INTERIOR PHOTO OF THE REMOTE ANALYTICAL FACILITY OF SHIELDED GLOVE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR PHOTO OF THE REMOTE ANALYTICAL FACILITY OF SHIELDED GLOVE BOXES IN OPERATING CORRIDOR (CPP-627). INL PHOTO NUMBER NRTS-55-1524. Unknown Photographer, 1955 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST WEST NORTH ELEVATIONS OF MULTICURIE CELL ARCHITECTURAL DETAILS REMOTE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST WEST NORTH ELEVATIONS OF MULTICURIE CELL ARCHITECTURAL DETAILS REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-00627-00-706-050245. ALTERNATE ID NUMBER AED-D-245. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

FACILITY LAYOUT OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FACILITY LAYOUT OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS, FUEL ELEMENT CUTTING FACILITY, AND DRY GRAPHITE STORAGE FACILITY. INL DRAWING NUMBER 200-0603-00-030-056329. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

PLOT PLAN OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PLOT PLAN OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS AND PROPOSED LOCATION OF FUEL ELEMENT CUTTING FACILITY. INL DRAWING NUMBER 200-0603-00-706-051287. ALTERNATE ID NUMBER CPP-C-1287. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

29. FLOOR PLAN OF WASTE CALCINATION FACILITY SHOWING MAIN ABOVEGRADE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. FLOOR PLAN OF WASTE CALCINATION FACILITY SHOWING MAIN ABOVE-GRADE FLOOR LEVEL. INEEL DRAWING NUMBER 200-0633-00-287-106354. FLUOR NUMBER 5775-CPP-633-A-4. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

31. FLOOR PLANS OF WASTE CALCINATION FACILITY. SHOWS ACCESS CORRIDOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

31. FLOOR PLANS OF WASTE CALCINATION FACILITY. SHOWS ACCESS CORRIDOR AT MEZZANINE AND LOWER LEVELS. INEEL DRAWING NUMBER 200-0633-00-287-106352. FLUOR NUMBER 5775-CPP-633-A-2. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

30. FLOOR PLANS OF WASTE CALCINATION FACILITY. SHOWS LEVELS ABOVE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

30. FLOOR PLANS OF WASTE CALCINATION FACILITY. SHOWS LEVELS ABOVE GRADE AND AT LEVEL OF OPERATING CORRIDOR. INEEL DRAWING NUMBER 200-0633-00-287-106351. FLUOR NUMBER 5775-CPP-633-A-1. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

32. SECTIONS AA, BB, CC, DD, AND EE WASTE CALCINATION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. SECTIONS A-A, B-B, C-C, D-D, AND E-E WASTE CALCINATION FACILITY SHOWING RELATIONSHIPS OF DIFFERENT FLOOR LEVELS TO ONE ANOTHER. INEEL DRAWING NUMBER 200-0633-00-287-106353. FLUOR NUMBER 5775-CPP-633-A-3. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

38. SECTIONS OF ACCESS CORRIDOR, INCLUDES SECTION SHOWING ARRANGEMENT OF ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

38. SECTIONS OF ACCESS CORRIDOR, INCLUDES SECTION SHOWING ARRANGEMENT OF NAVY GUN BARRELS. INEEL DRAWING NUMBER 200-0633-00-287-106454. FLUOR NUMBER 5775-CPP-633-P-59. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

Research of beam smoothing technologies using CPP, SSD, and PS

NASA Astrophysics Data System (ADS)

Zhang, Rui; Su, Jingqin; Hu, Dongxia; Li, Ping; Yuan, Haoyu; Zhou, Wei; Yuan, Qiang; Wang, Yuancheng; Tian, Xiaocheng; Xu, Dangpeng; Dong, Jun; Zhu, Qihua

2015-02-01

Precise physical experiments place strict requirements on target illumination uniformity in Inertial Confinement Fusion. To obtain a smoother focal spot and suppress transverse SBS in large aperture optics, Multi-FM smoothing by spectral dispersion (SSD) was studied combined with continuous phase plate (CPP) and polarization smoothing (PS). New ways of PS are being developed to improve the laser irradiation uniformity and solve LPI problems in indirect-drive laser fusion. The near field and far field properties of beams using polarization smoothing were studied and compared, including birefringent wedge and polarization control array. As more parameters can be manipulated in a combined beam smoothing scheme, quad beam smoothing was also studies. Simulation results indicate through adjusting dispersion directions of one-dimensional (1-D) SSD beams in a quad, two-dimensional SSD can be obtained. Experiments have been done on SG-III laser facility using CPP and Multi-FM SSD. The research provides some theoretical and experimental basis for the application of CPP, SSD and PS on high-power laser facilities.

10 CFR 2.627 - Partial decision on site suitability issues in combined license proceeding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... license proceeding. 2.627 Section 2.627 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR... License To Construct Certain Utilization Facilities; and Advance Issuance of Limited Work Authorizations... accordance with this subpart. A limited work authorization may not be issued under 10 CFR 50.10(e) and no...

Research of beam smoothing technology on the technical integration line

NASA Astrophysics Data System (ADS)

Zhang, Rui; Su, Jingqin; Li, Ping; Zhang, Ying; Wang, Jianjun; Dong, Jun; Yang, Dong; Jing, Feng; Xu, Lixin; Ming, Hai

2013-05-01

This paper is focused on the research of SSD and CPP carried out on TIL. A bulk phase modulator with 9.2-GHz modulation frequency is adopted in SSD. The output spectrum of the phase modulator is stable and the residual amplitude modulation is small. FM-to-AM effect caused by free-space propagation after using smoothing by spectral dispersion is theoretically and experimentally studied. Results indicate inserting a dispersion grating in places with larger beam aperture alleviates the FM-to-AM effect, suggesting minimizing free-space propagation and adopting image relay. Experiments indicate when the number of color cycles (Nc) adopts 1, imposing of SSD with 4.26 times diffraction limit (TDL) did not lead to pinhole closure in the spatial filters of the preamplifier with 20 TDL and main amplifier with 26 TDL. Experimental results also indicate SSD didn't influence the load capacity of the laser facility. The contrast of the 440-μm diameter focal spot with 95% energy included using SSD and CPP drops to 0.47, comparing to 1.71 not using SSD and CPP. When the pulse width of the third harmonic wave is 1 ns and the energy is 1115 J, no damage is found in CPP and other final optics. The experiments solves some key technical problems using SSD and CPP on high-power laser facilities, and provides a flexible platform for the laser-plasma interaction experiments.

Research of beam conditioning technologies on SG-III laser facility

NASA Astrophysics Data System (ADS)

Zhang, Rui; Su, Jingqin; Yuan, Haoyu; Li, Ping; Tian, Xiaocheng; Wang, Jianjun; Dong, Jun; Zhang, Ying; Yuan, Qiang; Wang, Yuancheng; Zhou, Wei; Peng, Zhitao; Wang, Fang; Hu, Dongxia; Zhu, Qihua; Zheng, Wanguo; Zhang, Xiaomin

2014-12-01

Multi-FM SSD and CPP was experimentally studied in high fluence and will be equipped on all the beams of SG-III laser facility. The output spectrum of the cascade phase modulators are stable and the residual amplitude modulation is small. FM-to-AM effect caused by free-space propagation after using smoothing by spectral dispersion is theoretically analyzed. Results indicate inserting a dispersion grating in places with larger beam aperture could alleviate the FM-to- AM effect, suggesting minimizing free-space propagation and adopting image relay. Experiments taken on SG-III laser facility indicate when the number of color cycles (Nc) adopts 1, imposing of SSD with 3.3 times diffraction limit (TDL) did not lead to pinhole closure in the spatial filters of the preamplifier and main amplifier with 30-TDL pinhole size. The nonuniformity of the focal spot using Multi-FM SSD and CPP drops to 0.26, comparing to 0.84 only using CPP. The experiments solve some key technical problems using SSD and CPP on SG-III laser facility, and provide a flexible platform for laser-plasma interaction experiments. Combined beam smoothing and polarization smoothing are also analyzed. Simulation results indicate through adjusting dispersion directions of one-dimensional SSD beams in a quad, two-dimensional SSD could be obtained. The near field and far field properties of beams using polarization smoothing were also studied, including birefringent wedge and polarization control plate (PCP). By using PCP, cylindrical vector beams could be obtained. New solutions will be provided to solve the LPI problem encountered in indirect drive laser fusion.

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601) BASEMENT SHOWING PROCESS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601) BASEMENT SHOWING PROCESS CORRIDOR AND EIGHTEEN CELLS. TO LEFT IS LABORATORY BUILDING (CPP-602). INL DRAWING NUMBER 200-0601-00-706-051981. ALTERNATE ID NUMBER CPP-E-1981. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery.

PubMed

Lin, Wen; Xie, Xiangyang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yang

2016-01-01

A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.

Efficacy of CPP-ACP and CPP-ACPF on enamel remineralization - an in vitro study using scanning electron microscope and DIAGNOdent.

PubMed

Jayarajan, Jayanth; Janardhanam, P; Jayakumar, P

2011-01-01

Remineralization as a treatment procedure has received a lot of attention both from clinicians as well researchers. The objective of this in vitro study was to find out the efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) in remineralizing enamel surface on which artificial caries lesion had been created. The changes were analyzed using DIAGNOdent (KaVo) and scanning electron microscope (SEM). Ninety maxillary premolars were selected and divided into three groups of 30 teeth each: A (artificial saliva), B (CPP-ACP), and C (CPP-ACPF). All the samples were assessed using DIAGNOdent at the baseline and after demineralization and remineralization. Three samples were randomly selected from each group after remineralization for surface evaluation using SEM. Statistical analysis showed that group B {CPP-ACP (4.1 ± 1.8)} and group C {CPP-ACPF (4.8 ± 1.2)} had a significantly higher amount of remineralization than group A (1.7 ± 0.7). All the three groups showed a statistically significant amount of remineralization. However, because of the added benefit of fluoride (NaF 0.2%), CPP-ACPF (Tooth Mousse-Plus) showed marginally more amount of remineralization than CPP-ACP (Tooth Mousse).

Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.

PubMed

Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang

2016-10-01

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.

A noninvasive estimation of cerebral perfusion pressure using critical closing pressure.

PubMed

Varsos, Georgios V; Kolias, Angelos G; Smielewski, Peter; Brady, Ken M; Varsos, Vassilis G; Hutchinson, Peter J; Pickard, John D; Czosnyka, Marek

2015-09-01

Cerebral blood flow is associated with cerebral perfusion pressure (CPP), which is clinically monitored through arterial blood pressure (ABP) and invasive measurements of intracranial pressure (ICP). Based on critical closing pressure (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP (eCPP). Data from 280 head-injured patients with ABP, ICP, and transcranial Doppler ultrasonography measurements were retrospectively examined. CrCP was calculated with a noninvasive version of the cerebrovascular impedance method. The eCPP was refined with a predictive regression model of CrCP-based estimation of ICP from known ICP using data from 232 patients, and validated with data from the remaining 48 patients. Cohort analysis showed eCPP to be correlated with measured CPP (R = 0.851, p < 0.001), with a mean ± SD difference of 4.02 ± 6.01 mm Hg, and 83.3% of the cases with an estimation error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area under the curve of 0.913 (95% CI 0.883-0.944). When each recording session of a patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD for estimating CPP between multiple recording sessions of 1.89-5.01 mm Hg. Overall, CrCP-based eCPP was strongly correlated with invasive CPP, with sensitivity and specificity for detection of low CPP that show promise for clinical use.

Incorporation of carrot pomace powder in wheat flour: effect on flour, dough and cookie characteristics.

PubMed

Ahmad, Mukhtar; Wani, Touseef Ahmed; Wani, S M; Masoodi, F A; Gani, Adil

2016-10-01

Carrot pomace powder (CPP) of 72 and 120 mesh sizes was incorporated in wheat flour at 10, 15 and 20 % level and its impact on flour, dough and cookie characteristics was evaluated. Protein content of the flour blends (8.84-7.88 %) decreased and fibre content (4.63-6.68 %) increased upon blending of CPP in wheat flour. Wheat flour containing 120 mesh CPP showed better functional properties [water absorption (1.16-1.47 %), oil absorption (1.11-1.39 %), solubility index (41-50 %) and swelling power (1.34-1.39)] than those containing 72 mesh. Water solvent retention capacity and sucrose solvent retention capacity increased while lactic acid solvent retention capacity and sodium carbonate solvent retention capacity decreased with blending of CPP. Water absorption, dough development time and degree of softening increased whereas, dough stability and mixing tolerance decreased with increasing CPP. The highest decrease in pasting was observed flour containing 72 mesh CPP. Rheology of dough containing 120 mesh CPP closely resembled the control. Color of flour and cookies increased with blending of CPP irrespective of mesh size. Antioxidant activity of cookies was higher than the flour blends. The cookies containing CPP of 72 mesh showed the lowest hardness. However, cookies containing CPP of 120 mesh showed the best sensory properties. Incorporation of 120 mesh CPP produced low gluten cookies with manageable flour and dough characteristics and better antioxidant and sensory properties.

Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology.

PubMed

Tsaltas, Eleftheria; Kontis, Dimitris; Chrysikakou, Sofia; Giannou, Haralambos; Biba, Angeliki; Pallidi, Stella; Christodoulou, Angeliki; Maillis, Antonis; Rabavilas, Andreas

2005-05-15

This study introduces a laboratory model of compulsive behavior based on persistence in the context of rewarded spatial alternation. Rats were screened for spontaneous persistence during T-maze reinforced alternation. Experiment 1: One high and one low spontaneous persistence group (n = 8) received 20 injections of fluoxetine, a matched pair saline, both followed by 4 days of meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP, desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine in mCPP group). After washout, animals received 2 days of naratriptan, followed by another 2-day mCPP challenge. In both experiments mCPP significantly increased persistence in saline controls. Fluoxetine also acutely increased persistence scores: after a gradual return to baseline, these scores showed tolerance to mCPP. Experiment 1: This pattern was significant in high but not low initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross-tolerance. Neither desipramine nor diazepam protected against mCPP challenge. Persistence scores returned to baseline during washout and naratriptan and were thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP groups, suggesting 5-HT2C receptor mediation. This model is based on spontaneous persistence behavior showing pharmacological responses concordant with those of compulsive symptomatology.

PLAN VIEW OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PLAN VIEW OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS. INL DRAWING NUMBER 200-0603-00-706-051285. ALTERNATE ID NUMBER CPP-D-1285. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Efficacy of pastes containing CPP-ACP and CPP-ACFP in patients with Sjögren's syndrome.

PubMed

Peric, Tamara; Markovic, Dejan; Petrovic, Bojan; Radojevic, Vesna; Todorovic, Tatjana; Radicevic, Biljana Andjelski; Heinemann, Radmila Jancic; Susic, Gordana; Popadic, Aleksandra Peric; Spiric, Vesna Tomic

2015-12-01

The purpose of this study was to evaluate efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) containing pastes among individuals with Sjögren's syndrome (SS). Thirty patients were randomised into three groups: CPP-ACP, CPP-ACFP, and 0.05 % NaF to be used two times a day during a 28-day experimental period. Saliva was analysed for flow rate, pH, buffering capacity and mineral concentrations. Dental plaque was examined for pH. Following the formation of artificial carious lesion, participants wore enamel slabs for an in situ remineralisation study. Remineralisation potential was examined using scanning electron microscope (SEM) and energy dispersive spectroscopic (EDS) technique. SE microphotographs were subsequently analysed for area, diameter, perimeter, roundness and the number of enamel defects and percentage of tooth surface affected by defects. At the end of the experimental period, a slight increase of salivary pH could have been observed. No differences in mineral composition of saliva were noted. The use of CPP-ACP and CPP-ACFP contributed to a significant rise of plaque pH. Image analysis revealed excessive reduction of defects' dimensions in the three experimental groups, and a decrease of the number of enamel defects in the CPP-ACP and CPP-ACFP groups. The EDS analysis did not show differences in Ca/P, Ca/O and P/O ratios in any of the treatment groups. CPP-ACP and CPP-ACFP hold promise as remineralising agents for patients with SS. Pastes containing CPP-ACP/CPP-ACFP show enhanced remineralisation potential compared with NaF mouthrinse in patients with SS.

30 CFR 585.627 - What information and certifications must I submit with my COP to assist the BOEM in complying...

Code of Federal Regulations, 2013 CFR

2013-07-01

....627 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY AND ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Plans and Information... total suspended solids from construction. (3) Biological resources Benthic communities, marine mammals...

30 CFR 585.627 - What information and certifications must I submit with my COP to assist the BOEM in complying...

Code of Federal Regulations, 2014 CFR

2014-07-01

....627 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY AND ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Plans and Information... total suspended solids from construction. (3) Biological resources Benthic communities, marine mammals...

30 CFR 585.627 - What information and certifications must I submit with my COP to assist the BOEM in complying...

Code of Federal Regulations, 2012 CFR

2012-07-01

....627 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE RENEWABLE ENERGY AND ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Plans and Information... total suspended solids from construction. (3) Biological resources Benthic communities, marine mammals...

Partial extinction of a conditioned context enhances preference for elements previously associated with cocaine but not with chocolate.

PubMed

Orsini, C; Bonito-Oliva, A; Montanari, C; Conversi, D; Cabib, S

2013-08-15

Drug-associated stimuli are crucial to reinstatement of drug-seeking after periods of abstinence, representing a central problem in treatment of addiction. The present study investigated the influence of partial extinction of the conditioned context on the expression of conditioned place preference (CPP). Mice of the inbred DBA/2J strain were conditioned with cocaine or chocolate in a context identified by multiple elements (A+B) and subsequently CPP expression was evaluated in a context containing only one element (A or B) or both (A+B). Cocaine- and chocolate-conditioned mice showed CPP in presence of the original compound stimulus. However, cocaine-conditioned mice did not show CPP when tested in A or B context, while chocolate-conditioned mice did show CPP to single element context. After conditioning mice were exposed to extinction training of the context A or B and then tested for CPP 1 and 9 days after the end of the extinction (days 9 and 18). Cocaine-conditioned mice showed CPP 9 days after extinction while chocolate-conditioned mice were relatively insensitive to the extinction procedure on day 1 after extinction, but they did not show CPP for the partial or the original compound 9 days after extinction. Cocaine-conditioned mice not submitted to the extinction training (simple passage of time) or submitted to a Sham-extinction procedure (saline injections and confinement in a new environment) did not show CPP on day 9 or 18. Cocaine-conditioned mice exposed to extinction training showed increased c-Fos expression in several brain areas in comparison to mice exposed to Sham-extinction. The extinction procedure did not specifically reduce behavioral sensitization. The results suggest that extinction training involving only elements of a drug-associated context can result in increased associative strength of those elements. © 2013.

30 CFR 285.627 - What information and certifications must I submit with my COP to assist the MMS in complying with...

Code of Federal Regulations, 2010 CFR

2010-07-01

... ENERGY ALTERNATE USES OF EXISTING FACILITIES ON THE OUTER CONTINENTAL SHELF Plans and Information Requirements Contents of the Construction and Operations Plan § 285.627 What information and certifications... the proposed activities described in detail in your plans comply with the State(s) approved coastal...

SOUTH ELEVATION OF IRRADIATED FUEL STORAGE FACILITY LOCATED IN FUEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH ELEVATION OF IRRADIATED FUEL STORAGE FACILITY LOCATED IN FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTH. INL PHOTO NUMBER HD-54-15-2. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH ELEVATION OF IRRADIATED FUEL STORAGE FACILITY LOCATED IN FUEL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH ELEVATION OF IRRADIATED FUEL STORAGE FACILITY LOCATED IN FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING SOUTH. INL PHOTO NUMBER HD-54-16-1. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Cell-penetrating peptide-siRNA conjugate loaded YSA-modified nanobubbles for ultrasound triggered siRNA delivery.

PubMed

Xie, Xiangyang; Yang, Yanfang; Lin, Wen; Liu, Hui; Liu, Hong; Yang, Yang; Chen, Ying; Fu, Xudong; Deng, Jianping

2015-12-01

Due to the absence of effective in vivo delivery systems, the employment of small interference RNA (siRNA) in the clinic has been hindered. In this paper, a new siRNA targeting system for EphA2-positive tumors was developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, a CPP-siRNA conjugate (CPP-siRNA) was entrapped in an ephrin mimetic peptide (YSA peptide)-modified NB (CPP-siRNA/YSA-NB) and the penetration of the CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research demonstrated that the CPP-siRNA/YSA-NBs had particle sizes of approximately 200 nm and a siRNA entrapment efficiency of more than 85%. The in vitro release results showed that over 90% of the encapsulated CPP-siRNA released from the NBs in the presence of ultrasound, while less than 1.5% of that (30 min) released without ultrasound. Cell experiments showed a the higher CPP-siRNA cellular uptake of CPP-siRNA/YSA-NB among the various formulations in human breast adenocarcinoma cells (MCF-7, EphA2 positive cells). Additionally, after systemic administration in mice, CPP-siRNA/YSA-NB accumulated in the tumor, augmented c-Myc silencing and delayed tumor progression. In conclusion, the application of CPP-siRNA/YSA-NB with ultrasound may provide a strategy for the selective and efficient delivery of siRNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

PubMed

Bahi, Amine; Dreyer, Jean-Luc

2014-01-01

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

PubMed

Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

2016-05-01

We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. © 2015 Society for the Study of Addiction.

Learning from bottom-up dissemination: Importing an evidence-based trauma intervention for infants and young children to Israel.

PubMed

David, Paula; Schiff, Miriam

2015-12-01

This article describes a pilot study of a "bottom up" dissemination process of a new evidence based intervention for treating early childhood trauma. Clinicians applied to learn Child-Parent Psychotherapy (CPP), imported to Israel from the U.S. A focus group of six graduates of a CPP training program responded to questions concerning their experiences learning and using CPP. All 39 CPP graduates from two cohorts also completed a cross sectional survey related to their use of CPP. Within the focus group, the openness of the workplace and the intervention's characteristics were considered major factors impacting CPP use; the training program was perceived to promote CPP implementation, and lack of supervision and secondary traumatic stress were the major inhibiting factors. Using CPP-informed therapy, as opposed to CPP with fidelity, was perceived to be one of the main outcomes of the training. Survey results showed that 53% of graduates were using CPP in over three cases, and almost all intended to use CPP within the next year. Ninety-five percent were using CPP principles in their therapeutic work. The implications of importing a new evidence based intervention to a foreign country that utilizes a different dissemination system within a different professional culture are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

1. CONTEXTUAL VIEW OF WASTE CALCINING FACILITY. CAMERA FACING NORTHEAST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. CONTEXTUAL VIEW OF WASTE CALCINING FACILITY. CAMERA FACING NORTHEAST. ON RIGHT OF VIEW IS PART OF EARTH/GRAVEL SHIELDING FOR BIN SET. AERIAL STRUCTURE MOUNTED ON POLES IS PNEUMATIC TRANSFER SYSTEM FOR DELIVERY OF SAMPLES BEING SENT FROM NEW WASTE CALCINING FACILITY TO THE CPP REMOTE ANALYTICAL LABORATORY. INEEL PROOF NUMBER HD-17-1. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

[Effect of casein phosphopeptide-amorphouscalcium phosphate (CPP-ACP) treatment on the shear bond strength of orthodontic brackets after tooth bleaching].

PubMed

Lu, Jing; Ding, Xiao-jun; Yu, Xiao-ping; Gong, Yi-ming

2015-10-01

To evaluate the effect of casein phosphopeptide-amorphouscalcium phosphate (CPP-ACP) treatment on the shear bond strength of orthodontic brackets after tooth bleaching. One hundred extracted human premolars were randomly divided and treated according to 5 groups (n=20) : (1) no treatment; (2) 10% carbamide peroxide bleaching; (3) 38% hydrogen peroxide bleaching; (4)10% carbamide peroxide bleaching and CPP-ACP paste; (5)38% hydrogen peroxide bleaching and CPP-ACP paste. In all groups, the brackets were bonded using a conventional acid-etch and bond system (Transbond XT, 3M Unitek, Monrovia, Calif). The shear bond strength adhesive remnant index (ARI) of the brackets were determined and the data was analyzed by ANOVA and Bonferroni test using SPSS13.0 software package. The use of 10% carbamide peroxide and 38% hydrogen peroxide bleaching significantly decreased the shear bond strength of orthodontic brackets when compared with untreated group (P<0.05). After combination of tooth bleaching and CPP-ACP treatment, group 4 (10% carbamide peroxide bleaching + CPP-ACP) and group 5 (38% hydrogen peroxide bleaching + CPP-ACP) showed higher levels of shear bond strength than group 2 and 3; however, no significant difference was found (P>0.05). The ARI did not show any significant difference before and after CPP-ACP treatment. After tooth bleaching, CPP-ACP treatment have little influence on the shear bond strength of orthodontic brackets.

Enhanced current-perpendicular-to-plane giant magnetoresistance effect in half-metallic NiMnSb based nanojunctions with multiple Ag spacers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wen, Zhenchao; Yamamoto, Tatsuya; Kubota, Takahide

2016-06-06

Current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) heterostructure devices using half-metallic NiMnSb Heusler alloy electrodes with single, dual, and triple Ag spacers were fabricated. The NiMnSb alloy films and Ag spacers show (001) epitaxial growth in all CPP-GMR multilayer structures. The dual-spacer CPP-GMR nanojunction exhibited an enhanced CPP-GMR ratio of 11% (a change in the resistance-area product, ΔRA, of 3.9 mΩ μm{sup 2}) at room temperature, which is approximately twice (thrice) of 6% (1.3 mΩ μm{sup 2}) in the single-spacer device. The enhancement of the CPP-GMR effects in the dual-spacer devices could be attributed to improved interfacial spin asymmetry. Moreover, it was observedmore » that the CPP-GMR ratios increased monotonically as the temperatures decreased. At 4.2 K, a CPP-GMR ratio of 41% (ΔRA = 10.5 mΩ μm{sup 2}) was achieved in the dual-spacer CPP-GMR device. This work indicates that multispacer structures provide an efficient enhancement of CPP-GMR effects in half-metallic material-based CPP-GMR systems.« less

Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

PubMed

Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

2016-05-01

Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting

PubMed Central

Song, Young Hyun; Ji, Eun Kyung; Jeong, Byung Woo; Jung, Mong Kwon; Kim, Eun Young; Yoon, Dae Ho

2016-01-01

We report on Y3Al5O12: Ce3+ ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce3+ concentration. The luminous properties of the Y3Al5O12: Ce3+ CPP nano phosphor are improved when compared to the Y3Al5O12: Ce3+ CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce3+ CPP with an optimal Ce3+ content of 0.5 mol % shows 2733 lm/mm2 value under high power blue radiant flux density of 19.1 W/mm2. The results indicate that Y3Al5O12: Ce3+ CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications. PMID:27502730

High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting.

PubMed

Song, Young Hyun; Ji, Eun Kyung; Jeong, Byung Woo; Jung, Mong Kwon; Kim, Eun Young; Yoon, Dae Ho

2016-08-09

We report on Y3Al5O12: Ce(3+) ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce(3+) concentration. The luminous properties of the Y3Al5O12: Ce(3+) CPP nano phosphor are improved when compared to the Y3Al5O12: Ce(3+) CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce(3+) CPP with an optimal Ce(3+) content of 0.5 mol % shows 2733 lm/mm(2) value under high power blue radiant flux density of 19.1 W/mm(2). The results indicate that Y3Al5O12: Ce(3+) CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications.

Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone.

PubMed

Kast, Richard E

2009-01-01

Since deleterious effects of m-CPP, the primary catabolic metabolite of trazodone, were last reviewed 2 years ago, research data continue to accrue showing that clinically significant levels of m-CPP (a) are generated in patients using trazodone for sleep and (b) are present 24 h a day and (c) have potentially serious ill effects. This commentary argues that the documented potential for harm and multiple risks of m-CPP outweigh potential benefits of trazodone, given the development and marketing of many safer alternatives since trazodone's introduction in the 1980s.

Changes in regional gray matter volume in women with chronic pelvic pain - a voxel based morphometry study

PubMed Central

As-Sanie, Sawsan; Harris, Richard; Napadow, Vitaly; Kim, Jieun; Neshewat, Gina; Kairys, Anson; Williams, David; Clauw, Daniel; Schmidt-Wilcke, Tobias

2012-01-01

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15-20% of women in the United States. Endometriosis is often associated with CPP, however other factors, such as pre-existing or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing.Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, as well as 23 healthy controls. All patients with endometriosis and/or CPP were surgically-confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception including the left thalamus, left cingulategyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis that had no CPP. We conclude thatCPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis. PMID:22387096

Intracranial pressure and cerebral perfusion pressure in patients developing brain death.

PubMed

Salih, Farid; Holtkamp, Martin; Brandt, Stephan A; Hoffmann, Olaf; Masuhr, Florian; Schreiber, Stephan; Weissinger, Florian; Vajkoczy, Peter; Wolf, Stefan

2016-08-01

We investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). We retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. Intracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (-8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. Brain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow. Copyright © 2016 Elsevier Inc. All rights reserved.

Cycling peak power in obese and lean 6- to 8-year-old girls and boys.

PubMed

Aucouturier, Julien; Lazaar, Nordine; Doré, Eric; Meyer, Martine; Ratel, Sebastien; Duché, Pascale

2007-06-01

The purpose of this study was to investigate the possible effect of the difference in percentage body fat (%BF) and fat-free mass (FFM) on cycling peak power (CPP) in 6- to 8-year-old obese and lean untrained girls and boys. Obese (35 girls, 35 boys) and lean (35 girls, 35 boys) children were measured for obesity, %BF, calculated from skinfold measurements. FFM was calculated as body mass (BM) minus body fat. A force-velocity test on a cycle ergometer was used to measure CPP. CPP was related to anthropometric variables using standard and allometric models. CPP in absolute terms was higher in obese children than in lean children irrespective of gender. BM-related CPP was significantly lower in obese children than in lean ones, whereas no effect of obesity appeared on FFM-related CPP. Velocity at CPP (Vopt) was significantly lower and force at CPP (Fopt) was significantly higher in girls than in boys. Muscle power production was unaffected by obesity in children. Low BM-related CPP could explain the difficulty of taking up physical activities that are body-mass related in obese children. Gender difference for Vopt and Fopt shows that girls and boys may have different maturation patterns affecting CPP.

Incorporation of casein phosphopeptide-amorphous calcium phosphate into a glass-ionomer cement.

PubMed

Mazzaoui, S A; Burrow, M F; Tyas, M J; Dashper, S G; Eakins, D; Reynolds, E C

2003-11-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes have been shown to prevent demineralization and promote remineralization of enamel subsurface lesions in animal and in situ caries models. The aim of this study was to determine the effect of incorporating CPP-ACP into a self-cured glass-ionomer cement (GIC). Incorporation of 1.56% w/w CPP-ACP into the GIC significantly increased microtensile bond strength (33%) and compressive strength (23%) and significantly enhanced the release of calcium, phosphate, and fluoride ions at neutral and acidic pH. MALDI mass spectrometry also showed casein phosphopeptides from the CPP-ACP nanocomplexes to be released. The release of CPP-ACP and fluoride from the CPP-ACP-containing GIC was associated with enhanced protection of the adjacent dentin during acid challenge in vitro.

Feasibility study for early removal of HEU from CPP-651-Phase II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, C.V.; Henry, R.; Milligan, C.

1997-09-01

A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology andmore » the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.« less

CALCIPROTEIN PARTICLE FORMATION IN PERITONEAL DIALYSIS EFFLUENT IS DEPENDENT ON DIALYSATE CALCIUM CONCENTRATION.

PubMed

Cai, Michael M; Smith, Edward R; Kent, Annette; Huang, Louis; Hewitson, Tim D; McMahon, Lawrence P; Holt, Stephen G

2018-05-23

The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo Method: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo , compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.

Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum.

PubMed

Reynolds, E C; Cai, F; Shen, P; Walker, G D

2003-03-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to compare the ability of CPP-ACP, with that of other forms of calcium, to be retained in supragingival plaque and remineralize enamel subsurface lesions in situ when delivered in a mouthrinse or sugar-free gum in randomized, double-blind trials. In the mouthrinse study, only the CPP-ACP-containing mouthrinse significantly increased plaque calcium and inorganic phosphate levels, and the CPP were immunolocalized to the surfaces of bacterial cells as well as the intercellular matrix. In the chewing gum studies, the gum containing the CPP-ACP, although not containing the most calcium per piece of gum, produced the highest level of enamel remineralization independent of gum-chewing frequency and duration. The CPP could be detected in plaque extracts 3 hrs after subjects chewed the CPP-ACP-containing gum. The results showed that CPP-ACP were superior to other forms of calcium in remineralizing enamel subsurface lesions.

35. MISCELLANEOUS ARCHITECTURAL AND STRUCTURAL DETAILS. INEEL DRAWING NUMBER 200063300287106359. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

35. MISCELLANEOUS ARCHITECTURAL AND STRUCTURAL DETAILS. INEEL DRAWING NUMBER 200-0633-00-287-106359. FLUOR NUMBER 5775-CPP-633-A-9. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

34. DOOR AND WINDOW DETAILS. INEEL DRAWING NUMBER 200063300287106358. FLUOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

34. DOOR AND WINDOW DETAILS. INEEL DRAWING NUMBER 200-0633-00-287-106358. FLUOR NUMBER 5775-CPP-633-A-8. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

33. ROOF PLAN AND DETAILS. INEEL DRAWING NUMBER 200063300287106357. FLUOR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

33. ROOF PLAN AND DETAILS. INEEL DRAWING NUMBER 200-0633-00-287-106357. FLUOR NUMBER 5775-CPP-633-A-7. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

Biochemical transformation of calciprotein particles in uraemia.

PubMed

Smith, Edward R; Hewitson, Tim D; Hanssen, Eric; Holt, Stephen G

2018-05-01

Calciprotein particles (CPP) have emerged as nanoscale mediators of phosphate-induced toxicity in Chronic Kidney Disease (CKD). Uraemia favors ripening of the particle mineral content from the amorphous (CPP-I) to the crystalline state (CPP-II) but the pathophysiological significance of this transformation is uncertain. Clinical studies suggest an association between CPP ripening and inflammation, vascular dysfunction and mortality. Although ripening has been modelled in vitro, it is unknown whether particles synthesised in serum resemble their in vivo counterparts. Here we show that in vitro formation and ripening of CPP in uraemic serum is characterised by extensive physiochemical rearrangements involving the accretion of mineral, loss of surface charge and transformation of the mineral phase from a spherical arrangement of diffuse domains of amorphous calcium phosphate to densely-packed lamellar aggregates of crystalline hydroxyapatite. These physiochemical changes were paralleled by enrichment with small soluble apolipoproteins, complement factors and the binding of fatty acids. In comparison, endogenous CPP represent a highly heterogeneous mixture of particles with characteristics mostly intermediate to synthetic CPP-I and CPP-II, but are also uniquely enriched for carbonate-substituted apatite, DNA fragments, small RNA and microbe-derived components. Pathway analysis of protein enrichment predicted the activation of cell death and pro-inflammatory processes by endogenous CPP and synthetic CPP-II alike. This comprehensive characterisation validates the use of CPP-II generated in uraemic serum as in vitro equivalents of their endogenous counterparts and provides insight into the nature and pathological significance of CPP in CKD, which may act as vehicles for various bioactive ligands. Copyright © 2018 Elsevier Inc. All rights reserved.

