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Sample records for high dose rats

  1. Proconvulsant effects of high doses of venlafaxine in pentylenetetrazole-convulsive rats

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    J.G. Santos Junior

    2002-04-01

    Full Text Available Venlafaxine, an atypical antidepressant drug, has been used to treat several neurological disorders, presenting excellent efficacy and tolerability. Clinical seizures after venlafaxine treatment have occasionally been reported when the drug was used at very high doses or in combination with other medications. The aim of the present study was to investigate the convulsant effects of venlafaxine in rats under controlled laboratory conditions. Adult male Wistar rats (8 per group receiving venlafaxine or saline at the doses of 25-150 mg/kg were subjected 30 min later to injections of pentylenetetrazole at the dose of 60 mg/kg. The animals receiving 75, 100 and 150 mg/kg venlafaxine presented increased severity of convulsion when compared to controls (P = 0.02, P = 0.04, and P = 0.0004, respectively. Indeed, an increased percentage of death was observed in these groups (50, 38, and 88%, respectively when compared to the percentage of death in the controls (0%. The group receiving 150 mg/kg showed an reduction in death latency (999 ± 146 s compared to controls (1800 ± 0 s; cut-off time. Indeed, in this group, all animals developed seizures prior to pentylenetetrazole administration. Surprisingly, the groups receiving venlafaxine at the doses of 25 and 50 mg/kg showed a tendency towards an increase in the latency to the first convulsion. These findings suggest that venlafaxine at doses of 25 and 50 mg/kg has some tendency to an anticonvulsant effect in the rat, whereas doses of 75, 100 and 150 mg/kg presented clear proconvulsant effects in rats submitted to the pentylenetetrazole injection. These findings are the first report in the literature concerning the role of venlafaxine in seizure genesis in the rat under controlled conditions.

  2. Dietary intake of high-dose biotin inhibits spermatogenesis in young rats.

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    Sawamura, Hiromi; Ikeda, Chieko; Shimada, Ryoko; Yoshii, Yui; Watanabe, Toshiaki

    2015-02-01

    To characterize a new function of the water-soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats. © 2014 Japanese Teratology Society.

  3. High dose rate (HDR) and low dose rate (LDR) interstitial irradiation (IRT) of the rat spinal cord

    International Nuclear Information System (INIS)

    Pop, Lucas A.M.; Plas, Mirjam van der; Skwarchuk, Mark W.; Hanssen, Alex E.J.; Kogel, Albert J. van der

    1997-01-01

    Purpose: To describe a newly developed technique to study radiation tolerance of rat spinal cord to continuous interstitial irradiation (IRT) at different dose rates. Material and methods: Two parallel catheters are inserted just laterally on each side of the vertebral bodies from the level of Th 10 to L 4 . These catheters are afterloaded with two 192 Ir wires of 4 cm length each (activity 1-2.3 mCi/cm) for the low dose rate (LDR) IRT or connected to the HDR micro-Selectron for the high dose rate (HDR) IRT. Spinal cord target volume is located at the level of Th 12 -L 2 . Due to the rapid dose fall-off around the implanted sources, a dose inhomogeneity across the spinal cord thickness is obtained in the dorso-ventral direction. Using the 100% reference dose (rate) at the ventral side of the spinal cord to prescribe the dose, experiments have been carried out to obtain complete dose response curves at average dose rates of 0.49, 0.96 and 120 Gy/h. Paralysis of the hind-legs after 5-6 months and histopathological examination of the spinal cord of each irradiated rat are used as experimental endpoints. Results: The histopathological damage seen after irradiation is clearly reflected the inhomogeneous dose distribution around the implanted catheters, with the damage predominantly located in the dorsal tract of the cord or dorsal roots. With each reduction in average dose rate, spinal cord radiation tolerance is significantly increased. When the dose is prescribed at the 100% reference dose rate, the ED 50 (induction of paresis in 50% of the animals) for the HDR-IRT is 17.3 Gy. If the average dose rate is reduced from 120 Gy/h to 0.96 or 0.49 Gy/h, a 2.9- or 4.7-fold increase in the ED 50 values to 50.3 Gy and 80.9 Gy is observed; for the dose prescribed at the 150% reference dose rate (dorsal side of cord) ED 50 values are 26.0, 75.5 and 121.4 Gy, respectively. Using different types of analysis and in dependence of the dose prescription and reference dose rate, the

  4. Inhibitory Effect of High Dose of the Flavonoid Quercetin on Amygdala Electrical Kindling in Rats

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    Tourandokht Baluchnejadmojarad

    2010-05-01

    Full Text Available A B S T R A C T Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. Therefore, the anti-convulsant effect of a high dose of quercetin was evaluated in amygdala kindling model in male rats. Methods: Rats were divided into sham-operated group, quercetintreated SH, kindled, and quercetin-treated kindled rats. Quercetin was administered i.p. one day before amygdale kindling for 3 weeks (40 mg/kg/day. The parameters seizure stage, AD duration, the latency to the onset of stage 4, and the duration of stage 5 were analyzed. Results: The results showed that quercetin pretreatment causes a lower seizure intensity in treated kindled rats (p<0.05-0.01, a lower after-discharge duration (p<0.05-0.01, and a higher latency to stage IV (p<0.05 as compared to untreated kindled ones. Discussion: To conclude, chronic administration of quercetin inhibits amygdala electrical kindling and more studies are warranted to clarify its underlying mechanisms.

  5. Efeitos das isoflavonas em altas doses sobre o útero da rata Effects of high-dose isoflavones on rat uterus

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    Adriana Aparecida Ferraz Carbonel

    2011-10-01

    Full Text Available OBJETIVO: Avaliar o efeito de altas doses de isoflavonas no útero de ratas adultas castradas. MÉTODOS: Ratas virgens ovariectomizadas (n = 40 foram tratadas por 30 dias consecutivos com veículo (GCtrl ou genisteína nas concentrações 42 (GES42, 125 (GES125 e 250 (GES250 µg/g de peso corporal ao dia. O extrato de soja e o veículo (propilenoglicol foram administrados por gavagem. Ao final do experimento, foi realizada dosagem sérica de 17 β-estradiol e progesterona, avaliou-se o peso dos animais e dos úteros e foi feito exame colpocitológico. Fragmentos do terço médio dos cornos uterinos foram fixados em formol a 10% e processados para inclusão em parafina para estudo histológico. Cortes de 5 µm de espessura foram corados pelo HE e destinados a estudo em microscopia de luz. Analisou-se a histomorfologia do endométrio, área endometrial, número e área ocupada pelas glândulas, assim como a concentração de eosinófilos presentes na lâmina própria. Os dados numéricos obtidos foram submetidos à análise de variância complementada pelo teste de Tukey-Kramer (p GES125 do que nos outros grupos (GES250 > GES125 > GES42 = GCtrl; p OBJECTIVE: To evaluate the effects of high-dose isoflavones on the uterus of castrated adult rats. METHODS: Adult, ovariectomized virgin rats (n = 40 were treated by gavage during 30 consecutive days with vehicle (propylene glycol, group GCtrl or different doses of genistein: 42 (group GES42, 125 (GES125, or 250 (GES250 µg/g body weight per day. Animals were killed, weighed, vaginal and uterine samples were taken for cytologic evaluation, and serum levels of 17 β-estradiol and progesterone were determined. The middle third of the uterine horns was dissected, fixed in 10% formaldehyde and processed for paraffin inclusion; 5-µm thick sections were obtained and stained with HE for further histological study under light microscopy. The endometrial morphology and area, number and area of glands, and number

  6. Effects of high dose olive leaf extract on haemodynamic and oxidative stress parameters in normotensive and spontaneously hypertensive rats

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    Dekanski Dragana

    2014-01-01

    Full Text Available Antihypertensive activity of natural antioxidant, olive leaf extract (OLE is known, but its influence on cardiovascular system when administered in a high dose has not been investigated yet. Our aim was to determine the acute effects of excessive intake of standardized OLE on blood pressure, heart rate and oxidative status in both spontaneously hypertensive rats and normotensive Wistar rats. Systolic arterial pressure and heart rate were measured using a tail-cuff, pneumatic pulse detector, before, 60 and 120 minutes after intragastric OLE administration. Activities of catalase, glutathione peroxidase, superoxide dismutase (SOD and glutathione reductase in erythrocytes, as well as lipid peroxidation in plasma (pTBARS were measured at the same time points, spectrophotometrically. High-dose OLE did not influence blood pressure, heart rate and pTBARS in normotensive rats, while SOD, catalase, and glutathione reductase activities significantly increased. The same dose significantly decreased blood pressure in hypertensive rats, but increased pTBARS and SOD activity. Excessive oral intake of OLE induced moderate hypotensive effects in spontaneously hypertensive rats only, suggesting absence of harmful haemodynamic effects after oral overdose in both rats strain. However, its prooxidative role when given in high dose in hypertensive organism should not be neglected. [Projekat Ministarstva nauke Republike Srbije, br. 175096

  7. High-dose fasudil preserves postconditioning against myocardial infarction under hyperglycemia in rats: role of mitochondrial KATP channels

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    Ichinomiya Taiga

    2012-03-01

    Full Text Available Abstract Background The current study was carried out to determine whether fasudil hydrochloride (fasudil, a Rho-kinase inhibitor, has myocardial postconditioning (PostC activity under hyperglycemia as well as normoglycemia, and if so, whether the effects could be mediated by mitochondrial ATP-sensitive potassium (m-KATP channels. Methods Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. After opening the chest, all rats underwent 30-min coronary artery occlusion followed by 2-h reperfusion. The rats received low-dose (0.15 mg/kg or high-dose (0.5 mg/kg fasudil or diazoxide, an m-KATP channel opener, at 10 mg/kg, just before reperfusion under normoglycemic or hyperglycemic conditions. In another group, rats received 5-hydroxydecanoic acid (5HD, an m-KATP channel blocker, at 10 mg/kg, before high-dose fasudil. Myocardial infarct size was expressed as a percentage of area at risk (AAR. Results Under normoglycemia, low-dose and high-dose fasudil and diazoxide reduced myocardial infarct size (23 ± 8%, 21 ± 9% and 21 ± 10% of AAR, respectively compared with that in the control (42 ± 7%. Under hyperglycemia, low-dose fasudil (40 ± 11% and diazoxide (44 ± 14% could not exert this beneficial effect, but high-dose fasudil reduced myocardial infarct size in the same manner as under normoglycemia (21 ± 13%. 5HD prevented fasudil-induced reduction of myocardial infarct size (42 ± 13%. Conclusion Fasudil induces PostC against myocardial infarction via activation of m-KATP channels in the rat. Although hyperglycemia attenuates the PostC, high-dose fasudil can restore cardioprotection.

  8. Early Effect of High Dose of Ionizing Radiation Exposure on Plasma Lipids Profile and Liver Fatty Acids Composition in Rats

    International Nuclear Information System (INIS)

    Noaman, E.; Mansour, S.Z.; Ibrahim, N.K.

    2005-01-01

    The present study was conducted to analyze the effect of acute gamma-irradiation on rats at supralethal doses of 20 Gy to determine the synthesis and amounts of free fatty acids, neutral lipids and phospholipids of plasma and liver after 24 and 48 h of gamma-irradiation. Male Wistar rats weighing 120+- 20 g were exposed to 20 Gy of gamma radiation (dose rate of 0.59 Gy/min). Exposure of rats to ionizing radiation resulted in significant alterations in the assayed parameters indicating lipid metabolism disturbance. Plasma cholesterol and phospholipid levels increased up to 71.3 and 71.5 %, respectively, after 24 h from radiation exposure and then returned to 28 and 27 % change in-compare with control values after 48 h post-irradiation. Plasma triacylglycerol concentrations increased concomitantly with irradiation, but their values are less high than cholesterol and phospholipid levels recording significant changes at 19 and 9 % comparing with control rats. Lipid peroxidation measured as MDA recorded significant elevation after 24 and 48 h post irradiation. It was shown that the synthesis of free fatty acids, cholesterol, cholesterol ethers and phospholipids was activated 48 h after irradiation at 20 Gy. The amount of free fatty acids of the rat liver decreased at 20 Gy exposures. This is assumed to be a result of the radioresistance to some degree in the system of free fatty acid synthesis of the rat to the gamma-irradiation in the lethal doses

  9. Effect of high doses of L-ascorbic acid on the antioxidative/oxidative state in the rats

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    Niemiec, T.; Sawosz, E.; Chwalibog, André

    2005-01-01

    The objective of this study was to determine the effects of mega-doses of vitamin C (0.3, 0.6 and 0.9% of diet) as a dietary supplement for rats on selected indices of the antioxidative/oxidative state in 40 growing Wistar rats (4x10). It was found that L-ascorbic acid and Total Antioxidative State...... (TAS) in plasma did not increase with increasing vitamin C supply. The results indicate that high doses of L-ascorbic acid (0.3 and 0.9 but not 0.6%) increased the concentration of this antioxidant in plasma. Supplementation of vitamin C above 0.3% to the diets had pro-oxidative effects on lipid...... structures, while application of 0.9% promoted oxidative degradation of rat livers....

  10. Sensitivity and proportionality assessment of metabolites from microdose to high dose in rats using LC-MS/MS.

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    Ni, Jinsong; Ouyang, Hui; Seto, Carmai; Sakuma, Takeo; Ellis, Robert; Rowe, Josh; Acheampong, Andrew; Welty, Devin; Szekely-Klepser, Gabriella

    2010-03-01

    The objective of this study was to evaluate the sensitivity requirement for LC-MS/MS as an analytical tool to characterize metabolites in plasma and urine at microdoses in rats and to investigate proportionality of metabolite exposure from a microdose of 1.67 µg/kg to a high dose of 5000 µg/kg for atorvastatin, ofloxacin, omeprazole and tamoxifen. Only the glucuronide metabolite of ofloxacin, the hydroxylation metabolite of omeprazole and the hydration metabolite of tamoxifen were characterized in rat plasma at microdose by LC-MS/MS. The exposure of detected metabolites of omeprazole and tamoxifen appeared to increase in a nonproportional manner with increasing doses. Exposure of ortho- and para-hydroxyatorvastatin, but not atorvastatin and lactone, increased proportionally with increasing doses. LC-MS/MS has demonstrated its usefulness for detecting and characterizing the major metabolites in plasma and urine at microdosing levels in rats. The exposure of metabolites at microdose could not simply be used to predict their exposure at higher doses.

  11. A magnetic resonance imaging study on changes in rat mandibular bone marrow and pulp tissue after high-dose irradiation

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    Lee, Wan; Lee, Byung Do [Dept. of Oral and Maxillofacial Radiology and Wonkwang Dental Research Institute, College of Dentistry, Wonkwang University, Iksan (Korea, Republic of); Lee, Kang Kyoo [Dept. of Radiation Oncology, School of Medicine, Wonkwang University, Iksan (Korea, Republic of); Koh, Kwang Joon [Dept. of Oral and Maxillofacial Radiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju (Korea, Republic of)

    2014-03-15

    This study was designed to evaluate whether magnetic resonance imaging (MRI) is appropriate for detecting early changes in the mandibular bone marrow and pulp tissue of rats after high-dose irradiation. The right mandibles of Sprague-Dawley rats were irradiated with 10 Gy (Group 1, n=5) and 20 Gy (Group 2, n=5). Five non-irradiated animals were used as controls. The MR images of rat mandibles were obtained before irradiation and once a week until week 4 after irradiation. From the MR images, the signal intensity (SI) of the mandibular bone marrow and pulp tissue of the incisor was interpreted. The MR images were compared with the histopathologic findings. The SI of the mandibular bone marrow had decreased on T2-weighted MR images. There was little difference between Groups 1 and 2. The SI of the irradiated groups appeared to be lower than that of the control group. The histopathologic findings showed that the trabecular bone in the irradiated group had increased. The SI of the irradiated pulp tissue had decreased on T2-weighted MR images. However, the SI of the MR images in Group 2 was high in the atrophic pulp of the incisor apex at week 2 after irradiation. These patterns seen on MRI in rat bone marrow and pulp tissue were consistent with histopathologic findings. They may be useful to assess radiogenic sclerotic changes in rat mandibular bone marrow.

  12. High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats

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    Hai-Quyen Tran

    2016-10-01

    Full Text Available Dextromethorphan (DM administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed.

  13. High-dose dextromethorphan produces myelinoid bodies in the hippocampus of rats.

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    Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Kim, Won Ki; Lee, Jae-Chul; Jeong, Ji Hoon; Wie, Myung Bok; Jang, Choon-Gon; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

    2016-10-01

    Dextromethorphan (DM) administered at supra-antitussive doses produce psychotoxic and neurotoxic effects in humans. We administered DM (80 mg/kg) to rats intraperitoneally to determine the ultrastructural change induced by DM, because intraperitoneal route is sensitive for the behavioral responses. Treatment with DM resulted in mitochondrial dysfunction and formation of myelinoid bodies in the hippocampus. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] attenuated DM-induced cytosolic oxidative burdens. However, neither MK-801 nor naloxone affected DM-induced mitochondrial dysfunction and formation of myelinoid bodies, indicating that the neurotoxic mechanism needs to be further elucidated. Therefore, the spectrum of toxicological effects associated with DM need to be reassessed. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  14. High-dose thiamine therapy counters dyslipidemia and advanced glycation of plasma protein in streptozotocin-induced diabetic rats.

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    Karachalias, Nikolaos; Babaei-Jadidi, Roya; Kupich, Christian; Ahmed, Naila; Thornalley, Paul J

    2005-06-01

    The streptozotocin-induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high-dose thiamine and S-benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy. Recently, we reported that high-dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G-H1 and MG-H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only. The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid-derived aldehydes.

  15. Subchronic exposure to high-dose ACE-inhibitor moexipril induces catalase activity in rat liver.

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    Adeghate, E; Hasan, M Y; Ponery, A S; Nurulain, S M; Petroianu, G A

    2005-12-01

    The long-term clinical effects of ACE-inhibitors have similarities with those of both fibrates and glitazones, activators of peroxisome proliferator activator receptor (PPAR) alpha and gamma, respectively. The antioxidant enzyme catalase, a heme protein that degrades hydrogen peroxide, is found at high concentrations in peroxisomes. Catalase activity is one of the recognized surrogate markers indicative of PPAR activation in the rat liver. The purpose of the study was to establish the effect of moexipril on catalase activity and to compare it with the effect of both saline controls and that of the known PPAR agonist clofibrate (positive control). Three groups of seven rats were used. All substances were applied i.p. daily for 5 days, followed by a 2-day break. The cycle was repeated eight times. After the final cycle (day 56) the animals were sacrificed and liver tissue collected. The number of catalase positive cells in both moexipril group (95% CI 57-61) and clofibrate group (95% CI 72-80) is higher than in controls (95% CI 3-16) (p catalase positive cells in the clofibrate group is higher than in the moexipril group (p inhibitor moexipril induces catalase activity in the rat liver to an extent comparable to fibrates. We suggest that some of the long-term advantages of ACE inhibitor use - beyond mere BP lowering - might be due to a PPAR mediated effect.

  16. Dexamethasone hepatic induction in rats subsequently treated with high dose buprenorphine does not lead to respiratory depression

    International Nuclear Information System (INIS)

    Hreiche, Raymond; Megarbane, Bruno; Pirnay, Stephane; Borron, Stephen W.; Monier, Claire; Risede, Patricia; Milan, Nathalie; Descatoire, Veronique; Pessayre, Dominique; Baud, Frederic J.

    2006-01-01

    In humans, asphyxic deaths and severe poisonings have been attributed to high-dosage buprenorphine, a maintenance therapy for heroin addiction. However, in rats, intravenous buprenorphine at doses up to 90 mg kg -1 was not associated with significant effects on arterial blood gases. In contrast, norbuprenorphine, the buprenorphine major cytochrome P450 (CYP) 3A-derived metabolite, is a potent respiratory depressant. Thus, our aim was to study the consequences of CYP3A induction on buprenorphine-associated effects on resting ventilation in rats. We investigated the effects on ventilation of 30 mg kg -1 buprenorphine alone or following cytochrome P450 (CYP) 3A induction with dexamethasone, using whole body plethysmography (N = 24) and arterial blood gases (N = 12). Randomized animals in 4 groups received sequential intraperitoneal dosing with: (dexamethasone [days 1-3] + buprenorphine [day 4]), (dexamethasone solvent [days 1-3] + buprenorphine [day 4]), (dexamethasone [days 1-3] + buprenorphine solvent [day 4]), or (dexamethasone solvent [days 1-3] + buprenorphine solvent [day 4]). Buprenorphine alone caused a significant rapid and sustained increase in the inspiratory time (P -1 buprenorphine on rat ventilation. Our results suggest a limited role of drug-mediated CYP3A induction in the occurrence of buprenorphine-attributed respiratory depression in addicts

  17. high doses of prolactin inhibit testosterone secretion in rat leydig cells

    African Journals Online (AJOL)

    Femi Olaleye

    1 The effect of prolactin on dispersed rat Leydig cells was investigated. Leydig cells from adult rat testes of proven fertility were isolated via collagenase digestion and dispersion. About 100,000 Leydig .... Hormones, Drugs and Reagents.

  18. Long term evolution of the immune response in the rat irradiated at mean and high doses

    International Nuclear Information System (INIS)

    Malarbet, J.L.; Veyrat, M.; Le Go, R.; Prudhomme, J.; Genest, L.; Castelnau, L.

    1977-01-01

    In irradiated animals, the lymphocytes, immunity vectors, are quickly and quantitatively depressed. Their ability to respond to an antigenic stimulus was tested in rats during post-irradiation lymphopenia and after restoration of normal lymphocytosis. The antigenic stimulus, sheep erythrocytes, was applied first 2 and 3 weeks, then 1, 2 and 3 months after exposures to 60 Co gamma rays (doses 300 and 600 rads). This study covered the 3rd through the 10th day after immunisation. Blood lymphocytes were separated by the Ficoll-Contrix gradient method and spleen lymphocytes were obtained by crushing. A lymphocyte sub-population separation was obtained from centrifugation on 4 discontinuous Ficoll-Contrix gradients. Size distribution spectra show that the lighter sub-population is made up of large-sized cells and that the heavier the cells, the smaller they are. The determination of surface immunoglobulins with fluorescent antigens shows that cells bearing immunoglobulins are predominant in the low-density sub-population. The measurement of electrophoretic mobility shows a low-mobility, low-density population and a higher density, faster mobility population which could reflect a higher proportion of B-cells in the low density population and of T-cells in the higher density population. The immune response was tested on the sub-populations. The rosette-forming ability was depressed during 1 month after irradiation then became progressively normal. The cellular plaque-forming ability was markedly suppressed 15 days after irradiation, but was soon active again. These results show the qualitative aspect of the post-irradiation immune defect [fr

  19. Antidiabetic Effect of Fresh Nopal (Opuntia ficus-indica in Low-Dose Streptozotocin-Induced Diabetic Rats Fed a High-Fat Diet

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    Seung Hwan Hwang

    2017-01-01

    Full Text Available The objective of the present study was to evaluate α-glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE and Nopal dry power (NADP in low-dose streptozotocin- (STZ- induced diabetic rats fed a high-fat diet (HFD. The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1 nondiabetic rats fed a regular diet (RD-Control; (2 low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control; (3 low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE; and (4 low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone. In results, NPWE and NADP had IC50 values of 67.33 and 86.68 μg/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05 μg/mL while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model (P<0.05. Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower (P<0.05 than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.

  20. Antidiabetic Effect of Fresh Nopal (Opuntia ficus-indica) in Low-Dose Streptozotocin-Induced Diabetic Rats Fed a High-Fat Diet.

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    Hwang, Seung Hwan; Kang, Il-Jun; Lim, Soon Sung

    2017-01-01

    The objective of the present study was to evaluate α -glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE) and Nopal dry power (NADP) in low-dose streptozotocin- (STZ-) induced diabetic rats fed a high-fat diet (HFD). The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1) nondiabetic rats fed a regular diet (RD-Control); (2) low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control); (3) low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE); and (4) low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone). In results, NPWE and NADP had IC 50 values of 67.33 and 86.68  μ g/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05  μ g/mL) while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model ( P < 0.05). Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower ( P < 0.05) than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.

  1. High Doses of Caffeine during the Peripubertal Period in the Rat Impair the Growth and Function of the Testis

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    Minji Park

    2015-01-01

    Full Text Available Prenatal caffeine exposure adversely affects the development of the reproductive organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine exposure would also influence physiologic gonadal changes and function during this critical period for sexual maturation. This study investigated the impact of high doses of caffeine on the testes of prepubertal male rats. A total of 45 immature male rats were divided randomly into three groups: a control group and 2 groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4 weeks. Caffeine caused a significant decrease in body weight gain, accompanied by proportional decreases in lean body mass and body fat. The caffeine-fed animals had smaller and lighter testes than those of the control that were accompanied by negative influences on the histologic parameters of the testes. In addition, stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine consumption can interfere with the maturation and function of the testis, possibly by interrupting endogenous testosterone secretion and reducing the sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we confirmed that pubertal administration of caffeine reduced testis growth and altered testis histomorphology.

  2. Transient alterations in neurotransmitter activity in the caudate nucleus of rat brain after a high dose of ionizing radiation

    International Nuclear Information System (INIS)

    Hunt, W.A.; Dalton, T.K.; Darden, J.H.

    1979-01-01

    A single 10,000-rad dose of high-energy electrons induced an increase in dopaminergic and cholinergic activity in the caudate nucleus of the rat brain as assessed by K + -stimulated dopamine release in vitro and high-affinity choline uptake. These alterations occur during early transient incapacitation (ETI) and dissipate as the animal recovers behaviorally, in about 30 min after irradiation. Although the responses observed resemble those that result from blockade of dopamine receptors, no radiation-induced changes were found in dopamine-sensitive adenylate cyclase activity and [ 3 H]haloperidol binding, two indices of dopaminergic receptor function. The data suggest that changes in dopaminergic and cholinergic activity are associated with the development of ETI and may play a role in the behavioral decrement observed under this condition

  3. Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane.

    Science.gov (United States)

    Benveniste, Helene; Lee, Hedok; Ding, Fengfei; Sun, Qian; Al-Bizri, Ehab; Makaryus, Rany; Probst, Stephen; Nedergaard, Maiken; Stein, Elliot A; Lu, Hanbing

    2017-12-01

    The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not. Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats. Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats. We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.

  4. In vivo dosimetry of high-dose fractionated irradiation in an experimental set-up with rats

    Energy Technology Data Exchange (ETDEWEB)

    Fortan, L; Van Hecke, H; Van Duyse, B; De Neve, W; De Meerleer, B [Ghent Rijksuniversiteit (Belgium). Kliniek voor Radiotherapie en Kerngeneeskunde; Pattyn, P; Van Renthergem, K [Ghent University (Belgium). Dept. of Surgery

    1995-12-01

    The feasibility to irradiate a limited section of a rat abdomen with well-defined edges was assessed. Because of the relative small volume involved, in vivo dosimetry with TLDs was necessary in providing us information about the accuracy of the irradiation method. Three to five days prior to the start of the radiotherapy treatment, two plastic strips - each containing a TLD-dosimeter (Harshaw TLD10 LiF rods, 1 mm dia x 6 mm) sealed in polyethylene tubing, and a lead bean - were implanted in the rat abdomen. The plastic strips made a closed loop around the bowel, through the mesenterium, and were fixed with a single stitch on the inner abdominal wall. One loop was made in the hepatic area; another was made in the lower abdomen, around the rectosigmoid. Conscious animals were irradiated using a purpose-build plexi-holder, with rear legs immobilised to avoid longitudinal movements. The implanted lead beans enabled us to simulate the rat prior to each radiation session. This way, the radiation field could be set up individually for each rat, in such way that the rectosigmoid area received full dose and the hepatic area received no irradiation dose at all. Irradiation was carried out, using 5 MV photons of a linear accelerator. Fifteen animals per group were irradiated according a conventional (2.0 Gy / fraction; 5 fractions / week) or a hyperfractionated (1.6 Gy / fraction; 2 daily fractions; 5 days / week) schedule, with different total doses. Prior to implantation, TLDs were individually calibrated and checked for stability. After removal from the abdomen . TLDs were tested again for accuracy. TLDs with an unacceptable read-out curve were rejected (about 2 to 4 TLDs per group of 15). The obtained accumulated doses - as determined by TLD read-outs-were comparable to the theoretical doses, indicating that fractionated radiation of small fields, with well defined mark off, in rats is feasible.

  5. In vivo dosimetry of high-dose fractionated irradiation in an experimental set-up with rats

    International Nuclear Information System (INIS)

    Fortan, L.; Van Hecke, H.; Van Duyse, B.; De Neve, W.; De Meerleer, B.; Pattyn, P.; Van Renthergem, K.

    1995-01-01

    The feasibility to irradiate a limited section of a rat abdomen with well-defined edges was assessed. Because of the relative small volume involved, in vivo dosimetry with TLDs was necessary in providing us information about the accuracy of the irradiation method. Three to five days prior to the start of the radiotherapy treatment, two plastic strips - each containing a TLD-dosimeter (Harshaw TLD10 LiF rods, 1 mm dia x 6 mm) sealed in polyethylene tubing, and a lead bean - were implanted in the rat abdomen. The plastic strips made a closed loop around the bowel, through the mesenterium, and were fixed with a single stitch on the inner abdominal wall. One loop was made in the hepatic area; another was made in the lower abdomen, around the rectosigmoid. Conscious animals were irradiated using a purpose-build plexi-holder, with rear legs immobilised to avoid longitudinal movements. The implanted lead beans enabled us to simulate the rat prior to each radiation session. This way, the radiation field could be set up individually for each rat, in such way that the rectosigmoid area received full dose and the hepatic area received no irradiation dose at all. Irradiation was carried out, using 5 MV photons of a linear accelerator. Fifteen animals per group were irradiated according a conventional (2.0 Gy / fraction; 5 fractions / week) or a hyperfractionated (1.6 Gy / fraction; 2 daily fractions; 5 days / week) schedule, with different total doses. Prior to implantation, TLDs were individually calibrated and checked for stability. After removal from the abdomen . TLDs were tested again for accuracy. TLDs with an unacceptable read-out curve were rejected (about 2 to 4 TLDs per group of 15). The obtained accumulated doses - as determined by TLD read-outs-were comparable to the theoretical doses, indicating that fractionated radiation of small fields, with well defined mark off, in rats is feasible

  6. [Changes in gastric function in rats after intragastric introduction of corvitin at high doses].

    Science.gov (United States)

    Vovkun, T V; Ianchuk, P I; Shtanova, L Ia; Vesel'skyĭ, S P; Baranovs'kyĭ, V A

    2014-01-01

    Intragastric administration of corvitin at doses of 10, 20 and 40 mg/kg dose-dependently increased the volume of gastric juice and the total production of hydrochloric acid (HA). Amplification of hexosamines and cysteine production was observed only when the study drug was administered at a dose of 10 mg/kg. When corvitin was used at 20 and 40 mg/kg, these parameters were at the level of control values. Protein production increased in response to 10 and 20 mg/kg corvitin, but fell below the control values after administration of 40 mg/kg of the drug. The level of blood flow in the gastric mucosa increased following administration of 10 mg/kg corvitin, was not different from the baseline after 20 mg/kg of the drug and significantly decreased in response to 40 mg/kg of flavonoid. Our results indicate that a single intragastric application of corvitin at dose of 10 mg/kg activates gastric defense mechanisms. At 20 and 40 mg/kg, corvitin does not affect them but gradually reduces blood flow in gastric mucosa, causes a disturbance of protein synthesis and hypersecretion of HA into the cavity of the stomach, which can lead to disruption of the digestive process and the integrity of gastric mucosa.

  7. Clinical doses of citalopram or reboxetine differentially modulate passive and active behaviors of female Wistar rats with high or low immobility time in the forced swimming test.

    Science.gov (United States)

    Flores-Serrano, Ana Gisela; Vila-Luna, María Leonor; Álvarez-Cervera, Fernando José; Heredia-López, Francisco José; Góngora-Alfaro, José Luis; Pineda, Juan Carlos

    2013-09-01

    The sensitivity of immobility time (IT) to antidepressant-drugs differs in rats expressing high or low motor activity during the forced swimming test (FST). However, whether this heterogeneity is expressed after the administration of the most selective serotonin and norepinephrine reuptake inhibitors (SSRIs and SNRIs, respectively) is unknown. We compared the influence of either the SSRI citalopram or the SNRI reboxetine with the tricyclic antidepressant amitriptyline on two subgroups of female Wistar rats expressing high IT (HI; at or above the mean value) or low IT (LI; below the mean) during the initial 5 min of the first session of the FST. None of the tested drugs increased motor activity in the open field test. When vehicle was applied to either HI or LI rats, IT increased in the second session of the FST. This increment concurred with a simultaneous climbing time (CT) decrement. When amitriptyline (15 mg/kg) was tested the CT increased for both HI and LI rats. This increment was accompanied by an IT decrement in HI and LI rats. Reboxetine (0.16 or 1 mg/kg) precluded IT and CT changes in both HI and LI rats and produced a swimming time reduction. Citalopram (0.4, 1, and 3 mg/kg) essentially mimicked the influence of reboxetine on the IT and CT in LI rats, as well as in HI rats, but in the latter case only at 3 mg/kg. Yet, at the dose of 10 mg/kg citalopram lacked this effect in both subgroups. No differences were detected when the IT of LI rats was evaluated with citalopram (3 mg/kg) during estrus or diestrus stage. These results show that clinical doses of citalopram produced an antidepressant-like effect selectively in LI rats, while amitriptyline or reboxetine produced this effect in both LI and HI animals. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. High-dose stabilized chlorite matrix WF10 prolongs cardiac xenograft survival in the hamster-to-rat model without inducing ultrastructural or biochemical signs of cardiotoxicity

    DEFF Research Database (Denmark)

    Hansen, A; Kemp, K; Kemp, E

    2001-01-01

    of high dose WF10 as a single drug regimen in the hamster-to-rat xenotransplantation model and searched for possible cardiotoxic side effects. WF10 prolonged cardiac xenograft survival, but did not induce tolerence or inhibit pathological signs of acute rejection. Hamsters from the donor population...

  9. Phenolics composition and antidiabetic property of Brachystegia eurycoma seed flur in high-fat diet, low-dose streptozotocin-induced type 2 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Emmanuel Anyachukwu Irondi

    2015-06-01

    Full Text Available Objective: To quantify some major pharmacologically important flavonoids and phenolic acids in Brachystegia eurycoma seed flour (BESF and evaluate its antidiabetic activity in type 2 diabetic rats. Method: Flavonoids and phenolic acids were quantified using a reverse-phase high pressure liquid chromatrography coupled with diode array detection. Type 2 diabetes was induced in rats using high-fat diet, low-dose streptozotocin (HFD/STZ model, by feeding the rats with HFD for 2 weeks followed by single dose administration of STZ (40 mg/kg body weight, intraperitoneally. The diabetic rats were later fed BESF-supplemented (10% and 20% diets, or administered with metformin (25 mg/kg b.w. for 21 days; the control rats were fed basal diet during this period. After the dietary regimen, the rats were sacrificed, and their blood, liver and pancreas samples were collected for biochemical assays. Results: The flavonoids (catechin, rutin, quercitrin, quercetin and kaempferol and phenolic acids (gallic acid, caffeic, chlorogenic and ellagic acid were abundant in BESF. BESFsupplemented diets (BESF-SD significantly (P 0.05 with metformin administration in some of the biomarkers. Conclusion: The flavonoids and phenolic acids in BESF may have acted synergistically to produce the observed antidiabetic effects. BESF could therefore be an effective and affordable dietary therapy for the management of T2DM; and an excellent source for drug discovery.

  10. High dose intravenous iron, mineral homeostasis and intact FGF23 in normal and uremic rats

    DEFF Research Database (Denmark)

    Gravesen, Eva; Hofman-Bang, Jacob; Mace, Maria L.

    2013-01-01

    High iron load might have a number of toxic effects in the organism. Recently intravenous (iv) iron has been proposed to induce elevation of fibroblast growth factor 23 (FGF23), hypophosphatemia and osteomalacia in iron deficient subjects. High levels of FGF23 are associated with increased...

  11. Protective effect of pioglitazone on cardiomyocyte apoptosis in low-dose streptozotocin & high-fat diet-induced type-2 diabetes in rats

    Directory of Open Access Journals (Sweden)

    Uma Bhandari

    2015-01-01

    Full Text Available Background & objectives: Cardiomyocyte apoptosis is one of the pathologic phenomena associated with diabetes and related conditions including obesity, insulin resistance and hyperlipidaemia. In the present study, the protective effects of pioglitazone on cardiomyocyte apoptosis was evaluated in experimental diabetes induced by low dose of streptozoticin (STZ combined with high fat diet (HFD in rats. Methods: Male Wistar rats (150-200 g were injected with low-dose STZ (45 mg/kg, i.v., single dose and orally fed with a HFD (20 g/day/rat for a period of 28 days and simultaneously treated with pioglitazone (20 mg/kg/p.o. for a period of 21 days (from 8 th day to 28 th day. On 29 th day blood was collected, serum separated and used for biochemical parameters. Heart tissue was used for cardiomyocyte apoptosis measurement and also for histopathological examination. Results: Pioglitazone treatment resulted in a decrease in cardiomyocyte apoptosis as revealed by a decrease in cardiac caspase-3, lactate dehydrogenase (LDH levels and DNA fragmentation, and an increase in Na+K+ATPase levels in diabetic rats. Cardiac histology of diabetic control rats showed dense focal fatty infiltration in the myocardial cells whereas normal architecture with regular morphology and well preserved cytoplasm was observed with pioglitazone treatment. Pioglitazone treatment significantly reduced the heart rate, mean arterial blood pressure, body mass index (BMI and levels of serum glucose, leptin, insulin, HOMA-IR, total cholesterol (TC and triglycerides (TGs, apoliproprotein-B glycosylated haemoglobin (HbA1c levels and atherogenic index, and increased the levels of serum high density lipoprotein cholesterol (HDL-C and cardiac antioxidant enzymes. Interpretation & conclusions: The present study results suggest that pioglitazone possesses cardiac anti-apoptotic potential in diabetic rat model and can be further explored for its use for treatment of diabetic cardiomyopathy.

  12. SR-TXRF analysis of trace elements in whole blood and heart of rats: effects of irradiation with low and high doses

    Science.gov (United States)

    Mota, C. L.; Pickler, A.; Braz, D.; Barroso, R. C.; Mantuano, A.; Salata, C.; Ferreira-Machado, S. C.; Lau, C. C.; de Almeida, C. E.

    2018-04-01

    In the last decades, studies showed that the exposure to low doses of ionizing radiation of the body could sense and activate the cell signaling pathways needed to respond to any induced cellular damage. This procedure reduces cell killing compared with a single dose of high radiation dose. Damage to the vasculature can affect the function of most body organs by restricting blood flow and oxygen to tissues; however, the heart and brain are of main concern. The precise relationship between long-term health effects and low-dose exposures remain poorly understood. Biological markers are powerful tools that can be used to determine dose- response relationships and to estimate risk, especially when dealing with, the effects of low dose exposures in humans. These markers should be specific, sensitive, as well as easy and fast to quantify. Various types of biologic specimens are potential candidates for identifying biomarkers but blood has the advantage of being minimally invasive to obtain. In this study, we propose to apply total reflection X-ray fluorescence to quantify possible chemical elemental concentration (sulfer, iron, zinc, potassium and calcium) changes in blood and heart tissues of Wistar rats after total body irradiation with low (0.1 Gy) and high (2.5 Gy) doses. The fluorescence measurements were carried out at the X-ray Fluorescence beamline in the Brazilian Synchrotron Light Laboratory. The results showed that the irradiated animals with low doses have significant alterations in blood and cardiac tissue when compared with animals that received high doses of radiation. Taken together the analysis of all the elements, we can observe that the radiation induced oxidative stress may be the leading cause for alteration of the elemental level in the studied samples.

  13. Swim Training Improves HOMA-IR in Type 2 Diabetes Induced by High Fat Diet and Low Dose of Streptozotocin in Male Rats.

    Science.gov (United States)

    Ghiasi, Rafigheh; Ghadiri Soufi, Farhad; Somi, Mohammad Hossein; Mohaddes, Gisou; Mirzaie Bavil, Fariba; Naderi, Roya; Alipour, Mohammad Reza

    2015-09-01

    Insulin resistance plays a key role in the onset and development of type 2 diabetes mellitus (T2DM) and its complications. In this study, we evaluated the effect of swim training on insulin resistance in diabetic rats. Forty male Wistar rats were randomly divided into four groups (n=10): sedentary control (Con), sedentary diabetic (Dia), swim trained control (Exe) and swim trained diabetic (Dia+Exe) rats. Diabetes was induced by high fat diet (HFD) and a low dose of streptozotocin (35 mg/kg, i.p). In trained groups, one week after the induction of diabetes, animals were subjected to swimming (60 min/5 days a week) for 10 weeks. At the end of training, fasting blood sugar (FBS), oral glucose tolerance test (OGTT), fasting/basal insulin, glycosylated hemoglobin (HbA1c) levels, insulin resistance index, homeostasis model assessment method (HOMA-IR), triglycerides (TG,) total cholesterol (TCh), and high density lipoprotein (HDL) levels in blood were measured. Swimming significantly improved OGTT (PHOMA-IR (P<0.01). Swim training also significantly decreased FBS (p<0.01), fasting/basal insulin (P<0.01), HbA1C (p<0.01), TG (P<0.05), and TCh (P<0.05) levels. It also significantly increased HDL (p<0.05) level. Our findings indicate that swim training improved glycemic control and insulin sensitivity in type 2 diabetes caused by high fat diet in male rats.

  14. Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homocysteine administration in rats.

    Science.gov (United States)

    Zhao, H; Ji, Z-H; Liu, C; Yu, X-Y

    2015-04-02

    Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Opposite effects of low and high doses of Abeta42 on electrical network and neuronal excitability in the rat prefrontal cortex.

    Science.gov (United States)

    Wang, Yun; Zhang, Guangping; Zhou, Hongwei; Barakat, Amey; Querfurth, Henry

    2009-12-21

    Changes in neuronal synchronization have been found in patients and animal models of Alzheimer's disease (AD). Synchronized behaviors within neuronal networks are important to such complex cognitive processes as working memory. The mechanisms behind these changes are not understood but may involve the action of soluble beta-amyloid (Abeta) on electrical networks. In order to determine if Abeta can induce changes in neuronal synchronization, the activities of pyramidal neurons were recorded in rat prefrontal cortical (PFC) slices under calcium-free conditions using multi-neuron patch clamp technique. Electrical network activities and synchronization among neurons were significantly inhibited by low dose Abeta42 (1 nM) and initially by high dose Abeta42 (500 nM). However, prolonged application of high dose Abeta42 resulted in network activation and tonic firing. Underlying these observations, we discovered that prolonged application of low and high doses of Abeta42 induced opposite changes in action potential (AP)-threshold and after-hyperpolarization (AHP) of neurons. Accordingly, low dose Abeta42 significantly increased the AP-threshold and deepened the AHP, making neurons less excitable. In contrast, high dose Abeta42 significantly reduced the AP-threshold and shallowed the AHP, making neurons more excitable. These results support a model that low dose Abeta42 released into the interstitium has a physiologic feedback role to dampen electrical network activity by reducing neuronal excitability. Higher concentrations of Abeta42 over time promote supra-synchronization between individual neurons by increasing their excitability. The latter may disrupt frontal-based cognitive processing and in some cases lead to epileptiform discharges.

  16. Opposite effects of low and high doses of Abeta42 on electrical network and neuronal excitability in the rat prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Yun Wang

    Full Text Available Changes in neuronal synchronization have been found in patients and animal models of Alzheimer's disease (AD. Synchronized behaviors within neuronal networks are important to such complex cognitive processes as working memory. The mechanisms behind these changes are not understood but may involve the action of soluble beta-amyloid (Abeta on electrical networks. In order to determine if Abeta can induce changes in neuronal synchronization, the activities of pyramidal neurons were recorded in rat prefrontal cortical (PFC slices under calcium-free conditions using multi-neuron patch clamp technique. Electrical network activities and synchronization among neurons were significantly inhibited by low dose Abeta42 (1 nM and initially by high dose Abeta42 (500 nM. However, prolonged application of high dose Abeta42 resulted in network activation and tonic firing. Underlying these observations, we discovered that prolonged application of low and high doses of Abeta42 induced opposite changes in action potential (AP-threshold and after-hyperpolarization (AHP of neurons. Accordingly, low dose Abeta42 significantly increased the AP-threshold and deepened the AHP, making neurons less excitable. In contrast, high dose Abeta42 significantly reduced the AP-threshold and shallowed the AHP, making neurons more excitable. These results support a model that low dose Abeta42 released into the interstitium has a physiologic feedback role to dampen electrical network activity by reducing neuronal excitability. Higher concentrations of Abeta42 over time promote supra-synchronization between individual neurons by increasing their excitability. The latter may disrupt frontal-based cognitive processing and in some cases lead to epileptiform discharges.

  17. Effects of dose, species, and dosing vehicle on the disposition of methacrylonitrile (MAN) in male rats

    International Nuclear Information System (INIS)

    Sanchez, I.M.; Ghanayem, B.I.

    1991-01-01

    MAN is structurally similar to known carcinogen acrylontrile (AN), with nitriles having similar industrial uses. Current studies were designed to investigate the biological fate of 2- 14 C-MAN in rats. After gavage administration of 115, 11.5 or 1.15 mg MAN/kg in water, F344 male rats were placed in glass metabolism cages and urine, expired air and feces were collected. Rats were sacrificed at various times and concentration of MAN-derived radioactivity in tissues was determined. MAN was rapidly absorbed from the GI tract and distributed to all major tissues. Sixty-70% of the low and medium doses were exhaled as 14 CO 2 in 72 hr compared to 25% of the highest dose. While 40% of the highest dose was expired as organic volatiles in 72 hr, only 9-12% of the low and accounted for 20-30% of all doses within 72 hr after dosing. Comparison of MAN disposition in Sprague-Dawley (SD) and F344 rats at 115 mg/kg revealed that SD rats excreted a greater % of the dose as 14 CO 2 and in the urine than did F344 rats. Administration of 115 mg MAN/kg to SD male rats in safflower oil resulted in increased elimination of MAN-derived radioactivity as CO 2 , volatiles, and in the urine over that observed when administered in water. These results suggest that: (1) saturation of MAN metabolism occurs at high doses: (2) MAN metabolism and disposition differ with the strain of rats studied; (3) MAN disposition may vary with the dosing vehicle used; and (4) MAN metabolism and disposition is apparently different from that reported on AN

  18. High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

    Science.gov (United States)

    Laorden, M L; Miralles, F S; Puig, M M

    1988-03-01

    The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

  19. Anti-diabetic effects of shubat in type 2 diabetic rats induced by combination of high-glucose-fat diet and low-dose streptozotocin.

    Science.gov (United States)

    Manaer, Tabusi; Yu, Lan; Zhang, Yi; Xiao, Xue-Jun; Nabi, Xin-Hua

    2015-07-01

    Shubat, probiotic fermented camel milk, has been used both as a drink with ethnic flavor and a medicine among Kazakh population for diabetic patients. Kazakh people have lower diabetic prevalence and impaired fasting glucose (IFG) than do other ethnic groups living in Xinjiang China, which might be related to the beneficial properties of shubat. We therefore prepared shubat in laboratory and tested anti-diabetic activity and evaluated its possible hypolipidemic and renoprotective effects in type 2 diabetic rats. Type 2 diabetic rats were induced by an administration of high-glucose-fat diet for 6 weeks and an intraperitoneal injection of streptozotocin (STZ, 30mg/kg). Diabetic rats were divided randomly into four groups and treated for 28 days with sitagliptin (30mg/kg) or shubat (6.97×10(6) lactic acid bacteria+2.20×10(4) yeasts) CFU/mL, (6.97×10(7) lactic acid bacteria+2.20×10(5) yeasts) CFU/mL and (6.97×10(8) lactic acid bacteria+2.20×10(6) yeasts) CFU/mL. In addition, a normal control group and a diabetic control group were used for comparison. All drugs were given orally once daily 10mL/kg for 4 weeks. Fasting blood glucose (FBG) and body weight (BW) were measured before treatment and every week thereafter. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), serum creatinine (SCr), blood urea nitrogen (BUN), C-peptide, glycated hemoglobin (HbAlc), glucagon-like peptide-1 (GLP-1) levels and pancreas tissue sections were tested after 4 weeks. Shubat demonstrated positive hypoglycemic activity on FBG, HbAlc, C-peptide and GLP-1 levels, high dose shubat decreased FBG (Pdiabetic controls. Histological analysis showed shubat protected the function of islets of type 2 diabetic rats. The results of this study indicate that shubat has significant hypoglycemic potential in T2D rats and may modulate lipid metabolism and protect renal function in the type 2 diabetic condition, which

  20. Chronic high-dose creatine has opposing effects on depression-related gene expression and behavior in intact and sex hormone-treated gonadectomized male and female rats.

    Science.gov (United States)

    Allen, Patricia J; DeBold, Joseph F; Rios, Maribel; Kanarek, Robin B

    2015-03-01

    Creatine is an antioxidant, neuromodulator and key regulator of energy metabolism shown to improve depressive symptoms in humans and animals, especially in females. To better understand the pharmacological effects of creatine, we examined its influence on depression-related hippocampal gene expression and behaviors in the presence and absence of sex steroids. Sham-operated and gonadectomized male and female rats were fed chow alone or chow blended with either 2% or 4% w/w creatine monohydrate for five weeks before forced swim, open field, and wire suspension tests, or seven weeks total. Before supplementation, males were chronically implanted with an empty or a testosterone-filled (T) capsule (10-mm surface release), and females were administered progesterone (P, 250 μg), estradiol benzoate (EB, 2.5 μg), EB+P, or sesame oil vehicle weekly. Relative to non-supplemented shams, all hippocampal plasticity-related mRNAs measured, including brain-derived neurotrophic factor (BDNF), tyrosine kinase B, doublecortin, calretinin, and calbindin, were downregulated in sham males given 4% creatine, and BDNF, doublecortin, and calbindin mRNAs were downregulated in sham females given 4% creatine. In contrast, combined 4% creatine+T in castrates prevented downregulation of BDNF, doublecortin, and calretinin mRNAs. Similarly, combined 4% creatine+EB+P in ovariectomized females attenuated downregulation of BDNF and calbindin mRNA levels. Moderate antidepressant and anxiolytic-like behaviors were observed in EB+P-treated ovariectomized females fed creatine, with similar trends in T-treated castrates fed creatine. Altogether, these data show that chronic, high-dose creatine has opposing effects on neuroplasticity-related genes and depressive behavior in intact and gonadectomized male and female rats. The dose and schedule of creatine used negatively impacted hippocampal neuronal integrity in otherwise healthy brains, possibly through negative compensatory changes in energy

  1. Dose dependent disposition of gallium-67 in rats

    International Nuclear Information System (INIS)

    Gautam, S.R.

    1982-01-01

    Radioactive gallium-67 has been employed as a diagnostic and follow-up agent for cancer therapy. Currently gallium nitrate is undergoing Phase I clinical studies. A million fold increase in the concentration of the carrier gallium citrate over the range of carrier-free gallium-67 (pgm) to 1.0 μg caused no significant alteration in the disposition of gallium-67 in rats.Gallium-67 was eliminated from blood with a biological t1/2 of 4.1 days. A linear tissue binding profile was observed for gallium-67 over this concentration range. A multi-compartment pharmacokinetic model was developed in which all the tissues studied were treated as separate compartments. At 1.0 mg dose level, significant alteration in the disposition of gallium-67 was observed in rats, > 95% of the initial radioactivity was characteristic reappearance of the radioactivity in the blood approximately 4 hours after dosing leading to a ''hump'' in the blood concentration-time profiles. Following the 1.0 mg dose low tissue levels were observed, except for the kidneys, which contained about 8% of the administered dose per gram of the tissue one-half hour after dosing. A non-linear tissue binding profile was observed to be associated with gallium at high doses. It was hypothesized that the rapid loss of gallium-67 from the vascular system following the high doses of gallium citrate was due to the accumulation of the drug in the kidneys where it was eventually eliminated via urine. The kidneys thus would act as a temporary storage site for gallium. It was concluded that the dose-related renal toxicity associated with gallium therapy may be attributed to the kidney's role as a temporary storage site following high doses

  2. Gamma dosimetry of high doses

    International Nuclear Information System (INIS)

    Martinez C, T.; Galvan G, A.; Canizal, G.

    1991-01-01

    The gamma dosimetry of high doses is problematic in almost all the classic dosemeters either based on the thermoluminescence, electric, chemical properties, etc., because they are saturated to very high dose and they are no longer useful. This work carries out an investigation in the interval of high doses. The solid system of heptahydrate ferrous sulfate, can be used as solid dosemeter of routine for high doses of radiation. The proposed method is simple, cheap and it doesn't require sophisticated spectrophotometers or spectrometers but expensive and not common in some laboratories

  3. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young [Department of Biomedical Engineering, and Research Institute of Biomedical Engineering, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2014-06-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  4. SU-E-I-34: Intermittent Low- and High-Dose Ethanol Exposure Alters Neurochemical Responses in Adult Rat Brain: An Ex Vivo 1H NMR Spectroscopy at 11.7 T

    International Nuclear Information System (INIS)

    Lee, Do-Wan; Kim, Sang-Young; Song, Kyu-Ho; Choe, Bo-Young

    2014-01-01

    Purpose: The first goal of this study was to determine the influence of the dose-dependent effects of intermittent ethanol intoxication on cerebral neurochemical responses among sham controls and low- and high-dose-ethanol-exposed rats with ex vivo high-resolution spectra. The second goal of this study was to determine the correlations between the metabolite-metabolite levels (pairs-of-metabolite levels) from all of the individual data from the frontal cortex of the intermittent ethanol-intoxicated rats. Methods: Eight-week-old male Wistar rats were divided into 3 groups. Twenty rats in the LDE (n = 10) and the HDE (n = 10) groups received ethanol doses of 1.5 g/kg and 2.5 g/kg, respectively, through oral gavage every 8-h for 4 days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz proton nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the 3 groups). Results: Normalized total-N-acetylaspartate (tNAA: NAA + NAAG [N-acetylaspartyl-glutamate]), gamma-aminobutyric acid (GABA), and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The 6 pairs of normalized metabolite levels were positively (+) or negatively (−) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and Aspartate (Asp) (−), myo-Inositol (mIns) and Asp (−), mIns and Alanine (+), mIns and Taurine (+), and mIns and tNAA (−). Conclusion: Our results suggested that repeated intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo 1H high-resolution-magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose

  5. The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Kira V. Derkach

    2015-01-01

    Full Text Available In the last years the treatment of type 2 diabetes mellitus (DM2 was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC activity in the hypothalamus and normalized AC stimulation by β-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.

  6. Conditioned instrumental behaviour in the rat: Effects of prenatal irradiation with various low dose-rate doses

    International Nuclear Information System (INIS)

    Klug, H.

    1986-01-01

    4 groups of rats of the Wistar-strain were subjected to γ-irradiation on the 16th day of gestation. 5 rats received 0,6 Gy low dose rate irradiation, 5 animals received 0,9 Gy low dose and 6 high dose irradiation, 3 females were shamirradiated. The male offspring of these 3 irradiation groups and 1 control group were tested for locomotor coordination on parallel bars and in a water maze. The female offspring were used in an operant conditioning test. The locomotor test showed slight impairment of locomotor coordination in those animals irradiated with 0,9 Gy high dose rate. Swimming ability was significantly impaired by irradiation with 0,9 Gy high dose rate. Performance in the operant conditioning task was improved by irradiation with 0,9 Gy both low and high dose rate. The 0,9 Gy high dose rate group learned faster than all the other groups. For the dose of 0,9 Gy a significant dose rate effect could be observed. For the dose of 0,6 Gy a similar tendency was observed, differences between 0,6 Gy high and low dose rate and controls not being significant. (orig./MG) [de

  7. Antidiabetic and Hypolipidemic Activities of Curculigo latifolia Fruit:Root Extract in High Fat Fed Diet and Low Dose STZ Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Nur Akmal Ishak

    2013-01-01

    Full Text Available Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD and 40 mg streptozotocin (STZ induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT, gamma glutamyltransferase (GGT, urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P<0.05 increase in body weight, high density lipoprotein (HDL, insulin, and adiponectin levels and decreased glucose, total cholesterol (TC, triglycerides (TG, low density lipoprotein (LDL, urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPARα, PPARγ, AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.

  8. Reproductive toxicity in rats after chronic oral exposure to low dose of depleted uranium

    International Nuclear Information System (INIS)

    Li Rong; Ai Guoping; Xu Hui; Su Yongping; Cheng Tianmin; Leng Yanbing

    2007-01-01

    Objective: To study the reproductive toxicity in rats induced by low dose of depleted uranium (DU). Methods: Male and female rats(F 0 generation) were exposed to DU in food at doses of 0, 0.4, 4 and 40 mg·kg -1 ·d -1 for 160 days, respectively. Then the activities of enzymes in testis and sexual hormone contents in serum were detected. Mature male rats were mated with female rats exposed to the same doses for 14 days. Pregnant rate and normal labor rate in F 0 rats were detected, as well as the survival rate and weight of F 1 rats within 21 d after birth. Results: No adverse effects of DU on fertility were evident at any dose in F 0 rats. Compared with control group, the rate of pregnancy, normal labor, survival of offspring birth and offspring nurture in F 1 generation of high-dose group reduced to 40.0%, 33.3%, 33.3%, and 33.3%, respectively. The sexual hormone contents in F 0 generation exposed increased, but those in Fl rats decreased significantly. The activities of lactate dehydrogenase-X (LDH-X) decreased in F 1 rats exposed to high-dose of DU, and those of sorbitol dehydrogenase (SDH), LDH and Na + -K + -ATPase decreased in F 1 rats exposed to DU. Conclusions: Reproduction function, growth and development of F 0 rats are not obviously affected after chronic oral exposure to DU, while the toxicity effects in F 1 generation was observed at any dose. (authors)

  9. High doses of garlic extract significantly attenuated the ratio of serum LDL to HDL level in rat-fed with hypercholesterolemia diet.

    Science.gov (United States)

    Ebrahimi, Tahereh; Behdad, Behnoosh; Abbasi, Maryam Agha; Rabati, Rahman Ghaffarzadegan; Fayyaz, Amir Farshid; Behnod, Vahid; Asgari, Ali

    2015-06-20

    Hypercholesterolemia is associated with an increased risk of heart disease. In this study, we investigated the antihyperlipidemic effects of garlic (Allium sativum L.) in rat models of hypercholesterolemic. Wistar male rats were randomly divided into 4 diet groups with garlic supplementation. Male Wistar rats were fed by standard pellet diet (group I), standard diet supplemented with 4% garlic (group II), lipogenic diet (containing sunflower oil, cholesterol and ethanol) equivalent to 200 mg raw garlic/kg body weight (raw) (group III) and lipogenic diet equivalent to 400 mg raw garlic/kg body weight (raw) (group IV). Rats fed 400 g/kg garlic extract(GE), had a significantly lower concentration of serum low-density lipoprotein cholesterol (LDL-C) cholesterol and elevated HDL -C cholesterol at day 28 (P garlic supplementation (P garlic in reducing lateral side effects of hyperlipidemia. Our data demonstrate that GE has protective effects on HDL in rats with high LDL intake. Therefore, it could be used to remedy hypercholesterolemia with help reduce risk of coronary heart disease The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1834155749171141.

  10. Dynamics of pathomorphological changes in rat brain as a function of γ-radiation dose

    International Nuclear Information System (INIS)

    Fedorov, V.P.

    1990-01-01

    Neurohistological, histochemical, electron-microscopic and biometric techniques were used to study the response of rat brain to irradiation within a wide range of doses. Nerve cells were shown to be highly radioresistant. At the same time, synapses and blood-brain barrier structures were highly radiosensitive. The pathomorphologic changes in different brain areas followed a dose-time function

  11. Photochemically-induced ischemia of the rat sciatic nerve produces a dose-dependent and highly reproducible mechanical, heat and cold allodynia, and signs of spontaneous pain.

