Blood clearance of 3H-thymidine and 3H-uridine ingrowing rats

International Nuclear Information System (INIS)

Carlsson, J.; Johansson, K.J.; Saefwenberg, J.O.

1976-01-01

The clearance of 3 H-thymidine and 3 H-uridine from the blood was studied in rats of ages 5, 15 and 30 days. The clearance curves were integrated to get measure of the total availability of the precursors. Age-dependent differences were found, especially for uridine, which showed a lower availability when the animals became older. In the case of thymidine lesser differences were found. The catabolic rate, as measured by the appearance of 3 H-water, was much increased, both in case of 3 H-thymidine and 3 H -uridine as the rats became older. It was observed that the amount of catabolic products (except 3 H-water) in the blood was much larger for uridine than for thymidine. Rats were given 160 rad on the first day after birth. Only in the case of 3 H-thymidine, in 5-days-old rats, an effect of irradiation could be seen, i.e. a somewhat lowered efficiency to catabolize thymidine. (author)

Transdifferentiated rat pancreatic progenitor cells (AR42J-B13/H) respond to phenobarbital in a rat hepatocyte-specific manner.

Science.gov (United States)

Osborne, M; Haltalli, M; Currie, R; Wright, J; Gooderham, N J

2016-07-01

Phenobarbital (PB) is known to produce species-specific effects in the rat and mouse, being carcinogenic in certain mouse strains, but only in rats if treated after a DNA damaging event. PB treatment in the rat and mouse also produces disparate effects on cell signalling and miRNA expression profiles. These responses are induced by short term and prolonged PB exposure, respectively, with the latter treatments being difficult to examine mechanistically in primary hepatocytes due to rapid loss of the original hepatic phenotype and limited sustainability in culture. Here we explore the rat hepatocyte-like B13/H cell line as a model for hepatic response to PB exposure in both short-term and longer duration treatments. We demonstrate that PB with Egf treatment in the B13/H cells resulted in a significant increase in Erk activation, as determined by the ratio of phospho-Erk to total Erk, compared to Egf alone. We also show that an extended treatment with PB in the B13/H cells produces a miRNA response similar to that seen in the rat in vivo, via the time-dependent induction of miR-182/96. Additionally, we confirm that B13/H cells respond to Car activators in a typical rat-specific manner. These data suggest that the B13/H cells produce temporal responses to PB that are comparable to those reported in short-term primary rat hepatocyte cultures and in the longer term are similar to those in the rat in vivo. Finally, we also show that Car-associated miR-122 expression is decreased by PB treatment in B13/H cells, a PB-induced response that is common to the rat, mouse and human. We conclude that the B13/H cell system produces a qualitative response comparable to the rat, which is different to the response in the mouse, and that this model could be a useful tool for exploring the functional consequences of PB-sensitive miRNA changes and resistance to PB-mediated tumours in the rat. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Tx1, from Phoneutria nigriventer spider venom, interacts with dihydropyridine sensitive-calcium channels in GH3 cells

International Nuclear Information System (INIS)

Gouvea dos Santos, R.; Soares, M.A.; Pimenta, A.M.; De Lima, M.E.; ICB, UFMG, Belo Horizonte

2006-01-01

The aim of this work was to use the binding assay of tritiated-dihydropyridine and radioiodinated Tx1, isolated from the Phoneutria nigriventer venom, in order to show the presence of Ca v 1 calcium channels on pituitary tumour cell (GH3). We showed that GH3 cells have specific sites for 125 I-Tx1, which are sensitive to nifedipine (∼20%). Reverse competition assay with 3 H-PN200-110 (40% inhibition) and electrophysiological data (50% inhibition) suggest that Ca v 1 calcium channels are target sites for this toxin. To summarize, Tx1 binds to specific sites on GH3 cells and this interaction results in Ca v 1 calcium channel blockade. 3 H-PN200-110 and 125 I-Tx1 binding assays proved to be useful tools to show the presence of calcium channels on GH3 cells. (author)

Peptide LyeTx I mnΔk: A potential antimicrobial agent

International Nuclear Information System (INIS)

Fuscaldi, Leonardo Lima; Avelar Júnior, Joaquim T. de; Boff, Daiane; Santos, Daniel M. dos; Oliveira, Vívian L.S. de; Mata, Lays M. da; Contarini, Sara M. Lopes; Miranda, Sued E. Mendes; Amaral, Flavio Almeida; Diniz, Simone O.F.; Lima, Maria Elena de; Cardoso, Valbert N.

2017-01-01

Full text: Introduction: The emergence of resistance to current antibiotics and the incidence of opportunistic bacterial infections have stimulated the search for new antibiotic agents. In this sense, antimicrobial peptides are promising molecules due to their different mechanisms of action compared to classic antibiotics. Peptides LyeTx I (Lycosa erythrognatha venom) and LyeTx I mnΔK (truncated and modified derivative) present in vitro antimicrobial activity. Aim: To evaluate in vivo antimicrobial activity of LyeTx I mnΔK in an experimental model of septic arthritis. Methods: CEUA/UFMG: protocol nº 236/2014. At day 0, male C57/BL6 mice (∼7 weeks; (∼25 g) were inoculated with 10 μL of a S. aureus (ATCC® 6538) suspension (8 x 107 CFU/mL) or of sterile PBS (negative control group) by intraarticular injection (i.a.) in the right posterior articulation. At days 2, 4 and 6, mice were treated, by i.a., with clindamycin, LyeTx I or LyeTx I mnΔK (7.35, 0.08, 0.08 nmol/i.a., respectively). The positive control group received saline as treatment. At day 2 (before the first dose) and at day 7, an aliquot containing 7.4 MBq of technetium- 99m -Ceftizoxime ( 99m Tc-CFT) was injected into the tail vein of mice. At 2 h postradiopharmaceutical injection, animals were anesthetized and placed under a gamma camera (NuclideTM TH 22). Images were acquired during 5 min and quantitative analyzed to determine 99m Tc-CFT uptake by infectious focus, by means of target to non-target ratio (t/n-t) determination. Beyond scintigraphic images, animals were conducted to some other investigations post-treatment (at day 7). First, bacterial recovery assay was performed in order to assess pathogen reduction in the infected joint. Then, inflammatory process reduction was evaluated by the determination of immune cells recruitment. Finally, the removal threshold hypernociception was measured aiming to estimate pain. Quantitative data were expressed as 'mean±error' (n=4-6) and

Peptide LyeTx I mnΔk: A potential antimicrobial agent

Energy Technology Data Exchange (ETDEWEB)

Fuscaldi, Leonardo Lima; Avelar Júnior, Joaquim T. de; Boff, Daiane; Santos, Daniel M. dos; Oliveira, Vívian L.S. de; Mata, Lays M. da; Contarini, Sara M. Lopes; Miranda, Sued E. Mendes; Amaral, Flavio Almeida; Diniz, Simone O.F.; Lima, Maria Elena de; Cardoso, Valbert N. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

2017-07-01

Full text: Introduction: The emergence of resistance to current antibiotics and the incidence of opportunistic bacterial infections have stimulated the search for new antibiotic agents. In this sense, antimicrobial peptides are promising molecules due to their different mechanisms of action compared to classic antibiotics. Peptides LyeTx I (Lycosa erythrognatha venom) and LyeTx I mnΔK (truncated and modified derivative) present in vitro antimicrobial activity. Aim: To evaluate in vivo antimicrobial activity of LyeTx I mnΔK in an experimental model of septic arthritis. Methods: CEUA/UFMG: protocol nº 236/2014. At day 0, male C57/BL6 mice (∼7 weeks; (∼25 g) were inoculated with 10 μL of a S. aureus (ATCC® 6538) suspension (8 x 107 CFU/mL) or of sterile PBS (negative control group) by intraarticular injection (i.a.) in the right posterior articulation. At days 2, 4 and 6, mice were treated, by i.a., with clindamycin, LyeTx I or LyeTx I mnΔK (7.35, 0.08, 0.08 nmol/i.a., respectively). The positive control group received saline as treatment. At day 2 (before the first dose) and at day 7, an aliquot containing 7.4 MBq of technetium-{sup 99m}-Ceftizoxime ({sup 99m}Tc-CFT) was injected into the tail vein of mice. At 2 h postradiopharmaceutical injection, animals were anesthetized and placed under a gamma camera (NuclideTM TH 22). Images were acquired during 5 min and quantitative analyzed to determine {sup 99m}Tc-CFT uptake by infectious focus, by means of target to non-target ratio (t/n-t) determination. Beyond scintigraphic images, animals were conducted to some other investigations post-treatment (at day 7). First, bacterial recovery assay was performed in order to assess pathogen reduction in the infected joint. Then, inflammatory process reduction was evaluated by the determination of immune cells recruitment. Finally, the removal threshold hypernociception was measured aiming to estimate pain. Quantitative data were expressed as 'mean±error' (n=4

Streptomyces venezuelae TX-TL - a next generation cell-free synthetic biology tool.

Science.gov (United States)

Moore, Simon J; Lai, Hung-En; Needham, Hannah; Polizzi, Karen M; Freemont, Paul S

2017-04-01

Streptomyces venezuelae is a promising chassis in synthetic biology for fine chemical and secondary metabolite pathway engineering. The potential of S. venezuelae could be further realized by expanding its capability with the introduction of its own in vitro transcription-translation (TX-TL) system. TX-TL is a fast and expanding technology for bottom-up design of complex gene expression tools, biosensors and protein manufacturing. Herein, we introduce a S. venezuelae TX-TL platform by reporting a streamlined protocol for cell-extract preparation, demonstrating high-yield synthesis of a codon-optimized sfGFP reporter and the prototyping of a synthetic tetracycline-inducible promoter in S. venezuelae TX-TL based on the tetO-TetR repressor system. The aim of this system is to provide a host for the homologous production of exotic enzymes from Actinobacteria secondary metabolism in vitro. As an example, the authors demonstrate the soluble synthesis of a selection of enzymes (12-70 kDa) from the Streptomyces rimosus oxytetracycline pathway. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer

Science.gov (United States)

Garateix, Anoland; Salceda, Emilio; Zaharenko, André Junqueira; Pons, Tirso; Santos, Yúlica; Arreguín, Roberto; Ständker, Ludger; Forssmann, Wolf-Georg; Tytgat, Jan; Vega, Rosario

2018-01-01

Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC) inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM), and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG) neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae. PMID:29414882

PhcrTx2, a New Crab-Paralyzing Peptide Toxin from the Sea Anemone Phymanthus crucifer

Directory of Open Access Journals (Sweden)

Armando Alexei Rodríguez

2018-02-01

Full Text Available Sea anemones produce proteinaceous toxins for predation and defense, including peptide toxins that act on a large variety of ion channels of pharmacological and biomedical interest. Phymanthus crucifer is commonly found in the Caribbean Sea; however, the chemical structure and biological activity of its toxins remain unknown, with the exception of PhcrTx1, an acid-sensing ion channel (ASIC inhibitor. Therefore, in the present work, we focused on the isolation and characterization of new P. crucifer toxins by chromatographic fractionation, followed by a toxicity screening on crabs, an evaluation of ion channels, and sequence analysis. Five groups of toxic chromatographic fractions were found, and a new paralyzing toxin was purified and named PhcrTx2. The toxin inhibited glutamate-gated currents in snail neurons (maximum inhibition of 35%, IC50 4.7 µM, and displayed little or no influence on voltage-sensitive sodium/potassium channels in snail and rat dorsal root ganglion (DRG neurons, nor on a variety of cloned voltage-gated ion channels. The toxin sequence was fully elucidated by Edman degradation. PhcrTx2 is a new β-defensin-fold peptide that shares a sequence similarity to type 3 potassium channels toxins. However, its low activity on the evaluated ion channels suggests that its molecular target remains unknown. PhcrTx2 is the first known paralyzing toxin in the family Phymanthidae.

Effects of triiodothyronine on turnover rate and metabolizing enzymes for thyroxine in thyroidectomized rats.

Science.gov (United States)

Nagao, Hidenori; Sasaki, Makoto; Imazu, Tetsuya; Takahashi, Kenjo; Aoki, Hironori; Minato, Kouichi

2014-10-29

Previous studies in rats have indicated that surgical thyroidectomy represses turnover of serum thyroxine (T4). However, the mechanism of this process has not been identified. To clarify the mechanism, we studied adaptive variation of metabolic enzymes involved in T4 turnover. We compared serum T4 turnover rates in thyroidectomized (Tx) rats with or without infusion of active thyroid hormone, triiodothyronine (T3). Furthermore, the levels of mRNA expression and activity of the metabolizing enzymes, deiodinase type 1 (D1), type 2 (D2), uridine diphosphate-glucuronosyltransferase (UGT), and sulfotransferase were also compared in several tissues with or without T3 infusion. After the T3 infusion, the turnover rate of serum T4 in Tx rats returned to normal. Although mRNA expression and activity of D1 decreased significantly in both liver and kidneys without T3 infusion, D2 expression and activity increased markedly in the brain, brown adipose tissue, and skeletal muscle. Surprisingly, hepatic UGT mRNA expression and activity in Tx rats increased significantly in comparison with normal rats, and returned to normal after T3 infusion. This study suggests that repression of the disappearance of serum T4 in rats after Tx is a homeostatic response to decreased serum T3 concentrations. Additionally, T4 glucuronide is a storage form of T4, but may also have biological significance. These results suggest strongly that repression of deiodination of T4 by D1 in the liver and kidneys plays a major role in thyroid hormone homeostasis in Tx rats, and that hepatic UGT also plays a key role in this mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative studies of the endonucleases from two related Xenopus laevis retrotransposons, Tx1L and Tx2L: target site specificity and evolutionary implications.

Science.gov (United States)

Christensen, S; Pont-Kingdon, G; Carroll, D

2000-01-01

In the genome of the South African frog, Xenopus laevis, there are two complex families of transposable elements, Tx1 and Tx2, that have identical overall structures, but distinct sequences. In each family there are approximately 1500 copies of an apparent DNA-based element (Tx1D and Tx2D). Roughly 10% of these elements in each family are interrupted by a non-LTR retrotransposon (Tx1L and Tx2L). Each retrotransposon is flanked by a 23-bp target duplication of a specific D element sequence. In earlier work, we showed that the endonuclease domain (Tx1L EN) located in the second open reading frame (ORF2) of Tx1L encodes a protein that makes a single-strand cut precisely at the expected site within its target sequence, supporting the idea that Tx1L is a site-specific retrotransposon. In this study, we express the endonuclease domain of Tx2L (Tx2L EN) and compare the target preferences of the two enzymes. Each endonuclease shows some preference for its cognate target, on the order of 5-fold over the non-cognate target. The observed discrimination is not sufficient, however, to explain the observation that no cross-occupancy is observed - that is, L elements of one family have never been found within D elements of the other family. Possible sources of additional specificity are discussed. We also compare two hypotheses regarding the genome duplication event that led to the contemporary pseudotetraploid character of Xenopus laevis in light of the Tx1L and Tx2L data.

Subthalamic hGAD65 Gene Therapy and Striatum TH Gene Transfer in a Parkinson’s Disease Rat Model

Science.gov (United States)

Zheng, Deyu; Jiang, Xiaohua; Zhao, Junpeng; Duan, Deyi; Zhao, Huanying; Xu, Qunyuan

2013-01-01

The aim of the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson’s disease (PD). Here, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human glutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex vivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior was improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65 gene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in the internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control groups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This study suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD model rats, independent of the protection the DA neurons from death. PMID:23738148

Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

Science.gov (United States)

Uhlig, S; Nüsing, R; von Bethmann, A; Featherstone, R L; Klein, T; Brasch, F; Müller, K M; Ullrich, V; Wendel, A

1996-05-01

Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. LPS induced the release of TX and caused increased airway resistance after about 30 min. Both TX formation and LPS-induced bronchoconstriction were prevented by treatment with the unspecific COX inhibitor acetyl salicylic acid, the specific COX-2 inhibitor CGP-28238, dexamethasone, actinomycin D, or cycloheximide. LPS-induced bronchoconstriction was also inhibited by the TX receptor antagonist BM-13177. The TX-mimetic compound, U-46619, increased airway resistance predominantly by constricting terminal bronchioles. COX-2-specific mRNA in lung tissue was elevated after LPS exposure, and this increase was attenuated by addition of dexamethasone or of actinomycin D. In contrast to LPS, platelet-activating factor (PAF) induced immediate TX release and bronchoconstriction that was prevented by acetyl salicylic acid, but not by CGP-28238. LPS elicits the following biochemical and functional changes in rat lungs: (i) induction of COX-2; (ii) formation of prostaglandins and TX; (iii) activation of the TX receptor on airway smooth muscle cells; (iv) constriction of terminal bronchioles; and (v) increased airway resistance. In contrast to LPS, the PAF-induced TX release is likely to depend on COX-1.

The tarantula toxins ProTx-II and huwentoxin-IV differentially interact with human Nav1.7 voltage sensors to inhibit channel activation and inactivation.

Science.gov (United States)

Xiao, Yucheng; Blumenthal, Kenneth; Jackson, James O; Liang, Songping; Cummins, Theodore R

2010-12-01

The voltage-gated sodium channel Na(v)1.7 plays a crucial role in pain, and drugs that inhibit hNa(v)1.7 may have tremendous therapeutic potential. ProTx-II and huwentoxin-IV (HWTX-IV), cystine knot peptides from tarantula venoms, preferentially block hNa(v)1.7. Understanding the interactions of these toxins with sodium channels could aid the development of novel pain therapeutics. Whereas both ProTx-II and HWTX-IV have been proposed to preferentially block hNa(v)1.7 activation by trapping the domain II voltage-sensor in the resting configuration, we show that specific residues in the voltage-sensor paddle of domain II play substantially different roles in determining the affinities of these toxins to hNa(v)1.7. The mutation E818C increases ProTx-II's and HWTX-IV's IC(50) for block of hNa(v)1.7 currents by 4- and 400-fold, respectively. In contrast, the mutation F813G decreases ProTx-II affinity by 9-fold but has no effect on HWTX-IV affinity. It is noteworthy that we also show that ProTx-II, but not HWTX-IV, preferentially interacts with hNa(v)1.7 to impede fast inactivation by trapping the domain IV voltage-sensor in the resting configuration. Mutations E1589Q and T1590K in domain IV each decreased ProTx-II's IC(50) for impairment of fast inactivation by ~6-fold. In contrast mutations D1586A and F1592A in domain-IV increased ProTx-II's IC(50) for impairment of fast inactivation by ~4-fold. Our results show that whereas ProTx-II and HWTX-IV binding determinants on domain-II may overlap, domain II plays a much more crucial role for HWTX-IV, and contrary to what has been proposed to be a guiding principle of sodium channel pharmacology, molecules do not have to exclusively target the domain IV voltage-sensor to influence sodium channel inactivation.

76 FR 70365 - Prevailing Rate Systems; Redefinition of the Austin, TX and Waco, TX, Appropriated Fund Federal...

Science.gov (United States)

2011-11-14

... 3206-AM50 Prevailing Rate Systems; Redefinition of the Austin, TX and Waco, TX, Appropriated Fund... the Federal Prevailing Rate Advisory Committee to best match the counties proposed for redefinition to... Prevailing Rate Advisory Committee (FPRAC), the national labor-management committee responsible for advising...

Hanford Single Shell Tank Leak Causes and Locations - 241-TX Farm

Energy Technology Data Exchange (ETDEWEB)

Girardot, C. L.; Harlow, D> G.

2014-07-22

This document identifies 241-TX Tank Farm (TX Farm) leak causes and locations for the 100 series leaking tanks (241-TX-107 and 241-TX-114) identified in RPP-RPT-50870, Rev. 0, Hanford 241-TX Farm Leak Inventory Assessment Report. This document satisfies the TX Farm portion of the target (T04) in the Hanford Federal Facility Agreement and Consent Order milestone M-045-91F.

The TX-model - a quantitative heat loss analysis of district heating pipes by means of IR surface temperature measurements

Energy Technology Data Exchange (ETDEWEB)

Zinki, Heimo [ZW Energiteknik, Nykoeping (Sweden)

1996-11-01

The aim of this study was to investigate the possibility of analysing the temperature profile at the ground surface above buried district heating pipes in such a way that would enable the quantitative determination of heat loss from the pair of pipes. In practical applications, it is supposed that this temperature profile is generated by means of advanced IR-thermography. For this purpose, the principle of the TX - model has been developed, based on the fact that the heat losses from pipes buried in the ground have a temperature signature on the ground surface. Qualitative analysis of this temperature signature is very well known and in practical use for detecting leaks from pipes. These techniques primarily make use of relative changes of the temperature pattern along the pipe. In the quantitative heat loss analysis, however, it is presumed that the temperature profile across the pipes is related to the pipe heat loss per unit length. The basic idea is that the integral of the temperature profile perpendicular to the pipe, called TX, is a function of the heat loss, but is also affected by other parameters such as burial depth, heat diffusivity, wind, precipitation and so on. In order to analyse the parameters influencing the TX- factor, a simulation model for the energy balance at the ground surface has been developed. This model includes the heat flow from the pipe to the surface and the heat exchange at the surface with the environment due to convection, latent heat change, solar and long wave radiation. The simulation gives the surprising result that the TX factor is by and large unaffected during the course of a day even when the sun is shining, as long as other climate conditions are relatively stable (low wind, no rain, no shadows). The results from the simulations were verified at different sites in Denmark, Finland, Sweden and USA through a co-operative research program organised and partially financed by the IEA District Heating Programme, Task III, and

Suv39h1 Protects from Myocardial Ischemia-Reperfusion Injury in Diabetic Rats

Directory of Open Access Journals (Sweden)

Bo Yang

2014-04-01

Full Text Available Background: Patients with diabetes are at increased risk of ischemic events. Suv39h1 is a histone methyltransferase that catalyzes the methylation of histone 3 lysine 9, which is associated with the suppression of inflammatory genes in diabetes. However, the role of Suv39h1 in myocardial ischemia/reperfusion (I/R injury under diabetic condition has not been evaluated. Methods: To generate diabetic model, male SD rats were fed with 60% fat diet followed by intraperitoneal injection with 40mg/kg streptozotocin. Adenovirus encoding Suv39h1 gene was used for Suv39h1 overexpression. Each rat received injections of adenovirus at five myocardial sites. Three days after gene transfection, each rat was subjected to left main coronary artery occlusion and reperfusion. After 30 min ischemia and reperfusion for 4 h, the rats were euthanized for real-time PCR, Western blot, immunohistochemical staining, and morphometric analysis. Results: Delivery of Ad-Suv39h1 into the hearts of diabetic rats could markedly increase Suv39h1 expression. Up-regulation of Suv39h1 significantly reduced infarct size and tissue damage after I/R injury, which was associated with protection from apoptosis of cardiac myocytes and reduction of inflammatory response. In addition, compared with injury group, Ad-Suv39h1 led to a decreased activity of mitogen-activated protein kinase family and its down-steam transcriptional factor NF-κB. Conclusion: Overexpression of Suv39h1 results in the de-activation of proinflammatory pathways and reduced apoptosis and myocardial injury. Therefore, Suv39h1 might represent a novel therapeutic strategy to reduce I/R injury under diabetic condition.

75 FR 8994 - Certification of the Attorney General; Williamson County, TX

Science.gov (United States)

2010-02-26

... DEPARTMENT OF JUSTICE Certification of the Attorney General; Williamson County, TX In accordance... within the scope of the determinations of the Attorney General and the Director of the Census made under... September 23, 1975 (40 FR 43,746). Dated: February 23, 2010. Eric H. Holder Jr., Attorney General of the...

Proton Testing of nVidia Jetson TX1

Science.gov (United States)

Wyrwas, Edward J.

2017-01-01

Single-Event Effects (SEE) testing was conducted on the nVidia Jetson TX1 System on Chip (SOC); herein referred to as device under test (DUT). Testing was conducted at Massachusetts General Hospitals (MGH) Francis H. Burr Proton Therapy Center on October 16th, 2016 using 200MeV protons. This testing trip was purposed to provide a baseline assessment of the radiation susceptibility of the DUT as no previous testing had been conducted on this component.

TxDOT can help pave the way for distribution centers.

Science.gov (United States)

2010-05-01

TxDOT supports economic development in Texas. : Working through its district offices, TxDOT can help : developers avoid common transportation-related : problems associated with selected center sites. TxDOT : may also be able to help distribution cent...

Stability of binary complexes of Pb(II, Cd(II and Hg(II with maleic acid in TX100-water mixtures

Directory of Open Access Journals (Sweden)

M. Ramanaiah

2014-09-01

Full Text Available Binary complexes of maleic acid with toxic metal ions such as Pb(II, Cd(II and Hg(II have been studied in 0.0-2.5% v/v tritonX-100 (TX100 - water media at 303 K at an ionic strength of 0.16 M. The active forms of the ligand are LH2, LH- and L2-. The derived ‘best fit’ chemical speciation models are based on crystallographic R-factors, χ2 and Skewness and Kurtosis factors. The predominant species formed are of the type ML2, ML2H and ML3. The trend in variation of complex stability constants with change in the mole fraction of the medium is explained on the basis of prevailing electrostatic and non-electrostatic forces. The species distribution as a function of pH at different compositions of TX100-water mixtures and plausible speciation equilibria are presented and discussed. DOI: http://dx.doi.org/10.4314/bcse.v28i3.7

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-{sup 99m}

Energy Technology Data Exchange (ETDEWEB)

Fuscaldi, Leonardo Lima; Santos, Daniel Moreira dos; Pinheiro, Natalia Gabriela Silva; Araujo, Raquel Silva; Barros, Andre Luis Branco de; Resende, Jarbas Magalhaes; Fernandes, Simone Odilia Antunes; Lima, Maria Elena de; Cardoso, Valbert Nascimento, E-mail: valbertncardoso@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Analises Clinicas Toxicologica

2016-11-01

Background: Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with {sup 99m}Tc. Methods: Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with {sub 99m}Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl{sub 2} . 2H{sub 2}O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Results: Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol. L−1 (S. aureus) and 10.10 μmol. L−1 (E. coli

75 FR 31677 - Amendment of Class E Airspace; Corpus Christi, TX

Science.gov (United States)

2010-06-04

... Jose Island Airport, TX (Lat. 27[deg]56'40'' N., long. 96[deg]59'06'' W.) Rockport, Aransas County... Meacham Blvd., Fort Worth, TX 76137; telephone (817) 321- 7716. SUPPLEMENTARY INFORMATION: History On... Corpus Christi, TX [Amended] Corpus Christi International Airport, TX (Lat. 27[deg]46'13'' N., long. 97...

LyeTxI-b, a Synthetic Peptide Derived From Lycosa erythrognatha Spider Venom, Shows Potent Antibiotic Activity in Vitro and in Vivo

Directory of Open Access Journals (Sweden)

Pablo V. M. Reis

2018-04-01

Full Text Available The antimicrobial peptide LyeTxI isolated from the venom of the spider Lycosa erythrognatha is a potential model to develop new antibiotics against bacteria and fungi. In this work, we studied a peptide derived from LyeTxI, named LyeTxI-b, and characterized its structural profile and its in vitro and in vivo antimicrobial activities. Compared to LyeTxI, LyeTxI-b has an acetylated N-terminal and a deletion of a His residue, as structural modifications. The secondary structure of LyeTxI-b is a well-defined helical segment, from the second amino acid to the amidated C-terminal, with no clear partition between hydrophobic and hydrophilic faces. Moreover, LyeTxI-b shows a potent antimicrobial activity against Gram-positive and Gram-negative planktonic bacteria, being 10-fold more active than the native peptide against Escherichia coli. LyeTxI-b was also active in an in vivo model of septic arthritis, reducing the number of bacteria load, the migration of immune cells, the level of IL-1β cytokine and CXCL1 chemokine, as well as preventing cartilage damage. Our results show that LyeTxI-b is a potential therapeutic model for the development of new antibiotics against Gram-positive and Gram-negative bacteria.

Safranal, a saffron constituent, attenuates retinal degeneration in P23H rats.

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Laura Fernández-Sánchez

Full Text Available Saffron, an extract from Crocus sativus, has been largely used in traditional medicine for its antiapoptotic and anticarcinogenic properties. In this work, we investigate the effects of safranal, a component of saffron stigmas, in attenuating retinal degeneration in the P23H rat model of autosomal dominant retinitis pigmentosa. We demonstrate that administration of safranal to homozygous P23H line-3 rats preserves both photoreceptor morphology and number. Electroretinographic recordings showed higher a- and b-wave amplitudes under both photopic and scotopic conditions in safranal-treated versus non-treated animals. Furthermore, the capillary network in safranal-treated animals was preserved, unlike that found in untreated animals. Our findings indicate that dietary supplementation with safranal slows photoreceptor cell degeneration and ameliorates the loss of retinal function and vascular network disruption in P23H rats. This work also suggests that safranal could be potentially useful to retard retinal degeneration in patients with retinitis pigmentosa.

Optical photometry of TX0506+056

Science.gov (United States)

Keel, William; Santander, Marcos

2017-10-01

The blazar TX0506+056 has attracted recent attention through its location in the error box of a high-energy Ice Cube neutrino detection (https://gcn.gsfc.nasa.gov/gcn3/21916.gcn3) and gamma-ray flaring (Atel #10791) We report recent photometry of TX0506+056 obtained in Johnson V and Cousins R passbands using the 1-meter Kapteyn telescope at La Palma, operated remotely by the SARA consortium.

75 FR 66301 - Amendment of Class E Airspace; Corpus Christi, TX

Science.gov (United States)

2010-10-28

..., TX (Lat. 27[deg]48'43'' N., long. 97[deg]05'20'' W.) Rockport, San Jose Island Airport, TX (Lat. 27... Meacham Blvd., Fort Worth, TX 76137; telephone (817) 321- 7716. SUPPLEMENTARY INFORMATION: History On July... Christi International Airport, TX (Lat. 27[deg]46'13'' N., long. 97[deg]30'04'' W.) Corpus Christi NAS...

Characteristics of recombinantly expressed rat and human histamine H3 receptors.

Science.gov (United States)

Wulff, Birgitte S; Hastrup, Sven; Rimvall, Karin

2002-10-18

Human and rat histamine H(3) receptors were recombinantly expressed and characterized using receptor binding and a functional cAMP assay. Seven of nine agonists had similar affinities and potencies at the rat and human histamine H(3) receptor. S-alpha-methylhistamine had a significantly higher affinity and potency at the human than rat receptor, and for 4-[(1R*,2R*)-2-(5,5-dimethyl-1-hexynyl)cyclopropyl]-1H-imidazole (Perceptin) the preference was the reverse. Only two of six antagonists had similar affinities and potencies at the human and the rat histamine H(3) receptor. Ciproxifan, thioperamide and (1R*,2R*)-trans-2-imidazol-4 ylcyclopropyl) (cyclohexylmethoxy) carboxamide (GT2394) had significantly higher affinities and potencies at the rat than at the human histamine H(3) receptor, while for N-(4-chlorobenzyl)-N-(7-pyrrolodin-1-ylheptyl)guanidine (JB98064) the preference was the reverse. All antagonists also showed potent inverse agonism properties. Iodoproxyfan, Perceptin, proxyfan and GR175737, compounds previously described as histamine H(3) receptor antagonists, acted as full or partial agonists at both the rat and the human histamine H(3) receptor. Copyright 2002 Elsevier Science B.V.

Efficacy of Live-Attenuated H9N2 Influenza Vaccine Candidates Containing NS1 Truncations against H9N2 Avian Influenza Viruses

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Sujuan Chen

2017-06-01

Full Text Available H9N2 avian influenza virus is a zoonotic agent with a broad host range that can contribute genetic information to H5 or H7N9 subtype viruses, which are significant threats to both humans and birds. Thus, there is a great need for a vaccine to control H9N2 avian influenza. Three mutant viruses of an H9N2 virus A/chicken/Taixing/10/2010 (rTX-NS1-73, rTX-NS1-100, and rTX-NS1-128 were constructed with different NS1 gene truncations and confirmed by western blot analysis. The genetic stability, pathogenicity, transmissibility, and host immune responses toward these mutants were evaluated. The mutant virus rTX-NS1-128 exhibited the most attenuated phenotype and lost transmissibility. The expression levels of interleukin 12 in the nasal and tracheal tissues from chickens immunized with rTX-NS1-128 were significantly upregulated on day 3 post-immunization and the IgA and IgG antibody levels were significantly increased on days 7, 14, and 21 post-immunization when compared to chickens that received an inactivated vaccine. rTX-NS1-128 also protected chickens from challenge by homologous and heterologous H9N2 avian influenza viruses. The results indicate that rTX-NS1-128 can be used as a potential live-attenuated vaccine against H9N2 avian influenza.

Thyroxine binding to serum thyronine-binding globulin in thyroidectomized adult and normal neonatal rats

International Nuclear Information System (INIS)

Young, R.A.; Meyers, B.; Alex, S.; Fang, S.L.; Braverman, L.E.

1988-01-01

The amount of tracer [125I]T4 bound to serum thyronine-binding globulin (TBG) was measured by polyacrylamide gel electrophoresis in adult thyroidectomized (TX) rats and normal 1-day to 4-week-old rat puts. Thyroidectomy was associated with the appearance of significant amounts of [125I]T4 binding to serum TBG in lean rats, but not in obese Zucker rats. Treatment of the TX rats in vivo with replacement doses of T4 prevented this increase in TBG binding, but enrichment of serum from TX rats with T4 did not. Significant amounts of tracer [125I]T4 binding to TBG was present in serum from 1- to 3-week-old normal rat pups, but not in 1-day- or 4-week-old pups. There were significantly higher levels of TBG binding of [125I]T4 in serum from 2-week-old rat pups raised in litters of 16 pups compared to those raised in litters of 4 pups. All manipulations that result in the appearance of TBG in rat serum also result in either weight loss or a slowing in the rate of growth, suggesting that the appearance of TBG in rat serum has a nutritional component. This possibility is further supported by the observations that increases in TBG binding of [125I]T4 are not found in obese Zucker rats fed a low protein-high carbohydrate diet for 14 days or fasted for 7 days, or after thyroidectomy, perhaps owing to the large stores of fuel in the obese rat

76 FR 52563 - Special Local Regulations; Sabine River, Orange, TX

Science.gov (United States)

2011-08-23

...-AA08 Special Local Regulations; Sabine River, Orange, TX AGENCY: Coast Guard, DHS. ACTION: Temporary... Regulations; Sabine River, Orange, TX in the Federal Register (76 FR 103). We received no comments on the... Regulations for Marine Events; Sabine River, Orange, TX. (a) Definitions. As used in this section...

75 FR 31677 - Amendment of Class E Airspace; Austin, TX

Science.gov (United States)

2010-06-04

...-1152; Airspace Docket No. 09-ASW-31] Amendment of Class E Airspace; Austin, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends Class E airspace for the Austin, TX... Procedures (SIAPs) at Austin Executive Airport, Austin, TX. The FAA is taking this action to enhance the...

Additive effect of mesenchymal stem cells and defibrotide in an arterial rat thrombosis model.

Science.gov (United States)

Dilli, Dilek; Kılıç, Emine; Yumuşak, Nihat; Beken, Serdar; Uçkan Çetinkaya, Duygu; Karabulut, Ramazan; Zenciroğlu, Ayşegu L

2017-06-01

In this study, we aimed to investigate the additive effect of mesenchymal stem cells (MSC) and defibrotide (DFT) in a rat model of femoral arterial thrombosis. Thirty Sprague Dawley rats were included. An arterial thrombosis model by ferric chloride (FeCl3) was developed in the left femoral artery. The rats were equally assigned to 5 groups: Group 1-Sham-operated (without arterial injury); Group 2-Phosphate buffered saline (PBS) injected; Group 3-MSC; Group 4-DFT; Group 5-MSC + DFT. All had two intraperitoneal injections of 0.5 ml: the 1st injection was 4 h after the procedure and the 2nd one 48 h after the 1st injection. The rats were sacrificed 7 days after the 2nd injection. Although the use of human bone marrow-derived (hBM) hBM-MSC or DFT alone enabled partial resolution of the thrombus, combining them resulted in near-complete resolution. Neovascularization was two-fold better in hBM-MSC + DFT treated rats (11.6 ± 2.4 channels) compared with the hBM-MSC (3.8 ± 2.7 channels) and DFT groups (5.5 ± 1.8 channels) (P < 0.0001 and P= 0.002, respectively). The combined use of hBM-MSC and DFT in a rat model of arterial thrombosis showed additive effect resulting in near-complete resolution of the thrombus.

Behavioral Evaluation of hMSC-GFP+ Transplantation in an Hemiparkinson Experimental Model in Wistar Rat

Directory of Open Access Journals (Sweden)

Jéssica Paola Alcázar Arzuza

2017-05-01

Full Text Available The effect of hMSCs-GFP+ transplantation was evaluated in an experimental model of Parkinson's disease (PD in 27 Wistar rats, or in three experimental groups: control (CON  n=7, injured (LES n=10 and transplanted (LES+T n=10. In order to evaluate the influence of the transplantation on the motor behavior, one month after the injury, rotation behavior induced by apomorphine, neurological test, transversal bar and SNpc cells positive to TH were developed. Using the Anova test, there was a decrease in the number of turns in transplanted animals (p=0.005 as well as in the neurological test (p=0.0004 and in the transverse bar that lead to this group in an intermediate position regarding LES and CON groups. There is a possible recovery of the transplantation-mediated nigroestriatal pathway of hMSC-GFP +.

Non-imidazole-based histamine H3 receptor antagonists with anticonvulsant activity in different seizure models in male adult rats

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Sadek B

2016-11-01

Full Text Available Bassem Sadek,1 Ali Saad,1 Gniewomir Latacz,2 Kamil Kuder,2 Agnieszka Olejarz,2 Tadeusz Karcz,2 Holger Stark,3 Katarzyna Kieć-Kononowicz2 1Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates; 2Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland; 3Department of Pharmaceutical and Medicinal Chemistry, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University, Düsseldorf, Germany Abstract: A series of twelve novel non-imidazole-based ligands (3–14 was developed and evaluated for its in vitro binding properties at the human histamine H3 receptor (hH3R. The novel ligands were investigated for their in vivo protective effects in different seizure models in male adult rats. Among the H3R ligands (3–14 tested, ligand 14 showed significant and dose-dependent reduction in the duration of tonic hind limb extension in maximal electroshock (MES-induced seizure model subsequent to acute systemic administration (5, 10, and 20 mg/kg, intraperitoneally, whereas ligands 4, 6, and 7 without appreciable protection in MES model were most promising in pentylenetetrazole (PTZ model. Moreover, the protective effect observed for ligand 14 in MES model was lower than that observed for the reference drug phenytoin and was entirely abrogated when rats were co-administered with the brain-penetrant H1R antagonist pyrilamine (PYR but not the brain-penetrant H2R antagonist zolantidine (ZOL, demonstrating that histaminergic neurotransmission by activation of postsynaptically located H1Rs seems to be involved in the protective action. On the contrary, PYR and ZOL failed to abrogate the full protection provided by 4 in PTZ model and the moderate protective effect by 14 in strychnine (STR model. Moreover, the experimental and in silico estimation of properties such as metabolism was

"60x30TX" 2017 Progress Report

Science.gov (United States)

Texas Higher Education Coordinating Board, 2017

2017-01-01

Central to the goals of "60x30TX" is maintaining Texas as a global economic player by having an educated population, making them aware of their marketable skills, and helping them manage their student loan debt. If the 2016 progress report for "60x30TX" was about getting out the word, this report is about expanding that reach…

Tracking of In-111-labeled human umbilical tissue-derived cells (hUTC) in a rat model of cerebral ischemia using SPECT imaging

International Nuclear Information System (INIS)

Arbab, Ali S; Chopp, Michael; Thiffault, Christine; Navia, Bradford; Victor, Stephen J; Hong, Klaudyne; Zhang, Li; Jiang, Quan; Varma, Nadimpalli RS; Iskander, ASM

2012-01-01

In order to increase understanding of how infused cells work, it becomes important to track their initial movement, localization, and engraftment efficiency following transplantation. However, the available in vivo cell tracking techniques are suboptimal. The study objective was to determine the biodistribution of intravenously administered Indium-111 (In-111) oxine labeled human umbilical tissue-derived cells (hUTC) in a rat model of transient middle cerebral occlusion (tMCAo) using single photon emission computed tomography (SPECT). Rats received 3 million In-111 labeled hUTC (i.v.) 48 hrs after tMCAo. Following the administration of either hUTC or equivalent dose of In-111-oxine (18.5 MBq), animals underwent SPECT imaging on days 0, 1, and 3. Radioactivity in various organs as well as in the stroke area and contralateral hemisphere was determined, decay corrected and normalized to the total (whole body including head) radioactivity on day 0. Immunohistochemical analysis was also performed to confirm the beneficial effects of hUTC on vascular and synaptic density, and apoptosis. Most of the radioactivity (43.36±23.07% on day 0) trafficked to the lungs immediately following IV administration of In-111 labeled hUTC (day 0) and decreased drastically to 8.81±7.75 and 4.01±4.52% on days 1 and 3 post-injection, respectively. In contrast, radioactivity measured in the lung of animals that received In-111-oxine alone remained relatively unchanged from day 0 to day 1 (18.38±5.45% at day 0 to 12.59±5.94%) and decreased to 8.34±4.25% on day 3. Significantly higher radioactivity was observed in stroke areas of animals that received In-111 labeled hUTC indicating the presence of cells at the site of injury representing approximately 1% of total administered dose. In addition, there was significant increase in vascular and synaptophysin immunoreactivity in stroke areas of rats that received In-111 labeled hUTC. The present studies showed the tracking of In-111 labeled h

75 FR 52065 - SharePlus Federal Bank, Plano, TX; Approval of Conversion Application

Science.gov (United States)

2010-08-24

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision [AC-50: OTS Nos. 17972 and H4743] SharePlus Federal Bank, Plano, TX; Approval of Conversion Application Notice is hereby given that on August 12, 2010, the Office of Thrift Supervision approved the application of SharePlus Federal Bank, Piano...

Accumulation of radioactivity after repeated infusion of 3H-adrenaline and 3H-noradrenaline in the rat as a model animal.

Science.gov (United States)

Lepschy, M; Filip, T; Palme, R G

2014-10-01

Besides enzymatic inactivation, catecholamines bind non-enzymatically and irreversible to proteins. The physiological impact of these catecholamine adducts is still unclear. We therefore collected basic data about the distribution of catecholamine adducts in the rat after repeated intravenous administration of (3)H-adrenaline and (3)H-noradrenaline. In all animals radioactivity in blood increased until the last injection on Day 7 and decreased then slowly close to background values (plasma) or remained higher (erythrocytes). In all sampled tissues radioactivity could be found, but only in hair high amounts remained present even after 3 weeks. Half-life of rat serum albumin loaded with (3)H-adrenaline or (3)H-noradrenaline was not altered. This study provides basic knowledge about the distribution of catecholamines or their adducts, but physiological effects could not be demonstrated. However, for the first time deposition and accumulation of catecholamines (adducts) in the hair could be proven, suggesting that hair might be used for evaluating long term stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

TxDOT administration research : tasks completed in FY2009.

Science.gov (United States)

2010-01-01

Texas Department of Transportation (TxDOT) Project 0-6581-TI, TxDOT Administration : Research, encompasses multiple tasks that explore and support administrative aspects of : transportation research. : The project term began in October 2008 and has b...

Naked DNA Immunization for Prevention of Prostate Cancer in a Dunning Rat Prostate Tumor Model

National Research Council Canada - National Science Library

Mincheff, Milcho

2003-01-01

...: H-PSMA-T, R-"PSMA"-T, H-PSA, H-PSA-T, H-PAP-T and R"PSMA"-S. Preliminary studies using the Copenhagen rat tumor prostate model showed uniform tumor development in rats that were injected subcutaneously with 100 000 AT3B-lPSMA,PSA cells...

75 FR 15360 - Proposed Amendment of Class E Airspace; Austin, TX

Science.gov (United States)

2010-03-29

...-1152; Airspace Docket No. 09-ASW-31] Proposed Amendment of Class E Airspace; Austin, TX AGENCY: Federal... proposes to amend Class E airspace in the Austin, TX area. Additional controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAPs) at Austin Executive Airport, Austin, TX. The...

Characterization of (/sup 3/H)paroxetine binding in rat brain

Energy Technology Data Exchange (ETDEWEB)

Marcusson, J.O.; Bergstroem, M.E.; Eriksson, K.; Ross, S.B.

1988-06-01

The binding of the 5-hydroxytryptamine (5-HT, serotonin) uptake inhibitor (3H)paroxetine to rat cortical homogenates has been characterized. The effect of tissue concentration was examined and, with 0.75 mg wet weight tissue/ml in a total volume of 1,600 microliter, the binding was optimized with an apparent dissociation constant (KD) of 0.03-0.05 nM. Competition experiments with 5-HT, citalopram, norzimeldine, and desipramine revealed a high (90%) proportion of displaceable binding that fitted a single-site binding model. Fluoxetine and imipramine revealed, in addition to a high-affinity (nanomolar) site, also a low-affinity (micromolar) site representing approximately 10% of the displaceable binding. The specificity of the (3H)paroxetine binding was emphasized by the fact that 5-HT was the only active neurotransmitter bound and that the serotonin S1 and S2 antagonist methysergide was without effect on the binding. Both 5-HT- and fluoxetine-sensitive (3H)paroxetine binding was completely abolished after protease treatment, suggesting that the binding site is of protein nature. Saturation studies with 5-HT (100 microM) sensitive (3H)paroxetine binding were also consistent with a single-site binding model, and the binding was competitively inhibited by 5-HT and imipramine. The number of binding sites (Bmax) for 5-HT-sensitive (3H)paroxetine and (3H)imipramine binding was the same, indicating that the radioligands bind to the same sites. Lesion experiments with p-chloroamphetamine resulted in a binding in frontal and parietal cortices becoming undetectable and a greater than 60% reduction in the striatum and hypothalamus, indicating a selective localization on 5-HT terminals. Together these findings suggest that (3H)paroxetine specifically and selectively labels the substrate recognition site for 5-HT uptake in rat brain.

2H Kinetic Isotope Effects and pH Dependence of Catalysis as Mechanistic Probes of Rat Monoamine Oxidase A: Comparisons with the Human Enzyme‡

Science.gov (United States)

Wang, Jin; Edmondson, Dale E.

2011-01-01

Monoamine oxidase A (MAO A) is a mitochondrial outer membrane-bound flavoenzyme important in the regulation of serotonin and dopamine levels. Since the rat is extensively used as an animal model in drug studies, it is important to understand how rat MAO A behaves in comparison with the more extensively studied human enzyme. For many reversible inhibitors, rat MAO A exhibits Ki values similar to those of human MAO A. The pH profile of kcat for rat MAO A shows a pKa of 8.2±0.1 for the benzylamine ES complex and pKa values of 7.5±0.1 and 7.6±0.1 for the respective ES complexes with p-CF3-1H and p-CF3-2H-benzylamine. In contrast to the human enzyme, the rat enzyme exhibits a single pKa value (8.3±0.1) with kcat/Km benzylamine vs. pH and pKa values of 7.8±0.1 and 8.1±0.2 are found for the ascending limbs, respectively, of kcat/Km vs. pH profiles for p-CF3-1H and p-CF3-2H-benzylamine and 9.3±0.1 and 9.1±0.2 for their respective descending limbs. The oxidation of para-substituted benzylamine substrate analogues by rat MAO A exhibit large deuterium kinetic isotope effects on kcat and on kcat/Km. These effects are pH-independent, and range from 7 to 14, demonstrating a rate-limiting α-C-H bond cleavage step in catalysis. Quantitative structure-activity correlations of log kcat with the electronic substituent parameter (σ) at pH 7.5 and at 9.0 show a dominant contribution with positive ρ values (+1.2 – 1.3) and a pH-independent negative contribution from the steric term. Quantitative structure-activity relationship analysis of the binding affinities of the para-substituted benzylamine analogues to rat MAO A show an increased van der Waals volumes (Vw) increases the affinity of the deprotonated amine for the enzyme. These results demonstrate that rat MAO A exhibits similar but not identical functional properties with the human enzyme and provide additional support for C-H bond cleavage via a polar nucleophilic mechanism. PMID:21819071

²H kinetic isotope effects and pH dependence of catalysis as mechanistic probes of rat monoamine oxidase A: comparisons with the human enzyme.

Science.gov (United States)

Wang, Jin; Edmondson, Dale E

2011-09-06

Monoamine oxidase A (MAO A) is a mitochondrial outer membrane-bound flavoenzyme important in the regulation of serotonin and dopamine levels. Because the rat is extensively used as an animal model in drug studies, it is important to understand how rat MAO A behaves in comparison with the more extensively studied human enzyme. For many reversible inhibitors, rat MAO A exhibits K(i) values similar to those of human MAO A. The pH profile of k(cat) for rat MAO A shows a pK(a) of 8.2 ± 0.1 for the benzylamine ES complex and pK(a) values of 7.5 ± 0.1 and 7.6 ± 0.1 for the ES complexes with p-CF(3)-(1)H- and p-CF(3)-(2)H-benzylamine, respectively. In contrast to the human enzyme, the rat enzyme exhibits a single pK(a) value (8.3 ± 0.1) with k(cat)/K(m) for benzylamine versus pH and pK(a) values of 7.8 ± 0.1 and 8.1 ± 0.2 for the ascending limbs, respectively, of k(cat)/K(m) versus pH profiles for p-CF(3)-(1)H- and p-CF(3)-(2)H-benzylamine and 9.3 ± 0.1 and 9.1 ± 0.2 for the descending limbs, respectively. The oxidation of para-substituted benzylamine substrate analogues by rat MAO A has large deuterium kinetic isotope effects on k(cat) and on k(cat)/K(m). These effects are pH-independent and range from 7 to 14, demonstrating a rate-limiting α-C-H bond cleavage step in catalysis. Quantitative structure-activity correlations of log k(cat) with the electronic substituent parameter (σ) at pH 7.5 and 9.0 show a dominant contribution with positive ρ values (1.2-1.3) and a pH-independent negative contribution from the steric term. Quantitative structure-activity relationship analysis of the binding affinities of the para-substituted benzylamine analogues for rat MAO A shows an increased van der Waals volume (V(w)) increases the affinity of the deprotonated amine for the enzyme. These results demonstrate that rat MAO A exhibits functional properties similar but not identical with those of the human enzyme and provide additional support for C-H bond cleavage via a polar

Greening America's Capitals - Austin, TX

Science.gov (United States)

Report on the technical assistance project to help Austin, TX, develop a vision for the South Central Waterfront that incorporates green infrastructure to manage stormwater runoff, makes streets safer, and spurs investment.

Human metabolites of brevetoxin PbTx-2: Identification and confirmation of structure

Science.gov (United States)

Guo, Fujiang; An, Tianying; Rein, Kathleen S.

2010-01-01

Four metabolites were identified upon incubation of brevetoxin (PbTx-2) with human liver microsomes. Chemical transformation of PbTx-2 confirmed the structures of three known metabolites BTX-B5, PbTx-9 and 41, 43-dihydro-BTX-B5 and a previously unknown metabolite, 41, 43-dihydro-PbTx-2. These metabolites were also observed upon incubation of PbTx-2 with nine human recombinant cytochrome P450s (1A1, 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5). Cytochrome P450 3A4 produced oxidized metabolites while other CYPs generated the reduced products. PMID:20600229

Tx-Rx Isolation Exploiting Tunable Balanced-Unbalanced Antennas Architecture

DEFF Research Database (Denmark)

Tatomirescu, Alexandru; Alrabadi, Osama; Pedersen, Gert Frølund

2012-01-01

The duplex filter is probably still the most expensive component in mobile handsets for the significant Transmitter (Tx) — Receiver (Rx) isolation required. This paper suggests to relax or even replace the duplex filter by equipping the Tx and the Rx with two separate antennas. The two antennas a...

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m.

Science.gov (United States)

Fuscaldi, Leonardo Lima; Dos Santos, Daniel Moreira; Pinheiro, Natália Gabriela Silva; Araújo, Raquel Silva; de Barros, André Luís Branco; Resende, Jarbas Magalhães; Fernandes, Simone Odília Antunes; de Lima, Maria Elena; Cardoso, Valbert Nascimento

2016-01-01

Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with (99m)Tc. Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with (99m)Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2 (.) 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values EDDA). The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

The characterization of obese polycystic ovary syndrome rat model suitable for exercise intervention.

