we have developed a method of monitoring protein-protein proximity in vivo. For this purpose, the BirA was fused to one of the interaction partners, whereas the BAP was modified to make the detection of its biotinylation possible by mass spectrometry. Results: Using several experimental systems, we showed that the biotinylation is interaction dependent. In addition, we demonstrated that BAP domains with different primary amino acid structures and thus with different molecular weights can be used in the same experiment, providing the possibility of multiplexing. Alternatively to the changes in primary amino acid structure, the stable isotope format can also be used, providing another way to perform multiplexing experiments. Finally, we also demonstrated that our system could help to overcome another limitation of current methodologies to detect protein-protein proximity. For example, one can follow the state of a protein of interest at a defined

  2. Manganese superoxide dismutase interacts with a large scale of cellular and mitochondrial proteins in low dose radiation-induced adaptive radioprotection

    Science.gov (United States)

    Eldridge, Angela; Fan, Ming; Woloschak, Gayle; Grdina, David J.; Chromy, Brett A.; Li, Jian Jian

    2012-01-01

    Cellular adaptive response to certain low level genotoxic stresses including the exposure to low dose ionizing radiation (LDIR) shows promise as a tool to enhance radioprotection in normal cells but not in tumor cells. Manganese superoxide dismutase (MnSOD), a fundamental mitochondrial antioxidant in mammalian cells plays a key role in LDIR-induced adaptive response. In this study, we aim to elucidate the signaling network associated with the MnSOD-induced radiation protection. A MnSOD-interacting protein profile was established in LDIR-treated human skin cells. Human skin keratinocytes (HK18) were irradiated with a single dose LDIR (10 cGy x-ray) and the cell lysates were immunoprecipitated using α-MnSOD and applied to two different gel-based proteomics followed by mass spectrometry for protein identification. Analysis of the profiles of MnSOD interacting partners before and after LDIR detected different patterns of MnSOD protein-protein interactions in response to LDIR. Interestingly, many of the MnSOD interacting proteins are known to have functions related to mitochondrial regulations on cell metabolism, apoptosis and DNA repair. These results provide the evidence indicating that in addition to the enzymatic action detoxifying superoxide, the antioxidant MnSOD may function as a signaling regulator in stress induced adaptive protection through cell survival pathways. PMID:23000060

  3. The effects of substance p on tendinopathy are dose-dependent: an in vitro and in vivo model study.

    Science.gov (United States)

    Zhou, Y; Zhou, B; Tang, K

    2015-05-01

    Substance P (SP) is known to be involved in neuropathic pain, chronic inflammation, and tendinopathy. The present study evaluated the effects of different doses of SP on tendon-derived stem cells (TDSCs) in vitro and tendons in vivo. For the in vitro study, TDSCs cultured in growth medium with different concentrations of SP (negative control, 0.1 nM, and 1.0 nM). The effects of SP on TDSCs were examined with respect to their ability to proliferate and differentiate. For the in vivo study, we injected different doses of SP (saline control, 0.5 nmol, and 5.0 nmol) into rat patella tendons to investigate the effects of SP on tendons. Low and high doses SP significantly enhanced the proliferation ability of TDSCs. Low-dose of SP induced the expression of tenocyte-related genes; however, high-dose of SP induced the expression of non-tenocyte genes, which was evident by the high expression of PPARγ and collagen type II. In the in vivo study, only high-doses of SP (5.0 nmol) induced the tendinosis-like changes in the patella tendon injection model. Low doses of SP (0.5 nmol) enhanced the tenogenesis compared with saline injection and the high-dose SP group. SP enhances the proliferation of TDSCs in vitro and the effects of SP on tendinopathy are dose-dependent in vivo.

  4. Visualization studies of human skin in vitro/in vivo under the influence of an electrical field

    NARCIS (Netherlands)

    Fatouros, N.E.; Groenink, H.W.M.; Graaff, de A.M.; Aelst, van A.C.; Koerten, H.K.; Bouwstra, J.A.

    2006-01-01

    The aim of this study was to investigate the local changes in the ultrastructure of human skin after iontophoresis, using cryo-scanning, transmission and freeze fracture electron microscopy in human skin in vitro and in vivo. Human dermatomed skin was subjected to passive diffusion for 6 hours

  5. Initial studies on the variations of load-displacement curves of in vivo human healthy heel pads

    DEFF Research Database (Denmark)

    Matteoli, Sara; Wilhjelm, Jens E.; Virga, Antonio

    2011-01-01

    The aim of this study was to quantify on the measurement variation of in vivo load-displacement curves by using a group of human healthy heel pads. The recordings were done with a compression device measuring force and displacement. Twenty three heel pads, one from each of 23 subjects aged 20...

