Synthesis and Characterization of Two Chiral Pyrrolyl α-Nitronyl Nitroxide Radicals and Determination of their Cytotoxicity and Radioprotective Properties in C6 Cells and Mice under Ionizing Radiation

In this study, two chiral nitronyl nitroxyl radicals, L1 and D1, were synthesized and evaluated for their potential radioprotective properties invitro and invivo. We synthesized the new stable nitronyl nitroxide radicals, L1 and D1, according to Ullman’s method, and their chemical structures were characterized using UV-vis absorption, electron spin resonance (ESR), and circular dichroism (CD) spectra. The cytotoxicity of L1 and D1 on C6 glioma cells (C6 cells) was examined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. To study the anti-radiation effects of L1 and D1 on C6 cells, we determined the optical density (OD) values of irradiated C6 cells using the MTT assay. The effects of L1 and D1 on the survival rate of mice after radiation exposure was evaluated. To demonstrate the influence of L1 and D1 pre-treatment on the antioxidant enzyme system, we studied the activities of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH) in mouse plasma after exposure to 6.5 Gy gamma radiation. The results showed that L1 and D1 did not have any obvious cytotoxicity at concentrations below 125μgmL−1. Moreover, L1 and D1 had the same cytotoxic effects on C6 cells. L1 and D1 significantly enhanced C6 cell survival after 8, 10, and 12 Gy radiation exposure, and there was no significant difference in the OD values between L1 and D1. The effects of these drugs on mouse survival rates were dose-dependent. Pre-treatment with different concentrations of L1, D1, or WR2721 significantly increased the activity of SOD, CAT, and GSH and significantly decreased the activity of MDA compared with radiation exposure only. In addition, the activities of SOD, CAT, and GSH in the L1 group were higher than those in the D1 group, whereas the activity of MDA was lower. Therefore, L1 and D1 have potential as safe and efficient therapeutic drugs against radiation damage.

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Organic Ferromagnets. Hydrogen Bonded Supramolecular Magnetic Organizations Derived from Hydroxylated Phenyl ?-Nitronyl Nitroxide Radicals

Journal de Physique I ◽

10.1051/jp1:1996199 ◽

1996 ◽

Vol 6 (12) ◽

pp. 1967-1986 ◽

Cited By ~ 13

Author(s):

J. Veciana ◽

J. Cirujeda ◽

C. Rovira ◽

E. Molins ◽

J. J. Novoa

Keyword(s):

Nitronyl Nitroxide ◽

Nitroxide Radicals ◽

Organic Ferromagnets ◽

Hydrogen Bonded

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Strahlenwirkung am Normalgewebe

Nuklearmedizin ◽

10.1055/s-0038-1626537 ◽

2010 ◽

Vol 49 (S 01) ◽

pp. S53-S58 ◽

Cited By ~ 1

Author(s):

W. Dörr

Keyword(s):

Radiation Exposure ◽

Normal Tissue ◽

Radiation Effects ◽

A Priori ◽

Cell Loss ◽

Turnover Time ◽

Complete Healing ◽

Internal Radiotherapy ◽

Normal Tissues ◽

Chronic Radiation

SummaryThe curative effectivity of external or internal radiotherapy necessitates exposure of normal tissues with significant radiation doses, and hence must be associated with an accepted rate of side effects. These complications can not a priori be considered as an indication of a too aggressive therapy. Based on the time of first diagnosis, early (acute) and late (chronic) radiation sequelae in normal tissues can be distinguished. Early reactions per definition occur within 90 days after onset of the radiation exposure. They are based on impairment of cell production in turnover tissues, which in face of ongoing cell loss results in hypoplasia and eventually a complete loss of functional cells. The latent time is largely independent of dose and is defined by tissue biology (turnover time). Usually, complete healing of early reactions is observed. Late radiation effects can occur after symptom-free latent times of months to many years, with an inverse dependence of latency on dose. Late normal tissue changes are progressive and usually irreversible. They are based on a complex interaction of damage to various cell populations (organ parenchyma, connective tissue, capillaries), with a contribution from macrophages. Late effects are sensitive for a reduction in dose rate (recovery effects).A number of biologically based strategies for protection of normal tissues or for amelioration of radiation effects was and still is tested in experimental systems, yet, only a small fraction of these approaches has so far been introduced into clinical studies. One advantage of most of the methods is that they may be effective even if the treatment starts way after the end of radiation exposure. For a clinical exploitation, hence, the availability of early indicators for the progression of subclinical damage in the individual patient would be desirable. Moreover, there is need to further investigate the molecular pathogenesis of normal tissue effects in more detail, in order to optimise biology based preventive strategies, as well as to identify the precise mechanisms of already tested approaches (e. g. stem cells).