    Science.gov (United States)

    Kupers, R; Yu, W; Persson, J K; Xu, X J; Wiesenfeld-Hallin, Z

    1998-05-01

    Sensory abnormalities and changes in spontaneous behavior were examined after a photochemically induced ischemic lesion of the rat sciatic nerve. Male adult rats were anesthetized and the sciatic nerve was exposed. After the intravenous injection of a photosensitizing dye, erythrosin B, the exposed nerve was irradiated just proximal to the nerve trifurcation with light from an argon laser. Three different irradiation times were used, 30 s, 1 and 2 min. In sham-operated rats, the exposed sciatic nerve was irradiated for 2 min without prior injection of the erythrosin B. Rats were tested for the presence of mechanical, cold and heat allodynia or hyperalgesia. All the animals in the 1- and 2-min irradiation groups developed mechanical, cold and heat allodynia after nerve irradiation. A significant dose-dependent effect of laser exposure time was observed for all modalities tested (2 min > 1 min > 30 s = sham). The maximum effects were observed at 3 and 7 days postirradiation and remained present for up to 10 weeks. No significant contralateral effects were observed in any of the groups. In three separate groups of rats (1, 2 and 4 min of laser exposure), the presence of possible signs of spontaneous pain (paw shaking, paw elevation and freezing behavior) was tested. A significant and exposure time-dependent increase in spontaneous paw elevation and paw shaking was observed which was maximal at week 1, but resolved at 4 weeks (4 min > 2 min > 1 min > sham). In addition, animals in all ischemic groups, but not in the sham group, showed a significant increase in freezing behavior up to 4 weeks after nerve irradiation. Light microscopic evaluation of nerves removed 7 days post-irradiation, i.e. when maximal allodynia was observed, showed clear evidence of demyelination of large myelinated fibers. These data indicate that photochemically-induced peripheral nerve ischemia is associated with abnormal pain-related behaviors, including mechanical, thermal and cold allodynia

  12. Performance of rats orogastrically dosed with faecal strains of ...

    African Journals Online (AJOL)

    Albino rats (Rattus norvegicus) were orogastrically dosed with faecal strains of Lactobacillus acidophilus and simultaneously infected with Escherichia coli, while the control was challenged with E. coli alone. The treatment was repeated the second day and post ingestion period of 18 days follow. It was observed that rats ...

  13. Immune reactivity after high-dose irradiation

    International Nuclear Information System (INIS)

    Gassmann, W.; Wottge, H.U.; von Kolzynski, M.; Mueller-Ruchholtz, W.

    1986-01-01

    Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient

  14. CONTRASTING DOSE-RATE EFFECTS OF GAMMA-IRRADIATION ON RAT SALIVARY-GLAND FUNCTION

    NARCIS (Netherlands)

    VISSINK, A; DOWN, JD; KONINGS, AWT

    The aim of this study was to investigate the effects of Co-60 irradiation delivered at high (HDR) and low (LDR) dose-rates on rat salivary gland function. Total-body irradiation (TBI; total doses 7.5, 10 and 12.5 Gy) was applied from a Co-60 source at dose-rates of 1 cGy/min (LDR) and 40 cGy/min

  15. High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats.

    Science.gov (United States)

    Brückner, Melanie; Lasarzik, Irina; Jahn-Eimermacher, Antje; Peetz, Dirk; Werner, Christian; Engelhard, Kristin; Thal, Serge C

    2013-09-13

    Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mm Hg for 14 min and a subsequent 5h-infusion of rhAPC (2mg/kg bolus+6 mg/kg/h continuous IV) or vehicle (0.9% NaCl). The dosage was calculated to maintain plasma hAPC activity at 150%. Cerebral inflammation, apoptosis and neuronal survival was determined at day 10. rhAPC infusion did not influence cortical cerebral perfusion during reperfusion and failed to reduce neuronal cell loss, microglia activation, and caspase 3 activity. Even an optimized rhAPC infusion protocol designed to maintain a high level of APC plasma activity failed to improve the sequels following GI. Despite positive reports about protective effects of APC following, e.g., ischemic stroke, the present study supports the notion that infusion of APC during the early reperfusion phase does not result in sustained neuroprotection and fails to improve outcome after global cerebral ischemia. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Optimized dose distribution of a high dose rate vaginal cylinder

    International Nuclear Information System (INIS)

    Li Zuofeng; Liu, Chihray; Palta, Jatinder R.

    1998-01-01

    Purpose: To present a comparison of optimized dose distributions for a set of high-dose-rate (HDR) vaginal cylinders calculated by a commercial treatment-planning system with benchmark calculations using Monte-Carlo-calculated dosimetry data. Methods and Materials: Optimized dose distributions using both an isotropic and an anisotropic dose calculation model were obtained for a set of HDR vaginal cylinders. Mathematical optimization techniques available in the computer treatment-planning system were used to calculate dwell times and positions. These dose distributions were compared with benchmark calculations with TG43 formalism and using Monte-Carlo-calculated data. The same dwell times and positions were used for a quantitative comparison of dose calculated with three dose models. Results: The isotropic dose calculation model can result in discrepancies as high as 50%. The anisotropic dose calculation model compared better with benchmark calculations. The differences were more significant at the apex of the vaginal cylinder, which is typically used as the prescription point. Conclusion: Dose calculation models available in a computer treatment-planning system must be evaluated carefully to ensure their correct application. It should also be noted that when optimized dose distribution at a distance from the cylinder surface is calculated using an accurate dose calculation model, the vaginal mucosa dose becomes significantly higher, and therefore should be carefully monitored

  17. Glucemia, insulinemia y secreción de insulina en ratas prepúberes hiperandrogenizadas e hiperestrogenizadas Glycemia, insulinemia and insulin secretion in prepubescent rats receiving high doses of androgens and strogens

    Directory of Open Access Journals (Sweden)

    Aimée Álvarez Álvarez

    2001-04-01

    Full Text Available Se estudió el efecto de una sobredosis de enantato de testosterona y de benzoato de estradiol en ratas machos prepúberes, sobre el comportamiento de la glucemia y la insulinemia in vivo, durante una prueba de tolerancia a la glucosa. Adicionalmente se exploró, in vitro, la capacidad de secreción de insulina estimulada por glucosa de los islotes de Langerhans de estas ratas hiperandrogenizadas e hiperestrogenizadas. Se encontró que la hiperandrogenización se acompañaba de un deterioro de la sensibilidad a la insulina, con hiperinsulinemia, que no se corresponde con un aumento de la capacidad de secreción de insulina de los islotes de Langerhans. Sin embargo, se comprobó que la hiperestrogenización no indujo cambios en los perfiles de glucemia, ni de insulinemia, ni en la capacidad de secreción de insulina de los islotes de Langerhans de este grupo de ratas hiperestrogenizadas.The effect of an overdose of testosterone heptanoate and estradiol in male prepubescent rats on the behavior of glycemia and insulinemia was studied in vivo during a glucose tolerance test. The capacity of insulin secretion stimulated by glucose from the islets of Langerhans of these rats that were administered a high dose of androgens and estrogens was explored in vitro. It was found that the high level of circulating androgens was accompanied by a deterioration of sensitivity to insulin with hyperinsulinemia that does not correspond to an increase of the insulin secreting capacity of the islets of Langerhans. However, it was demonstrated that the high level of circulating estrogens did not produce changes either in the glycemia and insulinemia profiles or in the insulin secreting capacity of the islets of Langerhans in this group of rats that received an elevated dose of estrogens.

  18. Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

    Directory of Open Access Journals (Sweden)

    Kristen Ashley eHorner

    2011-05-01

    Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

  19. Biochemical parameters of pregnant rats and their offspring exposed to different doses of inorganic mercury in drinking water.

    Science.gov (United States)

    Oliveira, Cláudia S; Oliveira, Vitor A; Ineu, Rafael P; Moraes-Silva, Lucélia; Pereira, Maria E

    2012-07-01

    This work investigated the effects of low and high doses of inorganic mercury in drinking water on biochemical parameters of pregnant rats and their offspring. Female Wistar rats were treated during pregnancy with 0, 0.2, 0.5, 10 or 50 μg Hg(2+)/mL as HgCl(2). Rats were euthanized on day 20 of pregnancy. Pregnant rats presented a decrease in total water intake in all doses of mercury tested. At high doses, a decrease in the total food intake and in body weight gain was observed. Pregnant rats exposed to 50 μg Hg(2+)/mL presented an increase in kidney relative weight. Mercury exposure did not change serum urea and creatinine levels in any of the doses tested. Moreover, mercury exposure did not change porphobilinogen synthase activity of kidney, liver and placenta from pregnant rats in any of the doses tested, whereas fetuses of pregnant rats exposed to 50 μg Hg(2+)/mL presented an increase in the hepatic porphobilinogen synthase activity. In general, pregnant rats presented alterations due to HgCl(2) exposure in drinking water. However, only the dose 50 μg Hg(2+)/mL appeared to be enough to cross the blood-placenta barrier, since at this dose the fetuses presented change in the porphobilinogen synthase activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. Chronic treatment of (R)-α-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats.

    Science.gov (United States)

    Ghelani, Hardik; Razmovski-Naumovski, Valentina; Nammi, Srinivas

    2017-06-01

    (R)- α -lipoic acid ( ALA ), an essential cofactor in mitochondrial respiration and a potential antioxidant, possesses a wide array of metabolic benefits including anti-obesity, glucose lowering, insulin-sensitizing, and lipid-lowering effects. In this study, the curative effects of ALA (100 mg/kg) on a spectrum of conditions related to metabolic syndrome and type 2 diabetes ( T2D ) were investigated in a high-fat diet (HFD)-fed and low-dose streptozotocin (STZ)-induced rat model of metabolic syndrome and T2D . The marked rise in the levels of glucose, triglycerides, total-cholesterol, LDL-cholesterol, and VLDL-cholesterol in the blood of HFD-fed and low-dose STZ-injected rats were significantly reduced by ALA treatment. Furthermore, ALA treatment significantly increased the serum HDL-cholesterol levels and tended to inhibit diabetes-induced weight reduction. Mathematical computational analysis revealed that ALA also significantly improved insulin sensitivity and reduced the risk of atherosclerotic lesions and coronary atherogenesis. This study provides scientific evidence to substantiate the use of ALA to mitigate the glucose and lipid abnormality in metabolic syndrome and T2D .

  1. Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol

    Directory of Open Access Journals (Sweden)

    Reihaneh Sadeghian

    2012-11-01

    Full Text Available The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001. The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1 than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively. Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001. These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.

  2. Performance of rats orogastrically dosed with faecal strains of ...

    African Journals Online (AJOL)

    Administrator

    strains of Lactobacillus acidophilus and challenged ... Albino rats (Rattus norvegicus) were orogastrically dosed with faecal strains of Lactobacillus .... Chang et al. (2001) reported a similar observation in piglets fed probiotic strain, Lactobacillus reuteri BSA 131. Francisco et al. (1995) had earlier reported that selected ...

  3. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo

    2013-05-01

    Full Text Available In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001. In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001. In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001. It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

  4. Dose and time dependent ototoxicity of aspartame in rats.

    Science.gov (United States)

    Ozturan, Orhan; Dogan, Remzi; Tugrul, Selahattin; Gedik, Ozge; Sjostrand, Alev Pektas; Yildirim, Yavuz Selim

    2017-04-01

    Low-dose administration of Aspartame (Ap) did not produce a significant ototoxic effect at the end of the 6th month. However, duration of the ototoxic effect is shortened and severity of the effect is increased as dose and duration of Ap administration is increased. While Ap toxicity has been studied in short- and long-term studies, its effects on hearing have not been investigated. This study was conducted to evaluate the effects of long-term consumption of Ap administered in various doses on hearing status of rats. The study included 54 female Wistar Albino rats. Ap was given for 6 months to the rats. The groups were assigned according to levels of Ap dosage. DPOAE and ABR tests were utilized for serial hearing evaluations. Serial hearing measurement times were designed as baseline, 1st week, 2nd week, 1st, 2nd, 3rd, and 6th months. While audiological parameters deteriorated with 100 mg/kg/day dose after the 3rd month, ABR thresholds were elevated and DPOAE values were significantly decreased in 500 mg/kg/day and 1000 mg/kg/day applications after the 2nd month. In 2000 mg/kg/day and 4000 mg/kg/day applications, deteriorations in audiological parameters were detected as early as the first and second months; respectively.

  5. Pharmacokinetically guided dosing of (high-dose) chemotherapeutic agents

    NARCIS (Netherlands)

    Attema-de Jonge, M.E. (Milly Ellen)

    2004-01-01

    Due to variation in drug distribution, metabolism and elimination processes between patients, systemic exposure to chemotherapeutic agents may be highly variable from patient to patient after administration of similar doses. This pharmacokinetic variability may explain in part the large variability

  6. Safety assessments of subcutaneous doses of aragonite calcium carbonate nanocrystals in rats

    Science.gov (United States)

    Jaji, Alhaji Zubair; Zakaria, Zuki Abu Bakar; Mahmud, Rozi; Loqman, Mohamad Yusof; Hezmee, Mohamad Noor Mohamad; Abba, Yusuf; Isa, Tijani; Mahmood, Saffanah Khuder

    2017-05-01

    Calcium carbonate nanoparticles have shown promising potentials in the delivery of drugs and metabolites. There is however, a paucity of information on the safety of their intentional or accidental over exposures to biological systems and general health safety. To this end, this study aims at documenting information on the safety of subcutaneous doses of biogenic nanocrystals of aragonite polymorph of calcium carbonate derived from cockle shells (ANC) in Sprague-Dawley (SD) rats. ANC was synthesized using the top-down method, characterized using the transmission electron microscopy and field emission scanning electron microscope and its acute and repeated dose 28-day trial toxicities were evaluated in SD rats. The results showed that the homogenous 30 ± 5 nm-sized spherical pure aragonite nanocrystals were not associated with mortality in the rats. Severe clinical signs and gross and histopathological lesions, indicating organ toxicities, were recorded in the acute toxicity (29,500 mg/m2) group and the high dose (5900 mg/m2) group of the repeated dose 28-day trial. However, the medium- (590 mg/m2 body weight) and low (59 mg/m2)-dose groups showed moderate to mild lesions. The relatively mild lesions observed in the low toxicity dosage group marked the safety margin of ANC in SD rats. It was concluded from this study that the toxicity of CaCO3 was dependent on the particulate size (30 ± 5 nm) and concentration and the route of administration used.

  7. Fiber optics in high dose radiation fields

    International Nuclear Information System (INIS)

    Partin, J.K.

    1985-01-01

    A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

  8. Postnatal development of resistance to short-term high-dose toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in TCDD-resistant and -semiresistant rats

    International Nuclear Information System (INIS)

    Simanainen, Ulla; Tuomisto, Jouni T.; Pohjanvirta, Raimo; Syrjaelae, Paula; Tuomisto, Jouko; Viluksela, Matti

    2004-01-01

    Despite great interspecies differences in adult 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) sensitivity, the toxic potency of TCDD is similar across species in fetal mortality. Han/Wistar (Kuopio; H/W) rats are exceptionally resistant to acute toxicity of TCDD, but show sensitivity to embryotoxicity and teratogenicity. The resistance of adult H/W rats to acute TCDD toxicity is based on a point mutation in the transactivation domain of the aryl hydrocarbon receptor (AHR) and to an unknown gene ''B''. This study investigated the time course of postnatal development of resistance to TCDD and the significance of genotypic variation in resistance development. H/W, line A (a new line with the H/W-type mutated AHR), and line B rats (a line with normal AHR but moderately resistant because of gene ''B'') were exposed to a single dose of TCDD 2-56 days after birth. H/W and line A rats received 1000 μg/kg; male and female B rats received 200 and 100 μg/kg, respectively. Survival was monitored for 42 days. Interestingly, although TCDD ceased growth and weight gain in all TCDD groups, the younger dosed animals did not seem to reach the body weight of the older dosed animals even in 100 days. The survival results after 42 days showed that line A rats are fairly resistant to TCDD immediately after birth, and their full TCDD resistance develops during the first week of life. The moderate resistance of line B rats develops approximately at the time of weaning. This difference in the time course of resistance development suggests that there are basic differences in pathways mediating resistance in lines A and B rats

  9. Dose response of rat retinal microvessels to proton dose schedules used clinically: a pilot study

    International Nuclear Information System (INIS)

    Archambeau, John O.; Mao, Xiao W.; McMillan, Paul J.; Gouloumet, Vanessa L.; Oeinck, Steven C.; Grove, Roger; Yonemoto, Leslie T.; Slater, Jerry D.; Slater, James M.

    2000-01-01

    Purpose: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation Methods and Materials: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. Results: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p 0 phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. Conclusion: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density

  10. Metabolic kinetics and absorbed doses of 137Cs in lactating rats and progeny during suckling

    International Nuclear Information System (INIS)

    Lyaginskaya, A.M.; Osipov, V.A.; Dement'ev, S.I.; Ermalitskij, A.P.

    2000-01-01

    The transfer of 137 Cs with maternal milk to progeny was studied in rats The rats were administered with 25 kBq/g of 137 Cs nitrate (pH = 6) in a single oral dose immediately after delivery. Nonpregnant females served as control. Absorbed doses per activity unit to lactating rats were 23 % lover than to nonlactating ones. Over the suckling period absorbed doses to young rats amounted to about 35 % of the absorbed dose to the nursing female. For nonlactating females the internal dose approximately equalled the sum of doses to the nursing female and young rats. Lactating is the effective way for removal of 1 '3 7 Cs from organism of the rats. Content of 1 '3 7 Cs in lactating rat becomes on 42.9 % lower than in organism of nonlactating rat during period of lactating (near 20 days) [ru

  11. Endorectal high dose rate brachytherapy quality assurance

    International Nuclear Information System (INIS)

    Devic, S.; Vuong, T.; Evans, M.; Podgorsak, E.

    2008-01-01

    We describe our quality assurance method for preoperative high dose rate (HDR) brachytherapy of endorectal tumours. Reproduction of the treatment planning dose distribution on a daily basis is crucial for treatment success. Due to the cylindrical symmetry, two types of adjustments are necessary: applicator rotation and dose distribution shift along the applicator axis. (author)

  12. The Effect of Different Doses of Vitamin D Supplementation on Insulin Resistance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Rastegar Hoseini

    2016-04-01

    Full Text Available Background and Aim: Type 2 diabetes mellitus (T2DM and vitamin D deficiency are both too common during menopause. Since the effect of different doses of vitamin D supplements on blood sugar, insulin concentration  and insulin resistance are unknown, the present study aimed at investigating the effects of different doses of the vitamin D supplements on visceral fat, blood sugar, insulin concentration,  and insulin resistance in ovariectomized rats. Materials and Methods: In this randomized experimental study, 32 female Wistar rats were divided into 4 equal groups  as follows: three groups . that received vitamin D supplements (high, moderate, and low dose and one control group. After 8 weeks of different doses of vitamin D supplementation plasma concentration of glucose, insulin and HOMA-IR were measured  in the three groups. The obtained data  was statistically analyzed by means of dependent t-test and ANOVA . at the significance level of P<0.05. Results: After a period of eight-week  intervention, body weight, BMI, waist circumference, visceral fat, insulin, blood glucose and HOMA-IR at high, moderate, and low doses of vitamin D supplementation were significantly lower than those in the control group (P<0.05. High dose of vitamin D compared with moderate and low doses significantly caused reduction in insulin, blood glucose, and HOMA-IR (P<0.001 for all three variables. Conclusion: The findings of the current study showed that a high dose of vitamin D causes significant improvements in FPG, insulin, and insulin resistance  evaluated by HOMA-IR. It was also found that adding vitamin D supplements can improve glucose control in menopause model of rats.

  13. Progress in high-dose radiation dosimetry

    International Nuclear Information System (INIS)

    Ettinger, K.V.; Nam, J.W.; McLaughlin, W.L.; Chadwick, K.H.

    1981-01-01

    The last decade has witnessed a deluge of new high-dose dosimetry techniques and expanded applications of methods developed earlier. Many of the principal systems are calibrated by means of calorimetry, although production of heat is not always the final radiation effect of interest. Reference systems also include a number of chemical dose meters: ferrous sulphate, ferrous-cupric sulphate, and ceric sulphate acidic aqueous solutions. Requirements for stable and reliable transfer dose meters have led to further developments of several important high-dose systems: amino acids and saccharides analysed by ESR or lyoluminescence, thermoluminescent materials, radiochromic dyes and plastics, ceric-cerous solutions analysed by potentiometry, and ethanol-chlorobenzene solutions analysed by high-frequency oscillometry. A number of other prospective dose meters are also treated in this review. In addition, an IAEA programme of high-dose standardization and intercomparison for industrial radiation processing is described. (author)

  14. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration

    OpenAIRE

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2011-01-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent (i.e., postnatal day (PND) 40) rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a “challenge” high-dose METH regimen when administered ...

  15. Histopathological, Ultrastructural, and Immunohistochemical Assessment of Hippocampus Structures of Rats Exposed to TCDD and High Doses of Tocopherol and Acetylsalicylic Acid

    Directory of Open Access Journals (Sweden)

    Joanna Rosińczuk

    2015-01-01

    Full Text Available The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD on central nervous system consists of changing expression of estrogen receptors, whereas the result of chronic inflammatory reaction caused by dioxin is occurrence of destructive changes in various organs connected with disturbed metabolism of connective tissue and damage of cells. The aim of the study was to determine the effect of dioxins on function, ultrastructure, and cytological and histological structure of hippocampus, particularly on expression of estrogen receptors in central nervous system as well as to define protective influence of tocopherol (TCP and acetylsalicylic acid (ASA on the decrease in activity of proinflammatory effects in central nervous system. It was shown that TCDD contributes to destructive and inflammatory changes along with demyelization of myelin sheaths and atrophy of estrogen receptors in hippocampus. Dioxin contributes to atrophy of estrogen receptors in hippocampus, in which also destructive and inflammatory changes were found along with demyelination of myelin sheaths. Histopathological and ultrastructural image of hippocampus areas in rats, in which both TCP and ASA were used, is characterized by poorly expressed degenerative changes and smaller inflammatory reactivity. Using both TCP and ASA has a protective effect on functions of central nervous system.

  16. Escalating dose, multiple binge methamphetamine regimen does not impair recognition memory in rats.

    Science.gov (United States)

    Clark, Robert E; Kuczenski, Ronald; Segal, David S

    2007-07-01

    Rats exposed to methamphetamine (METH) in an acute high dose "binge" pattern have been reported to exhibit a persistent deficit in a novel object recognition (NOR) task, which may suggest a potential risk for human METH abusers. However, most high dose METH abusers initially use lower doses before progressively increasing the dose, only eventually engaging in multiple daily administrations. To simulate this pattern of METH exposure, we administered progressively increasing doses of METH to rats over a 14 day interval, then treated them with daily METH binges for 11 days. This treatment resulted in a persistent deficit in striatal dopamine (DA) levels of approximately 20%. We then tested them in a NOR task under a variety of conditions. We could not detect a deficit in their performance in the NOR task under any of the testing conditions. These results suggest that mechanisms other than or additional to the decrement in striatal DA associated with an acute METH binge are responsible for the deficit in the NOR task, and that neuroadaptations consequential to prolonged escalating dose METH pretreatment mitigate against these mechanisms.

  17. Monte Carlo-based dose reconstruction in a rat model for scattered ionizing radiation investigations.

    Science.gov (United States)

    Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Anna; Kolb, Bryan; Kovalchuk, Olga

    2013-09-01

    In radiation biology, rats are often irradiated, but the precise dose distributions are often lacking, particularly in areas that receive scatter radiation. We used a non-dedicated set of resources to calculate detailed dose distributions, including doses to peripheral organs well outside of the primary field, in common rat exposure settings. We conducted a detailed dose reconstruction in a rat through an analog to the conventional human treatment planning process. The process consisted of: (i) Characterizing source properties of an X-ray irradiator system, (ii) acquiring a computed tomography (CT) scan of a rat model, and (iii) using a Monte Carlo (MC) dose calculation engine to generate the dose distribution within the rat model. We considered cranial and liver irradiation scenarios where the rest of the body was protected by a lead shield. Organs of interest were the brain, liver and gonads. The study also included paired scenarios where the dose to adjacent, shielded rats was determined as a potential control for analysis of bystander effects. We established the precise doses and dose distributions delivered to the peripheral organs in single and paired rats. Mean doses to non-targeted organs in irradiated rats ranged from 0.03-0.1% of the reference platform dose. Mean doses to the adjacent rat peripheral organs were consistent to within 10% those of the directly irradiated rat. This work provided details of dose distributions in rat models under common irradiation conditions and established an effective scenario for delivering only scattered radiation consistent with that in a directly irradiated rat.

  18. Growth of extrapulmonary tumours after inhalation of small doses of plutonium oxide by rats

    International Nuclear Information System (INIS)

    Nolibe, D.; Masse, R.; L'Hullier, I.; Metivier, H.; Lafuma, J.

    1983-01-01

    After inhalation of plutonium oxide ( 239 PuO 2 ) involving initial lung burdens ranging from 74 to 103 Bq, male rats of the Wistar strain are kept in conditions allowing maximum survival; tumour incidences for the target organ (lung) and for the rest of the organs are calculated separately after the death of the animals. In the outbred Wistar rat the incidence of lung tumours is 18.5% for an initial lung burden of 74 Bq. The mean survival time of animals having such tumours is 973 days after inhalation. For an initial burden of 103 Bq syngenetic Wistar AG rats show a lower frequency of lung tumours (6.1%), but also a much reduced mean survival time, namely 757 days. Compared with the frequencies observed in the corresponding control groups, the frequency of non-pulmonary tumours is twice as high (12%) in consanguineous rats and six times as high (25.9%) in conventional rats. A supralinear dose-effect relationship at very low doses seems improbable in view of the dose delivered ( -3 Gy in the most exposed organs, such as the liver) and, in particular, because there is no correlation between the dose delivered to the organs and the location of the tumours. The exposed animals show, on the one hand, no specificity of organs for the surplus extrapulmonary tumours observed, and on the other, an inhibition by about 45% in the natural cytotoxic activity (natural killers) measured one year after inhalation. These observations suggest the hypothesis that an anti-tumour control mechanism is affected, perhaps as a result of the irradiation experienced during the circulation of blood cells in the lung capillaries. The failure of this system would in that case allow the expression of neoplastic characters as ageing progresses. A non-specific BCG immunotherapy does not restore this anti-tumour control system. (author)

  19. Beneficial effects of low dose Musa paradisiaca on the semen quality of male Wistar rats.

    Science.gov (United States)

    Alabi, A S; Omotoso, Gabriel O; Enaibe, B U; Akinola, O B; Tagoe, C N B

    2013-03-01

    This study aimed at determining the effects of administration of mature green fruits of Musa paradisiaca on the semen quality of adult male Wistar rats. THE ANIMALS USED FOR THE STUDY WERE GROUPED INTO THREE: the control group, given 2 ml of double distilled water, a low dose group given 500 mg/kg/day and a high dose group given 1000 mg/kg/day of the plantain fruits, which was made into flour, and dissolved in 2 ml of double distilled water for easy oral administration. Significant increment in the semen parameters was noticed in animals that received a lower dose of the plantain flour, but those animals who received the high dose had marked and very significant reduction in sperm cell concentration and percentage of morphologically normal spermatozoa. Musa paradisiaca should be consumed in moderate quantities in order to derive its beneficial effects of enhancing male reproductive functions.

  20. Serum metabonomics of rats irradiated by low-dose γ-rays

    Directory of Open Access Journals (Sweden)

    Ying HE

    2014-08-01

    Full Text Available Objective To explore the effect of low-dose γ-rays on the metabolites in rat serum. Methods Sixteen healthy male SD rats were randomly divided into control group and irradiated group (n=8. The rats in irradiated group were irradiated by 60Co γ-rays with a dose rate of 72mGy/h for 7 days (1 hour per day. At the 7th day after irradiation, blood samples were taken from abdominal aorta to obtain the serum. The metabolic fingerprints of serum were obtained from the two groups of rats, and 1H nuclear magnetic resonance (NMR spectroscopy, principal component analysis (PCA and orthogonal signal correction-partial least squares (OSC-PLS method were used for pattern recognition, and the difference in metabolite profile between two groups was identified by SIMCA-P software. Results The rat serum 1H NMR spectra revealed a significant difference between control group and irradiated group, the OSC-PLS plots of the serum samples presented marked clustering between two groups. Compared with the control group, the content of lipid, glucose, creatine, glycine/glucose, high density lipoprotein, low density lipoprotein, very low density lipoprotein/low density lipoprotein and unsaturated fatty acid increased, while the content of lactic acid, threonine/lipid, alanine, N-acetyl glycoprotein 1, N-acetyl glycoprotein 2, saturated fatty acid and phosphatidyl choline decreased in irradiated group. Conclusion Irradiation with low-dose γ-ray could induce changes in metabolites in rat serum, concerning mainly immune function, energy metabolism, carbohydrate metabolism and lipid metabolism. DOI: 10.11855/j.issn.0577-7402.2014.07.02

  1. Influence of different doses of octenidine hexafluorosilicate on parodontotium state of rat, which received cariesogenic ration

    Directory of Open Access Journals (Sweden)

    V. Yu. Anisimov

    2017-06-01

    Full Text Available Aim: To determine of parodontium state of rat, which received cariesogenic ration and different doses of octenidine hexafluorosilicate (O-HFS. Methods: The octenidine hexafluorosilicate was synthesized by us and was used into mucoso-adgesive gels (Na-CMC in next concentrations: 1 mg/ml, 2 mg/ml and 4 mg/ml. The rats received high-sugar cariesogenic ration and oral applications of gels with O-HFS in doses of 0,3 ml (daily doses of O-HFS were 1,4 mg/kg, 2,8 mg/kg and 5,6 mg/kg. The duration of experiment was 35 days. The activities of urease, lysozyme and elastase were determined into gum. The activities of urease, lysozyme, ALT and alkaline phosphatase (APh were determined into serum. The degree of dysbiosis calculated by ration urease and lysozyme. The degree of atrophy of parodontale bone was determined by Nicolaeva method. Results: The activities of elastase and urease, the degree of atrophy and dysbiosis were raised into gum of rat, which received cariesogenic ration. The activities of ALT and APh, the degree of dysbiosis were raised into serum. The oral application of O-HFS-gels decreased the all these indices. The maximal action made O-HFS-gel in dose 2,8 mg/kg. Conclusion: The oral application of O-HFS-gel make parodontoprotective action.

  2. Dose dependent transfer of 203lead to milk and tissue uptake in suckling offspring studied in rats and mice

    International Nuclear Information System (INIS)

    Palminger Hallen, I.; Oskarsson, A.

    1993-01-01

    The dose-dependent transfer of 203 Pb to milk and uptake in suckling rats and mice during a three-day nursing period was studied. On day 14 of lactation, the dams were administered a single intravenous dose of lead, labelled with 203 Pb, in four or five doses from 0.0005 to 2.0 mg Pb/kg b.wt. There was a linear relationship between Pb levels in plasma and milk of both species. The Pb milk: plasma ratios at 24 hr after administration were 119 and 89 in mice and rats, respectively. At 72 hr the Pb milk: plasma ratio had decreased to 72 in mice and 35 in rats. The tissue levels of lead in the suckling rats and mice were also linearly correlated with lead concentration in milk at 72 hr, showing that milk could be used as an indicator of lead exposure to the suckling offspring. It is concluded that lead is transported into rat and mouse milk to a very high extent and the excretion into milk is more efficient in mice than in rats. On the other hand, rat pups had higher lead levels in tissues than mice pups, which might be due to a higher bioavailability and/or a lower excretion of lead in rat pups. Thus, lead in breast milk could be used as a biological indicator of lead exposure in the mother as well as in the suckling offspring. (au) (38 refs.)

  3. Doping dose of salbutamol and exercise training: impact on the skeleton of ovariectomized rats.

    Science.gov (United States)

    Bonnet, N; Laroche, N; Beaupied, H; Vico, L; Dolleans, E; Benhamou, C L; Courteix, D

    2007-08-01

    Previous studies in healthy rats have demonstrated a deleterious bone impact of beta-agonist treatment. The purpose of this study was to examine the trabecular and cortical effects of beta(2)-agonists at doping dose on treadmill exercising rats with estrogen deficiency. Adult female rats were ovariectomized (OVX; n = 44) or sham operated (n = 12). Then, OVX rats received a subcutaneous injection of salbutamol (SAB) or vehicle with (EXE) or without treadmill exercise for 10 wk. Bone mineral density (BMD) was analyzed by densitometry. Microcomputed tomography and histomorphometric analysis were performed to study trabecular bone structure and bone cell activities. After 10 wk, SAB rats presented a much more marked decrease of BMD and trabecular parameters. Exercise did not change the high level of bone resorption in OVX EXE SAB compared with OVX SAB group (both on COOH-terminal collagen cross-links and osteoclast number). These results confirm the deleterious effect of beta(2)-agonists on bone quantity (femoral BMD gain: OVX EXE, +6.8%, vs. OVX EXE SAB, -1.8%; P exercise was mainly localized in the tibia. These findings indicate the presence of a bone alteration threshold below which there is no more alteration in structural bone quantity and quality. The negative effects of SAB on bone observed in this study in trained rats may indicate potential complications in doping female athletes with exercise-induced amenorrhea.

  4. High-dose irradiation of food

    International Nuclear Information System (INIS)

    Diehl, J.F.

    1999-01-01

    Studies performed on behalf of the International Project on Food Irradiation in the period from 1971 until 1980 resulted in the concluding statement that ''.the irradiation of any food commodity up to an overall average dose of 10 kGy presents no toxicological hazard; hence, toxicological testing of foods so treated is no longer required.'' Since then, licenses for food irradiation have been restricted to this maximum dose in any country applying this technology. Further testing programmes have been carried out investigating the wholesomeness or hazards of high-dose irradiation, but there has been little demand so far by the food industry for licensing of high-dose irradiation, as there is only a small range of products whose irradiation at higher doses offers advantages for given, intended use. These include eg. spices, dried herbs, meat products in flexible pouch packagings for astronauts, or patients with immune deficiencies. (orig./CB) [de

  5. "Ecstasy" toxicity to adolescent rats following an acute low binge dose.

    Science.gov (United States)

    Teixeira-Gomes, Armanda; Costa, Vera Marisa; Feio-Azevedo, Rita; Duarte, José Alberto; Duarte-Araújo, Margarida; Fernandes, Eduarda; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo

    2016-06-28

    3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") is a worldwide drug of abuse commonly used by adolescents. Most reports focus on MDMA's neurotoxicity and use high doses in adult animals, meanwhile studies in adolescents are scarce. We aimed to assess in rats the acute MDMA toxicity to the brain and peripheral organs using a binge dose scheme that tries to simulate human adolescent abuse. Adolescent rats (postnatal day 40) received three 5 mg/kg doses of MDMA (estimated equivalent to two/three pills in a 50 kg adolescent), intraperitoneally, every 2 h, while controls received saline. After 24 h animal sacrifice took place and collection of brain areas (cerebellum, hippocampus, frontal cortex and striatum) and peripheral organs (liver, heart and kidneys) occurred. Significant hyperthermia was observed after the second and third MDMA doses, with mean increases of 1 °C as it occurs in the human scenario. MDMA promoted ATP levels fall in the frontal cortex. No brain oxidative stress-related changes were observed after MDMA. MDMA-treated rat organs revealed significant histological tissue alterations including vascular congestion, but no signs of apoptosis or necrosis were found, which was corroborated by the lack of changes in plasma biomarkers and tissue caspases. In peripheral organs, MDMA did not affect significantly protein carbonylation, glutathione, or ATP levels, but liver presented a higher vulnerability as MDMA promoted an increase in quinoprotein levels. Adolescent rats exposed to a moderate MDMA dose, presented hyperthermia and acute tissue damage to peripheral organs without signs of brain oxidative stress.

  6. Concomitant chemoradiotherapy with high dose rate brachytherapy ...

    African Journals Online (AJOL)

    Concomitant chemoradiotherapy with high dose rate brachytherapy as a definitive treatment modality for locally advanced cervical cancer. T Refaat, A Elsaid, N Lotfy, K Kiel, W Small Jr, P Nickers, E Lartigau ...

  7. Radiation effects of high and low doses

    International Nuclear Information System (INIS)

    El-Naggar, A.M.

    1998-01-01

    The extensive proliferation of the uses and applications of atomic and nuclear energy resulted in possible repercussions on human health. The prominent features of the health hazards that may be incurred after exposure to high and low radiation doses are discussed. The physical and biological factors involved in the sequential development of radiation health effects and the different cellular responses to radiation injury are considered. The main criteria and features of radiation effects of high and low doses are comprehensively outlined

  8. Treatment with low-dose resveratrol reverses cardiac impairment in obese prone but not in obese resistant rats.

    Science.gov (United States)

    Louis, Xavier L; Thandapilly, Sijo J; MohanKumar, Suresh K; Yu, Liping; Taylor, Carla G; Zahradka, Peter; Netticadan, Thomas

    2012-09-01

    We hypothesized that a low-dose resveratrol will reverse cardiovascular abnormalities in rats fed a high-fat (HF) diet. Obese prone (OP) and obese resistant (OR) rats were fed an HF diet for 17 weeks; Sprague-Dawley rats fed laboratory chow served as control animals. During the last 5 weeks of study, treatment group received resveratrol daily by oral gavage at a dosage of 2.5 mg/kg body weight. Assessments included echocardiography, blood pressure, adiposity, glycemia, insulinemia, lipidemia, and inflammatory and oxidative stress markers. Body weight and adiposity were significantly higher in OP rats when compared to OR rats. Echocardiographic measurements showed prolonged isovolumic relaxation time in HF-fed OP and OR rats. Treatment with resveratrol significantly improved diastolic function in OP but not in OR rats without affecting adiposity. OP and OR rats had increased blood pressure which remained unchanged with treatment. OP rats had elevated fasting serum glucose and insulin, whereas OR rats had increased serum glucose and normal insulin concentrations. Resveratrol treatment significantly reduced serum glucose while increasing serum insulin in both OP and OR rats. Inflammatory and oxidative stress markers, serum triglycerides and low-density lipoprotein were higher in OP rats, which were significantly reduced with treatment. In conclusion, HF induced cardiac dysfunction in both OP and OR rats. Treatment reversed abnormalities in diastolic heart function associated with HF feeding in OP rats, but not in OR rats. The beneficial effects of resveratrol may be mediated through regression of hyperglycemia, oxidative stress and inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

  9. [Influence of dose regimen on gentamycin nephrotoxicity in rats].

    Science.gov (United States)

    Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

    2001-06-01

    The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

  10. Intermittent hypoxia alters dose dependent caffeine effects on renal prostanoids and receptors in neonatal rats.

    Science.gov (United States)

    Beharry, Kay D; Cai, Charles L; Soontarapornchai, Kultida; Ahmad, Taimur; Valencia, Gloria B; Aranda, Jacob V

    2018-01-01

    Caffeine, one of the most commonly prescribed drugs in preterm neonates, is given in standard or suprapharmacologic doses. Although known as a diuretic, its effects in the neonatal kidneys are not well studied. We tested the hypothesis that neonatal intermittent hypoxia (IH) and high caffeine doses (HCD) alter renal regulators of vasomotor tone and water balance. Newborn rats were randomized to room air, hyperoxia, or IH and treated with standard or high caffeine doses; or placebo saline. Renal prostanoids; histopathology; and cyclooxygenase (COX), prostanoid receptor, and aquaporin (AQP) immunoreactivity were determined. HCD in IH caused severe pathological changes in the glomeruli and proximal tubules, consistent with acute kidney injury. This was associated with reductions in anthropometric growth, PGI 2, and IP, DP, and AQP-4 immunoreactivity, well as a robust increase in COX-2, suggesting that the use of HCD should be avoided in preterm infants who experience frequent IH episodes. Published by Elsevier Inc.

  11. Ionization chamber for high dose measurements

    International Nuclear Information System (INIS)

    Rodrigues Junior, Ary de Araujo

    2005-01-01

    Industrial gamma irradiators facilities are designed for processing large amounts of products, which are exposed to large doses of gamma radiation. The irradiation, in industrial scale, is usually carried out in a dynamic form, where the products go through a 60 Co gamma source with activity of TBq to P Bq (k Ci to MCi). The dose is estimated as being directly proportional to the time that the products spend to go through the source. However, in some situations, mainly for research purposes or for validation of customer process following the ISO 11137 requirements, it is required to irradiate small samples in a static position with fractional deliver doses. The samples are put inside the irradiation room at a fixed distance from the source and the dose is usually determined using dosimeters. The dose is only known after the irradiation, by reading the dosimeter. Nevertheless, in the industrial irradiators, usually different kinds of products with different densities go through between the source and the static position samples. So, the dose rate varies in function of the product density. A suitable methodology would be to monitor the samples dose in real time, measuring the dose on line with a radiation detector, which would improve the dose accuracy and avoid the overdose. A cylindrical ionization chamber of 0.9 cm 3 has been developed for high-doses real-time monitoring, during the sample irradiation at a static position in a 60 Co gamma industrial plant. Nitrogen and argon gas at pressure of 10 exp 5 Pa (1 bar) was utilized to fill the ionization chamber, for which an appropriate configuration was determined to be used as a detector for high-dose measurements. To transmit the signal generated in the ionization chamber to the associated electronic and processing unit, a 20 m mineral insulated cable was welded to the ionization chamber. The signal to noise ratio produced by the detector was about 100. The dosimeter system was tested at a category I gamma

  12. Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

    Science.gov (United States)

    Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit

    2011-01-01

    Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.

  13. Subhypnotic doses of propofol impair spatial memory retrieval in rats

    Directory of Open Access Journals (Sweden)

    Hu Liu

    2016-01-01

    Full Text Available Abundant evidence indicates that propofol profoundly affects memory processes, although its specific effects on memory retrieval have not been clarified. A recent study has indicated that hippocampal glycogen synthase kinase-3β (GSK-3β activity affects memory. Constitutively active GSK-3β is required for memory retrieval, and propofol has been shown to inhibit GSK-3β. Thus, the present study examined whether propofol affects memory retrieval, and, if so, whether that effect is mediated through altered GSK-3β activity. Adult Sprague-Dawley rats were trained on a Morris water maze task (eight acquisition trials in one session and subjected under the influence of a subhypnotic dose of propofol to a 24-hour probe trial memory retrieval test. The results showed that rats receiving pretest propofol (25 mg/kg spent significantly less time in the target quadrant but showed no change in locomotor activity compared with those in the control group. Memory retrieval was accompanied by reduced phosphorylation of the serine-9 residue of GSK-3β in the hippocampus, whereas phosphorylation of the tyrosine-216 residue was unaffected. However, propofol blocked this retrieval-associated serine-9 phosphorylation. These findings suggest that subhypnotic propofol administration impairs memory retrieval and that the amnestic effects of propofol may be mediated by attenuated GSK-3β signaling in the hippocampus.

  14. Intracranial meningiomas after high-dose irradiation

    International Nuclear Information System (INIS)

    Soffer, D.; Gomori, J.M.; Siegal, T.; Shalit, M.N.

    1989-01-01

    Three patients who presented with intracranial meningiomas 12, 15, and 20 years, respectively, after therapeutic high-dose irradiation of a primary brain tumor are described. Analysis of these cases and similar documented cases suggests that meningiomas after high-dose irradiation constitute a recognizable entity. Patients with such tumors received radiation therapy at a young age (mean age, 9.4 years). After a latent period of 2 to 47 years (mean, 19.8 years) they developed meningiomas at the site of irradiation, at a much younger age than patients with ''spontaneous'' meningiomas. Similar to the situation with meningiomas after low-dose irradiation, a relatively high proportion of meningiomas induced by high-dose irradiation tend to be malignant and biologically aggressive. A very young age at the time of irradiation seems to predispose to the induction of malignant meningiomas, rather than benign tumors. These unusual features provide indirect evidence that high-dose radiation may play a role in the pathogenesis of meningiomas.41 references

  15. Some characteristics of the retention distribution and internal doses of 59Fe in rats

    International Nuclear Information System (INIS)

    Wang Deheng; Tian Wuxun; Zhang Hongyuan; Wen Quanfa; Hu Yuexin; Zhao Shanyin

    1993-01-01

    After gastric incubation, the whole body 59 Fe-retentions in rats were fit to two compartment exponential equations. The biological half life for 59 Fe in the slow compartment are 95 and 109 days for young and adult rats respectively, not statistically significantly different. The main 59 Fe-accumulative organs are liver and bone marrow. The biological eliminations of 59 Fe from most organs in young rats are faster than in adult rats. The young rats get more total accumulative dose in organs except liver and total body and have a faster dose accumulative speed than the adult rats. Equal quantities of 59 Fe P.O. may probably give young rats more intensive biological effects than adult rats

  16. Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence of the microbeam width at constant valley dose

    International Nuclear Information System (INIS)

    Serduc, Raphael; Fonta, Caroline; Renaud, Luc; Bouchet, Audrey; Braeuer-Krisch, Elke; Sarun, Sukhena; Bravin, Alberto; Le Duc, Geraldine; Laissue, Jean A; Spiga, Jenny; Boutonnat, Jean; Siegbahn, Erik Albert; Esteve, Francois

    2009-01-01

    To analyze the effects of the microbeam width (25, 50 and 75 μm) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MRT50, MRT75), each using two orthogonally intersecting arrays of either 25, 50 or 75 μm wide microbeams, all spaced 211 μm on center, were tested. For each configuration, peak entrance doses of 860, 480 and 320 Gy, respectively, were calculated to produce an identical valley dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days after radiation treatment, 42 rats were killed to evaluate histopathologically the extent of tumor necrosis, and the presence of proliferating tumors cells and tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48 days for MRT25, 50 and 75, respectively. The combination of the highest entrance doses (860 Gy per array) with 25 μm wide beams (MRT25) resulted in a cumulative valley dose of 36 Gy and was excessively toxic, as it led to early death of all normal rats and of ∼50% of tumor-bearing rats. The short survival times, particularly of rats in the MRT25 group, restricted adequate observance of the therapeutic effect of the method on tumor-bearing rats. However, microbeams of 50 μm width led to the best median survival time after 9L gliosarcoma MRT treatment and appeared as the better compromise between tumor control and normal brain toxicity compared with 75 μm or 25 μm widths when used with a 211 μm on-center distance. Despite very high radiation doses, the tumors were not sterilized; viable proliferating tumor cells remained present at the tumor margin. This study shows that microbeam width and peak entrance doses strongly influence tumor responses and normal brain toxicity, even if valley doses are kept constant in all groups. The use

  17. Synchrotron microbeam radiation therapy for rat brain tumor palliation-influence of the microbeam width at constant valley dose

    Energy Technology Data Exchange (ETDEWEB)

    Serduc, Raphael; Fonta, Caroline; Renaud, Luc [Universite de Toulouse, UPS, Centre de Recherche Cerveau et Cognition (France); Bouchet, Audrey; Braeuer-Krisch, Elke; Sarun, Sukhena; Bravin, Alberto; Le Duc, Geraldine [European Synchrotron Radiation Facility, F38043 Grenoble (France); Laissue, Jean A [Institute of Pathology, University of Bern (Switzerland); Spiga, Jenny [Department of Physics, University of Cagliari, s.p. Monserrato-Sestu, Monserrato (Canada) 09042 (Italy); Boutonnat, Jean [TIMC lab, UMR CNRS 5525, Univ Joseph Fourier, CHU, Grenoble (France); Siegbahn, Erik Albert [Department of Medical Physics, Karolinska Universitetssjukhuset, 17176 Stockholm (Sweden); Esteve, Francois [INSERM U836, Equipe 6, Institut des Neurosciences de Grenoble, 38043 Grenoble Cedex (France)], E-mail: raph.serduc@gmail.com

    2009-11-07

    To analyze the effects of the microbeam width (25, 50 and 75 {mu}m) on the survival of 9L gliosarcoma tumor-bearing rats and on toxicity in normal tissues in normal rats after microbeam radiation therapy (MRT), 9L gliosarcomas implanted in rat brains, as well as in normal rat brains, were irradiated in the MRT mode. Three configurations (MRT25, MRT50, MRT75), each using two orthogonally intersecting arrays of either 25, 50 or 75 {mu}m wide microbeams, all spaced 211 {mu}m on center, were tested. For each configuration, peak entrance doses of 860, 480 and 320 Gy, respectively, were calculated to produce an identical valley dose of 18 Gy per individual array at the center of the tumor. Two, 7 and 14 days after radiation treatment, 42 rats were killed to evaluate histopathologically the extent of tumor necrosis, and the presence of proliferating tumors cells and tumor vessels. The median survival times of the normal rats were 4.5, 68 and 48 days for MRT25, 50 and 75, respectively. The combination of the highest entrance doses (860 Gy per array) with 25 {mu}m wide beams (MRT25) resulted in a cumulative valley dose of 36 Gy and was excessively toxic, as it led to early death of all normal rats and of {approx}50% of tumor-bearing rats. The short survival times, particularly of rats in the MRT25 group, restricted adequate observance of the therapeutic effect of the method on tumor-bearing rats. However, microbeams of 50 {mu}m width led to the best median survival time after 9L gliosarcoma MRT treatment and appeared as the better compromise between tumor control and normal brain toxicity compared with 75 {mu}m or 25 {mu}m widths when used with a 211 {mu}m on-center distance. Despite very high radiation doses, the tumors were not sterilized; viable proliferating tumor cells remained present at the tumor margin. This study shows that microbeam width and peak entrance doses strongly influence tumor responses and normal brain toxicity, even if valley doses are kept constant in

  18. Standardization of high-dose measurement of electron and gamma ray absorbed doses and dose rates

    International Nuclear Information System (INIS)

    McLaughlin, W.L.

    1985-01-01

    Intense electron beams and gamma radiation fields are used for sterilizing medical devices, treating municipal wastes, processing industrial goods, controlling parasites and pathogens, and extending the shelf-life of foods. Quality control of such radiation processes depends largely on maintaining measurement quality assurance through sound dosimetry procedures in the research leading to each process, in the commissioning of that process, and in the routine dose monitoring practices. This affords documentation as to whether satisfactory dose uniformity is maintained throughout the product and throughout the process. Therefore, dosimetry at high doses and dose rates must in many radiation processes be standardized carefully, so that 'dosimetry release' of a product is verified. This standardization is initiated through preliminary dosimetry intercomparison studies such as those sponsored recently by the IAEA. This is followed by establishing periodic exercises in traceability to national or international standards of absorbed dose and dose rate. Traceability is achieved by careful selection of dosimetry methods and proven reference dosimeters capable of giving sufficiently accurate and precise 'transfer' dose assessments: (1) they must be calibrated or have well-established radiation-yield indices; (2) their radiation response characteristics must be reproducible and cover the dose range of interest; (3) they must withstand the rigours of back-and-forth mailing between a central standardizing laboratory and radiation processing facilities, without excessive errors arising due to instabilities, dosimeter batch non-uniformities, and environmental and handling stresses. (author)

  19. Low dose DDT inhibition of hepatocarcinogenesis initiated by diethylnitrosamine in male rats: Possible mechanisms

    International Nuclear Information System (INIS)

    Kushida, Masahiko; Sukata, Tokuo; Uwagawa, Satoshi; Ozaki, Keisuke; Kinoshita, Anna; Wanibuchi, Hideki; Morimura, Keiichirou; Okuno, Yasuyoshi; Fukushima, Shoji

    2005-01-01

    Previously we reported a tendency for reduction of the development of glutathione-S-transferase placental form (GST-P) positive foci, recognized as preneoplastic changes in rat liver, by a low dose of 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT), which belongs to the same group of hepatic cytochrome P-450 inducers as phenobarbital and is itself a non-genotoxic hepatocarcinogen. In order to clarify the biological significance of this phenomenon, we investigated the reproducibility and changes in other parameters using an initiation-promotion model in which male F344 rats were treated with DDT at doses of 0, 0.005, 0.5, 500 ppm in the diet for 11 or 43 weeks after initiation of hepatocarcinogenesis with N-diethylnitrosamine (DEN). When 500 ppm DDT was applied, the formation of GST-P positive foci and tumor were markedly elevated. In contrast, induction of GST-P positive foci and liver tumors tended to be inhibited at a dose of 0.005 ppm, correlating with protein levels of cytochrome P450 2B1 and 3A2 (CYP2B1 and 3A2) and generation of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage. mRNA levels for 8-oxoguanine glycosylase 1 (OGG1), an 8-OHdG repair enzyme, connexin 32 (Cx32), a major component of Gap junctions, and hepatic nuclear factor 1α (HNF-1α), a Cx32 regulator, were inversely correlated with GST-P positive foci and tumor formation. These results indicate that low dose DDT may indeed exhibit inhibitory effects on chemically initiated-rat hepatocarcinogenicity, in contrast to the promotion observed with high doses, and that this is related to changes in metabolizing enzymes, cell communication, and DNA damage and its repair

  20. Dose-volume effects in the rat cervical spinal cord after proton irradiation

    International Nuclear Information System (INIS)

    Bijl, Hendrik P.; Vuijk, Peter van; Coppes, Rob P.; Schippers, Jacobus M.; Konings, Antonius W.T.; Kogel, Albert J. van der

    2002-01-01

    Purpose: To estimate dose-volume effects in the rat cervical spinal cord with protons. Methods and Materials: Wistar rats were irradiated on the cervical spinal cord with a single fraction of unmodulated protons (150-190 MeV) using the shoot through method, which employs the plateau of the depth-dose profile rather than the Bragg peak. Four different lengths of the spinal cord (2, 4, 8, and 20 mm) were irradiated with variable doses. The endpoint for estimating dose-volume effects was paralysis of fore or hind limbs. Results: The results obtained with a high-precision proton beam showed a marginal increase of ED 50 when decreasing the irradiated cord length from 20 mm (ED 50 = 20.4 Gy) to 8 mm (ED 50 = 24.9 Gy), but a steep increase in ED 50 when further decreasing the length to 4 mm (ED 50 = 53.7 Gy) and 2 mm (ED 50 = 87.8 Gy). These results generally confirm data obtained previously in a limited series with 4-6-MV photons, and for the first time it was possible to construct complete dose-response curves down to lengths of 2 mm. At higher ED 50 values and shorter lengths irradiated, the latent period to paralysis decreased from 125 to 60 days. Conclusions: Irradiation of variable lengths of rat cervical spinal cord with protons showed steeply increasing ED 50 values for lengths of less than 8 mm. These results suggest the presence of a critical migration distance of 2-3 mm for cells involved in regeneration processes

  1. Alterations in water and electrolyte absorption in the rat colon following neutron irradiation: influence of neutron component and irradiation dose.

    Science.gov (United States)

    Dublineau, I; Ksas, B; Joubert, C; Aigueperse, J; Gourmelon, P; Griffiths, N M

    2002-12-01

    To study the absorptive function of rat colon following whole-body exposure to neutron irradiation, either to the same total dose with varying proportion of neutrons or to the same neutron proportion with an increasing irradiation dose. Different proportions of neutron irradiation were produced from the reactor SILENE using a fissile solution of uranium nitrate (8, 47 and 87% neutron). Water and electrolyte fluxes were measured in the rat in vivo under anaesthesia by insertion into the descending colon of an agarose gel cylinder simulating the faeces. Functional studies were completed by histological analyses. In the first set of experiments, rats received 3.8 Gy with various neutron percentages and were studied from 1 to 14 days after exposure. In the second set of experiments, rats were exposed to increasing doses of irradiation (1-4Gy) with a high neutron percentage (87%n) and were studied at 4 days after exposure. The absorptive capacity of rat colon was diminished by irradiation at 3-5 days, with a nadir at 4 days. The results demonstrate that an increase in the neutron proportion is associated with an amplification of the effects. Furthermore, a delay in the re-establishment of normal absorption was observed with the high neutron proportion (87%n). A dose-dependent reduction of water absorption by rat colon was also observed following neutron irradiation (87%n), with a 50% reduction at 3 Gy. Comparison of this dose-effect curve with the curve obtained following gamma (60)Co-irradiation indicates an RBE of 2.2 for absorptive colonic function in rat calculated at 4 days after exposure.

  2. Dosimetric systems of high dose, dose rate and dose uniformity in food and medical products

    International Nuclear Information System (INIS)

    Vargas, J.; Vivanco, M.; Castro, E.

    2014-08-01

    In the Instituto Peruano de Energia Nuclear (IPEN) we use the chemical dosimetry Astm-E-1026 Fricke as a standard dosimetric system of reference and different routine dosimetric systems of high doses, according to the applied doses to obtain the desired effects in the treated products and the doses range determined for each type of dosimeter. Fricke dosimetry is a chemical dosimeter in aqueous solution indicating the absorbed dose by means an increase in absorbance at a specific wavelength. A calibrated spectrophotometer with controlled temperature is used to measure absorbance. The adsorbed dose range should cover from 20 to 400 Gy, the Fricke solution is extremely sensitive to organic impurities, to traces of metal ions, in preparing chemical products of reactive grade must be used and the water purity is very important. Using the referential standard dosimetric system Fricke, was determined to March 5, 2013, using the referential standard dosimetric system Astm-1026 Fricke, were irradiated in triplicate Fricke dosimeters, to 5 irradiation times (20; 30; 40; 50 and 60 seconds) and by linear regression, the dose rate of 5.400648 kGy /h was determined in the central point of the irradiation chamber (irradiator Gamma cell 220 Excel), applying the decay formula, was compared with the obtained results by manufacturers by means the same dosimetric system in the year of its manufacture, being this to the date 5.44691 kGy /h, with an error rate of 0.85. After considering that the dosimetric solution responds to the results, we proceeded to the irradiation of a sample of 200 g of cereal instant food, 2 dosimeters were placed at the lateral ends of the central position to maximum dose and 2 dosimeters in upper and lower ends as minimum dose, they were applied same irradiation times; for statistical analysis, the maximum dose rate was 6.1006 kGy /h and the minimum dose rate of 5.2185 kGy /h; with a dose uniformity of 1.16. In medical material of micro pulverized bone for

  3. Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

    Science.gov (United States)

    Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

    2018-06-01

    This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  4. Dose-dependent metabolic disposition of hydroxytyrosol and formation of mercapturates in rats.

    Science.gov (United States)

    Kotronoulas, Aristotelis; Pizarro, Nieves; Serra, Aida; Robledo, Patricia; Joglar, Jesús; Rubió, Laura; Hernaéz, Alvaro; Tormos, Carmen; Motilva, Ma José; Fitó, Montserrat; Covas, Maria-Isabel; Solà, Rosa; Farré, Magí; Saez, Guillermo; de la Torre, Rafael

    2013-11-01

    Hydroxytyrosol (HT), one of the major polyphenols present in olive oil, is known to possess a high antioxidant capacity. The aim of the present study was to investigate dose dependent (0, 1, 10 and 100 mg/kg) alterations in the metabolism of HT in rats since it has been reported that metabolites may contribute to biological effects. Special attention was paid to the activation of the semiquinone-quinone oxidative cycle and the formation of adducts with potential deleterious effects. Thus, we developed a novel analytical methodology to monitor the in vivo formation of the HT mercapturate, N-acetyl-5-S-cysteinyl-hydroxytyrosol in urine samples. Biomarkers of hepatic and renal toxicity were evaluated within the dose range tested. Following HT administration, dose-dependent effects were observed for the recovery of all the metabolites studied. At the lowest dose of 1 mg/kg, the glucuronidation pathway was the most relevant (25-30%), with lower recoveries for sulfation (14%), while at the highest dose of 100 mg/kg, sulfation was the most prevalent (75%). In addition, we report for the first time the formation of the mercapturate conjugate of HT in a dose-dependent manner. The biochemical data did not reveal significant toxic effects of HT at any of the doses studied. An increase in the GSH/GSSG ratio at the highest dose was observed indicating that the products of HT autoxidation are counteracted by glutathione, resulting in their detoxification. These results indicate that the metabolic disposition of HT is highly dependent on the dose ingested. Copyright © 2013. Published by Elsevier Ltd.

  5. Nonlinear model of high-dose implantation

    International Nuclear Information System (INIS)

    Danilyuk, A.

    2001-01-01

    The models of high-dose implantation, using the distribution functions, are relatively simple. However, they must take into account the variation of the function of distribution of the implanted ions with increasing dose [1-4]. This variation takes place owing to the fact that the increase of the concentration of the implanted ions results in a change of the properties of the target. High-dose implantation is accompanied by sputtering, volume growth, diffusion, generation of defects, formation of new phases, etc. The variation of the distribution function is determined by many factors and is not known in advance. The variation within the framework of these models [1-4] is taken into account in advance by the introduction of intuitive assumptions on the basis of implicit considerations. Therefore, these attempts should be regarded as incorrect. The model prepared here makes it possible to take into account the sputtering of the target, volume growth and additional declaration on the implanted ions. Without any assumptions in relation to the variation of the distribution function with increasing dose. In our model it is assumed that the type of distribution function for small doses in a pure target substance is the same as in substances with implanted ions. A second assumption relates to the type of the distribution function valid for small doses in the given substances. These functions are determined as a result of a large number of theoretical and experimental investigations and are well-known at the present time. They include the symmetric and nonsymmetric Gauss distribution, the Pearson distribution, and others. We examine implantation with small doses of up to 10 14 - 10 15 cm -2 when the accurately known distribution is valid

  6. High dose gamma-ray standard

    International Nuclear Information System (INIS)

    Macrin, R.; Moraru, R.