  6. Influence of hemodilution of plasma proteins on erythrocyte aggregability : An in vivo study in patients undergoing cardiopulmonary bypass

    NARCIS (Netherlands)

    Gu, YJ; Graaff, R; de Hoog, E; Veeger, NJGM; Panday, G; Boonstra, PW; van Oeveren, W

    2005-01-01

    Erythrocyte aggregation is known to be affected by a number of factors including the concentration of various plasma proteins. This study was performed to examine the in vivo effect of hemodilution of plasma proteins on erythrocyte aggregation in patients undergoing cardiopulmonary bypass (CPB)

  7. Inhibition of early biofilm formation by glass-ionomer incorporated with chlorhexidine in vivo: a pilot study.

    NARCIS (Netherlands)

    Du, X.; Huang, X.; Huang, C.; Frencken, J.E.F.M.; Yang, T.

    2012-01-01

    BACKGROUND: This pilot study investigated the antibiofilm effects of glass-ionomer cements (GICs) and resin-modified glass-ionomer cements (RMGICs) incorporated with chlorhexidine (CHX) in vivo. METHODS: Experimental GICs and RMGICs containing 2% CHX were obtained by mixing CHX with the powder of

  8. Effects of Low-Level Laser Irradiation on the Pathogenicity of Candida albicans: In Vitro and in Vivo Study

    NARCIS (Netherlands)

    Seyedmousavi Tasieh, S.; Hashemi, S.J.; Rezaie, S.; Fateh, M.; Djavid, G.E.; Zibafar, E.; Morsali, F.; Zand, N.; Alinaghizadeh, M.; Ataie-Fashtami, L.

    2014-01-01

    Abstract Objective: The purpose of this study was to evaluate the effects of low-level laser irradiation (LLLI) on the in vitro growth characteristics and in vivo pathogenicity of Candida albicans in a murine model in the absence of a photosensitizer. Background data: C. albicans is an opportunistic

  9. In vivo pharmacological study on the effectiveness of available polyclonal antivenom against Hemiscorpius lepturus venom

    Directory of Open Access Journals (Sweden)

    A Jalali

    2011-01-01

    Full Text Available The available Razi Institute antivenom is still, empirically, used by intramuscular (IM administration for the treatment of scorpion stings in humans by six medically dangerous species including Hemiscorpius lepturus (H. lepturus. The aim of this study was to assess the neutralizing ability and effectiveness of the antivenom in inhibiting hemoglobinuria, biochemical changes, increased microalbuminuria and urinary lactate dehydrogenase (LDH following H. lepturus sting. Simultaneous intramuscular administration of 10 μL and 100 μL of antivenom, after 24 hours, had no significant preventive effect on the extent and degree of hemoglobinuria or proteinuria produced in venom-treated rats. After IM administration of antivenom, no significant changes in decreased red blood cell (RBC count and hemoglobin were observed. Immediate intramuscular administration of 10 μL of antivenom had no significant effects on both LDH and microalbuminuria. The present findings did not present correlation with clinical signs. Therefore, to fully assess the efficacy of the available antivenom and make appropriate recommendations, more in vivo or in vitro investigations including antigen-antibody interaction, enzymatic analysis and route-dependent administration are required.

  10. Antidiabetic Properties of Azardiracta indica and Bougainvillea spectabilis: In Vivo Studies in Murine Diabetes Model

    Directory of Open Access Journals (Sweden)

    Menakshi Bhat

    2011-01-01

    Full Text Available Diabetes mellitus is a metabolic syndrome characterized by an increase in the blood glucose level. Treatment of diabetes is complicated due to multifactorial nature of the disease. Azadirachta indica Adr. Juss and Bougainvillea spectabilis are reported to have medicinal values including antidiabetic properties. In the present study using in vivo diabetic murine model, A. indica and B. spectabilis chloroform, methanolic and aqueous extracts were investigated for the biochemical parameters important for controlling diabetes. It was found that A. indica chloroform extract and B. spectabilis aqueous, methanolic extracts showed a good oral glucose tolerance and significantly reduced the intestinal glucosidase activity. Interestingly, A. indica chloroform and B. spectabilis aqueous extracts showed significant increase in glucose-6-phosphate dehydrogenase activity and hepatic, skeletal muscle glycogen content after 21 days of treatment. In immunohistochemical analysis, we observed a regeneration of insulin-producing cells and corresponding increase in the plasma insulin and c-peptide levels with the treatment of A. indica chloroform and B. spectabilis aqueous, methanolic extracts. Analyzing the results, it is clear that A. indica chloroform and B. spectabilis aqueous extracts are good candidates for developing new neutraceuticals treatment for diabetes.