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The Effect of Antiplatelet Drugs on Plasma Betathromboglobulin in Coronary Artery Disease

10.1055/s-0038-1665677 ◽

1979 ◽

Cited By ~ 1

Author(s):

P Han ◽

A Turpie ◽

E Genton ◽

M Gent

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Crossover Trial ◽

Specific Protein ◽

Antiplatelet Drugs ◽

Significant Difference ◽

Pre Treatment ◽

Artery Disease ◽

Therapeutic Doses ◽

Granule Release

Platelets play a role in the development and complications of coronary artery disease (CAD) and a number of abnormalities of platelet function which can be corrected by antiplatelet drugs have been described. Betathromboglobulin (BTG), a platelet-specific protein which is released from α-granules during platelet activation is significantly elevated in patients with angiographically demonstrated CAD (51.0 ± 31.0 ng/ml., n = 50) compared to normal (28.0 ± 8.0 ng/ml., n = 70) p < 0.001. The effect of sulphinpyrazone (800 mg.) or aspirin (1200 mg.)/dipyridamole (200 mg.) on plasma BTG in CAD was studied in a blind prospective crossover trial in 25 patients. Mean BTG concentration pre-treatment was 52.3 ng/ml. and after 1 month’s treatment with placebo, sulphinpyrazone or aspirin/dipyridamole mean plasma BTG concentrations were 53.5, 49.6 and 56.7 ng/ml. respectively. Analysis of variance showed no significant difference between the means (p > 0.1) . This study confirms increased plasma BTG concentrations in patients with CAD and indicates that therapeutic doses of these antiplatelet drugs do not significantly effect the BTG level and thus appear not to prevent α-granule release in CAD.

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STUDIES ON SULFATION FACTOR (SF) ACTIVITY OF HUMAN SERUM

Acta Endocrinologica ◽

10.1530/acta.0.xxxv0381 ◽

1960 ◽

Vol XXXV (III) ◽

pp. 381-396 ◽

Cited By ~ 14

Author(s):

Sven Almqvist

Keyword(s):

Human Serum ◽

Normal Serum ◽

Treatment Level ◽

Response Curves ◽

Normal Children ◽

Significant Difference ◽

Human Sera ◽

Normal Humans ◽

Pre Treatment ◽

Dose Levels

ABSTRACT The sulfation factor (SF) activity of human sera has been estimated using a modification of the method of Daughaday et al. (1959). Each assay was statistically evaluated. The method had a mean precision of 0.14 and, used as an assay of GH of human serum, a sensitivity in three pituitary dwarfs of 0.1 to 0.6 μg of HGH/ml of serum. SF activity was found at all ages between 1 month and 75 years. There was a significantly lower mean SF activity below the age of half a year. Three cases of pituitary dwarfism had significantly low SF activities of sera. There was no significant difference between the SF activities of sera from untreated pituitary dwarfs and the sera from normal children below half a year of age. Dose-response curves with large volumes of sera from pituitary dwarfs and small volumes of sera from normal humans had the same slopes. Four mg of HGH prepared according to the method of Li & Papkoff (1956) resulted in a normal serum SF activity in each of the three dwarfs. A significant (P < 0.01) linear relationship was found between the concentration of SF activity of sera from these subjects and the logarithm of the dose of HGH given with dose levels of 1, 2 and 4 mg daily for three days. The decline of serum SF activity to the pre-treatment level following HGH in one dwarf suggested a half life not different from that indicated by others for growth hormone.

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Radiosensitivity of glioma to Gamma Knife treatment enhanced in vitro and in vivo by RNA interfering Ku70 that is mediated by a recombinant adenovirus

Journal of Neurosurgery ◽

10.3171/2010.7.gks10972 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 228-235 ◽

Cited By ~ 4

Author(s):

Qiang Jia ◽

Yanhe Li ◽

Desheng Xu ◽

Zhenjiang Li ◽

Zhiyuan Zhang ◽

...

Keyword(s):