Directory of Open Access Journals (Sweden)

Chuyan Wu

Full Text Available To develop a new polycystic ovary syndrome (PCOS rat model suitable for exercise intervention.Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24, PCOS rats with ordinary diet (PO, n = 6, and control rats with ordinary diet (CO, n = 6. Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6, sedentary with a continuation of high-fat diet (PF-SF, n = 6, exercise with an ordinary diet (PF-EO, n = 6. Fasting blood glucose (FBG and insulin (FINS, estrogen (E2, progesterone (P, and testosterone (T in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0.Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1, 2 h postprandial blood glucose (PBG2, FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO.By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention.

Effects of Forced Swimming Stress on ERK and Histone H3 Phosphorylation in Limbic Areas of Roman High- and Low-Avoidance Rats.

Science.gov (United States)

Morello, Noemi; Plicato, Ornella; Piludu, Maria Antonietta; Poddighe, Laura; Serra, Maria Pina; Quartu, Marina; Corda, Maria Giuseppa; Giorgi, Osvaldo; Giustetto, Maurizio

2017-01-01

Stressful events evoke molecular adaptations of neural circuits through chromatin remodeling and regulation of gene expression. However, the identity of the molecular pathways activated by stress in experimental models of depression is not fully understood. We investigated the effect of acute forced swimming (FS) on the phosphorylation of the extracellular signal-regulated kinase (ERK)1/2 (pERK) and histone H3 (pH3) in limbic brain areas of genetic models of vulnerability (RLA, Roman low-avoidance rats) and resistance (RHA, Roman high-avoidance rats) to stress-induced depression-like behavior. We demonstrate that FS markedly increased the density of pERK-positive neurons in the infralimbic (ILCx) and the prelimbic area (PrLCx) of the prefrontal cortex (PFCx), the nucleus accumbens, and the dorsal blade of the hippocampal dentate gyrus to the same extent in RLA and RHA rats. In addition, FS induced a significant increase in the intensity of pERK immunoreactivity (IR) in neurons of the PFCx in both rat lines. However, RHA rats showed stronger pERK-IR than RLA rats in the ILCx both under basal and stressed conditions. Moreover, the density of pH3-positive neurons was equally increased by FS in the PFCx of both rat lines. Interestingly, pH3-IR was higher in RHA than RLA rats in PrLCx and ILCx, either under basal conditions or upon FS. Finally, colocalization analysis showed that in the PFCx of both rat lines, almost all pERK-positive cells express pH3, whereas only 50% of the pH3-positive neurons is also pERK-positive. Moreover, FS increased the percentage of neurons that express exclusively pH3, but reduced the percentage of cells expressing exclusively pERK. These results suggest that (i) the distinctive patterns of FS-induced ERK and H3 phosphorylation in the PFCx of RHA and RLA rats may represent molecular signatures of the behavioural traits that distinguish the two lines and (ii) FS-induced H3 phosphorylation is, at least in part, ERK-independent.

High affinity binding of [3H]cocaine to rat liver microsomes

International Nuclear Information System (INIS)

El-Maghrabi, E.A.; Calligaro, D.O.; Eldefrawi, M.E.

1988-01-01

] 3 H]cocaine bound reversible, with high affinity and stereospecificity to rat liver microsomes. Little binding was detected in the lysosomal, mitochondrial and nuclear fractions. The binding kinetics were slow and the kinetically calculated K/sub D/ was 2 nM. Induction of mixed function oxidases by phenobarbital did not produce significant change in [ 3 H]cocaine binding. On the other hand, chronic administration of cocaine reduced [ 3 H]cocaine binding drastically. Neither treatment affected the affinity of the liver binding protein for cocaine. Microsomes from mouse and human livers had less cocaine-binding protein and lower affinity for cocaine than those from rat liver. Binding of [ 3 H]cocaine to rat liver microsomes was insensitive to monovalent cations and > 10 fold less sensitive to biogenic amines than the cocaine receptor in rat striatum. However, the liver protein had higher affinity for cocaine and metabolites except for norcocaine. Amine uptake inhibitors displaced [ 3 H]cocaine binding to liver with a different rank order of potency than their displacement of [ 3 H]cocaine binding to striatum. This high affinity [ 3 H]cocaine binding protein in liver is not likely to be monooxygenase, but may have a role in cocaine-induced hepatotoxicity

75 FR 64972 - Proposed Revocation of Class E Airspace; Lone Star, TX

Science.gov (United States)

2010-10-21

...-0772; Airspace Docket No. 10-ASW-10] Proposed Revocation of Class E Airspace; Lone Star, TX AGENCY... action proposes to remove Class E airspace at Lone Star, TX. Abandonment of the former Lone Star Steel... need for controlled airspace in the Lone Star, TX, area. The FAA is taking this action to ensure the...

Antibody Contributes to Heterosubtypic Immunity In the Cotton Rat Model of Influenza

Science.gov (United States)

2010-09-29

H1N2 swine influenza virus in pigs previously infected with H1N1 and/or H3N2 subtypes. Vaccine 21: 1375–1381. Wei, C.J., J.C. Boyington, P.M...contributes to heterosubtypic protection against influenza A-induced tachypnea in cotton rats" Name of Candidate: r. Timothy M. Straight Doctor of...Heterosubtypic Immunity In the Cotton Rat Model of Influenza " is appropriately acknowledged and, beyond brief excerpts, is with the permission of the

The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1α targeted gene expression

International Nuclear Information System (INIS)

Miyake, Kotaro; Nishioka, Masanori; Imura, Satoru; Batmunkh, Erdenebulgan; Uto, Yoshihiro; Nagasawa, Hideko; Hori, Hitoshi; Shimada, Mitsuo

2012-01-01

Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P < 0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P < 0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules. -- Highlights: ► We designed and synthesized novel hypoxic cytoxin, TX-2098. ► TX-2098 inhibited the proliferation of human pancreatic cancer cells than TPZ. ► TX-2098 reduced VEGF protein level than TPZ. ► TX-2098 inhibited mRNA expression of VEGF, GLUT1 and Aldolase A, not HIF-1α. ► TX-2098 improved the survival in

The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1{alpha} targeted gene expression

Energy Technology Data Exchange (ETDEWEB)

Miyake, Kotaro, E-mail: hif.panc@gmail.com [Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503 (Japan); Nishioka, Masanori; Imura, Satoru; Batmunkh, Erdenebulgan [Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503 (Japan); Uto, Yoshihiro [Department of Biological Science and Technology, Institute of Socio Technosciences, The University of Tokushima Graduate School, Tokushima 770-8503 (Japan); Nagasawa, Hideko [Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu 501-1196 (Japan); Hori, Hitoshi [Department of Biological Science and Technology, Institute of Socio Technosciences, The University of Tokushima Graduate School, Tokushima 770-8503 (Japan); Shimada, Mitsuo [Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503 (Japan)

2012-08-01

Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1{alpha} (HIF-1{alpha}), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P < 0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P < 0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules. -- Highlights: Black-Right-Pointing-Pointer We designed and synthesized novel hypoxic cytoxin, TX-2098. Black-Right-Pointing-Pointer TX-2098 inhibited the proliferation of human pancreatic cancer cells than TPZ. Black-Right-Pointing-Pointer TX-2098 reduced VEGF protein level than TPZ. Black-Right-Pointing-Pointer TX-2098

Tank 241-TX-113 rotary mode core sampling and analysis plan

International Nuclear Information System (INIS)

McCain, D.J.

1998-01-01

This sampling and analysis plan (SAP) identities characterization objectives pertaining to sample collection, laboratory analytical evaluation, and reporting requirements for push mode core samples from tank 241-TX-113 (TX-113). The Tank Characterization Technical Sampling Basis document identities Retrieval, Pretreatment and Immobilization as an issue that applies to tank TX-113. As a result, a 150 gram composite of solids shall be made and archived for that program. This tank is not on a Watch List

78 FR 48298 - Amendment of Class E Airspace; Commerce, TX

Science.gov (United States)

2013-08-08

...-0269; Airspace Docket No. 13-ASW-3] Amendment of Class E Airspace; Commerce, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends Class E airspace at Commerce, TX. Additional controlled airspace is necessary to accommodate new Area Navigation (RNAV...

Ethanol intake and 3H-serotonin uptake I: A study in Fawn-Hooded rats

International Nuclear Information System (INIS)

Daoust, M.; Compagnon, P.; Legrand, E.; Boucly, P.

1991-01-01

Ethanol intake and synaptosomal 3 H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased in alcoholized Fawn-Hooded rats. These results indicate that synaptosomal 3 H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces 3 H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system

Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

Science.gov (United States)

Zhang, Yu; Niewiesk, Stefan; Li, Jianrong

2014-01-01

Human metapneumovirus (hMPV) is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU) of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU) of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection. PMID:25438015

Characteristics of central binding sites for [3H] DAMGO in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Gulati, A.; Bhargava, H.N.

1990-01-01

The binding of [ 3 H] DAMGO, a highly selective ligand for μ-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. [ 3 H] DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B max value) and apparent dissociation constant (K d value) of [ 3 H] DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B max value of [ 3 H] DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K d values in the two strains did not differ. On the other hand, the B max value of [ 3 H] DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K d values in the two strains were similar

Alkali/TX sub 2 catalysts for CO/H sub 2 conversion to C sub 1 -C sub 4 alcohols

Energy Technology Data Exchange (ETDEWEB)

Klier, K.; Herman, R. G.; Bastian, R.

1990-01-01

The objective of this research is to investigate and develop novel catalysts for the conversion of coal-derived synthesis gas into C{sub 1}-C{sub 4} alcohols by a highly selective process. Therefore, the variations of catalyst activity and selectivity for the synthesis of alcohols from H{sub 2}/CO {le}1 synthesis gas for a series of A/TX{sub 2} compounds, where A is a surface alkali dopant, T is a transition metal, and X ia a S, Se, or Te, will be determined. This quarter, a fresh batch of MoS{sub 2} was synthesized, and new Cs/MoS{sub 2} catalysts were prepared by alkali doping and were tested to demonstrate that the preparation and testing procedures were reproducible by different personnel. Preparations of RuS{sub 2} and Cs/RuS{sub 2} catalysts were initiated, and the preparations and testing of these catalysts will be described in the next quarterly report. 2 refs., 1 fig., 1 tab.

Photometric Orbit of TX UMa

Directory of Open Access Journals (Sweden)

Kyu-Dong Oh

1986-06-01

Full Text Available Two-color photometric light curves (Oh and Chan 1984 of the eclipsing binary TX UMa have been analyzed by the method of differential corrections of the model of Wilson and Devinney(1971. The system found to be simi-detached with cooler and less massive component filling its Roche lobe. The absolute dimensions have been derived from the results of the photometric solutions with spectroscopic elements of Hiltner(1945. It is assumed that the B8V primary component is on the zero age main sequence stage of the core hydrogen burning and the secondary os at the core contraction stage after the shell hydrogen burning stage according to the Iben's (1967 evolutional tracks for 3.0m_solar and 1.0m_solar.

75 FR 41119 - Special Local Regulations; Sabine River, Orange, TX

Science.gov (United States)

2010-07-15

...-AA08 Special Local Regulations; Sabine River, Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of... the Port Arthur Captain of the Port Zone on the Sabine River, Orange, Texas. This Special Local... Orange, TX, Thunder on the Sabine boat races. The powerboat race and associated testing will occur...

78 FR 48294 - Amendment of Class E Airspace; Mason, TX

Science.gov (United States)

2013-08-08

...-1141; Airspace Docket No. 12-ASW-12] Amendment of Class E Airspace; Mason, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends Class E airspace at Mason, TX... Approach Procedures at Mason County Airport. This action enhances the safety and management of Instrument...

Radiolabelling of phoneutria nigriventer spider toxin (Tx1): a tool to study its binding site

International Nuclear Information System (INIS)

Santos, Raquel Gouvea dos; Diniz, Carlos Roberto; Nascimento, Marta Cordeiro; Lima, Maria Elena de

1996-01-01

The neurotoxin Tx1, isolated from the venom of the South American spider Phoneutria nigriventer produces tail elevation and spastic paralysis of posterior limbs after intracerebral ventricular injection in mice. Tx1 also produces ileum contraction in bioassay. We have investigated the binding of radioiodinated-Tx1 ( 125 I-Tx1) on the preparation of myenteric plexus-longitudinal muscle membrane from guinea pig ileum (MPLM) as a tool to characterize the interaction of this neurotoxin with its site. The neurotoxin Tx1 was radioiodinated with Na 125 I by the lactoperoxidase method. 125 I-Tx1 specifically binds to a single class of noninteracting binding sites of high affinity (Kd= 3.5 x 10 -10 M) and low capacity (1.2 pmol/mg protein). The specific binding increased in parallel with the protein concentration. In competition experiments the ligands of ionic channels used (sodium, potassium and calcium) did not affect the binding of 125 I-Tx1 to MPLM neither did the cholinergic ligands (hemicholinium-3, hexamethonium, d-tubocurarine and atropine). Another neurotoxin (Tx2-6, one of the isoforms of Tx2 pool) decreased toxin with MPLM and showed that toxin has a specific and saturable binding site in guinea pig ileum and this binding site appears to be related to the Tx2 site. (author)

Acetylcholinesterase potentiates [3H]fluorowillardiine and [3H]AMPA binding to rat cortical membranes

International Nuclear Information System (INIS)

Olivera, S.; Rodriguez-Ithurralde, D.; Henley, J.M.

1999-01-01

In addition to its action at cholinergic synapses acetylcholinesterase (AChE) has been proposed to modulate neuronal activity by mechanisms unrelated to the hydrolysis of acetylcholine. We have investigated the effects of AChE on the binding of the specific AMPA receptor agonists (S)-[ 3 H]5-fluorowillardiine ([ 3 H]FW) and [ 3 H]AMPA to rat cortical membranes. Pretreatment of membranes with AChE causes a dose-dependent increase in the binding of both radiolabelled agonists with a maximal increase to ∼60% above control. This increase is completely blocked by the specific AChE inhibitors propidium, physostigmine, DFP and BW 284C51. AChE pretreatment had no effect on [ 3 H]kainate binding. [ 3 H]FW binding to membranes from young (15-day-old) rats is four orders of magnitude more sensitive to AChE modulation than membranes from adult rats (EC 50 values of 4x10 -5 and 0.1 unit/ml, respectively) although the total percentage increase in binding is similar. Furthermore, the AChE-induced potentiation of [ 3 H]FW binding is Ca 2+ - and temperature-dependent suggesting an enzymatic action for AChE in this system. Saturation binding experiments with [ 3 H]FW to adult membranes reveal high and low affinity binding sites and demonstrate that the main action of AChE is to increase the B max of both sites. These findings suggest that modulation of AMPA receptors could provide a molecular mechanism of action for the previously reported effects of AChE in synapse formation, synaptic plasticity and neurodegeneration. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

75 FR 55968 - Special Local Regulations, Sabine River; Orange, TX

Science.gov (United States)

2010-09-15

...-AA08 Special Local Regulations, Sabine River; Orange, TX AGENCY: Coast Guard, DHS. ACTION: Temporary... Arthur Captain of the Port Zone on the Sabine River, Orange, Texas. This Special Local Regulation is... River, Orange, TX in the Federal Register (75 FR 41119). We received no comments on the proposed rule...

Hypothiocyanite produced by human and rat respiratory epithelial cells inactivates extracellular H1N2 influenza A virus.

Science.gov (United States)

Gingerich, Aaron; Pang, Lan; Hanson, Jarod; Dlugolenski, Daniel; Streich, Rebecca; Lafontaine, Eric R; Nagy, Tamás; Tripp, Ralph A; Rada, Balázs

2016-01-01

Our aim was to study whether an extracellular, oxidative antimicrobial mechanism inherent to tracheal epithelial cells is capable of inactivating influenza H1N2 virus. Epithelial cells were isolated from tracheas of male Sprague-Dawley rats. Both primary human and rat tracheobronchial epithelial cells were differentiated in air-liquid interface cultures. A/swine/Illinois/02860/09 (swH1N2) influenza A virions were added to the apical side of airway cells for 1 h in the presence or absence of lactoperoxidase or thiocyanate. Characterization of rat epithelial cells (morphology, Duox expression) occurred via western blotting, PCR, hydrogen peroxide production measurement and histology. The number of viable virions was determined by plaque assays. Statistical difference of the results was analyzed by ANOVA and Tukey's test. Our data show that rat tracheobronchial epithelial cells develop a differentiated, polarized monolayer with high transepithelial electrical resistance, mucin production and expression of dual oxidases. Influenza A virions are inactivated by human and rat epithelial cells via a dual oxidase-, lactoperoxidase- and thiocyanate-dependent mechanism. Differentiated air-liquid interface cultures of rat tracheal epithelial cells provide a novel model to study airway epithelium-influenza interactions. The dual oxidase/lactoperoxidase/thiocyanate extracellular oxidative system producing hypothiocyanite is a fast and potent anti-influenza mechanism inactivating H1N2 viruses prior to infection of the epithelium.

Reduced permeation of 14C-sucrose, 3H-mannitol and 3H-inulin across blood-brain barrier in nephrectomized rats

International Nuclear Information System (INIS)

Preston, E.; Haas, N.; Allen, M.

1984-01-01

Experiments were carried out to determine if changes in the concentration-time profile of a blood-borne radiotracer such as 14 C-sucrose would spuriously alter measurements of its permeation across the blood-brain barrier (permeability-area product, PA) based on a 2-compartment (plasma/brain) simple diffusion model. Anesthetized rats which were bilaterally nephrectomized and given a standard intravenous bolus injection of 14 C-sucrose, 3 H-mannitol or 3 H-inulin exhibited an elevated plasma tracer concentration compared to control animals. However, tracer concentration measured in brain parenchyma after 30 min was not proportionally elevated, and PA calculated from the ratio, parenchymal tracer concentration: plasma concentration-time integral, was significantly reduced below control values. In control rats, distortion and elevation of the plasma 14 C-sucrose profile by continuous intravenous infusion did not result in lowered PA values. This suggested that the lowering of PA by nephrectomy reflected reduced cerebrovascular permeability or area or other cerebral influence rather than a deficiency in the 2-compartment model for PA measurement

Gender differences in organ density in a rat simulated microgravity model

Science.gov (United States)

Pettis, Christopher Ryan; Witten, Mark Lee

2004-01-01

Research investigating the physiological effects of microgravity on the human body has demonstrated a shift of body fluids in actual spaceflight and in simulated Earth-based microgravity models in both males and females, possibly causing many deleterious physiological effects. Twenty-five anatomically normal female (NF) and 20 ovariectomized (OE) Fischer 344 rats were randomly selected to be in an experimental ( 1 h of 45° head-down tilt, 45HDT) or control ( 1 h of prone position) group. At the end of the hour experimental period, the density of the brain, lungs, heart, liver, and left and right kidneys were measured using spiral computed tomography (SCT) while the rats remained in their experimental positions. A sub-group of OE rats ( N=6) was administered estrogen replacement therapy on a daily basis ( 5 μg/kg body weight, s.c.) for 4 days and then underwent 1 h of 45HDT and SCT analysis at one day, 2 days, and 5 days to determine if estrogen replacement therapy would alter organ densities. Our data demonstrate that 1 h of 45HDT produced significant increases ( pbrain, liver, left kidney, and lung of the OE female group compared to their prone controls. However, only the brain density was significantly increased in the NF group. Estrogen replacement therapy caused a significant decrease in brain organ density at the 5 day time point compared to the 24 h time point. We conclude that estrogen plays a role in fluid distribution in a rat 45HDT model.

ASIC-like, proton-activated currents in rat hippocampal neurons.

Science.gov (United States)

Baron, Anne; Waldmann, Rainer; Lazdunski, Michel

2002-03-01

The expression of mRNA for acid sensing ion channels (ASIC) subunits ASIC1a, ASIC2a and ASIC2b has been reported in hippocampal neurons, but the presence of functional hippocampal ASIC channels was never assessed. We report here the first characterization of ASIC-like currents in rat hippocampal neurons in primary culture. An extracellular pH drop induces a transient Na(+) current followed by a sustained non-selective cation current. This current is highly sensitive to pH with an activation threshold around pH 6.9 and a pH(0.5) of 6.2. About half of the total peak current is inhibited by the spider toxin PcTX1, which is specific for homomeric ASIC1a channels. The remaining PcTX1-resistant ASIC-like current is increased by 300 microM Zn(2+) and, whereas not fully activated at pH 5, it shows a pH(0.5) of 6.0 between pH 7.4 and 5. We have previously shown that Zn(2+) is a co-activator of ASIC2a-containing channels. Thus, the hippocampal transient ASIC-like current appears to be generated by a mixture of homomeric ASIC1a channels and ASIC2a-containing channels, probably heteromeric ASIC1a+2a channels. The sustained non-selective current suggests the involvement of ASIC2b-containing heteromeric channels. Activation of the hippocampal ASIC-like current by a pH drop to 6.9 or 6.6 induces a transient depolarization which itself triggers an initial action potential (AP) followed by a sustained depolarization and trains of APs. Zn(2+) increases the acid sensitivity of ASIC channels, and consequently neuronal excitability. It is probably an important co-activator of ASIC channels in the central nervous system.

Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

Directory of Open Access Journals (Sweden)

Pooladi A

2011-01-01

Full Text Available Background and Objectives: Gastric cancer is one of the most common gastrointestinal tumors; the incidence and mortality of gastric cancer are on the increase nowadays. Helicobacter pylori(H.Pylori causes chronic active gastritis and peptic ulcer disease. Cycloocygenase-2 (COX-2 is the central enzyme in the biosynthetic pathway to prostaglandins. Studies from different laboratories suggested that over-expression of COX-2 was detected in colon and other tumors. To obtain direct evidence concerning this relationship, we investigated the immunohistochemical findings of gastric mucosa using an animal model of gastric cancer induced by H. pylori in sprague dawley rat.Methods: The rats were randomly assigned into three groups(n=5. Those of experimental group2 were given MNU. one week after completion of MNU administration, rats in experimental groups 1 were inoculated with H. pylori three times every other day. Rats in control group(group 3 received neither MNU nor H. pylori. Rats of groups 1, 2, and control group were maintained on standard diets throughout the experiment. Rat were weighed and sacrificed under anesthesia with ether at 20 weeks after infection. One half of the excised stomachs, were fixed in neutral-buffered 10% formalin and were cut into approximately six strips, which were processed by standard methods, embedded in paraffin, sectioned at 6 µm, and stained with hematoxylin and eosin (H&E and immunohistochemistry for Cox-2 protein detection. To confirm H. pylori infection, samples ( 3-mm2 of stomach mucosa transferred to appropriate medium and Colonies were identified by characteristic Gram’s stain morphology, and by urease, catalase, and oxidase activity sample was also placed into the gel of a rapid urease test kit.Results: Data showed a significant decrease of animal body weight in experimental groups compared with control group. Histopathological studies showed severe infiltration of the lamina propria and submucusaal layer by

The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays.

Science.gov (United States)

Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong

2016-08-01

Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies.

The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays

Energy Technology Data Exchange (ETDEWEB)

Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong [Fudan University, Department of Radiation Biology, Institute of Radiation Medicine, Shanghai (China)

2016-08-15

Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies. (orig.)

The profiles of gamma-H2AX along with ATM/DNA-PKcs activation in the lymphocytes and granulocytes of rat and human blood exposed to gamma rays

International Nuclear Information System (INIS)

Wang, Jing; Yin, Lina; Zhang, Junxiang; Zhang, Yaping; Zhang, Xuxia; Ding, Defang; Gao, Yun; Li, Qiang; Chen, Honghong

2016-01-01

Establishing a rat model suitable for γ-H2AX biodosimeter studies has important implications for dose assessment of internal radionuclide contamination in humans. In this study, γ-H2AX, p-ATM and p-DNA-PKcs foci were enumerated using immunocytofluorescence method, and their protein levels were measured by Western blot in rat blood lymphocytes and granulocytes exposed to γ-rays compared with human blood lymphocytes and granulocytes. It was found that DNA double-strand break repair kinetics and linear dose responses in rat lymphocytes were similar to those observed in the human counterparts. Moreover, radiation induced clear p-ATM and p-DNA-PKcs foci formation and an increase in ratio of co-localization of p-ATM or p-DNA-PKcs with γ-H2AX foci in rat lymphocytes similar to those of human lymphocytes. The level of γ-H2AX protein in irradiated rat and human lymphocytes was significantly reduced by inhibitors of ATM and DNA-PKcs. Surprisingly, unlike human granulocytes, rat granulocytes with DNA-PKcs deficiency displayed a rapid accumulation, but delayed disappearance of γ-H2AX foci with essentially no change from 10 h to 48 h post-irradiation. Furthermore, inhibition of ATM activity in rat granulocytes also decreased radiation-induced γ-H2AX foci formation. In comparison, human granulocytes showed no response to irradiation regarding γ-H2AX, p-ATM or p-DNA-PKcs foci. Importantly, incidence of γ-H2AX foci in lymphocytes after total-body radiation of rats was consistent with that of in vitro irradiation of rat lymphocytes. These findings show that rats are a useful in vivo model for validation of γ-H2AX biodosimetry for dose assessment in humans. ATM and DNA-PKcs participate together in DSB repair in rat lymphocytes similar to that of human lymphocytes. Further, rat granulocytes, which have the characteristic of delayed disappearance of γ-H2AX foci in response to radiation, may be a useful experimental system for biodosimetry studies. (orig.)

76 FR 30890 - Special Local Regulations; Sabine River, Orange, TX

Science.gov (United States)

2011-05-27

...-AA08 Special Local Regulations; Sabine River, Orange, TX AGENCY: Coast Guard, DHS. ACTION: Notice of... the Port Arthur Captain of the Port Zone on the Sabine River, Orange, Texas on September 24-25, 2011... race in conjunction with the Orange, TX S.P.O.R.T. boat races. The powerboat race and associated...

Cerium intermetallics CeTX. Review III

Energy Technology Data Exchange (ETDEWEB)

Poettgen, Rainer; Janka, Oliver [Muenster Univ. (Germany). Inst. fuer Anorganische und Analytische Chemie; Chevalier, Bernard [Bordeaux Univ., Pessac (France). Inst. de Chimie de la Matiere Condensee de Bordeaux

2016-05-01

The structure-property relationships of CeTX intermetallics with structures other than the ZrNiAl and TiNiSi type are systematically reviewed. These CeTX phases form with electron-poor and electron-rich transition metals (T) and X = Mg, Zn, Cd, Hg, Al, Ga, In, Tl, Si, Ge, Sn, Pb, P, As, Sb, and Bi. The review focusses on the crystal chemistry, the chemical bonding peculiarities, and the magnetic and transport properties. Furthermore {sup 119}Sn Moessbauer spectroscopic data, high-pressure studies, hydrogenation reactions and the formation of solid solutions are reviewed. This paper is the third of a series of four reviews on equiatomic intermetallic cerium compound [Part I: R. Poettgen, B. Chevalier, Z. Naturforsch. 2015, 70b, 289; Part II: R. Poettgen, B. Chevalier, Z. Naturforsch. 2015, 70b, 695].

Vapor space characterization of waste Tank 241-TX-118 (in situ): Results from samples collected on 9/7/94

International Nuclear Information System (INIS)

Thomas, B.L.; Clauss, T.W.; Ligotke, M.W.; Pool, K.H.; McVeety, B.D.; Olsen, K.B.; Fruchter, J.S.; Goheen, S.C.

1995-10-01

This report describes inorganic and organic analyses results from in situ samples obtained from the headspace of the Hanford waste storage Tank 241-TX-118 (referred to as Tank TX-118). The results described here were obtained to support safety and toxicological evaluations. A summary of the results for inorganic and organic analytes is listed in Table 1. Detailed descriptions of the results appear in the text. Quantitative results were obtained for the inorganic compounds ammonia (NH 3 ), nitrogen dioxide (NO 2 ), nitric oxide (NO), hydrogen cyanide (CHN), and water (H 2 O). Sampling for sulfur oxides (SO x ) was not requested. In addition, quantitative results were obtained for the 39 TO-14 compounds plus an additional 13 analytes. Hexane, normally included in the additional analytes, was removed because a calibration standard was not available during analysis of Tank TX-118 SUMMA trademark canisters. Of these, 12 were observed above the 5-ppbv reporting cutoff. Fourteen tentatively identified compounds (TICs) were observed above the reporting cutoff of (ca.) 10 ppbv and are reported with concentrations that are semiquantitative estimates based on internal-standard response factors. The 10 organic analytes with the highest estimated concentrations are listed in Table 1 and account for approximately 86% of the total organic components in Tank TX-118. Permanent gas analysis was not conducted on the tank-headspace samples. Tank TX-118 is on both the Ferrocyanide and Organic Watch List

Biochemical, Pharmacological, and Structural Characterization of New Basic Bbil-TX from Bothriopsis bilineata Snake Venom

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Victor Corasolla Carregari

2013-01-01

Full Text Available Bbil-TX, a PLA2, was purified from Bothriopsis bilineata snake venom after only one chromatographic step using RP-HPLC on μ-Bondapak C-18 column. A molecular mass of 14243.8 Da was confirmed by Q-Tof Ultima API ESI/MS (TOF MS mode mass spectrometry. The partial protein sequence obtained was then submitted to BLASTp, with the search restricted to PLA2 from snakes and shows high identity values when compared to other PLA2s. PLA2 activity was presented in the presence of a synthetic substrate and showed a minimum sigmoidal behavior, reaching its maximal activity at pH 8.0 and 25–37∘C. Maximum PLA2 activity required Ca2+ and in the presence of Cd2+, Zn2+, Mn2+, and Mg2+ it was reduced in the presence or absence of Ca2+. Crotapotin from Crotalus durissus cascavella rattlesnake venom and antihemorrhagic factor DA2-II from Didelphis albiventris opossum sera under optimal conditions significantly inhibit the enzymatic activity. Bbil-TX induces myonecrosis in mice. The fraction does not show a significant cytotoxic activity in myotubes and myoblasts (C2C12. The inflammatory events induced in the serum of mice by Bbil-TX isolated from Bothriopsis bilineata snake venom were investigated. An increase in vascular permeability and in the levels of TNF-a, IL-6, and IL-1 was was induced. Since Bbil-TX exerts a stronger proinflammatory effect, the phospholipid hydrolysis may be relevant for these phenomena.

Characteristics of central binding sites for ( sup 3 H) DAMGO in spontaneously hypertensive rats

Energy Technology Data Exchange (ETDEWEB)

Gulati, A.; Bhargava, H.N. (Univ. of Illinois, Chicago (USA))

1990-01-01

The binding of ({sup 3}H) DAMGO, a highly selective ligand for {mu}-opiate receptors, to membranes of discrete brain regions and spinal cord of 10 week old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were determined. The brain regions examined were hypothalamus, amygdala, hippocampus, corpus striatum, pons and medulla, midbrain and cortex. ({sup 3}H) DAMGO bound to membranes of brain regions and spinal cord at a single high affinity site. The receptor density (B{sub max} value) and apparent dissociation constant (K{sub d} value) of ({sup 3}H) DAMGO to bind to membranes of hippocampus, corpus striatum, pons and medulla, cortex and spinal cord of WKY and SHR rats did not differ. The B{sub max} value of ({sup 3}H) DAMGO in membranes of hypothalamus and midbrain of SHR rats was significantly higher than in WKY rats but the K{sub d} values in the two strains did not differ. On the other hand, the B{sub max} value of ({sup 3}H) DAMGO in membranes of amygdala of SHR rats was lower than that of WKY rats but the K{sub d} values in the two strains were similar.

RCRA Assessment Plan for Single-Shell Tank Waste Management Area TX-TY

Energy Technology Data Exchange (ETDEWEB)

Horton, Duane G.

2007-03-26

WMA TX-TY contains underground, single-shell tanks that were used to store liquid waste that contained chemicals and radionuclides. Most of the liquid has been removed, and the remaining waste is regulated under the RCRA as modi¬fied in 40 CFR Part 265, Subpart F and Washington State’s Hazardous Waste Management Act . WMA TX-TY was placed in assessment monitoring in 1993 because of elevated specific conductance. A groundwater quality assessment plan was written in 1993 describing the monitoring activities to be used in deciding whether WMA TX-TY had affected groundwater. That plan was updated in 2001 for continued RCRA groundwater quality assessment as required by 40 CFR 265.93 (d)(7). This document further updates the assessment plan for WMA TX-TY by including (1) information obtained from ten new wells installed at the WMA after 1999 and (2) information from routine quarterly groundwater monitoring during the last five years. Also, this plan describes activities for continuing the groundwater assessment at WMA TX TY.

75 FR 18047 - Amendment of Low Altitude Area Navigation Route T-254; Houston, TX

Science.gov (United States)

2010-04-09

...-254; Houston, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action amends low altitude Area Navigation (RNAV) route T-254 in the Houston, TX, terminal area by... Houston, TX, terminal area. DATES: Effective Dates: 0901 UTC, June 3, 2010. The Director of the Federal...

The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats.

Science.gov (United States)

Ezzat, Bassant A; Abbass, Marwa M S

2014-02-01

The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss. Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA). Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group. In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Unmasking Snake Venom of Bothrops leucurus: Purification and Pharmacological and Structural Characterization of New PLA2 Bleu TX-III

Science.gov (United States)

Marangoni, Fábio André; Ponce-Soto, Luis Alberto; Marangoni, Sergio; Landucci, Elen Cristina Teizem

2013-01-01

Bleu TX-III was isolated from Bothrops leucurus snake venom on one-step analytical chromatography reverse phase HPLC, was homogeneous on SDS-PAGE, and was confirmed by Q-Tof Ultima API ESI/MS (TOF MS mode) mass spectrometry in 14243.8 Da. Multiple alignments of Bleu TX-III show high degree of homology with basic PLA2 myotoxins from other Bothrops venoms. Our studies on local and systemic myotoxicity “in vivo” reveal that Bleu TX-III is myotoxin with local but not systemic action due to the decrease in the plasmatic CK levels when Bleu TX-III is administrated by intravenous route in mice (dose 1 and 5 μg). And at a dose of 20 μg myotoxin behaves like a local and systemic action. Bleu TX-III induced moderate marked paw edema, evidencing the local increase in vascular permeability. The inflammatory events induced in the mice (I.M.) were investigated. The increase in the levels of IL-1, IL-6, and TNF-α was observed in the plasma. It is concluded that Bleu TX-III induces inflammatory events in this model. The enzymatic phospholipid hydrolysis may be relevant to these phenomena. Bothrops leucurus venom is still not extensively explored, and the knowledge of its toxins separately through the study of structure/function will contribute for a better understanding of its action mechanism. PMID:23509815

Validation of an amino-acid-based radionuclide therapy plus external beam radiotherapy in heterotopic glioblastoma models

Energy Technology Data Exchange (ETDEWEB)

Israel, Ina [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany); Blass, Georg [Department of Radiotherapy and Radiooncology, Saarland University Medical Center, Homburg (Germany); Reiners, Christoph [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany); Samnick, Samuel, E-mail: samnick_s@klinik.uni-wuerzburg.d [Department of Nuclear Medicine, University of Wuerzburg, D-97080 Wuerzburg (Germany)

2011-05-15

Background and purpose: Malignant gliomas represent a major therapeutic challenge because no efficient treatment is currently available. p-[{sup 131}I]iodo-L-phenylalanine ([{sup 131}I]IPA) is a glioma avid radiopharmaceutical that demonstrated antiproliferative and tumoricidal effects in gliomas. The present study validated the therapeutic efficiency of [{sup 131}I]IPA combined with external beam radiotherapy in experimental gliomas. Materials and methods: Glioma cells derived from the primary human A1207, T5135, Tx3868 and M059K glioblastoma cell lines or rat F98 glioma cell line were treated with various doses of [{sup 131}I]IPA, external photon irradiation (RT) or combined [{sup 131}I]IPA/RT treatment. Responsiveness of glioma cells to the different therapy modalities was investigated at 24, 48 and 72 h after treatments by trypan blue, WST-1 assay, propidium iodide and bisbenzimide staining as well as by clonogenic assay. In addition, the therapy-induced DNA damage and repair were evaluated using phosphorylated histone H2AX ({gamma}-H2AX). In vivo, the effectiveness of the combination treatment was validated in human Tx3868 and A1207 glioblastoma xenografts in CD1 nu/nu mice and RNU rats. Results: In vitro, the combination treatment resulted in a greater than additive increase in cytotoxic effect in glioma cell lines. Cell survival rate following a treatment with 1.0 {mu}Ci (37 kBq) of [{sup 131}I]IPA amounted to 70%{+-}15% and 60%{+-}10% after 48 and 72 h, respectively, and decreased under 20% after additional RT with 5 Gy. At higher RT doses, cell survival rate decreased below 5%. As a measure of DNA double-strand break, nuclear {gamma}-H2AX foci were determined as a function of time. Within 24 h, the number of {gamma}-H2AX foci per cell was significantly greater after combined modality compared with the individual treatments. In vivo, when combined with RT, the radionuclide therapy with [{sup 131}I]IPA resulted in an extended tumor growth delay, a reduction

78 FR 33019 - Proposed Amendment of Class E Airspace; Commerce, TX

Science.gov (United States)

2013-06-03

...-0269; Airspace Docket No. 13-ASW-3] Proposed Amendment of Class E Airspace; Commerce, TX AGENCY... action proposes to amend Class E airspace at Commerce, TX. Additional controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAPs) at Commerce Municipal Airport (AAF). The FAA...

Establishment of a reversible model of prehepatic portal hypertension in rats.

Science.gov (United States)

Zhao, Xin; Dou, Jian; Gao, Qing-Jun

2016-08-01

The aim of the present study was to improve upon the traditional model of pre-hepatic portal hypertension in rats, and simulate the anhepatic phase of orthotopic liver transplantation without veno-venous bypass. A reversible model of portal hypertension was induced by portal vein ligation, with a label ring ligated along the portal vein. A total of 135 male Wistar rats were divided into three groups: i) Normal control (NC) group; ii) portal hypertensive control (PHTC) group; and iii) reperfusion (R) group. In the R group, rats with portal hypertension underwent simultaneous clamping of the portal triad and retrohepatic vena cava for 1 h, followed by removal of the clamps to enable blood reperfusion. Portal venography and portal vein pressure were recorded during the surgery. Arterial oxygen pressure (PaO 2 ), and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) levels were determined, and pathological changes of the liver were investigated by immunohistochemical staining. The results demonstrated that, 3 weeks after portal vein ligation, the vein area and the free portal pressures in the PHTC group were significantly increased compared with those in the NC group. The serum ALT and AST levels in the R group at different time points were significantly elevated compared with those in the PHTC group, and reached their maximal levels at 24 h after reperfusion. Furthermore, the PaO 2 at 24 h after reperfusion was significantly decreased. In conclusion, the reversible model of pre-hepatic portal hypertension in rats was successfully established using the introduction of a label ring. This model may be useful for basic research focusing on the anhepatic phase of orthotopic liver transplantation without veno-venous bypass.

Double-contained receiver tank 244-TX, grab samples, 244TX-97-1 through 244TX-97-3 analytical results for the final report

International Nuclear Information System (INIS)

Esch, R.A.

1997-01-01

This document is the final report for the double-contained receiver tank (DCRT) 244-TX grab samples. Three grabs samples were collected from riser 8 on May 29, 1997. Analyses were performed in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO). The analytical results are presented in a table

78 FR 31429 - Proposed Amendment of Class E Airspace; Mason, TX

Science.gov (United States)

2013-05-24

...-1141; Airspace Docket No. 12-ASW-12] Proposed Amendment of Class E Airspace; Mason, TX AGENCY: Federal... proposes to amend Class E airspace at Mason, TX. Additional controlled airspace is necessary to accommodate new Standard Instrument Approach Procedures (SIAP) at Mason County Airport. The FAA is taking this...

Reproduction and evaluation of a rat model of inhalation lung injury caused by black gunpowder smog

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Yi-fan LIU

2013-09-01

Full Text Available Objective　To reproduce and evaluate a rat model of inhalation lung injury caused by black gunpowder smog. Methods　The smog composition was analyzed and a rat model of inhalation lung injury was reproduced. Forty two healthy male Wistar rats were randomly divided into normal control (NC group and 1h, 2h, 6h, 24h, 48h and 96h after inhalation group (n=6. The arterial blood gas, wet to dry weight ratio (W/D of lung, leukocyte count, and protein concentration in broncho-alveolar lavage fluid (BALF were determined. Macroscopic and microscopic changes in lung tissue were observed. Results　The composition of black gunpowder smog was composed mainly of CO2 and CO, and their concentrations remained stable within 12 minutes. Smog inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 1h, and the W/D of lung reached peak value 2h after inhalation (P<0.05. The amount of leukocytes and content of protein in BALF increased significantly within 24h after inhalation (P<0.05. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in lung tissue as manifestations of acute lung injury, and the injury did not recover at 96h after inhalation. Conclusion　The rat model of inhalation lung injury can be reproduced using black gunpowder smog, and it has the advantages of its readiness for reproduction, reliability and stability, and it could be used for the experiment of inhalation injury in a battlefield environment.

Electroacupuncture improves gait locomotion, H-reflex and ventral root potentials of spinal compression injured rats.

Science.gov (United States)

Escobar-Corona, Carlos; Torres-Castillo, Sergio; Rodríguez-Torres, Erika Elizabeth; Segura-Alegría, Bertha; Jiménez-Estrada, Ismael; Quiroz-González, Salvador

2017-05-01

This study explored the effect of electroacupuncture stimulation (EA) on alterations in the Hoffman reflex (H-reflex) response and gait locomotion provoked by spinal cord injury (SCI) in the rat. A compression lesion of the spinal cord was evoked by insufflating a Fogarty balloon located in the epidural space at the T8-9 spinal level of adult Wistar male rats (200-250 gr; n=60). In different groups of SCI rats, EA (frequencies: 2, 50 and 100Hz) was applied simultaneously to Huantiao (GB30), Yinmen (BL37), Jizhong (GV6) and Zhiyang (GV9) acupoints from the third post-injury day until the experimental session. At 1, 2, 3 and 4 post-injury weeks, the BBB scores of the SCI group of rats treated with EA at 50Hz showed a gradual but greater enhancement of locomotor activity than the other groups of rats. Unrestrained gait kinematic analysis of SCI rats treated with EA-50Hz stimulation showed a significant improvement in stride duration, length and speed (p<0.05), whereas a discrete recovery of gait locomotion was observed in the other groups of animals. After four post-injury weeks, the H-reflex amplitude and H-reflex/M wave amplitude ratio obtained in SCI rats had a noticeable enhancement (217%) compared to sham rats (n=10). Meanwhile, SCI rats treated with EA at 50Hz manifested a decreased facilitation of the H-reflex amplitude and H/M amplitude ratio (154%) and a reduced frequency-dependent amplitude depression of the H-reflex (66%). In addition, 50 Hz-EA treatment induced a recovery of the presynaptic depression of the Gs-VRP evoked by PBSt conditioning stimulation in the SCI rat (63.2±8.1%; n=9). In concordance with the latter, it could be suggested that 50 Hz-EA stimulation reduced the hyper-excitability of motoneurons and provokes a partial improvement of the locomotive performance and H reflex responses by a possible recovery of presynaptic mechanisms in the spinal cord of experimentally injured rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Changes of blood and myocardial tissue contents of IGF-I after development of acute myocardial infarction in rat models

International Nuclear Information System (INIS)

Cao Heng; Wei Youquan

2006-01-01

Objective: To study the changes of IGF-I contents in blood and myocardium after experimental acute myocardial infarction in rat models. Methods: Rat models of acute myocardial infarction were prepared with intraperitoneal injection of isoproterenol. Eight models were sacrificed 48h later and another 8 models were sacrificed 14 days after preparation. Serum and myocardium homogenate contents of IGF-I were measured with RIA in these models as well as 8 control rats. Results: The serum and myocardial contents of IGF-I increased in the models sacrificed at 48h, but were not significantly higher than those in the controls (P>0.05). At 14 th day, the levels were significantly higher than those in controls and at 48h (both P<0.05). The serum and myocardial contents of IGF-I were mutually correlated in the controls and 14 day models (r=0.9987, r=0.9992; P<0.01). Conclusion After myocardial infarction, the serum and myocardial IGF-I contents increased along with the course of disease in the rat models. (authors)

Study of Cyclooxygenase-2 Expression in Sprague Dawley Rat Gastric Cancer Induced by H. Pylori

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F Aeini

2012-05-01

Full Text Available

Background and Objectives: Gastric cancer is one of the most common gastrointestinal tumors; the incidence and mortality of gastric cancer are on the increase nowadays. Helicobacter pylori(H.Pylori causes chronic active gastritis and peptic ulcer disease. Cycloocygenase-2 (COX-2 is the central enzyme in the biosynthetic pathway to prostaglandins. Studies from different laboratories suggested that over-expression of COX-2 was detected in colon and other tumors. To obtain direct evidence concerning this relationship, we investigated the immunohistochemical findings of gastric mucosa using an animal model of gastric cancer induced by H. pylori in sprague dawley rat. Methods: The rats were randomly assigned into three groups(n=5. Those of experimental group2 were given MNU. one week after completion of MNU administration, rats in experimental groups 1 were inoculated with H. pylori three times every other day. Rats in control group(group 3 received neither MNU nor H. pylori. Rats of groups 1, 2, and control group were maintained on standard diets throughout the experiment. Rat were weighed and sacrificed under anesthesia with ether at 20 weeks after infection. One half of the excised stomachs, were fixed in neutral-buffered 10% formalin and were cut into approximately six strips, which were processed by standard methods, embedded in paraffin, sectioned at 6 µm, and stained with hematoxylin and eosin (H&E and immunohistochemistry for Cox-2 protein detection. To confirm H. pylori infection, samples ( 3-mm² of stomach mucosa transferred to appropriate medium  and Colonies were identified by characteristic Gram’s stain morphology, and by urease, catalase, and oxidase activity sample was also placed into the gel of a rapid urease test kit. Results: Data showed a significant decrease of animal body weight in experimental groups compared with control group

Tempol moderately extends survival in a hSOD1(G93A ALS rat model by inhibiting neuronal cell loss, oxidative damage and levels of non-native hSOD1(G93A forms.

Directory of Open Access Journals (Sweden)

Edlaine Linares

Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease characterized by the progressive dysfunction and death of motor neurons by mechanisms that remain unclear. Evidence indicates that oxidative mechanisms contribute to ALS pathology, but classical antioxidants have not performed well in clinical trials. Cyclic nitroxides are an alternative worth exploring because they are multifunctional antioxidants that display low toxicity in vivo. Here, we examine the effects of the cyclic nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl on ALS onset and progression in transgenic female rats over-expressing the mutant hSOD1(G93A . Starting at 7 weeks of age, a high dose of tempol (155 mg/day/rat in the rat´s drinking water had marginal effects on the disease onset but decelerated disease progression and extended survival by 9 days. In addition, tempol protected spinal cord tissues as monitored by the number of neuronal cells, and the reducing capability and levels of carbonylated proteins and non-native hSOD1 forms in spinal cord homogenates. Intraperitoneal tempol (26 mg/rat, 3 times/week extended survival by 17 days. This group of rats, however, diverted to a decelerated disease progression. Therefore, it was inconclusive whether the higher protective effect of the lower i.p. dose was due to higher tempol bioavailability, decelerated disease development or both. Collectively, the results show that tempol moderately extends the survival of ALS rats while protecting their cellular and molecular structures against damage. Thus, the results provide proof that cyclic nitroxides are alternatives worth to be further tested in animal models of ALS.

Sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured rat caput epididymal epithelium.

Science.gov (United States)

Zuo, Wu-Lin; Li, Sheng; Huang, Jie-Hong; Yang, Deng-Liang; Zhang, Geng; Chen, Si-Liang; Ruan, Ye-Chun; Ye, Ke-Nan; Cheng, Christopher H K; Zhou, Wen-Liang

2011-01-01

The epithelium lining the epididymis provides an optimal acidic fluid microenvironment in the epididymal tract that enable spermatozoa to complete the maturation process. The present study aims to investigate the functional role of Na(+)/HCO(3)(-) cotransporter in the pH regulation in rat epididymis. Immunofluorescence staining of pan cytokeratin in the primary culture of rat caput epididymal epithelium showed that the system was a suitable model for investigating the function of epididymal epithelium. Intracellular and apical pH were measured using the fluorescent pH sensitive probe carboxy-seminaphthorhodafluor-4F acetoxymethyl ester (SNARF-4F) and sparklet pH electrode respectively to explore the functional role of rat epididymal epithelium. In the HEPES buffered Krebs-Henseleit (KH) solution, the intracellular pH (pHi) recovery from NH(4)Cl induced acidification in the cultured caput epididymal epithelium was completely inhibited by amiloride, the inhibitor of Na(+)/H(+) exchanger (NHE). Immediately changing of the KH solution from HEPES buffered to HCO(3)(-) buffered would cause another pHi recovery. The pHi recovery in HCO(3)(-) buffered KH solution was inhibited by 4, 4diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), the inhibitor of HCO(3)(-) transporter or by removal of extracellular Na(+). The extracellular pH measurement showed that the apical pH would increase when adding DIDS to the apical side of epididymal epithelial monolayer, however adding DIDS to the basolateral side had no effect on apical pH. The present study shows that sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured caput epididymal epithelium.

DRG Voltage-Gated Sodium Channel 1.7 Is Upregulated in Paclitaxel-Induced Neuropathy in Rats and in Humans with Neuropathic Pain.

Science.gov (United States)

Li, Yan; North, Robert Y; Rhines, Laurence D; Tatsui, Claudio Esteves; Rao, Ganesh; Edwards, Denaya D; Cassidy, Ryan M; Harrison, Daniel S; Johansson, Caj A; Zhang, Hongmei; Dougherty, Patrick M

2018-01-31

Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na v 1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na v 1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na v 1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na v 1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na v 1.7 associated with spontaneous activity. Na v 1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na v 1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain. SIGNIFICANCE STATEMENT This work demonstrates that the expression and function of the voltage-gated sodium channel Na

75 FR 6319 - Proposed Amendment of Low Altitude Area Navigation Route T-254; Houston, TX

Science.gov (United States)

2010-02-09

... Amendment of Low Altitude Area Navigation Route T-254; Houston, TX AGENCY: Federal Aviation Administration... altitude Area Navigation (RNAV) route T-254 in the Houston, TX, terminal area by eliminating the segment... safety and the efficient use of the navigable airspace in the Houston, TX, terminal area. DATES: Comments...

Establishment and evaluation of a rat model of inhalation lung injury induced by ship smog

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Xin-xin DUAN

2018-03-01

Full Text Available Objective To establish and evaluate a rat model of inhalation lung injury induced by ship smog. Methods A rat model of inhalation lung injury was established by analyzing the composition of ship materials after combustion. Forty- two healthy male Wistar rats were randomly divided into normal control group and 2, 6, 12, 24, 48 and 72h groups (6 eachafter inhalation, these rats were killed at each time point, and the changes of arterial blood gas, coagulation function, the lung water content (% were detected. Macroscopic and microscopic changes in lung tissues were observed to judge the degree of lung injury. Results The main components after combustion of 7 kinds of nonmetal materials on ship included CO, CO2, H2S, NOx and other harmful gases in this study, AIKE in one gas detector was used to monitor O2, CO, CO2 and H2S, and their concentrations remained relatively stable within 15 minutes, and the injury time was 15 minutes. The rats presented with shortness of breath and mouth breathing. Smoke inhalation caused a significant hypoxemia, the concentration of blood COHb reached a peak value 2h and the lung water content (% did 6h after inhalation (P<0.05. It is metabolic acidosis in the early stage after inhalation, but metabolic acidosis combined with respiratory acidosis in the later period. Histopathological observation showed diffuse hemorrhage, edema and inflammatory cell infiltration in the lung tissue as manifestations of lung injury, and the injury did not recover at 72h after inhalation, the change of blood coagulation function was not statistically significant. Conclusion A rat model of inhalation lung injury induced by ship smog has been successfully established, and has the advantages of easy replication, stability and reliability, thus can be used to research and treat inhalation lung injury induced by ship smog in naval war environment and other cases. DOI: 10.11855/j.issn.0577-7402.2018.03.14

Time Course of the Soleus M Response and H Reflex after Lidocaine Tibial Nerve Block in the Rat

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Kévin Buffenoir

2013-01-01

Full Text Available Aims. In spastic subjects, lidocaine is often used to induce a block predictive of the result provided by subsequent surgery. Lidocaine has been demonstrated to inhibit the Hoffmann (H reflex to a greater extent than the direct motor (M response induced by electrical stimulation, but the timecourse of these responses has not been investigated. Methods. An animal (rat model of the effects of lidocaine on M and H responses was therefore developed to assess this time course. M and H responses were recorded in 18 adult rats before and after application of lidocaine to the sciatic nerve. Results. Two to five minutes after lidocaine injection, M responses were markedly reduced (mean reduction of 44% and H reflexes were completely abolished. Changes were observed more rapidly for the H reflex. The effects of lidocaine then persisted for 100 minutes. The effect of lidocaine was therefore more prolonged on the H reflex than on the M response. Conclusion. This study confirms that lidocaine blocks not only alpha motoneurons but also Ia afferent fibres responsible for the H reflex. The authors describe, for the first time, the detailed time course of the effect of lidocaine on direct or reflex activation of motoneurons in the rat.