An in vitro comparison of casein phosphopeptide-amorphous calcium phosphate paste, casein phosphopeptide-amorphous calcium phosphate paste with fluoride and casein phosphopeptide-amorphous calcium phosphate varnish on the inhibition of demineralization and promotion of remineralization of enamel.

PubMed

Thakkar, Prachi Jayesh; Badakar, Chandrashekhar M; Hugar, Shivayogi M; Hallikerimath, Seema; Patel, Punit M; Shah, Parin

2017-01-01

This study aims to determine and compare the extent of inhibition of demineralization and promotion of remineralization of permanent molar enamel with and without application of three remineralizing agents. Forty extracted permanent molars were randomly divided into two groups 1 and 2, longitudinally sectioned into four and divided into subgroups A, B, C, and D. The sections were coated with nail varnish leaving a window of 3 mm × 3 mm. All sections of Group 1 were treated with their respective subgroup-specific agent: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste for subgroup A, CPP-amorphous calcium phosphate fluoride (ACPF) paste for subgroup B, CPP-ACPF varnish for subgroup C and subgroup D served as a control. The sections were then subjected to demineralization for 12 days following which lesional depth was measured under the stereomicroscope. All the sections of Group 2 were subjected to demineralization for 12 days, examined for lesional depth, then treated with their respective subgroup specific agents and immersed in artificial saliva for 7 days. The sections were then examined again under the stereomicroscope to measure the lesional depth. CPP-ACPF varnish caused significant inhibition of demineralization. All three agents showed significant remineralization of previously demineralized lesions. However, CPP-ACPF varnish showed the greatest remineralization, followed by CPP-ACPF paste and then CPP-ACP paste. This study shows that CPP-ACPF varnish is effective in preventing demineralization as well as promoting remineralization of enamel. Thus, it can be used as an effective preventive measure for pediatric patients where compliance with the use of tooth mousse may be questionable.

THE ENDOCANNABINOID SYSTEM MODULATES THE VALENCE OF THE EMOTION ASSOCIATED TO FOOD INGESTION

PubMed Central

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, O.

2010-01-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant, or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide and if such CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. PMID:21182571

Design, synthesis, and functional testing of recombinant cell penetrating peptides

NASA Astrophysics Data System (ADS)

Widyaningtyas, S. T.; Soebandrio, A.; Ibrahim, F.; Bela, B.

2017-08-01

Cell penetrating peptides (CPP) are one of the most attractive DNA delivery systems currently in development. In this research, in silico CPP development was performed based on a literature study to look for peptides that induce endosome escape, have the ability to bind DNA, and pass through cell membranes and/or nuclear membranes with a final goal of creating a new CPP to be used as a DNA delivery system. We report herein the successful isolation of three candidate CPP molecules, which have all been successfully expressed and purified by NiNTA. One of the determinants of CPP success as a DNA carrier is the ability of the CPP to bind and protect DNA from the effects of nucleases. The DNA binding test results show that all three CPPs can bind to DNA and protect it from the effects of serum nucleases. These three CPP candidates designed in silico and synthesized in the prokaryote system are eligible candidates for further testing of their ability to deliver DNA in vitro and in vivo.

7. WASTE CALCINING FACILITY, LOOKING AT NORTH END OF BUILDING. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

7. WASTE CALCINING FACILITY, LOOKING AT NORTH END OF BUILDING. CAMERA FACING SOUTH. TENT-ROOFED COVER IN RIGHT OF VIEW IS A TEMPORARY WEATHER-PROOFING SHELTER OVER THE BLOWER PIT IN CONNECTION WITH DEMOLITION PROCEDURES. SMALL BUILDING CPP-667 IN CENTER OF VIEW WAS USED FOR SUPPLEMENTARY OFFICE SPACE BY HEALTH PHYSICISTS AND OTHERS. INEEL PROOF SHEET NOT NUMBERED. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

27. ELEVATIONS OF EAST AND WEST SIDES. INEEL DRAWING NUMBER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

27. ELEVATIONS OF EAST AND WEST SIDES. INEEL DRAWING NUMBER 200-0633-00-287-106355. FLUOR NUMBER 5775-CPP-633-A-5. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

28. NORTH AND SOUTH ELEVATIONS AND TWO SECTIONS. INEEL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

28. NORTH AND SOUTH ELEVATIONS AND TWO SECTIONS. INEEL DRAWING NUMBER 200-0633-00-287-106356. FLUOR NUMBER 5775-CPP-633-A-6. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

Storage study and quality evaluation of coconut protein powder.

PubMed

Naik, Aduja; Prakash, Maya; R, Ravi; Raghavarao, Ksms

2013-11-01

Coconut skim milk and insoluble protein are 2 major byproducts in the production of virgin coconut oil. Coconut skim milk was homogenized along with insoluble protein and spray dried to obtain a value-added product, namely, coconut protein powder (CPP). This study deals with the storage study of CPP under different conditions (refrigerated [control], ambient and accelerated). CPP samples were withdrawn periodically at designated intervals of 15 d for accelerated and control, and 30 d for ambient condition. CPP stored at different conditions exhibited marginal moisture uptake (by 0.74 % w/w for control, 0.76 % w/w for ambient, and 1.26 % w/w for accelerated condition) and as a result, had very little effect on the functional properties of the powder. Withdrawn CPP was tested for sensory quality aspects and subjected to instrumental analysis as well. Withdrawn CPP was incorporated as a milk substitute in dessert (Kheer). Quantitative descriptive analysis of the powder and product (Kheer) showed no significant difference in attributes of CPP during the storage period of 2 mo. Electronic nose analysis revealed that CPP samples were not much different with respect to aroma pattern matching, respectively. © 2013 CSIR-Central Food Technological Research Institute.

Reinstatement of Morphine-Induced Conditioned Place Preference in Mice by Priming Injections

PubMed Central

Do Couto, B. Ribeiro; Aguilar, M. A.; Manzanedo, C.; Rodríguez-Arias, M.; Miñarro, J.

2003-01-01

To construct a model of relapse of drug abuse in mice, the induction, we evaluated the extinction and reinstatement of morphine-induced place preference. In Experiment 1, we examined the effects of morphine (0, 2, 3, 5, 10, 20 and 40 mg/kg) in the conditioned place preference (CPP) paradigm. Mice showed CPP with 5, 10, 20 and 40 mg/kg. In Experiment 2, we evaluated the effects of two different extinction procedures. After conditioning with 40 mg/kg of morphine, the mice underwent daily extinction sessions of 60 or 15 min of duration. CPP was extinguished after seven and nine sessions, respectively. In Experiment 3, we tested the reinstating effects of several priming doses of morphine. Mice were conditioned with 40 mg/kg of morphine and underwent the daily 15 min extinction sessions until CPP was no longer evident. Then, the effects of morphine (0, 2, 3, 5, 10, 20, 40 mg/kg, i.p.) were evaluated. CPP was reinstated by doses from 5 mg/kg upward. The results show that morphine priming injections are effective in reactivating opiateseeking behavior in mice, and thus, the CPP paradigm might be useful to investigate the mechanisms underlying relapse of drug abuse. PMID:15152982

Extraction optimization and influences of drying methods on antioxidant activities of polysaccharide from cup plant (Silphium perfoliatum L.)

PubMed Central

Li, Ran; Duan, Meng-Ying; Wu, Hong-Xin

2017-01-01

Response surface methodology (RSM) was used to investigate the extraction condition of polysaccharide from cup plant (Silphium perfoliatum L.) (named CPP). Water to raw material ratio (10–30 mL/g), extraction time (40–80 min) and extraction temperature (60–100°C) were set as the 3 independent variables, and their effects on the extraction yield of CPP were measured. In addition, the effects of drying methods including hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activities of CPP were evaluated. The results showed that the optimal condition to extract CPP was: water to raw material ratio (15 mL/g), extraction time (61 min), and extraction temperature (97°C), a maximum CPP yield of 6.49% was obtained under this condition. CPP drying with FD method showed stronger reducing power (0.943 at 6 mg/mL) and radical scavenging capacities against DPPH radical (75.71% at 1.2 mg/mL) and ABTS radical (98.06 at 1.6 mg/mL) than CPP drying with HD and VD methods. Therefore, freeze drying served as a good method for keeping the antioxidant activities of polysaccharide from cup plant. The polysaccharide from cup plant has potential to use as a natural antioxidant. PMID:28837625

CONSTRUCTION VIEW FUEL STORAGE BUILDING (CPP603) LOOKING EAST SHOWING ASBESTOS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW FUEL STORAGE BUILDING (CPP-603) LOOKING EAST SHOWING ASBESTOS SIDING. INL PHOTO NUMBER NRTS-51-1543. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING MAIN PROCESSING BUILDING (CPP601) LOOKING NORTH. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTH. INL PHOTO NUMBER NRTS-51-1387. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING FUEL STORAGE BUILDING (CPP603) LOOKING NORTHWEST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING FUEL STORAGE BUILDING (CPP-603) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-50-895. Unknown Photographer, 10/30/1950 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

41. OPERATING CORRIDOR PLAN AND SECTIONS, INCLUDING SOME ISOMETRIC DETAILS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

41. OPERATING CORRIDOR PLAN AND SECTIONS, INCLUDING SOME ISOMETRIC DETAILS. INEEL DRAWING NUMBER 200-0633-00-287-106455. FLUOR NUMBER 5775-CPP-633-P-60 - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

The endocannabinoid system modulates the valence of the emotion associated to food ingestion.

PubMed

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, Oscar

2012-07-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive-valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. © 2010 The Authors. Addiction Biology © 2010 Society for the Study of Addiction.

INTERIOR VIEW OF FUEL STORAGE BUILDING (CPP603) SHOWING CRANE ASSEMBLY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR VIEW OF FUEL STORAGE BUILDING (CPP-603) SHOWING CRANE ASSEMBLY FOR TRANSFER PIT. INL PHOTO NUMBER NRTS-51-2404. Unknown Photographer, 5/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Cannabinoid 1 receptor blockade in the dorsal hippocampus prevents the reinstatement but not acquisition of morphine-induced conditioned place preference in rats.

PubMed

Zhao, Xin; Yao, Li; Wang, Fang; Zhang, Han; Wu, Li

2017-07-05

The cannabinoid 1 receptors (CB1Rs) signaling is strongly linked to conditioned rewarding effects of opiates. Learned associations between environmental contexts and discrete cues and drug use play an important role in the maintenance and/or relapse of morphine addiction. Although previous studies suggest that context-dependent morphine treatment alters endocannabinoid signaling and synaptic plasticity in the hippocampus, the role of endocannabinoid in morphine conditioned place preference (CPP) and reinstatement remains unknown. In the present study, we found daily escalating doses of morphine induce significant CPP in rats. After the extinction of CPP, a priming dose of morphine was sufficient to reinstate morphine CPP and was associated with the elevated CB1R levels compared with saline control groups, suggesting upregulation of CB1R pathway in the hippocampus contribute to the reinstatement of morphine CPP. By using a pharmacological inhibitor of CB1R administered into the dorsal hippocampus, we showed that blockade of CB1R signaling did not alter the morphine CPP acquisition but inhibited the reinstatement of morphine CPP. In addition, no effects were induced upon CB1R blockade in the prefrontal cortex on reinstatement of morphine CPP. These studies reveal region-specific effects of hippocampal blockade of CB1R signaling pathway on the reinstatement of morphine CPP.

Randomized clinical trial of the effect of NovaMin and CPP-ACPF in combination with dental bleaching.

PubMed

Alexandrino, Larissa Dias; Alencar, Cristiane de Melo; Silveira, Ana Daniela Silva da; Alves, Eliane Bemerguy; Silva, Cecy Martins

2017-01-01

This randomized, controlled, double-blind clinical study evaluated the effect of calcium sodium phosphosilicate (NovaMin) and casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) on the prevention of post-operative sensitivity and on the effects of clinical bleaching treatment. Sixty volunteers were selected according to inclusion and exclusion criteria and were randomly assigned into three groups (n=20): CG (control group) patients, who were treated with 35% hydrogen peroxide; NOVAG (NovaMin group) patients, who were treated with 35% hydrogen peroxide followed by the application of NovaMin; and CPPG (CPP group) patients, who were treated with 35% hydrogen peroxide followed by the application of CPP-ACPF. Both bioactive agents were applied for five minutes. An evaporative stimulus associated with a modified visual scale was used to analyze sensitivity 24 hours after each bleaching session. The color evaluation was performed on the maxillary central incisors using a spectrophotometer. Associations between the intervention group, bleaching session, and reported sensitivity were tested using Chi-square partitioning. Color change values (ΔE) were analyzed using analysis of variance (ANOVA). The significance level used for both tests was 5%. In the intragroup assessment, the Friedman test showed that only the CPP-ACPF group showed no statistically significant difference (p<0.05) between baseline and first bleaching session. In the intergroup assessment, the Kruskal-Wallis test showed that the CPPG had less postoperative sensitivity after the first session, when compared to the other groups (p<0.05). Color change analysis (ΔE) showed a significant difference between the means obtained in the different bleaching sessions in all groups (p<0.05). This study showed that the combination of CPP-ACPF with 35% hydrogen peroxide significantly reduced post-operative sensitivity in the first session, compared with the other evaluated treatments. The association of CPP-ACPF and NovaMin did not affect the color change induced by tooth bleaching.

Evaluation of rainfall retrievals from SEVIRI reflectances over West Africa using TRMM-PR and CMORPH

NASA Astrophysics Data System (ADS)

Wolters, E. L. A.; van den Hurk, B. J. J. M.; Roebeling, R. A.

2011-02-01

This paper describes the evaluation of the KNMI Cloud Physical Properties - Precipitation Properties (CPP-PP) algorithm over West Africa. The algorithm combines condensed water path (CWP), cloud phase (CPH), cloud particle effective radius (re), and cloud-top temperature (CTT) retrievals from visible, near-infrared and thermal infrared observations of the Spinning Enhanced Visible and Infrared Imager (SEVIRI) onboard the Meteosat Second Generation (MSG) satellites to estimate rain occurrence frequency and rain rate. For the 2005 and 2006 monsoon seasons, it is investigated whether the CPP-PP algorithm is capable of retrieving rain occurrence frequency and rain rate over West Africa with sufficient accuracy, using Tropical Monsoon Measurement Mission Precipitation Radar (TRMM-PR) as reference. As a second goal, it is assessed whether SEVIRI is capable of monitoring the seasonal and daytime evolution of rainfall during the West African monsoon (WAM), using Climate Prediction Center Morphing Technique (CMORPH) rainfall observations. The SEVIRI-detected rainfall area agrees well with TRMM-PR, with the areal extent of rainfall by SEVIRI being ~10% larger than from TRMM-PR. The mean retrieved rain rate from CPP-PP is about 8% higher than from TRMM-PR. Examination of the TRMM-PR and CPP-PP cumulative frequency distributions revealed that differences between CPP-PP and TRMM-PR are generally within +/-10%. Relative to the AMMA rain gauge observations, CPP-PP shows very good agreement up to 5 mm h-1. However, at higher rain rates (5-16 mm h-1) CPP-PP overestimates compared to the rain gauges. With respect to the second goal of this paper, it was shown that both the accumulated precipitation and the seasonal progression of rainfall throughout the WAM is in good agreement with CMORPH, although CPP-PP retrieves higher amounts in the coastal region of West Africa. Using latitudinal Hovmüller diagrams, a fair correspondence between CPP-PP and CMORPH was found, which is reflected by high correlation coefficients (~0.7) for both rain rate and rain occurrence frequency. The daytime cycle of rainfall from CPP-PP shows distinctly different patterns for three different regions in West Africa throughout the WAM, with a decrease in dynamical range of rainfall near the Inter Tropical Convergence Zone (ITCZ). The dynamical range as retrieved from CPP-PP is larger than that from CMORPH. It is suggested that this results from both the better spatio-temporal resolution of SEVIRI, as well as from thermal infrared radiances being partly used by CMORPH, which likely smoothes the daytime precipitation signal, especially in case of cold anvils from convective systems. The promising results show that the CPP-PP algorithm, taking advantage of the high spatio-temporal resolution of SEVIRI, is of added value for monitoring daytime precipitation patterns in tropical areas.

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

PubMed Central

Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2016-01-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

PubMed

Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2015-12-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Multidisciplinary pain facility treatment outcome for pain-associated fatigue.

PubMed

Fishbain, David A; Lewis, John; Cole, Brandly; Cutler, Brian; Smets, Eve; Rosomoff, Hubert; Rosomoff, Rennee Steele

2005-01-01

Fatigue is frequently found in chronic pain patients (CPPs) and may be etiologically related to the presence of pain. Fishbain et al. have recently demonstrated that chronic low back pain (LBP) and chronic neck pain patients are more fatigued than controls. The purpose of this study was to determine whether chronic LBP- and chronic neck pain-associated fatigue responded to multidisciplinary multimodal treatment not specifically targeted to the treatment of fatigue. A total of 85 chronic LBP and 33 chronic neck pain patients completed the Multidimensional Fatigue Inventory (MFI), Neuropathic Pain Scale (NPS), and Beck Depression Inventory on admission. In addition, an information tool was completed on each CPP by the senior author. This tool listed demographic information, primary and secondary pain diagnoses, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) psychiatric diagnoses assigned, pain location, pain precipitating event, type of injury, years in pain, number of surgeries, type of surgery, type of pain pattern, opioids consumed per day in morphine equivalents, worker compensation status, and whether, according to the clinical examination, the CPP had a neuropathic pain component. At completion of the multidisciplinary multimodal treatment, each CPP again completed the MFI. Student's t-test was utilized to test for statistical changes on the MFI five scales from pre- to post-treatment. Pearson and point-biserial correlations were utilized to determine which variables significantly correlated with MFI change scores. Variables found significant at less than or equal to 0.01 were utilized in a stepwise aggression analysis to find variables predictive of change in MFI scores. Multidisciplinary pain facility. Chronic LBP and chronic neck pain patients. Multidisciplinary multimodal treatment significantly improved CPP fatigue as measured by the MFI. The available variables utilized to predict fatigue best explained only a small percentage (28.9%) of the variance. Improvement in fatigue was related to NPS-10 scale scores (neuropathic pain) and a previous diagnosis of fibromyalgia. Multidisciplinary multimodal pain facility treatment improves chronic LBP- and neck pain-associated fatigue. At the present time we cannot predict this improvement with significant accuracy.

Prenatal stress increases adult vulnerability to cocaine reward without affecting pubertal anxiety or novelty response.

PubMed

Pastor, Verónica; Pallarés, María Eugenia; Antonelli, Marta C

2018-02-26

Prenatal stress (PS) induces long-lasting molecular alterations in brain circuits of the offspring and increases the propensity to develop neuropsychiatric diseases during adulthood, including mood disorders and drug addiction. A major goal of this study was to assess the impact of PS on pubertal behaviour and adult vulnerability to cocaine-induced conditioning place preference (CPP). We therefore evaluated pubertal novelty response and anxiety-like behaviour in control (C) and PS rats, and then, we examined cocaine-induced CPP in those animals during adulthood. We found no differences between C and PS groups on pubertal behaviour, however, only PS rats showed a significant cocaine-induced CPP. To further analyze our results, we classified cocaine-treated rats regarding their CPP score in Low CPP or High CPP and we then analysed their pubertal behaviour. We found different relations of anxiety-like behaviour to cocaine reward as a function of PS exposure: for C group, High CPP and Low CPP had shown similar levels of anxiety-like behaviour at puberty; on the contrary, for PS group, High CPP had shown lower anxiety-like behaviour than Low CPP rats. This study underscores the importance of considering prenatal exposure to stress when analysing the relationship between anxiety and cocaine vulnerability. Moreover, the evaluation of behavioural traits at puberty opens the possibility of early intervention and will allow the development of specific prevention strategies to avoid the devastating consequences of drug addiction later in life. Copyright © 2017 Elsevier B.V. All rights reserved.

A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR.

PubMed

Lum, G; Freeman, K; Nguyen, N L; Limnios, E A; Tabrizi, S N; Carter, I; Chambers, I W; Whiley, D M; Sloots, T P; Garland, S M; Tapsall, J W

2005-10-01

To describe the prevalence and characteristics of isolates of Neisseria gonorrhoeae grown from urine samples that produced negative results with nucleic acid amplification assays (NAA) targeting the cppB gene. An initial cluster of culture positive, but cppB gene based NAA negative, gonococcal infections was recognised. Urine samples and suspensions of gonococci isolated over 9 months in the Northern Territory of Australia were examined using cppB gene based and other non-cppB gene based NAA. The gonococcal isolates were phenotyped by determining the auxotype/serovar (A/S) class and genotyped by pulsed field gel electrophoresis (PFGE). 14 (9.8%) of 143 gonococci isolated were of A/S class Pro(-/)Brpyut, indistinguishable on PFGE and negative in cppB gene based, but not other, NAA. This cluster represents a temporal and geographic expansion of a gonococcal subtype lacking the cppB gene with consequent loss of sensitivity of NAA dependent on amplification of this target. Gonococci lacking the cppB gene have in the past been more commonly associated with the PAU-/PCU- auxotype, a gonococcal subtype hitherto infrequently encountered in Australia. NAA based on the cppB gene as a target may produce false positive as well as false negative NAA. This suggests that unless there is continuing comparison with culture to show their utility, cppB gene based NAA should be regarded as suboptimal for use either as a diagnostic or supplemental assay for diagnosis of gonorrhoea, and NAA with alternative amplification targets should be substituted.

Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.

PubMed

Schindler, Abigail G; Li, Shuang; Chavkin, Charles

2010-08-01

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice.

PubMed

Singh, Prableen K; Lutfy, Kabirullah

2017-08-01

Previous preclinical studies have shown that nicotine pretreatment during adolescence increases the reinforcing actions of cocaine. However, little is known about the effect of prior nicotine administration on cocaine-induced conditioned place preference (CPP) and its reinstatement in adult mice. Besides, little information is available regarding the role of sex in this cross-talk between nicotine and cocaine. Thus, we examined if nicotine administration during adulthood would differentially alter cocaine-induced CPP, its extinction and reinstatement in male versus female mice and if the dose of nicotine was important in this regard. To this end, mice were pretreated with saline or nicotine (0.25 or 1mg/kg; twice daily for seven days) and then tested for place preference before and after single and repeated conditioning with cocaine (15mg/kg). Mice were then exposed to extinction training and tested for reinstatement of CPP. Our results showed that male and female mice pretreated with saline and conditioned with cocaine each exhibited a robust CPP after a single cocaine conditioning. However, this response was blunted in mice pretreated with the lower but not higher dose of nicotine. Female mice pretreated with the lower dose nicotine also failed to show CPP after repeated conditioning. Reinstatement of cocaine-induced CPP was also blunted in these mice compared to their respective controls. Together, these results suggest that nicotine administration during adulthood exerts differential effects on cocaine-induced CPP and its reinstatement in male and female mice and the dose of nicotine is important in this regard. Copyright © 2017 Elsevier Inc. All rights reserved.

Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice.

PubMed

Pandy, Vijayapandi; Khan, Yasmin

2016-11-01

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings.

Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice

PubMed Central

Pandy, Vijayapandi; Khan, Yasmin

2016-01-01

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings. PMID:27333840

Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.

PubMed

Bryant, Camron D; Kole, Loren A; Guido, Michael A; Cheng, Riyan; Palmer, Abraham A

2012-01-01

The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.

Casein phosphopeptide-amorphous calcium phosphate and shear bond strength of adhesives to primary teeth enamel.

PubMed

Farokh Gisovar, Elham; Hedayati, Nassim; Shadman, Niloofar; Shafiee, Leila

2015-02-01

CPP-ACP (Phosphopeptide-Amorphous Calcium Phosphate) has an important role in caries prevention in pediatric patients. This study was done, because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations. This study aimed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on shear bond strength of dental adhesives to enamel of primary teeth molars. This in vitro study was conducted on 180 extracted primary molars. They were randomly divided into 6 groups and each group was divided into 2 subgroups (treated with CPP-ACP and untreated). In subgroups with CPP-ACP, enamel was treated with CPP-ACP paste 1 h/d for 5 days. Types of adhesives that were evaluated in this study were Tetric N-Bond, AdheSE, AdheSE One F, single Bond 2, SE Bond, and Adper Prompt L-Pop. Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope. Data were analyzed by T test, 2-way analysis of variance (ANOVA), Tukey and Fisher exact test using SPSS18. P < 0.05 was considered as significance level. Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference (P > 0.05). Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type. Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel. To have a successful and durable composite restoration, having a high strength bonding is essential. Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength (SBS) in success of composite restoration, we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel.

Taming the Wildness of "Trojan-Horse" Peptides by Charge-Guided Masking and Protease-Triggered Demasking for the Controlled Delivery of Antitumor Agents.

PubMed

Shi, Nian-Qiu; Qi, Xian-Rong

2017-03-29

Cell-penetrating peptide (CPP), also called "Trojan Horse" peptide, has become a successful approach to deliver various payloads into cells for achieving the intracellular access. However, the "Trojan Horse" peptide is too wild, not just to "Troy", but rather widely distributed in the body. Thus, there is an urgent need to tame the wildness of "Trojan Horse" peptide for targeted delivery of antineoplastic agents to the tumor site. To achieve this goal, we exploit a masked CPP-doxorubicin conjugate platform for targeted delivery of chemotherapeutic drugs using charge-guided masking and protease-triggered demasking strategies. In this platform, the cell-penetrating function of the positively CPP (d-form nonaarginine) is abrogated by a negatively shielding peptide (masked CPP), and between them is a cleavable substrate peptide by the protease (MMP-2/9). Protease-triggered demasking would occur when the masked CPP reached the MMP-2/9-riched tumor. The CPP-doxorubicin conjugate (CPP-Dox) and the masked CPP-Dox conjugate (mCPP-Dox) were used as models for the evaluation of masking and demasking processes. It was found that exogenous MMP-2/9 could effectively trigger the reversion of CPP-cargo in this conjugate, and this trigger adhered to the Michaelis-Menten kinetics profile. This conjugate was sensitive to the trigger of endogenous MMP-2/9 and could induce enhanced cytotoxicity toward MMP-2/9-rich tumor cells. In vivo antitumor efficacy revealed that this masked conjugate had considerable antitumor activity and could inhibit the tumor growth at a higher level relative to CPP-cargo. Low toxicity in vivo showed the noticeably decreased wildness of this conjugate toward normal tissues and more controllable entry of antitumor agents into "Troy". On the basis of analyses in vitro and in vivo, this mCPP-cargo conjugate delivery system held an improved selectivity toward MMP-2/9-rich tumors and would be a promising strategy for tumor-targeted treatment.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Viability of Existing INL Facilities for Dry Storage Cask Handling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Randy Bohachek; Charles Park; Bruce Wallace

2013-04-01

This report evaluates existing capabilities at the INL to determine if a practical and cost effective method could be developed for opening and handling full-sized dry storage casks. The Idaho Nuclear Technology and Engineering Center (INTEC) CPP-603, Irradiated Spent Fuel Storage Facility, provides the infrastructure to support handling and examining casks and their contents. Based on a reasonable set of assumptions, it is possible to receive, open, inspect, remove samples, close, and reseal large bolted-lid dry storage casks at the INL. The capability can also be used to open and inspect casks that were last examined at the TAN Hotmore » Shop over ten years ago. The Castor V/21 and REA-2023 casks can provide additional confirmatory information regarding the extended performance of low-burnup (<45 GWD/MTU) used nuclear fuel. Once a dry storage cask is opened inside CPP-603, used fuel retrieved from the cask can be packaged in a shipping cask, and sent to a laboratory for testing. Testing at the INL’s Materials and Fuels Complex (MFC) can occur starting with shipment of samples from CPP-603 over an on-site road, avoiding the need to use public highways. This reduces cost and reduces the risk to the public. The full suite of characterization methods needed to establish the condition of the fuel exists and MFC. Many other testing capabilities also exist at MFC, but when those capabilities are not adequate, samples can be prepared and shipped to other laboratories for testing. This report discusses how the casks would be handled, what work needs to be done to ready the facilities/capabilities, and what the work will cost.« less

Viability of Existing INL Facilities for Dry Storage Cask Handling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bohachek, Randy; Wallace, Bruce; Winston, Phil

2013-04-30

This report evaluates existing capabilities at the INL to determine if a practical and cost effective method could be developed for opening and handling full-sized dry storage casks. The Idaho Nuclear Technology and Engineering Center (INTEC) CPP-603, Irradiated Spent Fuel Storage Facility, provides the infrastructure to support handling and examining casks and their contents. Based on a reasonable set of assumptions, it is possible to receive, open, inspect, remove samples, close, and reseal large bolted-lid dry storage casks at the INL. The capability can also be used to open and inspect casks that were last examined at the TAN Hotmore » Shop over ten years ago. The Castor V/21 and REA-2023 casks can provide additional confirmatory information regarding the extended performance of low-burnup (<45 GWD/MTU) used nuclear fuel. Once a dry storage cask is opened inside CPP-603, used fuel retrieved from the cask can be packaged in a shipping cask, and sent to a laboratory for testing. Testing at the INL’s Materials and Fuels Complex (MFC) can occur starting with shipment of samples from CPP-603 over an on-site road, avoiding the need to use public highways. This reduces cost and reduces the risk to the public. The full suite of characterization methods needed to establish the condition of the fuel exists and MFC. Many other testing capabilities also exist at MFC, but when those capabilities are not adequate, samples can be prepared and shipped to other laboratories for testing. This report discusses how the casks would be handled, what work needs to be done to ready the facilities/capabilities, and what the work will cost.« less

PBF Reactor Building (PER620). Plot plan shows layout, including auxiliary ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PBF Reactor Building (PER-620). Plot plan shows layout, including auxiliary buildings: Emergency Generator (621), Hose House (622), Cooling Tower Auxiliary (624), Maintenance and Storage Warehouse (625), Gas Cylinder Storage (627), Hose House (628), Cooling Tower (720), Substation (719), and other features. Road connections between PBF Reactor, its control building, and SPERT-I site. Note cable trenches along road to control building. Date: July 1965. Ebasco Services, PER-U-101. INEEL index no. 761-0100-00-205-123005 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

Effect of baclofen on morphine-induced conditioned place preference, extinction, and stress-induced reinstatement in chronically stressed mice.

PubMed

Meng, Shanshan; Quan, Wuxing; Qi, Xu; Su, Zhiqiang; Yang, Shanshan

2014-01-01

A stress-induced increase in excitability can result from a reduction in inhibitory neurotransmission. Modulation of gamma-aminobutyric acid (GABA)ergic transmission is an effective treatment for drug seeking and relapse. This study investigated whether baclofen, a GABA(B) receptor agonist, had an impact on morphine-induced conditioned place preference (CPP), extinction, and stress-induced relapse in chronically stressed mice. Chronic stress was induced by restraining mice for 2 h for seven consecutive days. We first investigated whether chronic stress influenced morphine-induced CPP, extinction, and stress-induced relapse in the stressed mice. Next, we investigated whether three different doses of baclofen influenced chronic stress as measured by the expression of morphine-induced CPP. We chose the most effective dose for subsequent extinction and reinstatement experiments. Reinstatement of morphine-induced CPP was induced by a 6-min forced swim stress. Locomotor activity was also measured for each test. Chronic stress facilitated the expression of morphine-induced CPP and prolonged extinction time. Forced swim stress primed the reinstatement of morphine-induced CPP in mice. Baclofen treatment affected the impact of chronic stress on different phases of morphine-induced CPP. Our results showed that baclofen antagonized the effects of chronic stress on morphine-induced CPP. These findings suggest the potential clinical utility of GABA(B) receptor-positive modulators as an anti-addiction agent in people suffering from chronic stress.

Caries-Preventive Effect of NaF, NaF plus TCP, NaF plus CPP-ACP, and SDF Varnishes on Sound Dentin and Artificial Dentin Caries in vitro.

PubMed

Wierichs, Richard J; Stausberg, Sabrina; Lausch, Julian; Meyer-Lueckel, Hendrik; Esteves-Oliveira, Marcella

2018-01-01

The aim of this study was to compare the caries-preventive effect of different fluoride varnishes on sound dentin as well as on artificial dentin caries-like lesions. Bovine dentin specimens (n = 220) with one sound surface (ST) and one artificial caries lesion (DT) were prepared and randomly allocated to 11 groups. The interventions before pH cycling were as follows: application of a varnish containing NaF (22,600 ppm F-; Duraphat [NaF0/NaF1]), NaF plus tricalcium phosphate (22,600 ppm F-; Clinpro White Varnish Mint [TCP0/TCP1]), NaF plus casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP; 22,600 ppm F-; MI Varnish [CPP0/CPP1]), or silver diamine fluoride (SDF; 35,400 ppm F-; Cariestop 30% [SDF0/SDF1]) and no intervention (NNB/N0/N1). During pH cycling (14 days, 6 × 120 min demineralization/day) half of the specimens in each group were brushed (10 s; 2 times/day) with either fluoride-free ("0"; e.g., TCP0) or 1,100 ppm F- ("1"; e.g., TCP1) dentifrice slurry. In another subgroup, the specimens were pH cycled but not brushed (NNB). Differences in integrated mineral loss (ΔΔZ), lesion depth (ΔLD), and colorimetric values (ΔΔE) were calculated between the values after initial demineralization and those after pH cycling, using transversal microradiography and photographic images. After pH cycling, no discoloration could be observed. Furthermore, NNB, N0, and N1 showed significantly increased ΔZDT/LDDT and ΔZST/LDST values, indicating further demineralization. In contrast, CPP0, CPP1, SDF0, and SDF1 showed significantly decreased ΔZDT/LDDT values, indicating remineralization (p ≤ 0.004; paired t test). CPP0, CPP1, SDF0, and SDF1 showed significantly higher changes in ΔΔZDT/ΔLDDT and ΔΔZST/ΔLDST than NNB, N0, and N1 (p < 0.001; Bonferroni post hoc test). In conclusion, under the conditions chosen, all fluoride varnishes prevented further demineralization. However, only NaF plus CPP-ACP and SDF could remineralize artificial dentin caries-like lesions under net-demineralizing conditions, thereby indicating that NaF plus CPP-ACP and SDF may be helpful to high-caries-risk patients. © 2018 S. Karger AG, Basel.

Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish.

PubMed

Faillace, M P; Pisera-Fuster, A; Bernabeu, R

2018-06-08

The rewarding properties of drugs in zebrafish can be studied using the conditioned place preference (CPP) paradigm. Most devices that have been used for CPP consist of two-half tanks with or without a central chamber. Here we evaluated the rewarding effects of nicotine and caffeine using a tank with five arms distributed radially from a central chamber that we have denoted Fish Tank Radial Maze (FTRM). Zebrafish were trained to associate nicotine or caffeine with a coloured arm. In testing sessions to assess CPP induction, between two and five different arms were available to explore. We found that when offering the two arms, one of them associated to the drug mediating conditioning for 14 days, zebrafish showed nicotine-induced CPP but not caffeine-induced CPP. When zebrafish had the option to explore drug-paired arms together with new coloured arms as putative distractors, the nicotine-CPP strength was maintained for at least three days. The presence of novel environments induced caffeine-CPP, which was still positive after three days of testing sessions. Complementary behavioural data supported these findings. Nicotine-CPP was prevented by the histone deacetylase inhibitor phenylbutyrate administered during conditioning; however, there were no effects on caffeine-CPP. The specific acetylation of lysine 9 in histone 3 (H3-K9) was increased in nicotine-conditioned zebrafish brains. This study suggests that novel environmental cues facilitate drug-environment associations, and hence, the use of drugs of abuse. Copyright © 2018 Elsevier Inc. All rights reserved.

Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas

PubMed Central

El Rawas, Rana; Klement, Sabine; Salti, Ahmad; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction. PMID:22403532

39. CALCINER CELL PLANS. TOGETHER WITH HAER ID33C37 ILLUSTRATES COMPLEXITY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

39. CALCINER CELL PLANS. TOGETHER WITH HAER ID-33-C-37 ILLUSTRATES COMPLEXITY OF PIPING. INEEL DRAWING NUMBER 200-0633-00-287-106445. FLUOR NUMBER 5775-CPP-633-P-50 - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

40. CALCINER CELL SECTIONS. TOGETHER WITH HAER ID33C37 ILLUSTRATES COMPLEXITY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

40. CALCINER CELL SECTIONS. TOGETHER WITH HAER ID-33-C-37 ILLUSTRATES COMPLEXITY OF PIPING. INEEL DRAWING NUMBER 200-0633-00-287-106446. FLUOR NUMBER 5775-CPP-P-51. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

37. PLAN OF ACCESS CORRIDOR PIPING INCLUDES WASTE HOLD TANK ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. PLAN OF ACCESS CORRIDOR PIPING INCLUDES WASTE HOLD TANK CELL, OFFGAS CELL, ADSORBER CELL, AND OFFGAS FILTER CELL. INEEL DRAWING NUMBER 200-0633-00-287-106453. FLUOR NUMBER 5775-CPP-P-58. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

The role of ovarian hormones in sexual reward states of the female rat.

PubMed

Parada, Mayte; Vargas, Erica Barbosa; Kyres, Maria; Burnside, Kimberly; Pfaus, James G

2012-09-01

To what extent does the reward value of sexual stimulation in females depend on ovarian hormones? The effects of estradiol benzoate (EB) and progesterone (P) were examined on the acquisition and expression of sexual reward induced by paced copulation and clitoral stimulation (CLS) in ovariectomized (OVX) rats. In experiment 1 we examined the expression of a pacing-induced conditioned place preference (CPP). Ovariectomized, hormone-primed rats were given experience with paced copulation associated with one side of a CPP apparatus. Changing hormonal status prior to the final CPP test did not alter pacing-induced CPP. However, subsequent partial extinction of CPP was observed only in rats primed with EB+P, a treatment previously shown to induce sexual desire and receptivity. In Experiment 2, significant CLS-induced CPP developed in ovariectomized rats regardless of hormone priming. Our results show that the expression of the sexual reward state induced by paced copulation, and CLS in particular, is independent of hormone priming. We propose that ovarian hormones sensitize sensory and motor pathways necessary for sexual behavior and stimulation to induce reward. Copyright © 2012 Elsevier Inc. All rights reserved.

Casein Phosphopeptide-Amorphous Calcium Phosphate and Shear Bond Strength of Adhesives to Primary Teeth Enamel

PubMed Central

Farokh Gisovar, Elham; Hedayati, Nassim; Shadman, Niloofar; Shafiee, Leila

2015-01-01

Background: CPP-ACP (Phosphopeptide-Amorphous Calcium Phosphate) has an important role in caries prevention in pediatric patients. This study was done, because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations. Objectives: This study aimed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on shear bond strength of dental adhesives to enamel of primary teeth molars. Materials and Methods: This in vitro study was conducted on 180 extracted primary molars. They were randomly divided into 6 groups and each group was divided into 2 subgroups (treated with CPP-ACP and untreated). In subgroups with CPP-ACP, enamel was treated with CPP-ACP paste 1 h/d for 5 days. Types of adhesives that were evaluated in this study were Tetric N-Bond, AdheSE, AdheSE One F, single Bond 2, SE Bond, and Adper Prompt L-Pop. Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope. Data were analyzed by T test, 2-way analysis of variance (ANOVA), Tukey and Fisher exact test using SPSS18. P < 0.05 was considered as significance level. Results: Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference (P > 0.05). Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type. Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel. Conclusions: To have a successful and durable composite restoration, having a high strength bonding is essential. Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength (SBS) in success of composite restoration, we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel. PMID:25793113

A 10-yr Analysis of Chronic Pelvic Pain and Chronic Opioid Therapy in the Women Veteran Population.

PubMed

Cichowski, Sara B; Rogers, Rebecca G; Komesu, Yuko; Murata, Erin; Qualls, Clifford; Murata, Allison; Murata, Glen

2018-05-18

Chronic pelvic pain (CPP) affects an estimated 30% of women Veterans. Previous research shows high rates of narcotic abuse in the women Veteran population. Narcotics are not recommended for the treatment of CPP. Understanding how CPP impacts narcotic prescribing in the women Veteran population is critical to addressing the public health crisis of opioid abuse. Our objective was to compare chronic opioid therapy (COT) prescribed 5 yr prior to and following CPP diagnosis and to identify predictors of COT as well as adverse events associated with COT. We choose to look at 10 yr of data because we thought this time period would provide unique insight into the longitudinal associations of CPP and COT and was available in the database. Women with non-cancer CPP were included for analyses from the Veteran's Affairs Corporate Database Warehouse. COT was defined as 90 d of opiates/calendar year for each of the 5 yr proceeding and following the diagnosis of CPP. Patient characteristics and potential variables influencing COT were collected. We compared baseline demographics between the women who received COT to the women who did not receive COT to find additional demographic predictors of COT in association with CPP. Multivariable analysis identified predictors of COT in this population of women with CPP. We utilized an interrupted time series analysis to understand the impact of the diagnosis of CPP on COT. A total of 49,601 women met inclusion criteria with an average age of 40.1 ± 11.5 yr; 37.3% self-characterized as being a racial minority and 24% had a history of military sexual trauma. Chronic use increased significantly (p < 0.001) in the 5 yr preceding the diagnosis of CPP from 6.3% (n = 3124) of women at time -5 to 13.6% (n = 6746) at time 0. In the first year following the diagnosis of CPP, 16.8% (n = 8,333) of women with CPP met the criteria for COT (p < 0.001) and 15% (n = 7440) of women with CPP remained in the COT group for the remaining 5 yr following the diagnosis. On average women in the COT group had 250-292 d of opioids/year. When comparing women who received chronic narcotics following the diagnosis of CPP versus those who did not receive chronic narcotics, women who received COT were older, more likely to smoke and more frequently diagnosed with other pain conditions such as back pain, headaches, and fibromyalgia. (All p < 0.001). In the multivariable model, predictors of COT following CPP diagnosis included prior COT (OR = 10.0 (95% CI 9.4, 10.6), a positive history of military sexual trauma, smoking, and other chronic pain conditions. The distinct pattern of prescribing shown in this cohort may mean COT is prescribed for CPP and this prescribing pattern contributes to the adverse events associated with COT. As COT is not recommended for CPP, physicians need more education on the therapies available to help CPP patients.

IET. Tank building (TAN627). Plans, elevation, details. shows position of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

IET. Tank building (TAN-627). Plans, elevation, details. shows position of tanks within building and concrete supports. Ralph M. Parsons 902-4-ANP-627-A&S 420. Date: Fabruary 1954. Approved by INEEL Classification Office for public release. INEEL index code no. 035-0627-00-693-106975 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

Multidisciplinary Cleft Palate Program at BC Children's Hospital: Are We Meeting the Standards of Care?

PubMed

Dahiya, Anita; Courtemanche, Rebecca; Courtemanche, Douglas J

2018-05-01

To characterize current Cleft Palate Program (CPP) practices and evaluate the timeliness of appointments with respect to patient age and diagnosis based on American Cleft Palate-Craniofacial Association (ACPA) population guidelines and CPP patient-specific recommendations. A retrospective review of CPP patient appointments from November 6, 2012, to March 31, 2015, was done. Data were analyzed using descriptive and inferential statistics. The study was conducted using data from the CPP at BC Children's Hospital. A total of 1214 appointments were considered in the analysis, including syndromic and nonsyndromic patients of 0 to 27 years of age. Percentage of patients meeting follow-up targets by ACPA standards and CPP team recommendations. Our results showed patients 5 years and younger or nonsyndromic were more likely to be seen on time ( P < .001). No relationship between the timeliness of an appointment and specific patient diagnoses or distance to clinic was found. With the exception of nursing (97% of appointments were on time), all disciplines had less than 45% of appointments on time with 51% of appointments meeting ACPA guidelines for timeliness and 32% of all appointments meeting CPP recommendations. Timely care for the cleft/craniofacial patient populations represents a challenge for the CPP. Although half of patients may meet the general ACPA guidelines, only 32% of patients are meeting the CPP patient-specific recommendations. To provide better patient care, future adjustments are needed, which may include improved resource allotment and program support.

INTERIOR VIEW OF FUEL STORAGE BUILDING (CPP603) LOOKING SOUTHWEST SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR VIEW OF FUEL STORAGE BUILDING (CPP-603) LOOKING SOUTHWEST SHOWING STORAGE BASIN IN FOREGROUND, TRANSFER CRANE AND UNLOADER TO LEFT OF NORTH SIDE OF HOT CELL. INL PHOTO NUMBER NRTS-58-157. J. Anderson, Photographer, 1/15/1958 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Context-dependent effects of rimonabant on ethanol-induced conditioned place preference in female mice.

PubMed

Silva, Aline A F; Barbosa-Souza, Evelyn; Confessor-Carvalho, Cassio; Silva, Raiany R R; De Brito, Ana Carolina L; Cata-Preta, Elisangela G; Silva Oliveira, Thaynara; Berro, Lais F; Oliveira-Lima, Alexandre J; Marinho, Eduardo A V

2017-10-01

The CB1 receptor antagonist rimonabant has been previously found to prevent behavioral effects of drugs of abuse in a context-dependent manner, suggesting an important role of endocannabinoid signaling in drug-induced environmental conditioning. The aim of the present study was to evaluate the effects of rimonabant on ethanol-induced conditioned place preference (CPP) in female mice. Animals were conditioned with saline or ethanol (1.8g/kg) during 8 sessions, and subsequently treated with either saline or rimonabant (1 or 10mg/kg) in the CPP environment previously associated with saline (unpaired) or ethanol (paired) for 6 consecutive days. Animals were then challenged with ethanol (1.8g/kg) in the ethanol-paired environment and ethanol-induced CPP was quantified on the following day. While treatment with 1mg/kg rimonabant in the saline-associated environment had no effects on the subsequent expression of ethanol-induced CPP, it blocked the expression of CPP to ethanol when paired to the ethanol-associated environment. When given in the ethanol-paired environment, 10mg/kg rimonabant induced aversion to the ethanol-associated environment. The same aversion effect was observed for 10mg/kg rimonabant when given in the saline-associated environment, thereby potentiating the expression of ethanol-induced CPP. Importantly, rimonabant did not induce CPP or conditioned place aversion on its own. Controlling for the estrous cycle phase showed no influences of hormonal cycle on the development and expression of ethanol-induced CPP. Our data suggest that rimonabant reduces the rewarding properties of ethanol by abolishing drug-environment conditioning in the CPP paradigm in a context-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

The physical properties and ion release of CPP-ACP-modified calcium silicate-based cements.

PubMed

Dawood, A E; Manton, D J; Parashos, P; Wong, Rhk; Palamara, Jea; Stanton, D P; Reynolds, E C

2015-12-01

This study investigated the physical properties and ion release of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-modified calcium silicate-based cements (CSCs) and compared the properties of a trial mineral trioxide aggregate (MTA) with two commercially available CSCs, Biodentine(™) and Angelus(®) MTA. The setting time, solubility, compressive strength and Vickers surface microhardness of the three CSCs incorporated with 0%, 0.5%, 1.0%, 2.0% and 3.0% (w/w) CPP-ACP were investigated. Release of calcium (Ca(2+) ), phosphate ions (Pi ) and pH of the test cements were measured after 24, 72, 168 and 336 h of storage. The addition of up to 1.0% CPP-ACP into Biodentine(™) and 0.5% into the other cements did not adversely affect their physical properties except for the setting time. The addition of 0.5% CPP-ACP increased Ca(2+) released from Biodentine(™) (after 168 and 336 h), Angelus(®) MTA (after 168 h) and the trial MTA (after 72 h). The addition of 1.0-3.0% CPP-ACP increased Ca(2+) and Pi released from all the cements. Biodentine(™) released more Ca(2+) particularly in the early stages and showed shorter setting time and higher mechanical properties than the other cements. The mechanical properties of Angelus(®) MTA and the trial MTA were similar. All the cements produced highly alkaline storage solutions. Up to 1.0% CPP-ACP in Biodentine(™) improves Ca(2+) and Pi release and 0.5% CPP-ACP in Angelus(®) MTA and the trial MTA improves Ca(2+) release without altering the mechanical properties and solubility. The addition of CPP-ACP into CSCs prolonged the setting time. © 2015 Australian Dental Association.

Dopaminergic and serotonergic modulation of persistent behaviour in the reinforced spatial alternation model of obsessive-compulsive disorder.

PubMed

Kontis, Dimitris; Boulougouris, Vasileios; Papakosta, Vasiliki Maria; Kalogerakou, Stamatina; Papadopoulos, Socrates; Poulopoulou, Cornelia; Papadimitriou, George N; Tsaltas, Eleftheria

2008-11-01

We have proposed rewarded T-maze alternation as a model of obsessive-compulsive disorder (OCD): the serotonin agonist m-chlorophenylpiperazine (mCPP) increments persistence therein, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increase, counteracted by mCPP pretreatment. This study (a) further explores the cross-tolerance between fluoxetine and mCPP and (b) extends the model by investigating its sensitivity to dopaminergic manipulations (D2, 3 agonism--quinpirole). In both experiments, baseline and drug testing were carried out under daily T-maze alternation training. Exp. 1: Matched group (n = 8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration): (1) saline, (2) low-dose fluoxetine (2.5 mg/kg), (3) low-dose mCPP (0.5 mg/kg) or (4) combined fluoxetine + mCPP. One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10 mg/kg), the other with high-dose mCPP (2.5 mg/kg). Exp. 2: One group (n = 12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg). Exp. 1: Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine + mCPP pretreatment afforded full protection from either challenge. Exp. 2: Quinpirole significantly increased directional persistence after 13 administration days. These results establish the sensitivity of the rewarded alternation OCD model to D2, 3 receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

An in vitro Comparative Evaluation of Three Remineralizing Agents using Confocal Microscopy

PubMed Central

Chokshi, Achala; Konde, Sapna; Shetty, Sunil Raj; Chandra, Kumar Narayan; Jana, Sinjana; Mhambrey, Sanjana; Thakur, Sneha

2016-01-01

Introduction The caries process has been thought to be irreversible, resulting in the permanent loss of tooth substance and eventually the development of a cavity. Recent approaches focused on application of remineralizing agents to incipient carious lesions, aim at controlling demineralization and promoting remineralization. Remineralizing agents create a supersaturated environment around the lesion; thus, preventing mineral loss and forces calcium and phosphate ions in the vacant areas. Aim To compare and evaluate the remineralization potential of Fluoride Varnish, CPP-ACP Paste (Casein Phosphopeptide-Amorphous Calcium Phosphate) and fTCP Paste (functionalized Tricalcium Phosphate) using confocal microscope. Materials and Methods Two windows of 3X3mm were created on the labial cervical and incisal thirds in 60 permanent maxillary central incisors. The teeth were demineralized to create artificial caries and divided into three groups of 20 each. Group I specimens were coated with Fluoride Varnish once whereas those in CPP-ACP paste group and fTCP group were brushed for 2 minutes, twice daily for 20 and 40 days. The specimens were stored in artificial saliva during the study period and were later sectioned and observed under confocal microscope. Data obtained was statistically analyzed using Fischer’s exact test, ANOVA and post-hoc Bonferroni’s test. Results Fluoride Varnish, CPP-ACP Paste and fTCP Paste showed remineralization of artificial carious lesions at both the time intervals. Fluoride varnish showed the highest remineralization followed by CPP-ACP Paste and fTCP Paste. A statistically significant increase in remineralization potential of CPP-ACP Paste and fTCP Paste was observed at the end of 40 days as compared to 20 days. Conclusion Fluoride varnish showed the greatest remineralization potential of artificial carious lesions followed by CPP-ACP Paste and fTCP Paste respectively. PMID:27504408

Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp; Umeda, Sachiko; Yasuda, Takeshi

2014-02-01

Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation withmore » γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the intestine against radiation-induced injury through its internalization, independently of FGFRs, suggesting that cellular uptake of FGF12 is an alternative signaling pathway useful for cancer radiation therapy.« less

Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

PubMed

Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

2001-01-01

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP.

PubMed

Wen, Di; Cong, Bin; Ma, Chunling; Yang, Shengchang; Yu, Hailei; Ni, Zhiyu; Li, Shujin

2012-02-21

Cholecystokinin octapeptide (CCK-8) is the most potent endogenous anti-opioid peptide and regulates a variety of physiological processes. In our previous study, we found that exogenous CCK-8 attenuated naloxone-induced withdrawal symptoms, but the possible regulative effects of CCK-8 on the rewarding effects of morphine were not examined. In the present study, we aimed to determine the exact effects of exogenous CCK-8 at various doses on the rewarding action of morphine by utilizing the unbiased conditioned place preference (CPP) paradigm. We therefore examined the effects of CCK-8 on the acquisition, expression and extinction of morphine-induced CPP and on locomotor activity. The results showed that CCK-8 (0.01-1μg, i.c.v.), administered alone, induced neither CPP nor place aversion, but blocked the acquisition of CPP when administered with 10mg/kg morphine. The highest dose of CCK-8 (1μg) administered before CPP testing increased CPP and, along with lower doses (0.1μg), reduced its extinction. In addition, the highest dose (1μg) of CCK-8 suppressed locomotor activity. Our study provides the first behavioral evidence for the inhibitory effects of exogenous CCK-8 on rewarding activity and reveals significant effects of exogenous CCK-8 on various stages of place preference and the development of opioid dependence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice.

PubMed

Mattioli, Laura; Titomanlio, Federica; Perfumi, Marina

2012-05-01

Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy. The present study investigated the effects of a Rhodiola rosea L. hydroalcoholic extract (RHO), a well-known traditional oriental medicine, on establishment and reinstatement of morphine-induced conditioned place preference (CPP) in mice. CPP was induced by intraperitoneal injection of morphine (10 mg/kg) as an 8-day conditioning schedule. The effects of RHO on the rewarding properties of morphine were tested in mice receiving oral administration of RHO (10, 15, and 20 mg/kg) 60 min prior to each morphine injection (acquisition) or prior to the CPP test on day 9 (expression). Once established, CPP was extinguished by repeated testing, during which conditioned mice were injected daily with different doses of RHO. Finally, the efficacy of RHO in blocking reinstatement of CPP provoked by priming injections and physical stress was also evaluated. RHO administration showed dose dependency for prevention of establishment of CPP and was effective in facilitating extinction of morphine-induced CPP. RHO suppressed both priming- and stress-induced reinstatement of CPP in a dose-dependent manner. In conclusion, as RHO was effective for reducing craving and vulnerability to relapse, it might be a very effective natural remedy for the treatment of opioid addiction.

110. ARAI support facilities. Index of drawings related to initial ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

110. ARA-I support facilities. Index of drawings related to initial construction of hot cell building ARA-626, shop and maintenance building ARA-627, and other buildings at ARA-I. Date: Circa January 1959. Norman Engineering Company. Ineel index code no. 068-9999-80-613-102703. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

36. ARCHITECTURAL AND STRUCTURAL DETAILS OF ELEVATOR HOUSING, NaK HEATER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

36. ARCHITECTURAL AND STRUCTURAL DETAILS OF ELEVATOR HOUSING, NaK HEATER STACK ROOF FLASHING, HOOD ELEVATION DETAIL. INCLUDES PARTIAL 'BILL OF MATERIAL.' INEEL DRAWING NUMBER 200-0633-00-287-106361. FLUOR NUMBER 5775-CPP-633-A-11. - Idaho National Engineering Laboratory, Old Waste Calcining Facility, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP640) LOOKING NORTHEAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP-640) LOOKING NORTHEAST SHOWING OVERALL BLOCK EXTERIOR WALLS; CONSTRUCTION 65 PERCENT COMPLETE. INL PHOTO NUMBER NRTS-60-4976. Holmes, Photographer, 9/26/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP640) LOOKING EAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP-640) LOOKING EAST SHOWING EXCAVATION AND FORMING; CONSTRUCTION 6 PERCENT COMPLETE. INL PHOTO NUMBER NRTS-59-4935. J. Anderson, Photographer, 9/21/1959 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EQUIPMENT LAYOUT OF MAIN PROCESSING BUILDING (CPP601) LCELL PLAN AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EQUIPMENT LAYOUT OF MAIN PROCESSING BUILDING (CPP-601) L-CELL PLAN AND SECTION SHOWS COMPLEXITY OF CELLS. INL DRAWING NUMBER 200-0601-00-098-105687. ALTERNATE ID NUMBER 4289-20-301. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Dopamine mediates testosterone-induced social reward in male Syrian hamsters.

PubMed

Bell, Margaret R; Sisk, Cheryl L

2013-03-01

Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.

38 CFR 14.627 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... functioning representative of another organization. (k) Facilities means equipment and furnishings that... claimants: (a) Accreditation means the authority granted by VA to representatives, agents, and attorneys to... of original jurisdiction means the VA activity or administration that made the initial determination...

In situ effect of a CPP-ACP chewing gum on enamel erosion associated or not with abrasion.

PubMed

de Oliveira, Andressa Feitosa Bezerra; de Oliveira Diniz, Luciana Vilar; Forte, Franklin Delano Soares; Sampaio, Fabio Correia; Ccahuana-Vásquez, Renzo Alberto; Tochukwu Amaechi, Bennett

2017-01-01

The purpose of this study is to analyze the in situ effect of a casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) chewing gum on human enamel erosion lesion associated or not with abrasion. A three-way crossover study of 7 days was conducted involving 10 volunteers subjected to the same protocol: (G1) CPP-ACP sugar-free chewing gum, (G2) regular sugar-free chewing gum without CPP-ACP, and (G3) saliva-no chewing gum. An abrasion test was included in each phase. A 3D non-contact profilometry measurement of lesion depth and surface roughness was obtained of sound and eroded surfaces. A salivary calcium concentration was determined for all volunteers. ANOVA followed by Tukey's test were used with a p < 0.05. The enamel depth and the enamel surface roughness of the CPP-ACP gum group were significantly lower than the others (ANOVA, p < 0.05). No significant differences were observed between the treatments when associated with abrasion (p > 0.05). A positive and significant correlation was seen between the lesion depth and enamel surface roughness for GI (r = 0.87, p = 0.00) and GIII (r = 0.79, p = 0.00) groups. The estimated total calcium presented in the saliva after the chewed CPP-ACP gum showed no statistical significance between the mean absorbance values at the different time collections (p > 0.05). It is demonstrated that the incorporation of the CPP-ACP into a sugar-free gum significantly increased the remineralization/protection of eroded enamel surface. The CPP-ACP added to gum may be a suitable alternative vehicle, to deliver calcium ions to saliva and therefore protecting enamel.

Multimodality Monitoring for Cerebral Perfusion Pressure Optimization in Comatose Patients with Intracerebral Hemorrhage

PubMed Central

Ko, Sang-Bae; Choi, H. Alex; Parikh, Gunjan; Helbok, Raimund; Schmidt, J. Michael; Lee, Kiwon; Badjatia, Neeraj; Claassen, Jan; Connolly, E. Sander; Mayer, Stephan A.

2011-01-01

Background and Purpose Limited data exists to recommend specific cerebral perfusion pressure (CPP) targets in patients with intracerebral hemorrhage (ICH). We sought to determine the feasibility of brain multimodality monitoring (MMM) for optimizing CPP and potentially reducing secondary brain injury after ICH. Methods We retrospectively analyzed brain MMM data targeted at perihematomal brain tissue in 18 comatose ICH patients (median monitoring: 164 hours). Physiological measures were averaged over one-hour intervals corresponding to each microdialysis sample. Metabolic crisis (MC) was defined as a lactate/pyruvate ratio (LPR) >40 with a brain glucose concentration <0.7 mmol/L. Brain tissue hypoxia (BTH) was defined as PbtO2 <15 mm Hg. Pressure reactivity index (PRx) and oxygen reactivity index (ORx) were calculated. Results Median age was 59 years, median GCS score 6, and median ICH volume was 37.5 ml. The risk of BTH, and to a lesser extent MC, increased with lower CPP values. Multivariable analyses showed that CPP <80 mm Hg was associated with a greater risk of BTH (OR 1.5, 95% CI 1.1–2.1, P=0.01) compared to CPP >100 mm Hg as a reference range. Six patients died (33%). Survivors had significantly higher CPP and PbtO2 and lower ICP values starting on post-bleed day 4, whereas LPR and PRx values were lower, indicating preservation of aerobic metabolism and pressure autoregulation. Conclusions PbtO2 monitoring can be used to identify CPP targets for optimal brain tissue oxygenation. In patients who do not undergo MMM, maintaining CPP >80 mm Hg may reduce the risk of BTH. PMID:21852615

[Diagnostic value of baseline serum luteinizing hormone level for central precocious puberty in girls].

PubMed

Ou-Yang, Li-Xue; Yang, Fan

2017-07-01

To evaluate the diagnostic value of baseline serum luteinizing hormone (LH) level for central precocious puberty (CPP) in girls. A total of 279 girls with precocious puberty were subjected to assessment of growth and development, bone age determination, baseline LH test, and follicle-stimulating hormone (FSH) test, gonadotropin-releasing hormone stimulation test, and other related examinations. Of the 279 patients, 175 were diagnosed with CPP and 104 with premature thelarche (PT). The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of baseline LH and FSH levels and their peak levels for CPP, and the correlation between the baseline LH level and the peak LH level was analyzed. The CPP group had significantly higher bone age, baseline LH and FSH levels, peak LH and FSH levels, and ratio of peak LH level to peak FSH level than the PT group (P<0.01). The ROC curve proved that baseline LH level and peak LH level had good diagnostic values for CPP. Among the three bone age subgroups in the CPP group (7.0-9.0 years, 9.0-11.0 years, and >11.0 years), baseline LH level showed the best diagnostic value in the >11.0 years subgroup, with the largest area under the ROC curve. At a baseline LH level of 0.45 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 66.7% and 80% respectively, for the diagnosis of CPP. At a peak LH level of 9.935 IU/L, the Youden index reached the peak value, and the sensitivity and specificity were 74.8% and 100% respectively, for the diagnosis of CPP. The baseline LH level was positively correlated with the peak LH level (r=0.440, P<0.01). Baseline LH level can be used as an primary screening index for the diagnosis of CPP. It has a certain diagnostic value for CPP at different bone ages, and may be used as a monitoring index during the treatment and follow-uP.

Dynamic NMDAR-mediated properties of place cells during the object place memory task.

PubMed

Faust, Thomas W; Robbiati, Sergio; Huerta, Tomás S; Huerta, Patricio T

2013-01-01

N-methyl-D-aspartate receptors (NMDAR) in the hippocampus participate in encoding and recalling the location of objects in the environment, but the ensemble mechanisms by which NMDARs mediate these processes have not been completely elucidated. To address this issue, we examined the firing patterns of place cells in the dorsal CA1 area of the hippocampus of mice (n = 7) that performed an object place memory (OPM) task, consisting of familiarization (T1), sample (T2), and choice (T3) trials, after systemic injection of 3-[(±)2-carboxypiperazin-4yl]propyl-1-phosphate (CPP), a specific NMDAR antagonist. Place cell properties under CPP (CPP-PCs) were compared to those after control saline injection (SAL-PCs) in the same mice. We analyzed place cells across the OPM task to determine whether they signaled the introduction or movement of objects by NMDAR-mediated changes of their spatial coding. On T2, when two objects were first introduced to a familiar chamber, CPP-PCs and SAL-PCs showed stable, vanishing or moving place fields in addition to changes in spatial information (SI). These metrics were comparable between groups. Remarkably, previously inactive CPP-PCs (with place fields emerging de novo on T2) had significantly weaker SI increases than SAL-PCs. On T3, when one object was moved, CPP-PCs showed reduced center-of-mass (COM) shift of their place fields. Indeed, a subset of SAL-PCs with large COM shifts (>7 cm) was largely absent in the CPP condition. Notably, for SAL-PCs that exhibited COM shifts, those initially close to the moving object followed the trajectory of the object, whereas those far from the object did the opposite. Our results strongly suggest that the SI changes and COM shifts of place fields that occur during the OPM task reflect key dynamic properties that are mediated by NMDARs and might be responsible for binding object identity with location.

Preparation and bioactive properties of chitosan and casein phosphopeptides composite coatings for orthopedic implants.

PubMed

Qin, Liguo; Dong, Huanhuan; Mu, Ziqing; Zhang, Yali; Dong, Guangneng

2015-11-20

Using the layer-by-layer deposition method, functional chitosan/casein phospopeptides (CS/CPP) composite coatings were produced on Co-Cr-Mo alloy. The CS/CPP composite coatings had the dendritic topography, and were quite hydrophilic. Zeta potential measurements showed the composite coatings were negative charged at neural pH. XPS results indicated that the CS/CPP composite coatings were covalently bond to the substrate. When MC3T3-E1 cells were seeded on the CS/CPP composite coatings, no cytotoxicity was observed. The bone morphogenetic protein-2 (BMP-2) mRNA expression was significantly up-regulated in MC3T3-E1 cells cultured on the composite coatings and it was twice as much as that of cells cultured on the bare substrate. The expression of osteoprotegerin (OPG) mRNA and the ratio of OPG/receptor activator of nuclear factor-κB ligand (RNAKL) mRNA were increased 5-fold and 55-fold, respectively. These results suggested the CS/CPP composite coatings may have potential application in cobalt matrix orthopaedic implants. Copyright © 2015 Elsevier Ltd. All rights reserved.

30 CFR 285.810 - What must I include in my Safety Management System?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Environmental and Safety Management, Inspections, and Facility Assessments for Activities Conducted Under SAPs... under § 285.627(d)) and, when required by this part, your SAP (as provided in § 285.614(b)) or GAP (as...

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP640) LOOKING NORTHEAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP-640) LOOKING NORTHEAST SHOWING DECK FORMING FOR SOUTH SECTION OF OPERATING CORRIDOR; CONSTRUCTION 44 PERCENT COMPLETE. INL PHOTO NUMBER NRTS-60-3624. Holmes, Photographer, 7/25/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP640) LOOKING NORTHWEST, ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP-640) LOOKING NORTHWEST, SHOWING FORMING FOR NORTH WALLS OF CELLS 1, 4 AND 5; CONSTRUCTION 21 PERCENT COMPLETE. INL PHOTO NUMBER NRTS-60-1874. Holmes, Photographer, 4/21/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Purification, physicochemical characterisation and anticancer activity of a polysaccharide from Cyclocarya paliurus leaves.

PubMed

Xie, Jian-Hua; Liu, Xin; Shen, Ming-Yue; Nie, Shao-Ping; Zhang, Hui; Li, Chang; Gong, De-Ming; Xie, Ming-Yong

2013-02-15

A Cyclocarya paliurus (Batal.) Iljinskaja polysaccharide (CPP) was isolated and purified by hot water extraction, ethanol precipitation, deproteinisation and anion-exchange chromatography. Its physicochemical properties were characterised by gel permeation chromatography (GPC), gas chromatography-mass spectrometry (GC-MS), thermal gravimetric analysis (TGA), Fourier transform infrared spectrometry (FTIR), UV-visible spectrophotometry, dynamic light scattering (DLS) and viscometry analysis. The anticancer effect of CPP in human gastric cancer HeLa cells was also evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results showed that the molecular weight of CPP was 900 kDa, and it contained 64.8% total sugar, 23.5% uronic acid, 9.26% protein, and six kinds of monosaccharides, including glucose, rhamnose, arabinose, xylose, mannose and galactose, with molar percentages of 32.7%, 9.33%, 30.6%, 3.48%, 10.4%, and 13.5%, respectively. Furthermore, the results showed that CPP exhibited a strong inhibition effect on the growth of human gastric cancer HeLa cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

Common experience modifies the reinforcing properties of methamphetamine-injected cage mates but not morphine-injected cage mates in C57 mice.

PubMed

Watanabe, Shigeru

2015-10-01

The aim of this study was to determine whether previous exposure to a drug affects the social facilitation of conditioned place preference (CPP) for a drug-injected cage mate. Twenty-two male C57/BL6J mice received drug injections (methamphetamine or morphine) and 22 male C57/BL6J mice received saline injections. All 44 mice then received CPP training, during which one compartment of a conventional CPP apparatus was associated with a drug-injected cage mate (stimulus mouse) and the other compartment was associated with a saline-injected cage mate (stimulus mouse). The subject mice did not receive any drug injection during this CPP training. Time spent in the compartment associated with the drug-injected cage mate was measured before and after training. Subject mice that had previously received methamphetamine injections showed an increase in the time spent in the compartment associated with the methamphetamine-injected cage mate after CPP training. This effect was not observed in subject mice that had previously received saline injections. Subject mice did not show an increase in the time spent in the compartment associated with the morphine-injected cage mate irrespective of whether they had previously received morphine or saline injections. Therefore, in agreement with previous reports, common experience with methamphetamine induced reinforcing properties, but that with morphine did not.

Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes

NASA Astrophysics Data System (ADS)

Weinberger, Andreas; Walter, Vivien; MacEwan, Sarah R.; Schmatko, Tatiana; Muller, Pierre; Schroder, André P.; Chilkoti, Ashutosh; Marques, Carlos M.

2017-03-01

Although cationic cell-penetrating peptides (CPPs) are able to bind to cell membranes, thus promoting cell internalization by active pathways, attachment of cargo molecules to CPPs invariably reduces their cellular uptake. We show here that CPP binding to lipid bilayers, a simple model of the cell membrane, can be recovered by designing cargo molecules that self-assemble into spherical micelles and increase the local interfacial density of CPP on the surface of the cargo. Experiments performed on model giant unilamellar vesicles under a confocal laser scanning microscope show that a family of thermally responsive elastin-like polypeptides that exhibit temperature-triggered micellization can promote temperature triggered attachment of the micelles to membranes, thus rescuing by self-assembly the cargo-induced loss of the CPP affinity to bio-membranes.

Balance ability and posture in postmenopausal women with chronic pelvic pain.

PubMed

Fuentes-Márquez, Pedro; Rodríguez-Torres, Janet R; Valenza, Marie C; Ortíz-Rubio, Araceli; Ariza-Mateos, María J; Cabrera-Martos, Irene

2018-04-09

The aim of the present study was to analyze balance ability and posture in postmenopausal women with chronic pelvic pain (CPP). This study includes a sample of 48 women with CPP recruited from the Gynecology Service of Virgen de las Nieves and San Cecilio Hospitals in Granada (Spain) and 48 healthy control women matched with respect to age and anthropometric characteristics. Outcome variables collected included: balance ability (Mini-Balance Evaluation Systems Test and Timed Up an Go Test) and posture (photogrammetry and Spinal Mouse). Significant differences were found in all Mini Best Test subscales: total (P < 0.001), anticipatory (P = 0.002), reactive postural control (P < 0.001), sensory orientation (P < 0.001), and dynamic gait (P < 0.001), and all Timed Up and Go test subscales: alone (P < 0.001), with manual (P = 0.002) and cognitive task (P = 0.030). Significant differences were also found on spinal cervical angles with a forward head posture in women with CPP; global spine alignment exhibited more deviation in the women with CPP (P < 0.001); and a higher percentage of women with CPP (58%) presented with increased thoracic kyphosis and lumbar lordosis. Cohen's d was used to calculate the effect size. Some subscales of balance and posture tests showed a large effect size (d ≥0.8), indicating a more consistent result. Women with CPP presented poor balance including anticipatory, reactive postural control, sensory orientation, dynamic gait, and dual task-related conditions. Posture showed higher values on the dorsal angle and lower sacral inclination, less spine alignment, and a more prevalent posture with increased kyphosis and lumbar lordosis.

Select corn coproducts from the ethanol industry and their potential as ingredients in pet foods.

PubMed

de Godoy, M R C; Bauer, L L; Parsons, C M; Fahey, G C

2009-01-01

The objectives of this study were to determine the chemical composition and nutritive value of corn protein product 1 (CPP 1), corn protein product 2 (CPP 2), and corn fiber (CF), novel coproducts of the ethanol industry, and compare these feed ingredients with standard plant protein ingredients [soybean meal (SBM), distillers dried grains with solubles (DDGS), corn gluten meal (CGlM), and corn germ meal (CGeM)], and to compare CF sources (CF control 1 and control 2) with standard fiber sources (peanut hulls, Solka-Floc, and beet pulp) commonly used in pet foods. Corn fiber, CPP 1, and CPP 2 were produced at a pilot-scale modified dry-grind plant, with CPP 2 having a greater degree of purification than CPP 1. Crude protein values for CPP 2 and CPP 1 were 57.3 and 49.7%, respectively. Total dietary fiber concentration was 29% for CPP 2 and 23.5% for CPP 1. Acid-hydrolyzed fat and GE concentrations were similar for these ingredients. In a protein efficiency ratio assay, no differences (P > 0.05) in feed intake, BW gain, or CP intake were noted for CPP 2, CPP 1, or CGlM. However, feeding CPP 2 resulted in a greater (P < 0.05) G:F ratio and protein efficiency ratio than CPP 1 and CGlM. In a cecectomized rooster assay, CGlM had numerically the greatest standardized total AA, total essential AA, and total nonessential AA digestibilities, but they were not different (P > 0.05) from CPP 1 or SBM values. Corn germ meal resulted in the least values, but they were not different from those for DDGS and CPP 1. The greatest values for true nitrogen-corrected ME were obtained with CGlM, followed by CPP 2, DDGS, CPP 1, SBM, and CGeM. Distillers dried grains with solubles and CPP 1 had similar true nitrogen-corrected ME values, and they were not different from values for CPP 2 and SBM. In vitro CP disappearance was greatest (P < 0.05) for CGlM (94.1%), intermediate for DDGS (76.8%) and CPP 1 (77.5%), and least for CPP 2 (74.1%) and CGeM (67.7%). Corn fibers contained predominantly insoluble dietary fiber (1% or less of soluble dietary fiber), with a moderate CP concentration. In vitro OM disappearance for the fiber sources, when using inoculum from dog feces, revealed that with the exception of beet pulp, which had a moderate disappearance value after 16 h of fermentation (17.7%), all fiber substrates had a nonsignificant extent of fermentation. In conclusion, novel corn coproducts had properties comparable with the standard protein and fiber sources used in animal nutrition.

The PB2-K627E mutation attenuates H3N2 swine influenza virus in cultured cells and in mice.

PubMed

Gong, Xiao-Qian; Ruan, Bao-Yang; Liu, Xiao-Min; Zhang, Peng; Wang, Xiu-Hui; Wang, Qi; Shan, Tong-Ling; Tong, Wu; Zhou, Yan-Jun; Li, Guo-Xin; Zheng, Hao; Tong, Guang-Zhi; Yu, Hai

2018-04-01

PB2-627K is an important amino acid that determines the virulence of some influenza A viruses. However, it has not been experimentally investigated in the H3N2 swine influenza virus. To explore the potential role of PB2-K627E substitution in H3N2 swine influenza virus, the growth properties and pathogenicity between H3N2 swine influenza virus and its PB2-K627E mutant were compared. For the first time, our results showed that PB2-K627E mutation attenuates H3N2 swine influenza virus in mammalian cells and in mice, suggesting that PB2-627K is required for viral replication and pathogenicity of H3N2 swine influenza virus. Copyright © 2017 Elsevier Ltd. All rights reserved.

Monitoring of Intracranial Pressure in Meningitis.

PubMed

Depreitere, Bart; Bruyninckx, Dominike; Güiza, Fabian

2016-01-01

The literature on intracranial pressure (ICP) monitoring in meningitis is limited to case reports and a handful of descriptive series. The aim of this study is to investigate relationships among ICP, cerebral perfusion pressure (CPP), and outcome in meningitis and to identify whether ICP affected clinical decisions. Between 1999 and 2011, a total of 17 patients with meningitis underwent ICP monitoring at the University Hospitals Leuven. Charts were reviewed for clinical history, ICP/CPP data, imaging findings, and Glasgow Outcome Scale score. Univariate correlations were computed for outcome and ICP/CPP variables, computed tomography characteristics, and Corticosteroid Randomization After Significant Head Injury outcome model variables. Treatment decisions were assessed regarding whether or not they were based on ICP. At drain placement, Glasgow Coma Scale scores showed a median of 8 (range 3-12). Six of 17 patients had either one or two nonreactive pupils. Significant correlations with outcome were found for the highest documented ICP value (r = -0.70), the number of episodes when CPP <50 mmHg (r =-0.50), the lowest documented CPP value (r = 0.61), and pupil reactivity (r = 0.57). Treatment was influenced by ICP in all patients. The results support the notion that in meningitis high ICP and low CPP represent secondary insults. The poor condition of the patients illustrates that the level of suspicion for increased ICP in meningitis may not be high enough.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss.

PubMed

Alencar, Catarina Ribeiro Barros de; Oliveira, Gabriela Cristina de; Magalhães, Ana Carolina; Buzalaf, Marília Afonso Rabelo; Machado, Maria Aparecida de Andrade Moreira; Honório, Heitor Marques; Rios, Daniela

2017-01-01

This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI - Sugar free chewing gum with CPP-ACP; GII - Conventional sugar free chewing gum; and GIII - No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey's test (p<0.05). The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss

PubMed Central

de ALENCAR, Catarina Ribeiro Barros; de OLIVEIRA, Gabriela Cristina; MAGALHÃES, Ana Carolina; BUZALAF, Marília Afonso Rabelo; MACHADO, Maria Aparecida de Andrade Moreira; HONÓRIO, Heitor Marques; RIOS, Daniela

2017-01-01

Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is able to increase salivary calcium and phosphate levels at an acidic pH. Previous studies demonstrated that a CPP-ACP chewing gum was able to enhance the re-hardening of erosion lesions, but could not diminish enamel hardness loss. Therefore, there is no consensus regarding the effectiveness of CPP-ACP on dental erosion. Objective This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI – Sugar free chewing gum with CPP-ACP; GII – Conventional sugar free chewing gum; and GIII – No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey’s test (p<0.05). Results The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). Conclusion The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss. PMID:28678944

Effects of the addition of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on mechanical properties of luting and lining glass ionomer cement

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-07-01

Recently, the addition of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into glass ionomer cements (GICs) has attracted interest due to its remineralization of teeth and its antibacterial effects. However, it should be investigated to ensure that the incorporation of CPP-ACP does not have significant adverse effects on its mechanical properties. The purpose of this study was to evaluate the effects of the addition of CPP-ACP on the mechanical properties of luting and lining GIC. The first step was to synthesize the CPP-ACP. Then the CPP-ACP at concentrations of 1%, 1.56% and 2% of CPP-ACP was added into a luting and lining GIC. GIC without CPP-ACP was used as a control group. The results revealed that the incorporation of CPP-ACP up to 1.56%(w/w) increased the flexural strength (29%), diametral tensile strength (36%) and microhardness (18%), followed by a reduction in these mechanical properties at 2%(w/w) CPP-ACP. The wear rate was significantly decreased (23%) in 1.56%(w/w) concentration of CPP-ACP and it was increased in 2%(w/w). Accordingly, the addition of 1.56%(w/w) CPP-ACP into luting and lining GIC had no adverse effect on the mechanical properties of luting and lining GIC and could be used in clinical practice.

Before the Emergency: A Framework for Evaluating Emergency Preparedness Alternatives at Higher Education Institutions

DTIC Science & Technology

2010-09-01

Operations and Procedures • Logistics and Facilities • Training • Exercises, Evaluation and Corrective Actions • Crisis Communications ...Assessment Team BCA Benefit-cost analysis CEO Chief Executive Officer CERT Community Emergency Response Team CFR Code of Federal Regulations...CHDS Center for Homeland Defense and Security CPG 101 Comprehensive Preparedness Guidelines 101 CPP Community Preparedness and Participation CPW

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice

PubMed Central

Golden, Sam A.; Aleyasin, Hossein; Heins, Robert; Flanigan, Meghan; Heshmati, Mitra; Takahashi, Aki; Russo, Scott J.; Shaham, Yavin

2016-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3–4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1xC57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening didn’t develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1xD1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. PMID:27457669

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice.

PubMed

Golden, S A; Aleyasin, H; Heins, R; Flanigan, M; Heshmati, M; Takahashi, A; Russo, S J; Shaham, Y

2017-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Lianwei; Cai, Zhengxu; Wu, Qinghe

Developing high efficient photocatalyts for splitting water into oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this paper, we report our effort in rationally designing conjugated porous polymer (CPP) photocatalysts for photocatalytic hydrogen production (PHP) from water. A series of CPP photocatalysts with different chromophore components and bipyridyl (bpy) contents were synthesized and found to evolve hydrogen photocatalytically from water. The PHP activity of bpy-containing CPPs can be greatly enhanced due to the improved light absorption, better wettability, higher crystallinity and the improved charge separation process. Moreover, the CPP photocatalyst made of strongmore » and fully conjugated donor chromo-phore DBD shows the highest hydrogen production rate ~ 33 μmol/h. The results indicate that copolymerization between a strong donor and weak acceptor is a useful strategy for the devel-opment of efficient photocatalysts. This study clarifies that the residual palladium in the CPP networks plays a key role for the catalytic performance. The PHP activity of CPP photocatalyst can be further enhanced to 164 μmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt% of extra platinum cocat-alyst.« less

Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.

PubMed

Mu, Ying; Ren, Zhaoxiang; Jia, Jia; Gao, Bo; Zheng, Longtai; Wang, Guanghui; Friedman, Eitan; Zhen, Xuechu

2014-09-25

Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP). The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP. Additionally, chronic treatment with 2.5 mg/kg MP-10 decreased expression of phosphorylated CREB (pCREB), activated cAMP response element binding protein, in dorsomedial striatum, in shell of NAc, and in anterior cingulate cortex (ACC) as well as decreased expression of ΔFosB in the shell of NAc and ACC. The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.

A National Trial on Differences in Cerebral Perfusion Pressure Values by Measurement Location.

PubMed

McNett, Molly M; Bader, Mary Kay; Livesay, Sarah; Yeager, Susan; Moran, Cristina; Barnes, Arianna; Harrison, Kimberly R; Olson, DaiWai M

2018-04-01

Cerebral perfusion pressure (CPP) is a key parameter in management of brain injury with suspected impaired cerebral autoregulation. CPP is calculated by subtracting intracranial pressure (ICP) from mean arterial pressure (MAP). Despite consensus on importance of CPP monitoring, substantial variations exist on anatomical reference points used to measure arterial MAP when calculating CPP. This study aimed to identify differences in CPP values based on measurement location when using phlebostatic axis (PA) or tragus (Tg) as anatomical reference points. The secondary study aim was to determine impact of differences on patient outcomes at discharge. This was a prospective, repeated measures, multi-site national trial. Adult ICU patients with neurological injury necessitating ICP and CPP monitoring were consecutively enrolled from seven sites. Daily MAP/ICP/CPP values were gathered with the arterial transducer at the PA, followed by the Tg as anatomical reference points. A total of 136 subjects were enrolled, resulting in 324 paired observations. There were significant differences for CPP when comparing values obtained at PA and Tg reference points (p < 0.000). Differences remained significant in repeated measures model when controlling for clinical factors (mean CPP-PA = 80.77, mean CPP-Tg = 70.61, p < 0.000). When categorizing CPP as binary endpoint, 18.8% of values were identified as adequate with PA values, yet inadequate with CPP values measured at the Tg. Findings identify numerical differences for CPP based on anatomical reference location and highlight importance of a standard reference point for both clinical practice and future trials to limit practice variations and heterogeneity of findings.

The effects of piracetam on heroin-induced CPP and neuronal apoptosis in rats.

PubMed

Xu, Peng; Li, Min; Bai, Yanping; Lu, Wei; Ling, Xiaomei; Li, Weidong

2015-05-01

Piracetam is a positive allosteric modulator of the AMPA receptor that has been used in the treatment of cognitive disorders for decades. Recent surveys and drug analyses have demonstrated that a heroin mixture adulterated with piracetam has spread rapidly in heroin addicts in China, but its addictive properties and the damage it causes to the central neural system are currently unknown. The effect of piracetam on the reward properties of heroin was assessed by conditioned place preference (CPP). Electron microscopy and radioimmunoassay were used to compare the effects of heroin mixed with equivalent piracetam (HP) and heroin alone on neuronal apoptosis and the levels of beta-endorphin (β-EP) in different brain subregions within the corticolimbic system, respectively. Piracetam significantly enhanced heroin-induced CPP expression while piracetam itself didn't induce CPP. Morphological observations showed that HP-treated rats had less neuronal apoptosis than heroin-treated group. Interestingly, HP normalized the levels of β-EP in the medial prefrontal cortex (mPFC) and core of the nucleus accumbens (AcbC) subregions, in where heroin-treated rats showed decreased levels of β-EP. These results indicate that piracetam potentiate the heroin-induced CPP and protect neurons from heroin-induced apoptosis. The protective role of HP might be related to the restoration of β-EP levels by piracetam. Our findings may provide a potential interpretation for the growing trend of HP abuse in addicts in China. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of CPP-ACP on the remineralization of acid-eroded human tooth enamel: nanomechanical properties and microtribological behaviour study

NASA Astrophysics Data System (ADS)

Zheng, L.; Zheng, J.; Zhang, Y. F.; Qian, L. M.; Zhou, Z. R.

2013-10-01

Casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) has been used to enhance tooth remineralization in the dental clinic. But the contribution of CPP-ACP to the remineralization of acid-eroded human tooth enamel is of widespread controversy. To confirm the application potential of CPP-ACP in the remineralization repair of tooth erosion caused by acid-attack, the effect of remineralization in vitro in 2% w/v CPP-ACP solution on the acid-eroded human tooth enamel was investigated in this study. The repair of surface morphology and the improvement of nanomechanical and microtribological properties were characterized with laser confocal scanning microscope, scanning electron microscope, nanoindentation tester and nanoscratch tester. Results showed that a layer of uneven mineral deposits, which were mainly amorphous calcium phosphate (ACP) in all probability, was observed on the acid-eroded enamel surface after remineralization. Compared with the acid-eroded enamel surface, the nanoindentation hardness and Young's modulus of the remineralized enamel surface obviously increased. Both the friction coefficient and wear volume of the acid-eroded enamel surface decreased after remineralization. However, both the nanomechanical and the anti-wear properties of the remineralized enamel surface were still inferior to those of original enamel surface. In summary, tooth damage caused by acid erosion could be repaired by remineralization in CPP-ACP solution, but the repair effect, especially on the nanomechanical and anti-wear properties of the acid-eroded enamel, was limited. These results would contribute to a further exploration of the remineralization potential of CPP-ACP and a better understanding of the remineralization repair mechanism for acid-eroded human tooth enamel.

Novel cell-penetrating peptide-loaded nanobubbles synergized with ultrasound irradiation enhance EGFR siRNA delivery for triple negative Breast cancer therapy.

PubMed

Jing, Hui; Cheng, Wen; Li, Shouqiang; Wu, Bolin; Leng, Xiaoping; Xu, Shouping; Tian, Jiawei

2016-10-01

The lack of safe and effective gene delivery strategies remains a bottleneck for cancer gene therapy. Here, we describe the synthesis, characterization, and application of cell-penetrating peptide (CPP)-loaded nanobubbles (NBs), which are characterized by their safety, strong penetrating power and high gene loading capability for gene delivery. An epidermal growth factor receptor (EGFR)-targeted small interfering RNA (siEGFR) was transfected into triple negative breast cancer (TNBC) cells via prepared CPP-NBs synergized with ultrasound-targeted microbubble destruction (UTMD) technology. Fluorescence microscopy showed that siEGFR and CPP were loaded on the shells of the NBs. The transfection efficiency and cell proliferation levels were evaluated by FACS and MTT assays, respectively. In addition, in vivo experiments showed that the expression of EGFR mRNA and protein could be efficiently downregulated and that the growth of a xenograft tumor derived from TNBC cells could be inhibited. Our results indicate that CPP-NBs carrying siEGFR could potentially be used as a promising non-viral gene vector that can be synergized with UTMD technology for efficient TNBC therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Sleep deprivation precipitates the development of amphetamine-induced conditioned place preference in rats.

PubMed

Berro, Laís F; Tufik, Sergio B; Frussa-Filho, Roberto; Andersen, Monica L; Tufik, Sergio

2018-04-03

Sleep deprivation (SD) and amphetamine use are commonly associated conditions. SD shares similar neurobiological effects with psychostimulants, playing an important role in drug addiction, especially through conditioning manipulations. The aim of the present study was to investigate the effects of SD on the development of amphetamine-induced conditioned place preference (CPP) in a protocol with a reduced number of conditioning sessions. Male adult Wistar rats were submitted to 4 conditioning sessions (2 sessions/day) in the CPP apparatus, half with saline (non-drug-paired compartment) and half with 2 mg/kg amphetamine (drug-paired compartment) after control (home-cage maintained) or SD (6 h gentle handling method) conditions. Control animals did not express a preference for the amphetamine-paired compartment, showing that 2 conditioning sessions with the drug were not sufficient to establish CPP. On the other hand, animals submitted to SD during the conditioning sessions expressed a preference for the amphetamine-paired compartment, which was maintained across the entire test session. SD precipitated the development of CPP to amphetamine, showing that lack of sleep can contribute to the establishment of a conditioning between the drug effect and environmental cues. Copyright © 2018 Elsevier B.V. All rights reserved.

Increased repetitive behaviours and prolactin responsivity to oral m-chlorophenylpiperazine in adults with autism spectrum disorders.

PubMed

Novotny, Sherie; Hollander, Eric; Phillips, Ann; Allen, Andrea; Wasserman, Stacey; Iyengar, Rupa

2004-09-01

Autism is a neurodevelopmental disorder characterized by dysfunction in three primary behavioural domains: repetitive behaviours, social deficits, and language abnormalities. There is evidence that abnormalities exist in the serotonin (5-HT) system in autism spectrum patients. Furthermore, 5-HT is known to play a role in repetitive and social behaviours. This study examined the effect of m-chlorophenylpiperazine (m-CPP) on repetitive behaviours and prolactin response in 11 adults with autism or Aspergers disorder and 8 age- and gender-matched healthy controls via randomized double-blind, m-CPP and placebo challenges. The primary outcome measure was an instrument rating six repetitive behaviours: need to know, repeating, ordering, need to tell/ask, self-injury, and touching. Patients with autism spectrum disorders showed a significant increase in repetitive behaviours at end-point following oral m-CPP in comparison to placebo. Additionally subjects with autism spectrum disorders showed a significantly increased prolactin response to m-CPP compared to normal controls, with neither group responding to placebo. This study provides further evidence for altered 5-HT sensitivity in individuals with autism spectrum disorders, as well as a possible relationship between repetitive behaviours in autism spectrum disorders and abnormalities in the 5-HT system.

Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.; Thanos, P.K.; Bermeo, C.

Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with themore » therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs. Thus, individuals with D4 receptor polymorphisms might show enhanced reinforcing responses to MP and AMPH and attenuated locomotor response to AMPH.« less

Remineralization effect of CPP-ACP and fluoride for white spot lesions in vitro.

PubMed

Oliveira, Gustavo M S; Ritter, André V; Heymann, Harald O; Swift, Edward; Donovan, Terry; Brock, Guy; Wright, Tim

2014-12-01

This in vitro study compared the remineralization effect on white spot lesions of casein phosphopeptide-amorphous calcium phosphate crème, or CPP-ACP (MI Paste™), 1.1% NaF dentifrice containing 5000ppm of fluoride (ControlRX™), or CPP-ACP crème with 900ppm of fluoride (MI Paste Plus™) with that of a control. Artificial white spot lesions were created on smooth enamel surfaces of sound molars using a previously reported demineralization model. Specimens were randomly assigned to four treatments (n=35) with a pH-cycling model over 30 days: Control (no treatment); MI Paste (10% CPP-ACP crème); F5000 (1.1% NaF dentifrice); or MI Paste Plus (10% CPP-ACP plus 900ppm fluoride crème). Products were applied following manufacturers' directions. Changes in mean lesion depth expressed by percent fluorescence loss (ΔF%), and lesion area (mm(2)) from baseline to after treatment were measured with light-induced fluorescence (QLF). Mean values of each parameter were compared between groups (p<0.05). The remineralization pattern for the F5000 group was unique with marked initial remineralization during the first 10 days and little subsequent change. Based on mean lesion area, the F5000 demonstrated greater remineralization than Control, MI Paste and MI Paste Plus groups. Based on mean fluorescence loss, the F5000 group showed improved remineralization relative to MI Paste Plus, but did not differ statistically from the Control at the end of 30 days. The 1.1% NaF dentifrice demonstrated overall greater remineralization ability than 10% CPP-ACP crème. However, the 1.1% NaF dentifrice was only as effective as the Control to reduce fluorescence loss. This study showed that a 1.1% NaF dentifrice (5000ppm) demonstrated greater remineralization ability than the CPP-ACP topical tooth crème and that the addition of fluoride to its formulation seems to enhance remineralization. Saliva also has the ability to exert an important remineralization effect over time. Copyright © 2014 Elsevier Ltd. All rights reserved.

The effect of CPP-ACP-propolis chewing gum on calcium and phosphate ion release on caries-active subjects’ saliva and the formation of Streptococcus mutans biofilm

NASA Astrophysics Data System (ADS)

Hasnamudhia, F.; Bachtiar, E. W.; Sahlan, M.; Soekanto, S. A.

2017-08-01

The aim of this study was to analyze the effect of CPP-APP and propolis wax if they are combined in a chewing gum formulation, observed from the calcium and phosphate ion level released by CPP-ACP and the emphasis of Streptococcus mutans mass in the biofilm by propolis wax on caries-active subjects’ saliva. Chewing gum simulation was done in vitro on 25 caries-active subjects’ saliva using five concentrations of chewing gum (0% propolis + 0% CPP-ACP, 0% propolis + CPP-ACP, 2% propolis + CPP-ACP, 4% propolis + CPP-ACP, and 6% propolis + CPP-ACP) and was then tested using an atomic absorption spectrophotometer to analyze calcium ion levels, an ultraviolet-visible spectrophotometer to analyze phosphate ion levels, and a biofilm assay using crystal violet to analyze the decline in biofilm mass. After the chewing simulation, calcium ion levels on saliva+gum eluent increased significantly compared to the saliva control, with the highest calcium level released by CPP-ACP + 2% propolis chewing gum. There was an insignificant phosphate level change between the saliva control and saliva+gum eluent. There was also a significant decline of S. mutans biofilm mass in the saliva+gum eluent, mostly by the CPP-ACP chewing gum and CPP-ACP + 6% propolis. The CPP-ACP-propolis chewing gum simulation generated the largest increase in calcium and phosphate ion level and the largest decline in S. mutans biofilm mass.

120. ARAI Expansion of ARA627 shop and maintenance building for ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

120. ARA-I Expansion of ARA-627 shop and maintenance building for new use as materials and metallurgy laboratory. Shows ground floor plan addition of gas analyzer room, fatigue testing room, microscope room, and offices. Idaho Nuclear Corporation 1230-ARA-627-A-5. Date: June 1970. Ineel index code no. 068-0627-00-400-154062. - Idaho National Engineering Laboratory, Army Reactors Experimental Area, Scoville, Butte County, ID

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children

PubMed Central

Poureslami, H.; Hoseinifar, Ra.; Khazaeli, P.; Hoseinifar, Re.; Sharifi, H.; Poureslami, P.

2017-01-01

Statement of Problem: The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. Objectives: The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. Materials and Methods: One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Results: Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. Conclusions: CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene. PMID:28959766

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children.

PubMed

Poureslami, H; Hoseinifar, Ra; Khazaeli, P; Hoseinifar, Re; Sharifi, H; Poureslami, P

2017-03-01

The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene.

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

PubMed

Galaj, E; Shukur, A; Manuszak, M; Newman, K; Ranaldi, R

2017-05-01

Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor. In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP. In Experiment 2, locomotor activity in response to repeated injections of saline or cocaine was measured in rats raised with EE or non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on food-based conditioned approach learning. In Experiment 4, rats were exposed to cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after which they were tested for cocaine CPP. Our results show that rearing in EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments 1 and 2) but significantly facilitated conditioned approach learning (Experiment 3). On the other hand, EE treatment introduced after cocaine conditioning significantly reduced the expression of cocaine CPP (Experiment 4). These findings suggest that EE does not protect against cocaine's rewarding and stimulant effects but can reduce already established cocaine effects, suggesting that EE might be an effective treatment for cocaine addiction-related behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

PubMed

Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

2016-07-01

The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference.

PubMed

Lubbers, Bart R; Matos, Mariana R; Horn, Annemarie; Visser, Esther; Van der Loo, Rolinka C; Gouwenberg, Yvonne; Meerhoff, Gideon F; Frischknecht, Renato; Seidenbecher, Constanze I; Smit, August B; Spijker, Sabine; van den Oever, Michel C

2016-06-01

Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at ~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextual-fear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Post-conditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

Food Restriction Increases Acquisition, Persistence and Drug Prime-Induced Expression of a Cocaine-Conditioned Place Preference in Rats

PubMed Central

Zheng, Danielle; de Vaca, Soledad Cabeza; Carr, Kenneth D.

2011-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. PMID:22074687

Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats.

PubMed

Zheng, Danielle; Cabeza de Vaca, Soledad; Carr, Kenneth D

2012-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. Copyright © 2011 Elsevier Inc. All rights reserved.

The impact of a highly visible display of cerebral perfusion pressure on outcome in individuals with cerebral aneurysms.

PubMed

Kirkness, Catherine J; Burr, Robert L; Cain, Kevin C; Newell, David W; Mitchell, Pamela H

2008-01-01

Nurses' ability to rapidly detect decreases in cerebral perfusion pressure (CPP), which may contribute to secondary brain injury, may be limited by poor visibility of CPP displays. To evaluate the impact of a highly visible CPP display on the functional outcome in individuals with cerebral aneurysms. Patients with cerebral aneurysms (n = 100) who underwent continuous CPP monitoring were enrolled and randomized to beds with or without the additional CPP display. Six-month outcome was assessed. Functional outcome was not significantly different between control and intervention groups after controlling for initial neurologic condition (odds ratio .904, 95% confidence interval 0.317 to 2.573). However, greater time below CPP thresholds (55 to 70 mm Hg) was significantly associated with poorer outcome (P = .005 to .010). Although the enhanced CPP display was not associated with significantly better outcome, longer periods of CPP below set levels were associated with poorer outcome.

Plan-graph Based Heuristics for Conformant Probabilistic Planning

NASA Technical Reports Server (NTRS)

Ramakrishnan, Salesh; Pollack, Martha E.; Smith, David E.

2004-01-01

In this paper, we introduce plan-graph based heuristics to solve a variation of the conformant probabilistic planning (CPP) problem. In many real-world problems, it is the case that the sensors are unreliable or take too many resources to provide knowledge about the environment. These domains are better modeled as conformant planning problems. POMDP based techniques are currently the most successful approach for solving CPP but have the limitation of state- space explosion. Recent advances in deterministic and conformant planning have shown that plan-graphs can be used to enhance the performance significantly. We show that this enhancement can also be translated to CPP. We describe our process for developing the plan-graph heuristics and estimating the probability of a partial plan. We compare the performance of our planner PVHPOP when used with different heuristics. We also perform a comparison with a POMDP solver to show over a order of magnitude improvement in performance.

Structure-based design and mechanisms of allosteric inhibitors for mitochondrial branched-chain α-ketoacid dehydrogenase kinase

PubMed Central

Qi, Xiangbing; Gui, Wen-Jun; Morlock, Lorraine K.; Wallace, Amy L.; Ahmed, Kamran; Laxman, Sunil; Campeau, Philippe M.; Lee, Brendan H.; Hutson, Susan M.; Tu, Benjamin P.; Williams, Noelle S.; Tambar, Uttam K.; Wynn, R. Max; Chuang, David T.

2013-01-01

The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are elevated in maple syrup urine disease, heart failure, obesity, and type 2 diabetes. BCAA homeostasis is controlled by the mitochondrial branched-chain α-ketoacid dehydrogenase complex (BCKDC), which is negatively regulated by the specific BCKD kinase (BDK). Here, we used structure-based design to develop a BDK inhibitor, (S)-α-chloro-phenylpropionic acid [(S)-CPP]. Crystal structures of the BDK-(S)-CPP complex show that (S)-CPP binds to a unique allosteric site in the N-terminal domain, triggering helix movements in BDK. These conformational changes are communicated to the lipoyl-binding pocket, which nullifies BDK activity by blocking its binding to the BCKDC core. Administration of (S)-CPP to mice leads to the full activation and dephosphorylation of BCKDC with significant reduction in plasma BCAA concentrations. The results buttress the concept of targeting mitochondrial BDK as a pharmacological approach to mitigate BCAA accumulation in metabolic diseases and heart failure. PMID:23716694

Sexual functioning in women with chronic pelvic pain: the role of anxiety and depression.

PubMed

ter Kuile, Moniek M; Weijenborg, Philomeen T M; Spinhoven, Philip

2010-05-01

Chronic pelvic pain (CPP) in women is a long lasting and often disabling condition. It seems reasonable to expect that as a result of the pain, extreme fatigue and/or emotional problems, women with CPP may report a variety of sexual problems. The present study investigated differences in the report of sexual problems in women with CPP compared with healthy controls, and whether the association of CPP with sexual problems was moderated or mediated by somatic and psychological factors as manifested in women suffering from CPP. One hundred fifty-four women with CPP and 58 age-matched controls completed self-report measures for sexual functioning, pain, physical impairment, anxiety, depression, and sexual and physical abuse. Golombok Rust Inventory of Sexual Satisfaction. Women with CPP reported higher levels of vaginistic complaints, sexual avoidance, nonsensuality and sexual dissatisfaction than healthy controls. Sexual problems were associated with anxiety, depression, and sexual abuse history but not with somatic factors as pain and physical impairment. Anxiety as well as depression, irrespective of the report of sexual abuse experiences, mediated the effect of CPP on sexual problems. Sexual abuse was a general predictor of sexual problems in both women with CPP and controls. Anxiety and depression constitute important factors in the evaluation of sexual problems in women with CPP.

[How can we determine the best cerebral perfusion pressure in pediatric traumatic brain injury?].

PubMed

Vuillaume, C; Mrozek, S; Fourcade, O; Geeraerts, T

2013-12-01

The management of cerebral perfusion pressure (CPP) is the one of the main preoccupation for the care of paediatric traumatic brain injury (TBI). The physiology of cerebral autoregulation, CO2 vasoreactivity, cerebral metabolism changes with age as well as the brain compliance. Low CPP leads to high morbidity and mortality in pediatric TBI. The recent guidelines for the management of CPP for the paediatric TBI indicate a CPP threshold 40-50 mmHg (infants for the lower and adolescent for the upper). But we must consider the importance of age-related differences in the arterial pressure and CPP. The best CPP is the one that allows to avoid cerebral ischaemia and oedema. In this way, the adaptation of optimal CPP must be individual. To assess this objective, interesting tools are available. Transcranial Doppler can be used to determine the best level of CPP. Other indicators can predict the impairment of autoregulation like pressure reactivity index (PRx) taking into consideration the respective changes in ICP and CPP. Measurement of brain tissue oxygen partial pressure is an other tool that can be used to determine the optimal CPP. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

δ-aminolevulinic acid–induced protoporphyrin IX concentration correlates with histopathologic markers of malignancy in human gliomas: the need for quantitative fluorescence-guided resection to identify regions of increasing malignancy

PubMed Central

Valdés, Pablo A.; Kim, Anthony; Brantsch, Marco; Niu, Carolyn; Moses, Ziev B.; Tosteson, Tor D.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.; Harris, Brent T.

