Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

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Bae, Woo Kyun; Lee, JongUn; Park, Jeong Woo; Bae, Eun Hui; Ma, Seong Kwon; Kim, Suhn Hee

2008-01-01

The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT. PMID:19967075

Decreases in soil microbial function and functional diversity in response to depleted uranium

International Nuclear Information System (INIS)

Meyer, M.C.; Paschke, M.W.; McLendon, T.

1998-01-01

A soil microcosm experiment was used to analyze effects of depleted uranium (DU) on soil function, and the concomitant changes in bacterial functional diversity. Uranium treatment levels were 0, 50, 500, 5000, 10,000 and 25,000 mg DU kg -1 soil. Three measures of soil function were made. Overall soil biological activity was assessed via measurement of soil respiration. Decomposition was assessed by measurement of mass loss of four different plant litter types: wood sticks, cellulose paper, high-N grass, and low-N grass. Mineral N availability in the microcosms was estimated using ion-exchange resin bags. Functional diversity of the microcosms was analyzed through the use of the Biolog-system of sole-C-utilization patterns. Soil respiration was the most sensitive measure of functional changes, with significant decreases observed starting at the 500 mg kg -1 treatment. No differences in N availability were observed across the U treatments. Litter decomposition was significantly decreased at the 25,000 mg kg -1 level relative to the control for all litter types except the high-N grass. Wood decomposition was reduced by 84% at the 25,000 mg kg - treatment, cellulose paper by 68%, and low-N grass by 15%. Decreases in the functional diversity of the bacterial community were related to the observed decrease in soil respiration, and to the greater effect on decomposition of the lower-quality litter types

Interleukin-1 Antagonism Decreases Cortisol Levels in Obese Individuals.

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Urwyler, Sandrine Andrea; Schuetz, Philipp; Ebrahimi, Fahim; Donath, Marc Y; Christ-Crain, Mirjam

2017-05-01

Increased cortisol levels in obesity may contribute to the associated metabolic syndrome. In obesity, the activated innate immune system leads to increased interleukin (IL)-1β, which is known to stimulate the release of adrenocorticotropin hormone (ACTH). We hypothesized that in obesity IL-1 antagonism would result in downregulation of the hypothalamo-pituitary-adrenal axis, leading to decreased cortisol levels. In this prospective intervention study, we included 73 patients with obesity (body mass index [BMI] ≥30 kg/m2) and at least one additional feature of the metabolic syndrome. The primary end point was change in morning cortisol from baseline to after the administration of the IL-1 receptor antagonist (anakinra/Kineret®, total dose 3 × 100 mg). Secondary end points were effects on salivary cortisol and ACTH. Median age was 56 years, 50.7% of patients were female, and median BMI was 36.3 kg/m2. Median morning serum cortisol levels (nmol/L) decreased significantly after IL-1 antagonism [from baseline, 452 to 423; absolute difference, -38.7; 95% confidence interval (CI), -64 to -13.4; P = 0.0019]. Similar effects were found for salivary cortisol levels (-2.8; 95% CI, -4.4 to -1.3; P = 0.0007), ACTH levels (-2.2; 95% CI; -4.2 to -0.1; P = 0.038), systolic blood pressure (-5.2, 95% CI, -8.5 to -1.8; P = 0.0006), and heart rate (-2.9; 95% CI, -4.7 to -1.0; P = 0.0029). IL-1 antagonism in obese individuals with features of the metabolic syndrome leads to a decrease in serum cortisol, salivary cortisol, and ACTH levels along with a reduction in systolic blood pressure and heart rate. Copyright © 2017 Endocrine Society

Curcuma longa (curcumin) decreases in vivo cisplatin-induced ototoxicity through heme oxygenase-1 induction.

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Fetoni, Anna R; Eramo, Sara L M; Paciello, Fabiola; Rolesi, Rolando; Podda, Maria Vittoria; Troiani, Diana; Paludetti, Gaetano

2014-06-01

To investigate whether curcumin may have in vivo protective effects against cisplatin ototoxicity by its direct scavenger activity and/or by curcumin-mediated upregulation of HO-1. Cisplatin-induced ototoxicity is a major dose-limiting side effect in anticancer chemotherapy. A protective approach to decrease cisplatin ototoxicity without compromising its therapeutic efficacy remains a critical goal for anticancer therapy. Recent evidences indicate that curcumin exhibits antioxidant, anti-inflammatory, and chemosensitizer activities. In male adult Wistar rats, a curcumin dose of 200 mg/kg, selected from a dose-response curve, was injected 1 hour before cisplatin administration and once daily for the following 3 days. A single dose of cisplatin (16 mg/kg) was administered intraperitoneally. Rats were divided as follows: 1) control, 2) curcumin control, 3) vehicle control, 4) cisplatin, 5) cisplatin+ vehicle, and 6) curcumin+cisplatin. ABRs were measured before and at Days 3 and 5 after cisplatin administration. Rhodamine-phalloidin staining, 4-hydroxy-2-nonenal and heme-oxigenase-1 immunostainings, and Western blot analyses were performed to assess and quantify OHC loss, lipid peroxidation, and the endogenous response to cisplatin-induced damage and to curcumin protection. Curcumin treatment attenuated hearing loss induced by cisplatin, increased OHC survival, decreased 4-HNE expression, and increased HO-1 expression. This preclinical study demonstrates that systemic curcumin attenuates ototoxicity and provides molecular evidence for a role of HO-1 as an additional mediator in attenuating cisplatin-induced damage.

Inhibition of prolyl 4-hydroxylase decreases muscle fibrosis following chronic rotator cuff tear.

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Gumucio, J P; Flood, M D; Bedi, A; Kramer, H F; Russell, A J; Mendias, C L

2017-01-01

Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair. At two weeks following repair, treatment groups showed increased muscle mass but there was a 15% decrease in force production in the 10 mg/kg group from controls, and no difference between the 0 mg/kg and the 3 mg/kg groups. There was a decrease in the expression of several gene transcripts related to matrix accumulation and fibrosis, and a 50% decrease in collagen content in both treated groups compared with controls. Additionally, the expression of inflammatory genes was reduced in the treated groups compared with controls. Finally, PHD inhibition improved the maximum stress and displacement to failure in repaired tendons. GSK1120360A resulted in improved enthesis mechanics with variable effects on muscle function. PHD inhibition may be beneficial for connective tissue injuries in which muscle atrophy has not occurred.Cite this article: J. P. Gumucio, M. D. Flood, A. Bedi, H. F. Kramer, A. J

Cafeína (150 mg/kg y aprendizaje espacial (retención y adquisición en ratones

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María del Pilar Santacruz

2003-01-01

Full Text Available En este trabajo se evaluó el papel que juega la cafeína (150mg/kg en el aprendizaje espacial (adquisición y retención en ratones mediante las mediciones de la latencia de salida, velocidad, aciertos, regresos, errores y excretas en un laberinto de 3 x 3 metros. Los sujetos fueron moldeados para una ruta en el laberinto y luego se aleatorizaron 20 machos y 20 hembras para la administración de cafeína (s.c. y solución salina durante ocho días consecutivos; luego se observó la retención de este aprendizaje y se moldeó otra ruta para evaluar su retención 24 horas después: La cafeína incrementó la retención del aprendizaje 1, donde hubo los mayores aciertos, y en el segundo las hembras con cafeína exhibieron mayor velocidad y aciertos mientras que los machos, presentaron menores aciertos y velocidad que todos los grupos; como vemos, en el segundo caso, la cafeína fortaleció la retención del aprendizaje 2 en las hembras y la debilitó en los machos. Se concluye que la cafeína (150mg/kg influyó positivamente en la retención del aprendizaje espacial, mas no en la adquisición. Este artículo está asociado a la línea de investigación en Cafeína y Cognición de la Universidad de la Sabana.

Isopiestic Investigation of the Osmotic and Activity Coefficients of {yMgCl2 + (1 - y)MgSO4}(aq) and the Osmotic Coefficients of Na2SO4.MgSO4(aq) at 298.15 K

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Miladinovic, J; Ninkovic, R; Todorovic, M; Rard, J A

2007-06-06

Isopiestic vapor pressure measurements were made for {l_brace}yMgCl{sub 2} + (1-y)MgSO{sub 4}{r_brace}(aq) solutions with MgCl{sub 2} ionic strength fractions of y = 0, 0.1997, 0.3989, 0.5992, 0.8008, and (1) at the temperature 298.15 K, using KCl(aq) as the reference standard. These measurements for the mixtures cover the ionic strength range I = 0.9794 to 9.4318 mol {center_dot} kg{sup -1}. In addition, isopiestic measurements were made with NaCl(aq) as reference standard for mixtures of {l_brace}xNa{sub 2}SO{sub 4} + (1-x)MgSO{sub 4}{r_brace}(aq) with the molality fraction x = 0.50000 that correspond to solutions of the evaporite mineral bloedite (astrakanite), Na{sub 2}Mg(SO{sub 4}){sub 2} {center_dot} 4H{sub 2}O(cr). The total molalities, m{sub T} = m(Na{sub 2}SO{sub 4}) + m(MgSO{sub 4}), range from m{sub T} = 1.4479 to 4.4312 mol {center_dot} kg{sup -1} (I = 5.0677 to 15.509 mol {center_dot} kg{sup -1}), where the uppermost concentration is the highest oversaturation molality that could be achieved by isothermal evaporation of the solvent at 298.15 K. The parameters of an extended ion-interaction (Pitzer) model for MgCl2(aq) at 298.15 K, which were required for an analysis of the {l_brace}yMgCl{sub 2} + (1-y)MgSO{sub 4}{r_brace}(aq) mixture results, were evaluated up to I = 12.025 mol {center_dot} kg{sup -1} from published isopiestic data together with the six new osmotic coefficients obtained in this study. Osmotic coefficients of {l_brace}yMgCl{sub 2} + (1-y)MgSO{sub 4}{r_brace}(aq) solutions from the present study, along with critically-assessed values from previous studies, were used to evaluate the mixing parameters of the extended ion-interaction model.

Five-year field results and long-term effectiveness of 20 mg/kg liposomal amphotericin B (Ambisome for visceral leishmaniasis in Bihar, India.

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Sakib Burza

Full Text Available BACKGROUND: Visceral Leishmaniasis (VL; also known as Kala-azar is an ultimately fatal disease endemic in Bihar. A 2007 observational cohort study in Bihar of 251 patients with VL treated with 20 mg/Kg intravenous liposomal amphotericin B (Ambisome demonstrated a 98% cure rate at 6-months. Between July 2007 and August 2012, Médecins Sans Frontières (MSF and the Rajendra Memorial Research Institute (RMRI implemented a VL treatment project in Bihar, India-an area highly endemic for Leishmania donovani-using this regimen as first-line treatment. METHODS AND PRINCIPAL FINDINGS: Intravenous Ambisome 20 mg/kg was administered in four doses of 5 mg/kg over 4-10 days, depending on the severity of disease. Initial clinical cure at discharge was defined as improved symptoms, cessation of fever, and recession of spleen enlargement. This observational retrospective cohort study describes 8749 patients with laboratory-confirmed primary VL treated over a 5-year period: 1396 at primary healthcare centers, 7189 at hospital, and 164 at treatment camps. Initial clinical cure was achieved in 99.3% of patients (8692/8749; 0.3% of patients (26/8749 defaulted from treatment and 0.4% (31/8749 died. Overall, 1.8% of patients (161/8749 were co-infected with HIV and 0.6% (51/8749 with tuberculosis. Treatment was discontinued because of severe allergic reactions in 0.1% of patients (7/8749. Overall, 27 patients (0.3% were readmitted with post Kala-azar dermal leishmaniasis (PKDL. Risk factors for late presentation included female sex, age >15 years and being from a scheduled caste. In 2012, a long-term efficacy survey in the same area of Bihar determined relapse rates of VL after 5 years' intervention with Ambisome. Of 984 immunocompetent patients discharged between September 2010 and December 2011, 827 (84.0% were traced in order to determine their long-term outcomes. Of these, 20 patients (2.4% had relapsed or received further treatment for VL. Of those completing 6

Morphine decreases social interaction of adult male rats, while THC does not affect it.

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Šlamberová, R; Mikulecká, A; Macúchová, E; Hrebíčková, I; Ševčíková, M; Nohejlová, K; Pometlová, M

2016-12-22

The aim of the present study was to compare effect of three low doses of morphine (MOR) and delta9-tetrahydrocannabinol (THC) on social behavior tested in Social interaction test (SIT). 45 min prior to testing adult male rats received one of the drugs or solvents: MOR (1; 2.5; 5 mg/kg); saline as a solvent for MOR; THC (0.5; 1; 2 mg/kg); ethanol as a solvent for THC. Occurrence and time spent in specific patterns of social interactions (SI) and non-social activities (locomotion and rearing) was video-recorded for 5 min and then analyzed. MOR in doses of 1 and 2.5 mg/kg displayed decreased SI in total. Detailed analysis of specific patterns of SI revealed decrease in mutual sniffing and allo-grooming after all doses of MOR. The highest dose (5 mg/kg) of MOR decreased following and increased genital investigation. Rearing activity was increased by lower doses of MOR (1 and 2.5 mg/kg). THC, in each of the tested doses, did not induce any specific changes when compared to matching control group (ethanol). However, an additional statistical analysis showed differences between all THC groups and their ethanol control group when compared to saline controls. There was lower SI in total, lower mutual sniffing and allo-grooming, but higher rearing in THC and ethanol groups than in saline control group. Thus, changes seen in THC and ethanol groups are seemed to be attributed mainly to the effect of the ethanol. Based on the present results we can assume that opioids affect SI more than cannabinoid.

Effect of naftopidil on brain noradrenaline-induced decrease in arginine-vasopressin secretion in rats

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Masaki Yamamoto

2016-09-01

Full Text Available Naftopidil, an α1-adrenoceptor antagonist, has been shown to inhibit nocturnal polyuria in patients with lower urinary tract symptom. However, it remains unclear how naftopidil decreases nocturnal urine production. Here, we investigated the effects of naftopidil on arginine-vasopressin (AVP plasma level and urine production and osmolality in rats centrally administered with noradrenaline (NA. NA (3 or 30 μg/kg was administered into the left ventricle (i.c.v. of male Wistar rats 3 h after naftopidil pretreatment (10 or 30 mg/kg, i.p.. Blood samples were collected from the inferior vena cava 1 h after NA administration or 4 h after peritoneal administration of naftopidil; plasma levels of AVP were assessed by ELISA. Voiding behaviors of naftopidil (30 mg/kg, i.p.-administered male Wistar rats were observed during separate light- and dark cycles. Administration of NA decreased plasma AVP levels and elevated urine volume, which were suppressed by systemic pretreatment with naftopidil (30 mg/kg, i.p.. Urine osmolality decreased 1 h after NA administration. However, naftopidil by itself had no effect on plasma AVP levels or urodynamic parameters during light- and dark cycles. Our findings suggest that systemic administration of naftopidil could prevent central noradrenergic nervous system-mediated decline in AVP secretion and increase in urine production in rats.

The hallucinogen d-lysergic diethylamide (LSD) decreases dopamine firing activity through 5-HT1A, D2 and TAAR1 receptors.

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De Gregorio, Danilo; Posa, Luca; Ochoa-Sanchez, Rafael; McLaughlin, Ryan; Maione, Sabatino; Comai, Stefano; Gobbi, Gabriella

2016-11-01

d-lysergic diethylamide (LSD) is a hallucinogenic drug that interacts with the serotonin (5-HT) system binding to 5-HT 1 and 5-HT 2 receptors. Little is known about its potential interactions with the dopamine (DA) neurons of the ventral tegmental area (VTA). Using in-vivo electrophysiology in male adult rats, we evaluated the effects of cumulative doses of LSD on VTA DA neuronal activity, compared these effects to those produced on 5-HT neurons in the dorsal raphe nucleus (DRN), and attempted to identify the mechanism of action mediating the effects of LSD on VTA DA neurons. LSD, at low doses (5-20μg/kg, i.v.) induced a significant decrease of DRN 5-HT firing activity through 5-HT 2A and D 2 receptors. At these low doses, LSD did not alter VTA DA neuronal activity. On the contrary, at higher doses (30-120μg/kg, i.v.), LSD dose-dependently decreased VTA DA firing activity. The depletion of 5-HT with p-chlorophenylalanine did not modulate the effects of LSD on DA firing activity. The inhibitory effects of LSD on VTA DA firing activity were prevented by the D 2 receptor antagonist haloperidol (50μg/kg, i.v.) and by the 5-HT 1A receptor antagonist WAY-100,635 (500μg/kg, i.v.). Notably, pretreatment with the trace amine-associate receptor 1 (TAAR 1 ) antagonist EPPTB (5mg/kg, i.v.) blocked the inhibitory effect of LSD on VTA DA neurons. These results suggest that LSD at high doses strongly affects DA mesolimbic neuronal activity in a 5-HT independent manner and with a pleiotropic mechanism of action involving 5-HT 1A, D 2 and TAAR 1 receptors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

Science.gov (United States)

Schneider, M; Paulin, A; Dron, F; Woehrlé, F

2014-12-01

The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

Humic Acid and Water Management to Decrease Ferro (Fe2+ Solution and Increase Productivity of Established New Rice Field

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Amrizal Saidi

2012-01-01

Full Text Available The purpose of this research was to gain a technological breakthrough in controlling Fe toxicity (Fe2+ on Ultisol ina new established rice field by using humic acid from rice straw compost and water management, so that optimalproduction of rice plants could be achieved. The experiment was designed using a 2 × 4 factorials with 3 replicationsin a split plot design. The main plot was water management consists of 2 levels: continuous and intermittentirrigation (2 weeks flooded and 2 weeks field capacity. Small plot was humic acid which was extracted from ricestraw compost by NaOH 0.5 N which consists of 4 levels: 0, 200, 400, and 600 mg kg-1. The results showed thatapplications of humic acid from 0 to 600 mg kg-1 that was followed by 2 weeks of intermittent irrigation decreasedFe2+ concentration. It was approaching levels that were not toxic to plants, with soil Fe2+ between 180-250 mg kg-1.The best treatment was found at the application of 600 mg kg-1 humic acid extracted from rice straw compostcombined with 2 week flooded – 2 weeks field capacity of water management. Those treatment decreased Fe2+concentration from 1,614 to 180 mg kg-1 and increased the dry weight of grain from 5.15 to 16.73 g pot-1 compared tocontinuous flooding and without humic acid application.

Efficacy and safety of intravenous alteplase at 0.6 mg/kg more than 3 h after acute middle cerebral artery occlusion in patients selected using perfusion-diffusion mismatch

International Nuclear Information System (INIS)

Nakashima, Kazuya; Ohnishi, Hideyuki; Taomoto, Katsushi; Kuga, Yoshihiro; Kodama, Yuuji; Kubota, Hisashi; Tominaga, Takashi; Hayashi, Masato; Miyata, Shiro

2011-01-01

Thrombolytic treatment with alteplase at 0.6 mg/kg is approved for use within 3 h of stroke onset in Japan. Thus, only a small percentage of patients can benefit. A meta-analysis and more recent studies suggest a benefit to patients beyond 3 h with alteplase at 0.9 mg/kg or desmoteplase. We assessed the efficacy and safety of intravenous alteplase at 0.6 mg/kg more than 3 h after stroke onset in patients with acute MCA occlusion who were selected using perfusion-diffusion mismatch. Patients with MCA occlusion eligible for intravenous alteplase within 3 h were selected using MRI (diffusion-weighted (DW), fluid-attenuated inversion recovery (FLAIR), T2*, T2)/MR angiography (MRA) and beyond 3 h using evidence of perfusion-diffusion mismatch. Recanalization was evaluated using MRA within 24 h after treatment. Baseline characteristics, recanalization rates, early and late good clinical outcomes (National Institute of Health Stroke Scale (NIHSS) scores of 0 to 1 or 8-points or greater improvement at 24 h and mRS scores of 0 or 1 on the 90th day), symptomatic intracranial hemorrhage (within 72 h) and mortality (at the 90th day) were evaluated for both groups. Also for both groups, the relationships between recanalization and early and late good clinical outcomes were evaluated. 63 patients with MCA occlusion were treated using intravenous alteplase within 3 h (n=53) and beyond 3 h (n=10). No statistically significant differences were found between the two groups for recanalization rates (52.8 vs. 70.0%), early and late good clinical outcomes (early: 41.5 vs. 60.0%, late: 37.7 vs. 50.0%), symptomatic intracranial hemorrhage (0 vs. 0%), or mortality (1.9 vs. 0%). Our data suggest that intravenous alteplase at 0.6 mg/kg beyond 3 h after MCA occlusion for patients selected using perfusion-diffusion mismatch has the same efficacy and safety as treatment within 3 h. However, a larger sample size is needed to evaluate the relationship between recanalization and clinical outcomes

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats.

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Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M; See, Ronald E; Reichel, Carmela M

2016-02-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin's impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin's attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin's effect on cocaine seeking may be mediated by different mechanisms in male and females. PsycINFO Database Record (c) 2016 APA, all rights reserved.

Twiny pro: 5.1 kg of propane dressed in apple green; Twiny pro: 5.1 kg de propane en habillage vert pomme

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Anon.

1998-05-01

Designed for professional and outdoors uses, Twini Pro - the new Primagaz 5.1 kg propane cylinder - is a complement to the Twiny butane 6 kg cylinder was launched during the first week of March in some 2,500 outlets, before 5,000 and 7,000 points later

Perbandingan Insidensi Hipotensi Saat Induksi Intravena Propofol 2 Mg/Kg Bb Pada Posisi Supine dengan Perlakuan dan Tanpa Perlakuan Elevasi Tungkai

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Beni Indra

2016-01-01

  of blood to venous reservoir, especially capacitance venule of legs. Leg elevation can provide hemodynamic stability by increases cardiac preload and recruits blood contained in the venous reservoir. This is Open Randomized Control Trial include 184 elective surgery patients with American Society of Anaesthesiologist (ASA physical status I and II. Anesthesia  was induced with propofol. Patients were randomly allocated into two groups with 92 patients in each. All the patients received Ringer’s Lactate (10 ml/kg and premedicated with fentanyl (2 mcg/kg and midazolam (0,05 mg/kg before induction of anesthesia. Group A was performed passive leg raising 45 degree 1 minute before injection of propofol until  the end of study and group B (control did not receive any maneuver. Parametric data were analyzed with t-test and categorical data was done by using Chi-square test. A p value of less than 0,05 was consider significant. Demografic characteristics (age, sex, body weight and height and  baseline haemodynamic parameters of the patients were similar in two groups (p > 0.05 except for BMI (p < 0.05 . The incidence of hypotension was significantly lower in group A (12 %, than group  B (27,2% at the first minute after propofol  injection, p value = 0.016 (p < 0,05. In the third minute, incidence of hypotension was also significantly lower in group A (15,2% than group B (23,9%, p value = 0,014 (p < 0,05. Leg elevation maneuver 45º significantly decrease incidence of hypotension after propofol induction. Keywords: Propofol, hypotension, leg elevation

Dose of rocuronium for rapid tracheal intubation following remifentanil 2 μg kg-1 and propofol 2 mg kg-1.

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Oh, Ah-Young; Cho, Suk-Ju; Seo, Kwang-Suk; Ryu, Jung-Hee; Han, Sung-Hee; Hwang, Jung-Won

2013-09-01

Full relaxation is not mandatory for successful tracheal intubation. We tried to find the dose of rocuronium that gave acceptable intubation conditions in a rapid sequence intubation with remifentanil and propofol. A dose-finding study of rocuronium using a modified Dixon's up-and-down method. A single tertiary care teaching hospital. Patients undergoing elective surgery under general anaesthesia. After premedication with midazolam and glycopyrrolate, anaesthesia was induced using remifentanil 2 μg kg and propofol 2 mg kg, and a predetermined dose of rocuronium was administered. The dose of rocuronium was determined by a modified Dixon's up-and-down method starting from 0.8 mg kg with an interval of 0.1 or 0.05 mg kg. Intubation was performed 60 s after the start of the rocuronium injection. Intubation conditions were graded as excellent, good or poor. Excellent or good were regarded as clinically acceptable. A dose of rocuronium needed for acceptable intubation condition in 50% of patients (ED50) during rapid tracheal intubation after induction of anaesthesia with remifentanil and propofol. Twenty-eight patients were enrolled to obtain six crossovers. The ED50 of rocuronium was 0.20 mg kg (95% confidence interval, CI 0.17 to 0.23 mg kg) by a modified Dixon's up-and-down method. After induction of anaesthesia with remifentanil 2 μg kg and propofol 2 mg kg, the ED50 of rocuronium for acceptable intubation condition was 0.20 mg kg (95% CI, 0.17 to 0.23 mg kg) for rapid sequence intubation. Thus, we recommend that the intubation dose should be 0.8 mg kg. Clinical trial registration KCT0000094.

[Comparison of 1 mg/body and 3 mg/body of intravenous granisetron for the prevention of chemotherapy-induced nausea and vomiting and adverse events in hematological malignancy patients].

Science.gov (United States)

Motohashi, Shinya; Hori, Katsuhito; Ono, Takaaki; Ohnishi, Kazunori; Kawakami, Junichi

2012-01-01

Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.

Omigapil treatment decreases fibrosis and improves respiratory rate in dy(2J mouse model of congenital muscular dystrophy.

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Qing Yu

Full Text Available Congenital muscular dystrophy is a distinct group of diseases presenting with weakness in infancy or childhood and no current therapy. One form, MDC1A, is the result of laminin alpha-2 deficiency and results in significant weakness, respiratory insufficiency and early death. Modification of apoptosis is one potential pathway for therapy in these patients.dy(2J mice were treated with vehicle, 0.1 mg/kg or 1 mg/kg of omigapil daily via oral gavage over 17.5 weeks. Untreated age matched BL6 mice were used as controls. Functional, behavioral and histological measurements were collected.dy(2J mice treated with omigapil showed improved respiratory rates compared to vehicle treated dy(2J mice (396 to 402 vs. 371 breaths per minute, p<0.03 and similar to control mice. There were no statistical differences in normalized forelimb grip strength between dy(2J and controls at baseline or after 17.5 weeks and no significant differences seen among the dy(2J treatment groups. At 30-33 weeks of age, dy(2J mice treated with 0.1 mg/kg omigapil showed significantly more movement time and less rest time compared to vehicle treated. dy(2J mice showed normal cardiac systolic function throughout the trial. dy(2J mice had significantly lower hindlimb maximal (p<0.001 and specific force (p<0.002 compared to the control group at the end of the trial. There were no statistically significant differences in maximal or specific force among treatments. dy(2J mice treated with 0.1 mg/kg/day omigapil showed decreased percent fibrosis in both gastrocnemius (p<0.03 and diaphragm (p<0.001 compared to vehicle, and in diaphragm (p<0.013 when compared to 1 mg/kg/day omigapil treated mice. Omigapil treated dy(2J mice demonstrated decreased apoptosis.Omigapil therapy (0.1 mg/kg improved respiratory rate and decreased skeletal and respiratory muscle fibrosis in dy(2J mice. These results support a putative role for the use of omigapil in laminin deficient congenital muscular dystrophy

Different flavonoids present in the micronized purified flavonoid fraction (Daflon 500 mg) contribute to its anti-hyperpermeability effect in the hamster cheek pouch microcirculation.

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Paysant, J; Sansilvestri-Morel, P; Bouskela, E; Verbeuren, T J

2008-02-01

This study evaluated microcirculatory effects of the flavonoid substances that constitute the micronized purified flavonoid fraction (MPFF) (Daflon 500 mg) in comparison to diosmin. In groups of 3 male hamsters, oral treatment with MPFF or diosmin (15 min before anesthesia) did not alter blood pressure. At 10 or 30 mg/kg, both MPFF and diosmin significantly decreased the leaky sites caused by ischemia/reperfusion (I/R) (30 min) in the hamster cheek pouch; the effect was significantly higher with MPFF (39+/-1% and 52+/-1%, respectively) than diosmin (18+/-1% and 37+/-3%, respectively). Eight groups of 3 hamsters each were treated with the components of MPFF. Diosmetin only decreased the number leaky sites at 30 mg/kg (decrease: 15+/-2%). The decrement at 10 and 30 mg/kg averaged at: 17+/-3% and 44+/-1%, respectively, for hesperidin; 19+/-1% and 46+/-2%, respectively, for linarin; and 30+/-1% and 44+/-1%, respectively, for isorhoifolin. Hesperidin, linarin, and isorhoifolin each displayed an anti-leakage effect comparable to or greater than diosmin. MPFF decreases permeability more than any of its single constituents, suggesting that the flavonoids present in its formulation have a synergistic action. These results illustrate that MPFF is more potent than single diosmin in this model of hyperpermeability and that each of the flavonoid substances present in MPFF contribute to its action.

Concentrations of tylvalosin and 3-O-acetyltylosin attained in the synovial fluid of swine after administration by oral gavage at 50 and 5 mg/kg.

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Canning, P; Bates, J; Hammen, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Karriker, L

2016-12-01

The objectives of this study were to determine the concentration of tylvalosin (TVN) and its metabolite, 3-O-acetyltylosin (3AT) in the synovial fluid of growing pigs when administered as a single bolus by oral gavage at target doses of 50 mg/kg (Trial 1) and 5 mg/kg (Trial 2). TVN is a water soluble macrolide antimicrobial used in swine production. The stability of the drug in synovial fluid samples stored at -70 °C up to 28 days was also evaluated in Trial 2. In Trial 1, eight pigs were randomly assigned to one of eight time points for euthanasia and synovial fluid collection: 0, 1, 2, 3, 4, 6, 9, 12 h postgavage. For Trial 2, 24 pigs were randomly allocated to one terminal collection time point at 0, 2, 4, 6, 8 or 10 h postgavage. Synovial fluid was analyzed to determine TVN and 3AT concentrations. TVN and 3AT were detected in Trial 1 at all time points, except 0 h. At 2 h postgavage for trial 2, the mean concentrations peaked at 31.17 ng/mL (95% CI: 18.62-52.16) for TVN and at 58.82 ng/mL (95% CI: 35.14-98.46) for 3AT. Storage duration did not impact TVN or 3AT concentrations (P-value 0.9732). © 2016 John Wiley & Sons Ltd.

Random comparison study of the clinical response to 153Sm-EDTMP 1.0 mCi/kg and 1.5 mCi/kg

International Nuclear Information System (INIS)

Pan, Z.; Zhu, S.

2001-01-01

Sixty-seven patient with painful bone metastases were randomized to two groups. Group 1 (n=34) received 1.0 mCi/kg of 153 Sm-EDTMP and group II (n=33) received 1.5 mCi/kg. All of them met inclusion criteria and there was no significantly difference between the basic conditions of two groups. After receiving 153 Sm-EDTMP intravenously, all patients were kept in close follow-up weekly with blood counting, physician visiting and collecting patient's self-filling-in diary including pain score, Karnofsky performance scale and analgesic consumption. The follow-up duration was six weeks. The final overall condition assessed by physician were graded into no change (including worse), slight relief, significant relief and complete relief. Only significant relief and complete relief were considered as effectiveness for pain relief. Haematological toxicity grade was evaluated based on the nadir of WBC ad PLT counts. The results indicated that the higher dosage group had a higher effectiveness rate (75.76%) compared to the lower dosage group (67.65%), but without statistic significance (x 2 =0.5365, 0.25 153 Sm-EDTMP could be used for those patients with better haematological function and 1.0 mCi/kg used for those patients with poorer haematological function. (author)

MgB2 and Mg1-xAlxB2 single crystals: high pressure growth and physical properties

International Nuclear Information System (INIS)

Karpinski, J.; Kazakov, S.M.; Jun, J.; Zhigadlo, N.D.; Angst, M.; Puzniak, R.; Wisniewski, A.

2004-01-01

Single crystals of MgB 2 have been grown with a high pressure cubic anvil technique. They grow via the peritectic decomposition of the MgNB 9 ternary nitride. The crystals are of a size up to 2 x 1 x 0.1 mm 3 with a weight up to 230 μg. Typically they have transition temperatures between 38 and 38.6 K with a width of 0.3-0.5 K. Investigations of the P-T phase diagram prove that the MgB 2 phase is stable at least up to 2190 deg. C at high hydrostatic pressure in the presence of Mg vapor under high pressure. Substitution of aluminum for magnesium in single crystals leads to stepwise decrease of T c . This indicates a possible appearance of superstructures or phases with different T c 's. The upper critical field decreases with Al doping

Systemic PD149163, a neurotensin receptor 1 agonist, decreases methamphetamine self-administration in DBA/2J mice without causing excessive sedation.

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Amanda L Sharpe

Full Text Available Methamphetamine (METH is a psychostimulant that exhibits significant abuse potential. Although METH addiction is a major health and societal concern, no drug is currently approved for its therapeutic management. METH activates the central dopaminergic "reward" circuitry, and with repeated use increases levels of the neuromodulatory peptide neurotensin in the nucleus accumbens and ventral tegmental area. Previous studies in rats suggest that neurotensin agonism decreases METH self-administration, but these studies did not examine the effect of neurotensin agonism on the pattern of self-administration or open field locomotion. In our studies, we established intravenous METH self-administration in male, DBA/2J mice (fixed ratio 3, 2 hr sessions and examined the effect of pretreatment with the NTS1 receptor agonist PD149163 on METH self-administration behavior. Locomotion following PD149163 was also measured up to 2 hours after injection on a rotarod and in an open field. Pretreatment with PD149163 (0.05 and 0.10 mg/kg, s.c. significantly decreased METH self-administration. The pattern of responding suggested that PD149163 decreased motivation to self-administer METH initially in the session with more normal intake in the second hour of access. Voluntary movement in the open-field was significantly decreased by both 0.05 and 0.10 mg/kg (s.c. PD149163 from 10-120 minutes after injection, but rotarod performance suggested that PD149163 did not cause frank sedation. These results suggest that a systemically delivered NTS1 receptor agonist decreases METH self-administration in mice. The pattern of self-administration suggests that PD149163 may acutely decrease motivation to self-administer METH before the drug is experienced, but cannot rule out that depression of voluntary movement plays a role in the decreased self-administration.

40 KG Sample of Fish-Clay from Stevns Klint, Denmark

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Gwozdz, R.; Hansen, H. J.; Rasmussen, K. L.

1992-07-01

In March 1986 a 50-m-long exposure of the cliff at Stevns Klint fell down and exposed about 40 square meters of Fish Clay. Due to this extraordinary event we were able to pick by hand about 50 kg black KT boundary layer material. After drying, the material was homogenized using a wooden pestle and an agate mortar. The powdered material was sieved through 200 mesh nylon gauze. The fraction larger than 200 mesh was collected and powdered again in an agate mortar. After four repetitions the amount of material with grain size less than 200 mesh was about 40 kg. The fraction larger than 200 mesh was reduced to about 7 kg. The 40-kg powder was mixed in a rotating polyethylene drum for three weeks. The material was analyzed by instrumental neutron activation analysis, atomic absorption and X-ray fluorescence analysis for about 40 elements. INAA was made on 20 aliquots with weight about 300 mg, 20 aliquots with weight about 80 mg, and 30 with weights between 10 and 20 mg. The preliminary results show that our KT boundary sample (1) is very homogeneous, (2) is very close in composition to other K-T boundary clays analyzed by us or described in the literature, and (3) has an Ir concentration of 32 +- 2 ng/g. We hope that our Fish Clay sample (termed by us "Mesozoic Midnight") after analysis in other laboratories and by other analytical methods may qualify as reference material in analytical work on boundary clay material.

Scutellaria barbata attenuates diabetic retinopathy by preventing retinal inflammation and the decreased expression of tight junction protein

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Xi-Yu Mei

2017-06-01

Full Text Available AIM: To observe the attenuation of ethanol extract of Herba Scutellaria barbata (SE against diabetic retinopathy (DR and its engaged mechanism. METHODS: C57BL/6J mice were intraperitoneally injected with streptozotocin (STZ, 55 mg/kg for 5 consecutive days to induce diabetes. The diabetic mice were orally given with SE (100, 200 mg/kg for 1mo at 1mo after STZ injection. Blood-retinal barrier (BRB breakdown was detected by using Evans blue permeation assay. Real-time polymerase chain reaction (RT-PCR, Western blot and immunofluorescence staining were used to detect mRNA and protein expression. Enzyme-linked immunosorbent assay (ELISA was used to detect serum contents of tumor necrosis factor-α (TNF-α and interleukin (IL-1β. RESULTS: SE (100, 200 mg/kg reversed the breakdown of BRB in STZ-induced diabetic mice. The decreased expression of retinal claudin-1 and claudin-19, which are both tight junction (TJ proteins, was reversed by SE. SE decreased the increased serum contents and retinal mRNA expression of TNF-α and IL-1β. SE also decreased the increased retinal expression of intercellular cell adhesion molecule-1 (ICAM-1. SE reduced the increased phosphorylation of nuclear factor kappa B (NFκB p65 and its subsequent nuclear translocation in retinas from STZ-induced diabetic mice. Results of Western blot and retinal immunofluorescence staining of ionized calcium-binding adapter molecule 1 (Iba1 demonstrated that SE abrogated the activation of microglia cells in STZ-induced diabetic mice. CONCLUSION: SE attenuates the development of DR by inhibiting retinal inflammation and restoring the decreased expression of TJ proteins including claudin-1 and claudin-19.

Comparison of 1 mg and 2 mg overnight dexamethasone suppression tests for the screening of Cushing's syndrome in obese patients.

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Sahin, Mustafa; Kebapcilar, Levent; Taslipinar, Abdullah; Azal, Omer; Ozgurtas, Taner; Corakci, Ahmet; Akgul, Emin Ozgur; Taslipinar, Mine Yavuz; Yazici, Mahmut; Kutlu, Mustafa

2009-01-01

Obesity is currently a major public health problem and one of the potential underlying causes of obesity in a minority of patients is Cushing's syndrome (CS). Traditionally, the gold standard screening test for CS is 1 mg dexamethasone overnight suppression test. However, it is known that obese subjects have high false positive results with this test. We have therefore compared the 1 mg and 2 mg overnight dexamethasone suppression tests in obese subjects. Patients whose serum cortisol after ODST was >50 nM underwent and a low-dose dexamethasone suppression test (LDDST); 24-hour urine cortisol was collected for basal urinary free cortisol (UFC). For positive results after overnight 1-mg dexamethasone suppression test we also performed the overnight 2-mg dexamethasone suppression test. We prospectively evaluated 100 patients (22 men and 78 women, ranging in age from 17 to 73 years with a body mass index (BMI) >30 kg/m2 who had been referred to our hospital-affiliated endocrine clinic because of simple obesity. Suppression of serum cortisol to suppression. Thyroid function tests, lipid profiles, homocysteine, antithyroglobulin, anti-thyroid peroxidase antibody levels, vitamin B12, folate levels, insulin resistance [by homeostasis model assessment (HOMA)] and 1.0 mg postdexamethasone (postdex) suppression cortisol levels were measured. We found an 8% false-positive rate in 1 mg overnight test and 2% in 2 mg overnight test (p=0.001). There was no correlation between the cortisol levels after ODST and other parameters. Our results indicate that the 2 mg overnight dexamethasone suppression test (ODST) is more convenient and accurate than 1-mg ODST as a screening test for excluding CS in subjects with simple obesity.

The effect of substrate temperature upon the compositions of Mg and Se in Zn{sub 1-x}Mg{sub x}Se{sub y}Te{sub 1-y} layer grown by MOVPE

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Nishio, M.; Ito, R.; Tanaka, K.; Urata, K.; Nakamura, Y.; Tanaka, T. [Department of Electrical and Electronic Engineering, Graduate School of Science and Engineering, Saga University, 1 Honjo, Saga 840-8502 (Japan); Saito, K.; Guo, Q.X. [Synchrotron Light Application Center, Saga University, 1 Honjo, Saga 840-8502 (Japan)

2014-07-15

The growth of Zn{sub 1-x}Mg{sub x}Se{sub y}Te{sub 1-y} layers was performed on (100) ZnTe substrate by metalorganic vapour phase epitaxy using dimethylzinc, bis-methylcyclopentadienyl-magnesium, diethyltelluride and diethylselenide. The effects of substrate temperature upon the compositions of Mg and Se have been investigated. The Mg composition in Zn{sub 1-x}Mg{sub x}Se{sub y}Te{sub 1-y} layer is significantly enhanced at low substrate temperature. Although the Se composition decreases with decreasing the substrate temperature, Zn{sub 1-x}Mg{sub x}Se{sub y}Te{sub 1-y} layer with a relatively high Se composition of 0.3 is obtainable at a low substrate temperature as low as 380 C. For all the layers, a two-mode behaviour with ZnTe- and MgTe-like longitudinal optical phonon modes is confirmed by Raman scattering. (copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis

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le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

2018-01-01

Objective To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Results Significantly greater weight loss (0–56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. Conclusion This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². PMID:29145215

Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene and tetryl in rats. Final report

Energy Technology Data Exchange (ETDEWEB)

Reddy, T.V.; Daniel, F.B.

1994-09-01

Toxic effects of 1,3-Dinitrobenzene (1,3-DNB) in male and female F344 rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of 1,3-DNB (0, 2.5, 10, 25, 75 and 150 mg/kg diet) for fourteen days. The average daily 1 ,3-DNB doses consumed were 0.21, 0.87, 2.02, 6.28 and 11.82 mg/kg b.w. for females and 0.21, 0.80, 1.98, 5.77 and 10.56 for males. Food consumption was significantly decreased in high dose animals of both sexes. Final body weights were not altered but relative organ weights were significantly changed in the 150 and 75 mg dose groups involving the spleen (males and females) and testes (males). Hematology and clinical chemistry studies indicated significantly increased values in both sexes relating to reticulocytes and methemoglobin in the 150 and 75 mg/kg dose groups while the red blood cell count, hemoglobin level and % hematocrit were decreased in these same groups. In addition, the levels of bilirubin, protein and albumin were increased in high dose males, Histopathological evaluations suggested that the susceptible organs for 1,3-DNB toxicity were kidneys (hyaline droplets), spleen (erythroid cell hyperplasia), brain (malacia and microgliosis), testes (seminiferous tubular degeneration). These changes were noted mainly in the 150 and 75 mg/kg dose groups except those changes involving the brain (150 mg/kg group only).

Supplementation of xanthophylls increased antioxidant capacity and decreased lipid peroxidation in hens and chicks.

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Gao, Yu-Yun; Xie, Qing-Mei; Ma, Jing-Yun; Zhang, Xiang-Bin; Zhu, Ji-Mei; Shu, Ding-Ming; Sun, Bao-Li; Jin, Ling; Bi, Ying-Zuo

2013-03-28

The present study investigated the effects of xanthophyll supplementation on production performance, antioxidant capacity (measured by glutathione peroxidase, superoxide dismutase (SOD), catalase, total antioxidant capacity (T-AOC), and reduced glutathione:oxidised glutathione ratio (GSH:GSSG)) and lipid peroxidation (measured by malondialdehyde (MDA)) in breeding hens and chicks. In Expt 1, 432 hens were fed diets supplemented with 0 (control group), 20 or 40 mg xanthophyll/kg diet. Blood samples were taken at 7, 14, 21, 28 and 35 d of the trial. Liver and jejunal mucosa were sampled at 35 d. Both xanthophyll groups improved serum SOD at 21 and 28 d, serum T-AOC at 21 d and liver T-AOC, and serum GSH:GSSG at 21, 28 and 35 d and liver GSH:GSSG. Xanthophylls also decreased serum MDA at 21 d in hens. Expt 2 was a 2 × 2 factorial design. Male chicks hatched from 0 or 40 mg in ovo xanthophyll/kg diet of hens were fed a diet containing either 0 or 40 mg xanthophyll/kg diet. Liver samples were collected at 0, 7, 14 and 21 d after hatching. Blood samples were also collected at 21 d. In ovo-deposited xanthophylls increased antioxidant capacity and decreased MDA in the liver mainly within 1 week after hatching. Maternal effects gradually vanished during 1-2 weeks after hatching. Dietary xanthophylls increased antioxidant capacity and decreased MDA in the liver and serum mainly from 2 weeks onwards. Data suggested that xanthophyll supplementation enhanced antioxidant capacity and reduced lipid peroxidation in different tissues of hens and chicks.

Maintenance on naltrexone+amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys.

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Moerke, Megan J; Banks, Matthew L; Cheng, Kejun; Rice, Kenner C; Negus, S Stevens

2017-12-01

Cocaine use disorder remains a significant public health issue for which there are no FDA-approved pharmacotherapies. Amphetamine maintenance reduces cocaine use in preclinical and clinical studies, but the mechanism of this effect is unknown. Previous studies indicate a role for endogenous opioid release and subsequent opioid receptor activation in some amphetamine effects; therefore, the current study examined the role of mu-opioid receptor activation in d-amphetamine treatment effects in an assay of cocaine-vs-food choice. Adult male rhesus monkeys with double-lumen intravenous catheters responded for concurrently available food pellets and cocaine injections (0-0.1mg/kg/injection) during daily sessions. Cocaine choice and overall reinforcement rates were evaluated during 7-day treatments with saline or test drugs. During saline treatment, cocaine maintained a dose-dependent increase in cocaine-vs.-food choice. The mu-opioid receptor agonist morphine (0.032-0.32mg/kg/h) dose-dependently increased cocaine choice and decreased rates of reinforcement. A dose of the mu-selective opioid receptor antagonist naltrexone (0.0032mg/kg/h) that completely blocked morphine effects had no effect on cocaine choice when it was administered alone, but it enhanced the effectiveness of a threshold dose of 0.032mg/kg/h amphetamine to decrease cocaine choice without also enhancing nonselective behavioral disruption by this dose of amphetamine. Conversely, the kappa-selective opioid antagonist norbinalorphimine did not enhance amphetamine effects on cocaine choice. These results suggest that amphetamine maintenance produces mu opioid-receptor mediated effects that oppose its anti-cocaine effects. Co-administration of naltrexone may selectively enhance amphetamine potency to decrease cocaine choice without increasing amphetamine potency to produce general behavioral disruption. Copyright © 2017 Elsevier B.V. All rights reserved.

Antagonistic targeting of the histamine H3 receptor decreases caloric intake in higher mammalian species.

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Malmlöf, Kjell; Hastrup, Sven; Wulff, Birgitte Schellerup; Hansen, Barbara C; Peschke, Bernd; Jeppesen, Claus Bekker; Hohlweg, Rolf; Rimvall, Karin

2007-04-15

The main purpose of this study was to examine the effects of a selective histamine H(3) receptor antagonist, NNC 38-1202, on caloric intake in pigs and in rhesus monkeys. The compound was given intragastrically (5 or 15 mg/kg), to normal pigs (n=7) and subcutaneously (1 or 0.1mg/kg) to obese rhesus monkeys (n=9). The energy intake recorded following administration of vehicle to the same animals served as control for the effect of the compound. In addition, rhesus monkey and pig histamine H(3) receptors were cloned from hypothalamic tissues and expressed in mammalian cell lines. The in vitro antagonist potencies of NNC 38-1202 at the H(3) receptors were determined using a functional GTPgammaS binding assay. Porcine and human H(3) receptors were found to have 93.3% identity at the amino acid level and the close homology between the monkey and human H(3) receptors (98.4% identity) was confirmed. The antagonist potencies of NNC 38-1202 at the porcine, monkey and human histamine H(3) receptors were high as evidenced by K(i)-values being clearly below 20 nM, whereas the K(i)-value on the rat H(3) receptor was significantly higher (56+/-6.0 nM). NNC 38-1202, given to pigs in a dose of 15 mg/kg, produced a significant (p<0.05) reduction (55%) of calorie intake compared with vehicle alone, (132.6+/-10.0 kcal/kgday versus 59.7+/-10.2 kcal/kgday). In rhesus monkeys administration of 0.1 and 1mg/kg decreased (p<0.05) average calorie intakes by 40 and 75%, respectively. In conclusion, the present study demonstrates that antagonistic targeting of the histamine H(3) receptor decreases caloric intake in higher mammalian species.

Comparison of Efficacy and Safety of Liraglutide 3.0 mg in Individuals with BMI above and below 35 kg/m²: A Post-hoc Analysis.

Science.gov (United States)

le Roux, Carel; Aroda, Vanita; Hemmingsson, Joanna; Cancino, Ana Paula; Christensen, Rune; Pi-Sunyer, Xavier

2017-01-01

To investigate whether the efficacy and safety of liraglutide 3.0 mg differed between two subgroups, BMI 27 to 3.0 mg were evaluated by testing the interaction between treatment group and baseline BMI subgroup. Significantly greater weight loss (0-56 weeks) was observed with liraglutide 3.0 mg versus placebo in all patient groups while on treatment. There was no evidence that the weight-lowering effect of liraglutide 3.0 mg differed between BMI subgroups (interaction p > 0.05). Similarly, for most secondary endpoints significantly greater improvements were observed with liraglutide 3.0 mg versus placebo, with no indication treatment effects differing between subgroups. The safety profile of liraglutide 3.0 mg was broadly similar across BMI subgroups. This post-hoc analysis did not indicate any differences in the treatment effects, or safety profile, of liraglutide 3.0 mg for individuals with BMI 27 to 3.0 mg can therefore be considered for individuals with a BMI of ≥35 as well as for those with a BMI of 27 to <35 kg/m². © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer.

Science.gov (United States)

Ide, Hisamitsu; Lu, Yan; Noguchi, Takahiro; Muto, Satoru; Okada, Hiroshi; Kawato, Suguru; Horie, Shigeo

2018-04-01

Intratumoral androgen biosynthesis has been recognized as an essential factor of castration-resistant prostate cancer. The present study investigated the effects of curcumin on the inhibition of intracrine androgen synthesis in prostate cancer. Human prostate cancer cell lines, LNCaP and 22Rv1 cells were incubated with or without curcumin after which cell proliferation was measured at 0, 24, 48 and 72 hours, respectively. Prostate tissues from the transgenic adenocarcinoma of the mouse prostate (TRAMP) model were obtained after 1-month oral administration of 200 mg/kg/d curcumin. Testosterone and dihydrotestosterone concentrations in LNCaP prostate cancer cells were determined through LC-MS/MS assay. Curcumin inhibited cell proliferation and induced apoptosis of prostate cancer cells in a dose-dependent manner. Curcumin decreased the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 in prostate cancer cell lines, supporting the decrease of testosterone production. After 1-month oral administration of curcumin, Aldo-Keto reductase 1C2 (AKR1C2) expression was elevated. Simultaneously, decreased testosterone levels in the prostate tissues were observed in the TRAMP mice. Meanwhile, curcumin treatments considerably increased the expression of AKR1C2 in prostate cancer cell lines, supporting the decrease of dihydrotestosterone. Taken together, these results suggest that curcumin's natural bioactive compounds could have potent anticancer properties due to suppression of androgen production, and this could have therapeutic effects on prostate cancer. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Neutron activation analysis of Ca, Cl, K, Mg, Mn, Na, P, and Sr contents in the crowns of human permanent teeth

International Nuclear Information System (INIS)

Zaichick, V.

2009-01-01

The effect of age and gender on chemical element contents in intact crowns of permanent teeth of 84 apparently healthy 15-55 year old women (n 38) and men (n = 46) was investigated. Mass fractions of Ca, Cl, K, Mg, Mn, Na, P, and Sr in crowns were determined by instrumental neutron activation analysis using short-lived radionuclides. Mean values (M ± SEL) for female and male combined were (on dry weight basis): 350 ± 5 g/kg, 2920± 150 mg/kg, 839 ± 80 mg/kg, 4880 ± 240 mg/kg, 3.20 ± 0.30 mg/kg, 6240 ± 140 mg/kg, 181 ± 4 g/kg, and 293 ± 24 mg/kg respectively. A statistically significant decrease of Sr (P ≤ 0.01) and increase of Na (P ≤ 0.01) content in the tooth crowns with age was found for women. Sex-related comparison did not show any differences. (author)

Adequacy of a hospital-wide standard dose of 7mg/kg bodyweight gentamicin sufficient to achieve an adequate prophylactic maximum serum concentration (Cmax) in burn patients undergoing surgical burn wound treatment

NARCIS (Netherlands)

Borra, L.C.P.; Bosch, T.M.; Baar, M.E. van; Dokter, J.; Oen, I.M.; Ruijgrok, E.J.

2016-01-01

INTRODUCTION: Pharmacokinetics of drugs can be significantly altered in burn patients. The aim of our study was to validate if the current hospital-wide standard dosage of 7mg/kg total bodyweight gentamicin is sufficient to achieve an adequate prophylactic Cmax (Cmax>/=20mg/L). MATERIALS AND

Mg-doped VO2 nanoparticles: hydrothermal synthesis, enhanced visible transmittance and decreased metal-insulator transition temperature.

Science.gov (United States)

Zhou, Jiadong; Gao, Yanfeng; Liu, Xinling; Chen, Zhang; Dai, Lei; Cao, Chuanxiang; Luo, Hongjie; Kanahira, Minoru; Sun, Chao; Yan, Liuming

2013-05-28

This paper reports the successful preparation of Mg-doped VO2 nanoparticles via hydrothermal synthesis. The metal-insulator transition temperature (T(c)) decreased by approximately 2 K per at% Mg. The Tc decreased to 54 °C with 7.0 at% dopant. The composite foils made from Mg-doped VO2 particles displayed excellent visible transmittance (up to 54.2%) and solar modulation ability (up to 10.6%). In addition, the absorption edge blue-shifted from 490 nm to 440 nm at a Mg content of 3.8 at%, representing a widened optical band gap from 2.0 eV for pure VO2 to 2.4 eV at 3.8 at% doping. As a result, the colour of the Mg-doped films was modified to increase their brightness and lighten the yellow colour over that of the undoped-VO2 film. A first principle calculation was conducted to understand how dopants affect the optical, Mott phase transition and structural properties of VO2.

Anti-Inflammatory Effect of Red Piper Crocatum Leaves Extract Decrease TNF-α and IL-6 Levels in Wistar Rat with Atherosclerosis

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Sri Wahjuni

2016-05-01

Full Text Available Background: This research aims to find a cure for anti-inflammation, based on the utilization of red piper crocatum. The research was started with descriptive study to explore active components of red piper crocatum leaf and followed by experimental study to investigate red piper crocatum activity of the leaf extract in anti-inflammation induced Wistar rat. In this research observed three dominant components: caryophyllene bicyclo [5.2.0] none,2 methylene-4,8,8-trimethyl-4-vinyl; phytol; 5,9-propano-5H-benzocycloheptene,6,7,8,9-tetrahydro-7,11-bis(methylene; 4,4-ethynedioxy-2-hexadecen-15-15 olide 1,4,9-trioxaspiro [4,15] eic os-6-en-8-one, 10 methyl; 1H-1,2,4-triazole-5(H-thione,4-allyl-3-(3-furyl; Benzofuran,2,3-dihydro-2-methyl-7-phenyl which are possibly active to inhibit anti-inflammation to atherosclerosis. Bad eating habits also can cause various health problems, such as obesity, dyslipidemia, inflammation to atherosclerosis. This study was conducted to investigate of red piper crocatum leaves extract as an anti-inflammation through decrease of biochemistry markers TNF-α and IL-6 levels. Method: This is a true experimental with randomized pre-test and post-test control group design, using 50 Wistar rats that are divided into 5 groups: control group using 0 mg/kg BW red piper crocatum leaves extract, treatment group 1 using 50 mg/kg BW red piper crocatum leaves extract, treatment group 2 using 100 mg/kg BW red piper crocatum leaves extract, treatment group 3 using 150 mg/kg BW red piper crocatum leaves extract, and treatment group 4 200mg/kg BW red piper crocatum leaves extract. Results: It was observed that intake of 150 mg/BW red piper crocatum leaves extract results in the highest significance decrease of 45.63% of TNF-α levels from (28.62 ± 1.25 to 15.56 ± 7.20 рg/mL and a significance decrease of 15.42% of IL-6 level from (134.64 ± 1.98 to 113.87 ± 4.30 рg/mL. Conclusion: It can be concluded that intake of red piper crocatum

Possible involvement of dopamine D-1 and D-2 receptors in diazepam-induced hyperphagia in rats.