About the nanostructure of the ternary system water - [BMIm]PF6 - TX-100.

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Bilgili, Harun; Bürger, Matthias; Stubenrauch, Cosima; Porada, Jan H

2016-12-15

Many efforts have been made to formulate water-IL microemulsions. One of the most intensely studied systems is H 2 O - 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIm]PF 6 ) - 4-octylphenol polyethoxylate (TX-100) and it is not questioned that this system forms microemulsions. The nanostructures observed for traditional microemulsions are postulated with the surfactant being adsorbed at the interface such that the hydrophilic EO sides intrude into the water domains, while the hydrophobic hydrocarbon chains are immersed into [BMIm]PF 6 . However, the high polarity of [BMIm]PF 6 and the observation that [BMIm]PF 6 mixes well with oligoethylene oxides but hardly with non-polar solvents like toluene or alkanes are not in line with this picture. We re-studied the ternary system H 2 O - [BMIm]PF 6 - TX-100 by measuring phase diagrams, determining tie-lines, and carrying out ROESY NMR and PFG NMR measurements. We found that the hydrophobic part of the surfactant interacts neither with water nor with [BMIm]PF 6 , while both solvents interact with the hydrophilic part of the surfactant. We suggest that the surfactant is not adsorbed at the interface between water and the IL, but forms normal spherical or elongated micelles or even continuous aggregates with the hydrocarbon chains forming the interior of the aggregates. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of Disulfide Connectivity on Structure and Bioactivity of α-Conotoxin TxIA

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Yong Wu

2014-01-01

Full Text Available Cone snails express a sophisticated arsenal of small bioactive peptides known as conopeptides or conotoxins (CTxs. Through evolutionary selection, these peptides have gained the ability to interact with a range of ion channels and receptors, such as nicotinic acetylcholine receptors (nAChRs. Here, we used reversed-phase high performance liquid chromatography (RP-HPLC and electrospray ionization-mass spectrometry (ESI-MS to explore the venom peptide diversity of Conus textile, a species of cone snail native to Hainan, China. One fraction of C. textile crude venom potently blocked α3β2 nAChRs. Subsequent purification, synthesis, and tandem mass spectrometric analysis demonstrated that the most active compound in this fraction was identical to α-CTx TxIA, an antagonist of α3β2 nAChRs. Then three disulfide isoforms of α-CTx TxIA were synthesized and their activities were investigated systematically for the first time. As we observed, disulfide isomerisation was particularly important for α-CTx TxIA potency. Although both globular and ribbon isomers showed similar retention times in RP-HPLC, globular TxIA potently inhibited α3β2 nAChRs with an IC50 of 5.4 nM, while ribbon TxIA had an IC50 of 430 nM. In contrast, beads isomer had little activity towards α3β2 nAChRs. Two-step oxidation synthesis produced the highest yield of α-CTx TxIA native globular isomer, while a one-step production process based on random oxidation folding was not suitable. In summary, this study demonstrated the relationship between conotoxin activity and disulfide connectivity on α-CTx TxIA.

The recombinant C-terminal fragment of tetanus toxin protects against cholinotoxicity by intraseptal injection of β-amyloid peptide (25-35) in rats.

Science.gov (United States)

Patricio-Martínez, A; Mendieta, L; Martínez, I; Aguilera, J; Limón, I D

2016-02-19

The recombinant C-terminal domain of tetanus toxin (Hc-TeTx) is a new non-toxic peptide of the tetanus toxin that exerts a protective action against glutamate excitotoxicity in motoneurons. Moreover, its efficacy as a neuroprotective agent has been demonstrated in several animal models of neurodegeneration. The eleven amino acids in the β amyloid peptide (Aβ25-35) mimic the toxic effects of the full β amyloid peptide (Aβ1-42), causing the impairment of the cholinergic system in the medial septum (MS) which, in turn, alters the septo-hippocampal pathway and leads to learning and memory impairments. The aim of this study was to examine the neuroprotective effects of the Hc-TeTx fragment against cholinotoxicity. The Hc-TeTx fragment (100 ng) was injected into the rats intercranially, with the Aβ(25-35) (2 μg) then injected into their MS. The animals were tested for spatial learning and memory in the eight-arm radial maze. The brains were removed to assess cholinergic markers, such as choline acetyltransferase (ChAT) and acetylcholinesterase (AChE), and to explore neurodegeneration in the MS and hippocampus, using amino-cupric silver and H&E staining. Finally, capase-3, a marker of apoptosis, was examined in the MS. Our results clearly demonstrate that the application of Hc-TeTx prevents the loss of cholinergic markers (ChAT and AChE), the activation of capase-3, and neurodegeneration in the MS and the CA1 and CA3 subfields of the hippocampus. All these improvements were reflected in spatial learning and memory performance, and were significantly higher compared with animals treated with Aβ(25-35). Interestingly, the single administration of Hc-TeTx into the MS modified the ChAT and AChE expression that affect cognitive processes, without inducing neurodegeneration or an increase in capase-3 expression in the MS and hippocampus. In summary, our findings suggest that the recombinant Hc-TeTx fragment offers effective protection for the septo-hippocampal pathway

A Novel Newborn Rat Kernicterus Model Created by Injecting a Bilirubin Solution into the Cisterna Magna

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Song, Sijie; Hu, Ying; Gu, Xianfang; Si, Feifei; Hua, Ziyu

2014-01-01

Background Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. Methods On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pH = 8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. Results The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (Pbilirubin-treated rats were both dramatically higher than those of the controls (P = 0.004 and 0.017, respectively). Apoptosis and necrosis in the hippocampal nerve cells in the bilirubin-treated rats were observed. The bilirubin-treated rats performed worse than the controls on the Morris water maze test. Conclusion By injecting bilirubin into the CM, we successfully created a new kernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy to perform; thus, more stable models for follow-up study are

Sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured rat caput epididymal epithelium.

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Wu-Lin Zuo

Full Text Available The epithelium lining the epididymis provides an optimal acidic fluid microenvironment in the epididymal tract that enable spermatozoa to complete the maturation process. The present study aims to investigate the functional role of Na(+/HCO(3(- cotransporter in the pH regulation in rat epididymis.Immunofluorescence staining of pan cytokeratin in the primary culture of rat caput epididymal epithelium showed that the system was a suitable model for investigating the function of epididymal epithelium. Intracellular and apical pH were measured using the fluorescent pH sensitive probe carboxy-seminaphthorhodafluor-4F acetoxymethyl ester (SNARF-4F and sparklet pH electrode respectively to explore the functional role of rat epididymal epithelium. In the HEPES buffered Krebs-Henseleit (KH solution, the intracellular pH (pHi recovery from NH(4Cl induced acidification in the cultured caput epididymal epithelium was completely inhibited by amiloride, the inhibitor of Na(+/H(+ exchanger (NHE. Immediately changing of the KH solution from HEPES buffered to HCO(3(- buffered would cause another pHi recovery. The pHi recovery in HCO(3(- buffered KH solution was inhibited by 4, 4diisothiocyanatostilbene-2,2-disulfonic acid (DIDS, the inhibitor of HCO(3(- transporter or by removal of extracellular Na(+. The extracellular pH measurement showed that the apical pH would increase when adding DIDS to the apical side of epididymal epithelial monolayer, however adding DIDS to the basolateral side had no effect on apical pH.The present study shows that sodium coupled bicarbonate influx regulates intracellular and apical pH in cultured caput epididymal epithelium.

Hanford Tank Farms Vadose Zone, Addendum to the TX Tank Farm Report

International Nuclear Information System (INIS)

Spatz, R.

2000-01-01

This addendum to the TX Tank Farm Report (GJO-97-13-TAR, GJO-HAN-11) published in September 1997 incorporates the results of high-rate and repeat logging activities along with shape factor analysis of the logging data. A high-rate logging system was developed and deployed in the TX Tank Farm to measure cesium-137 concentration levels in high gamma flux zones where the spectral gamma logging system was unable to collect usable data because of high dead times and detector saturation. This report presents additional data and revised visualizations of subsurface contaminant distribution in the TX Tank Farm at the DOE Hanford Site in the state of Washington

RadNet Air Data From Houston, TX

Science.gov (United States)

This page presents radiation air monitoring and air filter analysis data for Houston, TX from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

RadNet Air Data From Austin, TX

Science.gov (United States)

This page presents radiation air monitoring and air filter analysis data for Austin, TX from EPA's RadNet system. RadNet is a nationwide network of monitoring stations that measure radiation in air, drinking water and precipitation.

Quantitative autoradiography of [3H]ouabain binding sites in rat brain

International Nuclear Information System (INIS)

Spyropoulos, A.C.; Rainbow, T.C.

1984-01-01

In vitro quantitative autoradiography was used to localize in rat brain binding sites for [ 3 H]ouabain, an inhibitor of the Na + ,K + -ATPase. High levels of [ 3 H]ouabain sites were found in the superior and inferior colliculi, the mammillary nucleus, the interpeduncular nucleus, and in various divisions of the olfactory, auditory and somatomotor systems. The heterogeneous distribution of [ 3 H]ouabain binding closely parallels the regional brain glucose consumption as determined by the [ 14 C]deoxyglucose method. Lesion studies of the rat hippocampus using the excitotoxin, ibotenic acid, showed both a marked decrease of neuronal cell types on the injected side and a corresponding decrease in [ 3 H]ouabain binding, indicating that some of the [ 3 H]ouabain binding sites are localized to neurons. The close correlation between [ 3 H]ouabain binding and regional glucose utilization provides further evidence for a linkage between glucose utilization and the neuronal Na + ,K + -ATPase. (Auth.)

Acetylcholinesterase potentiates [{sup 3}H]fluorowillardiine and [{sup 3}H]AMPA binding to rat cortical membranes

Energy Technology Data Exchange (ETDEWEB)

Olivera, S.; Rodriguez-Ithurralde, D. [Department of Anatomy, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD (United Kingdom); Henley, J.M. [Molecular Neuroscience Unit, Division Neuromyology, Instituto de Investigaciones Biologicas Clemente Estable, 11600 Montevideo (Uruguay)

1999-04-01

In addition to its action at cholinergic synapses acetylcholinesterase (AChE) has been proposed to modulate neuronal activity by mechanisms unrelated to the hydrolysis of acetylcholine. We have investigated the effects of AChE on the binding of the specific AMPA receptor agonists (S)-[{sup 3}H]5-fluorowillardiine ([{sup 3}H]FW) and [{sup 3}H]AMPA to rat cortical membranes. Pretreatment of membranes with AChE causes a dose-dependent increase in the binding of both radiolabelled agonists with a maximal increase to {approx}60% above control. This increase is completely blocked by the specific AChE inhibitors propidium, physostigmine, DFP and BW 284C51. AChE pretreatment had no effect on [{sup 3}H]kainate binding. [{sup 3}H]FW binding to membranes from young (15-day-old) rats is four orders of magnitude more sensitive to AChE modulation than membranes from adult rats (EC{sub 50} values of 4x10{sup -5} and 0.1 unit/ml, respectively) although the total percentage increase in binding is similar. Furthermore, the AChE-induced potentiation of [{sup 3}H]FW binding is Ca{sup 2+}- and temperature-dependent suggesting an enzymatic action for AChE in this system. Saturation binding experiments with [{sup 3}H]FW to adult membranes reveal high and low affinity binding sites and demonstrate that the main action of AChE is to increase the B{sub max} of both sites. These findings suggest that modulation of AMPA receptors could provide a molecular mechanism of action for the previously reported effects of AChE in synapse formation, synaptic plasticity and neurodegeneration. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Establishing an experimental rat model of photodynamically-induced retinal vein occlusion using erythrosin B

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Wei Chen

2014-04-01

Full Text Available AIM:To develop a reliable, reproducible rat model of retinal vein occlusion (RVO with a novel photosensitizer (erythrosin B and study the cellular responses in the retina.METHODS:Central and branch RVOs were created in adult male rats via photochemically-induced ischemia. Retinal changes were monitored via color fundus photography and fluorescein angiography at 1 and 3h, and 1, 4, 7, 14, and 21d after irradiation. Tissue slices were evaluated histopathologically. Retinal ganglion cell survival at different times after RVO induction was quantified by nuclear density count. Retinal thickness was also observed.RESULTS:For all rats in both the central and branch RVO groups, blood flow ceased immediately after laser irradiation and retinal edema was evident at one hour. The retinal detachment rate was 100% at 3h and developed into bullous retinal detachment within 24h. Retinal hemorrhages were not observed until 24h. Clearance of the occluded veins at 7d was observed by fluorescein angiography. Disease manifestation in the central RVO eyes was more severe than in the branch RVO group. A remarkable reduction in the ganglion cell count and retinal thickness was observed in the central RVO group by 21d, whereas moderate changes occurred in the branch RVO group.CONCLUSION: Rat RVO created by photochemically-induced ischemia using erythrosin B is a reproducible and reliable animal model for mimicking the key features of human RVO. However, considering the 100% rate of retinal detachment, this animal model is more suitable for studying RVO with chronic retinal detachment.

Contribution of the collagen adhesin Acm to pathogenesis of Enterococcus faecium in experimental endocarditis.

Science.gov (United States)

Nallapareddy, Sreedhar R; Singh, Kavindra V; Murray, Barbara E

2008-09-01

Enterococcus faecium is a multidrug-resistant opportunist causing difficult-to-treat nosocomial infections, including endocarditis, but there are no reports experimentally demonstrating E. faecium virulence determinants. Our previous studies showed that some clinical E. faecium isolates produce a cell wall-anchored collagen adhesin, Acm, and that an isogenic acm deletion mutant of the endocarditis-derived strain TX0082 lost collagen adherence. In this study, we show with a rat endocarditis model that TX0082 Deltaacm::cat is highly attenuated versus wild-type TX0082, both in established (72 h) vegetations (P Acm the first factor shown to be important for E. faecium pathogenesis. In contrast, no mortality differences were observed in a mouse peritonitis model. While 5 of 17 endocarditis isolates were Acm nonproducers and failed to adhere to collagen in vitro, all had an intact, highly conserved acm locus. Highly reduced acm mRNA levels (>or=50-fold reduction relative to an Acm producer) were found in three of these five nonadherent isolates, including the sequenced strain TX0016, by quantitative reverse transcription-PCR, indicating that acm transcription is downregulated in vitro in these isolates. However, examination of TX0016 cells obtained directly from infected rat vegetations by flow cytometry showed that Acm was present on 40% of cells grown during infection. Finally, we demonstrated a significant reduction in E. faecium collagen adherence by affinity-purified anti-Acm antibodies from E. faecium endocarditis patient sera, suggesting that Acm may be a potential immunotarget for strategies to control this emerging pathogen.

Vapor space characterization of waste tank 241-TX-118: Results from samples collected on 12/16/94

International Nuclear Information System (INIS)

Lucke, R.B.; Ligotke, M.W.; McVeety, B.D.

1995-10-01

This report describes inorganic and organic analyses results from samples obtained from the headspace of the Hanford waste storage Tank 241-TX-118 (referred to as Tank TX-118). The results described here were obtained to support safety and toxicological evaluations. A summary of the results for inorganic and organic analytes is listed in Table 1. Detailed descriptions of the results appear in the text. Quantitative results were obtained for the inorganic compounds ammonia (NH 3 ), nitrogen dioxide (NO 2 ), nitric oxide (NO), and water (H 2 O). Sampling for hydrogen cyanide (HCN) and sulfur oxides (SO x ) was not requested. In addition, quantitative results were obtained for the 39 TO-14 compounds plus an additional 14 analytes. Of these, 3 were observed above the 5-ppbv reporting cutoff. Twenty three organic tentatively identified compounds (TICs) were observed above the reporting cutoff of (ca.) 10 ppbv, and are reported with concentrations that are semiquantitative estimates based on internal-standard response factors. The 10 organic analytes with the highest estimated concentrations are listed in Table 1 and account for approximately 84% of the total organic components in Tank TX-118. Two permanent gases, carbon dioxide (CO 2 ) and nitrous oxide (N 2 O), were also detected

Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model.

Science.gov (United States)

Suzuki, Masatoshi; Svendsen, Clive N

2016-01-01

Therapeutic protein and molecule delivery to target sites by transplanted human stem cells holds great promise for ex vivo gene therapy. Our group has demonstrated the therapeutic benefits of ex vivo gene therapy targeting the skeletal muscles in a transgenic rat model of familial amyotrophic lateral sclerosis (ALS). We used human mesenchymal stem cells (hMSCs) and genetically modified them to release neuroprotective growth factors such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF). Intramuscular growth factor delivery via hMSCs can enhance neuromuscular innervation and motor neuron survival in a rat model of ALS (SOD1(G93A) transgenic rats). Here, we describe the protocol of ex vivo delivery of growth factors via lentiviral vector-mediated genetic modification of hMSCs and hMSC transplantation into the skeletal muscle of a familial ALS rat model.

Evaluation of deltamethrin kinetics and dosimetry in the maturing rat using a PBPK model

International Nuclear Information System (INIS)

Tornero-Velez, Rogelio; Mirfazaelian, Ahmad; Kim, Kyu-Bong; Anand, Sathanandam S.; Kim, Hyo J.; Haines, Wendy T.; Bruckner, James V.; Fisher, Jeffrey W.

2010-01-01

Immature rats are more susceptible than adults to the acute neurotoxicity of pyrethroid insecticides like deltamethrin (DLM). A companion kinetics study (Kim et al., in press) revealed that blood and brain levels of the neuroactive parent compound were inversely related to age in rats 10, 21, 40 and 90 days old. The objective of the current study was to modify a physiologically based pharmacokinetic (PBPK) model of DLM disposition in the adult male Sprague-Dawley rat (Mirfazaelian et al., 2006), so blood and target organ dosimetry could be accurately predicted during maturation. Age-specific organ weights and age-dependent changes in the oxidative and hydrolytic clearance of DLM were modeled with a generalized Michaelis-Menten model for growth and the summary equations incorporated into the PBPK model. The model's simulations compared favorably with empirical DLM time-courses in plasma, blood, brain and fat for the four age-groups evaluated (10, 21, 40 and 90 days old). PND 10 pups' area under the 24-h brain concentration time curve (AUC 0-24h ) was 3.8-fold higher than that of the PND 90 adults. Our maturing rat PBPK model allows for updating with age- and chemical-dependent parameters, so pyrethroid dosimetry can be forecast in young and aged individuals. Hence, this model provides a methodology for risk assessors to consider age-specific adjustments to oral Reference Doses on the basis of PK differences.

75 FR 31463 - Comal County Regional Habitat Conservation Plan, Comal County, TX

Science.gov (United States)

2010-06-03

... Wildlife Service, 10711 Burnet Road, Suite 200, Austin, TX 78758 or 512-490-0057. SUPPLEMENTARY INFORMATION... prepare an EIS and hold public scoping meetings published in the Federal Register on October 16, 2008 (73..., Austin, TX 78758; or by phone at 512/490-0057; or by fax to 512/ 490-0974. A limited number of printed...

Na+-H+ exchange and Na+-dependent transport systems in streptozotocin diabetic rat kidneys

International Nuclear Information System (INIS)

El-Seifi, S.; Freiberg, J.M.; Kinsella, F.J.; Cheng, L.; Sacktor, B.

1987-01-01

The streptozotocin-induced diabetic rat was used to test the hypothesis that Na + -H + exchange activity in the proximal tubule luminal membrane would be increased in association with renal hypertrophy, altered glomerular hemodynamics, enhanced filtered load and tubular reabsorption of 22 Na + , and stimulated 22 Na= pump activity in the basolateral membrane, previously reported characteristics of this experimental animal model. Amiloride-sensitive H + gradient-dependent Na + uptake and Na + gradient-dependent H + flux were increased in brush-border membrane vesicles from the streptozotocin-treated animals. Na + gradient-dependent uptakes of phosphate, D-glucose, L-proline, and myoinositol were decreased in the drug-induced diabetic animals. These membrane transport alterations were not found when the streptozotocin-diabetic animals were treated with insulin

PET attenuation correction for rigid MR Tx/Rx coils from 176Lu background activity

Science.gov (United States)

Lerche, Christoph W.; Kaltsas, Theodoris; Caldeira, Liliana; Scheins, Jürgen; Rota Kops, Elena; Tellmann, Lutz; Pietrzyk, Uwe; Herzog, Hans; Shah, N. Jon

2018-02-01

One challenge for PET-MR hybrid imaging is the correction for attenuation of the 511 keV annihilation radiation by the required RF transmit and/or RF receive coils. Although there are strategies for building PET transparent Tx/Rx coils, such optimised coils still cause significant attenuation of the annihilation radiation leading to artefacts and biases in the reconstructed activity concentrations. We present a straightforward method to measure the attenuation of Tx/Rx coils in simultaneous MR-PET imaging based on the natural 176Lu background contained in the scintillator of the PET detector without the requirement of an external CT scanner or PET scanner with transmission source. The method was evaluated on a prototype 3T MR-BrainPET produced by Siemens Healthcare GmbH, both with phantom studies and with true emission images from patient/volunteer examinations. Furthermore, the count rate stability of the PET scanner and the x-ray properties of the Tx/Rx head coil were investigated. Even without energy extrapolation from the two dominant γ energies of 176Lu to 511 keV, the presented method for attenuation correction, based on the measurement of 176Lu background attenuation, shows slightly better performance than the coil attenuation correction currently used. The coil attenuation correction currently used is based on an external transmission scan with rotating 68Ge sources acquired on a Siemens ECAT HR  +  PET scanner. However, the main advantage of the presented approach is its straightforwardness and ready availability without the need for additional accessories.

The effects of female sex steroids on the development of autoimmune thyroiditis in thymectomized and irradiated rats

International Nuclear Information System (INIS)

Ahmed, S.A.; Young, P.R.; Penhale, W.J.

1983-01-01

Female PVG/c strain rats are more susceptible to induction of autoimmune thyroiditis initiated by thymectomy and irradiation (Tx-X) than similarly treated males. Pre-pubertal ovariectomy further augmented susceptibility. Administration of oestrogen or progesterone to groups of 4 weeks old ovariectomized Tx-X animals over a period of 15 weeks significantly altered induction of this condition. Oestrogen administered repeatedly at dose levels of 1 μg and 10 μg/100 g body weight resulted in partial suppression of thyroiditis with a corresponding change in the incidence of antibodies to thyroglobulin. Oestrogen administered by a single implantation had a suppressive effect on the development of autoimmunity in ovariectomized Tx-X females. Oestrogen given by either of these procedures also reduced the incidence of thyroiditis and autoantibody induction in orchidectomized male Tx-X rats. In contrast, repeated administration of progesterone at a dose of 250 mg and 1,500 μg/100 g body weight appeared to augment levels of autoimmunity. It is concluded that the differential susceptibility to the induction of autoimmunity by thymectomy and irradiation is the direct consequence of sex hormonal influences. The higher incidence of the disease in the female would appear to be determined by the balance between the activity of oestrogen and progesterone which would further appear to have antagonistic influences in this particular situation. (UK)

Use of hypoxia imaging agent 99mTc-HL91 in rat cerebral ischemia models

International Nuclear Information System (INIS)

Zhou Ying; Qu Wanying; Li Meng; Chen Fang; Yao Zhiming; Zhu Ming; Zhu Lin

1999-01-01

Objective: To explore the possibility of diagnosis for cerebrovascular disease by a novel synthetic hypoxia agent 99m Tc-HL91 used in rat cerebral ischemia models. Methods: Pharmacological experiments of 99m Tc-HL91 were carried out including common properties, radiochemical purity, stability in vitro, anomalous toxicity test and biodistribution in mice. Fifteen cerebral ischemic rat models were established and received 99m Tc-HL91 scintigraphy. Results: 1) HL91 kits were labelled with 99m Tc easily and showed high radiochemical purity and stability. 2) Rapid clearance in blood, heart and lungs and high activity in liver, kidneys and intestines were observed. Relatively low uptake in brain was identified. 3) The radioactivity in ischemic brain tissue increased significantly at 4h postinjection in both rat images and isolated brain images. 4) The radioactivity ratios of lesion to normal brain tissue by drawing ROIs in isolated brain planar images were 0.98 +- 0.06, 0.99 +- 0.05, 1.29 +- 0.03, 1.56 +- 0.14 and 1.66 +- 0.06 at 1,2,4,8 and 12 h postinjection, respectively. There were significant differences among all groups except for 1 h and 2 h, 8 h and 12 h postinjection (P 99m Tc-HL91 in the hypoxic, ischemic brain tissue have been proved. It is appropriate to perform imaging at 4 h postinjection

The novel hypoxic cytotoxin, TX-2098 has antitumor effect in pancreatic cancer; possible mechanism through inhibiting VEGF and hypoxia inducible factor-1α targeted gene expression.

Science.gov (United States)

Miyake, Kotaro; Nishioka, Masanori; Imura, Satoru; Batmunkh, Erdenebulgan; Uto, Yoshihiro; Nagasawa, Hideko; Hori, Hitoshi; Shimada, Mitsuo

2012-08-01

Tumor hypoxia has been considered to be a potential therapeutic target, because hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. In the present study, we investigated the antitumor effect of a novel hypoxic cytotoxin, 3-[2-hydroxyethyl(methyl)amino]-2-quinoxalinecarbonitrile 1,4-dioxide (TX-2098) in inhibiting the expression of hypoxia inducible factor-1α (HIF-1α), and consequently vascular endothelial cell growth factor (VEGF) expression in pancreatic cancer. The antitumor effects of TX-2098 under hypoxia were tested against various human pancreatic cancer cell lines using WST-8 assay. VEGF protein induced pancreatic cancer was determined on cell-free supernatant by ELISA. Moreover, nude mice bearing subcutaneously (s.c.) or orthotopically implanted human SUIT-2 were treated with TX-2098. Tumor volume, survival and expression of HIF-1 and associated molecules were evaluated in treatment versus control groups. In vitro, TX-2098 inhibited the proliferation of various pancreatic cancer cell lines. In s.c model, tumors from nude mice injected with pancreatic cancer cells and treated with TX-2098 showed significant reductions in volume (P<0.01 versus control). Quantitative real-time reverse transcription-PCR analysis revealed that TX-2098 significantly inhibited mRNA expression of the HIF-1 associated molecules, VEGF, glucose transporter 1 and Aldolase A (P<0.01 versus control). These treatments also prolong the survival in orthotopic models. These results suggest that the effect of TX-2098 in pancreatic cancer might be correlated with the expression of VEGF and HIF-1 targeted molecules. Copyright © 2012 Elsevier Inc. All rights reserved.

A four-disulphide-bridged toxin, with high affinity towards voltage-gated K+ channels, isolated from Heterometrus spinnifer (Scorpionidae) venom.

Science.gov (United States)

Lebrun, B; Romi-Lebrun, R; Martin-Eauclaire, M F; Yasuda, A; Ishiguro, M; Oyama, Y; Pongs, O; Nakajima, T

1997-11-15

A new toxin, named HsTX1, has been identified in the venom of Heterometrus spinnifer (Scorpionidae), on the basis of its ability to block the rat Kv1.3 channels expressed in Xenopus oocytes. HsTX1 has been purified and characterized as a 34-residue peptide reticulated by four disulphide bridges. HsTX1 shares 53% and 59% sequence identity with Pandinus imperator toxin1 (Pi1) and maurotoxin, two recently isolated four-disulphide-bridged toxins, whereas it is only 32-47% identical with the other scorpion K+ channel toxins, reticulated by three disulphide bridges. The amidated and carboxylated forms of HsTX1 were synthesized chemically, and identity between the natural and the synthetic amidated peptides was proved by mass spectrometry, co-elution on C18 HPLC and blocking activity on the rat Kv1.3 channels. The disulphide bridge pattern was studied by (1) limited reduction-alkylation at acidic pH and (2) enzymic cleavage on an immobilized trypsin cartridge, both followed by mass and sequence analyses. Three of the disulphide bonds are connected as in the three-disulphide-bridged scorpion toxins, and the two extra half-cystine residues of HsTX1 are cross-linked, as in Pi1. These results, together with those of CD analysis, suggest that HsTX1 probably adopts the same general folding as all scorpion K+ channel toxins. HsTX1 is a potent inhibitor of the rat Kv1.3 channels (IC50 approx. 12 pM). HsTX1 does not compete with 125I-apamin for binding to its receptor site on rat brain synaptosomal membranes, but competes efficiently with 125I-kaliotoxin for binding to the voltage-gated K+ channels on the same preparation (IC50 approx. 1 pM).

D-RATS 2011: RAFT Protocol Overview

Science.gov (United States)

Utz, Hans

2011-01-01

A brief overview presentation on the protocol used during the D-RATS2011 field test for file transfer from the field-test robots at Black Point Lava Flow AZ to Johnson Space Center, Houston TX over a simulated time-delay. The file transfer actually uses a commercial implementation of an open communications standard. The focus of the work lies on how to make the state of the distributed system observable.

Does Omegaven have beneficial effects on a rat model of ovarian ischemia/reperfusion?

Science.gov (United States)

Gungor, Ayse N Cakir; Turkon, Hakan; Albayrak, Aynur; Ovali, Mehmet; Islimye, Mine; Gencer, Meryem; Hacivelioglu, Servet; Cevizci, Sibel; Cesur, Ismet; Cosar, Emine

2014-10-01

The beneficial effects of omega-3 fatty acids on an intestinal ischemia/reperfusion (I/R) model was shown previously. Therefore, we aimed to examine the potential beneficial effects of parenteral omega-3 fatty acids, a safe and inexpensive product, on a rat model of ovarian I/R. A group of 39 rats was divided into six groups. Group 1 (Sham Group; n=6) underwent two laparotomies with a 3-h interval and their ovaries were removed 3h later. Group 2 (torsion-detorsion Group; n=7) had their ovaries torsioned clockwise and fixed at 720°; 3h later a detorsion operation was done and after another 3h, their ovaries were removed. Group 3 (n=7) and Group 4 (n=7) received the same treatment as Group 2; however, half an hour prior to detorsion, these rats received Omegaven at 1mL/kg and 5mL/kg, respectively. Group 5 (n=6) and Group 6 (n=6) received the same treatment as Group 1; however, half an hour prior to the second laparotomy, these rats received Omegaven at 1mL/kg and 5mL/kg, respectively. One ovary from each rat was evaluated histologically by hematoxylin and eosin (H&E) staining and the other ovary was homogenized and evaluated for total oxidant status (TOS), total antioxidant status (TAS) and oxidative stress index (OSI). While we failed to show any significant relationship among groups in oxidative parameters, there was a significant worsening in the torsion-detorsion group in histological evaluation. High Omegaven doses, but not low doses, improved tissue injury scores of torsioned and detorsioned ovaries to the levels observed in the control group. Omegaven improves the detrimental effects of ovarian I/R when used in sufficient doses. Its effects and dose adjustment on women with ovarian torsion must be investigated by further studies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Correlation between (3H)dopamine specific uptake and (3H)GBR 12783 specific binding during the maturation of rat striatum

International Nuclear Information System (INIS)

Bonnet, J.J.; Costentin, J.

1989-01-01

The development of the specific uptake of dopamine in the rat striatum during the early postnatal period is compared with the ontogenetic changes of the specific binding of ( 3 H)GBR 12783 to the site of uptake inhibition. During maturation, the increase in the specific binding of ( 3 H)GBR 12783 parallels the increase in the specific uptake of dopamine. ( 3 H)GBR 12783 specific binding sites increase in number from day 1 postpartum until 40 days, when they reach the adult level. In 40 day-old rats, the weight of the striatum represents 80% of adult values. The affinity of ( 3 H)GBR 12783 for the inhibition site is similar in membrane preparations obtained from 6 day-old pups and adults; this results in a same ability of the inhibitor to block the specific uptake of dopamine into synaptosomes obtained from pups or adult rats. These data support the hypothesis of the existence of a single molecular entity including both the inhibition site and the carrier itself

Tank 241-TX-118 tank characterization plan

International Nuclear Information System (INIS)

Carpenter, B.C.

1994-01-01

This document is a plan which serves as the contractual agreement between the Characterization Program, Sampling Operations, Oak Ridge National Laboratory, and PNL tank vapor program. The scope of this plan is to provide guidance for the sampling and analysis of vapor samples from tank 241-TX-118

Isolated secretion granules from parotid glands of chronically stimulated rats possess an alkaline internal pH and inward-directed H+ pump activity

International Nuclear Information System (INIS)

Arvan, P.; Castle, J.D.

1986-01-01

Secretion granules have been isolated from the parotid glands of rats that have been chronically stimulated with the β-adrenergic agonist, isoproterenol. These granules are of interest because they package a quantitatively different set of secretory proteins in comparison with granules from the normal gland. Polypeptides enriched in proline, glycine, and glutamine, which are known to have pI's >10, replace α-amylase (pI's = 6.8) as the principal content species. The internal pH of granules from the treated rats changes from 7.8 in a potassium sulfate medium to 6.9 in a choline chloride medium. The increased pH over that of normal parotid granules (∼6.8) appears to protect the change in composition of the secretory contents. Whereas normal mature parotide granules have practically negligible levels of H + pumping ATPase activity, the isolated granules from isoproterenol-treated rats undergo a time-dependent internal acidification that requires the presence of ATP and is abolished by an H + ionophore. Additionally, an inside-positive granule transmembrane potential develops after ATP addition that depends upon ATP hydrolysis. Two independent methods have been used that exclude the possibility that contaminating organelles are the source of the H + -ATPase activity. Together these data provide clear evidence for the presence of an H + pump in the membranes of parotid granules from chronically stimulated rats. However, despite the presence of H + -pump activity, fluorescence microscopy with the weak base, acridine orange, reveals that the intragranular pH in live cells is greater than that of the cytoplasm

Tank 241-TX-105 vapor sampling and analysis tank characterization report

International Nuclear Information System (INIS)

Huckaby, J.L.

1995-01-01

Tank 241-TX-105 headspace gas and vapor samples were collected and analyzed to help determine the potential risks to tank farm workers due to fugitive emissions from the tank. The drivers and objectives of waste tank headspace sampling and analysis are discussed in open-quotes Program Plan for the Resolution of Tank Vapor Issues.close quotes Tank 241-TX-105 was vapor sampled in accordance with open-quotes Data Quality Objectives for Generic In-Tank Health and Safety Issue Resolution.close quotes

A K/Ka band radiating element for Tx/Rx phased array

KAUST Repository

Sandhu, Ali Imran; Arnieri, E.; Amendola, G.; Boccia, L.; Meniconi, E.; Ziegler, V.

2017-01-01

The paper presents a K/Ka band radiating element for TX/RX phased arrays. Dual band operations is obtained using a single radiating surface: a novel radiator is adopted and placed in a configuration in which dual band and single band elements are interleaved. The array elements are optimized to scan the beam in excess of 50° in both bands. A subarray with 49 Rx elements and 105 Tx elements was built and measured confirming the results obtained in simulations.

Tank 241-TX-118 vapor sampling and analysis tank characterization report

International Nuclear Information System (INIS)

Huckaby, J.L.

1995-01-01

Tank 241-TX-118 headspace gas and vapor samples were collected and analyzed to help determine the potential risks to tank farm workers due to fugitive emissions from the tank. The drivers and objectives of waste tank headspace sampling and analysis are discussed in open-quotes Program Plan for the Resolution of Tank Vapor Issues.close quotes Tank 241-TX-118 was vapor sampled in accordance with open-quotes Data Quality Objectives for Generic In-Tank Health and Safety Issue Resolution.close quotes

A K/Ka band radiating element for Tx/Rx phased array

KAUST Repository

Sandhu, Ali Imran

2017-01-20

The paper presents a K/Ka band radiating element for TX/RX phased arrays. Dual band operations is obtained using a single radiating surface: a novel radiator is adopted and placed in a configuration in which dual band and single band elements are interleaved. The array elements are optimized to scan the beam in excess of 50° in both bands. A subarray with 49 Rx elements and 105 Tx elements was built and measured confirming the results obtained in simulations.

Ligation of the abdominal esophagus decreases scorpion toxin-induced gastric secretion in rats Ligadura do esôfago abdominal diminui a secreção gástrica induzida por toxina de escorpião em ratos

Directory of Open Access Journals (Sweden)

Claudia S. Vidal

2004-06-01

Full Text Available PURPOSE: Scorpion toxin purified from Tityus serrulatus venom (Tx induces an increase in volume, acidity and pepsin secretion in the gastric juice of rats. Ligation of oesophagus has been shown to reduce the acid gastric secretion in rats. The aim of this paper was to determine the influence of the esophageal ligation on gastric secretion induced by Tx in rats METHODS: Forty-four male albino rats were given water ad libitum, but no food for 20 to 24 hours, anesthetized with urethane and the trachea and jugular vein cannulated. Cervical or abdominal esophageal ligation or sham-operations were performed before and after the injection of 0.25 mg/kg of scorpion toxin (fraction T1 into the jugular vein. One hour later, the volume, acidity, pH and peptic activity of gastric juice were determined. RESULTS: The scorpion toxin induced an increase in gastric juice volume, acidity and pepsin output and a decrease in pH when injected into the vein of intact animals or in sham-operated animals. Cervical esophagus ligation did not interfere with the effects of toxin, however, ligation of the abdominal esophageal decreased the toxin effect on the rat stomach. CONCLUSION: Ligation of the abdominal esophagus decreases the gastric secretion induced by scorpion toxin.OBJETIVO: A toxina de escorpião purificada do veneno do escorpião Tityus serrulatus (Tx induz um aumento no volume, acidez e secreção de pepsina no suco gástrico de ratos. A ligadura do esôfago diminui a secreção ácida do estômago em ratos. O objetivo deste trabalho foi determinar a influência da ligadura do esôfago sobre a secreção gástrica induzida pela Tx em ratos. MÉTODOS: 44 ratos machos, brancos foram administrados água ad libitum, mas não alimentados por 20 a 24 horas, anestesiados com uretana e canulados a traquéia e a veia jugular. Foram realizadas as ligaduras do esôfago cervical ou abdominal ou operações simuladas antes e após a administração na veia jugular de 0

[Establishment of rat model of psychical erectile dysfunction].

Science.gov (United States)

Wang, Qiu-lin; Wang, Shu-ren; Duan, Jin

2006-01-01

To set up a method of establishing the animal model of psychical erectile dysfunction with emotional stress. All thirty-six male rats with normal sexual function were divided into three groups, i. e. normal group, model group and demasculinized group randomly according to their weights. The rats in the model group were suspended upside down in midair over the water and irritated repeatedly. Two weeks later, the sexual abilities of all rats, i. e. the times of mounting and intromitting the estrus female rats, the latent period of mounting, intromission and ejaculation, were recorded, and the number of rats that had sexual activities was also counted. And the hemorheology indices of the rats were measured. Compared with the normal rats, the latency of mounting [(152.5 +/- 24.6) s vs (42.4 +/- 9.6) s] and intromission [(437.0 +/- 67.7) s vs (130.8 +/- 39.1) s] of the model rats were longer (P 0.05). The hemorheology indices, e. g. blood viscosity, hematocrit (Hct) and red cell aggregation (RCA), of the model rats was significant higher than that of the normal and demasculinized rats (P erectile dysfunction can be made ideally with psychical stress.

[Establishment of rat model with diabetes mellitus and concomitant periodontitis and the carotid artery lesions in the model rats].

Science.gov (United States)

Ren, X Y; Wang, C; Liu, X; Li, H; Gao, J H; Ge, X J

2017-12-09

Objectives: To establish SD rat model with type 2 diabetes mellitus (DM) and concomitant chronic periodontitis (CP) and to evaluate the influence of periodontitis on the vascular lesions of type 2 diabetes rats. Methods: Totally 241 clean level SD rats were randomly divided into four groups, group A (normal control, NC, n= 27), group B (DM, n= 34), group C (CP, n= 90) and group D (DM+CP, n= 90). The rats of DM group were fed with high-fat and high-sugar diet for 8 to 10 weeks, and then were multiply injected with small dose streptozotocin under the condition of ice bath. Blood sugar levels after the injection were dynamically monitored at 72 h, 1 week, 2 weeks and 4 weeks, respectively. The CP model was established by means of ligation. Bilateral maxillary first and second molars were selected and ligated using 0.2 mm orthodontic wires binding with 4-0 surgical suture soaked with Porphyromonas gingivalis (Pg) suspension. After a period of 14 weeks, all the rats were put to death. Maxillary samples were subjected to methylene blue staining to observe alveolar bone loss. Bilateral carotid artery specimens were collected. The left carotid artery specimens were used to detect the prevalence of Pg using quantitative real-time PCR. The right carotid artery specimens were used to observe pathological changes. Results: Blood sugar levels of rats in group B and D increased and changed sharply after Streptozotocin injection with in 1 week. Symptoms of 'more drink, more food and body weight loss' appeared. The fasting blood glucose (FBG) was more than 7.8 mmol/L and (or) the random blood glucose (RBG) was more than 17.8 mmol/L. Both FBG and RBG became stable after 2 to 3 weeks. Levels of HbA1C in group B and D ([7.32±0.45]%, [9.41±0.45]%) were significantly higher than that of group A ([4.02±0.45]%) ( Pdiabetes vascular lesions.

H,K-ATPase and carbonic anhydrase response to chronic systemic rat gastric hypoxia

Directory of Open Access Journals (Sweden)

Ulfah Lutfiah

2015-11-01

Full Text Available Background: Hypoxia may induce gastric ulcer associated with excessive hidrogen chloride (HCl secretion. Synthesis of HCl involves 2 enzymes, H,K-ATPase and carbonic anhydrase (CA. This study aimed to clarify the underlying cause of gastric ulcer in chronic hypoxic condition, by investigating the H,K-ATPase and CA9 response in rats.Methods: This study was an in vivo experiment, to know the relationship between hypoxia to expression of H,K-ATPase and CA9 mRNA, and H,K-ATPase and total CA specific activity of chronic systemic rat gastric hypoxia. The result was compared to control. Data was analyzed by SPSS. If the data distribution was normal and homogeneous, ANOVA and LSD post-hoc test were used. However, if the distribution was not normal and not homogeneous, and still as such after transformation, data was treated in non-parametric using Kruskal-Wallis and Mann Whitney test. Twenty five male Sprague-Dawley rats were divided into 5 groups: rats undergoing hypoxia for 1, 3, 5, and 7 days placed in hypoxia chamber (10% O2, 90% N2, and one control group. Following this treatment, stomach of the rats was extracted and homogenized. Expression of H,K-ATPase and CA9 mRNA was measured using real time RT-PCR. Specific activity of H,K-ATPase was measured using phosphate standard solution, and specific activity of total CA was measured using p-nitrophenol solution.Results: The expression of H,K-ATPase mRNA was higher in the first day (2.159, and drastically lowered from the third to seventh day (0.289; 0.108; 0.062. Specific activities of H,K-ATPase was slightly higher in the first day (0.765, then was lowered in the third (0.685 and fifth day (0.655, and was higher in the seventh day (0.884. The expression of CA9 mRNA was lowered progressively from the first to seventh day (0.84; 0.766; 0.736; 0.343. Specific activities of total CA was low in the first day (0.083, and was higher from the third to seventh day (0.111; 0.136; 0.144.Conclusion: In hypoxia

/sup 3/H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((/sup 3/H)CTOP), a potent and highly selective peptide for mu opioid receptors in rat brain

Energy Technology Data Exchange (ETDEWEB)

Hawkins, K.N.; Knapp, R.J.; Lui, G.K.; Gulya, K.; Kazmierski, W.; Wan, Y.P.; Pelton, J.T.; Hruby, V.J.; Yamamura, H.I.

1989-01-01

The cyclic, conformationally restricted octapeptide (3H)-(H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) ((3H)CTOP) was synthesized and its binding to mu opioid receptors was characterized in rat brain membrane preparations. Association rates (k+1) of 1.25 x 10(8) M-1 min-1 and 2.49 x 10(8) M-1 min-1 at 25 and 37 degrees C, respectively, were obtained, whereas dissociation rates (k-1) at the same temperatures were 1.93 x 10(-2) min-1 and 1.03 x 10(-1) min-1 at 25 and 37 degrees C, respectively. Saturation isotherms of (3H)CTOP binding to rat brain membranes gave apparent Kd values of 0.16 and 0.41 nM at 25 and 37 degrees C, respectively. Maximal number of binding sites in rat brain membranes were found to be 94 and 81 fmol/mg of protein at 25 and 37 degrees C, respectively. (3H)CTOP binding over a concentration range of 0.1 to 10 nM was best fit by a one site model consistent with binding to a single site. The general effect of different metal ions and guanyl-5'-yl-imidodiphosphate on (3H)CTOP binding was to reduce its affinity. High concentrations (100 mM) of sodium also produced a reduction of the apparent mu receptor density. Utilizing the delta opioid receptor specific peptide (3H)-(D-Pen2,D-Pen5)enkephalin, CTOP appeared to be about 2000-fold more specific for mu vs. delta opioid receptor than naloxone. Specific (3H)CTOP binding was inhibited by a large number of opioid or opiate ligands.

A novel model for NSAID induced gastroenteropathy in rats.

Science.gov (United States)

Singh, Devendra Pratap; Borse, Swapnil P; Nivsarkar, Manish

2016-01-01

Progress in management of Nonsteroidal anti-inflammatory drug (NSAID) induced gastrointestinal toxicity requires the availability of appropriate experimental animal models that are as close to humans as feasible. Our objective was to develop a rat model for NSAID-induced gastroenteropathy and also to simulate the common clinical scenario of co-administration of NSAID and proton pump inhibitor (PPI) to explore if PPI contribute to exacerbation of NSAID-enteropathy. Rats were treated twice daily with pantoprazole sodium (PTZ; 10mg/kg peroral) or vehicle for a total of 10days. In some experiments, Diclofenac sodium (DCF; 9mg/kg) or vehicle was administered orally twice daily for the final 5days of PTZ/vehicle administration. After the last dose on 9th day, rats in all the groups were fasted but water was provided ad libitum. 12h after the last dose on 10th day, rats in all the groups were euthanized and their gastrointestinal tracts were assessed for haemorrhagic lesions, lipid peroxidation, intestinal permeability and gastrointestinal luminal pH alterations. Changes in haemoglobin, haematocrit and serum levels of albumin, total protein, ALT and bilirubin were calculated. The macroscopic and histological evidence suggested that administration of DCF resulted in significant gastroenteropathic damage and co-administration of PTZ resulted in significant exacerbation of NSAID enteropathy, while attenuation of NSAID induced gastropathy was observed. Our results were further supported by the significant decrease in haemoglobin and haematocrit levels and serum levels of albumin and total proteins, an increase in oxidative stress and intestinal permeability with the use of DCF either alone or in combination with PTZ. This model was developed to simulate the human clinical situation during NSAID therapy and indeed the present DCF regimen caused both gastric and small bowel alterations, such as multiple erosive lesions, together with a decrease in haemoglobin, haematocrit

TX-RX isolation method based on polarization diversity, spatial diversity and TX beamforming

DEFF Research Database (Denmark)

Foroozanfard, Ehsan; Carvalho, Elisabeth De; Pedersen, Gert F.

2016-01-01

In this paper, the feasibility of an antenna isolation technique based on null-steer beamforming, polarization diversity and spatial diversity is investigated. The proposed system consists of six patch antennas which are fed by a feeding network to obtain a null-steer beamformer. To achieve spatial...... diversity, antenna elements are located on two layers, facing in a different direction. Moreover, the antenna elements in two layers use different polarization. The measured results of the antenna system present a high TX-RX isolation in the order of 70 dB which shows the feasibility of such a system...

75 FR 16336 - Establishment of Low Altitude Area Navigation Route (T-284); Houston, TX

Science.gov (United States)

2010-04-01

... (T-284); Houston, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule. SUMMARY: This action establishes a low altitude area navigation (RNAV) route, designated T-284, in the Houston... navigable airspace in the Houston, TX, terminal area. DATES: Effective date 0901 UTC, July 29, 2010. The...

Alveolar macrophages have a dual role in a rat model for trimellitic anhydride-induced occupational asthma

International Nuclear Information System (INIS)

Valstar, Dingena L.; Schijf, Marcel A.; Nijkamp, Frans P.; Storm, Gert; Arts, Josje H.E.; Kuper, C. Frieke; Bloksma, Nanne; Henricks, Paul A.J.

2006-01-01

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter inhaled compounds. These cells can produce many different mediators that have a putative role in asthma. In this study, we examined the role of AMs in lung function and airway inflammation of rats exposed to TMA. Female Brown Norway rats were sensitized by dermal application of TMA or received vehicle alone on days 0 and 7. One day before challenge, rats received intratracheally either empty or clodronate-containing liposomes to deplete the lungs of AMs. On day 21, all rats were challenged by inhalation of TMA in air. Lung function parameters were measured before, during, within 1 h after, and 24 h after challenge. IgE levels and parameters of inflammation and tissue damage were assessed 24 h after challenge. Sensitization with TMA led to decreased lung function parameters during and within 1 h after challenge as compared to non-sensitized rats. AM depletion alleviated the TMA-induced drop in lung function parameters and induced a faster recovery compared to sham-depleted TMA-sensitized rats. It also decreased the levels of serum IgE 24 h after challenge, but did not affect the sensitization-dependent increase in lung lavage fluid IL-6 and tissue TNF-α levels. In contrast, AM depletion augmented the TMA-induced tissue damage and inflammation 24 h after challenge. AMs seem to have a dual role in this model for TMA-induced occupational asthma since they potentiate the immediate TMA-induced decrease in lung function but tended to dampen the TMA-induced inflammatory reaction 24 h later

Cytoprotective effects of hydrogen sulfide in novel rat models of non-erosive esophagitis.

Directory of Open Access Journals (Sweden)

Oksana Zayachkivska

Full Text Available Non-erosive esophagitis is a chronic inflammatory condition of the esophagus and is a form of gastroesophageal reflux disease. There are limited treatment options for non-erosive esophagitis, and it often progresses to Barrett's esophagus and esophageal carcinoma. Hydrogen sulfide has been demonstrated to be a critical mediator of gastric and intestinal mucosal protection and repair. However, roles for H2S in esophageal mucosal defence, inflammation and responses to injury have not been reported. We therefore examined the effects of endogenous and exogenous H2S in rat models of non-erosive esophagitis. Mild- and moderate-severity non-erosive esophagitis was induced in rats through supplementation of drinking water with fructose, plus or minus exposure to water-immersion stress. The effects of inhibitors of H2S synthesis or of an H2S donor on severity of esophagitis was then examined, along with changes in serum levels of a pro- and an anti-inflammatory cytokine (IL-17 and IL-10, respectively. Exposure to water-immersion stress after consumption of the fructose-supplemented water for 28 days resulted in submucosal esophageal edema and neutrophil infiltration and the development of lesions in the muscular lamina and basal cell hyperplasia. Inhibition of H2S synthesis resulted in significant exacerbation of inflammation and injury. Serum levels of IL-17 were significantly elevated, while serum IL-10 levels were reduced. Treatment with an H2S donor significantly reduced the severity of esophageal injury and inflammation and normalized the serum cytokine levels. The rat models used in this study provide novel tools for studying non-erosive esophagitis with a range of severity. H2S contributes significantly to mucosal defence in the esophagus, and H2S donors may have therapeutic value in treating esophageal inflammation and injury.

75 FR 9859 - Television Broadcasting Services; Beaumont, TX

Science.gov (United States)

2010-03-04

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 10-307; MB Docket No. 10-49; RM-11593] Television Broadcasting Services; Beaumont, TX AGENCY: Federal Communications Commission. ACTION: Proposed... 73 Television, Television broadcasting. For the reasons discussed in the preamble, the Federal...

Tensiometric, fluorescence and 1H NMR study of mixed micellization of non-steroidal anti-inflammatory drug sodium salt of ibuprofen in the presence of non-ionic surfactant in aqueous/urea solutions

International Nuclear Information System (INIS)

Rub, Malik Abdul; Khan, Farah; Sheikh, Mohmad Shafi; Azum, Naved; Asiri, Abdullah M.