2011-01-01

Extent of resection is a major goal and prognostic factor in the treatment of gliomas. In this study we evaluate whether quantitative ex vivo tissue measurements of δ-aminolevulinic acid–induced protoporphyrin IX (PpIX) identify regions of increasing malignancy in low- and high-grade gliomas beyond the capabilities of current fluorescence imaging in patients undergoing fluorescence-guided resection (FGR). Surgical specimens were collected from 133 biopsies in 23 patients and processed for ex vivo neuropathological analysis: PpIX fluorimetry to measure PpIX concentrations (CPpIX) and Ki-67 immunohistochemistry to assess tissue proliferation. Samples displaying visible levels of fluorescence showed significantly higher levels of CPpIX and tissue proliferation. CPpIX was strongly correlated with histopathological score (nonparametric) and tissue proliferation (parametric), such that increasing levels of CPpIX were identified with regions of increasing malignancy. Furthermore, a large percentage of tumor-positive biopsy sites (∼40%) that were not visibly fluorescent under the operating microscope had levels of CPpIX greater than 0.1 µg/mL, which indicates that significant PpIX accumulation exists below the detection threshold of current fluorescence imaging. Although PpIX fluorescence is recognized as a visual biomarker for neurosurgical resection guidance, these data show that it is quantitatively related at the microscopic level to increasing malignancy in both low- and high-grade gliomas. This work suggests a need for improved PpIX fluorescence detection technologies to achieve better sensitivity and quantification of PpIX in tissue during surgery. PMID:21798847

Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice.

PubMed

Mustroph, M L; Merritt, J R; Holloway, A L; Pinardo, H; Miller, D S; Kilby, C N; Bucko, P; Wyer, A; Rhodes, J S

2015-01-01

Recent evidence suggests that wheel running can abolish conditioned place preference (CPP) for cocaine in mice. Running significantly increases the number of new neurons in the hippocampus, and new neurons have been hypothesised to enhance plasticity and behavioral flexibility. Therefore, we tested the hypothesis that increased neurogenesis was necessary for exercise to abolish cocaine CPP. Male nestin-thymidine kinase transgenic mice were conditioned with cocaine, and then housed with or without running wheels for 32 days. Half of the mice were fed chow containing valganciclovir to induce apoptosis in newly divided neurons, and the other half were fed standard chow. For the first 10 days, mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. On the last 4 days, mice were tested for CPP, and then euthanized for measurement of adult hippocampal neurogenesis by counting the number of BrdU-positive neurons in the dentate gyrus. Levels of running were similar in mice fed valganciclovir-containing chow and normal chow. Valganciclovir significantly reduced the numbers of neurons (BrdU-positive/NeuN-positive) in the dentate gyrus of both sedentary mice and runner mice. Valganciclovir-fed runner mice showed similar levels of neurogenesis as sedentary, normal-fed controls. However, valganciclovir-fed runner mice showed the same abolishment of CPP as runner mice with intact neurogenesis. The results demonstrate that elevated adult hippocampal neurogenesis resulting from running is not necessary for running to abolish cocaine CPP in mice. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Post-Retrieval Extinction Attenuates Cocaine Memories

PubMed Central

Sartor, Gregory C; Aston-Jones, Gary

2014-01-01

Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine-related memories by using the post-retrieval extinction paradigm in male Sprague Dawley rats. Results revealed that starting extinction training 1 h after cocaine contextual memory was retrieved significantly attenuated cocaine-primed reinstatement of conditioned place preference (CPP) and relapse of cocaine CPP (drug-free and cocaine-primed) following 30 days of abstinence. However, animals that did not retrieve the contextual cocaine memory before extinction training, or animals that began extinction training 24 h after retrieval (outside of the reconsolidation window), demonstrated normal cocaine CPP. Conversely, animals that received additional CPP conditioning, rather than extinction training, 1 h after reactivation of cocaine memory showed enhanced cocaine CPP compared with animals that did not reactivate the cocaine memory before conditioning. These results reveal that a behavioral manipulation that takes advantage of reconsolidation and extinction of drug memories may be useful in decreasing preference for, and abuse of, cocaine. PMID:24257156

Increased cellular uptake of peptide-modified PEGylated gold nanoparticles.

PubMed

He, Bo; Yang, Dan; Qin, Mengmeng; Zhang, Yuan; He, Bing; Dai, Wenbing; Wang, Xueqing; Zhang, Qiang; Zhang, Hua; Yin, Changcheng

2017-12-09

Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP-modified gold nanoparticles. Copyright © 2017 Elsevier Inc. All rights reserved.

Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

PubMed Central

Liu, Yu; Le Foll, Bernard; Liu, Yanli; Wang, Xi; Lu, Lin

2008-01-01

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine. PMID:19082419

Conditioned place preference induced by licit drugs: establishment, extinction, and reinstatement.

PubMed

Liu, Yu; Le Foll, Bernard; Liu, Yanli; Wang, Xi; Lu, Lin

2008-12-14

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

η6-Cycloparaphenylene transition metal complexes: synthesis, structure, photophysical properties, and application to the selective monofunctionalization of cycloparaphenylenes.

PubMed

Kubota, Natsumi; Segawa, Yasutomo; Itami, Kenichiro

2015-01-28

The synthesis, structure, photophysical properties, and reactivity of cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are described. The η(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo, W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W). In the (1)H NMR spectra of these complexes, characteristic upfield-shifted singlet signals corresponding to the four hydrogen atoms attached to the coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the solid state and in solution. TD-DFT calculations suggested that the emerging high-wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP-Cr(CO)3, a rapid and highly monoselective CPP functionalization has been achieved. The established one-pot method, consisting of complexation, deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl-, boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to reacted starting material.

[Wavelet packet extraction and entropy analysis of telemetry EEG from the prelimbic cortex of medial prefrontal cortex in morphine-induced CPP rats].

PubMed

Bai, Yu; Bai, Jia-Ming; Li, Jing; Li, Min; Yu, Ran; Pan, Qun-Wan

2014-12-25

The purpose of the present study is to analyze the relationship between the telemetry electroencephalogram (EEG) changes of the prelimbic (PL) cortex and the drug-seeking behavior of morphine-induced conditioned place preference (CPP) rats by using the wavelet packet extraction and entropy measurement. The recording electrode was stereotactically implanted into the PL cortex of rats. The animals were then divided randomly into operation-only control and morphine-induced CPP groups, respectively. A CPP video system in combination with an EEG wireless telemetry device was used for recording EEG of PL cortex when the rats shuttled between black-white or white-black chambers. The telemetry recorded EEGs were analyzed by wavelet packet extraction, Welch power spectrum estimate, normalized amplitude and Shannon entropy algorithm. The results showed that, compared with operation-only control group, the left PL cortex's EEG of morphine-induced CPP group during black-white chamber shuttling exhibited the following changes: (1) the amplitude of average EEG for each frequency bands extracted by wavelet packet was reduced; (2) the Welch power intensity was increased significantly in 10-50 Hz EEG band (P < 0.01 or P < 0.05); (3) Shannon entropy was increased in β, γ₁, and γ₂waves of the EEG (P < 0.01 or P < 0.05); and (4) the average information entropy was reduced (P < 0.01). The results suggest that above mentioned EEG changes in morphine-induced CPP group rat may be related to animals' drug-seeking motivation and behavior launching.

Enhancement of biocompatibility of 316LVM stainless steel by cyclic potentiodynamic passivation.

PubMed

Shahryari, Arash; Omanovic, Sasha; Szpunar, Jerzy A

2009-06-15

Passivation of stainless steel implants is a common procedure used to increase their biocompatibility. The results presented in this work demonstrate that the electrochemical cyclic potentiodynamic polarization (CPP) of a biomedical grade 316LVM stainless steel surface is a very efficient passivation method that can be used to significantly improve the material's general corrosion resistance and thus its biocompatibility. The influence of a range of experimental parameters on the passivation/corrosion protection efficiency is discussed. The passive film formed on a 316LVM surface by using the CPP method offers a significantly higher general corrosion resistance than the naturally grown passive film. The corresponding relative corrosion protection efficiency measured in saline during a 2-month period was 97% +/- 1%, which demonstrates a very high stability of the CPP-formed passive film. Its high corrosion protection efficiency was confirmed also at temperatures and chloride concentrations well above normal physiological levels. It was also shown that the CPP is a significantly more effective passivation method than some other surface-treatment methods commonly used to passivate biomedical grade stainless steels. In addition, the CPP-passivated 316LVM surface showed an enhanced biocompatibility in terms of preosteoblast (MC3T3) cells attachment. An increased thickness of the CPP-formed passive film and its enrichment with Cr(VI) and oxygen was determined to be the origin of the material's increased general corrosion resistance, whereas the increased surface roughness and surface (Volta) potential were suggested to be the origin of the enhanced preosteoblast cells attachment. Copyright 2008 Wiley Periodicals, Inc.

An in vitro study on the retentive strength of orthodontic bands cemented with CPP-ACP-containing GIC

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-12-01

Caries and white spot lesions around orthodontic bands are well known occurrences in fixed orthodontic treatment. There are several methods to overcome these problems. One of these includes modification of the band cement with remineralizing agents such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). However, it should be evaluated that the cement modification has no significant negative effects on the retentive strength of the cemented orthodontic bands. In a continuation of our previous studies on the effects of the addition of CPP-ACP on the mechanical properties of luting and lining glass ionomer cement (GIC), this study aimed to investigate the retentive strength of orthodontic bands cemented with CPP-ACP containing GIC. Sixty extracted human pre molars teeth were embedded in acrylic resin and randomly divided into two groups of 30 specimens. In group 1, bands were cemented to the tooth with a GIC. In group 2, CPP-ACP (1.56% w/w) was added to the GIC before cementation. The retentive strength of each groups was determined with a universal testing machine. Further, the amount of cement remaining on the tooth surface was evaluated under a stereomicroscope, and the adhesive remnant index (ARI) score was determined. Results of this study showed that there were no significant differences between the groups in retentive strength and ARI score. In conclusion, modification of GIC with 1.56% w/w CPP-ACP had no negative effects on the retentive strength of the bands so can be used during fixed orthodontic treatment.

Cementitious porous pavement in stormwater quality control: pH and alkalinity elevation.

PubMed

Kuang, Xuheng; Sansalone, John

2011-01-01

A certain level of alkalinity acts as a buffer and maintains the pH value in a stable range in water bodies. With rapid urban development, more and more acidic pollutants flow to watersheds with runoff and drop alkalinity to a very low level and ultimately degrade the water environment. Cementitious porous pavement is an effective tool for stormwater acidic neutralization. When stormwater infiltrates cement porous pavement (CPP) materials, alkalinity and pH will be elevated due to the basic characteristics of cement concrete. The elevated alkalinity will neutralize acids in water bodies and maintain the pH in a stable level as a buffer. It is expected that CPP materials still have a certain capability of alkalinity elevation after years of service, which is important for CPP as an effective tool for stormwater management. However, few previous studies have reported on how CPP structures would elevate runoff alkalinity and pH after being exposed to rainfall-runoff for years. In this study, three groups of CPP specimens, all exposed to rainfall-runoff for 3 years, were used to test the pH and alkalinity elevation properties. It was found that runoff pH values were elevated from 7.4 to the range of 7.8-8.6 after infiltrating through the uncoated specimens, and from 7.4 to 8.5-10.7 after infiltrating through aluminum-coated specimens. Runoff alkalinity elevation efficiencies are 11.5-14.5% for uncoated specimens and 42.2% for coated specimens. The study shows that CPP is an effective passive unit operation for stormwater acid neutralization in our built environment.

D1- and D2-like dopamine receptors in the CA1 region of the hippocampus are involved in the acquisition and reinstatement of morphine-induced conditioned place preference.

PubMed

Assar, Nasim; Mahmoudi, Dorna; Farhoudian, Ali; Farhadi, Mohammad Hasan; Fatahi, Zahra; Haghparast, Abbas

2016-10-01

The hippocampus plays a vital role in processing contextual memories and reward related learning tasks, such as conditioned place preference (CPP). Among the neurotransmitters in the hippocampus, dopamine is deeply involved in reward-related processes. This study assessed the role of D1- and D2-like dopamine receptors within the CA1 region of the hippocampus in the acquisition and reinstatement of morphine-CPP. To investigate the role of D1 and D2 receptors in morphine acquisition, the animals received different doses of D1- and/or D2-like dopamine receptor antagonists (SCH23390 and sulpiride, respectively) into the CA1, 5min before the administration of morphine (5mg/kg, subcutaneously) during a 3-days conditioning phase. To evaluate the involvement of these receptors in morphine reinstatement, the animals received different doses of SCH23390 or sulpiride (after extinction period) 5min before the administration of a low dose of morphine (1mg/kg) in order to reinstate the extinguished morphine-CPP. Conditioning scores were recorded by Ethovision software. The results of this study showed that the administration of SCH23390 or sulpiride, significantly decreased the acquisition of morphine-CPP. Besides, the injection of these antagonists before the administration of a priming dose of morphine, following the extinction period, decreased the reinstatement of morphine-CPP in sacrificed rats. However, the effect of sulpiride on the acquisition and reinstatement of morphine-CPP was more significant than that of SCH23390. These findings suggested that D1- and D2-like dopamine receptors in the CA1 are involved in the acquisition and reinstatement of morphine-CPP, and antagonism of these receptors can reduce the rewarding properties of morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

[Remineralization of enamel promoted by casein phosphopeptide-amorphous calcium phosphate with different concentration of fluorin].

PubMed

Liu, Lu; Yang, Lin; Zou, Min

2013-10-01

To evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) combined with different concentrations of fluoride on demineralization of enamel remineralization. Extracted premolar teeth for orthodontic reason were immersed into lactic acid gel to prepare artificial white spot lesions. Then the specimens were randomly assigned to 3 groups: 5% CPP-ACP group as control, 5% CPP-ACP +500 mg/L F- group and 5% CPP-ACP +900 mg/L F- group, which were measured by micro-hardness tester. SPSS 18.0 software package was used for data analysis. There were significant differences in micro-hardness between control group and experimental group 1 and experimental group 2 by SNK-q test (P<0.05). CPP-ACP can make the demineralization of enamel remineralization occurs. F can promote the CPP-ACP remineralization. The increase of fluoride can make the CPP-ACP remineralization better below 1000-1500 mg/L.

Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core.

PubMed

Leite-Morris, Kimberly A; Kobrin, Kendra L; Guy, Marsha D; Young, Angela J; Heinrichs, Stephen C; Kaplan, Gary B

2014-04-15

Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10 mg/kg) experimental mice acquired a morphine CPP dose response with 10mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction. Published by Elsevier B.V.

Facilitated extinction of morphine conditioned place preference with Tat-GluA2(3Y) interference peptide.

PubMed

Dias, C; Wang, Y T; Phillips, A G

2012-08-01

Neuroplasticity including long-term depression (LTD) has been implicated in both learning processes and addiction. LTD can be blocked by intravenous administration of the interference peptide Tat-GluA2(3Y) that prevents regulated endocytosis of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor. In this study, Tat-GluA2(3Y) was used to assess the role of LTD in the induction, expression, extinction and reinstatement of morphine-induced conditioned place preference (CPP). CPP was established in rats by pairing morphine (5 mg/kg, i.p.) or saline with a specific environmental context using a balanced protocol. Tat-GluA2(3Y) (0; 1.5; 2.25 nmol/g; i.v.), scrambled peptide (Tat-GluA2(Sc)), or vehicle was administered during the acquisition phase or prior to the test for CPP. Tat-GluA2(3Y) had no effect on the induction or initial expression of morphine-induced CPP. Rats that received Tat-GluA2(3Y) or Tat-GluA2(Sc) during acquisition were subsequently tested for 11 consecutive days in order to extinguish morphine CPP. CPP was then reinstated by an injection of morphine (5 mg/kg, i.p.). Co-administration of morphine and Tat-GluA2(3Y) during acquisition greatly facilitated extinction of CPP without affecting morphine-induced reinstatement of CPP. Using an intermittent retest schedule with bi-weekly tests to measure the maintenance of CPP, Tat-GluA2(3Y) during the acquisition phase had no effect on the maintenance of CPP. We propose that co-administration of Tat-GluA2(3Y) with morphine during acquisition of CPP weakens the association between morphine and contextual cues leading to rapid extinction of morphine CPP with repeated daily testing. Copyright © 2012 Elsevier B.V. All rights reserved.

Reacquisition of cocaine conditioned place preference and its inhibition by previous social interaction preferentially affect D1-medium spiny neurons in the accumbens corridor.

PubMed

Prast, Janine M; Schardl, Aurelia; Schwarzer, Christoph; Dechant, Georg; Saria, Alois; Zernig, Gerald

2014-01-01

We investigated if counterconditioning with dyadic (i.e., one-to-one) social interaction, a strong inhibitor of the subsequent reacquisition of cocaine conditioned place preference (CPP), differentially modulates the activity of the diverse brain regions oriented along a mediolateral corridor reaching from the interhemispheric sulcus to the anterior commissure, i.e., the nucleus of the vertical limb of the diagonal band, the medial septal nucleus, the major island of Calleja, the intermediate part of the lateral septal nucleus, and the medial accumbens shell and core. We also investigated the involvement of the lateral accumbens core and the dorsal caudate putamen. The anterior cingulate 1 (Cg1) region served as a negative control. Contrary to our expectations, we found that all regions of the accumbens corridor showed increased expression of the early growth response protein 1 (EGR1, Zif268) in rats 2 h after reacquisition of CPP for cocaine after a history of cocaine CPP acquisition and extinction. Previous counterconditioning with dyadic social interaction inhibited both the reacquisition of cocaine CPP and the activation of the whole accumbens corridor. EGR1 activation was predominantly found in dynorphin-labeled cells, i.e., presumably D1 receptor-expressing medium spiny neurons (D1-MSNs), with D2-MSNs (immunolabeled with an anti-DRD2 antibody) being less affected. Cholinergic interneurons or GABAergic interneurons positive for parvalbumin, neuropeptide Y or calretinin were not involved in these CPP-related EGR1 changes. Glial cells did not show any EGR1 expression either. The present findings could be of relevance for the therapy of impaired social interaction in substance use disorders, depression, psychosis, and autism spectrum disorders.

[Preventive and remineralization effect over incipient lesions of caries decay by phosphopeptide-amorphous calcium phosphate].

PubMed

Juárez-López, María Lilia Adriana; Hernández-Palacios, Rosa Diana; Hernández-Guerrero, Juan Carlos; Jiménez-Farfán, Dolores; Molina-Frechero, Nelly

2014-01-01

INTRODUCTION. Dental caries continues to affect a large percentage of Mexican children and currently advises that if diagnosed at an early stage can be reversed with minimally invasive treatments. The casein phosphopeptide amorphous calcium phosphate known as CPP-ACP is a phosphoprotein capable of releasing calcium and phosphate ions in the oral environment promoting remineralization. OBJECTIVE. To evaluate the effect of CPP-ACP with fluoride added in a scholar preventive program. MATERIAL AND METHODS. A cuasi- experimental study was conducted in 104 schools of six years old. The children were classified into three groups and received six months biweekly applications of different treatments: casein phosphopeptide amorphous calcium phosphate added fluoride (CPP-ACPF), sodium fluoride (NaF) and a control group. Clinical evaluation was performed with the laser fluorescence technique (Diagnodent model 2095). 1340 teeth were included: 294 teeth with incipient lesions and 1,046 healthy teeth. Statistical tests of χ2 y Mc Nemar were used. RESULTS. In the group that received the application of CPP-ACPF, 38% of incipient carious lesions were remineralizing compared with 21% in the group receiving the NaF (p < 0.001) and 15% in the control group (p < 0.0001) The percentage of teeth free of caries were preserved in the therapy group phosphoprotein was the biggest. This group also showed the lower proportion of deep carious lesion development (p < 0.0001). CONCLUSION. The application biweekly for six months of CPP-ACPF showed a protective and remineralizing effect on incipient carious lesions. His action was better than the application of NaF. However, to reduce the impact from dental caries in schoolchildren is important to have a comprehensive preventive approach that includes promoting self-care, as well as the application of sealants.

Reacquisition of cocaine conditioned place preference and its inhibition by previous social interaction preferentially affect D1-medium spiny neurons in the accumbens corridor

PubMed Central

Prast, Janine M.; Schardl, Aurelia; Schwarzer, Christoph; Dechant, Georg; Saria, Alois; Zernig, Gerald

2014-01-01

We investigated if counterconditioning with dyadic (i.e., one-to-one) social interaction, a strong inhibitor of the subsequent reacquisition of cocaine conditioned place preference (CPP), differentially modulates the activity of the diverse brain regions oriented along a mediolateral corridor reaching from the interhemispheric sulcus to the anterior commissure, i.e., the nucleus of the vertical limb of the diagonal band, the medial septal nucleus, the major island of Calleja, the intermediate part of the lateral septal nucleus, and the medial accumbens shell and core. We also investigated the involvement of the lateral accumbens core and the dorsal caudate putamen. The anterior cingulate 1 (Cg1) region served as a negative control. Contrary to our expectations, we found that all regions of the accumbens corridor showed increased expression of the early growth response protein 1 (EGR1, Zif268) in rats 2 h after reacquisition of CPP for cocaine after a history of cocaine CPP acquisition and extinction. Previous counterconditioning with dyadic social interaction inhibited both the reacquisition of cocaine CPP and the activation of the whole accumbens corridor. EGR1 activation was predominantly found in dynorphin-labeled cells, i.e., presumably D1 receptor-expressing medium spiny neurons (D1-MSNs), with D2-MSNs (immunolabeled with an anti-DRD2 antibody) being less affected. Cholinergic interneurons or GABAergic interneurons positive for parvalbumin, neuropeptide Y or calretinin were not involved in these CPP-related EGR1 changes. Glial cells did not show any EGR1 expression either. The present findings could be of relevance for the therapy of impaired social interaction in substance use disorders, depression, psychosis, and autism spectrum disorders. PMID:25309368

Comparison of CPP-ACP, Tri-Calcium Phosphate and Hydroxyapatite on Remineralization of Artificial Caries Like Lesions on Primary Enamel -An in vitro Study.

PubMed

Bajaj, Meghna; Poornima, P; Praveen, S; Nagaveni, N B; Roopa, K B; Neena, I E; Bharath, K P

To compare CPP-ACP, Tri-calcium phosphate and Hydroxyapatite on remineralization of artificial caries like lesions on primary enamel. Ten extracted Primary molars coated with nail varnish, leaving a window of 2×4 mm on buccal and lingual surface were immersed in demineralizing solution for 96 hours and sectioned longitudinally to obtain 40 sections (4 sections per tooth) and were randomly divided into 4 groups (A to D) n=10; Group A: negative control, Group B: CPP-ACP, Group C: Tri-calcium phosphate, Group D: Hydroxyapatite. Sections were subjected to pH cycling for 10 days and were evaluated by polarized light microscope before and after treatment. Intra group comparison of demineralization and remineralization was done by paired t-test. One way ANOVA was used for multiple group comparisons followed by post HOC TUKEY'S Test for group wise comparisons. Remineralization was found more with Group D followed by Group B, C and A. Hydroxyapatite showed better remineralization when compared to CPP-ACP and Tri-calcium phosphate.

Effects of carrot pomace powder and a mixture of pectin and xanthan on the quality of gluten-free batter and cakes.

PubMed

Majzoobi, Mahsa; Vosooghi Poor, Zahra; Mesbahi, Gholamreza; Jamalian, Jalal; Farahnaky, Asgar

2017-12-01

Carrot pomace powder (CPP) is a valuable by-product of carrot processing containing nutrients and fiber and can be utilized for enrichment of gluten-free products. The main purpose of this study was to determine the effects of various levels of CPP (0, 10, 20, and 30%) and a mixture of hydrocolloids (HC) including pectin and xanthan (1.5% of each) on the quality of batter and gluten-free cakes. With increasing the level of CPP and inclusion of HC the viscosity of the batter increased significantly from 87 mPa s for the control to >7000 mPa s for 30%CCP + HC sample. The density of the control batter was 1.2 g/cm 3 which reduced significantly to 0.899 g/cm 3 for HC sample. The pH of the cake reduced from 7.23 to 6.78 with addition of CPP but increased slightly with inclusion of HC. The density of the cake reduced from 0.510 g/cm 3 for the control to 0.395 g/cm 3 for 20%CCP + C sample. The texture of the cakes became softer, more springy and chewable with addition of CPP, CPP + HC, and HC. The control sample had the lowest uniformity index (0.178) which improved with addition of CPP and CPP + HC and a highly uniform cake with a uniformity index of 0.045 was obtained for the 30%CCP + HC cake. Addition of CPP increased the dark color of the cakes while inclusion of HC had no effect on the appearance of the cake and color. It was concluded that inclusion of maximum 30%CCP and 20%CPP + HC promoted the quality and sensory attributes of gluten-free cakes. Although different types of gluten-free products are available in the market, most of them contain insufficient amount of fiber and nutrients. Despite popularity, gluten-free cakes are poor in fiber and nutrient contents. Therefore, improving the nutritional value of these products has received an increasing attention by the food industry. Carrot pomace powder (CPP) is an available source of fiber and nutrients and hence can be utilized for enrichment of gluten-free products. This study showed that the inclusion of up to 30% CPP or 20% CPP with a mixture of xanthan and pectin (3%, 1:1) improved the quality and sensory attributes of the cakes. Industrial implications of this study may lead to new product development and improved marketing due to the enhancement of quality, sensory attributes, and nutritional value of the products. © 2017 Wiley Periodicals, Inc.

Dopamine D3 receptors regulate reconsolidation of cocaine memory.

PubMed

Yan, Y; Kong, H; Wu, E J; Newman, A H; Xu, M

2013-06-25

Memories of learned associations between the rewarding properties of drugs of abuse and environmental cues contribute to craving and relapse in humans. Disruption of reconsolidation dampens or even erases previous memories. Dopamine (DA) mediates the acquisition of reward memory and drugs of abuse can pathologically change related neuronal circuits in the mesolimbic DA system. Previous studies showed that DA D3 receptors are involved in cocaine-conditioned place preference (CPP) and reinstatement of cocaine-seeking behavior. However, the role of D3 receptors in reconsolidation of cocaine-induced reward memory remains unclear. In the present study, we combined genetic and pharmacological approaches to investigate the role of D3 receptors in reconsolidation of cocaine-induced CPP. We found that the mutation of the D3 receptor gene weakened reconsolidation of cocaine-induced CPP in mice triggered by a 3-min (min) retrieval. Furthermore, treatment of a selective D3 receptor antagonist PG01037 immediately following the 3-min retrieval disrupted reconsolidation of cocaine-induced CPP in wild-type mice and such disruption remained at least 1 week after the 3-min retrieval. These results suggest that D3 receptors play a key role in reconsolidation of cocaine-induced CPP in mice, and that pharmacological blockade of these receptors may be therapeutic for the treatment of cocaine craving and relapse in clinical settings. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

[Effects of odor cue on morphine-induced dependence and craving in mice].

PubMed

Liu, Xiao-Fen; Yang, Guang; Yang, Rui; Jia, Qiang; Guan, Su-Dong

2012-04-01

The olfactory system may play a pivotal role in drug addiction. To clarify the issues, we investigated the morphine dependence and psychological craving in morphine addicted mice using the conditioned place preference (CPP) paradigm by taking an only odor cue as the conditioned stimulus (CS). The results showed that by pairing morphine with odor, the CPP could be induced in mice. When the morphine addicted mice were exposed to a novel environment during morphine withdrawal, they spent significantly longer time in the chamber with morphine-paired odor than in the control chamber. The effects of odor cue on the morphine CPP were blocked by the administration of dopamine D1 or D2 antagonists. The studies indicated that olfactory system plays an important role in drug addiction.

Intra-accumbal administration of AMN082, a metabotropic glutamate receptor type 7 allosteric agonist, inhibits the acquisition but not the expression of morphine-induced conditioned place preference in rats.

PubMed

Vatankhah, Mahsaneh; Karimi-Haghighi, Saeideh; Sarihi, Abdolrahman; Haghparast, Abbas

2018-05-22

The nucleus accumbens (NAc) plays a primary role in opioid reward. The actions of glutamate are mediated by the activation of ionotropic and metabotropic glutamate receptors (mGluRs). Previous documents have shown the extensive distributions of the different types of mGluRs, including mGluR7, in regions that are involved in opioid reward, such as the NAc. In this study, seventy male Wistar rats were used to investigate the role of mGluR7 receptors in the NAc on the acquisition and expression of morphine-induced conditioned place preference (CPP). In Experiment 1, to determine the effect of AMN082, a selective mGluR7 allosteric agonist, on the acquisition of morphine-induced conditioned place preference (CPP), the rats bilaterally received AMN082 (1, 3 and 5 μg/0.5 μL DMSO) during three-day conditioning by morphine (5 mg/kg). In Experiment 2, the rats bilaterally received AMN082 (5 μg/0.5 μL DMSO) 5 min prior to the post-conditioning test to investigate the effect of AMN082 on the expression of morphine-induced CPP. The results showed that the intra-accumbal injection of AMN082 prevents the acquisition of morphine-induced CPP in a dose-dependent manner. However, intra-accumbal injection of AMN082 had no effect on the expression of morphine-induced CPP. The findings propose that the mGluR7 in the NAc inhibits the acquisition of morphine-induced CPP that could be mediated by inhibition of NMDA receptors in the NAc. Copyright © 2018 Elsevier B.V. All rights reserved.

Inhibitory effects of forced swim stress and corticosterone on the acquisition but not expression of morphine-induced conditioned place preference: involvement of glucocorticoid receptor in the basolateral amygdala.

PubMed

Attarzadeh-Yazdi, Ghassem; Karimi, Sara; Azizi, Pegah; Yazdi-Ravandi, Saeid; Hesam, Soghra; Haghparast, Abbas

2013-09-01

Addiction is a common chronic psychiatric disease which represents a global problem and stress has an important role to increase drug addiction and relapse. In the present study, we investigated the effects of physical stress and exogenous corticosterone on the acquisition and expression of morphine-induced conditioned place preference (CPP). Also, we tried to find out the role of glucocorticoid receptors (GRs) of basolateral amygdala (BLA) in this regard. In the CPP paradigm, conditioning score and locomotion activity were recorded by Ethovision software. Male adult rats received forced swim stress (FSS) as a physical stress or corticosterone (10 mg/kg; ip) as a dominant stress hormone in rodents, 10min before morphine injection (5 mg/kg; sc) during three conditioning days (acquisition) or just prior to CPP test in the post-conditioning day (expression). In FSS procedure, animals were forced to swim for 6 min in cylinder filled with water (24-27 °C). To evaluate the role of glucocorticoid receptors in the BLA, different doses of mifepristone (RU38486) as a GR antagonist were injected into the BLA (0.3, 3 and 30 ng/side) during 3-day conditioning phase before FSS or injection of corticosterone in morphine-CPP paradigm. The results showed that FSS and corticosterone reduce the acquisition but not expression of morphine-induced CPP. Moreover, blockade of GRs in the BLA could diminish the inhibitory effects of FSS or corticosterone on the acquisition of morphine-induced CPP. It seems that stress exerts its effect on reward pathway via glucocorticoid receptors in the BLA. Copyright © 2013 Elsevier B.V. All rights reserved.

Efficient siRNA Delivery Using Novel Cell-Penetrating Peptide-siRNA Conjugate-Loaded Nanobubbles and Ultrasound.

PubMed

Xie, Xiangyang; Lin, Wen; Li, Mingyuan; Yang, Yang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yanfang

2016-06-01

Because of the absence of tolerable and effective carriers for in vivo delivery, the applications of small interfering RNA (siRNA) in the clinic for therapeutic purposes have been limited. In this study, development of a novel siRNA delivery system based on ultrasound-sensitive nanobubbles (NBs, nano-sized echogenic liposomes) and cell-permeable peptides (CPPs) is described. A CPP-siRNA conjugate was entrapped in an NB, (CPP-siRNA)-NB, and the penetration of CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research revealed that the (CPP-siRNA)-NBs had a mean particle size of 201 ± 2.05 nm and a siRNA entrapment efficiency >85%. In vitro release results indicated that >90% of the encapsulated CPP-siRNA was released from NBs in the presence of ultrasound, whereas <1.5% (30 min) was released in the absence of ultrasound. Cell experiments indicated higher cellular CPP-siRNA uptake of (CPP-siRNA)-NBs with ultrasound among the various formulations in human breast adenocarcinoma cells (HT-1080). Additionally, after systemic administration in mice, (CPP-siRNA)-NBs accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the application of (CPP-siRNA)-NBs with ultrasound may constitute an approach to selective targeted delivery of siRNA. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces Streptococcus mutans Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms

PubMed Central

Liu, Sze-Wei; Myroforidis, Helen; Zalizniak, Ilya; Palamara, Joseph E. A.; Huq, N. Laila; Reynolds, Eric C.

2016-01-01

Glass ionomer cements (GIC) are dental restorative materials that are suitable for modification to help prevent dental plaque (biofilm) formation. The aim of this study was to determine the effects of incorporating casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into a GIC on the colonisation and establishment of Streptococcus mutans biofilms and the effects of aqueous CPP-ACP on established S mutans biofilms. S. mutans biofilms were either established in flow cells before a single ten min exposure to 1% w/v CPP-ACP treatment or cultured in static wells or flow cells with either GIC or GIC containing 3% w/w CPP-ACP as the substratum. The biofilms were then visualised using confocal laser scanning microscopy after BacLight LIVE/DEAD staining. A significant decrease in biovolume and average thickness of S. mutans biofilms was observed in both static and flow cell assays when 3% CPP-ACP was incorporated into the GIC substratum. A single ten min treatment with aqueous 1% CPP-ACP resulted in a 58% decrease in biofilm biomass and thickness of established S. mutans biofilms grown in a flow cell. The treatment also significantly altered the structure of these biofilms compared with controls. The incorporation of 3% CPP-ACP into GIC significantly reduced S. mutans biofilm development indicating another potential anticariogenic mechanism of this material. Additionally aqueous CPP-ACP disrupted established S. mutans biofilms. The use of CPP-ACP containing GIC combined with regular CPP-ACP treatment may lower S. mutans challenge. PMID:27589264

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces Streptococcus mutans Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms.