    1999-01-01

    The high gamma-ray doses produced in a gamma irradiator are used, mainly, for radiation processing, i.e. sterilization of medical products, processing of food, modifications of polymers, irradiation of electronic devices, a.s.o. The used absorbed doses depend on the application and cover the range 10 Gy to 100 MGy. The regulations in our country require that the response of the dosimetry systems, used for the irradiation of food and medical products, be calibrated and traceable to the national standards. In order to be sure that the products receive the desired absorbed dose, appropriate dosimetric measurements must be performed, including the calibration of the dosemeters and their traceability to the national standards. The high dose gamma-ray measurements are predominantly based on the use of reference radiochemical dosemeters. Among them the ferrous sulfate can be used as reference dosemeter for low doses (up to 400 Gy) but due to its characteristics it deserves to be considered a standard dosemeter and to be used for transferring the conventional absorbed dose to other chemical dosemeters used for absorbed doses up to 100 MGy. The study of the ferrous sulfate dosemeter consisted in preparing many batches of solution by different operators in quality assurance conditions and in determining for all batches the linearity, the relative intrinsic error, the repeatability and the reproducibility. The principal results are the following: the linear regression coefficient: 0.999, the relative intrinsic error: max.6 %, the repeatability (for P* = 95 %): max.3 %, the reproducibility (P* = 95%): max.5 %. (authors)

  7. Dose formation and hematologic effects with prolonged internal exposure of rats by isotope 131I

    International Nuclear Information System (INIS)

    Sova, O.A.; Drozd, Yi.P.

    2013-01-01

    Processes in single dose formation and long-term domestic revenue 131 I in rats was investigated. Original method of estimating absorbed doses in hemacyte for macro-dosemeters indicators was proposed. Dose factors for hemacyte and the dynamics of the blood-forming organs doses for prolonged two cases of prolonged exposure was calculated. Hematologic effects were studied for two variants of entry of the isotope. Peculiarities of doses formation and identified hematological effects are discussed

  8. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron

    International Nuclear Information System (INIS)

    Ihlaseh-Catalano, Shadia M.; Bailey, Kathryn A.; Cardoso, Ana Paula F.; Ren, Hongzu; Fry, Rebecca C.; Camargo, João Lauro V.de; Wolf, Douglas C.

    2014-01-01

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder

  9. Dose and temporal effects on gene expression profiles of urothelial cells from rats exposed to diuron.

    Science.gov (United States)

    Ihlaseh-Catalano, Shadia M; Bailey, Kathryn A; Cardoso, Ana Paula F; Ren, Hongzu; Fry, Rebecca C; de Camargo, João Lauro V; Wolf, Douglas C

    2014-11-05

    Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide that at high dietary levels (2500 ppm) induces rat urinary bladder hyperplasia after 20 weeks of exposure and neoplasia after 2 years. The effects on the urothelium after short-term exposure have not been described. The present 7-day study evaluated the dose-dependency of urothelial alterations in the urinary bladder using light microscopy, scanning electron microscopy, and genome-wide transcriptional profiling. Male Wistar rats were fed 0, 125, 500, 2500 ppm diuron for 7 days. The urinary bladder and isolated urothelial cells of these animals were processed for microscopic examination and gene expression profiling, respectively. No significant treatment-related morphologic effects were observed. The number of differentially expressed genes (DEGs) in the exposed groups increased with diuron levels. Diuron-altered genes involved in cell-to-cell interactions and tissue organization were identified in all treatment groups. After 7 days of diuron exposure, transcriptional responses were observed in the urothelium in the absence of clear morphologic changes. These morphological findings are different from those observed in a previous study in which 20 weeks of diuron exposure was associated with simple hyperplasia secondary to the persistent cytotoxicity and necrosis associated with continuous cellular regeneration. Comparison of the gene expression profiles of rats exposed to the 2500 ppm carcinogenic diuron dose for 7 days versus 20 weeks revealed few similarities between these two time points at the gene or pathway level. Taken together, these data provide insight into the dose- and temporal-dependent morphological and transcriptional changes associated with diuron exposure that may lead to the development of tumors in the rat urinary bladder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Dose-ranging pharmacokinetics of colistin methanesulphonate (CMS) and colistin in rats following single intravenous CMS doses.

    Science.gov (United States)

    Marchand, Sandrine; Lamarche, Isabelle; Gobin, Patrice; Couet, William

    2010-08-01

    The aim of this study was to evaluate the effect of colistin methanesulphonate (CMS) dose on CMS and colistin pharmacokinetics in rats. Three rats per group received an intravenous bolus of CMS at a dose of 5, 15, 30, 60 or 120 mg/kg. Arterial blood samples were drawn at 0, 5, 15, 30, 60, 90, 120, 150 and 180 min. CMS and colistin plasma concentrations were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of CMS and colistin were calculated by non-compartmental analysis. Linear relationships were observed between CMS and colistin AUCs to infinity and CMS doses, as well as between CMS and colistin C(max) and CMS doses. CMS and colistin pharmacokinetics were linear for a range of colistin concentrations covering the range of values encountered and recommended in patients even during treatment with higher doses.

  11. Pharmacokinetic interaction of enrofloxacin/trimethoprim combination following single-dose intraperitoneal and oral administration in rats.

    Science.gov (United States)

    Choi, Myung-Jin; Yohannes, Sileshi Belew; Lee, Seung-Jin; Damte, Dereje; Kim, Jong-Choon; Suh, Joo-Won; Park, Seung-Chun

    2014-03-01

    The pharmacokinetic interaction of enrofloxacin and trimethoprim was evaluated after single-dose intraperitoneal or oral co-administration in rats. Plasma concentrations of the two drugs were determined by high-performance liquid chromatography. Following intraperitoneal combination, a significant (P trimethoprim, respectively. There was a significant (P trimethoprim. Further study is recommended in other species of animals.

  12. Microscopic dose distribution around PuO2 particles in lungs of hamsters, rats and dogs

    International Nuclear Information System (INIS)

    Diel, J.H.; Mewhinney, J.A.; Guilmette, R.A.

    1982-01-01

    Syrian hamsters, Fischer-344 rats and Beagle dogs inhaled monodisperse aerosols of PuO 2 and were sacrificed 1 to 16 days after exposure. The microscopic distribution of dose and tissue-at-risk around individual particles in lung was studied using autoradiographs of the lungs. The dose pattern in dogs and rats was more diffuse than in hamsters, resulting in a calculation of about twice the tumor incidence in rats and dogs as in hamsters on the basis of dose pattern using the same dose-effect model for all three species. The tumorigenic effect of inhaled insoluble PuO 2 particles depends on the species inhaling the material; Syrian hamsters are much less susceptible than are rats or dogs. It has been suggested that a difference in dose distribution resulting from differences in particle distributions in the two species may contribute to the differences in susceptibility in Syrian hamsters and rats. The role of dose distribution in lung cancer production is explored in this study by measuring microscopic dose patterns in regions surrounding single PuO 2 particles in lung. The alveolar structures of the dog and rat are different than those of the hamster. Based on these measurements, particles of PuO 2 in lung are more likely to cause lung cancer in dogs and rats than in hamsters

  13. Hormones of thyroid gland in sera of rats treated with different dose of concentrated potassium iodine solutions

    Directory of Open Access Journals (Sweden)

    Marković Ljiljana

    2010-01-01

    Full Text Available Introduction Potassium iodine (KI is used as a drug therapy for treating numerous diseases such as small-vessel vasculitis, erythema nodosum, vasculitis nodularis, Sweet's syndrome, tuberculosis and granulomatosis, and for iodized salt. At the same time, KI can be harmful. Iodine intake may increase the frequency of thyroiditis in humans, and may induce the occurrence of experimental thyroiditis (ET in animals. Investigations on an experimental model for the examination of thyroiditis in Wistar rats have clearly showed morphological changes in the rat thyroid evoked by KI administration. Objective The purpose of this study was to compare the effects of low and high doses of KI on the thyroid gland of Wistar rats and determine the effect on hormone status (T4, T3 and TSH in this rat strain. Methods Two groups of rats from the Wistar strain were treated with a low iodine dose (225 μg/g BW and with a high iodine dose (675 μg/g BW of KI solutions. Untreated nonimmunized animals served as controls. The solution was administrated daily intraperitoneally during the period of 26 consecutive days. Results Monitoring hormone status (TSH, T3 and T4 and morphological changes it was found that therapeutic doses of KI applied in treatment induced the occurrence of experimental thyroiditis (chronic destructive Hashimoto's thyroiditis in humans and cell necrosis in animals not carrying a genetic susceptibility. Significant inflammatory changes were observed in rats treated with a high iodine dose. Conclusion The early iodine induced cell necrosis and inflammation in the nonimmunized animals without genetic susceptibility is a new experimental model of thyroiditis. .

  14. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.T.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Howard, J.

    1982-01-01

    The thoraco-lumbar (T12-L1) region of the spinal cord of rats was exposed to either single or fractionated (four daily exposures) doses of X rays (230 kVp) or heavy ions. The heavy ions used were carbon and neon, and the relative biological effectiveness (RBE) of both the plateau ionization region and the midpeak region of 4-cm spread-out Bragg peaks of each heavy ion were investigated. For single doses of carbon and neon ions in the plateau ionization region, RBE values of 1.45 +/- 0.25 (propagated 95% confidence limits) and 1.46 +/- 0.33, respectively, were obtained. In the spread peak regions for carbon and neon ions, the RBE values were 1.48 +/- 0.18 and 1.86 +/- 0.42, respectively. These values were obtained using the dose needed to produce 50% paralysis in a group of irradiated rats as the isoeffect comparison dose (ED 50 dose). Similarly, in groups of rats receiving four daily exposures, the RBE values for carbon and neon ions in the plateau ionization region were 1.31 +/- 0.27 and 1.80 +/- 0.24, respectively. In the spread peak regions of ionization for carbon and neon ions, the RBE values were 1.95 +/- 0.19 and 2.18 +/- 0.23, respectively. Similar values for RBE were obtained using changes in the activity of enzymes in spinal cord tissue (cyclic nucleotide phosphohydrolase and γ-glutamyl transpeptidase). Also, it was estimated that, for X irradiation, the fractional amount of dose repaired (at the ED 50 dose) was 0.64 +/- 0.10 (95% confidence limits). For carbon and neon ions in the plateau ionization region, the values for the fractional amount of dose repaired were 0.70 +/- 0.27 and 0.48 +/- 0.20, and for carbon and neon ions in the spread peak region of ionization, the fractional repair values were 0.40 +/- 0.10 and 0.52 +/- 0.17. Spinal cord tissue therefore shows a high capacity for subeffective damage repair

  15. NIST high-dose calibration services

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1989-01-01

    There is a need for the standardization of high-dose measurements used in the radiation-processing industry in order to provide assured traceability to national standards. NIST provides dosimetry calibration services to this industry. One of these services involves administration of known absorbed doses of gamma rays to customer-supplied dosimeters. The dosimeters are packaged to provide electron equilibrium conditions and are irradiated in a standard 60 Co calibration facility; this provides a calibration of that batch of dosimeters. Another service consists of supplying to a customer calibrated transfer dosimeters for irradiation with the customer's radiation source. The irradiated transfer dosimeters are then returned to NIST for analysis; the results are reported to the customer, providing a calibration of the dose rate of the customer's source. (orig.)

  16. Lung cancer incidence after exposure of rats to low doses of radon: influence of dose rate

    Energy Technology Data Exchange (ETDEWEB)

    Morlier, J.P.; Morin, M.; Monchaux, G.; Fritsch, P.; Lafuma, J.; Masse, R. [CEA Centre d`Etudes Nucleaires de Fontenay-aux-Roses, 92 (France). Dept. de Protection Technique; Pineau, J.F. [ALGADE, Bessines (France); Chameaud, J. [Compagnie Generale des Matieres Nucleaires (COGEMA), 87 - Razes (France)

    1994-12-31

    To study the effect on lung cancer incidence of a long exposure to low levels of radon, 500 male 3-months-old Sprague-Dawley rats, were exposed to a cumulative dose of 25 WLM of radon and its daughters, 6 hours a day, 5 days a week, during 18 months. Exposure conditions were controlled in order to maintain a defined PAEC: 42 x 10{sup 6} J.m{sup -3} (2 WL), in the range of domestic and environmental exposures. Animals were kept until they died or given euthanasia when moribund. Mean survival times were similar in both irradiated and control groups: 828 days (SD = 169) and 830 days (SD = 137), as well as lung cancer incidence, 0.60% at 25 WLM and 0.63% for controls. The incidence of lung lesions was compared statistically with controls and those previously obtained at cumulative exposures of 25 and 50 WLM delivered over a 4-6 month period, inducing a significant increase of lung cancer, 2.2% and 3.8% respectively. Such a comparison showed a decreased lung cancer incidence related to a decrease in the dose rate for low levels of radon exposure. (author).

  17. Lung cancer incidence after exposure of rats to low doses of radon: influence of dose rate

    International Nuclear Information System (INIS)

    Morlier, J.P.; Morin, M.; Monchaux, G.; Fritsch, P.; Lafuma, J.; Masse, R.; Chameaud, J.

    1994-01-01

    To study the effect on lung cancer incidence of a long exposure to low levels of radon, 500 male 3-months-old Sprague-Dawley rats, were exposed to a cumulative dose of 25 WLM of radon and its daughters, 6 hours a day, 5 days a week, during 18 months. Exposure conditions were controlled in order to maintain a defined PAEC: 42 x 10 6 J.m -3 (2 WL), in the range of domestic and environmental exposures. Animals were kept until they died or given euthanasia when moribund. Mean survival times were similar in both irradiated and control groups: 828 days (SD = 169) and 830 days (SD = 137), as well as lung cancer incidence, 0.60% at 25 WLM and 0.63% for controls. The incidence of lung lesions was compared statistically with controls and those previously obtained at cumulative exposures of 25 and 50 WLM delivered over a 4-6 month period, inducing a significant increase of lung cancer, 2.2% and 3.8% respectively. Such a comparison showed a decreased lung cancer incidence related to a decrease in the dose rate for low levels of radon exposure. (author)

  18. Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

    International Nuclear Information System (INIS)

    Kal, H.B.; Bijman, J.Th.

    1981-01-01

    Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min -1 . The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

  19. Low-dose effects of bisphenol A on mammary gland development in rats

    DEFF Research Database (Denmark)

    Egebjerg, Karen Mandrup; Boberg, Julie; Isling, Louise Krag

    2016-01-01

    was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose–response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg...... intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may...

  20. High-dose erythropoietin for tissue protection

    DEFF Research Database (Denmark)

    Lund, Anton; Lundby, Carsten; Olsen, Niels Vidiendal

    2014-01-01

    BACKGROUND: The discovery of potential anti-apoptotic and cytoprotective effects of recombinant human erythropoietin (rHuEPO) has led to clinical trials investigating the use of high-dose, short-term rHuEPO therapy for tissue protection in conditions such as stroke and myocardial infarction....... Experimental studies have been favourable, but the clinical efficacy has yet to be validated. MATERIALS AND METHODS: We have reviewed clinical studies regarding the use of high-dose, short-term rHuEPO therapy for tissue protection in humans with the purpose to detail the safety and efficacy of r...... no effect of rHuEPO therapy on measures of tissue protection. Five trials including 1025 patients reported safety concerns in the form of increased mortality or adverse event rates. No studies reported reduced mortality. CONCLUSIONS: Evidence is sparse to support a tissue-protective benefit of r...

  1. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Mansonr, S.Z.

    2009-01-01

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  2. Protective Effect of Low Dose Gamma Irradiation against Oxidative Damage in Rats Administrated with Ferric- Nitrilotriacetate

    International Nuclear Information System (INIS)

    Mansonr, S.Z.

    2008-01-01

    Many studies have demonstrated the beneficial adaptive response of low dose gamma-irradiation. Low dose gamma-irradiation (LDR) might be effective for the prevention of various reactive oxygen species-related diseases. Ferric nitrilotriacetate (Fe-NTA) is a strong oxidant, which generates highly reactive hydroxyl radical and causes injuries of various organs including the kidney and liver. This study was designed to investigate the ability of low dose gamma-irradiation to restrain Fe-NT A induced oxidative stress. Sprague Dawley male albino rats were subjected to low dose gamma-irradiation (50 cGy). Animals were challenged with Fe-NT A (9 mg Fe/kg body weight, intraperitoneally). Results showed that Fe-NTA enhances lipid peroxidation (LPx) accompanied with reduction in glutathione (GSH) content, antioxidant enzymes, viz., glutathione peroxidase (GPX), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT) and phase-U metabolizing enzyme glutathione-S-transferase (GST). Fe-NTA also enhances the concentration of blood urea nitrogen (BUN) and serum creatinine as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) activities. Exposure to low dose gamma- irradiation (3 h after Fe-NTA administration) resulted in a significant decrease in LPx, BUN, serum creatinine contents as well as ALT, AST and GGT enzyme activities. GSH content; GST and antioxidant enzymes were also recovered to significant level. Thus, our data suggest that exposure to LDR might be a useful antioxidant mediator to suppress the Fe-NTA induced-oxidative damage in rats

  3. Effect of chromic γ-irradiation with small doses on candidiasis development in white rats

    International Nuclear Information System (INIS)

    Berchev, K.; Krushkov, Iv.

    1976-01-01

    Rats continuously exposed to 2 rads/day during eight months (cumulative dose of 400 rads) and nonirradiated rats were infected with a candida cells administered intravenously. All the irradiated animals died ten days after infection while only ten per cent of the control animals died for the same period of time. A morphological study has revealed candidiasis in the irradiated rats; changes, mainly in the kidneys, and formation of candidiasis granulomas have been detected in the control animals

  4. High dose rate brachytherapy for oral cancer

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Koizumi, Masahiko; Ogawa, Kazuhiko; Furukawa, Souhei

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer. (author)

  5. High dose rate brachytherapy for oral cancer.

    Science.gov (United States)

    Yamazaki, Hideya; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Furukawa, Souhei; Koizumi, Masahiko; Ogawa, Kazuhiko

    2013-01-01

    Brachytherapy results in better dose distribution compared with other treatments because of steep dose reduction in the surrounding normal tissues. Excellent local control rates and acceptable side effects have been demonstrated with brachytherapy as a sole treatment modality, a postoperative method, and a method of reirradiation. Low-dose-rate (LDR) brachytherapy has been employed worldwide for its superior outcome. With the advent of technology, high-dose-rate (HDR) brachytherapy has enabled health care providers to avoid radiation exposure. This therapy has been used for treating many types of cancer such as gynecological cancer, breast cancer, and prostate cancer. However, LDR and pulsed-dose-rate interstitial brachytherapies have been mainstays for head and neck cancer. HDR brachytherapy has not become widely used in the radiotherapy community for treating head and neck cancer because of lack of experience and biological concerns. On the other hand, because HDR brachytherapy is less time-consuming, treatment can occasionally be administered on an outpatient basis. For the convenience and safety of patients and medical staff, HDR brachytherapy should be explored. To enhance the role of this therapy in treatment of head and neck lesions, we have reviewed its outcomes with oral cancer, including Phase I/II to Phase III studies, evaluating this technique in terms of safety and efficacy. In particular, our studies have shown that superficial tumors can be treated using a non-invasive mold technique on an outpatient basis without adverse reactions. The next generation of image-guided brachytherapy using HDR has been discussed. In conclusion, although concrete evidence is yet to be produced with a sophisticated study in a reproducible manner, HDR brachytherapy remains an important option for treatment of oral cancer.

  6. Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.

    Science.gov (United States)

    Sorrentino, Annalise

    2005-04-01

    Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

  7. Rat skin carcinogenesis as a basis for estimating risks at low doses and dose rates of various types of radiation

    International Nuclear Information System (INIS)

    Burns, F.J.; Vanderlaan, M.; Strickland, P.; Albert, R.E.

    1976-01-01

    The recovery rate, age dependence and latent period for tumor induction in rat skin were measured for single and split doses of radiation, and the data were analyzed in terms of a general model in an attempt to estimate the expected tumor response for various types of radiation given at low dose rates for long periods of time. The dorsal skin of male rats was exposed to electrons, x rays, or protons in either single or split doses for several doses and the tumor responses were compared during 80 weeks of observation. A two stage model incorporating a reversible or recoverable mode was developed and various parameters in the model, including recovery rate, dose-response coefficients, and indices of age sensitivity, were evaluated experimentally. The measured parameters were then utilized to calculate expected tumor responses for exposure periods extending for duration of life. The calculations indicated that low dose rates could be markedly ( 1 / 100 to 1 / 1000 ) less effective in producing tumors than the same dose given in a short or acute exposure, although the magnitude of the reduction in effectiveness declines as the dose declines

  8. Hypofractionated stereotactic radiotherapy to the rat hippocampus. Determination of dose response and tolerance

    International Nuclear Information System (INIS)

    Ernst-Stecken, A.; Roedel, F.; Grabenbauer, G.; Sauer, R.; Jeske, I.; Bluemcke, I.; Hess, A.; Ganslandt, O.; Brune, K.

    2007-01-01

    Purpose: To determine the effect of hypofractionated stereotactic radiotherapy (hfSRT) on adult rat brain tissue (necrosis, impact on blood-brain barrier, signal changes on high-field magnetic resonance imaging [MRI]). Material and Methods: Adult male Wistar rats underwent MRI and CT scanning of the brain and respective images were introduced into the Novalis trademark radiosurgery device (BrainLab, Feldkirchen, Germany). All animals (body weight 350 g) were irradiated weekly with doses of 2 x 10 Gy (n = 3 animals), 3 x 10 Gy (n = 3 animals) and 4 x 10 Gy (n = 3 animals), targeted to the left hippocampus after image-guided positioning. 4.7-T T2-weighted MRI scanning was performed in each animal. Animals were sacrificed 8, 12, and 16 weeks after hfSRT and brains were immersion-fixed in 4% paraformaldehyde for subsequent histopathologic analysis. Results: In concordance with isodose distributions, pathologic signal hyperintensities in MRI were recorded from 4 x 10 Gy after 8 weeks, 3 x 10 Gy after 12 weeks, while 2 x 10 Gy induced slight detectable alterations only after 16 weeks. Subsequent histopathologic analysis revealed hippocampal cell necrosis with significantly earlier and stronger occurrence for higher doses (40 Gy > 30 Gy > 20 Gy). Pial microvessel permeability also increased after 40 Gy, whereas 30 Gy induced moderate changes. Conclusion: Conclusion: Partial-brain irradiation with hfSRT (Novalis trademark System) was successfully adopted for small animals and histopathologic analysis confirmed its repositioning accuracy. The neuropathologic effects correlated with dose and observation time. The approach will be further developed for quality assurance in hfSRT of normal brain tissue, as well as novel treatment modalities in epileptic rats and orthotopic tumor models. (orig.)

  9. Late occurring lesions in the skin of rats after repeated doses of X-rays

    International Nuclear Information System (INIS)

    Hopewell, J.W.

    1985-01-01

    Late radiation damage, characterized by atrophy and necrosis in the skin and subcutaneous tissues, has been demonstrated in both the tail and feet of rats. The incidence of necrosis increased with total dose. These total doses, in the range 72-144 Gy, were given as 4-8 treatment of 18 Gy, each dose separated from the next by an interval of 28 days. This treatment protocol minimized acute epithelial skin reactions. The same regime applied to the skin on the back of rats resulted in a very severe acute reaction occurring after the second to fifth dose of 18 Gy. This was surprising since back skin, like tail skin, is less sensitive to large single doses of radiation than that of the foot. The late radiation reaction in the foot and tail of rats are compared and contrasted with other attempts to assess late effects in rodent skin and with late changes seen in pig skin. (author)

  10. Protective and Therapeutic Role of Low Dose Gamma Radiation on Streptozotocin Induced Diabetes in Rats

    International Nuclear Information System (INIS)

    Mansour, H.H.; Hafez, H.F.; Shouman, S.A.

    2011-01-01

    Diabetes mellitus is a multi-factorial disease which is characterized by vascular and renal complication. This study was initiated to investigate the protective and the therapeutic effect of low dose of gamma radiation (LDR) on diabetic complications. A total of 30 adult male rats were divided into 5 groups: Group I: served as control and injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group II: rats became diabetic via intraperitoneal injection with 60 mg/kg streptozotocin (STZ) dissolved in 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group III irradiated rats (IRR): submitted to fractionated dose of whole body gamma rays; 0.25 Gy for 2 consecutive days (whole dose 0.5 Gy), group IV diabetic irradiated rats (STZ + IRR): rats became diabetic as group II then four weeks after diabetes induction (day 28), rats were submitted to 2 fractions of whole body gamma rays as in group III, and group V irradiated diabetic rats (IRR + STZ): rats were injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer then submitted to whole body gamma rays; 0.25 Gy for 2 consecutive days then one hour after the last IRR dose, rats were made diabetic as group II. In pre and post-irradiation of STZ rats, significant changes were observed in serum lipid profiles, hepatic and cardiac serum enzymes. Significant decrease in hepatic and cardiac malondialdehyde (MDA) and total nitrate/nitrite (NO(x)) levels, and significant increase in superoxide dismutase (SOD) and glutathione (GSH) levels were observed as compared to diabetic group. The study suggests that LDR may provide useful protective and therapeutic option in the reversal of oxidative stress induced in diabetic rats

  11. Conditioned instrumental behaviour in the rat: Effects of prenatal irradiation with various low dose-rate doses. Instrumentelle Verhaltensuntersuchungen an der Ratte: Ueber die Wirkung verschiedener Dosen einer praenatalen Bestrahlung niedriger Dosisleistung

    Energy Technology Data Exchange (ETDEWEB)

    Klug, H.

    1986-01-01

    4 groups of rats of the Wistar-strain were subjected to ..gamma..-irradiation on the 16th day of gestation. 5 rats received 0,6 Gy low dose rate irradiation, 5 animals received 0,9 Gy low dose and 6 high dose irradiation, 3 females were shamirradiated. The male offspring of these 3 irradiation groups and 1 control group were tested for locomotor coordination on parallel bars and in a water maze. The female offspring were used in an operant conditioning test. The locomotor test showed slight impairment of locomotor coordination in those animals irradiated with 0,9 Gy high dose rate. Swimming ability was significantly impaired by irradiation with 0,9 Gy high dose rate. Performance in the operant conditioning task was improved by irradiation with 0,9 Gy both low and high dose rate. The 0,9 Gy high dose rate group learned faster than all the other groups. For the dose of 0,9 Gy a significant dose rate effect could be observed. For the dose of 0,6 Gy a similar tendency was observed, differences between 0,6 Gy high and low dose rate and controls not being significant.

  12. Epithelial regeneration of transposed intestine after high doses of X irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Both, N.J. de; Vermey, M [Erasmus Universiteit, Rotterdam (Netherlands)

    1976-01-01

    The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of x irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation.

  13. High dose rate endobronchial brachytherapy - treatment technique

    International Nuclear Information System (INIS)

    Carvalho, Heloisa de Andrade; Aisen, Salim; Haddad, Cecilia Maria Kalil; Nadalin, Wladimir; Pedreira Junior, Wilson Leite; Chavantes, Maria Cristina

    1998-01-01

    High dose rate endobronchial brachytherapy is efficient in symptom relief due to obstructive endobronchial malignancies. However, it's role in survival improvement for patients with lung cancer is not yet established. The use of this treatment in increasing, specially in the developing countries. The purpose of this paper is to present the treatment technique used in the Radiotherapy Department of the Hospital da Clinicas, University of Sao Paulo, based on an experience of 60 cases treated with 180 procedures. Some practical suggestions and rules adopted in the Department are described. The severe complications rate is 6.7%, demonstrating an adequate patient selection associated with the technique utilized. (author)

  14. Neuroprotective potential of high-dose biotin.

    Science.gov (United States)

    McCarty, Mark F; DiNicolantonio, James J

    2017-11-01

    A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain

  15. Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

    Directory of Open Access Journals (Sweden)

    Decramer Marc

    2010-12-01

    Full Text Available Abstract Background High dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids. Methods Rats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP or 30 mg/kg (high MP of methylprednisolone. Results Diaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only. Conclusions Administration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

  16. Basic study on low dose radiation effect: SOD activity of immune organs and hemogram in rats

    International Nuclear Information System (INIS)

    Yamaoka, Kiyonori; Kaneko, Ichiro; Mizutani, Takeo; Nakano, Kazushiro; Edamatsu, Rei; Mori, Akitane.

    1989-01-01

    We examined the effect of low dose radiation on SOD activities of immune organs such as thymus, spleen, bone marrow in rats and hematological findings changes. Animals were exposed to radiation in a wholebody fashion, 4 hours before sacrifice. SOD activities in thymus and bone marrow cells from the rats X-ray irradiated at doses of 0.25∼0.50 Gy/10 min were enhanced in comparison with those of non-irradiated rats. The enhancement was also observed in spleen cells obtained from group of rats irradiated at 0.05 Gy/10 min. Radiation exposure with over 0.50 Gy/10 min gave rats inhibitory responses in those immune organs. The changes in homogram were not observed with γ-ray exposure of less than 0.10 Gy/10 min. (author)

  17. Dose-response relationship of rat aryl hydrocarbon hydroxylase and epoxide hydratase induction

    Energy Technology Data Exchange (ETDEWEB)

    Gielen, J.E.; Goujon, F.M.; Sele-Doyen, J.; Van Cantfort, J.

    1980-01-01

    This paper summarizes our recent results supporting the hypothesis that different regulation mechanisms are involved in the control of AHH and EH activity and that the AHH induction in the extrahepatic tissues might also be affected by liver specific inducers. In the rat, lung and kidney AHH is highly sensitive to the inducers present in cigarette smoke and cigarette smoke condensate, the EH activity not being affected by the same agents. Phenobarbital is also able to protentiate the inducing action of low doses of benzo(a)pyrene on the lung AHH activity. In primary rat liver cells in culture, AHH and EH can be selectivly induced. Low doses of benz(a)anthracene preferentially enhance the AHH activity while trans-stilbene oxide an various antioxidants modify only the EH activity. Phenobarbital, which also induces the AHH activity in cell culture, produces a more than additive effect when added to the culture medium in a mixture with benz(a)anthracene. Trans-stilbene oxide prevents the AHH induction by phenobarbital and not by benz(a)anthracene. Our results suggest that, in addition to its own induction capacity, phenobarbital is also able to potentiate the action of chemicals belonging to a different class of inducers.

  18. Performance of thermoluminescent materials for high dose dosimetry

    International Nuclear Information System (INIS)

    Texeira, Maria I.; Cecatti, Sonia G.P.; Caldas, Linda V.E.

    2008-01-01

    Cases involving high-doses of ionizing radiation are becoming increasingly common.The objective of this work was to characterize thermoluminescent materials for the dosimetry of workers exposed to high doses. Samples of TLD-200, TLD-400 and TLD-800 pellets from Thermo Electron Corporation were studied in gamma high-doses. Dose-response curves were obtained for doses between 100 mGy and 100 Gy. The reproducibility, the lower detection limits and dose-response curves were obtained for all three materials. The different kinds of detectors show usefulness for dosimetry of workers exposed accidentally to high doses. (author)

  19. High-dose vitamin C and cancer

    Directory of Open Access Journals (Sweden)

    Ahmet Unlu, M.D.

    2016-01-01

    Full Text Available Vitamin C (ascorbic acid, ascorbate is a basic compound that is of great importance with its role in various enzymatic reactions including the synthesis of collagen, as well as with its redox functions. Vitamin C has become the center of interest in cancer studies, in consequence of the facts that connective tissue changes and vitamin C deficiency were first alleged to be associated with cancer in the 1950s; and that high doses of vitamin C was asserted to be cytotoxic for cancer cells, later on. The results of the first study carried out in the 1970s were promising; but afterwards, the studies were ascertained to be faulty. Despite the positive results achieved from some laboratory and animal experiments, randomized clinical trials did not verify those findings, and no clear benefit of vitamin C for cancer treatment could be demonstrated. As for studies, where its use in combination with other cancer treatment regimens was assessed, conflicting results were obtained. Although intake of high doses of vitamin C is alleged to be harmless, based on that it is in the group of water soluble vitamins and is not stored in the body, there are many side effects and drug interactions reported in the literature. For now, it is better to abstain from this treatment, until the benefit of the treatment (if any is clearly demonstrated, considering the potential side effects and interactions.

  20. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

    1980-01-01

    The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

  1. A 13-week repeated dose study of three 3-monochloropropane-1,2-diol fatty acid esters in F344 rats.

    Science.gov (United States)

    Onami, Saeko; Cho, Young-Man; Toyoda, Takeshi; Mizuta, Yasuko; Yoshida, Midori; Nishikawa, Akiyoshi; Ogawa, Kumiko

    2014-04-01

    3-monochloropropane-1,2-diol (3-MCPD), a rat renal and testicular carcinogen, has been reported to occur in various foods and food ingredients as free or esterified forms. Since reports about toxicity of 3-MCPD esters are limited, we conducted a 13-week rat subchronic toxicity study of 3-MCPD esters (palmitate diester: CDP, palmitate monoester: CMP, oleate diester: CDO). We administered a carcinogenic dose (3.6 × 10(-4) mol/kg B.W./day) of 3-MCPD or these esters at equimolar concentrations and two 1/4 lower doses by gavage with olive oil as a vehicle five times a week for 13 weeks to F344 male and female rats. As a result, five out of ten 3-MCPD-treated females died from acute renal tubular necrosis, but none of the ester-treated rats. Decreased HGB was observed in all high-dose 3-MCPD fatty acid ester-treated rats, except CDO-treated males. The absolute and relative kidney weights were significantly increased in the ester-treated rats at medium and high doses. Relative liver weights were significantly increased in the esters-treated rat at high dose, except for CMP females. Significant increase in apoptotic epithelial cells in the initial segment of the epididymis of high-dose ester-treated males was also observed. The results suggested that although acute renal toxicity was lower than 3-MCPD, these three 3-MCPD fatty acid esters have the potential to exert subchronic toxicity to the rat kidneys and epididymis, to a similar degree as 3-MCPD under the present conditions. NOAELs (no-observed-adverse-effect levels) of CDP, CMP and CDO were suggested to be 14, 8 and 15 mg/kg B.W./day, respectively.

  2. Effects of low-dose fractionated external irradiation on metabolic and structural characteristics of rat thyroid

    Energy Technology Data Exchange (ETDEWEB)

    Nadolnik, L.; Niatsetskaya, Z. [Institute of Biochemistry, National Academy of Sciences of Belarus, Grodno (Belarus)

    2006-07-01

    , the activity of thyroid-induced NADPH-malate-dehydrogenase in the rat liver cytosolic fraction was decreased to varying degrees in all the groups of irradiated animals (1.32 -2.36-fold). The decreased blood thyroid hormone concentration an d liver NADPH-MDH activity indicate development of radiation-induced hypothyrosis in the radiated animals. As early as after a day following the radiation, the morphologic examination revealed extension of follicular lumen, lymphocytic infiltration of the stroma, desquamation of the follicular epithelium. At remote periods, 0.1 Gy-irradiated animals were revealed thyroid stroma edema, reduction of the follicular dimensions and the presence of loose connective tissue interlayers. After the action of the higher ionizing irradiation doses, there was observed focal perivascular sclerosis, pronounced desquamation of the follicular epithelium with vacuolisation as well as accumulation of lymphoid cells and siderophages. The morphometric examination revealed thyrocytes decreased functional activity. Our research indicates high thyroid sensitivity to effect of external low-dose irradiation. The effect of ionizing irradiation is impaired thyroid iodide metabolism, disturbed thyroid structure and development of hypothyrosis. No pronounced injuring effects of ionizing radiation were revealed only at the 0.1 Gy radiation dose. We suggest the high thyroid radiosensitivity to be due to the specific metabolic features of its cells as well as the specific follicular tissue structure. (authors)

  3. Quality control of 192Ir high dose rate after loading brachytherapy dose veracity

    International Nuclear Information System (INIS)

    Feng Zhongsu; Xu Xiao; Liu Fen

    2008-01-01

    Recently, 192 Ir high dose rate (HDR) afterloading are widely used in brachytherapy. The advantage of using HDR systems over low dose rate systems are shorter treatment time and higher fraction dose. To guarantee the veracity of the delivery dose, several quality control methods are deseribed in this work. With these we can improve the position precision, time precision and dose precision of the brachytherapy. (authors)

  4. Dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action

    Directory of Open Access Journals (Sweden)

    Shu-Guang Cao

    2016-03-01

    Full Text Available The aim of this study was to investigate the dose-dependent effect of ghrelin on gastric emptying in rats and the related mechanism of action. Sixty Wistar rats were randomized into control and test groups, which respectively received intraperitoneal injection of normal saline and ghrelin at different doses (0.5 nmol/kg, 1.0 nmol/kg, 1.5 nmol/kg, 2.0 nmol/kg, and 2.5 nmol/kg. After 45 minutes, all rats were gavaged with semisolid paste. The gastric emptying rate was determined 30 minutes later, and the plasma cholecystokinin level was tested by radioimmunoassay. The mean gastric emptying rate in the test groups was significantly higher than in the control group (38.24 ± 7.15% and 27.18 ± 2.37%, respectively, p < 0.05. Medium and high doses of ghrelin (1.0 nmol/kg, 1.5 nmol/kg, 2.0 nmol/kg, and 2.5 nmol/kg, but not low dose (0.5 nmol/kg, accelerated the gastric emptying. In addition, the plasma cholecystokinin level in the test groups was significantly higher than in the control group (p < 0.01. The gastric emptying rate was positively correlated with the plasma cholecystokinin level (p < 0.01. Intraperitoneal injection of ghrelin at medium and high doses significantly accelerated gastric emptying in rats.

  5. Chemical dosimetry principles in high dose dosimetry

    International Nuclear Information System (INIS)

    Mhatre, Sachin G.V.

    2016-01-01

    In radiation processing, activities of principal concern are process validation and process control. The objective of such formalized procedures is to establish documentary evidence that the irradiation process has achieved the desired results. The key element of such activities is inevitably a well characterized reliable dosimetry system that is traceable to recognized national and international dosimetry standards. Only such dosimetry systems can help establish the required documentary evidence. In addition, industrial radiation processing such as irradiation of foodstuffs and sterilization of health careproducts are both highly regulated, in particular with regard to dose. Besides, dosimetry is necessary for scaling up processes from the research level to the industrial level. Thus, accurate dosimetry is indispensable

  6. Onyx as radiation detector for high doses

    International Nuclear Information System (INIS)

    Teixeira, Maria Inês; Souza, Divanizia N.; Caldas, Linda V.E.

    2011-01-01

    A study of the thermoluminescent (TL) characteristics of white, black and stripped onyx samples is reported in this work. Onyx is a variety of chalcedony, a form of quartz. The onyx stone is considered nobler than marble. The irradiations were performed using a Gamma-Cell 220 system ( 60 Co). The TL emission curves presented two peaks around 150 °C and 210 °C for all samples. The dose–response curves showed a sublinear behavior between 0.5 Gy and 5 kGy, and the lower detection limit for the white onyx pellets was 1.5 mGy. The main dosimetric characteristics were studied, and the material showed good performance for high dose dosimetry.

  7. The application of high dose food irradiation

    International Nuclear Information System (INIS)

    Bruyn, I. De

    1997-01-01

    During the 1950's to end 1970's the United States Army developed the basic methodology to produce shelf stable irradiated meat, seafood and poultry products. These products are normally packed without gravy, sauce or brine, as liquid is not required to sterilize the product as in the canning process. This leads to the distinctive 'dried cooked' taste normally associated with roasts opposed to the casserole taste usually associated with tinned meats. The meats are cooked, chilled, portioned, vacuum packed and irradiated to the required minimum dose of 25 to 45 kGy (depending on the product) at a temperature of between -20 and -40 Centigrade to ensure absolute sterility even under tropical conditions. The product is packaged in a high quality four layer laminate pouch and will therefore not rust or burst even under adverse weather conditions. The product can be guaranteed for more than two years as long as the integrity of the packaging is maintained. (Author)

  8. The application of high dose food irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Bruyn, I. De [Atomic Energy Corporation of South Africa LTD, Building 2000, P.O. Box 582, Pretoria 0001, (South Africa)

    1997-12-31

    During the 1950`s to end 1970`s the United States Army developed the basic methodology to produce shelf stable irradiated meat, seafood and poultry products. These products are normally packed without gravy, sauce or brine, as liquid is not required to sterilize the product as in the canning process. This leads to the distinctive `dried cooked` taste normally associated with roasts opposed to the casserole taste usually associated with tinned meats. The meats are cooked, chilled, portioned, vacuum packed and irradiated to the required minimum dose of 25 to 45 kGy (depending on the product) at a temperature of between -20 and -40 Centigrade to ensure absolute sterility even under tropical conditions. The product is packaged in a high quality four layer laminate pouch and will therefore not rust or burst even under adverse weather conditions. The product can be guaranteed for more than two years as long as the integrity of the packaging is maintained. (Author)

  9. Age influence on retention, distribution and internal doses of 85Sr in rat

    International Nuclear Information System (INIS)

    Tian Wuxun; Wang Decheng; Zhang Hongyuan

    1990-01-01

    After I.V. 85 Sr, the whole body 85 Sr-retentions in rats were fit to two compartment exponential equations. The equation parameters showed a significantly difference between the young group and both the adult and old groups (p 2 ) for 85 Sr in the slow compartment decreased in regular order from the young to the old groups. In the bone 85 Sr-retention equations Tb 2 of the slow compartment for 85 Sr in the young group was significantly lower than the adult and old groups. The doses of the whole body and red-marrow for young rats were 4.2 times as much as those of adult rats, and 6.2 and 5.9 times as much as those old rats. The dose-cumulative speeds was most quick in the young groups and similar in the adult and the old

  10. Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

    International Nuclear Information System (INIS)

    Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

    1986-01-01

    The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism

  11. Limitations of high dose carrier based formulations.

    Science.gov (United States)

    Yeung, Stewart; Traini, Daniela; Tweedie, Alan; Lewis, David; Church, Tanya; Young, Paul M

    2018-06-10

    This study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. Five formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). Increasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations. Copyright © 2018 Elsevier B.V. All

  12. The teratogenic effects of low dose 60Co γ-rays on the early pregnant rats

    International Nuclear Information System (INIS)

    Lu Chunlin

    1991-01-01

    The pregnant Wistar rats were exposed to 0.5 Gy and 1.0 Gy 60 Co γ-rays at the 9th day after conception. The results: 60 Co γ-rays at dose of 1.0 Gy could induced many defects: excenphaly, hydrocephalus, gastroschisis, cleft palate and cleft lip, anophthalmia, microphthalmia, shorten tail and absent tail in surviving fetuses. The growth retardation was found from the parameters of fetal weight, height, head circle and development of skeleton. In the group of radiation dose 0.5 Gy, only hydrocephalus, absent tail and growth retardation of skeleton appeared. The results suggest that low-dose exposure in the early pregnant rats can induce fetal defects and growth retardation. The probable mechanism of teratogen and growth retardation was discussed. The cAMP levels of brain and liver of rat fetuses were reported

  13. Boron neutron capture irradiation of the rat spinal cord: effects of variable doses of borocaptate sodium

    International Nuclear Information System (INIS)

    Morris, Gerard M.; Coderre, Jeffrey A.; Hopewell, John W.; Micca, Peggy L.; Fisher, Craig

    1996-01-01

    The Fischer 344 rat spinal cord model has been used to evaluate the response of the central nervous system to boron neutron capture irradiation with variable doses of the neutron capture agent, borocaptate sodium (BSH). Three doses of BSH, 190, 140 and 80 mg/kg body weight, administered by i.p. injection, were used to establish the time course of 10 B accumulation in and removal from the blood. After administration of the two lower doses of BSH, blood 10 B levels peaked at 0.5 h after injection, with no significant (P > 0.1) change at 1 h after injection. Beyond this time point, levels of 10 B in the blood began to decrease after a dose of 80 mg/kg BSH, but remained constant until 3 h after administration after the two higher doses of BSH. Myelopathy developed after latent intervals of 20.4 ± 0.1, 20.8 ± 1.4, 15.0 ± 0.8, 15.4 ± 0.4 and 15.6 ± 0.4 weeks, following irradiation with thermal neutrons in combination with BSH at doses of 20, 40, 80, 140 and 190 mg/kg body weight, respectively. The radiation-induced lesion in the spinal cord was white matter necrosis. ED 50 values for myelopathy were calculated from probit-fitted dose-effect curves. Expressed as total physical absorbed doses, these values were 20.7 ± 1.9, 24.9 ± 1.2, 27.2 ± 0.9, 28.4 ± 0.6 and 32.4 ± 1.9 Gy after irradiation with thermal neutrons in the presence of 20, 40, 80, 140 and 190 mg/kg body weight of BSH, respectively. The compound biological effectiveness (CBE) factor values, estimated from this data, were in the range 0.49-0.55. There was no significant (P >0.1) variation in the CBE factor for BSH as a function of increasing 10 B concentration in the blood. It was concluded that there was no significant synergistic interaction between the low and high linear energy transfer (LET) components of the boron neutron capture (BNC) radiation field

  14. Optimizing hyaluronidase dose and plasmid DNA delivery greatly improves gene electrotransfer efficiency in rat skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Vedel, Kenneth; Needham Andersen, Josefine

    2015-01-01

    Transfection of rat skeletal muscle in vivo is a widely used research model. However, gene electrotransfer protocols have been developed for mice and yield variable results in rats. We investigated whether changes in hyaluronidase pre-treatment and plasmid DNA delivery can improve transfection...... with a homogenous distribution. We also show that transfection was stable over five weeks of regular exercise or inactivity. Our findings show that species-specific plasmid DNA delivery and hyaluronidase pre-treatment greatly improves transfection efficiency in rat skeletal muscle....... efficiency in rat skeletal muscle. We found that pre-treating the muscle with a hyaluronidase dose suitable for rats (0.56. U/g b.w.) prior to plasmid DNA injection increased transfection efficiency by >200% whereas timing of the pre-treatment did not affect efficiency. Uniformly distributing plasmid DNA...

  15. Analysis of ethyl acrylate (EA) and acrylic acid (AA) residues from rat tissues following oral ea dosing

    International Nuclear Information System (INIS)

    Udinsky, J.R.; Frederick, C.B.

    1990-01-01

    Gavage dosing of rats with EA at high dose levels (100 or 200 mg/kg) has resulted in tumors at the dosing site, forestomach (FST), but no lesions of the glandular stomach (GST) or other remote tissues. Since previous in vitro studies have demonstrated that EA is very rapidly metabolized to AA and glutathione conjugates, EA and AA residues were analyzed 0-24 hr following gavage dosing of non-fasted F-344/N male rats with [1- 14 C]EA in corn oil at 10, 50, and 200 mg/kg. Analysis of total 14 C indicated that the dose solution was primarily in the FST at ≥5 min after dosing, although 14 C was detected in the GST, duodenum, and small intestine (attributed to distension of the FST and leakage from the FST to the GST). HPLC analysis of the gut contents, gut wall, liver, kidneys, lungs, and blood indicated that EA and AA could only be detected at ≥15 min in the FST and GST contents, and in the FST tissue. AA alone was detected in the GST tissue, duodenum tissue and contents, and small intestine tissue and contents. The minimum level of detection was 0.0005% of the dose. The remaining 14 C was primarily attributed to binding to the gut contents or bioincorporation of AA. The detection of EA and AA residues only in the upper gastrointestinal tract following gavage dosing is consistent with rapid detoxification of EA by hydrolysis and conjugation which prevents toxicity at sites remote form the site of dosing

  16. Evolution of late blood damage from decreasing doses of 241Am following injection in the rat

    International Nuclear Information System (INIS)

    Maillard, M.J.; Boncorps, Janine.

    1982-04-01

    Rats were given intravenous or intramuscular injections of 241 Am at decreasing doses ranging from 7.5 μCi to 0.075 μCi per kg of body weight. Blood examinations showed that higher doses exerted an irreversible destructive effect on all blood cells. As the administered doses decreased, the destructive effect of 241 Am dropped and even became reversible for white cells. Proliferative disorders such as leukocytosis with myelemias, leukemias -chiefly acute or chronic granulocytic leukemias- were then demonstrated. Red cells only dropped but more and more slowly. At the lowest doses, life-span shortening was the most evident effect [fr

  17. Dose-Related Effects of Acetylsalicylic acid (ASA) on Gamma Radiation-Induced Teratogenicity in Pregnant Albino Rats

    International Nuclear Information System (INIS)

    Ibrahim, M.F.

    2013-01-01

    Reviews of acetylsalicylic acid (ASA), a widely used nonsteroidal anti- inflammatory drug, has consistently suggested a possible association between prenatal ASA ingestion and adverse effects in the pregnant mothers and their developing fetuses. The objective of the current study was to comprehensively define the effect of relatively low and high doses of ASA (25 mg/kg body wt. and 200 mg/kg body wt. respectively) on gestating rats and their possible impact on the irradiated ones. Therefore 36 pregnant rats were randomly divided into 6 equal groups. Three rat groups were daily orally gavaged from the 7th to the 18th gestational days with: distilled water (Group 1), 25 mg/kg body wt. ASA (Group 2) and 200 mg/kg body wt. ASA (Group 3). The other three groups similarly received the same previous treatments besides 2 Gy whole body gamma irradiation of each, to serve as: Group 4 (distilled water + irradiation), Group 5 (25 mg/kg body wt. ASA + irradiation) and Group 6 (200 mg/kg body wt. ASA + irradiation). All rat groups were sacrificed on the 20th day of pregnancy and the uterine contents were examined. The lower ASA dose (25 mg/kg body wt.) treated group (Group 2) displayed healthy mothers and fetuses whereas that of the higher dose (200 mg/kg body wt.) (Group 3) despite not showing significant maternal or fetal mortalities, yet the intrauterine contents presented fetal developmental disorders including stunted growth and resorption together with some head and limb anomalies including plagiocephaly, marked acampsia and acrocontracture. Meanwhile, results have unexpectedly shown a radioprotective role of the lower ASA dose (25 mg/kg. body wt.) (Group 5) to pregnant rats and their fetuses as inspected by its efficacy in retrieving the radiation induced maternal weight loss together with its noticeable ameliorating effects on the intrauterine lethality of the affected fetuses and their externally detected abnormalities in addition toits effectiveness in retaining some

  18. ELDRS Characterization for a Very High Dose Mission

    Science.gov (United States)

    Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

    2010-01-01

    Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

  19. Brachytherapy treatment with high dose rate

    International Nuclear Information System (INIS)

    Santana Rodriguez, Sergio Marcelino; Rodriguez Rodriguez, Lissi Lisbet; Ciscal Chiclana, Onelio Alberto

    2009-01-01

    Retrospectively analyze results and prognostic factors of cervical cancer patients treated with radio concomitant cisplatin-based chemotherapy, radiation therapy combined modality. Methods: From January 2003 to December 2007, 198 patients with invasive cervical cancer were treated at the Oncology Department of Hospital Robau Celestino Hernandez (brachytherapy performed at INOR). The most common age group was 31 to 40 years. The histology in squamous cell carcinoma accounted for 84.3% of cases. The treatment consisted of external pelvic irradiation and vaginal brachytherapy, high dose rate. Concomitant chemotherapy consisted of cisplatin 40 mg/m2 weekly with a maximum of 70 mg for 5 weeks. Results: 66.2% of patients completed 5 cycles of chemotherapy. The median overall survival was 39 months, overall survival, disease-free survival and survival free of locoregional recurrence at 5 years of 78%, 76% and 78.6% respectively .. We found that clinical stage, histological type (adenocarcinoma worst outcome) were statistically related to level of response. Conclusions: Treatment with external pelvic radiation, brachytherapy and concurrent weekly cisplatin in patients with stage IIIB cervical cancer is feasible in the Chilean public health system, well tolerated and results comparable to international literature. (Author)

  20. The effect of sub-lethal doses on the ploidy level in rats hepatocytes with aging

    International Nuclear Information System (INIS)

    Ekhtiar, A. M.

    2004-11-01

    It has been shown that the polyploidization levels in rat's hepatocytes increased with aging. The high LET ionizing radiation also induce cell polyploidization by two different means: cells and nuclei fusion, and mitosis restriction after DNA replication. The purpose of the present study was to determine the kinetic of rat's hepatocytes polyploidization with ageing, and the late effects of low doses of gamma irradiation on polyploidization. To this end, three groups of rats were used. Each group composed of 175 four weeks old animals. The first was served as a control, the second and the third groups were irradiated with 4 and 2 Gy respectively, of gamma irradiation at the age of one month. Of each group, 7-8 animals were monthly scarified (for two years), and their liver tissues were used to obtain cell suspensions which were further fixed in gradual series concentrations of ethanol. After staining with Propidum Iodide 'PI' (10 6 cells per ml of PI used at 10 - 5 M final concentration), the cells were analyzed on a FACS Vantage Flow Cytometer (Becton Dickinson). In the control, the results showed: 1) A decrease of cell fraction that contained normal diploid until steady level. 2) Biphasic changes of fraction tetraploidy cells (increase until age of 4 month followed by decrease). 3) The fraction of octaploidy cells appeared at age of 3-4 month and increased continuously with the aging. In accompanied to life-span reductions of 4 Gy irradiated animals, the DNA contents were similar to those in control groups in addition to some quantities variation due to a programmed cell death (Apoptosis) induced by irradiation and regenerations. These variations persisted till the age of 7 month, in additional to reduce the spin-life of irradiated animals. The irradiation with 2 Gy induced some quantities variation in comparison with nonirradiated group, appeared in the reduction of rate conversion from one ploidy class to another, and in shift with 2-3 months of the second pike

  1. In vivo genotoxicity of furan in F344 rats at cancer bioassay doses

    International Nuclear Information System (INIS)

    Ding, Wei; Petibone, Dayton M.; Latendresse, John R.; Pearce, Mason G.; Muskhelishvili, Levan; White, Gene A.; Chang, Ching-Wei; Mittelstaedt, Roberta A.; Shaddock, Joseph G.; McDaniel, Lea P.; Doerge, Daniel R.; Morris, Suzanne M.; Bishop, Michelle E.; Manjanatha, Mugimane G.; Aidoo, Anane; Heflich, Robert H.

    2012-01-01

    Furan, a potent rodent liver carcinogen, is found in many cooked food items and thus represents a human cancer risk. Mechanisms for furan carcinogenicity were investigated in male F344 rats using the in vivo Comet and micronucleus assays, combined with analysis of histopathological and gene expression changes. In addition, formamidopyrimidine DNA glycosylase (Fpg) and endonuclease III (EndoIII)-sensitive DNA damage was monitored as a measure of oxidative DNA damage. Rats were treated by gavage on four consecutive days with 2, 4, and 8 mg/kg bw furan, doses that were tumorigenic in 2-year cancer bioassays, and with two higher doses, 12 and 16 mg/kg. Rats were killed 3 h after the last dose, a time established as producing maximum levels of DNA damage in livers of furan-treated rats. Liver Comet assays indicated that both DNA strand breaks and oxidized purines and pyrimidines increased in a near-linear dose-responsive fashion, with statistically significant increases detected at cancer bioassay doses. No DNA damage was detected in bone marrow, a non-target tissue for cancer, and peripheral blood micronucleus assays were negative. Histopathological evaluation of liver from furan-exposed animals produced evidence of inflammation, single-cell necrosis, apoptosis, and cell proliferation. In addition, genes related to apoptosis, cell-cycle checkpoints, and DNA-repair were expressed at a slightly lower level in the furan-treated livers. Although a mixed mode of action involving direct DNA binding cannot be ruled out, the data suggest that furan induces cancer in rat livers mainly through a secondary genotoxic mechanism involving oxidative stress, accompanied by inflammation, cell proliferation, and toxicity. -- Highlights: ► Furan is a potent rodent liver carcinogen and represents a human cancer risk. ► Furan induces DNA damage in rat liver at cancer bioassay doses. ► Furan induces oxidative stress, inflammation and cell proliferation in rat liver. ► Expression of

  2. Diethylene glycol-induced toxicities show marked threshold dose response in rats

    Energy Technology Data Exchange (ETDEWEB)

    Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

    2015-02-01

    Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

  3. Hepatocyte membrane injury and bleb formation following low dose comfrey toxicity in rats.

    Science.gov (United States)

    Yeong, M L; Wakefield, S J; Ford, H C

    1993-04-01

    Comfrey, a popular herbal remedy, contains hepatotoxic pyrrolizidine alkaloids and has been implicated in recent human toxicity. Although alkaloids from other plant sources have been extensively researched, studies on the hepatotoxic effects of comfrey alkaloids are scant. The effects of high dose comfrey toxicity have been studied and the present investigation was undertaken to identify changes associated with relatively low dose toxicity. Eight young adult rats were dosed weekly for six weeks with 50 mg/kg of comfrey derived alkaloids. The animals were dissected one week after the last dose and the livers examined by light and electron microscopy. Changes at the light microscopic level showed vascular congestion, mild zone 3 necrosis and loss of definition of hepatocyte cellular membranes. Extensive ultrastructural abnormalities were identified in the form of endothelial sloughing and the loss of hepatocyte microvilli. A striking finding was florid bleb formation on the sinusoidal borders of hepatocytes. Many blebs were shed into the space of Disse and extruded to fill, and sometimes occlude, sinusoidal lumina. Platelets were frequently found in areas of bleb formation. There was evidence of late damage in collagenization of Disse's space. Hepatocyte bleb formation is known to occur under a variety of pathological conditions but there is little to no information in the literature on the effects, if any, of bleb formation on fibrogenesis and the microcirculation and its role in the pathogenesis of liver disease. The pyrrolizidine alkaloids of comfrey may serve as an experimental tool to study the process of bleb formation and the intimate relationship between hepatocyte and sinusoidal injury in the liver.

  4. Effects of sublethal doses of gamma radiation on the developing rat brain

    International Nuclear Information System (INIS)

    Cerda, H.; Carlsson, J.; Larsson, B.; Saefwenberg, J.O.

    1975-01-01

    Newborn rats were irradiated with 60 Co gamma rays. Doses of 0, 80 or 160 rads were given to the whole body. The whole body and brain weights, DNA and RNA contents of the brain and 3 H-thymidine or 3 H-uridine incorporated by the brain were measured at 5, 10 or 15 days after birth. A dose of 160 rads produced clear alterations in the brain but no clear effects could be detected when 80 rads were given. (author)

  5. Organization of rat neuronal DNA as a function of dose, time after irradiation and age

    International Nuclear Information System (INIS)

    Jaberaboansari, A.

    1989-01-01

    The organization of DNA and chromatin structure were examined in male Fisher 344 rat cerebellar neurons at various times from < 5 min to 2 years after exposure to ionizing radiation. Immediately after irradiation, the organization of neuronal DNA was altered. First, the DNA superhelical structure was changed due to removal of the topological constraints on the supercoiled DNA loops. Secondly, the accessibility of bulk neuronal DNA to digestion by micrococcal nuclease was increased. This increase in the m. nuclease sensitivity of bulk DNA did not depend on the oxygen concentration during irradiation. Thirdly, the accessibility of the nuclear matrix-associated DNA to digestion by DNase I was decreased. This decrease was most likely caused by masking the DNA with additional nuclear matrix-associated proteins. This increase in protein content was independent of oxygen, but inhibited if irradiations were performed at 4 degree C. The kinetics were consistent with the saturation kinetics observed for DNA repair in cerebellar neurons. Thus, these proteins may be associated with repair of radiation-induced DNA damage. The neuronal DNA/chromatin structure was restored to its unirradiated state by 24 hr after irradiation with biphasic kinetics having half-times similar to those reported for repair of radiation-induced DNA damage. However, the evidence suggested that residual DNA damage occurred in aging rats that had received a relatively high radiation dose at 4 months of age. In those rats, there was: (a) a decrease in the total nuclear protein content with age, (b) an increase in the digestibility of bulk DNA by m. nuclease with age, and (c) a reduction in the amount of nuclear matrix-associated proteins that persisted with age

  6. High dose potassium-nitrate chemical dosimeter

    International Nuclear Information System (INIS)

    Dorda de Cancio, E.M.; Munoz, S.S.

    1982-01-01

    This dosimeter is used to control 10 kGY-order doses (1 Mrad). Nitrate suffers a radiolitic reduction phenomena, which is related to the given dose. The method to use potassium nitrate as dosimeter is described, as well as effects of the temperature of irradiation, pH, nitrate concentration and post-irradiation stability. Nitrate powder was irradiated at a Semi-Industrial Plant, at Centro Atomico Ezeiza, and also in a Gammacell-220 irradiator. The dose rates used were 2,60 and 1,80 KGY/hour, and the given doses varied between 1,0 and 150 KGY. The uncertainty was +-3% in all the range. (author) [es

  7. Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

    Energy Technology Data Exchange (ETDEWEB)

    Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Brandenburg, Sytze [KVI Center for Advanced Radiation Research, University of Groningen, Groningen (Netherlands); Langendijk, Johannes A. [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Coppes, Robert P. [Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands); Luijk, Peter van, E-mail: p.van.luijk@umcg.nl [Department of Radiation Oncology, University of Groningen, University Medical Center Groningen, Groningen (Netherlands)

    2016-01-01

    Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed the dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late

  8. Low-dose effects of bisphenol A on early sexual development in male and female rats

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Petersen, Marta Axelstad; Boberg, Julie

    2014-01-01

    the influence of BPA on early sexual development in male and female rats at dose levels covering both regulatory no observed adverse effect levels (NOAELs) (5 and 50 mg/kg bw per day) as well as doses in the microgram per kilogram dose range (0.025 and 0.25 mg/kg bw per day). Time-mated Wistar rats (n=22) were...... in both sexes indicates effects on prenatal sexual development and provides new evidence of low-dose adverse effects of BPA in rats in the microgram per kilogram dose range. The NOAEL in this study is clearly below 5 mg/kg for BPA, which is used as the basis for establishment of the current tolerable......Bisphenol A (BPA) is widely detected in human urine and blood. BPA has been reported to impair many endpoints for reproductive and neurological development; however, it is controversial whether BPA has effects in the microgram per kilogram dose range. The aim of the current study was to examine...