2016-01-01

Highlights: • Interaction between (IBF + TX-100) mixtures has been investigated. • (IBF + TX-100) mixtures exhibit synergistic behavior. • Urea increases the surface charge of the micelles resulting halt of the micelles formation. • N agg , K sv and dielectric constant of mixed systems have also been evaluated. • 1 H NMR data suggested that IBF and TX-100 interacts through hydrophobic as well as hydrophillic interaction. - Abstract: The desirable surface/bulk properties for specific applications of drug sodium salt of ibuprofen (IBF) and Triton X-100 (TX-100) can be achieved by adjusting mainly the composition of these systems. The interactions of anionic drug IBF with non-ionic surfactant TX-100 micelles have been investigated using tensiometry, fluorometry and 1 H NMR in aqueous as well in 250 mmol⋅kg −1 urea solutions. Different theoretical models like Clint, Rubingh, and Rosen, etc. were utilized to get information about the nature of interaction between these two in bulk and at the interface. These models disclose that the non-ideal behavior with attractive interaction in bulk and at the interface exists. The steady-state fluorescence quenching study was employed to evaluate micelle aggregation numbers (N agg ), which signify the involvement of surfactant was forever higher compared to IBF. Stern–Volmer binding constants (K sv ), micropolarity (I 1 /I 3 ) and dielectric constant (D exp ) of the mixtures are also obtained using fluorescence method. By the addition of urea raise in the surface charge of the micelles was observed followed by halt of the micellization of drug and surfactant as well as their mixture, therefore cmc values increases followed by decrease in aggregation number. The 1 H NMR resonance intensity variations were paralleled by upfield shifts in the resonance frequencies, due to an increased shielding of IBF happening from closeness of the non-ionic TX-100 surfactant.

Tank 241-TX-105 tank characterization plan

International Nuclear Information System (INIS)

Carpenter, B.C.

1995-01-01

This document is a plan which serves as the contractual agreement between the Characterization Program, Sampling Operations, WHC 222-S Laboratory, Oak Ridge National Laboratory, and PNL tank vapor program. The scope of this plan is to provide guidance for the sampling and analysis of vapor samples from tank 241-TX-105

Protective Effects of Dihydrocaffeic Acid, a Coffee Component Metabolite, on a Focal Cerebral Ischemia Rat Model

Directory of Open Access Journals (Sweden)

Kyungjin Lee

2015-06-01

Full Text Available We recently reported the protective effects of chlorogenic acid (CGA in a transient middle cerebral artery occlusion (tMCAo rat model. The current study further investigated the protective effects of the metabolites of CGA and dihydrocaffeic acid (DHCA was selected for further study after screening using the same tMCAo rat model. In the current study, tMCAo rats (2 h of MCAo followed by 22 h of reperfusion were injected with various doses of DHCA at 0 and 2 h after onset of ischemia. We assessed brain damage, functional deficits, brain edema, and blood-brain barrier damage at 24 h after ischemia. For investigating the mechanism, in vitro zymography and western blotting analysis were performed to determine the expression and activation of matrix metalloproteinase (MMP-2 and -9. DHCA (3, 10, and 30 mg/kg, i.p. dose-dependently reduced brain infarct volume, behavioral deficits, brain water content, and Evans Blue (EB leakage. DHCA inhibited expression and activation of MMP-2 and MMP-9. Therefore, DHCA might be one of the important metabolites of CGA and of natural products, including coffee, with protective effects on ischemia-induced neuronal damage and brain edema.

75 FR 39149 - Establishment of Low Altitude Area Navigation Route (T-284); Houston, TX

Science.gov (United States)

2010-07-08

... (T-284); Houston, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Final rule... area navigation (RNAV) route T-284 for the Houston, TX, terminal area, is being withdrawn. As a result of Houston Area Air Traffic System (HAATS) Project, Phase 3C, program actions, the route is pending...

Experimental models of longitudinal abdominal incisional hernia in rats Modelos experimentais de hérnias incisionais abdominais longitudinais, em ratos

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Danilo N. S. Paulo

1997-12-01

Full Text Available Abdominal incisional hernias in rats has been produced after resection of a segment of abdominal muscle. In a attempt to create a model of incisional hernia in rats, without resection of abdominal muscle, the following surgical procedures were performed: (a Rats anesthetized with ether were submitted to a 4 cm long median incision, supra and infraumbilical, followed by dissection of the subcutaneous tissue 1.5 cm laterally to the median line in each side; after, one incision was performed in the linea alba and peritoneum, with the same extension of the skin incision; the skin incision was sutured. (b Rats were submited to a suprapubic transversal incision and a scissors introduced through this incision and used to dissect the subcutaneous tissue at least 1.5 cm for each side of median line; after, the linea alba and peritoneoum were incised and the transversal skin incision sutured. (c For control, rats were submitted to a resection of a 2.5 x 4 cm of the abdominal muscles, creating a large defect in the abdominal wall. All the animal, submitted to the three different procedures, developed similar well constituted hernias. We concluded that abdominal incisonal hernias are easily induced in rats after an incision of the abdominal wall, without partial resection of abdominal muscle, since the subcutaneous have been dissected at least 1.5 cm laterally to the median line.Hérnias incisionais abdominais no rato têm sido produzidas pela ressecção de fragmento dos músculos de parede abdominal. Na tentativa de criar um modelo de hérnia incisional abdominal no rato, sem ressecção de fragmentos de músculo de parede abdominal, os seguintes procedimentos cirúrgicos foram realizados: (a Ratos anestesiados com vapores de éter foram submetidos à uma incisão longitudinal mediana supra e infra umbilical, de 4 cm de comprimento, seguida do descolamento do tecido celular subcutaneo em uma extensão de 1,5 cm lateralmente à linha mediana; de cada lado

Switch-task performance in rats is disturbed by 12 h of sleep deprivation but not by 12 h of sleep fragmentation.

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Leenaars, Cathalijn H C; Joosten, Ruud N J M A; Zwart, Allard; Sandberg, Hans; Ruimschotel, Emma; Hanegraaf, Maaike A J; Dematteis, Maurice; Feenstra, Matthijs G P; van Someren, Eus J W

2012-02-01

Task-switching is an executive function involving the prefrontal cortex. Switching temporarily attenuates the speed and/or accuracy of performance, phenomena referred to as switch costs. In accordance with the idea that prefrontal function is particularly sensitive to sleep loss, switch-costs increase during prolonged waking in humans. It has been difficult to investigate the underlying neurobiological mechanisms because of the lack of a suitable animal model. Here, we introduce the first switch-task for rats and report the effects of sleep deprivation and inactivation of the medial prefrontal cortex. Rats were trained to repeatedly switch between 2 stimulus-response associations, indicated by the presentation of a visual or an auditory stimulus. These stimulus-response associations were offered in blocks, and performance was compared for the first and fifth trials of each block. Performance was tested after exposure to 12 h of total sleep deprivation, sleep fragmentation, and their respective movement control conditions. Finally, it was tested after pharmacological inactivation of the medial prefrontal cortex. Controlled laboratory settings. 15 male Wistar rats. Both accuracy and latency showed switch-costs at baseline. Twelve hours of total sleep deprivation, but not sleep fragmentation, impaired accuracy selectively on the switch-trials. Inactivation of the medial prefrontal cortex by local neuronal inactivation resulted in an overall decrease in accuracy. We developed and validated a switch-task that is sensitive to sleep deprivation. This introduces the possibility for in-depth investigations on the neurobiological mechanisms underlying executive impairments after sleep disturbance in a rat model.

Extracellular pH modulates GABAergic neurotransmission in rat hypothalamus.

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Chen, Z L; Huang, R Q

2014-06-20

Changes in extracellular pH have a modulatory effect on GABAA receptor function. It has been reported that pH sensitivity of the GABA receptor is dependent on subunit composition and GABA concentration. Most of previous investigations focused on GABA-evoked currents, which only reflect the postsynaptic receptors. The physiological relevance of pH modulation of GABAergic neurotransmission is not fully elucidated. In the present studies, we examined the influence of extracellular pH on the GABAA receptor-mediated inhibitory neurotransmission in rat hypothalamic neurons. The inhibitory postsynaptic currents (IPSCs), tonic currents, and the GABA-evoked currents were recorded with whole-cell patch techniques on the hypothalamic slices from Sprague-Dawley rats at 15-26 postnatal days. The amplitude and frequency of spontaneous GABA IPSCs were significantly increased while the external pH was changed from 7.3 to 8.4. In the acidic pH (6.4), the spontaneous GABA IPSCs were reduced in amplitude and frequency. The pH induced changes in miniature GABA IPSCs (mIPSCs) similar to that in spontaneous IPSCs. The pH effect on the postsynaptic GABA receptors was assessed with exogenously applied varying concentrations of GABA. The tonic currents and the currents evoked by sub-saturating concentration of GABA ([GABA]) (10 μM) were inhibited by acidic pH and potentiated by alkaline pH. In contrast, the currents evoked by saturating [GABA] (1mM) were not affected by pH changes. We also investigated the influence of pH buffers and buffering capacity on pH sensitivity of GABAA receptors on human recombinant α1β2γ2 GABAA receptors stably expressed in HEK 293 cells. The pH influence on GABAA receptors was similar in HEPES- and MES-buffered media, and not dependent on protonated buffers, suggesting that the observed pH effect on GABA response is a specific consequence of changes in extracellular protons. Our data suggest that the hydrogen ions suppress the GABAergic neurotransmission

The Histamine H1 Receptor Participates in the Increased Dorsal Telencephalic Neurogenesis in Embryos from Diabetic Rats

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Karina H. Solís

2017-12-01

Full Text Available Increased neuron telencephalic differentiation during deep cortical layer formation has been reported in embryos from diabetic mice. Transitory histaminergic neurons within the mesencephalon/rhombencephalon are responsible for fetal histamine synthesis during development, fibers from this system arrives to the frontal and parietal cortex at embryo day (E 15. Histamine is a neurogenic factor for cortical neural stem cells in vitro through H1 receptor (H1R which is highly expressed during corticogenesis in rats and mice. Furthermore, in utero administration of an H1R antagonist, chlorpheniramine, decreases the neuron markers microtubuline associated protein 2 (MAP2 and forkhead box protein 2. Interestingly, in the diabetic mouse model of diabetes induced with streptozotocin, an increase in fetal neurogenesis in terms of MAP2 expression in the telencephalon is reported at E11.5. Because of the reported effects on cortical neuron differentiation of maternal diabetes in one hand and of histamine in the other, here the participation of histamine and H1R on the increased dorsal telencephalic neurogenesis was explored. First, the increased neurogenesis in the dorsal telencephalon at E14 in diabetic rats was corroborated by immunohistochemistry and Western blot. Then, changes during corticogenesis in the level of histamine was analyzed by ELISA and in H1R expression by qRT-PCR and Western blot and, finally, we tested H1R participation in the increased dorsal telencephalic neurogenesis by the systemic administration of chlorpheniramine. Our results showed a significant increase of histamine at E14 and in the expression of the receptor at E12. The administration of chlorpheniramine to diabetic rats at E12 prevented the increased expression of βIII-tubulin and MAP2 mRNAs (neuron markers and partially reverted the increased level of MAP2 protein at E14, concluding that H1R have an important role in the increased neurogenesis within the dorsal telencephalon

Plasma hormones facilitated the hypermotility of the colon in a chronic stress rat model.

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Chengbai Liang

Full Text Available OBJECTIVE: To study the relationship between brain-gut peptides, gastrointestinal hormones and altered motility in a rat model of repetitive water avoidance stress (WAS, which mimics the irritable bowel syndrome (IBS. METHODS: Male Wistar rats were submitted daily to 1-h of water avoidance stress (WAS or sham WAS (SWAS for 10 consecutive days. Plasma hormones were determined using Enzyme Immunoassay Kits. Proximal colonic smooth muscle (PCSM contractions were studied in an organ bath system. PCSM cells were isolated by enzymatic digestion and IKv and IBKca were recorded by the patch-clamp technique. RESULTS: The number of fecal pellets during 1 h of acute restraint stress and the plasma hormones levels of substance P (SP, thyrotropin-releasing hormone (TRH, motilin (MTL, and cholecystokinin (CCK in WAS rats were significantly increased compared with SWAS rats, whereas vasoactive intestinal peptide (VIP, calcitonin gene-related peptide (CGRP and corticotropin releasing hormone (CRH in WAS rats were not significantly changed and peptide YY (PYY in WAS rats was significantly decreased. Likewise, the amplitudes of spontaneous contractions of PCSM in WAS rats were significantly increased comparing with SWAS rats. The plasma of WAS rats (100 µl decreased the amplitude of spontaneous contractions of controls. The IKv and IBKCa of PCSMs were significantly decreased in WAS rats compared with SWAS rats and the plasma of WAS rats (100 µl increased the amplitude of IKv and IBKCa in normal rats. CONCLUSION: These results suggest that WAS leads to changes of plasma hormones levels and to disordered myogenic colonic motility in the short term, but that the colon rapidly establishes a new equilibrium to maintain the normal baseline functioning.

Trans-arterial xenotransplantation (Tx) of newborn porcine islet (NPI). A clinic trial for type I diabetes

International Nuclear Information System (INIS)

Wang Wei; Mo Zhaohui; Huang Zufa; Luo Xianming; Liu Sheng; Ye Bin; Li Bing; Liu Yingxin

2002-01-01

Objective: Liver is an important site to host transplanted islets, and implanting of islets by hepatic artery is simpler than by portal vein. Authors' study evaluated efficiency of the method and possible complication in a clinical setting. Methods: From October 1998 to June 2000, 4 type I diabetic patients received 4 x 10 6 (2 cases) and 8 x 10 6 (2 cases) of NPI through hepatic artery. Before Tx, all cases had the history with ketosis and acidosis. Exogenous insulin doses used for these cases were 25-48 units and their GHb was 9%-11%. After Tx, the NPI recipients were treated with immunosuppressants including cyclosporin 8 mg/kg for 12 months, cellcept 2 g/d for 25 days, and methylprednisolone 500 mg at 1 st day, then reduced to 50 mg for 3 days until to 10 mg for 1 month. Liver function and CD4/CD8 of the recipients were measured before and after Tx. Results: After Tx, the dose of exogenous insulin was increased to 60 mg due to methylprednisolone treatment. When methylprednisolone dose was decreased, the requirement for insulin was reduced to 32%-58% of the dose used before Tx. The reduction of required insulin for NPI recipients was proportional to the number of implanted NPI. In addition, GHb was also reduced to normal level (4%-6%) 3 months after Tx. No significant alterations of liver function and CD4 and CD8 in blood were observed after Tx. Conclusion: Trans-arterial intro-hepatic xenotransplantation of NPI is an efficient and safe therapeutic method for type I diabetes. Combination of cyclosporin, cellcept, and methylprednisolone is an effective immunosuppressive strategy for NPI xenograft transplantation

In Vivo Assessment of Gamma Rays, Electron-beam Irradiation plus a Commercial Toxin Binder (Milbond-TX As an Anti-Aflatoxin B1 in a Chicken Model

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Saeed Hasanpour

2018-02-01

Full Text Available Background: Aspergillus flavus is the most important fungus for production of Aflatoxin B1 (AFB1. This study evaluated the ability of gamma rays (GRs and electron-beam irradiation (EBI to counteract the deleterious effects of aflatoxin B1 (AFB1 in a chicken model. Methods: Overall, 168 one-day-old male Coturnix quails were assigned to eight treatments for 42 d in Tehran, Iran, in 2010 and 2011. Two dietary inclusion rates of AFB1 (0 and 2 ppm and toxin binders, such as 0, 27 kGy doses of GRs, 27 kGy doses of EBI, and 0.3% of commercial toxin binder-milbond-TX, were tested in a 2×4 factorial manner. Serum biochemical parameters, immune response, and dietary treatments on factors associated with kidney and lipid profiles were determined on day 42. Results: AFB1 significantly decreased the hematological parameters (Hematocrit in 21 and 42 d, immune response (White blood cell (WBC, heterophil to lymphocyte ratio (H/L and sheep red blood cell (SRBC, and blood chemical factors (glucose, albumin, total protein, and triglycerides compared to the control diet (P<0.05. It also significantly increased the calcium, phosphorus, uric acid, and low-density lipoprotein (LDL levels (P<0.05. The addition of toxin binders, such as GRs, EBI, and milbond-TX, in the contaminated diets significantly diminished the inhibitory effects of dietary AFB1 (P<0.05 on the hematological parameters, immune response, blood chemical factors, and factors associated with kidney and lipids profile with no differences compared to the control diet. Conclusion: The addition of these toxin binders may reduce the adverse effects produced by the presence of AFB1 in Japanese quails’ diets.

Characterization of [(3)H]harmane binding to rat whole brain membranes.

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Anderson, N J; Robinson, E S J; Husbands, S M; Delagrange, P; Nutt, D J; Hudson, A L

2003-12-01

This study investigates the binding of [(3)H]harmane to rat whole brain homogenates. Saturation studies revealed [(3)H]harmane labels a single, saturable, high-capacity population with high affinity. All the test compounds displaced [(3)H]harmane completely and in an apparently monophasic manner. The displacement profile of the test ligands indicated labeling of MAO-A. Given the high level of MAO-A binding, it is unlikely that a low-capacity I(2) site would be distinguishable from the total [(3)H]harmane population.

Autoradiographic localization of 3H-paroxetine-labeled serotonin uptake sites in rat brain

International Nuclear Information System (INIS)

De Souza, E.B.; Kuyatt, B.L.

1987-01-01

Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3H-paroxetine; 3H-paroxetine binding in slide-mounted sections of rat forebrain was of high affinity (KD = 10 pM) and the inhibition affinity constant (Ki) values of various drugs in competing 3H-paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3H-paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3H-paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3H-paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3H-paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4-methylenedioxyamphetamine caused large decreases in 3H-paroxetine binding. The autoradiographic distribution of 3H-paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin

Attention and executive functions in a rat model of chronic epilepsy.

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Faure, Jean-Baptiste; Marques-Carneiro, José E; Akimana, Gladys; Cosquer, Brigitte; Ferrandon, Arielle; Herbeaux, Karine; Koning, Estelle; Barbelivien, Alexandra; Nehlig, Astrid; Cassel, Jean-Christophe

2014-05-01

Temporal lobe epilepsy is a relatively frequent, invalidating, and often refractory neurologic disorder. It is associated with cognitive impairments that affect memory and executive functions. In the rat lithium-pilocarpine temporal lobe epilepsy model, memory impairment and anxiety disorder are classically reported. Here we evaluated sustained visual attention in this model of epilepsy, a function not frequently explored. Thirty-five Sprague-Dawley rats were subjected to lithium-pilocarpine status epilepticus. Twenty of them received a carisbamate treatment for 7 days, starting 1 h after status epilepticus onset. Twelve controls received lithium and saline. Five months later, attention was assessed in the five-choice serial reaction time task, a task that tests visual attention and inhibitory control (impulsivity/compulsivity). Neuronal counting was performed in brain regions of interest to the functions studied (hippocampus, prefrontal cortex, nucleus basalis magnocellularis, and pedunculopontine tegmental nucleus). Lithium-pilocarpine rats developed motor seizures. When they were able to learn the task, they exhibited attention impairment and a tendency toward impulsivity and compulsivity. These disturbances occurred in the absence of neuronal loss in structures classically related to attentional performance, although they seemed to better correlate with neuronal loss in hippocampus. Globally, rats that received carisbamate and developed motor seizures were as impaired as untreated rats, whereas those that did not develop overt motor seizures performed like controls, despite evidence for hippocampal damage. This study shows that attention deficits reported by patients with temporal lobe epilepsy can be observed in the lithium-pilocarpine model. Carisbamate prevents the occurrence of motor seizures, attention impairment, impulsivity, and compulsivity in a subpopulation of neuroprotected rats. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

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Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

2015-01-01

Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

Astrocytes and Müller cells changes during retinal degeneration in a transgenic rat model of retinitis pigmentosa.

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Laura eFernández-Sánchez

2015-12-01

Full Text Available Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer of P23H versus SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

Magnetic resonance spectroscopy of traumatic brain in SD rats model

International Nuclear Information System (INIS)

Li Ke; Li Yangbin; Li Zhiming; Huang Yong; Li Bin; Lu Guangming

2009-01-01

Objective: To assess the value and prospect of magnetic resonance spectroscopy (MRS) in early diagnosis of traumatic brain with traumatic brain model in SD rats. Methods: Traumatic brain modal was established in 40 male SD rats utilizing a weigh-drop device, and MRS was performed before trauma and 4,8,24 and 48 hours after trauma. The ratio of N-acetylaspartate/creatine (NAA/Ct) and choline/creatine (Cho/Cr) were calculated and compared with pathological findings respectively. Results: Axonal changes were confirmed in microscopic study 4 hours after injury. The ratio of NAA/Ct decreased distinctly at 4 hours after trauma, followed by a steadily recover at 8 hours, and no significant change from 24h to 48h. There was no significant change in the ratio of Cho/Cr before and after trauma. Conclusion: MRS can be used to monitor the metabolic changes of brain non-invasively. MRS could play a positive role in early diagnosis, prognosis and follow-up of traumatic brain. (authors)

Effect of sodium aescinate treatment on PCOS rat model with insulin resistance.

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Chen, L; Hu, L M; Wang, Y F; Yang, H Y; Huang, X Y; Zhou, W; Sun, H X

2017-01-01

Recent studies indicated that insulin resistance may contribute to the pathogenesis of polycystic ovary syndrome (PCOS); however, the specific mechanism is still unclear. To investigate the effect of sodium aescinate (SA) on PCOS-IR rat models. Sixty rats were randomly divided into the five groups: un-treated rats (n = 12), PCOS-IR group (n = 12), PCOS-IR group plus 50 mg/kg SA (n = 12), PCOS-IR group plus 10 mg/kg SA (n = 12), PCOS-IR group plus 150 mg/kg metformin (n = 12). On day 21, rats were sacrificed, and H(and)E staining was performed for histopathologic examination of the ovaries; moreover, the serum level of follicle-stimulating hormone (FSH), testosterone, and luteotropic hormone (LH) were measured, and the expression as well as phosphorylation of PI3K, Akt and Gsk-3β were examined using western blot assay. High dosage of SA treatment improved the morphological features of the ovaries in PCOS rats, and also induced significant decrease in serum expression of testosterone and LH/FSH ratio and significant decrease in the expression of p-PI3K, p-Akt and p-Gsk-3β. Our results demonstrated that SA treatment could alleviate the symptom of PCOS in rat model through regulating the PI3K/Akt/GSK3-β pathway (Fig. 4, Ref. 22).

Characterization with 3H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

International Nuclear Information System (INIS)

Nakajima, Tohru; Kuruma, Isami

1980-01-01

The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of 3 H-haloperidol binding. Binding of 3 H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the 3 H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum. (author)

Effect of triiodothyronine on the maxilla and masseter muscles of the rat stomatognathic system

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M.V. Mariúba

2011-07-01

Full Text Available The maxilla and masseter muscles are components of the stomatognathic system involved in chewing, which is frequently affected by physical forces such as gravity, and by dental, orthodontic and orthopedic procedures. Thyroid hormones (TH are known to regulate the expression of genes that control bone mass and the oxidative properties of muscles; however, little is known about the effects of TH on the stomatognathic system. This study investigated this issue by evaluating: i osteoprotegerin (OPG and osteopontine (OPN mRNA expression in the maxilla and ii myoglobin (Mb mRNA and protein expression, as well as fiber composition of the masseter. Male Wistar rats (~250 g were divided into thyroidectomized (Tx and sham-operated (SO groups (N = 24/group treated with T3 or saline (0.9% for 15 days. Thyroidectomy increased OPG (~40% and OPN (~75% mRNA expression, while T3 treatment reduced OPG (~40% and OPN (~75% in Tx, and both (~50% in SO rats. Masseter Mb mRNA expression and fiber type composition remained unchanged, despite the induction of hypo- and hyperthyroidism. However, Mb content was decreased in Tx rats even after T3 treatment. Since OPG and OPN are key proteins involved in the osteoclastogenesis inhibition and bone mineralization, respectively, and that Mb functions as a muscle store of O2 allowing muscles to be more resistant to fatigue, the present data indicate that TH also interfere with maxilla remodeling and the oxidative properties of the masseter, influencing the function of the stomatognathic system, which may require attention during dental, orthodontic and orthopedic procedures in patients with thyroid diseases.

Radiating Elements for Shared Aperture Tx/Rx Phased Arrays at K/Ka Band

KAUST Repository

Sandhu, Ali Imran; Arnieri, E.; Amendola, Giandomenico; Boccia, L.; Meniconi, Erika; Ziegler, Volker

2016-01-01

A dual band, Tx/Rx, self-diplexing phased array is presented. The antenna has been designed to cover Tx/Rx satellite communications at K/Ka band with a frequency ratio 1.5:1. To obtain dual band operations with a single radiating surface, a novel dual band radiator is adopted and placed in a configuration in which dual band and single band elements are interleaved. The proposed configuration reduces the number of radiating elements required by other solutions while avoiding the insurgence of grating lobes. The tightly packed arrangement of the elements poses many integration issues, which are solved with a novel integration technique. The array elements are optimized to scan the beam in excess of ° in both bands. A subarray with 49 Rx elements and 105 Tx elements was built and measured confirming the results obtained in simulations.

Radiating Elements for Shared Aperture Tx/Rx Phased Arrays at K/Ka Band

KAUST Repository

Sandhu, Ali Imran

2016-04-11

A dual band, Tx/Rx, self-diplexing phased array is presented. The antenna has been designed to cover Tx/Rx satellite communications at K/Ka band with a frequency ratio 1.5:1. To obtain dual band operations with a single radiating surface, a novel dual band radiator is adopted and placed in a configuration in which dual band and single band elements are interleaved. The proposed configuration reduces the number of radiating elements required by other solutions while avoiding the insurgence of grating lobes. The tightly packed arrangement of the elements poses many integration issues, which are solved with a novel integration technique. The array elements are optimized to scan the beam in excess of ° in both bands. A subarray with 49 Rx elements and 105 Tx elements was built and measured confirming the results obtained in simulations.

High affinity [3H]glibenclamide binding sites in rat neuronal and cardiac tissue: Localization and developmental characteristics

International Nuclear Information System (INIS)

Miller, J.A.; Velayo, N.L.; Dage, R.C.; Rampe, D.

1991-01-01

We examined the binding of the antidiabetic sulfonylurea [3H] glibenclamide to rat brain and heart membranes. High affinity binding was observed in adult rat forebrain (Kd = 137.3 pM, maximal binding site density = 91.8 fmol/mg of protein) and ventricle (Kd = 77.1 pM, maximal binding site density = 65.1 fmol/mg of protein). Binding site density increased approximately 250% in forebrain membranes during postnatal development but was constant in ventricular membranes. Quantitative autoradiography was used to examine the regional distribution of [3H] glibenclamide binding sites in sections from rat brain, spinal cord and heart. The greatest density of binding in adult brain was found in the substantia nigra and globus pallidus, whereas the other areas displayed heterogenous binding. In agreement with the membrane binding studies, 1-day-old rat brain had significantly fewer [3H]glibenclamide binding sites than adult brain. Additionally, the pattern of distribution of these sites was qualitatively different from that of the adult. In adult rat spinal cord, moderate binding densities were observed in spinal cord gray and displayed a rostral to caudal gradient. In adult rat heart, moderate binding densities were observed and the sites were distributed homogeneously. In conclusion, significant development of [3H]glibenclamide binding sites was seen in the brain but not the heart during postnatal maturation. Furthermore, a heterogeneous distribution of binding sites was observed in both the brain and spinal cord of adult rats

Molecular characterization of barley 3H semi-dwarf genes.

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Haobing Li

Full Text Available The barley chromosome 3H accommodates many semi-dwarfing genes. To characterize these genes, the two-rowed semi-dwarf Chinese barley landrace 'TX9425' was crossed with the Australian barley variety 'Franklin' to generate a doubled haploid (DH population, and major QTLs controlling plant height have been identified in our previous study. The major QTL derived from 'TX9425' was targeted to investigate the allelism of the semi-dwarf gene uzu in barley. Twelve sets of near-isogenic lines and a large NILF2 fine mapping population segregating only for the dwarfing gene from 'TX9425' were developed. The semi-dwarfing gene in 'TX9425' was located within a 2.8 cM region close to the centromere on chromosome 3H by fine mapping. Molecular cloning and sequence analyses showed that the 'TX9425'-derived allele contained a single nucleotide substitution from A to G at position 2612 of the HvBRI1 gene. This was apparently the same mutation as that reported in six-rowed uzu barley. Markers co-segregating with the QTL were developed from the sequence of the HvBRI1 gene and were validated in the 'TX9425'/'Franklin' DH population. The other major dwarfing QTL derived from the Franklin variety was distally located on chromosome 3HL and co-segregated with the sdw1 diagnostic marker hv20ox2. A third dwarfing gene, expressed only in winter-sown trials, was identified and located on chromosome 3HS. The effects and interactions of these dwarfing genes under different growing conditions are discussed. These results improve our understanding of the genetic mechanisms controlling semi-dwarf stature in barley and provide diagnostic markers for the selection of semi-dwarfness in barley breeding programs.

Absence of “Warm-Up” during Active Avoidance Learning in a Rat Model of Anxiety Vulnerability: Insights from Computational Modeling

Science.gov (United States)

Myers, Catherine E.; Smith, Ian M.; Servatius, Richard J.; Beck, Kevin D.

2014-01-01

Avoidance behaviors, in which a learned response causes omission of an upcoming punisher, are a core feature of many psychiatric disorders. While reinforcement learning (RL) models have been widely used to study the development of appetitive behaviors, less attention has been paid to avoidance. Here, we present a RL model of lever-press avoidance learning in Sprague-Dawley (SD) rats and in the inbred Wistar Kyoto (WKY) rat, which has been proposed as a model of anxiety vulnerability. We focus on “warm-up,” transiently decreased avoidance responding at the start of a testing session, which is shown by SD but not WKY rats. We first show that a RL model can correctly simulate key aspects of acquisition, extinction, and warm-up in SD rats; we then show that WKY behavior can be simulated by altering three model parameters, which respectively govern the tendency to explore new behaviors vs. exploit previously reinforced ones, the tendency to repeat previous behaviors regardless of reinforcement, and the learning rate for predicting future outcomes. This suggests that several, dissociable mechanisms may contribute independently to strain differences in behavior. The model predicts that, if the “standard” inter-session interval is shortened from 48 to 24 h, SD rats (but not WKY) will continue to show warm-up; we confirm this prediction in an empirical study with SD and WKY rats. The model further predicts that SD rats will continue to show warm-up with inter-session intervals as short as a few minutes, while WKY rats will not show warm-up, even with inter-session intervals as long as a month. Together, the modeling and empirical data indicate that strain differences in warm-up are qualitative rather than just the result of differential sensitivity to task variables. Understanding the mechanisms that govern expression of warm-up behavior in avoidance may lead to better understanding of pathological avoidance, and potential pathways to modify these processes. PMID

T-x projections of phase diagrams of the MeF-BeF2 systems

International Nuclear Information System (INIS)

Korenev, Yu.M.; Rykov, A.N.; Novoselova, A.V.

1976-01-01

The T-x projections of the state diagrams of the systems MeF-BeF 2 (Me=Li-Rb) have been plotted. Transformation of P-x cross sections of the system state diagrams with decreasing temperature have been considered with the aid, of the general view of T-x projections. The nature of sublimation of the compounds formed in these systems is discussed

Risk Assessment of Deoxynivalenol by Revisiting Its Bioavailability in Pig and Rat Models to Establish Which Is More Suitable

Directory of Open Access Journals (Sweden)

Manuel Jimmy Saint-Cyr

2015-12-01

Full Text Available Due to its toxic properties, high stability, and prevalence, the presence of deoxynivalenol (DON in the food chain is a major threat to food safety and therefore a health risk for both humans and animals. In this study, experiments were carried out with sows and female rats to examine the kinetics of DON after intravenous and oral administration at 100 µg/kg of body weight. After intravenous administration of DON in pigs, a two-compartment model with rapid initial distribution (0.030 ± 0.019 h followed by a slower terminal elimination phase (1.53 ± 0.54 h was fitted to the concentration profile of DON in pig plasma. In rats, a short elimination half-life (0.46 h and a clearance of 2.59 L/h/kg were estimated by sparse sampling non-compartmental analysis. Following oral exposure, DON was rapidly absorbed and reached maximal plasma concentrations (Cmax of 42.07 ± 8.48 and 10.44 ± 5.87 µg/L plasma after (tmax 1.44 ± 0.52 and 0.17 h in pigs and rats, respectively. The mean bioavailability of DON was 70.5% ± 25.6% for pigs and 47.3% for rats. In the framework of DON risk assessment, these two animal models could be useful in an exposure scenario in two different ways because of their different bioavailability.

Pharmacologic studies on ET-26 hydrochloride in a rat model of lipopolysaccharide-induced sepsis.

Science.gov (United States)

Wang, Bin; Jiang, Junli; Yang, Jun; Chen, Jun; Zhu, Zhaoqiong; Liu, Jin; Zhang, Wensheng

2017-11-15

ET-26 hydrochloride (ET-26 HCl) is a promising sedation-hypnotic compound with stable hemodynamic features that elicits virtually no adrenocortical suppression. However, whether it preserves better pharmacologic characteristics in a rat model of sepsis is not known. This study compared the survival rate, levels of corticosterone and pro-inflammatory cytokines, and histologic injury in the lungs and kidneys of rats suffering from sepsis treated with ET-26 HCl, etomidate, or normal saline (NS). Rats were given lipopolysaccharide (1mg/kg body weight, i.v.) to establish a sepsis model. Thirty minutes after lipopolysaccharide administration, ET-26 HCl, etomidate or NS were given as a bolus injection at equivalent doses. Plasma levels of corticosterone, interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α were measured 1, 2, 4, 6 and 24h after administration. Histologic injury was observed at the time of death or 24h after drug administration. The survival rate for rats in the etomidate, ET-26 HCl and NS groups was 40%, 90% and 90%, respectively. Corticosterone concentrations in the etomidate group were lower than those in the other groups 1h after administration of hypnotic compounds. Concentrations of pro-inflammatory cytokines in the ET-26 HCl group and NS group were not significantly different, but were significantly lower than those in the etomidate group. The injury scores of kidneys and lungs in the etomidate group were higher than those in ET-26 HCl and NS groups. ET-26 HCl showed virtually no suppression of corticosterone synthesis, lower concentrations of pro-inflammatory cytokines, higher survival rate, and less organ injury in rats suffering from sepsis compared with the etomidate group. It may be safer to induce anesthesia using ET-26 HCl, rather than etomidate, in patients suffering from sepsis. Copyright © 2017 Elsevier B.V. All rights reserved.

The cerebroprotective effect of dextromethorphan assessed by 1H and 31P NMR spectroscopy during global forebrain ischemia in the rat

International Nuclear Information System (INIS)

Tulleken, C.A.F.; Rijen, P.C. van; Berkelbach van der Sprenkel, J.W.; Verheul, H.B.; Echteld, C.J.A. van; Balasz, R.; Lewis, P.

1991-01-01

Global forebrain ischemia was induced in the rat model by occlusion of both carotid arteries and subsequent lowering of the blood pressure. After 30 minutes of ischemia reperfusion was established. Using 1H and 31P NMR spectroscopy tissue pH values, lactate production, cellular energy index and N-acetyl-aspartate content were determined. The survival rates and histological damage were counted. (author)

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

International Nuclear Information System (INIS)

Trifilieff, Alexandre; Ethell, Brian T.; Sykes, David A.; Watson, Kenny J.; Collingwood, Steve; Charlton, Steven J.; Kent, Toby C.

2015-01-01

Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED 50 values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M 2 muscarinic receptor occupancy, which predicted significantly higher M 2 receptor blockade at ED 50 doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED 50 doses for bronchoprotection we model systemic M 2 receptor occupancy. • Glycopyrrolate demonstrates lower M 2 occupancy at

Comparing the cardiovascular therapeutic indices of glycopyrronium and tiotropium in an integrated rat pharmacokinetic, pharmacodynamic and safety model

Energy Technology Data Exchange (ETDEWEB)

Trifilieff, Alexandre; Ethell, Brian T. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); Sykes, David A. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); School of Life Sciences, Queen' s Medical Centre, University of Nottingham, Nottingham, NG7 2UH (United Kingdom); Watson, Kenny J.; Collingwood, Steve [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); Charlton, Steven J. [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom); School of Life Sciences, Queen' s Medical Centre, University of Nottingham, Nottingham, NG7 2UH (United Kingdom); Kent, Toby C., E-mail: tobykent@me.com [Respiratory Disease Area, Novartis Institutes for Biomedical Research, Wimblehurst Road, Horsham, West Sussex RH12 5AB (United Kingdom)

2015-08-15

Long acting inhaled muscarinic receptor antagonists, such as tiotropium, are widely used as bronchodilator therapy for chronic obstructive pulmonary disease (COPD). Although this class of compounds is generally considered to be safe and well tolerated in COPD patients the cardiovascular safety of tiotropium has recently been questioned. We describe a rat in vivo model that allows the concurrent assessment of muscarinic antagonist potency, bronchodilator efficacy and a potential for side effects, and we use this model to compare tiotropium with NVA237 (glycopyrronium bromide), a recently approved inhaled muscarinic antagonist for COPD. Anaesthetized Brown Norway rats were dosed intratracheally at 1 or 6 h prior to receiving increasing doses of intravenous methacholine. Changes in airway resistance and cardiovascular function were recorded and therapeutic indices were calculated against the ED{sub 50} values for the inhibition of methacholine-induced bronchoconstriction. At both time points studied, greater therapeutic indices for hypotension and bradycardia were observed with glycopyrronium (19.5 and 28.5 fold at 1 h; > 200 fold at 6 h) than with tiotropium (1.5 and 4.2 fold at 1 h; 4.6 and 5.5 fold at 6 h). Pharmacokinetic, protein plasma binding and rat muscarinic receptor binding properties for both compounds were determined and used to generate an integrated model of systemic M{sub 2} muscarinic receptor occupancy, which predicted significantly higher M{sub 2} receptor blockade at ED{sub 50} doses with tiotropium than with glycopyrronium. In our preclinical model there was an improved safety profile for glycopyrronium when compared with tiotropium. - Highlights: • We use an in vivo rat model to study CV safety of inhaled muscarinic antagonists. • We integrate protein and receptor binding and PK of tiotropium and glycopyrrolate. • At ED{sub 50} doses for bronchoprotection we model systemic M{sub 2} receptor occupancy. • Glycopyrrolate demonstrates lower M

Characterizing urbanization impacts on floodplain through integrated land use, hydrologic, and hydraulic modeling: Applications to a watershed in northwest Houston, TX

Science.gov (United States)

Gori, A.; Juan, A.; Blessing, R.; Brody, S.; Bedient, P. B.

2017-12-01

The FEMA 100 year floodplain serves as the benchmark for characterizing and managing flood risk in the United States. However, it is usually generated by using methodologies that are too simplistic to accurately depict the spatial reality of flood risk, and often fail to consider non-stationary variables such as changing land use conditions or precipitation patterns. The impacts of these limitations are evidenced in Houston, TX, where rainfall-induced flooding has resulted in billions of dollars in commercial and residential damage over the past two decades, much of which has occurred outside of the 100 year floodplain. Specifically, rapid urbanization has drastically increased overland runoff and resulting peak flows, thereby exposing new areas to flood risks. It is therefore crucial to examine the impacts of future land development on floodplain depth and extent in order to develop effective long-term stormwater management and mitigation strategies. This study presents a methodology for characterizing the impacts of future development on flood risk in an urbanizing watershed by integrating land use projection and high-resolution hydrologic / hydraulic modeling. Development projections are generated by identifying historical land use/ land cover change (LULCC) drivers, which are incorporated into an artificial neural network (ANN) to predict development conditions out to 2040. Hydrologic modeling of current and projected land cover conditions is achieved through a physics-based distributed hydrologic model. Finally, a coupled 1D/2D unsteady hydraulic model is used to simulate floodplain depths and extents, and to generate floodplain maps for all considered scenarios. This methodology is applied to the Cypress Creek watershed in northwest Houston, TX, a partially-developed watershed which is expected to rapidly urbanize for the next few decades. The study quantifies floodplain changes (i.e., extent and depth) and the number of impacted residences, and also

75 FR 19907 - Television Broadcasting Services; Beaumont, TX

Science.gov (United States)

2010-04-16

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 10-606; MB Docket No. 10-49; RM-11593] Television Broadcasting Services; Beaumont, TX AGENCY: Federal Communications Commission. ACTION: Final rule... Congressional review Act, see 5 U.S.C. 801(a)(1)(A). List of Subjects in 47 CFR Part 73 Television, Television...

Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

Directory of Open Access Journals (Sweden)

Dinani Matoso Fialho de Oliveira Armstrong

2013-04-01

Full Text Available PURPOSE: To investigate the effect of sildenafil citrate (SC on skeletal muscle ischemia-reperfusion (IR injury in rats. METHODS: Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG, sildenafil citrate-treated (SCG, and sham group (SG. CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion. Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells. Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS: Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05. The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05. CONCLUSION: Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model.

Effects of panaxadiol saponins on contents of TNF-α and IL-6 in two-hit rat models with hemorrhage and lipopolysaech

International Nuclear Information System (INIS)

Yu Zhenxiang; Ding Yanhua; Li Lu; Zhao Xuejian

2005-01-01

Objective: To explore the changes of serum TNF-α and IL-6 contents in the two-hit rat models with hemorrhage and lipopolysaech (LPS) and the effects of panaxadiol saponins (PDS) on TNF-α and contents IL-6. Methods: Adult Wistar rats were randomly divided into 5 groups: sham operational group (S), hemorrhage group (H), two-hit group with hemorrhage and LPS groups (HL), Dexamethasone pretreatment group (HLD), PDS pretreatment group (HLP). The rat models were made by hemorrhagic shock as the first hit and with endotoxin as the second hit. Then the rats were killed after 6 h. The contents of serum TNF-α and IL-6 in rats were measured by radioimmunoassay. Results: The serum TNF-α and IL-6 contents in HL group were increased significantly compared with S group or H group (P<0.001). The TNF-α and IL-6 contents in HLP group and HLD group were significantly lower than those in HL group (P<0.01). Conclusion: LPS can increase significantly the contents of serum TNF-α and IL-6 in rats with hemorrhagic shock. PDS can inhibit the release of serum TNF-α and IL-6, and has the same effects with DEX to protect against the tissue injuries of two-hit rats with hemorrhage and LPS. (authors)

Micro Electrochemical pH Sensor Applicable for Real-Time Ratiometric Monitoring of pH Values in Rat Brains.

Science.gov (United States)

Zhou, Jie; Zhang, Limin; Tian, Yang

2016-02-16

To develop in vivo monitoring meter for pH measurements is still the bottleneck for understanding the role of pH plays in the brain diseases. In this work, a selective and sensitive electrochemical pH meter was developed for real-time ratiometric monitoring of pH in different regions of rat brains upon ischemia. First, 1,2-naphthoquinone (1,2-NQ) was employed and optimized as a selective pH recognition element to establish a 2H(+)/2e(-) approach over a wide range of pH from 5.8 to 8.0. The pH meter demonstrated remarkable selectivity toward pH detection against metal ions, amino acids, reactive oxygen species, and other biological species in the brain. Meanwhile, an inner reference, 6-(ferrocenyl)hexanethiol (FcHT), was selected as a built-in correction to avoid the environmental effect through coimmobilization with 1,2-NQ. In addition, three-dimensional gold nanoleaves were electrodeposited onto the electrode surface to amplify the signal by ∼4.0-fold and the measurement was achieved down to 0.07 pH. Finally, combined with the microelectrode technique, the microelectrochemical pH meter was directly implanted into brain regions including the striatum, hippocampus, and cortex and successfully applied in real-time monitoring of pH values in these regions of brain followed by global cerebral ischemia. The results demonstrated that pH values were estimated to 7.21 ± 0.05, 7.13 ± 0.09, and 7.27 ± 0.06 in the striatum, hippocampus, and cortex in the rat brains, respectively, in normal conditions. However, pH decreased to 6.75 ± 0.07 and 6.52 ± 0.03 in the striatum and hippocampus, upon global cerebral ischemia, while a negligible pH change was obtained in the cortex.

Establishment of a rat model of portal vein ligation combined with in situ splitting.

Science.gov (United States)

Yao, Libin; Li, Chonghui; Ge, Xinlan; Wang, Hongdong; Xu, Kesen; Zhang, Aiqun; Dong, Jiahong

2014-01-01

Portal vein ligation (PVL) combined with in situ splitting (ISS) has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR), Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (pprotein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS.

Randomized structured triglycerides increase lymphatic absorption of tocopherol and retinol compared with the equivalent physical mixture in a rat model of fat malabsorption.

Science.gov (United States)

Tso, P; Lee, T; DeMichele, S J

2001-08-01

Previously we demonstrated that the digestion, absorption and lymphatic transport of lipid and key essential fatty acids (EFA) from randomly interesterified fish oil/medium-chain structured triglycerides (STG) were significantly higher than an equivalent physical mixture (PM) in a normal lymph fistula rat model and in a rat model of lipid malabsorption caused by ischemia/reperfusion (I/R) injury. The goals of this study were to further explore the potential absorptive benefits of STG by comparing the intestinal absorption and lymphatic transport of tocopherol and retinol when delivered gastrically with either STG or PM under normal conditions and after I/R injury to the small bowel. Food-deprived male Sprague-Dawley rats were randomly assigned to two treatments (sham controls or I/R). Under halothane anesthesia, the superior mesenteric artery (SMA) was occluded for 20 min and then reperfused in I/R rats. The SMA was isolated but not occluded in control rats. In both groups, the mesenteric lymph duct was cannulated and a gastric tube was inserted. Each treatment group received 1 mL of the fish oil/MCT STG or PM (7 rats/group) along with (14)C-alpha-tocopherol and (3)H-retinol through the gastric tube followed by an infusion of PBS at 3 mL/h for 8 h. Lymph was collected hourly for 8 h. Under steady-state conditions, the amount of (14)C-alpha-tocopherol and (3)H-retinol transported into lymph was significantly higher in the STG-fed rats compared with those fed PM in both control and I/R groups. In addition, control and I/R rats given STG had earlier steady-state outputs of (14)C-alpha-tocopherol and (3)H-retinol and maintained approximately 30% higher outputs in lymph throughout the 8-h lymph collection period compared with rats given the PM. We conclude that STG provides the opportunity to potentiate improved absorption of fat-soluble vitamins under normal and malabsorptive states.

Acute exposure to high-peak-power pulsed microwaves affecting the histamine H3 receptor expression in rat hippocampus

International Nuclear Information System (INIS)

Yu Xiaodong; Li Bo; Li Dehua; He Qiyi; Yu Zhengping

2006-01-01

In the Morris Water test, high-peak-power pulsed microwave (MW)-exposed rats displayed some learning and memory behavior dysfunctions, and their escape time and swimming distance to the submerged platform were longer than those of the sham-exposed rats. to understand the molecular mechanism involved, the reverse transcription-polymerase chain reation (RT-PCR) and the Western-blotting technique were used for investigating the mRNA and protein expression patterns of the histamine H 3 receptor (H 3 R) in rat hippocampus. High-peak-power pulsed microwave-exposure did not remarkably lead to the change in expression of H 3 R mRNA in rat hippocampi; however, it promoted the up-regulatory expression of the H 3 R protein, which was possibly triggered through the mitogen-activated protein kinase (MAPK) pathways. Therefore, further investigation of the molecular mechanism of the MW effects on the learning and memory behaviors is required. (authors)

Acute exposure to high-peak-power pulsed microwaves affecting the histamine H3 receptor expression in rat hippocampus

Institute of Scientific and Technical Information of China (English)

无

2006-01-01

In the Morris Water Maze test, high-peak-power pulsed microwave (MW)-exposed rats displayed some learning and memory behavior dysfunctions, and their escape time and swimming distance to the submerged platform were longer than those of the sham-exposed rats. To understand the molecular mechanism involved, the reverse transcription-polymerase chain reaction (RT-PCR) and the Western-blotting technique were used for investigating the mRNA and protein expression patterns of the histamine H3 receptor (H3R) in rat hippocampus. High-peak-power pulsed microwave-exposure did not remarkably lead to the change in expression of H3R mRNA in rat hippocampi;however, it promoted the up-regulatory expression of the H3R protein, which was possibly triggered through the mitogen-activated protein kinase (MAPK) pathways. Therefore, further investigation of the molecular mechanism of the MW effects on the learning and memory behaviors is required.

hHGF overexpression in myoblast sheets enhances their angiogenic potential in rat chronic heart failure.

Directory of Open Access Journals (Sweden)

Antti Siltanen

2011-04-01

Full Text Available After severe myocardial infarction (MI, heart failure results from ischemia, fibrosis, and remodeling. A promising therapy to enhance cardiac function and induce therapeutic angiogenesis via a paracrine mechanism in MI is myoblast sheet transplantation. We hypothesized that in a rat model of MI-induced chronic heart failure, this therapy could be further improved by overexpression of the antiapoptotic, antifibrotic, and proangiogenic hepatocyte growth factor (HGF in the myoblast sheets. We studied the ability of wild type (L6-WT and human HGF-expressing (L6-HGF L6 myoblast sheet-derived paracrine factors to stimulate cardiomyocyte, endothelial cell, or smooth muscle cell migration in culture. Further, we studied the autocrine effect of hHGF-expression on myoblast gene expression profiles by use of microarray analysis. We induced MI in Wistar rats by left anterior descending coronary artery (LAD ligation and allowed heart failure to develop for 4 weeks. Thereafter, we administered L6-WT (n = 15 or L6-HGF (n = 16 myoblast sheet therapy. Control rats (n = 13 underwent LAD ligation and rethoracotomy without therapy, and five rats underwent a sham operation in both surgeries. We evaluated cardiac function with echocardiography at 2 and 4 weeks after therapy, and analyzed cardiac angiogenesis and left ventricular architecture from histological sections at 4 weeks. Paracrine mediators from L6-HGF myoblast sheets effectively induced migration of cardiac endothelial and smooth muscle cells but not cardiomyocytes. Microarray data revealed that hHGF-expression modulated myoblast gene expression. In vivo, L6-HGF sheet therapy effectively stimulated angiogenesis in the infarcted and non-infarcted areas. Both L6-WT and L6-HGF therapies enhanced cardiac function and inhibited remodeling in a similar fashion. In conclusion, L6-HGF therapy effectively induced angiogenesis in the chronically failing heart. Cardiac function, however, was not further

Incorporating sustainability into TxDOT's transportation decision making : summary of work performed, methods used, and results achieved.

Science.gov (United States)

2011-02-01

This report summarizes the work performed in Fiscal Year (FY) 2009 and 2010 under TxDOT : Implementation Project 5-5541-01 Regional Workshops on Sustainability Enhancement : Tool. TxDOT Research Project 0-5541, Developing Sustainable Tra...

76 FR 19276 - Television Broadcasting Services; El Paso, TX

Science.gov (United States)

2011-04-07

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-4; RM-11616, DA 11-530] Television Broadcasting Services; El Paso, TX AGENCY: Federal Communications Commission. ACTION: Final rule... Part 73 Television. Federal Communications Commission. Barbara A. Kreisman, Chief, Video Division...

76 FR 28946 - Television Broadcasting Services; El Paso, TX

Science.gov (United States)

2011-05-19

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-74, RM-11630; DA 11-746] Television Broadcasting Services; El Paso, TX AGENCY: Federal Communications Commission. ACTION: Proposed... of Subjects in 47 CFR Part 73 Television Federal Communications Commission. Barbara A. Kreisman...

76 FR 5120 - Television Broadcasting Services; El Paso, TX

Science.gov (United States)

2011-01-28

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [DA 11-74; MB Docket No. 11-4; RM-11616] Television Broadcasting Services; El Paso, TX AGENCY: Federal Communications Commission. ACTION: Proposed... 73 Television, Television broadcasting. For the reasons discussed in the preamble, the Federal...

Altered expression pattern of clock genes in a rat model of depression

DEFF Research Database (Denmark)

Christiansen, Sofie; Bouzinova, Elena; Fahrenkrug, Jan

2016-01-01

BACKGROUND: Abnormalities in circadian rhythms may be causal factors in development of major depressive disorder. The biology underlying a causal relationship between circadian rhythm disturbances and depression is slowly being unraveled. Although there is no direct evidence of dysregulation...... of clock gene expression in depressive patients many studies have reported single-nucleotide polymorphisms in clock genes in these patients. METHODS: In the present study we investigated whether a depression-like state in rats associates with alternations of the diurnal expression of clock genes....... The validated chronic mild stress (CMS) animal model of depression was used to investigate rhythmic expression of three clock genes; Per1, Per2 and Bmal1. Brain and liver tissue was collected from 96 animals after 3.5 weeks of CMS (48 control and 48 depression-like rats) at 4 h sampling interval within 24 h. We...

Selective labelling of 5-HT7 receptor recognition sites in rat brain using [3H]5-carboxamidotryptamine

International Nuclear Information System (INIS)

Stowe, R.L.; Barnes, N.M.