  11. Methyglyoxal administration induces modification of hemoglobin in experimental rats: An in vivo study.

    Science.gov (United States)

    Banerjee, Sauradipta

    2017-02-01

    Methylglyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. In the present study, the effect of methylglyoxal on experimental rat hemoglobin in vivo has been investigated with respect to structural alterations and amino acid modifications, after external administration of the α-dicarbonyl compound in animals. Different techniques, mostly biophysical, were used to characterize and compare methylglyoxal-treated rat hemoglobin with that of control, untreated rat hemoglobin. In comparison with methylglyoxal-untreated, control rat hemoglobin, hemoglobin of methylglyoxal-treated rats (32mg/kgbodywt.dose) exhibited slightly decreased absorbance around 280nm, reduced intrinsic fluorescence and lower surface hydrophobicity. The secondary structures of hemoglobin of control and methylglyoxal-treated rats were more or less identical with the latter exhibiting slightly increased α-helicity compared to the former. Compared to control rat hemoglobin, methylglyoxal-treated rat hemoglobin showed higher stability. Peptide mass fingerprinting analysis revealed modifications of Arg-31α, Arg-92α and Arg-104β of methylglyoxal-treated rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to be associated with the observed structural alterations of the heme protein. Considering the increased level of methylglyoxal in diabetes mellitus as well as its high reactivity, AGE-induced modifications may have physiological significance. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Clinical study of noninvasive in vivo melanoma and nonmelanoma skin cancers using multimodal spectral diagnosis

    Science.gov (United States)

    Lim, Liang; Nichols, Brandon; Migden, Michael R.; Rajaram, Narasimhan; Reichenberg, Jason S.; Markey, Mia K.; Ross, Merrick I.; Tunnell, James W.

    2014-11-01

    The goal of this study was to determine the diagnostic capability of a multimodal spectral diagnosis (SD) for in vivo noninvasive disease diagnosis of melanoma and nonmelanoma skin cancers. We acquired reflectance, fluorescence, and Raman spectra from 137 lesions in 76 patients using custom-built optical fiber-based clinical systems. Biopsies of lesions were classified using standard histopathology as malignant melanoma (MM), nonmelanoma pigmented lesion (PL), basal cell carcinoma (BCC), actinic keratosis (AK), and squamous cell carcinoma (SCC). Spectral data were analyzed using principal component analysis. Using multiple diagnostically relevant principal components, we built leave-one-out logistic regression classifiers. Classification results were compared with histopathology of the lesion. Sensitivity/specificity for classifying MM versus PL (12 versus 17 lesions) was 100%;/100%;, for SCC and BCC versus AK (57 versus 14 lesions) was 95%;/71%, and for AK and SCC and BCC versus normal skin (71 versus 71 lesions) was 90%/85%. The best classification for nonmelanoma skin cancers required multiple modalities; however, the best melanoma classification occurred with Raman spectroscopy alone. The high diagnostic accuracy for classifying both melanoma and nonmelanoma skin cancer lesions demonstrates the potential for SD as a clinical diagnostic device.

  13. Enterococcus faecalis leakage of root canal sealers: an ex vivo study.

    Science.gov (United States)

    D'Ercole, S; Filippakos, A; De Toledo Leonardo, R; Pameijer, C H; Tripodi, D

    2012-01-01

    The aim of this ex vivo study was to evaluate bacterial penetration after filling root canals using 3 different techniques. Three experimental groups of 25 teeth each, obturated with lateral-warm-vertical condensation of gutta-percha, Microseal technique and EndoREZ system, respectively, were tested in a split chamber model system using Enterococcus faecalis and monitored for 180 days to determine bacterial penetration. A statistical analysis was performed using the Kaplan-Meier method. Median survival time was 25 days for Microseal system, 41 for lateral-warm-vertical condensation and 81 for EndoREZ®. Significant differences were demonstrated between Microseal and EndoREZ (p less than 0.001) and between Microseal and lateral-warm-vertical condensation technique (p less than 0.05). No statistically significant differences were observed between EndoREZ and lateral-warm-vertical condensation. After 180 days of assessment, 20 percent of the EndoREZ samples resisted bacterial penetration and furthermore, the EndoREZ system has the potential to be a filler system compatible with other currently used systems.