PubMed

Dashper, Stuart G; Catmull, Deanne V; Liu, Sze-Wei; Myroforidis, Helen; Zalizniak, Ilya; Palamara, Joseph E A; Huq, N Laila; Reynolds, Eric C

2016-01-01

Glass ionomer cements (GIC) are dental restorative materials that are suitable for modification to help prevent dental plaque (biofilm) formation. The aim of this study was to determine the effects of incorporating casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into a GIC on the colonisation and establishment of Streptococcus mutans biofilms and the effects of aqueous CPP-ACP on established S mutans biofilms. S. mutans biofilms were either established in flow cells before a single ten min exposure to 1% w/v CPP-ACP treatment or cultured in static wells or flow cells with either GIC or GIC containing 3% w/w CPP-ACP as the substratum. The biofilms were then visualised using confocal laser scanning microscopy after BacLight LIVE/DEAD staining. A significant decrease in biovolume and average thickness of S. mutans biofilms was observed in both static and flow cell assays when 3% CPP-ACP was incorporated into the GIC substratum. A single ten min treatment with aqueous 1% CPP-ACP resulted in a 58% decrease in biofilm biomass and thickness of established S. mutans biofilms grown in a flow cell. The treatment also significantly altered the structure of these biofilms compared with controls. The incorporation of 3% CPP-ACP into GIC significantly reduced S. mutans biofilm development indicating another potential anticariogenic mechanism of this material. Additionally aqueous CPP-ACP disrupted established S. mutans biofilms. The use of CPP-ACP containing GIC combined with regular CPP-ACP treatment may lower S. mutans challenge.

NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

PubMed

Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

2013-04-01

Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

The effect of casein phosphopeptide-amorphous calcium phosphate and a cola soft drink on in vitro enamel hardness.

PubMed

Panich, Muratha; Poolthong, Suchit

2009-04-01

The authors conducted an in vitro study to compare the hardness of normal enamel with enamel eroded by a cola soft drink and enamel remineralized by casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) or artificial saliva. The authors immersed 40 extracted sound central and lateral incisors alternately in a cola soft drink or artificial saliva for 10 cycles of five seconds each. They repeated this procedure two times at six-hour intervals. They divided the samples randomly into four groups and applied CPP-ACP to the samples, immersed them in artificial saliva, deionized water or both. They measured the hardness on the labial surface at baseline, after erosion and after remineralization and analyzed the data with one-way repeated-measures analysis of variance and two-way analysis of variance. The cola soft drink significantly decreased enamel hardness. CPP-ACP and CPP-ACP and artificial saliva significantly increased the hardness of eroded enamel. CPP-ACP and CPP-ACP and artificial saliva increased the hardness of eroded enamel significantly more than artificial saliva did. CPP-ACP increased the hardness of eroded enamel. CPP-ACP had a greater effect on enamel hardness than did artificial saliva. Consumption of a cola soft drink can cause tooth erosion. CPP-ACP may significantly remineralize eroded enamel compared with artificial saliva.

Pathogenicity of swine influenza viruses possessing an avian or swine-origin PB2 polymerase gene evaluated in mouse and pig models.

PubMed

Ma, Wenjun; Lager, Kelly M; Li, Xi; Janke, Bruce H; Mosier, Derek A; Painter, Laura E; Ulery, Eva S; Ma, Jingqun; Lekcharoensuk, Porntippa; Webby, Richard J; Richt, Jürgen A

2011-02-05

PB2 627K is a determinant of influenza host range and contributes to the pathogenicity of human-, avian-, and mouse-adapted influenza viruses in the mouse model. Here we used mouse and pig models to analyze the contribution of a swine-origin and avian-origin PB2 carrying either 627K or 627E in the background of the classical swine H1N1 (A/Swine/Iowa/15/30; 1930) virus. The results showed PB2 627K is crucial for virulence in the mouse model, independent of whether PB2 is derived from an avian or swine influenza virus (SIV). In the pig model, PB2 627E decreases pathogenicity of the classical 1930 SIV when it contains the swine-origin PB2, but not when it possesses the avian-origin PB2. Our study suggests the pathogenicity of SIVs with different PB2 genes and mutation of codon 627 in mice does not correlate with the pathogenicity of the same SIVs in the natural host, the pig. Copyright © 2010 Elsevier Inc. All rights reserved.

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction.

PubMed

El Rawas, Rana; Klement, Sabine; Kummer, Kai K; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.

40 CFR 1039.627 - What are the incentives for equipment manufacturers to use cleaner engines?

Code of Federal Regulations, 2012 CFR

2012-07-01

... engines. (e) In-use fuel. If the engine manufacturer certifies using ultra low-sulfur diesel fuel, you... commits to a central-fueling facility with ultra low-sulfur diesel fuel throughout its lifetime would meet... 1039: If the engine's maximum power is . . . And you install . . . Certified early to the . . . You may...

40 CFR 1039.627 - What are the incentives for equipment manufacturers to use cleaner engines?

Code of Federal Regulations, 2013 CFR

2013-07-01

... engines. (e) In-use fuel. If the engine manufacturer certifies using ultra low-sulfur diesel fuel, you... commits to a central-fueling facility with ultra low-sulfur diesel fuel throughout its lifetime would meet... 1039: If the engine's maximum power is . . . And you install . . . Certified early to the . . . You may...

40 CFR 1039.627 - What are the incentives for equipment manufacturers to use cleaner engines?

Code of Federal Regulations, 2014 CFR

2014-07-01

... engines. (e) In-use fuel. If the engine manufacturer certifies using ultra low-sulfur diesel fuel, you... commits to a central-fueling facility with ultra low-sulfur diesel fuel throughout its lifetime would meet... 1039: If the engine's maximum power is . . . And you install . . . Certified early to the . . . You may...

The impact of a private group practice of converting to an automated medical information system.

PubMed

Templeton, J; Bernes, M; Ostrowski, M

1983-08-01

As hardware and software developments make medical information systems increasingly available to physicians office practices and outpatients facilities, there is a need to focus on systems installation and conversion issues. In addition to the detailed step-by-step implementation plan, the overall impact of the new system should be anticipated. The purchasers should consider such issues as new information flow and user communication patterns between patient care and ancillary and support departments; restructuring of fundamental approaches to work allocation for either batch or real-time systems; and new emphasis on any departments vital to problem-spotting and solving. At California Primary Physicians (CPP), an awareness of these changes did not develop until well after the official "live" data had passed and the staff had been successfully using the system for several months. This paper explains how the above issues have emerged and the impact they have had on CPP, and provides a framework for anticipating such matters in any system installation.

Surface bioengineering of diatomite based nanovectors for efficient intracellular uptake and drug delivery

NASA Astrophysics Data System (ADS)

Terracciano, Monica; Shahbazi, Mohammad-Ali; Correia, Alexandra; Rea, Ilaria; Lamberti, Annalisa; de Stefano, Luca; Santos, Hélder A.

2015-11-01

Diatomite is a natural porous silica material of sedimentary origin. Due to its peculiar properties, it can be considered as a valid surrogate of synthetic porous silica for nano-based drug delivery. In this work, we exploit the potential of diatomite nanoparticles (DNPs) for drug delivery with the aim of developing a successful dual-biofunctionalization method by polyethylene glycol (PEG) coverage and cell-penetrating peptide (CPP) bioconjugation, to improve the physicochemical and biological properties of the particles, to enhance the intracellular uptake in cancer cells, and to increase the biocompatibility of 3-aminopropyltriethoxysilane (APT) modified-DNPs. DNPs-APT-PEG-CPP showed hemocompatibility for up to 200 μg mL-1 after 48 h of incubation with erythrocytes, with a hemolysis value of only 1.3%. The cytotoxicity of the modified-DNPs with a concentration up to 200 μg mL-1 and incubation with MCF-7 and MDA-MB-231 breast cancer cells for 24 h, demonstrated that PEGylation and CPP-bioconjugation can strongly reduce the cytotoxicity of DNPs-APT. The cellular uptake of the modified-DNPs was also evaluated using the above mentioned cancer cell lines, showing that the CPP-bioconjugation can considerably increase the DNP cellular uptake. Moreover, the dual surface modification of DNPs improved both the loading of a poorly water-soluble anticancer drug, sorafenib, with a loading degree up to 22 wt%, and also enhanced the drug release profiles in aqueous solutions. Overall, this work demonstrates that the biofunctionalization of DNPs is a promising platform for drug delivery applications in cancer therapy as a result of its enhanced stability, biocompatibility, cellular uptake, and drug release profiles.Diatomite is a natural porous silica material of sedimentary origin. Due to its peculiar properties, it can be considered as a valid surrogate of synthetic porous silica for nano-based drug delivery. In this work, we exploit the potential of diatomite nanoparticles (DNPs) for drug delivery with the aim of developing a successful dual-biofunctionalization method by polyethylene glycol (PEG) coverage and cell-penetrating peptide (CPP) bioconjugation, to improve the physicochemical and biological properties of the particles, to enhance the intracellular uptake in cancer cells, and to increase the biocompatibility of 3-aminopropyltriethoxysilane (APT) modified-DNPs. DNPs-APT-PEG-CPP showed hemocompatibility for up to 200 μg mL-1 after 48 h of incubation with erythrocytes, with a hemolysis value of only 1.3%. The cytotoxicity of the modified-DNPs with a concentration up to 200 μg mL-1 and incubation with MCF-7 and MDA-MB-231 breast cancer cells for 24 h, demonstrated that PEGylation and CPP-bioconjugation can strongly reduce the cytotoxicity of DNPs-APT. The cellular uptake of the modified-DNPs was also evaluated using the above mentioned cancer cell lines, showing that the CPP-bioconjugation can considerably increase the DNP cellular uptake. Moreover, the dual surface modification of DNPs improved both the loading of a poorly water-soluble anticancer drug, sorafenib, with a loading degree up to 22 wt%, and also enhanced the drug release profiles in aqueous solutions. Overall, this work demonstrates that the biofunctionalization of DNPs is a promising platform for drug delivery applications in cancer therapy as a result of its enhanced stability, biocompatibility, cellular uptake, and drug release profiles. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05173h

Effects of the κ-opioid receptor on the inhibition of 100 Hz electroacupuncture on cocaine-induced conditioned place preference

PubMed Central

Hou, Bingjun

2016-01-01

The administration of 100 Hz electroacupuncture has been demonstrated to suppress cocaine-induced conditioned place preference (CPP) in rats, and there is evidence that the κ-opioid receptor may have a role in cocaine addiction. The present study sought to explore the mechanisms underlying the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP in rats. A rat model of cocaine-induced CPP was used in the present study to investigate the following: i) Naloxone treatment (5 and 10 mg/kg) following 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, revealing that a high dose (10 mg/kg) of naloxone blocked the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP; ii) nor-binaltorphimine (nor-BNI) on 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, which indicated that administration of 10 µg/5 µl and 0.3 µg/1 µl nor-BNI intracerebroventricularly and via the nucleus accumbens, respectively, reversed the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP, and that injection of nor-BNI in different brain areas of rats blocks the inhibitory effects of electroacupuncture on cocaine-induced CPP; and iv) 100 Hz electroacupuncture on the mRNA expression levels of the κ-opioid receptor in the rat nucleus accumbens and amygdala, which established that mRNA expression levels of κ-opioid receptor in the nucleus accumbens were increased with 100 Hz electroacupuncture plus cocaine-induced CPP. Overall, the results of the present study indicated that 100 Hz electroacupuncture was able to suppress cocaine-induced CPP via the κ-opioid receptor in the nucleus accumbens. PMID:27588082

Inhibitory effects of processed Aconiti tuber on morphine-induced conditioned place preference in rats.

PubMed

Wu, Guiyun; Huang, Wenqi; Zhang, Hui; Li, Qiaobo; Zhou, Jun; Shu, Haihua

2011-06-14

Our previous studies indicated that processed Aconiti tuber (PAT), a traditional Chinese herbal medicine, had antinociceptive effects and inhibitory effects on morphine tolerance by activation of kappa-opioid receptor (KOR). Preclinical studies also demonstrated that KOR agonists functionally attenuate addictive behaviors of morphine, such as conditioned place preference (CPP). Therefore, we hypothesize that PAT may inhibit morphine-induced CPP in rats. (1) Five groups of rats (n=8 for each group) were alternately subcutaneous (s.c.) injected with morphine 10mg/kg (one group receive normal saline as a control) and normal saline for 8 days and oral co-administrated with distilled water or PAT 0.3, 1.0, or 3.0 g/kg daily on days 2-9 during CPP training, respectively. (2) Other four groups of rats were randomly s.c. injected with nor-binaltorphimine (nor-BNI; 5mg/kg) or normal saline (as a control) 120 min before alternately s.c. with morphine and normal saline and oral co-administrated with distilled water or PAT 3.0 g/kg daily. Each rat was acquired pre-conditioning and post-conditioning CPP data and assayed dynorphin concentrations by radioimmunoassay in rat's nucleus accumbens (NAc) after CPP training. (1) PAT 1.0 or 3.0 g/kg dose-dependently decreased the morphine-induced increase of CPP scores. (2) Nor-BNI completely antagonized the inhibition of PAT on morphine-induced CPP. (3) PAT dose-dependently increased dynorphin content in rats' NAc after CPP training. (1) PAT dose-dependently inhibited morphine-induced CPP. (2) The inhibition of PAT on morphine-induced CPP was probably due to activation of KOR by increasing dynorphin release in rats' NAc. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction

PubMed Central

El Rawas, Rana; Klement, Sabine; Kummer, Kai K.; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex—nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction. PMID:23015784

18-methoxycoronaridine blocks acquisition but enhances reinstatement of a cocaine place preference

PubMed Central

McCallum, Sarah E.; Glick, Stanley D.

2009-01-01

The iboga alkaloid congener, 18-methoxycoronaridine (18-MC), decreases self-administration of multiple drugs of abuse. Here, in a biased procedure, we investigated whether 18-MC would have a similar effect on the acquisition, expression and reinstatement of a cocaine conditioned place preference (CPP) in male, Sprague-Dawley rats. While 18-MC attenuated acquisition of a cocaine CPP, it had no effect on CPP expression, and enhanced the reinstatement of cocaine CPP following extinction. Our results are consistent with those obtained using ibogaine, but reinforce the notion that acquisition, expression and reinstatement of a CPP likely involve separate mechanisms. PMID:19442876

Acute social defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.

PubMed

Montagud-Romero, S; Aguilar, M A; Maldonado, C; Manzanedo, C; Miñarro, J; Rodríguez-Arias, M

2015-08-01

Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute social defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to social defeat in an agonistic encounter before each session of conditioning with 1mg/kg or 25mg/kg of cocaine. The effects of social defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25mg/kg. Adult mice exposed to social defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of social defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced. Copyright © 2015 Elsevier Inc. All rights reserved.

Preventive Interventions and Sustained Attachment Security in Maltreated Children

PubMed Central

Stronach, Erin Pickreign; Toth, Sheree L.; Rogosch, Fred; Cicchetti, Dante

2013-01-01

Thirteen-month-old maltreated infants (n = 137) and their mothers were randomly assigned to one of three conditions: child-parent psychotherapy (CPP), psychoeducational parenting intervention (PPI), and community standard (CS). A fourth group of nonmaltreated infants (n =52) and their mothers served as a normative comparison (NC) group. A prior investigation found that the CPP and PPI groups demonstrated substantial increases in secure attachment at post-intervention, whereas this change was not found in the CS and NC groups. The current investigation involved the analysis of data obtained at a follow-up assessment that occurred 12-months after the completion of treatment. At follow-up, children in the CPP group had higher rates of secure and lower rates of disorganized attachment than did children in the PPI or CS groups. Rates of disorganized attachment did not differ between the CPP and NC groups. Intention-to-treat analyses (ITT) also showed higher rates of secure attachment at follow-up in the CPP group relative to the PPI and CS groups. However, groups did not differ on disorganized attachment. Both primary and ITT analyses demonstrated that maternal reported child behavior problems did not differ among the four groups at the follow-up assessment. This is the first investigation to demonstrate sustained attachment security in maltreated children 12 months after the completion of an attachment theory-informed intervention. Findings also suggest that, while effective in the short term, parenting interventions alone may not be effective in maintaining secure attachment in children over time. PMID:24229539

Atomic force microscopic comparison of remineralization with casein-phosphopeptide amorphous calcium phosphate paste, acidulated phosphate fluoride gel and iron supplement in primary and permanent teeth: An in-vitro study

PubMed Central

Agrawal, Nikita; Shashikiran, N. D.; Singla, Shilpy; Ravi, K. S.; Kulkarni, Vinaya Kumar

2014-01-01

Context: Demineralization of tooth by erosion is caused by frequent contact between the tooth surface and acids present in soft drinks. Aim: The present study objective was to evaluate the remineralization potential of casein-phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste, 1.23% acidulated phosphate fluoride (APF) gel and iron supplement on dental erosion by soft drinks in human primary and permanent enamel using atomic force microscopy (AFM). Materials and Methods: Specimens were made from extracted 15 primary and 15 permanent teeth which were randomly divided into three treatment groups: CPP-ACP paste, APF gel and iron supplement. AFM was used for baseline readings followed by demineralization and remineralization cycle. Results and Statistics: Almost all group of samples showed remineralization that is a reduction in surface roughness which was higher with CPP-ACP paste. Statistical analysis was performed using by one-way ANOVA and Mann-Whitney U-test with P < 0.05. Conclusions: It can be concluded that the application of CPP-ACP paste is effective on preventing dental erosion from soft drinks. PMID:24808700

Methylone and mCPP, two new drugs of abuse?

PubMed

Bossong, M G; Van Dijk, J P; Niesink, R J M

2005-12-01

Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called 'Explosion'. mCPP (meta-chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.

Obesity-resistant S5B rats showed great cocaine conditioned place preference than the obesity-prone OM rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thanos, P.K.; Wang, G.; Thanos, P.K..

Dopamine (DA) and the DA D2 receptor (D2R) are involved in the rewarding and conditioned responses to food and drug rewards. Osborne-Mendel (OM) rats are genetically prone and S5B/P rats are genetically resistant to obesity when fed a high-fat diet. We hypothesized that the differential sensitivity of these two rat strains to natural rewards may also be reflected in sensitivity to drugs of abuse. Therefore, we tested whether OM and S5B/P rats showed a differential preference to cocaine using conditioned place preference (CPP). To also evaluate whether there is specific involvement of the D2R in this differential conditioning sensitivity, wemore » then tested whether the D2R agonist bromocriptine (BC) would differentially affect the effects of cocaine in the two strains. OM and S5B/P rats were conditioned with cocaine (5 or 10 mg/kg) in one chamber and saline in another for 8 days. Rats were then tested for cocaine preference. The effects of BC (0.5, 1, 5, 10, 20 mg/kg) on cocaine preference were then assessed in subsequent test sessions. OM rats did not show a significant preference for the cocaine-paired chamber on test day. Only the S5B/P rats showed cocaine CPP. Later treatment with only the highest dose of BC resulted in reduced cocaine CPP in S5B/P rats when treated with 5 mg/kg cocaine and in OM rats treated with 10 mg/kg cocaine. Our results indicated that obesity-resistant S5B rats showed greater cocaine CPP than the obesity-prone OM rats. These findings do not support a theory of common vulnerability for reinforcer preferences (food and cocaine). However, they show that BC reduced cocaine conditioning effects supporting at least a partial regulatory role of D2R in conditioned responses to drugs.« less

Overexpression of Thioredoxin-1 Blocks Morphine-Induced Conditioned Place Preference Through Regulating the Interaction of γ-Aminobutyric Acid and Dopamine Systems.

PubMed

Li, Xiang; Huang, Mengbing; Yang, Lihua; Guo, Ningning; Yang, Xiaoyan; Zhang, Zhimin; Bai, Ming; Ge, Lu; Zhou, Xiaoshuang; Li, Ye; Bai, Jie

2018-01-01

Morphine is one kind of opioid, which is currently the most effective widely utilized pain relieving pharmaceutical. Long-term administration of morphine leads to dependence and addiction. Thioredoxin-1 (Trx-1) is an important redox regulating protein and works as a neurotrophic cofactor. Our previous study showed that geranylgeranylaceton, an inducer of Trx-1 protected mice from rewarding effects induced by morphine. However, whether overexpression of Trx-1 can block morphine-induced conditioned place preference (CPP) in mice is still unknown. In this study, we first examined whether overexpression of Trx-1 affects the CPP after morphine training and further examined the dopamine (DA) and γ-aminobutyric acid (GABA) systems involved in rewarding effects. Our results showed that morphine-induced CPP was blocked in Trx-1 overexpression transgenic (TG) mice. Trx-1 expression was induced by morphine in the ventral tegmental area (VTA) and nucleus accumbens (NAc) in wild-type (WT) mice, which was not induced in Trx-1 TG mice. The DA level and expressions of tyrosine hydroxylase (TH) and D1 were induced by morphine in WT mice, which were not induced in Trx-1 TG mice. The GABA level and expression of GABA B R were decreased by morphine, which were restored in Trx-1 TG mice. Therefore, Trx-1 may play a role in blocking CPP induced by morphine through regulating the expressions of D1, TH, and GABA B R in the VTA and NAc.

SEM investigation on casein phosphopeptides capability in contrasting cola drinks enamel erosion: an in vitro preliminary study.

PubMed

Ferrazzano, G F; Coda, M; Cantile, T; Sangianantoni, G; Ingenito, A

2012-12-01

Erosion of dental hard tissues induced by acidic dietary components is a high-prevalence finding, especially among children and adolescents. Acidic soft drinks are frequently implicated in dental erosion. The aim of this in vitro study was to assess if CPP-ACP preparation is capable of reducing enamel erosion caused by a cola-type drink. Twenty-five sound human permanent premolars, extracted for orthodontic reasons in patients of 12-16 years old, were used. The roots were removed and the crowns were sectioned in order to obtain 3 enamel sections from each tooth. The specimens were immersed in: (A) cola-type drink; (B) cola-type drink plus CPP-ACP; (C) deionised water (control) for: 48 h, 24 h, 12 h, 6 h and 3 h, respectively. pH values were constantly monitored. Statistical analysis was performed using ANOVA. The enamel samples were evaluated for surface changes using scanning electron microscopy (SEM). Specimens subjected to cola-type drink (treatment A) showed wide areas of enamel dissolution, while the treatment B specimens showed a few areas of little enamel erosion, different from control samples. Adding CPP-ACP to the cola-type drinks influenced pH levels of the solutions, but always in the acidity range. CPP-ACP provides protection against dental erosion from cola-type drinks in vitro. Therefore, further studies are necessary to evaluate if adding casein phosphopeptide-stabilised amorphous calcium phosphate complex to acidic cola drinks could reduce their erosive potential in vivo as well.

Conditioned Place Preference and Aversion for Music in a Virtual Reality Environment

PubMed Central

Molet, Mikaël; Billiet, Gauthier; Bardo, Michael T.

2012-01-01

The use of a virtual reality environment (VRE) enables behavioral scientists to create different spatial contexts in which human participants behave freely, while still confined to the laboratory. In this article, VRE was used to study conditioned place preference (CPP) and aversion (CPA). In Experiment 1, half of the participants were asked to visit a house for two min with consonant music and then they were asked to visit an alternate house with static noise for two min, whereas the remaining participants did the visits in reverse order. In Experiment 2, we used the same design as Experiment 1, except for replacing consonant music with dissonant music. After conditioning in both experiments, the participants were given a choice between spending time in the two houses. In Experiment 1, participants spent more time in the house associated with the consonant music, thus showing a CPP toward that house. In Experiment 2, participants spent less time in the house associated with the dissonant music, thus showing a CPA for that house. These results support VRE as a tool to extend research on CPP/CPA in humans. PMID:23089383

[Triptorelin therapy in girls with central precocious puberty increases body mass index].

PubMed

Martín Díaz, M J; Soriano Guillén, L; Muñoz Calvo, M T; Pozo Román, J; Argente Oliver, J

2006-11-01

The most important complications of central precocious puberty (CPP) in girls are loss of height and multiple psychosocial problems. To study the effect of triptorelin therapy in a cohort of girls with CPP. Thirty-four girls diagnosed with organic or idiopathic CPP and treated with monthly triptorelin were studied. Age, height in standard deviation (SD), bone age (Greulich and Pyle), height prediction (Bayle-Pinneau), body mass index (BMI) in SD, uterine size (pelvic ultrasound), target height, cranial magnetic resonance imaging, triptorelin dose, and treatment duration were studied. Triptorelin produced a statistically significant reduction in growth velocity and an increase in BMI after 1 year of therapy and these changes were maintained after discontinuation of therapy. Adult height in these patients was in accordance with their target genetic height, as well as with their predicted height according to the method of Bayley-Pinneau. No significant differences were found between age of menarche in our patients and in controls. Adult height in patients with organic CPP was significantly lower than that in patients with idiopathic CPP. 1. Triptorelin can increase BMI in girls with CPP. 2. The presence of an organic cause in patients with CPP worsens the prognosis for adult height. 3. The Bayley-Pinneau prediction method for "average" bone age is useful for establishing a prognosis of adult height in girls with CPP treated with triptorelin.

Assessment of White Spot Lesions and In-Vivo Evaluation of the Effect of CPP-ACP on White Spot Lesions in Permanent Molars of Children.

PubMed

Munjal, Deepti; Garg, Shalini; Dhindsa, Abhishek; Sidhu, Gagandeep Kaur; Sethi, Harsimran Singh

2016-05-01

As hindrance of remineralisation process occurs during orthodontic therapy resulting in decalcification of enamel because number of plaque retention sites increases due to banding and bonding of appliances to teeth. The present analytic study was undertaken to assess the occurrence of white spot lesions in permanent molars of children with and without orthodontic therapy and to evaluate the effect of Casein PhosphoPeptide-Amorphous Calcium Phosphate (CPP-ACP) on white spot lesions in post-orthodontic patients in a given period of time. The study comprised of examination of 679 first permanent molars which were examined to assess the occurrence of smooth surface white spot lesions in children of 8 to 16 years age group. Group I comprised subjects without any orthodontic treatment and Group II comprised of subjects who had undergone orthodontic therapy. The sample size was calculated using the epi-info6 computer package. Treatment group included 20 post-orthodontic patients examined with at least one white spot lesion within the enamel who received remineralizing cream (GC Tooth Mousse, Recaldent, GC Corporation.) i.e., CPP-ACP cream two times a day for 12 consecutive weeks. Computerized image analysis method was taken to evaluate white spot lesions. These frequency and percentages were compared with chi-square test. For comparison of numeric data, paired t-test was used. Of the total 278 (49.6%) first permanent molars showed occurrence of smooth surface white spot lesions out of 560 in Group I and 107 (89.9%) first permanent molars showed presence of white spot lesions out of 119 debanded first permanent molars of children examined in Group II. CPP-ACP therapy group showed reduction in severity of codes which was found to be highly significant after 12 weeks and eight weeks on gingival-third, p-value (<0.001) and significant after eight weeks and four weeks on middle-third according to ICDAS II criteria and computerized image analysis. CPP-ACP therapy minimum for 12 weeks is highly recommended as post-orthodontic treatment need in management of smooth surface white spot lesions on teeth undergoing fixed orthodontic therapy according to the present study.

The Effect of Casein Phosphopeptide-Amorf Calcium Phosphate and Acidulated Phosphate Fluoride Gel on Dental Erosion in Primary Teeth: An in Vitro Study.

PubMed

Maden, Eda Arat; Acar, Özge; Altun, Ceyhan; Polat, Günseli Güven

This study aimed to investigate the effect of acidulated phosphate fluoride (APF) gel and casein phosphopeptide/amorphous calciumphosphate (CPP-ACP) on the dental erosion produced by carbonated soft drink in primary teeth. This study evaluated by an in vitro model the effect of APF gel and CPP-ACP on the dental enamel previously subjected to erosive challenge with carbonated soft drink. Sixty sound human primary molars were prepared by embedding the crown sections in acrylic resin blocks leaving the enamel surfaces exposed. The surface roughness of the enamel was measured with prophilometry at baseline. Specimens were randomly divided into three treatment groups (n:20): artificial saliva, CPP-ACP, 1.23% APF gel. All specimens were then exposed to an erosive challenge of carbonated soft drink and artificial saliva for 20 cycles of 20 seconds each. Demineralization-remineralization cycles was repeated twice at eight-hour intervals and roughness values were measured. Enamel samples were treated with artificial saliva, CPP-ACP, 1.23% APF gel applied for 10 min after erosive challenge. The arithmetic average roughness (Ra) readings were recorded after remineralization agents were applied. The mean surface roughness in all groups increased significantly after erosion process and decreased after remineralization treatment. After treatment, the mean surface roughness of the 1.23% APF gel group was significantly less than the other groups and the mean surface roughness of the artificial saliva group was significantly more than the other groups. 1.23% APF gel showed the highest protective effect against erosive enamel loss. Under the conditions of this study, artificial saliva, CPP-ACP and 1.23% APF treatments were able to reduce erosive enamel loss produced by carbonated soft drink in primary teeth. However, 1.23% APF gel showed the highest protective effect against erosive enamel loss.

Complementary and Alternative Medicine in the Treatment of Chronic Pelvic Pain in Women: What Is the Evidence?

PubMed

Paiva, Sara; Carneiro, Márcia Mendonça

2013-01-01

Chronic pelvic pain (CPP) is defined as pain of at least 6 months' duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.

[Effects of propranolol on acquisition and retrieval of morphine- induced conditioned place preference memories in ICR mice].

PubMed

Mao, Yu; Yang, Shang-Chuan; Liu, Chang; Ma, Yuan-Ye; Hu, Xin-Tian

2011-12-01

To interfere with the drug-cue memory processes of addicts such as reconsolidation by the administration of the β-adrenergic receptor (β-AR) of norepinephrine (NE) antagonist propranolol (PRO) has become a potential therapy in the future to decrease or inhibit relapse. However, the relationship between PRO and the acquisition or retrieval of morphine-cue memory is not clear. This study examined the effects of PRO on the acquisition and retrieval of memories in morphine-induced conditioned place preference (CPP) mice model. We found that during memory acquisition period, PRO had no effects on the expression and extinction of morphine-CPP, which suggests that the β-AR was irrelevant to the CPP memory acquisition. However, during memory retrieval period, although PRO did not affect the expression of CPP, but it delayed the occurrence of CPP extinction, which indicates that PRO has an inhibit effect on CPP memory extinction, and β-AR plays an important role in modulating the extinction of morphine-CPP. Our study further improved the relationship between drug addiction and β-AR, and proposed a new theory to help developing potential therapy to cure addiction and other neuropsychiatric disorders.

ARCHITECTURAL WALL SECTIONS OF HOT PILOT PLANT (CPP640). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL WALL SECTIONS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111682. ALTERNATE ID NUMBER 8952-CPP-640-A-5. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

MISCELLANEOUS ARCHITECTURAL DETAILS OF HOT PILOT PLANT (CPP640). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS ARCHITECTURAL DETAILS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-640-00-279-111684. ALTERNATE ID NUMBER 8952-CPP-640-A-7. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1S,3S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115)

PubMed Central

2016-01-01

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5′-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5′-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general. PMID:25616005

Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1 S ,3 S )-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hyunbeom; Doud, Emma H.; Wu, Rui

gamma-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently,more » CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.« less

In vitro effect of amorphous calcium phosphate paste applied for extended periods of time on enamel remineralization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vieira, Ana Elisa de Mello; Danelon, Marcelle; Camara, Danielle Mendes da

Dental applications based on the unique characteristics of amorphous calcium phosphate stabilized by casein phosphopeptides (CPP-ACP) have been proposed, as well as the improvement of its properties. The objective of this study was to determine the ability of topically applied CPP-ACP from a commercial product to remineralize subsurface lesions when applied for extended periods of time (3 h and 8 h). Artificially induced carious lesions were produced in 50 bovine enamel blocks previously selected by surface hardness. After treatments with gel without F and CPP-ACP applied for 1 minute (Placebo); 2% NaF neutral gel applied for 1 minute (Fluoride 1more » min); CPP-ACP applied for 3 min (ACP 3 min); and CPP-ACP applied for 3 h (ACP 3 h) and for 8 h (ACP 8 h), the enamel blocks were submitted to the remineralization pH-cycling. Surface hardness and synchrotron micro-tomography were used to determine the percentage of surface hardness recovery (%SHR) and to calculate mineral concentration (g HAp.cm -3), respectively. The data were submitted to ANOVA followed by the Student-Newman-Keuls test (p<0.05). Fluoride gel presented higher %SHR followed by ACP 3 min (p<0.001). No difference (p = 0.148) was found for Placebo, ACP 3 h and ACP 8 h groups for %SHR. Fluoride gel showed greater mineral concentration (p<0.001) when compared with the other groups. ACP 3 min demonstrated a significant difference (p<0.001) from ACP 3 h and ACP 8 h. The ACP 3 h and 8 h presented a subsurface lesion with development of laminations in all blocks. In this in vitro study the use of CPP-ACP for extended periods of time did not produce an additive effect in the remineralization process.« less

In vitro effect of amorphous calcium phosphate paste applied for extended periods of time on enamel remineralization

DOE PAGES

Vieira, Ana Elisa de Mello; Danelon, Marcelle; Camara, Danielle Mendes da; ...

2017-12-01

Dental applications based on the unique characteristics of amorphous calcium phosphate stabilized by casein phosphopeptides (CPP-ACP) have been proposed, as well as the improvement of its properties. The objective of this study was to determine the ability of topically applied CPP-ACP from a commercial product to remineralize subsurface lesions when applied for extended periods of time (3 h and 8 h). Artificially induced carious lesions were produced in 50 bovine enamel blocks previously selected by surface hardness. After treatments with gel without F and CPP-ACP applied for 1 minute (Placebo); 2% NaF neutral gel applied for 1 minute (Fluoride 1more » min); CPP-ACP applied for 3 min (ACP 3 min); and CPP-ACP applied for 3 h (ACP 3 h) and for 8 h (ACP 8 h), the enamel blocks were submitted to the remineralization pH-cycling. Surface hardness and synchrotron micro-tomography were used to determine the percentage of surface hardness recovery (%SHR) and to calculate mineral concentration (g HAp.cm -3), respectively. The data were submitted to ANOVA followed by the Student-Newman-Keuls test (p<0.05). Fluoride gel presented higher %SHR followed by ACP 3 min (p<0.001). No difference (p = 0.148) was found for Placebo, ACP 3 h and ACP 8 h groups for %SHR. Fluoride gel showed greater mineral concentration (p<0.001) when compared with the other groups. ACP 3 min demonstrated a significant difference (p<0.001) from ACP 3 h and ACP 8 h. The ACP 3 h and 8 h presented a subsurface lesion with development of laminations in all blocks. In this in vitro study the use of CPP-ACP for extended periods of time did not produce an additive effect in the remineralization process.« less

Mechanism of inactivation of γ-aminobutyric acid aminotransferase by (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115).