1998-01-01

The aim of the present study was to establish a radioligand binding assay to selectively label the native 5-HT 7 receptor expressed in rat brain. In rat whole brain (minus cerebellum and striatum) homogenate, (±)-pindolol (10 μM)-insensitive [ 3 H]5-CT ([ 3 H]5-carboxamidotryptamine; 0.5 nM) specific binding (defined by 5-HT, 10 μM) displayed a pharmacological profile similar to the recombinant 5-HT 7 receptor, although the Hill coefficients for competition curves generated by methiothepin, ritanserin, sumatriptan, clozapine and pimozide were significantly less than unity. In homogenates of rat hypothalamus, (±)-pindolol (10 μM)-insensitive [ 3 H]5-CT recognition sites also resembled, pharmacologically, the 5-HT 7 receptor, although pimozide still generated Hill coefficients significantly less than unity. Subsequent studies were performed in the additional presence of WAY100635 (100 nM) to prevent [ 3 H]5-CT binding to residual, possibly, 5-HT 1A sites. Competition for this [ 3 H]5-CT binding indicated the labelling in whole rat brain homogenate of a homogenous population of sites with the pharmacological profile of the 5-HT 7 receptor. Saturation studies also indicated that (±)-pindolol (10 μM)/WAY 100635 (100 nM)-insensitive [ 3 H]5-CT binding to homogenates of whole rat brain was saturable and to an apparently homogenous population of sites which were labelled with nanomolar affinity (B max =33.2±0.7 fmol mg -1 protein, pK d =8.78±0.05, mean±S.E.M., n=3). The development of this 5-HT 7 receptor binding assay will aid investigation of the rat native 5-HT 7 receptor. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage.

Science.gov (United States)

Kuo, Chang-Po; Lu, Chueng-He; Wen, Li-Li; Cherng, Chen-Hwan; Wong, Chih-Shung; Borel, Cecil O; Ju, Da-Tong; Chen, Chun-Mei; Wu, Ching-Tang

2011-12-01

Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

Curative effect of sesame oil in a rat model of chronic kidney disease.

Science.gov (United States)

Liu, Chuan-Teng; Chien, Se-Ping; Hsu, Dur-Zong; Periasamy, Srinivasan; Liu, Ming-Yie

2015-12-01

Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate (DOCA) and 1% NaCl [DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. © 2015 Asian Pacific Society of Nephrology.

GOC-TX: A Reliable Ticket Synchronization Application for the Open Science Grid

Science.gov (United States)

Hayashi, Soichi; Gopu, Arvind; Quick, Robert

2011-12-01

One of the major operational issues faced by large multi-institutional collaborations is permitting its users and support staff to use their native ticket tracking environment while also exchanging these tickets with collaborators. After several failed attempts at email-parser based ticket exchanges, the OSG Operations Group has designed a comprehensive ticket synchronizing application. The GOC-TX application uses web-service interfaces offered by various commercial, open source and other homegrown ticketing systems, to synchronize tickets between two or more of these systems. GOC-TX operates independently from any ticketing system. It can be triggered by one ticketing system via email, active messaging, or a web-services call to check for current sync-status, pull applicable recent updates since prior synchronizations to the source ticket, and apply the updates to a destination ticket. The currently deployed production version of GOC-TX is able to synchronize tickets between the Numara Footprints ticketing system used by the OSG and the following systems: European Grid Initiative's system Global Grid User Support (GGUS) and the Request Tracker (RT) system used by Brookhaven. Additional interfaces to the BMC Remedy system used by Fermilab, and to other instances of RT used by other OSG partners, are expected to be completed in summer 2010. A fully configurable open source version is expected to be made available by early autumn 2010. This paper will cover the structure of the GOC-TX application, its evolution, and the problems encountered by OSG Operations group with ticket exchange within the OSG Collaboration.

GOC-TX: A Reliable Ticket Synchronization Application for the Open Science Grid

International Nuclear Information System (INIS)

Hayashi, Soichi; Gopu, Arvind; Quick, Robert

2011-01-01

One of the major operational issues faced by large multi-institutional collaborations is permitting its users and support staff to use their native ticket tracking environment while also exchanging these tickets with collaborators. After several failed attempts at email-parser based ticket exchanges, the OSG Operations Group has designed a comprehensive ticket synchronizing application. The GOC-TX application uses web-service interfaces offered by various commercial, open source and other homegrown ticketing systems, to synchronize tickets between two or more of these systems. GOC-TX operates independently from any ticketing system. It can be triggered by one ticketing system via email, active messaging, or a web-services call to check for current sync-status, pull applicable recent updates since prior synchronizations to the source ticket, and apply the updates to a destination ticket. The currently deployed production version of GOC-TX is able to synchronize tickets between the Numara Footprints ticketing system used by the OSG and the following systems: European Grid Initiative's system Global Grid User Support (GGUS) and the Request Tracker (RT) system used by Brookhaven. Additional interfaces to the BMC Remedy system used by Fermilab, and to other instances of RT used by other OSG partners, are expected to be completed in summer 2010. A fully configurable open source version is expected to be made available by early autumn 2010. This paper will cover the structure of the GOC-TX application, its evolution, and the problems encountered by OSG Operations group with ticket exchange within the OSG Collaboration.

1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats

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Atul Rawat

2016-01-01

Full Text Available Introduction: Erythromycin (ERY is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism. Objective: To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics. Experimental: Fourteen male rats were randomly divided into two groups (n = 7 in each group: control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group. Results: The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a decreased TCA cycle activity and enhanced fatty acid oxidation, (b dysfunction of lipid and amino acid metabolism and (c oxidative stress. Conclusion and Recommendations: Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new

ENU mutagenesis to generate genetically modified rat models.

Science.gov (United States)

van Boxtel, Ruben; Gould, Michael N; Cuppen, Edwin; Smits, Bart M G

2010-01-01

The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach for generating genetically modified rats has been the target-selected N-ethyl-N-nitrosourea (ENU) mutagenesis-based technology. Here, we describe the detailed protocols for ENU mutagenesis and mutant retrieval in the rat model organism.

Characterization with /sup 3/H-haloperidol of the dopamine receptor in the rat kidney particulate preparation

Energy Technology Data Exchange (ETDEWEB)

Nakajima, T; Kuruma, I [Nippon Roche Research Center, Kanagawa (Japan)

1980-12-01

The dopamine receptor of rat kidney particulate preparation was identified and characterized by the use of /sup 3/H-haloperidol binding. Binding of /sup 3/H-haloperidol to the kidney particulate preparation was slow and saturable. The dissociation constants (K sub(D)) were 0.41 nM and 5.88 nM, respectively, according to the model of two classes of independent binding sites. Maximal binding of high affinity site was obtained with 166 fmole/mg protein which was about 40% of the total receptor density. A wide variety of neuroleptics at specifically low concentrations in nanomolar range inhibited the /sup 3/H-haloperidol binding. There was an excellent correlation between the affinity of numerous neuroleptics for the kidney particulate preparation and that for the brain striatum.

Software development to implement the TxDOT culvert rating guide.

Science.gov (United States)

2013-05-01

This implementation project created CULVLR: Culvert Load Rating, Version 1.0.0, a Windows-based : desktop application software package that automates the process by which Texas Department of Transportation : (TxDOT) engineers and their consultants ...

Differential blood-brain barrier permeabilities to [14C]sucrose and [3H]inulin after osmotic opening in the rat

International Nuclear Information System (INIS)

Ziylan, Y.Z.; Robinson, P.J.; Rapoport, S.I.

1983-01-01

The blood-brain barrier (B-BB) in 3-month-old rats was opened unilaterally by infusing 1.8 m L(+)arabinose in water into the internal carotid artery through a catheter in the external carotid. Two poorly penetrating uncharged test radiotracers of differing molecular weight and size, [ 14 C]sucrose (340 daltons, radius 5 A) and [ 3 H]inulin (5500 daltons, radius 15 A), were simultaneously injected i.v. in untreated rats, or rats at 1, 30, or 50 min after infusion of hypertonic arabinose solution. Evans-blue solution was injected 5 min prior to osmotic treatment as a visual indicator of barrier integrity. In regions of uninfused control brains, the [ 14 C]sucrose permeability-surface area (PA) product approximated 10(-5) s-1, whereas PA was not measurable for [ 3 H]inulin. In arabinose-infused animals, PA products on the ipsilateral hemisphere for both [ 14 C]sucrose and [ 3 H]inulin were markedly elevated 6 min after infusion, but decreased by 35 and 55 min. In nearly all regions, statistically significant differences were not found between 6-min [ 14 C]sucrose- and [ 3 H]inulin-PA values (P greater than 0.05). However, at 35 and 55 min in most regions, the PA for [ 3 H]inulin was significantly lower (P less than 0.05) than PA for [ 14 C]sucrose. The results indicated that the B-BB closed more rapidly to larger than to smaller molecules after osmotic treatment and were consistent with a pore model for osmotic B-BB opening

Neuroprotective effect of Buddleja cordata methanolic extract in the 1-methyl-4-phenylpyridinium Parkinson's disease rat model.

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Pérez-Barrón, Gabriela; Avila-Acevedo, José Guillermo; García-Bores, Ana María; Montes, Sergio; García-Jiménez, Sara; León-Rivera, Ismael; Rubio-Osornio, Moisés; Monroy-Noyola, Antonio

2015-01-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the irreversible loss of dopaminergic neurons in the nigrostriatal pathway with subsequent dopamine deficiency. Environmental causes have been proposed through molecules, such as 1-methyl-4-phenylpyridinium (MPP(+)), to induce oxidative stress. The methanolic extract of plants of the genus Buddleja has been reported to have in vitro and in vivo antioxidant properties to protect against neuronal death. In the present study, the neuroprotective effect of Buddleja cordata methanolic extract in the MPP(+) PD rat model was investigated. Animals were administered orally with 50 or 100 mg/kg of methanolic extract every 24 h for 14 days. Twenty hours later, rats were infused with an intrastriatal stereotaxic microinjection of 10 µg MPP(+) in 8 μl sterile saline solution. Six days later, the animals were treated with 1 mg/kg apomorphine to record ipsilateral rotations for 1 h. All the rats were killed by decapitation and the lesioned striatum was dissected for dopamine and lipid peroxidation quantifications. Both methanolic extract doses led to a significantly lower (P Buddleja cordata methanolic extract in the MPP(+) PD rat model, possibly due to the involvement of phenylpropanoids.

Studies on absorption, distribution, excretion and metabolism of 3H-1α-hydroxycholecalciferol in vitamin D deficient rats

International Nuclear Information System (INIS)

Tohira, Yasuo; Hinohara, Yoshikazu; Kamiyama, Hiroshi; Ogawa, Machiko; Nakano, Hideki

1978-01-01

The absorption, distribution, excretion and metabolism of 2- 3 H-1α-OH-D 3 (4.2 Ci/mmol) were studied in vitamin D deficient rats in comparison with the normal rats after oral or intravenous dosing. (1) Maximum blood level of administered radioactivity was observed at 8 hours after oral administration with apparent half life of 3.8 days. This blood level was higher than that in normal rat. (2) As in the normal rat, administered radioactivity was distributed relatively high in the liver, while any other specific distribution or accumulation was not observed in the another tissues, which was consistent to the finding in the normal rat. The tissue levels of the radioactivity were higher than these in the normal rat. (3) Urinary excretion of administered radioactivity was significantly higher, fecal and biliary excretion was significantly lower than that in the normal rat after intravenous dosing. (4) Relative percentage of 3 H-1α, 25-(OH) 2 -D 3 content to 3 H-1α-OH-D 3 content in tissues and blood was higher than that in the normal one. Above results suggest that in the vitamin D deficient state, the tissue accumulation of 1α-OH-D 3 was significantly augmented than in the normal rat, thus resulting increased bioavailability of its active metabolite, 1α, 25-(OH) 2 -D 3 . (author)

In vivo determination of triglyceride (TG) secretion in rats fed different dietary saturated fats using [2-3H]-glycerol

International Nuclear Information System (INIS)

Lai, H.C.; Yang, H.; Lasekan, J.; Clayton, M.; Ney, D.M.

1990-01-01

Male, Sprague-Dawley rats (154±1 g) were fed diets containing 2% corn oil (CO) + 14% butterfat (BF), beef tallow (BT), olive oil (OO) or coconut oil (CN) vs a 16% CO control diet for 5 weeks. Changes in plasma TG specific activity (dpm/mg TG) were determined in individual unanesthetized rats after injection of 100 μCi [2- 3 H]-glycerol via a carotid cannula. Fractional rate constants were obtained using a 2-compartment model and nonlinear regression analysis. Results demonstrated no difference in the fractional rate constants among dietary groups; but, differences in the rates of hepatic TG secretion were noted. Rats fed BT showed a higher rate of hepatic TG secretion than rats fed CO. Rats fed BF, OO or CN showed somewhat higher rates of hepatic TG secretion than CO. VLDL TG, phospholipid, and apolipoprotein B and E levels were higher with saturated fats vs CO. The data suggest that the higher plasma TG levels noted in response to feeding saturated fats vs corn oil can be explained, in part, by an increased flux of hepatic TG secretion

Ranitidine reduced levodopa-induced dyskinesia in a rat model of Parkinson’s disease

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Cui G

2013-12-01

Full Text Available Guiyun Cui,1,* Xinxin Yang,1,* Xiaoying Wang,2,* Zunsheng Zhang,1 Xuanye Yue,1 Hongjuan Shi,1 Xia Shen11Department of Neurology, 2Department of Ultrasound, the Affiliated Hospital of Xuzhou Medical College, Jiangsu, People’s Republic of China *These authors contributed equally to this workBackground: Chronic administration of levodopa in Parkinson’s disease leads to debilitating involuntary movements, termed levodopa-induced dyskinesia (LID. The pathogenesis of LID is poorly understood. Previous research has shown that histamine H2 receptors are highly expressed in the input (striatum and output (globus pallidus, substantia nigra regions of the basal ganglia, particularly in the GABAergic striatopallidal and striatonigral pathways. Therefore, a histamine H2 receptor antagonist could be used to reduce LID. In the present work, we investigated whether ranitidine has the potential to diminish LID in rats with dyskinesia and explored the underlying mechanisms involved.Methods: A rat model of PD was induced by 6-hydroxydopamine. Valid PD rats were then treated with levodopa (25 mg/kg, intraperitoneally and benserazide (12.5 mg/kg, intraperitoneally for 21 days to induce a rat model of LID. The acute and chronic effects of administration of ranitidine at different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg on abnormal involuntary movements, levodopa-induced rotations, and the forelimb adjusting steps test were investigated in LID rats. The chronic effect of ranitidine (10 mg/kg on the expression of Arc and proenkephalin was also evaluated.Results: Levodopa elicited increased dyskinesia in PD rats. Acute ranitidine treatment had no effect on LID, but chronic ranitidine administration (10 mg/kg, 20 mg/kg reduced LID in rats with dyskinesia. Importantly, levodopa-induced rotations were not affected by chronic treatment with ranitidine. In addition, chronic ranitidine (10 mg/kg, 20 mg/kg significantly improved stepping of the lesioned forepaw. Real

The cardioprotective efficacy of TVP1022 in a rat model of ischaemia/reperfusion.

Science.gov (United States)

Ertracht, Offir; Liani, Esti; Bachner-Hinenzon, Noa; Bar-Am, Orit; Frolov, Luba; Ovcharenko, Elena; Awad, Huda; Blum, Shany; Barac, Yaron; Amit, Tamar; Adam, Dan; Youdim, Moussa; Binah, Ofer

2011-06-01

Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischaemia and reperfusion (I/R) damage is the focus of intense research. Based on our in vitro findings showing that TVP1022 (the S-enantiomer of rasagiline, an anti-Parkinsonian drug) possesses cardioprotective effects, in the present study we investigated the hypothesis that TVP1022 can attenuate myocardial damage in an I/R model in rats. The model consisted of 30-min occlusion of the left anterior descending artery followed by 4 or 24 h reperfusion. In addition, we investigated the possible mechanisms of cardioprotection in H9c2 cells and neonatal rat ventricular myocytes (NRVM) exposed to oxidative stress induced by H(2) O(2) . TVP1022 (20 and 40 mg·kg(-1) ) administered 5 min before reperfusion followed by an additional dose 4 h after reperfusion reduced the infarct size and attenuated the decline in ventricular function. TVP1022 also attenuated I/R-induced deterioration in cardiac mitochondrial integrity evaluated by mitochondrial swelling capacity. In vitro, using H9c2 cells and NRVM, TVP1022 attenuated both serum free- and H(2) O(2) -induced damage, preserved mitochondrial membrane potential and Bcl-2 levels, inhibited mitochondrial cytochrome c release and the increase in cleaved caspase 9 and 3 levels, and enhanced the phosphorylation of protein kinase C and glycogen synthase kinase-3β. TVP1022 provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage resulting from I/R injuries. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Oxidative stress of crystalline lens in rat menopausal model

OpenAIRE

Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

2016-01-01

ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Gro...

Protection of visual functions by human neural progenitors in a rat model of retinal disease.

Directory of Open Access Journals (Sweden)

David M Gamm

2007-03-01

Full Text Available A promising clinical application for stem and progenitor cell transplantation is in rescue therapy for degenerative diseases. This strategy seeks to preserve rather than restore host tissue function by taking advantage of unique properties often displayed by these versatile cells. In studies using different neurodegenerative disease models, transplanted human neural progenitor cells (hNPC protected dying host neurons within both the brain and spinal cord. Based on these reports, we explored the potential of hNPC transplantation to rescue visual function in an animal model of retinal degeneration, the Royal College of Surgeons rat.Animals received unilateral subretinal injections of hNPC or medium alone at an age preceding major photoreceptor loss. Principal outcomes were quantified using electroretinography, visual acuity measurements and luminance threshold recordings from the superior colliculus. At 90-100 days postnatal, a time point when untreated rats exhibit little or no retinal or visual function, hNPC-treated eyes retained substantial retinal electrical activity and visual field with near-normal visual acuity. Functional efficacy was further enhanced when hNPC were genetically engineered to secrete glial cell line-derived neurotrophic factor. Histological examination at 150 days postnatal showed hNPC had formed a nearly continuous pigmented layer between the neural retina and retinal pigment epithelium, as well as distributed within the inner retina. A concomitant preservation of host cone photoreceptors was also observed.Wild type and genetically modified human neural progenitor cells survive for prolonged periods, migrate extensively, secrete growth factors and rescue visual functions following subretinal transplantation in the Royal College of Surgeons rat. These results underscore the potential therapeutic utility of hNPC in the treatment of retinal degenerative diseases and suggest potential mechanisms underlying their effect in

Comparison of high affinity binding of 3H-proadifen and 3H-(-)-cocaine t rat liver membranes

International Nuclear Information System (INIS)

Ross, S.B.

1995-01-01

The characteristics of the binding of 3 H-proadifen to rat liver membranes were studied and compared to those of 3 H-cocaine. It was found that 3 H-proadifen was bound reversibly with high affinity (K D =1.8±0.5 nM) and large capacity (B max =2010±340 pmol/g wet tissue) to liver membranes. The corresponding values for the 3 H-cocaine binding were 3.5 nM and 1000 pmol/g wet tissue. The binding of 3 H-proadifen was mainly localised to the microsomal fraction. The number of binding sites was not increased by treatment of rats with phenobarbitone. With 1 μM CdCl 2 in the incubation buffer it was possible to differentiate between two 3 H-cocaine binding sites with K d values of 1.6 and 7.7 nM and B max values of 280 and 940 pmol/g wet liver tissue. S-(-)-Alaproclate inhibited the binding of 3 H-proadifen and 3 H-cocaine inhibited the binding of 3 H-proadifen (IC 50 =10 nM) and proadifen that of 3 H-cocaine (IC 50 =1 nM). There was a high correlation coefficient (r r =0.972; P 50 =100-500 nM): chloroquine, phenoxybenzamine, amitriptyline, ajmaline, remoxipride, imipramine and (-)-alaprenolol. CdCl 2 , ZnCl 2 and CuCl 2 inhibited the binding of both ligands with low Hill coefficients, indicating heterogeneous binding sites. The inhibition curve of Cd 2+ on the cocaine binding was biphasic with a high affinity part around 50 nM and a low affinity part at 15μM. The similarity of the characteristics of the binding of these ligands with that of 3 H-alaproclate is discussed. It is suggested that all three compounds bind to the same sites, although additional binding sites seem to exist for proadifen. (au) (9 refs.)

H2S induced coma and cardiogenic shock in the rat: Effects of phenothiazinium chromophores

Science.gov (United States)

SONOBE, TAKASHI; HAOUZI, PHILIPPE

2015-01-01

Context Hydrogen sulfide (H2S) intoxication produces an acute depression in cardiac contractility-induced circulatory failure, which has been shown to be one of the major contributors to the lethality of H2S intoxication or to the neurological sequelae in surviving animals. Methylene blue (MB), a phenothiazinium dye, can antagonize the effects of the inhibition of mitochondrial electron transport chain, a major effect of H2S toxicity. Objectives We investigated whether MB could affect the immediate outcome of H2S-induced coma in unanesthetized animals. Second, we sought to characterize the acute cardiovascular effects of MB and two of its demethylated metabolites—azure B and thionine—in anesthetized rats during lethal infusion of H2S. Materials and methods First, MB (4 mg/kg, intravenous [IV]) was administered in non-sedated rats during the phase of agonal breathing, following NaHS (20 mg/kg, IP)-induced coma. Second, in 4 groups of urethane-anesthetized rats, NaHS was infused at a rate lethal within 10 min (0.8 mg/min, IV). Whenever cardiac output (CO) reached 40% of its baseline volume, MB, azure B, thionine, or saline were injected, while sulfide infusion was maintained until cardiac arrest occurred. Results Seventy-five percent of the comatose rats that received saline (n = 8) died within 7 min, while all the 7 rats that were given MB survived (p = 0.007). In the anesthetized rats, arterial, left ventricular pressures and CO decreased during NaHS infusion, leading to a pulseless electrical activity within 530 s. MB produced a significant increase in CO and dP/dtmax for about 2 min. A similar effect was produced when MB was also injected in the pre-mortem phase of sulfide exposure, significantly increasing survival time. Azure B produced an even larger increase in blood pressure than MB, while thionine had no effect. Conclusion MB can counteract NaHS-induced acute cardiogenic shock; this effect is also produced by azure B, but not by thionine, suggesting

76 FR 44280 - Television Broadcasting Services; El Paso, TX

Science.gov (United States)

2011-07-25

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 73 [MB Docket No. 11-74; RM-11630, DA 11-1185] Television Broadcasting Services; El Paso, TX AGENCY: Federal Communications Commission. ACTION: Final rule... U.S.C. 801(a)(1)(A). List of Subjects in 47 CFR Part 73 Television. Federal Communications...

Incorporating sustainability into TxDOT's transportation decision-making : interactive workshop

Science.gov (United States)

2010-01-01

The workshop is intended for new and experienced technical staff in TxDOT headquarters, district, and area offices to better understand how sustainability performance measures can be used at the sketch-planning level of project consideration. The wor...

Expression of Toll-like receptor 4 in hippocampus of rat model with temporal lobe epilepsy

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PAN Li-ping

2013-12-01

Full Text Available Objective To investigate the expression of Toll-like receptor 4 (TLR4 protein in hippocampus of rat model with temporal lobe epilepsy after status epilepticus (SE and explore its function in the pathogenesis of temporal lobe epilepsy. Methods Rat model with temporal lobe epilepsy was induced by lithium chloride (LiCl-pilocarpine. Total protein was extracted from hippocampus and rat brain slices were obtained at different time points (0, 1, 6, 12, 24, 48 h and 7, 10, 30, 50 d after SE. Western blotting and immunohistochemical staining were used for detection of the expression of TLR4 in the hippocampus. Results The results of Western blotting showed the TLR4 protein expression at 0, 1, 6, 12, 24, 48 h and 7, 10, 30 d after SE was higher than that in the control group (P 0.05. Conclusion TLR4 protein was mainly expressed in cytoplasm of pyramidal cells in CA3 area of hippocampus. TLR4 protein expression in the hippocampus was increased in varying degrees at different observation time points after SE, indicating that TLR4 may play an important role in the development of epilepsy.

78 FR 55214 - Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX

Science.gov (United States)

2013-09-10

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 100 [Docket No. USCG-2013-0723] Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX AGENCY: Coast Guard, DHS... Neches River in Orange, TX from 3 p.m. on September 20, 2013, through 6 p.m. on September 22, 2013. This...

77 FR 47519 - Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX

Science.gov (United States)

2012-08-09

... DEPARTMENT OF HOMELAND SECURITY Coast Guard 33 CFR Part 100 [Docket No. USCG-2012-0656] Annual Marine Events in the Eighth Coast Guard District, Sabine River; Orange, TX AGENCY: Coast Guard, DHS... Regulations for the S.P.O.R.T. Power Boat Neches River in Orange, TX from 3 p.m. on September 21, 2012...

Concentration of rat brown adipose tissue uncoupling protein may not be correlated with 3H-GDP binding

International Nuclear Information System (INIS)

Henningfield, M.F.; Swick, A.G.; Swick, R.W.

1986-01-01

Rats fed diets low in protein or exposed to cold show an increase in brown adipose tissue (BAT) mitochondrial 3 H-GDP binding. To investigate this phenomenon further, the uncoupling protein associated with BAT function was measured immunochemically on nitrocellulose blots. Quantitation of uncoupling protein was achieved by densitometer scanning with a BioRad densitometer. Peaks were integrated with Chromatochart software and an Apple IIe computer. A standard curve of purified uncoupling protein (50 to 500 ng) was used to calculate uncoupling protein concentration. There is a 1.5-fold increase in uncoupling protein per mg of protein in BAT mitochondria from rats exposed to cold for 15 days. There was no decrease in uncoupling protein from rats exposed to the cold followed by 24 h at 27 0 C although 3 H-GDP binding had decreased by half. Rats fed diets containing either 5 or 15% lactalbumin for 3 weeks did not show differences in uncoupling protein concentration although 3 H-GDP binding was 1.5-fold greater in BAT mitochondria from the low protein group. These results indicate that GDP binding does not necessarily reflect the concentration of uncoupling protein in BAT mitochondria

Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia.

Science.gov (United States)

Rojas, Santiago; Herance, José Raul; Abad, Sergio; Jiménez, Xavier; Pareto, Deborah; Ruiz, Alba; Torrent, Èlia; Figueiras, Francisca P; Popota, Foteini; Fernández-Soriano, Francisco J; Planas, Anna M; Gispert, Juan D

2011-06-01

[¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes. Rats (n = 14) were subjected to permanent ischemia by intraluminal occlusion of the middle cerebral artery in order to assess by PET the uptake of ¹⁸F-FMISO at various times over 24 h following ischemia. The PET results were compared to histological changes with Nissl and 2,3,5 triphenyltetrazolium chloride staining. Elevated uptake of ¹⁸F-FMISO was detected in the infarcted area up to 8 h after occlusion but was no longer detected at 24 h, a time point coincident with pan necrosis of the tissue. Our findings suggest that salvageable tissue persists for up to 8 h in this rat model of brain ischemia. We propose ¹⁸F-FMISO PET as a tool for evaluating the ischemic penumbra after cerebral ischemia.

Molecular hydrogen ameliorates several characteristics of preeclampsia in the Reduced Uterine Perfusion Pressure (RUPP) rat model.

Science.gov (United States)

Ushida, Takafumi; Kotani, Tomomi; Tsuda, Hiroyuki; Imai, Kenji; Nakano, Tomoko; Hirako, Shima; Ito, Yumiko; Li, Hua; Mano, Yukio; Wang, Jingwen; Miki, Rika; Yamamoto, Eiko; Iwase, Akira; Bando, Yasuko K; Hirayama, Masaaki; Ohno, Kinji; Toyokuni, Shinya; Kikkawa, Fumitaka

2016-12-01

Oxidative stress plays an important role in the pathogenesis of preeclampsia. Recently, molecular hydrogen (H 2 ) has been shown to have therapeutic potential in various oxidative stress-related diseases. The aim of this study is to investigate the effect of H 2 on preeclampsia. We used the reduced utero-placental perfusion pressure (RUPP) rat model, which has been widely used as a model of preeclampsia. H 2 water (HW) was administered orally ad libitum in RUPP rats from gestational day (GD) 12-19, starting 2 days before RUPP procedure. On GD19, mean arterial pressure (MAP) was measured, and samples were collected. Maternal administration of HW significantly decreased MAP, and increased fetal and placental weight in RUPP rats. The increased levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and diacron reactive oxygen metabolites as a biomarker of reactive oxygen species in maternal blood were decreased by HW administration. However, vascular endothelial growth factor level in maternal blood was increased by HW administration. Proteinuria, and histological findings in kidney were improved by HW administration. In addition, the effects of H 2 on placental villi were examined by using a trophoblast cell line (BeWo) and villous explants from the placental tissue of women with or without preeclampsia. H 2 significantly attenuated hydrogen peroxide-induced sFlt-1 expression, but could not reduce the expression induced by hypoxia in BeWo cells. H 2 significantly attenuated sFlt-1 expression in villous explants from women with preeclampsia, but not affected them from normotensive pregnancy. The prophylactic administration of H 2 attenuated placental ischemia-induced hypertension, angiogenic imbalance, and oxidative stress. These results support the theory that H 2 has a potential benefit in the prevention of preeclampsia. Copyright © 2016 Elsevier Inc. All rights reserved.

[3H]AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin

International Nuclear Information System (INIS)

Mah, S.C.; Whitebread, S.E.; De Gasparo, M.; Hofbauer, K.G.

1988-01-01

The interaction of an antagonist of arginine vasopressin (AVP), d(CH2)5-D-Tyr(Et)VAVP, with renal tubular V2 receptors were studied in medullary membrane preparations from kidneys of Sprague-Dawley and Brattleboro rats. In both rat strains, V2 receptors had comparable KD and Bmax values for binding of [3H]AVP. In vitro studies revealed that the V2-antagonist was more potent than cold AVP in displacing [3H]AVP. In vivo treatment of Sprague-Dawley rats with the antagonist over one week resulted only in a transient state of diabetes insipidus (DI). No specific [3H]AVP binding was detectable throughout the period of administration. Chronic treatment of Brattleboro rats resulted in a complete normalization of water intake. This agonistic effect was also associated with undetectable [3H]AVP binding. After stopping the infusion of d(CH2)5-D-Tyr(Et)VAVP, Bmax values tended to rise but had still not reached base line values after 6 days. In contrast, the chronic infusion of AVP in Brattleboro rats resulted in a reduction in water intake which was accompanied by a decreased Bmax. [3H]AVP binding remained detectable during the entire treatment period. Thereafter Bmax was restored to base line values within 2 days of stopping the infusion. These results suggest that d(CH2)5-D-Tyr(Et)VAVP has a high affinity for V2 receptors in both Sprague-Dawley and Brattleboro rats. Its rate of dissociation from the receptor appears to be much slower than that of AVP. In Brattleboro rats, the binding of d(CH2)5-D-Tyr(Et)VAVP leads to an antidiuretic response. In Sprague-Dawley rats, a transient diuretic response is followed by a progressive normalization in water intake. This occurs despite persistent and complete blockade of renal medullary V2 receptors

Receptor macroautoradiography of 3H-spiroperidol binding in rat brain

International Nuclear Information System (INIS)

Mori, Hirofumi; Shiba, Kazuhiro; Tsuji, Shiro; Matsuda, Hiroshi; Hisada, Kinichi; Kojima, Kazuhiko

1985-01-01

The kinetic and pharmacological characteristics of 3 H-spiroperidol binding sites were studied in slide mounted sections of rat forebrain, and optical binding conditions were defined. Using the receptor macroautoradiographic techniques with tritium-sensitive LKB sheet film, the distribution of dopamine (D 2 ) receptor was determined in slices including striatum of rat brain. The autoradiograms were analyzed using Video Digitizer System combined with video camera and minicomputer, and the subtraction images were obtained. These studies suggest that this quantitative receptor macroautoradiography might be useful in the explanation of etiology in the field of neuro-psychiatric diseases and the fundamental studies of positron emission computed tomography, since this method has several advantages over in vivo autoradiography and in vitro receptor assay. (author)

Cyclosporin A significantly improves preeclampsia signs and suppresses inflammation in a rat model.

Science.gov (United States)

Hu, Bihui; Yang, Jinying; Huang, Qian; Bao, Junjie; Brennecke, Shaun Patrick; Liu, Huishu

2016-05-01

Preeclampsia is associated with an increased inflammatory response. Immune suppression might be an effective treatment. The aim of this study was to examine whether Cyclosporin A (CsA), an immunosuppressant, improves clinical characteristics of preeclampsia and suppresses inflammation in a lipopolysaccharide (LPS) induced preeclampsia rat model. Pregnant rats were randomly divided into 4 groups: group 1 (PE) rats each received LPS via tail vein on gestational day (GD) 14; group 2 (PE+CsA5) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (5mg/kg, ip) on GDs 16, 17 and 18; group 3 (PE+CsA10) rats were pretreated with LPS (1.0 μg/kg) on GD 14 and were then treated with CsA (10mg/kg, ip) on GDs 16, 17 and 18; group 4 (pregnant control, PC) rats were treated with the vehicle (saline) used for groups 1, 2 and 3. Systolic blood pressure, urinary albumin, biometric parameters and the levels of serum cytokines were measured on day 20. CsA treatment significantly reduced LPS-induced systolic blood pressure and the mean 24-h urinary albumin excretion. Pro-inflammatory cytokines IL-6, IL-17, IFN-γ and TNF-α were increased in the LPS treatment group but were reduced in (LPS+CsA) group (Ppreeclampsia signs and attenuated inflammatory responses in the LPS induced preeclampsia rat model which suggests that immunosuppressant might be an alternative management option for preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

pH dependent fluorescence switching in salicylideneaniline: ‘off–on–off’ operation controlled by surfactant micelles

Energy Technology Data Exchange (ETDEWEB)

Das, Diganta Kumar, E-mail: digkdas@yahoo.com; Dutta, Kaku

2014-01-15

Salaniline, a condensation product of salicylaldehyde and aniline, shows “off–on” fluorescent behaviour with pH in 1:1 (v/v) CH{sub 3}CN:H{sub 2}O and when 3% (w/v) anionic sodium dodecylsulphate (SDS) surfactant is present. The fluorescent switch behaviour of salaniline is forced to “off–on–off” type by 3% (w/v) neutral triton X-100 (TX-100) and 3% (w/v) cationic cetyltrimethylammonium bromide (CTAB) surfactant. The fluorescent “on” window is observed in the pH range 8.0–12.5 for TX-100 and 7.0–11.0 for CTAB. Different charge nature of the surfactants affects the protonation/deprotonation behaviour of salaniline differently, hence the photoinduced electron transfer (PET) processes and the fluorescent switch behaviour. -- Highlights: • Salicylideneaniline act as pH dependent “off–on” fluorescent switch in 1:1 (v/v) CH{sub 3}CN:H{sub 2}O. • In surfactant micelles TX-100 (neutral) and CTAB (positive) make the fluorescent switch “off–on–off” type while in. • In surfactant micelle SDS (negative) the pH dependent fluorescent switch is “off–on” type.

Improvement and application of an acute blood stasis rat model aligned with the 3Rs (reduction, refinement and replacement) of humane animal experimentation.

Science.gov (United States)

Huang, Shuai; Xu, Feng; Wang, Yin-Ye; Shang, Ming-Ying; Wang, Chao-Qun; Wang, Xuan; Cai, Shao-Qing

2014-12-23

To establish a novel cardiocentesis method for withdrawing venous blood from the right atrium, and to improve an acute blood stasis rat model using an ice bath and epinephrine hydrochloride (Epi) while considering the 3Rs (reduction, refinement, and replacement) of humane animal experimentation. An acute blood stasis model was established in male Sprague-Dawley rats by subcutaneous injection (s.c.) Epi (1.2 mg/kg) administration at 0 h, followed by a 5-min exposure to an ice-bath at 2 h and s.c. Epi administration at 4 h. Control rats received physiological saline. Rats were fasted overnight and treated with Angelicae Sinensis Lateralis Radix (ASLR) and Pheretima the following day. Venous blood was collected using our novel cardiocentesis method and used to test whole blood viscosity (WBV), prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen (FIB) content. The rats survived the novel cardiocentesis technique; WBV value returned to normal while hematological parameters such as hemoglobin level and red blood cell count were restored to >94% of the corresponding values in normal rats following a 14-day recovery. Epi (1.2 mg/kg, s.c.) combined with a 5-min exposure to the ice bath replicated the acute blood stasis rat model and was associated with the highest WBV value. In rats showing acute blood stasis, ASLR treatment [4 g/(kg·d) for 8 days] decreased WBV by 9.98%, 11.09%, 9.34%, 9.00%, 7.66%, and 7.03% (P<0.05), while Pheretima treatment [2.6 g/(kg·d), for 8 days] decreased WBV by 25.49%, 25.94%, 16.28%, 17.76%, 11.07%, and 7.89% (P<0.01) at shear rates of 1, 3, 10, 30, 100, and 180 s -1 , respectively. Furthermore, Pheretima treatment increased APTT significantly (P<0.01). We presented a stable, reproducible, and improved acute blood stasis rat model, which could be applied to screen drugs for promoting blood circulation and eliminating blood stasis.

[3H]-beta-endorphin binding in rat brain

International Nuclear Information System (INIS)

Houghten, R.A.; Johnson, N.; Pasternak, G.W.

1984-01-01

The binding of [ 3 H]-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the 3 H-ligand is binding to more than one class of site. A portion of [ 3 H]-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of [ 3 H]-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers [ 3 H]-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of [ 3 H]-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo

Modeling of biodistribution of 90 Y-DOTA-hR3 by using artificial intelligence techniques

International Nuclear Information System (INIS)

Ondarse, Dianelys; Quiza, Ramon; Leyva, Rene; Zamora, Minely; Ducat, Luis; Hernandez, Ignacio; Alonso, Luis Michel

2011-01-01

In this work the biodistribution of radioimmunoconjugate 9 0Y-DOTA-hR3 was modeled by using an artificial neural network. In vivo stability of 9 0Y-DOTA-hR3 was determined in healthy male Wistar rats at 4, 24 and 48 hours, in different organs. A model describing the relationship between, by one hand, the incorporated dose and, by the other hand, organ and time was developed by using a multilayer perceptron neural network. Adjusted model was analyzed by several statistical tests. Outcomes shown that proposed neural model describes the relationship between the studied variables in a proper way. (Author)

Omega-3 Fatty Acids: Possible Neuroprotective Mechanisms in the Model of Global Ischemia in Rats

OpenAIRE

Nobre, Maria Elizabeth Pereira; Correia, Alyne Oliveira; Mendon?a, Francisco Nilson Maciel; Uchoa, Luiz Ricardo Ara?jo; Vasconcelos, Jessica Tamara Nunes; de Ara?jo, Carlos Ney Alencar; Brito, Gerly Anne de Castro; Siqueira, Rafaelly Maria Pinheiro; Cerqueira, Gilberto dos Santos; Neves, Kelly Rose Tavares; Arida, Ricardo M?rio; Viana, Glauce Socorro de Barros

2016-01-01

Background. Omega-3 (ω3) administration was shown to protect against hypoxic-ischemic injury. The objectives were to study the neuroprotective effects of ω3, in a model of global ischemia. Methods. Male Wistar rats were subjected to carotid occlusion (30 min), followed by reperfusion. The groups were SO, untreated ischemic and ischemic treated rats with ω3 (5 and 10 mg/kg, 7 days). The SO and untreated ischemic animals were orally treated with 1% cremophor and, 1 h after the last administrati...

Shift in Food Intake and Changes in Metabolic Regulation and Gene Expression during Simulated Night-Shift Work : A Rat Model

NARCIS (Netherlands)

Marti, Andrea Rørvik; Meerlo, Peter; Grønli, Janne; van Hasselt, Sjoerd Johan; Mrdalj, Jelena; Pallesen, Ståle; Pedersen, Torhild Thue; Henriksen, Tone Elise Gjøtterud; Skrede, Silje

2016-01-01

Night-shift work is linked to a shift in food intake toward the normal sleeping period, and to metabolic disturbance. We applied a rat model of night-shift work to assess the immediate effects of such a shift in food intake on metabolism. Male Wistar rats were subjected to 8 h of forced activity

Reduction in (/sup 3/H)-corticosterone binding to cytoplasmic receptors in the brain of diabetic rats

Energy Technology Data Exchange (ETDEWEB)

Fridman, O; Foglia, V G; de Nicola, A F [Instituto de Biologia y Medicina Experimental, Buenos Aires (Argentina). Lab. de Esteroides

1978-07-01

The binding of (1,2,6,7-/sup 3/H)-corticosterone was studied in brain cytosol from normal and streptozotocin-diabetic male rats. The experiments were performed under conditions of incubation time (4h), temperature (0-4/sup 0/C), time after adrenalectomy (6 days) and corticosterone concentrations (1.2 x 10/sup -8/ and 1.15 x 10/sup -9/M) previously established for determining binding activity in the brain of normal rats. The binding of (/sup 3/H)-corticosterone was found invariably lower in cytosol of the brain from diabetic rats, studied under three different conditions in non-adrenalectomized animals, in adrenalectomized using a non-saturating corticosterone concentration, and in adrenalectomized plus a saturating steroid concentration. These results support previous contentions that the diminished sensitivity to the negative feedback for steroids which is present in diabetics, may be related to a reduction in binding capacity for corticoids in the central nervous system.

Dragon's blood dropping pills have protective effects on focal cerebral ischemia rats model.

Science.gov (United States)

Xin, Nian; Yang, Fang-Ju; Li, Yan; Li, Yu-Juan; Dai, Rong-Ji; Meng, Wei-Wei; Chen, Yan; Deng, Yu-Lin

2013-12-15

Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (ppills had protective effects on focal cerebral ischemia rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Protective Effects of Salubrinal on Liver Injury in Rat Models of Brain Death

Institute of Scientific and Technical Information of China (English)

Tao Wang; Shui-Jun Zhang; Sheng-Li Cao; Wen-Zhi Guo; Bing Yan; Hong-Bo Fang

2015-01-01

Background:Previous studies have indicated that endoplasmic reticulum stress participates in and mediates liver injury and apoptosis in brain-dead (BD) rats.In this study,we observed the effect ofsalubrinal (Sal,Sigma,USA) on liver cells in BD rats and explored its relevant mechanisms.Methods:Thirty Sprague-Dawley rats were equally randomized into three groups:BD group,Sal group,and DMSO group.The BD models were established by increasing intracranial pressure in a modified,slow,and intermittent way.In the drug groups,Sal was administered l h before the induction of BD.After modeling was completed,the blood and liver samples were harvested.CHOP and Caspase-12 mRNA expression was detected using quantitative polymerase chain reaction.PKR-like ER kinase (PERK),P-eukaryotic translation initiation factor 2α (eIF2α),eIF2α,CHOP and caspase-12 expression was detected using western blotting (WB).CHOP and caspase-12 distribution and expression in liver tissues were determined using immunohistochemistry (IHC).Alanine aminotransferase and aspartate aminotransferase level were detected using an automatic biochemical analyzer.Hepatic cell apoptosis was detected using TUNEL.The results were analyzed using Quantity-one v4.62 software (Bio-Rad,USA).Results:CHOP and caspase-12 expression and PERK,eIF2α,and P-eIF2α protein expression showed no significant difference between BD group and DMSO group.Compared with BD group,Sal group had a significantly higher P-eIF2C level and a lower P-PERK level 2 h and 6 h after BD (P ＜ 0.05).However,eIF2α expression showed no significant difference (P ＞ 0.05).After the Sal treatment,CHOP and caspase-12 mRNA expression significantly decreased 4 h after BD (P ＜ 0.05).WB and IHC indicated that CHOP and caspase-12 expression also significantly decreased after Sal treatment.Sal was associated with improved liver function and decreased hepatic cell apoptosis.Conclusions:Sal can significantly reduce apoptosis in hepatic cells of BD rats

Tank 241-TX-118, core 236 analytical results for the final report

International Nuclear Information System (INIS)

ESCH, R.A.

1998-01-01

This document is the analytical laboratory report for tank 241-TX-118 push mode core segments collected between April 1, 1998 and April 13, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-TX-118 Push Mode Core sampling and Analysis Plan (TSAP) (Benar, 1997), the Safety Screening Data Quality Objective (DQO) (Dukelow, et al., 1995), the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al, 1995) and the Historical Model Evaluation Data Requirements (Historical DQO) (Sipson, et al., 1995). The analytical results are included in the data summary table (Table 1). None of the samples submitted for Differential Scanning Calorimetry (DSC) and Total Organic Carbon (TOC) exceeded notification limits as stated in the TSAP (Benar, 1997). One sample exceeded the Total Alpha Activity (AT) analysis notification limit of 38.4microCi/g (based on a bulk density of 1.6), core 236 segment 1 lower half solids (S98T001524). Appropriate notifications were made. Plutonium 239/240 analysis was requested as a secondary analysis. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and are not considered in this report

Steroid-associated osteonecrosis animal model in rats

Directory of Open Access Journals (Sweden)

Li-Zhen Zheng

2018-04-01

Full Text Available Summary: Objective: Established preclinical disease models are essential for not only studying aetiology and/or pathophysiology of the relevant diseases but more importantly also for testing prevention and/or treatment concept(s. The present study proposed and established a detailed induction and assessment protocol for a unique and cost-effective preclinical steroid-associated osteonecrosis (SAON in rats with pulsed injections of lipopolysaccharide (LPS and methylprednisolone (MPS. Methods: Sixteen 24-week-old male Sprague–Dawley rats were used to induce SAON by one intravenous injection of LPS (0.2 mg/kg and three intraperitoneal injections of MPS (100 mg/kg with a time interval of 24 hour, and then, MPS (40 mg/kg was intraperitoneally injected three times a week from week 2 until sacrifice. Additional 12 rats were used as normal controls. Two and six weeks after induction, animals were scanned by metabolic dual energy X-ray absorptiometry for evaluation of tissue composition; serum was collected for bone turnover markers, Microfil perfusion was performed for angiography, the liver was collected for histopathology and bilateral femora and bilateral tibiae were collected for histological examination. Results: Three rats died after LPS injection, i.e., with 15.8% (3/19 mortality. Histological evaluation showed 100% incidence of SAON at week 2. Dual energy X-ray absorptiometry showed significantly higher fat percent and lower lean mass in SAON group at week 6. Micro-computed tomography (Micro-CT showed significant bone degradation at proximal tibia 6 weeks after SAON induction. Angiography illustrated significantly less blood vessels in the proximal tibia and significantly more leakage particles in the distal tibia 2 weeks after SAON induction. Serum amino-terminal propeptide of type I collagen and osteocalcin were significantly lower at both 2 and 6 weeks after SAON induction, and serum carboxy-terminal telopeptide was significantly

Borehole data package for well 299-W15-41 at single-shell tank waste management Area TX-TY

International Nuclear Information System (INIS)

Horton, D.G.; Hodges, F.N.

2000-01-01

One new Resource Conservation and Recovery Act (RCRA) groundwater monitoring well was installed at the single-shell tank farm Waste Management Area (WMA) TX-TY during December 1999 and January 2000 in fulfillment of Tri-Party Agreement (Ecology 1996) milestone M-24-43. The well is 299-W15-41 and is located south of the 241-TX tank farm and south of 20th Street in the 200 West Area. A figure shows the locations of all wells in the WMA TX-TY monitoring network. The new well was constructed to the specifications and requirements described in Washington Administrative Code (WAC) 173-160 and WAC 173-303, the groundwater monitoring plan for WMA TX-TY (Caggiano and Goodwin 1991), the assessment plan for WMA TX-TY (Caggiano and Chou 1993), and the description of work for well drilling and installation. This document compiles information on the drilling and construction, well development, pump installation, and sediment testing applicable to well 299-W1 5-41. Appendix A contains the geologist's log, the Well Construction Summary Report, and Well Summary Sheet (as-built diagram) and Appendix B contains borehole geophysical logs. Additional documentation concerning well construction is on file with Bechtel Hanford, Inc., Richland, Washington

Prenatal Alcohol Exposure Increases Histamine H3 Receptor-Mediated Inhibition of Glutamatergic Neurotransmission in Rat Dentate Gyrus.

Science.gov (United States)

Varaschin, Rafael K; Allen, Nyika A; Rosenberg, Martina J; Valenzuela, C Fernando; Savage, Daniel D

2018-02-01

We have reported that prenatal alcohol exposure (PAE)-induced deficits in dentate gyrus, long-term potentiation (LTP), and memory are ameliorated by the histamine H 3 receptor inverse agonist ABT-239. Curiously, ABT-239 did not enhance LTP or memory in control offspring. Here, we initiated an investigation of how PAE alters histaminergic neurotransmission in the dentate gyrus and other brain regions employing combined radiohistochemical and electrophysiological approaches in vitro to examine histamine H 3 receptor number and function. Long-Evans rat dams voluntarily consumed either a 0% or 5% ethanol solution 4 hours each day throughout gestation. This pattern of drinking, which produces a mean peak maternal serum ethanol concentration of 60.8 ± 5.8 mg/dl, did not affect maternal weight gain, litter size, or offspring birthweight. Radiohistochemical studies in adult offspring revealed that specific [ 3 H]-A349821 binding to histamine H 3 receptors was not different in PAE rats compared to controls. However, H 3 receptor-mediated G i /G o protein-effector coupling, as measured by methimepip-stimulated [ 35 S]-GTPγS binding, was significantly increased in cerebral cortex, cerebellum, and dentate gyrus of PAE rats compared to control. A LIGAND analysis of detailed methimepip concentration-response curves in dentate gyrus indicated that PAE significantly elevates receptor-effector coupling by a lower affinity H 3 receptor population without significantly altering the affinities of H 3 receptor subpopulations. In agreement with the [ 35 S]-GTPγS studies, a similar range of methimepip concentrations also inhibited electrically evoked field excitatory postsynaptic potential responses and increased paired-pulse ratio, a measure of decreased glutamate release, to a significantly greater extent in dentate gyrus slices from PAE rats than in controls. These results suggest that a PAE-induced elevation in H 3 receptor-mediated inhibition of glutamate release from

Effects of onion extract on endogenous vascular H2S and adrenomedulin in rat atherosclerosis.

Science.gov (United States)

Li, Wei; Tang, Chaoshu; Jin, Hongfang; Du, Junbao

2011-09-01

This study aimed to explore the effect of onion extract on endogenous hydrogen sulfide (H2S) and adrenomedulin (ADM) and on atherosclerotic progression in rats with atherosclerosis (AS). Male Sprague-Dawley rats were randomly divided into control, AS and AS+onion groups. Ultrastructure of aorta and atherosclerotic lesions both in aorta and in coronary artery were detected. Plasma and aortic H2S were detected by using a sulfide- sensitive electrode. Plasma and aortic ADM was determined with radioimmunoassay. Cystathionine-γ-lyase (CSE), calcitonin receptor-like receptor (CRLR), receptor activity-modifying protein (RAMP1, RAMP2 and RAMP3) mRNA expressions were analysed. Glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and NO synthase (NOS) contents in plasma, SOD1, SOD2 and ICAM-1 expressions in aorta were detected. Rats in the AS group showed marked atherosclerotic lesions both in aorta and in coronary artery but decreased aortic H2S production. Decreased plasma and aortic ADM content, but increased levels of aortic CRLR, RAMP2 and RAMP3 mRNAs were observed. Plasma GSH-PX and SOD were reduced but MDA elevated. Plasma ICAM-1 and NO contents and iNOS activity were increased. Onion extract, however, lessened atherosclerotic lesions and increased endogenous aortic H2S production, but decreased plasma ADM content, aortic ADM content and aortic CRLR, RAMP2 and RAMP3 mRNAs. In addition, it increased plasma GSH-PX level and SOD activities but reduced MDA; it decreased inflammatory response but increased plasma eNOS activity and NO content. Onion extract exerted a marked antiatherogenic effect in association with the up-regulation of the endogenous CSE/H2S pathway but down-regulation of the ADM/CRLR family in atherosclerotic rats.

78 FR 14909 - Amendment of Class B Airspace Description; Houston, TX

Science.gov (United States)

2013-03-08

...-0079; Airspace Docket No. 13-AWA-1] RIN 2120-AA66 Amendment of Class B Airspace Description; Houston.... SUMMARY: This action amends the description of the Houston, TX, Class B airspace area by changing the... 14910

Delayed perfusion phenomenon in a rat stroke model at 1.5 T MR: An imaging sign parallel to spontaneous reperfusion and ischemic penumbra?