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Naruse, T; Amano, H; Koizumi, Y

1991-01-01

Possible involvement of dopamine receptors in diazepam-induced (1 mg/kg, subcutaneous (sc] hyperphagia was studied in nondeprived rats. Pretreatment with the selective D-1 antagonist, SCH23390 (0.03 mg/kg, sc) inhibited diazepam-induced hyperphagia. In addition, pretreatment with the preferential D-2 antagonists, haloperidol (0.1 to 0.3 mg/kg, sc) and clebopride (0.1 to 0.3 mg/kg, sc) inhibited diazepam-induced hyperphagia in a dose-dependent manner. Pretreatment with co-administration of SCH23390 (0.1 mg/kg, sc) and clebopride (0.03 mg/kg, sc) completely inhibited this hyperphagia. The selective D-2 antagonist, sulpiride (40 mg/kg, sc) and the peripheral D-2 antagonist, domperidone (10 mg/kg, sc) did not affect diazepam-induced hyperphagia. However, sulpiride (10 micrograms, icv) or domperidone (2 micrograms, icv) administered centrally inhibited this hyperphagia. The highest dose of haloperidol (0.3 mg/kg, sc) or clebopride (0.3 mg/kg, sc) and higher doses of SCH23390 (0.01 and 0.03 mg/kg, sc) or SCH23390/clebopride (0.01/0.03 and 0.01/0.1 mg/kg, sc) tended to decrease spontaneous feeding in non-deprived rats. In addition, the highest dose of haloperidol, clebopride or SCH23390/clebopride inhibited spontaneous feeding in deprived rats. Interestingly, diazepam-induced hyperphagia was inhibited significantly by doses of haloperidol (0.1 mg/kg, sc), clebopride (0.1 mg/kg, sc) and SCH23390/clebopride (0.003/0.03 and 0.003/0.1 mg/kg, sc) which did not affect spontaneous feeding in non-deprived or deprived rats. Pretreatment with alpha-methyl-p-tyrosine (40 mg/kg, IP x 2, 6 and 2 h prior to diazepam administration) failed to inhibit this hyperphagia. Furthermore, pretreatment with a large dose of haloperidol (5 mg/kg, sc, 4 days before diazepam administration) augmented the sub-hyperphagic effect to diazepam (0.5 mg/kg, sc). Thus, these findings suggest that hyperphagia to diazepam is mediated in part by both dopamine D-1 and D-2 receptors in non-deprived rats.

NFKB activity decreased in BALB/c mice with high fat diet and fructose

Science.gov (United States)

Nur'aini, Farida Dewi; Rahayu, Sri; Rifa'i, Muhaimin

2017-05-01

Excessive consumption of fat and fructose leads to obesity due to lipid accumulation. The excessive lipid causes hypertrophy in the adipocytes which lead to cell death. Consequently, dead adipocytes will produce adipokines, which cause macrophages and lymphocytes to infiltrate into the adipose tissue, elevating pro-inflammatory cytokines, thus triggering the production of pro-inflammatory cytokines through NFκB activity. Elicited soybeans extract (ESE) with bacteria and light contain Glyceollin and Isoflavones, which inhibit the activation of NFKB and reduce plasma cholesterol levels by upregulating cholesterol metabolism. This study aimed to analyze the effect of ESE against the relative number of CD4+ NFκB+ cells in BALB/c mice spleen after administrated by high-fat diet food and fructose (HFD) for 20 weeks. Mice were given orally with ESE after administrated by HFD at dose 78 mg/kgBW (D1), 104 mg/kgBW (D2), and 130 mg/kgBW (D3) for 4 weeks. This study also used positive control (HFD mice model without ESE treatment) and normal mice. Identification of NFKB activation was conducted using Flowcytometry analytical methods. Our result indicated that ESE could decrease significantly activation of NFκB in CD4 cell compare than positive control. The optimum dose that can decrease the relative number of CD4+ NFκB+ cells is dose 3.

Decreasing the infusion rate reduces the proarrhythmic risk of NS-7

DEFF Research Database (Denmark)

Detre, Elke; Thomsen, Morten Bækgaard; Beekman, Jet D

2005-01-01

1 The rate of infusion has been suggested to be important for drug-induced torsades de pointes (TdP) arrhythmias. We investigated the repolarisation-prolonging effects and proarrhythmic properties of NS-7, a neuroprotective drug in development, using two different infusion rates. 2 A fast (5 min...... intravenously (i.v.)) escalating dosing regimen (0.3 and 3.0 mg kg(-1), n=4) of NS-7 was investigated in anaesthetised control dogs in sinus rhythm (SR). This was compared to a slow infusion (60 min i.v.) of one dose (3.0 mg kg(-1), n=4) NS-7. The similar dosing regimens were investigated in anaesthetised dogs...... with chronic, complete AV block (CAVB), an animal model of TdP (n=6). 3 No electrophysiological effects were seen after 0.3 mg kg(-1) NS-7. Fast infusion of 3.0 mg kg(-1) caused prolongation of repolarisation, for example, heart rate corrected QT interval (QT(c)): in SR: 6+/-1%; in CAVB: 10+/-7%, which...

Arbuscular mycorrhizal fungi can decrease the uptake of uranium by subterranean clover grown at high levels of uranium in soil

International Nuclear Information System (INIS)

Rufyikiri, Gervais; Huysmans, Lien; Wannijn, Jean; Hees, May van; Leyval, Corinne; Jakobsen, Iver

2004-01-01

Subterranean clover inoculated or not with the arbuscular mycorrhizal (AM) fungus Glomus intraradices was grown on soil containing six levels of 238 U in the range 0-87 mg kg -1 . Increasing U concentration in soil enhanced the U concentration in roots and shoots of both mycorrhizal and nonmycorrhizal plants but had no significant effects on plant dry matter production or root AM colonization. Mycorrhizas increased the shoot dry matter and P concentration in roots and shoots, while in most cases, it decreased the Ca, Mg and K concentrations in plants. The AM fungus influenced U concentration in plants only in the treatment receiving 87 mg U kg -1 soil. In this case, U concentration in shoots of nonmycorrhizal plants was 1.7 times that of shoots of mycorrhizal plants. These results suggested that mycorrhizal fungi can limit U accumulation by plants exposed to high levels of U in soil. - Plant mycorrhization may decrease U concentration in shoots of plants grown at high level of U in soil

Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

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Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

1999-12-01

The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary

Supplementation of xanthophylls decreased proinflammatory and increased anti-inflammatory cytokines in hens and chicks.

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Gao, Yu-Yun; Xie, Qing-Mei; Jin, Ling; Sun, Bao-Li; Ji, Jun; Chen, Feng; Ma, Jing-Yun; Bi, Ying-Zuo

2012-11-28

The present study investigated the effects of xanthophylls (containing 40 % of lutein and 60 % of zeaxanthin) on proinflammatory cytokine (IL-1β, IL-6, interferon (IFN)-γ and lipopolysaccharide-induced TNF-α factor (LITAF)) and anti-inflammatory cytokine (IL-4 and IL-10) expression of breeding hens and chicks. In Expt 1, a total of 432 hens were fed diets supplemented with 0 (as the control group), 20 or 40 mg/kg xanthophylls (six replicates per treatment). The liver, duodenum, jejunum and ileum were sampled at 35 d of the trial. The results showed that both levels of xanthophyll addition decreased IL-1β mRNA in the liver and jejunum, IL-6 mRNA in the liver, IFN-γ mRNA in the jejunum and LITAF mRNA in the liver compared to the control group. Expt 2 was a 2 × 2 factorial design. Male chicks hatched from 0 or 40 mg/kg xanthophyll diet of hens were fed a diet containing either 0 or 40 mg/kg xanthophylls. The liver, duodenum, jejunum and ileum were collected at 0, 7, 14 and 21 d after hatching. The results showed that in ovo xanthophylls decreased proinflammatory cytokine expression (IL-1β, IL-6, IFN-γ and LITAF) in the liver, duodenum, jejunum and ileum and increased anti-inflammatory cytokine expression (IL-4 and IL-10) in the liver, jejunum and ileum mainly at 0-7 d after hatching. In ovo effects gradually vanished and dietary effects began to work during 1-2 weeks after hatching. Dietary xanthophylls modulated proinflammatory cytokines (IL-1β, IL-6 and IFN-γ) in the liver, duodenum, jejunum and ileum and anti-inflammatory cytokine (IL-10) in the liver and jejunum mainly from 2 weeks onwards. In conclusion, xanthophylls could regulate proinflammatory and anti-inflammatory cytokine expression in different tissues of hens and chicks.

Luminescent and structural properties of Zn_xMg_1_-_xWO_4 mixed crystals

International Nuclear Information System (INIS)

Krutyak, N.; Nagirnyi, V.; Spassky, D.; Tupitsyna, I.; Dubovik, A.; Belsky, A.

2016-01-01

The structural and luminescent properties of perspective scintillating Zn_xMg_1_-_xWO_4 mixed crystals were studied. The following characteristics were found to depend linearly on x value: the energy of several vibrational modes detected by Raman spectroscopy, the bandgap width deduced from the shift of the excitation spectrum onset of a self-trapped exciton (STE) emission, the position of thermally stimulated luminescence peaks. It is also shown that the thermal stability of the STE luminescence decreases gradually when x decreases. These data indicate that each Zn_xMg_1_-_xWO_4 mixed crystal is not a mixture of two constituents, but possesses its original crystalline structure, as well as optical and luminescent properties. - Highlights: • The structural and luminescent properties of Zn_xMg_1_-_xWO_4 were studied. • The energy of Raman modes, the bandgap width, TSL peak position linearly depend on x. • Each Zn_xMg_1_-_xWO_4 possesses its original crystalline structure.

ATR-101, a selective ACAT1 inhibitor, decreases ACTH-stimulated cortisol concentrations in dogs with naturally occurring Cushing's syndrome.

Science.gov (United States)

Langlois, Daniel K; Fritz, Michele C; Schall, William D; Bari Olivier, N; Smedley, Rebecca C; Pearson, Paul G; Bailie, Marc B; Hunt, Stephen W

2018-05-02

Cushing's syndrome in humans shares many similarities with its counterpart in dogs in terms of etiology (pituitary versus adrenal causes), clinical signs, and pathophysiologic sequelae. In both species, treatment of pituitary- and adrenal-dependent disease is met with limitations. ATR-101, a selective inhibitor of ACAT1 (acyl coenzyme A:cholesterol acyltransferase 1), is a novel small molecule therapeutic currently in clinical development for the treatment of adrenocortical carcinoma, congenital adrenal hyperplasia, and Cushing's syndrome in humans. Previous studies in healthy dogs have shown that ATR-101 treatment led to rapid, dose-dependent decreases in adrenocorticotropic hormone (ACTH) stimulated cortisol levels. The purpose of this clinical study was to investigate the effects of ATR-101 in dogs with Cushing's syndrome. ATR-101 pharmacokinetics and activity were assessed in 10 dogs with naturally-occurring Cushing's syndrome, including 7 dogs with pituitary-dependent disease and 3 dogs with adrenal-dependent disease. ATR-101 was administered at 3 mg/kg PO once daily for one week, followed by 30 mg/kg PO once daily for one (n = 4) or three (n = 6) weeks. Clinical, biochemical, adrenal hormonal, and pharmacokinetic data were obtained weekly for study duration. ATR-101 exposure increased with increasing dose. ACTH-stimulated cortisol concentrations, the primary endpoint for the study, were significantly decreased with responders (9 of 10 dogs) experiencing a mean ± standard deviation reduction in cortisol levels of 50 ± 17% at study completion. Decreases in pre-ACTH-stimulated cortisol concentrations were observed in some dogs although overall changes in pre-ACTH cortisol concentrations were not significant. The compound was well-tolerated and no serious drug-related adverse effects were reported. This study highlights the potential utility of naturally occurring canine Cushing's syndrome as a model for human disease and provides proof of

Microstructural evolution in Mg-rich Mg-Zn-Y alloys

International Nuclear Information System (INIS)

Biswas, T.; Ranganathan, S.; Nair, S.; Bajargan, G.

2005-01-01

Mg-rich Mg-Zn-Y alloys with nominal compositions Mg 97 Zn 1 Y 2 , Mg 97 Zn 2 Y 1 , Mg 92 Zn 6.5 Y 1.5 and Mg 97-x Zn 1 Y 2 Zr x have been chosen for the present study. These alloys are prepared by using sand casting mold. The sand cast alloys are remelted and subjected to copper mold casting and melt spinning techniques. The effect of cooling rate on microstructures was studied. It is observed that the size of the precipitates decreases with an increase of cooling rate. The formation of nano precipitates results in higher strength of the alloy as compared to the conventional alloys. The microstructures of melt spun ribbons are compared with RS/PM (rapidly solidified power metallurgy) Mg 97 Zn 1 Y 2 alloy, obtained from a different source. (author)

Performance of Mg-14Li-1Al-0.1Ce as anode for Mg-air battery

Energy Technology Data Exchange (ETDEWEB)

Ma, Yibin; Li, Deyu [School of Chemical Engineering and Technology, Harbin Institute of Technology, West Street No. 92, Harbin 150001 (China); Li, Ning [School of Chemical Engineering and Technology, Harbin Institute of Technology, West Street No. 92, Harbin 150001 (China); Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin Engineering University, Harbin 150001 (China); Zhang, Milin; Huang, Xiaomei [Key Laboratory of Superlight Materials and Surface Technology, Ministry of Education, Harbin Engineering University, Harbin 150001 (China)

2011-02-15

In this research, a new Mg-air battery based on Mg-14Li-1Al-0.1Ce was prepared and the battery performance was investigated by constant current discharge test. The corrosion behavior of Mg, AZ31 and Mg-Li-Al-Ce were studied by self-corrosion rate measurement and potentiodynamic polarization measurement. The characteristics of Mg-Li-Al-Ce after discharge were investigated by electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results show that Mg-Li-Al-Ce is more active than Mg and AZ31. The self-corrosion rate is found to be in the order: Mg-Li-Al-Ce < Mg < AZ31. It has been observed that the Mg-air battery based on Mg-Li-Al-Ce offers higher operating voltage, anodic efficiency and capacity than those with Mg and AZ31. SEM and EIS results show that the discharge product of Mg-Li-Al-Ce is loosely adhered to the alloy surface, and thus Mg-Li-Al-Ce could keep high discharge activity during discharge. (author)

A temporary decrease in twitch response during reversal of rocuronium-induced muscle relaxation with a small dose of sugammadex

NARCIS (Netherlands)

Eleveld, Douglas J.; Kuizenga, Karel; Proost, Johannes H.; Wierda, J. Mark K. H.

BACKGROUND: We present a case in which a temporary decrease in train-of-four (TOF) response was observed after reversal of muscle relaxation with a small dose (0.5 mg/kg) of sugammadex administered 42 min after 0.9 mg/kg of rocuronium. At the end of the operation, the TOF ratio was > 0.9, and the

Beneficial metabolic effects of CB1R anti-sense oligonucleotide treatment in diet-induced obese AKR/J mice.

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Yuting Tang

Full Text Available An increasing amount of evidence supports pleiotropic metabolic roles of the cannibinoid-1 receptor (CB1R in peripheral tissues such as adipose, liver, skeletal muscle and pancreas. To further understand the metabolic consequences of specific blockade of CB1R function in peripheral tissues, we performed a 10-week-study with an anti-sense oligonucleotide directed against the CB1R in diet-induced obese (DIO AKR/J mice. DIO AKR/J mice were treated with CB1R ASO Isis-414930 (6.25, 12.5 and 25 mg/kg/week or control ASO Isis-141923 (25 mg/kg/week via intraperitoneal injection for 10 weeks. At the end of the treatment, CB1R mRNA from the 25 mg/kg/week CB1R ASO group in the epididymal fat and kidney was decreased by 81% and 63%, respectively. Body weight gain was decreased in a dose-dependent fashion, significantly different in the 25 mg/kg/week CB1R ASO group (46.1±1.0 g vs veh, 51.2±0.9 g, p<0.05. Body fat mass was reduced in parallel with attenuated body weight gain. CB1R ASO treatment led to decreased fed glucose level (at week 8, 25 mg/kg/week group, 145±4 mg/dL vs veh, 195±10 mg/dL, p<0.05. Moreover, CB1R ASO treatment dose-dependently improved glucose excursion during an oral glucose tolerance test, whereas control ASO exerted no effect. Liver steatosis was also decreased upon CB1R ASO treatment. At the end of the study, plasma insulin and leptin levels were significantly reduced by 25 mg/kg/week CB1R ASO treatment. SREBP1 mRNA expression was decreased in both epididymal fat and liver. G6PC and fatty acid translocase/CD36 mRNA levels were also reduced in the liver. In summary, CB1R ASO treatment in DIO AKR/J mice led to improved insulin sensitivity and glucose homeostasis. The beneficial effects of CB1R ASO treatment strongly support the notion that selective inhibition of the peripheral CB1R, without blockade of central CB1R, may serve as an effective approach for treating type II diabetes, obesity and the metabolic syndrome.

Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

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Ayyalasomayajula Vajreswari

2011-06-01

Full Text Available Abstract Background 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat. Results Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα, the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα, a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly

Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia.

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Abbie Chapman Johnson

Full Text Available Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4 is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP was combined with a high cholesterol diet (HC to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg required to elicit seizure in RUPP + HC ± MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20. RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼ 65% lower vs. control (12.4 ± 1.7 vs. 36.7 ± 3.9 mg/kg PTZ; p<0.05 that was reversed by MgSO4 (45.7 ± 8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC. BBB permeability to sodium fluorescein, measured in-vivo (n = 5-7/group, was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9 ± 1.0 vs. 12.2 ± 0.3 counts/gram ×1000; p<0.05 and was unaffected by MgSO4 (15.6 ± 1.0 counts/gram ×1000; p<0.05 vs. controls. In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35 ± 2% of microglia being active compared to 9 ± 2% in normal pregnancy (p<0.01; n = 3-8/group. MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6 ± 2% (p<0.01 vs. RUPP+HC. Overall, RUPP+HC rats were in a state of augmented

Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

International Nuclear Information System (INIS)

Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka; Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

2015-01-01

Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3 + apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB + interneurons, although the number of reelin + interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of cholinergic

Cuprizone decreases intermediate and late-stage progenitor cells in hippocampal neurogenesis of rats in a framework of 28-day oral dose toxicity study

Energy Technology Data Exchange (ETDEWEB)

Abe, Hajime; Tanaka, Takeshi; Kimura, Masayuki; Mizukami, Sayaka [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193 (Japan); Saito, Fumiyo; Imatanaka, Nobuya; Akahori, Yumi [Chemicals Evaluation and Research Institute, Japan, 1-4-25 Koraku, Bunkyo-ku, Tokyo 112-0004 (Japan); Yoshida, Toshinori [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan); Shibutani, Makoto, E-mail: mshibuta@cc.tuat.ac.jp [Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509 (Japan)

2015-09-15

Developmental exposure to cuprizone (CPZ), a demyelinating agent, impairs intermediate-stage neurogenesis in the hippocampal dentate gyrus of rat offspring. To investigate the possibility of alterations in adult neurogenesis following postpubertal exposure to CPZ in a framework of general toxicity studies, CPZ was orally administered to 5-week-old male rats at 0, 120, or 600 mg/kg body weight/day for 28 days. In the subgranular zone (SGZ), 600 mg/kg CPZ increased the number of cleaved caspase-3{sup +} apoptotic cells. At ≥ 120 mg/kg, the number of SGZ cells immunoreactive for TBR2, doublecortin, or PCNA was decreased, while that for SOX2 was increased. In the granule cell layer, CPZ at ≥ 120 mg/kg decreased the number of postmitotic granule cells immunoreactive for NEUN, CHRNA7, ARC or FOS. In the dentate hilus, CPZ at ≥ 120 mg/kg decreased phosphorylated TRKB{sup +} interneurons, although the number of reelin{sup +} interneurons was unchanged. At 600 mg/kg, mRNA levels of Bdnf and Chrna7 were decreased, while those of Casp4, Casp12 and Trib3 were increased in the dentate gyrus. These data suggest that CPZ in a scheme of 28-day toxicity study causes endoplasmic reticulum stress-mediated apoptosis of granule cell lineages, resulting in aberrations of intermediate neurogenesis and late-stage neurogenesis and following suppression of immediate early gene-mediated neuronal plasticity. Suppression of BDNF signals to interneurons caused by decreased cholinergic signaling may play a role in these effects of CPZ. The effects of postpubertal CPZ on neurogenesis were similar to those observed with developmental exposure, except for the lack of reelin response, which may contribute to a greater decrease in SGZ cells. - Highlights: • Effect of 28-day CPZ exposure on hippocampal neurogenesis was examined in rats. • CPZ suppressed intermediate neurogenesis and late-stage neurogenesis in the dentate gyrus. • CPZ suppressed BDNF signals to interneurons by decrease of

Effects of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in Wistar rats.

Science.gov (United States)

Olatunji, Lawrence A; Usman, Taofeek O; Adebayo, Joseph O; Olatunji, Victoria A

2012-09-01

To investigate the effects of oral administration of aqueous extract of Hibiscus sabdariffa on renal Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in rats. The 25 and 50 mg/(kg·d) of aqueous extracts of H. sabdariffa were respectively given to rats in the experimental groups for 28 d, and rats in the control group received an appropriate volume of distilled water as vehicle. Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase activities in the kidney were assayed by spectrophotometric method. Administrations of 25 and 50 mg/(kg·d) of aqueous extract of H. sabdariffa significantly decreased the Ca(2+)-Mg(2+)-ATPase activity in the kidney of rats (Psabdariffa may preserve the renal function despite a decreased renal Ca(2+)-Mg(2+)-ATPase activity.

Dietary Lecithin Decreases Skeletal Muscle COL1A1 and COL3A1 Gene Expression in Finisher Gilts

Directory of Open Access Journals (Sweden)

Henny Akit

2016-06-01

Full Text Available The purpose of this study was to investigate the effect of dietary lecithin on skeletal muscle gene expression of collagen precursors and enzymes involved in collagen synthesis and degradation. Finisher gilts with an average start weight of 55.9 ± 2.22 kg were fed diets containing either 0, 4, 20 or 80 g/kg soybean lecithin prior to harvest for six weeks and the rectus abdominis muscle gene expression profile was analyzed by quantitative real-time PCR. Lecithin treatment down-regulated Type I (α1 procollagen (COL1A1 and Type III (α1 procollagen (COL3A1 mRNA expression ( p < 0.05, respectively, indicating a decrease in the precursors for collagen synthesis. The α-subunit of prolyl 4-hydroxylase (P4H mRNA expression also tended to be down-regulated ( p = 0.056, indicating a decrease in collagen synthesis. Decreased matrix metalloproteinase-1 (MMP-1 mRNA expression may reflect a positive regulatory response to the reduced collagen synthesis in muscle from the pigs fed lecithin ( p = 0.035. Lecithin had no effect on tissue inhibitor metalloproteinase-1 (TIMP-1, matrix metalloproteinase-13 (MMP-13 and lysyl oxidase mRNA expression. In conclusion, lecithin down-regulated COL1A1 and COL3A1 as well as tended to down-regulate α-subunit P4H expression. However, determination of muscle collagen content and solubility are required to support the gene functions.

Interaction between behavioral and pharmacological treatment strategies to decrease cocaine choice in rhesus monkeys.

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Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

2013-02-01

Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently, the FR response requirement for cocaine or food was varied (food, FR 100; cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine on cocaine vs food choice were redetermined. Decreases in the cocaine FR or increases in the food FR resulted in leftward shifts in the cocaine choice dose-effect curve, whereas increases in the cocaine FR or decreases in the food FR resulted in rightward shifts in the cocaine choice dose-effect curve. The efficacy of phenmetrazine to decrease cocaine choice varied systematically as a function of the prevailing response requirements, such that phenmetrazine efficacy was greatest when cocaine choice was maintained by relatively low unit cocaine doses. These results suggest that efficacy of pharmacotherapies to modulate cocaine use can be influenced by behavioral contingencies of cocaine availability. Agonist medications may be most effective under contingencies that engender choice of relatively low cocaine doses.

Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

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Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

2010-10-27

Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

Silymarin and caffeine combination ameliorates experimentally-induced hepatic fibrosis through down-regulation of LPAR1 expression.

Science.gov (United States)

Eraky, Salma M; El-Mesery, Mohamed; El-Karef, Amro; Eissa, Laila A; El-Gayar, Amal M

2018-05-01

Lysophosphatidic acid is a lipid mediator that is supposed to be implicated in hepatic fibrosis. Silymarin and caffeine are natural compounds known for their anti-inflammatory and antioxidant effects. Our study aimed to explore the effect of silymarin, caffeine, and their combination on lysophosphatidic acid receptor 1 (LPAR1) pathway in thioacetamide (TAA)-induced hepatic fibrosis. Hepatic fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 200 mg/kg of TAA twice a week for 8 weeks. Silymarin (50 mg/kg), caffeine (50 mg/kg), and their combination (50 mg/kg silymarin + 50 mg/kg caffeine) were orally given to rats every day for 8 weeks along with TAA injection. Liver functions were measured. Histopathological examination of liver tissues was performed using hematoxylin and eosin and Masson's trichrome staining. mRNA expressions of LPAR1, transforming growth factor beta 1 (TGF-β1), connective tissue growth factor (CTGF), and alpha smooth muscle actin (α-SMA) were measured using RT-PCR. LPAR1 tissue expression was scored using immunohistochemistry. Silymarin, caffeine, and their combination significantly improved liver function. They caused significant decrease in fibrosis and necro-inflammatory scores. Combination of silymain and caffeine caused a significant decrease in the necro-inflammatory score than the single treatment with silymarin or caffeine. In addition, silymarin, caffeine, and their combination significantly decreased hepatic LPAR1, TGF-β1, CTGF, and α-SMA gene expressions and LPAR1 tissue expression. Silymarin, caffeine, and their combination protect against liver fibrosis through down-regulation of LPAR1, TGF-β1, and CTGF. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Avaliação da tolerância e nefrotoxicidade do antimonial pentavalente administrado na dose de 40mg Sb v/kg/dia, de 12/12h, por 30 dias na forma cutaneo-mucosa de leishmaniose

Directory of Open Access Journals (Sweden)

Raimunda N.R. Sampaio

1997-12-01

Full Text Available Foi avaliada a função renal de 11 pacientes com leishmaniose cutâneo-mucosa tratados com antimonial pentavalente na dose de 40mg SbV/kg/dia aplicada de 12/12 horas, em esquema contínuo, durante trinta dias. No estudo, um paciente apresentou insuficiência renal reversível e dois desenvolveram alterações enzimáticas hepáticas e eletrocardiográficas sendo o esquema terapêutico interrompido. Nos demais pacientes observou-se efeitos nefrotóxicos tais como diminuição da taxa de filtração glomerular, diminuição da capacidade de concentração urinária, avaliada por um jejum hídrico de 16 horas e aumento na fração de excreção de sódio. No exame do sedimento urinário observou-se um aumento no número de leucócitos e cilindros. Os resultados encontrados neste estudo sugerem que o tratamento com antimonial pentavalente na dose de 40mg SbV/kg/dia foi menos tolerado em virtude de seus efeitos tóxicos, não parecendo apresentar índice de cura superior ao esquema atualmente preconizado de 20mg SbV/kg/dia.The renal function of eleven patients with mucocutaneous leishmaniasis was analyzed in a prospective study realized at the School Hospital of University of Brasília. The patients were treated with doses of 40mg/kg/day of pentavalent antimony (SbV, in a continuous scheme during thirty days. In this study three patients were excluded, one patient with reversible renal failure and two patients with hepatic and cardiac malfunctions. In the other eight patients, severe nephrotoxics effects were observed, like reduction of glomerular filtration rate, reduction of the urinary concentration capacity, evaluated by a sixteen hours hydric fasting and an increase of sodium fractional excretion. An increase in the number of leucocytes and cylinders were observed at the urinary sediment exam. Finally, the results shows that the treatment with pentavalent antimony in doses of 40mg Sb/kg/day was less tolerated on account of its renal toxics

Comparative trial of two intravenous doses of granisetron (1 versus 3 mg) in the prevention of chemotherapy-induced acute emesis: a double-blind, randomized, non-inferiority trial.

Science.gov (United States)

Tsuji, Daiki; Kim, Yong-Il; Taku, Keisei; Nakagaki, Shigeru; Ikematsu, Yoshito; Tsubota, Hiromi; Maeda, Masato; Hashimoto, Naoya; Kimura, Masayuki; Daimon, Takashi

2012-05-01

A single 3 mg or 40 μg/kg intravenous dose of granisetron combined with dexamethasone is routinely used in several countries, although the antiemetic guidelines have recommended granisetron at the dose of 1 mg or 10 μg/kg. A randomized, multicenter trial was conducted to determine the optimal intravenous granisetron dose, 1 or 3 mg, in cancer patients receiving emetogenic chemotherapy. We enrolled 365 patients and randomly assigned them to receive intravenous granisetron 3 mg (3-mg group) or 1 mg (1-mg group), combined with dexamethasone at an adequate dose fixed as per the emetic risk category. The primary end point was the proportion of patients with a complete response during the first 24 h after chemotherapy. The study demonstrated that 1 mg of granisetron was not inferior in effect to 3 mg. For the primary end point, 359 patients were evaluable according to the modified intention-to-treat (ITT) analysis. Complete protection was achieved in the modified ITT population, 90.6% and 88.8% for the 3- and 1-mg groups, respectively (p granisetron is not inferior to 3 mg when both doses are combined with dexamethasone. Therefore, 1-mg dose of intravenous granisetron should be the recommended prophylactic regimen for the prevention of acute emesis.

HYDROXYUREA TREATMENT DECREASES GLOMERULAR HYPERFILTRATION IN CHILDREN WITH SICKLE CELL ANEMIA

Science.gov (United States)

Aygun, Banu; Mortier, Nicole A.; Smeltzer, Matthew P.; Shulkin, Barry L.; Hankins, Jane S.; Ware, Russell E.

2015-01-01

Background Glomerular hyperfiltration and microalbuminuria/proteinuria are early manifestations of sickle nephropathy. The effects of hydroxyurea therapy on these renal manifestations of sickle cell anemia (SCA) are not well defined. Objective To investigate the effects of hydroxyurea on glomerular filtration rate (GFR) measured by 99mTc-DTPA clearance, and on microalbuminuria/proteinuria in children with SCA. Study Design Hydroxyurea Study of Long-Term Effects (HUSTLE) is a prospective study (NCT00305175) with the goal of describing the long-term cellular, molecular, and clinical effects of hydroxyurea therapy in SCA. Glomerular filtration rate, urine microalbumin, and serum cystatin C were measured before initiating hydroxyurea therapy and then repeated after 3 years. Baseline and Year 3 values for HUSTLE subjects were compared using the Wilcoxon Signed Rank test. Associations between continuous variables were evaluated using Spearman correlation coefficient. Results Twenty-three children with SCA (median age 7.5 years, range 2.5–14.0 years) received hydroxyurea at maximum tolerated dose (MTD, 24.4 ± 4.5 mg/kg/day, range 15.3–30.6 mg/kg/day). After three years of treatment, GFR measured by 99mTc-DTPA decreased significantly from 167 ± 46 mL/min/1.73m2 to 145 ± 27 mL/min/1.73m2 (p=0.016). This decrease in GFR was significantly associated with increase in fetal hemoglobin (p= 0.042) and decrease in lactate dehydrogenase levels (p=0.035). Urine microalbumin and cystatin C levels did not change significantly. Conclusions Hydroxyurea at MTD is associated with a decrease in hyperfiltration in young children with SCA. PMID:23255310

Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

Science.gov (United States)

De, Soumita; Sen, Tuhinadri; Chatterjee, Mitali

2015-11-01

Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

Scutellarin inhibits cytochrome P450 isoenzyme 1A2 (CYP1A2) in rats.

Science.gov (United States)

Jian, Tun-Yu; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Li, Hong-Liang; Bai, Min; Xu, Gui-Li

2012-08-01

Scutellarin is the most important flavone glycoside in the herbal drug Erigeron breviscapus (Vant.) Hand.-Mazz. It is used frequently in the clinic to treat ischemic vascular diseases in China. However, the direct relationship between scutellarin and cytochrome P450 (CYP450) is unclear. The present study investigated the in vitro and in vivo effects of scutellarin on cytochrome P450 1A2 (CYP 1A2) metabolism. According to in vitro experiments, scutellarin (10-250 µM) decreased the formation of 4-acetamidophenol in a concentration-dependent manner, with an IC₅₀ value of 108.20 ± 0.657 µM. Furthermore, scutellarin exhibited a weak mixed-type inhibition against the activity of CYP1A2 in rat liver microsomes, with a K(i) value of 95.2 µM. Whereas in whole animal studies, scutellarin treatment for 7 days (at 5, 15, 30 mg/kg, i.p.) decreased the clearance (CL), and increased the T(1/2) (at 15, 30 mg/kg, i.p.), it did not affect the V(d) of phenacetin. Scutellarin treatment (at 5, 15, 30 mg/kg, i.p.) increased the AUC(0-∞) by 14.3%, 67.3% and 159.2%, respectively. Scutellarin at 30 mg/kg also weakly inhibited CYP1A2 activity, in accordance with our in vitro study. Thus, the results indicate that CYP1A2 is inhibited directly, but weakly, by scutellarin in vivo, and provide useful information on the safe and effective use of scutellarin in clinical practice. Copyright © 2012 John Wiley & Sons, Ltd.

Ionizing radiation effects on the KG1A primitive hematopoietic cell line

International Nuclear Information System (INIS)

Clave, Emmanuel; Carosella, Edgardo D.; Gluckman, Eliane; Dubray, Bernard; Socie, Gerard

1996-01-01

Purpose: Better understanding of radiation-induced effects on the hematopoietic system is important in both the context of therapeutic intervention and accidental exposure. However, direct study of these effects on the hematopoietic stem cell pool is hampered by the small number of accessible cells. We, thus, studied radiation-induced effects on the KG1a stem cell line. Methods and Materials: We confirmed and extended the immunophenotype of KG1a with monoclonal antibodies, established a radiation survival curve, and quantified mRNAs by Northern blotting 30 min after 1, 2, and 3 Gy of ionizing radiation (IR) and followed for up to 48 h after a 3 Gy dose. Cell cycle status and apoptosis were assessed by fluorescent-activated cell sorter (FACS) analysis, cell morphology, and DNA fragmentation. Results: KG1a was found to be CD34+, CD7+, Thy1 low, CD38 low, lineage negative (neg), C-KITneg and HLA-DRneg, a phenotype consistent with a primitive hematopoietic origin. This immunophenotype was not altered by x-ray irradiation. The D 0 value was 1.75 Gy. We showed a time-dependent variation of c-jun mRNA expression with an early and transient dose-dependent induction followed by a second increase at 24 and 48 h: a biphasic dose-dependent variation of bcl-2 expression 30 min after irradiation with a reduction of mRNA level at 1 Gy, and a normalization at higher doses and stable levels of mRNA for c-fos, c-myc, G-CSF, GM-CSF, IL-6, TNF-α, TGF-β, and MIP-1α genes. Cell cycle analysis showed the absence of G1/S phase arrest, a point consistent with the absence of detection of P53 mRNA by Northern blot analysis. The dose-dependent G2/M phase arrest was not followed by significant apoptotic cell death. Conclusion: Taken together, this data indicates that radiation-induced cell death of KG1a, a cell line that has a relatively high D 0 value, does not seem to be the result of the apoptotic pathway but occurs subsequent to a G2/M phase arrest

Lithium-induced neuroprotection in stroke involves increased miR-124 expression, reduced RE1-silencing transcription factor abundance and decreased protein deubiquitination by GSK3β inhibition-independent pathways.

Science.gov (United States)

Doeppner, Thorsten R; Kaltwasser, Britta; Sanchez-Mendoza, Eduardo H; Caglayan, Ahmet B; Bähr, Mathias; Hermann, Dirk M

2017-03-01

Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry. Lithium-induced neuroprotection persisted throughout the observation period of 56 days and was associated with enhanced neurological recovery. Poststroke angioneurogenesis and axonal plasticity were also enhanced by lithium. On the molecular level, lithium increased miR-124 expression, reduced RE1-silencing transcription factor abundance, and decreased protein deubiquitination in cultivated cortical neurons exposed to oxygen-glucose deprivation and in brains of mice exposed to cerebral ischemia. Notably, this effect was not mimicked by pharmacological GSK3β inhibition. This study for the first time provides efficacy data for lithium in the postacute ischemic phase, reporting a novel mechanism of action, i.e. increased miR-124 expression facilitating REST degradation by which lithium promotes postischemic neuroplasticity and angiogenesis.

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

Energy Technology Data Exchange (ETDEWEB)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Kalthur, Sneha Guruprasad; D' Souza, Antony Sylvan [Department of Anatomy, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Shetty, Pallavi K.; Mutalik, Srinivas [Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal 576 104 (India); Kalthur, Guruprasad, E-mail: guru.kalthur@manipal.edu [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India); Adiga, Satish Kumar [Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal 576 104 (India)

2014-09-15

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice

International Nuclear Information System (INIS)

Nair, Ramya; Singh, Vikram Jeet; Salian, Sujith Raj; Kalthur, Sneha Guruprasad; D'Souza, Antony Sylvan; Shetty, Pallavi K.; Mutalik, Srinivas; Kalthur, Guruprasad; Adiga, Satish Kumar

2014-01-01

Methyl parathion (MP) is one of the most commonly used and extremely toxic organophosphorous group of pesticide. A large number of studies in the literature suggest that it has adverse effects on the male reproductive system. However, there is limited information about its toxicity to the female reproductive system. In the present study we report the toxic effects of methyl parathion on the female reproductive system using Swiss albino mice as the experimental model. The female mice were administered orally with 5, 10 and 20 mg/kg of MP. One week later, the mice were superovulated with pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) to study the quality of the oocytes, spindle organization, developmental potential of early embryos and the DNA integrity in blastocysts. MP exposure resulted in a non-significant decrease in the number of primordial follicles and increased DNA damage in granulosa cells. Though MP did not have any effect on the ovulation it had a significant inhibitory effect on the nuclear maturity of oocytes which was associated with spindle deformity. In addition, the oocytes had higher cytoplasmic abnormalities with depleted glutathione level. Even though it did not have any effect on the fertilization and blastocyst rate at lower doses, at 20 mg/kg MP it resulted in a significant decrease in blastocyst hatching, decrease in cell number and high DNA damage. While low body weight gain was observed in F1 generation from 5 mg/kg group, at higher dose, the body weight in F1 generation was marginally higher than control. Post-natal death in F1 generation was observed only in mice treated with 20 mg/kg MP. In conclusion, we report that MP has adverse effects on the oocyte quality, developmental potential of the embryo and reproductive outcome. - Highlights: • Methyl parathion induces severe cytoplasmic abnormalities in oocytes. • Inhibits nuclear maturation and spindle damage • Poor blastocyst quality and high DNA

Isopiestic investigation of the osmotic coefficients of MgBr{sub 2}(aq) and study of bromide salts solubility in the (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) system at T = 323.15 K. Thermodynamic model of solution behaviour and (solid + liquid) equilibria in the MgBr{sub 2}(aq), and (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) systems to high concentration and temperature

Energy Technology Data Exchange (ETDEWEB)

Christov, Christomir, E-mail: christov@svr.igic.bas.b [Institute of General and Inorganic Chemistry, Bulgarian Academy of Sciences, ul. ' Acad. G. Bonchev' , bl. 11, 1113 Sofia (Bulgaria)

2011-03-15

The isopiestic method has been used to determine the osmotic coefficients of the binary solutions MgBr{sub 2}(aq) (from 0.4950 to 2.5197 mol {center_dot} kg{sup -1}) at the temperature T = 323.15 K. Sodium chloride solutions have been used as isopiestic reference standards. The solubility of the bromide minerals in the mixed system (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) has been investigated at T = 323.15 K by the physico-chemical analysis method. In addition to simple salts {l_brace}KBr(cr) and MgBr{sub 2} . 6H{sub 2}O(cr){r_brace}, equilibrium crystallization of the highly incongruent double salt with stoichiometric composition 1:1:6 {l_brace}bromcarnallite: KBr . MgBr{sub 2} . 6H{sub 2}O(cr){r_brace} was also established. The results obtained from the isopiestic and solubility measurements have been combined with all other experimental thermodynamic quantities available in the literature (osmotic coefficients, and solubility of the bromide mineral) to construct a chemical model that calculates solute and solvent activities and (solid + liquid) equilibria in the MgBr{sub 2}(aq) binary, and (m{sub 1}KBr + m{sub 2}MgBr{sub 2})(aq) mixed systems from dilute to high solution concentration within the (273.15 to 438.15) K temperature range. The solubility modelling approach based on fundamental Pitzer specific interaction equations is employed. It was found, that the standard for 2-1 type of electrolytes approach with three ({beta}{sup (0)}, {beta}{sup (1)}, and C{sup {phi}}) single electrolyte ion interaction parameters gives excellent agreement with osmotic coefficients from T = (298.15 to 373.45) K; up to saturation at 298.15 K, and up to m(MgBr{sub 2}) = 5.83 mol {center_dot} kg{sup -1} at 373.45 K, and with MgBr{sub 2} {center_dot} 6H{sub 2}O(cr) equilibrium pure water solubility data within the (273.15 to 438.15) K temperature range and up to {approx}8.5 mol {center_dot} kg{sup -1} used in parameterization. The model for the ternary system gives very good

The effects of necrotic enteritis, aflatoxin B1, and virginiamycin on growth performance, necrotic enteritis lesion scores, and mortality in young broilers.

Science.gov (United States)

Cravens, R L; Goss, G R; Chi, F; De Boer, E D; Davis, S W; Hendrix, S M; Richardson, J A; Johnston, S L

2013-08-01

The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on broilers with or without necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3 × 2 × 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were allowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10× dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis increased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin × virginiamycin × CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin × virginiamycin, P broiler performance and interact to decrease weight gain, virginiamycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of aflatoxin.

CDEX-1 1 kg point-contact germanium detector for low mass dark matter searches

International Nuclear Information System (INIS)

Kang Kejun; Yue Qian; Wu Yucheng

2013-01-01

The CDEX collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold point-contact p-type germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact P + electrode and the outside N + electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both P + and N + electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments. (authors)

Depletion of florfenicol amine in tilapia (Oreochromis sp.) maintained in a recirculating aquaculture system following Aquaflor(R)-medicated feed therapy (20 mg/kg BW/d for 10 days)

Science.gov (United States)

Gaikowski, Mark P.; Whitsel, Melissa K.; Charles, Shawn; Schleis, Susan M.; Crouch, Louis S.; Endris, Richard G.

2013-01-01

Aquaflor® [50% w w−1 florfenicol (FFC)], is approved for use in freshwater-reared warmwater finfish which include tilapia Oreochromis spp. in the United States to control mortality from Streptococcus iniae. The depletion of florfenicol amine (FFA), the marker residue of FFC, was evaluated after feeding FFC-medicated feed to deliver a nominal 20 mg FFC kg−1 BW d−1 dose (1.33× the label use of 15 mg FFC kg−1 BW d−1) to Nile tilapia O. niloticus and hybrid tilapia O. niloticus × O. aureus held in a recirculating aquaculture system (RAS) at production-scale holding densities. Florfenicol amine concentrations were determined in fillets taken from 10 fish before dosing and from 20 fish at nine time points after dosing (from 1 to 240 h post-dosing). Water samples were assayed for FFC before, during and after the dosing period. Parameters monitored included daily feed consumption and biofilter function (levels of ammonia, nitrite and nitrate). Mean fillet FFA concentration decreased from 13.77 μg g−1 at 1-h post dosing to 0.39 μg g−1 at 240-h post dosing. Water FFC concentration decreased from a maximum of 1400 ng mL−1 at 1 day post-dosing to 847 ng mL−1 at 240 h post-dosing. There were no adverse effects noted on fish, feed consumption or biofilter function associated with FFC-medicated feed administration to tilapia.

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

OpenAIRE

Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

2016-01-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxyt...

Structural and magnetic properties of Mg-Zn ferrites (Mg1−xZnxFe2O4) prepared by sol-gel method

International Nuclear Information System (INIS)

Reyes-Rodríguez, Pamela Yajaira; Cortés-Hernández, Dora Alicia; Escobedo-Bocardo, José Concepción; Almanza-Robles, José Manuel; Sánchez-Fuentes, Héctor Javier; Jasso-Terán, Argentina; De León-Prado, Laura Elena; Méndez-Nonell, Juan; Hurtado-López, Gilberto Francisco

2017-01-01

In this study, the Mg 1−x Zn x Fe 2 O 4 nanoparticles (x=0–0.9) were prepared by sol-gel method. These ferrites exhibit an inverse spinel structure and the lattice parameter increases as the substitution of Zn 2+ ions is increased. At lower Zn content (0.1≤x≤0.5), saturation magnetization (Ms) increases, while it decreases at higher Zn content (x≥6). The remnant magnetization (0.17–2.0 emu/g) and coercive field (6.0–60 Oe) indicate a ferrimagnetic behavior. The average core diameter of selected ferrites is around 15 nm and the nanoparticles morphology is quasi spherical. The heating ability of some Mg 0.9 Zn 0.1 Fe 2 O 4 and Mg 0.7 Zn 0.3 Fe 2 O 4 aqueous suspensions indicates that the magnetic nanoparticles can increase the medium temperature up to 42 °C in a time less than 10 min - Highlights: • Magnetic nanoparticles of Mg 1−x Zn x Fe 2 O 4 were synthesized by sol-gel method. • Nanoparticles showing a single spinel crystalline structure were obtained. • Aqueous suspensions of Mg 0.7 Zn 0.3 Fe 2 O 4 and Mg 0.9 Zn 0.1 Fe 2 O 4 show heating ability.

Three-dimensional contrast-enhanced magnetic-resonance angiography of the renal arteries: Interindividual comparison of 0.2 mmol/kg gadobutrol at 1.5 T and 0.1 mmol/kg gadobenate dimeglumine at 3.0 T

International Nuclear Information System (INIS)

Attenberger, Ulrike I.; Wintersperger, Bernd J.; Sourbron, Steven P.; Reiser, Maximilian F.; Michaely, Henrik J.; Schoenberg, Stefan O.; Lodemann, Klaus-Peter

2008-01-01

The purpose was to evaluate the image quality of high-spatial resolution MRA of the renal arteries at 1.5 T after contrast-agent injection of 0.2 mmol/kg body weight (BW) in an interindividual comparison to 3.0 T after contrast-agent injection of 0.1 mmol/kg BW contrast agent (CA). After IRB approval and informed consent, 40 consecutive patients (25 men, 15 women; mean age 53.9 years) underwent MRA of the renal arteries either at a 1.5-T MR system with 0.2 mmol/kg BW gadobutrol or at a 3.0-T MR scanner with 0.1 mmol/kg BW gadobenate dimeglumine used as CA in a randomized order. A constant volume of 15 ml of these contrast agents was applied. The spatial resolution of the MRA sequences was 1.0 x 0.8 x 1.0 mm 3 at 1.5 T and 0.9 x 0.8 x 0.9 mm 3 at 3.0 T, which was achieved by using parallel imaging acceleration factors of 2 at 1.5 T and 3 at 3.0 T, respectively. Two radiologists blinded to the administered CA and the field strength assessed the image quality and the venous overlay for the aorta, the proximal and distal renal arteries independently on a four-point Likert-type scale. Phantom measurements were performed for a standardized comparison of SNR at 1.5 T and 3.0 T. There was no significant difference (p > 0.05) between the image quality at 3.0 T with 0.1 mmol/kg BW gadobenate dimeglumine compared to the exams at 1.5 T with 0.2 mmol/kg BW gadobutrol. The median scores were between 3 and 4 (good to excellent vessel visualization) for the aorta (3 at 1.5 T/4 at 3.0 T for reader 1 and 2). For the proximal renal arteries, median scores were 3 for the left and right renal artery at 1.5 T for both readers. At 3.0 T, median scores were 3 (left proximal renal artery) and 4 (right proximal renal artery) for reader 1 and 3 (left/right) for reader 2 at 3.0 T. For the distal renal arteries, median scores were between 2 and 3 at both field strengths (moderate and good) for both readers. The κ values for both field strengths were comparable and ranged between 0

Three-dimensional contrast-enhanced magnetic-resonance angiography of the renal arteries: Interindividual comparison of 0.2 mmol/kg gadobutrol at 1.5 T and 0.1 mmol/kg gadobenate dimeglumine at 3.0 T

Energy Technology Data Exchange (ETDEWEB)

Attenberger, Ulrike I.; Wintersperger, Bernd J.; Sourbron, Steven P.; Reiser, Maximilian F. [University Hospitals-Grosshadern, Ludwig-Maximilians-University Munich, Institute of Clinical Radiology, Munich (Germany); Michaely, Henrik J.; Schoenberg, Stefan O. [University Hospital Mannheim, University of Heidelberg, Institute of Clinical Radiology, Mannheim (Germany); Lodemann, Klaus-Peter [Bracco-Altana Pharma, Konstanz (Germany)

2008-06-15

The purpose was to evaluate the image quality of high-spatial resolution MRA of the renal arteries at 1.5 T after contrast-agent injection of 0.2 mmol/kg body weight (BW) in an interindividual comparison to 3.0 T after contrast-agent injection of 0.1 mmol/kg BW contrast agent (CA). After IRB approval and informed consent, 40 consecutive patients (25 men, 15 women; mean age 53.9 years) underwent MRA of the renal arteries either at a 1.5-T MR system with 0.2 mmol/kg BW gadobutrol or at a 3.0-T MR scanner with 0.1 mmol/kg BW gadobenate dimeglumine used as CA in a randomized order. A constant volume of 15 ml of these contrast agents was applied. The spatial resolution of the MRA sequences was 1.0 x 0.8 x 1.0 mm{sup 3} at 1.5 T and 0.9 x 0.8 x 0.9 mm{sup 3} at 3.0 T, which was achieved by using parallel imaging acceleration factors of 2 at 1.5 T and 3 at 3.0 T, respectively. Two radiologists blinded to the administered CA and the field strength assessed the image quality and the venous overlay for the aorta, the proximal and distal renal arteries independently on a four-point Likert-type scale. Phantom measurements were performed for a standardized comparison of SNR at 1.5 T and 3.0 T. There was no significant difference (p > 0.05) between the image quality at 3.0 T with 0.1 mmol/kg BW gadobenate dimeglumine compared to the exams at 1.5 T with 0.2 mmol/kg BW gadobutrol. The median scores were between 3 and 4 (good to excellent vessel visualization) for the aorta (3 at 1.5 T/4 at 3.0 T for reader 1 and 2). For the proximal renal arteries, median scores were 3 for the left and right renal artery at 1.5 T for both readers. At 3.0 T, median scores were 3 (left proximal renal artery) and 4 (right proximal renal artery) for reader 1 and 3 (left/right) for reader 2 at 3.0 T. For the distal renal arteries, median scores were between 2 and 3 at both field strengths (moderate and good) for both readers. The {kappa} values for both field strengths were comparable and ranged

Green tea diet decreases PCB 126-induced oxidative stress in mice by upregulating antioxidant enzymes

Science.gov (United States)

Newsome, Bradley J; Petriello, Michael C; Han, Sung Gu; Murphy, Margaret O; Eske, Katryn E; Sunkara, Manjula; Morris, Andrew J; Hennig, Bernhard

2013-01-01

Superfund chemicals such as polychlorinated biphenyls pose a serious human health risk due to their environmental persistence and link to multiple diseases. Selective bioactive food components such as flavonoids have been shown to ameliorate PCB toxicity, but primarily in an in vitro setting. Here, we show that mice fed a green tea-enriched diet and subsequently exposed to environmentally relevant doses of coplanar PCB exhibit decreased overall oxidative stress primarily due to the upregulation of a battery of antioxidant enzymes. C57BL/6 mice were fed a low fat diet supplemented with green tea extract (GTE) for 12 weeks and exposed to 5 μmol PCB 126/kg mouse weight (1.63 mg/kg-day) on weeks 10, 11 and 12 (total body burden: 4.9 mg/kg). F2-Isoprostane and its metabolites, established markers of in vivo oxidative stress, measured in plasma via HPLC-MS/MS exhibited five-fold decreased levels in mice supplemented with GTE and subsequently exposed to PCB compared to animals on a control diet exposed to PCB. Livers were collected and harvested for both mRNA and protein analyses, and it was determined that many genes transcriptionally controlled by AhR and Nrf2 proteins were upregulated in PCB-exposed mice fed the green tea supplemented diet. An increased induction of genes such as SOD1, GSR, NQO1 and GST, key antioxidant enzymes, in these mice (green tea plus PCB) may explain the observed decrease in overall oxidative stress. A diet supplemented with green tea allows for an efficient antioxidant response in the presence of PCB 126 which supports the emerging paradigm that healthful nutrition may be able to bolster and buffer a physiological system against the toxicities of environmental pollutants. PMID:24378064

Industrial production of MgH2 and its application

International Nuclear Information System (INIS)

Uesugi, H.; Sugiyama, T.; Nii, H.; Ito, T.; Nakatsugawa, I.

2011-01-01

Research highlights: → Tablet and powder Mg were hydrogenated in a 50 kg batch furnace based on thermal equilibrium method. → Compression of Mg tablet improved the hydrogenation yield. → Hydrolysis of MgH 2 using citric acid generated hydrogen under 373 K. → A MgH 2 -hydrogen reactor utilizing hydraulic head pressure was developed. → - Abstract: A process for the industrial production of magnesium hydride (MgH 2 ) based on a thermal equilibrium method and its application to portable hydrogen sources is proposed. Mg powders and tablets compressed with mechanically ground Mg ribbons were successfully hydrogenated in a 50-kg-batch furnace. The resultant MgH 2 showed a hydrogen yield of around 96% with good reproducibility. The compression ratio of Mg tablets was found to be an important factor in the hydrogenation yield. A hydrolysis technique using citric acid as an additive was employed to generate hydrogen under 373 K. Increasing the concentration of citric acid and the temperature accelerated the hydrolysis reactivity. A hydrogen reactor utilizing hydraulic head pressure was developed. It generated hydrogen continuously for 1 h at a flow rate of 100 ml min -1 with hydrolysis of 5 g of tablet-form MgH 2 . The conversion yield was around 70%, regardless of the flow rate.