PubMed

Lee, Hyunbeom; Doud, Emma H; Wu, Rui; Sanishvili, Ruslan; Juncosa, Jose I; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

2015-02-25

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently, CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. This represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.

Mechanism of Inactivation of γ-Aminobutyric Acid Aminotransferase by (1 S ,3 S)-3-Amino-4-difluoromethylene-1-cyclopentanoic Acid (CPP-115)

DOE PAGES

Lee, Hyunbeom; Doud, Emma H.; Wu, Rui; ...

2015-01-23

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently,more » CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. Ultimately, this represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.« less

Bioactive ceramic coating of cancellous screws improves the osseointegration in the cancellous bone.

PubMed

Lee, Jae Hyup; Nam, Hwa; Ryu, Hyun-Seung; Seo, Jun-Hyuk; Chang, Bong-Soon; Lee, Choon-Ki

2011-05-01

A number of methods for coating implants with bioactive ceramics have been reported to improve osseointegration in bone, but the effects of bioactive ceramic coatings on the osseointegration of cancellous screws are not known. Accordingly, biomechanical and histomorphometric analyses of the bone-screw interface of uncoated cancellous screws and cancellous screws coated with four different bioactive ceramics were performed. After coating titanium alloy cancellous screws with calcium pyrophosphate (CPP), CaO-SiO(2)-B(2)O(3) glass-ceramics (CSG), apatite-wollastonite 1:3 glass-ceramics (W3G), and CaO-SiO(2)-P(2)O(5)-B(2)O(3) glass-ceramics (BGS-7) using an enameling method, the coated and the uncoated screws were inserted into the proximal tibia and distal femur metaphysis of seven male mongrel dogs. The torque values of the screws were measured at the time of insertion and at removal after 8 weeks. The bone-screw contact ratio was analyzed by histomorphometry. There was no significant difference in the insertion torque between the uncoated and coated screws. The torque values of the CPP and BGS-7 groups measured at removal after 8 weeks were significantly higher than those of the uncoated group. Moreover, the values of the CPP and BGS-7 groups were significantly higher than the insertion torques. The fraction of bone-screw interface measured from the undecalcified histological slide showed that the CPP, W3G, and BGS-7 groups had significantly higher torque values in the cortical bone area than the uncoated group, and the CPP and BGS-7 groups had significantly higher torque values in the cancellous bone area than the uncoated group. In conclusion, a cancellous screw coated with CPP and BGS-7 ceramic bonds directly to cancellous bone to improve the bone-implant osseointegration. This may broaden the indications for cancellous screws by clarifying their contribution to improving osseointegration, even in the cancellous bone area.

Sex-specific effects of developmental alcohol exposure on cocaine-induced place preference in adulthood.

PubMed

Macht, Victoria A; Kelly, Sandra J; Gass, Justin T

2017-08-14

Fetal Alcohol Syndrome (FAS) is associated with high rates of drug addiction in adulthood. One possible basis for increased drug use in this population is altered sensitivity to drug-associated contexts. This experiment utilized a rat model of FASD to examine behavioral and neural changes in the processing of drug cues in adulthood. Alcohol was given by intragastric intubation to pregnant rats throughout gestation and to rat pups during the early postnatal period (ET group). Controls consisted of a non-treated group (NC) and a pair-fed group given the intubation procedure without alcohol (IC). On postnatal day (PD) 90, rats from all treatment groups were given saline, 0.3mg/kg, 3.0mg/kg, or 10.0mg/kg cocaine pairings with a specific context in the conditioned place preference (CPP) paradigm. While control animals of both sexes showed cocaine CPP at the 3.0 and 10.0mg/kg doses, ET females also showed cocaine CPP at 0.3mg/kg. This was accompanied by a decrease in c-Fos/GAD 67 cells in the nucleus accumbens (NAc) shell and GAD 67 -only cells in the NAc shell and PFC at this 0.3mg/kg dose. ET males failed to show cocaine CPP at the 3.0mg/kg dose. This was associated with an increase in c-Fos only-labeled cells in the NAc core and PFC at this 3.0mg/kg dose. These results suggest that developmental alcohol exposure has a sexually-dimorphic effect on cocaine's conditioning effects in adulthood and the NAc. Copyright © 2017 Elsevier B.V. All rights reserved.

The selective dopamine D3 receptor antagonist, SR 21502, reduces cue-induced reinstatement of heroin seeking and heroin conditioned place preference in rats.

PubMed

Galaj, Ewa; Manuszak, Monica; Babic, Sandra; Ananthan, Subramaniam; Ranaldi, Robert

2015-11-01

Because the role of dopamine (DA) D3 receptors has been investigated primarily in relation to cocaine-related behaviors little is known of the role of these receptors in heroin seeking. To investigate the effect of the selective DA D3 receptor antagonist, SR 21502, on cue-induced reinstatement of heroin seeking and heroin conditioned place preference (CPP). In experiment 1, rats were trained to self-administer intravenous heroin for 15 days followed by extinction. Following extinction animals were treated with one of several SR 21502 doses (0, 7.5, 10 or 15mg/kg) and a cue-induced reinstatement test was conducted. In experiment 2, animals were conditioned to experience heroin in one compartment of a CPP apparatus and saline in the other. On the test day animals were treated with 0, 3.75, 7.5, 10 or 15mg/kg of SR 21502 and tested for their CPP. The results from experiment 1 showed a significant dose-related reduction in cue-induced reinstatement of active lever pressing in the 7.5 and 10mg groups and an absence of the reinstatement effect in the 15mg group. In experiment 2, animals treated with vehicle or 3.75mg of SR 21502 showed significant heroin place preferences but those treated with the higher doses showed no CPP. Our findings suggest that DA D3 receptors play a significant role in heroin approach behaviors driven by conditioned stimuli. As such, we propose that SR 21502 holds potential as an effective pharmacotherapeutic agent for relapse prevention and should be studied further. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Hybrid 2D photonic crystal-assisted Lu3Al5O12:Ce ceramic-plate phosphor and free-standing red film phosphor for white LEDs with high color-rendering index.

PubMed

Park, Hoo Keun; Oh, Ji Hye; Kang, Heejoon; Zhang, Jian; Do, Young Rag

2015-03-04

This paper reports the combined optical effects of a two-dimensional (2D) SiNx photonic crystal layer (PCL)-assisted Lu3Al5O12:Ce (LuAG:Ce) green ceramic-plate phosphor (CPP) and a free-standing (Sr,Ca)AlSiN3:Eu red film phosphor to enhance luminous efficacy, color rendering index (CRI), and special CRI (R9) of LuAG:Ce CPP-capped white light-emitting diodes (LEDs) for high-power white LEDs at 350 mA. By introducing the 2D SiNx PCL, the luminous efficacy was improved by a factor of 1.25 and 1.15 compared to that of the conventional flat CPP-capped LED and the thickness-increased CPP-capped LED (with a thickness of 0.15 mm), respectively, while maintaining low color-rendering properties. The combining of the free-standing red film phosphor in the flat CPP-capped, the 2D PCL-assisted CPP-capped, and the thickness-increased CPP-capped LEDs led to enhancement of the CRI and the special CRI (R9); it also led to a decrease of the correlated color temperature (CCT) due to broad wavelength coverage via the addition of red emission. High CRI (94), natural white CCT (4450 K), and acceptable luminous efficacy (71.1 lm/W) were attained from the 2D PCL-assisted LuAG:Ce CPP/free-standing red film phosphor-based LED using a red phosphor concentration of 7.5 wt %. It is expected that the combination of the 2D PCL and the free-standing red film phosphor will be a good candidate for achieving a high-power white CPP-capped LED with excellent CRI.

The effects of d-govadine on conditioned place preference with d-amphetamine or food reward.

PubMed

Nesbit, Maya O; Dias, Carine; Phillips, Anthony G

2017-03-15

Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

Toward an understanding of disequilibrium dihedral angles in mafic rocks

USGS Publications Warehouse

Holness, Marian B.; Humphreys, Madeleine C.S.; Sides, Rachel; Helz, Rosalind T.; Tegner, Christian

2012-01-01

The median dihedral angle at clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, Θcpp, is generally lower than equilibrium (109˚ {plus minus} 2˚). Observation of a wide range of mafic bodies demonstrates that previous work on systematic variations of Θcpp is incorrect in several important respects. Firstly, the spatial distribution of plagioclase compositional zoning demonstrates that the final geometry of three-grain junctions, and hence Θcpp, is formed during solidification (the igneous process): sub-solidus textural modification in most dolerites and gabbros, previously thought to be the dominant control on Θcpp, is insignificant. Θcpp is governed by mass transport constraints, the inhibiting effects of small pore size on crystallization, and variation in relative growth rates of pyroxene and plagioclase. During rapid cooling, pyroxene preferentially fills wider pores while the narrower pores remain melt-filled, resulting in an initial value of Θcpp of 78˚, rather than 60˚ which would be expected if all melt-filled pores were filled with pyroxene. Lower cooling rates create a higher initial Θcpp due to changes in relative growth rates of the two minerals at the nascent three-grain junction. Low Θcpp (associated with cuspate clinopyroxene grains at triple junctions) can also be diagnostic of infiltration of previously melt-free rocks by late-stage evolved liquids (the metasomatic process). Modification of Θcpp by sub-solidus textural equilibration (the metamorphic process) is only important for fine-grained mafic rocks such as chilled margins and intra-plutonic chill zones. In coarse-grained gabbros from shallow crustal intrusions the metamorphic process occurs only in the centres of oikocrysts, associated with rounding of chadacrysts.

Regulation of extinction of cocaine-induced place preference by midkine is related to a differential phosphorylation of peroxiredoxin 6 in dorsal striatum.

PubMed

Gramage, Esther; Pérez-García, Carmen; Vicente-Rodríguez, Marta; Bollen, Silke; Rojo, Loreto; Herradón, Gonzalo

2013-09-15

The neurotrophic factors Midkine (MK) and Pleiotrophin (PTN) have been suggested to modulate drugs of abuse-induced effects. To test this hypothesis, cocaine (10 and 15mg/kg)-induced conditioned place preference (CPP) was rendered in PTN knockout (PTN-/-), MK knockout (MK-/-) and wild type (WT+/+) mice, and then extinguished after repeated saline injections (distributed in 4 extinction sessions). Cocaine induced a similar CPP in all the three genotypes. We found a significantly increased percentage of MK-/- mice that did not extinguish cocaine CPP at the end of the extinction sessions. Particularly, 40% of MK-/- mice did not extinguish cocaine (15mg/kg)-induced CPP compared to WT+/+ and PTN-/- mice (∼0-6%). Interestingly, we found that a greater magnitude of extinction of CPP after the first extinction session (5 days after last administration of cocaine) correlates with increased tyrosine phosphorylation of the enzyme peroxiredoxin 6 in the dorsal striatum of MK-/- mice. On the other hand, a greater magnitude of CPP extinction correlates with increased tyrosine phosphorylation of aconitase 2 in the prefrontal cortex of WT+/+ mice. In contrast, a lower magnitude of CPP extinction correlates with increased phosphorylation of aconitase 2 in the prefrontal cortex of PTN-/- mice, suggesting that the correlation between the tyrosine phosphorylation levels of aconitase 2 and magnitude of CPP extinction depends on the genotype considered. The data demonstrate that MK is a novel genetic factor that plays a role in the extinction of cocaine-induced CPP by mechanisms that may involve specific phosphorylation of striatal peroxiredoxin 6. Copyright © 2013 Elsevier B.V. All rights reserved.

A survey to assess the extent of public-private mix DOTS in the management of tuberculosis in Zambia

PubMed Central

Kapata, Nathan; Maboshe, Mwendaweli; Michelo, Charles; Babaniyi, Olusegun

2015-01-01

Background Involving all relevant healthcare providers in tuberculosis (TB) management through public-private mix (PPM) approaches is a vital element in the World Health Organization's (WHO) Stop TB Strategy. The control of TB in Zambia is mainly done in the public health sector, despite the high overall incidence rates. Aim We conducted a survey to determine the extent of private-sector capacity, participation, practices and adherence to national guidelines in the control of TB. Setting This survey was done in the year 2012 in 157 facilities in three provinces of Zambia where approximately 85% of the country's private health facilities are found. Methods We used a structured questionnaire to interview the heads of private health facilities to assess the participation of the private health sector in TB diagnosis, management and prevention activities. Results Out of 157 facilities surveyed, 40.5% were from the Copperbelt, 4.4% from Central province and 55.1% from Lusaka province. Only 23.8% of the facilities were able to provide full diagnosis and management of TB patients. Although 47.4% of the facilities reported that they do notify their cases to the National TB control programme, the majority (62.7%) of these facilities did not show evidence of notifications. Conclusion Our results show that the majority of the facilities that diagnose and manage TB in the private sector do not report their TB activities to the National TB Control Programme (NTP). There is a need for the NTP to improve collaboration with the private sector with respect to TB control activities and PPM for Directly Observed Treatment, Short Course (DOTS). PMID:26245591

Cocaine enhances the conditioned rewarding effects of MDMA in adolescent mice.

PubMed

Aguilar, M A; Roger-Sánchez, C; Rodríguez-Arias, M; Miñarro, J

2015-04-01

Although the consumption of cocaine is frequent in young users of MDMA (3,4-methylenedioxymethamphetamine), the influence of exposure to cocaine on the rewarding effects of MDMA in adolescents has not been studied. The purpose of the present work was to evaluate the effect of co-administration of cocaine (1 and 10 mg/kg) and a sub-threshold dose of MDMA (1.25 mg/kg) on the acquisition of conditioned place preference (CPP) (experiment 1). In addition, the effect of pre-treatment with cocaine on MDMA-induced CPP was evaluated (experiment 2). Levels of monoamines in striatum, hippocampus and cortex were measured in both experiments. Our hypotheses were that cocaine co-administration or pre-treatment would increase the rewarding effects of MDMA, and that these effects would be related with changes in brain monoamine levels. Our results showed that cocaine potentiated the rewarding effects of MDMA, since a sub-threshold dose of MDMA, which did not induce CPP by itself, induced a significant CPP in adolescent mice when administered along with cocaine during conditioning (experiment 1). Moreover, pre-treatment with cocaine several days before conditioning also increased the rewarding effects of MDMA (experiment 2). No significant changes in the levels of biogenic amines, which correlated with these behavioural effects, were observed. Our results confirm the involvement of the dopaminergic system in MDMA-induced CPP in adolescent mice and suggest that combined consumption with or pre-exposure to cocaine increases the conditioned rewarding effects of MDMA, which may enhance the capacity of MDMA to induce dependence. Copyright © 2015 Elsevier Inc. All rights reserved.

Efficacy and safety of triptorelin 6-month formulation in patients with central precocious puberty.

PubMed

Klein, Karen; Yang, Joshua; Aisenberg, Javier; Wright, Nancy; Kaplowitz, Paul; Lahlou, Najiba; Linares, Jeannete; Lundström, Eija; Purcea, Daniela; Cassorla, Fernando

2016-11-01

Triptorelin is an established treatment for central precocious puberty (CPP) as 1- and 3-month formulations. The current triptorelin 22.5 mg 6-month formulation is approved for prostate cancer therapy. This is the first study in patients with CPP. The efficacy and safety of the triptorelin 6-month formulation in CPP were investigated. The primary objective was to evaluate the efficacy in achieving luteinizing hormone (LH) suppression to pre-pubertal levels at month 6. This was an international, non-comparative phase III study over 48 weeks. Eighteen medical centers in the US, Chile and Mexico participated. Forty-four treatment naïve patients (39 girls and five boys) aged at treatment start 2-8 years for girls and 2-9 years for boys with an advancement of bone age over chronological age ≥1 year were to be included. Triptorelin was administered im twice at an interval of 24 weeks. LH, follicle stimulating hormone (FSH) (basal and stimulated), estradiol (girls), testosterone (boys), auxological parameters, clinical signs of puberty and safety were assessed. Forty-one patients (93.2%) showed pre-pubertal LH levels (stimulated LH ≤5 IU/L) at month 6 and maintained LH suppression through month 12. The percentage of patients with LH suppression exceeded 93% at each time point and reached 97.7% at month 12. No unexpected drug-related adverse events were reported. The triptorelin 6-month formulation was safe and effective in suppressing the pituitary-gonadal axis in children with CPP. The extended injection interval may improve compliance and increase comfort in the management of CPP.

Anaerobic cycling performance characteristics in prepubescent, adolescent and young adult females.

PubMed

Doré, E; Bedu, M; França, N M; Van Praagh, E

2001-05-01

The purpose of this study was to determine whether the relationships between short-term power and body dimensions in young females were similar whatever the age of the individuals. A cohort of 189 prepubescent (mean age 9.5 years), adolescent (mean age 14.4 years) and young adult (mean age 18.2 years) females performed three all-out sprints on a friction-loaded cycle ergometer against three braking forces corresponding to applied loads of 25, 50 and 75 g.kg-1 body mass (BM). For each sprint, peak power including flywheel inertia was calculated. Results showed that a braking load of 75 g.kg-1 BM was too high for prepubescent and adolescent girls. Therefore, when measuring short-term cycling performance in heterogeneous female populations, a braking load of 50 g.kg-1 BM (0.495 N.kg-1 BM) is recommended. During growth, cycling peak power (CPP; defined as the highest peak power obtained during the three sprints) increased, as did total BM, fat-free mass (FFM) and lean leg volume (LLV) (P < 0.001). Analysis of covariance revealed that the slopes of the linear relationships between CPP and biometric characteristics were similar in the three groups (P > 0.7 for the CPP/BM and CPP/FFM relationships, and P > 0.2 for the CPP/LLV relationship). However, the adjusted means were always significantly higher in young women (P < 0.001) compared with both of the other groups. Although differences in performance during anaerobic cycling in growing females are primarily dependent upon body dimensions, other as yet undetermined factors may be involved during late adolescence.

The bed nucleus of the stria terminalis regulates ethanol-seeking behavior in mice.

PubMed

Pina, Melanie M; Young, Emily A; Ryabinin, Andrey E; Cunningham, Christopher L

2015-12-01

Drug-associated stimuli are considered important factors in relapse to drug use. In the absence of drug, these cues can trigger drug craving and drive subsequent drug seeking. One structure that has been implicated in this process is the bed nucleus of the stria terminalis (BNST), a chief component of the extended amygdala. Previous studies have established a role for the BNST in cue-induced cocaine seeking. However, it is unclear if the BNST underlies cue-induced seeking of other abused drugs such as ethanol. In the present set of experiments, BNST involvement in ethanol-seeking behavior was assessed in male DBA/2J mice using the conditioned place preference procedure (CPP). The BNST was inhibited during CPP expression using electrolytic lesions (Experiment 1), co-infusion of GABAA and GABAB receptor agonists muscimol and baclofen (M+B; Experiment 2), and activation of inhibitory designer receptors exclusively activated by designer drugs (hM4Di-DREADD) with clozapine-N-oxide (CNO; Experiment 3). The magnitude of ethanol CPP was reduced significantly by each of these techniques. Notably, infusion of M+B (Exp. 2) abolished CPP altogether. Follow-up studies to Exp. 3 showed that ethanol cue-induced c-Fos immunoreactivity in the BNST was reduced by hM4Di activation (Experiment 4) and in the absence of hM4Di, CNO did not affect ethanol CPP (Experiment 5). Combined, these findings demonstrate that the BNST is involved in the modulation of cue-induced ethanol-seeking behavior. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mesolimbic leptin signaling negatively regulates cocaine-conditioned reward.

PubMed

Shen, M; Jiang, C; Liu, P; Wang, F; Ma, L

2016-12-06

The regulatory mechanisms underlying the response to addictive drugs are complex, and increasing evidence indicates that there is a role for appetite-regulating pathways in substance abuse. Leptin, an important adipose hormone that regulates energy balance and appetite, exerts its physiological functions via leptin receptors. However, the role of leptin signaling in regulating the response to cocaine remains unclear. Here we examined the potential role of leptin signaling in cocaine reward using a conditioned place preference (CPP) procedure. Our results showed that inhibition of leptin signaling by intracerebroventricular infusion of the leptin receptor (LepR) antagonist SMLA during cocaine conditioning increased the cocaine-CPP and upregulated the level of dopamine and its metabolites in the nucleus accumbens (NAc). We then selectively knocked down the LepR in the mesolimbic ventral tegmental area (VTA), NAc core and central amygdala (CeA) by injecting AAV-Cre into Lepr flox/flox mice. LepR deletion in the VTA increased the dopamine levels in the NAc and enhanced the cocaine-conditioned reward. LepR deletion in the NAc core enhanced the cocaine-conditioned reward and impaired the effect of the D2-dopamine receptor on cocaine-CPP, whereas LepR deletion in the CeA had no effect on cocaine-CPP but increased the anxiety level of mice. In addition, prior exposure to saccharin increased LepR mRNA and STAT3 phosphorylation in the NAc and VTA and impaired cocaine-CPP. These results indicate that leptin signaling is critically involved in cocaine-conditioned reward and the regulation of drug reward by a natural reward and that these effects are dependent on mesolimbic LepR.

Large-Scale Conformational Dynamics Control H5N1 Influenza Polymerase PB2 Binding to Importin α.

PubMed

Delaforge, Elise; Milles, Sigrid; Bouvignies, Guillaume; Bouvier, Denis; Boivin, Stephane; Salvi, Nicola; Maurin, Damien; Martel, Anne; Round, Adam; Lemke, Edward A; Jensen, Malene Ringkjøbing; Hart, Darren J; Blackledge, Martin

2015-12-09

Influenza A RNA polymerase complex is formed from three components, PA, PB1, and PB2. PB2 is independently imported into the nucleus prior to polymerase reconstitution. All crystallographic structures of the PB2 C-terminus (residues 536-759) reveal two globular domains, 627 and NLS, that form a tightly packed heterodimer. The molecular basis of the affinity of 627-NLS for importins remained unclear from these structures, apparently requiring large-scale conformational changes prior to importin binding. Using a combination of solution-state NMR, small-angle neutron scattering, small-angle X-ray scattering (SAXS), and Förster resonance energy transfer (FRET), we show that 627-NLS populates a temperature-dependent dynamic equilibrium between closed and open states. The closed state is stabilized by a tripartite salt bridge involving the 627-NLS interface and the linker, that becomes flexible in the open state, with 627 and NLS dislocating into a highly dynamic ensemble. Activation enthalpies and entropies associated with the rupture of this interface were derived from simultaneous analysis of temperature-dependent chemical exchange saturation transfer measurements, revealing a strong temperature dependence of both open-state population and exchange rate. Single-molecule FRET and SAXS demonstrate that only the open-form is capable of binding to importin α and that, upon binding, the 627 domain samples a dynamic conformational equilibrium in the vicinity of the C-terminus of importin α. This intrinsic large-scale conformational flexibility therefore enables 627-NLS to bind importin through conformational selection from a temperature-dependent equilibrium comprising both functional forms of the protein.

ARCHITECTURAL FLOOR PLAN OF OPERATING AREA HOT PILOT PLANT (CPP640). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL FLOOR PLAN OF OPERATING AREA HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111678. ALTERNATE ID NUMBER 8952-CPP-640-A-1. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

ARCHITECTURAL DOOR DETAILS AND SCHEDULE OF HOT PILOT PLANT (CPP640). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL DOOR DETAILS AND SCHEDULE OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-640-00-279-111683. ALTERNATE ID NUMBER 8952-CPP-640-A-6. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists.

PubMed

Grabus, Sheri D; Martin, Billy R; Brown, Sharon E; Damaj, M Imad

2006-03-01

Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.

Disequilibrium dihedral angles in dolerite sills

USGS Publications Warehouse

Holness, Marian B.; Richardson, Chris; Helz, Rosalind T.

2012-01-01

The geometry of clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, measured by the median dihedral angle Θcpp, is created during solidification. In the solidifying Kilauea Iki (Hawaii) lava lake, the wider junctions between plagioclase grains are the first to be filled by pyroxene, followed by the narrower junctions. The final Θcpp, attained when all clinopyroxene-plagioclase-plagioclase junctions are formed, is 78° in the upper crust of the lake, and 85° in the lower solidification front. Θcpp in the 3.5-m-thick Traigh Bhàn na Sgùrra sill (Inner Hebrides) is everywhere 78°. In the Whin Sill (northern England, 38 m thick) and the Portal Peak sill (Antarctica, 129 m thick), Θcpp varies symmetrically, with the lowest values at the margins. The 266-m-thick Basement Sill (Antarctica) has asymmetric variation of Θcpp, attributed to a complex filling history. The chilled margins of the Basement Sill are partially texturally equilibrated, with high Θcpp. The plagioclase grain size in the two widest sills varies asymmetrically, with the coarsest rocks found in the upper third. Both Θcpp and average grain size are functions of model crystallization times. Θcpp increases from 78° to a maximum of ∼100° as the crystallization time increases from 1 to 500 yr. Because the use of grain size as a measure of crystallization time is dependent on an estimate of crystal growth rates, dihedral angles provide a more direct proxy for cooling rates in dolerites.

The Selective D3 Receptor Antagonist SB277011A Attenuates Morphine-Triggered Reactivation of Expression of Cocaine-Induced Conditioned Place Preference

PubMed Central

Rice, Onarae V.; Heidbreder, Christian A.; Gardner, Eliot L.; Schonhar, Charles D.; Ashby, Charles R.

2014-01-01

We examined the effect of acute administration of the selective D3 receptor antagonist SB277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB277011 decreases the incentive motivational actions of morphine. The present findings suggest that central D3 dopamine receptors are involved in relapse to cocaine-seeking behavior that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D3 receptor antagonists constitute promising compounds for treating addiction. PMID:23404528

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) ON THE RIGHT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) ON THE RIGHT AND LABORATORY (CPP-602) ON THE LEFT. INL PHOTO NUMBER NRTS-51-3373. Unknown Photographer, 9/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Quantitative Analysis of Remineralization of Artificial Carious Lesions with Commercially Available Newer Remineralizing Agents Using SEM-EDX- In Vitro Study”

PubMed Central

Rambabu, Tanikonda; Sajjan, Girija; Varma, Madhu; Satish, Kalyan; Raju, Vijayalakshmi Bhupathi; Ganguru, Sirisha; Ventrapati, Nagalkashmi

2017-01-01

Introduction The basic principle of remineralization is by advocating a biological or non-invasive approach rather than the surgical approach for early enamel lesions. There are relatively newer products available for remineralization, latest being the resin-infiltration technique, commercially available as Icon. Aim The aim of the study was to evaluate the remineralizing potential of Casein Phosphopeptide-Amorphous Calcium Phosphate (CPP-ACP), Vantej and Icon by the quantitative evaluation of mineral gain. Materials and Methods Seventy eight maxillary premolars were decoronated at Cemento-Enamel Junction (CEJ) and then sectioned mesio-distally using diamond disc into two halves. Mineral content of the sound specimens were recorded using Energy Dispersive X-ray (EDAX) micro-analyser. The samples were then subjected to demineralization by using demineralizing solution. The samples were grouped (n=26) based on the remineralizing agent used, Group 1: Vantej, Group 2: CPP-ACP, Group 3: Icon. After the application of remineralizing agent, the mineral content was measured using EDAX. Results After remineralization, there was a significant difference between the groups when calcium and phosphorous ratios (Ca:P) were compared, showing greater potential of remineralization for CPP-ACP followed by Vantej and Icon group. Conclusion CPP-ACP performed better than Vantej and Icon in remineralizing the demineralized enamel. PMID:28571254

On the molecular structure, vibrational spectra, HOMO-LUMO, molecular electrostatic potential, UV-Vis, first order hyperpolarizability, and thermodynamic investigations of 3-(4-chlorophenyl)-1-(1yridine-3-yl) prop-2-en-1-one by quantum chemistry calculations

NASA Astrophysics Data System (ADS)

Rahmani, Rachida; Boukabcha, Nourdine; Chouaih, Abdelkader; Hamzaoui, Fodil; Goumri-Said, Souraya

2018-03-01

A recent experimental study has allowed synthesis of a new organic nonlinear optical material 3-(4-chlorophenyl)-1-(pyridin-3-yl)prop-2-en-1-one(CPP) with a high second harmonic generation efficiency. We apply density functional theory (DFT, GGA and B3LYP) and Hartree-Fock (HF) methods to calculate the vibrational wavenumbers. They are assigned with by using the potential energy distribution method. The calculated first hyperpolarizability of the title compound is comparable with the reported values of similar derivatives and 25 times that of the standard NLO material urea. The HOMO-LUMO calculations lead to consider GGA-PBE as the best functional to determine the electronic band gap of CPP molecule. We complete this study with assignment of the vibrational modes and perform a comparison with the experimental results. The analysis of MEP map shows that the most reactive site of the CPP molecule is the site containing the oxygen atom. Furthermore, because of the enhancement of molecular vibration within the CPP molecule, the thermodynamic parameters are increasing with the increase of temperature. The FTIR, Raman and NMR spectra are calculated using DFT approach and corroborate the experimental available data.

Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

PubMed

Bahi, Amine

2013-07-01

Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

The effect of phosphodiesterase inhibitors on the extinction of cocaine-induced conditioned place preference in mice.

PubMed

Liddie, Shervin; Anderson, Karen L; Paz, Andres; Itzhak, Yossef

2012-10-01

Several phosphodiesterase inhibitors (PDEis) improve cognition, suggesting that an increase in brain cAMP and cGMP facilitates learning and memory. Since extinction of drug-seeking behavior requires associative learning, consolidation and formation of new memory, the present study investigated the efficacy of three different PDEis in the extinction of cocaine-induced conditioned place preference (CPP) in B6129S mice. Mice were conditioned by escalating doses of cocaine which was resistant to extinction by free exploration. Immediately following each extinction session mice received (a) saline/vehicle, (b) rolipram (PDE4 inhibitor), (c) BAY-73-6691 (PDE9 inhibitor) or (d) papaverine (PDE10A inhibitor). Mice that received saline/vehicle during extinction training showed no reduction in CPP for >10 days. BAY-73-6691 (a) dose-dependently increased cGMP in hippocampus and amygdala, (b) significantly facilitated extinction and (c) diminished the reinstatement of cocaine CPP. Rolipram, which selectively increased brain cAMP levels, and papaverine which caused increases in both cAMP and cGMP levels, had no significant effect on the extinction of cocaine CPP. The results suggest that increase in hippocampal and amygdalar cGMP levels via blockade of PDE9 has a prominent role in the consolidation of extinction learning.

Novel Treatment of Chronic Bladder Pain Syndrome and Other Pelvic Pain Disorders by OnabotulinumtoxinA Injection.

PubMed

Jhang, Jia-Fong; Kuo, Hann-Chorng

2015-06-18

Chronic pelvic pain (CPP) is defined as pain in the pelvic organs and related structures of at least 6 months' duration. The pathophysiology of CPP is uncertain, and its treatment presents challenges. Botulinum toxin A (BoNT-A), known for its antinociceptive, anti-inflammatory, and muscle relaxant activity, has been used recently to treat refractory CPP with promising results. In patients with interstitial cystitis/bladder pain syndrome, most studies suggest intravesical BoNT-A injection reduces bladder pain and increases bladder capacity. Repeated BoNT-A injection is also effective and reduces inflammation in the bladder. Intraprostatic BoNT-A injection could significantly improve prostate pain and urinary frequency in the patients with chronic prostatitis/chronic pelvic pain syndrome. Animal studies also suggest BoNT-A injection in the prostate decreases inflammation in the prostate. Patients with CPP due to pelvic muscle pain and spasm also benefit from localized BoNT-A injections. BoNT-A injection in the pelvic floor muscle improves dyspareunia and decreases pelvic floor pressure. Preliminary studies show intravesical BoNT-A injection is useful in inflammatory bladder diseases such as chemical cystitis, radiation cystitis, and ketamine related cystitis. Dysuria is the most common adverse effect after BoNT-A injection. Very few patients develop acute urinary retention after treatment.

EAST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTHWEST. MAINTENANCE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. MAINTENANCE SHOP AND OFFICE BUILDING (CPP-630) ON RIGHT IN PHOTO. INL PHOTO NUMBER HD-22-3-2. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Entropy as an indicator of cerebral perfusion in patients with increased intracranial pressure.

PubMed

Khan, James; Mariappan, Ramamani; Venkatraghavan, Lashmi

2014-07-01

Changes in electroencephalogram (EEG) patterns correlate well with changes in cerebral perfusion pressure (CPP) and hence entropy and bispectral index values may also correlate with CPP. To highlight the potential application of entropy, an EEG-based anesthetic depth monitor, on indicating cerebral perfusion in patients with increased intracranial pressure (ICP), we report two cases of emergency neurosurgical procedure in patients with raised ICP where anesthesia was titrated to entropy values and the entropy values suddenly increased after cranial decompression, reflecting the increase in CPP. Maintaining systemic blood pressure in order to maintain the CPP is the anesthetic goal while managing patients with raised ICP. EEG-based anesthetic depth monitors may hold valuable information on guiding anesthetic management in patients with decreased CPP for better neurological outcome.

Toward global standards for comparator pharmaceutical products: case studies of amoxicillin, metronidazole, and zidovudine in the Americas.

PubMed

Löbenberg, Raimar; Chacra, Nadia B; Stippler, Erika S; Shah, Vinod P; DeStefano, Anthony J; Hauck, Walter W; Williams, Roger L

2012-09-01

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats.

PubMed

Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

2018-06-01

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA B receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA B receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA B receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA B receptor. Copyright © 2018 Elsevier B.V. All rights reserved.

Ayahuasca and Its DMT- and β-carbolines - Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment.

PubMed

Cata-Preta, Elisangela G; Serra, Yasmim A; Moreira-Junior, Eliseu da C; Reis, Henrique S; Kisaki, Natali D; Libarino-Santos, Matheus; Silva, Raiany R R; Barros-Santos, Thaísa; Santos, Lucas C; Barbosa, Paulo C R; Costa, José L; Oliveira-Lima, Alexandre J; Berro, Lais F; Marinho, Eduardo A V

2018-01-01

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N -dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice.

Use of dynamic weight bearing as a novel end-point for the assessment of abdominal pain in the LPS-induced peritonitis model in the rat.