Energy Technology Data Exchange (ETDEWEB)

Chen Feng [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Radiology, Zhong Da Hospital, Southeast University, 87 Ding Jia Qiao Road, Nanjing 210009, Jiangsu Province (China); Suzuki, Yasuhiro [Department of Molecular and Cellular Medicine, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Pharmacology, Hamamatsu University School of Medicine, 1-20-1 Handayama, 431-3192 Hamamatsu (Japan); Nagai, Nobuo [Department of Molecular and Cellular Medicine, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Sun Xihe [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Department of Radiology, the Affiliated Hospital of Weifang Medical University, Weifang 261031, Shandong Province (China); Coudyzer, Walter [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Yu Jie [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Marchal, Guy [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium); Ni Yicheng [Department of Radiology, University Hospitals, Catholic University of Leuven, Herestraat 49, B-3000 Leuven (Belgium)]. E-mail: Yicheng.Ni@med.kuleuven.ac.be

2007-01-15

Introduction: Delayed perfusion (DP) sign at MR imaging was reported in stroke patients. We sought to experimentally elucidate its relation to spontaneous reperfusion and ischemic penumbra. Methods: Stroke was induced by photothrombotic occlusion of middle cerebral artery in eight rats and studied up to 72 h using a 1.5 T MR scanner with T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI). Relative signal intensity (rSI), relative lesion volume (rLV), relative cerebral blood flow (rCBF), PWI{sub rLV}-DWI{sub rLV} mismatch (penumbra) and DP{sub rLV} were quantified and correlated with neurological deficit score (NDS), triphenyl tetrazolium chloride (TTC) staining, microangiography (MA) and histopathology. Results: The rSI and rLV characterized this stroke model on different MRI sequences and time points. DSC-PWI reproduced cortical DP in all rats, where rCBF evolved from 88.9% at 1 h through 64.9% at 6 h to 136.3% at 72 h. The PWI{sub rLV}-DWI{sub rLV} mismatch reached 10 {+-} 5.4% at 1 h, remained positive through 12 h and decreased to -3.3 {+-} 4.5% at 72 h. The incidence and rLV of the DP were well correlated with those of the penumbra (p < 0.01, r {sup 2} = 0.85 and p < 0.0001, r {sup 2} = 0.96, respectively). Shorter DP durations and more collateral arterioles occurred in rats without (n = 4) than with (n = 4) cortex involvement (p < 0.05). Rats without cortex involvement tended to earlier reperfusion and a lower NDS. Microscopy confirmed MRI, MA and TTC findings. Conclusions: In this rat stroke model, we reproduced clinically observed DP on DSC-PWI, confirmed spontaneous reperfusion, and identified the penumbra extending to 12 h post-ischemia, which appeared interrelated.

Selective labelling of 5-HT{sub 7} receptor recognition sites in rat brain using [{sup 3}H]5-carboxamidotryptamine

Energy Technology Data Exchange (ETDEWEB)

Stowe, R.L.; Barnes, N.M. [Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT (United Kingdom)

1998-12-01

The aim of the present study was to establish a radioligand binding assay to selectively label the native 5-HT{sub 7} receptor expressed in rat brain. In rat whole brain (minus cerebellum and striatum) homogenate, ({+-})-pindolol (10 {mu}M)-insensitive [{sup 3}H]5-CT ([{sup 3}H]5-carboxamidotryptamine; 0.5 nM) specific binding (defined by 5-HT, 10 {mu}M) displayed a pharmacological profile similar to the recombinant 5-HT{sub 7} receptor, although the Hill coefficients for competition curves generated by methiothepin, ritanserin, sumatriptan, clozapine and pimozide were significantly less than unity. In homogenates of rat hypothalamus, ({+-})-pindolol (10 {mu}M)-insensitive [{sup 3}H]5-CT recognition sites also resembled, pharmacologically, the 5-HT{sub 7} receptor, although pimozide still generated Hill coefficients significantly less than unity. Subsequent studies were performed in the additional presence of WAY100635 (100 nM) to prevent [{sup 3}H]5-CT binding to residual, possibly, 5-HT{sub 1A} sites. Competition for this [{sup 3}H]5-CT binding indicated the labelling in whole rat brain homogenate of a homogenous population of sites with the pharmacological profile of the 5-HT{sub 7} receptor. Saturation studies also indicated that ({+-})-pindolol (10 {mu}M)/WAY 100635 (100 nM)-insensitive [{sup 3}H]5-CT binding to homogenates of whole rat brain was saturable and to an apparently homogenous population of sites which were labelled with nanomolar affinity (B{sub max}=33.2{+-}0.7 fmol mg{sup -1} protein, pK{sub d}=8.78{+-}0.05, mean{+-}S.E.M., n=3). The development of this 5-HT{sub 7} receptor binding assay will aid investigation of the rat native 5-HT{sub 7} receptor. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

99mTc-Annexin-V uptake in a rat model of variable ischemic severity and reperfusion time

International Nuclear Information System (INIS)

Taki, Junichi; Higuchi, Takahiro; Kawashima, Atsuhiro; Muramori, Akira; Nakajima, Kenichi; Tait, J.F.; Matsunari, Ichiro; Vanderheyden, J.L.; Strauss, H.W.

2007-01-01

The background of this study was to determine whether mild to moderate ischemia that is not severe enough to induce myocardial infarction will cause myocardial cell damage or apoptosis, the 99m Tc-Annexin-V (Tc-A) uptake was studied in groups of rats with various intervals of coronary occlusion and reperfusion times. After left coronary artery occlusion for 15 min (n=23), 10 min (n=23), or 5 min (n=12), Tc-A (80-150 MBq) was injected at 0.5, 1.5, 6, or 24 h after reperfusion. One hour later, to verify the area at risk, 201 Tl (0.74 MBq) was injected just after left coronary artery re-occlusion and the rats were killed 1 min later. Dual tracer autoradiography was performed to assess Tc-A uptake and area at risk. In all 5-min occlusion and reperfusion models, no significant Tc-A uptake was observed in the area at risk. Tc-A uptake ratios in the 15-min and 10-min ischemia models were 4.46±3.16 and 2.02±0.47 (p=0.078) at 0.5 h after reperfusion, 3.49±1.78 and 1.47±0.11 (p<0.05) at 1.5 h after reperfusion, 1.60±0.43 and 1.34±0.23 (p=0.24) at 6 h after reperfusion, 1.50±0.33 and 1.28±0.33 (p=0.099) at 24 h after reperfusion, respectively. With 15-min ischemia, in 3 of the 5 rats there were a few micro-foci of myocardial cell degeneration and cell infiltration in less than 1% of the ischemic area at 24 h after reperfusion. No significant histological change was observed in rats with 10-min or 5-min ischemia. The data indicate that Tc-A binding depends on the severity of ischemia even without a significant amount of histological change or infarction. (author)

Transplantation of human umbilical cord blood-derived mononuclear cells induces recovery of motor dysfunction in a rat model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Chen C

2016-04-01

Full Text Available Chao Chen,1,* Jing Duan,1,* Aifang Shen,2,* Wei Wang,1 Hao Song,1 Yanming Liu,1 Xianjie Lu,1 Xiaobing Wang,2 Zhiqing You,1 Zhongchao Han,3,4 Fabin Han1 1Center for Stem Cells and Regenerative Medicine, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 2Department of Gynecology and Obstetrics, The Liaocheng People's Hospital, Affiliated Liaocheng Hospital, Taishan Medical University, Shandong, People's Republic of China; 3The State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences, Peking Union of Medical College, Tianjin, People's Republic of China; 4National Engineering Research Center of Cell Products, AmCellGene Co. Ltd., TEDA, Tianjin, People's Republic of China*These authors contributed equally to this workAbstract: Human umbilical cord blood-derived mononuclear cells (hUCB-MNCs were reported to have neurorestorative capacity for neurological disorders such as stroke and traumatic brain injury. This study was performed to explore if hUCB-MNC transplantation plays any therapeutic effects for Parkinson's disease (PD in a 6-OHDA-lesioned rat model of PD. hUCB-MNCs were isolated from umbilical cord blood and administered to the striatum of the 6-OHDA-lesioned rats. The apomorphine-induced locomotive turning-overs were measured to evaluate the improvement of motor dysfunctions of the rats after administration of hUCB-MNCs. We observed that transplanted hUCB-MNCs significantly improve the motor deficits of the PD rats and that grafted hUCB-MNCs integrated to the host brains and differentiated to neurons and dopamine neurons in vivo after 16 weeks of transplantation. Our study provided evidence that transplanted hUCB-MNCs play therapeutic effects in a rat PD model by differentiating to neurons and dopamine neurons. Keywords: hUCB-MNCs, Parkinson's disease, transplantation

Synthesis and binding of [125I2]philanthotoxin-343, [125I2]philanthotoxin-343-lysine, and [125I2]philanthotoxin-343-arginine to rat brain membranes

International Nuclear Information System (INIS)

Goodnow, R.A. Jr.; Bukownik, R.; Nakanishi, K.; Usherwood, P.N.; Eldefrawi, A.T.; Anis, N.A.; Eldefrawi, M.E.

1991-01-01

125I2-iodinated philanthotoxin-343 (PhTX-343), [125I2]PhTX-343-arginine, and [125I2]PhTX-343-lysine were synthesized and evaluated as probes for glutamate receptors in rat brain synaptic membranes. It was found that these probes were not specific for the glutamate receptors but may be useful for investigating the polyamine binding site. Filtration assays with Whatman GF/B fiber glass filters were unsuitable because the iodinated PhTX-343 analogues exhibited high nonspecific binding to the filters, thus hindering detection of specific binding to membranes. When binding was measured by a centrifugal assay, [125I2]PhTX-343-lysine bound with low affinity (KD = 11.4 ± 2 microM) to a large number of sites (37.2 ± 9.1 nmol/mg of protein). The binding of [125I2]PhTX-343-lysine was sensitive only to the polyamines spermine and spermidine, which displaced [125I2]PhTX-343-lysine with Ki values of (3.77 ± 1.4) x 10(-5) M and (7.51 ± 0.77) x 10(-5) M, respectively. The binding was insensitive to glutamate receptor agonists and antagonists. Binding results with [125I2]PhTX-343-arginine were similar to those of [125I2]-PhTX-343-lysine. Considering the high number of toxin binding sites (10000-fold more than glutamate) in these membranes and the insensitivity of the binding to almost all drugs that bind to glutamate receptors, it is evident that most of the binding observed is not to glutamate receptors. On the other hand, PhTX analogues with photoaffinity labels may be useful in the isolation/purification of various glutamate and nicotinic acetylcholine receptors; they could also be useful in structural studies of receptors and their binding sites

Comparison of 3H-galactose and 3H-glucose as precursors of hepatic glycogen in control-fed rats

International Nuclear Information System (INIS)

Michaels, J.E.; Garfield, S.A.; Hung, J.T.; Cardell, R.R. Jr.

1989-01-01

Labeling of hepatic glycogen derived from 3H-galactose and 3H-glucose was compared shortly after intravenous injection in control-fed rats. The rats were allowed to accumulate 5-8% glycogen prior to receiving label. Fifteen minutes to 2 hours after labeling, liver was excised and processed for routine light (LM) and electron microscopic (EM) radioautography (RAG) or biochemical analysis. After injection of 3H-galactose, LM-RAGs revealed that the percentage of heavily labeled hepatocytes increased from 37% after 15 minutes to 68% after 1 hour but showed no further increase after 2 hours. alpha-Amylase treatment removed most glycogen and incorporated label; thus few silver grains were observed, indicating little incorporation of label except into glycogen. EM-RAGs demonstrated that most label occurred where glycogen was located. Biochemical analysis showed initially a high blood level of label that rapidly plateaued at a reduced level by 5 minutes. Concomitantly, glycogen labeling determined by liquid scintillation counting reflected the increases observed in the RAGs. After injection of 3H-glucose, LM-RAGs revealed that only 12% of the hepatocytes were heavily labeled at 1 hour and 20% at 2 hours. In tissue treated with alpha-amylase, glycogen was depleted and label was close to background level at each interval observed. EM-RAGs showed most grains associated with glycogen deposits. Biochemically, blood levels of label persisted at a high level for 30 minutes and tissue levels increased slowly over the 2-hour period. This study shows that incorporation from 3H-galactose was more rapid than incorporation of 3H-glucose; however, label derived from both carbohydrates appeared to be incorporated mainly into glycogen

Significance of the expression of matrix metalloproteinase-9 (MMP-9) in brain tissue of rat models of experimental intracerebral haemorrhage (ICH)

International Nuclear Information System (INIS)

Wu Jiami; Liu Shengda

2005-01-01

Objective: To study the relationship between the brain tissue expression of MMP-9 and brain water content in rat models of experimental ICH. Methods: Rat models of ICH were prepared with intracerebral (caudate nuclei) injection of autologous noncoagulated blood (50 μl). Animals were sacrificed at 6h, 12h, 24h, 48h, 72h, 120h, lw, 2w and the MMP-9 expressions at the periphery of intracerebral hematoma were examined with immunohisto chemistry. The brain water content was also determined at the same time. Control models were prepared with intracerebral sham injection of normal saline. Results: (1) In the ICH models, the number of MMP-9 positive capillaries at the periphery of hematoma began to rise at 6h (vs that of sham group, P < 0.01 ) with peak at 48h, then gradually dropped. At lwk, the number was still significantly higher than that in the sham group (P <0.01 ). However, there were no expression at 2wk. (2) The brain water content in the ICH group was significantly increased at 12h (vs sham group, P < 0.05) with peak at 72h. At lwk, the brain water content was still significantly higher in the ICH group (P <0.01 ) but at 2wk, the brain water content was about the same in both groups. (3) Animals injected with different amounts of blood (30 μl, 50 μl, 100 μl) showed increased expression of MMP-9 along with the increase of dose (P<0.01). (4) The MMP-9 expression was positively correlated with the brain water content (r=0.8291, P<0.05). Conclusion: In the rat models, MMP-9 expression was activated after ICH. The increase paralleled that of the amount of haemorrhage and brain water content. It was postulated that MMP-9 enhanced development of brain edema through degrading of the blood brain barrier component substances. (authors)

Effects of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats

Directory of Open Access Journals (Sweden)

Mingsan Miao

2017-05-01

Full Text Available The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA, and then expose external carotid artery (ECA and internal carotid artery (ICA. The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18–20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire. Finally it is gently pulled out the plug line after 2 h. Results: Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P < 0.05, P < 0.01; and reduce the serum S-100β protein content. Each dose group of the Rabdosia rubescens total flavonoids has a better Improvement effect on focal cerebral ischemia reperfusion model in rats.

Variation in energy sorghum hybrid TX08001 biomass composition and lignin chemistry during development under irrigated and non-irrigated field conditions

Science.gov (United States)

Olson, Sara N.; Ritter, Kimberley B.; Herb, Dustin W.; Karlen, Steven D.; Lu, Fachuang; Ralph, John; Rooney, William L.; Mullet, John E.

2018-01-01

This study was conducted to document the extent and basis of compositional variation of shoot biomass of the energy Sorghum bicolor hybrid TX08001 during development under field conditions. TX08001 is capable of accumulating ~40 Mg/ha of dry biomass under good growing conditions and this genotype allocates ~80% of its shoot biomass to stems. After 150 days of growth TX08001 stems had a fresh/dry weight ratio of ~3:1 and soluble biomass accounted for ~30% of stem biomass. A panel of diverse energy sorghum genotypes varied ~6-fold in the ratio of stem structural to soluble biomass after 150 days of growth. Near-infrared spectroscopic analysis (NIRS) showed that TX08001 leaves accumulated higher levels of protein, water extractives and ash compared to stems, which have higher sugar, cellulose, and lignin contents. TX08001 stem sucrose content varied during development, whereas the composition of TX08001 stem cell walls, which consisted of ~45–49% cellulose, ~27–30% xylan, and ~15–18% lignin, remained constant after 90 days post emergence until the end of the growing season (180 days). TX08001 and Della stem syringyl (S)/guaiacyl (G) (0.53–0.58) and ferulic acid (FA)/para-coumaric acid (pCA) ratios were similar whereas ratios of pCA/(S+G) differed between these genotypes. Additionally, an analysis of irrigated versus non-irrigated TX08001 revealed that non-irrigated hybrids exhibited a 50% reduction in total cell wall biomass, an ~2-fold increase in stem sugars, and an ~25% increase in water extractives relative to irrigated hybrids. This study provides a baseline of information to help guide further optimization of energy sorghum composition for various end-uses. PMID:29684037

Cyclooxygenase-2-dependent bronchoconstriction in perfused rat lungs exposed to endotoxin.

OpenAIRE

Uhlig, S.; Nüsing, R.; von Bethmann, A.; Featherstone, R. L.; Klein, T.; Brasch, F.; Müller, K. M.; Ullrich, V.; Wendel, A.

1996-01-01

BACKGROUND: Lipopolysaccharides (LPS), widely used to study the mechanisms of gram-negative sepsis, increase airway resistance by constriction of terminal bronchioles. The role of the cyclooxygenase (COX) isoenzymes and their prostanoid metabolites in this process was studied. MATERIALS AND METHODS: Pulmonary resistance, the release of thromboxane (TX) and the expression of COX-2 mRNA were measured in isolated blood-free perfused rat lungs exposed to LPS. RESULTS: LPS induced the release of T...

PhTX-II a Basic Myotoxic Phospholipase A2 from Porthidium hyoprora Snake Venom, Pharmacological Characterization and Amino Acid Sequence by Mass Spectrometry

Science.gov (United States)

Huancahuire-Vega, Salomón; Ponce-Soto, Luis Alberto; Marangoni, Sergio

2014-01-01

A monomeric basic PLA2 (PhTX-II) of 14149.08 Da molecular weight was purified to homogeneity from Porthidium hyoprora venom. Amino acid sequence by in tandem mass spectrometry revealed that PhTX-II belongs to Asp49 PLA2 enzyme class and displays conserved domains as the catalytic network, Ca2+-binding loop and the hydrophobic channel of access to the catalytic site, reflected in the high catalytic activity displayed by the enzyme. Moreover, PhTX-II PLA2 showed an allosteric behavior and its enzymatic activity was dependent on Ca2+. Examination of PhTX-II PLA2 by CD spectroscopy indicated a high content of alpha-helical structures, similar to the known structure of secreted phospholipase IIA group suggesting a similar folding. PhTX-II PLA2 causes neuromuscular blockade in avian neuromuscular preparations with a significant direct action on skeletal muscle function, as well as, induced local edema and myotoxicity, in mice. The treatment of PhTX-II by BPB resulted in complete loss of their catalytic activity that was accompanied by loss of their edematogenic effect. On the other hand, enzymatic activity of PhTX-II contributes to this neuromuscular blockade and local myotoxicity is dependent not only on enzymatic activity. These results show that PhTX-II is a myotoxic Asp49 PLA2 that contributes with toxic actions caused by P. hyoprora venom. PMID:25365526

PhTX-II a Basic Myotoxic Phospholipase A2 from Porthidium hyoprora Snake Venom, Pharmacological Characterization and Amino Acid Sequence by Mass Spectrometry

Directory of Open Access Journals (Sweden)

Salomón Huancahuire-Vega

2014-10-01

Full Text Available A monomeric basic PLA2 (PhTX-II of 14149.08 Da molecular weight was purified to homogeneity from Porthidium hyoprora venom. Amino acid sequence by in tandem mass spectrometry revealed that PhTX-II belongs to Asp49 PLA2 enzyme class and displays conserved domains as the catalytic network, Ca2+-binding loop and the hydrophobic channel of access to the catalytic site, reflected in the high catalytic activity displayed by the enzyme. Moreover, PhTX-II PLA2 showed an allosteric behavior and its enzymatic activity was dependent on Ca2+. Examination of PhTX-II PLA2 by CD spectroscopy indicated a high content of alpha-helical structures, similar to the known structure of secreted phospholipase IIA group suggesting a similar folding. PhTX-II PLA2 causes neuromuscular blockade in avian neuromuscular preparations with a significant direct action on skeletal muscle function, as well as, induced local edema and myotoxicity, in mice. The treatment of PhTX-II by BPB resulted in complete loss of their catalytic activity that was accompanied by loss of their edematogenic effect. On the other hand, enzymatic activity of PhTX-II contributes to this neuromuscular blockade and local myotoxicity is dependent not only on enzymatic activity. These results show that PhTX-II is a myotoxic Asp49 PLA2 that contributes with toxic actions caused by P. hyoprora venom.

EnviroAtlas - Austin, TX - Meter-Scale Urban Land Cover (MULC) Data (2010)

Data.gov (United States)

U.S. Environmental Protection Agency — The Austin, TX EnviroAtlas One Meter-scale Urban Land Cover (MULC) Data were generated from United States Department of Agriculture (USDA) National Agricultural...

Growth of Pseudomonas sp. TX1 on a wide range of octylphenol polyethoxylate concentrations and the formation of dicarboxylated metabolites.

Science.gov (United States)

Lin, Yi-Wen; Guo, Gia-Luen; Hsieh, Hsiao-Cheng; Huang, Shir-Ly

2010-04-01

Pseudomonas sp. TX1, is able to use octylphenol polyethoxylates (OPEO(n), or Triton X-100; average n = 9.5) as a sole carbon source. It can grow on 0.05-20% of OPEO(n) with a specific growth rate of 0.34-0.44 h(-1). High-performance liquid chromatography-mass spectrometer analysis of OPEO(n) degraded metabolites revealed that strain TX1 was able to shorten the ethoxylate chain and produce octylphenol (OP). Furthermore, formation of the short carboxylate metabolites, such as carboxyoctylphenol polyethoxylates (COPEO(n), n = 2, 3) and carboxyoctylphenol polyethoxycarboxylates (COPEC(n), n = 2, 3) began at the log stage, while octylphenol polyethoxycarboxylates (OPEC(n), n = 1-3) was formed at the stationary phase. All the short-ethoxylated metabolites, OPEO(n), OPEC(n), COPEO(n), and COPEC(n), accumulated when the cells were in the stationary phase. This study is the first to demonstrate the formation of COPEO(n) and COPEC(n) from OPEO(n) by an aerobic bacterium. Copyright 2009 Elsevier Ltd. All rights reserved.

Clinical significance of changes of serum IL-6 and TNF-α levels in rat models of hypoxic-ischemia brain injury

International Nuclear Information System (INIS)

Niu Tingxian; Shi Zhiyong; Luo Jianjun

2009-01-01

Objective: To explore the clinical significance of changes of serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels in rat models of hypoxic-ischemia (HI) brain injury. Methods: Seventy five rat HI brain injury nodels were prepared with bilateral occlusion of common carotid artery for 24rs followed 2hrs later by hypoxia (breathing 8% oxygen) for 2hrs. One fifth of the animals were sacrificed at 4h, 8h, 12h, 24h and 48h later respectively, the serum and brain homogenate concentrations of IL-6 and TNF-α were determined with RIA and brain tissues were pathologically examined. Results: The concentrations of IL-6 and TNF-α were dynamically changed within 48h in serum and brain homogenate. Peak values occurred at 24h with serum and at 12h with brain homogenate. Meanwhile, levels of both cytokines were significantly higher in the models than those in controls (P<0.01 or P<0.05). Conclusion: The concentrations of IL-6 and TNF-α were dynamically(sham operation only, 15 animals) changed and might be regarded as the clinical markers of degree of HI brain injury. (authors)

DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

DEFF Research Database (Denmark)

Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian......Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...

Preliminary X-ray crystallographic studies of BthTX-II, a myotoxic Asp49-phospholipase A2 with low catalytic activity from Bothrops jararacussu venom

International Nuclear Information System (INIS)

Corrêa, L. C.; Marchi-Salvador, D. P.; Cintra, A. C. O.; Soares, A. M.; Fontes, M. R. M.

2006-01-01

A myotoxic Asp49-PLA 2 with low catalytic activity from B. jararacussu (BthTX-II) was crystallized in the monoclinic crystal system; a complete X-ray diffraction data set was collected and a molecular-replacement solution was obtained. The oligomeric structure of BthTX-II resembles those of the Asp49-PLA 2 PrTX-III and all bothropic Lys49-PLA 2 s. For the first time, a complete X-ray diffraction data set has been collected from a myotoxic Asp49-phospholipase A 2 (Asp49-PLA 2 ) with low catalytic activity (BthTX-II from Bothrops jararacussu venom) and a molecular-replacement solution has been obtained with a dimer in the asymmetric unit. The quaternary structure of BthTX-II resembles the myotoxin Asp49-PLA 2 PrTX-III (piratoxin III from B. pirajai venom) and all non-catalytic and myotoxic dimeric Lys49-PLA 2 s. In contrast, the oligomeric structure of BthTX-II is different from the highly catalytic and non-myotoxic BthA-I (acidic PLA 2 from B. jararacussu). Thus, comparison between these structures should add insight into the catalytic and myotoxic activities of bothropic PLA 2 s

Modulating effects of thyroid state on the induction of biotransformation enzymes byu 2,3,7,8-tetrachlorodibenzo-p-dioxin.

NARCIS (Netherlands)

Schuur, A.G.; Tacken, P.J.; Visser, T.J.; Brouwer, A.

1998-01-01

In this study we investigated to what extent the induction of detoxification enzymes by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is modulated by concomitant TCDD-induced changes in thyroid state. Euthyroid (Eu) male Sprague-Dawley rats, surgically thyroidectomized (Tx) rats and Tx rats receiving

Resveratrol prevents alveolar bone loss in an experimental rat model of periodontitis.

Science.gov (United States)

Bhattarai, Govinda; Poudel, Sher Bahadur; Kook, Sung-Ho; Lee, Jeong-Chae

2016-01-01

Resveratrol is an antioxidant and anti-inflammatory polyphenol. Periodontitis is induced by oral pathogens, where a systemic inflammatory response accompanied by oxidative stress is the major event initiating disease. We investigated how resveratrol modulates cellular responses and the mechanisms related to this modulation in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (hGFs). We also explored whether resveratrol protects rats against alveolar bone loss in an experimental periodontitis model. Periodontitis was induced around the first upper molar of the rats by applying ligature infused with LPS. Stimulating hGFs with 5μg/ml LPS augmented the expression of cyclooxygenase-2, matrix metalloproteinase (MMP)-2, MMP-9, and Toll-like receptor-4. LPS treatment also stimulated the production of reactive oxygen species (ROS) and the phosphorylation of several protein kinases in the cells. However, the expression of heme oxygenase-1 (HO-1) and nuclear factor-E2 related factor 2 (Nrf2) was inhibited by the addition of LPS. Resveratrol treatment almost completely inhibited all of these changes in LPS-stimulated cells. Specifically, resveratrol alone augmented HO-1 induction via Nrf2-mediated signaling. Histological and micro-CT analyses revealed that administration of resveratrol (5mg/kg body weight) improved ligature/LPS-mediated alveolar bone loss in rats. Resveratrol also attenuated the production of inflammation-related proteins, the formation of osteoclasts, and the production of circulating ROS in periodontitis rats. Furthermore, resveratrol suppressed LPS-mediated decreases in HO-1 and Nrf2 levels in the inflamed periodontal tissues. Collectively, our findings suggest that resveratrol protects rats from periodontitic tissue damage by inhibiting inflammatory responses and by stimulating antioxidant defense systems. The aims of this study were to investigate how resveratrol modulates cellular responses and the mechanisms related to this modulation in

Presynaptic localization of histamine H3-receptors in rat brain

International Nuclear Information System (INIS)

Fujimoto, K.; Mizuguchi, H.; Fukui, H.; Wada, H.

1991-01-01

The localization of histamine H3-receptors in subcellular fractions from the rat brain was examined in a [3H] (R) alpha-methylhistamine binding assay and compared with those of histamine H1- and adrenaline alpha 1- and alpha 2-receptors. Major [3H](R) alpha-methylhistamine binding sites with increased specific activities ([3H]ligand binding vs. protein amount) were recovered from the P2 fraction by differential centrifugation. Minor [3H](R)alpha-methylhistamine binding sites with increased specific activities were also detected in the P3 fraction. Further subfractionation of the P2 fraction by discontinuous sucrose density gradient centrifugation showed major recoveries of [3H](R)alpha-methylhistamine binding in myelin (MYE) and synaptic plasma membrane (SPM) fractions. A further increase in specific activity was observed in the MYE fraction, but the SPM fraction showed no significant increase in specific activity. Adrenaline alpha 2-receptors, the pre-synaptic autoreceptors, in a [3H] yohimbine binding assay showed distribution patterns similar to histamine H3-receptors. On the other hand, post-synaptic histamine H1- and adrenaline alpha 1-receptors were closely localized and distributed mainly in the SPM fraction with increased specific activity. Only a negligible amount was recovered in the MYE fraction, unlike the histamine H3- and adrenaline alpha 2-receptors

78 FR 52714 - Proposed Amendment of Class E Airspace; Gainesville, TX

Science.gov (United States)

2013-08-26

...: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed rulemaking (NPRM). SUMMARY: This action proposes to amend Class E airspace at Gainesville, TX. Decommissioning of the Gainesville radio... developing reasoned regulatory decisions on the proposal. Comments are specifically invited on the overall...

TIA model is attainable in Wistar rats by intraluminal occlusion of the MCA for 10min or shorter.

Science.gov (United States)

Durukan Tolvanen, A; Tatlisumak, E; Pedrono, E; Abo-Ramadan, U; Tatlisumak, T

2017-05-15

Transient ischemic attack (TIA) has received only little attention in the experimental research field. Recently, we introduced a TIA model for mice, and here we set similar principles for simulating this human condition in Wistar rats. In the model: 1) transient nature of the event is ensured, and 2) 24h after the event animals are free from any sensorimotor deficit and from any detectable lesion by magnetic resonance imaging (MRI). Animals experienced varying durations of ischemia (5, 10, 12.5, 15, 25, and 30min, n=6-8pergroup) by intraluminal middle cerebral artery occlusion (MCAO). Ischemia severity and reperfusion rates were controlled by cerebral blood flow measurements. Sensorimotor neurological evaluations and MRI at 24h differentiated between TIA and ischemic stroke. Hematoxylin and eosin staining and apoptotic cell counts revealed pathological correlates of the event. We found that already 12.5min of ischemia was long enough to induce ischemic stroke in Wistar rats. Ten min or shorter durations induced neither gross neurological deficits nor infarcts visible on MRI, but histologically caused selective neuronal necrosis. A separate group of animals with 10min of ischemia followed up to 1week after reperfusion remained free of infarction and any MRI signal change. Thus, 10min or shorter focal cerebral ischemia induced by intraluminal MCAO in Wistar rats provides a clinically relevant TIA the rat. This model is useful for studying molecular correlates of TIA. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation of rat gastric heavy and light microsomal membranes enriched in (H+-K+)-ATPase using 2H2O and Percoll gradients

International Nuclear Information System (INIS)

Im, W.B.; Davis, J.P.; Blakeman, D.P.

1985-01-01

Gastric heavy microsomal membranes highly enriched in (H + -K + )-ATPase were obtained from cimetidine- or carbachol-treated rats through 2 H 2 O and Percoll gradient centrifugations. Both the resting (cimetidine-treated) and the stimulated (carbachol-treated) heavy membranes which presumably represent the apical membrane of gastric parietal cells were enriched with the polypeptides of 81,000 and 45,000 besides that of 93,000 representing (H + -K + )-ATPase. No apparent differences could be detected between the resting and the stimulated heavy membranes in their polypeptide profiles or their specific activity of (H + -K + )-ATPase. Nevertheless, the level of 86 RbCl uptake was greater in the stimulated than the resting heavy microsomal membrane vesicles. The light gastric microsomes which abound in intracellular tubulovesicles containing reserve (H + -K + )-ATPase as isolated from cimetidine-treated rats were similarly purified with respect to (H + -K + )-ATPase. The purified light gastric membranes were largely devoid of the polypeptides of 81,000 and 45,000 found in the heavy gastric membranes. These observations further support the current hypothesis that secretagogues bring about changes in the environment of (H + -K + )-ATPase and induce KCl permeability in the apical membrane of the parietal cells, although at present the authors have been unable to identify the polypeptide(s) responsible for the KCl pathway

Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

Science.gov (United States)

Tsao, L I; Su, T P

1997-02-01

A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

Uptake of [14C]deoxyglucose into brain of young rats with inherited hydrocephalus

International Nuclear Information System (INIS)

Richards, H.K.; Bucknall, R.M.; Jones, H.C.; Pickard, J.D.

1989-01-01

The effect of hydrocephalus on cerebral glucose utilization as reflected by deoxyglucose uptake has been examined in rats with inherited hydrocephalus at 10, 20, and 28 days after birth using a semiquantitative method. Injection of [14C]deoxyglucose intraperitoneally was followed by freezing the brain, sectioning, and quantitative autoradiography of 10 brain regions. Brain [14C] concentration, cortical thickness, and plasma glucose concentrations were measured. Maximal thinning of the cerebral cortex had already occurred by 10 days after birth, although obvious symptoms such as gait disturbance developed after 20 days. In control rats, the cerebral isotope concentration was lower and more homogeneous at 10 days than at 20 or 28 days, which may be a reflection of the use of metabolic substrates other than glucose in younger animals. In order to make comparisons between control and hydrocephalic groups, tissue isotope concentrations were normalized to cerebellar cortex which was not affected by the hydrocephalus at any age. In hydrocephalic rats at 10 and 20 days, the concentration of [14C] was lower in all areas except the inferior colliculi and pons but the reduction was only significant in the sensory-motor cortex at 10 days and in the caudate nuclei at 20 days. By 28 days after birth, all areas except the cerebellum (six cortical regions, inferior colliculi, pons, and caudate) had significantly lower isotope concentrations in the hydrocephalic group. It is concluded that cerebral glucose metabolism is significantly reduced by 28 days after birth in H-Tx rats with congenital hydrocephalus and that less marked reductions occur prior to 28 days

Rotary mode core sampling approved checklist: 241-TX-113

International Nuclear Information System (INIS)

Fowler, K.D.

1998-01-01

The safety assessment for rotary mode core sampling was developed using certain bounding assumptions, however, those assumptions were not verified for each of the existing or potential flammable gas tanks. Therefore, a Flammable Gas/Rotary Mode Core Sampling Approved Checklist has been completed for tank 241-TX-113 prior to sampling operations. This transmittal documents the dispositions of the checklist items from the safety assessment

Rotary mode core sampling approved checklist: 241-TX-116

International Nuclear Information System (INIS)

FOWLER, K.D.

1999-01-01

The safety assessment for rotary mode core sampling was developed using certain bounding assumptions, however, those assumptions were not verified for each of the existing or potential flammable gas tanks. Therefore, a Flammable Gas/Rotary Mode Core Sampling Approved Checklist has been completed for tank 241-TX-116 prior to sampling operations. This transmittal documents the dispositions of the checklist items from the safety assessment

Fluoride Alteration of [3H]Glucose Uptake in Wistar Rat Brain and Peripheral Tissues.

Science.gov (United States)

Rogalska, Anna; Kuter, Katarzyna; Żelazko, Aleksandra; Głogowska-Gruszka, Anna; Świętochowska, Elżbieta; Nowak, Przemysław

2017-04-01

The present study was designed to investigate the role of postnatal fluoride intake on [3H]glucose uptake and transport in rat brain and peripheral tissues. Sodium fluoride (NaF) in a concentration of 10 or 50 ppm was added to the drinking water of adult Wistar rats. The control group received distilled water. After 4 weeks, respective plasma fluoride levels were 0.0541 ± 0.0135 μg/ml (control), 0.0596 ± 0.0202 μg/ml (10 ppm), and 0.0823 ± 0.0199 μg/ml (50 ppm). Although plasma glucose levels were not altered in any group, the plasma insulin level in the fluoride (50 ppm) group was elevated (0.72 ± 0.13 μg/ml) versus the control group (0.48 ± 0.24 μg/ml) and fluoride (10 ppm) group. In rats receiving fluoride for 4 weeks at 10 ppm in drinking water, [3H]glucose uptake was unaltered in all tested parts of the brain. However, in rats receiving fluoride at 50 ppm, [3H]glucose uptake in cerebral cortex, hippocampus, and thalamus with hypothalamus was elevated, versus the saline group. Fluoride intake had a negligible effect on [3H]glucose uptake by peripheral tissues (liver, pancreas, stomach, small intestine, atrium, aorta, kidney, visceral tissue, lung, skin, oral mucosa, tongue, salivary gland, incisor, molars, and jawbone). In neither fluoride group was glucose transporter proteins 1 (GLUT 1) or 3 (GLUT 3) altered in frontal cortex and striatum versus control. On the assumption that increased glucose uptake (by neural tissue) reasonably reflects neuronal activity, it appears that fluoride damage to the brain results in a compensatory increase in glucose uptake and utilization without changes in GLUT 1 and GLUT 3 expression.

Quantitative autoradiography of [3H]corticosterone receptors in rat brain

International Nuclear Information System (INIS)

Sapolsky, R.M.; McEwen, B.S.; Rainbow, T.C.

1983-01-01

The authors have quantified corticosterone receptors in rat brain by optical density measurements of tritium-film autoradiograms. Rats were injected i.v. with 500 μCi [ 3 H]corticosterone to label brain receptors. Frozen sections of brain were cut with a cryostat and exposed for 2 months against tritium-sensitive sheet film (LKB Ultrofilm). Tritium standards were used to convert optical density readings into molar concentrations of receptor. High levels of corticosterone receptors were present throughout the pyramidal and granule cell layers of the hippocampus. Moderate levels of receptors were found in the neuropil of the hippocampus, the lateral septum, the cortical nucleus of the amygdala and the entorhinal cortex. All other brain regions had low levels of receptors. These results extend previous non-quantitative autoradigraphic studies of corticosterone receptors and provide a general procedure for the quantitative autoradiography of steroid hormone receptors in brain tissue. (Auth.)

78 FR 19985 - Modification of VOR Federal Airways V-68, V-76, V-194, and V-548 in the Vicinity of Houston, TX

Science.gov (United States)

2013-04-03

..., and V-548 in the Vicinity of Houston, TX AGENCY: Federal Aviation Administration (FAA), DOT. ACTION... airways V-68, V-76, V-194, and V-548 in the vicinity of Houston, TX. The FAA is taking this action to... vicinity of Houston, TX. Specifically, the FAA amends V-68 and V-76 to reflect the Hobby VOR/DME 289[deg...

BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells promote erectile function in a rat model of cavernous nerve electrocautery injury.

Science.gov (United States)

Song, Lujie; Zhu, Jianqiang; Zhang, Xiong; Cui, Zhiqiang; Fu, Qiang; Huang, Jianwen; Lu, Hongkai

2016-01-01

Erectile dysfunction (ED) continues to be a significant problem for men following radical prostatectomy. We hypothesize that intracavernous injection of BDNF-hypersecreting human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) can ameliorate ED in a rat model of cavernous nerve electrocautery injury (CNEI). Forty-two male Sprague-Dawley rats were randomly divided into four groups: sham + PBS (n = 6), CNEI + PBS (n = 12), CNEI + hUCB-MSCs (n = 12) and CNEI + BDNF-hUCB-MSCs (n = 12). At day 28 post-surgery, erectile function was examined and specimens were harvested for histology. Immunofluorescence staining, Masson's trichrome staining and transmission electron microscopy were performed to determine the structural changes in corpus cavernosum. Cells that are injected into penis were labeled by BrdU and tracked by immunofluorescence staining. Three days post-surgery, the concentration of BDNF protein in penile tissues was measured by Western blotting. Rats intracavernosally injected with BDNF-hUCB-MSCs showed the most significant improvement in the ratio of maximal ICP to MAP (ICP/MAP). Histological examinations showed moderate recovery of nNOS-positive nerve fibers, ratio of smooth muscle to collagen and smooth muscle content in the CNEI + hUCB-MSCs group and remarkable recovery in the CNEI + BDNF-hUCB-MSCs group compared to the CNEI + PBS group. By TEM examination, atrophy of myelinated and non-myelinated nerve fibers was noted in CNEI + PBS group and significant recovery was observed in two treated groups. There were more BrdU-positive cells in the BDNF-hUCB-MSCs group than in the hUCB-MSCs group both in the penis and in the MPG. Three days post-surgery, the concentration of BDNF protein in penile tissues in BDNF-hUCB-MSCs group was much higher than in other groups. Intracavernous injection of BDNF-hypersecreting hUCB-MSCs can enhance the recovery of erectile function, promote the CNs regeneration and inhibit corpus cavernosum fibrosis after CNEI in a rat

(/sup 3/H)-beta-endorphin binding in rat brain

Energy Technology Data Exchange (ETDEWEB)

Houghten, R.A.; Johnson, N.; Pasternak, G.W.

1984-10-01

The binding of (/sup 3/H)-beta-endorphin to rat brain homogenates is complex. Although Scatchard analysis of saturation studies yields a straight line, detailed competition studies are multiphasic, suggesting that even at low concentrations of the compound, the /sup 3/H-ligand is binding to more than one class of site. A portion of (/sup 3/H)-beta-endorphin binding is sensitive to low concentrations of morphine or D-Ala2-Leu5-enkephalin (less than 5 nM). The inhibition observed with each compound alone (5 nM) is the same as that seen with both together (each at 5 nM). Thus, the binding remaining in the presence of both morphine and the enkephalin does not correspond to either mu or delta sites. The portion of (/sup 3/H)-beta-endorphin binding that is inhibited under these conditions appears to be equally sensitive to both morphine and the enkephalin and may correspond to mu1 sites. Treating membrane homogenates with naloxonazine, a mu1 selective antagonist, lowers (/sup 3/H)-beta-endorphin binding to the same degree as morphine and D-Ala2-Leu5-enkephalin alone or together. This possible binding of (/sup 3/H)-beta-endorphin to mu1 sites is consistent with the role of mu1 sites in beta-endorphin analgesia and catalepsy in vivo.

Solubilization of rat kidney plasma membrane proteins associated with 3H-aldosterone

International Nuclear Information System (INIS)

Ozegovic, B.; Dobrovic-Jenik, D.; Milkovic, S.

1988-01-01

The treatment of rat kidney plasma membranes with sodium dodecyl sulphate (SDS) did not essentially affect the ability of the membranes for 3 H-aldosterone binding as compared with the intact plasma membranes (Ozegovic et al., 1977). A gel filtration of 3 H-aldosterone - kidney plasma membranes complex on Sepharose 6B yielded 2 protein and 2 3 H-aldosterone peaks. The proteins which were eluted in the first peak were associated with the first 3 H-aldosterone peak while the second 3 H-aldosterone peak was eluted with Ve corresponding to Ve of free 3 H-aldosterone. Spironolactone, a competitive antagonist of aldosterone, prevented the binding of 3 H-aldosterone to the membrane proteins. The results demonstrated a high affinity of the kidney plasma membranes solubilized with SDS and a specificity of aldosterone binding to the plasma membrane proteins of higher molecular mass. (author)

Phenoxybenzamine Is Neuroprotective in a Rat Model of Severe Traumatic Brain Injury

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Thomas F. Rau

2014-01-01

Full Text Available Phenoxybenzamine (PBZ is an FDA approved α-1 adrenergic receptor antagonist that is currently used to treat symptoms of pheochromocytoma. However, it has not been studied as a neuroprotective agent for traumatic brain injury (TBI. While screening neuroprotective candidates, we found that phenoxybenzamine reduced neuronal death in rat hippocampal slice cultures following exposure to oxygen glucose deprivation (OGD. Using this system, we found that phenoxybenzamine reduced neuronal death over a broad dose range (0.1 µM–1 mM and provided efficacy when delivered up to 16 h post-OGD. We further tested phenoxybenzamine in the rat lateral fluid percussion model of TBI. When administered 8 h after TBI, phenoxybenzamine improved neurological severity scoring and foot fault assessments. At 25 days post injury, phenoxybenzamine treated TBI animals also showed a significant improvement in both learning and memory compared to saline treated controls. We further examined gene expression changes within the cortex following TBI. At 32 h post-TBI phenoxybenzamine treated animals had significantly lower expression of pro-inflammatory signaling proteins CCL2, IL1β, and MyD88, suggesting that phenoxybenzamine may exert a neuroprotective effect by reducing neuroinflammation after TBI. These data suggest that phenonxybenzamine may have application in the treatment of TBI.

Characterization of Vadose Zone Sediments Below the TX Tank Farm: Probe Holes C3830, C3831, C3832 and 299-W10-27

Energy Technology Data Exchange (ETDEWEB)

Serne, R JEFFREY.; Bjornstad, Bruce N.; Horton, Duane G.; Lanigan, David C.; Lindenmeier, Clark W.; Lindberg, Michael J.; Clayton, Ray E.; LeGore, Virginia L.; Orr, Robert D.; Kutnyakov, Igor V.; Baum, Steven R.; Geiszler, Keith N.; Valenta, Michelle M.; Vickerman, Tanya S.

2004-04-01

identify the maximum vertical penetration of the tank related plumes. However, the more elevated portions of the electrical conductivity (EC) profile at probe hole C3830 currently resides at the bottom of a fine-grained thin lens in the Hanford H2 unit at 87 ft bgs. At C3831, we lack good sample coverage to ascertain whether the salt plume has significantly descended into the Cold Creek Unit. There is strong indication at probe hole C3832 that the saline plume has descended into the Cold Creek Unit. The profiles do collectively suggest that the deepest penetration of tank related fluids is found in probe hole C3832. The water potential data from 299-W10-27?s H2 unit, the unit where most of the contaminants reside in the TX probe holes, are consistent with a draining profile. Despite the evidence that elevated EC values may be present in all three probe holes to their depth of refusal, the concentrations of long-term risk drivers are not large. The inventories of potential contaminants of concern, nitrate, technetium-99, uranium, and chromium, are provided. In addition, in situ desorption Kd values for these contaminants are provided. For conservative modeling purposes, we recommend using Kd values of 0 mL/g for nitrate and technetium-99, a value of 1 mL/g for uranium, and 10 mL/g for chromium to represent the entire vadose zone profile from the bottoms of the tanks to the water table. These conservative Kd values along with the provided inventories in the vadose zone sediments obtained from the three probe holes can be used in long-term risk projections that rely on estimates of water recharge and vadose zone and aquifer transport calculations.

The physiological response of obese rat model with rambutan peel extract treatment

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Sri Rahayu Lestari

2014-09-01

Full Text Available Objective: To determine body weight gain, expression of Igf-1 and Igf-1 receptor on obese rat model treated with rambutan peel extract (RPE as a physiological response. Methods: Normal and obese rat feed with normal and high calorie diet around 1 2 weeks and continued to treat with ellagic acid, RPE 15, 30 and 60 mg/kg body weight respectively. Physiological responses observed were weight gain and expression of Igf-1 with its receptor. Body weight of rat was weighed once per week. Expression of Igf-1 and igf-1R observed with fluorescence immunohistochemistry. The intensity of Igf-1 and Igf-1R expression was analysis using FSX-BSW software. Results: The lowest weight gain was obtained on obese rat model treated with RPE 30 mg/kg body weight. The expression of Igf-1 and Igf-1R were reduced on obese rat model treated with RPE compared with obese rat model of non treatment (P<0.05. The low expression of Igf-1 and Igf-1R was found on obese rat model treated with ellagic acid and RPE 30 mg/kg body weight. Conclusions: The RPE was effecting to the physiological response on obese rat model. The RPE 30 mg/kg body weight inhibited body weight gain and decreased the expression of Igf-1 and Igf- 1R of obese rat model.

Changes in erectile organ structure and function in a rat model of chronic prostatitis/chronic pelvic pain syndrome.

Science.gov (United States)

Wang, X-J; Xia, L-L; Xu, T-Y; Zhang, X-H; Zhu, Z-W; Zhang, M-G; Liu, Y; Xu, C; Zhong, S; Shen, Z-J

2016-04-01

There is a growing recognition of the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED); however, most of the reports are based on questionnaires which cannot distinguish between organic and functional ED. The purpose of this study was to determine the exact relationship between CP/CPPS and ED, and to investigate the changes in erectile organ structure and function in a rat model of CP/CPPS. We established a rat model of experimental autoimmune prostatitis (EAP), which is a valid model for CP/CPPS. Erectile function in EAP and normal rats was comparable after cavernous nerve electrostimulation. The serum testosterone and oestradiol levels, ultrastructure of the corpus cavernosum and expression of endothelial nitric oxide synthase and neuronal nitric oxide synthase in the two groups were similar; however, there was a decrease in smooth muscle-to-collagen ratio and alpha-smooth muscle actin expression and an increase in transforming growth factor-beta 1 expression was observed in EAP rats. Thus, organic ED may not exist in EAP rats. We speculate that ED complained by patients with CP/CPPS may be psychological, which could be caused by impairment in the quality of life; however, further studies are needed to fully understand the potential mechanisms underlying the penile fibrosis in EAP rats. © 2015 Blackwell Verlag GmbH.

Intervention of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma

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Xiao-Xuan Fan

2017-07-01

Full Text Available Objective: To study the intervention effect of Peiyuan Huayu Decoction on the neuron damage in model rats with acute subdural hematoma (ASDH. Methods: 160 SD rats were randomly divided into four groups, and the ASDH model rats were made by stereotactic autoblood injection, and sham operation group received craniotomy without blood injection. Sham operation group and model group were normally bred after model establishment, and 6 h after model establishment, the treatment group received intragastric administration of Peiyuan Huayu Decoction, and control group received intragastric administration of Piracetam Tablets, 1 time a day. On the 1d, 3d, 5d and 7d after model establishment, the general conditions of rats (activity, food intake and mental state were observed, blood was collected via auricula dextra, ELISA method was used to determine peripheral plasma NSE and S100毬 protein contents, routine HE staining was conducted after perfusion fixation, the neurons in blood injection side of brain tissue were counted, and the neuron damage was observed. Results: 26 rats were dead in the experiment. The general conditions of sham operation group were significantly better than those of other groups, treatment group was significantly better than model group and control group on the 5d group (P0.05; neuron count of sham operation group was basically stable, treatment group was not different from model group and control group on the 1d (P>0.05, treatment group was better than model group (P0.05 on the 3d, and treatment group was better than model group and control group on the 5d and 7d (P0.05, S100毬 protein and NSE contents decreased significantly on the 3d, and treatment group was significantly different from model group and control group (P<0.05, S100毬 protein and NSE contents increased on the 5d and 7d, the increase in treatment group was slower than that in model group and control group, and there was significant difference (P<0.05. Conclusion

(1)H NMR-based metabonomics revealed protective effect of Naodesheng bioactive extract on ischemic stroke rats.

Science.gov (United States)

Luo, Lan; Zhen, Lifeng; Xu, Yatao; Yang, Yongxia; Feng, Suxiang; Wang, Shumei; Liang, Shengwang

2016-06-20

Stroke is a leading cause of death and disability in the world. However, current therapies are limited. Naodesheng, a widely used traditional Chinese medicine prescription, has shown a good clinical curative effect on ischemic stroke. Also, Naodesheng has been suggested to have neuroprotective effect on focal cerebral ischemia rats, but the underlying molecular mechanism remains unclear. The present study was designed to evaluate the effect of Naodesheng bioactive extract on the metabolic changes in brain tissue, plasma and urine induced by cerebral ischemia perfusion injury, and explore the possible metabolic mechanisms by using a (1)H NMR-based metabonomics approach. A middle cerebral artery occlusion rat model was established and confirmed by the experiments of neurobehavioral abnormality evaluation, brain tissue TTC staining and pathological examination. The metabolic changes in brain tissue, plasma and urine were then assessed by a (1)H NMR technique combined with multivariate statistical analysis method. These NMR data showed that cerebral ischemia reperfusion induced great metabolic disorders in brain tissue, plasma and urine metabolisms. However, Naodesheng bioactive extract could reverse most of the imbalanced metabolites. Meanwhile, it was found that both the medium and high dosages of Naodesheng bioactive extract were more effective on the metabolic changes than the low dosage, consistent with histopathological assessments. These results revealed that Naodesheng had protective effect on ischemic stroke rats and the underlying mechanisms involved multiple metabolic pathways, including energy metabolism, amino acid metabolism, oxidative stress and inflammatory injury. The present study could provide evidence that metabonomics revealed its capacity to evaluate the holistic efficacy of traditional Chinese medicine and explore the underlying mechanisms. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Acoustic noise improves motor learning in spontaneously hypertensive rats, a rat model of attention deficit hyperactivity disorder.