  9. Lifetime exposure to low doses of lead in rats: effect on selected parameters of carbohydrate metabolism.

    Science.gov (United States)

    Nováková, Jaroslava; Lukačínová, Agnesa; Lovásová, Eva; Cimboláková, Iveta; Rácz, Oliver; Ništiar, František

    2015-05-01

    The aim of the study was to assess the effects of exposure to low doses of lead dissolved in drinking water (average daily dose of 2.2 mg kg(-1) day(-1)) on selected carbohydrate metabolism parameters in 20 wistar rats. Animals were divided into two groups - control (C) (group drinking clear water) and experimental group (Pb; group exposed to low doses of lead acetate in a concentration of 100 μmol l(-1) of drinking water). In this study, we studied the biochemical parameters (glucose, haemoglobin (Hb), glycated haemoglobin (HbA1c), lactate dehydrogenase (LDH) and amylase (AMS)) in rat blood. Glucose and Hb concentration and AMS activity decreased, LDH activity increased but HbA1c concentration levels did not change in rats exposed to lead. Our results well documented that lifetime exposure to lead affected carbohydrate metabolism of rats. Some parameters like concentration of Hb as well as activities of AMS and LDH are useful markers of intoxication of rats with lead. For the evaluation of results (e.g. AMS), not only the data at the end of the experiment should be taken into account but also the entire duration of trials (i.e. more time steps) that makes results more objective should be considered. © The Author(s) 2013.

  10. Dose-rate effects on gamma-induced genetic injury in rat spermatogonia

    International Nuclear Information System (INIS)

    Vyglenov, A.

    1990-01-01

    Data for correlation between the reciprocal translocations (RT) yield in rat germ cells and the doses of 0.5 - 3.0 Gy are presented. A 60 Co source has been used with dose rates of 0.25, 8 x 10 -2 and 7 x 10 -3 Gy/min. The results from the cytogenetic analysis made 6 months after irradiation have shown an increase of the yield with the increase of the dose, which can be described as a linear unthreshold dependence. The dose rate effect is expressed in decrease of mutation frequency. The comparison with earlier author's data from similar experiments for acute irradiation allows to determine the RBE of gamma irradiation at the three dose rates investigated as 0.6, 0.2 and 0.1 respectively. The reported results are connected with the problem of variety specificity of the dose rate effect. 2 figs., 2 tabs., 15 refs

  11. Low-dose acute vanillin is beneficial against harmaline-induced tremors in rats.

    Science.gov (United States)

    Abdulrahman, Al Asmari; Faisal, Kunnathodi; Meshref, Ali Al Amri; Arshaduddin, Mohammed

    2017-03-01

    To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

  12. Metabolic Effects of Two Different Doses of Venlafaxine Therapy on Rats

    Directory of Open Access Journals (Sweden)

    Annamária Imre

    2015-09-01

    Full Text Available Objectives: Venlafaxine is an antidepressant, categorized as a serotonin-norepinephrine reuptake inhibitor (SNRI with suspected metabolic side effects. The aim of our study was to assess these metabolic effects in rats, using two different doses of venlafaxine.

  13. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats Authors: Gary E. Hatch, John McKee, James Brown, Bill McDonnell, Elston Seal, Joleen Soukup, Ralph Slade, Kay Crissman and Robert Devlin, National Health and Environmental...

  14. Effect of action of fractioned ionizing radiation in small dose on thyroid gland of rats

    OpenAIRE

    О. О. Prykhodko; V. V. Lizogubov; V. S. Usenko

    2005-01-01

    The effect of fractionated X-irradiation by 0.25 Gy dose to rat thyroid gland was studied . It was shown the decrease of thyrocyte proliferative activity that can induce the late effect of pathogenesis to thyroid land and biochemical pathways that control by thyroid hormones. Additional effect by any mutagenic factor may induce thyroid tumor development.

  15. Changes in Plasma Corticosterone and Catecholamine Contents Induced by Low Doses of Deltamethrin in Rats

    NARCIS (Netherlands)

    Boer, Sietse F. de; Gugten, Jan van der; Slangen, Jef. L.; Hijzen, Theo H.

    1988-01-01

    The effects of low doses of (S)-α-cyano-3-phenoxybenzyl (1R)-cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate (Roussel UCLAF, Paris, France), (deltamethrin) upon sympathetic-adrenomedullary and pituitary-adrenocortical activity were investigated in rats by measuring plasma noradrenaline

  16. Pharmacological dose of alpha-tocopherol induces cardiotoxicity in Wistar rats determined by echocardiography and histology

    Science.gov (United States)

    The effect of pharmacological dose of alpha-tocopherol on heart health was determined in Wistar rats. Animals were randomly assigned to either C (control, n = 11) or E (alpha-tocopherol, n = 11) group. Animals received corn oil (C) or alpha-tocopherol dissolved in corn oil (250 mg alpha-tocopherol/[...

  17. Effects of low doses of gamma radiation on DNA synthesis in the developing rat brain

    International Nuclear Information System (INIS)

    Cerda, H.

    1983-01-01

    Rats of one or ten days of age were irradiated with low doses of gamma radiation, and synthesis of DNA was examined by the incorporation of 3 H-thymidine in the cerebellum and the rest of the brain in vivo. DNA synthesis was depressed in both parts of the brain but the effects were larger in cerebellum. A minimum was found about 10 hours after irradiation in the older rats and later (18 h) in the younger ones. The dose response in 10 day-old rats, was biphasic and showed that cerebellum was more affected. Autoradiographs showed that fewer cells entered the cycle and those synthesizing showed a depressed rate of synthesis. These findings are discussed in relation to induction of cell death. (Auth.)

  18. Lung tumors and radon inhalation in over 2000 rats: Approximate linearity across a wide range of doses and potentiation by tobacco smoke

    International Nuclear Information System (INIS)

    Gray, R.G.; Lafuma, J.; Parish, S.E.; Peto, R.; CEA Centre d'Etudes Nucleaires de Fontenay-aux-Roses

    1986-01-01

    More than 2000 rats were exposed to cumulative doses of up to 28,000 WLMs of radon gas. More than 300 pulmonary tumors were induced by this exposure, most being nonfatal lesions detected only at autopsy of animals that had died of unrelated causes. Above 6000 WLMs rats suffered increasingly from life shortening due to radiation-induced nonneoplastic causes and so had less time in which to develop tumors. When adjusted for these competing causes of death, the hazard function for the excess risk of developing pulmonary tumors was approximately linearly related to dose throughout the range of doses studied. This suggests that some previously reported high-dose ''reductions'' in radiogenic tumor-induction rates may chiefly have involved the killing of rats rather than the killing of precursor cells. Rats exposed to radon and then to six months of inhalation of tobacco smoke had a four times greater age-specific prevalence of pulmonary tumors than rats exposed to an identical radon dose either alone or preceded by tobacco smoke inhalation. This suggests that tobacco smoke may accelerate the carcinogenic process by acting as a promoter of radiation-induced somatic damage. These data suggest that, for assessing human risk from exposure to radon, the linear model should be assumed, but that the WLM is not on its own an adequate index of carcinogenic insult. 7 refs., 2 figs., 4 tabs

  19. No priming of the immune response in newborn Brown Norway rats dosed with ovalbumin in the mouth

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Pilegaard, Kirsten

    2003-01-01

    with ovalbumin and if this method could be used in an animal model for food allergy. Methods: Newborn Brown Norway rats were dosed with ovalbumin in the mouth (100 mug or 6 mg). As young adults, the animals were dosed by gavage for 35 days with 1 mg ovalbumin/day or once intraperitoneally with 100 mug. Control......E and IgG responses were decreased compared to the control groups, however, not always reaching statistical significance. A statistical significant decrease in the specific immune response was found in young adult rats dosed in the mouth as compared to by gavage. Conclusions: Dosing Brown Norway rats...

  20. ''Low dose'' and/or ''high dose'' in radiation protection: A need to setting criteria for dose classification

    International Nuclear Information System (INIS)

    Sohrabi, M.

    1997-01-01

    The ''low dose'' and/or ''high dose'' of ionizing radiation are common terms widely used in radiation applications, radiation protection and radiobiology, and natural radiation environment. Reading the title, the papers of this interesting and highly important conference and the related literature, one can simply raise the question; ''What are the levels and/or criteria for defining a low dose or a high dose of ionizing radiation?''. This is due to the fact that the criteria for these terms and for dose levels between these two extreme quantities have not yet been set, so that the terms relatively lower doses or higher doses are usually applied. Therefore, setting criteria for classification of radiation doses in the above mentioned areas seems a vital need. The author while realizing the existing problems to achieve this important task, has made efforts in this paper to justify this need and has proposed some criteria, in particular for the classification of natural radiation areas, based on a system of dose limitation. (author)

  1. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    International Nuclear Information System (INIS)

    Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

    2011-01-01

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

  2. High dose radiotherapy for pituitary tumours

    International Nuclear Information System (INIS)

    Mead, K.W.

    1981-01-01

    The results of treatment of 120 pituitary tumours are presented. Based on this experience operable chromophobe adenomas are now treated with 5,000 rads in 4 weeks and inoperable ones receive an additional central dose to 7,500 rads. Pituitary Cushing's tumours are given 10,000 rads in 5 weeks using small fields and acromegalics 5,000 rads to the whole sella and 7,500 to its lower half. The absence of complications at these dose levels is attributed to the use of small fields and the precise application of treatment

  3. High dose radiotherapy for pituitary tumours

    Energy Technology Data Exchange (ETDEWEB)

    Mead, K.W. (Queensland Radium Inst., Herston (Australia))

    1981-11-01

    The results of treatment of 120 pituitary tumours are presented. Based on this experience operable chromophobe adenomas are now treated with 5,000 rads in 4 weeks and inoperable ones receive an additional central dose to 7,500 rads. Pituitary Cushing's tumours are given 10,000 rads in 5 weeks using small fields and acromegalics 5,000 rads to the whole sella and 7,500 to its lower half. The absence of complications at these dose levels is attributed to the use of small fields and the precise application of treatment.

  4. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  5. Study on serum metabonomics of rats exposed to low-dose ionizing radiation, carbon monoxide, benzene and noise

    Directory of Open Access Journals (Sweden)

    Qing-rong WANG

    2015-07-01

    Full Text Available Objective To investigate the combined effects of low-dose ionizing radiation, carbon monoxide, benzene and noise on serum metabolites and the mechanism of injury induced by these complex environmental factors in rats. Methods  Sixteen adult SD rats were randomly divided into control group and exposed group (8 each. The exposed group received the combined effect every day for 7 days. At the end of experiment, sera were collected from the abdominal aorta of rats. The metabolic fingerprint of serum was obtained by 1H nuclear magnetic resonance (1H NMR spectroscopy and determined with pattern recognition techniques of principal component analysis (PCA and orthogonal signal correction-partial least squares (OSC-PLS. The similarities and differences in metabolic profiles between two groups were visualized by SIMCA-P software. Results The rat serum 1H NMR spectra revealed different metabolic spectra between the control group and exposed group. The OSC-PLS plots of the serum samples presented respectively marked clustering between the two groups. Compared with the control group, the contents of lipid, high density lipoprotein, glycine/glucose, N-acetyl glycoprotein 1, N-acetyl glycoprotein 2, phosphatidyl choline and unsaturated fatty acid increased, while those of lactic acid, threonine/lipid, alanine, creatine, glycerylphosphorylcholine/ trimethylamine oxide, low density lipoprotein/high density lipoprotein, low density lipoprotein, very low density lipoprotein/ low density lipoprotein, very low density lipoprotein and saturated fatty acid decreased. Conclusions Combination of low-dose ionizing radiation, carbon monoxide, benzene and noise could induce changes of serum metabolites in rats, involving in immune function, renal function and energy metabolism. The NMR-based-metabonomics method has potential of application in research on combined biological effects of the complex environmental factors. DOI: 10.11855/j.issn.0577-7402.2015.07.09

  6. High dose rate brachytherapy in treatment of high grade astrocytomas

    International Nuclear Information System (INIS)

    Garcia-Alejo, R.; Delgado, J.M.; Cerro, E. del; Torres, J.J.; Martinez, R.

    1996-01-01

    From May 1994 to June 1995, 18 patients with high grade astrocytomas were entered prospectively on a selective protocol combining surgery, external beam radiotherapy, stereotactic interstitial implantation with HDR Iridium 192 and chemotherapy. Only those patients with tumor size 100cc or less average dimension, high grade astrocytoma, Karnofsky 70 or greater, unilateral, circumscribed, unifocal, tumor stable or responding to external radiation and supratentorial were included in the study. Ages ranged from 16 to 69 years. There were 13 males and 5 females. Surgery consisted of biopsy only in 3 patients, subtotal resection in 11, and gross total resection in 4 patients. Focal external beam radiation portals included the contrast enhancing mass on CT scan plus a 3 cm margin. The protocol called for minimum tumor dose of 60 Gy to be given in 2 Gy daily fractions. An interstitial brachytherapy boost was to be performed two weeks after the conclusion of external beam radiation. The dose was 30 Gy in 4 fractions. The authors analyze on basis on their personal experience, the possibilities and the limits offered by this therapeutic procedure in neuro-oncology. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically possible with negligible acute morbidity and mortality, and appeared to be effective and may provide for an increase in tumor control in selected cases

  7. Evaluation of the dose uniformity for double-plane high dose rate interstitial breast implants with the use of dose reference points and dose non-uniformity ratio

    International Nuclear Information System (INIS)

    MAjor, T.; Polgar, C.; Somogyi, A.; Nemeth, G.

    2000-01-01

    This study investigated the influence of dwell time optimizations on dose uniformity characterized by dose values in dose points and dose non-uniformity ratio (DNR) and analyzed which implant parameters have influence on the DNR. Double-plane breast implants with catheters arranged in triangular pattern were used for the calculations. At a typical breast implant, dose values in dose reference points inside the target volume and volumes enclosed by given isodose surfaces were calculated and compared for non-optimized and optimized implants. The same 6-cm treatment length was used for the comparisons. Using different optimizations plots of dose non-uniformity ratio as a function of catheter separation, source step size, number of catheters, length of active sections were drawn and the minimum DNR values were determined. Optimization resulted in less variation in dose values over dose points through the whole volume and in the central plane only compared to the non-optimized case. At implant configurations consisting of seven catheters with 15-mm separation, 5-mm source step size and various active lengths adapted according to the type of optimization, the no optimization, geometrical (volume mode) and dose point (on dose points and geometry) optimization resulted in similar treatment volumes, but an increased high dose volume was observed due to the optimization. The dose non-uniformity ratio always had the minimum at average dose over dose normalization points, defined in the midpoints between the catheters through the implant volume. The minimum value of DNR depended on catheter separation, source step size, active length and number of catheters. The optimization had only a small influence on DNR. In addition to the reference points in the central plane only, dose points positioned in the whole implant volume can be used for evaluating the dose uniformity of interstitial implants. The dose optimization increases not only the dose uniformity within the implant but

  8. Oral exposure to low-dose of nonylphenol impairs memory performance in Sprague-Dawley rats.

    Science.gov (United States)

    Kawaguchi, Shinichiro; Kuwahara, Rika; Kohara, Yumi; Uchida, Yutaro; Oku, Yushi; Yamashita, Kimihiro

    2015-02-01

    Nonylphenol ethoxylate (NPE) is a non-ionic surfactant, that is degraded to short-chain NPE and 4-nonylphenol (NP) by bacteria in the environment. NP, one of the most common environmental endocrine disruptors, exhibits weak estrogen-like activity. In this study, we investigated whether oral administration of NP (at 0.5 and 5 mg/kg doses) affects spatial learning and memory, general activity, emotionality, and fear-motivated learning and memory in male and female Sprague-Dawley (SD) rats. SD rats of both sexes were evaluated using a battery of behavioral tests, including an appetite-motivated maze test (MAZE test) that was used to assess spatial learning and memory. In the MAZE test, the time required to reach the reward in male rats treated with 0.5 mg/kg NP group and female rats administered 5 mg/kg NP was significantly longer than that for control animals of the corresponding sex. In other behavioral tests, no significant differences were observed between the control group and either of the NP-treated groups of male rats. In female rats, inner and ambulation values for animals administered 0.5 mg/kg NP were significantly higher than those measured in control animals in open-field test, while the latency in the group treated with 5 mg/kg NP was significantly shorter compared to the control group in step-through passive avoidance test. This study indicates that oral administration of a low-dose of NP slightly impairs spatial learning and memory performance in male and female rats, and alters emotionality and fear-motivated learning and memory in female rats only.

  9. Dosimetry in high dose rate endoluminal brachytherapy

    International Nuclear Information System (INIS)

    Uno, Takashi; Kotaka, Kikuo; Itami, Jun

    1994-01-01

    In endoluminal brachytherapy for the tracheobronchial tree, esophagus, and bile duct, a reference point for dose calculation has been often settled at 1 cm outside from the middle of source travel path. In the current study, a change in the ratio of the reference point dose on the convex to concave side (Dq/Dp) was calculated, provided the source travel path bends as is the case in most endoluminal brachytherapies. Point source was presumed to move stepwise at 1 cm interval from 4 to 13 locations. Retention time at each location was calculated by personal computer so as to deliver equal dose at 1 cm from the linear travel path. With the retention time remaining constant, the change of Dq/Dp was assessed by bending the source travel path. Results indicated that the length of the source travel path and radius of its curve influenced the pattern of change in Dq/Dp. Therefore, it was concluded that the difference in reference dose on the convex and concave side of the curved path is not negligible under certain conditions in endoluminal brachytherapy. In order to maintain the ratio more than 0.9, relatively greater radius was required when the source travel path was decreased. (author)

  10. Cutaneous dosimetry at low and high dose

    International Nuclear Information System (INIS)

    Martin, M.

    2009-01-01

    As radiodermatitis is a complication related to the exposure to ionizing radiation after an accidental exposition or a medical examination (radiotherapy or interventional radiology), the author briefly reports an investigation of the response of the human keratinocyte to irradiation for different dose levels, and the search for exposure markers

  11. Dosing-time-dependent variation in biliary excretion of flomoxef in rats.

    Science.gov (United States)

    Hishikawa, Shuji; Sugimoto, Koh-ichi; Kobayashi, Eiji; Kumagai, Yuji; Fujimura, Akio

    2003-05-01

    We previously reported that the biliary excretion of flomoxef, an oxacephem antibiotic, was greater after dosing at 21:00 than at 09:00 h in diurnally active human subjects. The present study was undertaken to examine whether the biliary excretion of flomoxef is also dependent on its dosing time in rats. Adult male Wistar rats were housed under light on at 07:00 h and off at 19:00 h. Bile fluid was completely drained through a polyethylene catheter from conscious animals. Flomoxef (20 mg/kg) was injected into the tail vein at 09:00 or 21:00 h by a cross-over design, and drained bile fluid was collected for 8 h after each dosing. The maximum concentration of biliary flomoxef was significantly greater and its total excretion tended to be greater after dosing at 09:00 than 21:00 h. These results suggest the biliary excretion of flomoxef is enhanced after dosing at the beginning of the rest period in rats, as it is in humans.

  12. Dose volume assessment of high dose rate 192IR endobronchial implants

    International Nuclear Information System (INIS)

    Cheng, B. Saw; Korb, Leroy J.; Pawlicki, Todd; Wu, Andrew

    1996-01-01

    Purpose: To study the dose distributions of high dose rate (HDR) endobronchial implants using the dose nonuniformity ratio (DNR) and three volumetric irradiation indices. Methods and Materials: Multiple implants were configured by allowing a single HDR 192 Ir source to step through a length of 6 cm along an endobronchial catheter. Dwell times were computed to deliver a dose of 5 Gy to points 1 cm away from the catheter axis. Five sets of source configurations, each with different dwell position spacings from 0.5 to 3.0 cm, were evaluated. Three-dimensional (3D) dose distributions were then generated for each source configuration. Differential and cumulative dose-volume curves were generated to quantify the degree of target volume coverage, dose nonuniformity within the target volume, and irradiation of tissues outside the target volume. Evaluation of the implants were made using the DNR and three volumetric irradiation indices. Results: The observed isodose distributions were not able to satisfy all the dose constraints. The ability to optimally satisfy the dose constraints depended on the choice of dwell position spacing and the specification of the dose constraint points. The DNR and irradiation indices suggest that small dwell position spacing does not result in a more homogeneous dose distribution for the implant. This study supports the existence of a relationship between the dwell position spacing and the distance from the catheter axis to the reference dose or dose constraint points. Better dose homogeneity for an implant can be obtained if the spacing of the dwell positions are about twice the distance from the catheter axis to the reference dose or dose constraint points

  13. Effect of kefir and low-dose aspirin on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet.

    Science.gov (United States)

    Kanbak, Güngör; Uzuner, Kubilay; Kuşat Ol, Kevser; Oğlakçı, Ayşegül; Kartkaya, Kazım; Şentürk, Hakan

    2014-01-01

    Abstract We aim to study the effect of low-dose aspirin and kefir on arterial blood pressure measurements and renal apoptosis in unhypertensive rats with 4 weeks salt diet. Forty adult male Sprague-Dawley rats were divided into five groups: control, high-salt (HS) (8.0% NaCl), HS+aspirin (10 mg/kg), HS+kefir (10.0%w/v), HS+aspirin +kefir. We measured sistolic blood pressure (SBP), mean arterial pressure (MAP), diastolic pressure, pulse pressure in the rats. Cathepsin B, L, DNA fragmentation and caspase-3 activities were determined from rat kidney tissues and rats clearance of creatinine calculated. Although HS diet increased significantly SBP, MAP, diastolic pressure, pulse pressure parameters compared the control values. They were not as high as accepted hypertension levels. When compared to HS groups, kefir groups significantly decrease Cathepsin B and DNA fragmentation levels. Caspase levels were elevated slightly in other groups according to control group. While, we also found that creatinine clearance was higher in HS+kefir and HS+low-dose aspirin than HS group. Thus, using low-dose aspirin had been approximately decreased of renal function damage. Kefir decreased renal function damage playing as Angiotensin-converting enzyme inhibitor. But, low-dose aspirin together with kefir worsened rat renal function damage. Cathepsin B might play role both apoptosis and prorenin-processing enzyme. But not caspase pathway may be involved in the present HS diet induced apoptosis. In conclusion, kefir and low-dose aspirin used independently protect renal function and renal damage induced by HS diet in rats.

  14. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2012-01-01

    The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

  15. Development of a simple and sensitive liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS) method for the determination of cannabidiol (CBD), Δ9-tetrahydrocannabinol (THC) and its metabolites in rat whole blood after oral administration of a single high dose of CBD.

    Science.gov (United States)

    Palazzoli, Federica; Citti, Cinzia; Licata, Manuela; Vilella, Antonietta; Manca, Letizia; Zoli, Michele; Vandelli, Maria Angela; Forni, Flavio; Cannazza, Giuseppe

    2018-02-20

    The investigation of the possible conversion of cannabidiol (CBD) into Δ 9 -tetrahydrocannabinol (THC) in vivo after oral administration of CBD is reported herein since recent publications suggested a rapid conversion in simulated gastric fluid. To this end, single high dose of CBD (50mg/kg) was administered orally to rats and their blood was collected after 3 and 6h. A highly sensitive and selective LC-MS/MS method was developed and fully validated in compliance with the Scientific Working Group of Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology. This method also involved the optimization of cannabinoids and their metabolites extraction in order to remove co-eluting phospholipids and increase the sensitivity of the MS detection. Neither THC nor its metabolites were detected in rat whole blood after 3 or 6h from CBD administration. After oral administration, the amount of CBD dissolved in olive oil was higher than that absorbed from an ethanolic solution. This could be explained by the protection of lipid excipients towards CBD from acidic gastric juice. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. The effect of small radiation doses on the rat spinal cord: the concept of partial tolerance

    International Nuclear Information System (INIS)

    Ang, K.K.; Van Der Kogel, A.J.; Van Der Schueren, E.

    1983-01-01

    To evaluate the tolerance of the rat spinal cord to small radiation doses per fraction, an increasing number of fractions is required for induction of paralysis. The assessment of doses of 1-2 Gy, as used in the clinic, would require that over 100 fractions be given. The validity of replacing part of a fractionated irradiation of the spinal cord by a single large dose has been tested. Fractionated irradiation doses with 18 MeV X rays were followed by a ''top-up'' dose of 15 Gy as a single treatment. This is the fraction size of a treatment with two irradiation doses leading to paralysis in 50% of the animals (ED 50). Fractionated treatments were carried out with 2, 5, 10 and 20 fractions followed by the top-up dose of 15 Gy. the isoeffect curve, as a function of the number of fractions, has the same slope as experiments performed without top-up dose. The results show that the quality and quantity of cellular repair is not modified when part of a multifractionated exposure is replaced by a larger top-dose. An important consequence of this finding is, that in treatments with unequal fraction sizes, the partial tolerances can simply be added. Since a top-up dose can replace a sizable number of irradiation treatments, its application will allow investigations of the extent of sublethal damage repair for fraction sizes as low as 1 Gy

  17. Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  18. Dose and elasticity of demand for self-administered cocaine in rats.

    Science.gov (United States)

    Kearns, David N; Silberberg, Alan

    2016-04-01

    The present experiment tested whether the elasticity of demand for self-administered cocaine in rats is dose-dependent. Subjects lever pressed for three different doses of intravenous cocaine - 0.11, 0.33, and 1.0 mg/kg/infusion - on a demand procedure where the number of lever presses required per infusion increased within a session. The main finding was that demand for the 0.11 mg/kg dose was more elastic than it was for the two larger doses. There was no difference in demand elasticity between the 0.33 and 1.0 mg/kg doses. These results parallel findings previously reported in monkeys. The present study also demonstrated that a within-session procedure can be used to generate reliable demand curves.

  19. Radiation doses to the tissues of rat from tritiated thymidine administered by three different routes

    International Nuclear Information System (INIS)

    Takeda, Hiroshi; Iwakura, Tetsuo; Mabuchi, Yasuo.

    1984-01-01

    Biological behaviour of tritiated thymidine were investigated in rat over 120 days after oral, intraperitoneal or intravenous administration and the absorbed doses to different tissues were estimated. The result of present study revealed that the absorbed dose from tritiated thymidine varied with the route of administration. Among the three routes of administration, intraperitoneal injection gave the highest dose to all of the tissues examined. A significant difference due to the route of administration was found in spleen and small intestine, where the doses were, respectively, 3.3 and 4.5 times higher after intraperitoneal injection than after oral ingestion. The difference was substantially dependent on the dose value from non-volatile tritium which would be incorporated into DNA. Present observation suggests that the radiation hazards of tritiated thymidine differ depending on the route of entry into the body. (author)

  20. measurement of high dose radiation using yellow perspex dosimeter

    International Nuclear Information System (INIS)

    Thamrin, M Thoyib; Sofyan, Hasnel

    1996-01-01

    Measurement of high dose radiation using yellow perspex dosemeter has been carried out. Dose range used was between 0.1 to 3.0 kGy. Measurement of dose rate against Fricke dosemeter as a standard dose meter From the irradiation of Fricke dosemeter with time variation of 3,6,9,12,15 and 18 minute, it was obtained average dose rate of 955.57 Gy/hour, linear equation of dose was Y= 2.333+15.776 X with its correlation factor r = 0.9999. Measurement result using yellow perspex show that correlation between net optical density and radiation dose was not linear with its equation was ODc exp. [Bo + In(dose).Bi] Value of Bo = -0.215 and Bi=0.5020. From the experiment it was suggested that routine dosimeter (yellow perspex) should be calibrated formerly against standard dosemeters

  1. Disposition of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats dosed orally and dermally

    International Nuclear Information System (INIS)

    Pelletier, O.; Ritter, L.; Caron, J.; Somers, D.

    1989-01-01

    The dimethylamine salt of 14C-ring-labeled 2,4-D was administered to Fischer 344 rats orally (1 and 0.4 mg/kg body weight) and dermally (10 mg/kg body weight). Absorption, distribution, and elimination were determined from 14C-labeled 2,4-D in blood, tissues, and excreta. Quantitatively, most of the orally administered dose (94-96%) became systemically available within 6 h. Following dermal administration 10% of the dose became systemically available over 72 h. However, peak concentrations in blood and kidneys were achieved within 30 min of dosing by either route. By 1.5 h after dosing, 2,4-D concentrations in blood, muscle, liver, and kidneys had decreased in both the orally dosed and dermally dosed animals. Between 2 and 8 h, the blood, muscle, liver and kidney concentrations in dermally dosed animals maintained a plateau while urinary excretion increased, presumably due to continued absorption of 2,4-D from the skin. The concentrations in orally dosed animals continued to decrease. Following 7 h of dermal exposure, skin cleansing removed about 63% of the applied dose; about 17% of the applied dose remained at the site of dermal dosing. At 8 h, 2,4-D concentrations in blood, muscle, liver, and kidneys of dermally dosed animals began to decrease, most likely a result of the removal of the reservoir on the skin. However, 2,4-D continued to be absorbed from skin site, resulting in a slower decline of the 2,4-D concentrations in these tissues over remainder of the 72-h study period. By comparison, in animals that had been orally dosed, the absorbed dose was almost completely excreted within 24 h

  2. Methodology of high dose research in medical radiodiagnostic

    International Nuclear Information System (INIS)

    Barboza, Adriana E.; Martins, Cintia P. de S.

    2013-01-01

    This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations

  3. Epithelial regeneration of transposed intestine after high doses of X-irradiation

    International Nuclear Information System (INIS)

    Both, N.J. de; Vermey, M.

    1976-01-01

    The regeneration capacities of normal and transposed small bowel epithelium were compared in rats after applying high doses of X-irradiation. It has been shown that the potency of the mucosa to regenerate was much higher than assumed and that the mucosa could regenerate after single doses varying from 2000 to 5000 R. Even in the villus epithelium and in flat epithelium covering infiltrates of the lamina propria cells survived, which were still able to resume proliferative activity several days after irradiation. (author)

  4. Dose-reduction techniques for high-dose worker groups in nuclear power plants

    International Nuclear Information System (INIS)

    Khan, T.A.; Baum, J.W.; Dionne, B.J.

    1991-03-01

    This report summarizes the main findings of a study of the extent of radiation dose received by special work groups in the nuclear power industry. Work groups which chronically get large doses were investigated, using information provided by the industry. The tasks that give high doses to these work groups were examined and techniques described that were found to be particularly successful in reducing dose. Quantitative information on the extent of radiation doses to various work groups shows that significant numbers of workers in several critical groups receive doses greater than 1 and even 2 rem per year, particularly contract personnel and workers at BWR-type plants. The number of radiation workers whose lifetime dose is greater than their age is much less. Although the techniques presented would go some way in reducing dose, it is likely that a sizeable reduction to the high-dose work groups may require development of new dose-reduction techniques as well as major changes in procedures. 10 refs., 26 tabs

  5. Improvement of attention with amphetamine in low- and high-performing rats.

    Science.gov (United States)

    Turner, Karly M; Burne, Thomas H J

    2016-09-01

    Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents. This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats. Sprague-Dawley rats were trained on the SDT prior to amphetamine challenge (0.1, 0.25, 0.75 and 1.25 mg/kg). This dose range was predicted to enhance and disrupt cognition with the effect differing between individuals depending on baseline performance. Acute low dose amphetamine (0.1 and 0.25 mg/kg) improved accuracy, while the highest dose (1.25 mg/kg) significantly disrupted performance. The effects differed for low- and high-performing groups across these doses. The effect of amphetamine on accuracy was found to significantly correlate with baseline performance in rats. This study demonstrates that improvement in attentional performance with systemic amphetamine is dependent on baseline accuracy in rats. Indicative of the inverted U-shaped relationship between dopamine and cognition, there was a baseline-dependent shift in performance with increasing doses of amphetamine. The SDT may be a useful tool for investigating individual differences in attention and response to psychostimulants in rodents.

  6. Response of rat spinal cord to very small doses per fraction: lack of enhanced radiosensitivity

    International Nuclear Information System (INIS)

    Shun, Wong C.; Yong, Hao; Hill, Richard P.

    1995-01-01

    Our previous work with rat spinal cord demonstrated that the linear quadratic (LQ) model based on data for large fraction sizes ((α(β)) of 2.4 Gy) failed to predict isoeffective doses between 1 and 2 Gy per fraction, and under-estimated the sparing effect of small doses per fraction given once daily. In contrast, data from mouse skin and kidney, and recent in vitro results revealed a paradoxical increase in radiosensitivity at below 1 Gy per fraction. To assess whether enhanced radiosensitivity is present in the spinal cord below 1 Gy per fraction, the rat spinal cord (C2-T2) was irradiated initially with three daily doses of 10.25 Gy (top-up doses representing 90% of tolerance), followed by graded single doses or fractionated doses in 1.5, 1.0, 0.8, 0.6 or 0.4 Gy fractions given once daily. To limit the overall treatment time to ≤ 8 weeks, a small number of the 0.6- and 0.4-Gy fractions were given twice daily with an interfraction interval of 16 h. The end-point was forelimb paralysis secondary to white matter necrosis, confirmed histologically. The ED 50 values, excluding the top-up doses, were 5.8, 10.6, 14.8, 15.2, 15.9 and 19.1 Gy for a single dose and doses in 1.5-, 1.0-, 0.8-, 0.6- and 0.4-Gy fractions, respectively. The data gave an (α(β)) of 2.1 Gy (95% CI, 1.4, 2.7 Gy). Pooling the data separately, the (α(β)) value was 2.3 Gy (95% CI, 0.82, 3.7 Gy) for fraction sizes ≥ 1 Gy, and 1.2 Gy (95% CI, 0.16, 2.3 Gy) for the 0.8-, 0.6- and 0.4-Gy experiments. These results in which top-up doses were given initially are consistent with a large sparing effect of very small fraction sizes in rat spinal cord provided sufficient time is allowed for repair of sublethal damage between fractions, and provide no evidence for a paradoxical increase in radiosensitivity in the rat spinal cord below 1 Gy down to 0.4 Gy per fraction

  7. Study on a 4-Week Recovery Test of Sweet Bee Venom after a 13-Week, Repeated, Intramuscular Dose Toxicity Test in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Chungsan Lim

    2014-06-01

    Full Text Available Objectives:This study was performed to check for reversibility in the changes induced by a 13-week, repeated, dose toxicity test of Sweet Bee Venom (SBV in Sprague-Dawley (SD rats. Methods:Fifteen male and 15 female SD rats were treated with 0.28 mg/kg of SBV (high-dosage group and the same numbers of male and female SD rats were treated with 0.2 mL/kg of normal saline (control group for 13 weeks. We selected five male and five female SD rats from the high-dosage group and the same numbers of male and female SD rats from the control group, and we observed these rats for four weeks. We conducted body-weight measurements, ophthalmic examinations, urinalyses and hematology, biochemistry, histology tests. Results:(1 Hyperemia and movement disorder were observed in the 13-week, repeated, dose toxicity test, but these symptoms were not observed during the recovery period. (2 The rats in the high-dose group showed no significant changes in weight compared to the control group. (3 No significant differences in the ophthalmic parameters, urine analyses, complete blood cell counts (CBCs, and biochemistry were observed among the recovery groups. (4 No changes in organ weights were observed during the recovery period. (5 Histological examination of the thigh muscle indicated cell infiltration, inflammation, degeneration, necrosis of muscle fiber, and fibrosis during the treatment period, but these changes were not observed during the recovery period. The fatty liver change that was observed during the toxicity test was not observed during the recovery period. No other organ abnormalities were observed. Conclusion:The changes that occurred during the 13-week, repeated, dose toxicity test are reversible, and SBV can be safely used as a treatment modality.

  8. Radiation-induced rectal complications are not influenced by age: a dose fractionation study in the rat.

    Science.gov (United States)

    van den Aardweg, Gerard J M J; Olofsen-van Acht, Manouk J J; van Hooije, Christel M C; Levendag, Peter C

    2003-05-01

    Radiation-induced complications of the rectum are an important dose-limiting factor in radiotherapy of pelvic malignancies. In general, animal studies demonstrated no differences in acute and late normal tissue toxicity with age, but little is known about rectal complications in relation to age. For this purpose, an extensive histological and dose fractionation study was carried out on the rectum of young (12 weeks) and older (77-80 weeks) rats. In this paper, the results of dose fractionation are presented in relation to age at the time of irradiation. Young and older animals were irradiated with single and fractionated doses. After irradiation, rectal complications could lead to occlusion and stenosis, eventually resulting in the clinical symptoms of a megacolon and a possible fistula. For each dose group, cumulative survival rates were obtained with Kaplan-Meier analysis, from which dose-effect curves and the associated LD(50) values for a megacolon/fistula were calculated. The majority of responders died between 8 and 24 weeks after irradiation, irrespective of age. For both age groups, only the fractionation data showed a reduction in the mean latency with increasing dose. In the older age group, 39% of the responders developed a fistula compared to 26% for the younger animals. The LD(50) values increased from around 30 Gy after single doses to nearly 65 Gy after 10 fractions. The increases in LD(50) values with the number of fractions were independent of the age of the rats. For each of the dose fractionation schedules, log-rank testing indicated no significant differences in cumulative survival rates between younger and older animals (P > 0.10). The high alpha/beta ratios obtained for both the young and older animals strongly suggested that the late rectal complications were a consequence of early epithelial injury. Associated histological findings indicated that blood vessel damage, which was already evident at a high incidence at 4 weeks after irradiation

  9. Influence of large testicular dose on neuroendocrine function in rats

    International Nuclear Information System (INIS)

    Gong Shouliang; Liu Shuzheng

    1992-01-01

    In present study, the changes of hypothalamic endogenous opiate peptides and the endocrine function of pituitary and testes were observed at 1, 23, 63 and 97 days after exposure of testes to 10 Gy X-rays in male Wistar rats to attempt to clarify the neuroendocrine effect of ionizing radiation and its mechanism. One day after irradiation, hypothalamic β-endorphin (β-EP) content increased significantly, but serum luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (TS) and cAMP content in tests were lowered in varying degrees. Twenty three days after irradiation, hypothalamic β-EP content decreased, while serum LH, FSH, TS and testicular cAMP content increased very significantly. Sixty three days after irradiation, the level of hypothalamic β-EP still was the same as that at 23 days after irradiation, hypothalamic leu-enkephalin (L-Enk) content decreased significantly, serum LH and FSH levels still continued to increase up, while serum TS and testicular cAMP contents declined very significantly. Ninety seven days after irradiation, serum LH and FSH levels returned to lower, serum TS and testicular cAMP content still continued to decrease, and in testicular tissue, serious lesion occurred

  10. Impact of catheter reconstruction error on dose distribution in high dose rate intracavitary brachytherapy and evaluation of OAR doses

    International Nuclear Information System (INIS)

    Thaper, Deepak; Shukla, Arvind; Rathore, Narendra; Oinam, Arun S.

    2016-01-01

    In high dose rate brachytherapy (HDR-B), current catheter reconstruction protocols are relatively slow and error prone. The purpose of this study is to evaluate the impact of catheter reconstruction error on dose distribution in CT based intracavitary brachytherapy planning and evaluation of its effect on organ at risk (OAR) like bladder, rectum and sigmoid and target volume High risk clinical target volume (HR-CTV)

  11. High Fidelity Ion Beam Simulation of High Dose Neutron Irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Was, Gary; Wirth, Brian; Motta, Athur; Morgan, Dane; Kaoumi, Djamel; Hosemann, Peter; Odette, Robert

    2018-04-30

    Project Objective: The objective of this proposal is to demonstrate the capability to predict the evolution of microstructure and properties of structural materials in-reactor and at high doses, using ion irradiation as a surrogate for reactor irradiations. “Properties” includes both physical properties (irradiated microstructure) and the mechanical properties of the material. Demonstration of the capability to predict properties has two components. One is ion irradiation of a set of alloys to yield an irradiated microstructure and corresponding mechanical behavior that are substantially the same as results from neutron exposure in the appropriate reactor environment. Second is the capability to predict the irradiated microstructure and corresponding mechanical behavior on the basis of improved models, validated against both ion and reactor irradiations and verified against ion irradiations. Taken together, achievement of these objectives will yield an enhanced capability for simulating the behavior of materials in reactor irradiations

  12. Can prenatal low-dose irradiation affect behavior of adult rats?

    International Nuclear Information System (INIS)

    Smajda, B.; Tomasova, L.; Kokocova, N.

    2011-01-01

    The aim of our study was to determine whether exposure of very low dose gamma-rays during the critical phase of brain development affects some selected behavioral parameters in adult rats. Pregnant female Wistar rats were irradiated with 1 Gy gamma-rays from a cobalt source at 17 th day of pregnancy. The progeniture of irradiated as well as non-irradiated females have undergone behavioral tests at the age of 3 months. Irradiated animals exhibited lower locomotor and exploratory activity in the open field test. (authors)

  13. Effect of dose rate on the translocation yield in rat spermatogonia

    International Nuclear Information System (INIS)

    Vyglenov, A.; Rudnitski, T.; Kokhmanska-Tvardovska, A.

    1987-01-01

    The effectiveness of chronic gamma-irradiation with dose rate 1.10 -4 Gy/min on the yield of reciprocal translocations in rat spermatogonia was studied. Comparsion was made with acute gamma-irradiation at emissive power 1,23 Gy/min. Emissive power decrease by four orders reduced 12 times the extent of genetic injury - from 34,9 down to 3 translocations per cellx10 -5 /cGy. In this respect, the rat is close to the laboratory mouse

  14. An evaluation of high-dose jobs for ALARA improvement

    International Nuclear Information System (INIS)

    Mun, J. H.; Kim, H. S.

    1997-01-01

    It is well known that about 70 percent of occupational dose have incurred from maintenance jobs at outage period. To reduce occupational dose, first, the high-dose jobs at the outage period should be identified and evaluated. For this, the database program is used, which contains the ORE data of reference plants, Kori Units 3 and 4. As a result, it is found that the jobs related to steam generator are the highest dose jobs in terms of collective ORE dose. From the analysis of the job procedures of those jobs, the ALARA improvements are also derived

  15. Development of computerized dose planning system and applicator for high dose rate remote afterloading irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Choi, T. J. [Keimyung Univ., Taegu (Korea); Kim, S. W. [Fatima Hospital, Taegu (Korea); Kim, O. B.; Lee, H. J.; Won, C. H. [Keimyung Univ., Taegu (Korea); Yoon, S. M. [Dong-a Univ., Pusan (Korea)

    2000-04-01

    To design and fabricate of the high dose rate source and applicators which are tandem, ovoids and colpostat for OB/Gyn brachytherapy includes the computerized dose planning system. Designed the high dose rate Ir-192 source with nuclide atomic power irradiation and investigated the dose characteristics of fabricated brachysource. We performed the effect of self-absorption and determining the gamma constant and output factor and determined the apparent activity of designed source. he automated computer planning system provided the 2D distribution and 3D includes analysis programs. Created the high dose rate source Ir-192, 10 Ci(370GBq). The effective attenuation factor from the self-absorption and source wall was examined to 0.55 of the activity of bare source and this factor is useful for determination of the apparent activity and gamma constant 4.69 Rcm{sup 2}/mCi-hr. Fabricated the colpostat was investigated the dose distributions of frontal, axial and sagittal plane in intra-cavitary radiation therapy for cervical cancer. The reduce dose at bladder and rectum area was found about 20 % of original dose. The computerized brachytherapy planning system provides the 2-dimensional isodose and 3-D include the dose-volume histogram(DVH) with graphic-user-interface mode. emoted afterloading device was built for experiment of created Ir-192 source with film dosimetry within {+-}1 mm discrepancy. 34 refs., 25 figs., 11 tabs. (Author)

  16. Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Ozyigit, Filiz; Kucuk, Aysegul; Akcer, Sezer; Tosun, Murat; Kocak, Fatma Emel; Kocak, Cengiz; Kocak, Ahmet; Metineren, Hasan; Genc, Osman

    2015-08-26

    Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R) injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group). Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA) and nitric oxide (NO), and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (pebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (pebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

  17. Dielectric parameters of blood plasma in rats at external and internal irradiation with sublethal doses

    International Nuclear Information System (INIS)

    Khadzhidekova, E.; Kiradzhiev, G.

    1991-01-01

    Sexually mature male rats have received external gamma irradiation with 50, 200 or 380 cGy, treated with 89 Sr (333 or 1665 kBq per rat, femur dose 70, resp. 290 cGy), or 144 Ce (370 kBq per rat, liver dose 70 cGy). Dielectric parameters (permittivity and conductivity) have been measured in the frequency range 1.4 - 17 Mhz on different terms (1 to 30th day after the treatment). For all groups and terms the coefficients and equations describing the relationship between the dielectric permittivity ε and the frequency ν of the changing electric field have been calculated. On the basis of dielectric parameters the relaxation time of the plasma protein molecules is determined. It has been shown that the changes in dielectric permittivity are expressed at different frequencies specific for a given dose; the same is established for the conditions of internal irradiation. The frequency dependence of the permittivity is described as an exponential curve analogous to that of the control but with a changed exponent. In applying higher doses or activities the relationship turns from exponential to parabolic. The relaxation time, expressing the changes in conformal state of macromolecules, varies but is in all cases longer than one of the controls for the whole period of study at external irradiation with 50 and 380 cGy. It is lower at irradiation with 200 cGy, as well as at internal irradiation. 3 tabs., 13 refs

  18. Dose-response studies of depletion and repopulation of rat intestinal mucosal mast cells after irradiation

    International Nuclear Information System (INIS)

    Sedgwick, D.M.; Ferguson, A.

    1994-01-01

    The effects of radiation on gut mucosal mast cells (MMC) and tissue eosinophils were examined. Groups of rats were given single doses of whole-body irradiation from 0.5 to 5 Gy. Serum rat mast cell protease II (RMCPII) concentration showed a significant dose-dependent fall after 1 Gy on day 3 and 1.5 Gy on day 7. MMC counts and tissue RMCPII values on day 7 decreased significantly by 70% after 1 Gy and were undetectable with larger doses. Rats with normal and expanded MMC populations were irradiated or given anaphylaxis. Serum RMCPII concentrations did not change after irradiation, but there was a 10-fold increase in RMCPII after anaphylaxis. Tissue eosinophils in jejunum were 50% of control at 7 days after 2 Gy, and this effect was progressively more marked with higher doses. Similar effects on MMC and eosinophils were demonstrated in ileum, ascending colon and rectum. After 4.5 Gy, repopulation of the gut with MMC did not occur until week 3-4 postirradiation and MMC counts were still 50% below those of controls at 5 weeks postirradiation. Counts of tisse eosinophils 5 weeks after 4.5 Gy irradiation had returned to control levels in jejunum but were still significantly depleted in colon. (Author)

  19. The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible

    International Nuclear Information System (INIS)

    Monson, Laura A; Cavaliere, Christi M; Deshpande, Sagar S; Ayzengart, Alexander L; Buchman, Steven R

    2012-01-01

    The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague–Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction

  20. Effect of Different Doses of Soy Isoflavones on Spatial Learning and Memory in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Maryam Safahani

    2011-08-01

    Full Text Available Introduction: Several studies indicate that estrogen use increase performance on some tests of cognition especially in postmenopausal women. These steroids have many side effects, thus, other estrogenic agents with fewer side effects are needed to develop alternative treatment strategies. The main objection of this study was to evaluate the effects of different doses of dietary soy meals (with or without isoflavone on spatial learning and memory in ovariectomized (OVX rats. Methods: Female Wistar rats with the exception of intact group were ovariectomized at the first line of study. Subjects were divided into six groups. The control group rats (c were gonadally intact, while the others were OVX. OVX groups received normal diet (0, treated with 10 gr soy (10, 20 gr soy (20, 10 gr isoflavone free soy (-10 or 20 gr isoflavone free soy (-20 in daily diet for four weeks. The spatial learning and memory were tested using Morris water maze. Rats were trained in water maze to find a hidden escape Platform. Rats received 6 blocks that each block consisted of 3 trials. Following acquisition trials, one probe trial were conducted in which the platform was removed. Results: Soy meal diet (with or without isoflavone in ovariectomized rats caused improvement of performance across 18 trials of Acquisition. Discussion: Our results suggest that soy consumption apart from containing isoflavone or not is a potential alternative to estrogen in the improvement of cognition.

  1. Myelin basic protein in brains of rats with low dose lead encephalopathy

    Energy Technology Data Exchange (ETDEWEB)

    Sundstroem, R; Karlsson, B

    1987-02-01

    In the present study control rats and lead exposed rats which did not have any retardation of growth were examined by radioimmunological assay of myelin basic protein (MBP) of homogenates of cerebrum and cerebellum at 30, 60 and 120 days of age. Lead was administered on postnatal days 1-15 by daily intraperitoneal injections of 10 mg lead nitrate/kg body weight. This lead dose results in light microscopically discernible hemorrhagic encephalopathy in the cerebellum of 15-day old rats, but does not induce growth retardation. The controls were injected with vehicle only. The amount of lead in the blood and brain homogenates of lead-exposed and control rats 15-200 days old was estimated by atomic absorption spectrophotometry. Significant differences between the lead-exposed and control rats were not found in the cerebral or cerebellar content of MBP. Considering the results of previous investigations, the findings do not exclude a hypo-myelinating effect of lead, but they suggest that exposure to lead without concomitant malnutrition does not cause hypo-myelination in the cerebrum and cerebellum of the developing rat.

  2. Favorable effect of moderate dose caffeine on the skeletal system in ovariectomized rats.

    Science.gov (United States)

    Folwarczna, Joanna; Pytlik, Maria; Zych, Maria; Cegieła, Urszula; Kaczmarczyk-Sedlak, Ilona; Nowińska, Barbara; Sliwiński, Leszek

    2013-10-01

    Caffeine, a methylxanthine present in coffee, has been postulated to be responsible for an increased risk of osteoporosis in coffee drinkers; however, the data are inconsistent. The aim of the present study was to investigate the effects of a moderate dose of caffeine on the skeletal system of rats with normal and decreased estrogen level (developing osteoporosis due to estrogen deficiency). The experiments were carried out on mature nonovariectomized and ovariectomized Wistar rats, divided into control rats and rats receiving caffeine once daily, 20 mg/kg p.o., for 4 wk. Serum bone turnover markers, bone mass, mass of bone mineral, calcium and phosphorus content, histomorphometric parameters, and bone mechanical properties were examined. Caffeine favorably affected the skeletal system of ovariectomized rats, slightly inhibiting the development of bone changes induced by estrogen deficiency (increasing bone mineralization, and improving the strength and structure of cancellous bone). Moreover, it favorably affected mechanical properties of compact bone. There were no significant effects of caffeine in rats with normal estrogen levels. In conclusion, results of the present study indicate that low-to-moderate caffeine intake may exert some beneficial effects on the skeletal system of mature organisms. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Acute renal failure in high dose carboplatin chemotherapy

    NARCIS (Netherlands)

    Frenkel, J.; Kool, G.; de Kraker, J.

    1995-01-01

    Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial

  4. Pharmacogenetics and Pharmacokinetics in high-dose alkylating chemotherapy

    NARCIS (Netherlands)

    Ekhart, G.C. (Corine)

    2008-01-01

    High-dose chemotherapy in combination with peripheral blood progenitor cell transplantation has been developed as a possible curative treatment modality in several solid tumours. A frequently used high-dose regimen in the Netherlands is the CTC regimen, which is a 4-day course of cyclophosphamide,

  5. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

  6. Estimation of the transit dose component in high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Garcia Romero, A.; Millan Cebrian, E.; Lozano Flores, F.J.; Lope Lope, R.; Canellas Anoz, M.

    2001-01-01

    Current high dose rate brachytherapy (HDR) treatment planning systems usually calculate dose only from source stopping positions (stationary component), but fails to account for the administered dose when the source is moving (dynamic component or transit dose). Numerical values of this transit dose depends upon the source velocity, implant geometry, source activity and prescribed dose. In some HDR treatments using particular geometry the transit dose cannot be ignored because it increases the dose at the prescriptions points and also could increase potential late tissue complications as predicted by the linear quadratic model. International protocols recommend to verify this parameter. The aim of this paper has been to establish a procedure for the transit dose calculation for the Gammamed 12i equipment at the RT Department in the Clinical University Hospital (Zaragoza-Spain). A numeric algorithm was implemented based on a dynamic point approximation for the moving HDR source and the calculated results for the entrance-exit transit dose was compared with TLD measurements made in some discrete points. (author) [es

  7. Effects of enoxaparin and unfractionated heparin in prophylactic and therapeutic doses on the fertility of female Wistar rats.

    Science.gov (United States)

    Figueiró-Filho, Ernesto Antonio; Aydos, Ricardo Dutra; Senefonte, Flávio Renato de Almeida; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos; Oliveira, Vanessa Marcon de; Menezes, Giovanna Pádoa de; Bósio, Marco Antonio Costa

    2014-07-01

    To evaluate the effects of exposure of enoxaparin and unfractionated heparin (UFH) in prophylactic and therapeutic doses on the fertility rates of pregnant healthy Wistar rats. Enoxaparin and UFH were administered in prophylactic doses 1 mg/Kg/day 72 UI/Kg/day, and in therapeutic doses at 2 mg/kg/day 400UI/Kg/day. The rats were divided into five groups. The number of live and dead foetuses was quantified. The uterine horns were dissected and the presence of early and late reabsorptions (abortions) was determined. A peffect on fertility with the use of anticoagulant drugs in pregnant healthy Wistar rats.

  8. Statistical behavior of high doses in medical radiodiagnosis

    International Nuclear Information System (INIS)

    Barboza, Adriana Elisa

    2014-01-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  9. Study of teflon pads as high doses dosemeters

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2013-01-01

    The aim of this work is to study the Teflon, which is used as a binder in the manufacture of dosimetric tablets, for the feasibility of this material as high dose dosemeter. In this paper we used the technique of thermally stimulated luminescence (OSL) to characterize the dosimetric properties of Teflon. Teflon samples were exposed to different doses of radiation, using a source of gamma radiation ( 60 Co). It was obtained dose-response curve between 100 Gy to 50 kGy and reproducibility of OSL response. The preliminary results show that Teflon is a useful material to high dose dosimetry

  10. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer.

    Science.gov (United States)

    Martinez, Alvaro A; Gustafson, Gary; Gonzalez, José; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

    2002-06-01

    To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level >or=10.0 ng/mL, Gleason score >or=7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause-specific survival with higher doses. These results, coupled with the low risk of complications, the advantage of not being radioactive after implantation, and the real-time interactive planning, define a new standard for treatment.

  11. Reparative processes in spleen of rats irradiated with higher daily dose rates of continuous irradiation

    International Nuclear Information System (INIS)

    Mackova, N.; Praslicka, M.; Misurova, E.

    1975-01-01

    Histological and DNA content values were used in evaluating repair processes in the spleen of rats at various intervals following continuous irradiation with daily doses of 50 R, 100 R, 200 R and 500 R (a total dose of 1000 R), and following a single exposure to 1000 R. Histological changes found immediately after irradiation indicated the induction of significant injuries, this mainly as a result of daily doses of 200 R and 500 R. The complete repair of the DNA content and of a number of erythroid elements and also a 70 to 80% regeneration of the white pulp took place within 25 days. The same period was found to be insufficient for the complete repair of megakaryocytes. No signs of repair were observed in spleen in the histological picture or DNA content after a single irradiation with a dose of 1000 R. (author)

  12. Reparative processes in spleen of rats irradiated with higher daily dose rates of continuous irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mackova, N; Praslicka, M; Misurova, E [Univerzita P.J. Safarika, Kosice (Czechoslovakia). Prirodovedecka Fakulta

    1975-01-01

    Histological and DNA content values were used in evaluating repair processes in the spleen of rats at various intervals following continuous irradiation with daily doses of 50 R, 100 R, 200 R and 500 R (a total dose of 1000 R), and following a single exposure to 1000 R. Histological changes found immediately after irradiation indicated the induction of significant injuries, this mainly as a result of daily doses of 200 R and 500 R. The complete repair of the DNA content and of a number of erythroid elements and also a 70 to 80% regeneration of the white pulp took place within 25 days. The same period was found to be insufficient for the complete repair of megakaryocytes. No signs of repair were observed in spleen in the histological picture or DNA content after a single irradiation with a dose of 1000 R.

  13. Hesperidin and low dose gamma irradiation alleviate rosiglitazone -induced cardiotoxicity in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Morcos, N.Y.; Abdel-Ghaffar, A.B.; Osman, S.A.; Mohamed, M.Kh.; Arbid, M.S.; El-Eraky, W.I.

    2012-01-01

    Aim: The present study was designed to investigate the cardio protective effect of hesperidin and low dose γ- irradiation (LDR) against rosiglitazone cardiotoxicity. Experiment: Type 2 diabetes mellitus (T2DM) was induced in rats by single intraperitoneal injection of streptozotocin (STZ) followed by nicotinamide (NIC) (65 and 110 mg/kg b.wt, respectively). The diabetic rats were divided into 5 groups: untreated, LDR, LDR+ rosiglitazone, LDR + Hesperidin, LDR+ rosiglitazone + Hesperidin for one month, and blood and tissue samples were collected. Results: The diabetic rats showed elevated serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), C-reactive protein (CRP), hyaluronidase activity, and reduced serum nitric oxide (NO) level, hematocrit % as well as final body weight, and pathological alterations in myocardial tissue. Treatment with LDR + rosiglitazone + Hesperidin ameliorated all these abnormalities approaching control levels. Conclusion: Results indicate the possible cardio protective role of hesperidin and LDR against rosiglitazone cardiotoxicity.

  14. Assessment of human effective absorbed dose of 67 Ga-ECC based on biodistribution rat data.

    Science.gov (United States)

    Shanehsazzadeh, Saeed; Yousefnia, Hassan; Lahooti, Afsaneh; Zolghadri, Samaneh; Jalilian, Amir Reza; Afarideh, Hossien

    2015-02-01

    In a diagnostic context, determination of absorbed dose is required before the introduction of a new radiopharmaceutical to the market to obtain marketing authorization from the relevant agencies. In this work, the absorbed dose of [67 Ga]-ethylenecysteamine cysteine [(67 Ga)ECC] to human organs was determined by using distribution data for rats. For biodistribution data, the animals were sacrificed by CO2 asphyxiation at selected times after injection (0.5, 2 and 48 h, n = 3 for each time interval), then the tissue (blood, heart, lung, brain, intestine, feces, skin, stomach, kidneys, liver, muscle and bone) were removed. The absorbed dose was determined by Medical Internal Radiation Dose (MIRD) method after calculating cumulated activities in each organ. Our prediction shows that a 185-MBq injection of (67)Ga-ECC into the humans might result in an estimated absorbed dose of 0.029 mGy in the whole body. The highest absorbed doses are observed in the spleen and liver with 33.766 and 16.847 mGy, respectively. The results show that this radiopharmaceutical can be a good SPECT tracer since it can be produced easily and also the absorbed dose in each organ is less than permitted absorbed dose.

  15. Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts

    International Nuclear Information System (INIS)

    Myhrer, Trond; Nguyen, Nga H.T.; Andersen, Jannike M.; Aas, Paal

    2004-01-01

    The combined effects of physostigmine and procyclidine (antagonizing muscarinic, nicotinic, and NMDA receptors) were tested against various doses of soman. Physostigmine (0.1 mg/kg) in combination with procyclidine doses of 1, 3, or 6 mg/kg effectively prevented the development of convulsions and hippocampally monitored seizures when the doses of soman were 1.3, 1.6, or 2 x LD50, respectively. Results from [ 3 H]MK-801-binding experiments showed that procyclidine inhibits the phencyclidine site at the NMDA receptor in a concentration-dependent manner. Physostigmine (0.1 mg/kg) and procyclidine in a dose of 1 mg/kg did not prevent convulsions or seizures when the soman dose was 1.6 x LD50. Subsequent treatment with scopolamine in doses of 0.5 or 1 mg/kg immediately after (3 min) seizure onset showed that only the highest dose produced a reliable termination. When scopolamine (1 mg/kg) was given later (10 min) after onset of seizures, no effect was obtained. The sustained seizures were subsequently treated with diazepam (10 mg/kg) and pentobarbital (30 mg/kg) and finally terminated 25 min after onset. In rats given inadequate prophylaxis, both modified convulsions and seizures were seen. It is suggested that moderate doses of prophylactics should be preferred to avoid adverse effects on cognitive functions because insufficient prophylaxis can be compensated for by adjunct treatment

  16. Protective effects of orally applied fullerenol nano particles in rats after a single dose of doxorubicin

    Directory of Open Access Journals (Sweden)

    Ičević Ivana Đ.