[Pharmacology of a new sleep inducer, 1H-1,2,4-triazolyl benzophenone derivative, 450191-S (II). Sleep-inducing activity and effect on the motor system].

Science.gov (United States)

Yamamoto, K; Matsushita, A; Sawada, T; Naito, Y; Yoshimura, K; Takesue, H; Utsumi, S; Kawasaki, K; Hirono, S; Koshida, H

1984-07-01

The sleep-inducing activity and effect on the motor system of the 1H-1,2,4-triazolyl benzophenone derivative 450191-S were examined behaviorally, electroencephalographically and electro-physiologically with various species of animals and were compared with those of diazepam, nitrazepam, estazolam and triazolam. In the rhesus monkey, rabbit and rat with chronically indwelling brain electrodes, 0.6 to 3 mg/kg, p.o. of 450191-S caused a shorter latency of sleep onset, an increase of and a stable continuity of slow wave deep sleep (SWDS) with higher amplitude, and the appearance of clear spindle bursts in the slow wave light sleeping (SWLS) state with little muscle relaxation. Animals treated with nitrazepam and/or estazolam showed a smaller increase in SWDS and its unstable continuity with remarkable disturbance of gait. The doses needed to induce sleep in the rhesus monkey were 0.6 to 1 mg/kg p.o. for 450191-S, 3 mg/kg for nitrazepam, 1 mg/kg for estazolam and 0.3 mg/kg for triazolam. The cat treated with 450191-S showed the phenomena caused by benzodiazepines (BDZ), i.e., behavioral excitation and decrease of frequencies in the hippocampal theta waves. The suppressive effects of 450191-S on the EEG arousal reaction and/or blood pressure elevation induced by hypothalamic stimulation in the rabbit suggested that the inhibitory effects acted on the posterior hypothalamus to the limbic system. The inhibitory effect of 450191-S on the amygdaloid kindling in the rat was as potent as those of diazepam and nitrazepam. Successive daily oral administration of both 3 mg/kg of 450191-S and/or 3 to 6 mg/kg of nitrazepam for 15 days in the rabbit caused slight decrease of SWDS and increase of fast wave (REM) sleep (FWS). During the withdrawal period of both compounds, a slight but insignificant increase in the waking state was noticed for 1 to 2 days, but not a rebound increase of FWS. Intravenously administered 450191-S showed the same action as BDZ on the spinal reflex and the

Epitaxial growth of bcc-FexCo100-x thin films on MgO(1 1 0) single-crystal substrates

International Nuclear Information System (INIS)

Ohtake, Mitsuru; Nishiyama, Tsutomu; Shikada, Kouhei; Kirino, Fumiyoshi; Futamoto, Masaaki

2010-01-01

Fe x Co 100-x (x=100, 65, 50 at%) epitaxial thin films were prepared on MgO(1 1 0) single-crystal substrates heated at 300 deg. C by ultra-high vacuum molecular beam epitaxy. The film structure and the growth mechanism are discussed. FeCo(2 1 1) films with bcc structure grow epitaxially on MgO(1 1 0) substrates with two types of variants whose orientations are rotated around the film normal by 180 deg. each other for all compositions. Fe x Co 100-x film growth follows the Volmer Weber mode. X-ray diffraction analysis indicates the out-of-plane and the in-plane lattice spacings are in agreement with the values of respective bulk Fe x Co 100-x crystals with very small errors less than ±0.4%, suggesting the strains in the films are very small. High-resolution cross-sectional transmission electron microscopy shows that periodical misfit dislocations are preferentially introduced in the film at the Fe 50 Co 50 /MgO interface along the MgO[1 1-bar 0] direction. The presence of such periodical dislocations decreases the large lattice mismatch of about -17% existing at the FeCo/MgO interface along the MgO[1 1-bar 0] direction.

Microarray analysis of thioacetamide-treated type 1 diabetic rats

International Nuclear Information System (INIS)

Devi, Sachin S.; Mehendale, Harihara M.

2006-01-01

It is well known that diabetes imparts high sensitivity to numerous hepatotoxicants. Previously, we have shown that a normally non-lethal dose of thioacetamide (TA, 300 mg/kg) causes 90% mortality in type 1 diabetic (DB) rats due to inhibited tissue repair allowing progression of liver injury. On the other hand, DB rats exposed to 30 mg TA/kg exhibit delayed tissue repair and delayed recovery from injury. The objective of this study was to investigate the mechanism of impaired tissue repair and progression of liver injury in TA-treated DB rats by using cDNA microarray. Gene expression pattern was examined at 0, 6, and 12 h after TA challenge, and selected mechanistic leads from microarray experiments were confirmed by real-time RT-PCR and further investigated at protein level over the time course of 0 to 36 h after TA treatment. Diabetic condition itself increased gene expression of proteases and decreased gene expression of protease inhibitors. Administration of 300 mg TA/kg to DB rats further elevated gene expression of proteases and suppressed gene expression of protease inhibitors, explaining progression of liver injury in DB rats after TA treatment. Inhibited expression of genes involved in cell division cycle (cyclin D1, IGFBP-1, ras, E2F) was observed after exposure of DB rats to 300 mg TA/kg, explaining inhibited tissue repair in these rats. On the other hand, DB rats receiving 30 mg TA/kg exhibit delayed expression of genes involved in cell division cycle, explaining delayed tissue repair in these rats. In conclusion, impaired cyclin D1 signaling along with increased proteases and decreased protease inhibitors may explain impaired tissue repair that leads to progression of liver injury initiated by TA in DB rats

Selective activation of estrogen receptors, ERα and GPER-1, rapidly decreases food intake in female rats.

Science.gov (United States)

Butler, Michael J; Hildebrandt, Ryan P; Eckel, Lisa A

2018-05-25

Many of estradiol's behavioral effects are mediated, at least partially, via extra-nuclear estradiol signaling. Here, we investigated whether two estrogen receptor (ER) agonists, targeting ERα and G protein-coupled ER-1 (GPER-1), can promote rapid anorexigenic effects. Food intake was measured in ovariectomized (OVX) rats at 1, 2, 4, and 22 h following subcutaneous (s.c.) injection of an ERα agonist (PPT; 0-200 μg/kg), a GPER-1 agonist (G-1; 0-1600 μg/kg), and a GPER-1 antagonist (G-36; 0-80 μg/kg). To investigate possible cross-talk between ERα and GPER-1, we examined whether GPER-1 blockade affects the anorexigenic effect of PPT. Feeding was monitored in OVX rats that received s.c. injections of vehicle or 40 μg/kg G-36 followed 30 min later by s.c. injections of vehicle or 200 μg/kg PPT. Selective activation of ERα and GPER-1 alone decreased food intake within 1 h of drug treatment, and feeding remained suppressed for 22 h following PPT treatment and 4 h following G-1 treatment. Acute administration of G-36 alone did not suppress feeding at any time point. Blockade of GPER-1 attenuated PPT's rapid (within 1 h) anorexigenic effect, but did not modulate PPT's ability to suppress food intake at 2, 4 and 22 h. These findings demonstrate that selective activation of ERα produces a rapid (within 1 h) decrease in food intake that is best explained by a non-genomic signaling pathway and thus implicates the involvement of extra-nuclear ERα. Our findings also provide evidence that activation of GPER-1 is both sufficient to suppress feeding and necessary for PPT's rapid anorexigenic effect. Copyright © 2017. Published by Elsevier Inc.

No sign of decreased burrowing behavior in the genetically depressive flinders rats

DEFF Research Database (Denmark)

Baastrup, C. S.; Wegener, Gregers; Finnerup, N. B.

2012-01-01

outcome. Rats were trained in the procedure for 3 consecutive days. In a randomly allocated balanced cross-over design the rats were treated with saline 0.9% w/w, imipramin 15 mg/kg or citalopram-S 10 mg/kg 24, 6 and 1 hours before test start. A 2 day wash-out period were allowed between administrations...

Decrease in spermatic parameters of mice treated with hydroalcoholic extract Tropaeolum tuberosum “mashua”

Directory of Open Access Journals (Sweden)

Jonathan H. Vásquez

2012-10-01

Full Text Available In this work, we provided a Tropaeolum tuberosum hydroalcoholic extract to male mice (780 mg kg-1 for 7, 14 and 21 days treatment, there was no significant difference in body weight gain, testes, epididymides and prostate weight (p> 0.05, nevertheless progressive motility decreased and immobile sperm count increased significantly after 21 days treatment (p <0.05. The sperm count in the epididymis cauda decreased in the 3 three assessments, concentration on 21 days treatment was significantly lower than those of 7 and 14 days treatments (p <0.05. Our results suggest, that T. tuberosum has a direct action on the male reproductive system decreasing spermatic parameters without exerting toxic effects on mice.

Role of the route of leukotrienes in an experimental model of oral mucositis induced by 5-fluorouracil 1.

Science.gov (United States)

Silva, Viviane Carvalho da; Leitão, Renata Ferreira de Carvalho; Brito, Gerly Anne de Castro; Martins, Conceição da Silva; Freire, Gildenio Estevam; Aragão, Karoline Saboia; Wanderley, Carlos Wagner de Souza; Freitas, Marcos Rabelo de

2017-09-01

To investigate the participation of cysteinyl leukotrienes in the pathophysiology of oral mucositis. Oral mucositis was induced in hamsters using 5-fluorouracil (5-FU; 60 and 40 mg/kg; i.p., on days 1 and 2, respectively, and with excoriations in jugal mucosa on day 4). Montelukast (10, 20, or 40 mg/kg/d; gavage), MK886 (3 mg/kg/d, i.p.), or saline or celecoxib (7.5 mg/kg/d; i.p.) was administered 1 h prior to 5-FU and daily, until the fourth (MK886) or tenth day, when the animals were euthanized and their jugal mucosa was collected for macroscopic, histopathological, and immunohistochemical evaluation. Neither montelukast nor MK-886 prevented the oral mucositis induced by 5-FU, as observed by histopathological evaluation. In addition, we did not find significant differences in the expression of inducible nitric oxide synthase-2, cyclooxygenase-2, or interleukin (IL)-1β between the experimental and control groups. However, we did observe a significant decrease in tumor necrosis factor (TNF)-α expression for all doses of montelukast; we also observed a significant decrease in IL-10 with 40 mg/kg/d and MK 886. Cysteinyl leukotrienes do not play an important role in experimental oral mucositis induced by 5-FU. There is a modulating action specifically on TNF-α.

Concentrations of moxifloxacin in serum and pulmonary compartments following a single 400 mg oral dose in patients undergoing fibre-optic bronchoscopy.

Science.gov (United States)

Soman, A; Honeybourne, D; Andrews, J; Jevons, G; Wise, R

1999-12-01

The concentrations of moxifloxacin achieved after a single 400 mg dose were measured in serum, epithelial lining fluid (ELF), alveolar macrophages (AM) and bronchial mucosa (BM). Concentrations were determined using a microbiological assay. Nineteen patients undergoing fibre-optic bronchoscopy were studied. Mean serum, ELF, AM and BM concentrations at 2.2, 12 and 24 h were as follows: 2.2 h: 3.2 mg/L, 20.7 mg/L, 56.7 mg/L, 5.4 mg/kg; 12 h: 1.1 mg/L, 5.9 mg/L, 54.1 mg/L, 2.0 mg/kg; 24 h: 0.5 mg/L, 3.6 mg/L, 35.9 mg/L, 1.1 mg/kg, respectively. These concentrations exceed the MIC(90)s for common respiratory pathogens such as Streptococcus pneumoniae (0.25 mg/L), Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.12 mg/L), Chlamydia pneumoniae (0.12 mg/L) and Mycoplasma pneumoniae (0. 12 mg/L) and indicate that moxifloxacin should be effective in the treatment of community-acquired, lower respiratory tract infections.

Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes.

Science.gov (United States)

Newsome, Bradley J; Petriello, Michael C; Han, Sung Gu; Murphy, Margaret O; Eske, Katryn E; Sunkara, Manjula; Morris, Andrew J; Hennig, Bernhard

2014-02-01

Superfund chemicals such as polychlorinated biphenyls pose a serious human health risk due to their environmental persistence and link to multiple diseases. Selective bioactive food components such as flavonoids have been shown to ameliorate PCB toxicity, but primarily in an in vitro setting. Here, we show that mice fed a green tea-enriched diet and subsequently exposed to environmentally relevant doses of coplanar PCB exhibit decreased overall oxidative stress primarily due to the up-regulation of a battery of antioxidant enzymes. C57BL/6 mice were fed a low-fat diet supplemented with green tea extract (GTE) for 12 weeks and exposed to 5 μmol PCB 126/kg mouse weight (1.63 mg/kg-day) on weeks 10, 11 and 12 (total body burden: 4.9 mg/kg). F2-isoprostane and its metabolites, established markers of in vivo oxidative stress, measured in plasma via HPLC-MS/MS exhibited fivefold decreased levels in mice supplemented with GTE and subsequently exposed to PCB compared to animals on a control diet exposed to PCB. Livers were collected and harvested for both messenger RNA and protein analyses, and it was determined that many genes transcriptionally controlled by aryl hydrocarbon receptor and nuclear factor (erythroid-derived 2)-like 2 proteins were up-regulated in PCB-exposed mice fed the green tea-supplemented diet. An increased induction of genes such as SOD1, GSR, NQO1 and GST, key antioxidant enzymes, in these mice (green tea plus PCB) may explain the observed decrease in overall oxidative stress. A diet supplemented with green tea allows for an efficient antioxidant response in the presence of PCB 126, which supports the emerging paradigm that healthful nutrition may be able to bolster and buffer a physiological system against the toxicities of environmental pollutants. Copyright © 2014 Elsevier Inc. All rights reserved.

Transesterification of palm oil on K{sub y}Mg{sub 1} {sub -} {sub x}Zn{sub 1} {sub +} {sub x}O{sub 3} catalyst: Effect of Mg-Zn interaction

Energy Technology Data Exchange (ETDEWEB)

Olutoye, M.A.; Hameed, B.H. [School of Chemical Engineering, Engineering Campus, Universiti Sains Malaysia, 14300 Nibong Tebal, Penang (Malaysia)

2010-06-15

The Mg-Zn interaction effect of K{sub y}Mg{sub 1} {sub -} {sub x}Zn{sub 1} {sub +} {sub x}O{sub 3} heterogeneous type catalyst and its performance on transesterification of palm oil have been studied using the response surface methodology and the factorial design of experiments. The catalyst was synthesized using the co-precipitation method and the activity was assessed by transesterification of palm oil into fatty acid methyl esters. The ratio of the Mg/Zn metal interaction, temperature and time of calcination were found to have positive influence on the conversion of palm oil to fatty acid methyl ester (FAME) with the effect of metal to metal ratio and temperature of calcination being more significant. The catalytic activity was found to decrease at higher calcination temperature and the catalyst type K{sub 2}Mg{sub 0.34}Zn{sub 1.66}O{sub 3} with Mg/Zn ratio of 4.81 gave FAME content of 73% at a catalyst loading of 1.404 wt.% of oil with molar ratio of methanol to oil being 6:1 at temperature of 150 C in 6 h. A regression model was obtained to predict conversions to methyl esters as a function of metal interaction ratio, temperature of calcination and time. The observed activity of the synthesized catalyst was due to its synergetic structure and composition. (author)

Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1α expression

Energy Technology Data Exchange (ETDEWEB)

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J.L. [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012 (India); Bal, Amanjit [Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Gill, Kiran Dip, E-mail: kdgill2002@yahoo.co.in [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012 (India)

2013-12-01

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1α (PGC-1α) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10 mg/kg b.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits–NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1α was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1α seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. - Highlights: • Aluminium decreases the mRNA levels of mitochondrial and nuclear encoded

Enhanced Performance of Mg0.1Zn0.9O UV Photodetectors Using Photoelectrochemical Treatment and Silica Nanospheres

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Hsin-Ying Lee

2014-01-01

Full Text Available The Mg0.1Zn0.9O films were grown using atomic layer deposition (ALD system and applied to metal-semiconductor-metal ultraviolet photodetectors (MSM-UPDs as an active layer. To suppress the dangling bonds on the Mg0.1Zn0.9O surface, the photoelectrochemical (PEC treatment was used to passivate the Mg0.1Zn0.9O surface, which could reduce the dark current of the MSM-UPDs about one order. Beside, to increase more incident light into the Mg0.1Zn0.9O active layer of the MSM-UPDs, the 500-nm-diameter silica nanospheres were spin-coated on the Mg0.1Zn0.9O active layer to improve the antireflection capability at the wavelength of 340 nm. The reflectivity of the Mg0.1Zn0.9O films with silica nanospheres antireflection layer decreased about 7.0% in comparison with the Mg0.1Zn0.9O films without silica nanospheres. The photocurrent and UV-visible ratio of the passivated Mg0.1Zn0.9O MSM-UPDs with antireflection layer were enhanced to 5.85 μA and 1.44×104, respectively, at the bias voltage of 5 V. Moreover, the noise equivalent power and the specific detectivity of the passivated Mg0.1Zn0.9O MSM-UPDs with antireflection layer were decreased to 2.60×10-13 W and increased to 1.21×1012 cmHz1/2W−1, respectively, at the bias voltage of 5 V. According to the above mentions, the PEC treatment and silica nanospheres antireflection layer could effectively enhance the performance of Mg0.1Zn0.9O MSM-UPDs.

Finding the optimal dose of vitamin K1 to treat vitamin K deficiency and to avoid anaphylactoid reactions.

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Mi, Yan-Ni; Ping, Na-Na; Li, Bo; Xiao, Xue; Zhu, Yan-Bing; Cao, Lei; Ren, Jian-Kang; Cao, Yong-Xiao

2017-10-01

Vitamin K1 injection induces severe dose-related anaphylactoid reactions and overdose for the treatment of vitamin K deficiency. We aimed to find an optimal and small dose of vitamin K1 injection to treat vitamin K deficiency and avoid anaphylactoid reactions in animal. Rats were administered a vitamin K-deficient diet and gentamicin to establish vitamin K deficiency model. Behaviour tests were performed in beagle dogs to observe anaphylactoid reactions. The results showed an increased protein induced by vitamin K absence or antagonist II (PIVKA-II) levels, a prolonging of prothrombin time (PT) and activated partial thromboplastin time (APTT) and a decrease in vitamin K-dependent coagulation factor (F) II, VII, IX and X activities in the model group. In vitamin K1 0.01 mg/kg group, the liver vitamin K1 levels increased fivefold and the liver vitamin K2 levels increased to the normal amount. Coagulation markers PT, APTT, FVII and FIX activities returned to normal. Both in the 0.1 and 1.0 mg/kg vitamin K1 groups, coagulation functions completely returned to normal. Moreover, the amount of liver vitamin K1 was 40 (0.1 mg/kg) or 100 (1.0 mg/kg) times as in normal. Vitamin K2 was about 4 (0.1 mg/kg) or 5 (1.0 mg/kg) times as the normal amount. There was no obvious anaphylactoid symptom in dogs with the dose of 0.03 mg/kg, which is equivalent to the dose of 0.01 mg/kg in rats. These results demonstrated that a small dose of vitamin K1 is effective to improve vitamin K deficiency and to prevent anaphylactoid reactions, simultaneously. © 2017 Société Française de Pharmacologie et de Thérapeutique.

Mifepristone 5 mg versus 10 mg for emergency contraception: double-blind randomized clinical trial

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Carbonell JL

2015-01-01

Full Text Available Josep Lluis Carbonell,1 Ramon Garcia,2 Adriana Gonzalez,2 Andres Breto,2 Carlos Sanchez2 1Mediterranea Medica Clinic, Valencia, Spain; 2Eusebio Hernandez Gynecology and Obstetrics Teaching Hospital, Havana, Cuba Purpose: To estimate the efficacy and safety of 5 mg and 10 mg mifepristone for emergency contraception up to 144 hours after unprotected coitus. Methods: This double-blind randomized clinical trial was carried out at Eusebio Hernandez Hospital (Havana, Cuba. A total of 2,418 women who requested emergency contraception after unprotected coitus received either 5 mg or 10 mg mifepristone. The variables for assessing efficacy were the pregnancies that occurred and the fraction of pregnancies that were prevented. Other variables assessed were the side effects of mifepristone, vaginal bleeding, and changes in the date of the following menstruation. Results: There were 15/1,206 (1.2% and 9/1,212 (0.7% pregnancies in the 5 mg and 10 mg group, respectively (P=0.107. There were 88% and 93% prevented pregnancies in the 5 mg and 10 mg group, respectively. The side effect profiles were similar in both groups. Delayed menstruation ≥7 days was experienced by 4.9% and 11.0% of subjects in the 5 mg and 10 mg group, respectively (P=0.001. There was a significant high failure rate for women weighing >75 kg in the 5 mg group. Conclusion: It would be advisable to use the 10 mg dose of mifepristone for emergency contraception as there was a trend suggesting that the failure rate of the larger dose was lower. Keywords: mifepristone, emergency contraception

Effect of the La/Mg ratio on the structure and electrochemical properties of La xMg 3- xNi 9 ( x=1.6-2.2) hydrogen storage electrode alloys for nickel-metal hydride batteries

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Liao, B.; Lei, Y. Q.; Chen, L. X.; Lu, G. L.; Pan, H. G.; Wang, Q. D.

Effect of La/Mg ratio on the structure and electrochemical properties of La xMg 3- xNi 9 ( x=1.6-2.2) ternary alloys was investigated. All alloys are consisted of a main phase with hexagonal PuNi 3-type structure and a few impurity phases (mainly LaNi 5 and MgNi 2). The increase of La/Mg ratio in the alloys leads to an increase in both the cell volume and the hydride stability. The discharge capacity of the alloys at 100 mA/g increases with the increase of La/Mg ratio and passes though a maximum of 397.5 mAh/g at x=2.0. As the La/Mg ratio increases, the high-rate dischargeability of the alloy electrodes at 1200 mA/g HRD 1200 decreases from 66.7% ( x=1.6) to 26.5% ( x=2.2). The slower decrease of HRD 1200 (from 66.7 to 52.7%) of the alloys with x=1.6-2.0 is mainly attributed to the decrease of electrocatalytic activity of the alloys for charge-transfer reaction, the more rapid decrease of HRD 1200 of the alloys with x>2.0 is mainly attributed to the lowering of the hydrogen diffusion rate in the bulk of alloy. The cycling capacity degradation of the alloys is rather fast for practical application due to the corrosion of La and Mg and the large VH in the hydride phase.

Effect of the CB1 cannabinoid agonist WIN 55212-2 on the acquisition and reinstatement of MDMA-induced conditioned place preference in mice

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Miñarro José

2010-03-01

Full Text Available Abstract Background Numerous reports indicate that MDMA users consume other psychoactive drugs, among which cannabis is one of the most common. The aim of the present study was to evaluate, using the conditioned place preference, the effect of the cannabinoid agonist WIN 55,212-2 on the rewarding effects of MDMA in mice. Methods In the first experiment adolescent mice were initially conditioned with 1.25, 2.5 or 5 mg/kg of MDMA or 0.1 or 0.5 mg/kg of WIN and subsequently with both drugs. Reinstatement of the extinguished preference by priming doses was performed in the groups that showed CPP. In the second experiment, animals were conditioned with 2.5 or 5 mg/kg of MDMA and, after extinction, reinstatement of the preference was induced by 0.5 or 0.1 mg/kg of WIN. Results A low dose of WIN 55212-2 (0.1 mg/kg increased the rewarding effects of low doses of MDMA (1.25 mg/kg, although a decrease in the preference induced by MDMA (5 and 2.5 mg/kg was observed when the dose of WIN 55212-2 was raised (0.5 mg/kg. The CB1 antagonist SR 141716 also increased the rewarding effects of the lowest MDMA dose and did not block the effects of WIN. Animals treated with the highest WIN dose plus a non-neurotoxic dose of MDMA exhibited decreases of striatal DA and serotonin in the cortex. On the other hand, WIN 55212-2-induced CPP was reinstated by priming injections of MDMA, although WIN did not reinstate the MDMA-induced CPP. Conclusions These results confirm that the cannabinoid system plays a role in the rewarding effects of MDMA and highlights the risks that sporadic drug use can pose in terms of relapse to dependence. Finally, the potential neuroprotective action of cannabinoids is not supported by our data; on the contrary, they are evidence of the potential neurotoxic effect of said drugs when administered with MDMA.

Ameliorative Effects of Grape Seed Proanthocyanidin Extract on Growth Performance, Immune Function, Antioxidant Capacity, Biochemical Constituents, Liver Histopathology and Aflatoxin Residues in Broilers Exposed to Aflatoxin B1

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Sun, Lvhui; Zhang, Niya; Ling, Zhao; Zhu, Luoyi; Khan, Farhan Anwar; Zhang, Jiacai; Qi, Desheng

2017-01-01

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B1-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB1 in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB1 contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB1 (1 mg/kg) + GSPE 250 mg/kg; (AFB1 + GSPE 250 mg/kg) 5. Basal diet + AFB1 (1mg/kg) + GSPE 500 mg/kg, (AFB1 + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB1 alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB1 significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB1 contaminated diet reduced AFB1 residue in the liver and significantly mitigated AFB1 negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB1 in broiler chickens. PMID:29140290

Ekstrak Sambiloto (Andrographis paniculata Menurunkan Jumlah Skizon, Mikrogamet, Makrogamet, dan Oosista Eimeria tenella (EXTRACT OF ANDROGRAPHIS PANICULATA DECREASED SCHIZONTS, MICROGAMETES, MACROGAMETES AND OOCYSTS NUMBER OF EIMERIA TENELLA

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UMI CAHYANINGSIH

2013-07-01

Full Text Available The aim of this research was to observe the effect of ethanol extract of Andrographis paniculata givenin grading doses to the schizonts, microgamete, macrogamete, and oocytes counts of Eimeria tenella inchicken caecum. A total of ninety day old broiler chicks were used in the study. At two weeks old the broilerswere divided into six groups. Each group consisted of 15 broilers, the 6 groups were: (i negative control(broilers did not receive any treatment; (ii positive control (each animal were infected with 104 E. tenellaoocytes; (iii medicine control (each animal were infected with 104 E. tenella oocytes and coccidiostat; (ivA1 (each animal were infected with 104 E. tenella oocytes and paniculata extract 90 mg/kg body weight; (vA2 (each animal were infected with 104 E. tenella oocytes and paniculata extract 180 mg/kg body weight;and (vi A3 (each animal were infected with 104 E. tenella oocytes and paniculata extract 360 mg/kg bodyweight. At day 6, 9, 13, 16, and 22 post infection three broilers from each group were sacrificed and theirceca were collected for histopathological examination. The results showed that paniculata extract at dose90 mg/kg body weight and 180 mg/kg body weight was able to decrease the numbers of shizont, microgamete,macrogamete, and oocytes of E. tenella in the chicken caecum.

Rice straw incorporated just before soil flooding increases acetic acid formation and decreases available nitrogen

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Ronaldir Knoblauch

2014-02-01

Full Text Available Incorporation of rice straw into the soil just before flooding for water-seeded rice can immobilize mineral nitrogen (N and lead to the production of acetic acid harmful to the rice seedlings, which negatively affects grain yield. This study aimed to evaluate the formation of organic acids and variation in pH and to quantify the mineral N concentration in the soil as a function of different times of incorporation of rice straw or of ashes from burning the straw before flooding. The experiment was carried out in a greenhouse using an Inceptisol (Typic Haplaquept soil. The treatments were as follows: control (no straw or ash; incorporation of ashes from previous straw burning; rice straw incorporated to drained soil 60 days before flooding; straw incorporated 30 days before flooding; straw incorporated 15 days before flooding and straw incorporated on the day of flooding. Experimental units were plastic buckets with 6.0 kg of soil. The buckets remained flooded throughout the trial period without rice plants. Soil samples were collected every seven days, beginning one day before flooding until the 13th week of flooding for determination of mineral N- ammonium (NH4+ and nitrate (NO3-. Soil solution pH and concentration of organic acids (acetic, propionic and butyric were determined. All NO3- there was before flooding was lost in approximately two weeks of flooding, in all treatments. There was sigmoidal behavior for NH4+ formation in all treatments, i.e., ammonium ion concentration began to rise shortly after soil flooding, slightly decreased and then went up again. On the 91st day of flooding, the NH4+ concentrations in soil was 56 mg kg-1 in the control treatment, 72 mg kg-1 for the 60-day treatment, 73 mg kg-1 for the 30-day treatment and 53 mg kg-1 for the ash incorporation treatment. These ammonium concentrations correspond to 84, 108, 110 and 80 kg ha-1 of N-NH4+, respectively. When the straw was incorporated on the day of flooding or 15 days

Nuclear factor κB inhibitor BAY 11-7082 suppresses oxidative stress induced by endothelin-1 (ET-1) in rat kidney.

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Kowalczyk, Agata; Kołodziejczyk, Michał; Gorąca, Anna

2015-12-31

The aim of the study was to evaluate the effect of BAY 11-7082, an NF-κB inhibitor, on basal and ET-1-induced production of reactive oxygen species (ROS), TNF-α and p65 protein in rat kidney. The experimental animals were divided into five groups (n=7) receiving: 1) saline (control); 2 and 3) ET-1 in a dose of 3 μg/kg body weight (b.w.) or 12.5 μg/kg b.w.; 4) BAY 11-7082 (10 mg/kg b.w.); 5) BAY 11-7082 (10 mg/kg b.w.) and ET-1 (12.5 μg/kg b.w.), respectively. In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, TNF-α, p65 protein and GSH/GSSG ratio were determined. ET-1 resulted in a dose-dependent increase in TBARS and hydrogen peroxide (H2O2) levels, and a decrease in GSH/GSSG ratio when compared to the controls. BAY 11-7082 administered 1 h before ET-1 administration at a dose of 12.5 μg/kg resulted in a decrease (PET-1 groups. The level of TNF-α was increased (PET-1, while BAY 11-7082 reduced the TNF-α level (PET-1 induced oxidative stress in kidney tissue. These actions of BAY 11-7082 may result from reduced activity of NF-κB signaling pathways. Inhibition of the NF-κB pathway may be a promising strategy for preventing the progression of kidney damage.

Comparison of the Effect of Ondansetrone - Dexamethasone, Dexamethasone – Metoclopeamide and Ondansetron - Normal Saline in Decreasing Post Operative Nausa and Vomitting (PONV after Middle Ear Surgery

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Haddadi Soudabeh

2009-09-01

Full Text Available Background: The incidence of post-operative nausea and vomitting (PONV is increased after middle ear surgery and it may complicate and interact with reconstruction after surgery, so prevention and treatment of these complications are necessary.The aim of this study was to evaluate the efficacy of anti-emetic combinations in decreasing the PONV after middle ear surgery.Materials and methods: This double blind clinical trial was carried out during 2007-2008 on 111 patients of 15-45 years old with ASA I-II who were candidates for elective middle ear surgery under general anesthesia. The patients were divided into three groups. Patients in the ON group received Ondansetrone 0.1mg/kg + Nacl 0.9% 2cc, OD group received Ondansetrone 0.1mg/kg + Dexamethasone 0.15mg/kg and MD group received Dexamethasone 0.15mg/kg+ Metoclopramide 0.15mg/kg intravenously just before the end of surgery. The patients were evaluated for nausea, vomiting, need of anti-emetic drugs and drug dosage in recovery, 1-6, 6-12 and 12-24 hours after operation and then all data were statistically analyzed by SPSS software, Chi-square, ANOVA and t- Test. P<0.05 was significant.Results: There were no significant differences among three groups in age and sex. The incidence of PONV among 3 groups was not significantly different during 24 hours after operation. (P=0.271 but the incidence of PONV in the first six hours was different among 3 groups (P=0.007 (ON: 8.1%, OD: 0%, MD: 21.6%. Also Metoclopramide consumption was significant between three groups. Conclusion: This study showed that the need to anti-emetic drugs in first 6 hours was the least in OD group, but the difference in the incidence of PONV was not significant otherwise.

Synthesis and Anti-hyperlipidemic Activity of 3H-benzo [4, 5] thieno [2, 3-d] [1, 2, 3] triazin-4-ones: Possible Mechanism of Altered Lipid Metabolism

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Gollapalle L. Viswanatha

2012-09-01

Full Text Available Objectives: The present study was aimed to evaluate the anti-hyperlipidemic activity of newly synthesized tricyclic benzothieno 1, 2, 3-triazine derivatives namely CP-1 (3-(methyl-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one, CP-2 (3-(ethyl- 5,6,7,8-tetrahydro,3H-benzo[4,5] thieno[2,3-d][1,2,3] triazin-4-one and CP-6 (3-(2-chloro phenyl-5,6,7,8-tetrahydro,3H-benzo[4,5] thieno [2,3-d][1,2,3] triazin-4-one against dexamethasone and Triton WR-1339-induced hyper-lipidemia in rats.Methods: Anti-hyperlipidemic activity of the test compounds were evaluated against dexamethasone (10 mg/kg, subcutaneous [s.c.] and Triton WR-1339 (200 mg/kg, intraperitoneal [i.p] induced hyperlipidemia in rats.Results: Administration of single dose of Triton WR-1339 (200 mg/kg i.p and dexamethasone (10 mg/kg s.c. for 8 consecutive days to adult wistar rats caused severe hyperlipidemia characterized by marked increase in serum cholesterol, LDL-C, VLDL-C and triglyceride levels along with an increase in atherogenic index. Serum HDL-C levels were decreased significantly compare to normal control. Pretreatment with Atorvastatin (10 mg/kg, p.o., CP-1 (25 & 50 mg/kg, CP-2 (25 & 50 mg/kg and CP-6 (25 & 50mg/kg showed significant and dose-dependent protection against dexamethasone and Triton WR-1339-induced hyperlipidemia in rats by maintaining serum total cholesterol, LDL-C, VLDL-C and HDL-C levels within the normal range. Also, a significant decrease in atherogenic index was observed. The anti-hyperlipidemic effect of CP-6 was comparable with reference standard Atorvastatin. Furthermore, CP-6 was found to be more potent than CP-1 and CP-2.Conclusion: These findings suggest that CP-1, CP-2 and CP-6 possess significant anti-hyperlipidemic activity against experimental animal models of hyperlipidemia.

Effects on proliferation and cell cycle of irradiated KG-1 cells stimulated by CM-CSF

International Nuclear Information System (INIS)

Guo Dehuang; Dong Bo; Wen Gengyun; Luo Qingliang; Mao Bingzhi

2000-01-01

In order to explore the variety of cell proliferation and cell cycle after exposure to ionizing radiation, the responses of irradiated KG-1 cells of the human myeloid leukemia stimulated by GM-CSF, the most common used cytokine in clinic, were investigated. The results showed that GM-CSF enhance KG-1 cells proliferation, reduce G0/G1 block, increase S phase and G2/M phase. The stimulation effects of the GM-CSF are more effective in irradiated group than in control group

The application of 1,8-cineole, a terpenoid oxide present in medicinal plants, inhibits castor oil-induced diarrhea in rats.

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Jalilzadeh-Amin, Ghader; Maham, Massoud

2015-04-01

1,8-Cineole, a terpene, characterized as a major constituent occurring in the essential oils of several aromatic plants. It is widely used in pharmaceutical industry, as a food additive and for culinary purposes. This study investigates the inhibitory effect of 1,8-cineole on transit time and diarrhea in animal models. Acute toxicity and lethality of 1-8-cineole was determined by Lork's guidelines. The antidiarrheal effect of 1,8-cineole was investigated by determining the intestinal transit and enterpooling in rats. In all experiments, different doses of 1,8-cineole (20-120 mg/kg), atropine, and loperamide were administered orally. The LD50 of 1,8-cineole for oral administration was estimated to be 1280 mg/kg. 1,8-Cineole (20-120 mg/kg) did not show a significant decrease in small intestine transit (p > 0.05); however, the highest dose displayed a significant decrease in comparison with atropine (p castor oil transit test. 1,8-Cineole significantly delayed the onset of diarrhea to -142.33 ± 6.08 min at 120 mg/kg, while the time was 103.66 ± 20.73 min for the control and >240 min for the loperamide. Moreover, 1,8-cineole significantly decreased intestinal fluid accumulation (p < 0.05). This study demonstrated antispasmodic and antisecretory activities of 1,8-cineole and rationalized the traditional use of the plant containing various levels of this terpene in the treatment of gastrointestinal complains such as diarrhea.

The structural, electrical and optical properties of Mg-doped ZnO with different interstitial Mg concentration

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Hu, Yonghong, E-mail: hchyh@njust.edu.cn [School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100 (China); Institute of Optoelectronics & Nanomaterials, College of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Zeng, Haibo [Institute of Optoelectronics & Nanomaterials, College of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China); Du, Jifu [School of Nuclear Technology and Chemistry & Biology, Hubei University of Science and Technology, Xianning 437100 (China); Hu, Ziyu [Beijing Computational Science Research Center, Beijing 100084 (China); Zhang, Shengli [Institute of Optoelectronics & Nanomaterials, College of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing 210094 (China)

2016-10-01

Through first principle calculations, we studied the structural, electronic and optical properties of ZnO doped by interstitial Mg. With the increase of Mg content (x), the derivations of lattice parameters from the wurtzite ZnO become more and more significant. The Mg-doped ZnO with x below 15.79% is found to be n-type semiconductor. The minimum of energy band gap and light transmittance in high energy region (7.5–25 eV) decrease while the conductivity and refractive index increase with increasing x. Further increasing x up to 20%, the Mg-doped ZnO is found to be direct-band-gap semiconductor with great structural derivation from wurtzite phase. The light transmittance increases while the refractive index decreases with the increase of x due to the change of geometry and electronic structure. So, it’s concluded that the electronic and optical properties of ZnO doped by interstitial Mg may be greatly influenced by Mg content. - Graphical abstract: The minimum of energy gap decreases while the corresponding relative number of electrons into the conduction bands increases when the interstitial Mg content x in Mg-doped ZnO increases (0 ≤ x ≤ 15.79%). - Highlights: • The energy band gap decreases with the increase of interstitial Mg content from 5.88% to 15.79%. • The conductivity increases with the increase of interstitial Mg content from 5.88% to 15.79%. • The Mg{sub x}Zn{sub 1-x}O (interstitial Mg content x= 20%) is found to be a direct-band-gap semiconductor. • The light transmittance decreases with the increase of interstitial Mg content from 5.88% to 15.79%. • The refractive index increases with the increase of interstitial Mg content from 5.88% to 15.79%.

Effects of caffeine, theophylline and theobromine on scheduled controlled responding in rats.

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Carney, J. M.

1982-01-01

1 Rats were trained to respond under a variable interval 30 s (VI 30) schedule of food reinforcement. Caffeine (0.32-32 mg/kg), theophylline (1.0-56 mg/kg) and theobromine (10-320 mg/kg) in general produced dose-related decreases in operant responding. At relatively low doses, caffeine (1.0 mg/kg) and theophylline (3.2 mg/kg) produced slight but nonsignificant increases in VI 30 responding. 3 The rank order of potency for producing decreases in responding was caffeine greater than theophylline greater than theobromine. 4 Daily caffeine injections (32 mg/kg, i.p.) resulted in the development of caffeine tolerance. This tolerance was characterized by a 6 fold shift to the right in the caffeine dose-effect curve. Saline substitution for the 32.0 mg/kg caffeine maintenance dose resulted in a substantial decrease in responding. PMID:7066599

[Influence of ET-1 and ETA receptor blocker (BQ123) on the level of TNF-α in the brain rat].

Science.gov (United States)

Gorąca, Anna; Skibska, Beata

2016-06-01

Endothelin 1 (ET-1) in addition to the vasoconstriction, also has mitogenic, proinflammatory and proagregation activities. The mediators of inflammatory responses are cytokines, including special role attributed to tumor necrosis factor (TNF-α). The aim of this study was to evaluate the effect of ET-1 and its receptor blocker (BQ123) on the level of TNF-α in the brain rat. Experiments were performed on four groups of Wistar-Kyoto rats. Animals were divided into four groups of 8 rats. Group I - control was administered into the tail vein solution of 0.9 % NaCl. Group II - saline followed by ET-1 (3 μg/kg b.w.). Group III - saline followed by BQ123 (1 mg/kg b.w.). Group IV (BQ123/ET-1) - BQ123 (1 mg/kg b.w.) administered 30 min before ET-1 (3 μg/kg b.w.). Administration of ET-1 at doses of 3 μg/kg b.w. resulted in a statistically significant increase in TNF-α concentrations in brain homogenates compared to the control group (pET(A) receptor blocker - BQ123 (1mg/kg b.w.) 30 min before administration of ET-1 significantly decreased in TNF-α concentrations in brain homogenates (p ET-1 is significantly increased in TNF-α levels in brain homogenates, while BQ123 given 30 min before administration of ET-1 caused a significant decrease in TNF-α levels, suggesting that its anti-inflammatory activity. © 2016 MEDPRESS.

Astrocytic expression of GFAP and serum levels of IL-1β and TNF-α in rats treated with different pain relievers

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Gisele Ferreira Amaral

Full Text Available ABSTRACT Pro-inflammatory cytokines and glial cells, especially microglial cells, have been implicated in persistent pain sensitization. Less is known about the role of astrocytes in pain regulation. This study aimed to observe the expression of the astrocytic biomarker glial fibrillary acidic protein (GFAP and the serum levels of interleukin 1 beta (IL-1β and tumor necrosis factor alpha (TNF-α after short-term administration of central pain relievers in rats not submitted to noxious stimuli. Male Wistar rats were divided into five groups, receiving for nine days- (1 amitriptyline (Amt-10 mg/kg/day, by gavage; (2 gabapentin (Gb-60 mg/kg/day, by gavage; (3 methadone (Me-4.5 mg/kg/day, intraperitoneal route [IP]; (4 morphine (Mo-10 mg/kg/day, IP; or (5 0.9% saline solution, IP. Brain samples were collected for immunohistochemical study of GFAP expression in the mesencephalon and nucleus accumbens (NAc. The area of GFAP-positive cells was calculated using MetaMorph software and serum levels of IL-1β and TNF-α were measured by enzyme-linked immunosorbent assay. Serum TNF-α levels were decreased in the groups treated with Mo, Me and Gb, but not in the Amt-treated group. IL-1β decreased only in rats treated with Me. The astrocytic expression of GFAP was decreased in the brainstem with all drugs, while it was increased in the NAc with Amt, Me and Mo.

Decrease of Pirimiphos-Methyl and Deltamethrin Residues in Stored Rice with Post-Harvest Treatment

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Chuanshan Yu

2014-05-01

Full Text Available A modified quick, easy, cheap, effective, rugged (QuEChERS method with multi-walled carbon nanotubes (MWCNTs as reversed-dispersive solid phase extraction (r-DSPE material was applied to the analysis of pirimiphos-methyl and deltamethrin residues in stored rice. Two dustable powder (DP formulations (2% pirimiphos-methyl and deltamethrin DP; 5% pirimiphos-methyl DP were applied in simulated storehouse trials in the lab. The residues and dissipation of the two pesticides in stored rice were investigated. Slow dissipation of both pesticides was observed in stored rice. The half-lives of pirimiphos-methyl were 23.9–28.9 days, and those of deltamethrin were 23.9–24.8 days. Residues of pirimiphos-methyl from application rates of 4.5–6.75 a.i. mg/kg (active ingredient milligram per kilogram and 10–15 a.i. mg/kg were 1.6–3.8 mg/kg and 3.0–4.5 mg/kg at 60 days Pre-harvest Interval (PHI. Residues of deltamethrin from an application rate of 0.5–0.75 a.i. mg/kg were 0.13–0.14 mg/kg at 60 days PHI. Both pesticides residues were below the Maximum Residue Limits (MRLs established by the Codex Alimentarius Commission (CAC. Therefore, at the recommended dosages they are safe for use on stored rice.

Concentration of Potassium in Plasma, Erythrocytes, and Muscle Tissue in Cows with Decreased Feed Intake and Gastrointestinal Ileus.

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Schneider, S; Müller, A; Wittek, T

2016-01-01

Healthy cows consume large amounts of potassium and a sudden loss in appetite can lead to hypokalemia. The routine method to evaluate potassium homeostasis is the measurement of the extracellular potassium in plasma or serum, but this does not provide information about the intracellular potassium pool. To evaluate potassium homeostasis by comparing the extracellular and intracellular potassium concentration in cows with reduced feed intake and gastrointestinal ileus. Twenty cows 1-3 days postpartum (group 1) and 20 cows with gastrointestinal ileus (group 2). Observational cross-sectional study. Plasma potassium was measured by using an ion-sensitive electrode. Intracellular potassium was measured in erythrocytes and muscle tissue (muscle biopsy) by using inductively coupled plasma optical emission spectroscopy. Cows of group 1 did not have hypokalemia. Overall cows with gastrointestinal ileus were hypokalemic (mean ± SD, 2.9 mmol/L ± 0.78), but potassium concentration in erythrocytes and muscle tissue was not lower than in postpartum cows. Intracellular potassium in erythrocytes varied very widely; group 1: 3497-10735 mg/kg (5559 ± 2002 mg/kg), group 2: 4139-21678 mg/kg (7473 ± 4034 mg/kg). Potassium in muscle tissue did not differ between group 1 (3356 ± 735 mg/kg wet weight) and group 2 (3407 ± 1069 mg/kg wet weight). No association between extracellular and intracellular potassium concentrations was detected. That measurement of plasma potassium concentration is not sufficient to evaluate potassium metabolism of cows. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Elemental sulfur amendment decreases bio-available Cr-VI in soils impacted by leather tanneries.

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Shi, Jingjing; Chen, Hualin; Arocena, Joselito M; Whitcombe, Todd; Thring, Ronald W; Memiaghe, Jeff Nze

2016-05-01

This study investigated the potential use of elemental S (S(0)) to convert Cr-VI to Cr-III which should decrease the bio-availability hence, toxicity of Cr-VI in soils. The bio-available fraction of Cr in soil was measured by phosphate buffer extraction (PBE) and the results showed that the fraction is about 10% of the total Cr-VI and varied from 12.8 to 42.5 mg kg(-1). The addition of 4.0 mg g(-1) S(0) decreased PBE Cr-VI to soils. Synchrotron-based X-ray absorption near-edge structure (XANES), X-ray fluorescence (XRF) and micro-XRD revealed that Cr-III was the dominant species (99% of total Cr) and Cr was retained by hematite and goethite in soil. Fe-containing minerals may have provided sufficient protection to render the dominant Cr-III species biochemically inert to redox processes in soils. It is concluded that S(0)amendment is a promising approach to remediate Cr-VI contaminated soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

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Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

2018-05-18

Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

PKC/CREB pathway mediates the expressions of GABAA receptor subunits in cultured hippocampal neurons after low-Mg2+ solution treatment.

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Wu, Guofeng; Yu, Jinpeng; Wang, Likun; Ren, Siying; Zhang, Yixia

2018-02-01

To investigate the potential effects of the PKC/CREB pathway on the expressions of GABA A receptor subunits α1, γ2, and δ in cultured hippocampal neurons using a model of epilepsy that employed conditions of low magnesium (Mg 2+ ). A total of 108 embryonic rats at the age of 18 embryonic days (E18)prepared from adult female SD rats were used as experimental subjects. Primary rat hippocampal cultures were prepared from the embryonic 18 days rats. The cultured hippocampal neurons were then treated with artificial cerebrospinal fluid containing low Mg 2+ solutions to generate a low Mg 2+ model of epilepsy. The low Mg 2+ stimulation lasted for 3 h and then returned to in maintenance medium for 20 h. The changes of the GABA A receptor subunit α1, γ2, δ were observed by blocking or activating the function of the CREB. The quantification of the GABA A receptor subunit α1, γ2, δ and the CREB were determined by a qRT-PCR and a Western blot method. After the neurons were exposed to a low-Mg 2+ solution for 3 h, GABA A receptor mRNA expression markedly increased compared to the control, and then gradually decreased. In contrast, CREB mRNA levels exhibited a dramatic down-regulation 3 h after terminating low-Mg 2+ treatment, and then peaked at 9 h. Western blot analyses verified that staurosporine suppressed CREB phosphorylation (p-CREB). The mRNA expression of GABA A receptor subunit α1 increased only in the presence of staurosporine, whereas the expressions of subunits γ2 and δ significantly increased in the presence of either KG-501 or staurosporine. Furthermore, phorbol 12-myristate 13-acetate (PMA) decreased the expressions of GABA A subunits α1, γ2, and δ when administered alone. However, the administration of either KG-501 or staurosporine reversed the inhibitory effects of PMA. The PKC/CREB pathway may negatively regulate the expressions of GABA A receptor subunits α1, γ2, and δ in cultured hippocampal neurons in low Mg 2+ model of

Intra-individual comparison of different contrast media concentrations (300 mg, 370 mg and 400 mg iodine) in MDCT

Energy Technology Data Exchange (ETDEWEB)

Behrendt, Florian F.; Keil, Sebastian; Plumhans, Cedric; Guenther, Rolf W. [RWTH Aachen University, Department of Diagnostic Radiology, University Hospital, Aachen (Germany); Pietsch, Hubertus; Jost, Gregor; Sieber, Martin A.; Seidensticker, Peter [Bayer Schering Pharma AG, Berlin (Germany); Mahnken, Andreas H. [RWTH Aachen University, Department of Diagnostic Radiology, University Hospital, Aachen (Germany); RWTH Aachen University, Applied Medical Engineering, Helmholtz-Institute for Biomedical Engineering, Aachen (Germany)

2010-07-15

To compare intra-individual contrast enhancement in multi-detector-row computed tomography (MDCT) using contrast media (CM) containing 300, 370 and 400 mg iodine per ml (mgI/ml). Six pigs underwent repeated chest MDCT using three different CM (iopromide 300, iopromide 370, iomeprol 400). An identical iodine delivery (IDR) rate of 1.5 gI/s and a constant total iodine dose of 300 mg/kg body weight were used. Dynamic CT were acquired at the level of the pulmonary artery, and the ascending and descending aorta. After the time enhancement curves were computed, the pulmonary and aortic peak enhancement, time to peak and plateau time above 300 HU were calculated. Intra-individual peak contrast enhancement was significantly higher for the 300 mgI/ml contrast medium compared with the 370 and 400 mgI/ml media: pulmonary trunk 595 HU vs 516 HU (p = 0.0093) vs 472HU (p = 0.0005), and aorta 505 HU vs 454 HU (p = 0.0008) vs 439 HU (p = 0.0001), respectively. Comparison of time to peaks showed no significant difference. Plateau times were significantly longer for the 300 mgI/ml than for the 370 and 400 mgI/ml CM at all anatomical sites. Given normalised IDR and total iodine burden, the use of CM with a standard concentration with 300 mg iodine/ml provides improved contrast enhancement compared with highly concentrated CM in the chest. (orig.)

Mott transition in Ga-doped Mg{sub x}Zn{sub 1-x}O: A direct observation

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Wei Wei; Nori, Sudhakar [Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC (United States); Jin Chunming [Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Campus Box 7115, Raleigh, NC 27695-7115 (United States); Narayan, Jagdish [Department of Materials Science and Engineering, North Carolina State University, Raleigh, NC (United States); Narayan, Roger J., E-mail: roger_narayan@unc.edu [Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Campus Box 7115, Raleigh, NC 27695-7115 (United States); Ponarin, Dmtri; Smirnov, Alex [Department of Chemistry, North Carolina State University, Raleigh, NC (United States)

2010-07-25

This paper reports the direct evidence for Mott transition in Ga-doped Mg{sub x}Zn{sub 1-x}O thin films. Highly transparent Ga-doped Mg{sub x}Zn{sub 1-x}O thin films were grown on c-plane sapphire substrates using pulsed laser deposition. 0.1 at.%, 0.5 at.% and 1 at.% Ga-doped Mg{sub 0.1}Zn{sub 0.9}O films were selected for resistivity measurements in the temperature range from 250 K to 40 mK. The 0.1 at.% Ga-doped Mg{sub 0.1}Zn{sub 0.9}O thin film showed typical insulator-like behavior and the 1 at.% Ga-doped Mg{sub 0.1}Zn{sub 0.9}O thin film showed typical metal-like behavior. The 0.5 at.% Ga-doped Mg{sub 0.1}Zn{sub 0.9}O film showed increasing resistivity with decreasing temperature; resistivity was saturated with a value of 1.15 x 10{sup -2} {Omega} cm at 40 mK, which is characteristic of the metal-insulator transition region. Temperature-dependent conductivity {sigma}(T) in the low temperature range revealed that the electron-electron scattering is the dominant dephasing mechanism. The inelastic scattering time is found to vary as T{sup -3/2}.

Chemopreventive effect of artesunate in 1,2-dimethylhydrazine-induced rat colon carcinogenesis

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Sazal Patyar

2017-01-01

Full Text Available Artesunate (ART is a semisynthetic derivative of artemisinin. Artemisinin and its derivatives have shown profound cytotoxicity and antitumor activity in addition to antimalarial activity in various studies. As the in vivo chemopreventive efficacy of ART in colon carcinogenesis has not been investigated so far, the aim of the current study was to study the chemopreventive effect of ART in 1,2-dimethylhydrazine (DMH-induced rat colon carcinogenesis. Animals were divided into four groups (n = 6: Group I - vehicle (1 mM ethylenediaminetetraacetic acid, Group II - DMH (20 mg/kg, Group III - DMH + 5-fluorouracil (81 mg/kg, Group IV - DMH + ART (6.7 mg/kg. After completion of 15 weeks of treatment, rats were sacrificed under ether anesthesia by cervical dislocation for assessment of lipid peroxidation (LPO, antioxidant status, average number of aberrant crypt foci (ACF, and cytokine levels. ART administration significantly decreased the average number of ACF/microscopic field. Similarly, LPO level was decreased and antioxidant activities were enhanced after ART treatment. ART decreased the levels of proinflammatory cytokines and induced apoptosis in the colons of DMH-treated rats. The results of this study suggest that ART has a beneficial effect against chemically induced colonic preneoplastic progression in rats.

Protective effect of lemongrass oil against dexamethasone induced hyperlipidemia in rats: possible role of decreased lecithin cholesterol acetyl transferase activity.

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Kumar, V R Santhosh; Inamdar, Md Naseeruddin; Nayeemunnisa; Viswanatha, G L

2011-08-01

To evaluate the anti-hyperlipidemic activity of lemongrass oil against in dexamethasone induced hyperlipidemia in rats. Administration of dexamethasone was given at 10 mg/kg, sc. to the adult rats for 8 d induces hyperlipidemia characterized by marked increase in serum cholesterol and triglyceride levels along with increase in atherogenic index. Lemongrass oil (100 and 200 mg/kg, po.) treatment has showed significant inhibition against dexamethasone hyperlipidemia by maintaining the serum levels of cholesterol, triglycerides and atherogenic index near to the normal levels and the antihyperlipidemic effect of the lemongross oil was comparable with atorvastatin 10 mg/kg, po. The possible mechanism may be associated with decrease in lecithin cholesterol acetyl transferase (LCAT) activity. These results suggested that Lemon gross oil possess significant anti-hyperlipidemic activity. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Fatal cardiac arrhythmia after repeated exposure to 1,1-difluoroethane (DFE).