Science.gov (United States)

Söderlund, Göran B W; Eckernäs, Daniel; Holmblad, Olof; Bergquist, Filip

2015-03-01

The spontaneously hypertensive (SH) rat model of ADHD displays impaired motor learning. We used this characteristic to study if the recently described acoustic noise benefit in learning in children with ADHD is also observed in the SH rat model. SH rats and a Wistar control strain were trained in skilled reach and rotarod running under either ambient noise or in 75 dBA white noise. In other animals the effect of methylphenidate (MPH) on motor learning was assessed with the same paradigms. To determine if acoustic noise influenced spontaneous motor activity, the effect of acoustic noise was also determined in the open field activity paradigm. We confirm impaired motor learning in the SH rat compared to Wistar SCA controls. Acoustic noise restored motor learning in SH rats learning the Montoya reach test and the rotarod test, but had no influence on learning in Wistar rats. Noise had no effect on open field activity in SH rats, but increased corner time in Wistar. MPH completely restored rotarod learning and performance but did not improve skilled reach in the SH rat. It is suggested that the acoustic noise benefit previously reported in children with ADHD is shared by the SH rat model of ADHD, and the effect is in the same range as that of stimulant treatment. Acoustic noise may be useful as a non-pharmacological alternative to stimulant medication in the treatment of ADHD. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Antagonism by supidimide of haloperidol-induced augmentation of [3H]-spiperone binding in rat striatum

International Nuclear Information System (INIS)

Hennies, H.H.; Hess, V.; Flohe, L.

1984-01-01

Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D 2 receptor density in the striatum was investigated after a drug-free period of five days. The D 2 receptor system as analysed by [ 3 H]-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective. (orig./MG) [de

Pancreatic Transdifferentiation and Glucose-Regulated Production of Human Insulin in the H4IIE Rat Liver Cell Line

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Binhai Ren

2016-04-01

Full Text Available Due to the limitations of current treatment regimes, gene therapy is a promising strategy being explored to correct blood glucose concentrations in diabetic patients. In the current study, we used a retroviral vector to deliver either the human insulin gene alone, the rat NeuroD1 gene alone, or the human insulin gene and rat NeuroD1 genes together, to the rat liver cell line, H4IIE, to determine if storage of insulin and pancreatic transdifferentiation occurred. Stable clones were selected and expanded into cell lines: H4IIEins (insulin gene alone, H4IIE/ND (NeuroD1 gene alone, and H4IIEins/ND (insulin and NeuroD1 genes. The H4IIEins cells did not store insulin; however, H4IIE/ND and H4IIEins/ND cells stored 65.5 ± 5.6 and 1475.4 ± 171.8 pmol/insulin/5 × 106 cells, respectively. Additionally, several β cell transcription factors and pancreatic hormones were expressed in both H4IIE/ND and H4IIEins/ND cells. Electron microscopy revealed insulin storage vesicles in the H4IIE/ND and H4IIEins/ND cell lines. Regulated secretion of insulin to glucose (0–20 mmol/L was seen in the H4IIEins/ND cell line. The H4IIEins/ND cells were transplanted into diabetic immunoincompetent mice, resulting in normalization of blood glucose. This data shows that the expression of NeuroD1 and insulin in liver cells may be a useful strategy for inducing islet neogenesis and reversing diabetes.

HPLC-ICP-MS compared with radiochemical detection for metabolite profiling of H-3-bromohexine in rat urine and faeces

DEFF Research Database (Denmark)

Jensen, B.P.; Gammelgaard, B.; Hansen, S.H.

2005-01-01

H-3-Bromohexine was dosed to rats as a model compound to allow comparison of HPLC-ICP-MS detection on bromine to radiochemical detection in an in vivo drug metabolism study. Metabolite profiles were obtained in urine and faeces extracts. No influence of the methanol gradient on the bromine response...... was observed in the range of 18 - 75% methanol. The sensitivity obtained by HPLC- ICP-MS was almost two orders of magnitude better than on-line H-3 radiochemical detection. For ICP- MS, the limit of detection was calculated to be 69 nM Br ( injection volume 100 mu l), corresponding to an absolute limit...

Phosphorylation of histone H2AX as an indicator of received dose of gamma radiation after whole-body irradiation of rats

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Radim Havelek

2011-01-01

Full Text Available The aim of our study was to determine whether phosphorylation of histone H2AX can be used as an indicator of received dose of gamma radiation after whole-body irradiation of rats. Wistar rats were irradiated by 1-10 Gy of gamma radiation by 60Co source. Value LD50/60 was 7.37 (4.68-8.05 Gy. Histone H2AX is phosphorylated by ATM kinase on serine 139 (γH2AX quickly after the irradiation. It forms microscopically visible foci in the site of double strand breaks of DNA. Flow-cytometric method was used for quantitative detection. This study is the first one that evaluated dose-dependency of H2AX phosphorylation in peripheral lymphocytes of rats irradiated by whole-body dose 1-10 Gy. Our data show a dose-dependent increase in γH2AX in rat peripheral blood lymphocytes 1 h after whole-body irradiation by the dose of 1-10 Gy. We proved that phosphorylation of histone H2AX is a prompt and reliable indicator of the received radiation dose suitable for rapid measurement before the number of lymphocytes in peripheral blood starts to decrease. It can be used already 1 h after the irradiation for an estimation of the received dose of radiation. Blood samples can be stored in 4 °C for 23 h without significantly affecting the result.

Functional characteristics of a renal H+/lipophilic cation antiport system in porcine LLC-PK1 cells and rats.

Science.gov (United States)

Matsui, Ryutaro; Hattori, Ryutaro; Usami, Youhei; Koyama, Masumi; Hirayama, Yuki; Matsuba, Emi; Hashimoto, Yukiya

2018-02-01

We have recently found an H + /quinidine (a lipophilic cation, QND) antiport system in Madin-Darby canine kidney (MDCK) cells. The primary aim of the present study was to evaluate whether the H + /lipophilic cation antiport system is expressed in porcine LLC-PK 1 cells. That is, we investigated uptake and/or efflux of QND and another cation, bisoprolol, in LLC-PK 1 cells. In addition, we studied the renal clearance of bisoprolol in rats. Uptake of QND into LLC-PK 1 cells was decreased by acidification of the extracellular pH or alkalization of the intracellular pH. Cellular uptake of QND from the apical side was much greater than from the basolateral side. In addition, apical efflux of QND from LLC-PK 1 cells was increased by acidification of the extracellular pH. Furthermore, lipophilic cationic drugs significantly reduced uptake of bisoprolol in LLC-PK 1 cells. Renal clearance of bisoprolol in rats was approximately 7-fold higher than that of creatinine, and was markedly decreased by alkalization of the urine pH. The present study suggests that the H + /lipophilic cation antiport system is expressed in the apical membrane of LLC-PK 1 cells. Moreover, the H + /lipophilic cation antiport system may be responsible for renal tubular secretion of bisoprolol in rats. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Multiple [3H]imipramine binding sites in brains of male and female Fawn-Hooded and Long-Evans rats

International Nuclear Information System (INIS)

Ieni, J.R.; Zukin, S.R.; Praag, H.M. van; Tobach, E.; Barr, G.A.

1985-01-01

Comparisons of high- and low-affinity [ 3 H]imipramine binding to whole brain homogenates from adult male and female rats of the Fawn-Hooded and Long-Evans strains were performed. Most strikingly, no significant differences were observed between the two strains in any of the binding parameters, indicating that brain [ 3 H]imipramine binding sites, which may be related to the serotonergic uptake process, appear normal in a strain of rats with serotonin platelet storage pool disease. However, a significant sex difference in high- but not low-affinity whole brain [ 3 H]imipramine Bsub(max) values was observed, with females of both strains having higher densities than males. (Auth.)

The effect of amperozide on uptake and release of [3H]-dopamine in vitro from perfused rat striatal and limbic brain areas

International Nuclear Information System (INIS)

Eriksson, E.; Christensson, E.

1990-01-01

Amperozide, a putatively antipsychotic drug, was studied for its effects on uptake and release of [ 3 H]-dopamine in rat brain in vitro. Amperozide inhibited uptake of [ 3 H]-dopamine in striatal chopped tissue in vitro with an IC 50 of 18 μM. It also increased basal release of [ 3 H]-dopamine from perfused rat striatal and limbic tissue in vitro at concentrations above 5 μM. Release of [ 3 H]-dopamine from perfused rat striatal and limbic tissue stimulated with 5 μM amphetamine, was inhibited by 1 μM amperozide to 46%. No significant difference was found for the effect of amperozide on in vitro release of [ 3 H]-dopamine from corpus striatum compared to tissue from limbic grain regions; neither on basal release nor on amphetamine-stimulated release of dopamine. (author)

Urinary composition and postprandial blood changes in H-secoisolariciresinol diglycoside (SDG) metabolites in rats do not differ between acute and chronic SDG treatments.

Science.gov (United States)

Rickard, S E; Thompson, L U

2000-09-01

Although chronic exposure to secoisolariciresinol diglycoside (SDG) was shown to alter (3)H-SDG metabolite disposition in rats, the proportion of measured radioactivity attributed to known or unknown SDG metabolites was not determined. Using HPLC and GC-MS, two experiments were conducted to determine the effect of acute (1 d) vs. chronic (10 d) SDG treatment on major urinary metabolites of (3)H-SDG in female, Sprague-Dawley rats (70-72-d-old) over a 48-h period and if new urinary metabolites were detectable in rats fed nonradioactive flaxseed or SDG. A third experiment was conducted to determine changes in postprandial blood levels of (3)H-SDG metabolites over a 24-h period with acute or chronic SDG treatment. Regardless of treatment, enterodiol, enterolactone and secoisolariciresinol accounted for 75-80% of urine radioactivity. Four potential new lignan metabolites, two of which were detected in the urine of rats fed nonradioactive flaxseed or SDG, were found. Type of treatment had no effect on levels of individual urinary metabolites of (3)H-SDG. As observed for plasma lignans in women fed flaxseed, blood radioactivity peaked at 9 h and remained high until 24 h in both treatment groups, suggesting that blood lignan kinetics might be similar with flaxseed or SDG consumption and that they were comparable between humans and rats. In conclusion, the main urinary lignan metabolites were enterodiol, enterolactone and secoisolariciresinol. Urinary composition or blood levels of radioactive lignans were not affected by the duration of SDG exposure. Thus, while chronic SDG exposure alters lignan disposition in rats, it does not change the metabolite profile.

Use of Liposomal Bupivacaine for Postoperative Analgesia in an Incisional Pain Model in Rats (Rattus norvegicus).

Science.gov (United States)

Kang, Stacey C; Jampachaisri, Katechan; Seymour, Travis L; Felt, Stephen A; Pacharinsak, Cholawat

2017-01-01

The local anesthetic bupivacaine is valuable for perioperative analgesia, but its use in the postoperative period is limited by its short duration of action. Here, we evaluated the application of a slow-release liposomal formulation of bupivacaine for postoperative analgesia. The aim was to assess whether liposomal bupivacaine effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Rats (n = 36) were randomly assigned to 1 of 5 treatment groups: saline, 1 mL/kg SC every 12 h for 2 d; buprenorphine HCl, 0.05 mg/kg SC every 12 h for 2 d (Bup HCl); 0.5% bupivacaine, 2 mg/kg SC local infiltration once (Bupi); liposomal bupivacaine, 1 mg/kg SC local infiltration once (Exp1); and liposomal bupivacaine, 6 mg/kg SC local infiltration once (Exp6). Mechanical and thermal hypersensitivity were evaluated daily on days -1, 0, 1, 2, 3, and 4. The saline group exhibited both hypersensitivities through all 4 evaluated postoperative days. Bup HCl attenuated mechanical hypersensitivity for 2 d and thermal hypersensitivity for 1 d. Bupi attenuated only thermal hypersensitivity for 4 d. Rats in the Exp1 group showed attenuation of both mechanical and thermal hypersensitivity for 4 d, and those in the Exp6 group had attenuation of mechanical hypersensitivity on day 0 and thermal hypersensitivity for 4 d. These data suggest that a single local infiltration of liposomal bupivacaine at a dose of 1 mg/kg SC effectively attenuates postoperative mechanical and thermal hypersensitivity for 4 d in a rat model of incisional pain.

78 FR 73109 - Radio Broadcasting Services; Benjamin and Cisco, TX; De Beque, CO; Port Lions, AK; Rule and...

Science.gov (United States)

2013-12-05

... Broadcasting Services; Benjamin and Cisco, TX; De Beque, CO; Port Lions, AK; Rule and Shamrock, TX AGENCY... 237C3 at Benjamin, Texas; Channel 261C3 at Cisco, Texas; Channel 288C2 at Rule, Texas; and Channel 225C2..., Channel 237C3; by removing Cisco, Channel 261C3; by removing Channel 288C2 at Rule; and by removing...

Comparison of high affinity binding of {sup 3}H-proadifen and {sup 3}H-(-)-cocaine t rat liver membranes

Energy Technology Data Exchange (ETDEWEB)

Ross, S.B. [Astra Arcus AB, Dept. of Neuropharmacology, Soedertaelje (Sweden)

1995-06-01

The characteristics of the binding of {sup 3}H-proadifen to rat liver membranes were studied and compared to those of {sup 3}H-cocaine. It was found that {sup 3}H-proadifen was bound reversibly with high affinity (K{sub D}=1.8{+-}0.5 nM) and large capacity (B{sub max}=2010{+-}340 pmol/g wet tissue) to liver membranes. The corresponding values for the {sup 3}H-cocaine binding were 3.5 nM and 1000 pmol/g wet tissue. The binding of {sup 3}H-proadifen was mainly localised to the microsomal fraction. The number of binding sites was not increased by treatment of rats with phenobarbitone. With 1 {mu}M CdCl{sub 2} in the incubation buffer it was possible to differentiate between two {sup 3}H-cocaine binding sites with K{sub d} values of 1.6 and 7.7 nM and B{sub max} values of 280 and 940 pmol/g wet liver tissue. S-(-)-Alaproclate inhibited the binding of {sup 3}H-proadifen and {sup 3}H-cocaine inhibited the binding of {sup 3}H-proadifen (IC{sub 50}=10 nM) and proadifen that of {sup 3}H-cocaine (IC{sub 50}=1 nM). There was a high correlation coefficient (r{sub r}=0.972; P<0.01; n=12) in the Spearman rank test between the inhibitory potencies of compounds examined in both systems. Beside some potent alaproclate analogues a couple of compounds had moderately high affinity (IC{sub 50}=100-500 nM): chloroquine, phenoxybenzamine, amitriptyline, ajmaline, remoxipride, imipramine and (-)-alaprenolol. CdCl{sub 2}, ZnCl{sub 2} and CuCl{sub 2} inhibited the binding of both ligands with low Hill coefficients, indicating heterogeneous binding sites. The inhibition curve of Cd{sup 2+} on the cocaine binding was biphasic with a high affinity part around 50 nM and a low affinity part at 15{mu}M. The similarity of the characteristics of the binding of these ligands with that of {sup 3}H-alaproclate is discussed. It is suggested that all three compounds bind to the same sites, although additional binding sites seem to exist for proadifen. (au) (9 refs.).

Effects of Post-Treatment Hydrogen Gas Inhalation on Uveitis Induced by Endotoxin in Rats.

Science.gov (United States)

Yan, Weiming; Chen, Tao; Long, Pan; Zhang, Zhe; Liu, Qian; Wang, Xiaocheng; An, Jing; Zhang, Zuoming

2018-06-07

BACKGROUND Molecular hydrogen (H2) has been widely reported to have benefiicial effects in diverse animal models and human disease through reduction of oxidative stress and inflammation. The aim of this study was to investigate whether hydrogen gas could ameliorate endotoxin-induced uveitis (EIU) in rats. MATERIAL AND METHODS Male Sprague-Dawley rats were divided into a normal group, a model group, a nitrogen-oxygen (N-O) group, and a hydrogen-oxygen (H-O) group. EIU was induced in rats of the latter 3 groups by injection of lipopolysaccharide (LPS). After that, rats in the N-O group inhaled a gas mixture of 67% N2 and 33% O2, while those in the H-O group inhaled a gas mixture of 67% H2 and 33% O2. All rats were graded according to the signs of uveitis after electroretinography (ERG) examination. Protein concentration in the aqueous humor (AqH) was measured. Furthermore, hematoxylin-eosin staining and immunostaining of anti-ionized calcium-binding adapter molecule 1 (Iba1) in the iris and ciliary body (ICB) were carried out. RESULTS No statistically significant differences existed in the graded score of uveitis and the b-wave peak time in the Dark-adapted 3.0 ERG among the model, N-O, and H-O groups (P>0.05), while rats of the H-O group showed a lower concentration of AqH protein than that of the model or N-O group (P0.05), while the activation of microglia cells in the H-O group was somewhat reduced (Ptreatment hydrogen gas inhalation did not ameliorate the clinical signs, or reduce the infiltrating cells of EIU. However, it inhibited the elevation of protein in the AqH and reduced the microglia activation.

Histamine Excites Rat Superior Vestibular Nuclear Neurons via Postsynaptic H1 and H2 Receptors in vitro

Directory of Open Access Journals (Sweden)

Qian-Xing Zhuang

2012-09-01

Full Text Available The superior vestibular nucleus (SVN, which holds a key position in vestibulo-ocular reflexes and nystagmus, receives direct hypothalamic histaminergic innervations. By using rat brainstem slice preparations and extracellular unitary recordings, we investigated the effect of histamine on SVN neurons and the underlying receptor mechanisms. Bath application of histamine evoked an excitatory response of the SVN neurons, which was not blocked by the low-Ca2+/high-Mg2+ medium, indicating a direct postsynaptic effect of the amine. Selective histamine H1 receptor agonist 2-pyridylethylamine and H2 receptor agonist dimaprit, rather than VUF8430, a selective H4 receptor agonist, mimicked the excitation of histamine on SVN neurons. In addition, selective H1 receptor antagonist mepyramine and H2 receptor antagonist ranitidine, but not JNJ7777120, a selective H4 receptor antagonist, partially blocked the excitatory response of SVN neurons to histamine. Moreover, mepyramine together with ranitidine nearly totally blocked the histamine-induced excitation. Immunostainings further showed that histamine H1 and H2 instead of H4 receptors existed in the SVN. These results demonstrate that histamine excites the SVN neurons via postsynaptic histamine H1 and H2 receptors, and suggest that the central histaminergic innervation from the hypothalamus may actively bias the SVN neuronal activity and subsequently modulate the SVN-mediated vestibular functions and gaze control.

Structure-Activity Relationship Models for Rat Carcinogenesis and Assessing the Role Mutagens Play in Model Predictivity

Science.gov (United States)

Carrasquer, C. Alex; Batey, Kaylind; Qamar, Shahid; Cunningham, Albert R.; Cunningham, Suzanne L.

2016-01-01

We previously demonstrated that fragment based cat-SAR carcinogenesis models consisting solely of mutagenic or non-mutagenic carcinogens varied greatly in terms of their predictive accuracy. This led us to investigate how well the rat cancer cat-SAR model predicted mutagens and non-mutagens in their learning set. Four rat cancer cat-SAR models were developed: Complete Rat, Transgender Rat, Male Rat, and Female Rat, with leave-one-out (LOO) validation concordance values of 69%, 74%, 67%, and 73%, respectively. The mutagenic carcinogens produced concordance values in the range of 69–76% as compared to only 47–53% for non-mutagenic carcinogens. As a surrogate for mutagenicity comparisons between single site and multiple site carcinogen SAR models was analyzed. The LOO concordance values for models consisting of 1-site, 2-site, and 4+-site carcinogens were 66%, 71%, and 79%, respectively. As expected, the proportion of mutagens to non-mutagens also increased, rising from 54% for 1-site to 80% for 4+-site carcinogens. This study demonstrates that mutagenic chemicals, in both SAR learning sets and test sets, are influential in assessing model accuracy. This suggests that SAR models for carcinogens may require a two-step process in which mutagenicity is first determined before carcinogenicity can be accurately predicted. PMID:24697549

Solid-phase synthesis and pharmacological evaluation of analogues of PhTX-12-A potent and selective nicotinic acetylcholine receptor antagonist

DEFF Research Database (Denmark)

Strømgaard, Kristian; Mellor, Ian R; Andersen, Kim

2002-01-01

Philanthotoxin-12 (PhTX-12) is a novel potent and selective, noncompetitive antagonist of nicotinic acetylcholine receptors (nAChRs). Homologues of PhTX-12 with 7-11 methylene groups between the primary amino group and the aromatic head-group were synthesized using solid-phase methodology. In vitro...

Fluoride absorption from the rat urinary bladder: a pH-dependent event

International Nuclear Information System (INIS)

Whitford, G.M.; Pashley, D.H.; Reynolds, K.E.

1977-01-01

Urinary bladder absorption of stable and radiofluoride was studied as a function of pH in anesthetized rats to further evaluate the influence of pH gradients on fluoride transport. Buffered pH values and stable fluoride concentrations ranged from 1.85 to 7.90 and from 0.012 to 8.81 mM, respectively. [ 14 C]inulin served as a marker for solute concentration changes due to water migration or dilution. The results indicate that bladder fluoride absorption is inversely related to pH over the 1.85 to 5.50 range. Mean, 15-min radiofluoride absorption values of 70 percent at pH 1.85, 37 percent at pH 3.95, and 5 percent at pH 5.50 were observed. These fractional absorption values were not significantly influenced by carrier fluoride concentration, the buffers used, or the presence of urine. Above pH 5.50, pH-independent absorption occurs to a slight extent. The results are consistent with a first-order absorptive process which occurs by the nonionic diffusion of hydrogen fluoride

Lactate/H+ transport kinetics in rat skeletal muscle related to fibre type and changes in transport capacity

DEFF Research Database (Denmark)

Juel; Pilegaard

1998-01-01

muscles, muscles of old rats and rats that had been subjected to high-intensity training, endurance training, repeated exposure to hypoxia, and hypothyroid or hyperthyroid treatments. The lactate/H+ transport capacity of red muscles was greater than that of white muscles, and this difference...... and hypothyroidism was due to a decrease in Vmax. The denervation-induced decline in lactate/H+ transport capacity resulted from both an increased Km and a reduced Vmax. The present data show that muscle type differences and most changes in the lactate/H+ transport capacity are mediated by modifications in Vmax......, which is expected to represent the number of membrane transporter molecules. Km is unaffected by most treatments and appears to be independent of fibre type....

Establishment of a rat model of portal vein ligation combined with in situ splitting.

Directory of Open Access Journals (Sweden)

Libin Yao

Full Text Available BACKGROUND: Portal vein ligation (PVL combined with in situ splitting (ISS has been shown to induce remarkable liver regeneration in patients. The purpose of this study was to establish a model of PVL+ISS in rats for exploring the possible mechanisms of liver regeneration using these techniques. MATERIALS AND METHODS: Rats were randomly assigned to three experimental groups: selective PVL, selective PVL+ISS and sham operation. The hepatic regeneration rate (HRR, Ki-67, liver biochemical determinations and histopathology were assessed at 24, 48, and 72 h and 7 days after the operation. The microcirculation of the median lobes before and after ISS was examined by laser speckle contrast imaging. Meanwhile, cytokines such as TNF-α, IL-6, HGF and HSP70 in regenerating liver lobes at 24 h was investigated by RT-PCR and ELISA. RESULTS: The HRR of PVL+ISS was much higher than that of the PVL at 72 h and 7 days after surgery (p<0.01. The expression of Ki-67 in hepatocytes in the regenerating liver lobe was stronger in the PVL+ISS group than in the PVL group at 48 and 72 h (p<0.01. There was a significant reduction in microcirculation blood perfusion of the left median lobe before and after ISS. Liver biochemical determinations and histopathology demonstrated more severe hepatocyte injury in the PVL+ISS group. Both the mRNA levels of TNF-α and IL-6 and the protein levels of TNF-α, IL-6 and HGF in regenerating liver lobes were higher in the PVL+ISS than the PVL alone. CONCLUSIONS: The higher HRR in the PVL+ISS compared with the PVL confirmed that we had successfully established a PVL+ISS model in rats. The possible mechanisms included the reduced microcirculation blood perfusion of the left median lobe and up-regulation of cytokines in the regenerating lobes after ISS.

Active Oxygen Metabolites and Thromboxane in Phorbol Myristate Acetate Toxicity to the Isolated, Perfused Rat Lung.

Science.gov (United States)

Carpenter, Laurie Jean

this model. To determine whether TxA_2 was involved in toxicity induced by PMN and PMA, lungs were coperfused with the cyclooxygenase inhibitor, indomethacin or the thromboxane synthase inhibitor, Dazmegrel. Experiments were also performed using lungs and/or PMN that had been pretreated with aspirin. These drug treatments had little effect, if any, on the pressure increase; however, they protected lungs against edema development. These results suggest that TxA_2 may participate in the pathogenesis of edema by some other mechanism than by increasing vascular pressure. In conclusion, results from studies performed in this thesis suggest that both active oxygen species and thromboxane are involved in toxicity to the isolated rat lung induced by PMA and PMN. How both of these interact to produce lung injury is a question which remains to be answered.

The role of urinary pH in o-phenylphenol-induced cytotoxicity and chromosomal damage in the bladders of F344 rats.

Science.gov (United States)

Balakrishnan, S; Hasegawa, L; Eastmond, D A

2016-04-01

o-Phenylphenol (OPP) is a widely used fungicide and antibacterial agent that at high doses has been shown to cause bladder cancer in male F344 rats. The mechanisms underlying OPP-induced bladder carcinogenicity remain unclear but it has been proposed that a non-enzymatic pH-dependent autoxidation of phenylhydroquinone (PHQ), a primary metabolite of OPP, may be a key step in OPP-induced rat bladder carcinogenesis. To investigate this mechanism and to provide insights into the potential human health relevance of OPP-induced cancer, a series of in vitro and in vivo experiments were conducted. In human lymphoblastoid TK-6 cells and rat bladder epithelial NBT-II cells, strong increases in cytotoxicity were seen at a constant concentration of PHQ by increasing the buffer pH as well as by increasing concentrations of PHQ at a constant pH. In in vivo studies, male rats were administered OPP (4,000 and 8,000 ppm) in a diet supplemented with either 1% ammonium chloride or 3% sodium bicarbonate to produce acidic and alkaline urinary pH, respectively. Significant increases in cell proliferation as detected by 5-bromo-2'-deoxyuridine incorporation and micronucleus formation were seen in the bladder cells of OPP-treated rats with neutral or alkaline urinary pH but not in animals with the acidified urine. The results from these in vitro and in vivo studies provide support for the autoxidation hypothesis of bioactivation, and provide additional evidence that urinary pH can significantly influence the genotoxicity and carcinogenicity of this important agent. © 2016 Wiley Periodicals, Inc.

Significant effect of surfactant micelles on pH dependent fluorescent off-on-off behavior of Salicylaldehyde-2,4-Dinitrophenylhydrazone

Energy Technology Data Exchange (ETDEWEB)

Goswami, Priyanka [Department of Chemistry, Gauhati University, Guwahati 781 014 (India); Das, Diganta K., E-mail: digkdas@yahoo.co [Department of Chemistry, Gauhati University, Guwahati 781 014 (India)

2011-04-15

The fluorescence response to pH of 2,4 dinitrophenolhydrazone in 1:1 CH{sub 3}OH:H{sub 2}O and micellar mediums-negatively charged sodium dodecylsulphate (SDS), positively charged cetyltrimethyl ammonium bromide (CTAB) and neutral Triton X-100 (TX-100), is reported. At pH 4.0 the fluorescence of the molecule can be switched 'on' by selecting CTAB as the solvent. At pH 6.0 if the medium is TX-100 the fluorescence is 'off', but remains 'on' for the other three solvents. At pH 8.0, fluorescence is 'on' in the solvents except CTAB. SDS and TX-100 switch the fluorescence 'on' at pH 13.0 but for the other two solvents the fluorescence is 'off'. - Research highlights: The fluorescence response to pH of Salicylaldehyde-2,4 Dinitrophenolhydrazone in 1:1 CH{sub 3}OH:H{sub 2}O and in positively charged cetyltrimethyl ammonium bromide (CTAB) micellar medium shows 'off-on-off' behavior. In negatively charged sodium dodecylsulphate (SDS) the response of fluorescence of Salicylaldehyde-2,4 Dinitrophenolhydrazone to pH is 'off-on-on' type while in neutral Triton X-100 it is 'off-on-1/2on' type. At a given pH, fluorescence of 2,4 dinitrophenolhydrazone can be made 'on' or 'off' by selecting an appropriate pH.

The pH dependence of silicon-iron interaction in rats.

Science.gov (United States)

Jia, X; Emerick, R J; Kayongo-Male, H

1997-01-01

A 2 x 2 x 3 factorial experiment was conducted to study the pH dependence of a silicon-iron interaction in vivo. The dietary treatments used in the factorial design were the following (mg/kg of diet): silicon, 0 and 500; iron, 35 and 187; acid-base, ammonium chloride as 0.5% of total diet (acidic), sodium bicarbonate as 1.0% of total diet (basic), or no supplementation of acid or base (control). The supplementation of 500 mg silicon/kg of diet increased plasma-iron concentration in rats fed the acidic or control diets, but not in rats fed the basic diet. A high dietary-iron level suppressed copper absorption and utilization and subsequently imposed a negative effect on its own utilization. An increase in the plasma total-cholesterol concentration caused by high dietary-iron level was likely a consequence of the antagonistic effect of iron on copper absorption and utilization. The use of cupric sulfate pentahydrate as the dietary-copper source in this study resulted in plasma copper concentrations that were approximately twice those obtained in a related study using cupric carbonate. Also, a 42% coefficient of variation (C.V.) for plasma-copper concentrations of rats fed cupric sulfate in this study was greatly reduced from the C.V. = 108% previously associated with the dietary cupric carbonate.

Oxidative stress of crystalline lens in rat menopausal model.

Science.gov (United States)

Acer, Semra; Pekel, Gökhan; Küçükatay, Vural; Karabulut, Aysun; Yağcı, Ramazan; Çetin, Ebru Nevin; Akyer, Şahika Pınar; Şahin, Barbaros

2016-01-01

To evaluate lenticular oxidative stress in rat menopausal models. Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1). From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2), 10 were administered a daily injection of methylprednisolone until the end of the study (Group 3), and the remaining 10 rats were administered intraperitoneal streptozocin to induce diabetes mellitus (Group 4). Total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) measurements of the crystalline lenses were analyzed. The mean OSI was the lowest in group 1 and highest in group 4. Nevertheless, the difference between the groups was not statistically significant in terms of OSI (p >0.05). The mean TOS values were similar between the groups (p >0.05), whereas the mean TAC of group 1 was significantly higher than that of the other groups (p <0.001). Our results indicate that menopause may not promote cataract formation.

Release of /sup 3/H-. cap alpha. -methyl-m-tyramine from rat striatum in vitro

Energy Technology Data Exchange (ETDEWEB)

Dorris, R L [Baylor College of Dentistry, Dallas, Tex. (USA). Dept. of Pharmacology

1976-01-01

Release of /sup 3/H-d-..cap alpha..-methyl-m-tyramine (/sup 3/H-MMTA), a false dopaminergic transmitter from rat striatum was studied in vitro. After its initial uptake, /sup 3/H-MMTA was released by high K/sup +/ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that /sup 3/H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro.

76 FR 33333 - Use of Small Area Fair Market Rents for Project Base Vouchers in the Dallas TX Metropolitan Area

Science.gov (United States)

2011-06-08

... DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT [Docket No. FR-5525-N-01] Use of Small Area Fair Market Rents for Project Base Vouchers in the Dallas TX Metropolitan Area AGENCY: Office of the Assistant... Small Area Fair Market Rents (SAFMRs) for Project-Based Vouchers (PBVs) located in the Dallas, TX...

Thrombolytic and anticoagulation treatment in a rat embolic stroke model

DEFF Research Database (Denmark)

Rasmussen, Rune Skovgaard; Overgaard, K; Meden, P

2003-01-01

OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilateral...... alone or combined with rt-PA did not significantly increase mortality or tendency for hemorrhage.......OBJECTIVES: The effects of pentasaccharide (PENTA), given alone or combined with thrombolysis using recombinant tissue plasminogen activator (rt-PA), on infarct size and clinical outcome were evaluated in a rat embolic stroke model. MATERIALS AND METHODS: Ninety-two rats were embolized unilaterally...

Incorporation of DL-methionine /sup 3/H into the rat brain in the course of triethyl tin sulphate intoxication

Energy Technology Data Exchange (ETDEWEB)

Kozik, M B; Ozarzewska, E; Piechowski, A [Akademia Medyczna, Poznan (Poland)

1976-01-01

The incorporation of DL-methionine /sup 3/H into the rat brain in the course of acute edema caused by the triethyl tin sulphate (TET) was investigated by autoradiography. The results indicate that TET intoxication effects in lower incorporation of methionine into the experimental rat brain in comparison to that in normal animals. The changes in dynamics of DL-methionine /sup 3/H incorporation after TET intoxication are presented. The possible pathogenetic mechanism of the observed changes is discussed.

Immature rats show ovulatory defects similar to those in adult rats lacking prostaglandin and progesterone actions

Directory of Open Access Journals (Sweden)

Sanchez-Criado Jose E

2004-09-01

Full Text Available Abstract Gonadotropin-primed immature rats (GPIR constitute a widely used model for the study of ovulation. Although the equivalence between the ovulatory process in immature and adult rats is generally assumed, the morphological and functional characteristics of ovulation in immature rats have been scarcely considered. We describe herein the morphological aspects of the ovulatory process in GPIR and their response to classical ovulation inhibitors, such as the inhibitor of prostaglandin (PG synthesis indomethacin (INDO and a progesterone (P receptor (PR antagonist (RU486. Immature Wistar rats were primed with equine chorionic gonadotropin (eCG at 21, 23 or 25 days of age, injected with human chorionic gonadotropin (hCG 48 h later, and sacrificed 16 h after hCG treatment, to assess follicle rupture and ovulation. Surprisingly, GPIR showed age-related ovulatory defects close similar to those in adult rats lacking P and PG actions. Rats primed with eCG at 21 or 23 days of age showed abnormally ruptured corpora lutea in which the cumulus-oocyte complex (COC was trapped or had been released to the ovarian interstitum, invading the ovarian stroma and blood and lymphatic vessels. Supplementation of immature rats with exogenous P and/or PG of the E series did not significantly inhibit abnormal follicle rupture. Otherwise, ovulatory defects were practically absent in rats primed with eCG at 25 days of age. GPIR treated with INDO showed the same ovulatory alterations than vehicle-treated ones, although affecting to a higher proportion of follicles. Blocking P actions with RU486 increased the number of COC trapped inside corpora lutea and decreased ovulation. The presence of ovulatory defects in GPIR, suggests that the capacity of the immature ovary to undergo the coordinate changes leading to effective ovulation is not fully established in Wistar rats primed with eCG before 25 days of age.

Release-Active Dilutions of Diclofenac Enhance Anti-inflammatory Effect of Diclofenac in Carrageenan-Induced Rat Paw Edema Model

OpenAIRE

Sakat, Sachin S.; Mani, Kamaraj; Demidchenko, Yulia O.; Gorbunov, Evgeniy A.; Tarasov, Sergey A.; Mathur, Archna; Epstein, Oleg I.

2013-01-01

The study was aimed to investigate the effect of technologically treated diclofenac (release-active dilutions of diclofenac (RAD of diclofenac)) on anti-inflammatory activity of diclofenac in carrageenan-induced rat paw edema model. Ninety male Wistar albino rats (6–8 weeks) divided into nine groups (n = 10) were used. Anti-inflammatory activity was assessed at 1, 2, 3, 4, and 6 h after subplantar injection of carrageenan (0.1 ml of a 1 % solution in normal saline). Diclofenac alone was studi...

Determination of Disulfide Bond Connectivity of Cysteine-rich Peptide IpTx{sub a}

Energy Technology Data Exchange (ETDEWEB)

Lee, Chul Won; Kim, Jim Il [Chonnam National Univ., Gwangju (Korea, Republic of); Sato, Kazuki [Fukuoka Women' s Univ., Fukuoka (Japan)

2013-06-15

Cysteine-rich peptides stabilized by intramolecular disulfide bonds have often been isolated from venoms of microbes, animals and plants. These peptides typically have much higher stability and improved biopharmaceutical properties compared to their linear counterparts. Therefore the correct disulfide bond formation of small proteins and peptides has been extensively studied for a better understanding of their folding mechanism and achieving efficient generation of the naturally occurring biologically active product. Imperatoxin A (IpTx{sub a}), a peptide toxin containing 6 cysteine residues, was isolated from the venom of scorpion Pandinus imperator, selectively binds the ryanodine receptors and activates Ca{sup 2+} release from sarcoplasmic reticulum (SR). IpTx{sub a} increases the binding of ryanodine to ryanodine receptors (RyRs) and encourages reconstituted single channel to induce subconductance states.

Tank characterization report for single-shell tank 241-TX-104

International Nuclear Information System (INIS)

FIELD, J.G.

1999-01-01

A major function of the Tank Waste Remediation System (TWRS) is to characterize waste in support of waste management and disposal activities at the Hanford Site. Analytical data from sampling and analysis and other available information about a tank are compiled and maintained in a tank characterization report (TCR). This report and its appendices serve as the TCR for single-shell tank 241-TX-104. The objectives of this report are (1) to use characterization data in response to technical issues associated with tank 241-TX-104 waste, and (2) to provide a standard characterization of this waste in terms of a best-basis inventory estimate. Section 2.0 summarizes the response to technical issues, Section 3.0 shows the best-basis inventory estimate, Section 4.0 makes recommendations about the safety status of the tank and additional sampling needs. The appendices contain supporting data and information. This report supports the requirements of the Hanford Federal Facility Agreement and Consent Order (Ecology et al. 1997), Milestone M-44-15c, change request M-44-97-03 to ''issue characterization deliverables consistent with the Waste Information Requirements Document developed for FY 1999'' (Adams et al. 1998)

Characterization of high-affinity (/sup 3/H)ouabain binding in the rat central nervous system

Energy Technology Data Exchange (ETDEWEB)

Hauger, R.; Luu, H.M.; Meyer, D.K.; Goodwin, F.K.; Paul, S.M.

1985-06-01

The characteristics of (/sup 3/H)ouabain binding were examined in various areas of rat brain. In the striatum, Scatchard analysis revealed a single class of high-affinity binding sites with an apparent binding affinity (KD) of 10.4 +/- 0.9 nM and an estimated binding capacity (Bmax) of 7.6 +/- 1.9 pmol/mg protein. Similar monophasic Scatchard plots were found in the brainstem, cerebellum, hypothalamus, and frontal cerebral cortex. (/sup 3/H)Ouabain binding to rat brain was sodium- and ATP-dependent and strongly inhibited by potassium. Proscillariden A was the most potent cardiac glycoside tested in inhibiting specific (/sup 3/H)ouabain binding to brain membranes, and the rank order of inhibitory potencies for a series of cardiac glycosides was similar to that previously reported for inhibition of heart Na,K-ATPase. To assess whether the high-affinity binding sites for (/sup 3/H)ouabain were localized to neuronal or nonneuronal membranes, the effect of discrete kainic acid lesions on striatal (/sup 3/H)ouabain binding was examined. Kainic acid lesions of the striatum reduced (/sup 3/H)ouabain binding to striatal homogenates by 79.6 +/- 1.6%. This suggests that the high-affinity (/sup 3/H)ouabain binding sites measured in our experiments are localized to neuronal elements. Thus, the high-affinity binding of (/sup 3/H)ouabain to brain membranes may selectively label a neuronal form or conformation of Na,K-ATPase.

ENU mutagenesis to generate genetically modified rat models

NARCIS (Netherlands)

van Boxtel, R.; Gould, M.; Cuppen, E.; Smits, B.M.

2010-01-01

The rat is one of the most preferred model organisms in biomedical research and has been extremely useful for linking physiology and pathology to the genome. However, approaches to genetically modify specific genes in the rat germ line remain relatively scarce. To date, the most efficient approach

[3H]Dopamine accumulation and release from striatal slices in young, mature and senescent rats

International Nuclear Information System (INIS)

Thompson, J.M.

1981-01-01

Examinations of [ 3 H]dopamine ([ 3 H]DA) release following KCl or amphetamine administration in striatal slices from young (7 month), mature (12 month) and senescent (24 month) Wistar rats showed no age-related changes. Further, the amount of [ 3 H]DA accumulated in the striatal slices showed no changes with age. Thus, previously reported age-related deficits in motor behavior (i.e. rotational) are not produced by changes in striatal DA accumulation or release. (Auth.)

Bone pain caused by swelling of mouse ear capsule static xylene and effects on rat models of cervical spondylosis

Science.gov (United States)

Zhang, Xuhui; Xia, Lei; Hao, Shaojun; Chen, Weiliang; Guo, Junyi; Ma, Zhenzhen; Wang, Huamin; Kong, Xuejun; Wang, Hongyu; Zhang, Zhengchen

2018-04-01

To observe the effect of intravenous bone pain Capsule on the ear of mice induced by xylene, swelling of rat models of cervical spondylosis. Weighing 18 ˜ 21g 50 mice, male, were randomly divided into for five groups, which were fed with service for bone pain static capsule suspension, Jingfukang granule suspension 0.5%CMC liquid and the same volume of. Respectively to the mice ear drop of xylene 0.05 ml, 4h after cervical dislocation, the mice were sacrificed and the cut two ear, rapid analytical balance weighing, and calculate the ear swelling degree and the other to take the weight of 200 - 60 250g male SD rats, were randomly divided into for 6 groups, 10 rats in each group, of which 5 groups made cervical spondylosis model. Results: with the blank group than bone pain static capsule group and Jingfukang granule group can significantly reduce mouse auricular dimethylbenzene swelling, significantly reduce ear swelling degree (P cervical spondylosis. With the model group ratio, large, medium and small dose of bone pain static capsule group, Jingfukang granule group (P pain static capsule group, Jingfukang granule group can significantly reduce the rat X-ray scores (P pain static capsule can significantly reduce mouse auricular dimethylbenzene swelling. The bone pain capsule has a good effect on the rat model of cervical spondylosis.

γ-H2AX as a marker for dose deposition in the brain of wistar rats after synchrotron microbeam radiation.

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Cristian Fernandez-Palomo

Full Text Available Synchrotron radiation has shown high therapeutic potential in small animal models of malignant brain tumours. However, more studies are needed to understand the radiobiological effects caused by the delivery of high doses of spatially fractionated x-rays in tissue. The purpose of this study was to explore the use of the γ-H2AX antibody as a marker for dose deposition in the brain of rats after synchrotron microbeam radiation therapy (MRT.Normal and tumour-bearing Wistar rats were exposed to 35, 70 or 350 Gy of MRT to their right cerebral hemisphere. The brains were extracted either at 4 or 8 hours after irradiation and immediately placed in formalin. Sections of paraffin-embedded tissue were incubated with anti γ-H2AX primary antibody.While the presence of the C6 glioma does not seem to modulate the formation of γ-H2AX in normal tissue, the irradiation dose and the recovery versus time are the most important factors affecting the development of γ-H2AX foci. Our results also suggest that doses of 350 Gy can trigger the release of bystander signals that significantly amplify the DNA damage caused by radiation and that the γ-H2AX biomarker does not only represent DNA damage produced by radiation, but also damage caused by bystander effects.In conclusion, we suggest that the γ-H2AX foci should be used as biomarker for targeted and non-targeted DNA damage after synchrotron radiation rather than a tool to measure the actual physical doses.

Immediate and Long-Term Outcome of Acute H2S Intoxication Induced Coma in Unanesthetized Rats: Effects of Methylene Blue.

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Takashi Sonobe

Full Text Available Acute hydrogen sulfide (H2S poisoning produces a coma, the outcome of which ranges from full recovery to severe neurological deficits. The aim of our study was to 1--describe the immediate and long-term neurological effects following H2S-induced coma in un-anesthetized rats, and 2--determine the potential benefit of methylene blue (MB, a compound we previously found to counteract acute sulfide cardiac toxicity.NaHS was administered IP in un-sedated rats to produce a coma (n = 34. One minute into coma, the rats received MB (4 mg/kg i.v. or saline. The surviving rats were followed clinically and assigned to Morris water maze (MWM and open field testing then sacrificed at day 7.Sixty percent of the non-treated comatose rats died by pulseless electrical activity. Nine percent recovered with neurological deficits requiring euthanasia, their brain examination revealed major neuronal necrosis of the superficial and middle layers of the cerebral cortex and the posterior thalamus, with variable necrosis of the caudate putamen, but no lesions of the hippocampus or the cerebellum, in contrast to the typical distribution of post-ischemic lesions. The remaining animals displayed, on average, a significantly less effective search strategy than the control rats (n = 21 during MWM testing. Meanwhile, 75% of rats that received MB survived and could perform the MWM test (P<0.05 vs non-treated animals. The treated animals displayed a significantly higher occurrence of spatial search than the non-treated animals. However, a similar proportion of cortical necrosis was observed in both groups, with a milder clinical presentation following MB.In conclusion, in rats surviving H2S induced coma, spatial search patterns were used less frequently than in control animals. A small percentage of rats presented necrotic neuronal lesions, which distribution differed from post-ischemic lesions. MB dramatically improved the immediate survival and spatial search strategy in the

Development of LC-MS determination method and back-propagation ANN pharmacokinetic model of corynoxeine in rat.

Science.gov (United States)

Ma, Jianshe; Cai, Jinzhang; Lin, Guanyang; Chen, Huilin; Wang, Xianqin; Wang, Xianchuan; Hu, Lufeng

2014-05-15

Corynoxeine(CX), isolated from the extract of Uncaria rhynchophylla, is a useful and prospective compound in the prevention and treatment for vascular diseases. A simple and selective liquid chromatography mass spectrometry (LC-MS) method was developed to determine the concentration of CX in rat plasma. The chromatographic separation was achieved on a Zorbax SB-C18 (2.1 mm × 150 mm, 5 μm) column with acetonitrile-0.1% formic acid in water as mobile phase. Selective ion monitoring (SIM) mode was used for quantification using target ions m/z 383 for CX and m/z 237 for the carbamazepine (IS). After the LC-MS method was validated, it was applied to a back-propagation artificial neural network (BP-ANN) pharmacokinetic model study of CX in rats. The results showed that after intravenous administration of CX, it was mainly distributed in blood and eliminated quickly, t1/2 was less than 1h. The predicted concentrations generated by BP-ANN model had a high correlation coefficient (R>0.99) with experimental values. The developed BP-ANN pharmacokinetic model can be used to predict the concentration of CX in rats. Copyright © 2014 Elsevier B.V. All rights reserved.

Electrophoretic separation of cells and particles from rat pituitary and rat spleen

Science.gov (United States)

Hymer, Wesley C.

1993-01-01

There are 3 parts to the IML-2 TX-101 experiment. Part 1 is a pituitary cell culture experiment. Part 2 is a pituitary cell separation experiment using the Japanese free flow electrophoresis unit (FFEU). Part 3 is a pituitary secretory granule separation experiment using the FFEU. The objectives of this three part experiment are: (1) to determine the kinetics of production of biologically active growth hormone (GH) and prolactin (PRL) in rat pituitary GH and PRL cells in microgravity (micro-g); (2) to investigate three mechanisms by which a micro-g-induced lesion in hormone production may occur; and (3) to determine the quality of separations of pituitary cells and organelles by continuous flow electrophoresis (CFE) in micro-g under conditions where buoyancy-induced convection is eliminated.

Photoaffinity labeling of [3H]flunitrazepam- and [3H]Ro15-4513-bound pellets in rat cerebral cortex and cerebellum

International Nuclear Information System (INIS)

Chiu, T.H.; Yu, Onnfoh; Rosenberg, H.C.

1989-01-01

Irreversible incorporation of [ 3 H]flunitrazepam and [ 3 H]Ro15-4513 into GABA/benzodiazepine receptor subunits was studied by UV/irradiation using ligand-bound membrane pellets from rat cerebral cortical and cerebellar synaptic membranes. Specific incorporation for [ 3 H]flunitrazepam was greater in the pellet than in the suspension. The incorporation was identical for [ 3 H]Ro15-4513 in both pellet and suspension. With the ligand-bound pellets, 50% of the available binding sites were photolabeled by both ligands in cortex and cerebellum. SDS polyacrylamide gel electrophoresis and fluorography of [ 3 H]flunitrazepam photo-labeled receptor revealed the same number of major sites in both brain regions. In contrast, [ 3 H]Ro15-4513 appears to label fewer sites in cortex and cerebellum. Photoaffinity labeling with [ 3 H]flunitrazepam in ligand-bound membrane pellet provides a more selective and reliable method for studying the subunit structure of GABA/benzodiazepine receptor complex

Beneficial effects of Acer okamotoanum sap on L-NAME-induced hypertension-like symptoms in a rat model.

Science.gov (United States)

Yang, Hyun; Hwang, Inho; Koo, Tae-Hyoung; Ahn, Hyo-Jin; Kim, Sun; Park, Mi-Jin; Choi, Won-Sil; Kang, Ha-Young; Choi, In-Gyu; Choi, Kyung-Chul; Jeung, Eui-Bae

2012-02-01

The sap of Acer okamotoanum has been termed 'bone-benefit-water' in Korea owing to its mineral and sugar content. In particular, the calcium (Ca) and potassium (K) concentrations of the sap of Acer okamotoanum are 40- and 20-times higher, respectively, than commercial spring water. In the present study, we examined whether Acer okamotoanum sap improves or prevents hypertension-like symptoms in a rat model. Male Sprague-Dawley rats (8-weeks-old) were provided commercial spring water supplemented with 25, 50 or 100% Acer okamotoanum sap, 3% potassium ions (K+) or captopril, and treated daily for 2 weeks with NG-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg/day) by subcutaneous injection, in order to induce hypertensive symptoms. Rats were euthanized 6 h following the final injection. To assess the effect of the sap on hypertension-like symptoms, we examined the mean blood pressure (BP), protein levels and localization of endothelial nitric oxide synthase (eNOS) in the descending aorta of the rats. BP levels were significantly lower in hypertensive rats received 25, 50 and 100% sap compared with rats who were administered only commercial spring water. Protein levels of eNOS were repressed in L-NAME-only-treated rats, but were elevated in the descending aorta of rats administered captopril, K+ water and Acer okamotoanum sap (25, 50 and 100%) up to the level of the sham group provided commercial spring water, and then injected with dimethyl sulfoxide for the same period of time. Localized eNOS protein was abundantly expressed in the perivascular descending aorta adipose tissue of the rats. Taken together, these results demonstrated that the sap of Acer okamotoanum ameliorated high BP induced by L-NAME treatment in a rat model.

Antagonism by supidimide of haloperidol-induced augmentation of (/sup 3/H)-spiperone binding in rat striatum

Energy Technology Data Exchange (ETDEWEB)

Hennies, H H; Hess, V; Flohe, L

1984-01-01

Rats were treated for two weeks with haloperidol alone or with additional test drugs and the D/sub 2/ receptor density in the striatum was investigated after a drug-free period of five days. The D/sub 2/ receptor system as analysed by (/sup 3/H)-spinerone binding was best characterized by a model with two binding sites of different affinity. Chronic haloperidol treatment substantially augmented the total binding capacity 2-(2-Oxo-3-piperidyl)-1,2-benzisothiazoline-3-one-1,1-dioxide (supidimide), a functional synergist of neuroleptics in acute experiments, surprisingly antagonized the haloperidol-induced receptor augmentation, whereas other CNS depressants (diazepam and phenobarbital) were ineffective.

Treatment with escitalopram but not desipramine decreases escape latency times in a learned helplessness model using juvenile rats.

Science.gov (United States)

Reed, Abbey L; Anderson, Jeffrey C; Bylund, David B; Petty, Frederick; El Refaey, Hesham; Happe, H Kevin

2009-08-01

The pharmacological treatment of depression in children and adolescents is different from that of adults due to the lack of efficacy of certain antidepressants in the pediatric age group. Our current understanding of why these differences occur is very limited. To develop more effective treatments, a juvenile animal model of depression was tested to validate it as a possible model to specifically study pediatric depression. Procedures for use with juvenile rats at postnatal day (PND) 21 and 28 were adapted from the adult learned helplessness model in which, 24 h after exposure to inescapable stress, animals are unable to remove themselves from an easily escapable stressor. Rats were treated for 7 days with either the selective serotonin reuptake inhibitor escitalopram at 10 mg/kg or the tricyclic antidepressant desipramine at 3, 10, or 15 mg/kg to determine if treatment could decrease escape latency times. Escitalopram treatment was effective at decreasing escape latency times in all ages tested. Desipramine treatment did not decrease escape latency times for PND 21 rats, but did decrease times for PND 28 and adult animals. The learned helplessness model with PND 21 rats predicts the efficacy of escitalopram and the lack of efficacy of desipramine seen in the treatment of pediatric depression. These findings suggest that the use of PND 21 rats in a modified learned helplessness procedure may be a valuable model of human pediatric depression that can predict pediatric antidepressant efficacy and be used to study antidepressant mechanisms involved in pediatric depression.