Western Blot ◽

Gamma Knife ◽

Blot Analysis ◽

Western Blot Analysis ◽

Glioma Cells ◽

C6 Glioma ◽

C6 Glioma Cells ◽

C6 Cells

Object The authors sought to evaluate modification of the radiation response of C6 glioma cells in vitro and in vivo by inhibiting the expression of Ku70. To do so they investigated the effect of gene transfer involving a recombinant replication-defective adenovirus containing Ku70 short hairpin RNA (Ad-Ku70shRNA) combined with Gamma Knife treatment (GKT). Methods First, Ad-Ku70shRNA was transfected into C6 glioma cells and the expression of Ku70 was measured using Western blot analysis. In vitro, phenotypical changes in C6 cells, including proliferation, cell cycle modification, invasion ability, and apoptosis were evaluated using the MTT (3′(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide) assay, Western blot analysis, and cell flow cytometry. In vivo, parental C6 cells transfected with Ad-Ku70shRNA were implanted stereotactically into the right caudate nucleus in Sprague-Dawley rats. After GKS, apoptosis was analyzed using the TUNEL (terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling) method. The inhibitory effects on growth and invasion that were induced by expression of proliferating cell nuclear antigen and matrix metalloproteinase–9 were determined using immunohistochemical analyses. Results The expression of Ku70 was clearly inhibited in C6 cells after transfection with Ad-Ku70shRNA. In vitro following transfection, the C6 cells showed improved responses to GKT, including suppression of proliferation and invasion as well as an increased apoptosis index. In vivo following transfection of Ad-Ku70shRNA, the therapeutic efficacy of GKT in rats with C6 gliomas was greatly enhanced and survival times in these animals were prolonged. Conclusions Our data support the potential for downregulation of Ku70 expression in enhancing the radiosensitivity of gliomas. The findings of our study indicate that targeted gene therapy–mediated inactivation of Ku70 may represent a promising strategy in improving the radioresponsiveness of gliomas to GKT.

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Isolation of an Anti-fatigue Preparation from Cellulase-treated Maca by Hydroalcoholic Extraction

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:93-98 ◽

2017 ◽

Vol 17 (1) ◽

pp. 93-98

Author(s):

Zheng Yue ◽

Zhang Wen-Cheng ◽

Wu Ze-Yu ◽

Fu Chuan-Xiang ◽

Gao Han ◽

...

Keyword(s):

Positive Control ◽

Glycogen Storage ◽

Hepatic Glycogen ◽

Time To Exhaustion ◽

High Dose ◽

Hydroalcoholic Extract ◽

Swimming Time ◽

Significant Difference ◽

Pre Treatment ◽

Better Than

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.

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α-Conotoxins and α-Cobratoxin Promote, while Lipoxygenase and Cyclooxygenase Inhibitors Suppress the Proliferation of Glioma C6 Cells

Marine Drugs ◽

10.3390/md19020118 ◽

2021 ◽

Vol 19 (2) ◽

pp. 118

Author(s):

Tatiana I. Terpinskaya ◽

Alexey V. Osipov ◽

Elena V. Kryukova ◽

Denis S. Kudryavtsev ◽

Nina V. Kopylova ◽

...

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

Acetylcholine Receptors ◽

Glioma Cells ◽

Nordihydroguaiaretic Acid ◽

C6 Glioma ◽

Cyclooxygenase Inhibitors ◽

C6 Glioma Cells ◽

C6 Cells ◽

Lipoxygenase Inhibitor ◽

Glioma C6

Among the brain tumors, glioma is the most common. In general, different biochemical mechanisms, involving nicotinic acetylcholine receptors (nAChRs) and the arachidonic acid cascade are involved in oncogenesis. Although the engagement of the latter in survival and proliferation of rat C6 glioma has been shown, there are practically no data about the presence and the role of nAChRs in C6 cells. In this work we studied the effects of nAChR antagonists, marine snail α-conotoxins and snake α-cobratoxin, on the survival and proliferation of C6 glioma cells. The effects of the lipoxygenase and cyclooxygenase inhibitors either alone or together with α-conotoxins and α-cobratoxin were studied in parallel. It was found that α-conotoxins and α-cobratoxin promoted the proliferation of C6 glioma cells, while nicotine had practically no effect at concentrations below 1 µL/mL. Nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor, and baicalein, a 12-lipoxygenase inhibitor, exerted antiproliferative and cytotoxic effects on C6 cells. nAChR inhibitors weaken this effect after 24 h cultivation but produced no effects at longer times. Quantitative real-time polymerase chain reaction showed that mRNA for α4, α7, β2 and β4 subunits of nAChR were expressed in C6 glioma cells. This is the first indication for involvement of nAChRs in mechanisms of glioma cell proliferation.

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Organ motion in linac-based SBRT for glottic cancer

Radiation Oncology ◽

10.1186/s13014-021-01833-2 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Annarita Perillo ◽

Valeria Landoni ◽

Alessia Farneti ◽

Giuseppe Sanguineti

Keyword(s):

Early Stage ◽

Displacement Vector ◽

Thyroid Cartilage ◽

Three Dimensional ◽

Target Volume ◽

Glottic Cancer ◽

Organ Motion ◽

Delivery Times ◽

Significant Difference ◽

Pre Treatment

Abstract Purpose The purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer. Methods and materials Stereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated. Results For the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively). Conclusions In the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

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