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Avella, Joseph; Wilson, James C; Lehrer, Michael

2006-03-01

A 42-year-old man was found dead after repeated exposure to 1,1-difluoroethane (DFE, Freon 152a), a propellant found in CRC Duster, a product intended for the removal of dust and lint. Toxicologic analysis detected DFE in femoral blood 136.3 mg/L, brain 117.5 mg/kg, liver 87.6 mg/kg, lung 60.3 mg/kg, adipose 235.7 mg/kg, and vitreous fluid 25.1 mg/L. The cause of death was determined to be a fatal cardiac arrhythmia due to intoxication with 1,1-difluoroethane. After comparison to previously published cases involving DFE, we suggest that analysis of adipose tissue for DFE and similar compounds, along with blood and other tissues, may be useful in distinguishing between acute versus chronic exposure. Adipose may also be a valuable alternate specimen for detection in cases where loss or elimination from blood is likely to have occurred.

AY Bala, T. Adamu, U. Abubakar, MJ Ladan and MG Abubakar

African Journals Online (AJOL)

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About 20 – 25 parasites per microscope field were dosed with 1, 2 and 4mg/ml of aqueous extracts of .... brucei as test organisms. It is hoped ... in open air in the laboratory to avoid denaturing .... extract of Terminalia spp at 150mg/kg in mice.

The antidepressant-like effect of 7-fluoro-1,3-diphenylisoquinoline-1-amine in the mouse forced swimming test is mediated by serotonergic and dopaminergic systems.

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Pesarico, Ana Paula; Sampaio, Tuane Bazanella; Stangherlin, Eluza Curte; Mantovani, Anderson C; Zeni, Gilson; Nogueira, Cristina Wayne

2014-10-03

The aim of the present study was to investigate the role of monoaminergic system in the antidepressant-like action of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a derivative of isoquinoline class, in Swiss mice. The antidepressant-like effect of FDPI was characterized in the modified forced swimming test (FST) and the possible mechanism of action was investigated by using serotonergic, dopaminergic and noradrenergic antagonists. Monoamine oxidase (MAO) activity and [(3)H]serotonin (5-HT) uptake were determined in prefrontal cortices of mice. The results showed that FDPI (1, 10 and 20mg/kg, i.g.) reduced the immobility time and increased the swimming time but did not alter climbing time in the modified FST. These effects were similar to those of paroxetine (8mg/kg, i.p.), a positive control. Pretreatments with p-chlorophenylalanine (100mg/kg, i.p., an inhibitor of 5-HT synthesis), WAY100635 (0.1mg/kg, s.c., 5-HT1A antagonist), ondansetron (1mg/kg, i.p., a 5-HT3 receptor antagonist), haloperidol (0.2mg/kg, i.p., a non-selective D2 receptor antagonist) and SCH23390 (0.05mg/kg, s.c., a D1 receptor antagonist) were effective to block the antidepressant-like effect of FDPI at a dose of 1mg/kg in the FST. Ritanserin (1mg/kg, i.p., a 5-HT2A/2C receptor antagonist), sulpiride (50mg/kg, i.p., a D2 and D3 receptor antagonist), prazosin (1mg/kg, i.p., an α1 receptor antagonist), yohimbine (1mg/kg, i.p., an α2 receptor antagonist) and propranolol (2mg/kg, i.p., a β receptor antagonist) did not modify the effect of FDPI in the FST. FDPI did not change synaptosomal [(3)H]5-HT uptake. At doses of 10 and 20mg/kg FDPI inhibited MAO-A and MAO-B activities. These results suggest that antidepressant-like effect of FDPI is mediated mostly by serotonergic and dopaminergic systems. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of heavy metals on pH buffering capacity and solubility of Ca, Mg, K, and P in non-spiked and heavy metal-spiked soils.

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Najafi, Sarvenaz; Jalali, Mohsen

2016-06-01

In many parts of the world, soil acidification and heavy metal contamination has become a serious concern due to the adverse effects on chemical properties of soil and crop yield. The aim of this study was to investigate the effect of pH (in the range of 1 to 3 units above and below the native pH of soils) on calcium (Ca), magnesium (Mg), potassium (K), and phosphorus (P) solubility in non-spiked and heavy metal-spiked soil samples. Spiked samples were prepared by cadmium (Cd), copper (Cu), nickel (Ni), and zinc (Zn) as chloride salts and incubating soils for 40 days. The pH buffering capacity (pHBC) of each sample was determined by plotting the amount of H(+) or OH(-) added (mmol kg(-1)) versus the related pH value. The pHBC of soils ranged from 47.1 to 1302.5 mmol kg(-1) for non-spiked samples and from 45.0 to 1187.4 mmol kg(-1) for spiked soil samples. The pHBC values were higher in soil 2 (non-spiked and spiked) which had higher calcium carbonate content. The results indicated the presence of heavy metals in soils generally decreased the solution pH and pHBC values in spiked samples. In general, solubility of Ca, Mg, and K decreased with increasing equilibrium pH of non-spiked and spiked soil samples. In the case of P, increasing the pH to about 7, decreased the solubility in all soils but further increase of pH from 7, enhanced P solubility. The solubility trends and values for Ca, Mg, and K did not differed significantly in non-spiked and spiked samples. But in the case of P, a reduction in solubility was observed in heavy metal-spiked soils. The information obtained in this study can be useful to make better estimation of the effects of soil pollutants on anion and cation solubility from agricultural and environmental viewpoints.

Gynura procumbens Merr. decreases blood pressure in rats by vasodilatation via inhibition of calcium channels

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See-Ziau Hoe

2011-01-01

Full Text Available INTRODUCTION: Gynura procumbens has been shown to decrease blood pressure via inhibition of the angiotensinconverting enzyme. However, other mechanisms that may contribute to the hypotensive effect have not been studied. OBJECTIVES: To investigate the cardiovascular effects of a butanolic fraction of Gynura procumbens in rats. METHODS: Anaesthetized rats were given intravenous bolus injections of butanolic fraction at doses of 2.5-20 mg/kg in vivo. The effect of butanolic fraction on vascular reactivity was recorded in isolated rat aortic rings in vitro. RESULTS: Intravenous administrations of butanolic fraction elicited significant (p<0.001 and dose-dependent decreases in the mean arterial pressure. However, a significant (p<0.05 decrease in the heart rate was observed only at the higher doses (10 and 20 mg/kg. In isolated preparations of rat aortic rings, phenylephrine (1×10-6 M- or potassium chloride (8×10-2 M-precontracted endothelium-intact and -denuded tissue; butanolic fraction (1×10-6-1×10-1 g/ml induced similar concentration-dependent relaxation of the vessels. In the presence of 2.5×10-3 and 5.0×10-3 g/ml butanolic fraction, the contractions induced by phenylephrine (1×10-9-3×10-5 M and potassium chloride (1×10-2-8×10-2 M were significantly antagonized. The calcium-induced vasocontractions (1×10-4-1×10-2 M were antagonized by butanolic fraction concentration-dependently in calcium-free and high potassium (6×10-2 M medium, as well as in calcium- and potassium-free medium containing 1×10-6 M phenylephrine. However, the contractions induced by noradrenaline (1×10-6 M and caffeine (4.5×10-2 M were not affected by butanolic fraction. CONCLUSION: Butanolic fraction contains putative hypotensive compounds that appear to inhibit calcium influx via receptor-operated and/or voltage-dependent calcium channels to cause vasodilation and a consequent fall in blood pressure.

Determination of the overall migration from silicone baking moulds into simulants and food using 1H-NMR techniques.

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Helling, Ruediger; Mieth, Anja; Altmann, Stefan; Simat, Thomas Joachim

2009-03-01

Different silicone baking moulds (37 samples) were characterized with respect to potential migrating substances using 1H-NMR, RP-HPLC-UV/ELSD and GC techniques. In all cases cyclic organosiloxane oligomers with the formula [Si(CH3)2-O]n were identified (n = 6 ... 50). Additionally, linear, partly hydroxyl-terminated organosiloxanes HO-[Si(CH3)2-O]n-H (n = 7 ... 20) were found in 13 samples. No substances other than siloxanes could be detected, meaning the migrants mainly consist of organopolysiloxanes. Based on this knowledge, a 1H-NMR quantification method for siloxanes was established for the analysis of both simulants and foodstuffs. Validation of the 1H-NMR method gave suitable performance characteristics: limit of detection 8.7 mg kg(-1) oil, coefficient of variation 7.8% (at a level of 1.0 mg kg(-1) food). Migration studies were carried out with simulants (olive oil, isooctane, ethanol (95%), Tenax) as well as preparation of different cakes. From the 1st to 10th experiment, siloxane migration into cakes only slightly decreased, with a significant dependence on fat content. Migration never exceeded a level of 21 mg kg(-1) (3 mg dm(-2)) and was, therefore, well below the overall migration limit of 60 mg kg(-1) (10 mg dm(-2)). However, migration behaviour into simulants differed completely from these results.

Reducing Mg Acceptor Activation-Energy in Al0.83Ga0.17N Disorder Alloy Substituted by Nanoscale (AlN)5/(GaN)1 Superlattice Using MgGa δ-Doping: Mg Local-Structure Effect

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Zhong, Hong-Xia; Shi, Jun-Jie; Zhang, Min; Jiang, Xin-He; Huang, Pu; Ding, Yi-Min

2014-10-01

Improving p-type doping efficiency in Al-rich AlGaN alloys is a worldwide problem for the realization of AlGaN-based deep ultraviolet optoelectronic devices. In order to solve this problem, we calculate Mg acceptor activation energy and investigate its relationship with Mg local structure in nanoscale (AlN)5/(GaN)1 superlattice (SL), a substitution for Al0.83Ga0.17N disorder alloy, using first-principles calculations. A universal picture to reduce acceptor activation energy in wide-gap semiconductors is given for the first time. By reducing the volume of the acceptor local structure slightly, its activation energy can be decreased remarkably. Our results show that Mg acceptor activation energy can be reduced significantly from 0.44 eV in Al0.83Ga0.17N disorder alloy to 0.26 eV, very close to the Mg acceptor activation energy in GaN, and a high hole concentration in the order of 1019 cm-3 can be obtained in (AlN)5/(GaN)1 SL by MgGa δ-doping owing to GaN-monolayer modulation. We thus open up a new way to reduce Mg acceptor activation energy and increase hole concentration in Al-rich AlGaN.

Activation of TRPV1 by capsaicin induces functional Kinin B1 receptor in rat spinal cord microglia

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Talbot Sébastien

2012-01-01

Full Text Available Abstract Background The kinin B1 receptor (B1R is upregulated by pro-inflammatory cytokines and oxydative stress, which are enhanced by transient receptor potential vanilloid subtype 1 (TRPV1 activation. To examine the link between TRPV1 and B1R in inflammatory pain, this study aimed to determine the ability of TRPV1 to regulate microglial B1R expression in the spinal cord dorsal horn, and the underlying mechanism. Methods B1R expression (mRNA, protein and binding sites was measured in cervical, thoracic and lumbar spinal cord in response to TRPV1 activation by systemic capsaicin (1-50 mg/kg, s.c in rats pre-treated with TRPV1 antagonists (capsazepine or SB-366791, the antioxidant N-acetyl-L-cysteine (NAC, or vehicle. B1R function was assessed using a tail-flick test after intrathecal (i.t. injection of a selective B1R agonist (des-Arg9-BK, and its microglial localization was investigated by confocal microscopy with the selective fluorescent B1R agonist, [Nα-bodipy]-des-Arg9-BK. The effect of i.t. capsaicin (1 μg/site was also investigated. Results Capsaicin (10 to 50 mg/kg, s.c. enhanced time-dependently (0-24h B1R mRNA levels in the lumbar spinal cord; this effect was prevented by capsazepine (10 mg/kg, i.p.; 10 μg/site, i.t. and SB-366791 (1 mg/kg, i.p.; 30 μg/site, i.t.. Increases of B1R mRNA were correlated with IL-1β mRNA levels, and they were significantly less in cervical and thoracic spinal cord. Intrathecal capsaicin (1 μg/site also enhanced B1R mRNA in lumbar spinal cord. NAC (1 g/kg/d × 7 days prevented B1R up-regulation, superoxide anion production and NF-kB activation induced by capsaicin (15 mg/kg. Des-Arg9-BK (9.6 nmol/site, i.t. decreased by 25-30% the nociceptive threshold at 1 min post-injection in capsaicin-treated rats (10-50 mg/kg while it was without effect in control rats. Des-Arg9-BK-induced thermal hyperalgesia was blocked by capsazepine, SB-366791 and by antagonists/inhibitors of B1R (SSR240612, 10 mg/kg, p

Detection of Respiratory Adverse Events in Pediatric Dental Patients Sedated With 0.75mg/Kg of Midazolam and Oxygen by Continuous Pretracheal Auscultation: A Prospective Randomized Controlled Trial.

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Somri, Mostafa; Matter, Ibrahim; Hadjittofi, Christopher; Hoash, Naser; Moaddi, Bian; Kharouba, Johnny; Parisinos, Constantinos A; Peretz, Benjamin

Sedation is becoming more commonplace for pediatric patients undergoing minor procedures. Fortunately, electronic monitors have contributed to a reduction in the associated respiratory adverse events (RAEs). To test the hypothesis that adding the pretracheal stethoscope (PTS) to standard monitoring methods (SMMs) may improve RAE detection in sedated pediatric dental patients, the frequency of RAEs detected by SMMs (i.e. visual observation, capnography, and pulse oximetry) was compared to that detected by SMMs alongside continuous PTS auscultation. A prospective, randomised, controlled trial was performed with 100 pediatric patient participants of ASA≤2, who were scheduled to receive dental treatment under 0.75 mg/kg and oxygen. Patients were randomised into Groups A (n=50; SMMs) and B (n=50; SMMs+PTS). Inclusion criteria were behavioral management problems and intolerance to dental treatment despite behavioral management techniques or nitrous oxide administration. Exclusion criteria were high-risk conditions for RAEs, altered mental status, gastrointestinal disorders, parental refusal of conscious sedation and failure of previous conscious sedation. An anesthesist was present throughout the dental treatments. RAEs were detected in 10 (20%) and 22(44%) Group A and B patients respectively (p=0.01). The majority of RAEs within Group B were detected by PTS auscultation (n=19). Capnography produced 13 and 15 false-positive results in Groups A and B respectively, whereas the PTS produced 4(8%) false-positive results in Group B (p=0.009). PTS was found to be useful for detecting RAEs during pediatric dental sedation with 0.75mg/kg midazolam and oxygen, in the presence of an anesthesist.

Decreased arachidonic acid content and metabolism in tissues of NZB/W F1 females fed a diet containing 0.45% dehydroisoandrosterone (DHA)

International Nuclear Information System (INIS)

Matsunaga, A.; Cottam, G.L.

1987-01-01

A diet containing 0.45% DHA fed to NZB/W mice, a model of systemic lupus erythematosus, delays the time of onset, improves survival and decreases the formation of antibodies to ds-DNA. Essential fatty acid-deficient diets or inclusion of eicosapentaenoic acid have similar beneficial effects and led them to investigate arachidonic acid metabolism in response to feeding DHA. The arachidonic acid content of plasma cholesteryl ester decreased from 37.4 +/- 2.2 to 28.2 +/- 1.3 mg%. In total liver phospholipid the value decreased from 18.1 +/- 0.52 to 13.7 +/- 1.3 mg%, in total kidney phospholipid the value decreased from 24.10 +/- 0.87 to 20.7 +/- 0.32 mg% and in resident peritoneal macrophages the value decreased from 15.4 +/- 4.6 to 3.6 +/- 1.4 mg%. The metabolism of exogenous [1- 14 C]arachidonic acid by resident peritoneal macrophages in response to Zymosan stimulation for 2 hr was examined by extraction of metabolites and separation by HPLC. Cells isolated from DHA-fed animals produced less PGE2 than controls, yet similar amounts of 6-keto PGF1α were produced. Arachidonic acid metabolites have significant effects on the immune system and may be a mechanism involved in the benefits obtained by inclusion of DHA in the diet

Cardiovascular activity of rasagiline, a selective and potent inhibitor of mitochondrial monoamine oxidase B: comparison with selegiline.

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Abassi, Zaid A; Binah, Ofer; Youdim, Moussa B H

2004-10-01

Selegiline is used for treating Parkinson's disease. Despite its efficacy, the clinical use of selegiline in combination with l-dihydroxphenylalanine in Parkinsonian patients is hampered by cardiovascular complications, such as hypotension. This study was designed to compare in rats the cardiovascular effects of selegiline and rasagiline, their metabolites l-methamphetamine and aminoindan (TVP-136), respectively, and the second rasagiline metabolite non-monoamine oxidase (MAO) inhibitor TVP-1022 (N-propargyl-1S(-)aminoindan). Intravenous (i.v.) administration of selegiline and rasagiline (1 mg kg(-1)) to anaesthetized rats (thiobutabarbital, 100 mg kg(-1), i.p.) did not affect mean arterial pressure (MAP), carotid blood flow (CBF) or carotid vascular resistance (CVR). Selegiline (10 mg kg(-1), i.v.) decreased MAP, CBF and increased CVR. In contrast, rasagiline (10 mg kg(-1), i.v.) caused a small transient decrease in MAP, while CBF and CVR were unchanged. l-methamphetamine (1 mg kg(-1), i.v.) administration provoked a dramatic and long-lasting depressor response, decreased CBF and increased CVR. In contrast, injection of aminoindan or TVP-1022 at a similar dose produced gradual nonsignificant decreases in MAP and CBF. Chronic oral treatment (21 days) of awake rats with selegiline at 10 mg kg(-1) decreased systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP, whereas heart rate was unaffected. Since the effective MAO-B inhibitory and clinical dose of rasagiline is about one-tenth that of selegiline, administration of 1 mg kg(-1) day(-1) rasagiline resulted in moderate decreases in SBP, DBP, and MAP, which were significantly lower than those caused by the 10 mg kg(-1) day(-1) dose of selegiline. These findings indicate that rasagiline, when given at doses equivalent to selegiline, is less likely to be hypotensive.

Effects of rolipram and zaprinast on learning and memory in the Morris water maze and radial arm maze tests in naive mice.

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Akar, F; Mutlu, O; Celikyurt, I K; Ulak, G; Erden, F; Bektas, E; Tanyeri, P

2015-02-01

Inhibition of phosphodiesterase 5 (PDE) improved recognition memory and counteracted spatial learning impairment induced by nitric oxide synthase (NOS) inhibition in recent studies. Aim of this study was to investigate effects of rolipram, a PDE4 inhibitor and zaprinast, a PDE5 inhibitor, on learning and memory in Morris water maze (MWM) and radial arm maze (RAM) tests in naive mice. Male Balb-c mice were treated subchronically with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) for 6 days in the MWM test and acutely before the retention trial of radial arm maze test. Rolipram (0.05 and 0.1 mg/kg) significantly decreased escape latency between 2(nd) and 5(th) sessions, while zaprinast (10 mg/kg) significantly decreased escape latency only in 2(nd) session. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly increased time spent in escape platform's quadrant in probe trial of MWM test; only rolipram decreased mean distance to platform, while zaprinast had no effect on mean distance to platform. Zaprinast (3 and 10 mg/kg) significantly decreased number of errors compared to control group, while rolipram (0.05 and 0.1mg/kg) had no effect on number of errors in retention trial of RAM test. Rolipram (0.05 and 0.1 mg/kg) and zaprinast (10 mg/kg) significantly decreased time spent to complete retention trial (latency) compared to control group. Our study revealed that both zaprinast and rolipram enhanced spatial memory in MWM, while zaprinast seems to have more memory enhancing effects compared to rolipram in radial arm maze test. © Georg Thieme Verlag KG Stuttgart · New York.

Interference-free determination of sub ng kg-1 levels of long-lived 93Zr in the presence of high concentrations (μg kg-1) of 93Mo and 93Nb using ICP-MS/MS.

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Petrov, Panayot; Russell, Ben; Douglas, David N; Goenaga-Infante, Heidi

2018-01-01

Long-lived high abundance radionuclides are of increasing interest with regard to decommissioning of nuclear sites and longer term nuclear waste storage and disposal. In many cases, no routine technique is available for their measurement in nuclear waste and low-level (ng kg -1 ) environmental samples. Recent advances in ICP-MS technology offer attractive features for the selective and sensitive determination of a wide range of long-lived radionuclides. In this work, inductively coupled plasma-tandem mass spectrometry (ICP-MS/MS)-based methodology, suitable for accurate routine determinations of 93 Zr at very low (ng kg -1 ) levels in the presence of high levels (μg kg -1 ) of the isobaric interferents 93 Nb and 93 Mo (often present in nuclear waste samples), is reported for the first time. Additionally, a novel and systematic strategy for method development based on the use of non-radioactive isotopes is proposed. It relies on gas-phase chemical reactions for different molecular ion formation to achieve isobaric interference removal. Using cell gas mixtures of NH 3 /He/H 2 or H 2 /O 2 , and suitable mass shifts, the signal from the 93 Nb and 93 Mo isobaric interferences on 93 Zr were suppressed by up to 5 orders of magnitude. The achieved limit of detection for 93 Zr was 1.3 × 10 -5  Bq g -1 (equivalent to 0.14 ng kg -1 ). The sample analysis time is 2 min, which represents a significant improvement in terms of sample throughput, compared to liquid scintillation counting methods. The method described here can be used for routine measurements of 93 Zr at environmentally relevant levels. It can also be combined with radiometric techniques for use towards the standardisation of 93 Zr measurements. Graphical abstract Interference-free determination of 93 Zr in the presence of high concentrations of isobaric 93 Mo and 93 Nb by ICP-MS/MS.

Uso de sal durante o transporte de juvenis (1kg de pirarucu (Arapaima gigas Use of salt during the transportation of pirarucu juveniles (1kg (Arapaima gigas

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Franmir Rodrigues Brandão

2008-12-01

Full Text Available O pirarucu é um peixe nativo da bacia Amazônica cuja criaçãovem sendo estudada em algumas partes do Brasil. O objetivo desse trabalho foi testar o sal de cozinha como mitigador de estresse durante o transporte de juvenis de pirarucu (1 kg. Para isso, os peixes foram transportados em dois diferentes sistemas: caixas sem adição de oxigênio (transporte aberto e sacos plásticos com injeção de oxigênio e lacrado (transporte fechado. Nos dois sistemas os peixes foram transportados em três diferentes tratamentos: controle e duas concentrações de sal na água (3 e 6 g.L-1. Após o transporte os peixes foram colocados em viveiros para avaliação da recuperação. Foram analisados parâmetros do metabolismo energético (cortisol, glicose e lactato e de hematologia (hematócrito. O sal de cozinha não foi eficiente em mitigar as respostas de estresse no transporte em nenhum dos dois sistemas de transporte estudados.Pirarucu is a native fish of the Amazon basin, widely used in culture systems in some parts of Brazil. The objective of this work was to test table salt as a stress mitigator during transportation of pirarucu juveniles (1kg. Fish were transported by two different systems: boxes without addition of oxygen (open system and closed oxygen filled plastic bags (closed system. To both systems fish were transported at three different treatments: control and two table salt concentration (3 and 6 gL-1. After transportation, fish were stocked in ponds to monitor recovery. Metabolic (cortisol, glucose and lactate and hematological (hematocrit parameters were analyzed. The table salt was not efficient in mitigating stress response during the both tested transport system.

Concentrations of garenoxacin in plasma, bronchial mucosa, alveolar macrophages and epithelial lining fluid following a single oral 600 mg dose in healthy adult subjects.

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Andrews, J; Honeybourne, D; Jevons, G; Boyce, M; Wise, R; Bello, A; Gajjar, D

2003-03-01

A microbiological assay was used to measure concentrations of garenoxacin (BMS-284756) in plasma, bronchial mucosa (BM), alveolar macrophages (AM) and epithelial lining fluid (ELF), following a single 600 mg oral dose. Twenty-four healthy subjects were allocated into four nominal time intervals after the dose, 2.5-3.5, 4.5-5.5, 10.5-11.5 and 23.5-24.5 h. Mean concentrations in plasma, BM, AM and ELF, respectively, for the four nominal time windows were for 2.5-3.5 h 10.0 mg/L (S.D. 2.8), 7.0 mg/kg (S.D. 1.3), 106.1 mg/L (S.D. 60.3) and 9.2 mg/L (S.D. 3.6); 4.5-5.5 h 8.7 mg/L (S.D. 2.2), 6.0 mg/kg (S.D. 1.9), 158.6 mg/L (S.D. 137.4) and 14.3 mg/L (S.D. 8.2); 10.5-11.5 h 6.1 mg/L (S.D. 1.9), 4.0 mg/kg (S.D. 1.4), 76.0 mg/L (S.D. 47.7) and 7.9 mg/L (S.D. 4.6); and 23.5-24.5 h 2.1 mg/L (S.D. 0.5), 1.7 mg/kg (S.D. 0.7), 30.7 mg/L (S.D. 12.9) and 3.3 mg/L (S.D. 2.3). Concentrations at all sites exceeded MIC(90)s for the common respiratory pathogens Haemophilus influenzae (0.03 mg/L), Moraxella catarrhalis (0.015 mg/L) and Streptococcus pneumoniae (0.06 mg/L). These data suggest that garenoxacin should be effective in the treatment of community-acquired pneumonia and chronic obstructive pulmonary disease.

Epitaxial growth of bcc-Fe{sub x}Co{sub 100-x} thin films on MgO(1 1 0) single-crystal substrates

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Ohtake, Mitsuru, E-mail: ohtake@futamoto.elect.chuo-u.ac.j [Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551 (Japan); Nishiyama, Tsutomu; Shikada, Kouhei [Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551 (Japan); Kirino, Fumiyoshi [Graduate School of Fine Arts, Tokyo National University of Fine Arts and Music, 12-8 Ueno-koen, Taito-ku, Tokyo 110-8714 (Japan); Futamoto, Masaaki [Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551 (Japan)

2010-07-15

Fe{sub x}Co{sub 100-x} (x=100, 65, 50 at%) epitaxial thin films were prepared on MgO(1 1 0) single-crystal substrates heated at 300 deg. C by ultra-high vacuum molecular beam epitaxy. The film structure and the growth mechanism are discussed. FeCo(2 1 1) films with bcc structure grow epitaxially on MgO(1 1 0) substrates with two types of variants whose orientations are rotated around the film normal by 180 deg. each other for all compositions. Fe{sub x}Co{sub 100-x} film growth follows the Volmer Weber mode. X-ray diffraction analysis indicates the out-of-plane and the in-plane lattice spacings are in agreement with the values of respective bulk Fe{sub x}Co{sub 100-x} crystals with very small errors less than +-0.4%, suggesting the strains in the films are very small. High-resolution cross-sectional transmission electron microscopy shows that periodical misfit dislocations are preferentially introduced in the film at the Fe{sub 50}Co{sub 50}/MgO interface along the MgO[1 1-bar 0] direction. The presence of such periodical dislocations decreases the large lattice mismatch of about -17% existing at the FeCo/MgO interface along the MgO[1 1-bar 0] direction.

Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

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Bao-Fei Sun

Full Text Available High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g. was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF and phosphorylated cAMP-response element binding protein (pCREB in the CA1 and dentate gyrus areas (DG of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

The adsorption capacity of an ocher decreases arsenic intake in maize; Adsorpcna kapacita okru znizuje prijem arzenu pri kukurici

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Drlickova, G; Vaculik, M; Lux, A [Univerzita Komenskeho v Bratislave, Prirodovedecka fakulta, Katedra fyziologie rastlin, 84215 Bratislava (Slovakia)

2012-04-25

The aim of the experiment was to compare the growth of maize (Zea mays L.), hybrid Valentine, in two types of contaminated soil substrate (ocher and stacks) with different concentrations of arsenic (As) derived from an old mining site in Pernek in the Small Carpathians. Plants were grown in a greenhouse for 15 weeks. We found that although the total concentration of As in stacks was 2.6 times lower than in ocher (90.05 mg kg{sup -1} in stacks and 236.8 mg kg{sup -1} in ocher) the plants grown in stacks accumulated in their tissues more As compared to the plants growing in ocher. Moreover, plants in stacks were significantly smaller, they produced less biomass and bloomed later. This paradox can be explained by reduced mobility of As in ocher substrates characteristic by high content of hydro-oxides of Fe. These compounds are in fact capable of binding arsenates, what leads to decrease of their concentration in the soil solution, and thus the availability for the plants. (authors)

Rhynchophylla total alkaloid rescues autophagy, decreases oxidative stress and improves endothelial vasodilation in spontaneous hypertensive rats.

Science.gov (United States)

Li, Chao; Jiang, Feng; Li, Yun-Lun; Jiang, Yue-Hua; Yang, Wen-Qing; Sheng, Jie; Xu, Wen-Juan; Zhu, Qing-Jun

2018-03-01

Autophagy plays an important role in alleviating oxidative stress and stabilizing atherosclerotic plaques. However, the potential role of autophagy in endothelial vasodilation function has rarely been studied. This study aimed to investigate whether rhynchophylla total alkaloid (RTA) has a positive role in enhancing autophagy through decreasing oxidative stress, and improving endothelial vasodilation. In oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs), RTA (200 mg/L) significantly suppressed ox-LDL-induced oxidative stress through rescuing autophagy, and decreased cell apoptosis. In spontaneous hypertensive rats (SHR), administration of RTA (50 mg·kg -1 ·d -1 , ip, for 6 weeks) improved endothelin-dependent vasodilation of thoracic aorta rings. Furthermore, RTA administration significantly increased the antioxidant capacity and alleviated oxidative stress through enhancing autophagy in SHR. In ox-LDL-treated HUVECs, we found that the promotion of autophagy by RTA resulted in activation of the AMP-activated protein kinase (AMPK) signaling pathway. Our results show that RTA treatment rescues the ox-LDL-induced autophagy impairment in HUVECs and improves endothelium-dependent vasodilation function in SHR.

Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice

International Nuclear Information System (INIS)

Smith, Matthew J.; Germolec, Dori R.; Frawley, Rachel P.; White, Kimber L.

2013-01-01

Black cohosh extracts (BCE; Actaea racemosa) are being used worldwide as an alternative to hormone replacement therapy for the management of menstrual and menopausal symptoms, yet the effects of BCE on the immune system are largely unknown. Female B 6 C 3 F 1 /N mice were treated daily with BCE (0, 62.5, 125, 250, 500, or 1000 mg/kg) for 28 days by oral gavage. Liver weights were significantly increased (26–32%) at the 1000 mg/kg dose. Dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin were observed. Decreasing trends were observed in all thymic T cell populations, with the most notable dose-responsive effects on immature thymocytes. In the spleen, dose-related decreases were observed in all cell phenotypes evaluated, reaching the level of statistical significance at the 1000 mg/kg BCE dose. Splenic natural killer (NK) cell numbers were significantly decreased at all BCE doses, with the exception of absolute NK numbers at the 125 mg/kg dose. No effects were observed on T-dependent antibody responses of the humoral immune system, including the antibody-forming cell response to sheep erythrocytes (sRBC) and IgM antibody levels to both sRBC and keyhole limpet hemocyanin. Cytotoxic T cell (T CTL ) activity was increased, as was the mixed leukocyte response in one of two studies. Anti-CD3 mediated proliferation and the delayed-type hypersensitivity response were unaffected. No effects were observed on innate immunity or on bone marrow cellularity and colony-forming units. Overall, BCE exposure in B 6 C 3 F 1 /N mice for 28 days at doses up to 1000 mg/kg had minimal immune effects, with the exception of an increased T CTL response

Behavioural profiles in the mouse defence test battery suggest anxiolytic potential of 5-HT(1A) receptor antagonists.

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Griebel, G; Rodgers, R J; Perrault, G; Sanger, D J

1999-05-01

Compounds varying in selectivity as 5-HT1A receptor antagonists have recently been reported to produce anxiolytic-like effects comparable to those of benzodiazepines in the mouse elevated plus-maze procedure. In view of the potential clinical significance of these findings, the present experiments compared the behavioural effects of diazepam (0.5-3.0 mg/kg) with those of several non-selective 5-HT1A receptor antagonists [NAN-190, 0.1-3.0 mg/kg, MM-77, 0.03-1.0 mg/kg, (S)-UH-301, 0.3-3.0 mg/kg and pindobind-5-HT1A, 0.03-1.0 mg/kg], and three selective 5-HT1A receptor antagonists (WAY100635, 0.01-3.0 mg/kg, p-MPPI, 0.1-3.0 mg/kg and SL88.0338, 0.3-3.0 mg/kg) in the mouse defence test battery (MDTB). In this well-validated anxiolytic screening test, Swiss mice are directly confronted with a natural threat (a rat) as well as situations associated with this threat. Primary measures taken during and after rat confrontation were flight, risk assessment (RA), defensive threat/attack and escape attempts. Diazepam significantly decreased flight reactions after the rat was introduced into the runway, reduced RA activities of mice chased by the rat, increased RA responses displayed when subjects were constrained in a straight alley and reduced defensive upright postures and biting upon forced contact. All the selective 5-HT1A receptor antagonists and NAN-190 also reduced flight, RA in the chase test, and defensive threat and attack behaviours. (S)-UH-301 and pindobind-5-HT1A reduced RA in the chase test, but only partially modified defensive threat and attack. Unlike the other drugs tested, MM-77 produced significant effects only at doses which also markedly reduced spontaneous locomotor activity, suggesting a behaviourally non-specific action. In contrast to diazepam, the 5-HT1A receptor ligands failed to affect RA in the straight alley test. Following removal of the rat from the test area, only diazepam and (S)-UH-301 reduced escape behaviour (contextual defence) at doses

Microstructure and properties of Mg-Al binary alloys

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ZHENG Wei-chao

2006-11-01

Full Text Available The effects of different amounts of added Al, ranging from 1 % to 9 %, on the microstructure and properties of Mg-Al binary alloys were investigated. The results showed that when the amount of added Al is less than 5%, the grain size of the Mg-Al binary alloys decreases dramatically from 3 097 μm to 151 μm with increasing addition of Al. Further addition of Al up to 9% makes the grain size decrease slowly to 111 μm. The α-Mg dendrite arms are also refined. Increasing the amount of added Al decreases the hot cracking susceptibility of the Mg-Al binary alloys remarkably, and enhances the micro-hardness of the α-Mg matrix.

Low FEV1, smoking history, and obesity are factors associated with oxygen saturation decrease in an adult population cohort

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Vold ML

2014-10-01

Full Text Available Monica Linea Vold,1,3 Ulf Aasebø,1,2 Hasse Melbye3 1Department of Respiratory Medicine, University Hospital of North Norway, 2Department of Clinical Medicine, 3Department of Community Medicine, University of Tromsø, Tromsø, Norway Background: Worsening of pulmonary diseases is associated with a decrease in oxygen saturation (SpO2. Such a decrease in SpO2 and associated factors has not been previously evaluated in a general adult population. Aim: We sought to describe SpO2 in a sample of adults, at baseline and after 6.3 years, to determine whether factors predicting low SpO2 in a cross-sectional study were also associated with a decrease in SpO2 in this cohort. Methods: As part of the Tromsø Study, 2,822 participants were examined with pulse oximetry in Tromsø 5 (2001/2002 and Tromsø 6 (2007/2008. Low SpO2 by pulse oximetry was defined as an SpO2 ≤95%, and SpO2 decrease was defined as a ≥2% decrease from baseline to below 96%. Results: A total of 139 (4.9% subjects had a decrease in SpO2. Forced expiratory volume in 1 second (FEV1 <50% of the predicted value and current smoking with a history of ≥10 pack-years were the baseline characteristics most strongly associated with an SpO2 decrease in multivariable logistic regression (odds ratio 3.55 [95% confidence interval (CI 1.60–7.89] and 2.48 [95% CI 1.48–4.15], respectively. Male sex, age, former smoking with a history of ≥10 pack-years, body mass index ≥30 kg/m2, and C-reactive protein ≥5 mg/L were also significantly associated with an SpO2 decrease. A significant decrease in FEV1 and a new diagnosis of asthma or chronic obstructive pulmonary disease during the observation period most strongly predicted a fall in SpO2. A lower SpO2 decrease was observed in those who quit smoking and those who lost weight, but these tendencies were not statistically significant. Conclusion: A decrease in SpO2 was most strongly associated with severe airflow limitation and a history of

Decreased Rac1 Cardiac Expression in Nitrofen-Induced Diaphragmatic Hernia.

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Nakamura, Hiroki; Zimmer, Julia; Puri, Prem

2018-02-01

 The high incidence of cardiac malformations in humans and animal models with congenital diaphragmatic hernia (CDH) is well known. The hypoplasia of left heart is common among fetuses with CDH and has been identified as a poor prognostic factor. However, the precise mechanisms underlying cardiac maldevelopment in CDH are not fully understood. Ras-related C3 botulinum toxin substrate 1 (Rac1) plays a key role in cardiomyocyte polarity and embryonic heart development. Deficiency of Rac1 is reported to impair elongation and cytoskeletal organization of cardiomyocytes, resulting in congenital cardiac defects. We designed this study to test the hypothesis that Rac1 expression is downregulated in the developing hearts of rats with nitrofen-induced CDH.  Following ethical approval (REC1103), time-pregnant Sprague Dawley rats received nitrofen or vehicle on gestational day 9 (D9). Fetuses were sacrificed on D18 and D21 and divided into CDH and control (CTRL) ( n  = 6 for each group and time point). Quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and confocal-immunofluorescence microscopy were performed to detect cardiac gene and protein expression of Rac1.  qRT-PCR and Western blot analysis revealed that Rac1 expression was significantly decreased in the CDH group compared with controls ( p  Rac1 cardiac expression was markedly decreased in the CDH group compared with controls.  Decreased cardiac Rac1 expression in the nitrofen-induced CDH suggests that Rac1 deficiency during morphogenesis may impair structural cardiac remodeling, resulting in congenital cardiac defects. Georg Thieme Verlag KG Stuttgart · New York.

Density functional theory study of hydrogenation mechanism in Fe-doped Mg(0 0 0 1) surface

International Nuclear Information System (INIS)

Wu Guangxin; Zhang Jieyu; Wu Yongquan; Li Qian; Chou Kuochih; Bao Xinhua

2009-01-01

Using density functional theory (DFT) in combination with nudged elastic band (NEB) method, the dissociative chemisorptions and diffusion processes of hydrogen on both pure and Fe-doped Mg(0 0 0 1) surfaces are studied. Firstly, the dissociation pathway of H 2 and the relative barrier were investigated. The calculated dissociation barrier (1.08 eV) of hydrogen molecule on a pure Mg(0 0 0 1) surface is in good agreement with comparable experimental and theoretical studies. For the Fe-doped Mg(0 0 0 1) surface, the activated barrier decreases to 0.101 eV due to the strong interaction between the s orbital of H and the d orbital of Fe. Then, the diffusion processes of atomic hydrogen on pure and Fe-doped Mg(0 0 0 1) are presented. The obtained diffusion barrier to the first subsurface is 0.45 eV and 0.98 eV, respectively. Finally, Chou method was used to investigate the hydrogen sorption kinetic mechanism of pure MgH 2 and Mg mixed with 5 at.% Fe atoms composites. The obtained activation energies are 0.87 ± 0.02 and 0.31 ± 0.01 eV for H 2 dissociation on the pure surface and H atom diffusion in Fe-doped Mg surfaces, respectively. It suggests that the rate-controlling step is dissociation of H 2 on the pure Mg surface while it is diffusion of H atom in the Fe-doped Mg surface. And both of fitting data are matching well with our calculation results.

Structural and physical properties of Mg3-xZnxSb2 (x=0-1.34)

International Nuclear Information System (INIS)

Ahmadpour, Faraz; Kolodiazhnyi, Taras; Mozharivskyj, Yurij

2007-01-01

The Mg 3-x Zn x Sb 2 phases with x=0-1.34 were prepared by direct reactions of the elements in tantalum tubes. According to the X-ray single crystal and powder diffraction, the Mg 3-x Zn x Sb 2 phases crystallize in the same P3-bar m1 space group as the parent Mg 3 Sb 2 phase. The Mg 3-x Zn x Sb 2 structure is different from the other substituted structures of Mg 3 Sb 2 , such as (Ca, Sr, Ba) Mg 2 Sb 2 or Mg 5.23 Sm 0.77 Sb 4 , in a way that in Mg 3-x Zn x Sb 2 the Mg atoms on the tetrahedral sites are replaced, while in the other structures Mg on the octahedral sites is replaced. Thermoelectric performance for the two members of the series, Mg 3 Sb 2 and Mg 2.36 Zn 0.64 Sb 2 , was evaluated from low to room temperatures through resistivity, Seebeck coefficient and thermal conductivity measurements. In contrast to Mg 3 Sb 2 which is a semiconductor, Mg 2.36 Zn 0.64 Sb 2 is metallic and exhibits an 18-times larger dimensionless figure-of-merit, ZT, at room temperature. However, thermoelectric performance of Mg 2.36 Zn 0.64 Sb 2 is still poor and it is mostly due to its large electrical resistivity. - Graphical abstract: The Mg atoms in Mg 3 Sb 2 were successfully substituted with Zn, with Zn going exclusively into the tetrahedral sites. Zn substitution increases the electrical conductivity in Mg 2.36 Zn 0.64 Sb 2 by closing the band gap. This change combined with a decrease in the thermal conductivity improves the ZT value

Liraglutide 3.0 mg for Weight Management: A Population Pharmacokinetic Analysis.

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Overgaard, Rune V; Petri, Kristin C; Jacobsen, Lisbeth V; Jensen, Christine B

2016-11-01

This analysis used a population pharmacokinetic approach to identify covariates that influence plasma exposure of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management in overweight and obese individuals. Samples for pharmacokinetic analysis were drawn at weeks 2, 12 and 28 of the phase IIIa SCALE Obesity and Prediabetes (N = 2339) and SCALE Diabetes (N = 584) trials. Dose proportionality of liraglutide in obese subjects was investigated using data from a phase II dose-finding study (N = 331). Dose-proportional exposure of liraglutide up to and including 3.0 mg was confirmed. Body weight and sex influenced exposure of liraglutide 3.0 mg, while age ≥70 years, race, ethnicity and baseline glycaemic status did not. Compared with a reference subject weighing 100 kg, exposure of liraglutide 3.0 mg was 44 % lower for a subject weighing 234 kg (90 % CI 41-47), 41 % higher for a subject weighing 60 kg (90 % CI 37-46), and 32 % higher (90 % CI 28-35) in females than males with the same body weight. Neither injection site nor renal function significantly influenced exposure of liraglutide 3.0 mg (post hoc analysis). Population pharmacokinetics of liraglutide up to and including 3.0 mg daily in overweight and obese adults demonstrated dose-proportional exposure, and limited effect of covariates other than sex and body weight. These findings were similar to those previously observed with liraglutide up to 1.8 mg in subjects with type 2 diabetes mellitus. Further analysis of exposure-response relationship and its effect on dose requirements is addressed in a separate publication.

Efektifitas Fungsida Berbahan Aktif Pyraclostrobin 50 G/KG + Metiram G/KG untuk Mengendalikan Penyakit Embun Tepung (Podosphaera leucotrica Pada Tanaman Apel

Directory of Open Access Journals (Sweden)

Eli Korlina

2016-03-01

Full Text Available Pengujian efektifitas fungisida berbahan aktif pyraclostrobin 50 g/kg+metiram 550g/kg untuk mengendalian  penyakit embun tepung (Podosphaera leucotricha pada tanaman apel telah dilaksanakan di kebun apel milik petani Desa Wringinanom, Kecamatan Poncokusumo, Kabupaten Malang yang beriklim tinggi kering dengan ketinggian tempat ±  850 diatas permukaan laut (dpl, mulai bulan Pebruari sampai dengan April 2011, menggunakan kultivar apel  Manalagi yang telah berumur 8-10 tahun.  Perlakuan terdiri atas Fungisida berbahan aktif pyraclostrobin 50 g/kg+metiram 550g/kg dengan 4 (empat tingkat konsentrasi yaitu 0,5; 1,0; 1,5; dan 2,0 g/l air, dan kontrol (tanpa perlakuan, disusun dalam rancangan acak kelompok  (RAK dan diulang 4 kali. Hasil pengujian menunjukkan bahwa Fungisida berbahan aktif pyraclostrobin 50 g/kg+metiram 550g/kg konsentrasi 0,5-2 g/l air telah efektif mengendalikan penyakit embun tepung P. leucotricha pada tanaman apel dengan penekanan  serangan sebesar 44,42-54,73%.  Rata-rata produksi buah apel berkisar antara 8,49 – 10,38 kg/pohon. Tanaman apel yang diaplikasi dengan fungisida tersebut tidak mengalami fitotoksisitas.Kata Kunci: Apel, penyakit embun tepung (Podosphaera leucotricha.

Methamphetamine- and 1-methyl-4-phenyl- 1,2,3, 6-tetrahydropyridine-induced dopaminergic neurotoxicity in inducible nitric oxide synthase-deficient mice.

Science.gov (United States)

Itzhak, Y; Martin, J L; Ali, S F

1999-12-15

Previous studies have suggested a role for the retrograde messenger, nitric oxide (NO), in methamphetamine (METH)- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- induced dopaminergic neurotoxicity. Since evidence supported the involvement of the neuronal nitric oxide synthase (nNOS) isoform in the dopaminergic neurotoxicity, the present study was undertaken to investigate whether the inducible nitric oxide synthase (iNOS) isoform is also associated with METH- and MPTP-induced neurotoxicity. The administration of METH (5mg/kg x 3) to iNOS deficient mice [homozygote iNOS(-/-)] and wild type mice (C57BL/6) resulted in significantly smaller depletion of striatal dopaminergic markers in the iNOS(-/-) mice compared with the wild-type mice. METH-induced hyperthermia was also significantly lower in the iNOS(-/-) mice than in wild-type mice. In contrast to the outcome of METH administration, MPTP injections (20 mg/kg x 3) resulted in a similar decrease in striatal dopaminergic markers in iNOS(-/-) and wild-type mice. In the set of behavioral experiments, METH-induced locomotor sensitization was investigated. The acute administration of METH (1.0 mg/kg) resulted in the same intensity of locomotor activity in iNOS(-/-) and wild-type mice. Moreover, 68 to 72 h after the exposure to the high-dose METH regimen (5 mg/kg x 3), a marked sensitized response to a challenge injection of METH (1.0 mg/kg) was observed in both the iNOS(-/-) and wild-type mice. The finding that iNOS(-/-) mice were unprotected from MPTP-induced neurotoxicity suggests that the partial protection against METH-induced neurotoxicity observed was primarily associated with the diminished hyperthermic effect of METH seen in the iNOS(-/-) mice. Moreover, in contrast to nNOS deficiency, iNOS deficiency did not affect METH-induced behavioral sensitization. Copyright 1999 Wiley-Liss, Inc.

Parenteral magnesium load testing with 28Mg in weanling and young adult rats

International Nuclear Information System (INIS)

Caddell, J.L.; Calhoun, N.R.; Howard, M.P.; Patterson, K.Y.; Smith, J.C. Jr.

1981-01-01

A sound diagnostic test for Mg deficiency is needed. This is a report of the parenteral Mg load test conducted in weanling and young adult rats fed a purified basal diet containing 3 mg magnesium/100 g with 150 mg of added magnesium/100 g (control) or 0 added magnesium (deficient). Weanlings were studied at about 1 week of dietary treatment and young adults at 2 weeks. The protocol included: a) a 6-hour preload urinary collection; b) an intraperitoneal load of 15 mg of magnesium/kg (weanlings) or 12 mg/kg (young adults) with 2 microCi 28Mg given simultaneously with each load; c) a 6-hour postload urinary collection; d) chemical analysis of selected tissues and urine for Mg; and e) 28Mg counting 6 and 24 hours postload. Controls all excreted large amounts of Mg pre- and postload, retaining less than 26% of nonradioactive loads. They had high urinary 28Mg counts. In Mg-deficient animals, the concentration of Mg in bone more than halved. These animals avidly conserved Mg and retained over 85% of nonradioactive Mg loads. Their 28Mg activity in vital organs was 3--6 times greater than in controls. We concluded that the parenteral Mg load test reliably identifies severe Mg deficiency

Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody.

Science.gov (United States)

Fu, Jie; Wang, Fang; Dong, Li-Hou; Zhang, Jing; Deng, Cheng-Lian; Wang, Xue-Li; Xie, Xin-Yao; Zhang, Jing; Deng, Ruo-Xian; Zhang, Li-Bo; Wu, Hai; Feng, Hui; Chen, Bo; Song, Hai-Feng

2017-05-01

JS-001 is the first monoclonal antibody (mAb) against programmed cell death protein-1 (PD-1) approved by the China Food and Drug Administration (CFDA) into the clinical trails. To date, however, no pre-clinical pharmacological and pharmacokinetic (PK) data are available. In this study, we investigated the efficacy of JS-001 and conducted a preclinical PK study, including the monitoring of anti-drug antibodies (ADAs). We found that JS-001 specifically bound to PD-1 antigen with an EC 50 of 21 nmol/L, and competently blocked the binding of PD-1 antigen to PD-L1 and PD-L2 with IC 50 of 3.0 and 3.1 nmol/L, respectively. Furthermore, JS-001 displayed distinct species cross-reactivity: it could bind to the PD-1 antigen on the peripheral blood mononuclear cells (PBMCs) of humans and cynomolgus monkeys, but not to those of mice and woodchucks; the K d values for the interaction between JS-001 and PD-1 antigens on CD8 + T cells of human and cynomolgus monkey were 2.1 nmol/L and 1.2 nmol/L, respectively. In vitro, treatment with JS-001 (0.01-10 μg/mL) dose-dependently stimulated human T cell proliferation, as well as IFN-γ and TNF-α secretion. In HBsAg-vaccinated cynomolgus monkeys, the expression of PD-1 + /CD4 + and PD-1 + /CD8 + was significantly elevated, intramuscular injection of JS-001 (1 and 10 mg/kg) resulted in dramatic decreases in PD-1 + /CD4 + and PD-1 + /CD8 + expression in a dose-dependent manner, which was supported by PD-1 receptor occupancy (RO) results. In the PK study, 18 cynomolgus monkeys treated with single, ascending doses of 1, 10, and 75 mg/kg, and another 6 cynomolgus monkeys received 10 mg/kg successive administration. The plasma clearance of JS-001 followed a linear PK profile with single administration in the 1 and 10 mg/kg groups and a non-linear PK profile in the 75 mg/kg group. In the successive 10 mg/kg administration group, no drug accumulation was observed. But the AUC from the last exposure was lower than that of the first

5-HT1A receptor antagonists reduce food intake and body weight by reducing total meals with no conditioned taste aversion.

Science.gov (United States)

Dill, M Joelle; Shaw, Janice; Cramer, Jeff; Sindelar, Dana K

2013-11-01

Serotonin acts through receptors controlling several physiological functions, including energy homeostasis regulation and food intake. Recent experiments demonstrated that 5-HT1A receptor antagonists reduce food intake. We sought to examine the microstructure of feeding with 5-HT1A receptor antagonists using a food intake monitoring system. We also examined the relationship between food intake, inhibition of binding and pharmacokinetic (PK) profiles of the antagonists. Ex vivo binding revealed that, at doses used in this study to reduce food intake, inhibition of binding of a 5-HT1A agonist by ~40% was reached in diet-induced obese (DIO) mice with a trend for higher binding in DIO vs. lean animals. Additionally, PK analysis detected levels from 2 to 24h post-compound administration. Male DIO mice were administered 5-HT1A receptor antagonists LY439934 (10 or 30 mg/kg, p.o.), WAY100635 (3 or 10mg/kg, s.c.), SRA-333 (10 or 30 mg/kg, p.o.), or NAD-299 (3 or 10mg/kg, s.c.) for 3 days and meal patterns were measured. Analyses revealed that for each antagonist, 24-h food intake was reduced through a specific decrease in the total number of meals. Compared to controls, meal number was decreased 14-35% in the high dose. Average meal size was not changed by any of the compounds. The reduction in food intake reduced body weight 1-4% compared to Vehicle controls. Subsequently, a conditioned taste aversion (CTA) assay was used to determine whether the feeding decrease might be an indicator of aversion, nausea, or visceral illness caused by the antagonists. Using a two bottle preference test, it was found that none of the compounds produced a CTA. The decrease in food intake does not appear to be a response to nausea or malaise. These results indicate that 5-HT1A receptor antagonist suppresses feeding, specifically by decreasing the number of meals, and induce weight loss without an aversive side effect. © 2013 Elsevier Inc. All rights reserved.

Structural and magnetic properties of Mg-Zn ferrites (Mg{sub 1−x}Zn{sub x}Fe{sub 2}O{sub 4}) prepared by sol-gel method

Energy Technology Data Exchange (ETDEWEB)

Reyes-Rodríguez, Pamela Yajaira, E-mail: pamela2244_4@hotmail.com [Cinvestav-Unidad Saltillo, Av. Industrial Metalúrgica #1062, Parque Industrial Saltillo-Ramos Arizpe, CP 25900, México (Mexico); Cortés-Hernández, Dora Alicia; Escobedo-Bocardo, José Concepción; Almanza-Robles, José Manuel; Sánchez-Fuentes, Héctor Javier; Jasso-Terán, Argentina; De León-Prado, Laura Elena [Cinvestav-Unidad Saltillo, Av. Industrial Metalúrgica #1062, Parque Industrial Saltillo-Ramos Arizpe, CP 25900, México (Mexico); Méndez-Nonell, Juan [Centro de Investigación en Materiales Avanzados, Ave. Miguel Cervantes #120, Complejo Industrial Chihuahua, CP 31109 Chihuahua, México (Mexico); Hurtado-López, Gilberto Francisco [Centro de Investigación en Química Aplicada, Blvd. Enrique Reyna Hermosillo #140, CP 25294 Saltillo, Coahuila, México (Mexico)

2017-04-01

In this study, the Mg{sub 1−x}Zn{sub x}Fe{sub 2}O{sub 4} nanoparticles (x=0–0.9) were prepared by sol-gel method. These ferrites exhibit an inverse spinel structure and the lattice parameter increases as the substitution of Zn{sup 2+} ions is increased. At lower Zn content (0.1≤x≤0.5), saturation magnetization (Ms) increases, while it decreases at higher Zn content (x≥6). The remnant magnetization (0.17–2.0 emu/g) and coercive field (6.0–60 Oe) indicate a ferrimagnetic behavior. The average core diameter of selected ferrites is around 15 nm and the nanoparticles morphology is quasi spherical. The heating ability of some Mg{sub 0.9}Zn{sub 0.1}Fe{sub 2}O{sub 4} and Mg{sub 0.7}Zn{sub 0.3}Fe{sub 2}O{sub 4} aqueous suspensions indicates that the magnetic nanoparticles can increase the medium temperature up to 42 °C in a time less than 10 min - Highlights: • Magnetic nanoparticles of Mg{sub 1−x}Zn{sub x}Fe{sub 2}O{sub 4} were synthesized by sol-gel method. • Nanoparticles showing a single spinel crystalline structure were obtained. • Aqueous suspensions of Mg{sub 0.7}Zn{sub 0.3}Fe{sub 2}O{sub 4} and Mg{sub 0.9}Zn{sub 0.1}Fe{sub 2}O{sub 4} show heating ability.