    2011-01-01

    Full Text Available Polyhydroxylated, water soluble, fullerenol C60(OH24 nano particles (FNP in vitro and in vivo models, showed an expressive biological activity. The goal of this work was to investigate the potential protective effects of orally applied FNP on rats after a single dose of doxorubicin (DOX (8 mg/kg (i.p. 6 h after the last application of FNP. After the last drug administration, the rats were sacrificed, and the blood and tissues were taken for the analysis. Biochemical and pathological results obtained in this study indicate that fullerenol (FNP, in H2O:DMSO (80:20, w/w solution given orally in final doses of 10, 14.4, and 21.2 mg/kg three days successively, has the protective (hepatoprotective and nephroprotective effect against doxorubicin-induced cytotoxicity via its antioxidant properties.

  17. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (2)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    In order to study the molecular mechanisms of neuronal migration on developing rat cerebral cortex, we need a tissue culture system in which neuronal migration can be observed. We prepared a tissue culture system of embryonic rat cerebral cortex starting on embryonic day 16 and cultivating it for 48 hours. The autoradiographic study in this system revealed not only the migration of 3 H-thymidine labeled neurons but also neuronal migration delays from low doses of ionizing radiation of more than 10 cGy. In addition, on immunohistochemical study, cell-cell adhesion molecule N-CAM staining was remarkably decreased in the matrix cell layer. In the tissue culture system where monoclonal anti-N-CAM antibodies were added, neuronal migration delay comparable to that of 20 cGy radiation was found. In conclusion, it was speculated that neuronal migration delay might be caused by disturbed N-CAM synthesis in matrix cells after low dose ionizing radiation. (author)

  18. Effect of a mild dose of X-irradiation on rats under stress

    International Nuclear Information System (INIS)

    Khan, N.A.; Hasan, S.S.

    1984-01-01

    This investigation was apt at studying the effect of a mild dose of X-rays on the normal and shock administered rats. Administration of stress brought about a marked depression in the contents of DNA, RNA and protein in the brain. On the other hand, total body exposure to X-rays was found to increase the levels of DNA, RNA and protein in the brain. Thus, the use of a mild dose of X-rays in stressed animals seems to be stimulatory to the diminished levels of DNA, RNA and protein in the brain. There were rising levels of 5-hydroxy indol acetic acid and Vinyl mandelic acid in the urine of stress administered rats and the enhanced levels of these urinary metabolites appeared to be refractory to the application of X-rays. (orig.) [de

  19. Effect of superlarge dose of gamma radiation on the rat cerebral cortex (ultrastructural aspects)

    International Nuclear Information System (INIS)

    Abdrakhmanov, A.A.; AN Kazakhskoj SSR, Alma-Ata

    1988-01-01

    Puberal Wistar line mall rats (180-210 g) were subjected to single whole-body gamma irradiation with 150 Gy dose and 75 Gy/min dose rate. Electron-microscopic investigation into dynamics of sensory-motor cortex ultrastructural changes during 24 hours after irradiation is conducted. Along with destructive changes compensator-reduction processes are developed in brain tissue at this period. Already during the first hours after irradiation the neutron ultrastructure change dynamics has been determined, alongside with direct radiation effect, by indirect effects juries of neuroglia and microcirculatory channel

  20. Effect of superlarge dose of gamma radiation on the rat cerebral cortex (ultrastructural aspects)

    Energy Technology Data Exchange (ETDEWEB)

    Abdrakhmanov, A A

    1988-06-01

    Puberal Wistar line mall rats (180-210 g) were subjected to single whole-body gamma irradiation with 150 Gy dose and 75 Gy/min dose rate. Electron-microscopic investigation into dynamics of sensory-motor cortex ultrastructural changes during 24 hours after irradiation is conducted. Along with destructive changes compensator-reduction processes are developed in brain tissue at this period. Already during the first hours after irradiation the neutron ultrastructure change dynamics has been determined, alongside with direct radiation effect, by indirect effects juries of neuroglia and microcirculatory channel.

  1. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    Science.gov (United States)

    Pawluski, Jodi L.; van Donkelaar, Eva; Abrams, Zipporah; Steinbusch, Harry W. M.; Charlier, Thierry D.

    2014-01-01

    Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat. PMID:24757568

  2. Fluoxetine Dose and Administration Method Differentially Affect Hippocampal Plasticity in Adult Female Rats

    Directory of Open Access Journals (Sweden)

    Jodi L. Pawluski

    2014-01-01

    Full Text Available Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans, these medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent models is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present study was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine administration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment, adult female Sprague-Dawley rats were divided over the two administration methods: (1 cookie and (2 osmotic minipump and three fluoxetine treatment doses: 0, 5, or 10 mg/kg/day. Results show that a fluoxetine dose of 5 mg/kg/day, but not 10 mg/kg/day, results in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods. Furthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL at a 5 mg dose compared to a 10 mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine treatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can differentially affect hippocampal plasticity in the adult female rat.

  3. Linear-quadratic model underestimates sparing effect of small doses per fraction in rat spinal cord

    International Nuclear Information System (INIS)

    Shun Wong, C.; Toronto University; Minkin, S.; Hill, R.P.; Toronto University

    1993-01-01

    The application of the linear-quadratic (LQ) model to describe iso-effective fractionation schedules for dose fraction sizes less than 2 Gy has been controversial. Experiments are described in which the effect of daily fractionated irradiation given with a wide range of fraction sizes was assessed in rat cervical spine cord. The first group of rats was given doses in 1, 2, 4, 8 and 40 fractions/day. The second group received 3 initial 'top-up'doses of 9 Gy given once daily, representing 3/4 tolerance, followed by doses in 1, 2, 10, 20, 30 and 40 fractions/day. The fractionated portion of the irradiation schedule therefore constituted only the final quarter of the tolerance dose. The endpoint of the experiments was paralysis of forelimbs secondary to white matter necrosis. Direct analysis of data from experiments with full course fractionation up to 40 fractions/day (25.0-1.98 Gy/fraction) indicated consistency with the LQ model yielding an α/β value of 2.41 Gy. Analysis of data from experiments in which the 3 'top-up' doses were followed by up to 10 fractions (10.0-1.64 Gy/fraction) gave an α/β value of 3.41 Gy. However, data from 'top-up' experiments with 20, 30 and 40 fractions (1.60-0.55 Gy/fraction) were inconsistent with LQ model and gave a very small α/β of 0.48 Gy. It is concluded that LQ model based on data from large doses/fraction underestimates the sparing effect of small doses/fraction, provided sufficient time is allowed between each fraction for repair of sublethal damage. (author). 28 refs., 5 figs., 1 tab

  4. Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.

    Science.gov (United States)

    Udo, Mariana S B; Sandini, Thaísa M; Reis, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice S

    2014-01-01

    Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil

  5. Accelerated Irradiations for High Dose Microstructures in Fast Reactor Alloys

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhijie [Univ. of Michigan, Ann Arbor, MI (United States)

    2017-03-31

    The objective of this project is to determine the extent to which high dose rate, self-ion irradiation can be used as an accelerated irradiation tool to understand microstructure evolution at high doses and temperatures relevant to advanced fast reactors. We will accomplish the goal by evaluating phase stability and swelling of F-M alloys relevant to SFR systems at very high dose by combining experiment and modeling in an effort to obtain a quantitative description of the processes at high and low damage rates.

  6. Effect of aflatoxin-B1 doses simulating natural food contamination reproductive steroid hormones in rats

    International Nuclear Information System (INIS)

    Gamal, M.H.; EL-Banna, I.M.

    2002-01-01

    Aflatoxin B1 (AFB1) is the most toxic metabolite synthesized by aspergillus flavus. The mycotoxins was found to be endemic contaminant in underdeveloped countries and in egypt was documented as a pollutant of a wide variety of products for human and animal nutrition. Carcinogenic and mutagenic effects of AFB1 has been investigated extensively, while very scare information is available about other possible endocrine effects of the toxin which might precedes carcinogenic effects. This study was performed to investigate the effects of in vivo administration of AFB1 via intraperitoneal injection (I.P) in adult male rats to show its effects on rat reproductive function and to illucidate the effects of acute, chronic and sub toxic (endimomemitic) AFB1 doses on male rat steroid function. Intraperitoneal injection (I.P) of AFB 1 doses in adult male rats revealed that AFB1 caused significant decrease in serum testosterone and cortisol (early), while a significant increase was observed in progesterone (P 4 ) and Estrodial (E 2 ) (late)

  7. Toxicity of the styrene metabolite, phenylglyoxylic acid, in rats after three months' oral dosing

    DEFF Research Database (Denmark)

    Ladefoged, Ole; Lam, Henrik Rye; Ostergaard, G.

    1998-01-01

    Male Wistar rats were dosed with 0, 1250, 3750 or 5000 mg/l of phenylglyoxylic acid (PGA) (CAS no. 611-73-4) in the drinking water ad libitum for 3 months. During the entire treatment period, there were no gross signs of toxicity related to PGA. No changes in neurobehavior were found after using ....... Alternatively, the ototoxicity of styrene, like toluene, may be caused the parent compound itself and not by a metabolite like PGA. (C) 1998 Inter Press, inc....

  8. Histological analysis of low dose NMU effects in the rat mammary gland

    Directory of Open Access Journals (Sweden)

    Sonnenschein Carlos

    2009-08-01

    Full Text Available Abstract Background Our objective was to assess the histological changes in mammary glands of the female Wistar-Furth rat as a result of low dose exposure to N-nitrosomethylurea (NMU. Methods Groups of 30–40 virgin female rats of between 49–58 days old received a single injection of 10, 20, 30 or 50 mg NMU/kg body weight (BW. A group of 10 control rats received 0.9% NaCl solution only. The formation of palpable mammary gland tumors was assessed weekly and, upon sacrifice at 12, 22 and 25–30 weeks after treatment, we performed a comprehensive histological analysis of all mammary gland lesions and tumors. Results Alongside the predicted increase in tumor number and decrease in tumor latency with increasing NMU dose, we observed a number of microscopic lesions and other epithelial abnormalities in the mammary glands for all NMU doses. Two types of non-neoplastic histological changes were observed in rats exposed to 10 or 20 mg NMU/kg BW: namely, (i an increase in the number of acinar structures often accompanied by secretion into the lumen which is normally associated with pregnancy and lactation, and (ii an increase in the number of epithelial cells sloughed into the lumen of the epithelial ducts. Conclusion This study establishes a baseline for low-dose exposure and defines the histological features in the mammary gland resulting from NMU exposure. Furthermore, this system provides an ideal platform for evaluating the relative susceptibility of animals protected from, or predisposed to, developing cancer through environmental influences.

  9. Avoidance behaviour and anxiety in rats irradiated with a sublethal dose of gamma-rays.

    Science.gov (United States)

    Tomášová, Lenka; Smajda, B; Bona, M

    2011-12-01

    The aim of this study was to assess, whether a sublethal dose of gamma-rays will influence the avoidance behaviour and anxiety in rats and whether the response to radiation depends on time of day of its application. Adult male Wistar rats were tested in elevated plus-maze, in hot plate test and in the light/dark box in 4 regular intervals during a day. After two weeks the animals were irradiated with a whole-body dose 6 Gy of gamma-rays. One day after irradiation the animals were repeatedly tested in the same way, as before irradiation. In the plus-maze test an increased level of anxiety was established. The irradiation significantly decreased the locomotor activity of rats, but the extent of exploratory and comfortable behaviour were not altered. After irradiation, an elevated aversion to the thermal stimulus was observed in the hot plate test. The effects of radiation were more pronounced in the light period of the day, than in the dark one. No significant differences in aversion to light were detected after irradiation. The obtained results indicate, that sublethal doses of ionizing radiation can markedly influence the reactivity of animals to adverse stimuli, their motoric activity and emotional status, as well.

  10. Radiobiological aspects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation

    International Nuclear Information System (INIS)

    Turesson, I.

    1990-01-01

    The biological effects of continuous low dose-rate irradiation and fractionated high dose-rate irradiation in interstitial and intracavitary radiotherapy and total body irradiation are discussed in terms of dose-rate fractionation sensitivity for various tissues. A scaling between dose-rate and fraction size was established for acute and late normal-tissue effects which can serve as a guideline for local treatment in the range of dose rates between 0.02 and 0.005 Gy/min and fraction sizes between 8.5 and 2.5 Gy. This is valid provided cell-cycle progression and proliferation can be ignored. Assuming that the acute and late tissue responses are characterized by α/β values of about 10 and 3 Gy and a mono-exponential repair half-time of about 3 h, the same total doses given with either of the two methods are approximately equivalent. The equivalence for acute and late non-hemopoietic normal tissue damage is 0.02 Gy/min and 8.5 Gy per fraction; 0.01 Gy/min and 5.5 Gy per fraction; and 0.005 Gy/min and 2.5Gy per fraction. A very low dose rate, below 0.005 Gy/min, is thus necessary to simulate high dose-rate radiotherapy with fraction sizes of about 2Gy. The scaling factor is, however, dependent on the repair half-time of the tissue. A review of published data on dose-rate effects for normal tissue response showed a significantly stronger dose-rate dependence for late than for acute effects below 0.02 Gy/min. There was no significant difference in dose-rate dependence between various acute non-hemopoietic effects or between various late effects. The consistent dose-rate dependence, which justifies the use of a general scaling factor between fraction size and dose rate, contrasts with the wide range of values for repair half-time calculated for various normal-tissue effects. This indicates that the model currently used for repair kinetics is not satisfactory. There are also few experimental data in the clinical dose-rate range, below 0.02 Gy/min. It is therefore

  11. High-temperature absorbed dose measurements in the megagray range

    International Nuclear Information System (INIS)

    Balian, P.; Ardonceau, J.; Zuppiroli, L.

    1988-01-01

    Organic conductors of the tetraselenotetracene family have been tested as ''high-temperature'' absorbed dose dosimeters. They were heated up to 120 0 C and irradiated at this temperature with 1-MeV electrons in order to simulate, in a short time, a much longer γ-ray irradiation. The electric resistance increase of the crystal can be considered a good measurement of the absorbed dose in the range 10 6 Gy to a few 10 8 Gy and presumably one order of magnitude more. This dosimeter also permits on-line (in-situ) measurements of the absorbed dose without removing the sensor from the irradiation site. The respective advantages of organic and inorganic dosimeters at these temperature and dose ranges are also discussed. In this connection, we outline new, but negative, results concerning the possible use of silica as a high-temperature, high-dose dosimeter. (author)

  12. Radiophotoluminescence light scope for high-dose dosimetry

    International Nuclear Information System (INIS)

    Sato, Fuminobu; Zushi, Naoki; Sakiyama, Tomoki; Kato, Yushi; Murata, Isao; Shimizu, Kikuo; Yamamoto, Takayoshi; Iida, Toshiyuki

    2015-01-01

    A radiophotoluminescence (RPL) light scope is a remote-sensing technique for measuring in situ the radiation dose in an RPL detector placed at a distance. The RPL light scope is mainly composed of an ultraviolet (UV) pulse laser, telescopic lenses, a photomultiplier tube, and camera modules. In a performance test, some RPL detectors were placed at distances up to 30 m and were illuminated with a pulsed UV laser beam. The photoluminescence responses of the RPL detectors were analyzed using this scope. Their radiation doses were determined from the amplitude of the given component of the photoluminescence responses. The RPL readout could be repeated without fading, and its amplitude exhibited good linearity at a dose ranging from 0.1 to 60 Gy. Furthermore, a two-dimensional distribution of radiation dose was obtained by laser scanning on an RPL detector. It was confirmed that the RPL light scope was a useful remote-sensing tool for high-dose dosimetry. - Highlights: • A radiophotoluminescence (RPL) light scope was developed for high-dose dosimetry. • The RPL light scope has high sensitivity and accuracy in high-dose dosimetry. • Two-dimensional radiation dose distribution was obtained by the RPL light scope.

  13. Relevance of high-dose chemotherapy in solid tumours

    NARCIS (Netherlands)

    Nieboer, P; de Vries, EGE; Mulder, NH; van der Graaf, WTA

    Drug resistance is a major problem in the treatment of solid tumours. Based on a steep dose-response relationship for especially alkylating agents on tumour cell survival, high-dose chemotherapy was considered of interest for the treatment of solid tumours. Results of phase 1 and 2 studies with

  14. Rectal dose assessment in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer

    International Nuclear Information System (INIS)

    Oliveira, Jetro Pereira de; Batista, Delano Valdivino Santos; Bardella, Lucia Helena; Carvalho, Arnaldo Rangel

    2009-01-01

    Objective: The present study was aimed at developing a thermoluminescent dosimetric system capable of assessing the doses delivered to the rectum of patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. Materials and methods: LiF:Mg,Ti,Na powder was the thermoluminescent material utilized for evaluating the rectal dose. The powder was divided into small portions (34 mg) which were accommodated in a capillary tube. This tube was placed into a rectal probe that was introduced into the patient's rectum. Results: The doses delivered to the rectum of six patients submitted to high-dose-rate brachytherapy for uterine cervix cancer evaluated by means of thermoluminescent dosimeters presented a good agreement with the planned values based on two orthogonal (anteroposterior and lateral) radiographic images of the patients. Conclusion: The thermoluminescent dosimetric system developed in the present study is simple and easy to be utilized as compared to other rectal dosimetry methods. The system has shown to be effective in the evaluation of rectal doses in patients submitted to high-dose-rate brachytherapy for uterine cervix cancer. (author)

  15. Influence of dosing times on cisplatin-induced peripheral neuropathy in rats

    International Nuclear Information System (INIS)

    Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto

    2016-01-01

    Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague–Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy. The online version of this article (doi:10.1186/s12885-016-2777-0) contains supplementary material, which is available to authorized users

  16. Hippocampal-dependent Pavlovian conditioning in adult rats exposed to binge-like doses of ethanol as neonates.

    Science.gov (United States)

    Lindquist, Derick H

    2013-04-01

    Binge-like postnatal ethanol exposure produces significant damage throughout the brain in rats, including the cerebellum and hippocampus. In the current study, cue- and context-mediated Pavlovian conditioning were assessed in adult rats exposed to moderately low (3E; 3g/kg/day) or high (5E; 5g/kg/day) doses of ethanol across postnatal days 4-9. Ethanol-exposed and control groups were presented with 8 sessions of trace eyeblink conditioning followed by another 8 sessions of delay eyeblink conditioning, with an altered context presented over the last two sessions. Both forms of conditioning rely on the brainstem and cerebellum, while the more difficult trace conditioning also requires the hippocampus. The hippocampus is also needed to gate or modulate expression of the eyeblink conditioned response (CR) based on contextual cues. Results indicate that the ethanol-exposed rats were not significantly impaired in trace EBC relative to control subjects. In terms of CR topography, peak amplitude was significantly reduced by both doses of alcohol, whereas onset latency but not peak latency was significantly lengthened in the 5E rats across the latter half of delay EBC in the original training context. Neither dosage resulted in significant impairment in the contextual gating of the behavioral response, as revealed by similar decreases in CR production across all four treatment groups following introduction of the novel context. Results suggest ethanol-induced brainstem-cerebellar damage can account for the present results, independent of the putative disruption in hippocampal development and function proposed to occur following postnatal ethanol exposure. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. γ-aminobutyric acidA (GABAA) receptor regulates ERK1/2 phosphorylation in rat hippocampus in high doses of Methyl Tert-Butyl Ether (MTBE)-induced impairment of spatial memory

    International Nuclear Information System (INIS)

    Zheng Gang; Zhang Wenbin; Zhang Yun; Chen Yaoming; Liu Mingchao; Yao Ting; Yang Yanxia; Zhao Fang; Li Jingxia; Huang Chuanshu; Luo Wenjing; Chen Jingyuan

    2009-01-01

    Experimental and occupational exposure to Methyl Tert-Butyl Ether (MTBE) has been reported to induce neurotoxicological and neurobehavioral effects, such as headache, nausea, dizziness, and disorientation, etc. However, the molecular mechanisms involved in MTBE-induced neurotoxicity are still not well understood. In the present study, we investigated the effects of MTBE on spatial memory and the expression and function of GABA A receptor in the hippocampus. Our results demonstrated that intraventricular injection of MTBE impaired the performance of the rats in a Morris water maze task, and significantly increased the expression of GABA A receptor α1 subunit in the hippocampus. The phosphorylation of ERK1/2 decreased after the MTBE injection. Furthermore, the decreased ability of learning and the reduction of phosphorylated ERK1/2 level of the MTBE-treated rats was partly reversed by bicuculline injected 30 min before the training. These results suggested that MTBE exposure could result in impaired spatial memory. GABA A receptor may play an important role in the MTBE-induced impairment of learning and memory by regulating the phosphorylation of ERK in the hippocampus.

  18. Dose escalation using conformal high-dose-rate brachytherapy improves outcome in unfavorable prostate cancer

    International Nuclear Information System (INIS)

    Martinez, Alvaro A.; Gustafson, Gary; Gonzalez, Jose; Armour, Elwood; Mitchell, Chris; Edmundson, Gregory; Spencer, William; Stromberg, Jannifer; Huang, Raywin; Vicini, Frank

    2002-01-01

    Purpose: To overcome radioresistance for patients with unfavorable prostate cancer, a prospective trial of pelvic external beam irradiation (EBRT) interdigitated with dose-escalating conformal high-dose-rate (HDR) prostate brachytherapy was performed. Methods and Materials: Between November 1991 and August 2000, 207 patients were treated with 46 Gy pelvic EBRT and increasing HDR brachytherapy boost doses (5.50-11.5 Gy/fraction) during 5 weeks. The eligibility criteria were pretreatment prostate-specific antigen level ≥10.0 ng/mL, Gleason score ≥7, or clinical Stage T2b or higher. Patients were divided into 2 dose levels, low-dose biologically effective dose 93 Gy (149 patients). No patient received hormones. We used the American Society for Therapeutic Radiology and Oncology definition for biochemical failure. Results: The median age was 69 years. The mean follow-up for the group was 4.4 years, and for the low and high-dose levels, it was 7.0 and 3.4 years, respectively. The actuarial 5-year biochemical control rate was 74%, and the overall, cause-specific, and disease-free survival rate was 92%, 98%, and 68%, respectively. The 5-year biochemical control rate for the low-dose group was 52%; the rate for the high-dose group was 87% (p<0.001). Improvement occurred in the cause-specific survival in favor of the brachytherapy high-dose level (p=0.014). On multivariate analysis, a low-dose level, higher Gleason score, and higher nadir value were associated with increased biochemical failure. The Radiation Therapy Oncology Group Grade 3 gastrointestinal/genitourinary complications ranged from 0.5% to 9%. The actuarial 5-year impotency rate was 51%. Conclusion: Pelvic EBRT interdigitated with transrectal ultrasound-guided real-time conformal HDR prostate brachytherapy boost is both a precise dose delivery system and a very effective treatment for unfavorable prostate cancer. We demonstrated an incremental beneficial effect on biochemical control and cause

  19. Adverse effects on sexual development in rat offspring after low dose exposure to a mixture of endocrine disrupting pesticides

    DEFF Research Database (Denmark)

    Hass, Ulla; Boberg, Julie; Christiansen, Sofie

    2012-01-01

    The present study investigated whether a mixture of low doses of five environmentally relevant endocrine disrupting pesticides, epoxiconazole, mancozeb, prochloraz, tebuconazole and procymidone, would cause adverse developmental toxicity effects in rats. In rat dams, a significant increase...... and cumulative intake, because of the potentially serious impact of mixed exposure on development and reproduction in humans....

  20. A NEW ANIMAL-MODEL FOR HUMAN PREECLAMPSIA - ULTRA-LOW-DOSE ENDOTOXIN INFUSION IN PREGNANT RATS

    NARCIS (Netherlands)

    FAAS, MM; SCHUILING, GA; BALLER, JFW; VISSCHER, CA; BAKKER, WW

    OBJECTIVE: An animal model for preeclampsia was developed by means of an ultra-low-dose endotoxin infusion protocol in conscious pregnant rats. STUDY DESIGN: Rats received a permanent jugular vein cannula on day 0 of pregnancy, through which endotoxin (1.0 mu/kg body weight) (n = 10) or saline

  1. Dependence of the average life span, mortality and osteosarcoma occurence in rats on the radiation dose absorbed (Sr 90)

    International Nuclear Information System (INIS)

    Shvedov, V.L.; Panteleev, L.I.

    1975-01-01

    The dose dependence of mortality and osteosarcoma development frequency is studied in white rats which have received 0.00005-5.0μCi/day of strontium-90 throughout their lives. It is shown that total mortality in the dose range 0-10 krad is a more sensitive test than osteosarcoma frequency, osteosarcomatosis hardly reducing the mean life span of the irradiated rats. (author)

  2. High-dose dosimetry using natural silicate minerals

    International Nuclear Information System (INIS)

    Carmo, Lucas S. do; Mendes, Leticia; Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina; Barbosa, Renata F.

    2015-01-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  3. High-dose dosimetry using natural silicate minerals

    Energy Technology Data Exchange (ETDEWEB)

    Carmo, Lucas S. do; Mendes, Leticia, E-mail: isatiro@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Watanabe, Shigueo; Rao, Gundu; Lucas, Natasha; Sato, Karina, E-mail: lacifid@if.usp.br [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Fisica. Departamento de Fisica Nuclear; Barbosa, Renata F., E-mail: profcelta@hotmail.com [Universidade Federal de Sao Paulo (UNIFESP), Santos, SP (Brazil). Departamento de Ciencias do Mar

    2015-07-01

    In the present study, certain natural silicate minerals such as aquamarine (AB), morganite (PB), goshenite (WB), white jadeite (JW), green jadeite (JG), pink tourmaline (PT) and two varieties of jadeite-like quartz, denoted here by JQ1 and JQ2, were investigated using the thermoluminescence technique to evaluate their potential for use as very-high- and high-dose dosimeters. These minerals respond to high doses of γ-rays of up to 1000 kGy and often to very high doses of up to 3000 kGy. The TL response of these minerals may be considered to be satisfactory for applications in high-dose dosimetry. Investigations of electron paramagnetic resonance and optically stimulated luminescence dosimetry are in progress. (author)

  4. Metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono-(2-ethylhexyl) phthalate (MEHP) in rats: in vivo and in vitro dose and time dependency of metabolism

    International Nuclear Information System (INIS)

    Lhuguenot, J.C.; Mitchell, A.M.; Milner, G.; Lock, E.A.; Elcombe, C.R.

    1985-01-01

    This study investigated the in vivo metabolism of di(2-ethylhexyl) phthalate (DEHP) and mono(2-ethylhexyl) phthalate (MEHP) in rats after multiple dosing, the metabolism of MEHP in primary rat hepatocyte cultures for periods of up to 3 days, and the biotransformation of some major metabolites of MEHP. Rats were orally administered [ 14 C]DEHP or [ 14 C]MEHP at doses of 50 and 500 mg/kg body wt for three consecutive days. Urine was collected at 24-hr intervals, and metabolite profiles were determined. After a single dose of either compound, urinary metabolite profiles were similar to those previously reported. However, after multiple administration of both DEHP and MEHP at 500 mg/kg, increases in omega-/beta-oxidation products [metabolites I and V, mono(3-carboxy-2-ethylpropyl) phthalate and mono(5-carboxy-2-ethylpentyl) phthalate, respectively] and decreases in omega - 1-oxidation products [metabolites VI and IX, mono(2-ethyl-5-oxohexyl) phthalate and mono(2-ethyl-5-hydroxyhexyl) phthalate, respectively] were seen. At the low dose of 50 mg/kg little or no alteration in urinary metabolite profiles was observed. At 500 mg/kg of MEHP a 4-fold stimulation of CN- -insensitive palmitoyl-CoA oxidation (a peroxisomal beta-oxidation marker) was seen after three consecutive daily doses. At the low dose of 50 mg/kg only a 1.8-fold increase was noted. Similar observations were made with rat hepatocyte cultures. MEHP at concentrations of 50 and 500 microM was extensively metabolized in the rat hepatocyte cultures. Similar metabolic profiles to those seen after in vivo administration of MEHP were observed. At the high (500 microM) concentration of MEHP, changes in the relative proportions of omega- and omega- 1-oxidized metabolites were seen

  5. Dynamic high resolution imaging of rats

    International Nuclear Information System (INIS)

    Miyaoka, R.S.; Lewellen, T.K.; Bice, A.N.

    1990-01-01

    A positron emission tomography with the sensitivity and resolution to do dynamic imaging of rats would be an invaluable tool for biological researchers. In this paper, the authors determine the biological criteria for dynamic positron emission imaging of rats. To be useful, 3 mm isotropic resolution and 2-3 second time binning were necessary characteristics for such a dedicated tomograph. A single plane in which two objects of interest could be imaged simultaneously was considered acceptable. Multi-layered detector designs were evaluated as a possible solution to the dynamic imaging and high resolution imaging requirements. The University of Washington photon history generator was used to generate data to investigate a tomograph's sensitivity to true, scattered and random coincidences for varying detector ring diameters. Intrinsic spatial uniformity advantages of multi-layered detector designs over conventional detector designs were investigated using a Monte Carlo program. As a result, a modular three layered detector prototype is being developed. A module will consist of a layer of five 3.5 mm wide crystals and two layers of six 2.5 mm wide crystals. The authors believe adequate sampling can be achieved with a stationary detector system using these modules. Economical crystal decoding strategies have been investigated and simulations have been run to investigate optimum light channeling methods for block decoding strategies. An analog block decoding method has been proposed and will be experimentally evaluated to determine whether it can provide the desired performance

  6. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

    International Nuclear Information System (INIS)

    Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael

    2005-01-01

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats

  7. The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

    OpenAIRE

    Mohammad Allahtavakoli; Fatemeh Amin; Elham Hakimizadeh; Ali Roohbakhsh; Sayed Ali Haeri Rohani; Ahmad Taghavi Rafsanjani; Abbas Haghparast; Ali Shamsizadeh

    2012-01-01

    Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later t...

  8. Hepatoprotection and neuroprotection induced by low doses of IGF-II in aging rats

    Directory of Open Access Journals (Sweden)

    Barhoum Rima

    2011-07-01

    Full Text Available Abstract Background GH and IGFs serum levels decline with age. Age-related changes appear to be associated to decreases in these anabolic hormones. We have previously demonstrated that IGF-I replacement therapy improves insulin resistance, lipid metabolism and reduces oxidative damage (in brain and liver in aging rats. Using the same experimental model, the aim of this work was to study whether the exogenous administration of IGF-II, at low doses, acts analogous to IGF-I in aging rats. Methods Three experimental groups were included in this study: young healthy controls (yCO, 17 weeks old; untreated old rats (O, 103 weeks old; and aging rats treated with IGF-II (O+IGF-II, 2 μg * 100 g body weight-1 * day-1 for 30 days. Analytical parameters were determined in serum by routine laboratory methods using an autoanalyzer (Cobas Mira; Roche Diagnostic System, Basel, Switzerland. Serum levels of hormones (testosterone, IGF-I and insulin were assessed by RIA. Serum Total Antioxidant Status was evaluated using a colorimetric assay. Mitochondrial membrane potential was evaluated using rhodamine 123 dye (adding different substrates to determine the different states. ATP synthesis in isolated mitochondria was determined by an enzymatic method. Results Compared with young controls, untreated old rats showed a reduction of IGF-I and testosterone levels with a decrease of serum total antioxidant status (TAS. IGF-II therapy improved serum antioxidant capability without modifying testosterone and IGF-I circulating concentrations. In addition, IGF-II treatment reduced oxidative damage in brain and liver, improving antioxidant enzyme activities and mitochondrial function. IGF-II was also able to reduce cholesterol and triglycerides levels increasing free fatty acids concentrations. Conclusions We demonstrate that low doses of IGF-II induce hepatoprotective, neuroprotective and metabolic effects, improving mitochondrial function, without affecting testosterone and

  9. The effects of rat's sperm bioassay for low dose X-ray

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Gye Hwan; Min, Soo Young; Lee, Sang Bock; Lee, Sam Yul; Lee, Jun Haeng [Nambu Univ., Gwangju (Korea, Republic of); Park, Jong Bae [Juseong College, Cheongwon (Korea, Republic of)

    2007-12-15

    In order to investigate the enhancement effects of low dose radiation on biological activation, this study applied low dose X-ray to the whole body of male rats to find out whether hormesis is induced in male germ cells. Total 36 Sprague-Dawley (SD) rats as experimental animal were subdivided into 6 groups(in 6 rats per group) such as control, 10 mGy, 20 mGy, 50 mGy, 100 mGy and 200 mGy radiation group. All the groups showed slightly increasing number of sperms per 0.1 g semen (14.216 x 10{sup 6}, 13.901 x 10{sup 6}, 14.153 x 10{sup 6}, 13.831 x 10{sup 6}, 14.137 x 10{sup 6}, 14.677 x 10{sup 6} respectively), and the motility of sperms amounted to 50.9%, 49.5%, 55.1%, 54.3%, 48.0% and 52.2% respectively. Particularly, compared to the control, the other 5 groups showed higher male hormone level, and the microscopic observations of testicle tissues showed no vacuolization in seminiferous tubules and testis cells. In the results of this experiment, no harmful effect was observed on Sprague-Dawley (SD) rats for which the dose of radiation was controlled as regulated legally by the Ministry of Science and Technology and the Ministry of Health and Welfare. However, as these results were obtained from a limited number of animals, we cannot maintain that the same effect will be observed in the human body. Therefore, there should be further research on the effect on other animals and ultimately on the human body.

  10. The effects of rat's sperm bioassay for low dose X-ray

    International Nuclear Information System (INIS)

    Jin, Gye Hwan; Min, Soo Young; Lee, Sang Bock; Lee, Sam Yul; Lee, Jun Haeng; Park, Jong Bae

    2007-01-01

    In order to investigate the enhancement effects of low dose radiation on biological activation, this study applied low dose X-ray to the whole body of male rats to find out whether hormesis is induced in male germ cells. Total 36 Sprague-Dawley (SD) rats as experimental animal were subdivided into 6 groups(in 6 rats per group) such as control, 10 mGy, 20 mGy, 50 mGy, 100 mGy and 200 mGy radiation group. All the groups showed slightly increasing number of sperms per 0.1 g semen (14.216 x 10 6 , 13.901 x 10 6 , 14.153 x 10 6 , 13.831 x 10 6 , 14.137 x 10 6 , 14.677 x 10 6 respectively), and the motility of sperms amounted to 50.9%, 49.5%, 55.1%, 54.3%, 48.0% and 52.2% respectively. Particularly, compared to the control, the other 5 groups showed higher male hormone level, and the microscopic observations of testicle tissues showed no vacuolization in seminiferous tubules and testis cells. In the results of this experiment, no harmful effect was observed on Sprague-Dawley (SD) rats for which the dose of radiation was controlled as regulated legally by the Ministry of Science and Technology and the Ministry of Health and Welfare. However, as these results were obtained from a limited number of animals, we cannot maintain that the same effect will be observed in the human body. Therefore, there should be further research on the effect on other animals and ultimately on the human body

  11. Disordered redox metabolism of brain cells in rats exposed to low doses of ionizing radiation or UHF electromagnetic radiation.

    Science.gov (United States)

    Burlaka, A P; Druzhyna, M O; Vovk, A V; Lukin, S М

    2016-12-01

    To investigate the changes of redox-state of mammalian brain cells as the critical factor of initiation and formation of radiation damage of biological structures in setting of continuous exposure to low doses of ionizing radiation or fractionated ultra high frequency electromagnetic radiation (UHF EMR) at non-thermal levels. The influence of low-intensity ionizing radiation was studied on outbred female rats kept for 1.5 years in the Chernobyl accident zone. The effects of total EMR in the UHF band of non-thermal spectrum were investigated on Wistar rats. The rate of formation of superoxide radicals and the rate of NO synthesis in mitochondria were determined by the EPR. After exposure to ionizing or UHF radiation, the levels of ubisemiquinone in brain tissue of rats decreased by 3 and 1.8 times, respectively. The content of NO-FeS-protein complexes in both groups increased significantly (р < 0.05). In the conditions of ionizing or EMR the rates of superoxide radical generation in electron-transport chain of brain cell mitochondria increased by 1.5- and 2-fold, respectively (р < 0.05). In brain tissue of rats kept in the Chernobyl zone, significant increase of NO content was registered; similar effect was observed in rats treated with UHFR (р < 0.05). The detected changes in the electron transport chain of mitochondria of brain cells upon low-intensity irradiation or UHF EMR cause the metabolic reprogramming of cell mitochondria that increases the rate of superoxide radical generation and nitric oxide, which may initiate the development of neurodegenerative diseases and cancer. This article is part of a Special Issue entitled "The Chornobyl Nuclear Accident: Thirty Years After".

  12. Study of a 13-weeks, Repeated, Intramuscular Dose, Toxicity Test of Sweet Bee Venom in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Hyunmin Kang

    2014-06-01

    Full Text Available Objectives:This study was performed to analyze a 13-week repeated dose toxicity test of Sweet Bee Venom (SBV extracted from bee venom and administered in Sprague-Dawley (SD rats. Methods:Male and female 5-week-old SD rats were treated once daily with SBV (high-dosage group: 0.28 mg/kg; medium-dosage group: 0.14 mg/kg; or low-dosage group: 0.07 mg/kg for 13 weeks. Normal saline was administered to the control group in a similar manner (0.2 mL/kg. We conducted clinical observations, body weight measurements, ophthalmic examinations, urinalyses, hematology and biochemistry tests, and histological observations using hematoxylin and eosin (H&E staining to identify any abnormalities caused by the SBV treatment. Results:During this study, no mortality was observed in any of the experimental groups. Hyperemia and a movement disorder were observed around the area of in all groups that received SBV treatment, with a higher occurrence in rats treated with a higher dosage. Male rats receiving in the high-dosage group showed a significant decrease in weight during the treatment period. Compared to the control group, no significant changes in the ophthalmic parameters, the urine analyses, the complete blood cell count (CBC, and the biochemistry in the groups treated with SBV. Compared to the control group, some changes in organ weights were observed in the medium-and the high-dosage groups, but the low-dosage group showed no significant changes. Histological examination of thigh muscle indicated cell infiltration, inflammation, degeneration, and necrosis of muscle fiber, as well as fibrosis, in both the medium- and the high-dosage groups. Fatty liver change was observed in the periportal area of rats receiving medium and high dosages of SBV. No other organ abnormalities were observed. Conclusion:Our findings suggest that the No Observed Adverse Effect Level (NOAEL of SBV is approximately 0.07 mg/kg in male and female SD rats.

  13. Treatment of the prostate cancer with high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Martinez, Alvaro; Torres Silva, Felipe

    2002-01-01

    The prostate cancer treatment in early stages is controversial. The high dose rate brachytherapy has been used like monotherapy or boost with external beam radiotherapy in advanced disease. This paper describes the technique and the advantages over other modalities

  14. Evaluation of sphingolipids in Wistar rats treated to prolonged and single oral doses of fumonisin b₁.

    Science.gov (United States)

    Direito, Glória M; Almeida, Adriana P; Aquino, Simone; dos Reis, Tatiana Alves; Pozzi, Claudia Rodrigues; Corrêa, Benedito

    2009-01-01

    The objective of the present study was to evaluate sphingolipid levels (sphingosine-So and sphinganine-Sa) and to compare the Sa/So ratio in liver, serum and urine of Wistar rats after prolonged administration (21 days) of fumonisin B(1) (FB(1)). In parallel, the kinetics of sphingolipid elimination in urine was studied in animals receiving a single dose of FB(1). Prolonged exposure to FB(1) caused an increase in Sa levels in urine, serum and liver. The most marked effect on sphingolipid biosynthesis was observed in animals treated with the highest dose of FB(1). Animals receiving a single dose of FB(1) presented variations in Sa and So levels and in the Sa/So ratio.

  15. Bile Salt Homeostasis in Normal and Bsep Gene Knockout Rats with Single and Repeated Doses of Troglitazone.

    Science.gov (United States)

    Cheng, Yaofeng; Chen, Shenjue; Freeden, Chris; Chen, Weiqi; Zhang, Yueping; Abraham, Pamela; Nelson, David M; Humphreys, W Griffith; Gan, Jinping; Lai, Yurong

    2017-09-01

    The interference of bile acid secretion through bile salt export pump (BSEP) inhibition is one of the mechanisms for troglitazone (TGZ)-induced hepatotoxicity. Here, we investigated the impact of single or repeated oral doses of TGZ (200 mg/kg/day, 7 days) on bile acid homoeostasis in wild-type (WT) and Bsep knockout (KO) rats. Following oral doses, plasma exposures of TGZ were not different between WT and KO rats, and were similar on day 1 and day 7. However, plasma exposures of the major metabolite, troglitazone sulfate (TS), in KO rats were 7.6- and 9.3-fold lower than in WT on day 1 and day 7, respectively, due to increased TS biliary excretion. With Bsep KO, the mRNA levels of multidrug resistance-associated protein 2 (Mrp2), Mrp3, Mrp4, Mdr1, breast cancer resistance protein (Bcrp), sodium taurocholate cotransporting polypeptide, small heterodimer partner, and Sult2A1 were significantly altered in KO rats. Following seven daily TGZ treatments, Cyp7A1 was significantly increased in both WT and KO rats. In the vehicle groups, plasma exposures of individual bile acids demonstrated variable changes in KO rats as compared with WT. WT rats dosed with TGZ showed an increase of many bile acid species in plasma on day 1, suggesting the inhibition of Bsep. Conversely, these changes returned to base levels on day 7. In KO rats, alterations of most bile acids were observed after seven doses of TGZ. Collectively, bile acid homeostasis in rats was regulated through bile acid synthesis and transport in response to Bsep deficiency and TGZ inhibition. Additionally, our study is the first to demonstrate that repeated TGZ doses can upregulate Cyp7A1 in rats. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Investigation of PBAT dosimetric properties for high gamma dose dosimetry

    International Nuclear Information System (INIS)

    Cunha, Elisete L.; Schimitberger, Thiago

    2017-01-01

    Poly(butylene adipate-co-terephthalate) (PBAT) is an aliphatic-aromatic copolyester which is biodegradable. It is a non-photoluminescent copolyester that becomes photoluminescent after previous exposure to gamma doses higher than 100 kGy. After the previous high energy irradiation, the material shows the highest photo-stimulated luminescence emission when excited with a LED source at wavelengths ranging from 370 to 405 nm. In this work we investigated the enhancement of the photoluminescence (PL) and dosimetric properties of PBAT, after exposure to high doses of gamma radiation ranging from 50 to 4,000 kGy. In this investigation we demonstrate that increasing the PBAT film thickness by 100 μm enhances the PL output by 3.5 times, when irradiated with 500 kGy. Also, besides the already known color green brightness, the PL intensity can also be used for high dose dosimetry purposes for doses ranging from 50 to 750 kGy. The FTIR analysis has demonstrated that the there is a linear relationship between peak intensity and dose for doses ranging from 100 and 2,000 kGy for the absorbance peaks at 3,241 cm -1 and 3271 cm -1 , with linear correlation coefficients of 0.9981 and 0.9992, respectively. The results indicate that PBAT has great potential for applications in bio-imaging devices and high gamma dose dosimetry. (author)

  17. Investigation of PBAT dosimetric properties for high gamma dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Cunha, Elisete L.; Schimitberger, Thiago, E-mail: elisete.cunha@cdtn.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Engenharia Nuclear; Oliveira, Cristiana M.; Faria, Luiz O., E-mail: farialo@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    Poly(butylene adipate-co-terephthalate) (PBAT) is an aliphatic-aromatic copolyester which is biodegradable. It is a non-photoluminescent copolyester that becomes photoluminescent after previous exposure to gamma doses higher than 100 kGy. After the previous high energy irradiation, the material shows the highest photo-stimulated luminescence emission when excited with a LED source at wavelengths ranging from 370 to 405 nm. In this work we investigated the enhancement of the photoluminescence (PL) and dosimetric properties of PBAT, after exposure to high doses of gamma radiation ranging from 50 to 4,000 kGy. In this investigation we demonstrate that increasing the PBAT film thickness by 100 μm enhances the PL output by 3.5 times, when irradiated with 500 kGy. Also, besides the already known color green brightness, the PL intensity can also be used for high dose dosimetry purposes for doses ranging from 50 to 750 kGy. The FTIR analysis has demonstrated that the there is a linear relationship between peak intensity and dose for doses ranging from 100 and 2,000 kGy for the absorbance peaks at 3,241 cm{sup -1} and 3271 cm{sup -1}, with linear correlation coefficients of 0.9981 and 0.9992, respectively. The results indicate that PBAT has great potential for applications in bio-imaging devices and high gamma dose dosimetry. (author)

  18. Acute toxicity and the 28-day repeated dose study of a Siddha medicine Nuna Kadugu in rats

    Directory of Open Access Journals (Sweden)

    Ramaswamy Ramaswamy

    2012-10-01

    Full Text Available Abstract Background Nuna Kadugu (NK, a Siddha medicine prepared from leaves and fruits of Morinda Pubescens, used for the treatment of various skin diseases. Though NK has been widely used for several decades, no scientific report was available on its safety. Present study was undertaken to demonstrate the oral toxicity of NK in Sprague Dawley rats. Methods Acute and 28-day repeated oral toxicity studies were performed following OECD test guidelines 423 and 407, respectively, with minor modifications. In acute oral toxicity study, NK was administered at 2000mg/kg b.wt., p.o and animals were observed for toxic signs at 0, 0.5, 1, 4, 24 h and for next 14 days. Gross pathology was performed at the end of the study. In repeated dose, the 28- day oral toxicity study, NK was administered at 300, 600 and 900 mg/kg b.wt./p.o/day. Two satellite groups (control and high dose were also maintained to determine the delayed onset toxicity of NK. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed. Results In acute toxicity study, no treatment related death or toxic signs were observed with NK administration. In the repeated dose study, no significant differences in body weight changes, food / water intake, haematology, clinical biochemistry and electrolytes content were observed between control and NK groups. No gross pathological findings and difference in relative organ weights were observed between control and NK treated rats. Histopathological examination revealed no abnormalities with NK treatment. Conclusion Acute study reveals that the LD50 of NK is greater than 2000mg/kg, b.wt. in fasted female rats and can be classified as Category 5. 28-day repeated oral toxicity demonstrates that the No Observed Adverse Effect Level of NK is greater than 900 mg/kg b.wt./day, p.o in rats

  19. Braquiterapia de alta taxa de dose no Brasil High-dose rate brachytherapy in Brazil

    Directory of Open Access Journals (Sweden)

    Sérgio Carlos Barros Esteves

    2004-10-01

    Full Text Available A braquiterapia de alta taxa de dose foi introduzida em nosso meio em janeiro de 1991. Desde então, houve uma mudança significativa na abordagem das neoplasias malignas em relação às vantagens do novo método, e também resolução da demanda reprimida de braquiterapia para as neoplasias ginecológicas. Nos primeiros dez anos de atividade, o Brasil tratou, em 31 serviços, 26.436 pacientes com braquiterapia, sendo mais de 50% das pacientes portadoras de neoplasias do colo uterino. Este estudo mostra o número e o perfil de pacientes tratados com esse método e a sua distribuição no território nacional, deixando explícito o benefício da braquiterapia de alta taxa de dose para o Brasil.High-dose rate brachytherapy was first introduced in Brazil in January 1991. Significant changes in the management of malignant neoplasms were observed since utilization of high-dose rate brachytherapy. The high number of gynecological patients awaiting for brachytherapy also decreased during this period. In the first ten years 26,436 patients were treated with high-dose rate brachytherapy. More than 50% of these patients presented neoplasms of the uterine cervix. In this study we present the number and profile of the patients treated with high-dose rate brachytherapy as well as the distribution of these patients in the Brazilian territory, proving the benefit of the use of high-dose rate brachytherapy in Brazil.

  20. [Effect of low dose aspirin on osseointegration around titanium implants in osteoporotic rats].

    Science.gov (United States)

    Yang, Q; Li, F L

    2018-02-09

    Objective: To investigate the effect of aspirin on osseointegration around titanium implants in ostoeporotic rats and to provide evidence for future researches and clinical application. Methods: A total of 60 female SD rats, aged 3-4 months, were divided into ovariectomy group (Ovx group, n= 48) and sham-ovariectomy group (Sham group, n= 12). The rats in Ovx group received ovariectomy and those in Sham group underwent sham-ovariectomy. Twelve weeks later, six rats in each group were randomly selected to confirm the osteoporosis models. The Ovx group was divided into 4 subgroups with 12 rats in each group, namely the osteoporosis group (OP group), and Aspirin groups (A1, A2, A3 group). Pure screw titanium implants were placed in the right tibia near metaphysis of all rats. Three days after implant surgery, aspirin groups were intragastrically administered aspirin at a dose of 2.06, 4.11, 8.21 mg·kg(-1)·d(-1) (A1, A2, A3), and OP group and Sham group were fed the same amount of normal saline. Four and 12 weeks following implantations surgery, half of the rats in each group were randomly chosen and sacrificed. Implant bone contact rate (IBCR), combined bone lamella width (CBLW) and trabercular width (TW) were observed and calculated using histomorphometric measurement. Results: Four weeks after implantations surgery, the TW and CBLW of rats in A1 group [(39.60±2.77) and (27.56±4.14) μm] and the IBCR, TW and CBLW of rats in A2 group and A3 group [A2: (47.21±4.19)%, (48.74±3.20) and (35.91±3.79) μm; A3: (47.35±6.07)%, (50.27±5.25) and (40.66±2.11) μm] were much higher than those in OP group [(33.89±7.17)%, (32.20±6.10) and (19.77±6.80) μm]( P 0.05). Twelve weeks after implantations surgery, the IBCR and CBLW of rats in A1 group [ (85.86±3.64) %, (53.12±8.68) μm], and the IBCR, TW and CBLW of rats in A2 group and A3 group [A2: (85.64±3.97)%, (69.42±6.78) and (54.19±3.12) μm; A3: (86.22±3.48)%, (75.43±3.50) and (55.79±5.60) μm] were much higher

  1. Effect of high dietary calcium on weight management in rats

    International Nuclear Information System (INIS)

    Mohamad, M.T.

    2012-01-01

    The present study was undertaken to find out a suitable dietary regime to maintain a lower prevalence of overweight or obesity by adjusting the diet components. Therefore, male Swiss albino rats were selected according to their ages and divided into two main groups, i.e., premature and mature groups. Each rat group was divided into 4 subgroups and each subgroup was fed on a diet of varied composition. Serum levels of lipids, calcium, phosphorous and testosterone were determined in addition to body weight measurement. The results indicate non-significant decrease of percentage of body weight gain in premature rats fed on high-calcium diets while significant decrease of percentage of body weight gain in mature rats fed on the same diet composition. The levels of serum HDL-C, LDL-C, triglycerides and testosterone were significantly decreased in premature rats fed high- calcium diets. In premature rats, only rat subgroup fed on high calcium from milk, showed a significant decrease in serum cholesterol levels. Calcium and phosphorus levels exhibited non- significant change between premature rats. In mature rats, LDL-C data demonstrate nonsignificant changes while cholesterol and triglyceride levels were significantly decreased in rats fed high -calcium diet compared to control. HDL-C level revealed a significant decrease in sera of mature rats fed on high calcium from milk. Serum testosterone levels were significantly decreased in mature rats fed low- fat diets or low fat diets supplemented with high- calcium level. In general, one would suggest to consume low fat diet (4%) supplemented with high calcium from dry skimmed milk fortified with hydroxyapatite as suitable dietary program to avoid overweight or obesity.

  2. Different dose-dependent effects of ebselen in sciatic nerve ischemia-reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Filiz Ozyigit

    2015-08-01

    Full Text Available Ebselen is an organoselenium compound which has strong antioxidant and anti-inflammatory effects. We investigated the neuroprotective role of ebselen pretreatment in rats with experimental sciatic nerve ischemia-reperfusion (I/R injury. Adult male Sprague Dawley rats were divided into four groups (N = 7 in each group. Before sciatic nerve I/R was induced, ebselen was injected intraperitoneally at doses of 15 and 30 mg/kg. After a 2 h ischemia and a 3 h reperfusion period, sciatic nerve tissues were excised. Tissue levels of malondialdehyde (MDA and nitric oxide (NO, and activities of superoxide dismutase (SOD, glutathione peroxidase (GPx, and catalase (CAT were measured. Sciatic nerve tissues were also examined histopathologically. The 15 mg/kg dose of ebselen reduced sciatic nerve damage and apoptosis (P < 0.01, levels of MDA, NO, and inducible nitric oxide synthase (iNOS positive cells (P < 0.01, P < 0.05, respectively, and increased SOD, GPx, and CAT activities (P < 0.001, P < 0.01, P < 0.05, respectively compared with the I/R group that did not receive ebselen. Conversely, the 30 mg/kg dose of ebselen increased sciatic nerve damage, apoptosis, iNOS positive cells (P < 0.01, P < 0.05, P < 0.001 and MDA and NO levels (P < 0.05, P < 0.01 and decreased SOD, GPx, and CAT activities (P < 0.05 compared with the sham group. The results of this study suggest that ebselen may cause different effects depending on the dose employed. Ebselen may be protective against sciatic nerve I/R injury via antioxidant and antiapoptotic activities at a 15 mg/kg dose, conversely higher doses may cause detrimental effects.

  3. Methamphetamine treatment during development attenuates the dopaminergic deficits caused by subsequent high-dose methamphetamine administration.

    Science.gov (United States)

    McFadden, Lisa M; Hoonakker, Amanda J; Vieira-Brock, Paula L; Stout, Kristen A; Sawada, Nicole M; Ellis, Jonathan D; Allen, Scott C; Walters, Elliot T; Nielsen, Shannon M; Gibb, James W; Alburges, Mario E; Wilkins, Diana G; Hanson, Glen R; Fleckenstein, Annette E

    2011-08-01

    Administration of high doses of methamphetamine (METH) causes persistent dopaminergic deficits in both nonhuman preclinical models and METH-dependent persons. Noteworthy, adolescent [i.e., postnatal day (PND) 40] rats are less susceptible to this damage than young adult (PND90) rats. In addition, biweekly treatment with METH, beginning at PND40 and continuing throughout development, prevents the persistent dopaminergic deficits caused by a "challenge" high-dose METH regimen when administered at PND90. Mechanisms underlying this "resistance" were thus investigated. Results revealed that biweekly METH treatment throughout development attenuated both the acute and persistent deficits in VMAT2 function, as well as the acute hyperthermia, caused by a challenge METH treatment. Pharmacokinetic alterations did not appear to contribute to the protection afforded by the biweekly treatment. Maintenance of METH-induced hyperthermia abolished the protection against both the acute and persistent VMAT2-associated deficits suggesting that alterations in thermoregulation were caused by exposure of rats to METH during development. These findings suggest METH during development prevents METH-induced hyperthermia and the consequent METH-related neurotoxicity. Copyright © 2011 Wiley-Liss, Inc.

  4. Effect of Low-Dose Aspirin on Chronic Acid Reflux Esophagitis in Rats.

    Science.gov (United States)

    Masuda, Takahiro; Yano, Fumiaki; Omura, Nobuo; Tsuboi, Kazuto; Hoshino, Masato; Yamamoto, Se Ryung; Akimoto, Shunsuke; Kashiwagi, Hideyuki; Yanaga, Katsuhiko

    2018-01-01

    Clinical role of low-dose aspirin (LDA) in pathogenesis of gastroesophageal reflux disease is by far controversial. This can be attributed to the paucity of basic research detailing the mechanism of LDA-induced esophageal mucosal injury (EI) on underlying chronic acid reflux esophagitis (RE). The aim of this study was to clarify the effect of LDA on chronic RE in rats. Esophagitis was induced in 8-week-old male Wistar rats by ligating the border between forestomach and glandular portion with a 2-0 silk tie and covering the duodenum with a small piece of 18-Fr Nélaton catheter. Seventy-eight chronic RE rat models were divided into five treatment groups, consisting of orally administered vehicle (controls), and aspirin doses of 2, 5, 50 or 100 mg/kg once daily for 28 days. EI was assessed by gross area of macroscopic mucosal injury, severity grade of esophagitis and microscopic depth of infiltration by inflammatory cells. Area of esophagitis in animals with aspirin dose of 100 mg/kg/day showed a 36.5% increase compared with controls, although it failed to achieve statistical significance (p = 0.812). Additionally, the rate of severe EI was increased in animals with aspirin dose of 100 mg/kg/day as compared with controls (p aspirin (100 mg/kg/day) contributed in exacerbating preexisting EI. LDA (2 and 5 mg/kg/day), on the other hand, did not affect chronic RE in this model. LDA seems to be safe for use in patients with chronic RE.

  5. Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

    Science.gov (United States)

    Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

    2016-10-01

    Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Effect of repeated oral therapeutic doses of methylphenidate on food intake and growth rate in rats.

    Science.gov (United States)

    Alam, Nausheen; Najam, Rahila

    2015-01-01

    Central nervous system stimulants are known to produce anorexia. Previous data suggest that methylphenidate can have variable effects on caloric intake and growth rate. A dose-response study was performed to monitor caloric intake, liquid intake and growth rate in rats following repeated administration of human oral therapeutic doses 2 mg/kg/day, 5mg/kg/day and 8mg/kg/day of methylphenidate. We found that food intake and water intake, increased in all weeks and at all doses used in the study. Growth rate increased more at higher dose (8mg/kg/day) and at low dose (2mg/kg/day) of methylphenidate in 1(st) and 2(nd) week whereas more decreased by the above doses in 3(rd) week, suggesting that food stimulation leads to initial increase in growth rate but long term administration of methylphenidate attenuate growth rate that is not due to modulation of appetite but may be due to anxiety and increased activity produce by stimulants. A possible role of DA, 5HT receptors in modulation of appetite and anxiety is discussed.

  7. Metabolomics reveals dose effects of low-dose chronic exposure to uranium in rats: identification of candidate biomarkers in urine samples.

    Science.gov (United States)

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Éric; Dublineau, Isabelle; Aigueperse, Jocelyne; Bohand, Sandra; Martin, Jean-Charles; Souidi, Maâmar

    2016-01-01

    Data are sparse about the potential health risks of chronic low-dose contamination of humans by uranium (natural or anthropogenic) in drinking water. Previous studies report some molecular imbalances but no clinical signs due to uranium intake. In a proof-of-principle study, we reported that metabolomics is an appropriate method for addressing this chronic low-dose exposure in a rat model (uranium dose: 40 mg L -1 ; duration: 9 months, n = 10). In the present study, our aim was to investigate the dose-effect pattern and identify additional potential biomarkers in urine samples. Compared to our previous protocol, we doubled the number of rats per group (n = 20), added additional sampling time points (3 and 6 months) and included several lower doses of natural uranium (doses used: 40, 1.5, 0.15 and 0.015 mg L -1 ). LC-MS metabolomics was performed on urine samples and statistical analyses were made with SIMCA-P+ and R packages. The data confirmed our previous results and showed that discrimination was both dose and time related. Uranium exposure was revealed in rats contaminated for 9 months at a dose as low as 0.15 mg L -1 . Eleven features, including the confidently identified N1-methylnicotinamide, N1-methyl-2-pyridone-5-carboxamide and 4-hydroxyphenylacetylglycine, discriminated control from contaminated rats with a specificity and a sensitivity ranging from 83 to 96 %, when combined into a composite score. These findings show promise for the elucidation of underlying radiotoxicologic mechanisms and the design of a diagnostic test to assess exposure in urine, in a dose range experimentally estimated to be above a threshold between 0.015 and 0.15 mg L -1 .

  8. Preclinical Study of 68Ga-DOTATOC: Biodistribution Assessment in Syrian Rats and Evaluation of Absorbed Dose in Human Organs.

    Science.gov (United States)

    Naderi, Mojdeh; Zolghadri, Samaneh; Yousefnia, Hassan; Ramazani, Ali; Jalilian, Amir Reza

    2016-01-01

    Gallium-68 DOTA-DPhe 1 -Tyr 3 -Octreotide ( 68 Ga-DOTATOC) has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for 68 Ga-DOTATOC preparation, using a novel germanium-68 ( 68 Ge)/ 68 Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy. The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method. 68 Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37°C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues (12.83 %ID/g and 0.91 %ID/g, respectively). Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses (0.105, 0.074 and 0.010 mGy/MBq, respectively). Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for 68 Ga-DOTATOC. The obtained results showed that 68 Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran.

  9. Retrospective analysis of dose delivery in intra-operative high dose rate brachytherapy

    International Nuclear Information System (INIS)

    Oh, M.; Avadhani, J.S.; Malhotra, H.K.; Cunningham, B.; Tripp, P.; Jaggernauth, W.; Podgorsak, M.B.