  14. Ex vivo feasibility study of endoscopic intraductal laser ablation of the breast.

    Science.gov (United States)

    de Boorder, Tjeerd; Waaijer, Laurien; van Diest, Paul J; Witkamp, Arjen J

    2017-10-09

    To determine the feasibility and safety of breast endoscopic thulium laser ablation for treatment of intraductal neoplasia. Ductoscopy is a minimally invasive endoscopic approach of the milk ducts of the breast via the nipple. Besides diagnosis in women with pathologic nipple discharge (PND), it allows non-invasive removal of intraductal lesions with a stalk like papillomas. Removal, however, is often incomplete and flat lesions cannot be targeted. We therefore developed laser ductoscopy. Dosimetry of laser ductoscopy was assessed in thirteen mastectomy specimens, applying power settings of 1-5 W with 100-1000 ms pulsed exposure to a 375-μm outer diameter thulium fiber laser. Subsequently histology was obtained from the breast tissue that was treated with the Thulium laser. Endoscopic view was maintained during ductoscopic laser ablation at 1-3 W. Increasing power to 4-5 W caused impaired vision due to shrinkage of the main duct around the ductoscope tip. Histology revealed localized ablation of the duct wall. We show for the first time that laser ductoscopy is technically feasible. The Thulium laser enables a superficial intraductal ablation and is a useful tool for intraductal interventions. An in vivo prospective study is needed to further demonstrate its potential. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Design studies related to an in vivo neutron activation analysis facility for measuring total body nitrogen.

    Science.gov (United States)

    Stamatelatos, I E; Chettle, D R; Green, S; Scott, M C

    1992-08-01

    Design studies relating to an in vivo prompt capture neutron activation analysis facility measuring total body nitrogen are presented. The basis of the design is a beryllium-graphite neutron collimator and reflector configuration for (alpha, n) type radionuclide neutron sources (238PuBe or 241AmBe), so as to reflect leaking, or out-scattered, neutrons towards the subject. This improves the ratio of thermal neutron flux to dose and the spatial distribution of thermal flux achieved with these sources, whilst retaining their advantage of long half-lives as compared to 252Cf based systems. The common problem of high count-rate at the detector, and therefore high nitrogen region of interest background due to pile-up, is decreased by using a set of smaller (5.1 cm diameter x 10.2 cm long) NaI(Tl) detectors instead of large ones. The facility described presents a relative error of nitrogen measurement of 3.6% and a nitrogen to background ratio of 2.3 for 0.45 mSv skin dose (assuming ten 5.1 cm x 10.2 cm NaI(Tl) detectors).

  16. Design studies related to an in vivo neutron activation analysis facility for measuring total body nitrogen

    Energy Technology Data Exchange (ETDEWEB)

    Stamatelatos, I.E.M.; Chettle, D.R.; Green, S.; Scott, M.C. (Birmingham Univ. (United Kingdom). School of Physics and Space Research)

    1992-08-01

    Design studies relating to an in vivo prompt capture neutron activation analysis facility measuring total body nitrogen are presented. The basis of the design is a beryllium-graphite neutron collimator and reflector configuration for ({alpha}, n) type radionuclide neutron sources ({sup 238}PuBe or {sup 241}AmBe), so as to reflect leaking, or out-scattered, neutrons towards the subject. This improves the ratio of thermal neutron flux to dose and the spatial distribution of thermal flux achieved with these sources, whilst retaining their advantage of long half-lives as compared to {sup 252}Cf based systems. The common problem of high count-rate at the detector, and therefore high nitrogen region of interest background due to pile-up, is decreased by using a set of smaller (5.1 cm diameter x 10.2 cm long) NaI(Tl) detectors instead of large ones. The facility described presents a relative error of nitrogen measurement of 3.6% and a nitrogen to background ratio of 2.3 for 0.45 mSv skin dose (assuming ten 5.1 cm x 10.2 cm NaI(Tl) detectors). (author).