Study on adsorption of O{sub 2} on LaFe{sub 1-x}Mg{sub x}O{sub 3} (0 1 0) surface by density function theory calculation

Energy Technology Data Exchange (ETDEWEB)

Liu, Xing, E-mail: liuxing0108@mail.sdu.edu.cn [Civil Engineer Department, Qingdao Technological University (Linyi), Easter Outer Ring Road 1, Linyi, 273400 (China); Cheng, Bin [Civil Engineer Department, Qingdao Technological University (Linyi), Easter Outer Ring Road 1, Linyi, 273400 (China); Hu, Jifan; Qin, Hongwei [State Key Laboratory of Crystal Material, Department of Physics, Shandong University, Hongjialou 5, Jinan, 250100 (China)

2012-09-01

Highlights: Black-Right-Pointing-Pointer Mg-doping can change the electronic properties of LaFeO{sub 3} (0 1 0) surface by decreasing the band gap. Black-Right-Pointing-Pointer The position and content of Mg-doping can both affect the ability to adsorb O{sub 2}. Black-Right-Pointing-Pointer The strong hybridization between O{sub 2} p and Fe d orbital is the origin of binding mechanism. - Abstract: The adsorption of O{sub 2} on the clean and Mg doped LaFeO{sub 3} (0 1 0) surface has been investigated using the density functional theory (DFT) method. Calculation results show that Mg-doping can change the electronic properties of LaFeO{sub 3} (0 1 0) surface by decreasing the band gap. When Mg ions were not on the first layer of the surface, with increasing Mg content the adsorption of O{sub 2} was enhanced. When Mg ions were on the first layer, the adsorption of O{sub 2} was weakened with the increase of Mg content. The analysis results of the DOS indicated that the Mg ion and adsorbed O{sub 2} had no strong hybridization, and the bonding mechanism was originated from the strong hybridization between the O p and Fe d orbital. Referring to all the calculation results, it was found that except for the increase of stability of oxygen adsorption, the Mg doping could not improve the sensitivity to O{sub 2}.

Guanosine may increase absence epileptic activity by means of A2A adenosine receptors in Wistar Albino Glaxo Rijswijk rats.

Science.gov (United States)

Lakatos, Renáta Krisztina; Dobolyi, Árpád; Todorov, Mihail Ivilinov; Kékesi, Katalin A; Juhász, Gábor; Aleksza, Magdolna; Kovács, Zsolt

2016-06-01

The non-adenosine nucleoside guanosine (Guo) was demonstrated to decrease quinolinic acid(QA)-induced seizures, spontaneously emerged absence epileptic seizures and lipopolysaccharide(LPS)-evoked induction of absence epileptic seizures suggesting its antiepileptic potential. It was also described previously that intraperitoneal (i.p.) injection of 20 and 50mg/kg Guo decreased the number of spike-wave discharges (SWDs) in a well investigated model of human absence epilepsy, the Wistar Albino Glaxo Rijswijk (WAG/Rij) rats during 4th (20mg/kg Guo) and 3rd as well as 4th (50mg/kg Guo) measuring hours. Guanosine can potentially decrease SWD number by means of its putative receptors but absence epileptic activity changing effects of Guo by means of increased extracellular adenosine (Ado) cannot be excluded. An increase in the dose of i.p. injected Guo is limited by its low solubility in saline, therefore, we addressed in the present study whether higher doses of Guo, diluted in sodium hydroxide (NaOH) solution, have more potent antiepileptic effect in WAG/Rij rats. We confirmed that i.p. 50mg/kg Guo decreased but, surprisingly, i.p. 100mg/kg Guo enhanced the number of SWDs in WAG/Rij rats. Combined i.p. injection of a non-selective Ado receptor antagonist theophylline (5mg/kg) or a selective Ado A2A receptor (A2AR) antagonist SCH 58261 (7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) (1mg/kg) and a cyclooxygenase 1 and 2/COX-1 and COX-2 inhibitor indomethacin (10mg/kg) with 100mg/kg Guo decreased the SWD number compared to i.p. 100mg/kg Guo alone. The results suggest that i.p. 100mg/kg Guo can increase SWD number by means of the adenosinergic system. Copyright © 2016 Elsevier Inc. All rights reserved.

Administration of caffeine inhibited adenosine receptor agonist-induced decreases in motor performance, thermoregulation, and brain neurotransmitter release in exercising rats.

Science.gov (United States)

Zheng, Xinyan; Hasegawa, Hiroshi

2016-01-01

We examined the effects of an adenosine receptor agonist on caffeine-induced changes in thermoregulation, neurotransmitter release in the preoptic area and anterior hypothalamus, and endurance exercise performance in rats. One hour before the start of exercise, rats were intraperitoneally injected with either saline alone (SAL), 10 mg kg(-1) caffeine and saline (CAF), a non-selective adenosine receptor agonist (5'-N-ethylcarboxamidoadenosine [NECA]: 0.5 mg kg(-1)) and saline (NECA), or the combination of caffeine and NECA (CAF+NECA). Rats ran until fatigue on the treadmill with a 5% grade at a speed of 18 m min(-1) at 23 °C. Compared to the SAL group, the run time to fatigue (RTTF) was significantly increased by 52% following caffeine administration and significantly decreased by 65% following NECA injection (SAL: 91 ± 14.1 min; CAF: 137 ± 25.8 min; NECA: 31 ± 13.7 min; CAF+NECA: 85 ± 11.8 min; pcaffeine injection inhibited the NECA-induced decreases in the RTTF, Tcore, heat production, heat loss, and extracellular DA release. Neither caffeine nor NECA affected extracellular noradrenaline or serotonin release. These results support the findings of previous studies showing improved endurance performance and overrides in body limitations after caffeine administration, and imply that the ergogenic effects of caffeine may be associated with the adenosine receptor blockade-induced increases in brain DA release. Copyright © 2015 Elsevier Inc. All rights reserved.

Indomethacin decreases furosemide-induced natriuresis and diuresis on the neonatal kidney.

Science.gov (United States)

Reyes, Jose L; Aldana, Irma; Barbier, Olivier; Parrales, Arlen A; Melendez, Estela

2006-11-01

Indomethacin is used to pharmacologically occlude patent ductus arteriosus in preterm infants. It induces renal untoward effects and furosemide is administered simultaneously to counteract them. The effect of furosemide is blunted by indomethacin. We analyzed comparatively the interactions of furosemide and indomethacin at the organic anion transport system in adult and newborn individuals. Adult and 5-day-old Wistar rats were allocated into three groups: (1) indomethacin (10 mg/kg, ip); (2) furosemide (2 mg/kg, ip); and (3) indomethacin/furosemide, at the same doses. Urinary flow, glomerular filtration rate (GFR), sodium and potassium fractional excretions, and free-water and osmolal clearances were estimated. Para-aminohippuric acid (PAH) uptake was measured in renal cortical slices to study the organic anion's secretory pathway. In adult and newborn rats, furosemide-induced increments in urinary fluxes and excretions of sodium and potassium were blunted by indomethacin administered simultaneously. PAH uptake was decreased to a further extent by indomethacin than by furosemide, suggesting that inhibition of the diuretic effect might be related to competition in the secretion of furosemide. Inhibitory interaction between indomethacin and furosemide was achieved at approximately 10-fold lower concentrations in the newborn than in the adult rats, suggesting that tubular secretion in the neonate is more sensitive to the action of these drugs than in the adult individual.

Evaluation of the levels of Br, Cl, K, Mg, Mn and V in Perna perna Mussels (Linnaeus, 1758: Mollusca, Bivalvia) collected in coast of Sao Paulo, Brazil

International Nuclear Information System (INIS)

Seo, Daniele; Vasconcellos, Marina B.A.; Saiki, Mitiki; Catharino, Marilia G.M.; Moreira, Edson G.; Sousa, Eduinetty C.P.M. de

2013-01-01

In this study the content of Br, Cl, K, Mg, Mn and V was evaluated in samples of Perna perna mussels collected in coastal regions of Sao Paulo (Ponta de Itaipu and Palmas Island, in Santos) subjected to anthropogenic contamination, to compare these values with those of mussels from reference site of Cocanha Beach (in Caraguatatuba). The mussels were collected seasonally from September 2008 to July 2009. They were cleaned, ground, homogenized, lyophilized and then analyzed by Instrumental Neutron Activation Analysis (INAA). The INAA procedure consisted in the irradiation of the samples and synthetic elemental standards for 8 and 10 s, under a thermal neutron flux of 6.6 x 10 12 n cm -2 s -1 in the IEA-R1 nuclear research reactor. For quality control of analytical results, certified reference materials NIST 1566b Oyster Tissue and NIST 2876 Mussel Tissue were analyzed and their results indicated good accuracy. The ranges of concentrations (dry basis) of the elements obtained in mussels collected for the four seasons of the year were: 173.80 to 358.99 mg kg -1 for Br; 45658 ± 1811 to 109166 ± 824 mg kg -1 for Cl; 7043 ± 856 to 12506 ± 675 mg kg -1 for K; 2774 ± 211 to 5691 ± 717 mg kg -1 for Mg; 7.01 ± 0.30 to 29.74 ± 3.32 mg kg -1 for Mn and 0.77 ± 0.02 to 3.43 ± 0.28 mg kg -1 for V. The seasonal and spatial variations of these element concentrations were in this study. (author)

Evaluation of the levels of Br, Cl, K, Mg, Mn and V in Perna perna Mussels (Linnaeus, 1758: Mollusca, Bivalvia) collected in coast of Sao Paulo, Brazil

Energy Technology Data Exchange (ETDEWEB)

Seo, Daniele; Vasconcellos, Marina B.A.; Saiki, Mitiki; Catharino, Marilia G.M.; Moreira, Edson G., E-mail: danyseo@uol.com.br, E-mail: mbvascon@ipen.br, E-mail: mitiko@ipen.br, E-mail: mgcatharino@uol.com.br, E-mail: emoreira@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Sousa, Eduinetty C.P.M. de, E-mail: edvinett@usp.br [Universidade de Sao Paulo (IO/USP), Sao Paulo, SP (Brazil). Instituto Oceanografico. Laboratorio de Ecotoxicologia Marinha e Microfitobentos

2013-07-01

In this study the content of Br, Cl, K, Mg, Mn and V was evaluated in samples of Perna perna mussels collected in coastal regions of Sao Paulo (Ponta de Itaipu and Palmas Island, in Santos) subjected to anthropogenic contamination, to compare these values with those of mussels from reference site of Cocanha Beach (in Caraguatatuba). The mussels were collected seasonally from September 2008 to July 2009. They were cleaned, ground, homogenized, lyophilized and then analyzed by Instrumental Neutron Activation Analysis (INAA). The INAA procedure consisted in the irradiation of the samples and synthetic elemental standards for 8 and 10 s, under a thermal neutron flux of 6.6 x 10{sup 12} n cm{sup -2} s{sup -1} in the IEA-R1 nuclear research reactor. For quality control of analytical results, certified reference materials NIST 1566b Oyster Tissue and NIST 2876 Mussel Tissue were analyzed and their results indicated good accuracy. The ranges of concentrations (dry basis) of the elements obtained in mussels collected for the four seasons of the year were: 173.80 to 358.99 mg kg{sup -1} for Br; 45658 ± 1811 to 109166 ± 824 mg kg{sup -1} for Cl; 7043 ± 856 to 12506 ± 675 mg kg{sup -1} for K; 2774 ± 211 to 5691 ± 717 mg kg{sup -1} for Mg; 7.01 ± 0.30 to 29.74 ± 3.32 mg kg{sup -1} for Mn and 0.77 ± 0.02 to 3.43 ± 0.28 mg kg{sup -1} for V. The seasonal and spatial variations of these element concentrations were in this study. (author)

MCPIP1 contributes to the toxicity of proteasome inhibitor MG-132 in HeLa cells by the inhibition of NF-κB.

Science.gov (United States)

Skalniak, Lukasz; Dziendziel, Monika; Jura, Jolanta

2014-10-01

Recently, we have shown that the treatment of cells with proteasome inhibitor MG-132 results in the induction of expression of monocyte chemotactic protein-1 induced protein 1 (MCPIP1). MCPIP1 is a ribonuclease, responsible for the degradation of transcripts encoding certain pro-inflammatory cytokines. The protein is also known as an inhibitor of NF-κB transcription factor. Thanks to its molecular properties, MCPIP1 is considered as a regulator of inflammation, differentiation, and survival. Using siRNA technology, we show here that MCPIP1 expression contributes to the toxic properties of MG-132 in HeLa cells. The inhibition of proteasome by MG-132 and epoxomicin markedly increased MCPIP1 expression. While MG-132 induces HeLa cell death, down-regulation of MCPIP1 expression by siRNA partially protects HeLa cells from MG-132 toxicity and restores Nuclear factor-κB (NF-κB) activity, inhibited by MG-132 treatment. Inversely, overexpression of MCPIP1 decreased constitutive activity of NF-κB and limited the survival of HeLa cells, as we have shown in the previous study. Interestingly, although MG-132 decreased the expression of IκBα and increased p65 phosphorylation, the inhibition of constitutive NF-κB activity was observed in MG-132-treated cells. Since the elevated constitutive activity of NF-κB is one of the mechanisms providing increased survival of cancer cells, including HeLa cells, we propose that death-promoting properties of MCPIP1 in MG-132-treated HeLa cells may, at least partially, derive from the negative effect on the constitutive NF-κB activity.

Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

Science.gov (United States)

Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

2015-02-01

Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

Toxicity of hydroxyurea in rats and dogs.

Science.gov (United States)

Morton, Daniel; Reed, Lori; Huang, Wenhu; Marcek, John M; Austin-LaFrance, Robert; Northcott, Carrie A; Schelling, Scott H; Enerson, Bradley E; Tomlinson, Lindsay

2015-06-01

The toxicity of hydroxyurea, a treatment for specific neoplasms, sickle-cell disease, polycythemia, and thrombocytosis that kills cells in mitosis, was assessed in repeat-dose, oral gavage studies in rats and dogs and a cardiovascular study in telemetered dogs. Hydroxyurea produced hematopoietic, lymphoid, cardiovascular, and gastrointestinal toxicity with steep dose response curves. In rats dosed for 10 days, 50 mg/kg/day was tolerated; 500 mg/kg/day produced decreased body weight gain; decreased circulating leukocytes, erythrocytes, and platelets; decreased cellularity of thymus, lymph nodes, and bone marrow; and epithelial degeneration and/or dysplasia of the stomach and small intestine; 1,500 mg/kg/day resulted in deaths on day 5. In dogs, a single dose at ≥ 250 mg/kg caused prostration leading to unscheduled euthanasia. Dogs administered 50 mg/kg/day for 1 month had decreased circulating leukocytes, erythrocytes, and platelets; increased bone marrow cellularity with decreased maturing granulocytes; increased creatinine kinase activity; and increased iron pigment in bone marrow and hepatic sinusoidal cells. In telemetered dogs, doses ≥ 15 mg/kg decreased systolic blood pressure (BP); 50 mg/kg increased diastolic BP, heart rate, and change in blood pressure over time (+dP/dt), and decreased QT and PR intervals and maximum left ventricular systolic and end diastolic pressures with measures returning to control levels within 24 hr. © 2014 by The Author(s).

Room temperature ferromagnetism in Mg-doped ZnO nanoparticles

International Nuclear Information System (INIS)

Singh, Jaspal; Vashihth, A.; Gill, Pritampal Singh; Verma, N. K.

2015-01-01

Zn 1-x Mg x O (x = 0, 0,10) nanoparticles were successfully synthesized using sol-gel method. X-ray diffraction (XRD) confirms that the synthesized nanoparticles possess wurtzite phase having hexagonal structure. Morphological analysis was carried out using transmission electron microscopy (TEM) which depicts the spherical morphology of ZnO nanoparticles. Energy dispersive spectroscopy (EDS) showed the presence of Mg in ZnO nanoparticles. Electron spin resonance (ESR) signal was found to be decreasing with increasing of Mg-doping concentration. The room temperature ferromagnetism was observed in undoped and Mg-doped ZnO nanoparticles. The increase of Mg-doping concentration resulted in decrease of saturation magnetization value which could be attributed to decrease of oxygen vacancies present in host nanoparticles

Dexmedetomidine reduces pain associated with rocuronium injection without causing a decrease in BIS values: a dose-response study.

Science.gov (United States)

Joo, Jin; Baek, Jungwon; Lee, Jaemin

2014-09-01

To examine whether dexmedetomidine reduces the injection pain of propofol and rocuronium and to investigate whether the decrease in injection pain is associated with the known sedative action of dexmedetomidine. Randomized, double-blind, placebo-controlled clinical comparison study. Patients undergoing general anesthesia with intubation received 40 mg of 1% lidocaine (lidocaine group; n = 28), 0.25 μg/kg of dexmedetomidine (low-dose group; n = 27), 0.5 μg/kg of dexmedetomidine (subclinical dose group; n = 28), 1.0 μg/kg of dexmedetomidine (clinical dose group, n = 27), or normal saline (saline group; n = 28) before anesthetic induction. Pain associated with propofol and rocuronium injection was assessed using a 10-point verbal analog scale (VAS) and a 4-point withdrawal movement scale, respectively. The BIS value was measured 60 seconds after administration of the study drug, and at the time of rocuronium injection and intubation. The overall incidence of withdrawal movements due to rocuronium decreased significantly as the dose of dexmedetomidine increased (92.8%, 85.2%, 78.6%, and 51.9% in the saline, low-dose, subclinical dose, and clinical dose groups, respectively; P = 0.001). There was no significant difference in BIS values among the groups 60 seconds after study drug administration or at the time of rocuronium injection. Dexmedetomidine reduced pain associated with rocuronium injection in a dose-dependent manner. This effect was not associated with the decrease in BIS value. Copyright © 2014 Elsevier Inc. All rights reserved.

Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial.

Science.gov (United States)

Griffiths, Roland R; Johnson, Matthew W; Carducci, Michael A; Umbricht, Annie; Richards, William A; Richards, Brian D; Cosimano, Mary P; Klinedinst, Margaret A

2016-12-01

Cancer patients often develop chronic, clinically significant symptoms of depression and anxiety. Previous studies suggest that psilocybin may decrease depression and anxiety in cancer patients. The effects of psilocybin were studied in 51 cancer patients with life-threatening diagnoses and symptoms of depression and/or anxiety. This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. Instructions to participants and staff minimized expectancy effects. Participants, staff, and community observers rated participant moods, attitudes, and behaviors throughout the study. High-dose psilocybin produced large decreases in clinician- and self-rated measures of depressed mood and anxiety, along with increases in quality of life, life meaning, and optimism, and decreases in death anxiety. At 6-month follow-up, these changes were sustained, with about 80% of participants continuing to show clinically significant decreases in depressed mood and anxiety. Participants attributed improvements in attitudes about life/self, mood, relationships, and spirituality to the high-dose experience, with >80% endorsing moderately or greater increased well-being/life satisfaction. Community observer ratings showed corresponding changes. Mystical-type psilocybin experience on session day mediated the effect of psilocybin dose on therapeutic outcomes. ClinicalTrials.gov identifier: NCT00465595. © The Author(s) 2016.

MgO–CaO–Cr2O3 composition as a novel refractory brick: Use of Cr2O3 nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Ghasemi-Kahrizsangi, S.; Dehsheikh, H.G.; Boroujerdnia, M.

2017-07-01

At this study the effect of Cr2O3 nanoparticles (up to 3wt.%) on the physical and mechanical properties of MgO–CaO refractory composition with emphasis on the hydration resistance improvement have been investigated. Specimens pressed at 90MPa then were sintered at 1650°C for 5h in an electric furnace. Properties such as bulk density, apparent porosity, cold crushing strength and hydration resistance were examined. The crystalline phases and microstructure characteristics of sintered specimens were studied by X-ray diffraction (XRD) and scanning electron microscopy (SEM/EDS), respectively. Results shown that add of the 1.5wt.% Cr2O3 nanoparticles have the best results i.e. increased the bulk density (3.41g/cm3), cold crushing strength (848kg/cm2), hydration resistance (1.5%) and decreased apparent porosity (5.58%), respectively. The mechanism of specimens hydration resistance improvement are: (i) decreasing the amount of free CaO and MgO with converted to high hydration resistance phases such as CaCr2O4 and MgCr2O4 phases, (ii) promotion of the densification as well as (iii) modification of the microstructure. (Author)

Metformin as an initial adjunct to low-dose liraglutide enhances the weight-decreasing potential of liraglutide in obese polycystic ovary syndrome: Randomized control study.

Science.gov (United States)

Jensterle, Mojca; Goricar, Katja; Janez, Andrej

2016-04-01

Liraglutide (LIRA) treatment is associated with the dose-dependent reduction of weight. Higher doses are more effective than lower doses, although higher doses are also more poorly tolerated. Metformin may enhance the weight-lowering potential of LIRA via the stimulatory modulation of incretin in addition to its direct beneficial effects in PCOS. The aim of the present study was to evaluate whether metformin as an adjunct to low-dose LIRA affects body weight with increased efficacy compared with low-dose LIRA alone in obese patients with PCOS. In a 12-week study, 44 obese women with PCOS were randomly offered either combined treatment (COMBO) with 1,000 mg metformin twice a day and 1.2 mg LIRA once a day, or treatment with 1.2 mg LIRA alone. The primary outcome of treatment was an alteration in the levels of obesity. A total of 43 patients [aged 30.3±4.4 years; body mass index (BMI) 37.2±4.5 kg/m 2 ; mean ± standard deviation] completed the study. The subjects treated with COMBO lost on average 6.2±2.4 kg compared with a 3.8±3.5 kg weight loss in the patients treated with LIRA alone (P=0.024). The BMI decreased by 2.2±0.8 kg/m 2 in patients treated with COMBO and by 1.4±1.2 kg/m 2 in patients treated with LIRA alone (P=0.024). A clinically significant ≥5% weight reduction was achieved in 59.1% of patients treated with COMBO and 42.9% of patients treated with LIRA alone. Reductions in glucose levels following oral glucose tolerance testing, as well as in androstenedione levels in the COMBO group were significantly greater compared with those in the LIRA group. The side effects were mild and transient in the two treatment groups. A combination of metformin and low-dose LIRA was more effective than low-dose LIRA alone in reducing body weight in obese patients with PCOS.

Phenolic extract of Parkia biglobosa fruit pulp stalls aflatoxin B1 – mediated oxidative rout in the liver of male rats

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Taofeek O. Ajiboye

Full Text Available The effect of phenolic extract of Parkia biglobosa (Jacq. R. Br. ex G. Don, Fabaceae, pulp on aflatoxin B1 induced oxidative imbalance in rat liver was evaluated. Thirty-five male rats were randomized into seven groups of five animals each. Rats in group A served as control and received vehicle for drug administration (0.5% DMSO once daily at 24 h intervals for six weeks. Rats in groups B, D, E, F and G, received aflatoxin B1 (167 μg/kg body weight in 0.5% DMSO for three weeks, starting from the third week of the experimental period. Rats in Group C received 400 mg/kg bodyweight of the extract for six weeks, while groups D, E and F rats were treated with 100, 200 and 400 mg/kg bodyweight of the extract for six weeks respectively. Group G rats received 100 mg/kg body weight of vitamin C. Aflatoxin B1-mediated decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were significantly attenuated. Aflatoxin B1 mediated the elevation in malondialdehyde, conjugated dienes, lipid hydroperoxides, protein carbonyl, and significantly lowered DNA fragmentation percentage. Overall, the phenolic extract of P. biglobosa pulp stalls aflatoxin B1-mediated oxidative rout by enhancing antioxidant enzyme activities leading to decreased lipid peroxidation, protein oxidation and DNA fragmentation.

Macleaya cordata Extract Decreased Diarrhea Score and Enhanced Intestinal Barrier Function in Growing Piglets

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Gang Liu

2016-01-01

Full Text Available Macleaya cordata extract is of great scientific and practical interest to researchers, due to its antimicrobial and anti-inflammatory responses within experimental animals. This study was designed to determine the diarrhea score and innate immunity of growing piglets after they had received Macleaya cordata extract supplements. A total of 240 growing pigs were randomly assigned to one of three dietary treatments, with 8 replicates per treatment and 10 piglets per replicate. All pigs received a basal diet containing similar amounts of nutrients. The three treatments were a control (no additive, an antibiotic (200 mg/kg colistin, and the Macleaya cordata extract supplement group (40 mg/kg Macleaya cordata extract. The diarrhea score was calculated after D 28. The jejunal samples were obtained from five piglets selected randomly from each treatment on D 28. In comparison with the control group, the dietary Macleaya cordata extract and colistin group demonstrated a substantially decreased diarrhea score. The introduction of Macleaya cordata extract supplements to the diet significantly increased volumes of ZO-1 and claudin-1, particularly in comparison with the pigs in the control group (P<0.05. The findings indicate that Macleaya cordata extract does enhance intestinal barrier function in growing piglets and that it could be used as a viable substitute for antibiotics.

Ketamine alters behavior and decreases BDNF levels in the rat brain as a function of time after drug administration

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Daiane B. Fraga

2013-09-01

Full Text Available Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF levels in rats subjected to ketamine administration (25 mg/kg for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug.

Hypocretin-1 receptors regulate the reinforcing and reward-enhancing effects of cocaine: Pharmacological and behavioral genetics evidence

Directory of Open Access Journals (Sweden)

Jonathan eHollander

2012-07-01

Full Text Available Considerable evidence suggests that transmission at hypocretin-1 (orexin-1 receptors (Hcrt-R1 plays an important role in the reinstatement of extinguished cocaine-seeking behaviors in rodents. However, far less is known about the role for hypocretin transmission in regulating ongoing cocaine-taking behavior. Here, we investigated the effects of the selective Hcrt-R1 antagonist SB-334867 on cocaine intake, as measured by intravenous (IV cocaine self-administration in rats. The stimulatory effects of cocaine on brain reward systems contribute to the establishment and maintenance of cocaine-taking behaviors. Therefore, we also assessed the effects of SB-334867 on the reward-enhancing properties of cocaine, as measured by cocaine-induced lowering of intracranial self-stimulation (ICSS thresholds. Finally, to definitively establish a role for Hcrt-R1 in regulating cocaine intake, we assessed IV cocaine self-administration in Hcrt-R1 knockout mice. We found that SB-334867 (1-4 mg/kg dose-dependently decreased cocaine (0.5 mg/kg/infusion self-administration in rats but did not alter responding for food rewards under the same schedule of reinforcement. This suggests that SB-334867 decreased cocaine reinforcement without negatively impacting operant performance. SB-334867 (1-4 mg/kg also dose-dependently attenuated the stimulatory effects of cocaine (10 mg/kg on brain reward systems, as measured by reversal of cocaine-induced lowering of ICSS thresholds in rats. Finally, we found that Hcrt-R1 knockout mice self-administered far less cocaine than wildtype mice across the entire dose-response function. These data demonstrate that Hcrt-R1 play an important role in regulating the reinforcing and reward-enhancing properties of cocaine, and suggest that hypocretin transmission is likely essential for establishing and maintaining the cocaine habit in human addicts.

A phase 1/2, dose-escalation trial of deferasirox for the treatment of iron overload in HFE-related hereditary hemochromatosis.

Science.gov (United States)

Phatak, Pradyumna; Brissot, Pierre; Wurster, Mark; Adams, Paul C; Bonkovsky, Herbert L; Gross, John; Malfertheiner, Peter; McLaren, Gordon D; Niederau, Claus; Piperno, Alberto; Powell, Lawrie W; Russo, Mark W; Stoelzel, Ulrich; Stremmel, Wolfgang; Griffel, Louis; Lynch, Nicola; Zhang, Yiyun; Pietrangelo, Antonello

2010-11-01

Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption that may result in iron overload. Although phlebotomy is widely practiced, it is poorly tolerated or contraindicated in patients with anemias, severe heart disease, or poor venous access, and compliance can vary. The once-daily, oral iron chelator, deferasirox (Exjade) may provide an alternative treatment option. Patients with HH carrying the HFE gene who were homozygous for the Cys282Tyr mutation, serum ferritin levels of 300-2000 ng/mL, transferrin saturation ≥ 45%, and no known history of cirrhosis were enrolled in this dose-escalation study to characterize the safety and efficacy of deferasirox, comprising a core and an extension phase (each 24 weeks). Forty-nine patients were enrolled and received starting deferasirox doses of 5 (n = 11), 10 (n = 15), or 15 (n = 23) mg/kg/day. Adverse events were generally dose-dependent, the most common being diarrhea, headache, and nausea (n = 18, n = 10, and n = 8 in the core and n = 1, n = 1, and n = 0 in the extension, respectively). More patients in the 15 mg/kg/day than in the 5 or 10 mg/kg/day cohorts experienced increases in alanine aminotransferase and serum creatinine levels during the 48-week treatment period; six patients had alanine aminotransferase > 3 × baseline and greater than the upper limit of normal range, and eight patients had serum creatinine > 33% above baseline and greater than upper limit of normal on two consecutive occasions. After receiving deferasirox for 48 weeks, median serum ferritin levels decreased by 63.5%, 74.8%, and 74.1% in the 5, 10, and 15 mg/kg/day cohorts, respectively. In all cohorts, median serum ferritin decreased to < 250 ng/mL. Deferasirox doses of 5, 10, and 15 mg/kg/day can reduce iron burden in patients with HH. Based on the safety and efficacy results, starting deferasirox at 10 mg/kg/day appears to be most appropriate for further study in this patient population.

Effect of excess Mg and Excess Nb incorporation into the B-site of pyrochlore in the Pb-Mg-Nb-O system

Directory of Open Access Journals (Sweden)

Mergen, A.

2002-12-01

Full Text Available In the Pb-Mg-Nb-O system, excess Mg and excess Nb incorporation into the B-site of PMN pyrochlore were investigated along the compositons of Pb1.83Mg0.29+xNb1.71-xO6.39-1.5x where x=0.1, 0.2, 0.3, 0.4, 0.522 and Pb1.83Mg0.29-xNb1.71+xO6.39+1.5x where x=0.1, 0.2, 0.29 respectively. Excess Mg incorporation led to the formation of perovskite and excess Nb resulted in formation of Pb2Nb2O7 monoclinic pyrochlore. The densities of the PMN pyrochlore-PMN perovskite mixtures decreased with an increase in Mg concentration. The relative permittivity of the mixtures increased with decreasing pyrochlore content. The effect of pyrochlore on the permittivity follows the Weiner’s mixture rule up to a pyrochlore content of 50 vol%.

Se investigó la incorporación en lugares B de pirocloro PMN de un exceso de Mg y un exceso de Nb. En el sistema Pb-Mg-Nb-O2 las composiciones analizadas fueron Pb1.83Mg0.29+xNb1.71-xO6.39-1.5x donde x=0.1, 0.2, 0.3, 0.4, 0.522 y en Pb1.83Mg0.29-xNb1.71+xO6.39+1.5x donde x= 0.1, 0.2,0.29. El exceso de Mg condujo a la formación de perovskita y el exceso de Nb resultó en la formación del pirocloro monolínico, Pb2Nb2O7. La densidad de la mezcla de PMN pirocloro-perovskita dismunuye con el aumento de la concentración de Mg. La permitividad dieléctrica de las mezclas aumenta con la disminución del contenido de pirocloro. El efecto del pirocloro sobre la permitividad sigue la regla de mezclas de Weiner hasta conenidos de pirocloro del 50%.

Tesofensine, a novel triple monoamine reuptake inhibitor, induces appetite suppression by indirect stimulation of alpha1 adrenoceptor and dopamine D1 receptor pathways in the diet-induced obese rat

DEFF Research Database (Denmark)

Axel, Anne Marie Dixen; Mikkelsen, Jens D; Hansen, Henrik H

2010-01-01

) and partially antagonized by co-administration of SCH23390 (0.03 mg/kg, DA D(1) receptor antagonist). In contrast, tesofensine-induced hypophagia was not affected by RX821002 (0.3 mg/kg, alpha(2) adrenoceptor antagonist), haloperidol (0.03 mg/kg, D(2) receptor antagonist), NGB2904 (0.1 mg/kg, D(3) receptor...

Comparison of the actions of gamma-butyrolactone and 1,4-butanediol in Swiss-Webster mice.

Science.gov (United States)

de Fiebre, Christopher M; de Fiebre, Nancy Ellen C; Coleman, Scott L; Forster, Michael J

2004-04-01

The abuse of gamma-hydroxybutyrate (GHB) and two of its precursors, gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are recognized as a public health concern. Here, we report dose-response and time-course analyses for effects of GBL and 1,4-BD on locomotor activity and body temperature in Swiss-Webster mice. Locomotor activity was measured for 2 h following a single injection of one of four doses of each agent plus a saline vehicle control. At 50 mg/kg, GBL produced an initial depression of locomotor activity which was followed by stimulation of locomotor activity. In contrast, 1,4-BD at 50 mg/kg stimulated locomotor activity without producing any depression of activity. At higher doses, GBL produced primarily a dose-dependent decrease in locomotor activity that returned to baseline within 50 min. In contrast, 1,4-BD produced an initial depression which was followed by stimulation of activity. Body temperature was measured rectally across a 2.5-h time course following injection with either agent. Both drugs produced hypothermia with peak effects occurring at 20 and 30 min for both drugs for the lower and higher dose, respectively. At 150 mg/kg, GBL produced a greater hypothermic response; however, no differences in hypothermic response were observed at 100 mg/kg. These studies demonstrate that the precursor drugs to GHB have some differential actions from each other.

Preparation and characterisation of Os doped MgB{sub 2}

Energy Technology Data Exchange (ETDEWEB)

Grivel, J.-C., E-mail: jean@dtu.dk; Namazkar, S.; Alexiou, A.; Holte, O.J.

2014-12-15

Highlights: • Polycrystalline osmium doped MgB{sub 2} samples were prepared by solid state route. • Up to 1 at.% Mg can be replaced by Os in the MgB{sub 2} lattice. • T{sub c} decreases at a rate of 2.1 K/at.% Os upon doping. - Abstract: Polycrystalline samples with Mg{sub 1−x}Os{sub x}B{sub 2.04} nominal stoichiometry were made by reacting elemental powders at 800 °C under argon atmosphere. Based on XRD diffraction patterns, EDS analysis and magnetisation measurements, it is found that Os can replace up to about 1 at.% Mg in the MgB{sub 2} lattice. Beyond this doping level, unreacted Os and Mg-rich Mg–Os impurity phases are formed. The a-axis parameter contracts upon doping while the superconducting transition temperature decreases at a rate of 2.1 K/at.% Os substitution. At 10 K, Os doping induces an improvement of the normalised critical current density under applied magnetic fields in excess of 0.5 T, indicating a modest enhancement of flux pinning in this range.

Pharmacokinetic and pharmacodynamic evaluations of a 10 mg/kg enrofloxacin intramuscular administration in bearded dragons (Pogona vitticeps): a preliminary assessment.

Science.gov (United States)

Salvadori, M; Vercelli, C; De Vito, V; Dezzutto, D; Bergagna, S; Re, G; Giorgi, M

2017-01-01

Enrofloxacin (E) is commonly used in veterinary medicine. It is necessary to perform pharmacokinetic/dynamic studies to minimize the selection of resistant mutants of bacteria and extend the efficacy of antimicrobial agents. Eight healthy adult Pogona vitticeps were assigned into two groups of equal size and treated with a single intramuscular injection of E at 10 mg/kg. Blood samples were withdrawn at different scheduled times for each group, and rectal swabs were collected. E and ciprofloxacin (active metabolite) blood concentrations were quantified by an HPLC validated method, while the in vitro antimicrobial susceptibility was evaluated by the Kirby-Bauer disc diffusion susceptibility test. The pharmacokinetic profiles of E gave similar pharmacokinetic parameters irrespective of the collection time schedule. Bacteria isolation showed the presence of both E. coli, Salmonella enterica subspecies enterica and subspecies 3a, Proteus spp., and Pseudomonas spp. The majority of isolated colonies were sensitive to E, but the treatment did not reduce the number of bacteria in faeces. Results suggest that E is able to reach blood concentrations high enough to kill susceptible bacteria (MIC < 0.9 μg/mL), but at the same time does not significantly affect intestinal bacteria. © 2016 John Wiley & Sons Ltd.

NTP Toxicology and Carcinogenesis of 1,2,3-Trichloropropane (CAS No. 96-18-4) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Science.gov (United States)

1993-08-01

1,2,3-Trichloropropane is a colorless liquid used as a paint and varnish remover, solvent, and degreasing agent, and as a crosslinking agent in the synthesis of polysulfides and hexafluoropropylene. 1,2,3-Trichloropropane may be found as an impurity in certain nematocides and soil fumigants and as a contaminant of drinking and ground water. Studies on the toxic and carcinogenic effects of 1,2,3-trichloropropane were initiated because of the close structural relationship of this chemical to other short-chain halogenated compounds that were demonstrated to be carcinogenic in experimental animals, and because of the potential for human exposure. Toxicology and carcinogenicity studies were conducted by administering 1,2,3-trichloropropane (greater than 99% pure) in corn oil by gavage to groups of F344/N rats and B6C3FI mice for 17 weeks and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium strains, mouse lymphoma cells, and Chinese hamster ovary cells. 17-Week Studies: Groups of 20 male and 20 female rats received 1,2,3-trichloropropane in corn oil by gavage at doses of 8, 16, 32, 63, 125, or 250 mg/kg body weight 5 days per week for up to 17 weeks; 30 male and 30 female rats received corn oil alone and served as controls. Animals were evaluated at 8 or 17 weeks. All rats in the 250 mg/kg groups died by week 5. One male and four female rats in the 125 mg/kg groups died during the study. The mean body weight gains and final mean body weights of males receiving 63 mg/kg and of males and females receiving 125 mg/kg were lower than those of the controls. Hematocrit values, hemoglobin concentrations, and erythrocyte counts decreased with dose in males and females. Serum alanine aminotransferase, aspartate aminotransferase, and sorbitol dehydrogenase activities were significantly increased in some female rats receiving 125 mg/kg. Serum pseudocholinesterase activity decreased with dose in females. Increases in kidney and liver weights were related

Recent history of sediment metal contamination in Lake Macquarie, Australia, and an assessment of ash handling procedure effectiveness in mitigating metal contamination from coal-fired power stations

Energy Technology Data Exchange (ETDEWEB)

Schneider, Larissa, E-mail: Larissa.Schneider@canberra.edu.au [Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 (Australia); Maher, William [Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 (Australia); Potts, Jaimie [New South Wales Office of Environmental and Heritage, Lidcombe, NSW, 2141 Australia (Australia); Gruber, Bernd [Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 (Australia); Batley, Graeme [CSIRO Land and Water, Lucas Heights, NSW 2234 (Australia); Taylor, Anne [Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 (Australia); Chariton, Anthony [CSIRO Land and Water, Lucas Heights, NSW 2234 (Australia); Krikowa, Frank [Institute for Applied Ecology, University of Canberra, Canberra, ACT 2601 (Australia); Zawadzki, Atun; Heijnis, Henk [Institute for Environmental Research, Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234 (Australia)

2014-08-15

This study assessed historical changes in metal concentrations in sediments of southern Lake Macquarie resulting from the activities of coal-fired power stations, using a multi-proxy approach which combines {sup 210}Pb, {sup 137}Cs and metal concentrations in sediment cores. Metal concentrations in the lake were on average, Zn: 67 mg/kg, Cu: 15 mg/kg, As: 8 mg/kg, Se: 2 mg/kg, Cd: 1.5 mg/kg, Pb: 8 mg/kg with a maximum of Zn: 280 mg/kg, Cu: 80 mg/kg, As: 21 mg/kg, Se: 5 mg/kg, Cd: 4 mg/kg, Pb: 48 mg/kg. The ratios of measured concentrations in sediment cores to their sediment guidelines were Cd 1.8, As 1.0, Cu 0.5, Pb 0.2 and Zn 0.2, with the highest concern being for cadmium. Of special interest was assessment of the effects of changes in ash handling procedures by the Vales Point power station on the metal concentrations in the sediments. Comparing sediment layers before and after ash handling procedures were implemented, zinc concentrations have decreased 10%, arsenic 37%, selenium 20%, cadmium 38% and lead 14%. An analysis of contaminant depth profiles showed that, after implementation of new ash handling procedures in 1995, selenium and cadmium, the main contaminants in Australian black coal had decreased significantly in this estuary. - Highlights: • The main sources of metals to Southern Lake Macquarie are coal-fired power stations. • The metal of highest concern in this estuary is cadmium. • Arsenic was mobile in sediments. • Selenium and cadmium decreased in sediments following new ash handling procedures.

Recent history of sediment metal contamination in Lake Macquarie, Australia, and an assessment of ash handling procedure effectiveness in mitigating metal contamination from coal-fired power stations

International Nuclear Information System (INIS)

Schneider, Larissa; Maher, William; Potts, Jaimie; Gruber, Bernd; Batley, Graeme; Taylor, Anne; Chariton, Anthony; Krikowa, Frank; Zawadzki, Atun; Heijnis, Henk

2014-01-01

This study assessed historical changes in metal concentrations in sediments of southern Lake Macquarie resulting from the activities of coal-fired power stations, using a multi-proxy approach which combines 210 Pb, 137 Cs and metal concentrations in sediment cores. Metal concentrations in the lake were on average, Zn: 67 mg/kg, Cu: 15 mg/kg, As: 8 mg/kg, Se: 2 mg/kg, Cd: 1.5 mg/kg, Pb: 8 mg/kg with a maximum of Zn: 280 mg/kg, Cu: 80 mg/kg, As: 21 mg/kg, Se: 5 mg/kg, Cd: 4 mg/kg, Pb: 48 mg/kg. The ratios of measured concentrations in sediment cores to their sediment guidelines were Cd 1.8, As 1.0, Cu 0.5, Pb 0.2 and Zn 0.2, with the highest concern being for cadmium. Of special interest was assessment of the effects of changes in ash handling procedures by the Vales Point power station on the metal concentrations in the sediments. Comparing sediment layers before and after ash handling procedures were implemented, zinc concentrations have decreased 10%, arsenic 37%, selenium 20%, cadmium 38% and lead 14%. An analysis of contaminant depth profiles showed that, after implementation of new ash handling procedures in 1995, selenium and cadmium, the main contaminants in Australian black coal had decreased significantly in this estuary. - Highlights: • The main sources of metals to Southern Lake Macquarie are coal-fired power stations. • The metal of highest concern in this estuary is cadmium. • Arsenic was mobile in sediments. • Selenium and cadmium decreased in sediments following new ash handling procedures

Positron annihilation 2D-ACAR study of semi-coherent Li nanoclusters in MgO(1 0 0) and MgO(1 1 0)

International Nuclear Information System (INIS)

Falub, C.V.; Mijnarends, P.E.; Eijt, S.W.H.; Huis, M.A. van; Veen, A. van; Schut, H.

2002-01-01

Depth selective positron annihilation two-dimensional angular correlation of annihilation radiation (2D-ACAR) is used to determine the electronic structure of Li nanoclusters formed by implantation of 10 16 cm -2 6 Li ions (with an energy of 30 keV) in MgO(1 0 0) and (1 1 0) crystals, and subsequently annealed at 950 K. The 2D-ACAR spectra of Li-implanted MgO obtained with 4 keV positrons reveal the semi-coherent ordering state of the embedded metallic Li nanoclusters. The results agree with ab initio Korringa-Kohn-Rostoker calculations

Positron annihilation 2D-ACAR study of semi-coherent Li nanoclusters in MgO(1 0 0) and MgO(1 1 0)

Energy Technology Data Exchange (ETDEWEB)

Falub, C.V. E-mail: c.falub@iri.tudelft.nl; Mijnarends, P.E.; Eijt, S.W.H.; Huis, M.A. van; Veen, A. van; Schut, H

2002-05-01

Depth selective positron annihilation two-dimensional angular correlation of annihilation radiation (2D-ACAR) is used to determine the electronic structure of Li nanoclusters formed by implantation of 10{sup 16} cm{sup -2} {sup 6}Li ions (with an energy of 30 keV) in MgO(1 0 0) and (1 1 0) crystals, and subsequently annealed at 950 K. The 2D-ACAR spectra of Li-implanted MgO obtained with 4 keV positrons reveal the semi-coherent ordering state of the embedded metallic Li nanoclusters. The results agree with ab initio Korringa-Kohn-Rostoker calculations.

Positron annihilation 2D-ACAR study of semi-coherent Li nanoclusters in MgO( 1 0 0 ) and MgO( 1 1 0 )

Science.gov (United States)

Falub, C. V.; Mijnarends, P. E.; Eijt, S. W. H.; van Huis, M. A.; van Veen, A.; Schut, H.

2002-05-01

Depth selective positron annihilation two-dimensional angular correlation of annihilation radiation (2D-ACAR) is used to determine the electronic structure of Li nanoclusters formed by implantation of 10 16 cm -26Li ions (with an energy of 30 keV) in MgO(1 0 0) and (1 1 0) crystals, and subsequently annealed at 950 K. The 2D-ACAR spectra of Li-implanted MgO obtained with 4 keV positrons reveal the semi-coherent ordering state of the embedded metallic Li nanoclusters. The results agree with ab initio Korringa-Kohn-Rostoker calculations.

Effect of Age on Energy Requirement for Maintenance and Growth of Dorper and Hu Crossbred F1 Ewes Weighing 20 to 50 kg

Science.gov (United States)

Nie, H. T.; Wan, Y. J.; You, J. H.; Wang, Z. Y.; Lan, S.; Fan, Y. X.; Wang, F.

2015-01-01

This research aimed to define the energy requirement of Dorper and Hu Hybrid F1 ewes 20 to 50 kg of body weight, furthermore to study energy requirement changes with age and evaluate the effect of age on energy requirement parameters. In comparative slaughter trial, thirty animals were divided into three dry matter intake treatments (ad libitum, n = 18; low restricted, n = 6; high restricted, n = 6), and were all slaughtered as baseline, intermediate, and final slaughter groups, to calculate body chemical components and energy retained. In digestibility trial, twelve ewes were housed in individual metabolic cages and randomly assigned to three feeding treatments in accordance with the design of a comparative slaughter trial, to evaluate dietary energetic values at different feed intake levels. The combined data indicated that, with increasing age, the net energy requirement for maintenance (NEm) decreased from 260.62±13.21 to 250.61±11.79 kJ/kg0.75 of shrunk body weight (SBW)/d, and metabolizable energy requirement for maintenance (MEm) decreased from 401.99±20.31 to 371.23±17.47 kJ/kg0.75 of SBW/d. Partial efficiency of ME utilization for maintenance (km, 0.65 vs 0.68) and growth (kg, 0.42 vs 0.41) did not differ (p>0.05) due to age; At the similar condition of average daily gain, net energy requirements for growth (NEg) and metabolizable energy requirements for growth (MEg) for ewes during late fattening period were 23% and 25% greater than corresponding values of ewes during early fattening period. In conclusion, the effect of age upon energy requirement parameters in the present study were similar in tendency with previous recommendations, values of energy requirement for growth (NEg and MEg) for Dorper and Hu crossbred female lambs ranged between the NRC (2007) recommendation for early and later maturating growing sheep. PMID:26104522

Turmeric (Curcuma longa) attenuates food allergy symptoms by regulating type 1/type 2 helper T cells (Th1/Th2) balance in a mouse model of food allergy.

Science.gov (United States)

Shin, Hee Soon; See, Hye-Jeong; Jung, Sun Young; Choi, Dae Woon; Kwon, Da-Ae; Bae, Min-Jung; Sung, Ki-Seung; Shon, Dong-Hwa

2015-12-04

Turmeric (Curcuma longa) has traditionally been used to treat pain, fever, allergic and inflammatory diseases such as bronchitis, arthritis, and dermatitis. In particular, turmeric and its active component, curcumin, were effective in ameliorating immune disorders including allergies. However, the effects of turmeric and curcumin have not yet been tested on food allergies. Mice were immunized with intraperitoneal ovalbumin (OVA) and alum. The mice were orally challenged with 50mg OVA, and treated with turmeric extract (100mg/kg), curcumin (3mg/kg or 30 mg/kg) for 16 days. Food allergy symptoms including decreased rectal temperature, diarrhea, and anaphylaxis were evaluated. In addition, cytokines, immunoglobulins, and mouse mast cell protease-1 (mMCP-1) were evaluated using ELISA. Turmeric significantly attenuated food allergy symptoms (decreased rectal temperature and anaphylactic response) induced by OVA, but curcumin showed weak improvement. Turmeric also inhibited IgE, IgG1, and mMCP-1 levels increased by OVA. Turmeric reduced type 2 helper cell (Th2)-related cytokines and enhanced a Th1-related cytokine. Turmeric ameliorated OVA-induced food allergy by maintaining Th1/Th2 balance. Furthermore, turmeric was confirmed anti-allergic effect through promoting Th1 responses on Th2-dominant immune responses in immunized mice. Turmeric significantly ameliorated food allergic symptoms in a mouse model of food allergy. The turmeric as an anti-allergic agent showed immune regulatory effects through maintaining Th1/Th2 immune balance, whereas curcumin appeared immune suppressive effects. Therefore, we suggest that administration of turmeric including various components may be useful to ameliorate Th2-mediated allergic disorders such as food allergy, atopic dermatitis, and asthma. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of 7-NI and ODQ on memory in the passive avoidance, novel object recognition, and social transmission of food preference tests in mice.

Science.gov (United States)

Akar, Furuzan; Mutlu, Oguz; Komsuoglu Celikyurt, Ipek; Bektas, Emine; Tanyeri, Pelin; Ulak, Guner; Erden, Faruk

2014-03-19

Nitric oxide (NO) is an intercellular messenger that plays a critical role in learning and memory processes. Effects of nitric oxide synthase (NOS) inhibitors and guanylate cyclase (GC) inhibitors on cognitive function remain controversial. The aim of this study was to investigate effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on different aspects of memory in passive avoidance (PA), novel object recognition (NOR), and social transmission of food preference (STFP) tests. Male Balb-c mice were treated intraperitoneally with 7-NI (15 mg/kg), ODQ (3,10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. ODQ (10 mg/kg) and 7-NI (15 mg/kg) significantly decreased second-day latency in PA test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly decreased the ratio index in the NOR test. 7-NI and ODQ (10 mg/kg) decreased cued/non-cued food eaten in STFP test. Amount of time spent in center zone significantly increased in ODQ (10 mg/kg) and 7-NI (15 mg/kg) groups in open field test, but there was no effect on total distance moved and speed of animals. ODQ (10 mg/kg) significantly increased number of entries into new compartments in exploratory activity apparatus, while 7-NI had no effect. Administration of L-arginine (100 mg/kg) before 7-NI reversed 7-NI-induced effects, supporting the role of NO in cognition. Our results confirm that inhibition of NO/cGMP/GS pathway might disturb emotional, visual, and olfactory memory in mice. Also, 7-NI and ODQ had anxiolytic effects in open field test, and ODQ also enhanced exploratory activity.

Mechanical properties, corrosion, and biocompatibility of Mg-Zr-Sr-Dy alloys for biodegradable implant applications.

Science.gov (United States)

Ding, Yunfei; Lin, Jixing; Wen, Cuie; Zhang, Dongmei; Li, Yuncang

2017-11-28

This study investigates the microstructure, mechanical properties, corrosion behavior, and biocompatibility of magnesium (Mg)-based Mg1Zr2SrxDy (x = 0, 1, 1.63, 2.08 wt %) alloys for biodegradable implant applications. The corrosion behavior of the Mg-based alloys has been evaluated in simulated body fluid using an electrochemical technique and hydrogen evolution. The biocompatibility of the Mg-based alloys has been assessed using SaSO2 cells. Results indicate that the addition of Dy to Mg-Zr-Sr alloy showed a positive impact on the corrosion behavior and significantly decreased the degradation rates of the alloys. The degradation rate of Mg1Zr2Sr1.0Dy decreased from 17.61 to 12.50 mm year -1 of Mg1Zr2Sr2.08Dy based on the hydrogen evolution. The ultimate compressive strength decreased from 270.90 MPa for Mg1Zr2Sr1Dy to 236.71 MPa for Mg1Zr2Sr2.08Dy. An increase in the addition of Dy to the Mg-based alloys resulted in an increase in the volume fraction of the Mg 2 Dy phase, which mitigated the galvanic effect between the Mg 17 Sr 2 phase and the Mg matrix, and led to an increase in the corrosion resistance of the base alloy. The biocompatibility of the Mg-based alloys was enhanced with decreasing corrosion rates. Mg1Zr2Sr2.08Dy exhibited the lowest corrosion rate and the highest biocompatibility compared with the other Mg-based alloys. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

The Protective Roles of Zinc and Magnesium in Cadmium-Induced Renal Toxicity in Male Wistar Rats

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Nasim Babaknejad

2014-12-01

Full Text Available Background: Cadmium (Cd is a heavy metal that has widespread use. It enters the food chain in different ways, including soil and water. Cadmium can cause dysfunction of different body organs. Zinc (Zn and magnesium (Mg supplementation can have protective effects against cadmium toxicity due to their antagonistic and antioxidants properties. This study examines the influence of supplemental Zn and Mg on Cd renal toxicity. Methods: Young male Wistar rats were divided into six groups of five. The Cd group received 1 mg Cd/kg and the control group received 0.5 mg/kg normal saline (i.p.. The other four groups were administered 1 mg/kg Cd+0.5 mg/kg Zn, 1 mg/kg Cd+1.5 mg/kg Zn, 1 mg/kg Cd+ 0.5 mg/kg Mg, and 1 mg/kg Cd+ 1.5 mg/kg Mg (i.p. for 21 days. Then, serum sodium, potassium, urea, creatinine, and protein levels were measured. Results: The results indicated that creatinine and protein levels decreased while urea, sodium, and potassium levels increased as a result of Cd exposure. Co-administered Cd and Zn and Mg decreased urea and increased sodium serum level in comparison to the cadmium group. Treatment by Mg, contrary to co-administered Cd and Zn, reduced serum protein level compared to the cadmium group. Compared to the cadmium treated group, Zn and Mg treatment enhanced serum creatinine level and reduced serum potassium level. Conclusion: The findings seem to suggest that zinc and magnesium compounds, due to their antagonistic and antioxidant activities, can protect Cd renal toxic effects in a dose-dependent manner.

Effect of Withania somnifera on forced swimming test induced immobility in mice and its interaction with various drugs.