    2007-01-01

    Background. This study was performed to quantify the inaccuracy in clinical dose delivery due to the incomplete scatter conditions inherent in intra-operative high dose rate (IOHDR) brachytherapy. Methods. Treatment plans of 10 patients previously treated in our facility, which had irregular shapes of treated areas, were used. Treatment geometries reflecting each clinical case were simulated using a phantom assembly with no added build-up on top of the applicator. The treatment planning geometry (full scatter surrounding the applicator) was subsequently simulated for each case by adding bolus on top of the applicator. Results. For geometries representing the clinical IOHDR incomplete scatter environment, measured doses at the 5 mm and 10 mm prescription depths were lower than the corresponding prescribed doses by about 7.7% and 11.1%, respectively. Also, for the two prescription methods, an analysis of the measured dose distributions and their corresponding treatment plans showed average decreases of 1.2 mm and 2.2 mm in depth of prescription dose, respectively. Conclusions. Dosimetric calculations with the assumption of an infinite scatter environment around the applicator and target volume have shown to result in dose delivery errors that significantly decrease the prescription depth for IOHDR treatment.(author)

  10. Phenobarbital at Low Dose in the presence of Curcumin Decreases Progress of Cancer in Rats

    International Nuclear Information System (INIS)

    Mazen, G.M.A.

    2011-01-01

    This current investigation was conducted on male albino rats to elucidate the effects of curcumin alone or in the presence of phenobarbital at low dose to decrease the progress of hepato-gastrointestinal carcinogenesis induced by N-diethylnitrosoamine (DEN) in rats. As a result of cancer induction, the levels of serum tumour markers [carcino-embryonic antigen (CEA), alpha-fetoprotein (AFP) and cancer antigen (CA19.9)] were significantly elevated. On the other hand, glutathione (GSH) and glutathione peroxidase (GPx) were decreased significantly in blood, liver, stomach and intestine whereas the levels of malondialdehyde (MAD) in liver, stomach and intestine were significantly elevated in the cancer group of rats in comparison to their corresponding control group. The administration of curcumin alone or together with phenobarbital ameliorated all these alterations depending on the time of administration. The data of this study suggested that low dose of phenobarbital in the presence of curcumin may inhibit the development of hepato-gastrointestinal carcinogenesis initiated with DEN.

  11. The effect of a single dose of morphine on muscle fatigue indices in male rats

    Directory of Open Access Journals (Sweden)

    Sedigheh Amiresmaili

    2016-09-01

    Full Text Available Background and Aim: Endogenous opioids and addictive opiate drugs change many body functions. . Previous studies have referred to the effects of morphine on smooth and pulmonary muscles ., but the  effects of opioids on skeletal muscles is not known well. Thus, the current study aimed at assessing the effect of a single dose of morphine on muscle fatigue in male rats. Materials and Methods: In this experimental study, 40 male Wistar rats weighing 220-270 g were randomly divided into four equal groups: control (the mice were kept in their cages and received food and water, morphine receiving group, fatigue group (the mice in this group were kept running on  a treadmill . for120 minutes at a rate of 20 meters per minute, and morphine plus fatigue group. At the end of the experiments, blood samples were obtained from the corner of their eyes and were sent to the laboratory for measurement of muscle fatigue indexes including lactate dehydrogenase (LDH and creatine phosphokinase (CPK. Results: Administration of morphine to the fatigue group decreased running time compared with the control group (P=0.009. Furthermore, administration of morphine to the fatigue group significantly increased serum levels of LDH (P=0.009 and CPK (P=0.008. Conclusion: The present study showed that administration of a single dose of morphine in rats increases muscle fatigue biomarkers (LDH, CPK.

  12. Proximity correction of high-dosed frame with PROXECCO

    Science.gov (United States)

    Eisenmann, Hans; Waas, Thomas; Hartmann, Hans

    1994-05-01

    Usefulness of electron beam lithography is strongly related to the efficiency and quality of methods used for proximity correction. This paper addresses the above issue by proposing an extension to the new proximity correction program PROXECCO. The combination of a framing step with PROXECCO produces a pattern with a very high edge accuracy and still allows usage of the fast correction procedure. Making a frame with a higher dose imitates a fine resolution correction where the coarse part is disregarded. So after handling the high resolution effect by means of framing, an additional coarse correction is still needed. Higher doses have a higher contribution to the proximity effect. This additional proximity effect is taken into account with the help of the multi-dose input of PROXECCO. The dose of the frame is variable, depending on the deposited energy coming from backscattering of the proximity. Simulation proves the very high edge accuracy of the applied method.

  13. Behavioral changes in rats prenatally irradiated with low dose of gamma-rays

    International Nuclear Information System (INIS)

    Kiskova, J.; Smajda, B.; Capicikova, M.; Lievajova, K.

    2006-01-01

    In this work, the effects of prenatal gamma-irradiation on behavior in adult Sprague-Dawley rats were studied. Four months old female rats were irradiated with a dose of 1 Gy of gamma-rays on day 15 of gestation. The offspring of irradiated mothers (n=26) and that of control, non-irradiated mothers (n=36) of both sexes at the age of 3 month were tested in Morris's water maze and in open field test. All experimental groups showed a tendency to shortening the time needed to reach the platform in each trial in Morris water maze. Statistically significant difference between irradiated and control rats was detected only in males on 3 rd experimental day. The ability to remember the position of the platform was not altered in irradiated animals after a 4 day pause. In open field test, statistically significant differences in comparison with controls were detected in number of squares entered and in crossings of the central square (P ≤ 0.05) in males. These findings suggest, when comparing with results of other authors, that irradiation effects on postnatal behavior in rats are extremely dependent on the time point of irradiation and that a correlation exist between the developmental stage of the individual brain structures at time of irradiation and the late behavioral effects. (authors)

  14. Effect of continuous low-dose γ-irradiation on rat Sertoli cell function

    International Nuclear Information System (INIS)

    Kamtchouing, P.; Papadopoulos, V.; Drosdowsky, M.A.; Carreau, S.; Pinon-Lataillade, G.; Maas, J.; Guillaumin, J.M.; Bardos, P.; Perreau, C.; Hochereau de Reviers, M.T.

    1988-01-01

    Continuous low-dose γ-irradiation of mature rats induced a progressive degeneration of the germ cells. Blood FSH increased by 127, 176 and 214%, respectively, after 55, 70 and 85 days of treatment when compared to FSH levels in control rats (8.50 ± 0.60 ng/ml); conversely, serum LH and testosterone levels were unchanged. The Sertoli cell function was affected by the treatment from 70 days on, as attested by androgen binding protein (ABP) and transferrin secretions which diminished 35-40%. Serum ABP levels were not altered, whatever the duration of irradiation, even though epididymal ABP contents (as well as concentrations) diminished 34-60% when compared to those of the controls. Moreover, in purified Leydig cells, LH-stimulated intracellular cAMP levels, which were decreased by seminiferous tubule medium (STM) from control rats, were enhanced in presence of STM from treated animals. Testosterone output was stimulated 9-fold in presence of oLH and further increased (46-76%) from stages XIV-V by STM prepared from control and irradiated rats, respectively. After 85 days the STM effects on both cAMP and testosterone syntheses were zero. These results demonstrate a probable alteration of Sertoli cell function after irradiation, but also a role of the germ cells in the regulation of the synthesis of ABP, transferrin and Sertoli cell paracrine factors

  15. Blood pressure reduction induced by low dose of epinephrine via different routes in rats.

    Science.gov (United States)

    Wu, Jing; Ji, Mu-Huo; Wang, Zhong-Yun; Zhu, Wei; Yang, Jian-Jun; Peng, Yong G

    2013-09-01

    Epinephrine was recently shown to induce a hypotension episode. Activation of β₂-adrenoceptors with smooth muscle relaxation may be the underlying mechanism. This study investigated the effects of ICI 118551, a β₂-adrenoceptors antagonist, on epinephrine-induced blood pressure reduction via different administration routes in rats. A total of 144 Sprague Dawley rats were equally randomized into 3 groups (intranasal, intravenous, and intra-arterial administration), each with 4 subgroups: saline + saline, ICI 118551 + saline, saline + epinephrine, and ICI 118551 + epinephrine. All rats were anesthetized while spontaneously breathing. Epinephrine was administered at doses of 5 μg/kg via nose, 0.25 μg/kg via femoral vein, and 0.1 μg/kg via aorta. Mean arterial pressure and heart rate were monitored. Mean arterial pressure decreased in all 3 saline + epinephrine subgroups after administration (P blood pressure reduction can be prevented by ICI 118551 in rats, suggesting that the activation of β₂-adrenoceptors contributes to blood pressure reduction.

  16. Effect of Whole Body Low Dose Radiation (WB-LDR) on diabetic rats

    International Nuclear Information System (INIS)

    Roy, B.G.

    2014-01-01

    Exposure of type II diabetic mice to LDR has been shown to significantly up regulate pancreatic antioxidants along with reduction of glucose levels. Present study was aimed to evaluate the effects of WB-LDR on type II diabetic rats. Sprague-Dawley male rats (n=18) were pre-treated with Alloxan Monohydrate (150 mg/kg body weight, IP) to induce hyperglycemia. Elevated level of blood glucose was monitored for consecutive 10 days by Glucometer (Accu-Chek, Active) before irradiation. Two group of rats (n=12) were exposed to single dose of 0.25 Gy and 0.5 Gy of gamma radiation at the rate of 1.02 Gy/minute. Blood glucose level, feed, water intake and body weight was monitored for 10 days post irradiation. Results revealed weight loss, polydipsia, polyphagia and elevated blood glucose level up to 10th day in diabetic control, whereas; reverse trend was observed from 7th day post irradiation in two treated groups. However, no significant difference was found between two treated groups. The results indicate that treatment with WB-LDR reduces the blood-glucose level and so its complications in diabetic rats. (author)

  17. Dose-response and histopathological study, with special attention to the hypophysis, of the differential effects of domoic acid on rats and mice.

    Science.gov (United States)

    Vieira, Andrés Crespo; Martínez, J Manuel Cifuentes; Pose, Roberto Bermúdez; Queijo, Álvaro Antelo; Posadas, Nuria Alemañ; López, Luis M Botana

    2015-05-01

    The effects of the neurotoxin domoic acid (DA) in the central nervous system of rodents (essentially rats and mice) after intraperitoneal administration have been profusely studied in the past. These observations have shown that the toxin induces similar symptoms and pathology in both species, but the lethality varies greatly. This article addresses the common and specific histopathological effects in rats and mice and the difference in sensitivity of these species to DA. Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8 mg/kg) to observe their neurotoxicity by using different histological techniques, and these results were compared with the pathological effects after the administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the presence of this toxin in various tissues by means of immunohistochemistry. Our results showed that rats are more vulnerable than mice to the neurotoxic effects of DA after intraperitoneal inoculation: lethality was extremely high in rats and the toxin produced hippocampal damage in rats surviving the intoxication, while lesions were not observed in DA-inoculated mice. As for similarities between rats and mice, both displayed similar clinical signs and in both the toxin was detected in the hypophysis by immunohistochemistry, a brain region not reported to date as target of the toxin. © 2015 Wiley Periodicals, Inc.

  18. Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

    DEFF Research Database (Denmark)

    Hadrup, Niels; Svingen, Terje; Egebjerg, Karen Mandrup

    2016-01-01

    of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid...

  19. Radiation Parameters of High Dose Rate Iridium -192 Sources

    Science.gov (United States)

    Podgorsak, Matthew B.

    A lack of physical data for high dose rate (HDR) Ir-192 sources has necessitated the use of basic radiation parameters measured with low dose rate (LDR) Ir-192 seeds and ribbons in HDR dosimetry calculations. A rigorous examination of the radiation parameters of several HDR Ir-192 sources has shown that this extension of physical data from LDR to HDR Ir-192 may be inaccurate. Uncertainty in any of the basic radiation parameters used in dosimetry calculations compromises the accuracy of the calculated dose distribution and the subsequent dose delivery. Dose errors of up to 0.3%, 6%, and 2% can result from the use of currently accepted values for the half-life, exposure rate constant, and dose buildup effect, respectively. Since an accuracy of 5% in the delivered dose is essential to prevent severe complications or tumor regrowth, the use of basic physical constants with uncertainties approaching 6% is unacceptable. A systematic evaluation of the pertinent radiation parameters contributes to a reduction in the overall uncertainty in HDR Ir-192 dose delivery. Moreover, the results of the studies described in this thesis contribute significantly to the establishment of standardized numerical values to be used in HDR Ir-192 dosimetry calculations.

  20. Dose intercomparison studies for standardization of high-dose dosimetry in Viet Nam

    International Nuclear Information System (INIS)

    Mai Hoang Hoa; Duong Nguyen Dinh; Kojima, T.

    1999-01-01

    The Irradiation Center of the Vietnam Atomic Energy Commission (IC-VAEC) is planning to establish a traceability system for high-dose dosimetry and to provide high-dose standards as a secondary standard dosimetry laboratory (SSDL) level in Vietnam. For countries which do not have a standard dosimetry laboratory, the participation in the International Dose Assurance Service (IDAS) operated by the International Atomic Energy Agency (IAEA) is the most common means to verify own dosimetry performance with a certain uncertainty. This is, however, only one-direction dose intercomparison with evaluation by IAEA including unknown parameter at participant laboratories. The SSDL level laboratory should have traceability as well as compatibility, ability to evaluate uncertainties of its own dosimetry performance by itself In the present paper, we reviewed our dosimetry performance through two-way dose intercomparison studies and self-evaluation of uncertainty in our dosimetry procedure. The performance of silver dichromate dosimeter as reference transfer dosimeter in IC-VAEC was studied through two-way blind dose intercomparison experiments between the IC-VAEC and JAERI. As another channel of dose intercomparison with IAEA, alanine dosimeters issued by IDAS were simultaneously irradiated with the IC-VAEC dichromate dosimeters at IC-VAEC and analyzed by IAEA. Dose intercomparison between IC-VAEC and JAERI results into a good agreement (better than ±2.5%), and IDAS results also show similar agreement within ±3.0%. The uncertainty was self-estimated on the basis of the JAERI alanine dosimetry, and a preliminary value of about 1.86% at a 68% confidence level is established. The results from these intercomparisons and our estimation of the uncertainty are consistent. We hope that our experience is valuable to other countries which do not have dosimetry standard laboratories and/or are planning to establish them. (author)

  1. Chromosomal aberrations in bone marrow cells of rats irradiated with different gamma-doses and protected with adeturon

    International Nuclear Information System (INIS)

    Ivanov, B.; Mileva, M.; Bulanova, M.; Pantev, T.

    1982-01-01

    Sexually mature wistor rats were irradiated on cesium gamma source ''IGUR-1'' with emissive power 3.25 mA/kg. The animals were divided in five groups of 10 rats each. They were irradiated respectively with 0.0129 C/kg, O, 0.0258 C/kg, 0.0516 C/kg, 0.1032 C/kg and control group. Five animals of each group received 300 meg/g weight Adeturone 15 minutes before exposure. The animals were sacrifices 20 hours after irradiation and preparations made from bone-marrow cells for chromosomal analysis. The number of structural chromosomal aberrations, aberrant cells and total number of aberrations in protected and in nonprotected cells were read under high-power microscope. The results were statistically processed by variation and regression analysis. It was found that Adeturone displays strong protective effect on the hereditary cell structures in all animals exposed to doses higher than 0.0129 C/kg, with the exception of chromatid fragments at a dose of 0.0258 C/kg. Mathematical models of the curves of the yields of chromatid and chromosomal fragments, aberrant cells and total number of aberrations in protected and nonprotected animals were described. (authors)

  2. Low dose prenatal alcohol exposure does not impair spatial learning and memory in two tests in adult and aged rats.

    Directory of Open Access Journals (Sweden)

    Carlie L Cullen

    Full Text Available Consumption of alcohol during pregnancy can have detrimental impacts on the developing hippocampus, which can lead to deficits in learning and memory function. Although high levels of alcohol exposure can lead to severe deficits, there is a lack of research examining the effects of low levels of exposure. This study used a rat model to determine if prenatal exposure to chronic low dose ethanol would result in deficits in learning and memory performance and if this was associated with morphological changes within the hippocampus. Sprague Dawley rats were fed a liquid diet containing 6% (vol/vol ethanol (EtOH or an isocaloric control diet throughout gestation. Male and Female offspring underwent behavioural testing at 8 (Adult or 15 months (Aged of age. Brains from these animals were collected for stereological analysis of pyramidal neuron number and dendritic morphology within the CA1 and CA3 regions of the dorsal hippocampus. Prenatal ethanol exposed animals did not differ in spatial learning or memory performance in the Morris water maze or Y maze tasks compared to Control offspring. There was no effect of prenatal ethanol exposure on pyramidal cell number or density within the dorsal hippocampus. Overall, this study indicates that chronic low dose prenatal ethanol exposure in this model does not have long term detrimental effects on pyramidal cells within the dorsal hippocampus or impair spatial learning and memory performance.

  3. Investigation of polymer composite for high dose dosimetry

    International Nuclear Information System (INIS)

    Pereira, E.L.M.; Batista, A.S.M.; Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H.

    2017-01-01

    Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO 2 ) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm -1 and 1730 cm -1 can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm -1 and 1730 cm -1 whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

  4. Investigation of polymer composite for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, E.L.M.; Batista, A.S.M., E-mail: adriananuclear@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Ribeiro, F.A.S.; Santos, A.P.; Faria, L.O.; Oliveira, A.H. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

    2017-07-01

    Introduction: This paper presents the efficacy evaluation of PVDF and nanocomposites of the PVDF films for high gamma dosimetry. Our scope in this first part of our studies is the selection of the most promising film for future dosimetry trials, where the proportionality of response of the selected material will be investigated over a large range of doses and dose rates. Methods: Was prepared nanocomposites made by mixing Poly(vinylidene fluoride) (PVDF), zirconium oxide (ZrO{sub 2}) and multi-walled carbon nanotubes (MWCNTs) aiming to find dosimetric properties for applications in high dose dosimetry. The samples were irradiated with a Co-60 source at constant dose rate (16.7 kGy/h), with doses ranging from 100 to 2750 kGy. The UV-Vis and FTIR spectrophotometry have been used to monitor the appearing of C=C conjugated bonds and radio-oxidation of carbon (C=O). Results: FTIR spectrometry has that the absorbance intensities at 1715 cm{sup -1} and 1730 cm{sup -1} can be used for high dosimetry purposes for gamma doses ranging from 400 to 2750 kGy. In this range, it is possible to observe a linear relationship between Abs & Dose. Fading of signal was evaluated for one month and reproducibility in 2000 kGy dose. Conclusion: FTIR spectroscopic data revealed two optical absorption bands at 1715 cm{sup -1} and 1730 cm{sup -1} whose intensities are unambiguously related to gamma delivered dose ranging from 400 kGy to 2750 kGy. (author)

  5. Prediction of the pharmacokinetic parameters of triptolide in rats based on endogenous molecules in pre-dose baseline serum.

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    Linsheng Liu

    Full Text Available BACKGROUND: Individual variances usually affect drug metabolism and disposition, and hence result in either ineffectiveness or toxicity of a drug. In addition to genetic polymorphism, the multiple confounding factors of lifestyles, such as dietary preferences, contribute partially to individual variances. However, the difficulty of quantifying individual diversity greatly challenges the realization of individualized drug therapy. This study aims at quantitative evaluating the association between individual variances and the pharmacokinetics. METHODOLOGY/PRINCIPAL FINDINGS: Molecules in pre-dose baseline serum were profiled using gas chromatography mass spectrometry to represent the individual variances of the model rats provided with high fat diets (HFD, routine chows and calorie restricted (CR chows. Triptolide and its metabolites were determined using high performance liquid chromatography mass spectrometry. Metabonomic and pharmacokinetic data revealed that rats treated with the varied diets had distinctly different metabolic patterns and showed differential C(max values, AUC and drug metabolism after oral administration of triptolide. Rats with fatty chows had the lowest C(max and AUC values and the highest percentage of triptolide metabolic transformation, while rats with CR chows had the highest C(max and AUC values and the least percentage of triptolide transformation. Multivariate linear regression revealed that in baseline serum, the concentrations of creatinine and glutamic acid, which is the precursor of GSH, were linearly negatively correlated to C(max and AUC values. The glutamic acid and creatinine in baseline serum were suggested as the potential markers to represent individual diversity and as predictors of the disposal and pharmacokinetics of triptolide. CONCLUSIONS/SIGNIFICANCE: These results highlight the robust potential of metabonomics in characterizing individual variances and identifying relevant markers that have the

  6. Prediction of the Pharmacokinetic Parameters of Triptolide in Rats Based on Endogenous Molecules in Pre-Dose Baseline Serum

    Science.gov (United States)

    Aa, Jiye; Zheng, Tian; Shi, Jian; Li, Mengjie; Wang, Xinwen; Zhao, Chunyan; Xiao, Wenjing; Yu, Xiaoyi; Sun, Runbin; Gu, Rongrong; Zhou, Jun; Wu, Liang; Hao, Gang; Zhu, Xuanxuan; Wang, Guangji

    2012-01-01

    Background Individual variances usually affect drug metabolism and disposition, and hence result in either ineffectiveness or toxicity of a drug. In addition to genetic polymorphism, the multiple confounding factors of lifestyles, such as dietary preferences, contribute partially to individual variances. However, the difficulty of quantifying individual diversity greatly challenges the realization of individualized drug therapy. This study aims at quantitative evaluating the association between individual variances and the pharmacokinetics. Methodology/Principal Findings Molecules in pre-dose baseline serum were profiled using gas chromatography mass spectrometry to represent the individual variances of the model rats provided with high fat diets (HFD), routine chows and calorie restricted (CR) chows. Triptolide and its metabolites were determined using high performance liquid chromatography mass spectrometry. Metabonomic and pharmacokinetic data revealed that rats treated with the varied diets had distinctly different metabolic patterns and showed differential Cmax values, AUC and drug metabolism after oral administration of triptolide. Rats with fatty chows had the lowest Cmax and AUC values and the highest percentage of triptolide metabolic transformation, while rats with CR chows had the highest Cmax and AUC values and the least percentage of triptolide transformation. Multivariate linear regression revealed that in baseline serum, the concentrations of creatinine and glutamic acid, which is the precursor of GSH, were linearly negatively correlated to Cmax and AUC values. The glutamic acid and creatinine in baseline serum were suggested as the potential markers to represent individual diversity and as predictors of the disposal and pharmacokinetics of triptolide. Conclusions/Significance These results highlight the robust potential of metabonomics in characterizing individual variances and identifying relevant markers that have the potential to facilitate

  7. Regularity of wound healing in rats irradiated locally with different doses of soft X-rays

    International Nuclear Information System (INIS)

    Liu Jianzhong; Zhou Yuanguo; Cheng Tianmin; Zhou Ping; Liu Xia; Li Ping

    2002-01-01

    Objective: To study the regular patter of wound healing in rats irradiated locally with different doses of soft X-rays. Methods: Rats were locally irradiated, and wounded immediately thereafter. Gross observation, histopathology and immunohistochemistry examinations, and image analysis were used to study the wound healing process. Results: The authors found that the delayed time of wound healing induced by soft X-ray irradiation of 0.50, 1.01, 1.96, 3,26, 4.00, 5.21 Gy was 1.6, 4.2, 5.4, 6.6, 8.2 and 9.4 days, respectively. Irradiation with 7.0 and 10.0 Gy caused failure of wound healing (up to 40 days). Compared to the non-irradiated wounds, the healing rates of irradiation-impaired wounds were lower during the whole healing process. From day 3 to day 9 after irradiation, the healing rates decreased along with increasing of the radiation dose, indicating the key phase of wound healing was delayed. After irradiation, the collagen synthesis was decreased, its arrangement was disordered, and the structure of granulation tissue was irregular. Conclusion: Soft X-rays irradiation may cause a delay of wound healing in a dose-dependent manner, and irradiation with 7.0 and 10.0 Gy cause failure of wound healing

  8. Single Dose Toxicity of Chukyu (spine-healing Pharmacopuncture Injection in the Muscle of Rats

    Directory of Open Access Journals (Sweden)

    Jeong Hohyun

    2014-03-01

    Full Text Available Objectives: This study was performed to analyze the single dose toxicity of Chukyu (spine-healing pharmacopuncture. Methods: All experiments were conducted at the Biotoxtech, an institution authorized to perform non-clinical studies under the regulations of Good Laboratory Practice (GLP regulations. Sprague-Dawley rats were chosen for the pilot study. Doses of Chukyu (spine-healing pharmacopuncture, 0.1, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was conducted under the approval of the Institutional Animal Ethic Committee. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To check for abnormalities in organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues except in one case, where interstitial infiltrating macrophages were found in one female rat in the 0.5-mL/animal experimental group. Conclusion: The above findings suggest that treatment with Chukyu (spine-healing pharmacopuncture is relatively safe. Further studies on this subject are needed to yield more concrete evidence.

  9. Serum protein concentration in low-dose total body irradiation of normal and malnourished rats

    International Nuclear Information System (INIS)

    Viana, W.C.M.; Lambertz, D.; Borges, E.S.; Neto, A.M.O.; Lambertz, K.M.F.T.; Amaral, A.

    2016-01-01

    Among the radiotherapeutics' modalities, total body irradiation (TBI) is used as treatment for certain hematological, oncological and immunological diseases. The aim of this study was to evaluate the long-term effects of low-dose TBI on plasma concentration of total protein and albumin using prematurely and undernourished rats as animal model. For this, four groups with 9 animals each were formed: Normal nourished (N); Malnourished (M); Irradiated Normal nourished (IN); Irradiated Malnourished (IM). At the age of 28 days, rats of the IN and IM groups underwent total body gamma irradiation with a source of cobalt-60. Total protein and Albumin in the blood serum was quantified by colorimetry. This research indicates that procedures involving low-dose total body irradiation in children have repercussions in the reduction in body-mass as well as in the plasma levels of total protein and albumin. Our findings reinforce the periodic monitoring of total serum protein and albumin levels as an important tool in long-term follow-up of pediatric patients in treatments associated to total body irradiation. - Highlights: • Low-dose total body irradiation (TBI) in children have repercussions in their body-mass. • Long-term total protein and albumin levels are affected by TBI. • The monitoring of total protein and albumin levels are useful in the follow-up of TBI pediatric patients.

  10. The effects of low dose ionizing radiation on the development of rat cerebral cortex, (1)

    International Nuclear Information System (INIS)

    Matsushita, Koji

    1993-01-01

    We obtained the following results with regards to the effects of low dose ionizing radiation (5, 10, 15 and 20 cGy) on neuronal migration of developing rat cerebral cortex. Neuronal migration delay was found by autoradiography after intraperitoneal labeling with 3 H-thymidine to pregnant Wistar rats embryonic 16, and low dose radiation an hour or 48 hours after labeling. In 15-20 cGy, N-CAM (neural cell adhesion molecules) staining patterns changed with immunohistochemical method, whereas those of L1 and cytoskeleton neurofilament (160 KD), tauprotein, MAP2 (microtubule associated protein 2) did not. After 24-48 hours of radiation, N-CAM were not detected on the matrix cell layer. After 72-96 hours of radiation, N-CAM staining recovered to a normal pattern. In conclusion, low dose radiation of 15-20 cGy gave rise to neuronal migration delay and it was suggested that N-CAM may be related to neuronal migration as one of the mechanisms involved. (author)

  11. Effect of feeding graded doses of Citrinin on clinical and teratology in female Wistar rats.

    Science.gov (United States)

    Singh, N D; Sharma, A K; Patil, R D; Rahman, S; Leishangthem, G D; Kumar, M

    2014-02-01

    Citrinin is the one of the well-known mycotoxins, which is possibly spread all over the world. The graded doses of citrinin (1, 3 and 5 ppm CIT in feed) in female Wistar rats 10 weeks prior to mating, during mating and during organogenesis resulted in resorptions and post implantation losses, decreased fetal body weights and crown-rump lengths in fetuses of all groups. Various developmental anomalies recorded in fetuses of treated rats included gross (wrist drop, curled tail, stretched forelimb, subcutaneous haematoma), skeletal (incomplete ossification of skull bones, incomplete fusion of vertebral bodies, complete and partial agenesis of sternaebrae, metacarpals, metatarsals and phalanges, fused ribs and swing out ribs) and visceral (internal and external hydrocephalus, cerebellar hypoplasia, microphthalmia, roundening of heart, contracted kidneys, dilated renal pelvis and cryptorchid testes). The results suggest that CIT has adverse effects on fetal development which may be due to the longer bioavailability of citrinin in the animals.

  12. High-dose contrast-enhanced MRI in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Koudriavtseva, T. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Pozzilli, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Di Biasi, C. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Iannilli, M. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Trasimeni, G. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy); Gasperini, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Argentino, C. [Department of Neurosciences, University of Rome ``La Sapienza`` Rome (Italy); Gualdi, G.F. [MR Unit, Clinica Medica 1, University of Rome ``La Sapienza``, Rome (Italy)

    1996-05-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs.

  13. High-dose contrast-enhanced MRI in multiple sclerosis

    International Nuclear Information System (INIS)

    Koudriavtseva, T.; Pozzilli, C.; Di Biasi, C.; Iannilli, M.; Trasimeni, G.; Gasperini, C.; Argentino, C.; Gualdi, G.F.

    1996-01-01

    Contrast-enhanced MRI is effective for assessing disease activity in multiple sclerosis (MS) and may provide an outcome measure for testing the efficacy of treatment in clinical trials. To compare the sensitivity of high-dose gadolinium-HP-DO3A with that of a standard dose of gadolinium-DTPA, we studied 16 patients with relapsing-remitting MS in the acute phase of the disease. Each underwent two MRI examinations within at most 48 h. The initial MRI study was with a standard dose of gadolinium-DTPA (0.1 mmol/kg), and the second one an experimental dose of gadolinium-HP-DO3A (0.3 mmol/kg). No adverse effects were attributed to the contrast media. The high-dose study revealed more enhancing lesions than the standard-dose study (56 vs 38). This difference was found to be more relevant for infratentorial and small lesions. Furthermore, with the higher dose, there was a marked qualitative improvement in the visibility and delineation of the lesions. (orig.). With 4 figs., 2 tabs

  14. Effects of testosterone dose on spatial memory among castrated adult male rats.

    Science.gov (United States)

    Wagner, Benjamin A; Braddick, Valerie C; Batson, Christopher G; Cullen, Brendan H; Miller, L Erin; Spritzer, Mark D

    2018-03-01

    Previous research on the activational effects of testosterone on spatial memory has produced mixed results, possibly because such effects are dose-dependent. We tested a wide range of testosterone doses using two spatial memory tasks: a working-reference memory version of the radial-arm maze (RAM) and an object location memory task (OLMT). Adult male Sprague-Dawley rats were castrated or sham-castrated and given daily injections of drug vehicle (Oil Sham and Oil GDX) or one of four doses of testosterone propionate (0.125, 0.250, 0.500, and 1.000 mg T) beginning seven days before the first day of behavioral tests and continuing throughout testing. For the RAM, four arms of the maze were consistently baited on each day of testing. Testosterone had a significant effect on working memory on the RAM, with the Oil Sham, 0.125 mg T, and 0.500 mg T groups performing better than the Oil GDX group. In contrast, there was no significant effect of testosterone on spatial reference memory on the RAM. For the OLMT, we tested long-term memory using a 2 h inter-trial interval between first exposure to two identical objects and re-exposure after one object had been moved. Only the 0.125 and 0.500 mg T groups showed a significant increase in exploration of the moved object during the testing trials, indicating better memory than all other groups. Testosterone replacement restored spatial memory among castrated male rats on both behavioral tasks, but there was a complex dose-response relationship; therefore, the therapeutic value of testosterone is likely sensitive to dose. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Changes in the endocrine system which controls reproduction in female rats neonatally exposed to a low-dose of gamma irradiation

    International Nuclear Information System (INIS)

    Freud, A.

    1988-06-01

    Exposure of animals to high doses of ionizing radiation causes irreversible damage to the reproductive system and brings upon infertility. The results of this work indicate that neonatal exposure of female rats on day 8 of life to gamma irradiation of 6 R and 15 R causes reduction in number of offspring these rats produce when mature. The latter results from hormonal changes in the endocrine system which controls reproduction. However, one could not define one site of the hypothalamo - hypophyseal - ovarian axis which when damaged would be responsible for the radiation-induced damage to the productive system. (Author)

  16. Establishment of a dosimetric system for high doses using glasses

    International Nuclear Information System (INIS)

    Correa Quezada, Valeria de la Asuncion

    1997-01-01

    A routine dosimetric system was developed using commercial glass samples. The dosimetric characteristics of national and imported samples were studied: batch uniformity, response repeatability, reutilization, absorbed dose response, detection range, response stability as a function of absorbed dose, storage temperature and thermal treatments pre- and post-irradiation, using the optical absorption technique. As an application, the dosimetric system was tested in a flower irradiation process at IPEN. All the obtained results show the usefulness of the proposed system for high dose dosimetry. (author)

  17. Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

    OpenAIRE

    Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

    2017-01-01

    Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blo...

  18. Sensitization of rat 9L gliosarcoma cells to low dose rate irradiation by long duration 41 degrees C hyperthermia.

    Science.gov (United States)

    Armour, E P; Wang, Z H; Corry, P M; Martinez, A

    1991-06-15

    Modification of survival by long duration, 41 degrees C hyperthermia in combination with low dose rate radiation (0.5 Gy/h) was determined in rat 9L gliosarcoma cells. Cells were exposed to radiation in a manner that simulated continuous irradiation at a dose rate relevant to clinical brachytherapy. High dose rate X-irradiation was fractionated in 1.0-Gy fractions at 2-h intervals (FLDRI). Previous studies had demonstrated that 9L cells exposed to FLDRI with these parameters have survival characteristics that are equivalent to continuous low dose rate irradiation. Cells exposed to 41 degrees C throughout FLDRI were sensitized significantly (thermal enhancement ratio of 2.07) compared with cells irradiated at 37 degrees C. Incubation for 24 h at 41 degrees C before and/or after FLDRI at either 37 degrees C or 41 degrees C did not increase the slope of the radiation survival curves but did reduce the shoulder. Similarly, heating at 43 degrees C for 30 or 60 min before and/or after irradiation at 0.5 Gy/h also did not enhance cell sensitivity. Survival of cells after irradiation at high dose rate (60 Gy/h) was independent of the temperature during irradiation. Preheat at 41 degrees C for 24 h did not sensitize cells to high dose rate irradiation by increasing the slope of the survival curve, although a loss of shoulder was observed. Sensitization of cells heated at 43 degrees C for 30 or 60 min before high dose rate irradiation was expressed as classical slope modification. Our results demonstrate that 41 degrees C heating during FLDRI greatly sensitizes cells to radiation-induced killing for exposure durations up to 36 h. Heating 9L cells at 41 degrees C or 43 degrees C adjacent to FLDRI at 0.5 Gy/h resulted in no additional enhancement of terminal sensitivity, although shoulder modification was observed. The sensitization by simultaneous heating described above occurred even though thermotolerance developed during extended incubation at 41 degrees C. These in vitro

  19. The effect of low dose radiation on the neuronal cell proliferation in diabetic rats

    International Nuclear Information System (INIS)

    Kim, Doo Soon; Kang, Jin Oh; Hong, Seong Eon; Kim, Sang Ki; Lee, Taeck Hyun; Kim, Chang Ju

    2005-01-01

    To investigate the effect of low dose radiation on neuronal cell proliferation in diabetic rats. A group of rats (first group) were divided into three subgroups (nondiabetic control, nondiabetic 0.1 Gy and nondiabetic 10 Gy groups) to determine the effect of radiation on normal hippocampal neuronal cell proliferation. A further group of rats (second group) were divided into six subgroups (nondiabetic control, diabetic control, diabetic 0.01 Gy, diabetic 0.1 Gy, diabetic 1 Gy and diabetic 10 Gy groups) to determine the effect of radiation on hippocampal neuronal cell proliferation under diabetic conditions. Using immunohistochemistry for 5-bromo-2'-deoxyuridine (BrdU), the number of neuronal cells in the dentate gyrus of all the groups was counted. The number of BrdU-positive cells in the dentate Gyrus of the nondiabetic control, nondiabetic 0.1 Gy and nondiabetic 10 Gy subgroups of the first group were 45.96 ± 3.42, 59.34 ± 5.20 and 19.26 ± 2.98/mm 2 , respectively. The number of BrdU-positive cells in the dentate gyrus of the diabetic control, diabetic 0.01 Gy, diabetic 0.1 Gy, diabetic 1 Gy and diabetic 10 Gy subgroups of the second group were 55.44 ± 8.57, 33.33 ±6.46, 67.75 ± 10.54, 66.63 ± 10.05, 23.59 ± 6.37 and 14.34± 7.22/mm 2 , respectively. Low dose radiation enhances cell proliferation in the dentate gyrus of STZ-induced diabetic rats

  20. Calibration procedure for thermoluminescent dosemeters in water absorbed doses for Iridium-192 high dose rate sources

    International Nuclear Information System (INIS)

    Reyes Cac, Franky Eduardo

    2004-10-01

    Thermoluminescent dosimeters are used in brachytherapy services quality assurance programs, with the aim of guaranteeing the correct radiation dose supplied to cancer patients, as well as with the purpose of evaluating new clinical procedures. This work describes a methodology for thermoluminescent dosimeters calibration in terms of absorbed dose to water for 192 Ir high dose rate sources. The reference dose used is measured with an ionization chamber previously calibrated for 192 Ir energy quality, applying the methodology proposed by Toelli. This methodology aims to standardizing the procedure, in a similar form to that used for external radiotherapy. The work evolves the adaptation of the TRS-277 Code of the International Atomic Energy Agency, for small and big cavities, through the introduction for non-uniform experimental factor, for the absorbed dose in the neighborhood of small brachytherapy sources. In order to simulate a water medium around the source during the experimental work, an acrylic phantom was used. It guarantees the reproducibility of the ionization chamber and the thermoluminescent dosimeter's location in relation to the radiation source. The values obtained with the ionization chamber and the thermoluminescent dosimeters, exposed to a 192 Ir high dose rate source, were compared and correction factors for different source-detector distances were determined for the thermoluminescent dosimeters. A numeric function was generated relating the correction factors and the source-detector distance. These correction factors are in fact the thermoluminescent dosimeter calibration factors for the 192 Ir source considered. As a possible application of this calibration methodology for thermoluminescent dosimeters, a practical range of source-detector distances is proposed for quality control of 192 Ir high dose rate sources. (author)

  1. Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

    International Nuclear Information System (INIS)

    Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

    2007-01-01

    Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers

  2. Dynamic Metabolic Disruption in Rats Perinatally Exposed to Low Doses of Bisphenol-A.

    Directory of Open Access Journals (Sweden)

    Marie Tremblay-Franco

    Full Text Available Along with the well-established effects on fertility and fecundity, perinatal exposure to endocrine disrupting chemicals, and notably to xeno-estrogens, is strongly suspected of modulating general metabolism. The metabolism of a perinatally exposed individual may be durably altered leading to a higher susceptibility of developing metabolic disorders such as obesity and diabetes; however, experimental designs involving the long term study of these dynamic changes in the metabolome raise novel challenges. 1H-NMR-based metabolomics was applied to study the effects of bisphenol-A (BPA, 0; 0.25; 2.5, 25 and 250 μg/kg BW/day in rats exposed perinatally. Serum and liver samples of exposed animals were analyzed on days 21, 50, 90, 140 and 200 in order to explore whether maternal exposure to BPA alters metabolism. Partial Least Squares-Discriminant Analysis (PLS-DA was independently applied to each time point, demonstrating a significant pair-wise discrimination for liver as well as serum samples at all time-points, and highlighting unequivocal metabolic shifts in rats perinatally exposed to BPA, including those exposed to lower doses. In BPA exposed animals, metabolism of glucose, lactate and fatty acids was modified over time. To further explore dynamic variation, ANOVA-Simultaneous Component Analysis (A-SCA was used to separate data into blocks corresponding to the different sources of variation (Time, Dose and Time*Dose interaction. A-SCA enabled the demonstration of a dynamic, time/age dependent shift of serum metabolome throughout the rats' lifetimes. Variables responsible for the discrimination between groups clearly indicate that BPA modulates energy metabolism, and suggest alterations of neurotransmitter signaling, the latter finding being compatible with the neurodevelopmental effect of this xenoestrogen. In conclusion, long lasting metabolic effects of BPA could be characterized over 200 days, despite physiological (and thus metabolic changes

  3. Low-Dose Aspirin Treatment Alleviates Gamma Irradiation Impaired Fertility in Female Albino Rats

    International Nuclear Information System (INIS)

    Ibrahim, M.F.

    2013-01-01

    Recent experimental evidence suggests that Aspirin (acetylsalicylic acid), the extensively prescribed analgesic, can improve female fertility by suppressing the prostaglandin (PG) biosynthesis and modulating the uterine circulation. Aspirin has also been found to exhibit a protective ability on the radiation induced oxidative stress. Thus the present work aims to investigate the effect of oral low-dose Aspirin treatment on the radiation induced female reproductive disturbance. Adult female rats were used in the current experiment. All rat group treatments started at the onset of the proestrus phase and terminated at the diestrus encompassing 2 complete estrus cycles. Subsequently, the rats were divided into 4 equal groups: Group 1-Control: female rats receiving distilled water via an oral gavage; Group 2- Irradiation: female rats subjected to 6 Gy gamma rays at the proestrus cycle and receiving distilled water; Group 3-Aspirin: rats orally administered a daily dose of 7mg/kg body weight aspirin dissolved in distilled water via an oral gavage and Group 4- Irradiation + Aspirin: female rats irradiated as group 2 and receiving aspirin treatment. A number of rats from each experimental group were allowed to mate following every treatment to serve as Control mated (Subgroup 1), Irradiated mated (Subgroup 2), Aspirin administered mated (Subgroup 3) and Irradiated + Aspirin treated mated (Subgroup 4). At the assigned day of the second estrus cycle completion, blood was collected from Groups 1-4 for subsequent hormonal assay, lipid peroxides and glutathione (GSH) estimation whereas Subgroups 1-4 were carefully monitored for reproduction and infertility rates. Results have shown that the 6 Gy γ- irradiation of the rats at the proestrus cycle (Group 2) caused a decrease in follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and estradiol (E2) levels associated with a drastic increase in the progesterone levels in addition to the significant

  4. Assessments for high dose radionuclide therapy treatment planning

    International Nuclear Information System (INIS)

    Fisher, D.R.

    2003-01-01

    Advances in the biotechnology of cell specific targeting of cancer and the increased number of clinical trials involving treatment of cancer patients with radiolabelled antibodies, peptides, and similar delivery vehicles have led to an increase in the number of high dose radionuclide therapy procedures. Optimised radionuclide therapy for cancer treatment is based on the concept of absorbed dose to the dose limiting normal organ or tissue. The limiting normal tissue is often the red marrow, but it may sometimes be the lungs, liver, intestinal tract, or kidneys. Appropriate treatment planning requires assessment of radiation dose to several internal organs and tissues, and usually involves biodistribution studies in the patient using a tracer amount of radionuclide bound to the targeting agent and imaged at sequential timepoints using a planar gamma camera. Time-activity curves are developed from the imaging data for the major organ tissues of concern, for the whole body and sometimes for selected tumours. Patient specific factors often require that dose estimates be customised for each patient. In the United States, the Food and Drug Administration regulates the experimental use of investigational new drugs and requires 'reasonable calculation of radiation absorbed dose to the whole body and to critical organs' using the methods prescribed by the Medical Internal Radiation Dose (MIRD) Committee of the Society of Nuclear Medicine. Review of high dose studies shows that some are conducted with minimal dosimetry, that the marrow dose is difficult to establish and is subject to large uncertainties. Despite the general availability of software, internal dosimetry methods often seem to be inconsistent from one clinical centre to another. (author)

  5. Safety and toxicology assessment of chicken breast for high-dose irradiation

    International Nuclear Information System (INIS)

    Zhu Jiating; Feng Min; Yan Jianmin; Yang Ping; Wang Dening; Gao Meixu; Ha Yiming; Liu Chunquan

    2011-01-01

    Feeding wholesomeness tests of irradiated chicken breast were studied by using acute oral toxicology, Ames, micronucleus of born marrow cell, sperm shape abnormality in mice and 30 d feeding test. The LD 50 of all the rats and mice were more than 10 g/kg · BW, which means that the pet foods belonged to actually non-toxic grade; ames test, and the tests of micronucleus of born marrow cell, sampan shape abnormality in mice were all negative results; 30 d feeding test in rats demonstrated that it had no distinctive effects on routine blood, body weight and biochemical index. It is concluded that pet foods irradiated up to 25 kGy high dose were no safety and toxicology problems. (authors)

  6. Interaction of 2-Gy Equivalent Dose and Margin Status in Perioperative High-Dose-Rate Brachytherapy

    International Nuclear Information System (INIS)

    Martinez-Monge, Rafael; Cambeiro, Mauricio; Moreno, Marta; Gaztanaga, Miren; San Julian, Mikel; Alcalde, Juan; Jurado, Matias

    2011-01-01

    Purpose: To determine patient, tumor, and treatment factors predictive of local control (LC) in a series of patients treated with either perioperative high-dose-rate brachytherapy (PHDRB) alone (Group 1) or with PHDRB combined with external-beam radiotherapy (EBRT) (Group 2). Patient and Methods: Patients (n = 312) enrolled in several PHDRB prospective Phase I-II studies conducted at the Clinica Universidad de Navarra were analyzed. Treatment with PHDRB alone, mainly because of prior irradiation, was used in 126 patients to total doses of 32 Gy/8 b.i.d. or 40 Gy/10 b.i.d. treatments after R0 or R1 resections. Treatment with PHDRB plus EBRT was used in 186 patients to total doses of 16 Gy/4 b.i.d. or 24 Gy/6 b.i.d. treatments after R0 or R1 resections along with 45 Gy of EBRT with or without concomitant chemotherapy. Results: No dose-margin interaction was observed in Group 1 patients. In Group 2 patients there was a significant interaction between margin status and 2-Gy equivalent (Eq2Gy) dose (p = 0.002): (1) patients with negative margins had 9-year LC of 95.7% at Eq2Gy = 62.9Gy; (2) patients with close margins of >1 mm had 9-year LC of 92.4% at Eq2Gy = 72.2Gy, and (3) patients with positive/close <1-mm margins had 9-year LC of 68.0% at Eq2Gy = 72.2Gy. Conclusions: Two-gray equivalent doses ≥70 Gy may compensate the effect of close margins ≥1 mm but do not counterbalance the detrimental effect of unfavorable (positive/close <1 mm) resection margins. No dose-margin interaction is observed in patients treated at lower Eq2Gy doses ≤50 Gy with PHDRB alone.

  7. Calcium carbonate as a possible dosimeter for high irradiation doses

    International Nuclear Information System (INIS)

    Negron M, A.; Ramos B, S.; Camargo R, C.; Uribe, R. M.; Gomez V, V.; Kobayashi, K.

    2014-08-01

    The aim of this work is to analyze the interactions of 5 MeV electron beam radiation and a 290 MeV/u Carbon beam with calcium carbonate (powder) at 298 K and at different irradiation doses, for the potential use of calcium carbonate as a high-dose dosimeter. The irradiation doses with the electron beam were from 0.015 to 9 MGy, and with Carbon beam from 1.5 kGy to 8 kGy. High-energy radiation induces the formation of free radicals in solid calcium carbonate that can be detected and measured by electron paramagnetic resonance (EPR). An increase of the EPR response for some of the free radicals produced in the sample was observed as a function of the irradiation dose. The response of one of the radicals decreased with the dose. These measurements are reproducible; the preparation of the sample is simple and inexpensive; and the signal is stable for several months. The response curves show that the dosimeter tends to saturate at 10 MGy. Based on these properties, we propose this chemical compound as a high-dose dosimeter, mainly for electron irradiation. (author)

  8. Calcium carbonate as a possible dosimeter for high irradiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Negron M, A.; Ramos B, S.; Camargo R, C. [UNAM, Instituto de Ciencias Nucleares, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Uribe, R. M. [Kent State University, College of Technology, Kent OH (United States); Gomez V, V. [UNAM, Instituto de Quimica, Ciudad Universitaria, 04510 Mexico D. F. (Mexico); Kobayashi, K., E-mail: negron@nucleares.unam.mx [Yokohama National University (Japan)

    2014-08-15

    The aim of this work is to analyze the interactions of 5 MeV electron beam radiation and a 290 MeV/u Carbon beam with calcium carbonate (powder) at 298 K and at different irradiation doses, for the potential use of calcium carbonate as a high-dose dosimeter. The irradiation doses with the electron beam were from 0.015 to 9 MGy, and with Carbon beam from 1.5 kGy to 8 kGy. High-energy radiation induces the formation of free radicals in solid calcium carbonate that can be detected and measured by electron paramagnetic resonance (EPR). An increase of the EPR response for some of the free radicals produced in the sample was observed as a function of the irradiation dose. The response of one of the radicals decreased with the dose. These measurements are reproducible; the preparation of the sample is simple and inexpensive; and the signal is stable for several months. The response curves show that the dosimeter tends to saturate at 10 MGy. Based on these properties, we propose this chemical compound as a high-dose dosimeter, mainly for electron irradiation. (author)

  9. Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

    Science.gov (United States)

    Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

    2011-01-01

    Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

  10. Dose-Dependent Effect of Curcumin on Learning and Memory Deficit in Kainate-Epileptic Rats

    Directory of Open Access Journals (Sweden)

    Zahra Kiasalari

    2014-09-01

    Full Text Available Background & objectives : Epileptic seizures accompany disturbances in learning, memory, and cognitive skills. With regard to antiepileptic potential of curcumin and its beneficial effect on memory, the effect of its administration on learning and memory in kainate-epileptic rats was investigated.   Methods: Forty male rats were divided into sham, positive control ( valproate-treated epileptic, epileptic, and two curcumin-treated epileptic groups. Rat model of epilepsy was induced by unilateral intrahippocampal administration of 4 μg of kainate per rat. Rats received intraperitoneal injection of curcumin (50 and 100 mg/kg daily for 1 week before surgery. For evaluation of learning and memory, initial (IL and step-through latencies (STL were determined using passive avoidance test and alternation behavior percentage was obtained according to Y maze test.   Results: Regarding IL, there was no significant difference between the groups. In contrast, STL significantly decreased in curcumin-50-treated epileptic group (p<0.05 (a change from 263.1 to 184.5 s. However, this parameter significantly increased in curcumin-100-treated epileptic group as compared to epileptic group (p<0.01 (a change from 263.1 to 220.3 s. In addition, STL was also significantly higher in valproic acid-treated epileptic group versus epileptic group (p<0.05 (a change from 145.7 to 210.3 s. Alternation percentage was also significantly higher in curcumin-50- and curcumin-100-treated epileptic groups relative to epileptic group (p<0.05 (a change from 60.5 to 77.6 and 80.3%.   Conclusion: Curcumin could dose-dependently enhance the consolidation and recall in epileptic animals and could improve spatial memory in such animals.

  11. High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

    Science.gov (United States)

    Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

    2011-05-01

    The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

  12. High-dose buprenorphine: perioperative precautions and management strategies.

    Science.gov (United States)

    Roberts, D M; Meyer-Witting, M

    2005-02-01

    Buprenorphine has been in clinical use in anaesthesia for several decades. Recently, the high-dose sublingual formulation (Subutex, Reckitt Benckiser, Slough, U.K.) has been increasingly used as maintenance therapy in opioid dependence, as an alternative to methadone and other pharmacological therapies. Buprenorphine has unique pharmacological properties making it well suited for use as a maintenance therapy in opioid dependence. However, these same properties may cause difficulty in the perioperative management of pain. Buprenorphine is a partial opioid agonist, attenuating the effects of supplemental illicit or therapeutic opioid agonists. As a result of its high receptor affinity, supplemental opioids do not readily displace buprenorphine from the opioid receptor in standard doses. High-dose buprenorphine has an extended duration of action that prolongs both of these effects. The perioperative management of patients stabilized on high-dose buprenorphine and undergoing surgery requires consideration of the likely analgesic requirements. Where possible the buprenorphine should be continued. Pain management should focus on maximizing non-opioid analgesia, local anaesthesia and non-pharmacological techniques. Where pain may not be adequately relieved by these methods, the addition of a full opioid agonist such as fentanyl or morphine at appropriate doses should be considered, accompanied by close monitoring in a high dependency unit. In situations where this regimen is unlikely to be effective, preoperative conversion to morphine or methadone may be an option. Where available, liaison with a hospital-based alcohol and drug service should always be considered.

  13. Radiobiological modelling of dose-gradient effects in low dose rate, high dose rate and pulsed brachytherapy

    International Nuclear Information System (INIS)

    Armpilia, C; Dale, R G; Sandilos, P; Vlachos, L

    2006-01-01

    This paper presents a generalization of a previously published methodology which quantified the radiobiological consequences of dose-gradient effects in brachytherapy applications. The methodology uses the linear-quadratic (LQ) formulation to identify an equivalent biologically effective dose (BED eq ) which, if applied uniformly to a specified tissue volume, would produce the same net cell survival as that achieved by a given non-uniform brachytherapy application. Multiplying factors (MFs), which enable the equivalent BED for an enclosed volume to be estimated from the BED calculated at the dose reference surface, have been calculated and tabulated for both spherical and cylindrical geometries. The main types of brachytherapy (high dose rate (HDR), low dose rate (LDR) and pulsed (PB)) have been examined for a range of radiobiological parameters/dimensions. Equivalent BEDs are consistently higher than the BEDs calculated at the reference surface by an amount which depends on the treatment prescription (magnitude of the prescribed dose) at the reference point. MFs are closely related to the numerical BED values, irrespective of how the original BED was attained (e.g., via HDR, LDR or PB). Thus, an average MF can be used for a given prescribed BED as it will be largely independent of the assumed radiobiological parameters (radiosensitivity and α/β) and standardized look-up tables may be applicable to all types of brachytherapy treatment. This analysis opens the way to more systematic approaches for correlating physical and biological effects in several types of brachytherapy and for the improved quantitative assessment and ranking of clinical treatments which involve a brachytherapy component

  14. Rats avoid exposure to HVdc electric fields: a dose response study.

    Science.gov (United States)

    Creim, J A; Lovely, R H; Weigel, R J; Forsythe, W C; Anderson, L E

    1993-01-01

    Rats, given the choice, avoid exposure to alternating current (ac) 60-Hz electric fields at intensities > or = 75 kV/m. This study investigated the generality of this behavior by studying the response of rats when exposed to high voltage direct current (HVdc) electric fields. Three hundred eighty male Long Evans rats were studied in 9 experiments with 40 rats per experiment and in one experiment with 20 rats to determine 1) if rats avoid exposure to HVdc electric fields of varying field strengths, and 2) if avoidance did occur, what role, if any, the concentration of air ions would have on the avoidance behavior. In all experiments a three-compartment glass shuttlebox was used; either the left or right compartment could be exposed to a combination of HVdc electric fields and air ions while the other compartment remained sham-exposed. The third, center compartment was a transition zone between exposure and sham-exposure. In each experiment, the rats were individually assessed in 1-h sessions where half of the rats (n = 20) had the choice to locomote between the two sides being exposed or sham-exposed, while the other half of the rats (n = 20) were sham-exposed regardless of their location, except in one experiment where there was no sham-exposed group. The exposure levels for the first six experiments were 80, 55, 42.5, 30, -36, and -55 kV/m, respectively. The air ion concentration was constant at 1.4 x 10(6) ions/cc for the four positive exposure levels and -1.4 x 10(6) ions/cc for the two negative exposure levels. Rats having a choice between exposure and non-exposure relative to always sham-exposed control animals significantly reduced the amount of time spent on the exposed side at 80 kV/m (P HVdc exposure level was held constant at either -55 kV/m (for three experiments) or -55 kV/m (for 1 experiment) while the air ion concentration was varied between experiments at 2.5 x 10(5) ions/cc, 1.0 x 10(4) for two of the experiments and was below the measurement limit

  15. Dose-response study in F344 rats exposed to (U,Pu)O2 or PuO2

    International Nuclear Information System (INIS)

    Mewhinney, J.A.; Eidson, A.F.; Hahn, F.F.; Scott, B.R.; Seiler, F.A.; Boecker, B.B.

    1987-01-01

    The relationship of radiation dose to lung and the biological effect observed was investigated following inhalation of two types of plutonium-containing particulate materials in rats. Bulk powder samples of the two materials were obtained from within gloveboxes used in the routine manufacture of mixed plutonium and uranium oxide nuclear fuel. The materials were a solid solution of uranium and plutonium treated at 1750 0 C and a PuO 2 feedstock. Groups of rats received a single inhalation exposure to a material to achieve one of three levels of initial pulmonary burden. Rats were maintained for their lifespan to observe the biological effects produced. These effects were observed in the lungs of rats exposed to either type of particle. The same types of lung cancer were produced by both particulate materials. The incidences of cancers were also similar at comparable levels of initial pulmonary burden for the two materials. The crude incidence of lung cancers for rats exposed to these materials was not different than those reported for similar studies that used laboratory-produced aerosols of PuO 2 . Using a linear dose-effect model, the relative risk of lung cancer for rats exposed to these industrial materials was 2.3 +- 1.0 (SE) at a lung dose of 100 rad. The doubling dose for lung cancers was 78 +- 63 rad to lung to median life span. 21 refs., 9 figs., 10 tabs

  16. Spectroscopic gamma camera for use in high dose environments

    Energy Technology Data Exchange (ETDEWEB)

    Ueno, Yuichiro, E-mail: yuichiro.ueno.bv@hitachi.com [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Takahashi, Isao; Ishitsu, Takafumi; Tadokoro, Takahiro; Okada, Koichi; Nagumo, Yasushi [Research and Development Group, Hitachi, Ltd., Hitachi-shi, Ibaraki-ken 319-1221 (Japan); Fujishima, Yasutake; Kometani, Yutaka [Hitachi Works, Hitachi-GE Nuclear Energy, Ltd., Hitachi-shi, Ibaraki-ken (Japan); Suzuki, Yasuhiko [Measuring Systems Engineering Dept., Hitachi Aloka Medical, Ltd., Ome-shi, Tokyo (Japan); Umegaki, Kikuo [Faculty of Engineering, Hokkaido University, Sapporo-shi, Hokkaido (Japan)

    2016-06-21

    We developed a pinhole gamma camera to measure distributions of radioactive material contaminants and to identify radionuclides in extraordinarily high dose regions (1000 mSv/h). The developed gamma camera is characterized by: (1) tolerance for high dose rate environments; (2) high spatial and spectral resolution for identifying unknown contaminating sources; and (3) good usability for being carried on a robot and remotely controlled. These are achieved by using a compact pixelated detector module with CdTe semiconductors, efficient shielding, and a fine resolution pinhole collimator. The gamma camera weighs less than 100 kg, and its field of view is an 8 m square in the case of a distance of 10 m and its image is divided into 256 (16×16) pixels. From the laboratory test, we found the energy resolution at the 662 keV photopeak was 2.3% FWHM, which is enough to identify the radionuclides. We found that the count rate per background dose rate was 220 cps h/mSv and the maximum count rate was 300 kcps, so the maximum dose rate of the environment where the gamma camera can be operated was calculated as 1400 mSv/h. We investigated the reactor building of Unit 1 at the Fukushima Dai-ichi Nuclear Power Plant using the gamma camera and could identify the unknown contaminating source in the dose rate environment that was as high as 659 mSv/h.

  17. A novel theory of radiation damage at high doses

    International Nuclear Information System (INIS)

    Seeger, A.; Stuttgart Univ.

    1989-01-01

    Deviations of radiation damage (in the case of metals usually monitored by the residual electrical resistivity) from proportionality with the irradiation dose have so far been analysed almost exclusively in terms of extensions of models originally developed for small doses. The present theory considers the opposite limit i.e. the quasi-saturated state. It is argued that at high doses the Lueck-Sizmann effect may result in a self-organization of clusters of vacancies and self-interstitials, forming a heterogeneous froth. Possible structures of this froth and its effect on the electrical resistivity of metals are discussed. The model is shown to account for the dependence of the ''saturation resistivity'' on the nature of the irradiation as well as for several other hitherto poorly explained observations. Among them are the electrical-resistivity variation induced by high-dose irradiation with heavy ions, the amorphization of certain alloys by high-dose electron irradiation, and the occurrence of ordered arrays of stacking-fault tetrahedra after in-situ irradiations in high-voltage electron microscopes. (author)

  18. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    International Nuclear Information System (INIS)

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

    2008-01-01

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD 10 dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-α, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 ± 14.0 nmol/min/g heart in ND versus 400.2 ± 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-α2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3

  19. Radiation shielding and dose rate distribution for the building of the high dose rate accelerator

    International Nuclear Information System (INIS)

    Matsuda, Koji; Takagaki, Torao; Nakase, Yoshiaki; Nakai, Yohta.

    1984-03-01

    A high dose rate electron accelerator was established at Osaka Laboratory for Radiation Chemistry, Takasaki Establishment, JAERI in the fiscal year of 1975. This report shows the fundamental concept for the radiation shielding of the accelerator building and the results of their calculations which were evaluated through the model experiments. After the construction of the building, the leak radiation was measured in order to evaluate the calculating method of radiation shielding. Dose rate distribution of X-rays was also measured in the whole area of the irradiation room as a data base. (author)

  20. Anxiogenic effects of chronic exposure to nandrolone decanoate (ND) at supraphysiological dose in rats: a brief report.