Oxidative stress of crystalline lens in rat menopausal model

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Semra Acer

Full Text Available ABSTRACT Purpose: To evaluate lenticular oxidative stress in rat menopausal models. Methods: Forty Wistar female albino rats were included in this study. A total of thirty rats underwent oophorectomy to generate a menopausal model. Ten rats that did not undergo oophorectomy formed the control group (Group 1. From the rats that underwent oophorectomy, 10 formed the menopause control group (Group 2, 10 were administered a daily injection of methylprednisolone until the end of the study (Group 3, and the remaining 10 rats were administered intraperitoneal streptozocin to induce diabetes mellitus (Group 4. Total oxidant status (TOS, total antioxidant capacity (TAC, and oxidative stress index (OSI measurements of the crystalline lenses were analyzed. Results: The mean OSI was the lowest in group 1 and highest in group 4. Nevertheless, the difference between the groups was not statistically significant in terms of OSI (p >0.05. The mean TOS values were similar between the groups (p >0.05, whereas the mean TAC of group 1 was significantly higher than that of the other groups (p <0.001. Conclusions: Our results indicate that menopause may not promote cataract formation.

Anti-ischemic effect of curcumin in rat brain.

Science.gov (United States)

Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

2008-06-01

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

Influence of gastric pH modifiers on development of intestinal metaplasia induced by X-irradiation in rats

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Okamoto, Taro; Fudaba, Yasuhiro; Ogundigie, P.S.; Ito, Akihiro

1993-01-01

The influence of gastric pH on intestinal metaplasia was examined in male Crj:CD(SD) rats. At the age of 5 weeks, animals were irradiated with two 10 Gy doses of X-rays to the gastric region at a 3-day interval (total 20 Gy), and 6 months after irradiation, received either secretin or histamine in silicon tubes for 2 months or had their bilateral submandibular salivary glands removed. The incidences of intestinal metaplasia in the fundus of animals after administration of secretin or histamine, or removal of the salivary glands were reduced, along with the pH values, as compared with values for rats given X-rays alone. In both the pyloric and the fundic gland mucosae, the numbers of alkaline phosphatase (ALP)-positive foci and type B metaplasias (intestinal crypts without Paneth cells) were also significantly decreased (P<0.01). In a second experiment, started six months after irradiation, rats were kept on 1% sodium chloride (NaCl) diet for 6 months. Subsequent removal of salivary glands along with histamine treatment brought about a marked drop in pH and in numbers of ALP-positive foci after three and five days. The present results thus indicated that development and maintenance of intestinal metaplasia can be influenced by a decrease of pH value. (author)

Characterization of rat lung ICAM-1

DEFF Research Database (Denmark)

Beck-Schimmer, B; Schimmer, R C; Schmal, H

1998-01-01

studies, rat pulmonary artery endothelial cells (RPAEC), rat alveolar macrophages and aortic rings were stimulated (as described below) and evaluated for ICAM-1 expression. TREATMENT: RPAEC and macrophages were stimulated with lipopolysaccharide (LPS) and recombinant murine tumour necrosis factor alpha...... peaked at 4 h, while lung ICAM- I protein peaked at 6 h. CONCLUSIONS: Quantitation of ICAM-1 expression in vitro and in vivo suggests that ICAM-1 plays a central role in two lung inflammatory models. Furthermore, lung ICAM-1 upregulation involves at least two cell types: vascular endothelial cells...

miR-494 up-regulates the PI3K/Akt pathway via targetting PTEN and attenuates hepatic ischemia/reperfusion injury in a rat model.

Science.gov (United States)

Su, Song; Luo, De; Liu, Xiangdong; Liu, Jiang; Peng, Fangyi; Fang, Cheng; Li, Bo

2017-10-31

A rat HIRI model was constructed and treated with an intraperitoneal injection of agomir- miR-494 or agomir-NC (negative control) for 7 days after the surgery. The pathophysiological changes in sham-operated rats, HIRI, HIRI + agomir- miR-494 , and HIRI + agomir-NC were compared. The effect of miR-494 was also assessed in an H 2 O 2 -induced apoptosis model. Hepatic AML12 cells were transfected with mimics NC or miR-494 mimics, followed by 6-h H 2 O 2 treatment. Cell proliferation and apoptosis were detected by CCK8 assay and flow cytometry, respectively. Further, the miR-494 target gene was identified by luciferase reporter assay, and verified both in vitro and in vivo experiments. The activity of AKT pathway was further analyzed in vivo by Western blot. HIRI + agomir- miR-494 rats exhibited significantly higher miR-494 expression, lower serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and glutamate dehydrogenase (GLDH) level, lower hepatic MDA, TOA, and OSI, alleviated hepatic necrosis, reduced hepatocyte apoptosis, and decreased expression of apoptosis-related proteins, when compared with HIRI + agomir-NC rats ( P <0.05 or 0.01). After H 2 O 2 treatment, AML-12 cells transfected with miR-494 mimics had significantly higher proliferation and lower apoptosis rate compared with mimics NC group ( P <0.01). PTEN was identified as an miR-494 target gene. PTEN expression was significantly down-regulated in AML12 cells transfected with miR-494 mimics, and was up-regulated by treatment of miR-494 inhibitor ( P <0.01). Moreover, HIRI + agomir- miR-494 rats exhibited significantly lower PTEN expression, and higher p-AKT, p-mTOR, and p-p70S6K levels compared with HIRI + agomir-NC rats. Therefore, miR-494 protected rats against hepatic ischemia/reperfusion (I/R) injury through down-regulating its downstream target gene PTEN , leading to the activation of PI3K/AKT signaling pathway. © 2017 The Author(s).

Survival and Functionality of hESC-Derived Retinal Pigment Epithelium Cells Cultured as a Monolayer on Polymer Substrates Transplanted in RCS Rats.

Science.gov (United States)

Thomas, Biju B; Zhu, Danhong; Zhang, Li; Thomas, Padmaja B; Hu, Yuntao; Nazari, Hossein; Stefanini, Francisco; Falabella, Paulo; Clegg, Dennis O; Hinton, David R; Humayun, Mark S

2016-05-01

To determine the safety, survival, and functionality of human embryonic stem cell-derived RPE (hESC-RPE) cells seeded on a polymeric substrate (rCPCB-RPE1 implant) and implanted into the subretinal (SR) space of Royal College of Surgeons (RCS) rats. Monolayers of hESC-RPE cells cultured on parylene membrane were transplanted into the SR space of 4-week-old RCS rats. Group 1 (n = 46) received vitronectin-coated parylene membrane without cells (rMSPM+VN), group 2 (n = 59) received rCPCB-RPE1 implants, and group 3 (n = 13) served as the control group. Animals that are selected based on optical coherence tomography screening were subjected to visual function assays using optokinetic (OKN) testing and superior colliculus (SC) electrophysiology. At approximately 25 weeks of age (21 weeks after surgery), the eyes were examined histologically for cell survival, phagocytosis, and local toxicity. Eighty-seven percent of the rCPCB-RPE1-implanted animals showed hESC-RPE survivability. Significant numbers of outer nuclear layer cells were rescued in both group 1 (rMSPM+VN) and group 2 (rCPCB-RPE1) animals. A significantly higher ratio of rod photoreceptor cells to cone photoreceptor cells was found in the rCPCB-RPE1-implanted group. Animals with rCPCB-RPE1 implant showed hESC-RPE cells containing rhodopsin-positive particles in immunohistochemistry, suggesting phagocytic function. Superior colliculus mapping data demonstrated that a significantly higher number of SC sites responded to light stimulus at a lower luminance threshold level in the rCPCB-RPE1-implanted group. Optokinetic data suggested both implantation groups showed improved visual acuity. These results demonstrate the safety, survival, and functionality of the hESC-RPE monolayer transplantation in an RPE dysfunction rat model.

O modelo experimental de carcinogênese gástrica induzido por n-methyl-n-nitrosourea em ratos F344 e camundongos C3H é válido para os ratos Wistar? Experimental model of gastric carcinogenesis with N-methyl-N-nitrosourea for F344 rats and C3H mices is valid for Wistar rats?

Directory of Open Access Journals (Sweden)

Lissandro Tarso

2011-03-01

Full Text Available INTRODUÇÃO: O N-metil-N-nitrosourea (MNU tem ação cancerígena direta, induzindo tumores em várias espécies em uma variedade de órgãos, incluindo o estômago de ratos. Tratamento do MNU na água de beber por 25-42 semanas, seletivamente, induz carcinoma gástrico glandular de ratos F344 e camundongos C3H. OBJETIVO: Estabelecer um modelo experimental para indução seletiva de câncer no estômago glandular de ratos Wistar com MNU. MÉTODOS: Um total de 48 ratos Wistar machos com oito semanas, foram utilizados no presente estudo. MNU (Sigma-Aldrich foi dissolvido em DMSO e liberada água potável ad libitum por um período variando de 16 a 70 semanas. Após 16 semanas, quatro ratos foram selecionados aleatoriamente e mortos. Depois, de seis em seis semanas, quatro animais também foram mortos até 70 semanas. RESULTADOS: A taxa de sobrevivência foi superior a 90%. Ocorreu a indução de dois adenocarcinomas, um carcinoma espinocelular e um sarcoma. A incidência de adenocarcinoma gástrico foi de 4,5% (0,5 a 15. CONCLUSÕES: O modelo experimental de carcinogênese gástrica em ratos Wistar, utilizando MNU dissolvido na água, não mostrou viabilidade prática neste estudo, devido à baixa taxa de adenocarcinoma gástrico que ocorreu.BACKGROUND: The N-methyl-N-nitrosourea (MNU is a direct acting carcinogen, inducing tumors in several species in a variety of organs, including stomach of rats. Treatment of MNU in the drinking water for 25-42 weeks selectively induced glandular gastric carcinoma in F344 rats and C3H mice. AIM: To establish an experimental model for selective MNU induction of glandular stomach cancer in Wistar rats. METHODS: A total of 48 males eight-week-old Wistar rats were used in the present study. MNU (Sigma-Aldrich was dissolved in DMSO and provided as the drinking water ad libitum for a period ranging from 16 to 70 weeks. After 16 weeks, four rats were randomly selected and killed. After every six weeks four animals

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

Energy Technology Data Exchange (ETDEWEB)

Kaminski, Rafal M [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Blaszczak, Piotr [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Dekundy, Andrzej [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Parada-Turska, Jolanta [Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland); Calderazzo, Lineu [Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil); Cavalheiro, Esper A [Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil); Turski, Waldemar A [Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland); Department of Experimental and Clinical Pharmacology, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland)

2007-03-15

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality.

Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

International Nuclear Information System (INIS)

Kaminski, Rafal M.; Blaszczak, Piotr; Dekundy, Andrzej; Parada-Turska, Jolanta; Calderazzo, Lineu; Cavalheiro, Esper A.; Turski, Waldemar A.

2007-01-01

Behavioral, electroencephalographic (EEG) and neuropathological effects of methomyl, a carbamate insecticide reversibly inhibiting acetylcholinesterase activity, were studied in naive or lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals, methomyl with equal potency produced motor limbic seizures and fatal status epilepticus. Thus, the CD50 values (50% convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of methomyl (13 mg/kg). Lithium pretreated rats were much more susceptible to convulsant, but not lethal effect of methomyl. CD50 values of methomyl for motor limbic seizures and status epilepticus were reduced by lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast, lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of methomyl (9.9 mg/kg). Moreover, lithium-methomyl treated animals developed a long-lasting status epilepticus, which was not associated with imminent lethality observed in methomyl-only treated rats. Scopolamine (10 mg/kg) or diazepam (10 mg/kg) protected all lithium-methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral seizures observed in lithium-methomyl treated rats. In addition, convulsions induced by lithium-methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that lithium pretreatment results in separation between convulsant and lethal effects of methomyl in rats. As such, seizures induced by lithium-methomyl administration may be an alternative to lithium-pilocarpine model of status epilepticus, which is associated with high lethality

Autoimmunity in type 1 diabetes mellitus: a rat model

International Nuclear Information System (INIS)

Liu, Z.

1987-01-01

In this study, we have sought to isolate in vitro, from acutely diabetic BB rats, cytotoxic T lymphocytes, which exhibit specific cytotoxicity toward islet cells. Thoracic duct lymphocytes (TDL) from acutely diabetic BB rats cultured with irradiated MHC matched (RT1.u) islet cells and dendritic cells in vitro were shown to be specifically cytotoxic to MHC matched and mismatched allogeneic (RT1.1) and xenogeneic (hamster) islet target cells in a 3 H-leucine release assay. Two cell lines (V1A8 and V1D11) derived from the TDL culture showed similar patterns of non-MHC restricted islet cell killing which could be blocked by islet cells and cultured rat insulinoma cells (RIN5mF) but not by non-islet cells of various tissue origins. Both V1A8 and V1D11 were not cytotoxic to Natural Killer (NK) sensitive target cells, G1TC and YAC-1. Conventional surface markers for rat helper and suppressor/cytotoxic T cells were not detectable on either cell lines. The V1D11 cell line was positive for W 3/13 (rat T/NK marker) on OX-19 (rat T/macrophage marker), whereas the V1A8 cell line was only positive for W 3/13

Cyclosporin safety in a simplified rat brain tumor implantation model

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Francisco H. C. Felix

2012-01-01

Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

Neuronal and glial release of (3H)GABA from the rat olfactory bulb

Energy Technology Data Exchange (ETDEWEB)

Jaffe, E.H.; Cuello, A.C.

1981-12-01

Neuronal versus glial components of the (3H)gamma-aminobutyric acid ((3H)GABA) release studies were performed with two different microdissected layers of the olfactory bulb of the rat. In some experiments substantia nigra was used as a GABAergic axonal system and the trigeminal ganglia as a peripheral glial model. Spontaneous release of (3H)GABA was always lower in neuronal elements as compared with glial cells. A veratridine-evoked release was observed from the ONL but not from the trigeminal ganglia. Tetrodotoxin (TTX) abolished the veratridine-evoked release from the ONL, which also showed a partial inhibition when high magnesium concentrations were used in a Ca2+-free solution. beta-Alanine was strongly exchanged with (3H)GABA from the ONL of animals with the olfactory nerve lesioned and from animals with no lesion; but only a small heteroexchange was found from the external plexiform layer. The beta-alanine heteroexchange was able to deplete the releasable GABA store from the ONL of lesioned animals. In nonlesioned animals and the external plexiform layer, the veratridine-stimulated release of (3H)GABA was not significantly reduced after the beta-alanine heteroexchange. Stimulation of the (3H)GABA release by high concentrations of potassium elicited a higher release rate from axonal terminals than from dendrites or glia. Neurones and glia showed a similar inhibition of (3H)GABA release when a high magnesium concentration was added to a calcium-free solution. When D-600 was used as a calcium-flux blocker no inhibition of the release was observed in glial cells, whereas an almost complete blockage was found in both neuronal preparations (substantia nigra and EPL). These results provide further evidence for differential release mechanisms of GABA from CNS neurones and glial cells.

The endozepine ODN stimulates [3H]thymidine incorporation in cultured rat astrocytes

International Nuclear Information System (INIS)

Gandolfo, P.; Patte, C.; Thoumas, J.L.; Leprince, J.; Vaudry, H.; Tonon, M.C.

1999-01-01

High concentrations of diazepam-binding inhibitor (DBI) mRNA have been detected in astrocytoma, suggesting that DBI-derived peptides may play a role in glial cell proliferation. In the present study, we have investigated the effect of a processing product of DBI, the octadecaneuropeptide ODN, on DNA synthesis in cultured rat astrocytes. At very low concentrations (10 -14 to 10 -11 M), ODN caused a dose-dependent increase of [ 3 H]thymidine incorporation. At higher doses (10 -10 to 10 -5 M), the effect of ODN gradually declined. The central-type benzodiazepine receptor antagonist flumazenil (10 -6 M) completely suppressed the stimulatory action of ODN whereas the peripheral-type benzodiazepine receptor ligand, PK11195 (10 -6 M) had no effect. The ODN-induced stimulation of [ 3 H]thymidine incorporation was mimicked by methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM). The GABA A receptor antagonist bicuculline (10 -4 M) suppressed the effect of both ODN and DMCM on DNA synthesis. Exposure of cultured astrocytes to the specific GABA A agonist 3APS (10 -10 to 10 -4 M) also induced a dose-related increase of [ 3 H]thymidine incorporation. The present study indicates that ODN, acting through central-type benzodiazepine receptors associated with the GABA A receptor complex, stimulates DNA synthesis in rat glial cells. These data provide evidence for an autocrine role of endozepines in the control of glial cell proliferation. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

Influence of whole-body gamma irradiation upon arachidonic acid metabolism in rat platelets

International Nuclear Information System (INIS)

Lognonne, J.L.; Ducousso, R.; Rocquet, G.; Kergonou, J.F.

1985-01-01

The effects of whole-body gamma irradiation (8.4 Gy) were studied on arachidonic acid (AA) metabolism in rat's blood platelets, from day D + 1 to day D + 10 after irradiation. AA conversion into thromboxane B 2 (TxB 2 ) increased at D + 1 and then gradually decreased to very low values from D + 7 to D + 10. This decrease in the conversion of exogenous AA into TxB 2 was due to a lower AA incorporation into platelets and not to a decrease of cyclooxygenase and thromboxane-synthetase activities. AA incorporation into membrane phospholipids of blood platelets was much more decreased than AA incorporation into whole platelets; moreover, the lipid composition of the platelet membranes was markedly modified after irradiation, which must have resulted in structural and functional changes in these membranes; from these effects of whole-body gamma irradiation on platelets, the latter's membranes appeared as a major site of in vivo radiation damage in these cells

A novel model of invasive fungal rhinosinusitis in rats.

Science.gov (United States)

Zhang, Fang; An, Yunfang; Li, Zeqing; Zhao, Changqing

2013-01-01

Invasive fungal rhinosinusitis (IFRS) is a life-threatening inflammatory disease that affects immunocompromised patients, but animal models of the disease are scarce. This study aimed to develop an IFRS model in neutropenic rats. The model was established in three consecutive steps: unilateral nasal obstruction with Merocel sponges, followed by administration of cyclophosphamide (CPA), and, finally, nasal inoculation with Aspergillus fumigatus. Fifty healthy Wistar rats were randomly divided into five groups, with group I as the controls, group II undergoing unilateral nasal obstruction alone, group III undergoing nasal obstruction with fungal inoculation, group IV undergoing nasal obstruction with administration of CPA, and group V undergoing nasal obstruction with administration of CPA and fungal inoculation. Hematology, histology, and mycology investigations were performed. The changes in the rat absolute neutrophil counts (ANCs) were statistically different across the groups. The administration of CPA decreased the ANCs, whereas nasal obstruction with fungal inoculation increased the ANCs, and nasal obstruction did not change them. Histological examination of the rats in group V revealed the hyphal invasion of sinus mucosa and bone, thrombosis, and tissue infarction. No pathology indicative of IFRS was observed in the remaining groups. Positive rates of fungal culture in tissue homogenates from the maxillary sinus (62.5%) and lung (25%) were found in group V, whereas groups I, II, III, and IV showed no fungal culture in the homogenates. A rat IFRS model was successfully developed through nasal obstruction, CPA-induced neutropenia, and fungal inoculation. The disease model closely mimics the pathophysiology of anthropic IFRS.

Mesenteric microcirculatory dysfunctions and translocation of indigenous bacteria in a rat model of strangulated small bowel obstruction

Directory of Open Access Journals (Sweden)

Fernando Luiz Zanoni

2009-01-01

Full Text Available PRUPOSE: Bacterial translocation has been shown to occur in critically ill patients after extensive trauma, shock, sepsis, or thermal injury. The present study investigates mesenteric microcirculatory dysfunctions, the bacterial translocation phenomenon, and hemodynamic/metabolic disturbances in a rat model of intestinal obstruction and ischemia. METHODS: Anesthetized (pentobarbital 50 mg/kg, i.p. male Wistar rats (250-350 g were submitted to intestinal obstruction or laparotomy without intestinal obstruction (Sham and were evaluated 24 hours later. Bacterial translocation was assessed by bacterial culture of the mesenteric lymph nodes (MLN, liver, spleen, and blood. Leukocyte-endothelial interactions in the mesenteric microcirculation were assessed by intravital microscopy, and P-selectin and intercellular adhesion molecule (ICAM-1 expressions were quantified by immunohistochemistry. Hematocrit, blood gases, lactate, glucose, white blood cells, serum urea, creatinine, bilirubin, and hepatic enzymes were measured. RESULTS: About 86% of intestinal obstruction rats presented positive cultures for E. coli in samples of the mesenteric lymph nodes, liver, and spleen, and 57% had positive hemocultures. In comparison to the Sham rats, intestinal obstruction induced neutrophilia and increased the number of rolling (~2-fold, adherent (~5-fold, and migrated leukocytes (~11-fold; this increase was accompanied by an increased expression of P-selectin (~2-fold and intercellular adhesion molecule-1 (~2-fold in the mesenteric microcirculation. Intestinal obstruction rats exhibited decreased PaCO2, alkalosis, hyperlactatemia, and hyperglycemia, and increased blood potassium, hepatic enzyme activity, serum urea, creatinine, and bilirubin. A high mortality rate was observed after intestinal obstruction (83% at 72 h vs. 0% in Sham rats. CONCLUSION: Intestinal obstruction and ischemia in rats is a relevant model for the in vivo study of mesenteric microcirculatory

Rat models of spinal cord injury: from pathology to potential therapies

Science.gov (United States)

2016-01-01

ABSTRACT A long-standing goal of spinal cord injury research is to develop effective spinal cord repair strategies for the clinic. Rat models of spinal cord injury provide an important mammalian model in which to evaluate treatment strategies and to understand the pathological basis of spinal cord injuries. These models have facilitated the development of robust tests for assessing the recovery of locomotor and sensory functions. Rat models have also allowed us to understand how neuronal circuitry changes following spinal cord injury and how recovery could be promoted by enhancing spontaneous regenerative mechanisms and by counteracting intrinsic inhibitory factors. Rat studies have also revealed possible routes to rescuing circuitry and cells in the acute stage of injury. Spatiotemporal and functional studies in these models highlight the therapeutic potential of manipulating inflammation, scarring and myelination. In addition, potential replacement therapies for spinal cord injury, including grafts and bridges, stem primarily from rat studies. Here, we discuss advantages and disadvantages of rat experimental spinal cord injury models and summarize knowledge gained from these models. We also discuss how an emerging understanding of different forms of injury, their pathology and degree of recovery has inspired numerous treatment strategies, some of which have led to clinical trials. PMID:27736748

76 FR 73587 - Foreign-Trade Zone 183-Austin, Tx; Site Renumbering Notice

Science.gov (United States)

2011-11-29

... DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Foreign-Trade Zone 183--Austin, Tx; Site... (Board Order 1366). FTZ 183 currently consists of 8 ``sites'' totaling some 2,818 acres in the Austin... Austin Enterprise Zone, located at Bolm Road and Gardner Road, Austin; Site 2 (50 acres)--Balcones...

NA62 Level 0 trigger: TELDES, TX mezzanine, RX mezzanine integration scenario

CERN Multimedia

Lupi, Matteo

2015-01-01

TELDES is a TEL62 daughter-board used in the generation of the Liquid Krypton Calorimeter primitive for the Level 0 Trigger of the NA62 Experiment. TX and RX mezzanines are daughter boards used in the same trigger system to communicate between different levels of the trigger.

Kinetic analysis of the rate of corneal wound healing in Otsuka long-evans Tokushima Fatty rats, a model of type 2 diabetes mellitus.

Science.gov (United States)

Nagai, Noriaki; Murao, Takatoshi; Okamoto, Norio; Ito, Yoshimasa

2010-01-01

Diabetic keratopathy is a well-known ocular complication secondary to type 2 diabetes mellitus. In this study, we performed a kinetic analysis of corneal wound healing in Long-Evans rats (normal rat) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Corneal wound healing in 7-week-old normal rats was mostly complete 24 h after corneal epithelial abrasion, and the process of corneal wound healing took place according to an equation with a first-order rate constant. The rate of corneal wound healing in normal rats decreased with aging. The process of corneal wound healing in 38- and 60-week-old normal and OLETF rats occurred in two phases with rate constants for the first and second phases represented as alpha and beta, respectively. The alpha and beta values in 38- and 60-week-old OLETF rats were lower than those in normal rats of the corresponding age. Furthermore, a close relationship was observed between the corneal wound healing rate constant and plasma glucose levels in OLETF rats. The present studies suggest the sequence of events that occur following damage to the corneal surface in OLETF rats as a model animal for a human type 2 diabetes mellitus.

Cannabis exacerbates depressive symptoms in rat model induced by reserpine.

Science.gov (United States)

Khadrawy, Yasser A; Sawie, Hussein G; Abdel-Salam, Omar M E; Hosny, Eman N

2017-05-01

Cannabis sativa is one of the most widely recreational drugs and its use is more prevalent among depressed patients. Some studies reported that Cannabis has antidepressant effects while others showed increased depressive symptoms in Cannabis users. Therefore, the present study aims to investigate the effect of Cannabis extract on the depressive-like rats. Twenty four rats were divided into: control, rat model of depression induced by reserpine and depressive-like rats treated with Cannabis sativa extract (10mg/kg expressed as Δ9-tetrahydrocannabinol). The depressive-like rats showed a severe decrease in motor activity as assessed by open field test (OFT). This was accompanied by a decrease in monoamine levels and a significant increase in acetylcholinesterase activity in the cortex and hippocampus. Na + ,K + -ATPase activity increased in the cortex and decreased in the hippocampus of rat model. In addition, a state of oxidative stress was evident in the two brain regions. This was indicated from the significant increase in the levels of lipid peroxidation and nitric oxide. No signs of improvement were observed in the behavioral and neurochemical analyses in the depressive-like rats treated with Cannabis extract. Furthermore, Cannabis extract exacerbated the lipid peroxidation in the cortex and hippocampus. According to the present findings, it could be concluded that Cannabis sativa aggravates the motor deficits and neurochemical changes induced in the cortex and hippocampus of rat model of depression. Therefore, the obtained results could explain the reported increase in the depressive symptoms and memory impairment among Cannabis users. Copyright © 2017 Elsevier B.V. All rights reserved.

Establishment of an ideal time window model in hypothermic-targeted temperature management after traumatic brain injury in rats.

Science.gov (United States)

Zhao, Wan-Yong; Chen, Shao-Bo; Wang, Jing-Jing; Xu, Chao; Zhao, Ming-Liang; Dong, Hua-Jiang; Liang, Hai-Qian; Li, Xiao-Hong; Tu, Yue; Zhang, Sai; Chen, Chong; Sun, Hong-Tao

2017-08-15

Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15mins, 2 h, 4 h respectively after TBI. The neurological function was evaluated with the modified neurological severity score and Morris water maze test. The brain edema and morphological changes were measured with the water content and H&E staining. Brain sections were immunostained with antibodies against DCX (a neuroblast marker) and GFAP (an astrocyte marker). The apoptosis levels in the ipsilateral hippocampi and cortex were examined with antibodies against the apoptotic proteins Bcl-2, Bax, and cleaved caspase-3 by the immunofluorescence and western blotting. The results indicated that each hypothermia therapy group could improve neurobehavioral and cognitive function, alleviate brain edema and reduce inflammation. Furthermore, we observed that therapeutic hypothermia increased DCX expression, decreased GFAP expression, upregulated Bcl-2 expression and downregulated Bax and cleaved Caspase-3 expression. The above results suggested that HTTM at 2h or even at 4h post-injury revealed beneficial brain protection similarly, despite the best effect at 15min post-injury. These findings may provide relatively ideal time window models, further making the following experimental results more credible and persuasive. Copyright © 2017 Elsevier B.V. All rights reserved.

Gut Microbial Diversity in Rat Model Induced by Rhubarb

Science.gov (United States)

Peng, Ying; Wu, Chunfu; Yang, Jingyu; Li, Xiaobo

2014-01-01

Rhubarb is often used to establish chronic diarrhea and spleen (Pi)-deficiency syndrome animal models in China. In this study, we utilized the enterobacterial repetitive intergenic consensus-polymerase chain reaction (ERIC-PCR) method to detect changes in bacterial diversity in feces and the bowel mucosa associated with this model. Total microbial genomic DNA from the small bowel (duodenum, jejunum, and ileum), large bowel (proximal colon, distal colon, and rectum), cecum, and feces of normal and rhubarb-exposed rats were used as templates for the ERIC-PCR analysis. We found that the fecal microbial composition did not correspond to the bowel bacteria mix. More bacterial diversity was observed in the ileum of rhubarb-exposed rats (Panalysis with the SPSS software, the Canonical Discriminant Function Formulae for model rats was established. PMID:25048267

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

Science.gov (United States)

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Copper absorption from human milk, cow's milk, and infant formulas using a suckling rat model

International Nuclear Information System (INIS)

Loennerdal, B.B.; Bell, J.G.; Keen, C.L.

1985-01-01

Since copper deficiency is known to occur during infancy, it becomes important to assess copper uptake from various infant diets. The authors have investigated the uptake of copper from human milk, cow's milk, cow's milk formulas, cereal/milk formula and soy formula, compensating for the decay of 64 Cu and using the suckling rat as a model. Radiocopper was added to the diet in trace amounts. Ultracentrifugation, ultrafiltration, and gel filtration were used to show that the added 64 Cu bound to milk fractions and individual binding compounds in a manner analogous to the distribution of native copper, thus validating the use of extrinsically labeled diets. Labeled diets were intubated into 14-day-old suckling rats. Animals were killed after 6 h and tissues removed and counted. Liver copper uptake was 25% from human milk, 23% from cow's milk formula, 18% from cow's milk, 17% from premature (cow's milk based) infant formula, 17% from cereal/milk formula and 10% from soy formula. These results show that the rat pup model may provide a rapid, inexpensive, and sensitive method to assay bioavailability of copper from infant foods

Structural and biophysical studies with the MjTX-I, a Lys49-phospholipase A2 homologue from Bothrops moojeni venom

International Nuclear Information System (INIS)

Salvador, G.H.M.; Fernandes, C.A.H.; Fernandez, R.M.; Fontes, M.R.M.; Marchi-Salvador, D.P.; Soares, A.M.; Oliveira, C.L.P

2012-01-01

Full text: Phospholipases A 2 (PLA 2 ) are small proteins found in a great diversity of organisms and belong to a superfamily of proteins involved in many important pharmacological processes, such as neurotoxicity, myotoxicity, platelet aggregation, and anticoagulant activity. Ophidic accidents caused by snakes from Bothrops genus are not efficiently neutralized by conventional serum therapy, and then detailed studies with this class of proteins may be very important to supplement this conventional therapy. Miotoxin-I (MjTX-I) is a basic Lys49-PLA 2 , isolated from Bothrops moojeni snake venom, which induces a drastic local myonecrosis. Crystal structure of MjTX-I shows four molecules in the asymmetric unit, an unusually oligomeric conformation for snake venom Lys49-PLA 2 s. However, bioinformatics techniques indicate a dimer as the biological oligomeric conformation. To get additional information of its biological conformation, we also performed Dynamic Light Scattering, Size Exclusion Chromatography and Small Angle X-ray Scattering experiments. These techniques showed a monomer as the most probable biological conformation in water; however small changes in pH and ionic strength result in different oligomeric assemblies. These novel information for Lys49-PLA 2 s may result in important conclusions for this intriguing class of toxins. (author)

Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure

Science.gov (United States)

Kuijk, Ewart W.; Rasmussen, Shauna; Blokzijl, Francis; Huch, Meritxell; Gehart, Helmuth; Toonen, Pim; Begthel, Harry; Clevers, Hans; Geurts, Aron M.; Cuppen, Edwin

2016-01-01

The rat is an important model for liver regeneration. However, there is no in vitro culture system that can capture the massive proliferation that can be observed after partial hepatectomy in rats. We here describe the generation of rat liver stem cell lines. Rat liver stem cells, which grow as cystic organoids, were characterized by high expression of the stem cell marker Lgr5, by the expression of liver progenitor and duct markers, and by low expression of hepatocyte markers, oval cell markers, and stellate cell markers. Prolonged cultures of rat liver organoids depended on high levels of WNT-signalling and the inhibition of BMP-signaling. Upon transplantation of clonal lines to a Fah−/− Il2rg−/− rat model of liver failure, the rat liver stem cells engrafted into the host liver where they differentiated into areas with FAH and Albumin positive hepatocytes. Rat liver stem cell lines hold potential as consistent reliable cell sources for pharmacological, toxicological or metabolic studies. In addition, rat liver stem cell lines may contribute to the development of regenerative medicine in liver disease. To our knowledge, the here described liver stem cell lines represent the first organoid culture system in the rat. PMID:26915950

Wendan decoction improves learning and memory deficits in a rat model of schizophrenia

Institute of Scientific and Technical Information of China (English)

Cuiping Yang; Changchun Cai; Xiaojin Yang; Yanping Yang; Zhigang Zhou; Jianhua Liu; Heping Ye; Hongjiao Wan

2012-01-01

An experimental model of schizophrenia was established using dizocilpine (MK-801). Rats were intragastrically administered with Wendan decoction or clozapine for 21 days prior to establishing the model. The results revealed that the latency of schizophrenia model rats to escape from the hidden platform in the Morris water maze was significantly shortened after administration of Wendan decoction or clozapine. In addition, the treated rats crossed the platform significantly more times than the untreated model rats. Moreover, the rate of successful long-term potentiation induction in the Wendan decoction group and clozapine group were also obviously increased compared with the model group, and the population spike peak latency was significantly shortened. These experimental findings suggest that Wendan decoction can improve the learning and memory ability of schizophrenic rats to the same extent as clozapine treatment.

Texas Higher Education Strategic Plan: 2015-2030. 60x30TX

Science.gov (United States)

Texas Higher Education Coordinating Board, 2015

2015-01-01

Higher education improves the lives of Texans. This new higher education plan, 60x30TX, focuses on the common goal by striving for 60 percent of the 25- to 34-year-old Texas population to hold a certificate or degree by 2030. The plan seeks to increase student success through the combined expertise and resources of many stakeholders. Because of…

In vitro evidence for impaired neuroprotective capacities of adult mesenchymal stem cells derived from a rat model of familial amyotrophic lateral sclerosis (hSOD1(G93A)).

Science.gov (United States)

Boucherie, Cédric; Caumont, Anne-Sophie; Maloteaux, Jean-Marie; Hermans, Emmanuel

2008-08-01

Protection of neurons by stem cells is an attractive challenge in the development of efficient therapies of neurodegenerative diseases. When giving preference to autologous grafts, the bone marrow constitutes a valuable source of adult stem cells. Therefore, we herein studied the acquisition of neuroprotective functions by cultured mesenchymal stem cells (MSCs) exposed to growth factors known to promote the differentiation of neural stem cells into astrocytes. In these conditions, MSCs showed increased transcription and expression of the high-affinity glutamate transporter GLT-1 and functional studies revealed increased aspartate uptake activity. In addition, differentiation was shown to endow the cells with the capacity to respond to riluzole which triggers a robust up-regulation of the GDNF production. In parallel, MSCs derived from the bone marrow of a transgenic rat model of familial ALS (hSOD1(G93A)) were also characterised. Unexpectedly, cells from this rat strain submitted to the differentiation protocol showed modest capacity to take up aspartate and did not respond to the riluzole treatments. These data highlight the neuroprotective potential attributable to MSCs, supporting their use as valuable tools for the treatment of neurodegenerative disorders. However, the cells from the transgenic animal model of ALS appeared deficient in their capacity to gain the neuroprotective properties, raising questions regarding the suitability of autologous stem cell grafts in future therapies against familial forms of this disease.

Antihypertensive effect of eicosapentaenoic acid (EPA) on spontaneously hypertensive rats (SHR)

International Nuclear Information System (INIS)

Lam, B.K.; Quilley, J.; Hirai, A.; Yoshida, S.; Tamura, Y.; Wong, P.Y.K.

1986-01-01

EPA ethyl ester (99.8% pure) was administered orally (300 mg/kg/d) to adult (25-wk-old) and young (11 1/2-wk-old) SHR rats for 2 weeks at which time systolic blood pressure (BP), platelet aggregation, glomerular leukotriene (LT)A 4 hydrolase activity, plasma renin activity (PRA), urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ and aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ were measured. EPA treatment decreased BP of adult SHR with established hypertension from 238.7 +/- 2 to 217 +/- 4 mmHg (M +/- SD, P 4 hydrolase activity was inhibited. PRA and urinary levels of TxB 2 and 6-keto-PGF/sub 1α/ were not changed. Similarly, there was no change in aortic conversion of [ 14 C]-AA to [ 14 C]-6-keto-PGF/sub 1α/ indicating that EPA treatment does not alter vascular cyclo-oxygenase activity. These results indicate that EPA treatment affects eicosanoid metabolism and cardiovascular function

A fast-response two-photon fluorescent probe for imaging endogenous H2O2 in living cells and tissues

Science.gov (United States)

Lu, Yanan; Shi, Xiaomin; Fan, Wenlong; Black, Cory A.; Lu, Zhengliang; Fan, Chunhua

2018-02-01

As a second messenger, hydrogen peroxide plays significant roles in numerous physiological and pathological processes and is related to various diseases including inflammatory disease, diabetes, neurodegenerative disorders, cardiovascular disease and Alzheimer's disease. Two-photon (TP) fluorescent probes reported for the detection of endogenous H2O2 are rare and most have drawbacks such as slow response and low sensitivity. In this report, we demonstrate a simple H2O2-specific TP fluorescent probe (TX-HP) containing a two-photon dye 6-hydroxy-2,3,4,4a-tetrahydro-1H-xanthen-1-one (TX) on the modulation of the ICT process. The probe exhibits a rapid fluorescent response to H2O2 in 9 min with both high sensitivity and selectivity. The probe can detect exogenous H2O2 in living cells. Furthermore, the probe is successfully utilized for imaging H2O2 in liver tissues.

1H nuclear magnetic resonance studies of sarcoplasmic oxygenation in the red cell-perfused rat heart

OpenAIRE

Jelicks, L.A.; Wittenberg, B.A.

1995-01-01

The proximal histidine N delta H proton of deoxymyoglobin experiences a large hyperfine shift resulting in its 1H nuclear magnetic resonance (NMR) signal appearing at approximately 76 ppm (at 35 degrees C), downfield of the diamagnetic spectral region. 1H NMR of this proton is used to monitor sarcoplasmic oxygen pressure in isolated perfused rat heart. This method monitors intracellular oxygenation in the whole heart and does not reflect oxygenation in a limited region. The deoxymyoglobin res...

The endogenous hydrogen sulfide producing enzyme cystathionine-β synthase contributes to visceral hypersensitivity in a rat model of irritable bowel syndrome

Directory of Open Access Journals (Sweden)

Chen Jiande DZ

2009-08-01

Full Text Available Abstract Background The pathogenesis of visceral hypersensitivity, a characteristic pathophysiological feature of irritable bowel syndrome (IBS, remains elusive. Recent studies suggest a role for hydrogen sulfide (H2S in pain signaling but this has not been well studied in visceral models of hyperalgesia. We therefore determined the role for the endogenous H2S producing enzyme cystathionine-β-synthetase (CBS in a validated rat model of IBS-like chronic visceral hyperalgesia (CVH. CVH was induced by colonic injection of 0.5% acetic acid (AA in 10-day-old rats and experiments were performed at 8–10 weeks of age. Dorsal root ganglion (DRG neurons innervating the colon were labeled by injection of DiI (1,1'-dioleyl-3,3,3',3-tetramethylindocarbocyanine methanesulfonate into the colon wall. Results In rat DRG, CBS-immunoreactivity was observed in approximately 85% of predominantly small- and medium-sized neurons. Colon specific DRG neurons revealed by retrograde labeling DiI were all CBS-positive. CBS-positive colon neurons co-expressed TRPV1 or P2X3 receptors. Western blotting analysis showed that CBS expression was significantly increased in colon DRGs 8 weeks after neonatal AA-treatment. Furthermore, the CBS inhibitor hydroxylamine markedly attenuated the abdominal withdrawal reflex scores in response to colorectal distention in rats with CVH. By contrast, the H2S donor NaHS significantly enhanced the frequency of action potentials of colon specific DRG neurons evoked by 2 times rheobase electrical stimulation. Conclusion Our results suggest that upregulation of CBS expression in colonic DRG neurons and H2S signaling may play an important role in developing CVH, thus identifying a specific neurobiological target for the treatment of CVH in functional bowel syndromes.

Isotope effects and their implications for the covalent binding of inhaled [3H]- and [14C]formaldehyde in the rat nasal mucosa

International Nuclear Information System (INIS)

Heck Hd'; Casanova, M.

1987-01-01

DNA-protein crosslinks were formed in the nasal respiratory mucosa of Fischer-344 rats exposed for 3 hr to selected concentrations of [ 3 H]- and [ 14 C]formaldehyde ( 3 HCHO and H 14 CHO). In rats depleted of glutathione (GSH) and exposed to 10 ppm of 3 HCHO and H 14 CHO, the 3 H/ 14 C ratio of the fraction of the DNA that was crosslinked to proteins was significantly (39 +/- 6%) higher than that of the inhaled gas. This suggests an isotope effect, either on the formation of DNA-protein crosslinks by labeled HCHO or on the oxidation of labeled HCHO catalyzed by formaldehyde (FDH) or aldehyde dehydrogenase (AldDH). The possibility of an isotope effect on the formation of crosslinks was investigated using rat hepatic nuclei incubated with [ 3 H]- and [ 14 C]formaldehyde (0.1 mM, 37 degrees C). A small (3.4 +/- 0.9%) isotope effect was detected on this reaction, which slightly favored 3 HCHO over H 14 CHO in binding to DNA. The magnitude of this isotope effect cannot account for the high isotope ratio observed in the crosslinked DNA in vivo. The possibility of an isotope effect on the oxidation of 3 HCHO and H 14 CHO catalyzed by FDH was investigated using homogenates of the rat nasal mucosa incubated with [ 3 H]- and [ 14 C]formaldehyde at total formaldehyde concentrations ranging from 0.1 to 11 microM, NAD+ (1 mM), GSH (15 mM), and pyrazole (1 mM). The experiments showed that 3 HCHO is oxidized significantly more slowly than H 14 CHO under these conditions (Vmax/Km (H 14 CHO) divided by Vmax/Km ( 3 HCHO) = 1.82 +/- 0.11). A similar isotope effect was observed in the absence of GSH, presumably due to the oxidation of 3 HCHO and H 14 CHO catalyzed by AldDH

Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

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Tadashi Okamura

2013-01-01

Full Text Available Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA rat derived from Long-Evans (LE strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction of β-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

Metabolic effects of basic fibroblast growth factor in streptozotocin-induced diabetic rats: A 1H NMR-based metabolomics investigation

OpenAIRE

Lin, Xiaodong; Zhao, Liangcai; Tang, Shengli; Zhou, Qi; Lin, Qiuting; Li, Xiaokun; Zheng, Hong; Gao, Hongchang

2016-01-01

The fibroblast growth factors (FGFs) family shows a great potential in the treatment of diabetes, but little attention is paid to basic FGF (bFGF). In this study, to explore the metabolic effects of bFGF on diabetes, metabolic changes in serum and feces were analyzed in the normal rats, the streptozocin (STZ)-induced diabetic rats and the bFGF-treated diabetic rats using a 1H nuclear magnetic resonance (NMR)-based metabolomic approach. Interestingly, bFGF treatment significantly decreased glu...

Autoradiographic localization of binding sites for (/sup 3/H). gamma. -aminobutyrate, (/sup 3/H) muscimol, (+) (/sup 3/H) bicuculline methiodide and (/sup 3/H) flunitrazepam in cultures of rat cerebellum and spinal cord

Energy Technology Data Exchange (ETDEWEB)

Hoesli, E; Hoesli, L [Basel Univ. (Switzerland); Moehler, H; Richards, J G [Hoffmann-La Roche (F.) and Co., Basel (Switzerland)

1980-01-01

Cultures of rat cerebellum and spinal cord were used to visualize sites for (/sup 3/H)..gamma..-aminobutyrate, (/sup 3/H)muscimol, (/sup 3/H)bicuculline methiodide and (/sup 3/H) flunitrazepam by autoradiography. In cerebellar cultures, many large neurons (presumably Purkinje cells) and interneurons were labelled. In spinal cord cultures, these compounds were mainly bound to small and medium-sized neurons, whereas the majority of large neurons were unlabelled. No binding sites for these radioligands were found on glial cells. Binding of (/sup 3/H)..gamma..-aminobutyrate, (/sup 3/H)muscimol and (/sup 3/H)bicuculline methiodide was markedly reduced or inhibited by adding unlabelled ..gamma..-aminobutyrate, muscimol and bicuculline (10/sup -3/M) respectively to the incubation medium. Addition of a thienobenzazepine markedly reduced binding with (/sup 3/H)flunitrazepam. It is concluded that tissues cultures are an excellent tool to visualize the cellular localization of binding sites for neurotransmitters and drugs using autoradiography.

Mechanism of aminopyridine-induced release of [3H]dopamine from rat brain synaptosomes.

Science.gov (United States)

Scheer, H W; Lavoie, P A

1991-01-01

1. Aminopyridines (APs) induced the release of [3H]dopamine (3H-DA) from rat synaptosomal preparations. 2. 4-AP and 3,4-DAP were of equal efficacy in inducing release of 3H-DA; 3-AP, 2-AP and 2,6-AP were less active; pyridine and pyridine-4-carboxylamide were inactive. 3. Cd2+ was more effective in inhibiting 4-AP-induced release of 3H-DA (IC50 approximately 4 microM) than Co2+ and Ni2+ (IC50s approximately 500 microM). 4. While 4-AP increased the 45Ca2+ content of whole synaptosomal preparations, no effect of 4-AP on 45Ca2+ content was observed in lysed synaptosomal preparations. 5. 4-AP-induced 45Ca2+ uptake was inhibited by Cd2+, Ni2+ and Co2+ in concentration ranges similar to those inhibiting 3H-DA release.

Quantified pH imaging with hyperpolarized 13C‐bicarbonate

DEFF Research Database (Denmark)

Scholz, David Johannes; Janich, Martin A.; Köllisch, Ulrich

2015-01-01

for various flip angles for bicarbonate (BiC) and CO2 with spectral‐spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction...... and interpreted within inflammation and acute metabolic alkalosis models. Magn Reson Med 73:2274–2282, 2015. © 2014 Wiley Periodicals, Inc....

33 CFR 165.813 - Security Zones; Ports of Houston and Galveston, TX.

Science.gov (United States)

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Security Zones; Ports of Houston... Security Zones; Ports of Houston and Galveston, TX. (a) Location. Within the Ports of Houston and Galveston... yards of a cruise ship unless expressly authorized by the Coast Guard Captain of the Port Houston...

Persistent estrus rat models of polycystic ovary disease: an update.

Science.gov (United States)

Singh, Krishna B

2005-10-01

To critically review published articles on polycystic ovary (PCO) disease in rat models, with a focus on delineating its pathophysiology. Review of the English-language literature published from 1966 to March 2005 was performed through PubMed search. Keywords or phrases used were persistent estrus, chronic anovulation, polycystic ovary, polycystic ovary disease, and polycystic ovary syndrome. Articles were also located via bibliographies of published literature. University Health Sciences Center. Articles on persistent estrus and PCO in rats were selected and reviewed regarding the methods for induction of PCO disease. Changes in the reproductive cycle, ovarian morphology, hormonal parameters, and factors associated with the development of PCO disease in rat models were analyzed. Principal methods for inducing PCO in the rat include exposure to constant light, anterior hypothalamic and amygdaloidal lesions, and the use of androgens, estrogens, antiprogestin, and mifepristone. The validated rat PCO models provide useful information on morphologic and hormonal disturbances in the pathogenesis of chronic anovulation in this condition. These studies have aimed to replicate the morphologic and hormonal characteristics observed in the human PCO syndrome. The implications of these studies to human condition are discussed.

Antiapoptotic Actions of Methyl Gallate on Neonatal Rat Cardiac Myocytes Exposed to H2O2

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Sandhya Khurana

2014-01-01

Full Text Available Reactive oxygen species trigger cardiomyocyte cell death via increased oxidative stress and have been implicated in the pathogenesis of cardiovascular diseases. The prevention of cardiomyocyte apoptosis is a putative therapeutic target in cardioprotection. Polyphenol intake has been associated with reduced incidences of cardiovascular disease and better overall health. Polyphenols like epigallocatechin gallate (EGCG can reduce apoptosis of cardiomyocytes, resulting in better health outcomes in animal models of cardiac disorders. Here, we analyzed whether the antioxidant N-acetyl cysteine (NAC or polyphenols EGCG, gallic acid (GA or methyl gallate (MG can protect cardiomyocytes from cobalt or H2O2-induced stress. We demonstrate that MG can uphold viability of neonatal rat cardiomyocytes exposed to H2O2 by diminishing intracellular ROS, maintaining mitochondrial membrane potential, augmenting endogenous glutathione, and reducing apoptosis as evidenced by impaired Annexin V/PI staining, prevention of DNA fragmentation, and cleaved caspase-9 accumulation. These findings suggest a therapeutic value for MG in cardioprotection.

MRI and morphological observation in C6 glioma model rats and significance

International Nuclear Information System (INIS)

Zhou Ying; Yuan Bo; Wang Hao; Lu Jin; Yuan Changji; Ma Yue; Tong Dan; Zhang Kun; Gao Feng; Wu Xiaogang

2013-01-01

Objective: To establish stable and reliable rat C6 glioma model, and to perform MRI dynamic observation and pathomorphological observation in model animal brain, and to provide experimental basis for pharmaceutical research on anti-glioma drugs. Methods: The C6 glioma cells were cultured and 20 μL cultural fluid containing 1×10 6 C6 cells was sterotactically implanted into the left caudate nuclei in 10 male Wistar rats, respectively. The changes in the behavior of the rats after implantation were observed and recorded. MRI dynamic scanning was performed in 10 rats 2, 3 and 4 weeks after implantation and the brain tissues were taken for general and pathological examination when the 10 rats were naturally dead. The survival period of tumor-bearing rats was calculated. Results: 2 weeks after implantation the rats showed decreased activities and food intake, fur lackluster, and conjunctival congestion and so on; 3 weeks later, some rats appeared nerve symptoms such as body twitch, body hemiplegy, body distortion, rotation and so on. All the 10 rats died in 8-30 d. The median survival period of the tumor-bearing rats was 18 d, the average survival period was (18.3±7.3) d. The pathological examination showed that the tumor cells were arranged irregularly closely and karyokinesis was easy to see; tumor vascular tissue proliferation and tumor invasive growth into surrounding normal tissues were found. The expression of glial fibrillary acidic protein (GFAP) was positive in the tumors. Conclusion: A stable animal model of intracranial glioma is successfully established by stereotactic implantation of C6 cells into the rat caudate nucleus. The results of MRI dynamic observation and pathohistological observation on the model animal brain tissue. Can provide experimental basis for selecting the appropriate time window to perform the pharmaceutical research on anti-glioma drugs. (authors)

Hormone-induced rat model of polycystic ovary syndrome: A systematic review.

Science.gov (United States)

Noroozzadeh, Mahsa; Behboudi-Gandevani, Samira; Zadeh-Vakili, Azita; Ramezani Tehrani, Fahimeh

2017-12-15

Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacodynamic/Pharmacogenomic Modeling of Insulin Resistance Genes in Rat Muscle After Methylprednisolone Treatment: Exploring Regulatory Signaling Cascades

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Zhenling Yao

2008-01-01

Full Text Available Corticosteroids (CS effects on insulin resistance related genes in rat skeletal muscle were studied. In our acute study, adrenalectomized (ADX rats were given single doses of 50 mg/kg methylprednisolone (MPL intravenously. In our chronic study, ADX rats were implanted with Alzet mini-pumps giving zero-order release rates of 0.3 mg/kg/h MPL and sacrificed at various times up to 7 days. Total RNA was extracted from gastrocnemius muscles and hybridized to Affymetrix GeneChips. Data mining and literature searches identified 6 insulin resistance related genes which exhibited complex regulatory pathways. Insulin receptor substrate-1 (IRS-1, uncoupling protein 3 (UCP3, pyruvate dehydrogenase kinase isoenzyme 4 (PDK4, fatty acid translocase (FAT and glycerol-3-phosphate acyltransferase (GPAT dynamic profiles were modeled with mutual effects by calculated nuclear drug-receptor complex (DR(N and transcription factors. The oscillatory feature of endothelin-1 (ET-1 expression was depicted by a negative feedback loop. These integrated models provide test- able quantitative hypotheses for these regulatory cascades.