Science.gov (United States)

Shah, P C; Trivedi, N A; Bhatt, J D; Hemavathi, K G

2006-01-01

The objective of the present study was to evaluate the antidepressant action of Withania somnifera (WS) as well as its interaction with the conventional antidepressant drugs and to delineate the possible mechanism of its antidepressant action using forced swimming model in mice. Effect of different doses of WS, fluoxetine and imipramine were studied on forced swimming test induced mean immobility time (MIT). Moreover effect of WS 100 mg/kg, i.p. was observed at different time intervals. Effect produced by combination of sub therapeutic doses of WS with imipramine (2.5 mg/kg, i.p.) as well as fluoxetine (2.5 mg/kg, i.p.) were also observed. Effect of WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) were observed in mice pretreated with reserpine (2 mg/kg, i.p.) and clonidine (0.15 mg/kg, i.p.). Effects of prazosin (3 mg/kg, i.p.) or haloperidol (0.1 mg/kg, i.p.) pre-treatment were also observed on WS induced decrease in MIT. WS produced dose dependent decrease in MIT. Maximum effect in MIT was observed after 30 min of treatment with WS 100 mg/kg, i.p. Combination of WS (37.5 mg/kg, i.p.) with imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.) also produced significant decrease in the MIT. Clonidine and reserpine induced increase in MIT, was significantly reversed by treatment with WS (100 mg/kg, i.p.) as well as combination of WS (37.5 mg/kg, i.p.) with either imipramine (2.5 mg/kg, i.p.) or fluoxetine (2.5 mg/kg, i.p.). Pre-treatment with prazosin but not haloperidol, significantly antagonized the WS (100 mg/kg, i.p.) induced decrease in MIT. It is concluded that, WS produced significant decrease in MIT in mice which could be mediated partly through a adrenoceptor as well as alteration in the level of central biogenic amines.

Neuropsychiatric safety with liraglutide 3.0 mg for weight management

DEFF Research Database (Denmark)

O'Neil, Patrick M; Aroda, V R; Astrup, Arne

2017-01-01

with liraglutide 3.0 mg were evaluated post hoc. METHODS: Data from the liraglutide weight-management programme were pooled. Across trials, individuals with a body mass index ≥30 kg/m(2) or ≥27 kg/m(2) with weight-related comorbidities were randomized to once-daily subcutaneous liraglutide 3.0 mg (n = 3384......) or placebo (n = 1941), both with a 500 kcal/day deficit diet plus exercise. Adverse events related to neuropsychiatric safety were collected in all trials. Additionally, in the phase 3a trials, validated mental-health questionnaires were prospectively and systematically administered. RESULTS: In the pooled...... analysis of 5325 randomized and exposed individuals, rates of depression (2.1 versus 2.1 events/100 person-years) and anxiety (1.9 versus 1.7 events/100 person-years) through adverse event reporting were similarly low in the liraglutide group and the placebo group. Nine (0.3%) individuals on liraglutide...

The Protective Role of Carbon Monoxide (CO Produced by Heme Oxygenases and Derived from the CO-Releasing Molecule CORM-2 in the Pathogenesis of Stress-Induced Gastric Lesions: Evidence for Non-Involvement of Nitric Oxide (NO

Directory of Open Access Journals (Sweden)

Katarzyna Magierowska

2016-03-01

Full Text Available Carbon monoxide (CO produced by heme oxygenase (HO-1 and HO-2 or released from the CO-donor, tricarbonyldichlororuthenium (II dimer (CORM-2 causes vasodilation, with unknown efficacy against stress-induced gastric lesions. We studied whether pretreatment with CORM-2 (0.1–10 mg/kg oral gavage (i.g., RuCl3 (1 mg/kg i.g., zinc protoporphyrin IX (ZnPP (10 mg/kg intraperitoneally (i.p., hemin (1–10 mg/kg i.g. and CORM-2 (1 mg/kg i.g. combined with NG-nitro-l-arginine (l-NNA, 20 mg/kg i.p., 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 mg/kg i.p., indomethacin (5 mg/kg i.p., SC-560 (5 mg/kg i.g., and celecoxib (10 mg/kg i.g. affects gastric lesions following 3.5 h of water immersion and restraint stress (WRS. Gastric blood flow (GBF, the number of gastric lesions and gastric CO and nitric oxide (NO contents, blood carboxyhemoglobin (COHb level and the gastric expression of HO-1, HO-2, hypoxia inducible factor 1α (HIF-1α, tumor necrosis factor α (TNF-α, cyclooxygenase (COX-2 and inducible NO synthase (iNOS were determined. CORM-2 (1 mg/kg i.g. and hemin (10 mg/kg i.g. significantly decreased WRS lesions while increasing GBF, however, RuCl3 was ineffective. The impact of CORM-2 was reversed by ZnPP, ODQ, indomethacin, SC-560 and celecoxib, but not by l-NNA. CORM-2 decreased NO and increased HO-1 expression and CO and COHb content, downregulated HIF-1α, as well as WRS-elevated COX-2 and iNOS mRNAs. Gastroprotection by CORM-2 and HO depends upon CO’s hyperemic and anti-inflammatory properties, but is independent of NO.

Atorvastatin 10 mg plus ezetimibe 10mg compared with atorvastatin 20 mg: impact on the lipid profile in Japanese patients with abnormal glucose tolerance and coronary artery disease.

Science.gov (United States)

Uemura, Yusuke; Watarai, Masato; Ishii, Hideki; Koyasu, Masayoshi; Takemoto, Kenji; Yoshikawa, Daiji; Shibata, Rei; Matsubara, Tatsuaki; Murohara, Toyoaki

2012-01-01

Oxidized low-density lipoprotein (LDL) cholesterol is a sensitive lipid marker for predicting atherosclerosis. Ezetimibe and statins are reported to decrease both LDL cholesterol and oxidized LDL cholesterol. This prospective randomized open-label crossover study compared combination therapy with atorvastatin plus ezetimibe versus high-dose atorvastatin monotherapy. Changes in serum lipids, including malondialdehyde-modified LDL (MDA-LDL) as a representative form of oxidized LDL cholesterol, and glucose metabolism were assessed. The subjects were 39 Japanese patients with coronary artery disease and type 2 diabetes or impaired glucose tolerance who were taking 10 mg/day of atorvastatin (30 men and 9 women with a mean age of 67.8 years). They were randomized to a group that first received add-on ezetimibe (10 mg/day) or a group that first received atorvastatin monotherapy at a higher dose of 20 mg/day. Both treatments were given for 12 weeks each in a crossover fashion. Add-on ezetimibe significantly decreased MDA-LDL (109.0 ± 31.9 mg/dl to 87.7 ± 29.4 mg/dl, p=0.0009), while up-titration of atorvastatin did not. The decrease with add-on ezetimibe was significantly greater than with up-titration of atorvastatin (p=0.0006). Total cholesterol and LDL cholesterol were significantly decreased by both treatments, but the percent reduction with add-on ezetimibe was significantly greater (pHigh-density lipoprotein cholesterol was significantly increased by both treatments and there was no significant difference between them. The apolipoprotein B/apolipoprotein A-I ratio and remnant-like particle cholesterol were only significantly decreased by add-on ezetimibe. Both treatments caused similar elevation of hemoglobin A(1c). In Japanese patients with type 2 diabetes or impaired glucose tolerance and coronary artery disease, adding ezetimibe (10 mg/day) to atorvastatin (10 mg/day) significantly improved the lipid profile compared with atorvastatin monotherapy at 20 mg

The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits.

Science.gov (United States)

Olson, M E; Vizzutti, D; Morck, D W; Cox, A K

1994-01-01

Nine groups of rats (n = 5 per group) received an intramuscular (IM) injection of one of the following drugs or drug combinations: saline, atropine (0.05 mg/kg), glycopyrrolate (0.5 mg/kg), ketamine:xylazine (85:15 mg/kg), ketamine:detomidine (60:10 mg/kg), atropine:ketamine:xylazine (0.05: 85:15 mg/kg), glycopyrrolate: ketamine:xylazine (0.5:85:15 mg/kg), atropine:ketamine:detomidine (0.05: 60:10 mg/kg) or glycopyrrolate: ketamine:detomidine (0.5:60:10). Similarly six groups of rabbits (n = 5) received an IM injection of either saline, atropine (0.2 mg/kg), atropine (2 mg/kg), glycopyrrolate (0.1 mg/kg), ketamine:xylazine (35:10 mg/kg) or glycopyrrolate:ketamine:xylazine (0.1:35:10 mg/kg). In rats, atropine sulfate (0.05 mg/kg) and glycopyrrolate (0.5 mg/kg) produced an increase in heart rate for 30 and 240 min, respectively. In rabbits atropine sulfate at either 0.2 or 2.0 mg/kg did not induce a significant increase in heart rate, but glycopyrrolate (0.1 mg/kg) elevated the heart rate above saline treated animals for over 50 min. Both atropine and glycopyrrolate provided protection against a decrease in heart rate in rats anesthetized with ketamine: xylazine (85:15 mg/kg) or ketamine: detomidine (60:10 mg/kg); however, glycopyrrolate was significantly more effective in maintaining the heart rate within the normal range. Glycopprrolate also prevented a decrease in heart rate in rabbits anesthetized with ketamine:xylazine (35:5 mg/kg). Neither glycopyrrolate nor atropine influenced respiration rate, core body temperature or systolic blood pressure when used alone or when combined with the injectable anesthetic. Glycopyrrolate is an effective anticholinergic agent in rabbits and rodents and more useful as a preanesthetic agent than atropine sulfate in these animals. PMID:7889456

Enact of Glutathione(GSH/GSSG) Contents of Fermented Ginseng on the γ-irradiated Liver of Mice

International Nuclear Information System (INIS)

Ko, In Ho

2006-01-01

The radioprotective effects of white and fermented ginseng on liver damage induced by 60 Co γ-ray were investigated. To one group of ICR male mice were given white(150 mg/kg/day for 7 days, orally) and fermented ginseng(150 mg/kg/day for 7 days, orally) before 60 Co γ--ray irradiation. To another group were irradiated by 5 Gy(1.01 Gy/min) dose of 60 Co γ--ray. Contrast group were given with saline(0.1 mL). The levels of reduced(GSH) and oxidized(GSSG) glutathione in liver tissue were measured. In the fermented(150 mg/kg) and white ginseng(150 mg/kg) groups than irradiation group, the GSH levels were significantly increased, but the GSSG levels were significantly decreased. The ratio of GSSG/total GSH was significantly decreased in the fermented(150 mg/kg) and white ginseng(150 mg/kg) groups than irradiation group. In the fermented(150 mg/kg) groups than white ginseng(150 mg/kg) groups the GSH levels were significantly increased. The radioprotective effects of fermented(150 mg/kg) groups than white ginseng(150 mg/kg) groups were increased.

Enact of Glutathione(GSH/GSSG) Contents of Fermented Ginseng on the {gamma}-irradiated Liver of Mice

Energy Technology Data Exchange (ETDEWEB)

Ko, In Ho [Dept. of Radiology Technology, Jeju Halla College, Jeju (Korea, Republic of)

2006-03-15

The radioprotective effects of white and fermented ginseng on liver damage induced by {sup 60}Co {gamma}-ray were investigated. To one group of ICR male mice were given white(150 mg/kg/day for 7 days, orally) and fermented ginseng(150 mg/kg/day for 7 days, orally) before {sup 60}Co {gamma}--ray irradiation. To another group were irradiated by 5 Gy(1.01 Gy/min) dose of {sup 60}Co {gamma}--ray. Contrast group were given with saline(0.1 mL). The levels of reduced(GSH) and oxidized(GSSG) glutathione in liver tissue were measured. In the fermented(150 mg/kg) and white ginseng(150 mg/kg) groups than irradiation group, the GSH levels were significantly increased, but the GSSG levels were significantly decreased. The ratio of GSSG/total GSH was significantly decreased in the fermented(150 mg/kg) and white ginseng(150 mg/kg) groups than irradiation group. In the fermented(150 mg/kg) groups than white ginseng(150 mg/kg) groups the GSH levels were significantly increased. The radioprotective effects of fermented(150 mg/kg) groups than white ginseng(150 mg/kg) groups were increased.

Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells

International Nuclear Information System (INIS)

Fuchs, Dominik; Daniel, Volker; Sadeghi, Mahmoud; Opelz, Gerhard; Naujokat, Cord

2010-01-01

Leukemia stem cells are known to exhibit multidrug resistance by expression of ATP-binding cassette (ABC) transporters which constitute transmembrane proteins capable of exporting a wide variety of chemotherapeutic drugs from the cytosol. We show here that human promyeloblastic leukemia KG-1a cells exposed to the histone deacetylase inhibitor phenylbutyrate resemble many characteristics of leukemia stem cells, including expression of functional ABC transporters such as P-glycoprotein, BCRP and MRP8. Consequently, KG-1a cells display resistance to the induction of apoptosis by various chemotherapeutic drugs. Resistance to apoptosis induction by chemotherapeutic drugs can be reversed by cyclosporine A, which effectively inhibits the activity of P-glycoprotein and BCRP, thus demonstrating ABC transporter-mediated drug resistance in KG-1a cells. However, KG-1a are highly sensitive to apoptosis induction by salinomycin, a polyether ionophore antibiotic that has recently been shown to kill human breast cancer stem cell-like cells and to induce apoptosis in human cancer cells displaying multiple mechanisms of drug and apoptosis resistance. Whereas KG-1a cells can be adapted to proliferate in the presence of apoptosis-inducing concentrations of bortezomib and doxorubicin, salinomycin does not permit long-term adaptation of the cells to apoptosis-inducing concentrations. Thus, salinomycin should be regarded as a novel and effective agent for the elimination of leukemia stem cells and other tumor cells exhibiting ABC transporter-mediated multidrug resistance.

Isoleucine requirement of pigs weighing 8 to 18 kg fed blood cell–free diets1

DEFF Research Database (Denmark)

Nørgaard, Jan Værum; Shresta, Aruna; Krogh, Uffe

2013-01-01

The aim of the present study was to determine the minimum requirement of Ile in young pigs, enabling feeding of balanced low-CP diets. Most previous studies have used experimental diets that included blood cells, which are particularly high in Leu and known to antagonize the use of Ile. One week....... In conclusion, the average estimation of requirement in this dose-response study using blood cell–free diets was 0.52 SID Ile:Lys during a 21-d experimental period from 8 kg BW....... after weaning at d 28, 100 crossbred female pigs weighing 7.9 ± 0.7 kg were allocated to 1 of 5 dietary treatments. Diets were formulated to contain 1.15 g standardized ileal digestible (SID) Lys/MJ NE and were free of blood cells. The SID Ile was 0.42, 0.47, 0.53, 0.58, and 0.62 relative to Lys...

Evaluation of Methane and Carbon Dioxide Emission Decrease Through Waste Composting

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Apinan Pitaratae

2017-01-01

Full Text Available The organic waste disposal under anaerobic conditions emits Methane, which causes increased global warming. This study attempts to find the emission factor in windrow waste composting systems from two sizes of gathered organic waste piles. Designed to compare two groups of composting piles, one pile consisted of 500 kilograms of waste originating from local authorities while the other amounted to 250 kilograms of waste collected from households. With six piles of each type, aeration was done by manual turning and emissions were sampled in closed flux chambers and analyzed by gas chromatographs. A control experiment, modeling landfill sites, was set up in a one x one x one meter hole. Results from the experiment showed that emission ratios from the 500 kg was 1.3613 x 10-3 g CO2-eq kg-1 wet waste, and 1.3427 x 10-3 g CO2-eq kg-1 wet waste from the 250 kg experiment. The 500 kg experiment decreased emissions by 0.059185 g CO2-eq kg-1 wet waste and the 250 kg experiment, emissions decreased by 0.059206 g CO2-eq kg-1 wet waste when compared to the control group. In summary, pile size has no effect on emission ratios. Statistical testing found no significance difference between emissions from the 500 kg compared with the 250 kg. This study tells us that massive landfill or waste composting is difference effect.INTERNATIONAL JOURNAL OF ENVIRONMENTVolume-5, Issue-4, Sep-Nov 2016, Page: 44-55

The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

Science.gov (United States)

Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

2016-04-01

Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Aspirin decreases platelet uptake on Dacron vascular grafts in baboons

International Nuclear Information System (INIS)

Mackey, W.C.; Connolly, R.J.; Callow, A.D.

1984-01-01

The influence of a single dose of aspirin (5.4-7.4 mg/kg) on platelet uptake on 4-mm Dacron interposition grafts was studied in a baboon model using gamma camera scanning for 111-Indium labeled platelets. In vitro assessment of platelet function after aspirin administration revealed that in the baboon, as in the human, aspirin abolished arachidonic acid-induced platelet aggregation, prolonged the lag time between exposure to collagen and aggregation, and decreased plasma thromboxane B2 levels. Aspirin also prolonged the template bleeding time. Scans for 111-Indium labeled platelets revealed that pretreatment with a single dose of aspirin decreased platelet uptake on 4-mm Dacron carotid interposition grafts. This decrease in platelet uptake was associated with a significant improvement in 2-hour graft patency and with a trend toward improved 2-week patency

A density functional study of NO{sub 2} adsorption on perfect and defective MgO (1 0 0) and Li/MgO (1 0 0) surfaces

Energy Technology Data Exchange (ETDEWEB)

Eid, Kh.M., E-mail: Khaled_eid@edu.asu.edu.eg [Physics Department, Faculty of Education, Ain Shams University, P.O. Box 11757, Cairo (Egypt); Ammar, H.Y. [Physics Department, Faculty of Education, Ain Shams University, P.O. Box 11757, Cairo (Egypt); Department of Physics, Faculty of Science, Najran University, Najran (Saudi Arabia)

2012-07-15

The density functional theory (DFT) in combination with embedded cluster model have been used to study the adsorption of nitrogen dioxide molecule (NO{sub 2}) on Li atom deposited on the surfaces of metal oxide MgO (1 0 0) on both anionic (O{sup 2-}) and defect (F{sub s} and F{sub s}{sup +}-centers) sites. The adsorption energy (E{sub ads}) of NO{sub 2} molecule (N-down as well as O-down) in different positions on O{sup -2}, F{sub s} and F{sub s}{sup +}-sites is considered. The geometrical optimizations have been done for the additive materials and MgO substrate surfaces. The formation energies have been evaluated for F{sub s} and F{sub s}{sup +} of MgO substrate surfaces. The ionization potential (IP) and electron affinity (eA) for defect free and defect containing surfaces have been calculated. The adsorption properties of NO{sub 2} are analyzed in terms of the adsorption energy, the electron donation (basicity), the elongation of N-O bond length and the atomic charges on adsorbed materials. The densities of states (DOS) have been calculated and used for examining the adsorption properties. The NO{sub 2} molecule is dissociated due to the interaction with the defective substrate surface (F{sub s}-site) producing an oxygen atom strongly chemisorbed to the vacancy of the substrate and gaseous NO far away from the surface. The presence of the Li atom increases the surface chemistry of the anionic O{sup 2-}-site of MgO substrate surfaces (converted from physisorption to chemisorption). On the other hand, the presence of the Li atom decreases the surface chemistry of the F{sub s} and F{sub s}{sup +}-sites of MgO substrate surfaces. Generally, the NO{sub 2} molecule is strongly adsorbed (chemisorption) on the MgO substrate surfaces containing F{sub s} and F{sub s}{sup +}-centers.

The H2O2 scavenger ebselen decreases ethanol-induced locomotor stimulation in mice.

Science.gov (United States)

Ledesma, Juan Carlos; Font, Laura; Aragon, Carlos M G

2012-07-01

In the brain, the enzyme catalase by reacting with H(2)O(2) forms Compound I (catalase-H(2)O(2) system), which is the main system of central ethanol metabolism to acetaldehyde. Previous research has demonstrated that acetaldehyde derived from central-ethanol metabolism mediates some of the psychopharmacological effects produced by ethanol. Manipulations that modulate central catalase activity or sequester acetaldehyde after ethanol administration modify the stimulant effects induced by ethanol in mice. However, the role of H(2)O(2) in the behavioral effects caused by ethanol has not been clearly addressed. The present study investigated the effects of ebselen, an H(2)O(2) scavenger, on ethanol-induced locomotion. Swiss RjOrl mice were pre-treated with ebselen (0-50mg/kg) intraperitoneally (IP) prior to administration of ethanol (0-3.75g/kg; IP). In another experiment, animals were pre-treated with ebselen (0 or 25mg/kg; IP) before caffeine (15mg/kg; IP), amphetamine (2mg/kg; IP) or cocaine (10mg/kg; IP) administration. Following these treatments, animals were placed in an open field to measure their locomotor activity. Additionally, we evaluated the effect of ebselen on the H(2)O(2)-mediated inactivation of brain catalase activity by 3-amino-1,2,4-triazole (AT). Ebselen selectively prevented ethanol-induced locomotor stimulation without altering the baseline activity or the locomotor stimulating effects caused by caffeine, amphetamine and cocaine. Ebselen reduced the ability of AT to inhibit brain catalase activity. Taken together, these data suggest that a decline in H(2)O(2) levels might result in a reduction of the ethanol locomotor-stimulating effects, indicating a possible role for H(2)O(2) in some of the psychopharmacological effects produced by ethanol. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Candesartan decreases the sympatho-adrenal and hormonal response to isolation stress

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Ines Armando

2001-03-01

Full Text Available A change from group housing to isolation in unfamiliar metabolic cages represents, for rodents, a significant emotional stress. We studied the effect of candesartan, a peripheral and central angiotensin II AT1-receptor antagonist, on the hormonal and sympathetic response to acute isolation. We pretreated rats with 1 mg/kg/day candesartan for 13 days via subcutaneously implanted osmotic minipumps, followed by 24-hour isolation in individual metabolic cages. We measured brain, pituitary and adrenal angiotensin II (Ang II receptor binding by quantitative autoradiography and adrenal hormones and catecholamines by RIA and HPLC. Isolation increased adrenal catecholamines, aldosterone and corticosterone, AT1-receptor binding in the zona glomerulosa and AT2-receptor binding in the adrenal medulla. Candesartan pretreatment decreased adrenal catecholamines, aldosterone and corticosterone, AT1-receptor binding in adrenal zona glomerulosa and medulla, pituitary gland and the hypothalamic paraventricular nucleus, and AT2-receptor binding in adrenal medulla, but increased AT2-receptor binding in zona glomerulosa. We conclude that peripheral and central AT1-receptor blockade with candesartan decreases the sympatho-adrenal and hormonal response to acute stress. Our results indicate that Ang II is an important stress hormone and suggest that blockade of the physiologically active AT 1-receptors could influence stress-related disorders.

Decreased bilirubin transport in the perfused liver of endotoxemic rats

NARCIS (Netherlands)

Roelofsen, H.; van der Veere, C. N.; Ottenhoff, R.; Schoemaker, B.; Jansen, P. L.; Oude Elferink, R. P.

1994-01-01

Hyperbilirubinemia associated with sepsis is frequently observed in humans. In this study, an experimental rat model was developed to study bilirubin metabolism and transport during endotoxemia. Rats were injected intravenously with a single bolus of lipopolysaccharide (1 mg/kg); after 18 hours, the

Effects of dietary probiotic supplementation on LXRα and CYP7α1 gene expression, liver enzyme activities and fat metabolism in ducks.

Science.gov (United States)

Huang, Z; Mu, C; Chen, Y; Zhu, Z; Chen, C; Lan, L; Xu, Q; Zhao, W; Chen, G

2015-04-01

1. The objective of this study was to investigate the effects of dietary probiotic supplementation on liver X receptor alpha (LXRα) and cholesterol 7α-hydroxylase (CYP7α1) mRNA levels, protein enzymatic activities and fat metabolism in Cherry Valley Pekin ducks. 2. A total of 750 one-day-old Cherry Valley Pekin ducks were randomly divided into 5 groups with three replicates of 50 ducks each in a completely randomised experiment. Each group was fed on a basal diet supplemented with 0, 500, 1000, 1500 or 2000 mg probiotics/kg. 3. Body rate and feed conversion ratio were highest and abdominal subcutaneous fat % was lowest at 1000 mg probiotic/kg. 4. The mRNA levels of LXRα and CYP7α1 in liver tissue was estimated by RT-PCR; serum triglyceride (TG) and total cholesterol (TC) concentrations were measured by ELISA. 5. The expression levels and enzyme activity of LXRα and CYP7α1 increased in conjunction with decreases in TG and TC concentrations following probiotic supplementation to a maximum at 1000 mg probiotics/kg and decreased thereafter. 6. It is concluded that dietary probiotics can enhance LXRα and CYP7α1 enzyme activities in the liver and reduce lipid concentrations and fat deposition in ducks.

Lithium, phenserine, memantine and pioglitazone reverse memory deficit and restore phospho-GSK3β decreased in hippocampus in intracerebroventricular streptozotocin induced memory deficit model.

Science.gov (United States)

Ponce-Lopez, Teresa; Liy-Salmeron, Gustavo; Hong, Enrique; Meneses, Alfredo

2011-12-02

Intracerebroventricular (ICV) streptozotocin (STZ) treated rat has been described as a suitable model for sporadic Alzheimer's disease (AD). Central application of STZ has demonstrated behavioral and neurochemical features that resembled those found in human AD. Chronic treatments with antioxidants, acetylcholinesterase (AChE) inhibitors, or improving glucose utilization drugs have reported a beneficial effect in ICV STZ-treated rats. In the present study the post-training administration of a glycogen synthase kinase (GSK3) inhibitor, lithium; antidementia drugs: phenserine and memantine, and insulin sensitizer, pioglitazone on memory function of ICV STZ-rats was assessed. In these same animals the phosphorylated GSK3β (p-GSK3β) and total GSK3β levels were determined, and importantly GSK3β regulates the tau phosphorylation responsible for neurofibrillary tangle formation in AD. Wistar rats received ICV STZ application (3mg/kg twice) and 2 weeks later short- (STM) and long-term memories (LTM) were assessed in an autoshaping learning task. Animals were sacrificed immediately following the last autoshaping session, their brains removed and dissected. The enzymes were measured in the hippocampus and prefrontal cortex (PFC) by western blot. ICV STZ-treated rats showed a memory deficit and significantly decreased p-GSK3β levels, while total GSK3β did not change, in both the hippocampus and PFC. Memory impairment was reversed by lithium (100mg/kg), phenserine (1mg/kg), memantine (5mg/kg) and pioglitazone (30 mg/kg). The p-GSK3β levels were restored by lithium, phenserine and pioglitazone in the hippocampus, and restored by lithium in the PFC. Memantine produced no changes in p-GSK3β levels in neither the hippocampus nor PFC. Total GSK3β levels did not change with either drug. Altogether these results show the beneficial effects of drugs with different mechanisms of actions on memory impairment induced by ICV STZ, and restored p-GSK3β levels, a kinase key of

Music and ambient operating room noise in patients undergoing spinal anesthesia.

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Ayoub, Chakib M; Rizk, Laudi B; Yaacoub, Chadi I; Gaal, Dorothy; Kain, Zeev N

2005-05-01

Previous studies have indicated that music decreases intraoperative sedative requirements in patients undergoing surgical procedures under regional anesthesia. In this study we sought to determine whether this decrease in sedative requirements results from music or from eliminating operating room (OR) noise. A secondary aim of the study was to examine the relationship of response to intraoperative music and participants' culture (i.e., American versus Lebanese). Eighty adults (36 American and 54 Lebanese) undergoing urological procedures with spinal anesthesia and patient-controlled IV propofol sedation were randomly assigned to intraoperative music, white noise, or OR noise. We found that, controlling for ambient OR noise, intraoperative music decreases propofol requirements (0.004 +/- 0.002 mg . kg(-1) . min(-1) versus 0.014 +/- 0.004 mg . kg(-1) . min(-1) versus 0.012 +/- 0.002 mg . kg(-1) . min(-1); P = 0.026). We also found that, regardless of group assignment, Lebanese patients used less propofol as compared with American patients (0.005 +/- 0.001 mg . kg(-1) . min(-1) versus 0.017 +/- 0.003 mg . kg(-1) . min(-1); P = 0.001) and that, in both sites, patients in the music group required less propofol (P noise, intraoperative music decreases propofol requirements of both Lebanese and American patients who undergo urological surgery under spinal anesthesia.

Z-contrast imaging of ordered structures in Pb(Mg1/3Nb2/3)O3 and Ba(Mg1/3Nb2/3)O3

International Nuclear Information System (INIS)

Yan, Y.; Pennycook, S.J.; Xu, Z.; Viehland, D.

1998-02-01

Lead-based cubic perovskites such as Pb(B 1/3 2+ B 2/3 5+ )O 3 (B 2+ Mg, Co, Ni, Zn; B 5+ = Nb, Ta) are relaxor ferroelectrics. Localized order and disorder often occur in materials of this type. In the Pb(Mg 1/3 Nb 2/3 )O 3 (PMN) family, previous studies have proposed two models, space-charge and charge-balance models. In the first model, the ordered regions carry a net negative charge [Pb(Mg 1/2 Nb 1/2 )O 3 ], while in the second model it does not carry a net charge [Pb((Mg 2/3 Nb 1/3 ) 1/2 Nb 1/2 )O 3 ]. However, no direct evidence for these two models has appeared in the literature yet. In this paper the authors report the first direct observations of local ordering in undoped and La-doped Pb(Mg 1/3 Nb 2/3 )O 3 , using high-resolution Z-contrast imaging. Because the ordered structure in Ba(Mg 1/3 Nb 2/3 )O 3 is well known, the Z-contrast image from an ordered domain is used as a reference for this study

In-situ thermal analysis and macroscopical characterization of Mg-xCa and Mg-0.5Ca-xZn alloy systems

Energy Technology Data Exchange (ETDEWEB)

Farahany, Saeed [Department of Materials Engineering, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Bakhsheshi-Rad, Hamid Reza, E-mail: Rezabakhsheshi@gmail.com [Department of Materials Engineering, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Idris, Mohd Hasbullah [Department of Materials Engineering, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Abdul Kadir, Mohammed Rafiq [Medical Implants Technology Group, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Department of Biomechanics and Biomedical Materials, Faculty of Biomedical Engineering and Health Sciences, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Lotfabadi, Amir Fereidouni [Department of Manufacturing and Industrial Engineering, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Ourdjini, Ali [Department of Materials Engineering, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia)

2012-01-10

Highlights: Black-Right-Pointing-Pointer The effect of Ca and Zn addition on Mg-Ca and Mg-Ca-Zn were investigated. Black-Right-Pointing-Pointer Ca and Zn addition decreased solid fraction at coherency point. Black-Right-Pointing-Pointer T{sub N}-T{sub DCP} increased by adding Ca and Zn in Mg-Ca and Mg-Ca-Zn, respectively. Black-Right-Pointing-Pointer Three reactions were detected when Zn/Ca atomic ratio less than 1.25 in Mg-Ca-Zn. Black-Right-Pointing-Pointer A new peak Mg{sub 51}Zn{sub 20} was identified in Mg-0.5Ca-9Zn in addition of other peaks. - Abstract: This research described the identification phases by thermal analysis and microscopy inspection of Mg-xCa and Mg-0.5%Ca-xZn alloys that were solidified at slow cooling rate. Analysis of cooling curve after Ca addition shows the evolution of the Mg{sub 2}Ca intermetallic phase at around 520 Degree-Sign C in addition to {alpha}-Mg phase. First derivative curves of alloys after the addition of Zn to Mg-0.5Ca alloy reveals three peaks related to {alpha}-Mg, Mg{sub 2}Ca and Ca{sub 2}Mg{sub 6}Zn{sub 3} for alloys that have Zn/Ca atomic ratio less than 1.23. The peak of Mg{sub 2}Ca reaction on the first derivative curves disappeared for alloys containing Zn/Ca ratio more than 1.23. A new peak was also observed at 330 Degree-Sign C for Mg-0.5Ca-9Zn which was identified as Mg{sub 51}Zn{sub 20}. Solid fraction at coherency point decreased with increasing Ca and Zn elements. However, coherency time and difference between the nucleation and coherency temperatures (T{sub N}-T{sub DCP}) increased by adding Ca and Zn in Mg-Ca and Mg-Ca-Zn systems.

Magnetic Modeling of Inflated Low-mass Stars Using Interior Fields No Larger than ˜10 kG

Science.gov (United States)

MacDonald, James; Mullan, D. J.

2017-11-01

We have previously reported on models of low-mass stars in which the presence of inflated radii is ascribed to magnetic fields that impede the onset of convection. Some of our magneto-convection models have been criticized because, when they were first reported by Mullan & MacDonald, the deep interior fields were found to be very large (50-100 MG). Such large fields are now known to be untenable. For example, Browning et al. used stability arguments to suggest that interior fields in low-mass stars cannot be larger than ˜1 MG. Moreover, 3D models of turbulent stellar dynamos suggest that fields generated in low-mass interiors may be not much stronger than 10-20 kG. In the present paper, we present magneto-convective models of inflated low-mass stars in which the interior fields are not permitted to be stronger than 10 kG. These models are used to fit empirical data for 15 low-mass stars for which precise masses and radii have been measured. We show that our 10 kG magneto-convective models can replicate the empirical radii and effective temperatures for 14 of the stars. In the case of the remaining star (in the Praesepe cluster), two different solutions have been reported in the literature. We find that one of these solutions can be fitted well with our model using the nominal age of Praesepe (800 Myr). However, the second solution cannot be fitted unless the star’s age is assumed to be much younger (˜150 Myr).

Vibrational spectra of 1-hydroxy- and 1,4-dihydroxyanthraquinones and their magnesium chelate complexes. I. Isotopic effects of OH/OD and 24Mg/26Mg substitutions

International Nuclear Information System (INIS)

Kirszenbaum, Marek

1977-01-01

The vibrational spectra of 1-hydroxy- and 1,4-dihydroxyanthraquinones, their deuterated derivatives and their 24 Mg/ 26 Mg chelate complexes are examined in the spectral region 1700-250cm -1 . The study of deuteroxyanthraquinones allow an assignment of the OH/OD group vibrations and show the multiple coupling of the delta OH vibrations with the vCC and delta CH quinonic vibrations. These results lead to a modification of some spectral assignments of magnesium chelate complexe of 1-OH-AQ. The isotopic 24 Mg/ 26 Mg substitution enables the chelate ring vibrations which depend on the motions of the magnesium atom to be observed. The vC=O and vC-O vibrations frequencies of magnesium chelate complexe [Mg(1,4-O 2 -AQ)]sub(n) show an important difference of the chelate ring electronic state in comparison of those of 1,4-(OH) 2 -AQ. The discussion of the infrared and Raman spectra in the Mg-O vibrations region lead to the conclusion that the configuration of oxygens arround the magnesium is tetrahedral [fr

Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

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Y. Li

2014-06-01

Full Text Available Alpha-lipoic acid (α-LA is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1. Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05 change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver.

The cost-effectiveness of dulaglutide versus liraglutide for the treatment of type 2 diabetes mellitus in Spain in patients with BMI ≥30 kg/m2.

Science.gov (United States)

Dilla, Tatiana; Alexiou, Dimitra; Chatzitheofilou, Ismini; Ayyub, Ruba; Lowin, Julia; Norrbacka, Kirsi

2017-05-01

Dulaglutide 1.5 mg once weekly is a novel glucagon-like peptide 1 (GLP-1) receptor agonist, for the treatment of type two diabetes mellitus (T2DM). The objective was to estimate the cost-effectiveness of dulaglutide once weekly vs liraglutide 1.8 mg once daily for the treatment of T2DM in Spain in patients with a BMI ≥30 kg/m 2 . The IMS CORE Diabetes Model (CDM) was used to estimate costs and outcomes from the perspective of Spanish National Health System, capturing relevant direct medical costs over a lifetime time horizon. Comparative safety and efficacy data were derived from direct comparison of dulaglutide 1.5 mg vs liraglutide 1.8 mg from the AWARD-6 trial in patients with a body mass index (BMI) ≥30 kg/m 2 . All patients were assumed to remain on treatment for 2 years before switching treatment to basal insulin at a daily dose of 40 IU. One-way sensitivity analyses (OWSA) and probabilistic sensitivity analyses (PSA) were conducted to explore the sensitivity of the model to plausible variations in key parameters and uncertainty of model inputs. Under base case assumptions, dulaglutide 1.5 mg was less costly and more effective vs liraglutide 1.8 mg (total lifetime costs €108,489 vs €109,653; total QALYS 10.281 vs 10.259). OWSA demonstrated that dulaglutide 1.5 mg remained dominant given plausible variations in key input parameters. Results of the PSA were consistent with base case results. Primary limitations of the analysis are common to other cost-effectiveness analyses of chronic diseases like T2DM and include the extrapolation of short-term clinical data to the lifetime time horizon and uncertainty around optimum treatment durations. The model found that dulaglutide 1.5 mg was more effective and less costly than liraglutide 1.8 mg for the treatment of T2DM in Spain. Findings were robust to plausible variations in inputs. Based on these results, dulaglutide may result in cost savings to the Spanish National Health System.

Safety and efficacy of fixed-dose 10 mg daily isotretinoin treatment for acne vulgaris in Malaysia.

Science.gov (United States)

Yap, Felix Boon-Bin

2017-09-01

Low-dose isotretinoin is used to reduce side effects albeit higher relapse. This study aimed to determine the efficacy and safety of fixed-dose 10 mg daily isotretinoin for the treatment of acne. This prospective study was performed between 2011 and 2015. All 150 patients were given 10 mg daily isotretinoin until a cumulative dose of 90-110 mg/kg. The mean age was 26.6 years with 64.7% moderate acne, 29.3% severe, and 6% very severe. The mean cumulative dose was 98.8 ± 6.05 mg/kg. All 150 patients had total clearance with a mean time to clearance of 24.0 weeks. Patients with severe/very severe acne had higher cumulative dosage (102.1 vs. 97.0, P < 0.001) and longer duration to clearance (32.9 weeks vs. 19.1 weeks, P < 0.001). Mild relapse was seen in 4%. The mean time to relapse was 32.3 weeks. Lip dryness was the commonest side effects (100%). Mild transient elevation of liver enzymes was detected in 3.3% and a slight increase of serum lipid in 2.7% with no treatment discontinuation. Fixed-dose 10 mg daily treatment with isotretinoin until a cumulative dose of 90-110 mg/kg is safe with low relapse rate. © 2016 Wiley Periodicals, Inc.

Decreased IgA+ B Cells Population and IgA, IgG, IgM Contents of the Cecal Tonsil Induced by Dietary High Fluorine in Broilers

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Kangping Wang

2013-05-01

Full Text Available Fluoride is an environmental and industrial pollutant that affects various organs in humans and animals. The cecal tonsil is an important component of the mucosal immune system and performs important and unique immune functions. In the present study, we investigated the effects of dietary high fluorine on the quantities of IgA+ B cells in the cecal tonsil by immunohistochemistry, and the immunoglobulin A (IgA, immunoglobulin G (IgG and immunoglobulin M (IgM contents in the cecal tonsil by ELISA. A total of 280 one-day-old avian broilers were divided into four groups and fed on a corn-soybean basal diet as control diet (fluorine 22.6 mg/kg or the same diet supplemented with 400, 800 and 1,200 mg/kg fluorine (high fluorine groups I, II and III in the form of sodium fluoride, respectively, throughout a 42-day experimental period. The results showed that the quantities of IgA+ B cells were lower (p < 0.05 or p < 0.01 and the IgA, IgG, and IgM contents were decreased (p < 0.05 or p < 0.01 in high fluorine groups II and III in comparison with those of control group. It was concluded that dietary fluorine, in the 800–1,200 mg/kg range, could reduce the numbers of the IgA+ B cells and immunoglobulin contents in the cecal tonsil, implying the local mucosal immune function was ultimately impacted in broilers.

Concentration effect on inter-mineral equilibrium isotope fractionation: insights from Mg and Ca isotopic systems

Science.gov (United States)

Huang, F.; Wang, W.; Zhou, C.; Kang, J.; Wu, Z.

2017-12-01

Many naturally occurring minerals, such as carbonate, garnet, pyroxene, and feldspar, are solid solutions with large variations in chemical compositions. Such variations may affect mineral structures and modify the chemical bonding environment around atoms, which further impacts the equilibrium isotope fractionation factors among minerals. Here we investigated the effects of Mg content on equilibrium Mg and Ca isotope fractionation among carbonates and Ca content on equilibrium Ca isotope fractionation between orthopyroxene (opx) and clinopyroxene (cpx) using first-principles calculations. Our results show that the average Mg-O bond length increases with decreasing Mg/(Mg+Ca) in calcite when it is greater than 1/48[1] and the average Ca-O bond length significantly decreases with decreasing Ca/(Ca+Mg+Fe) in opx when it ranges from 2/16 to 1/48[2]. Equilibrium isotope fractionation is mainly controlled by bond strengths, which could be measured by bond lengths. Thus, 103lnα26Mg/24Mg between dolomite and calcite dramatically increases with decreasing Mg/(Mg+Ca) in calcite [1] and it reaches a constant value when it is lower than 1/48. 103lnα44Ca/40Ca between opx and cpx significantly increases with decreasing Ca content in opx when Ca/(Ca+Mg+Fe) ranges from 2/16 to 1/48 [2]. If Ca/(Ca+Mg+Fe) is below 1/48, 103lnα44Ca/40Ca is not sensitive to Ca content. Based on our results, we conclude that the concentration effect on equilibrium isotope fractionation could be significant within a certain range of chemical composition of minerals, which should be a ubiquitous phenomenon in solid solution systems. [1] Wang, W., Qin, T., Zhou, C., Huang, S., Wu, Z., Huang, F., 2017. GCA 208, 185-197. [2] Feng, C., Qin, T., Huang, S., Wu, Z., Huang, F., 2014. GCA 143, 132-142.

Selenium, but not lycopene or vitamin E, decreases growth of transplantable dunning R3327-H rat prostate tumors.

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Brian L Lindshield

Full Text Available BACKGROUND: Lycopene, selenium, and vitamin E are three micronutrients commonly consumed and supplemented by men diagnosed with prostate cancer. However, it is not clear whether consumption of these compounds, alone or in combination, results in improved outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the effects of dietary lycopene (250 mg/kg diet, selenium (methylselenocysteine, 1 mg/kg diet, and vitamin E (gamma-tocopherol, 200 mg/kg diet alone and in combination on the growth of androgen-dependent Dunning R3327-H rat prostate adenocarcinomas in male, Copenhagen rats. AIN-93G diets containing these micronutrients were prefed for 4 to 6 weeks prior to tumor implantation by subcutaneous injection. Tumors were allowed to grow for approximately 18 weeks. Across diet groups, methylselenocysteine consumption decreased final tumor area (P = 0.003, tumor weight (P = 0.003, and the tumor weight/body weight ratio (P = 0.003, but lycopene and gamma-tocopherol consumption intake did not alter any of these measures. There were no significant interactions among nutrient combinations on tumor growth. Methylselenocysteine consumption also led to small, but significant decreases in body weight (P = 0.007, food intake (P = 0.012, and body weight gain/food intake ratio (P = 0.022. However, neither body weight nor gain/food intake ratio was correlated with tumor weight. Methylselenocysteine, lycopene, and gamma-tocopherol consumed alone and in combination did not alter serum testosterone or dihydrotestosterone concentrations; tumor proliferation or apoptosis rates. In addition, the diets also did not alter tumor or prostate androgen receptor, probasin, selenoprotein 15, selenoprotein P, or selenium binding protein 2 mRNA expression. However, using castration and finasteride-treated tissues from a previous study, we found that androgen ablation altered expression of these selenium-associated proteins. CONCLUSIONS: Of the three micronutrients tested, only

Thermoluminescence studies of γ-irradiated ZnO:Mg"2"+ nanoparticles

International Nuclear Information System (INIS)

Pushpa, N.; Kokila, M.K.; Nagabhushana, K.R.

2016-01-01

Pure and Mg"2"+ doped ZnO nanoparticles are synthesized by solution combustion method. X-ray diffraction studies of the samples confirm hexagonal phase. Crystallite size is calculated using Scherer formula and found to be ∼30 nm for undoped ZnO and 34–38 nm for Mg"2"+ doped ZnO. A broad PL emission in the range 400–600 nm with peaks at 400, 450, 468, 483, 492, 517, 553 nm are observed in both pure and Mg"2"+ doped nanoparticles. Near band edge emission of ZnO is observed at 400 nm. The broad band emissions are due to surface defects. PL emission intensity is found to increase with Mg"2"+ concentration up to 1.5 mol% and then decreases due to concentration quenching. Samples are irradiated with γ-rays in a dose range 0.05–8 kGy. Gamma irradiation doesn’t affect PL properties. Undoped samples exhibit unstructured low intense TL glow with peak at 720 K. Whereas Mg"2"+ doped samples exhibit well structured TL glow curves with peak at ∼618 K. TL glow peak intensity of Mg"2"+ doped samples increases with Mg"2"+ concentration up to 2 mol%, thereafter decreases. TL curves of Mg"2"+ (2 mol%) doped ZnO exhibit two glows, a high intense peak at 618 K and a weak one with peak at ∼485 K. TL intensity of Mg"2"+ (2 mol%) doped ZnO samples increases with gamma dose up to 1 kGy and then decreases. Kinetic parameters of TL glows are calculated by deconvolution technique. Activation energy and frequency factor are found to be 1.5 eV and 3.38 × 10"1"1 s"−"1 respectively.

Superconducting properties of Zn and Al double-doped Mg1-x(Zn0.5Al0.5)xB2

DEFF Research Database (Denmark)

Xu, G.J.; Grivel, Jean-Claude; Abrahamsen, A.B.

2004-01-01

(XRD), ac susceptibility, magnetization and resistivity. The double doping leads to decreases in both the lattice parameters a and c, and the T-c decreases with increasing dopant content. A systematical comparison with Al doped- and Li, Al double doped MgB2 of structure, superconducting transition......A series of polycrystalline samples of Mg1-x(Zn0.5Al0.5)(x)B-2 (0less than or equal toxless than or equal to0.8) were prepared by solid state reaction method and their structure, superconducting transition temperature (T-c) and transport properties were investigated by means of X-ray diffraction...

Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice.

Science.gov (United States)

Knaryan, Varduhi H; Samantaray, Supriti; Varghese, Merina; Srinivasan, Ambika; Galoyan, Armen A; Mohanakumar, Kochupurackal P

2006-08-01

Proline-rich-polypeptides (PRPs) isolated from bovine hypothalamus have been shown to render protection against neuronal injury of the brain and spinal cord. We examined two PRPs containing 15 and 10 amino acid residues (PRP-1 and PRP-4 synthetic polypeptide) for their effect, if any, on dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effects of these PRPs on hydroxyl radical ((*)OH) generation in a Fenton-like reaction as well as from isolated mitochondria were monitored, employing a sensitive salicylate hydroxylation procedure. Balb/c mice treated (i.p., twice, 16 h apart) with MPTP (30 mg/kg) or PRP-1 (1.6 mg/kg), but not PRP-4 (1.6 mg/kg) showed significant loss of striatal dopamine and norepinephrine as assayed by an HPLC-electrochemical procedure. Pretreatment with the PRPs, 30 min prior to the neurotoxin administration failed to attenuate MPTP-induced striatal dopamine or norepinephrine depletion, but significantly attenuated the MPTP-induced decrease in dopamine turnover. A significant increase in the generation of (*)OH by the PRPs in a Fenton-like reaction or from isolated mitochondria suggests their pro-oxidant action, and explains their failure to protect against MPTP-induced parkinsonism in mice.

Structurally characterized 1,1,3,3-tetramethylguanidine solvated magnesium aryloxide complexes: [Mg(mu-OEt)(DBP)(H-TMG)]2, [Mg(mu-OBc)(DBP)(H-TMG)]2, [Mg(mu-TMBA)(DBP)(H-TMG)]2, [Mg(mu-DPP)(DBP)(H-TMG)]2, [Mg(BMP)2(H-TMG)2], [Mg(O-2,6-Ph2C6H3)2 (H-TMG)2].

Science.gov (United States)

Monegan, Jessie D; Bunge, Scott D

2009-04-06

The synthesis and structural characterization of several 1,1,3,3-tetramethylguanidine (H-TMG) solvated magnesium aryloxide complexes are reported. Bu(2)Mg was successfully reacted with H-TMG, HOC(6)H(3)(CMe(3))(2)-2,6 (H-DBP), and either ethanol, a carboxylic acid, or diphenyl phosphate in a 1:1 ratio to yield the corresponding [Mg(mu-L)(DBP)(H-TMG)](2) where L = OCH(2)CH(3) (OEt, 1), O(2)CC(CH(3))(3) (OBc, 2), O(2)C(C(6)H(2)-2,4,6-(CH(3))(3)) (TMBA, 3), or O(2)P(OC(6)H(5))(2) (DPP, 4). Bu(2)Mg was also reacted with two equivalents of H-TMG and HOC(6)H(3)(CMe(3))-2-(CH(3))-6 (BMP) or HO-2,6-Ph(2)C(6)H(3) to yield [Mg(BMP)(2)(H-TMG)(2)] (5) and [Mg(O-2,6-Ph(2)C(6)H(3))(2)(H-TMG)(2)] (6). Compounds 1-6 were characterized by single-crystal X-ray diffraction. Polymerization of l- and rac-lactide with 1 was found to generate polylactide (PLA). A discussion concerning the relevance of compounds 2 - 4 to the structure of Mg-activated phosphatase enzymes is also provided. The bulk powders for all complexes were found to be in agreement with the crystal structures based on elemental analyses, FT-IR spectroscopy, and (1)H, (13)C and (31)P NMR studies.

MgO–CaO–Cr2O3 composition as a novel refractory brick: Use of Cr2O3 nanoparticles

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Salman Ghasemi-Kahrizsangi

2017-03-01

Full Text Available At this study the effect of Cr2O3 nanoparticles (up to 3 wt.% on the physical and mechanical properties of MgO–CaO refractory composition with emphasis on the hydration resistance improvement have been investigated. Specimens pressed at 90 MPa then were sintered at 1650 °C for 5 h in an electric furnace. Properties such as bulk density, apparent porosity, cold crushing strength and hydration resistance were examined. The crystalline phases and microstructure characteristics of sintered specimens were studied by X-ray diffraction (XRD and scanning electron microscopy (SEM/EDS, respectively. Results shown that add of the 1.5 wt.% Cr2O3 nanoparticles have the best results i.e. increased the bulk density (3.41 g/cm3, cold crushing strength (848 kg/cm2, hydration resistance (1.5% and decreased apparent porosity (5.58%, respectively. The mechanism of specimens hydration resistance improvement are: (i decreasing the amount of free CaO and MgO with converted to high hydration resistance phases such as CaCr2O4 and MgCr2O4 phases, (ii promotion of the densification as well as (iii modification of the microstructure.

Evaluation of cardiorespiratory and biochemical effects of ketamine-propofol and guaifenesin-ketamine-xylazine anesthesia in donkeys (Equus asinus).

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Molinaro Coelho, Cássia M; Duque Moreno, Juan C; Goulart, Daniel da S; Caetano, Leandro B; Soares, Lorena K; Coutinho, Gustavo H; Alves, Geraldo Es; da Silva, Luiz Antonio F

2014-11-01

To evaluate the cardiorespiratory and biochemical effects of ketamine-propofol (KP) or guaifenesin-ketamine-xylazine (GKX) anesthesia in donkeys. Prospective crossover trial. Eight healthy, standard donkeys, aged 10 ± 5 years and weighing 153 ± 23 kg. Donkeys were premedicated with 1.0 mg kg(-1) of xylazine (IV) in both treatments. Eight donkeys were administered ketamine (1.5 mg kg(-1)) and propofol (0.5 mg kg(-1) for induction, and anesthesia was maintained by constant rate infusion (CRI) of ketamine (0.05 mg kg(-1) minute(-1)) and propofol (0.15 mg kg(-1) minute(-1)) in the KP treatment. After 10 days, diazepam (0.05 mg kg(-1)) and ketamine (2.2 mg kg(-1)) were administered for induction, and anesthesia was maintained by a CRI (2.0 mL kg(-1) hour(-1)) of ketamine (2.0 mg mL(-1), xylazine (0.5 mg mL(-1)) and guaifenesin (50 mg mL(-1)) solution. Quality of anesthesia was assessed along with cardiorespiratory and biochemical measurements. Anesthetic induction took longer in GKX than in KP. The induction was considered good in 7/8 with KP and in 6/8 in GKX. Anesthetic recovery was classified as good in 7/8 animals in both treatments. Xylazine administration decreased heart rate (HR) in both treatments, but in KP the HR increased and was higher than GKX throughout the anesthetic period. Respiratory rate was higher in GKX than in KP. PaO(2) decreased significantly in both groups during the anesthetic period. Glucose concentrations [GLU] increased and rectal temperature and PCV decreased in both treatments. Arterial lactate [LAC] increased at recovery compared with all time points in KP. [GLU] and calcium were higher in GKX than in KP at recovery. These protocols induced significant hypoxemia but no other cardiorespiratory or metabolic changes. These protocols could be used to maintain anesthesia in donkeys, however, they were not tested in animals undergoing surgery. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia

Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

Science.gov (United States)

2012-07-01

rats given 3.52 mM acrylamide in drinking water. Mild to moderate degeneration of the germinal epithelium in the seminiferous tubules of the testes was noted microscopically in all male rats given 7.03 mM acrylamide in drinking water and in two of four male rats fed 370 mg acrylamide per kg diet. 2-WEEK STUDY IN MICE: Groups of four male and four female B6C3F1 mice were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. None of the mice administered 7.03 mM acrylamide in the drinking water survived the 14-day study. Mice administered 7.03 mM acrylamide in the drinking water showed marked decreases in body weight (greater than 25% compared to control mice) after seven days of treatment, and two of the mice displayed hind leg paralysis. No significant adverse effects were observed in mice administered 3.52 mM acrylamide in the drinking water for 14 days. Female B6C3F1 mice given 370 mg acrylamide per kg diet for 14 days showed a modest decrease (11%) in body weight. No other significant adverse effects were observed in mice administered any dose of acrylamide in the diet. 3-MONTH STUDY IN RATS: Groups of eight male and eight female F344/N rats were administered 0.0, 0.14, 0.35, 0.70, 1.41, or 3.52 mM acrylamide in the drinking water (0, 10, 25, 50, 100, or 250 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, or 185 mg acrylamide per kg diet for 13 weeks. After 13 weeks, male and female rats administered 3.52 mM acrylamide weighed 73% and 71% of the control rats, respectively. Male and female rats fed 185 mg acrylamide per kg diet for 13 weeks weighed 86% and 82% of the control rats, respectively. Hind-leg paralysis was observed in all rats administered 3.52 mM acrylamide in the drinking water or 185 mg acrylamide per kg diet. Four of eight female rats administered 1.41 mM acrylamide also displayed hind

Epidural morphine and detomidine decreases postoperative hindlimb lameness in horses after bilateral stifle arthroscopy.