    Science.gov (United States)

    Rosic, Gvozden; Joksimovic, Jovana; Selakovic, Dragica; Milovanovic, Dragan; Jakovljevic, Vladimir

    2014-01-01

    Nandrolone decanoate (ND) is frequently used anabolic androgenic steroid (AAS) among the athletes. Despite the health risks, there is significant increase in prevalence of AAS abuse. The aim of this study was to investigate the effects of chronic exposure to ND at supraphysiological dose (to mimic the doses for human AAS abusers) on anxiety levels in adult rats. We performed several behavioral tests (open field test, elevated plus maze test, beam-walking test, evoked beam-walking test and tail suspension test) for estimation of anxiety in rats. Adult rats received 20 mg/kg intraperitoneal injection of ND weekly for four weeks. Behavioral test were performed on the seventh day after the last dose of ND. Anxiogenic-like pattern of behavior was clearly observed in several behavioral tests, such as open field test (decrease of total distance moved and cumulative duration of moving, decrease of an average velocity of the animals, decrease of frequency and total time in centre zone); elevated plus maze (decreased total time spent in open arms and the number of entries in open arms of the elevated plus maze); evoked beam-walking test (decreased time to cross the beam) and tail suspension test (increased latency to first immobility and decreased total duration of immobility). Results of this study show that four-week treatment with the supraphysiological dose of ND produced anxiogenic effects in sedentary male rats. Our results show that rats after chronic treatment with a supraphysiological dose of ND exhibited anxiety-like behavior.

  1. Effective dose calculation in CT using high sensitivity TLDs

    International Nuclear Information System (INIS)

    Brady, Z.; Johnston, P.N.

    2010-01-01

    Full text: To determine the effective dose for common paediatric CT examinations using thermoluminescence dosimetry (TLD) mea surements. High sensitivity TLD chips (LiF:Mg,Cu,P, TLD-IOOH, Thermo Fisher Scientific, Waltham, MA) were calibrated on a linac at an energy of 6 MY. A calibration was also performed on a superricial X-ray unit at a kilovoltage energy to validate the megavoltage cali bration for the purpose of measuring doses in the diagnostic energy range. The dose variation across large organs was assessed and a methodology for TLD placement in a 10 year old anthropomorphic phantom developed. Effective dose was calculated from the TLD measured absorbed doses for typical CT examinations after correcting for the TLD energy response and taking into account differences in the mass energy absorption coefficients for different tissues and organs. Results Using new tissue weighting factors recommended in ICRP Publication 103, the effective dose for a CT brain examination on a 10 year old was 1.6 millisieverts (mSv), 4.9 mSv for a CT chest exa ination and 4.7 mSv for a CT abdomen/pelvis examination. These values are lower for the CT brain examination, higher for the CT chest examination and approximately the same for the CT abdomen/ pelvis examination when compared with effective doses calculated using ICRP Publication 60 tissue weighting factors. Conclusions High sensitivity TLDs calibrated with a radiotherapy linac are useful for measuring dose in the diagnostic energy range and overcome limitations of output reproducibility and uniformity asso ciated with traditional TLD calibration on CT scanners or beam quality matched diagnostic X-ray units.

  2. Perfluorononanoic acid in combination with 14 chemicals exerts low-dose mixture effects in rats

    DEFF Research Database (Denmark)

    Hadrup, Niels; Pedersen, Mikael; Skov, Kasper

    2016-01-01

    Humans are simultaneously exposed to several chemicals that act jointly to induce mixture effects. At doses close to or higher than no-observed adverse effect levels, chemicals usually act additively in experimental studies. However, we are lacking knowledge on the importance of exposure to complex...... real-world mixtures at more relevant human exposure levels. We hypothesised that adverse mixture effects occur at doses approaching high-end human exposure levels. A mixture (Mix) of 14 chemicals at a combined dose of 2.5 mg/kg bw/day was tested in combination with perfluorononanoic acid (PFNA...... pituitary-adrenal axis. In conclusion, our data suggest that mixtures of environmental chemicals at doses approaching high-end human exposure levels can cause a hormonal imbalance and disturb steroid hormones and their regulation. These effects may be non-monotonic and were observed at low doses. Whether...

  3. Implementation of high-dose chemical dosimetry for industrial facilities

    International Nuclear Information System (INIS)

    Conceicao, Cirilo Cezar Sant'Anna da

    2006-01-01

    The purpose of this work is the implementation of methodology for high dose measurements using chemical dosimeters in liquid phase, traceable to the international metrology system, and make available in the country, the standard of high-dose to industrial irradiation facilities and research irradiators, trough the quality program with comparative measurements and direct use of the standard dosimeters in routine. The use of these low cost dosimetry systems in industrial irradiation facilities, assists to the certification requirements and it can reduce the costs with dosimetry for approximately 20% of the total dosimetry costs, using these systems in routine measurements and validation process, largely substituting the imported PMMA dosimeters, among others. (author)

  4. Pharmacokinetics of [14C]teicoplanin in male rats after single intravenous dose

    International Nuclear Information System (INIS)

    Bernareggi, A.; Cavenaghi, L.; Assandri, A.

    1986-01-01

    The pharmacokinetic profile of [ 14 C]teicoplanin was studied in male Sprague-Dawley rats given a single 10,000-U/kg intravenous dose. The disposition of the antimicrobial activity in the body was estimated by a three-compartment open model. Plasma concentration data were fitted to a three-exponent equation. The profile of total 14 C in plasma was similar to that of the microbiological activity. The cumulative recovery of total 14 C 5 days after drug administration averaged 76.3% of the administered dose in the urine and 8.7% in the feces. The residual dose remaining in the animal carcasses was 11.1%. Teicoplanin was widely distributed in the body. In almost all organs, the maximum concentration of [ 14 C]teicoplanin was already reached at the first time of killing, which was 0.25 h after the administration of drug. The liver, kidneys, skin, and fat contained most of the residual dose found in the animal carcasses 120 h after administration and behaved as a deep compartment with the adrenal glands and spleen

  5. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  6. Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats Dano oxidativo ao tecido cerebral como possível mecanismo de efeito deletério da alta dose crônica de estradiol no aprendizado e memória de ratas ooforectomizadas

    Directory of Open Access Journals (Sweden)

    Fatimeh Khodabandehloo

    2013-05-01

    Full Text Available In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001. In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001. In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001. It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.Além dos efeitos antioxidantes, os estrógenos também têm ação pró-oxidativa. Foi investigado o efeito da administração crônica de alta dose de valereato de estradiol no desempenho do labirinto aquático de Morris e o dano oxidativo ao tecido cerebral. Os grupos Sham-Est e OVX-Est foram tratados com valereato de estradiol (4 mg/kg por 12 semanas. O tempo de latência para escapada e o caminho percorrido foram significativamente maiores nos grupos Sham-Est e OVX-Est em relação aos grupos Sham e OVX (p≪0,01 e p≪0,001. No estudo probe, os animais dos grupos Sham-Est e OVX-Est levaram menos tempo no Q1 em comparação aos grupos Sham e OVX (p≪0,05 e p≪0,001. Nos grupos Sham-Est e OVX-Est, a concentração total de tiol foi significativamente menor, enquanto a concentração de malondialdehydo (MDA for maior do que aquela dos grupos Sham e OVX (p≪0,05 e p≪0,001. Concluiu-se que a administração de altas doses de estradiol exógeno compromete o desempenho e aumenta o estresse oxidativo

  7. Absorption, Distribution, and Excretion of 14C-APX001 after Single-Dose Administration to Rats and Monkeys

    Science.gov (United States)

    Mansbach, Robert; Shaw, Karen J; Hodges, Michael R; Coleman, Samantha; Fitzsimmons, Michael E

    2017-01-01

    Abstract Background APX001 is a small-molecule therapeutic agent in clinical development for the treatment of invasive fungal infections (IFI). Methods The absorption, distribution and excretion profiles of [14C]APX001-derived radioactivity were determined in rats (albino and pigmented) and monkeys. Rats (some implanted with bile duct cannulae) were administered a single 100 mg/kg oral dose or a 30 mg/kg intravenous (IV) dose. Monkeys were administered a single 6 mg/kg IV dose. Samples of blood, urine, feces and bile, as well as carcasses, were collected through 168 hours after dosing. Samples were analyzed for total radioactivity content by liquid scintillation counting, and carcasses were analyzed by quantitative whole-body autoradiography. Results [14C]APX001-derived radioactivity was rapidly and extensively absorbed and extensively distributed to most tissues for both routes of administration in both species. In rats, tissues with the highest radioactivity Cmax values included bile, abdominal fat, reproductive fat, subcutaneous fat, and liver, but radioactivity was also detected in tissues associated with IFI, including lung, brain and eye. In monkeys, the highest Cmax values were in bile, urine, uveal tract, bone marrow, abdominal fat, liver, and kidney cortex. Liver and kidney were the tissues with highest radioactivity, but as in the rat, radioactivity was also detected in lung, brain and eye tissues. In pigmented rats, radiocarbon was densely distributed into pigmented tissue and more slowly cleared than from other tissues. Mean recovery of radioactivity in rats was approximately 95–100%. In bile duct-intact rats, >90% of radioactivity was recovered in feces. In cannulated rats, biliary excretion of radioactivity was the major route of elimination and accounted for 88.8% of the dose, whereas urinary and fecal excretion of radioactivity was minor and accounted for 2.56% and 5.42% of the dose, respectively. In monkeys, the overall recovery of radioactivity

  8. Rats bred for helplessness exhibit positive reinforcement learning deficits which are not alleviated by an antidepressant dose of the MAO-B inhibitor deprenyl.

    Science.gov (United States)

    Schulz, Daniela; Henn, Fritz A; Petri, David; Huston, Joseph P

    2016-08-04

    Principles of negative reinforcement learning may play a critical role in the etiology and treatment of depression. We examined the integrity of positive reinforcement learning in congenitally helpless (cH) rats, an animal model of depression, using a random ratio schedule and a devaluation-extinction procedure. Furthermore, we tested whether an antidepressant dose of the monoamine oxidase (MAO)-B inhibitor deprenyl would reverse any deficits in positive reinforcement learning. We found that cH rats (n=9) were impaired in the acquisition of even simple operant contingencies, such as a fixed interval (FI) 20 schedule. cH rats exhibited no apparent deficits in appetite or reward sensitivity. They reacted to the devaluation of food in a manner consistent with a dose-response relationship. Reinforcer motivation as assessed by lever pressing across sessions with progressively decreasing reward probabilities was highest in congenitally non-helpless (cNH, n=10) rats as long as the reward probabilities remained relatively high. cNH compared to wild-type (n=10) rats were also more resistant to extinction across sessions. Compared to saline (n=5), deprenyl (n=5) reduced the duration of immobility of cH rats in the forced swimming test, indicative of antidepressant effects, but did not restore any deficits in the acquisition of a FI 20 schedule. We conclude that positive reinforcement learning was impaired in rats bred for helplessness, possibly due to motivational impairments but not deficits in reward sensitivity, and that deprenyl exerted antidepressant effects but did not reverse the deficits in positive reinforcement learning. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  9. Characterization of Thymol blue Radiochromic dosimeters for high dose applications

    Directory of Open Access Journals (Sweden)

    Feras M. Aldweri

    2018-03-01

    Full Text Available Thymol blue (TB solutions and Thymol blue Polyvinyl Alcohol (TB-PVA films have been introduced as Radiochromic dosimeter for high dose applications. The dosimeters were irradiated with gamma ray (60Co source from 5 to 30 kGy for film, and from 0.150 kGy to 4 kGy for solution. The optical density of unirradiated and irradiated TB solution as well as TB-PVA film dosimeters were studied in terms of absorbance at 434 nm using UV/VIS spectrophotometer. The effects of scan temperature, light pre-gamma irradiation, dose rate, relative humidity and stability of the absorbance of solutions and films after irradiation were investigated. We found the dose sensitivity of TB solution and TB-PVA film dosimeters increases significantly with increases of the absorbed dose as well as with the increases of TB dye concentrations. The useful dose range of developed TB solutions and TB-PVA films dosimeters is in the range 0.125–1 kGy and of 5–20 kGy, respectively. Keywords: Dose sensitivity, Radio-chromic dosimeter, Thymol blue, Absorbance, Concentrations

  10. Acceleration of skin wound healing by low-dose indirect ionizing radiation in male rats.

    Science.gov (United States)

    Jabbari, Nasrollah; Farjah, Gholam Hossein; Ghadimi, Behnam; Zanjani, Hajar; Heshmatian, Behnam

    2017-08-01

    A recent hypothesis has revealed that low-dose irradiation (LDI) with ionizing radiation might have a promoting effect on fracture healing. The aim of this study was to investigate the influence of direct (electron beam) and indirect (gamma-ray) low-dose ionizing irradiations on the wound healing process in male rats. In 72 male rats, a full-thickness wound was incised. The animals were randomly assigned to three groups, each with 24 rats. The first two groups were named IG-I and IG-II and respectively exposed to electron and gamma-radiations (75 cGy) immediately after the surgical procedure. The third group was considered as the control (CG) and remained untreated. Skin biopsies from the subgroups were collected on days 3, 7, 15, and 21 after the operation and evaluated using histological and biomechanical methods. Data were analyzed by one-way ANOVA, followed by Tukey's post hoc test using SPSS 20 software. Histological studies of tissues showed that the mean number of fibroblasts, macrophages, blood vessel sections, and neutrophils on the third and seventh days after the surgery in the gamma-treated group was higher than that in both other groups. In contrast, on day 21, the mean number of mentioned cells in the gamma-treated group was lower than in the other two groups. In addition, the mean maximum stress value was significantly greater in the gamma-treated group. Results of this study showed that gamma-ray irradiation is effective in the acceleration of wound healing. Copyright © 2017. Published by Elsevier Taiwan.

  11. Acceleration of skin wound healing by low-dose indirect ionizing radiation in male rats

    Directory of Open Access Journals (Sweden)

    Nasrollah Jabbari

    2017-08-01

    Full Text Available A recent hypothesis has revealed that low-dose irradiation (LDI with ionizing radiation might have a promoting effect on fracture healing. The aim of this study was to investigate the influence of direct (electron beam and indirect (gamma-ray low-dose ionizing irradiations on the wound healing process in male rats. In 72 male rats, a full-thickness wound was incised. The animals were randomly assigned to three groups, each with 24 rats. The first two groups were named IG–I and IG–II and respectively exposed to electron and gamma-radiations (75 cGy immediately after the surgical procedure. The third group was considered as the control (CG and remained untreated. Skin biopsies from the subgroups were collected on days 3, 7, 15, and 21 after the operation and evaluated using histological and biomechanical methods. Data were analyzed by one-way ANOVA, followed by Tukey's post hoc test using SPSS 20 software. Histological studies of tissues showed that the mean number of fibroblasts, macrophages, blood vessel sections, and neutrophils on the third and seventh days after the surgery in the gamma-treated group was higher than that in both other groups. In contrast, on day 21, the mean number of mentioned cells in the gamma-treated group was lower than in the other two groups. In addition, the mean maximum stress value was significantly greater in the gamma-treated group. Results of this study showed that gamma-ray irradiation is effective in the acceleration of wound healing.

  12. BH3105 type neutron dose equivalent meter of high sensitivity

    International Nuclear Information System (INIS)

    Ji Changsong; Zhang Enshan; Yang Jianfeng; Zhang Hong; Huang Jiling

    1995-10-01

    It is noted that to design a neutron dose meter of high sensitivity is almost impossible in the frame of traditional designing principle--'absorption net principle'. Based on a newly proposed principle of obtaining neutron dose equi-biological effect adjustment--' absorption stick principle', a brand-new neutron dose-equivalent meter with high neutron sensitivity BH3105 has been developed. Its sensitivity reaches 10 cps/(μSv·h -1 ), which is 18∼40 times higher than one of foreign products of the same kind and is 10 4 times higher than that of domestic FJ342 neutron rem-meter. BH3105 has a measurement range from 0.1μSv/h to 1 Sv/h which is 1 or 2 orders wider than that of the other's. It has the advanced properties of gamma-resistance, energy response, orientation, etc. (6 tabs., 5 figs.)

  13. Safety and tolerability of high doses of glucocorticoides

    Directory of Open Access Journals (Sweden)

    Rakić Branislava D.

    2016-01-01

    Full Text Available Introduction: Treatment of acute lymphoblastic leukemia includes the use of high doses of glucocorticoides (prednisone and dexamethasone, which significantly increase the success of therapy due to lymphocytolitic effect. The aim: The aim of the study was to determine tolerability of high doses of prednisone and dexamethasone in children with acute lymphoblastic leukemia and the structure and the intensity of adverse effects, occurred after application of these medicines. Subjects and methods: In a prospective study, we analyzed adverse effects of high doses of glucocorticoides in children suffering acute lymphoblastic leukemia treated in the Institute for Child and Youth Health Care of Vojvodina, since December 2010. until October 2014, were analyzed. This study included 18 patients, aged from 2 to 15 years. Results: Hyperglycemia appeared in 89% of patients treated with prednisone and in 61% of patients treated with dexamethasone. In order to control the high blood glucose level (above 10 mmol /L, in 11% of patients insulin was used. Hypertension appeared in 28% patients treated with prednisone and dexamethasone. Antihypertensives were needed for regulation in 17% patients. Hypopotassemia and hypocalcaemia were significantly more expressed after the use of prednisone in comparison to dexamethasone. In 11% of patients, the treatment with dexamethasone caused depressive behavior, followed by agitation. Conclusion: Adverse effects of dexamethasone and prednisone, administered in high doses in children with ALL were known, expected and reversible. Adverse reactions usually disappeared spontaneously or after short-term symptomatic therapy.

  14. Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

    International Nuclear Information System (INIS)

    Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

    2008-01-01

    Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

  15. HIGH-DOSE RATE BRACHYTHERAPY IN CARCINOMA CERVIX STAGE IIIB

    Directory of Open Access Journals (Sweden)

    Sathya Maruthavanan

    2016-07-01

    Full Text Available INTRODUCTION Radiotherapy is the standard treatment in locally advanced (IIB-IVA and early inoperable cases. The current standard of practice with curable intent is concurrent chemoradiation in which intracavitary brachytherapy is an integral component of radiotherapy. This study aims at assessing the efficacy of HDR ICBT (High-dose rate intracavitary brachytherapy in terms local response, normal tissue reactions, and feasibility. METHODS AND MATERIALS A total of 20 patients of stage IIIB cancer of the uterine cervix were enrolled in the study and were planned to receive concurrent chemotherapy weekly along with EBRT (external beam radiotherapy to a dose of 50 Gy/25 Fr. Suitability for ICBT was assessed at 40 Gy/20 Fr. 6/20 patients were suitable at 40 Gy and received HDR ICBT with a dose of 5.5 Gy to point A in 4 sessions (5.5 Gy/4 Fr. The remaining 14/20 patients completed 50 Gy and received HDR ICBT with a dose of 6 Gy to point A in 3 sessions (6 Gy/3 Fr. RESULTS A total of 66 intracavitary applications were done and only one application required dose modification due to high bladder dose, the pelvic control rate was 85% (17/20. 10% (2/20 had stable disease and 5% (1/20 had progressive disease at one year of follow up. When toxicity was considered only 15% developed grade I and grade II rectal complications. Patient compliance and acceptability was 100%. Patients were very comfortable with the short treatment time as compared with patients on LDR ICBT (low-dose rate intracavitary brachytherapy treatment interviewed during the same period. CONCLUSION This study proves that HDR brachytherapy is efficacious and feasible in carcinoma of cervix stage IIIB. It also proves that good dose distribution can be achieved with HDR intracavitary facility by the use of dose optimization. The short treatment time in HDR ICBT makes it possible to maintain this optimised dose distribution throughout the treatment providing a gain in the therapeutic ratio and

  16. Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats

    OpenAIRE

    Lee, Hyun-Ho; Paudel, Keshav Raj; Jeong, Jieun; Wi, An-Jin; Park, Whoa-Shig; Kim, Dong-Wook; Oak, Min-Ho

    2016-01-01

    Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: ...

  17. Dose- and time-dependent changes in tissue levels of tetrabromobisphenol A (TBBPA and its sulfate and glucuronide conjugates following repeated administration to female Wistar Han Rats

    Directory of Open Access Journals (Sweden)

    S.J. Borghoff

    Full Text Available Tetrabromobisphenol A (TBBPA, a nongenotoxic flame retardant, causes uterine tumors in female rats. A proposed mode of action (MoA for these tumors involves an increase in the bioavailability of estradiol as a result of TBBPA inhibiting estrogen sulfotransferases (ES, the enzymes responsible for inactivating and enhancing the elimination of estradiol. The objective of this study was to evaluate the effect of dose and repeated administration of TBBPA on the level of TBBPA, TBBPA-glucuronide (GA and TBBPA-sulfate (S conjugates in plasma, liver and uterus of female Wistar Han rats administered TBBPA (50, 100, 250, 500 or 1000 mg/kg for 28 consecutive days. In accordance with this objective, TBBPA sulfation was used as a surrogate for evaluating the potential for estradiol sulfation to be limited at high dose levels of TBBPA. Blood samples were collected at 4 and 8 h post-dosing on study day 7, 14, and 28, while liver and uterus were collected at the same time points following 28 days of dosing. Tissue samples were analyzed for TBBPA, TBBPA-GA and TBBPA-S by LC–MS/MS. A dose-related increase in the concentration of all three analytes occurred in plasma (day 7, 14, and 28 as well as liver and uterus tissue (day 28 at both 4 and 8 h post dose. The plasma concentration of TBBPA-GA and TBBPA-S was higher in animals dosed for 28 days compared to those dosed for 7 or 14 days showing an increase in systemic circulation of these conjugates with repeated administration. The balance of these conjugates was also different in tissues with TBBPA-S > TBBPA-GA at high doses in the liver and TBBPA-GA > TBBPA-S in both plasma and uterus. In all three tissues the ratio of TBBPA-S/TBBPA-GA showed a decreasing trend with dose, suggesting that at high TBBPA dose levels sulfation of TBBPA becomes limited. This effect was most apparent in the liver and plasma at 28 days of administration. Together these data show that administration of high doses of TBBPA

  18. High-Dose Estradiol-Replacement Therapy Enhances the Renal Vascular Response to Angiotensin II via an AT2-Receptor Dependent Mechanism

    Directory of Open Access Journals (Sweden)

    Tahereh Safari

    2015-01-01

    Full Text Available Physiological levels of estrogen appear to enhance angiotensin type 2 receptor- (AT2R- mediated vasodilatation. However, the effects of supraphysiological levels of estrogen, analogous to those achieved with high-dose estrogen replacement therapy in postmenopausal women, remain unknown. Therefore, we pretreated ovariectomized rats with a relatively high dose of estrogen (0.5 mg/kg/week for two weeks. Subsequently, renal hemodynamic responses to intravenous angiotensin II (Ang II, 30–300 ng/kg/min were tested under anesthesia, while renal perfusion pressure was held constant. The role of AT2R was examined by pretreating groups of rats with PD123319 or its vehicle. Renal blood flow (RBF decreased in a dose-related manner in response to Ang II. Responses to Ang II were enhanced by pretreatment with estradiol. For example, at 300 ng kg−1 min−1, Ang II reduced RBF by 45.7±1.9% in estradiol-treated rats but only by 27.3±5.1% in vehicle-treated rats. Pretreatment with PD123319 blunted the response of RBF to Ang II in estradiol-treated rats, so that reductions in RBF were similar to those in rats not treated with estradiol. We conclude that supraphysiological levels of estrogen promote AT2R-mediated renal vasoconstriction. This mechanism could potentially contribute to the increased risk of cardiovascular disease associated with hormone replacement therapy using high-dose estrogen.

  19. The influence of high doses of radiation in citrine stones

    International Nuclear Information System (INIS)

    Teixeira, M. I.; Caldas, L. V. E.

    2014-08-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  20. TL response of citrine samples for high-dose dosimetry

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2011-01-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the thermoluminescence technique (TL). In this work, the TL properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tectosilicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The citrine stone samples were powdered, and the selected grains were mixed with Teflon in the proportion 2 (Teflon):1 (Citrine). The mixture was pressed and sintered for production of Citrine -Teflon pellets of 50 mg. The TL emission curve showed two peaks at 160 deg C and 220 deg C. To remove the TL peak (160 deg C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The TL dose-response curve between 50 Gy and 100 kGy, the reproducibility of TL response and the lower detection dose were obtained. The preliminary results show that citrine may be useful for high-dose dosimetry. (author)

  1. Multifocal Electroretinography after High Dose Chloroquine Therapy for Malaria

    Directory of Open Access Journals (Sweden)

    Aline Correa de Carvalho

    2013-01-01

    Full Text Available Purpose: To investigate changes in multifocal electroretinography (mfERG parameters associated with high dose chloroquine therapy for treatment of malaria in the Amazonia region of Brazil. Methods: Forty-eight subjects who had received chloroquine treatment for single or multiple malaria infections with a cumulative dose ranging from 1,050 to 27,000mg were included. The control group consisted of 37 healthy aged-matched subjects. Data was collected on amplitude and implicit time of the N1, P1 and N2 waves in the central macular hexagon (R1 and in five concentric rings at different retinal eccentricities (R2-R6. Results: No significant difference was observed in any mfERG parameter between chloroquine treated patients and control subjects. A comparison with previous data obtained from patients with rheumatologic disorders in the same region of Brazil who had received larger cumulative doses of chloroquine and had displayed mfERG changes, indicated that retinal toxicity seems to be dependent on cumulative dose. Conclusion: Lack of mfERG changes in the current study suggests that intensive high dose chloroquine therapy for treatment of malaria is not associated with retinal toxicity.

  2. The influence of high doses of radiation in citrine stones

    Energy Technology Data Exchange (ETDEWEB)

    Teixeira, M. I. [Universidade Nove de Julho - UNINOVE, Rua Vergueiro 235/249, 01504-001 Sao Paulo (Brazil); Caldas, L. V. E., E-mail: miteixeira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, jasper, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the techniques of optical absorption (Oa), thermoluminescent (Tl), optically stimulated luminescence (OSL) and resonance paramagnetic electron (EPR). In this work, the Tl properties of citrine samples were studied. They were exposed to different doses of gamma radiation ({sup 60}Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tecto silicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO{sub 2}), and it has a lower symmetry and more compact reticulum. The Tl emission curve showed two peaks at 160 grades C and 220 grades C. To remove the Tl peak (160 grades C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The Tl dose-response curve between 50 Gy and 100 kGy, the reproducibility of Tl response and the lower detection dose were obtained. The results show that citrine may be useful as high-dose detectors. (Author)

  3. Vitamin E can improve behavioral tests impairment, cell loss, and dendrite changes in rats' medial prefrontal cortex induced by acceptable daily dose of aspartame.

    Science.gov (United States)

    Rafati, Ali; Noorafshan, Ali; Jahangir, Mahboubeh; Hosseini, Leila; Karbalay-Doust, Saied

    2018-01-01

    Aspartame is an artificial sweetener used in about 6000 sugar-free products. Aspartame consumption could be associated with various neurological disorders. This study aimed to evaluate the effect of aspartame onmedial Prefrontal Cortex (mPFC) as well as neuroprotective effects of vitamin E. The rats were divided into seven groups, including distilled water, corn oil, vitamin E (100mg/kg/day), and low (acceptable daily dose) and high doses of aspartame (40 and 200mg/kg/day) respectively, with or without vitamin E consumption, for 8 weeks. Behavioral tests were recorded and the brain was prepared for stereological assessments. Novel objects test and eight-arm radial maze showed impairmentoflong- and short-termmemoriesin aspartame groups. Besides, mPFC volume, infralimbic volume, neurons number, glial cells number, dendrites length per neuron,and number of spines per dendrite length were decreased by 7-61% in the rats treated with aspartame. However, neurons' number, glial cells number, and rats' performance in eight-arm radial mazes were improved by concomitant consumption of vitamin E and aspartame. Yet, the mPFC volume and infralimbic cortex were protected only in the rats receiving the low dose of aspartame+vitamin E. On the other hand, dendrites length, spines number,and novel object recognition were not protected by treatment with vitamin E+aspartame. The acceptable daily dose or higher doses of aspartame could induce memory impairments and cortical cells loss in mPFC. However, vitamin E could ameliorate some of these changes. Copyright © 2017 Elsevier GmbH. All rights reserved.

  4. Use of glasses as radiation detectors for high doses

    International Nuclear Information System (INIS)

    Caldas, L.

    1989-08-01

    Glass samples were tested in relation to the possibility of use in high dose dosimetry in medical and industrial areas. The main characteristics were determined: detection threshold, reproducibility, response to gamma radiation of 137 Cs and 6 Co and thermal decay at ambient temperature, with the use of optical absorption and thermoluminesce techniques. (author) [pt

  5. Oval pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    Hoogendijk, JE; Wokke, JHJ; de Visser, M

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Sis patients responded. Side effects

  6. Oral pulsed high-dose dexamethasone for myositis

    NARCIS (Netherlands)

    van der Meulen, M. F.; Hoogendijk, J. E.; Wokke, J. H.; de Visser, M.

    2000-01-01

    To study the short-term effect of oral pulsed high-dose dexamethasone for myositis we treated eight newly diagnosed patients with three 28-day cycles of oral dexamethasone. Primary outcome measures were muscle strength, pain, and serum creatine kinase activity. Six patients responded. Side effects

  7. High-dose acetylcysteine in idiopathic pulmonary fibrosis

    NARCIS (Netherlands)

    Demedts, Maurits; Behr, Juergen; Buhl, Roland; Costabel, Ulrich; Dekhuijzen, Richard; Jansen, Henk M.; MacNee, William; Thomeer, Michiel; Wallaert, Benoit; Laurent, François; Nicholson, Andrew G.; Verbeken, Eric K.; Verschakelen, Johny; Flower, Christopher D. R.; Capron, Frédérique; Petruzzelli, Stefano; de Vuyst, Paul; van den Bosch, Jules M. M.; Rodriguez-Becerra, Eulogio; Corvasce, Giuseppina; Lankhorst, Ida; Sardina, Marco; Montanari, Mauro

    2005-01-01

    BACKGROUND Idiopathic pulmonary fibrosis is a chronic progressive disorder with a poor prognosis. METHODS We conducted a double-blind, randomized, placebo-controlled multicenter study that assessed the effectiveness over one year of a high oral dose of acetylcysteine (600 mg three times daily) added

  8. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma

    NARCIS (Netherlands)

    P.G. Richardson (Paul Gerard); P. Sonneveld (Pieter); M.W. Schuster (Michael); D. Irwin (David); E.A. Stadtmauer (Edward); T. Facon (Thierry); J-L. Harousseau (Jean-Luc); D. Ben-Yehuda (Dina); S. Lonial (Sagar); H. Goldschmidt (Hartmut); D. Reece (Donna); J.F. San Miguel (Jesús Fernando); J. Bladé (Joan); M. Boccadoro (Mario); J. Cavenagh (Jamie); W. Dalton (William); A.L. Boral (Anthony); D.-L. Esseltine (Dixie-Lee); J.B. Porter (Jane); D. Schenkein (David); K.C. Anderson (Kenneth)

    2005-01-01

    textabstractBACKGROUND: This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies. METHODS: We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3

  9. Unusual complication and successful high-dose chemotherapy ...

    African Journals Online (AJOL)

    ... treated with high-dose chemotherapy in our institution, complicated by unusual bilateral renal vein tumour thrombi and tumour lysis syndrome. We believe this unique case highlights the need for early recognition of current and potential complications on staging computed tomography imaging, as well as successful use of ...

  10. Exposure to low doses (20 cGy) of Hze results in spatial memory impairment in rats.

    Science.gov (United States)

    Britten, Richard; Johnson, Angela; Davis, Leslie; Green-Mitchell, Shamina; Chabriol, Olivia; Sanford, Larry; Drake, Richard

    Escape hole over the 5 days of training. There was a suggestion that there may be some recovery in spatial memory performance by 6 months post exposure. Our preliminary data on Hze-induced exposure on sleep, suggests that within 4 weeks of Hze exposure there is a change in sleep latency, raising the possibility that some of the observed decline in neurocognitive performance may arise due to perturbed sleep patterns. We have used MALDI-IMS to determine the Hze-induced changes in the neuroproteome with a high degree of spatial resolution. Using this technique we have found that a peptide with a m/z of 14207 is differentially elevated in the Thalamus of irradiated rats that have good spatial memory. MALDI-MSI thus appears to be a powerful tool that can be used to identify radiation-induced changes in ancillary brain regions that correlate with neurocognitive impairment, and will ultimately be useful for identifying proteins whose expression changes in parallel with Hze-induced neurocognitive deficits. SUMMARY. We have found that mission-relevant Hze doses (20 cGy) lead to significant neu-rocognitive defects. Clearly such low doses of Hze are unlikely to lead to a significant loss of neuronal cells, and have not been reported to lead to gliosis etc. We take this as further evi-dence that neurocognitive impairment is not solely dependent upon radiation-induced changes in neurogenesis and neuronal cell death. FUNDING: The authors gratefully acknowledge grant support from NASA (NNJ06HD89D).

  11. A 4-Week Repeated-Dose Oral Toxicity Study of Bojungikgi-Tang in Crl:CD Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Sae-Rom Yoo

    2017-01-01

    Full Text Available Traditional herbal medicines have been used for centuries in Asian countries. However, recent studies have led to increasing concerns about the safety and toxicity of herbal prescriptions. Bojungikgi-tang (BJIGT, a herbal decoction, has been used in Korea to improve physical strength. To establish the safety information, BJIGT water extract was evaluated in a 4-week repeated-dose oral toxicity test in Crl:CD Sprague Dawley rats. BJIGT was orally administered in daily doses of 0, 500, 1000, and 2000 mg/kg/day for 4 weeks via oral gavage in male and female rats. We examined the mortality, clinical signs, body weight change, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters. No significant changes were observed in mortality, clinical sings, body weight, food intake, organ weights, hematology, serum biochemistry, and urinalysis parameters between the control group and the BJIGT-treated groups in the rats of both sexes. The results indicate that BJIGT did not induce toxic effects at a dose level up to 2000 mg/kg in rats. Thus, this concentration is considered the nonobservable effect dose in rats and is appropriate for a 13-week subchronic toxicity study.

  12. A clinical comparison of high dose and low dose of Suxamethonium

    Directory of Open Access Journals (Sweden)

    RK Yadav

    2014-01-01

    Full Text Available Background: Suxamethonium having its rapid onset and short duration of action makes this drug unique amongst the neuromuscular blocking drugs described so far. However, use of suxamethonium is associated with a large number of undesirable side effects. Objective: To evaluate clinical effects of high and low dose of suxamethonium and to determine whether lower dose of suxamethonium can be used for any beneficial effects in terms of its various adverse effects e.g. cardiovascular responses, post-operative muscle pains and intraocular pressure. Methods: A total of 100 patients were included in this prospective study. All these patients on preoperative clinical evaluation were assessed to have adequate airway. All the patients were divided in two groups, low dose group (group I and High dose group (group II with 50 patients in each at random. A standard anesthetic technique was adhered to all the patients and following parameters were observed on comparative basis: a. Fasciculation and post operative myalgia. b. Cardiovascular effects, c. Intraocular pressure. Observation: The incidence of post Suxamethonium pain was significantly greater in group II. Increase in heart rate from baseline was significant in both groups. There was no significant difference between the two groups in the diastolic pressure but rise in systolic blood pressure was significant at all assessment times in both groups. This rise from control was statistically significant. Conclusion: Suxamethonium can be used in lower doses (0.5 mg/kg in elective cases without airway compromise. It gives benefits of reduced muscle pains, cardiovascular responses and intraocular hypertension. Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-2, 1-8 DOI: http://dx.doi.org/10.3126/jcmsn.v9i2.9677

  13. Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

    Directory of Open Access Journals (Sweden)

    Y. Sobita Devi

    2011-12-01

    Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

  14. The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats

    Directory of Open Access Journals (Sweden)

    O. Awodele, B.Pharm M.Sc MPH PhD D.Sc FPCPharm FASI

    Full Text Available The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT regimen was assessed in rats. Thirty-two (32 Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p  0.05 levels in the treated females. In addition, RIPE reduced (p < 0.05 total proteins levels and increased (p < 0.05, 53% catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy. Keywords: Fixed dose combined antituberculous drugs, Sub-chronic study, Reproductive toxicity, Rats

  15. Radiation processing and high-dose dosimetry at ANSTO

    International Nuclear Information System (INIS)

    Gant, G.J.; Saunders, M.; Banos, C.; Mo, L.; Davies, J.; Evans, O.

    2001-01-01

    The Radiation Technology group at ANSTO is part of the Physics Division and provides services and advice in the areas of gamma irradiation and high-dose dosimetry. ANSTO's irradiation facilities are designed for maximum dose uniformity and provide a precision irradiation service unique in Australia. Radiation Technology makes and sells reference and transfer standard dosimeters which are purchased by users and suppliers of commercial irradiation services in Australia and the Asia-Pacific region. A calibration service is also provided for dosimeters purchased from other suppliers

  16. Australian high-dose-rate brachytherapy protocols for gynaecological malignancy

    International Nuclear Information System (INIS)

    MacLeod, C.; Dally, M.; Stevens, M.; Thornton, D.; Carruthers, S.; Jeal, P.

    2001-01-01

    There is no consensus over the optimal dose fractionation schedules for high-dose-rate (HDR) brachytherapy used for gynaecological malignancy. In Australian public hospital departments of radiation oncology, HDR brachytherapy for gynaecological cancer is being more commonly used. A survey of public departments that are using this technology, or that plan to introduce this technology, was performed. Their current protocols are presented. In general, protocols are similar biologically; however, the practical aspects such as the number of fractions given do vary and may reflect resource restrictions or, alternatively, differences in interpretations of the literature and of the best protocols by clinicians. Copyright (2001) Blackwell Science Pty Ltd

  17. Effect of single dose, fractionated, and hyperfractionated trunk irradiation on weight gain, respiration frequency, and survival in rats

    International Nuclear Information System (INIS)

    Kimler, B.F.; Giri, P.G.S.; Giri, U.P.; Cox, G.G.

    1986-01-01

    It is concluded that, in this rat trunk irradiation model, fractionation of a single dose into two equal doses separated by 4-6 h produced a sparing effect of approx. 5Gy as measured by delay in weight gain; approx. 4Gy as measured by increased respiration frequency; and approx. 6Gy as measured by survival. Fractionation into daily doses or hyperfractionation into twice-daily doses permitted an approximate doubling of the dose required for the same suppression of weight gain. For the respiration rates and survival endpoints, fractionation or hyperfractionation produced an even greater sparing effect since there was no increase in the respiration frequency at twice the doses that would produce changes if delivered within a few hours; and since essentially no lethality was observed at twice the doses that would kill 70%-100% of animals if delivered in one day. (UK)

  18. Experimental Salmonella typhimurium infections in rats. II. Active and passive immunization as protection against a lethal bacterial dose

    DEFF Research Database (Denmark)

    Hougen, H P; Jensen, E T; Klausen, B

    1990-01-01

    Immunization against a lethal dose of Salmonella typhimurium was studied in athymic and thymus-bearing LEW rats. Active immunization was performed with formalin-killed whole cell vaccine or sublethal infection prior to the lethal infection. After vaccination with killed bacteria the euthymic...... from immunized thymus grafted animals provided only limited protective effect, and treatment with cells from athymic animals had no effect. The study shows that although isogeneic thymus-grafted nude rats become resistent to reinfection with S. typhimurium, only large doses of spleen cells from...

  19. Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

    Directory of Open Access Journals (Sweden)

    Zygmunt Warzecha

    2017-04-01

    Full Text Available Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

  20. Tolerance of the Brachial Plexus to High-Dose Reirradiation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Allen M., E-mail: achen5@kumc.edu; Yoshizaki, Taeko; Velez, Maria A.; Mikaeilian, Argin G.; Hsu, Sophia; Cao, Minsong

    2017-05-01

    Purpose: To study the tolerance of the brachial plexus to high doses of radiation exceeding historically accepted limits by analyzing human subjects treated with reirradiation for recurrent tumors of the head and neck. Methods and Materials: Data from 43 patients who were confirmed to have received overlapping dose to the brachial plexus after review of radiation treatment plans from the initial and reirradiation courses were used to model the tolerance of this normal tissue structure. A standardized instrument for symptoms of neuropathy believed to be related to brachial plexus injury was utilized to screen for toxicity. Cumulative dose was calculated by fusing the initial dose distributions onto the reirradiation plan, thereby creating a composite plan via deformable image registration. The median elapsed time from the initial course of radiation therapy to reirradiation was 24 months (range, 3-144 months). Results: The dominant complaints among patients with symptoms were ipsilateral pain (54%), numbness/tingling (31%), and motor weakness and/or difficulty with manual dexterity (15%). The cumulative maximum dose (Dmax) received by the brachial plexus ranged from 60.5 Gy to 150.1 Gy (median, 95.0 Gy). The cumulative mean (Dmean) dose ranged from 20.2 Gy to 111.5 Gy (median, 63.8 Gy). The 1-year freedom from brachial plexus–related neuropathy was 67% and 86% for subjects with a cumulative Dmax greater than and less than 95.0 Gy, respectively (P=.05). The 1-year complication-free rate was 66% and 87%, for those reirradiated within and after 2 years from the initial course, respectively (P=.06). Conclusion: The development of brachial plexus–related symptoms was less than expected owing to repair kinetics and to the relatively short survival of the subject population. Time-dose factors were demonstrated to be predictive of complications.

  1. Synergistic Effects of Ad-Libitum Low-Dose Fructose Drinking and Low-Dose Streptozotocin Treatment in Wistar Rats: A Mild Model of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Asie Sadeghi

    2017-07-01

    Full Text Available To develop a convenient animal model of T2D by pretreatment with low-dose 10% w/v fructose (FRC solution followed by the injection of low doses of streptozotocin (STZ in Wistar rats. For this 8-week experimental study; rats were first fed a standard chow ad-libitum diet and either tap water (n=40 or 10% w/v FRC solution (n=40 for 4 weeks. Next, rats in each category were randomly allocated to 4 subgroups (n=10 each of low-dose STZ (25,35, and 45 mg/kg. The final mean fasting blood sugar (FBG of FRC+STZ45 (197±55.87 mg/dl were significantly higher than that of the STZ45 (P=0.015 and FRC (P=0.019 groups. FRC+STZ45 showed the highest insulin resistance demonstrated by insulin tolerance test [area under the curve (AUC of insulin tolerance test; P<0.05]. AUC was not significantly different between the STZ45 and non-STZ groups and between FRC and non-FRC fed groups. Furthermore, FBG levels did not differ between FRC and non-FRC groups. Body weight measurement showed that the FRC+STZ45 group had the lowest body weight compared to all other groups. Our data provide the evidence that FRC and STZ45 synergistically could induce hyperglycemia and insulin resistance in Wistar rats. Here we presented a feasible model for initial forms of T2D by employing pretreatment with low-dose FRC solution and treatment with low-dose STZ.

  2. Eating high-fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning.

    Science.gov (United States)

    Baladi, Michelle G; France, Charles P

    2010-10-01

    Discriminative stimulus effects of direct acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high-fat chow increases sensitivity to quinpirole-induced yawning, and this study examined whether eating high-fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high-fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose-response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free-feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high-fat chow is likely because of enhanced sensitivity at D3 receptors. Thus, eating high-fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse.

  3. Eating high fat chow increases the sensitivity of rats to quinpirole-induced discriminative stimulus effects and yawning

    Science.gov (United States)

    Baladi, Michelle G; France, Charles P

    2010-01-01

    Discriminative stimulus effects of directly-acting dopamine receptor agonists (e.g. quinpirole) appear to be mediated by D3 receptors in free-feeding rats. Free access to high fat chow increases sensitivity to quinpirole-induced yawning and the current study examined whether eating high fat chow increases sensitivity to the discriminative stimulus effects of quinpirole. Five rats discriminated between 0.032 mg/kg quinpirole and vehicle while responding under a continuous reinforcement schedule of stimulus shock termination. When rats had free access to high fat chow (discrimination training was suspended), the quinpirole discrimination dose-response curve shifted leftward, possibly indicating enhanced sensitivity at D3 receptors. In the same rats, both the ascending (mediated by D3 receptors) and descending (mediated by D2 receptors) limbs of the dose- response curve for quinpirole-induced yawning shifted leftward. When rats had free access to a standard chow (discrimination training was suspended), the quinpirole discrimination and yawning dose-response curves did not change. Together with published data showing that the discriminative stimulus effects of quinpirole in free- feeding rats are mediated by D3 receptors and the insensitivity of this effect of quinpirole to food restriction (shown to increase sensitivity to D2 but not D3-mediated effects), these results suggest that the leftward shift of the discrimination dose-response curve when rats eat high fat chow is likely due to enhanced sensitivity at D3 receptors. Thus, eating high fat food enhances drug effects in a manner that might impact clinical effects of drugs or vulnerability to drug abuse. PMID:20729718

  4. Distribution and excretion after intravenous dosing of [{sup 14}C]micafungin to rats

    Energy Technology Data Exchange (ETDEWEB)

    Yamato, Yasuhiro; Kaneko, Hayato; Yamasaki, Sachiko; Fujiwara, Tomoichi; Katashima, Masataka; Kawamura, Akio; Terakawa, Masato; Kagayama, Akira [Fujisawa Pharmaceutical Co., Ltd., Osaka (Japan). Biopharmaceutical and Pharmacokinetic Research Lab.

    2002-12-01

    In this study, distribution and excretion after intravenous dosing of [{sup 14}C] micafungin (1 mg/kg) to rats and in vitro serum protein binding and distribution to blood cells in mouse, rat, dog and human were investigated. The concentration of radioactivity in plasma at 5 min, which was the first observation point, was 3,396 ng eq./mL and decreased triexponentially. At 24 h, the concentration had decreased to approximately 12.4% of that at 5 min, and thereafter it deceased with a half-time of 39.3 h. The blood to plasma radioactivity concentration ratios were in the range of 0.80 to 1.00 for up to 7 day after dosing, and were 1.00 or more thereafter. The radioactivity was widely distributed immediately after dosing. The highest radioactivity concentrations were observed in the lungs at 5 min and were 1.86 times higher than that in plasma, followed by the kidneys (1.09). The relative radioactivity concentrations in brain, eyeball, white fat and testis were less than 0.08 of that in plasma, and those in other tissues were in the range of 0.17 to 0.86. The radioactivity concentrations in all tissues examined at 24 h had decreased compared with those at 5 min or 6 h, and decreased almost in parallel with plasma radioactivity concentrations from 72 h with the exception of concentrations for white fat. Up to 240 h after intravenous dosing, 83.5% and 14.4% of the radioactivity had been excreted in feces and urine, respectively. At 240 h, 2.8% and 0.3% of the radioactivity were detected in carcass and gut, respectively. In the expired air, no radioactivity was detected up to 72 h. Up to 48 h after intravenous dosing, 43.9%, 13.2% and 8.3% of the radioactivity had been excreted in bile, urine and feces, respectively. At 48 h, 32.2% and 4.4% of radioactivity were detected in carcass and gut, respectively. (author)

  5. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.; Castro, J.R.; Chen, G.T.Y.; Collier, J.M.; Cartigny, A.; Blakely, E.A.; Lyman, J.T.; Zink, S.R.

    1985-02-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons.

  6. Precision, high dose radiotherapy: helium ion treatment of uveal melanoma

    International Nuclear Information System (INIS)

    Saunders, W.M.; Char, D.H.; Quivey, J.M.

    1985-01-01

    The authors report on 75 patients with uveal melanoma who were treated by placing the Bragg peak of a helium ion beam over the tumor volume. The technique localizes the high dose region very tightly around the tumor volume. This allows critical structures, such as the optic disc and the macula, to be excluded from the high dose region as long as they are 3 to 4 mm away from the edge of the tumor. Careful attention to tumor localization, treatment planning, patient immobilization and treatment verification is required. With a mean follow-up of 22 months (3 to 60 months) the authors have had only five patients with a local recurrence, all of whom were salvaged with another treatment. Pretreatment visual acuity has generally been preserved as long as the tumor edge is at least 4 mm away from the macula and optic disc. The only serious complication to date has been an 18% incidence of neovascular glaucoma in the patients treated at our highest dose level. Clinical results and details of the technique are presented to illustrate potential clinical precision in administering high dose radiotherapy with charged particles such as helium ions or protons

  7. The effective dose and pattern of soybean extract administration to regulate body weight of laboratory rats

    Directory of Open Access Journals (Sweden)

    Meilinah Hidayat

    2016-07-01

    the intake of protein and suppress appetite for short-term. Detam 1 variety is a high-quality soybean according to the Minister of Agriculture of Indonesia. Soybean protein extract Detam 1 by Deak method contains high levels of β conglycinin. The purpose of this study was to determine the effective dose of protein extract Detam 1 soybean Deak Method (PEDSDM in reducing food intake, regulate body weight, and plasma CCK level for 14 and 28 days at various dosage and pattern of treatment on male Wistar rats. Methods: There were eleven groups of treatment (n = 3, administrated with extracts at 5 mg/1x/day, 10 mg/1x/day, 20 mg/1x/day, 2.5 mg/2x/day, 5 mg/2x/day, 10 mg/2x/day and 1.7mg/3x/day, 3.4mg/3x/day, 6.7 mg/3x/day, negative control group (distilled water and positive control group (Sibutramine. Food intake (g, weight loss (g and measurement of plasma Cholecystokinin levels by ELISA (ng /ml Results: The results showed that the highest percentage decrease in food intake is: group 3.4mg /3x/ day (p <0.05, inhibition weight gain for 14 days: group 10 mg /1x/ day, for 28 days: group 1.7 mg/3x/day (p <0.05, increased plasma Cholecystokinin levels: group 20 mg /1x/day (p <0.05. Conclusions: The effective dose and pattern administrating the rats for 14 days is extract of 10 mg once a day in the morning, for 28 days is 1.7 mg three times a day. (Health Science Journal of Indonesia 2016;7:17-26 Keywords: Soybean var Detam 1 -effective dose - body weight - Cholecystokinin 

  8. Effects of prenatal low dose beta radiation from tritiated water on rat hippocampus neurons. Electrophysiological and neuro behavioural changes

    International Nuclear Information System (INIS)

    Gao Weimin; Zhou Xiangyan

    1997-01-01

    Pregnent Wistar rats were exposed to tritiated water (HTO) on day 13 of gestation so that for their offsprings, the absorbed doses were estimated to be 0.000, 0.044, 0.088 and 0.264 Gy. The influence of HTO to the morphology and number of hippocampus pyramidal neurons and the maximum electric current of Ca 2+ in neurons was observed for the in-vitro-cultured hippocampus of new-born rats and the learning and memory behaviours were assessed by the electric avoidance reflex test in a Y-maze and the condition reflex test for young rats. The results show that prenatal exposure to HTO in a cumulative dose of 0.088 Gy can cause a reduction in number of neurons in hippocampus cultured in vitro, and that the electric current of Ca 2+ tends to decline with cumulative dose increasing, with the significant decrease in offsprings prenatally exposed to HTO in dose of 0.264 Gy. The results of electric avoidance reflex test in a Y-maze and condition reflex test indicate that for young rats prenatally exposed to HTO, a cumulative dose of 0.088 Gy could induce damage in their learning and memory behaviours

  9. Dimethyl sulfoxyde diethyl fumarate solution for high dose dosimetry

    International Nuclear Information System (INIS)

    Al-Kassiri, H.; Kattan, M.; Daher, Y.

    2007-06-01

    Dosimetric characterization of diethyl fumarate DEF in dimethyl sulfoxyde DMSO solution has been studied spectrophotometrically for possible application at high dose radiation dosimetry in the range (0-225 kGy). The absorption spectra of irradiated solution showed broad absorption bands between (325-400 nm) with a shoulder at 332 nm. The absorption increases as the dose is increased. Absorbance at 332 nm were measured and plotted against absorbed dose. Linear relationship and good response were found between absorbed dose and absorbance of 20% DEF concentration in the range (0-225 kGy) at the wave length, and linearity up to 250 kGy of absorbance at 332 nm .Good dose rate independence was observed in the range (14-33 kGy/h). The effect of post irradiation storage in darkness and indirect daylight conditions were not found to influence the absorption up to 700 h after irradiation. The effect of irradiation temperature within the range (0 to 60 centigrade degree) on the dosimetry performance was discussed.(author)

  10. Dose and time relationships in the endocrine response of the irradiated adult rat testis

    International Nuclear Information System (INIS)

    Delic, J.I.; Hendry, J.H.; Morris, I.D.; Shalet, S.M.

    1986-01-01

    The dose- and time-dependent responses for the interstitial and tubular compartments in irradiated adult rat testes are described. Leydig cell dysfunction, as indicated by increased serum LH (to a maximum of 385% of control after 5 Gy) and decreased serum T (to a minimum of 30% of control after 10 Gy), was observed at 8 weeks postirradiation. Subsequent recovery of Leydig cell function was then observed, so that after 9 months serum T was normal but LH was still marginally elevated. The dysfunction, with a threshold of about 4 to 5 Gy, was associated with a loss of Leydig cells from the testis. Spermatogenic damage was observed; after doses of 3 Gy and above a marked dose-response was recorded as assessed by counts of tubule cross sections exhibiting spermatogenesis. Reduced serum levels of androgen binding protein indicated Sertoli cell dysfunction at 8 weeks after 3 Gy and above, with values of less than one half of those seen in the controls. Serum FSH also was elevated to between 150% and 200% of control, and after 9 months closely reflected androgen binding protein changes. Unlike the Leydig cell, no recovery with time was observed for this aspect of Sertoli cell function

  11. Physiologically based pharmacokinetic rat model for methyl tertiary-butyl ether; comparison of selected dose metrics following various MTBE exposure scenarios used for toxicity and carcinogenicity evaluation

    International Nuclear Information System (INIS)

    Borghoff, Susan J.; Parkinson, Horace; Leavens, Teresa L.

    2010-01-01

    There are a number of cancer and toxicity studies that have been carried out to assess hazard from methyl tertiary-butyl ether (MTBE) exposure via inhalation and oral administration. MTBE has been detected in surface as well as ground water supplies which emphasized the need to assess the risk from exposure via drinking water contamination. This model can now be used to evaluate route-to-route extrapolation issues concerning MTBE exposures but also as a means of comparing potential dose metrics that may provide insight to differences in biological responses observed in rats following different routes of MTBE exposure. Recently an updated rat physiologically based pharmacokinetic (PBPK) model was published that relied on a description of MTBE and its metabolite tertiary-butyl alcohol (TBA) binding to α2u-globulin, a male rat-specific protein. This model was used to predict concentrations of MTBE and TBA in the kidney, a target tissue in the male rat. The objective of this study was to use this model to evaluate the dosimetry of MTBE and TBA in rats following different exposure scenarios, used to evaluate the toxicity and carcinogenicity of MTBE, and compare various dose metrics under these different conditions. Model simulations suggested that although inhalation and drinking water exposures show a similar pattern of MTBE and TBA exposure in the blood and kidney (i.e. concentration-time profiles), the total blood and kidney levels following exposure of MTBE to 7.5 mg/ml MTBE in the drinking water for 90 days is in the same range as administration of an oral dose of 1000 mg/kg MTBE. Evaluation of the dose metrics also supports that a high oral bolus dose (i.e. 1000 mg/kg MTBE) results in a greater percentage of the dose exhaled as MTBE with a lower percent metabolized to TBA as compared to dose of MTBE that is delivered over a longer period of time as in the case of drinking water.

  12. Pulsed dose rate and fractionated high dose rate brachytherapy: choice of brachytherapy schedules to replace low dose rate treatments

    International Nuclear Information System (INIS)

    Visser, Andries G.; Aardweg, Gerard J.M.J. van den; Levendag, Peter C.

    1996-01-01

    Purpose: Pulsed dose rate (PDR) brachytherapy is a new type of afterloading brachytherapy (BT) in which a continuous low dose rate (LDR) treatment is simulated by a series of 'pulses,' i.e., fractions of short duration (less than 0.5 h) with intervals between fractions of 1 to a few hours. At the Dr. Daniel den Hoed Cancer Center, the term 'PDR brachytherapy' is used for treatment schedules with a large number of fractions (at least four per day), while the term 'fractionated high dose rate (HDR) brachytherapy' is used for treatment schedules with just one or two brachytherapy fractions per day. Both treatments can be applied as alternatives for LDR BT. This article deals with the choice between PDR and fractionated HDR schedules and proposes possible fractionation schedules. Methods and Materials: To calculate HDR and PDR fractionation schedules with the intention of being equivalent to LDR BT, the linear-quadratic (LQ) model has been used in an incomplete repair formulation as given by Brenner and Hall, and by Thames. In contrast to earlier applications of this model, both the total physical dose and the overall time were not kept identical for LDR and HDR/PDR schedules. A range of possible PDR treatment schedules is presented, both for booster applications (in combination with external radiotherapy (ERT) and for BT applications as a single treatment. Because the knowledge of both α/β values and the half time for repair of sublethal damage (T (1(2)) ), which are required for these calculations, is quite limited, calculations regarding the equivalence of LDR and PDR treatments have been performed for a wide range of values of α/β and T (1(2)) . The results are presented graphically as PDR/LDR dose ratios and as ratios of the PDR/LDR tumor control probabilities. Results: If the condition that total physical dose and overall time of a PDR treatment must be exactly identical to the values for the corresponding LDR treatment regimen is not applied, there appears

  13. High dose rate versus low dose rate interstitial radiotherapy for carcinoma of the floor of mouth

    International Nuclear Information System (INIS)

    Inoue, Takehiro; Inoue, Toshihiko; Yamazaki, Hideya; Koizumi, Masahiko; Kagawa, Kazufumi; Yoshida, Ken; Shiomi, Hiroya; Imai, Atsushi; Shimizutani, Kimishige; Tanaka, Eichii; Nose, Takayuki; Teshima, Teruki; Furukawa, Souhei; Fuchihata, Hajime

    1998-01-01

    Purpose: Patients with cancer of the floor of mouth are treated with radiation because of functional and cosmetic reasons. We evaluate the treatment results of high dose rate (HDR) and low dose rate (LDR) interstitial radiation for cancer of the floor of mouth. Methods and Materials: From January 1980 through March 1996, 41 patients with cancer of the floor of mouth were treated with LDR interstitial radiation using 198 Au grains, and from April 1992 through March 1996 16 patients with HDR interstitial radiation. There were 26 T1 tumors, 30 T2 tumors, and 1 T3 tumor. For 21 patients treated with interstitial radiation alone, a total radiation dose of interstitial therapy was 60 Gy/10 fractions/6-7 days in HDR and 85 Gy within 1 week in LDR. For 36 patients treated with a combination therapy, a total dose of 30 to 40 Gy of external radiation and a total dose of 48 Gy/8 fractions/5-6 days in HDR or 65 Gy within 1 week in LDR were delivered. Results: Two- and 5-year local control rates of patients treated with HDR interstitial radiation were 94% and 94%, and those with LDR were 75% and 69%, respectively. Local control rate of patients treated with HDR brachytherapy was slightly higher than that with 198 Au grains (p = 0.113). For late complication, bone exposure or ulcer occurred in 6 of 16 (38%) patients treated with HDR and 13 of 41 (32%) patients treated with LDR. Conclusion: HDR fractionated interstitial brachytherapy can be an alternative to LDR brachytherapy for cancer of the floor of mouth and eliminate radiation exposure for the medical staff

  14. Brachytherapy for early oral tongue cancer. Low dose rate to high dose rate

    International Nuclear Information System (INIS)

    Yamazaki, Hideya; Inoue, Takehiro; Yoshida, Ken; Yoshioka, Yasuo; Shimizutani, Kimishige; Inoue, Toshihiko; Furukawa, Souhei; Kakimoto, Naoya

    2003-01-01

    To examine the compatibility of low dose rate (LDR) with high dose rate (HDR) brachytherapy, we reviewed 399 patients with early oral tongue cancer (T1-2N0M0) treated solely by brachytherapy at Osaka University Hospital between 1967 and 1999. For patients in the LDR group (n=341), the treatment sources consisted of Ir-192 pin for 227 patients (1973-1996; irradiated dose, 61-85 Gy; median, 70 Gy), Ra-226 needle for 113 patients (1967-1986; 55-93 Gy; median, 70 Gy). Ra-226 and Ir-192 were combined for one patient. Ir-192 HDR (microSelectron-HDR) was used for 58 patients in the HDR group (1991-present; 48-60 Gy; median, 60 Gy). LDR implantations were performed via oral and HDR via a submental/submandibular approach. The dose rates at the reference point for the LDR group were 0.30 to 0.8 Gy/h, and for the HDR group 1.0 to 3.4 Gy/min. The patients in the HDR group received a total dose of 48-60 Gy (8-10 fractions) during one week. Two fractions were administered per day (at least a 6-h interval). The 3- and 5-year local control rates for patients in the LDR group were 85% and 80%, respectively, and those in the HDR group were both 84%. HDR brachytherapy showed the same lymph-node control rate as did LDR brachytherapy (67% at 5 years). HDR brachytherapy achieved the same locoregional result as did LDR brachytherapy. A converting factor of 0.86 is applicable for HDR in the treatment of early oral tongue cancer. (author)

  15. On the genetic risk after high dose radioiodine therapy with regard to the gonadal dose

    International Nuclear Information System (INIS)

    Ehrenheim, C.; Hauswirth, C.; Fitschen, J.; Martin, E.; Oetting, G.; Hundeshagen, H.