  17. Estrogenic activity of zinc pyrithione: an in vivo and in vitro study.

    Science.gov (United States)

    Yoon, Kyung Sik; Youn, Namhee; Gu, Hyungyung; Kwack, Seung Jun

    2017-01-01

    Zinc pyrithione (ZP) is commonly used to prevent dandruff and seborrheic dermatitis. Many consumers are exposed daily to high doses of ZP, causing serious concerns about its toxicity. The reproductive and developmental toxicities were previously reported in pregnant rats. However, the estrogenic activity of ZP at varying degrees of exposure has been rarely studied. Thus, we performed an uterotrophic assay, E-screen assay, and gene expression profiling to assess the estrogenic activity of ZP. For the uterotrophic assay, ZP (2, 10, or 50 mg/kg/d) was subcutaneously administered to ovariectomized rats every day for three days. Uteri were extracted 24 hours after the last dose. Then, wet and blotted uterine weights were measured. For the E-screen essay, MCF-7 cells (a breast cancer cell line) were exposed to 10(-9) to 10(-6) M of ZP, and cell proliferation was then measured. For the gene expression analysis, changes of gene expression levels in uterine samples taken for the uterotrophic assay were analyzed. In the uterotrophic assay, the concentration of ZP had no significant effect on uterine weight. In the E-screen assay, ZP at any concentration showed no significant increase in MCF-7 cell proliferation, compared to the control group. However, 10(-6) M of ZP significantly reduced cell viability. The changes in gene expression slightly differed between the ZP and control groups. The in vivo and in vitro assays, together with gene expression analysis, demonstrated that ZP showed no significant estrogenic activity.

  18. An ex vivo study of nitric oxide efflux from human erythrocytes in both genders.

    Science.gov (United States)

    Duarte, Catarina; Napoleão, Patrícia; Freitas, Teresa; Saldanha, Carlota

    2016-01-01

    Acetylcholinesterase (AChE) is located on outer surface of erythrocyte membrane. Gender-related differences in erythrocyte AChE enzyme activity had been verified in young adults. It is also known that binding of acetylcholine (ACh) with AChE on erythrocyte membrane initiates a signal transduction mechanism that stimulates nitric oxide (NO) efflux. This ex vivo study was done to compare the amount of NO efflux obtained from erythrocytes of healthy donors in males and females. We included 66 gender age-matched healthy donors (40-60 years old). We performed quantification of erythrocyte NO efflux from erythrocytes and of the membrane AChE enzyme activity. There are no significant differences in NO efflux from erythrocytes between men and women. Regarding AChE enzyme activity values, in this range of age, no differences between genders were obtained. However, the values of AChE enzyme activity in the third quartile of NO efflux values were significantly higher (p gender. For the same range of values of NO efflux from erythrocytes, in both gender, it was verified higher values of AChE enzyme activity in women.

  19. A new Fe-Mn-Si alloplastic biomaterial as bone grafting material: In vivo study

    Science.gov (United States)

    Fântânariu, Mircea; Trincă, Lucia Carmen; Solcan, Carmen; Trofin, Alina; Strungaru, Ştefan; Şindilar, Eusebiu Viorel; Plăvan, Gabriel; Stanciu, Sergiu

    2015-10-01

    Designing substrates having suitable mechanical properties and targeted degradation behavior is the key's development of bio-materials for medical application. In orthopedics, graft material may be used to fill bony defects or to promote bone formation in osseous defects created by trauma or surgical intervention. Incorporation of Si may increase the bioactivity of implant locally, both by enhancing interactions at the graft-host interface and by having a potential endocrine like effect on osteoblasts. A Fe-Mn-Si alloy was obtained as alloplastic graft materials for bone implants that need long recovery time period. The surface morphology of the resulted specimens was investigated using scanning electrons microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffractions (X'Pert equipment) or X-ray dispersive energy analyze (Bruker EDS equipment). This study objective was to evaluate in vivo the mechanisms of degradation and the effects of its implantation over the main metabolic organs. Biochemical, histological, plain X radiography and computed tomography investigations showed good compatibility of the subcutaneous implants in the rat organism. The implantation of the Fe-Mn-Si alloy, in critical size bone (tibiae) defect rat model, did not induced adverse biological reactions and provided temporary mechanical support to the affected bone area. The biodegradation products were hydroxides layers which adhered to the substrate surface. Fe-Mn-Si alloy assured the mechanical integrity in rat tibiae defects during bone regeneration.