Science.gov (United States)

Goodrich, Laurie R; Nixon, Alan J; Fubini, Susan L; Ducharme, Norm G; Fortier, Lisa A; Warnick, Lorin D; Ludders, John W

2002-01-01

To determine whether preoperative epidural administration of morphine and detomidine would decrease postoperative lameness after bilateral stifle arthroscopy in horses. Prospective clinical controlled study. Eight adult horses that had bilateral arthroscopic procedures, including drilling of cartilage and subchondral bone within the femoropatellar joints. Horses were randomly separated into 2 groups. Preoperatively, 4 horses were administered a combination of epidural morphine (0.2 mg/kg) and detomidine (30 microg/kg), and 4 horses were administered an equivalent volume of epidural saline (0.9% NaCl) solution. Postoperative pain was assessed using 6 video recordings made at hourly intervals of each horse at a walk. Assessments began 1 hour after recovery from anesthesia. The recordings were scrambled out of sequence and evaluated by 3 observers, unaware of treatment groups, who scored lameness from 0 to 4. Lameness scores of the 2 groups of horses were compared using a Wilcoxon's rank sum test. Heart and respiratory rates were also measured at each hourly interval and compared between groups using a repeated-measures ANOVA; statistical significance was set at P detomidine significantly decreased lameness and heart rates after bilateral stifle arthroscopy. The greatest decrease was detected at hours 1 and 2 after recovery from anesthesia. We conclude that horses undergoing a painful arthroscopic procedure of the stifle joint benefit from the administration of preoperative epidural morphine and detomidine. Preoperative epidural administration of detomidine and morphine may be useful in decreasing postoperative pain after stifle arthroscopy as well as pain associated with other painful disorders involving the stifle joint, such as septic arthritis and trauma. Copyright 2002 by The American College of Veterinary Surgeons

Green emission from ZnO–MgO nanocomposite due to Mg diffusion at the interface

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Sowri Babu, K.; Ramachandra Reddy, A.; Venugopal Reddy, K.

2015-01-01

The origin and electronic transitions responsible for green emission observed from ZnO–MgO nanocomposite are investigated. The photoluminescence (PL) spectrum of ZnO–MgO nanocomposite annealed at 600 °C showed only a sharp and intense UV emission peak centered at 396 nm. As the annealing temperature increased from 600 °C to 1000 °C, the green emission positioned at 503 nm is emerged and its intensity enhanced gradually and reached maximum value at 900 °C and then decreased at 1000 °C. It is observed that both UV and green emission intensities are enhanced with variation of atomic ratio (Zn/Mg=1.52, 0.50, 0.30, 0.21, 0.15). Our experiments confirmed that the enhancement of green emission intensity is due to the formation of oxygen vacancies (V o ) due to Mg doping at the interface of ZnO and MgO. This experimental observation is in good agreement with the recent theoretical predictions which states that Mg doping in ZnO lowers the formation energies of oxygen vacancies (V o ) and zinc interstitials (Zn i ) significantly. PL excitation and emission spectra analysis reveals that excited state for both UV and green emissions is same and lies 0.24 eV below the conduction band of ZnO. Hence, the green emission is attributed to the transition of an electron form the shallow donor (defect level of Zn i ) to the deep acceptor (defect level of V o ). - Highlights: • It is found that the UV emission intensity from ZnO–MgO nanocomposite enhanced with increase of Mg concentration. • The intensity of the green emission is enhanced gradually as the temperature increased from 600 °C to 900 °C and then decreased at 1000 °C. • The effect of Mg concentration, MgO, strain at the interface on green emission is investigated. • These experiments confirmed that green emission is due to the oxygen vacancies created in ZnO due to the Mg doping at the interface and it is in good agreement with the theoretical predictions. • The decrease of green emission intensity is

Chronic treatment with LY341495 decreases 5-HT2A receptor binding and hallucinogenic effects of LSD in mice

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Moreno, José L.; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C.; González-Maeso, Javier

2013-01-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24 mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5 mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [3H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT2A agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT2A receptor-dependent hallucinogenic effects of LSD. PMID:23333599

Chronic treatment with LY341495 decreases 5-HT(2A) receptor binding and hallucinogenic effects of LSD in mice.

Science.gov (United States)

Moreno, José L; Holloway, Terrell; Rayannavar, Vinayak; Sealfon, Stuart C; González-Maeso, Javier

2013-03-01

Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, alter perception and cognitive processes. All hallucinogenic drugs have in common a high affinity for the serotonin 5-HT(2A) receptor. Metabotropic glutamate 2/3 (mGlu2/3) receptor ligands show efficacy in modulating the cellular and behavioral responses induced by hallucinogenic drugs. Here, we explored the effect of chronic treatment with the mGlu2/3 receptor antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropan-1-yl)-3-(xanth-9-yl)-propionic acid (LY341495) on the hallucinogenic-like effects induced by LSD (0.24mg/kg). Mice were chronically (21 days) treated with LY341495 (1.5mg/kg), or vehicle, and experiments were carried out one day after the last injection. Chronic treatment with LY341495 down-regulated [(3)H]ketanserin binding in somatosensory cortex of wild-type, but not mGlu2 knockout (KO), mice. Head-twitch behavior, and expression of c-fos, egr-1 and egr-2, which are responses induced by hallucinogenic 5-HT(2A) agonists, were found to be significantly decreased by chronic treatment with LY341495. These findings suggest that repeated blockade of the mGlu2 receptor by LY341495 results in reduced 5-HT(2A) receptor-dependent hallucinogenic effects of LSD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Selected Heavy Metals Content in Soil and Arundina graminifolia from Pelepah Kanan Mine, Kota Tinggi, Johor, Malaysia

International Nuclear Information System (INIS)

Sahibin Abdul Rahim; Zulfahmi Ali Rahman; Wan Mohd Razi Idris; Azman Hashim; Tukimat Lihan; Muhd Barzani Gasim; Jumaat Adam; Lim, F.N.

2009-01-01

Heavy metals composition of Cd, Co, Cr, Ni, Pb and Zn in Arundina graminifolia collected from mining area at Lombong Pelepah Kanan, Kota Tinggi, Johor were determined. The heavy metal content was also analysed in their soil substrates. The plants were separated into different portions for example root, stem and leaf and extracted for their heavy metal content by digestion method whereas the soils heavy metal content was extracted by sequential extraction. Heavy metal content in soil and plant extract was determined using the Flame Atomic Absorption Spectrophotometer. Heavy metal contents of Cd, Cr, Ni and Pb in plants were compared with their content in the control plant, whereas the Co and Zn contents were three to five folds higher. As for heavy metal content in different plant parts, it was found that Cd concentration was high in roots (2.03 mg/ kg) followed by leaf (1.67 mg/ kg) and stem (1.49 mg/ kg). Co concentration was high in leaf (9.26 mg/ kg) followed by root (9.18 mg/ kg) and stem (6.94 mg/ kg). For Cr, the concentration in decreasing sequence was root (0.46 mg/ kg) > leaf (0.19 mg/ kg) > stem (0.08 mg/ kg). Ni concentration was higher in leaf (2.78 mg/ kg) followed by root (2.71 mg/ kg) and stem (1.66 mg/ kg). Concentration in decreasing order was root (10.34 mg/ kg) > leaf (4.18 mg/ kg) > stem (3.75 mg/ kg). Zn concentration was higher in leaf (44.03 mg/ kg) followed by root (32.30 mg/ kg) and stem (13.21 mg/ kg). Total heavy metal content in soil was 2.07 - 5.59 mg/ kg, 8.72 - 39.93 mg/ kg, 1.81 - 2.14 mg/ kg, 2.66 - 6.87 mg/ kg, 23.02 - 51.56 mg/ kg and 0.64 - 2.61 mg/ kg for Ni, Zn, Cd, Pb, Co and Cr, respectively. The available fraction of heavy metals in soil was 21.9 % for Ni, 15.3 % for Zn, 49.9 % for Cd, 19.3 % for Pb, 45.7 % for Co and nil percent for Cr. Biological adsorption coefficient for the heavy metals studied was very low except for Zn where BAC value slightly higher than 1. This plant was not suitable to be used as a phyto

Facile fabrication of hydrophobic surfaces on mechanically alloyed-Mg/HA/TiO{sub 2}/MgO bionanocomposites

Energy Technology Data Exchange (ETDEWEB)

Khalajabadi, Shahrouz Zamani [Medical Devices and Technology Group (MEDITEG), Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Abdul Kadir, Mohammed Rafiq, E-mail: rafiq@biomedical.utm.my [Medical Devices and Technology Group (MEDITEG), Faculty of Biosciences and Medical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia); Izman, Sudin; Mohd Yusop, Mohd Zamri [Department of Materials, Manufacturing and Industrial Engineering, Faculty of Mechanical Engineering, Universiti Teknologi Malaysia, 81310 Johor Bahru, Johor (Malaysia)

2015-01-01

Highlights: • Mg/HA/TiO{sub 2}-based nanocomposite was produced using mechanical alloying. • The hydrophobic surface coverage was fabricated on the mechanical alloyed samples by annealing. • The morphological characteristics, phase evolution and wettability of nanocomposites and the hydrophobic surface coverage were investigated. • The activation energies and reaction kinetic of the powder mixture of nanocomposites were calculated. - Abstract: The effect of mechanical alloying and post-annealing on the phase evolution, microstructure, wettability and thermal stability of Mg–HA–TiO{sub 2}–MgO composites was investigated in this study. Phase evolution and microstructure analysis were performed using X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy and atomic force microscopy, as well as the wettability determined by contact angle measurements with SBF. The 16-h mechanical alloying resulted in the formation of MgTiO{sub 3}, CaTiO{sub 3}, Mg{sub 3}(PO{sub 4}){sub 2} and Mg(OH){sub 2} phases and a decrease in wettability of the nanocomposites. A hydrophobic film with hierarchical structures comprising nanoflakes of MgTiO{sub 3}, nano-cuboids of CaTiO{sub 3}, microspheres of Mg{sub 3}(PO{sub 4}){sub 2} and Mg(OH){sub 2} was successfully constructed on the surface of the Mg-based nanocomposites substrates as a result of the post-annealing process. After 1-h annealing at 630 °C, the synthesized hydrophobic surface on the nanocomposite substrates decreased the wettability, as the 8-h-mechanically alloyed samples exhibited a contact angle close to 93°. The formation activation energies and reaction kinetics of the powder mixture were investigated using differential thermal analysis and thermal gravimetric analysis. The released heat, weight loss percentage and reaction kinetics increased, while the formation activation energies of the exothermic reactions decreased following an increase in the milling time.

Structural and optical properties of magnetron sputtered Mg{sub x}Zn{sub 1-x}O thin films

Energy Technology Data Exchange (ETDEWEB)

Kumar, Sanjeev; Gupte, Vinay; Sreenivas, K [Department of Physics and Astrophysics, University of Delhi, Delhi-110007 (India)

2006-04-05

Mg{sub x}Zn{sub 1-x}O (MZO) thin films prepared by an rf magnetron sputtering technique are reported. The films were grown at room temperature and at relatively low rf power of 50 W. MZO thin films were found to possess preferred c-axis orientation and exhibited hexagonal wurtzite structure of ZnO up to a Mg concentration of 42 mol%. A small variation in the c-axis lattice parameter of around 0.3% was observed with increasing Mg composition, showing the complete solubility of Mg in ZnO. The band gap of the MZO films in the wurtzite phase varied linearly with the Mg concentration and a maximum band gap {approx}4.19 eV was achieved at x = 0.42. The refractive indices of the MgO films were found to decrease with increasing Mg content. The observed optical dispersion data are in agreement with the single oscillator model. A photoluminescence study revealed a blue shift in the near band edge emission peak with increasing Mg content in the MZO films. The results show the potential of MZO films in various opto-electronic applications.

Characterization of the discriminative stimulus produced by the dopamine antagonist tiapride.

Science.gov (United States)

Cohen, C; Sanger, D J; Perrault, G

1997-11-01

The ability of tiapride, a selective D2/D3 dopamine receptor antagonist, to exert discriminative stimulus control of responding was investigated by training rats to discriminate this drug (30 mg/kg) from saline in a two-lever, food-reinforcement procedure. Acquisition of tiapride discrimination required a relatively lengthy training period (mean of 76 sessions) but stable performance was maintained throughout the 18- month study. The dose of tiapride eliciting 50% tiapride-lever choice (ED50) was 2.2 mg/kg. After determination of the dose-effect curve with tiapride, substitution tests with several dopamine antagonists and other reference compounds were performed. All dopamine antagonists, including amisulpride (ED50 4 mg/kg), sulpiride (18 mg/kg), sultopride (1.5 mg/kg), clebopride (0.13 mg/kg), raclopride (0.16 mg/kg), metoclopramide (1.4 mg/kg), remoxipride (4.8 mg/kg), pimozide (2.7 mg/kg), thioridazine (3.4 mg/kg), olanzapine (0.97 mg/kg), chlorpromazine (1.9 mg/kg), risperidone (0.22 mg/kg) and haloperidol (0.14 mg/kg), except clozapine (>10 mg/kg), produced dose-dependent substitution for tiapride. Tiapride-like stimulus effects were observed at doses that decreased response rates. However, ED50 values for substitution by tiapride, amisulpride, sulpiride, sultopride, pimozide, clebopride and thioridazine were lower than ED50 values for decreasing responding. Additional studies were conducted to evaluate the ability of direct and indirect dopamine agonists to attenuate the tiapride discriminative stimulus. Pretreatment with d-amphetamine and nomifensine antagonized the discriminative stimulus effects of tiapride. Quinpirole, 7-OH-DPAT, bromocriptine and apomorphine partially blocked the stimulus effects of tiapride whereas SKF 38393 did not affect the discrimination. These results from substitution and antagonism tests indicated that the discriminative effects of tiapride are mediated by activity at D2/D3 dopamine receptors.

Diagnose nutricional de cafeeiros da região do Alto Jequitinhonha (MG: normas dris e faixas críticas de nutrientes Nutritional diagnosis of coffee plantations in the Upper Jequitinhonha Valley, Minas Gerais State, Brazil: dris norms and critical nutrient ranges

Directory of Open Access Journals (Sweden)

Múcio Mágno de Melo Farnezi

2009-08-01

Full Text Available As normas do Sistema Integrado de Diagnose e Recomendação (DRIS ainda não foram estabelecidas para a cultura do café do Alto Jequitinhonha, MG, o que impede que o DRIS seja aplicado nos cafeeiros da região. A diagnose foliar, mediante o uso do DRIS e de faixas críticas de referência, destaca-se entre as ferramentas potenciais que permitem usar eficientemente os fertilizantes. Desse modo, este trabalho objetiva estabelecer as normas DRIS, bem como estimar os valores das faixas críticas dos nutrientes de referência para a diagnose nutricional de cafeeiros da região do Alto Jequitinhonha, por meio do DRIS. Determinaram-se os teores foliares de N, P, K, Ca, Mg, S, B, Cu, Fe, Mn e Zn em 52 lavouras cafeeiras, em duas safras (2005 e 2006. Foram selecionadas, para estabelecer as normas DRIS, 23 lavouras em cada safra com produtividade maior e igual a 30 sacas de grãos de café por hectare. As faixas críticas obtidas do DRIS, determinando-se a frequência com que o teor de cada nutriente das lavouras nas duas safras foi deficiente, adequado ou excessivo em relação aos padrões mencionados e teores considerados adequados pela literatura. As normas DRIS foram estabelecidas para cafeeiros da região do Alto Jequitinhonha e utilizadas para propor faixas críticas adequadas. Para isso, foram estabelecidos os valores para N (2,25-2,79 dag kg-1, P (0,18-0,22 dag kg-1, K (1,72-2,10 dag kg-1, Ca (1,26-1,51 dag kg-1, Mg (0,29-0,35 dag kg-1, S (0,13-0,32 dag kg-1, B (83,8-96,3 mg kg-1, Cu (5,7-9,3 mg kg-1, Fe (67,5-116,2 mg kg-1, Mn (219-422 mg kg-1 e Zn (17,4-30,0 mg kg-1, e faixas críticas adequadas para diagnose nutricional de cafeeiros da região do Alto Jequitinhonha, no Estado de Minas Gerais. Os cafezais da região em desequilíbrio apresentaram deficiência em P, K, S, B, Cu, Mn e Zn e excesso de Ca, Mg e Fe.In the Diagnosis and Recommendation Integrated System (DRIS, norms for coffee in the Upper Jequitinhonha Valley, Minas Gerais, Brazil

Interplay Between Structure and Conductivity in 1-Ethyl-3-methylimidazolium tetrafluoroborate/(δ-MgCl2)f Electrolytes for Magnesium Batteries

International Nuclear Information System (INIS)

Bertasi, Federico; Vezzù, Keti; Nawn, Graeme; Pagot, Gioele; Di Noto, Vito

2016-01-01

The synthesis, physicochemical properties and conductivity mechanism of a family of ionic liquid-based electrolytes for use in secondary Mg batteries are reported. The electrolytes are obtained by dissolving controlled amounts of δ-MgCl 2 salt into the ionic liquid (IL) 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF 4 ) which acts as a solvent. δ-MgCl 2 consists of an inorganic ribbon of Mg atoms covalently bonded together through bridging chlorine atoms. Due to this peculiar structural motif, with respect to the electrolytes based on conventional Mg salts, it is possible to achieve electrolytes of higher Mg concentration. Thus, concatenated anionic complexes bridged via halogen atoms are formed, improving the electrochemical performance of these materials. Electrolytes with a general formula EMImBF 4 /(δ-MgCl 2 ) f with f ranging from 0 to 0.117 are obtained. The composition of the obtained materials is determined by Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES). The properties of these systems are investigated by means of Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and vibrational spectroscopy in both medium (MIR) and far infrared (FIR). Finally, Broadband Electrical Spectroscopy (BES) is carried out with the aim to elucidate the electrical response of the electrolytes in terms of their polarization and relaxation phenomena and to propose a conductivity mechanism. At 20 °C the highest conductivity (0.007 S/cm) is observed for the electrolyte with c Mg = 0.00454 mol Mg /kg IL .

Perinatal exposure to BDE-99 causes decreased protein levels of cyclin D1 via GSK3β activation and increased ROS production in rat pup livers.

Science.gov (United States)

Blanco, Jordi; Mulero, Miquel; Domingo, Jose L; Sanchez, Domènec J

2014-02-01

We here examined the potential liver toxicity in rat pups from dams exposed during the gestational and lactation periods to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Dams were exposed to 0, 1, and 2mg/kg/day of BDE-99 from gestation day 6 to postnatal day 21. When the pups were weaning, the liver from 1 pup of each litter was excised to evaluate oxidative stress markers and the messenger RNA (mRNA) expression of multiple cytochrome P450 (CYP) isoforms. To determine whether thyroid hormone (TH) was disrupted, the protein and mRNA expressions of several TH receptor (TR) isoforms, as well as the protein levels of cyclin D1 and the phosphorylated protein kinases Akt and glycogen synthase kinase 3 beta (GSK3β), were evaluated. Perinatal exposure to BDE-99 produced decreased levels of cyclin D1 in rat pup livers. A decrease in the active form of Akt and an increase in the active form of GSK3β were observed. The decreased Akt pathway may be due to a potential disruption of the nongenomic actions of TH by BDE-99 and its metabolites. This possible TH disruption was noted as a decrease in TR isoforms expression. By contrast, we observed an upregulation of CYP2B1 gene expression, which is correlated with an increase in reactive oxygen species production. This outcome indicates activation of the nuclear constitutive androstane receptor, which could induce the expression of other enzymes capable of metabolizing TH. The present findings support the hypothesis that perinatal exposure to PBDEs, at levels found in humans, may have serious implications for metabolic processes in rat pup livers.

Formation of Aqueous MgUO2(CO3)32- Complex and Uranium Anion Exchange Mechanism onto an Exchange Resin

International Nuclear Information System (INIS)

Dong, Wenming; Brooks, Scott C

2008-01-01

The formation of and stability constants for aqueous Mg-UO2-CO3 complexes were determined using an anion exchange method. Magnesium concentration was varied (up to 20 mmol/L) at constant ionic strength (I = 0.101, 0.202, 0.304, 0.406, and 0.509 mol/kg NaNO3), pH = 8.1, total [U(VI)] = 10.4 mol/L under equilibrium with atmospheric CO2. The results indicate that only the MgUO2(CO3)32- complex is formed. The cumulative formation constant extrapolated to zero ionic strength is similar regardless of the activity correction convention used: log = 25.8 b 0.5 using Davies equation and = 25.02 b 0.08 using specific ion interaction theory (SIT). Uranium sorption onto the exchange resin decreased in the presence of Mg putatively due to the formation of MgUO2(CO3)32- that had a lower affinity for the resin than UO2(CO3)34-. Uranium sorption results are consistent with an equivalent anion exchange reaction between NO3- and UO2(CO3)34- species to retain charge neutrality regardless of Mg concentration. No Mg was associated with the anion exchange resin indicating that the MgUO2(CO3)32- complex did not sorb

Hydrogen storage of Mg1−xMxH2 (M = Ti, V, Fe) studied using first-principles calculations

International Nuclear Information System (INIS)

Bhihi, M.; Lakhal, M.; Benyoussef, A.; El Kenz, A.; Labrim, H.; Mounkachi, O.; Hlil, E.K.

2012-01-01

In this work, the hydrogen storage properties of the Mg-based hydrides, i.e., Mg 1−x M x H 2 (M = Ti, V, Fe, 0 ≤ x ≤ 0.1), are studied using the Korringa—Kohn—Rostoker (KKR) calculation with the coherent potential approximation (CPA). In particular, the nature and concentrations of the alloying elements and their effects are studied. Moreover, the material's stability and hydrogen storage thermodynamic properties are discussed. In particular, we find that the stability and the temperature of desorption decrease without significantly affecting the storage capacities

Decreased prefrontal cortical dopamine transmission in alcoholism.

Science.gov (United States)

Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

2014-08-01

Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

Exposure to di(n-butyl)phthalate and benzo(a)pyrene alters IL-1β secretion and subset expression of testicular macrophages, resulting in decreased testosterone production in rats

International Nuclear Information System (INIS)

Zheng Shanjun; Tian Huaijun; Cao Jia; Gao Yuqi

2010-01-01

Di(n-butyl)phthalate (DBP) and benzo(a)pyrene (BaP) are environmental endocrine disruptors that are potentially hazardous to humans. These chemicals affect testicular macrophage immuno-endocrine function and testosterone production. However, the underlying mechanisms for these effects are not fully understood. It is well known that interleukin-1 beta (IL-1β), which is secreted by testicular macrophages, plays a trigger role in regulating Leydig cell steroidogenesis. The purpose of this study was to reveal the effects of co-exposure to DBP and BaP on testicular macrophage subset expression, IL-1β secretion and testosterone production. Adult male Sprague-Dawley rats were randomly divided into seven groups; two groups received DBP plus BaP (DBP + BaP: 50 + 1 or 250 + 5 mg/kg/day) four groups received DBP or BaP alone (DBP: 50 or 250 mg/kg/day; BaP: 1 or 5 mg/kg/day), and one group received vehicle alone (control). After co-exposure for 90 days, the relative expression of macrophage subsets and their functions changed. ED2 + testicular macrophages (reactive with a differentiation-related antigen present on the resident macrophages) were activated and IL-1β secretion was enhanced. DBP and BaP acted additively, as demonstrated by greater IL-1β secretion relative to each compound alone. These observations suggest that exposure to DBP plus BaP exerted greater suppression on testosterone production compared with each compound alone. The altered balance in the subsets of testicular macrophages and the enhanced ability of resident testicular macrophages to secrete IL-1β, resulted in enhanced production of IL-1β as a potent steroidogenesis repressor. This may represent an important mechanism by which DBP and BaP repress steroidogenesis.

Effects of oral administration of aflatoxin B1 and fumonisin B1 in rabbits (Oryctolagus cuniculus).

Science.gov (United States)

Orsi, R B; Oliveira, C A F; Dilkin, P; Xavier, J G; Direito, G M; Corrêa, B

2007-12-15

The effects of prolonged oral administration (21 days) of fumonisin B(1) (FB(1)) and aflatoxin B(1) (AFB(1)) were studied in male New Zealand rabbits by clinical, pathological, biochemical and sphingolipid analyses. Twenty-four animals were randomly divided into the following four experimental groups: (A) 0 mg FB(1)+0 microg AFB(1)/(kg body weight(bw)day) (control); (B) 0 mg FB(1)+30 microg AFB(1)/(kg bw day); (C) 1.5 mg FB(1)/(kg bw day)+30 microg AFB(1)/(kg bw day); (D) 1.5 mg FB(1)/(kg bw day)+0 microg AFB(1). Animals from group B and principally from group C presented clinical signs of intoxication. Rabbits from group C presented a lower body weight gain than controls. Differences were observed between intoxicated rabbits and controls with respect to absolute and relative liver and kidney weight, hepatic function, serum urea and creatinine levels and Sa/So ratio. The most frequent hepatic and renal injuries were vacuolar degeneration of the liver and kidney as shown by the histopathological and serum biochemical results. Combined administration of AFB(1) and FB(1) resulted in synergistic toxic effects both in the liver and in the kidney, but hepatic injuries were more marked.

Mechanochemical Synthesis of Nanostructured MgXNi1-XO Compound by Mg-NiO Mixture

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Nader Setoudeh

2017-06-01

Full Text Available Synthesis of magnesium nickel oxide phase such as MgxNi1-xO solid solutions has been studied in this research article using mechnochmical reaction between magnesium and nickel oxide. Mixtures of magnesium powder and nickel oxide (Mg+NiO with stoichiometric compositions were milled for different times in a planetary ball mill. Reduction reaction of nickel oxide by magnesium via a mechanically induced self-sustaining reaction (MSR was confirmed in the XRD measurements of the as-milled samples. Formation of nanostructured magnesium nickel oxide phases (such as Mg0.4Ni0.6O or MgNiO2 was observed after isothermal heating of the 30 minutes milled samples at 1000°C where nickel phase seems to disappear in XRD patterns. The traces of phases such as Mg0.4Ni0.6O or MgNiO2 were also observed in the as-milled mixtures. Therefore, the XRD results of the as-milled samples suggested that the formation of magnesium nickel oxide phases could be possible even after prolonged milling. The XRD and SEM results of both as-milled and isothermally heated samples indicated that the crystallite size and particle size of the final products reached to nanoscale after milling. Morphological and compositional evolution of the samples after heat treatment was monitored through SEM imaging and elemental analyses. The results confirmed that the composition of final product is close to Mg0.4Ni0.6O compound.

Regulators of G-protein signaling 4: modulation of 5-HT1A-mediated neurotransmitter release in vivo.

Science.gov (United States)

Beyer, Chad E; Ghavami, Afshin; Lin, Qian; Sung, Amy; Rhodes, Kenneth J; Dawson, Lee A; Schechter, Lee E; Young, Kathleen H

2004-10-01

Regulators of G-protein signaling (RGS) play a key role in the signal transduction of G-protein-coupled receptors (GPCRs). Specifically, RGS proteins function as GTPase accelerating proteins (GAPs) to dampen or "negatively regulate" GPCR-mediated signaling. Our group recently showed that RGS4 effectively GAPs Galpha(i)-mediated signaling in CHO cells expressing the serotonin-1A (5-HT(1A)) receptor. However, whether a similar relationship exists in vivo has yet to be identified. In present studies, a replication-deficient herpes simplex virus (HSV) was used to elevate RGS4 mRNA in the rat dorsal raphe nuclei (DRN) while extracellular levels of 5-HT in the striatum were monitored by in vivo microdialysis. Initial experiments conducted with noninfected rats showed that acute administration of 8-OH-DPAT (0.01-0.3 mg/kg, subcutaneous [s.c.]) dose dependently decreased striatal levels of 5-HT, an effect postulated to result from activation of somatodendritic 5-HT(1A) autoreceptors in the DRN. In control rats receiving a single intra-DRN infusion of HSV-LacZ, 8-OH-DPAT (0.03 mg/kg, s.c.) decreased 5-HT levels to an extent similar to that observed in noninfected animals. Conversely, rats infected with HSV-RGS4 in the DRN showed a blunted neurochemical response to 8-OH-DPAT (0.03 mg/kg, s.c.); however, increasing the dose to 0.3 mg/kg reversed this effect. Together, these findings represent the first in vivo evidence demonstrating that RGS4 functions to GAP Galpha(i)-coupled receptors and suggest that drug discovery efforts targeting RGS proteins may represent a novel mechanism to manipulate 5-HT(1A)-mediated neurotransmitter release.

Selegiline Ameliorates Depression-Like Behavior in Mice Lacking the CD157/BST1 Gene, a Risk Factor for Parkinson’s Disease

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Satoka Kasai

2017-05-01

Full Text Available Parkinson’s disease (PD, a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions. A single administration of selegiline (1–10 mg/kg dose-dependently reduced immobility time in the forced swimming test (FST in CD157 KO mice, but not C57BL/6N wild-type (WT mice. At 10 mg/kg, but not 3 mg/kg, selegiline significantly increased climbing time in CD157 KO mice. A single administration of the antiparkinsonian drugs pramipexole (a dopamine (DA D2/D3 receptor agonist or rasagiline (another MAO-B inhibitor, and repeated injections of a noradrenergic and specific serotonergic antidepressant (NaSSA, mirtazapine, also decreased immobility time, but did not increase climbing time, in CD157 KO mice. The antidepressant-like effects of 10 mg/kg selegiline were comparable to those of 10 mg/kg rasagiline, and tended to be stronger than those of 1 mg/kg rasagiline. After the FST, CD157 KO mice showed decreases in striatal and hippocampal serotonin (5-HT content, cortical norepinephrine (NE content, and plasma corticosterone concentration. A single administration of selegiline at 10 mg/kg returned striatal 5-HT, cortical NE, and plasma corticosterone levels to those observed in WT mice. In the open field test (OFT, repeated administration of mirtazapine had anxiolytic effects

A 28-day oral gavage toxicity study of 3-monochloropropane-1,2-diol (3-MCPD) in CB6F1-non-Tg rasH2 mice.

Science.gov (United States)

Lee, Byoung-Seok; Park, Sang-Jin; Kim, Yong-Bum; Han, Ji-Seok; Jeong, Eun-Ju; Moon, Kyoung-Sik; Son, Hwa-Young

2015-12-01

3-Monochloro-1,2-propanediol (3-MCPD) is a well-known contaminant of foods containing hydrolyzed vegetable protein. However, limited toxicity data are available for the risk assessment of 3-MCPD and its carcinogenic potential is controversial. To evaluate the potential toxicity and determine the dose levels for a 26-week carcinogenicity test using Tg rasH2 mice, 3-MCPD was administered once daily by oral gavage at doses of 0, 25, 50, and 100 mg/kg body weight (b.w.)/day for 28 days to male and female CB6F1-non-Tg rasH2 mice (N = 5 males and females per dose). The standard toxicological evaluations were conducted during the in-life and post-mortem phase. In the 100 mg/kg b.w./day group, 3 males and 1 female died during the study and showed clinical signs such as thin appearance and subdued behavior accompanied by significant decreases in mean b.w. Microscopy revealed tubular basophilia in the kidneys, exfoliated degenerative germ cells in the lumen of the seminiferous tubule of the testes, vacuolation in the brain, axonal degeneration of the sciatic nerve, and cardiomyopathy in the 100, ≥25, ≥50, 100, and 100 mg/kg b.w./day groups, respectively. In conclusion, 3-MCPD's target organs were the kidneys, testes, brain, sciatic nerve, and heart. The "no-observed-adverse-effect level" (NOAEL) of 3-MCPD was ≤25 and 25 mg/kg b.w./day in males and females, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Contraction Twinning Dominated Tensile Deformation and Subsequent Fracture in Extruded Mg-1Mn (Wt Pct) at Ambient Temperature

Science.gov (United States)

Chakkedath, A.; Maiti, T.; Bohlen, J.; Yi, S.; Letzig, D.; Eisenlohr, P.; Boehlert, C. J.

2018-03-01

Due to their excellent strength-to-weight ratio, Mg alloys are attractive for applications where weight savings are critical. However, the limited cold formability of wrought Mg alloys severely restricts their widespread usage. In order to study the role that deformation twinning might play in limiting the elongation-to-failure ({ɛ} f ), in-situ tensile tests along the extrusion axis of Mg-1Mn (wt pct) were performed at 323 K, 423 K, and 523 K. The alloy exhibited a strong basal texture such that most of the grains experienced compression along their -axis during deformation. At 323 K, fracture occurred at about 10 pct strain. Although basal, prismatic, and pyramidal slip activity was observed along with extension twinning, contraction twinning significantly influenced the deformation, and such twins evolved into {10{\\bar{1}} 1}-{10{\\bar{1}} 2} double twins. Crystal plasticity simulation showed localized shear deformation within the contraction twins and double twins due to the enhanced activity of basal slip in the reoriented twin volume. Due to this, the twin-matrix interface was identified to be a potential crack initiation site. Thus, contraction twins were considered to have led to the failure of the material at a relatively low strain, suggesting that this deformation mode is detrimental to the cold formability of Mg and its alloys. With increasing temperature, there was a significant decrease in the activity of contraction twinning as well as extension twinning, along with a decrease in the tensile strength and an increase in the {ɛ} f value. A combination of basal, prismatic, and pyramidal slips accounted for a large percentage of the observed deformation activity at 423 K and 523 K. The lack of contraction twinning was explained by the expected decrease in the critical resolved shear stress values for pyramidal slip, and the improved {ɛ} f values at elevated temperatures were attributed to the vanishing activity of contraction twinning.

Contraction Twinning Dominated Tensile Deformation and Subsequent Fracture in Extruded Mg-1Mn (Wt Pct) at Ambient Temperature

Science.gov (United States)

Chakkedath, A.; Maiti, T.; Bohlen, J.; Yi, S.; Letzig, D.; Eisenlohr, P.; Boehlert, C. J.

2018-06-01

Due to their excellent strength-to-weight ratio, Mg alloys are attractive for applications where weight savings are critical. However, the limited cold formability of wrought Mg alloys severely restricts their widespread usage. In order to study the role that deformation twinning might play in limiting the elongation-to-failure ({ɛ} _{ {f}}), in-situ tensile tests along the extrusion axis of Mg-1Mn (wt pct) were performed at 323 K, 423 K, and 523 K. The alloy exhibited a strong basal texture such that most of the grains experienced compression along their -axis during deformation. At 323 K, fracture occurred at about 10 pct strain. Although basal, prismatic, and pyramidal slip activity was observed along with extension twinning, contraction twinning significantly influenced the deformation, and such twins evolved into {10{\\bar{1}}1}-{10{\\bar{1}}2} double twins. Crystal plasticity simulation showed localized shear deformation within the contraction twins and double twins due to the enhanced activity of basal slip in the reoriented twin volume. Due to this, the twin-matrix interface was identified to be a potential crack initiation site. Thus, contraction twins were considered to have led to the failure of the material at a relatively low strain, suggesting that this deformation mode is detrimental to the cold formability of Mg and its alloys. With increasing temperature, there was a significant decrease in the activity of contraction twinning as well as extension twinning, along with a decrease in the tensile strength and an increase in the {ɛ} _{ {f}} value. A combination of basal, prismatic, and pyramidal slips accounted for a large percentage of the observed deformation activity at 423 K and 523 K. The lack of contraction twinning was explained by the expected decrease in the critical resolved shear stress values for pyramidal slip, and the improved {ɛ} _{ {f}} values at elevated temperatures were attributed to the vanishing activity of contraction twinning.

Metabolic consequences of decreased nitric oxide synthesis in the hearth

International Nuclear Information System (INIS)

Pechanova, O.; Bernatova, I.; Pelouch, V.

1998-01-01

The aim of the present study was to determine long-term effect of NO-synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) on concentrations of cyclic nucleotides, nucleic acids and of collagenous proteins in the left ventricle. Male Wistar rats were investigated. NO-synthase activity in the homogenates of left ventricle was determined by measuring the formation of 3 H]-L-citrulline from [ 3 H]-L-arginine. Cyclic GMP and cAMP concentrations were determined by using radioimmunoassay procedures and commercial cGMP and cAMP 125 I scintillation proximity assay systems.Significantly more remarkable decrease of NO-synthase activity was recorded in the group with higher dose (40 mg/kg/day) of L-NAME. The changes in metabolic parameters corresponded well with the dose-depend decrease of NO-synthase activity. (authors)

Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

International Nuclear Information System (INIS)

Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

2009-01-01

Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl phthalate and genistein

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Lian-Dong Zhang

2013-01-01

Full Text Available Studies of developmental effects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive effects of the co-administration of di-2-(ethylhexyl phthalate (DEHP and genistein (GEN during pregnancy and lactation were studied in male rat offspring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg/kg body weight (bwyday, GEN 50 mg/kg bwday, GEN 400 mg/kg bwday, and two combinations of the two compounds (DEHP 250 mg/kg bwday + GEN 50 mg/kg bwday, DEHP 250 mg/kg bwday + GEN 400 mg/kg bwday. The outcomes studied were general morphometry (weight, AGD, testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coefficient, AGD / body weight1/3 י, serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bwday, GEN(50mg/kg bwday or GEN(400mg/kg bwday alone were not significantly different from the control group. When exposed to (DEHP 250mg/kg bwday +GEN 50mg/kg bwday together during pregnancy and lactation, serum testosterone concentration, epididymis coefficient and Cypal17a1,Scarb1 m RNA expression significantly decreased compared to the control and GEN(50mg/kg bwday. When exposed to (DEHP 250mg/kg bwday +GEN 400mg/kg bwday together during pregnancy and lactation, AGD / body weight1/3 י, serum testosterone concentration, testis and epididymis coefficient and Star, Cypal17a1 mRNA expression appeared significantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most significant alterations in the neonate, especially with GEN at high dose, although the effect of the DEHP

Structural and transport properties of Sn-Mg alloys

International Nuclear Information System (INIS)

Meydaneri, F.; Saatci, E.; Oezdemir, M.; Ari, M.; Durmus, S.

2010-01-01

The structural and temperature dependence transport of Sn-Mg alloys have been investigated for five different samples (Pure Sn, Sn-1.0 wt % Mg , Sn-2.0 wt % Mg , Sn-6.0 wt.% Mg and Pure Mg). Scanning Electron Microscopy (SEM), x-ray diffraction (XRD) and Energy Dispersive x-ray Analysis (EDX) measurements were carried out in order to clarify the structural properties of the samples. It has been found that, the samples have tetragonal crystal symmetry except the pure Mg which has hexagonal crystal symmetry. The cell parameters decrease slightly with addition of Mg element. The SEM micrographs of the samples show that, the samples have smooth surfaces with clear grain boundary. There is no crack, porosity or defects on the surfaces. The electrical resistivity of the samples increases almost linearly with the increasing temperature, which were measured by four-point probe technique. The thermal conductivity values are in between 0.60-1.00 W/Km, which are decrease slightly with temperature and increase with composition of Mg. The thermal conductivity values of the alloys are in between the values of the pure samples. Thermal conductivity results of the alloys have been compared with available other studies and a good agreement has been seen between the results. In addition, the temperature coefficients of electrical resistivity and thermal conductivity have been determined, which are independent with the compositions of alloying elements

Distinct neurobehavioural effects of cannabidiol in transmembrane domain neuregulin 1 mutant mice.

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Leonora E Long

Full Text Available The cannabis constituent cannabidiol (CBD possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ(9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT received vehicle or CBD (1, 50 or 100 mg/kg i.p. for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT(2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg also selectively increased GABA(A receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT(2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats.

Science.gov (United States)

Caires, A; Fernandes, G S; Leme, A M; Castino, B; Pessoa, E A; Fernandes, S M; Fonseca, C D; Vattimo, M F; Schor, N; Borges, F T

2017-12-11

Cyclosporin-A (CsA) is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF) and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1) receptor blockade with bosentan (BOS) and macitentan (MAC) antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR) were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg) for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg) or MAC (25 mg/kg) by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP), RBF and renal vascular resistance (RVR), and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Endothelin-1 receptor antagonists protect the kidney against the nephrotoxicity induced by cyclosporine-A in normotensive and hypertensive rats

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A. Caires

2017-12-01

Full Text Available Cyclosporin-A (CsA is an immunosuppressant associated with acute kidney injury and chronic kidney disease. Nephrotoxicity associated with CsA involves the increase in afferent and efferent arteriole resistance, decreased renal blood flow (RBF and glomerular filtration. The aim of this study was to evaluate the effect of Endothelin-1 (ET-1 receptor blockade with bosentan (BOS and macitentan (MAC antagonists on altered renal function induced by CsA in normotensive and hypertensive animals. Wistar and genetically hypertensive rats (SHR were separated into control group, CsA group that received intraperitoneal injections of CsA (40 mg/kg for 15 days, CsA+BOS and CsA+MAC that received CsA and BOS (5 mg/kg or MAC (25 mg/kg by gavage for 15 days. Plasma creatinine and urea, mean arterial pressure (MAP, RBF and renal vascular resistance (RVR, and immunohistochemistry for ET-1 in the kidney cortex were measured. CsA decreased renal function, as shown by increased creatinine and urea. There was a decrease in RBF and an increase in MAP and RVR in normotensive and hypertensive animals. These effects were partially reversed by ET-1 antagonists, especially in SHR where increased ET-1 production was observed in the kidney. Most MAC effects were similar to BOS, but BOS seemed to be better at reversing cyclosporine-induced changes in renal function in hypertensive animals. The results of this work suggested the direct participation of ET-1 in renal hemodynamics changes induced by cyclosporin in normotensive and hypertensive rats. The antagonists of ET-1 MAC and BOS reversed part of these effects.

Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist

DEFF Research Database (Denmark)

Iepsen, Eva W; Zhang, Jinyi; Thomsen, Henrik S

2018-01-01

Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA...... liraglutide 3.0 mg for 16 weeks in 14 obese individuals with pathogenic MC4R mutations (BMI 37.5 ± 6.8) and 28 matched control participants without MC4R mutation (BMI 36.8 ± 4.8). Liraglutide decreased body weight by 6.8 kg ± 1.8 kg in individuals with pathogenic MC4R mutations and by 6.1 kg ± 1.2 kg...... in control participants. Total body fat, waist circumference, and fasting and postprandial glucose concentrations similarly decreased in both groups. Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide...

Bis(tributyltin)oxide (TBTO) decreases the food allergic response against peanut and ovalbumin in Brown Norway rats

International Nuclear Information System (INIS)

Jonge, Jonathan D. de; Ezendam, Janine; Knippels, Leon M.J.; Odink, Jennie; Pourier, Milanthy S.; Penninks, Andre H.; Pieters, Raymond; Loveren, Henk van

2007-01-01

Other factors than the allergen itself may be of importance in the development of food allergy. This report describes the influence of the immunosuppressive compound bis(tributyltin)oxide (TBTO), present in the food chain, on the development of food allergy to peanut or ovalbumin in Brown Norway (BN) rats. To study these effects BN rats were sensitized to either 1 or 10 mg peanut or ovalbumin by daily oral gavage and the TBTO-groups were fed a diet containing 80 mg TBTO per kg diet. Co-exposure to TBTO not only resulted in decreased general immunologic parameters such as weights of mesenteric lymph nodes and Peyer's patches, lymphocyte proliferation rates in splenocytes, but also on allergic parameters. In the peanut allergen-model TBTO decreased allergen-specific Th2 cytokine production by spleen cells, number of eosinophilic and basophilic granulocytes in the blood and production of mast cell protease II after oral food challenge. In the ovalbumin allergen-model TBTO decreased the number of eosinophilic and basophilic granulocytes, allergen-specific IgE and production of mast cell protease II after oral food challenge. The data imply that in the process of risk assessment of food allergy attention should be given to immunomodulating compounds present in the diet

IL-6 Inhibition With MEDI5117 Decreases The Fraction of Head and Neck Cancer Stem Cells and Prevents Tumor Recurrence

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Kelsey A. Finkel

2016-05-01

Full Text Available Head and neck squamous cell carcinomas (HNSCC exhibit a small population of uniquely tumorigenic cancer stem cells (CSC endowed with self-renewal and multipotency. We have recently shown that IL-6 enhances the survival and tumorigenic potential of head and neck cancer stem cells (i.e. ALDHhighCD44high cells. Here, we characterized the effect of therapeutic inhibition of IL-6 with a novel humanized anti-IL-6 antibody (MEDI5117 using three low-passage patient-derived xenograft (PDX models of HNSCC. We observed that single agent MEDI5117 inhibited the growth of PDX-SCC-M1 tumors (P < .05. This PDX model was generated from a previously untreated HNSCC. In contrast, MEDI5117 was not effective at reducing overall tumor volume for PDX models representing resistant disease (PDX-SCC-M0, PDX-SCC-M11. Low dose MEDI5117 (3 mg/kg consistently decreased the fraction of cancer stem cells in PDX models of HNSCC when compared to IgG-treated controls, as follows: PDX-SCC-M0 (P < .001, PDX-SCC-M1 (P < .001, PDX-SCC-M11 (P = .04. Interestingly, high dose MEDI5117 (30 mg/kg decreased the CSC fraction in the PDX-SCC-M11 model (P = .002, but not in PDX-SCC-M0 and PDX-SCC-M1. MEDI5117 mediated a dose-dependent decrease in the number of orospheres generated by ALDHhighCD44high cells cultured in ultra-low attachment plates (P < .05, supporting an inhibitory effect on head and neck cancer stem cells. Notably, single agent MEDI5117 reduced the overall recurrence rate of PDX-SCC-M0, a PDX generated from the local recurrence of human HNSCC. Collectively, these data demonstrate that therapeutic inhibition of IL-6 with low-dose MEDI5117 decreases the fraction of cancer stem cells, and that adjuvant MEDI5117 inhibits recurrence in preclinical models of HNSCC.

Antidepressant-like effect of oleanolic acid in mice exposed to the repeated forced swimming test.

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Yi, Li-Tao; Li, Jing; Liu, Qing; Geng, Di; Zhou, Ya-Fei; Ke, Xiao-Qing; Chen, Huan; Weng, Lian-Jin

2013-05-01

The study aimed to explore the antidepressant-like effect of oleanolic acid and its possible mechanism related to the monoaminergic system and neurotrophin in mice exposed to the repeated forced swimming test (FST). Both the duration and the latency of immobility affected by oleanolic acid (10, 20 and 40 mg/kg) were evaluated in the FST repeated at intervals on days 1, 7 and 14, followed by neurochemical and brain-derived neurotrophic factor (BDNF) analyses in the mouse brain regions of frontal cortex and whole hippocampus. A repeated analysis of variance (ANOVA) indicated that over retesting the immobility time increased, whereas latency to immobility tended to decrease. Minute-by-minute analysis showed that immobility time also increased during the 4-min course of the test. In addition, post-hoc Dunnett's test demonstrated that sub-chronic and chronic, but not acute, oleanolic acid treatment reduced the immobility time (sub-chronic: 20 mg/kg, 43.5%; chronic: 10 mg/kg, 19.3%; 20 mg/kg, 31.8%) and increased the latency to immobility (sub-chronic: 10 mg/kg, 60.6%; 20 mg/kg, 80.1%; chronic: 10 mg/kg, 121.8%; 20 mg/kg, 140.8%; 40 mg/kg, 80.0%). Furthermore, chronic administration of oleanolic acid significantly increased serotonin (5-HT) levels (frontal cortex: 44.5%, 41.9%, 27.5% for 10, 20, 40 mg/kg; hippocampus: 57.2%, 80.9% for 10, 20 mg/kg), decreased 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio (frontal cortex: 31.6%, 30.1%, 23.5%; hippocampus: 40.6%, 47.7%, 29.2% for 10, 20, 40 mg/kg) and elevated norepinephrine (NE) levels (hippocampus: 20 mg/kg, 45.4%) but did not alter dopamine (DA) levels. Moreover, BDNF levels in the two brain regions were also elevated by chronic oleanolic acid treatment (frontal cortex: 20 mg/kg, 67.2%; hippocampus: 10 mg/kg, 36.4%; 20 mg/kg, 55.1%). Taken together, these findings imply that functions of 5-HT, NE and BDNF may be involved in the antidepressant-like effect of oleanolic acid.

The enhanced atorvastatin hepatotoxicity in diabetic rats was partly attributed to the upregulated hepatic Cyp3a and SLCO1B1

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Shu, Nan; Hu, Mengyue; Ling, Zhaoli; Liu, Peihua; Wang, Fan; Xu, Ping; Zhong, Zeyu; Sun, Binbin; Zhang, Mian; Li, Feng; Xie, Qiushi; Liu, Xiaodong; Liu, Li

2016-01-01

Liver injury is a common adverse effect of atorvastatin. This study aimed to investigate atorvastatin-induced hepatotoxicity in diabetic rats induced by high-fat diet combined with streptozotocin. The results showed that 40 mg/kg atorvastatin was lethal to diabetic rats, whose mean survival time was 6.2 days. Severe liver injury also occurred in diabetic rats treated with 10 mg/kg and 20 mg/kg atorvastatin. The in vitro results indicated that atorvastatin cytotoxicity in hepatocytes of diabetic rats was more severe than normal and high-fat diet feeding rats. Expressions and activities of hepatic Cyp3a and SLCO1B1 were increased in diabetic rats, which were highly correlated with hepatotoxicity. Antioxidants (glutathione and N-Acetylcysteine), Cyp3a inhibitor ketoconazole and SLCO1B1 inhibitor gemfibrozil suppressed cytotoxicity and ROS formation in primary hepatocytes of diabetic rats. In HepG2 cells, up-regulations of CYP3A4 and SLCO1B1 potentiated hepatotoxicity and ROS generation, whereas knockdowns of CYP3A4 and SLCO1B1 as well as CYP3A4/SLCO1B1 inhibitions showed the opposite effects. Phenobarbital pretreatment was used to induce hepatic Cyp3a and SLCO1B1 in rats. Phenobarbital aggravated atorvastatin-induced hepatotoxicity, while decreased plasma exposure of atorvastatin. All these findings demonstrated that the upregulations of hepatic Cyp3a and SLCO1B1 in diabetic rats potentiated atorvastatin-induced hepatotoxicity via increasing ROS formation. PMID:27624558

Effects of combined administration of 5-HT1A and/or 5-HT1B receptor antagonists and paroxetine or fluoxetine in the forced swimming test in rats.

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Tatarczyńska, Ewa; Kłodzińska, Aleksandra; Chojnacka-Wójcik, Ewa

2002-01-01

Clinical data suggest that coadministration of pindolol, a 5-HT1A/5-HT1B/beta-adrenoceptor antagonist, and selective serotonin reuptake inhibitors (SSRIs) may shorten the time of onset of a clinical action and may increase beneficial effects of the therapy of drug-resistant depression. Effects of combined administration of SSRIs and 5-HT receptor ligands are currently evaluated in animal models for the detection of an antidepressant-like activity; however, the obtained results turned out to be inconsistent. The aim of the present study was to investigate effects of a 5-HT1A antagonist (WAY 100635), 5-HT1B antagonists (SB 216641 and GR 127935) or pindolol, given in combination with paroxetine or fluoxetine (SSRIs), in the forced swimming test in rats (Porsolt test). When given alone, paroxetine (10 and 20 mg/kg), fluoxetine (10 and 20 mg/kg), WAY 100635 (0.1 and 1 mg/kg), SB 216641 (2 mg/kg), GR 127935 (10 and 20 mg/kg) and pindolol (4 and 8 mg/kg) did not shorten the immobility time of rats in that test. Interestingly, SB 216641 administered alone at a dose of 4 mg/kg produced a significant reduction of the immobility time in that test. A combination of paroxetine (20 mg/kg) and WAY 100635 or pindolol failed to reveal a significant interaction; on the other hand, when paroxetine was given jointly with SB 216641 (2 mg/kg) or GR 127935 (10 and 20 mg/kg), that combination showed a significant antiimmobility action in the forced swimming test in rats. The active behaviors in that test did not reflect increased general activity because combined administration of both the 5-HT1B antagonists and paroxetine failed to alter the locomotor activity of rats, measured in the open field test. Coadministration of fluoxetine and all the antagonists used did not affect the behavior of rats in the forced swimming test. The obtained results seem to indicate that blockade of 5-HT1B receptors, but not 5-HT1A ones, can facilitate the antidepressant-like effect of paroxetine in the

Decreased insulin clearance in individuals with elevated 1-h post-load plasma glucose levels.

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Maria Adelaide Marini

Full Text Available Reduced insulin clearance has been shown to predict the development of type 2 diabetes. Recently, it has been suggested that plasma glucose concentrations ≥ 8.6 mmol/l (155 mg/dl at 1 h during an oral glucose tolerance test (OGTT can identify individuals at high risk for type 2 diabetes among those who have normal glucose tolerance (NGT 1 h-high. The aim of this study was to examine whether NGT 1 h-high have a decrease in insulin clearance, as compared with NGT individuals with 1-h post-load glucose <8.6 mmol/l (l (155 mg/dl, NGT 1 h-low. To this end, 438 non-diabetic White individuals were subjected to OGTT and euglycemic-hyperinsulinemic clamp to evaluate insulin clearance and insulin sensitivity. As compared with NGT 1 h-low individuals, NGT 1 h-high had significantly higher 1-h and 2-h post-load plasma glucose and 2-h insulin levels as well as higher fasting glucose and insulin levels. NGT 1 h-high exhibited also a significant decrease in both insulin sensitivity (P<0.0001 and insulin clearance (P = 0.006 after adjusting for age, gender, adiposity measures, and insulin sensitivity. The differences in insulin clearance remained significant after adjustment for fasting glucose (P = 0.02 in addition to gender, age, and BMI. In univariate analyses adjusted for gender and age, insulin clearance was inversely correlated with body weight, body mass index, waist, fat mass, 1-h and 2-h post-load glucose levels, fasting, 1-h and 2-h post-load insulin levels, and insulin-stimulated glucose disposal. In conclusion, our data show that NGT 1 h-high have a reduction in insulin clearance as compared with NGT 1 h-low individuals; this suggests that impaired insulin clearance may contribute to sustained fasting and post-meal hyperinsulinemia.

Dose related anxiolytic effects of diazepam: relation with serum electrolytes, plasma osmolality and systolic blood pressure (sbp) in rats

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Farooq, R.; Haleem, D.J.; Haleem, M.A.

2008-01-01

Diazepam is an anxiolytic and anticonvulsant drug that also induces hypnosis. Changes in serum electrolyte balance, plasma osmolality and systolic blood pressure (SBP) are often associated with stress-induced anxiety. Administration of diazepam has been show to decrease stress-induced enhancement of hypothalamic pituitary adrenal cortical (HPA) axis. The present is designed to monitor the anxiolytic effects of different doses of diazepam (1 mg/kg, 2.5 mg/kg and 5 mg/kg) and its association with changes of serum electrolyte balance, plasma osmolality and SBP in rats. Administration of diazepam at doses of 1 mg/kg, 2.5 mg/kg and 5 mg/kg elicited anxiolytic effects monitored in light-dark transition test and increased serum concentration of electrolytes and plasma osmolality. Serum levels of magnesium as well as SBP decreased. The results are discussed in context of anxiolytic effects of diazepam to be mediated via a modulation of stress-induced increase in the activity of HPA-axis arid electrolytes balance. (author)

Hydriding and dehydriding rates of Mg, Mg-10TaF5, and Mg-10NbF5 prepared via reactive mechanical grinding

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Song, Myoung Youp; Kwak, Young Jun; Lee, Seong Ho; Park, Hye Ryoung

2015-01-01

In this work, TaF5 and NbF5 were chosen as additives to enhance the hydriding and dehydriding rates of Mg. Mg, Mg-10TaF5, and Mg-10NbF5 samples were prepared by reactive mechanical grinding. The hydriding and dehydriding properties of the samples were then examined. Mg-10TaF5 had the largest amount of hydrogen absorbed for 30 min and the highest initial dehydriding rate after incubation period, followed in order by Mg-10NbF5, and Mg. At 593 K under 12 bar H2 at the first cycle, Mg-10TaF5 absorbed 3.63 wt% H for 5 min and 4.53 wt% H for 30 min. At 593 K under 1.0 bar H2 at the first cycle, Mg-10TaF5 desorbed 0 wt% H for 2.5 min, 0.59 wt% H for 5 min, 3.42 wt% H for 30 min, and 4.24 wt% H for 60 min. The reactive mechanical grinding of Mg with TaF5 or NbF5 is believed to have facilitated the nucleation and to have decreased the diffusion distances of hydrogen atoms. These two effects are believed to have increased the hydriding and dehydriding rates of Mg. The MgF2 and Ta2H formed in Mg-10TaF5, and the MgF2, NbH2, and NbF3 formed in Mg-10NbF5 are considered to have enhanced both of these effects.