    1997-01-01

    Aim: The genetic risk for the offspring of patients treated with high doses of radioiodine was to be assessed with special regard to the gonadal dose caused by diagnostic and therapeutic procedures. Methods: 41 young females (aged between 19 and 39 years) and four young males (aged 26 to 36 years) treated with radioiodine because of a thyroid carcinoma were interviewed by use of a questionnaire. The course of pregnancy and birth history could be documented as well as the congenital and developmental conditions of 56 children. Results: The amount of radioactivity applied for therapy and whole body scans ranged over 4,144 and 35,15 GBq I-131; the individual gonadal dose was calculated based on the MIRD model and ranged over 0,2 and 2,2 Sv (0,51 Sv at a mean). The period of time between the last radioiodine application and confinement was at least 9 months, not exceeding 14 years. As to the course of pregnancy and birth two early abortions, one extrauterine gravidity and one premature birth due to an insufficiency of the placenta were stated. In one case a chromosomal translocation 7/14 occured as a genetic defect which lead to an interruption. The children's development was unconspicuous except of two cases of neurodermatitis as well as multiple allergies and an early closure of the anterior fontanelle in one child each. Conclusion: Although the genetic risk is supposed to increase with the gonadal dose achieved (doubling dose 1 Sv) and the increased risk of any congenital anomaly was calculated as about 13% at a mean in our patients, the rate of genetic determined diseases was not elevated (1,8% or 1/57). Thus, no increase of genetic defects or congenital malformations was reported in a total of 408 children described in the literature and in our group. (orig.) [de

  16. High dose calibrations at the Pacific Northwest Laboratory

    International Nuclear Information System (INIS)

    McDonald, J.C.; Fox, R.A.

    1988-10-01

    The need is increasing for both high radiation exposures and calibration measurements that provide traceability of such exposures to national standards. The applications of high exposures include: electronic component damage studies, sterilization of medical products and food irradiation. Accurate high exposure measurements are difficult to obtain and cannot, in general, be carried out with a single dose measurement system or technique because of the wide range of doses and the variety of materials involved. This paper describes the dosimetric measurement and calibration techniques used at the Pacific Northwest Laboratory (PNL) that make use of radiochromic dye films, thermoluminescent dosimeters (TLDs), ionization chambers, and calorimetric dosimeters. The methods used to demonstrate the consistency of PNL calibrations with national standards will also be discussed. 4 refs

  17. α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

    Science.gov (United States)

    Prabhakar, Pankaj; Reeta, K H; Maulik, Subir Kumar; Dinda, Amit Kumar; Gupta, Yogendra Kumar

    2017-01-01

    This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

  18. Low dose rate and high dose rate intracavitary treatment for cervical cancer

    International Nuclear Information System (INIS)

    Hareyama, Masato; Oouchi, Atsushi; Shidou, Mitsuo

    1997-01-01

    From 1984 through 1993, 144 previous untreated patients with carcinoma of uterine cervix were treated with either low dose rate 137 Cs therapy (LDR) or high dose rate 60 Co therapy (HDR). The local failure rates for more than 2-years for the primary lesions were 11.8% (8 of 63 patients) for LDR and 18.0% (11 of 61 patients). Rectal complication rates were significantly lower for HDR versus LDR (14.3% VS. 32.8%. p<0.01). Also, bladder complication rates were significantly lower for HDR versus LDR (0% VS. 10.4%, p<0.005). Treatment results in term of local control were equivalent for HDR and LDR treatment. However, the incidence of complications was higher for the LDR group than for the HDR group. (author)

  19. Effects of low dose rate fission neutron irradiation on the lymphocyte subpopulations of peripheral blood in rats

    International Nuclear Information System (INIS)

    Jiang Dingwen; Lei Chengxiang; Shen Xianrong; Ma Li; Yang Yifang; Peng Wulin; Dai Shourong

    2008-01-01

    Objective: To evaluate the effects of long-term, low dose rate fission neutron irradiation on lymphocyte subpopulations in peripheral blood of rats. Methods: Ninety-six rats were randomly divided into control group and irradiated group exposed to low dose rate fission neutron ( 252 Cf,0.35 mGy/h) for 20.5 h every day. At days 14,28,42,56 and 70 d after irradiation and 35 d after stopping irradiation, After 8 rats of each group were killed, WBC and lymphocyte subpopulations of CD4 + CD3 + , CD8 + CD3 + and CD45RA + /CD161α + in peripheral blood were estimated respectively. Results: Compared with the control group, WBC was reduced significantly at dose of 0.3, 0.4 and 0.5 Gy (P + CD3 - was evidently higher compared with control group at doses of 0.1,0.3, 0.4 and 0.5 Gy and 35 d after stopping irradiation (P + CD3 - was obviously higher compared with control group at dose of 0.2 and 0.3 Gy (P + CD3 + at dose of 0.1 Gy (P + CD3 + at doses of 0.1 and 0.2 Gy (P + CD45RA - ) was increased significantly at doses of 0.2-0.3 Gy, and peripheral blood B cells(CD161α - CD45RA + ) was reduced remarkably at doses of 0.1-0.5 Gy and 35 d after stopping irradiation compared with the control group. Conclusions: Long-term irradiation with low dose rate fission neutron could make TCR (T-cell-receptor) mutant, therefore, WBC, B cells in peripheral blood significantly reduced and NK cells increased. These changes may could not recover at 35 d after Stopping irradiation. (authors)

  20. Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

    Science.gov (United States)

    Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

    2007-03-05

    Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

  1. Protective Effects of Tamarillo (Cyphomandra betacea Extract against High Fat Diet Induced Obesity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Noor Atiqah Aizan Abdul Kadir

    2015-01-01

    Full Text Available This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet. Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea extract at low dose (150 mg kg−1, medium dose (200 mg kg−1, or high dose (300 mg kg−1 or placebo via oral gavages for another 7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and significant increase in HDL-C (p<0.05. Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated rats showed positive improvement of superoxide dismutase (SOD activity and glutathione peroxidase (GPx activity along with a significant increase of total antioxidant status (TAS (p<0.05. Further, rats treated with C. betacea show significantly lower in TNF-α and IL-6 activities (p<0.05. This study demonstrates the potential use of Cyphomandra betacea extract for weight maintenance and complimentary therapy to suppress some obesity complication signs.

  2. Role of ceftazidime dose regimen on the selection of resistant Enterobacter cloacae in the intestinal flora of rats treated for an experimental pulmonary infection

    NARCIS (Netherlands)

    W.H.F. Goessens (Wil); J.W. Mouton (Johan); M.T. ten Kate (Marian); A.J. Bijl; A. Ott (Alewijn); I.A.J.M. Bakker-Woudenberg (Irma)

    2007-01-01

    textabstractObjectives: The effect of ceftazidime dosing increments and frequency of dosing on the selection of ceftazidime-resistant Enterobacter cloacae in the intestine was studied in rats, during treatment of a pulmonary infection caused by Klebsiella pneumoniae. Methods: Rats with pulmonary

  3. Comparative evaluation of flavone from Mucuna pruriens and coumarin from Ionidium suffruticosum for hypolipidemic activity in rats fed with high fat diet.

    Science.gov (United States)

    Dharmarajan, Satheesh Kumar; Arumugam, Kottai Muthu

    2012-10-02

    The objective of the study is a comparative evaluation of flavone isolated from Mucuna pruriens and coumarin isolated from Ionidium suffruticosum was assessed for the hypolipidemic activity in rats fed with high fat diet. The acute toxicity study was found that flavone (M.pruriens) and coumarin (I.suffruticosum) are safe up to 100 mg/kg, so one tenth of this dose (10 mg/kg) was consider as a evaluation dose. High fat diet group of rats showed significant (ppruriens) and coumarin isolated from (I.suffruticosum) at the dose of 10mg/kg b.wt/day along with high fat diet significantly (ppruriens).

  4. Metabolism of T-2 toxin in rats: Effects of dose, route, and time

    International Nuclear Information System (INIS)

    Pfeiffer, R.L.; Swanson, S.P.; Buck, W.B.

    1988-01-01

    Metabolic profiles of the excreta from rats following iv, oral, and dermal administration of tritium-labeled T-2 toxin at 0.15 and 0.60 mg/kg were determined. The major metabolites in urine were 3'-OH HT-2, T-2 tetraol, and unknown metabolite M5, whereas the major metabolites in feces were deepoxy T-2 tetraol, 3'-OH HT-2, and unknown metabolites M5, M7, and M9. The metabolite labeled M9 (major metabolite) was tentatively identified as deepoxy 3'-OH HT-2. There was no significant effect on metabolic profiles due to dose, but there was a variable effect associated with the route of administration. The increase over time of appreciable levels of deepoxy metabolites as a percentage of extracted radioactivity was both consistent and statistically significant

  5. Effect of kasoline on male rats reproductive system in control and after irradiation in low dose

    International Nuclear Information System (INIS)

    Konoplya, E.F.; Vereshchako, G.G.; Khodosovskaya, A.M.

    2006-01-01

    It was studied morphofunctional status of reproductive system and several haematological parameters of male rats after administration of kasoline without any another treatment or before following irradiation in low dose (1 Gy). Kasoline is biological active substance obtained from castoreum. In intact animals this medical drug heightened relative weight of testis, epidydimisis, prostate gland and seminal vesicles; number of mature sex cells, extracted from epidydimisis and DNA contents in testiculare tissue. Kasoline possesses specific radioprotective properties that resulted in restoration of leukocytes number in blood, in grown number of spermatozoids, extracted from epidydimisis, and considerable increase of DNA value in the testis tissue. Obtained effects were more prominent at 30 and 90 days after irradiation. (authors)

  6. Correction of glutathione metabolism in the liver of albino rats affected by low radiation doses

    International Nuclear Information System (INIS)

    Moiseenok, A.G.; Slyshenkov, V.S.; Khomich, T.I.; Zimatkina, T.I.; Kanunnikova, N.P.

    1997-01-01

    The levels of total glutathione GSH, GSSG and the activities of glutathione reductase and glutathione peroxidase were studied in the liver of adult albino rats subjected to 3-fold external γ-irradiation throughout 2 weeks at the overall dose of 0.75 Gy after 15 h, 2 and 5 days from the last irradiation. Some animals were injected intraperitoneally with the pantothenate containing complex > 3 times on days 1-3 before the irradiation. The radiation related decrease of GSH, GSH/GSSG and the total glutathione level was prevented by the prophylactic administration of the complex and probably at the expense of the activation of the G-SH biosynthesis and/or transport in the liver by the CoA biosynthetic precursor. (author)

  7. Threshold dose to developing central nerve system of rats and mice from prenatal exposure to tritiated water

    International Nuclear Information System (INIS)

    Zhou Xiangyan; Wang Bing; Gao Weimin; Lu Huimin

    1999-01-01

    Objective: To study the threshold dose to the developing central nerve system of rats and mice from prenatal exposure to tritiated water. methods: Pregnant adult C 57 BL/6J strain mice and Wistar strain rats were irradiated with beta-rays from HTO by a single intraperitoneal injection on the 12.5 th and 13 th days of gestation. The activities of HTO were 24.09, 48.18 and 144.54 ( x 10 4 Bq/g bw), respectively. Fifty-six parameters including postnatal growth, neutro-behavior, pathology of brain, neuropeptide contents, changes of hippocampal neurons, Ca 2+ conductance of hippocampal neurons etc were used to test the teratogenic threshold dose the lowest dose was different from that of the control). Results: Of the observed 56 parameters of rats and mice 80.4% indicated that the threshold doses for prenatal HTO exposure ranged from 0.030 Gy to 0.092 Gy, and the other 19.6% showed the threshold doses from 0.093 to 0.300 Gy. Conclusions: There exists threshold dose from the low level tritiated water irradiation of the developing central nerve system

  8. The Impact of Heart Irradiation on Dose-Volume Effects in the Rat Lung

    International Nuclear Information System (INIS)

    Luijk, Peter van; Faber, Hette; Meertens, Harm; Schippers, Jacobus M.; Langendijk, Johannes A.; Brandenburg, Sytze; Kampinga, Harm H.; Coppes, Robert P. Ph.D.

    2007-01-01

    Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung

  9. Cardiovascular effects in rats following exposure to a high-boiling coal liquid.

    Science.gov (United States)

    Zangar, R C; Sasser, L B; Mahlum, D D; Abhold, R H; Springer, D L

    1987-11-01

    In previous work, increased blood pressure was observed in anesthetized rats following a subchronic aerosol exposure to solvent-refined coal heavy distillate (HD). To determine if this increase is a permanent, dose-related response, 11-week-old male rats were exposed by inhalation to 0, 0.24, or 0.70 mg/liter (control, low-exposure, and high-exposure groups, respectively) of HD for 6 hr/day, 5 days/week, for 6 weeks. In addition to blood pressure, select cardiovascular parameters were measured to obtain information on other possible toxic effects of the HD and also to gain some insight into potentially altered regulatory mechanisms that could be affecting the blood pressure. The angiotensin-aldosterone hormonal system, body fluid regulation, cardiac function and regulation, and pulmonary gas-exchange capabilities were examined. Two weeks after the end of exposure, mean blood pressures and heart rates of anesthetized animals in the low-and high-exposure groups were elevated relative to the controls. Plasma angiotensin concentrations decreased with increasing dose, whereas aldosterone concentrations were unaffected. In the high-dose group, blood and plasma volumes were 20 and 28%, respectively, higher than those of controls. Seven weeks after exposure, all measured cardiovascular parameters were similar to control values. Results from this study show that a 6-week exposure to HD resulted in dose-dependent, transient changes in a variety of physiological factors considered important in cardiovascular function.

  10. Study of four weeks repeated-dose toxic test of Sweet Bee Venom in rats Original Articles

    Directory of Open Access Journals (Sweden)

    Kwon Hae-Yon

    2011-03-01

    Full Text Available Objectives: This study was performed to analyse four weeks repeated -dose toxicity of Sweet Bee Venom (SBV-pure melittin, the major component of honey bee venom in rats. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLPat Biotoxtech Company, a non-clinical study authorized institution. Male and female rats of 5 weeks old were chosen for the pilot study of four weeks repeated-dose toxicity and was injected at the level of 0.56 mg/kg body weight (eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14 mg/kg as midium and low dosage, respectively. Equal amount of normal saline was injected as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups appealed pain sense in the treating time compared to the control group, and side effects such as hyperemia and movement disorder were observed around the area of injection in all experiment groups, and the higher dosage in treatment, the higher occurrence in side effects. 3. Concerning weight measurement, neither male nor female groups showed significant changes compared to the control group. 4. Concerning to the CBC and biochemistry, all experiment groups didn't show any significant changes compared to the control group. 5. Concerning weight measurement of organs, experiment groups didn't show any significant changes compared to the control group. 6. To verify abnormalities of organs and tissues, those such as cerebellum, cerebrum, liver, lung, kidney,and spinal cords were removed and we conducted histologocal observation with H-E staining.Concerning the histologocal observation of liver tissues, some fatty changes were observed around portal vein in 0.56 mg/kg experiment group. But another organs were not detected in any abnormalities. 7. The proper high dosage of SBV for the thirteen weeks repeated test in rats may be 0.28 mg

  11. Enzymatic activity of granulations tissues under low doses of radiation. Biochemical analysis in rats

    International Nuclear Information System (INIS)

    Tosoni, Guilherme Monteiro; Boscolo, Frab Norberto; Cury, Jaime Aparecido; Watanabe, Plauto Christopher Aranha

    1994-01-01

    This paper was designed to investigate in the rat subcutaneous sponge-induced granulation tissue under low doses of X-ray, the activity of alkaline phosphatase, 5'nucleotide phosphodiesterase and adenosine triphosphatase (ATPase) enzymes. One hundred and fourteen Wistar rats were divided into three groups, as follows: Group I as control, Group II that received single 7,14 R in split-dosis immediately after sponge-implantation at the third and fifth days postoperatively. Biopsies were taken after 7, 11, 14, 21 and 28 days and the activity of the three enzymes was determined. The results have shown that in Group II alkaline phosphatase had higher activity in the 14th day of tissue evolution when compared to Groups I and III . The 5'nucleotide phosphodiesterase activity in Group I was similar in all days checked, although in Group II the enzyme showed higher activity in 7th day and lower in 21st. In Group III the activity was higher after 14 and 7 days and lower after 28 and 21 days. There was no observation of changing in adenosine triphosphatase (ATPase) activity when the three groups were compared. (author)

  12. Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

    Directory of Open Access Journals (Sweden)

    Deise Riba Coelho

    2014-07-01

    Full Text Available Meglumine antimoniate (MA and sodium stibogluconate are pentavalent antimony (SbV drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous. Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h and a slow (t1/2 >> 24 h elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain. The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

  13. Dose patterns for 106RuO4 inhaled by Fischer-344 rats and Beagle dogs

    International Nuclear Information System (INIS)

    Runkle, G.E.; Snipes, M.B.

    1978-01-01

    Ruthenium-106 is an abundant fission product radionuclide in the nuclear fuel cycle which has potential for release as ruthenium tetroxide. Ruthenium tetroxide is a vapor, diffuses rapidly through air and porous materials, is chemically reactive and is rapidly reduced by any organic material to the dioxide form. Current ICRP recommendations consider the lung and gastrointestinal tract as critical organs for inhaled particles of radioactive ruthenium. This study was designed to provide additional data needed to adequately assess the risk for humans potentially exposed to 106 Ru encountered in this vapor form. Fischer-344 rats and Beagle dogs were given a nose-only exposure to 106 RuO 4 vapor to determine its distribution and retention patterns. The largest percentage of the initial body burden was found in the nasopharyngeal region of the respiratory tract. Less than 1% of the initial body burden was deposited in the pulmonary region. Most of the 106 Ru was cleared via the feces. A biomathematical simulation model was developed to fit the tissue and excreta data from the rat. This model was used to assess the short-term and long-term risks after inhalation of 106 RuO 4 . The observed deposition, retention and dose patterns for ruthenium tetroxide indicate the nasopharyngeal region should be considered as a critical region when considering the consequences of human exposure to this vapor

  14. Effects of multiple low dose radiation on spleen T lymphocyte subgroups in eight-week diabetic rats

    International Nuclear Information System (INIS)

    Guan Feng; Li Yanbo; Zhao Hongguang; Guo Wei; Wang Zhicheng; Gong Shouliang; Guo Caixia

    2008-01-01

    Objective: To explore the changes of spleen lymphocyte subgroups in diabetic rats after multiple low dose radiation (LDR). Methods: The experiment was divided into normal control group, pure diabetes mellitus (DM) group, and DM plus different doses of irradiation groups (the irradiation doses were 0.025, 0.050 and 0.075 Gy, respectively). The diabetic rat model was induced by intraperitoneal injection of streptozotocin. After the diabetic rats were irradiated 15 times, the percentages of spleen CD4 + and CD8 + T cells and ratio of CD4 + /CD8 + T cells were detected with flow cytometry on the fourth weekend. Results: The diabetic rats manifested obvious polydipsia, polyphagia, polyuria and weight loss. On the fourth weekend after irradiation, as compared with normal control group, the percentage of spleen CD4 + T cells increased significantly (P + T cells decreased significantly (P + /CD8 + T cells was increased significantly (P + T cells were declined markedly in both 0.050 and 0.075 Gy plus DM groups (P + T cells increased significantly in LDR plus DM groups (P + /CD8 + T cells was declined obviously (P<0.01). Conclusion: The multiple LDR could regulate the immune function in diabetic rats, and rectificate the immunological imbalance in order to protect body. (authors)

  15. Dose-rate effects for mammary tumor development in female Sprague-Dawley rats exposed to X and γ radiation

    International Nuclear Information System (INIS)

    Johnson, J.R.; Gragtmans, N.J.; Myers, D.K.; Jones, A.R.

    1989-01-01

    Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or γ rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic γ exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h -1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h -1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of γ rays. (author)

  16. High-dose secondary calibration laboratory accreditation program

    Energy Technology Data Exchange (ETDEWEB)

    Humphreys, J.C. [National Institute of Standards and Technology, Gaithersburg, MD (United States)

    1993-12-31

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program.

  17. High-dose secondary calibration laboratory accreditation program

    International Nuclear Information System (INIS)

    Humphreys, J.C.

    1993-01-01

    There is a need for high-dose secondary calibration laboratories to serve the multi-billion dollar radiation processing industry. This need is driven by the desires of industry for less costly calibrations and faster calibration-cycle response time. Services needed include calibration irradiations of routine processing dosimeters and the supply of reference standard transfer dosimeters for irradiation in the production processing facility. In order to provide measurement quality assurance and to demonstrate consistency with national standards, the high-dose secondary laboratories would be accredited by means of an expansion of an existing National Voluntary Laboratory Accreditation Program. A laboratory performance criteria document is under development to implement the new program

  18. Anticoagulation and high dose liver radiation. A preliminary report

    International Nuclear Information System (INIS)

    Lightdale, C.J.; Wasser, J.; Coleman, M.; Brower, M.; Tefft, M.; Pasmantier, M.

    1979-01-01

    Two groups of patients were observed for evidence of acute radiation hepatitis during high dose radiation to the liver. The first group of 18 patients with metastatic liver disease received an average of 4,050 rad to the whole liver. Half received anticoagulation with warfarin. One patient on anticoagulation developed evidence of acute radiation hepatitis while 2 patients did so without anticoagulation. Eleven patients with Hodgkin's disease received 4,000 rad to the left lobe of the liver during extended field radiation. Four of these 11 patients were anticoagulated to therapeutic range. Only one of the fully anticoagulated patients showed changes on liver scan consistent with radiation hepatitis whereas three did so without anticoagulation. No serious sequelae from anticoagulation occurred in either group. These preliminary data suggest that anticoagulation may be safely administered with high dose hepatic radiation and that further trials with anticoagulation are warranted

  19. Antihypertensive action of non-natriuretic doses of furosemide in Dahl salt-sensitive rats

    DEFF Research Database (Denmark)

    Haugan, Ketil; Petersen, Jørgen Søberg; Spannow, Jesper

    1997-01-01

    Farmakologi, blood pressure, Dahl rats, furosemide, sodium balance, total body sodium, non-natriuretic......Farmakologi, blood pressure, Dahl rats, furosemide, sodium balance, total body sodium, non-natriuretic...

  20. Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline

    DEFF Research Database (Denmark)

    Kaae, Rikke; Agertoft, Lone; Pedersen, Sören

    2004-01-01

    OBJECTIVES: To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. METHODS: Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxi...

  1. Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

    International Nuclear Information System (INIS)

    Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

    1999-01-01

    Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

  2. Biomarkers of Dose and Effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    Science.gov (United States)

    Background: Human controlled exposure studies have generally focused on subjects exposed to ozone (O3) while exercising while exposures in rats have been done at rest. We exposed resting subjects to labeled O3 (18O3, 0.4 ppm, for 2 hr) and compared O3 dose and effects with our...

  3. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  4. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  5. The influence of superlethal γ-radiation doses on the content and metabolism of serotonin in the rat brain

    International Nuclear Information System (INIS)

    Silina, A.G.; Sverdlov, A.G.

    1987-01-01

    As early as 60 min after γ-irradiation of Wistar rats with a dose of 150 Gy the content of serotonin and 5-hydroxyindoleacetic acid decreases in the midbrain, hippocampus, and cerebral hemisphere cortex. The decrease is most pronounced in the midbrain where serotoninergic neurons are located. The changes are accumulated during the first 24 h following irradiation h

  6. Distribution of 14C-lindane in the rat after a single dose intraperitoneal and intravenous injection

    International Nuclear Information System (INIS)

    Lievremont, Maurice; Le Flohic, J.-F.; Pascaud, Marc

    1981-01-01

    14 C-Lindane retentions in rat tissues were studied until 24 hrs after a single dose pesticide administration. Each organ shows particular kinetics. Adipose tissue is the most active in pesticide fixation but the lungs retain momentarily a large fraction of Lindane after intravenous injection [fr

  7. Dose characteristics of high-energy electrons, muons and photons

    International Nuclear Information System (INIS)

    Britvich, G.I.; Krupnyj, G.I.; Peleshko, V.N.; Rastsvetalov, Ya.N.

    1980-01-01

    Differential distribution of energy release at different depth of tissue-equivalent phantoms (plexiglas, polystyrene, polyethylene) at the energy of incident electrons, muons of 0.2-40 GeV and photons with the mean energy of 3.6 GeV are measured. The error of experimental results does not exceed 7%. On the basis of the data obtained dose characteristics of electrons, muons and photons for standard geometry are estimated. For all types of irradiation the maximum value of specific equivalent dose, nremxcm 2 /part. is presented. It is shown that published values of specific equivalent dose of electron radiation are higher in all the investigated energy range from 0.2 to 40 GeV, and for muon radiation a good agreement with the present experiment is observed. The highly precise results obtained which cover the wide dynamic range according to the energy of incident particles can serve as the basis for reconsidering the existing recommendations for dose characteristics of electron radiation [ru

  8. Ion exchange resins as high-dose radiation dosimeters

    International Nuclear Information System (INIS)

    Alian, A.; Dessouki, A.; El-Assay, N.B.

    1984-01-01

    This paper reports on the possibility of using various types of ion exchange resins as high-dose radiation dosimeters, by analysis of the decrease in exchange capacity with absorbed dose. The resins studied are Sojuzchim-export-Moscow Cation Exchanger KU-2 and Anion Exchanger AV-17 and Merck Cation Exchanger I, and Merck Anion Exchangers II and III. Over the dose range 1 to 100 kGy, the systems show linearity between log absorbed dose and decrease in resin ion exchange capacity. The slope of this response function differs for the different resins, depending on their ionic form and degree of cross-linking. The radiation sensitivity increases in the order KU-2; Exchanger I; AV-17; Exchanger II; Exchanger III. Merck resins with moisture content of 21% showed considerably higher radiation sensitivity than those with 2 to 3% moisture content. The mechanism of radiation-induced denaturing of the ion exchanger resins involves cleavage and decomposition of functional substituents, with crosslinking playing a stabilizing role, with water and its radiolytic products serving to inhibit radical recombination and interfering with the protection cage effect of crosslinking. (author)

  9. PLUTONIUM/HIGH-LEVEL VITRIFIED WASTE BDBE DOSE CALCULATION

    Energy Technology Data Exchange (ETDEWEB)

    J.A. Ziegler

    2000-11-20

    The purpose of this calculation is to provide a dose consequence analysis of high-level waste (HLW) consisting of plutonium immobilized in vitrified HLW to be handled at the proposed Monitored Geologic Repository at Yucca Mountain for a beyond design basis event (BDBE) under expected conditions using best estimate values for each calculation parameter. In addition to the dose calculation, a plutonium respirable particle size for dose calculation use is derived. The current concept for this waste form is plutonium disks enclosed in cans immobilized in canisters of vitrified HLW (i.e., glass). The plutonium inventory at risk used for this calculation is selected from Plutonium Immobilization Project Input for Yucca Mountain Total Systems Performance Assessment (Shaw 1999). The BDBE examined in this calculation is a nonmechanistic initiating event and the sequence of events that follow to cause a radiological release. This analysis will provide the radiological releases and dose consequences for a postulated BDBE. Results may be considered in other analyses to determine or modify the safety classification and quality assurance level of repository structures, systems, and components. This calculation uses best available technical information because the BDBE frequency is very low (i.e., less than 1.0E-6 events/year) and is not required for License Application for the Monitored Geologic Repository. The results of this calculation will not be used as part of a licensing or design basis.

  10. Features of aseptic granulomatous imflammation in rats subjected to the chronic action of gamma irradiation in small doses

    Energy Technology Data Exchange (ETDEWEB)

    Goranov, I; Krushkov, I; Statelov, V; Bratanov, M; Nacheva, V; Gospodinova, D; Serafimov, A

    1976-04-01

    Wistar rats were given a Co-60 dose of 2 r/day over a period of 8 months, or a total dose of 400 r. Two sterile sponge scraps of the same size and form were introduced subcutaneously into the intracapsular space of rats in the control and irradiated groups. Cuts were made in the subcutaneous tissue near the implanted foreign bodies. A vigorous inflammatory reaction developed in the unirradiated animals. The skin granulated normally. The irradiated animals showed a general bleeding of the tissues at the implantation site. A number of deviations were noted during the tissue granulation of the irradiated rats. The migration of leucocytes into the infected site was decreased. The formation of macrophage elements and their activity was lower in the irradiated animals. The reaction of the connective tissue turned out to be a rather sensitive test of the disruptive effects of long-term irradiation. 11 refs.

  11. Effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats

    International Nuclear Information System (INIS)

    Jiang Dingwen; Lei Chengxiang; Shen Xianrong; Ma Li; Yang Xufang; Peng Wulin; Dai Shourong

    2008-01-01

    Objective: To evaluate the effects of long-term, low dose rate fission neutron irradiation on the peripheral hematological cells in rats. Methods: 96 rats were randomly divided into the control group and the irradiation group with low dose rate fission neutron ( 252 Cf, 0.35 mGy/h) irradiation 20.5 h every day. 8 rats of each group were killed at 14 d, 28 d, 42d, 56d, 70d after irradiation and 35d after the irradiation, and their peripheral hematological cells were tested respectively. Results: Compared with the control group, peripheral blood WBC was reduced significantly at the dose of 0.3Gy and 0.4Gy (P < 0.05), and was reduced remarkably at dose of 0.5Gy (P<0.01) and 35d after stopping irradiation(P<0.01). At dose of 0.2Gy, Peripheral blood RBC was abnormally higher comparing with the control group (P<0.01), accompanying with higher HCT and HGB, which suggests condensed blood. At the other point, RBC tend to become lower, but only at dose 0.5Gy, and the difference is significant comparing with control group(P <0.05). At dose of 0.3Gy, 0.4Gy and 0.5Gy, HCT were significantly lower comparing with control group. Comparing with control group, MCV was higher at 35d after stopping irradiation, and PLT was significantly lower in dose of 0.2Gy. Conclusion: Long-term irradiation with low dose rate fission neutron could significantly reduce peripheral blood WBC, with less effects on RBC and PLT. The reduced WBC could not recover at 35d after stopping irradiation. (authors)

  12. Establishment and verification of dose-response curve of chromosomal aberrations after exposure to very high dose γ-ray

    International Nuclear Information System (INIS)

    Chen Ying; Luo Yisheng; Cao Zhenshan; Liu Xiulin

    2006-01-01

    To estimate accurately biological dose of the victims exposed to high dose, the dose-response curves of chromosome aberration induced by 6-22 Gy 60 Co γ-ray were established. Human peripheral blood in vitro was irradiated, then lymphocytes were concentrated, cultured 52h, 68h and 72h and harvested. The frequencies of dicentrics (multi-centrics) and rings were counted and compared between different culture times. The dose-response curves and equations were established, as well as verified with high dose exposure accidents. The experiment showed that the culture time should be prolonged properly after high dose exposure, and no significant differences were observed between 52-72h culture. The dose-response curve of 6-22 Gy fitted to linear-square model Y=-2.269 + 0.776D - 7.868 x 10 -3 D 2 and is reliable through verification of the accident dose estimations. In this study, the dose-response curve and equation of chromosome dic + r after 6-22 Gy high dose irradiation were established firstly, and exact dose estimation can be achieved according to it. (authors)

  13. Survey on patient doses in cardiology in Latin America. Criteria for high skin doses follow up

    International Nuclear Information System (INIS)

    Duran, Ariel; Duro, Ivanna; Lopez, Leonardo; Ramirez, Alfredo; Herrera, Carlos; Navarro, Joaquin; Rivarola, Carlos; Lopez, Jose A.

    2008-01-01

    Full text: As part of the International Action Plan for Protection of Patients and supporting by the IAEA, a survey on patient doses in fluoroscopy guided procedures in cardiology in Latin America has been conducted since 2006. One of the objectives of the survey was to set criteria for the identification and evaluation of high skin doses in a certain number of patients to recommend a clinical follow up for potential radiation injuries (more than 3 Gy at the skin). The used methodology for the survey was initiated with two dedicated workshops held in Santiago de Chile (2005) and San Jose de Costa Rica (2007) involving relevant cardiologists from 15 different Latin American Countries. Some sessions were also attended by experts from the Regulatory and Health Authorities. Standardized forms to collect demographic and patient dosimetric data were agreed. Considering that most of the involved centres had still not dosimeters installed in the cardiology x-ray systems, it was agreed to collect data on fluoroscopy time and total number of cine frames per procedure. Relevant factors influencing radio sensitivity of the skin were also collected. Data from 10 countries representing a sample of 709 patients were received during the first year. Procedures included were diagnostic (DG) (coronary angiography and electrophysiology studies), therapeutic (TH) (percutaneous transluminal coronary angioplasties, cardiac ablations and valvuloplasties) or including both DG and TH. A total of 26 patients (3.7%) were selected for potential high skin doses. Initial considered criteria for selection were more than 30 minutes of fluoroscopy, more than 3,000 cine frames per procedure or patients with more than 100 kg of weight. Maximum reported values were 72 minutes and 8,100 frames. In addition, 5 of these patients were diabetic, 6 have previous fluoroscopy procedures and 5 were over 95 kg. The percentage of selected cases for clinical follow up derived from potential skin injuries seem

  14. High performing rats are more sensitive toward catecholaminergic activity enhancer (CAE) compounds than their low performing peers.

    Science.gov (United States)

    Knoll, J; Knoll, B; Miklya, I

    1996-01-01

    Two breeds of rats, Charles River Wistar [Crl(Wi)Br.] and HSD Wistar [Wistar per LATI (Budapest) Br.], with remarkable difference in learning performance were selected. The rats were trained in the shuttle box with 100 trials per day and the number of conditioned avoidance responses (CARs), the escape failures (EFs) to the unconditioned stimulus and the intersignal reactions (IRs) were counted and evaluated by multi-way analysis of variance (ANOVA). Rats of the Crl (Wi) breed proved to be the 'low performing' (LP) animals and rats of the Wistar per LATI (Budapest) breed the 'high performing' (HP) ones. The HP rats produced higher number of CARs (pPPAP], which enhances action potential-transmitter release coupling in the catecholaminergic neurons, fully antagonized in a dose of 1 mg/kg, tetrabenazine-induced learning depression in HP rats and this dose was ineffective in LP rats. The findings were regarded as further support for the view that endogenous CAE substances regulate catecholaminergic activity in the brain and (-)PPAP acts via this regulation.

  15. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  16. Left ventricular wall stress and sarcoplasmic reticulum Ca(2+)-ATPase gene expression in renal hypertensive rats: dose-dependent effects of ACE inhibition and AT1-receptor blockade.

    Science.gov (United States)

    Zierhut, W; Studer, R; Laurent, D; Kästner, S; Allegrini, P; Whitebread, S; Cumin, F; Baum, H P; de Gasparo, M; Drexler, H

    1996-05-01

    Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals). We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

  17. Dose specification for 192Ir high dose rate brachytherapy in terms of dose-to-water-in-medium and dose-to-medium-in-medium

    International Nuclear Information System (INIS)

    Fonseca, Gabriel Paiva; Yoriyaz, Hélio; Tedgren, Åsa Carlsson; Nilsson, Josef; Persson, Maria; Reniers, Brigitte; Verhaegen, Frank

    2015-01-01

    Dose calculation in high dose rate brachytherapy with 192 Ir is usually based on the TG-43U1 protocol where all media are considered to be water. Several dose calculation algorithms have been developed that are capable of handling heterogeneities with two possibilities to report dose: dose-to-medium-in-medium (D m,m ) and dose-to-water-in-medium (D w,m ). The relation between D m,m and D w,m for 192 Ir is the main goal of this study, in particular the dependence of D w,m on the dose calculation approach using either large cavity theory (LCT) or small cavity theory (SCT). A head and neck case was selected due to the presence of media with a large range of atomic numbers relevant to tissues and mass densities such as air, soft tissues and bone interfaces. This case was simulated using a Monte Carlo (MC) code to score: D m,m, D w,m (LCT), mean photon energy and photon fluence. D w,m (SCT) was derived from MC simulations using the ratio between the unrestricted collisional stopping power of the actual medium and water. Differences between D m,m and D w,m (SCT or LCT) can be negligible (<1%) for some tissues e.g. muscle and significant for other tissues with differences of up to 14% for bone. Using SCT or LCT approaches leads to differences between D w,m (SCT) and D w,m (LCT) up to 29% for bone and 36% for teeth. The mean photon energy distribution ranges from 222 keV up to 356 keV. However, results obtained using mean photon energies are not equivalent to the ones obtained using the full, local photon spectrum. This work concludes that it is essential that brachytherapy studies clearly report the dose quantity. It further shows that while differences between D m,m and D w,m (SCT) mainly depend on tissue type, differences between D m,m and D w,m (LCT) are, in addition, significantly dependent on the local photon energy fluence spectrum which varies with distance to implanted sources. (paper)

  18. High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

    2006-09-01

    The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

  19. High-dose preoperative radiation for cancer of the rectum: Impact of radiation dose on patterns of failure and survival

    International Nuclear Information System (INIS)

    Ahmad, N.R.; Mohiuddin, M.; Marks, G.

    1993-01-01

    A variety of dose-time schedules are currently used for preoperative radiation therapy of rectal cancer. An analysis of patients treated with high-dose preoperative radiation therapy was undertaken to determine the influence of radiation dose on the patterns of failure, survival, and complications. Two hundred seventy-five patients with localized rectal cancer were treated with high-dose preoperative radiation therapy. One hundred fifty-six patients received 45 Gy (low-dose group). Since 1985, 119 patients with clinically unfavorable cancers were given a higher dose, 55 Gy using a shrinking field technique (high-dose group). All patients underwent curative resection. Median follow-up was 66 months in the low-dose group and 28 months in the high-dose group. Patterns of failure, survival, and complications were analyzed as a function of radiation dose. Fourteen percent of the total group developed a local recurrence; 20% in the low-dose group as compared with 6% in the high-dose group. The actuarial local recurrence rate at 5 years was 20% for the low-dose group and 8% for the high-dose group, and approached statistical significance with p = .057. For tethered/fixed tumors the actuarial local recurrence rates at 5 years were 28% and 9%, respectively, with p = .05. Similarly, for low-lying tumors (less than 6 cm from the anorectal junction) the rates were 24% and 9%, respectively, with p = .04. The actuarial rate of distant metastasis was 28% in the low-dose group and 20% in the high-dose group and was not significantly different. Overall actuarial 5-year survival for the total group of patients was 66%. No significant difference in survival was observed between the two groups, despite the higher proportion of unfavorable cancers in the high-dose group. The incidence of complications was 2%, equally distributed between the two groups. High-dose preoperative radiation therapy for rectal cancer results in excellent local control rates. 27 refs., 2 figs., 8 tabs

  20. Effects of single cyanamide dose on free amino acid pool in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ostrovskiy, S.Yu.

    Outbred rats were employed in trials on the effects of cyanamide - an inhibitor of aldehyde dehydrogenase proposed for the treatment of alcoholism - on the brain pool of essential and nonessential amino acid. Cyanamide was administered intraperitoneally in a dose of 60 mg/kg, followed in some experiments by intraperitoneal ethanol in a dose of 0.5 g/kg. Following cyanamide administration, marked enhancement of the levels of taurine, cystine, and GABA was noted, whereas the increase in serine was less pronounced. Cyanamide administration also induced depression of alanine, valine, leucine, phenylalanine, and of ethanolamine levels. Administration of ethanol after priming with cyanamide had only the additional effect of diminishing the levels of cysteic acid and ornithine in the brain. However, the differences between the cyanamide animals and the cyanamide + ethanol animals were not significant. With currently available data, it is difficult to tell whether the effects of cyanamide are due to elevation in acetaldehyde levels, or to some direct effect of the drug on protein or amino acid metabolism. 24 references.

  1. Methodology of high dose research in medical radiodiagnostic; Metodologia de investigacao de doses elevadas em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana E.; Martins, Cintia P. de S., E-mail: ird@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2013-11-01

    This work has as main purpose to study occupational exposure in diagnostic radiology in medical cases of high doses recorded in 2011 at the national level . These doses were recorded by monitoring individual of the occupationally exposed individuals (OEI's). This monitoring of the doses received by ionizing radiation has as main objective to ensure that the principle of dose limitation is respected. In this study it were evaluated doses of 372 OEI's radiology in different Brazilian states. Doses were extracted from the database of Sector Management Doses of the Institute for Radioprotection and Dosimetry - IRD/CNEN-RJ, Brazil. The information from the database provide reports of doses from several states, which allows to quantify statistically, showing those with the highest doses in four areas: dose greater than or equal to 20 mSv apron and chest and dose greater than or equal to 100 mSv apron and chest. The identification of these states allows the respective Sanitary Surveillance (VISA), be aware of the events and make plans to reduce them. This study clarified the required procedures when there is a record of high dose emphasizing the importance of using protective radiological equipment, dosimeter and provide a safety environment work by maintaining work equipment. Proposes the ongoing training of professionals, emphasizing the relevance of the concepts of radiation protection and the use of the questionnaire with their investigative systematic sequence, which will allow quickly and efficiently the success the investigations.

  2. Disposition of cefixime in the material-fetal unit after an i.v. dose to pregnant rats

    International Nuclear Information System (INIS)

    Halperin-Walega, E.; Barr, A.; Tonelli, A.P.; Shin, K.; Batra, V.K.

    1986-01-01

    Cefixime, a potent, broad spectrum oral cephalosporin, is currently undergoing clinical trials. To determine the extent of transfer of cefixime across the placenta to the fetus, a single dose of 17.8 mg/kg 14 C-cefixime was administered to rats on day 18 of gestation via the caudal vein. Maternal serum and urine, fetal plasma and tissues, and placentae were sampled at appropriate times after dosing. Separate rats were subjected to whole body autoradiography. The half-life for elimination of radioactivity from both maternal serum and placentae was 6.9 hours. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hours, respectively. However, based on a comparison of area under the curve, relative to maternal dose, exposure of the fetuses to cefixime was far less than that of placentae. Peak radioactivity in fetal plasma occurred at 2 hours and was less than 2% of the maternal peak at 0.5 hours after dosing. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney and intestines. Somewhat less radioactivity appeared in placentae and virtually none could be visualized within the amniotic sac. Overall, the data indicate that exposure of the rat fetus to cefixime after a single maternal dose is limited by the placenta

  3. The effect of different doses of epidermal growth factor on liver ornithine decarboxylase and Na-K ATPase activities in newborn rats.

    Science.gov (United States)

    Bilgihan, A; Turkozkan, N; Isman, F; Kilinc, M; Demirsoy, S

    1998-08-01

    1. Ornithine decarboxylase and Na-K ATPase activities were studied in rat livers that were treated with different doses of epidermal growth factor (EGF). 2. The ornithine decarboxylase activities were studied with spectrophotometry, and results were expressed as micromoles of putrescine per hour per milligram of protein. Na-K ATPase activities were studied on the basis of the principle of measuring the amount of inorganic phosphates released by the hydrolysis of ATP, and the results were expressed as micromoles of inorganic phosphate per hour per milligram of protein. 3. When compared with the controls, although the Na-K ATPase activities were decreased at low doses of EGF, their activities were found to be increased at high doses of EGF. On the other hand, there was a positive correlation between ornithine decarboxylase activities and EGF doses. 4. The results of this study suggest that, whereas the decrease in Na-K ATPase activities at low doses of EGF can be due to the utilization of the enzyme, the increase in Na-K ATPase activities at high doses of EGF can be attributed to its enhanced synthesis.

  4. Routine quality control of high dose rate brachytherapy equipment

    International Nuclear Information System (INIS)

    Guzman Calcina, Carmen S.; Almeida, Adelaide de; Rocha, Jose R. Oliveira

    2001-01-01

    A Quality Assurance program should be installed also for High Dose Rate brachytherapy, in the order to achieve a correct dose administration to the patient and for the safety to those involved directly with the treatment. The work presented here has the following purposes: Analyze the types of equipment tests presented by the official protocols (TG40, TG56 e ARCAL XXX), evaluate the brachytherapy routine tests of protocols from various national and international radiotherapy services and compare the latter with those presented in the official protocols. As a result, we conclude the following: TG56 presents a higher number of tests when compared to the other official protocols and most of the tests presented by the analyzed services are present in TG56. A suggestion for a basic protocol is presented, emphasizing the periodicity and tolerance level of each of the tests. (author)

  5. Development of miniature γ dose rate monitor with high sensitivity

    International Nuclear Information System (INIS)

    Shi Huilu; Tuo Xianguo; Xi Dashun; Tang Rong; Mu Keliang; Yang Jianbo

    2009-01-01

    This paper introduces a miniature γ dose rate monitor with high sensitivity which design based on single chip microcomputer, it can continue monitoring γ dose rate and then choose wire or wireless communications to sent the monitoring data to host according to the actual conditions. It has two kinds of power supply system, AC power supply system and battery which can be chose by concrete circumstances. The design idea and implementation technology of hardware and software and the system structure of the monitor are detailed illustrated in this paper. The experimental results show that measurable range is 0.1 mR/h-200 mR/h, the sensitivity of γ is 90 cps/mR/h, dead time below 200 us, error of stability below ±10%. (authors)

  6. High-dose dosimetry using electron spin resonance (ESR) spectroscopy

    International Nuclear Information System (INIS)

    Kojima, Takuji; Tanaka, Ryuichi

    1992-01-01

    An electron spin resonance (ESR) dosimeter capable of measuring large doses of radiation in radiotherapy and radiation processing is outlined. In particular, an alanine/ESR dosimeter is discussed, focusing on the development of elements, the development of the ESR dosimetric system, the application of alanine/ESR dosimeter, and basic researches. Rod elements for gamma radiation and x radiation and film elements for electron beams are described in detail. The following recent applications of the alanine/ESR dosimeter are introduced: using as a transfer dosimeter, applying to various types of radiation, diagnosing the deterioration of radiological materials and equipments, and applying to ESR imaging. The future subjects to be solved in the alanine/ESR dosimetric system are referred to as follows: (1) improvement of highly accurate elements suitable for the measurement of various types of radiation, (2) establishment of sensitive calibration method of the ESR equipment itself, and (3) calibration and standardization of radiation doses. (K.N.) 65 refs

  7. Use of high irradiation doses for preservation of canned beef

    International Nuclear Information System (INIS)

    Hammad, A.A.I; Salem, F.A.; El-Sahy, K.M.; Rady, A.; Badr, H.H.

    1997-01-01

    The effect of high irradiation doses (11.25,22.5 and 45 KGy) on the bacteriology, organoleptic quality and shelf - life extension of beef meat that are hermetically sealed in metal cans was investigated in comparison with commercial heat sterilization. The unirradiated cans of pre cooked (enzyme inactivated) unirradiated beef were swollen after only one month of storage at ambient temperature (20-30 degree). Application of 11.25 and 22.5 kGy to vacuum packed and enzyme inactivated beef was not enough for sterilization and only delayed swelling of beef cans. Application of 45 KGy irradiation dose prevented swelling of beef vans up to 12 months at ambient temperature and provided meat product, similar to the commercial heat sterilized one, organoleptically acceptable and microbiologically safe. Running title: Radiation sterilization of meat

  8. High and low dose-rate brachytherapy for cervical carcinoma

    International Nuclear Information System (INIS)

    Orton, C.G.

    1998-01-01

    For the brachytherapy component of the r[iation treatment of cervical carcinoma, high dose rate (HDR) is slowly replacing conventional low dose rate (LDR) due primarily to r[iation safety and other physical benefits attributed to the HDR modality. Many r[iation oncologists are reluctant to make this change because of perceived r[iobiological dis[vantages of HDR. However, in clinical practice HDR appears to be as effective as LDR but with a lower risk of late complications, as demonstrated by one randomized clinical trial and two comprehensive literature and practice surveys. The reason for this appears to be that the r[iobiological dis[vantages of HDR are outweighed by the physical [vantages. (orig.)

  9. Study on dose-response relationship between prenatal exposure to tritiated water and the developmental retardation of brain in rats

    International Nuclear Information System (INIS)

    Yang Zhiyuan; Guo Yuefeng; Wang Mingming

    1993-01-01

    The developmental retardation of brain in rats induced by parenatal exposure to HTO had observed by measuring the contents of cerebral amino acids. The HTO was injected intraperitoneally at the 11 th day of gestation with concentration of 7.4 x 10 3 -3.7 x 10 6 Bq/ml (body water). At 18-day-old the young rats were killed and their brains were separated from skulls. The brains were used to make biochemical specimens for measuring the contents of amino acids. The results showed that the contents of amino acids increases with the dose increased and the relationship between the percentage of the increased contents of amino acids in brain and logarithm of absorbed doses (D, Gy) give a good fit to liner regression equation in range of the absorbed doses from 0.0038-1.9 Gy

  10. Effect of low dose x irradiation on the succinate dehydrogenase activity of guinea pig, rat and mouse tissues

    Energy Technology Data Exchange (ETDEWEB)

    Shah, V C; Bhatavdekar, J M; Aravinda Babu, K [Gujarat Univ., Ahmedabad (India). Dept. of Zoology

    1976-07-01

    The histochemical changes in succinate dehydrogenase (SDH) were investigated in pectoralis major muscle of guinea pig, rat and mouse after level X-irradiation (72 R and 240 R) and compared with control animals. Biochemical studies were carried out on liver, kidney, muscle (pectoralis major), adrenal and spleen of these animals after low dose local X-irradiation and compared with control animals. Changes in SDH activity were studied up to 72-h post-irradiation, which shows that low dose local X-irradiation leads to increased enzymic activity. The increase in enzymic activity was remarkable in mouse tissues as compared with guinea pig and rat. Adrenals of all the three animals showed significant activation after all the doses of radiation studied. The significance of these results, with special reference to oxidative metabolism, has been discussed.

  11. Single-dose Intramuscular-injection Toxicology Test of Water-soluble Carthami-flos and Cervi cornu parvum Pharmacopuncture in a Rat Model

    Directory of Open Access Journals (Sweden)

    Sunju Park

    2015-09-01

    Full Text Available Objectives: The aim of the study is to investigate both the single-dose intramuscular injection toxicity and the approximate lethal dose of water-soluble Carthami-flos and Cervi cornu parvum pharmacopuncture (WCFC in male and female Sprague-Dawley (SD rats. Methods: The study was conducted at Biotoxtech Co. according to the Good Laboratory Practice (GLP regulation and the toxicity test guidelines of the Ministry of Food and Drug Safety (MFDS after approval of the Institutional Animal Care and Use Committee. Dosages for the control, high dose, middle dose and low dose groups were 0.5 mL/animal of saline and 0.5, 0.25 and 0.125 mL/animal of WCFC, respectively. WCFC was injected into the muscle of the left femoral region by using a disposable syringe (1 mL, 26 gauge. The general symptoms and mortality were observed 30 minutes, 1, 2, 4, and 6 hours after the first injection and then daily for 14 days after the injection. The body weights of the SD rats were measured on the day of the injection (before injection and on the third, seventh, and fourteenth days after the injection. Serum biochemical and hematologic tests, necropsy examinations, and histopathologic examinations at the injection site were performed after the observation period. Results: No deaths, abnormal clinical symptoms, or significant weight changes were observed in either male or female SD rats in the control or the test (0.125, 0.25, and 0.5 mL/animal groups during the observation period. No significant differences in hematology and serum biochemistry and no macroscopic abnormalities at necropsy were found. No abnormal reactions at injection sites were noted on the topical tolerance tests. Conclusion: The results of this single-dose toxicity study show that WCFC is safe, its lethal doses in male and female SD rats being estimated to be higher than 0.5 mL/animal.

  12. A 14-day repeated-dose oral toxicological evaluation of an isothiocyanate-enriched hydro-alcoholic extract from Moringa oleifera Lam. seeds in rats.

    Science.gov (United States)

    Kim, Youjin; Jaja-Chimedza, Asha; Merrill, Daniel; Mendes, Odete; Raskin, Ilya

    2018-01-01

    A 14-d short-term oral toxicity study in rats evaluated the safety of moringa isothiocyanate-1 (MIC-1)-enriched hydro-alcoholic moringa seeds extract (MSE). Rats (5 males/5 females per group) were gavaged daily for 14 d with the vehicle control or MSE, at 78 (low), 257 (mid-low), 772 (mid-high), or 2571 (high) mg/kg bw/d, standardized to MIC-1 (30, 100, 300, or 1000 mg/kg bw/d, respectively). Toxicological endpoints included body weight and weight gain, food consumption and feed efficiency, clinical observations, hematology, gross necropsy and histopathology, and relative organ weights. Mortality was only observed in the high dose group animals, both male and female, representing decreases in body weight/weight gain and food consumption/feed efficiency. Irregular respiratory patterns and piloerection were major clinical observations found primarily in the mid-high and high dose group animals. In the high dose group, gastrointestinal distention and stomach discoloration were observed in non-surviving males and females, and degeneration and necrosis of the testicular germinal cells and epididymal cells were also observed in a non-surviving male. Increased liver weights were found in females in the mid-high and high dose groups. Animals in the low and mid-low groups did not exhibit adverse effects of MSE (100 mg/kg bw/d MIC-1). A no observed adverse effect level (NOAEL) of the standardized MSE was determined as 257 mg/kg bw/d providing 100 mg/kg bw/d MIC-1.

  13. Low-dose effect of developmental bisphenol A exposure on sperm count and behaviour in rats.

    Science.gov (United States)

    Hass, U; Christiansen, S; Boberg, J; Rasmussen, M G; Mandrup, K; Axelstad, M

    2016-07-01

    Bisphenol A is widely used in food contact materials and other products and is detected in human urine and blood. Bisphenol A may affect reproductive and neurological development; however, opinion of the European Food Safety Authority (EFSA) on bisphenol A (EFSA J, 13, 2015 and 3978) concluded that none of the available studies were robust enough to provide a point of departure for setting a tolerable daily intake for bisphenol A. In the present study, pregnant Wistar rats (n = 17-21) were gavaged from gestation day 7 to pup day 22 with bisphenol A doses of 0, 25 μg, 250 μg, 5 mg or 50 mg/kg bw/day. In the offspring, growth, sexual maturation, weights and histopathology of reproductive organs, oestrus cyclicity and sperm counts were assessed. Neurobehavioural development was investigated using a behavioural testing battery including tests for motor activity, sweet preference, anxiety and spatial learning. Decreased sperm count was found at the lowest bisphenol A dose, that is 25 μg/kg/day, but not at the higher doses. Reproductive organ weight and histology were not affected and no behavioural effects were seen in male offspring. In the female offspring, exposure to 25 μg/kg bw/day bisphenol A dose resulted in increased body weight late in life and altered spatial learning in a Morris water maze, indicating masculinization of the brain. Decreased intake of sweetened water was seen in females from the highest bisphenol A dose group, also a possible sign of masculinization. The other investigated endpoints were not significantly affected. In conclusion, the present study using a robust experimental study design, has shown that developmental exposure to 25 μg/kg bw/day bisphenol A can cause adverse effects on fertility (decreased sperm count), neurodevelopment (masculinization of spatial learning in females) and lead to increased female body weight late in life. These results suggest that the new EFSA temporary tolerable daily intake of 4 μg/kg bw

  14. Calibration of high-dose radiation facilities (Handbook)

    International Nuclear Information System (INIS)

    Gupta, B.L.; Bhat, R.M.

    1986-01-01

    In India at present several high intensity radiation sources are used. There are 135 teletheraphy machines and 65 high intensity cobalt-60 sources in the form of gamma chambers (2.5 Ci) and PANBIT (50 Ci). Several food irradiation facilities and a medical sterilization plant ISOMED are also in operation. The application of these high intensity sources involve a wide variation of dose from 10 Gy to 100 kGy. Accurate and reproducible radiation dosimetry is essential in the use of these sources. This handbook is especially compiled for calibration of high-dose radiation facilities. The first few chapters discuss such topics as interaction of radiation with matter, radiation chemistry, radiation processing, commonly used high intensity radiation sources and their special features, radiation units and dosimetry principles. In the chapters which follow, chemical dosimeters are discussed in detail. This discussion covers Fricke dosimeter, FBX dosimeter, ceric sulphate dosimeter, free radical dosimetry, coloured indicators for irrdiation verification. A final chapter is devoted to practical hints to be followed in calibration work. (author)

  15. Low dose versus high dose anti-snake venom therapy in the treatment of haematotoxic snake bite in South India.

    Science.gov (United States)

    Joseph, Imanto M; Kuriakose, Cijoy K; Dev, Anand Vimal; Philip, George A

    2017-10-01

    Most of the studies on the appropriate dose of anti-snake venom (ASV) are from tertiary hospitals and the guidelines are unclear. Our observational study compared the outcomes of two prevalent treatment regimes for haematotoxic snake bite in a secondary care hospital in South India. The time to normalisation of whole blood clotting time, mortality and complications were not different between the groups. The average dose of ASV required in the low and high dose groups were 106 mL and 246 mL, respectively. Consequently, patients who received low dose ASV incurred approximately 50% less expense. Urticarial rashes were also significantly fewer in the low dose group.

  16. Low-dose in vivo pharmacokinetic and deuterium isotope effect studies of N-nitrosodimethylamine in rats

    International Nuclear Information System (INIS)

    Mico, B.A.; Swagzdis, J.E.; Hu, H.S.; Keefer, L.K.; Oldfield, N.F.; Garland, W.A.

    1985-01-01

    The rates of elimination of N-nitrosodimethylamine (NDMA) and its fully deuterated analogue (N-nitrosodi[ 2 H6]methylamine, [ 2 H6]NDMA) were studied in vivo to explore the origins of the difference in their carcinogenicity. Male Fischer 344 rats, 7.5 weeks of age, were given nitrosamine bolus doses of 1.35 mumol/kg by tail vein injection and 2.02 or 4.05 mumol/kg by p.o. gavage. Animals were sacrificed at various time points from 2.5 to 180 min after i.v. administration or 5 to 120 min after p.o. dosage, and their blood was analyzed for NDMA by gas chromatography-high resolution mass spectrometry. After i.v. injection, blood nitrosamine concentrations declined in an apparently biexponential manner with a terminal half-life of 10 min for NDMA and 12 min for [ 2 H6]NDMA. The apparent total systemic blood clearances for NDMA and [ 2 H6]NDMA were 39 and 26 ml/min/kg, respectively. The apparent steady-state volumes of distribution were nearly identical (297 and 309 ml/kg, respectively). The areas under the curve after 2.02- and 4.05-mumol/kg p.o. doses were proportional to dose. The apparent bioavailability of NDMA was 8%, while that of [ 2 H6]NDMA was 21%. Isotope effects calculated as the ratios of first-pass metabolism, total systemic clearances, bioavailabilities, and intrinsic hepatic clearances were 1.2, 1.5, 2.6, and 3.2, respectively. The isotope effect determined from blood concentrations measured after simultaneous administration of NDMA and [ 2 H6]NDMA by steady-state infusion (each at 1.5 mumol/kg/h) was 2.6 +/- 0.9 (SD)

  17. N-Acetylneuraminic acid attenuates hypercoagulation on high fat diet-induced hyperlipidemic rats

    Directory of Open Access Journals (Sweden)

    Zhang Yida

    2015-12-01

    Full Text Available Background and objective: N-Acetylneuraminic acid (Neu5Ac, a type of sialic acid, has close links with cholesterol metabolism and is often used as a biomarker in evaluating the risk of cardiovascular diseases. However, most studies on the health implications of Neu5Ac have focused on its effects on the nervous system, while its effects on cardiovascular risk factors have largely been unreported. Thus, the effects of Neu5Ac on coagulation status in high fat diet (HFD-induced hyperlipidemic rats were evaluated in this study. Methods: Sprague Dawley male rats were divided into five different groups and fed with HFD alone, HFD low-dose Neu5Ac, HFD high-dose Neu5Ac, HFD simvastatin (10 mg/kg day, and normal pellet alone. Food was given ad libitum while body weight of rats was measured weekly. After 12 weeks of intervention, rats were sacrificed and serum and tissue samples were collected for biochemistry and gene expression analysis, respectively. Results: The results showed that Neu5Ac could improve lipid metabolism and hyperlipidemia-associated coagulation. Neu5Ac exerted comparable or sometimes better physiological effects than simvastatin, at biochemical and gene expression levels. Conclusions: The data indicated that Neu5Ac prevented HFD-induced hyperlipidemia and associated hypercoagulation in rats through regulation of lipid-related and coagulation-related genes and, by extension, induced metabolite and protein changes. The implications of the present findings are that Neu5Ac may be used to prevent coagulation-related cardiovascular events in hyperlipidemic conditions. These findings are worth studying further.

  18. High Doses Gamma Radiolysis of PVC: Mechanisms of Degradation

    International Nuclear Information System (INIS)

    Colombani, J.

    2006-01-01

    PVC radiolysis leads to the formation of various degradation products: radicals, gas, oxidized products or polyenes. In order to predict the formation of the degradation products with regard to irradiation and ageing parameters, it is important to