  20. The Natural Fungal Metabolite Beauvericin Exerts Anticancer Activity In Vivo: A Pre-Clinical Pilot Study.

    Science.gov (United States)

    Heilos, Daniela; Rodríguez-Carrasco, Yelko; Englinger, Bernhard; Timelthaler, Gerald; van Schoonhoven, Sushilla; Sulyok, Michael; Boecker, Simon; Süssmuth, Roderich D; Heffeter, Petra; Lemmens-Gruber, Rosa; Dornetshuber-Fleiss, Rita; Berger, Walter

    2017-08-24

    Recently, in vitro anti-cancer properties of beauvericin, a fungal metabolite were shown in various cancer cell lines. In this study, we assessed the specificity of this effect by comparing beauvericin cytotoxicity in malignant versus non-malignant cells. Moreover, we tested in vivo anticancer effects of beauvericin by treating BALB/c and CB-17/SCID mice bearing murine CT-26 or human KB-3-1-grafted tumors, respectively. Tumor size and weight were measured and histological sections were evaluated by Ki-67 and H/E staining as well as TdT-mediated-dUTP-nick-end (TUNEL) labeling. Beauvericin levels were determined in various tissues and body fluids by LC-MS/MS. In addition to a more pronounced activity against malignant cells, we detected decreased tumor volumes and weights in beauvericin-treated mice compared to controls in both the allo- and the xenograft model without any adverse effects. No significant differences were detected concerning percentages of proliferating and mitotic cells in tumor sections from treated and untreated mice. However, a significant increase of necrotic areas within whole tumor sections of beauvericin-treated mice was found in both models corresponding to an enhanced number of TUNEL-positive, i.e., apoptotic, cells. Furthermore, moderate beauvericin accumulation was detected in tumor tissues. In conclusion, we suggest beauvericin as a promising novel natural compound for anticancer therapy.

  1. In vivo genotoxicity study of titanium dioxide nanoparticles using comet assay following intratracheal instillation in rats.

    Science.gov (United States)

    Naya, Masato; Kobayashi, Norihiro; Ema, Makoto; Kasamoto, Sawako; Fukumuro, Masahito; Takami, Shigeaki; Nakajima, Madoka; Hayashi, Makoto; Nakanishi, Junko

    2012-02-01

    Titanium dioxide (TiO₂) is widely used as a white pigment in paints, plastics, inks, paper, creams, cosmetics, drugs and foods. In the present study, the genotoxicity of anatase TiO₂ nanoparticles was evaluated in vivo using the comet assay after a single or repeated intratracheal instillation in rats. The nanoparticles were instilled intratracheally at a dosage of 1.0 or 5.0 mg/kg body weight (single instillation group) and 0.2 or 1.0 mg/kg body weight once a week for 5 weeks (repeated instillation group) into male Sprague-Dawley rats. A positive control, ethyl methanesulfonate (EMS) at 500 mg/kg, was administered orally 3 h prior to dissection. Histopathologically, macrophages and neutrophils were detected in the alveolus of the lung in the 1.0 and 5.0 mg/kg TiO₂ groups. In the comet assay, there was no increase in % tail DNA in any of the TiO₂ groups. In the EMS group, there was a significant increase in % tail DNA compared with the negative control group. TiO₂ nanoparticles in the anatase crystal phase are not genotoxic following intratracheal instillation in rats. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. In Vitro and In Vivo Infectious Potential of Coxiella burnetii: A Study on Belgian Livestock Isolates

    Science.gov (United States)

    Mori, Marcella; Boarbi, Samira; Michel, Patrick; Bakinahe, Raïssa; Rits, Katleen; Wattiau, Pierre; Fretin, David

    2013-01-01

    Q-fever is a zoonosis caused by the gram-negative obligate intracellular pathogen Coxiella burnetii. Since its discovery, and particularly following the recent outbreaks in the Netherlands, C. burnetii appeared as a clear public health concern. In the present study, the infectious potential displayed by goat and cattle isolates of C. burnetii was compared to a reference strain (Nine Mile) using both in vitro (human HeLa and bovine macrophage cells) and in vivo (BALB/c mice) models. The isolates had distant genomic profiles with one - the goat isolate - being identical to the predominant strain circulating in the Netherlands during the 2007–2010 outbreaks. Infective doses were established with ethidium monoazide-PCR for the first time here applied to C. burnetii. This method allowed for the preparation of reproducible and characterized inocula thanks to its capacity to discriminate between live and dead cells. Globally, the proliferative capacity of the Nine Mile strain in cell lines and mice was higher compared to the newly isolated field strains. In vitro, the bovine C. burnetii isolate multiplied faster in a bovine macrophage cell line, an observation tentatively explained by the preferential specificity of this strain for allogeneic host cells. In the BALB/c mouse model, however, the goat and bovine isolates multiplied at about the same rate indicating no peculiar hypervirulent behavior in this animal model. PMID:23840751

  3. NMR studies of renal phosphate metabolites in vivo: Effects of hydration and dehydration