Involvement of the cholinergic system of CA1 on harmane-induced amnesia in the step-down passive avoidance test.

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Nasehi, Mohammad; Sharifi, Shahrbano; Zarrindast, Mohammad Reza

2012-08-01

β-carboline alkaloids such as harmane (HA) are naturally present in the human food chain. They are derived from the plant Peganum harmala and have many cognitive effects. In the present study, effects of the nicotinic system of the dorsal hippocampus (CA1) on HA-induced amnesia and exploratory behaviors were examined. One-trial step-down and hole-board paradigms were used to assess memory retention and exploratory behaviors in adult male mice. Pre-training (15 mg/kg) but not pre-testing intraperitoneal (i.p.) administration of HA decreased memory formation but did not alter exploratory behaviors. Moreover, pre-testing administration of nicotine (0.5 µg/mouse, intra-CA1) decreased memory retrieval, but induced anxiogenic-like behaviors. On the other hand, pre-test intra-CA1 injection of ineffective doses of nicotine (0.1 and 0.25 µg/mouse) fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which did not alter exploratory behaviors. Furthermore, pre-testing administration of mecamylamine (0.5, 1 and 2 µg/mouse, intra-CA1) did not alter memory retrieval but fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which had no effect on exploratory behaviors. In conclusion, the present findings suggest the involvement of the nicotinic cholinergic system in the HA-induced impairment of memory formation.

Differential effects of a selective dopamine D1-like receptor agonist on motor activity and c-fos expression in the frontal-striatal circuitry of SHR and Wistar-Kyoto rats

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Diaz Heijtz Rochellys

2006-05-01

Full Text Available Abstract Background Molecular genetic studies suggest the dopamine D1 receptor (D1R may be implicated in attention-deficit/hyperactivity disorder (ADHD. As little is known about the potential motor role of D1R in ADHD, animal models may provide important insights into this issue. Methods We investigated the effects of a full and selective D1R agonist, SKF-81297 (0.3, 3 and 10 mg/kg, on motor behaviour and expression of the plasticity-associated gene, c-fos, in habituated young adult male Spontaneously Hypertensive Rats (SHR, the most commonly used animal model of ADHD, and Wistar-Kyoto (WKY; the strain from which SHR were derived. Results SHR rats were more behaviourally active than WKY rats after injection with vehicle. The 0.3 mg/kg dose of SKF-81297 increased motor behaviour (locomotion, sifting, rearing, and sniffing in both SHR and WKY rats. Total grooming was also stimulated, but only in WKY rats. The same dose increased c-fos mRNA expression in the piriform cortex of both strains. The 3 mg/kg dose increased sifting and sniffing in both strains. Locomotion was also stimulated towards the end of the testing period. The intermediate dose decreased total rearing in both strains, and produced a significant increase in c-fos mRNA in the striatum, nucleus accumbens, olfactory tuberculum, and in the cingulate, agranular insular and piriform cortices. The 10 mg/kg dose of SKF-81297 produced a biphasic effect on locomotion, which was characterized by an initial decrease followed by later stimulation. The latter stimulatory effect was more pronounced in SHR than in WKY rats when compared to their respective vehicle-injected groups. The 10 mg/kg dose also stimulated sifting and sniffing in both strains. Both the 3 and 10 mg/kg doses had no effect on total grooming. The 10 mg/kg dose induced significantly higher levels of c-fos mRNA expression in the nucleus accumbens and adjacent cortical regions (but not striatum of SHR when compared to WKY rats

Effects of Crocin on The Pituitary-Gonadal Axis and Hypothalamic Kiss-1 Gene Expression in Female Wistar Rats

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Dina Zohrabi

2018-01-01

Full Text Available Background Saffron (Crocus sativus L. has been traditionally used as a spice for coloring and flavoring in some countries cuisine. One of the main components of saffron is Crocin. Recent research have shown that crocin has various pharmacological effects. The aim of this study was to assess the effects of crocin on the Pituitary-Gonadal axis and Kiss-1 gene expression in hypothalamus and ovarian tissue organization in female Wistar rats. Materials and Methods In this experimental study, 18 adult female Wistar rats were randomly divided into three groups. Control group received normal saline and experimental groups received two different doses of crocin (100 and 200 mg/kg every two days for 30 days. After the treatment period, blood samples were obtained from the heart and centrifuged. Next, the serum levels of follicle-stimulating hormone (FSH and luteinizing hormone (LH, estrogen and progesterone hormones were measured by ELISA assay. The ovarian tissues were removed and fixed for histological investigation. The hypothalamic Kiss-1 gene expression was measured using real-time polymerase chain reaction (PCR. All data were analyzed using one-way ANOVA. Results A significant reduction (P=0.038 in the number of atretic graafian follicles (0.5 ± 0.31 was observed in rats treated with 200 mg/kg crocin. In addition, estrogen concentration in experimental groups (35.04 ± 0.85 and 36.18 ± 0.69 in crocin 100 and 200 mg/kg groups, respectively compared to control group (38.35 ± 0.64 and progesterone concentration in rats treated with crocin 200 mg/kg (2.06 ± 0.07 compared to control group (2.16 ± 0.04, significantly decreased. Interestingly, relative expressions of Kiss-1 mRNA significantly decreased in experimental groups (0.00053 ± 0.00051 and 0.0011 ± 0.00066 in crocin 100 and 200 mg/kg groups, respectively (P=0.000 compared to control group (1 ± 0. Conclusion Crocin, at hypothalamic level, reduces Kiss-1 gene expression and it can prevent

Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

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Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan

2015-09-25

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Linagliptin potentiates the effect of l-dopa on the behavioural, biochemical and immunohistochemical changes in experimentally-induced Parkinsonism: Role of toll-like receptor 4, TGF-β1, NF-κB and glucagon-like peptide 1.

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Kabel, Ahmed M; Omar, Mohamed S; Alhadhrami, A; Alharthi, Salman S; Alrobaian, Majed M

2018-05-01

Our aim was to assess the effect of different doses of linagliptin with or without l-dopa/Carbidopa on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. Eighty Balb/c mice were divided into 8 equal groups: Control; MPTP; MPTP + l-dopa/Carbidopa; MPTP + linagliptin 3 mg/kg/day; MPTP + linagliptin 10 mg/kg/day; MPTP + Carboxymethyl cellulose; MPTP + l-dopa/Carbidopa + linagliptin 3 mg/kg/day and MPTP + l-dopa/Carbidopa + linagliptin 10 mg/kg/day. Striatal dopamine, tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), transforming growth factor beta 1 (TGF-β1), toll-like receptor 4 (TLR4), antioxidant enzymes, adenosine triphosphate (ATP), glucagon-like peptide-1 (GLP-1), receptors of advanced glycation end products (RAGE), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), heme oxygenase-1 (HO-1), mitochondrial complex I activity, catalepsy and total swim scores were measured. Also, the substantia nigra was subjected to immunohistochemical examination. The combination of l-dopa/Carbidopa and linagliptin in a dose-dependent manner resulted in significant improvement of the behavioural changes, striatal dopamine, antioxidant parameters, Nrf2/HO-1 content, GLP-1, ATP and mitochondrial complex I activity with significant decrease in striatal RAGE, TGF-β1, TNF-α, IL-10, TLR4 and alleviated the immunohistochemical changes better than the groups that received either l-dopa/Carbidopa or linagliptin alone. The combination of l-dopa/Carbidopa and linagliptin might represent a promising therapeutic modality for management of parkinsonism. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of two major N-nitroso hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) metabolites on earthworm reproductive success

International Nuclear Information System (INIS)

Zhang Baohong; Cox, Stephen B.; McMurry, Scott T.; Jackson, W. Andrew; Cobb, George P.; Anderson, Todd A.

2008-01-01

Soil and topical tests were employed to investigate the effect of two N-nitroso metabolites of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) on earthworm reproduction. The lowest observed effect concentration (LOEC) for cocoon production and hatching was 50 mg/kg for both hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) in soil. MNX and TNX also significantly affected cocoon hatching in soil (p 20 values for MNX were 8.7 and 8.8 mg/kg for cocoon and juvenile production, respectively, compared to 9.2 and 9.1 mg/kg for TNX, respectively. The EC 20 values for the total number of cocoon hatchlings were 3.1 and 4.7 mg/kg for MNX and TNX, respectively, in soil and 4.5 and 3.1 mg/L in the topical test. Both MNX and TNX inhibited cocoon production and hatching, suggesting that they may have a negative affect on soil ecosystems at contaminated sites. - RDX metabolites affect earthworm cocoon production and hatching

Learning and memory in the forced swimming test: effects of antidepressants having varying degrees of anticholinergic activity.

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Enginar, Nurhan; Yamantürk-Çelik, Pınar; Nurten, Asiye; Güney, Dilvin Berrak

2016-07-01

The antidepressant-induced reduction in immobility time in the forced swimming test may depend on memory impairment due to the drug's anticholinergic efficacy. Therefore, the present study evaluated learning and memory of the immobility response in rats after the pretest and test administrations of antidepressants having potent, comparatively lower, and no anticholinergic activities. Immobility was measured in the test session performed 24 h after the pretest session. Scopolamine and MK-801, which are agents that have memory impairing effects, were used as reference drugs for a better evaluation of the memory processes in the test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased immobility time suggesting impaired "learning to be immobile" in the animals. The test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg), moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg) decreased immobility time, which suggested that the drugs exerted antidepressant activity or the animals did not recall that attempting to escape was futile. The test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg) produced no effect on immobility time. Even though the false-negative and positive responses made it somewhat difficult to interpret the findings, this study demonstrated that when given before the pretest antidepressants with or without anticholinergic activity seemed to be devoid of impairing the learning process in the test.

The impact of high intensity aerobic interval training (HIIT and flaxseed oil on ICAM-1 gene expression in heart tissue in male Wistar rats

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Y Khademi

2016-12-01

Full Text Available Abstract Background: The prevalence of cardiovascular disease may be due to inflammation and systemic inflammation plays an important role in the development and progression of atherosclerosis. ICAM-1 is one of the important factors in the pathogenesis of atherosclerosis is an inflammatory effect of physical activity and plant protection products on the response it is not well known. Methods  Thirty Wistar rats were selected as sample. Rats were randomly divided into six groups of five, including control, exercise, extracts dose of 10 mg / kg, extract dose 30 mg / kg, a dose of extract practice mg / kg 10, and extracts Practice dose of 30 mg / kg, respectively. Training groups, five sessions per week for 10 weeks, intense interval training involves running on a treadmill with an intensity of 90 to 95 percent of VO2max for rodents, at specified hours during the day. After the rats were sacrificed and the heart tissue, and to measure gene expression of ICAM-1 and LFA-1 were used. Result Data analysis showed that the expression of ICAM-1 has been reduced in training supplement groups The expression of intercellular adhesion molecule receptor (ITG has decreased in the exercise and supplement group. Conclusion: The results of this study show that both exercise and extract significant effect on gene expression of ICAM-1. And decreased expression of ICAM-1 was also flax oil ICAM-1 gene expression was also reduced. The findings of this study showed that the combination of training and flax oil reduces the expression of ICAM-1 compared to the control group. So it is likely that this method can be used as a way to prevent cardiovascular disease.

Possible mechanisms of thyroid hormone disruption in mice by BDE 47, a major polybrominated diphenyl ether congener

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Richardson, Vicki M.; Staskal, Daniele F.; Ross, David G.; Diliberto, Janet J.; DeVito, Michael J.; Birnbaum, Linda S.

2008-01-01

Polybrominated diphenyl ethers (PBDEs) are a class of polyhalogenated aromatic compounds commercially used as fire retardants in consumer products. These compounds have been shown to decrease thyroid hormone concentrations in rodents after acute exposures. This study examines the ability of 2,2',4,4'-tetrabromodiphenyl ether (BDE 47) to decrease circulating thyroid hormone concentrations and pairs this with BDE 47-induced effects on genes involved in thyroid hormone homeostasis. Female C57BL/6 mice (9 weeks old) were orally administered 3, 10, or 100 mg/kg/day of BDE 47 for 4 days. Animals were euthanized 24 h after the final dose (day 5) and liver, kidney, and serum were collected for analysis. BDE 47 caused a significant 43% decrease at 100 mg/kg/day in serum total thyroxine (T 4 ) concentrations. There was no increase in hepatic T 4 -glucuronidation activity, but significant increases in hepatic Ugt1a1, Ugt1a7, and Ugt2b5 mRNA expression accompany significant decreases in T 4 concentrations at 100 mg/kg/day of BDE 47. Induction of PROD activity occurred at the lowest dose (3 mg/kg/day). Cyp2b10 mRNA expression also increased significantly at 10 and 100 mg/kg/day. These key findings show that BDE activates the nuclear receptor, CAR. Decreases in Mdr1a mRNA expression also occurred at the lowest dose administered (3 mg/kg/day BDE 47). BDE 47 exposure also decreased hepatic transthyretin and monocarboxylate transporter 8 (Mct8) mRNA expression, suggesting that while induction of UGTs may be partly responsible for T 4 decreases, other mechanisms are also involved. No effects were seen in the kidney. We conclude that changes in hepatic UGTs and transporters may be involved in decreases in circulating T 4 following BDE 47 exposure

Alternaria sp. MG1, a resveratrol-producing fungus: isolation, identification, and optimal cultivation conditions for resveratrol production.

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Shi, Junling; Zeng, Qin; Liu, Yanlin; Pan, Zhongli

2012-07-01

Due to its potential in preventing or slowing the occurrence of many diseases, resveratrol (3,5,4'-trihydroxystilbene) has attracted great research interest. The objective of this study was to identify microorganisms from selected plants that produce resveratrol and to optimize the conditions for resveratrol production. Endophytes from Merlot wine grapes (Vitis vinifera L. cv. Merlot), wild Vitis (Vitis quinquangularis Rehd.), and Japanese knotweed (Polygonum cuspidatum Siebold & Zucc.) were isolated, and their abilities to produce resveratrol were evaluated. A total of 65 isolates were obtained and 21 produced resveratrol (6-123 μg/L) in liquid culture. The resveratrol-producing isolates belonged to seven genera, Botryosphaeria, Penicillium, Cephalosporium, Aspergillus, Geotrichum, Mucor, and Alternaria. The resveratrol-producing capability decreased or was completely lost in most isolates after three rounds of subculture. It was found that only the strain Alternaria sp. MG1 (isolated from cob of Merlot using GA1 medium) had stable and high resveratrol-producing capability in all subcultures. During liquid cultivation of Alternaria sp. MG1 in potato dextrose medium, the synthesis of resveratrol began on the first day, increased to peak levels on day 7, and then decreased sharply thereafter. Cell growth increased during cultivation and reached a stable and high level of biomass after 5 days. The best fermentation conditions for resveratrol production in liquid cultures of Alternaria sp. MG1 were an inoculum size of 6 %, a medium volume of 125 mL in a 250-mL flask, a rotation speed of 101 rpm, and a temperature of 27 °C.

Biochemical and genetic toxicity of the ionic liquid 1-octyl-3-methylimidazolium chloride on earthworms (Eisenia fetida).

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Guo, Yingying; Liu, Tong; Zhang, Jun; Wang, Jinhua; Wang, Jun; Zhu, Lusheng; Yang, Jinhui

2016-02-01

Ionic liquids also known as "green solvents," are used in many fields. However, the dispersion of ionic liquids in soil systems is likely to cause damage to soil organisms. The objective of the present study was to investigate the toxicity of 1-octyl-3-methylimidazolium chloride ([C8 mim]Cl) on earthworms (Eisenia fetida). For this purpose, earthworms were exposed to different concentrations of [C8 mim]Cl (0 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg, and 40 mg/kg artificial soil) and sampled at 7 d, 14 d, 21 d, and 28 d. The results indicated that [C8 mim]Cl could cause an accumulation of reactive oxygen species (ROS) in earthworms, even at the lowest concentration (5 mg/kg). Compared with the controls, during the [C8 mim]Cl exposure period, the activities of superoxide dismutase (SOD) and catalase (CAT) decreased and then increased, whereas the activities of peroxidase (POD) and glutathione S-transferase (GST) increased. These changes in the activities of antioxidant enzymes and GST indicated that [C8 mim]Cl could induce oxidative damage in earthworms. The malondialdehyde content was increased by high levels of [C8 mim]Cl at 14 d and 28 d, indicating that [C8 mim]Cl could lead to lipid peroxidation in earthworms. In addition, the degree of DNA damage significantly increased with increasing [C8 mim]Cl concentrations and exposure time. The present study shows that [C8 mim]Cl caused biochemical and genetic toxicity in earthworms. © 2015 SETAC.

Less is better? Intraindividual and interindividual comparison between 0.075 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadoterate meglumine for cranial MRI

Energy Technology Data Exchange (ETDEWEB)

Khouri Chalouhi, Katia, E-mail: khouri.katia@gmail.com [Scuola di Specializzazione in Radiodiagnostica, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan (Italy); Papini, Giacomo D.E., E-mail: docgde@gmail.com [Unità di Radiologia, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan (Italy); Bandirali, Michele, E-mail: michele.bandirali@hotmail.it [Scuola di Specializzazione in Radiodiagnostica, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan (Italy); Sconfienza, Luca M., E-mail: io@lucasconfienza.it [Unità di Radiologia, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan (Italy); Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Via Morandi 30, 20097 San Donato Milanese, Milano (Italy); Di Leo, Giovanni, E-mail: gianni.dileo77@gmail.com [Unità di Radiologia, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan (Italy); Sardanelli, Francesco, E-mail: francesco.sardanelli@unimi.it [Unità di Radiologia, IRCCS Policlinico San Donato, Via Morandi 30, 20097 San Donato Milanese, Milan (Italy); Dipartimento di Scienze Biomediche per la Salute, Università degli Studi di Milano, Via Morandi 30, 20097 San Donato Milanese, Milano (Italy)

2014-07-15

Purpose: To retrospectively compare a reduced dose (RD) (0.075 mmol/kg) of gadobenate dimeglumine (RD-gadobenate) with standard single dose (SSD) (0.1 mmol/kg) of gadoterate meglumine (SSD-gadoterate) for cranial MRI. Materials and methods: Thirty-one patients (12 males; aged 52 ± 16 years) underwent cranial MRI with SSD-gadoterate and repeated the examination with RD-gadobenate after a median interval of 10 months. Signal-to-noise ratio (SNR) was obtained on contrast-enhanced images for enhancing lesions (n = 10) as well as for right and left transverse venous sinuses, internal carotid arteries, and parotid glands. Moreover, a consecutive series of 100 cranial MRI with SSD-gadoterate (49 males; aged 51 ± 19 years) was compared with a consecutive series of 100 cranial MRI with RD-gadobenate (45 males; aged 54 ± 18 years). Two blinded neuroradiologists (R1, R2) judged contrast enhancement as sufficient, good, or optimal. Wilcoxon, Mann–Whitney, χ{sup 2}, and Cohen κ statistics were used. Results: At intraindividual analysis, median SNR ranged 57–88 for SSD-gadoterate and 79–99 for RD-gadobenate, the latter being systematically higher, the difference being significant for both transverse venous sinuses (p ≤ 0.011), not significant for both internal carotid arteries and both parotid glands, and enhancing lesions (p ≤ 0.101). The two series of interindividual analysis were not significantly different for gender/age (p > 0.415). Contrast enhancement was optimal in 59% (R1) and 76% (R2) of patients using RD-gadobenate, in 39% (R1) and 49% (R2) of patients using SSD-gadoterate (p ≤ 0.016), with substantial reproducibility (κ ≥ 0.606). Conclusion: Both analyses showed an equal or better contrast enhancement when using RD-gadobenate compared to SSD-gadoterate for routine cranial MRI. The high relaxivity of gadobenate allowed for a 25% dose reduction.

Less is better? Intraindividual and interindividual comparison between 0.075 mmol/kg of gadobenate dimeglumine and 0.1 mmol/kg of gadoterate meglumine for cranial MRI

International Nuclear Information System (INIS)

Khouri Chalouhi, Katia; Papini, Giacomo D.E.; Bandirali, Michele; Sconfienza, Luca M.; Di Leo, Giovanni; Sardanelli, Francesco

2014-01-01

Purpose: To retrospectively compare a reduced dose (RD) (0.075 mmol/kg) of gadobenate dimeglumine (RD-gadobenate) with standard single dose (SSD) (0.1 mmol/kg) of gadoterate meglumine (SSD-gadoterate) for cranial MRI. Materials and methods: Thirty-one patients (12 males; aged 52 ± 16 years) underwent cranial MRI with SSD-gadoterate and repeated the examination with RD-gadobenate after a median interval of 10 months. Signal-to-noise ratio (SNR) was obtained on contrast-enhanced images for enhancing lesions (n = 10) as well as for right and left transverse venous sinuses, internal carotid arteries, and parotid glands. Moreover, a consecutive series of 100 cranial MRI with SSD-gadoterate (49 males; aged 51 ± 19 years) was compared with a consecutive series of 100 cranial MRI with RD-gadobenate (45 males; aged 54 ± 18 years). Two blinded neuroradiologists (R1, R2) judged contrast enhancement as sufficient, good, or optimal. Wilcoxon, Mann–Whitney, χ 2 , and Cohen κ statistics were used. Results: At intraindividual analysis, median SNR ranged 57–88 for SSD-gadoterate and 79–99 for RD-gadobenate, the latter being systematically higher, the difference being significant for both transverse venous sinuses (p ≤ 0.011), not significant for both internal carotid arteries and both parotid glands, and enhancing lesions (p ≤ 0.101). The two series of interindividual analysis were not significantly different for gender/age (p > 0.415). Contrast enhancement was optimal in 59% (R1) and 76% (R2) of patients using RD-gadobenate, in 39% (R1) and 49% (R2) of patients using SSD-gadoterate (p ≤ 0.016), with substantial reproducibility (κ ≥ 0.606). Conclusion: Both analyses showed an equal or better contrast enhancement when using RD-gadobenate compared to SSD-gadoterate for routine cranial MRI. The high relaxivity of gadobenate allowed for a 25% dose reduction

Development of an MgO-based binder for stabilizing fine sediments and storing CO2.

Science.gov (United States)

Hwang, Kyung-Yup; Ahn, Jun-Young; Kim, Cheolyong; Seo, Jeong-Yun; Hwang, Inseong

2015-12-01

An MgO-based binder was developed that could stabilize fine dredged sediments for reuse and store CO2. Initially, a binder consisting of fly ash (FA) and blast furnace slag (BFS) was developed by using alkaline activators such as KOH, NaOH, and lime. The FA0.4-BFS0.6 binder (mixed at a FA-to-BFS weight ratio of 4:6) showed the highest compressive strength of 10.7 MPa among FA/BFS binders when 5 M KOH was used. When lime (L) was tested as an alkaline activator, the strength was comparable with those obtained when KOH or NaOH was used. The L0.1-(FA0.4BFS0.6)0.9 binder (10 % lime mixed with the FA/BFS binder) showed the highest strength of 11.0 MPa. Finally, by amending this L0.1-(FA0.4BFS0.6)0.9 binder with MgO, a novel MgO-based binder (MgO0.5-(L0.1-(FA0.4BFS0.6)0.9) 0.5) was developed, which demonstrated the 28th day strength of 11.9 MPa. The MgO-based binder was successfully applied to stabilize a fine sediment to yield a compressive strength of 4.78 MPa in 365 days, which was higher than that obtained by the Portland cement (PC) system (3.22 MPa). Carbon dioxide sequestration was evidenced by three observations: (1) the decrease in pH of the treated sediment from 12.2 to 11.0; (2) the progress of the carbonation front inward the treated sediment; and (3) the presence of magnesium carbonates. The thermogravimetric analysis (TGA) results showed that 67.2 kg of CO2 per ton of the treated sediment could be stored under the atmospheric condition during 1 year.

Structure and superconductivity of double-doped Mg1-x(Al0.5Li0.5)xB2

DEFF Research Database (Denmark)

Xu, G.J.; Grivel, Jean-Claude; Abrahamsen, A.B.

2003-01-01

A series of polycrystalline samples of Mg1-x(Al0.5Li0.5)(x)B-2 (0less than or equal toxless than or equal to0.6) were prepared by a solid state reaction method and their structure, superconducting transition temperature and magneto-transport properties were investigated by means of X-ray diffract......A series of polycrystalline samples of Mg1-x(Al0.5Li0.5)(x)B-2 (0less than or equal toxless than or equal to0.6) were prepared by a solid state reaction method and their structure, superconducting transition temperature and magneto-transport properties were investigated by means of X......-ray diffraction (XRD), ac-susceptibility and resistance in varied magnetic fields. The double doping leads to decreases in both the lattice parameters a and c. The superconducting transition temperature (T-c) decreases with double doping, but the T-c is systematically higher than that of the single Al......-doped samples. It is suggested that the hole band filling has little effect on T-c at high doping level, while the disorder induced by doping plays an important role in suppressing T-c. A systematic comparison with Al-doped MgB2 of the structure, superconducting transition and irreversibility field is made. (C...

Modulation of short-term social memory in rats by adenosine A1 and A(2A) receptors.

Science.gov (United States)

Prediger, Rui D S; Takahashi, Reinaldo N

2005-03-16

The recognition of an unfamiliar juvenile rat by an adult rat has been shown to imply short-term memory processes. The present study was designed to examine the role of adenosine receptors in the short-term social memory of rats using the social recognition paradigm. Adenosine (5.0-10.0 mg/kg), the selective adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.025-0.05 mg/kg) and the selective adenosine A(2A) receptor agonist N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA, 1.0-5.0 mg/kg), given by i.p. route 30 min before the test, disrupted the juvenile recognition ability of adult rats. This negative effect of adenosine (5.0 mg/kg, i.p.) on social memory was prevented by pretreatment with the non-selective adenosine receptor antagonist caffeine (10.0 mg/kg, i.p.), the adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1.0 mg/kg, i.p.) and the adenosine A(2A) antagonist 4-(2-[7-amino-2-{2-furyl}{1,2,4}triazolo-{2,3-a}{1,3,5}triazin-5-yl-amino]ethyl)phenol (ZM241385, 1.0 mg/kg, i.p.). Furthermore, acute administration of caffeine (10.0-30.0 mg/kg, i.p.), DPCPX (1.0-3.0 mg/kg, i.p.) or ZM241385 (0.5-1.0 mg/kg, i.p.) improved the short-term social memory in a specific manner. These results indicate that adenosine modulates the short-term social memory in rats by acting on both A1 and A(2A) receptors, with adenosine receptor agonists and antagonists, respectively, disrupting and enhancing the social memory.

Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid

Directory of Open Access Journals (Sweden)

Liu X

2014-02-01

Full Text Available Xudong Liu,1,* Yuchao Zhang,1,* Jinquan Li,1 Dong Wang,1 Yang Wu,1 Yan Li,2 Zhisong Lu,3 Samuel CT Yu,4 Rui Li,1 Xu Yang1 1Laboratory of Environmental Biomedicine, Hubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Science, Central China Normal University, Wuhan, People's Republic of China; 2Chemical and Biomolecular Engineering Department, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region; 3Institute for Clean Energy and Advanced Materials, Southwest University, Chongqing, People's Republic of China; 4Division of Environment, Hong Kong University of Science and Technology, Hong Kong Special Administrative Region *These authors contributed equally to this work Abstract: Single-walled carbon nanotubes (SWCNTs have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test, brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH], inflammation (nuclear factor κB, tumor necrosis factor a, interleukin-1β, and apoptosis (cysteine-aspartic acid protease 3 in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of

A randomized, phase II study of the anti-insulin-like growth factor receptor type 1 (IGF-1R) monoclonal antibody robatumumab (SCH 717454) in patients with advanced colorectal cancer

International Nuclear Information System (INIS)

Lin, Edward H; Lenz, Heinz-Josef; Saleh, Mansoor N; Mackenzie, Mary J; Knost, James A; Pathiraja, Kumudu; Langdon, Ronald B; Yao, Siu-Long; Lu, Brian D

2014-01-01

Overexpression of insulin-like growth factor receptor type 1 (IGF-1R) may promote tumor development and progression in some cancer patients. Our objective was to assess tumor uptake of fluorodeoxyglucose by positron-emission tomography in patients with chemotherapy-refractory colorectal cancer treated with an anti-insulin-like growth factor receptor type 1 (anti-IGF-1R) monoclonal antibody, robatumumab. This was a randomized, open-label study with two periods (P1 and P2). Patients were randomized 3:1 into treatment arms R/R and C/R that received, respectively, one cycle of 0.3 mg/kg robatumumab or one or more cycles of second-line chemotherapy in P1, followed in either case by 10 mg/kg robatumumab biweekly in P2. The primary measure of fluorodeoxyglucose uptake was maximum standardized uptake value (SUV max ). The primary endpoint was the proportion of patients in the R/R arm having a mean percent decrease from baseline in SUV max (DiSUV) greater than 20% 12–14 days postdose in P2. Secondary endpoints included Response Evaluation Criteria in Solid Tumors (RECIST)-defined tumor response and pharmacodynamic measures of target engagement. Among 41 patients who were evaluable for the primary endpoint, seven (17%, 95% CI 7%–32%) had DiSUV greater than 20%. Fifty robatumumab-treated patients were evaluable for RECIST-defined tumor response and six (12%) had stable disease lasting greater than or equal to 7 weeks in P2. Pharmacodynamic endpoints indicated target engagement after dosing with 10 mg/kg robatumumab, but not 0.3 mg/kg. The most frequently reported adverse events were fatigue/asthenia, nausea, anorexia, and gastrointestinal disturbances. In this study, few patients with chemotherapy-refractory colorectal cancer appeared to benefit from treatment with the IGF-1R antagonist robatumumab

Sildenafil Decreases BACE1 and Cathepsin B Levels and Reduces APP Amyloidogenic Processing in the SAMP8 Mouse.

Science.gov (United States)

Orejana, Lourdes; Barros-Miñones, Lucía; Jordan, Joaquin; Cedazo-Minguez, Angel; Tordera, Rosa M; Aguirre, Norberto; Puerta, Elena

2015-06-01

The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features of Alzheimer's disease. Cognitive impairments and increased levels of hyperphosphorylated tau are found in the hippocampus of SAMP8 mice along with an increased β-secretase activity and amyloid-β (Aβ) depositions that increase in number and extent with age. Based on a previous study from our laboratory showing an amelioration of cognitive impairments and tau pathology by sildenafil, in this study we tested whether this drug could also modulate the amyloid precursor protein amyloidogenic processing in this mouse model. Our results show that the protein levels of the β-secretases β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B are higher in the hippocampus of 9-month-old SAMP8 mice than those of age-matched senescence-resistant-1. Sildenafil (7.5mg/kg for 4 weeks) attenuated learning and memory impairments shown by SAMP8 mice in the passive avoidance test. The increased expression of β-site amyloid precursor protein cleaving enzyme 1 was also reduced by sildenafil, an effect paralleled to decreases in the activities of two β-site amyloid precursor protein cleaving enzyme 1 modulators, calpain and cyclin-dependent kinase 5 protein. Interestingly, sildenafil enhanced both Akt and glycogen synthase kinase-3β (ser9) phosphorylation, which could be mediating the reduction in cathepsin B levels found in the hippocampus of sildenafil-treated SAMP8 mice. Sildenafil-induced reduction in β-site amyloid precursor protein cleaving enzyme 1 and cathepsin B expression in SAMP8 mice was associated with a decrease in hippocampal Aβ42 levels which, in turn, could mediate the parallel decline in glial fibrillary acidic protein expression observed in these animals. These findings highlight the therapeutic potential of sildenafil in Alzheimer's disease pathogenesis. © The Author 2014. Published by Oxford University Press on behalf of

Two cases of bradyarrhythmia and hypotension after extradural injections in dogs.

Science.gov (United States)

Iff, Isabelle; Moens, Yves

2008-05-01

Two healthy obese, seven-year-old, female Rottweilers weighing 40 and 57 kg were submitted for cranial cruciate repair. They were premedicated with intravenous methadone (0.1 mg kg(-1)) and acepromazine (0.01 and 0.02 mg kg(-1)). Anesthesia was induced with propofol (3.6 and 2.5 mg kg(-1)) and maintained with isoflurane in oxygen using a circle breathing system. The dogs were placed in sternal recumbency and epidural injection of lidocaine/bupivacaine or lidocaine/bupivacaine/morphine (0.2 mL/kg, 8 and 11 mL) was carried out over 1.5 and 4 minutes. Epidural pressures were 79 and 72 mmHg at the end of the injections. The first dog's heart rate decreased from 80 to 65 beats minute(-1) with a second degree atrioventricular (AV) block. The arterial pressure decreased from 100 to 50 mmHg. These responded to atropine (0.01 mg kg(-1) IV). The second dog's heart rate decreased from 120 to 60 beats minute(-1) while arterial pressure decreased from 72 to 38 mmHg. No treatment was given and heart rate and arterial blood pressure returned to acceptable ranges. These cases suggest that large increases in epidural pressure may cause significant cardiovascular effects. This may be avoided by using lower volumes and discontinuing injection if significant back pressure is detected.

Aerobic exercise decreases the positive-reinforcing effects of cocaine.

Science.gov (United States)

Smith, Mark A; Schmidt, Karl T; Iordanou, Jordan C; Mustroph, Martina L

2008-11-01

Aerobic exercise can serve as an alternative, non-drug reinforcer in laboratory animals and has been recommended as a potential intervention for substance abusing populations. Unfortunately, relatively little empirical data have been collected that specifically address the possible protective effects of voluntary, long-term exercise on measures of drug self-administration. The purpose of the present study was to examine the effects of chronic exercise on sensitivity to the positive-reinforcing effects of cocaine in the drug self-administration procedure. Female rats were obtained at weaning and immediately divided into two groups. Sedentary rats were housed individually in standard laboratory cages that permitted no exercise beyond normal cage ambulation; exercising rats were housed individually in modified cages equipped with a running wheel. After 6 weeks under these conditions, rats were surgically implanted with venous catheters and trained to self-administer cocaine on a fixed-ratio schedule of reinforcement. Once self-administration was acquired, cocaine was made available on a progressive ratio schedule and breakpoints were obtained for various doses of cocaine. Sedentary and exercising rats did not differ in the time to acquire cocaine self-administration or responding on the fixed-ratio schedule of reinforcement. However, on the progressive ratio schedule, breakpoints were significantly lower in exercising rats than sedentary rats when responding was maintained by both low (0.3mg/kg/infusion) and high (1.0mg/kg/infusion) doses of cocaine. In exercising rats, greater exercise output prior to catheter implantation was associated with lower breakpoints at the high dose of cocaine. These data indicate that chronic exercise decreases the positive-reinforcing effects of cocaine and support the possibility that exercise may be an effective intervention in drug abuse prevention and treatment programs.

Involvement of dopamine D1/D2 receptors on harmane-induced amnesia in the step-down passive avoidance test.

Science.gov (United States)

Nasehi, Mohammad; Piri, Morteza; Nouri, Maryam; Farzin, Davood; Nayer-Nouri, Touraj; Zarrindast, Mohammad Reza

2010-05-25

Ingestion of harmane and other alkaloids derived from plant Peganum harmala has been shown to elicit profound behavioural and toxic effects in humans, including hallucinations, excitation, feelings of elation, and euphoria. These alkaloids in the high doses can cause a toxic syndrome characterized by tremors and convulsions. Harmane has also been shown to act on a variety of receptor systems in the mammalian brain, including those for serotonin, dopamine and benzodiazepines. In animals, it has been reported to affect short and long term memory. In the present study, effects of dopamine D1 and D2 receptor antagonists on the harmane (HA)-induced amnesia and exploratory behaviors were examined in mice. One-trial step-down and hole-board paradigms were used for the assessment of memory retention and exploratory behaviors in adult male NMRI mice respectively. Intraperitoneal (i.p.) administration of HA (5 and 10 mg/kg) immediately after training decreased memory consolidation, while had no effect on anxiety-like behavior. Memory retrieval was not altered by 15- or 30 min pre-testing administration of the D1 (SCH23390, 0.025, 0.05 and 0.1 mg/kg) or D2 (sulpiride 12.5, 25 and 50 mg/kg) receptor antagonists, respectively. In contrast, SCH23390 (0.05 and 0.1 mg/kg) or sulpiride (25 and 50 mg/kg) pre-test administration fully reversed HA-induced impairment of memory consolidation. Finally, neither D1 nor D2 receptor blockade affected exploratory behaviors in the hole-board paradigm. Altogether, these findings strongly suggest an involvement of D1 and D2 receptors modulation in the HA-induced impairment of memory consolidation. Copyright 2010 Elsevier B.V. All rights reserved.

49 CFR 173.477 - Approval of packagings containing greater than 0.1 kg of non-fissile or fissile-excepted uranium...

Science.gov (United States)

2010-10-01

... kg of non-fissile or fissile-excepted uranium hexafluoride. 173.477 Section 173.477 Transportation... non-fissile or fissile-excepted uranium hexafluoride. (a) Each offeror of a package containing more than 0.1 kg of uranium hexafluoride must maintain on file for at least one year after the latest...

EFEITO DA SUPLEMENTAÇÃO DE CAFEÍNA EM PARÂMETROS HEMATOLÓGICOS, IMUNOLÓGICOS E NO DESEMPENHO FÍSICO

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João Rafael Valentim-Silva

2014-02-01

Full Text Available Therefore was objected to identify the effects of acute supplementation of caffeine with 8 and 16 mg.kg-1 in hematological and immunological parameters and the performance of the Wistar rats submitted in intense exercise until exhaustion. Materials and Methods: was selected 24 Wistar male rats, adults and sedentary with average weight of 174.86 + 8.26g and were randomly divided in control group (water CON (n=8, CAF8 (n=8 (8mg/kg e CAF16 (n=8 (16mg/kg administered the caffeine by gavage 30 minutes before the begin of experiment. The swimming happened in an aquarium with 60 cm of depth, water at 28°C, until the exhaustion with overload of 7.5% from their weight and immediately euthanized for the withdrawal of 1ml of their blood for lab analyzes. Results: 8 mg.kg-1 e 16 mg.kg-1 do not change the performance and the last do not change both parameters. The supplementation whit 8 mg.kg-1 of caffeine was able only increase the platelets count (p<0.05 and tended decrease the immunosuppressive tendency. Conclusions 8 mg.kg-1 of caffeine was able of increase the platelets account and decrease the immunosuppressive tendency of exhaustive exercise, but, do not shows be able in increase performance and 16mg/kg of caffeine do not change all investigated parameters.

Delayed myelosuppression with acute exposure to hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and environmental degradation product hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX) in rats

Energy Technology Data Exchange (ETDEWEB)

Jaligama, Sridhar; Kale, Vijay M.; Wilbanks, Mitchell S. [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209 (United States); Perkins, Edward J. [US Army Engineer Research and Development Center, Vicksburg, MS 39180 (United States); Meyer, Sharon A., E-mail: meyer@ulm.edu [Department of Toxicology, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71209 (United States)

2013-02-01

Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a widely used munitions compound, and hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), its N-nitroso product of anaerobic microbial nitroreduction, are contaminants of military sites. Previous studies have shown MNX to be the most acutely toxic among the nitroreduced degradation products of RDX and to cause mild anemia at high dose. The present study compares hematotoxicity with acute oral exposure to MNX with parent RDX. Both RDX and MNX caused a modest decrease in blood hemoglobin and ∼ 50% loss of granulocytes (NOAELs = 47 mg/kg) in female Sprague–Dawley rats observed 14 days post-exposure. We explored the possibility that blood cell loss observed after 14 days was delayed in onset because of toxicity to bone marrow (BM) progenitors. RDX and MNX decreased granulocyte/macrophage-colony forming cells (GM-CFCs) at 14, but not 7, days (NOAELs = 24 mg/kg). The earliest observed time at which MNX decreased GM-CFCs was 10 days post-exposure. RDX and MNX likewise decreased BM burst-forming units-erythroid (BFU-Es) at 14, but not 7, days. Granulocyte–erythrocyte–monocyte–megakaryocyte (GEMM)-CFCs were unaffected by RDX and MNX at 7 days suggesting precursor depletion did not account for GM-CFC and BFU-E loss. MNX added to the culture media was without effect on GM-CFC formation indicating no direct inhibition. Flow cytometry showed no differential loss of BM multilineage progenitors (Thy1.1{sup +}) or erythroid (CD71{sup +}) precursors with MNX suggesting myeloid and erythroid lineages were comparably affected. Collectively, these data indicate that acute exposure to both RDX and MNX caused delayed suppression of myelo- and erythropoiesis with subsequent decrease of peripheral granulocytes and erythrocytes. Highlights: ► Acute oral exposure to munitions RDX causes myelosuppression. ► Environmental degradation product MNX is comparable in effect. ► RDX and MNX are cytotoxic to both myeloid and erythroid

The regulation effect of STAT 5 signaling pathway on the cell cycle progression of irradiated KG-1 cells

International Nuclear Information System (INIS)

Guo Dehuang; Dong Bo; Luo Qingliang; Wen Gengyun; Mao Bingzhi

2000-01-01

The author investigated the role of the JAK/STAT signaling pathway regulating cell cycle progression in the irradiated KG-1 cells. By permanent transfecting the cells with DN-STAT 5 cDNA to block the JAK/STAT signaling pathway and then transient transfecting with cyclin D 1 or cyclin B 1 cDNA, the effects of cyclin D 1 protein and cyclin B 1 protein on the cell cycle progression were examined. Results showed that after irradiation with 8Gy 60 Co rays, the irradiated KG-1 cells transfected with only DN-STAT 5 cDNA can not recover form the G 1 arrest, even though GM-CSF was added. Meanwhile, the cells transfected with both the DN-STAT 5 cDNA and cyclin D 1 cDNA or cyclin B 1 cDNA can recover from the G 1 arrest or the G 2 arrest to a great extent. Thus, it was proved indirectly that the JAK/STAT signaling pathway activated by GM-CSF regulated the cell cycle progression through cyclin D 1 and cyclin B 1 protein

Challenges in device closure of a large patent ductus arteriosus in infants weighing less than 6 kg.

Science.gov (United States)

Vijayalakshmi, I B; Chitra, Narasimhan; Praveen, Jayan; Prasanna, Simha Rao

2013-02-01

Transcatheter closure of patent ductus arteriosus (PDA) has replaced surgery in most institutions. Despite improvements in techniques and the devices available, closure of large PDA in very small infants remains a challenge. To assess the challenges, feasibility, and efficacy of device closure of large PDA, in infants weighing ≤6 kg. Analysis of device closure of a PDA was done in 61 infants ≤6 kg. Their ages, ranged from 9 days-12 months (mean 8.9 months), weight ranged from 2.2 to 6 kg (mean 5.3 kg), and PDA measured 3.2-8.7 mm (mean 4.8 mm). The fluoroscopy time was 3-18 minutes. The largest device used was 12 × 10 mm. Successful device placement was achieved in 60/61 infants (98.4%). Mild aortic obstruction occurred in 2 cases (3.3%), as the device got displaced towards the aorta after release. The device embolized in 2 cases (3.3%). In one it was retrieved by a novel method like fastening the screw in the aorta and was closed with a 4 × 6 ADO II. In the other infant, with a single kidney, died of uremia after device retrieval. Mild left pulmonary artery (LPA) obstruction occurred in one case (1.6%). Four cases (6.6%) had minor vascular complications. The postprocedure weight gain after 3 months was between 2.5 kg ± 250 mg. Device closure of large PDA in infants weighing ≤6 kg with left ventricular failure is challenging but possible, safe and effective. Retrieval of embolized device could be tricky. © 2012, Wiley Periodicals, Inc.

Laticifer proteins from Plumeria pudica inhibit the inflammatory and nociceptive responses by decreasing the action of inflammatory mediators and pro-inflammatory cytokines

Directory of Open Access Journals (Sweden)

Heliana B. Fernandes

Full Text Available AbstractSome publications have described the pharmacological properties of latices proteins. Thus, in the present study proteins from Plumeria pudica Jacq., Apocynaceae, latex were evaluated for anti-inflammatory and antinociceptive activities. Obtained data showed that an intraperitoneal administration of different doses of latex was able to reduce the paw edema induced by carrageenan in a dose-dependent manner (better dose 40 mg/kg; 72.7% inhibition at 3rd and 78.7% at 4th hour and the edema induced by dextran (40 mg/kg; 51.5% inhibition at 30 min and 93.0% at 1st hour. Inhibition of edema induced by carrageenan was accompanied by a reduction of myeloperoxidase activity. Pre-treating animals with latex (40 mg/kg also inhibited the paw edema induced by histamine, serotonin, bradykinin, prostaglandin E2, compound 48/80. Additionally, the latex (40 mg/kg reduced the leukocyte peritoneal migration induced by carrageenan and this event was followed by reduction of IL-1β and TNF-α in peritoneal fluid. The latex-treatment (40 mg/kg reduced the animal abdominal constrictions induced by acetic acid and the first phase on paw licking model induced by formalin. When latex was treated with heat (at 100 °C for 30 min, anti-edematogenic and myeloperoxidase activities were significantly reduced, indicating the involvement of heat-sensitive proteins on anti-inflammatory effect. Our results evidence that latex fluids are a source of proteins with pharmacological properties.

Protective effect of porphyran isolated from discolored nori (Porphyra yezoensis) on lipopolysaccharide-induced endotoxin shock in mice.

Science.gov (United States)

Nishiguchi, Tomoki; Cho, Kichul; Isaka, Shogo; Ueno, Mikinori; Jin, Jun-O; Yamaguchi, Kenichi; Kim, Daekyung; Oda, Tatsuya

2016-12-01

Porphyran, a sulfated polysaccharide, isolated from discolored nori (Porphyra yezoensis) (dc-porphyran) and one fraction (F1) purified from dc-porphyran by DEAE-chromatography showed the protective effects on LPS-induced endotoxin shock in mice. Intraperitoneal (i.p.) treatment with dc-porphyran or F1 (100mg/kg) 60min prior to i.p. injection of LPS (30mg/kg) completely protected mice from LPS lethality. At 10mg/kg concentration, F1 demonstrated more protection than dc-porphyran. Intravenous (i.v.) challenge of LPS, even at 20mg/kg, was more lethal than i.p. administration; i.v. injection of F1 (100mg/kg) with LPS significantly improved the survival rate. However, i.v. dc-porphyran (100mg/kg) produced an even lower survival rate than that of LPS alone. We examined pro-inflammatory mediators such as NO and TNF-α in serum. F1 significantly reduced the levels of these markers. Additionally, F1 significantly decreased the malondialdehyde level in the liver, a marker of oxidative stress, while dc-porphyran had almost no effect. Furthermore, F1 significantly decreased the production of TNF-α and NO in peritoneal exudate cells harvested from LPS-challenged mice, while dc-porphyran treatment showed a lesser decrease. Our results suggest that porphyran isolated from discolored nori, especially F1, is capable of suppressing LPS-induced endotoxin shock in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Electromagnetic and microwave absorption properties of BaMg{sub x}Co{sub 1−x}TiFe{sub 10}O{sub 19}

Energy Technology Data Exchange (ETDEWEB)

Chen, Jing [State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, Southwest University of Science and Technology, Mianyang 621010 (China); School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Meng, Pingyuan [Huzhou Innovation Center of Advanced Materials, Shanghai Institute of Ceramics Chinese Academy of Sciences, Huzhou 215100 (China); Wang, Meiling [State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, Southwest University of Science and Technology, Mianyang 621010 (China); School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Zhou, Guanchen [School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Wang, Xinqing [State Key Laboratory Cultivation Base for Nonmetal Composites and Functional Materials, Southwest University of Science and Technology, Mianyang 621010 (China); School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China); Xu, Guangliang, E-mail: xuguangliang@swust.edu.cn [School of Materials Science and Engineering, Southwest University of Science and Technology, Mianyang 621010 (China)

2016-09-15

To improve the impedance matching and then achieve a better microwave absorption performance in electromagnetic absorber, the Mg{sup 2+} was added to occupy the sites of Co{sup 2+} in hexagonal-type ferrite BaCoTiFe{sub 10}O{sub 19}. BaMg{sub x}Co{sub 1−x}TiFe{sub 10}O{sub 19} were synthesized by a simple sol-gel combustion technique and the phase of BaMg{sub x}Co{sub 1−x}TiFe{sub 10}O{sub 19} was confirmed by X-ray diffraction analysis (XRD). The grain size of BaMg{sub x}Co{sub 1−x}TiFe{sub 10}O{sub 19} was in the range of 100–400 nm and crystal particles were refined with the augment of doped Mg{sup 2+}. Based on the static magnetic measurement, the coercivity (H{sub c}) increased and the saturation magnetization (M{sub s}) decreased as the x increased. Moreover, it was found that BaMg{sub 0.4}Co{sub 0.6}TiFe{sub 10}O{sub 19} possessed a maximum reflection loss of −33.7 dB with a matching thickness of 2.0 mm measured by the vector net-analyzer in the frequency of 0.5–18 GHz, which also had a bandwidth below −20 dB ranging from 11.5 GHz to 17.2 GHz. Meanwhile, the permeability of the prepared ferrites could be adjusted and a proper match was provided between dielectric and magnetic properties by controlling the doped content of Mg{sup 2+}, which would be significant to the application of BaMg{sub x}Co{sub 1−x}TiFe{sub 10}O{sub 19} in the field of the microwave absorbing materials. - Highlights: • The Mg{sup 2+} ions were first employed to occupy the place of Co{sup 2+} ions in BaCoTiFe{sub 10}O{sub 19}. • The grains were refined as Co substitution by Mg in ferrite. • The peaks of complex permeability shift to high frequency with Mg{sup 2+} substituted. • The coercivity increased and saturation magnetization slightly decreased. • Substitution of Mg{sup 2+} enhanced microwave absorption and broadened bandwidth.

CSN1S2 protein of goat milk inhibits the decrease of viability and increases the proliferation of MC3T3E1 pre-osteoblast cell in methyl glyoxal exposure

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Choirunil Chotimah

2015-03-01

Full Text Available Objective: To investigate whether the CNS1S2 protein of goat milk is able to inhibit the toxicity of methyl glyoxal (MG towards MC3T3E1 pre-osteoblast cells. Methods: At confluency, pre-osteoblast cells were divided into five groups which included control (untreated, pre-osteoblast cells exposed to 5 µmol/L MG, pre-osteoblast cells exposed to MG in the presence of CSN1S2 protein at doses of 0.025, 0.050, and 0.100 mg/L, respectively. Analysis of reactive oxygen species was done with 2,7-dichlorodihydrofluorescein diacetate fluorochrome. The proliferation and viability of MC3T3E1 cells were measured by trypan blue staining. Malondialdehyde analysis was done colorimetrically. Results: Cell's viabilities were significantly lower in MG+0.050 mg/L CSN1S2 protein of goat milk compared to MG group (P<0.05. MG+0.100 mg/L CSN1S2 protein of goat milk significantly increased the cells viability compared to MG group (P<0.05. The levels of proliferation were significantly higher in MG+0.100 mg/L CSN1S2 protein of goat milk compared to control group and all treatment groups, respectively (P<0.05. Conclusions: High dose of CSN1S2 protein of goat milk (0.100 mg/L in high MG environment inhibits the decrease of viability due to the increases of the proliferation of MC3T3E1 preosteoblast cell.

Structural and electrical properties of (1-x)(Na1/2Bi1/2)TiO3-xPb(Mg1/3Nb2/3)O3 solid solution

International Nuclear Information System (INIS)

Lee, J.-K.; Yi, J.Y.; Hong, K.S.

2004-01-01

Structural, dielectric and piezoelectric properties of (1-x)(Na 1/2 Bi 1/2 )TiO 3 -xPb(Mg 1/3 Nb 2/3 )O 3 (NBT-xPMN) solid solution have been investigated. An addition of PMN into NBT transformed the structure of sintered samples from rhombohedral to pseudocubic phase where x is larger than 0.1. In calcined powders, however, the intermediate structure were observed between rhombohedral and cubic phases near x=0.1. The formation of solid solution between NBT and PMN modified the dielectric and piezoelectric properties of NBT to be suitable for high temperature dielectric and piezoelectric material. With increasing the content of PMN, the temperature-stability of ε r (T) increased and the high temperature dielectric loss decreased. In addition, the piezoelectric property of NBT-xPMN was enhanced, for the decrease of coercive field and conductivity promoted the domain reversal under the high electric field of the poling process

Composição corporal e exigências nutricionais em cálcio e fósforo para ganho e mantença de cordeiros Santa Inês dos 15 kg aos 25 kg de peso vivo Body composition and requirements for calcium and phosphorus for gain and maintenance of Santa Ines lambs from 15 to 25 kg of body weight

Directory of Open Access Journals (Sweden)

Luciana Castro Geraseev

2000-02-01

Full Text Available RESUMO - Este trabalho foi conduzido para determinar a composição corporal e estimar as exigências de cálcio e fósforo de cordeiros da raça Santa Inês. Foram utilizados 18 cordeiros machos inteiros, com peso médio inicial de 15 kg, divididos em três grupos: seis animais abatidos no início do experimento, para avaliar o conteúdo de cálcio e fósforo corporal, servindo como animais referência para o método do abate comparativo; seis animais alimentados ad libitum; e seis com alimentação restrita (em nível de mantença + 20%. Os cordeiros que receberam dietas ad libitum e restritas entraram no experimento aos pares e foram abatidos concomitantemente, quando o primeiro atingiu 25 kg de peso vivo. A composição corporal foi estimada a partir de equações de regressão do logaritmo da quantidade de cálcio e fósforo presentes no corpo vazio, em função do logaritmo do peso corporal vazio. As exigências líquidas de mantença e o coeficiente de absorção destes minerais foram determinados a partir da correlação entre a quantidade de mineral ingerida e a quantidade retida no corpo, enquanto as exigências líquidas para o ganho em peso foram estimadas a partir da derivação de equações de predição da composição corporal. As exigências líquidas de mantença, para animais entre 15 e 25 kg de peso vivo, foram 305 mg de Ca/dia e 325 mg de P/dia e as exigências líquidas por kg de ganho de peso vivo, para animais com 15 e 25 kg de peso vivo, 11,41 e 10,33 g Ca e 5,72 e 4,94 g P, respectivamente. Os coeficientes de absorção encontrados neste trabalho foram 0,44 e 0,55 para Ca e P, respectivamente.ABSTRACT - The research was carried out to determine body composition and calcium and phosphorus requirements of Santa Ines lambs. Eighteen entire male lambs with average initial live weight of 15 kg were used. The animals were allotted to three groups: six animals were slaughtered at the beginning of the experiment, to access the