PubMed

Gruen, Michael; Laux-Biehlmann, Alexis; Zollner, Thomas M; Nagel, Jens

2014-07-30

Chronic pelvic pain (CPP) is defined as long-lasting and severe pelvic pain persisting over six months in cyclic or non-cyclic chronic manner. Various pathologic conditions like endometriosis, abdominal infections, intra-peritoneal adhesions or infection, underlie CPP which is often the leading symptom of the associated diseases. Pharmacological approaches addressing CPP are hampered by the absence of a straight-forward, objective, and reliable method for the assessment of CPP in rodents. In the presented study, the dynamic weight bearing system (DWB) was employed for the first time for the evaluation of pelvic pain in a rat model of LPS-induced peritonitis. Rats were pretreated with the COX-2 inhibitor rofecoxib and PGE2 levels were evaluated in peritoneal lavage. DWB analysis revealed that rats treated with LPS showed a relief posture by a significantly increased weight distribution to the front when compared to vehicle-treated animals. This effect was prevented by rofecoxib treatment indicating the sensitivity of the model for pelvic pain related to peritonitis. Analysis of the PGE2 levels in the peritoneal fluid indicated a correlation with the relief posture intensity. In contrast to others weight bearing approaches, the use of DWB allows evaluation of spontaneous posture changes as a consequence of pelvic pain. Taken together, we were able to show, that DWB combined with LPS-induced peritonitis may deliver a new reliable animal model addressing pelvic pain with high construct validity (peritoneal inflammation), and face validity (pain related relief posture). Copyright © 2014 Elsevier B.V. All rights reserved.

The CPP-ACP relieved enamel erosion from a carbonated soft beverage: an in vitro AFM and XRD study.

PubMed

Wang, C P; Huang, S B; Liu, Y; Li, J Y; Yu, H Y

2014-03-01

To investigate the CPP-ACP's effect on enamel against carbonated beverage erosion and explore the potential mechanism. A total of 30 enamel samples were prepared from sound bovine incisors, divided into 3 groups. Samples in the control group were kept in artificial saliva. Specimens' surfaces were smeared with a CPP-ACP agent (Tooth Mousse, TM) for 3 min, rinsed with distilled water for 10s, merged into cola (Coca Cola, CC) for 4 intervals of 2 min, rinsed again for the TM+CC group. In the CC group, specimens were treated solely with cola for 4 intervals (2 min each). The cycles were applied at 0, 12, 24, 36, 48 and 60 h. The surface microhardness (SMH) alterations were measured using a microhardness tester, the surface profiles were analyzed using the atomic force microscope, and the surface crystalline amount (I%) and crystallinity (FWHM) were analyzed using X-ray diffractometer. The SMH were significantly decreased in CC group, showing the largest SMH alteration; the reduction of SMH in TM+CC group was lower than that in CC group, still larger than control. After cycles, the TM+CC group showed rougher surfaces than control, while the CC group had the roughest surfaces. The TM+CC had an I% higher than the CC, and lower than the control. The TM+CC group had a FWHM lower than CC, higher than control. CPP-ACP was able to relieve the erosion on enamel from carbonated beverage. Copyright © 2013 Elsevier Ltd. All rights reserved.

20 CFR 627.805 - Alternative dispute resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Alternative dispute resolution. 627.805 Section 627.805 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR GENERAL... Law Judges § 627.805 Alternative dispute resolution. (a) Parties to a complaint under § 627.801 of...

Baclofen facilitates the extinction of methamphetamine-induced conditioned place preference in rats

PubMed Central

Voigt, Robin M.; Herrold, Amy A.; Napier, T. Celeste

2011-01-01

The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABAB receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABAB receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused. PMID:21463025

Naloxone effects on extinction of ethanol- and cocaine-induced conditioned place preference in mice.

PubMed

Font, Laura; Houck, Christa A; Cunningham, Christopher L

2017-09-01

Previous studies found that naloxone (NLX) facilitated choice extinction of ethanol conditioned place preference (CPP) using long (60 min) test sessions, but there is little information on the variables determining this effect. These studies examined repeated exposure to NLX during extinction of ethanol- or cocaine-induced CPP using both short and long tests. DBA/2J mice were injected with NLX (0 or 10 mg/kg) before three 10- or 60-min choice extinction tests (experiment 1). All mice received a final 60-min test without NLX. Post-test NLX was given in experiment 2. Experiment 3 tested whether NLX would affect a forced extinction procedure. Experiment 4 tested its effect on extinction of cocaine-induced CPP. Pre-test (but not post-test) injections of NLX-facilitated choice extinction of ethanol CPP at both test durations. Pre-test NLX also facilitated forced extinction. However, pre-test NLX had no effect on choice extinction of cocaine CPP. Extinction test duration is not critical for engaging the opioid system during ethanol CPP extinction (experiment 1). Moreover, NLX's effect does not depend on CPP expression during extinction, just exposure to previously conditioned cues (experiment 3). The null effect of post-test NLX eliminates a memory consolidation interpretation (experiment 2) and the failure to alter cocaine CPP extinction argues against alteration of general learning or memory processes (experiment 4). Overall, these data suggest that the endogenous opioid system mediates a conditioned motivational effect that normally maintains alcohol-induced seeking behavior, which may underlie the efficacy of opiate antagonists in the treatment of alcoholism.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses

PubMed Central

Pildervasser, João V. N.; Abrahao, Karina P.; Souza-Formigoni, Maria L. O.

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties. PMID:25152719

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

PubMed

Muscatello, Luisa Vera; Avallone, Giancarlo; Serra, Fabienne; Seuberlich, Torsten; Mandara, Maria Teresa; Sisó, Silvia; Brunetti, Barbara; Oevermann, Anna

2018-05-01

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses.

PubMed

Pildervasser, João V N; Abrahao, Karina P; Souza-Formigoni, Maria L O

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

PubMed

de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

2017-05-01

To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

SOUTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. HEADEND PLANT BUILDING (CPP-640) APPEARS ON LEFT IN PHOTO. INL PHOTO NUMBER HD-22-3-3. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Referred Pain Patterns Provoked on Intra-Pelvic Structures among Women with and without Chronic Pelvic Pain: A Descriptive Study

PubMed Central

Butler, Stephen; Peterson, Magnus; Eriksson, Margaretha

2015-01-01

Objectives To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. Materials and Methods In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas. Results Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7) in women with CPP as compared to 3.2 mm² (1.0 to 5.1) in women without CPP, p< 0.0001. Conclusions Referred pain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis. PMID:25793999

Nicotine enhances the locomotor stimulating but not the conditioned rewarding effect of ethanol in DBA/2J mice.

PubMed

Gubner, Noah R; Cunningham, Christopher L; Phillips, Tamara J

2015-01-01

One hypothesis to explain the high rate of nicotine and alcohol (ethanol [EtOH]) co-abuse is that these drugs have enhanced rewarding effects when taken together. The goal of this work was to use the conditioned place preference (CPP) procedure to determine whether nicotine would enhance the development of EtOH-induced CPP. The conditioned rewarding effects of nicotine (1 or 2 mg/kg of nicotine tartrate), EtOH (1 g/kg), and nicotine plus EtOH in combination were assessed using a well-established CPP procedure chosen specifically for examining alterations in the development of EtOH-induced CPP by nicotine. In addition, the reference dose procedure was used to directly compare the conditioned rewarding effect of EtOH versus nicotine plus EtOH. DBA/2J mice were used because they are an inbred strain that has repeatedly been shown to develop CPP to EtOH. Neither dose of nicotine alone produced CPP, whereas EtOH did, using the standard EtOH CPP procedure. The magnitude of EtOH-induced CPP was not affected by co-administration of 1 mg/kg nicotine, but 2 mg/kg nicotine interfered with the development of EtOH-induced CPP. Using the reference dose procedure, there was no significant preference or aversion for either nicotine + EtOH dose combination versus EtOH alone. However, combined nicotine and EtOH had a larger effect on locomotor activity, during the conditioning trials, compared to their additive effect when given alone, consistent with previous data. These data do not support the hypothesis that nicotine enhances the conditioned rewarding effect of EtOH. This finding differs from the combined locomotor stimulant effects of nicotine and EtOH that were observed in this study and in our previously published work, and suggests that combined stimulant effects of nicotine and EtOH do not predict enhanced reward. Copyright © 2015 by the Research Society on Alcoholism.

Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory

PubMed Central

Otis, James M.; Dashew, Kidane B.; Mueller, Devin

2013-01-01

Drug use is provoked by the presentation of drug-associated cues, even following long periods of abstinence. Disruption of these learned associations would therefore limit relapse susceptibility. Drug-associated memories are susceptible to long-term disruption during retrieval and shortly after, during memory reconsolidation. Recent evidence reveals that retrieval and reconsolidation are dependent on β-adrenergic receptor (β-AR) activation. Despite this, whether retrieval and reconsolidation are dependent on identical or distinct neural mechanisms is unknown. The prelimbic medial prefrontal cortex (PL-mPFC) and basolateral amygdala (BLA) have been implicated in the expression and reconsolidation of associative memories. Therefore, we investigated the necessity of β-AR activation within the PL-mPFC and BLA for cocaine-associated memory retrieval and reconsolidation in rats. Before or immediately after a cocaine-induced conditioned place preference (CPP) retrieval trial, β-AR antagonists were infused into the PL-mPFC or BLA, followed by daily testing. PL-mPFC infusions before, but not after, a CPP trial disrupted CPP memory retrieval and induced a persistent deficit in retrieval during subsequent trials. In contrast, BLA β-AR blockade had no effect on initial CPP memory retrieval, but prevented CPP expression during subsequent trials indicative of reconsolidation disruption. Our results reveal a distinct dissociation between the neural mechanisms required for cocaine-associated memory retrieval and reconsolidation. Using patch-clamp electrophysiology, we also show that application of a β-AR antagonist prevents NE-induced potentiation of PL-mPFC pyramidal and GABAergic neuronal excitability. Thus, targeted β-AR blockade could induce long-term deficits in drug-associated memory retrieval by reducing neuronal excitability, providing a novel method of preventing cue-elicited drug seeking and relapse. PMID:23325262

Quality of cyclone early warning services: a case study in remote off-shore island in Bangladesh

NASA Astrophysics Data System (ADS)

Ashrafi, Z. M.; Mahmud, S.; Mahbub, A. Q. M.

2015-12-01

Geographic location, the unique natural setting of the country and its tropical monsoon climate modify and regulate the climatic condition, makes Bangladesh more vulnerable to cyclones and storm surges. Previous studies have showed that 80-90 % of global losses and 53 % of total cyclone-related deaths worldwide, occur in Bangladesh and out of which, 42% of cyclone-caused deaths were recorded in the last two centuries. The Cyclone Preparedness Program (CPP) is a unique joint program under the initiative of Government of Bangladesh and Bangladesh Red Crescent Society that provides a robust cyclone early warning (CEW) system for the 13 coastal districts in Bangladesh. CPP ensures rapid dissemination of official Bangladesh Meteorological Department's CEW signals to these communities. However, inconsistent CEW services are reported in several of these coastal communities. This study offered the quality assessment of CPP CEW services in Nijhum Island, a highly populated remotely located off-shore island in Bangladesh. Primary rural appraisal (household survey, focus group discussion and expert interview) were used for field data collection and Likert scale, for data analysis. Study revealed that cyclone early warning signal dissemination were restricted to small area covering only 35 percent of the total population. Moreover, local inhabitants had very poor understanding about disseminated CEW signals (flag signaling system, signal number & severity) although CPP initiated several training program to build and raise awareness. Consequently, people remained inactive during cyclone and reluctant to seek shelter which resulted in lack of proper post-disaster management. Moreover, local people had concern regarding accuracy of CEW signals disseminated by CPP. To ensure last mile connectivity of CEW services, it is highly recommended that local people should be given more training and awareness on CEW signals and how to respond to the same.

Preventive Effect of CPP-ACPF Paste and Fluoride Toothpastes Against Erosion and Erosion Plus Abrasion 
In Vitro - A 3D Profilometric Analysis.

PubMed

Soares, Genaina Guimarães; Magalhães, Pâmela Amorim; Fonseca, Ana Beatriz Monteiro; Tostes, Monica Almeida; Silva, Eduardo Moreira da; Coutinho, Thereza Christina Lopes

To evaluate the effect of CPP-ACPF paste and fluoride toothpastes on enamel subjected to erosion and erosion plus abrasion in vitro. A total of 220 human enamel blocks were divided into eleven groups (n = 20): CPP-ACPF paste (MPP), potassium nitrate/sodium fluoride toothpaste (PE), sodium fluoride toothpaste (FD), fluoride-free toothpaste (SO) and control (erosion only with no paste or toothpastes; CO) according to the experimental design: erosion or erosion plus abrasion immediately after erosion (ERO+I-ABR) or 30 min after erosion (ERO+30min-ABR). For 5 days, the specimens were subjected to: (1) erosive challenge (EC) (cola drink, 4 x 5 min/day), topical application of the undiluted paste or diluted toothpastes (1:2 w/w) (4 x 1 min/ day) plus 1 h in artificial saliva (AS) between cycles and overnight; or (2) EC plus abrasion (4 x /60 s/day) performed with the diluted toothpastes (no MMP) plus 1 h in AS between cycles and overnight. Erosion depth was quantified through a 3D profilometer. Data were analysed using Kruskal-Wallis, Mann-Whitney and Wilcoxon tests (p = 0.05). CPP-ACPF paste and NaF toothpaste showed lowest enamel wear among groups and reduced tissue loss by 89% in erosion challenge. Abrasion led to higher enamel wear than erosion only (p = 0.030). ERO+30min-ABR had no protective effect when compared to ERO+I-ABR (p > 0.05). A high frequency of CPP-ACPF paste application (4x daily) is effective in reducing the effects of erosion. A waiting period before performing toothbrushing does not protect enamel against erosion regardless the composition of the toothpastes.

Lysophosphatidic acid-induced increase in adult hippocampal neurogenesis facilitates the forgetting of cocaine-contextual memory.

PubMed

Ladrón de Guevara-Miranda, David; Moreno-Fernández, Román Darío; Gil-Rodríguez, Sara; Rosell-Valle, Cristina; Estivill-Torrús, Guillermo; Serrano, Antonia; Pavón, Francisco J; Rodríguez de Fonseca, Fernando; Santín, Luis J; Castilla-Ortega, Estela

2018-02-26

Erasing memories of cocaine-stimuli associations might have important clinical implications for addiction therapy. Stimulating hippocampal plasticity by enhancing adult hippocampal neurogenesis (AHN) is a promising strategy because the addition of new neurons may not only facilitate new learning but also modify previous connections and weaken retrograde memories. To investigate whether increasing AHN prompted the forgetting of previous contextual cocaine associations, mice trained in a cocaine-induced conditioned place preference (CPP) paradigm were administered chronic intracerebroventricular infusions of lysophosphatidic acid (LPA, an endogenous lysophospholipid with pro-neurogenic actions), ki16425 (an LPA 1/3 receptor antagonist) or a vehicle solution, and they were tested 23 days later for CPP retention and extinction. The results of immunohistochemical experiments showed that the LPA-treated mice exhibited reduced long-term CPP retention and an approximately twofold increase in the number of adult-born hippocampal cells that differentiated into mature neurons. Importantly, mediation analyses confirmed a causal role of AHN in reducing CPP maintenance. In contrast, the ki16425-treated mice displayed aberrant responses, with initially decreased CPP retention that progressively increased across the extinction sessions, leading to no effect on AHN. The pharmacological treatments did not affect locomotion or general exploratory or anxiety-like responses. In a second experiment, normal and LPA 1 -receptor-deficient mice were acutely infused with LPA, which revealed that LPA 1 -mediated signaling was required for LPA-induced proliferative actions. These results suggest that the LPA/LPA 1 pathway acts as a potent in vivo modulator of AHN and highlight the potential usefulness of pro-AHN strategies to treat aberrant cognition in those addicted to cocaine. © 2018 Society for the Study of Addiction.

Importance of Toxicokinetics to Assess the Utility of Zebrafish Larvae as Model for Psychoactive Drug Screening Using Meta-Chlorophenylpiperazine (mCPP) as Example

PubMed Central

Kirla, Krishna Tulasi; Groh, Ksenia J.; Poetzsch, Michael; Banote, Rakesh Kumar; Stadnicka-Michalak, Julita; Eggen, Rik I. L.; Schirmer, Kristin; Kraemer, Thomas

2018-01-01

The number of new psychoactive substances (NPS) increases rapidly, harming society and fuelling the need for alternative testing strategies. These should allow the ever-increasing number of drugs to be tested more effectively for their toxicity and psychoactive effects. One proposed strategy is to complement rodent models with zebrafish (Danio rerio) larvae. Yet, our understanding of the toxicokinetics in this model, owing to the waterborne drug exposure and the distinct physiology of the fish, is incomplete. We here explore the toxicokinetics and behavioral effects of an NPS, meta-chlorophenylpiperazine (mCPP), in zebrafish larvae. Uptake kinetics of mCPP, supported by toxicokinetic modeling, strongly suggested the existence of active transport processes. Internal distribution showed a dominant accumulation in the eye, implying that in zebrafish, like in mammals, melanin could serve as a binding site for basic drugs. We confirmed this by demonstrating significantly lower drug accumulation in two types of hypo-pigmented fish. Comparison of the elimination kinetics between mCPP and previously characterized cocaine demonstrated that drug affinities to melanin in zebrafish vary depending on the structure of the test compound. As expected from mCPP-elicited responses in rodents and humans, zebrafish larvae displayed hypoactive behavior. However, significant differences were seen between zebrafish and rodents with regard to the concentration-dependency of the behavioral response and the comparability of tissue levels, corroborating the need to consider the organism-internal distribution of the chemical to allow appropriate dose modeling while evaluating effects and concordance between zebrafish and mammals. Our results highlight commonalities and differences of mammalian versus the fish model in need of further exploration. PMID:29755353

Importance of Toxicokinetics to Assess the Utility of Zebrafish Larvae as Model for Psychoactive Drug Screening Using Meta-Chlorophenylpiperazine (mCPP) as Example.

PubMed

Kirla, Krishna Tulasi; Groh, Ksenia J; Poetzsch, Michael; Banote, Rakesh Kumar; Stadnicka-Michalak, Julita; Eggen, Rik I L; Schirmer, Kristin; Kraemer, Thomas

2018-01-01

The number of new psychoactive substances (NPS) increases rapidly, harming society and fuelling the need for alternative testing strategies. These should allow the ever-increasing number of drugs to be tested more effectively for their toxicity and psychoactive effects. One proposed strategy is to complement rodent models with zebrafish ( Danio rerio ) larvae. Yet, our understanding of the toxicokinetics in this model, owing to the waterborne drug exposure and the distinct physiology of the fish, is incomplete. We here explore the toxicokinetics and behavioral effects of an NPS, meta-chlorophenylpiperazine (mCPP), in zebrafish larvae. Uptake kinetics of mCPP, supported by toxicokinetic modeling, strongly suggested the existence of active transport processes. Internal distribution showed a dominant accumulation in the eye, implying that in zebrafish, like in mammals, melanin could serve as a binding site for basic drugs. We confirmed this by demonstrating significantly lower drug accumulation in two types of hypo-pigmented fish. Comparison of the elimination kinetics between mCPP and previously characterized cocaine demonstrated that drug affinities to melanin in zebrafish vary depending on the structure of the test compound. As expected from mCPP-elicited responses in rodents and humans, zebrafish larvae displayed hypoactive behavior. However, significant differences were seen between zebrafish and rodents with regard to the concentration-dependency of the behavioral response and the comparability of tissue levels, corroborating the need to consider the organism-internal distribution of the chemical to allow appropriate dose modeling while evaluating effects and concordance between zebrafish and mammals. Our results highlight commonalities and differences of mammalian versus the fish model in need of further exploration.

Testing peak cycling performance: effects of braking force during growth.

PubMed

Doré, E; Bedu, M; França, N M; Diallo, O; Duché, P; Van Praagh, E

2000-02-01

The purpose of this study was to investigate the relationship between cycling peak power (CPP; flywheel inertia included) and the applied braking force (F(B)) on a friction-loaded cycle ergometer in male children, adolescents, and adults. A total of 520 male subjects aged 8-20 yr performed three brief maximal sprints against three F(B): 0.245, 0.491, and 0.736 N x kg(-1) body mass (BM) (corresponding applied loads: 25 [F(B)25], 50 [F(B)50], and 75 [F(B)75] g x kg(-1) BM). For each F(B), peak power (PP) was measured (PP25, PP50 and PP75). For each subject, the highest PP was defined as CPP. Results showed that PP was dependent on F(B). In young adults PP25 underestimated CPP by more than 10%, and consequently, F(B)25 seemed to be too low for this population. However, in children, PP75 underestimated CPP by about 20%. A F(B) of 0.736 N x kg(-1) BM was definitively too high for the pediatric population. Therefore, the optimal F(B), even corrected for BM, was lower in children than in adults. The influence of growth and maturation on the force-generating capacity of the leg muscles may explain this difference. In this study, however, it was shown that the difference between PP50 and CPP was independent of age for the whole population investigated. Consequently, when flywheel inertia is included, one cycling sprint with a F(B) of 0.495 N x kg(-1) BM (corresponding applied load: 50 g x kg(-1) BM) is a feasible method for testing both children, adolescents, or young adults.

Inhibiting effects of rhynchophylline on zebrafish methamphetamine dependence are associated with amelioration of neurotransmitters content and down-regulation of TH and NR2B expression.

PubMed

Jiang, Mingjin; Chen, Yifei; Li, Chan; Peng, Qiuxian; Fang, Miao; Liu, Wei; Kang, Qunzhao; Lin, Yingbo; Yung, Ken Kin Lam; Mo, Zhixian

2016-07-04

Others and we have reported that rhynchophylline reverses amphetamine-induced conditioned place preference (CPP) effect which may be partly mediated by amelioration of central neurotransmitters and N-methyl-d-aspartate receptor 2B (NR2B) levels in the rat brains. The current study investigated the inhibiting effects of rhynchophylline on methamphetamine-induced (METH-induced) CPP in adult zebrafish and METH-induced locomotor activity in tyrosine hydroxylase-green fluorescent protein (TH-GFP) transgenic zebrafish larvae and attempted to confirm the hypothesis that these effects were mediated via regulation of neurotransmitters and dopaminergic and glutamatergic systems. After baseline preference test (on days 1-3), zebrafish were injected intraperitoneally METH (on days 4, 6 and 8) or the same volume of fish physiological saline (on days 5 and 7) and were immediately conditioned. Rhynchophylline was administered at 12h after injection of METH. On day 9, zebrafish were tested for METH-induced CPP. Results revealed that rhynchophylline (100mg/kg) significantly inhibited the acquisition of METH-induced CPP, reduced the content of dopamine and glutamate and down-regulated the expression of TH and NR2B in the CPP zebrafish brains. Furthermore, the influence of rhynchophylline on METH-induced locomotor activity was also observed in TH-GFP transgenic zebrafish larvae. Results showed that rhynchophylline (50mg/L) treatment led to a significant reduction on the locomotor activity and TH expression in TH-GFP transgenic zebrafish larvae. Taken together, these data indicate that the inhibition of the formation of METH dependence by rhynchophylline in zebrafish is associated with amelioration of the neurotransmitters dopamine and glutamate content and down-regulation of TH and NR2B expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Involvement of AMPA/Kainate Glutamate Receptor in the Extinction and Reinstatement of Morphine-Induced Conditioned Place Preference: A Behavioral and Molecular Study.

PubMed

Siahposht-Khachaki, Ali; Fatahi, Zahra; Yans, Asal; Khodagholi, Fariba; Haghparast, Abbas

2017-03-01

Glutamate receptors in mesolimbic areas such as the nucleus accumbens, ventral tegmental area, prefrontal cortex (PFC), and hippocampus (HIP) are a component of the mechanisms of drug-induced reward and can modulate the firing pattern of dopaminergic neurons in the reward system. In addition, several lines of study have indicated that cAMP response element-binding protein (CREB) and c-fos have important role in morphine-induced conditioned place preference (CPP) induced by drugs of abuse, such as morphine, cocaine, nicotine, and alcohol. Therefore, in the present study, we investigated the changes in phosphorylated CREB (p-CREB) and c-fos induction within the nucleus accumbens (NAc), HIP, and PFC after intracerebroventricular (ICV) administration of different doses of CNQX or vehicle during extinction period or reinstatement of morphine-induced CPP. In all groups, the CPP procedure was done; afterward, the conditioning scores were recorded by Ethovision software. After behavioral test recording, we dissected out the NAc, HIP, and PFC regions and measured the p-CREB/CREB ratio and c-fos level by Western blot analysis. Our results showed that administration of CNQX significantly shortened the extinction of morphine CPP. Besides, ICV microinjection of CNQX following extinction period decreased the reinstatement of morphine CPP in extinguished rats. In molecular section, in treatment group, all mentioned factors were dose-dependently decreased in comparison with vehicle group (DMSO) after ICV microinjection of different doses of CNQX but not in pre-extinction microinjection. These findings suggested that antagonism of AMPA receptor decreased p-CREB/CREB ratio and c-fos level in the PFC, NAc, and HIP. Modulation of the drug memory reconsolidation may be useful for faster extinction of drug-induced reward and attenuation of drug-seeking behavior.

Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory.

PubMed

Otis, James M; Dashew, Kidane B; Mueller, Devin

2013-01-16

Drug use is provoked by the presentation of drug-associated cues, even following long periods of abstinence. Disruption of these learned associations would therefore limit relapse susceptibility. Drug-associated memories are susceptible to long-term disruption during retrieval and shortly after, during memory reconsolidation. Recent evidence reveals that retrieval and reconsolidation are dependent on β-adrenergic receptor (β-AR) activation. Despite this, whether retrieval and reconsolidation are dependent on identical or distinct neural mechanisms is unknown. The prelimbic medial prefrontal cortex (PL-mPFC) and basolateral amygdala (BLA) have been implicated in the expression and reconsolidation of associative memories. Therefore, we investigated the necessity of β-AR activation within the PL-mPFC and BLA for cocaine-associated memory retrieval and reconsolidation in rats. Before or immediately after a cocaine-induced conditioned place preference (CPP) retrieval trial, β-AR antagonists were infused into the PL-mPFC or BLA, followed by daily testing. PL-mPFC infusions before, but not after, a CPP trial disrupted CPP memory retrieval and induced a persistent deficit in retrieval during subsequent trials. In contrast, BLA β-AR blockade had no effect on initial CPP memory retrieval, but prevented CPP expression during subsequent trials indicative of reconsolidation disruption. Our results reveal a distinct dissociation between the neural mechanisms required for cocaine-associated memory retrieval and reconsolidation. Using patch-clamp electrophysiology, we also show that application of a β-AR antagonist prevents norepinephrine-induced potentiation of PL-mPFC pyramidal cell and γ-aminobutyric-acid (GABA) interneuron excitability. Thus, targeted β-AR blockade could induce long-term deficits in drug-associated memory retrieval by reducing neuronal excitability, providing a novel method of preventing cue-elicited drug seeking and relapse.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Hyunbeom; Doud, Emma H.; Wu, Rui

γ-Aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that degrades GABA, the principal inhibitory neurotransmitter in mammalian cells. When the concentration of GABA falls below a threshold level, convulsions can occur. Inhibition of GABA-AT raises GABA levels in the brain, which can terminate seizures as well as have potential therapeutic applications in treating other neurological disorders, including drug addiction. Among the analogues that we previously developed, (1S,3S)-3-amino-4-difluoromethylene-1-cyclopentanoic acid (CPP-115) showed 187 times greater potency than that of vigabatrin, a known inactivator of GABA-AT and approved drug (Sabril) for the treatment of infantile spasms and refractory adult epilepsy. Recently,more » CPP-115 was shown to have no adverse effects in a Phase I clinical trial. Here we report a novel inactivation mechanism for CPP-115, a mechanism-based inactivator that undergoes GABA-AT-catalyzed hydrolysis of the difluoromethylene group to a carboxylic acid with concomitant loss of two fluoride ions and coenzyme conversion to pyridoxamine 5'-phosphate (PMP). The partition ratio for CPP-115 with GABA-AT is about 2000, releasing cyclopentanone-2,4-dicarboxylate (22) and two other precursors of this compound (20 and 21). Time-dependent inactivation occurs by a conformational change induced by the formation of the aldimine of 4-aminocyclopentane-1,3-dicarboxylic acid and PMP (20), which disrupts an electrostatic interaction between Glu270 and Arg445 to form an electrostatic interaction between Arg445 and the newly formed carboxylate produced by hydrolysis of the difluoromethylene group in CPP-115, resulting in a noncovalent, tightly bound complex. Ultimately, this represents a novel mechanism for inactivation of GABA-AT and a new approach for the design of mechanism-based inactivators in general.« less

Comparative evaluation of remineralization potential of casein phosphopeptide-amorphous calcium phosphate and casein phosphopeptide-amorphous calcium phosphate fluoride on artificial enamel white spot lesion: an in vitro light fluorescence study.

PubMed

Mehta, R; Nandlal, B; Prashanth, S

2013-01-01

World-wide, the contribution of dental caries to the burden of oral diseases is about 10 times higher than that of periodontal disease, the other common oral condition. Owing to its globally high prevalence, dental caries is a "pandemic" disease characterized by a high percentage of untreated carious cavities causing pain, discomfort and functional limitations. Untreated carious cavities; furthermore, have a significant impact on the general health of children and on the social and economic well-being of communities. A surgical approach to the elimination of carious lesion was developed a century ago; this approach was necessary at that time, because there was no valid alternative. The focus in caries has recently shifted to the development of methodologies for the detection of the early stages of caries lesions and the non-invasive treatment of these lesions. The non-invasive treatment of early lesions by remineralization has the potential to be a major advance in the clinical management of the disease. Remineralization of white-spot lesions may be possible with a variety of currently available agents containing fluoride, bioavailable calcium and phosphate and phosphate. This concept bridges the traditional gap between prevention and surgical procedures, which is just what dentistry needs today. The aim of this in vitro study was to evaluate and to compare the remineralization potential of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) on artificial white spot enamel lesions using the quantitative light fluorescence (QLF). A total of 45 caries-free extracted maxillary first premolars were embedded in acrylic resin. The samples were randomly divided into three groups namely control group, CPP-ACP group and CPP-ACFP group with 15 samples in each group. The samples of each group were subjected to demineralization process for a period of 96 h. The samples were then mounted in the artificial mouth model and subjected to remineralization and pH cycling for a period of 21 days. QLF readings were recorded at the end of demineralization (1st, 7th, 14th and 21st day) and were statistically analyzed. As compared with artificial saliva both CPP-ACP and CPP-ACFP produced significant amount of remineralization of the artificial enamel white spot lesion (P < 0.001), however when the remineralizing effect of CPP-ACP was compared with the remineralizing effect of CPP-ACFP there was no significant difference. Significant amount of remineralization was produced by CPP-ACP and CPP-ACFP only after the 7th day. After the 14th day, the remineralization produced by both CPP-ACP and CPP-ACFP as compared to artificial saliva was non-significant.

Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA.

PubMed

García-Pardo, Maria P; Escobar-Valero, Carla; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, Maria A

2015-08-01

Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In addition, the effects of memantine on acquisition of chocolate-induced CPP and the effects of memantine and MDMA on a passive avoidance task were evaluated. Memantine did not exert any motivational effects, but blocked the acquisition of MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP induced by priming with MDMA. Memantine did not block the CPP induced by chocolate, and it partially reversed the impairing effects of MDMA on memory. Our results demonstrate that NMDARs are involved in acquisition of the conditioned rewarding effects of MDMA and in priming-induced reinstatement of CPP following extinction. Moreover, they suggest the validity of memantine for the treatment of MDMA abuse.

DYNAMIC CEREBROVASCULAR AND INTRACRANIAL PRESSURE REACTIVITY ASSESMENT OF IMPAIRED CEREBROVASCULAR AUTOREGULATION IN INTRACRANIAL HYPERTENSION

PubMed Central

Bragin, Denis E.; Statom, Gloria; Nemoto, Edwin M.

2016-01-01

SUMMARY We previously suggested that the discrepancy between the critical cerebral perfusion pressures (CPP) of 30 mmHg, obtained by increasing intracranial pressure (ICP), and 60 mmHg, obtained by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP [1] and that the determination of the critical CPP by the static cerebral blood flow (CBF) autoregulation curve is not valid with intracranial hypertension. Here we demonstrated that critical CPP, measured by induced dynamic ICP reactivity (iPRx) and cerebrovascular reactivity (CVRx), accurately identifies the critical CPP in the hypertensive rat brain which differs from that obtained by the static autoregulation curve. Step changes in CPP from 70 to 50 and 30 mmHg were made by increasing ICP using an artificial cerebrospinal fluid reservoir connected to the cisterna magna. At each CPP, a transient 10-mmHg rise in arterial pressure was induced by bolus i.v. dopamine. iPRx and iCVRx were calculated as ΔICP/ΔMAP and as ΔCBF/ΔMAP, respectively. The critical CPP at high ICP, obtained by iPRx and iCVRx, is 50 mmHg, where compromised capillary flow, transition of blood flow to non-nutritive microvascular shunts, tissue hypoxia and BBB leakage begin to occur, which is higher than the 30 mmHg determined by static autoregulation. PMID:27165917

Subcutaneous gonadotropin-releasing hormone agonist (triptorelin) test for diagnosing precocious puberty.

PubMed

Poomthavorn, Preamrudee; Khlairit, Patcharin; Mahachoklertwattana, Pat

2009-01-01

A test involving 100 microg of intravenous gonadotropin-releasing hormone (GnRH) is a gold standard for confirming the diagnosis of central precocious puberty (CPP). However, intravenous GnRH for testing is commercially limited. To develop subcutaneous GnRH agonist (GnRH-A) testing and define a peak luteinizing hormone (LH) cutoff value in diagnosing CPP. A retrospective study of 101 girls with sexual precocity was undertaken. All girls underwent 100 microg subcutaneous GnRH-A (triptorelin) testing. Blood samples before and 30, 60, 90 and 120 min after GnRH-A injection were analyzed for LH and follicle-stimulating hormone levels. Criteria for diagnosing CPP include accelerated height, advanced bone age and pubertal-sized uterus and ovaries. Fifty-five girls were documented as having CPP. The remaining 46 girls were diagnosed with premature thelarche (PT). Peak LH concentration in the CPP group was significantly greater than that of the PT group with a median (range) of 10.0 IU/l (2.93-65.39) and 3.04 IU/l (0.19-8.82), respectively. Peak LH was achieved within 60 min following GnRH-A injection. Peak LH of 6 IU/l provided the most appropriate cutoff level in diagnosing CPP with a sensitivity of 89.1% and a specificity of 91.3%. Subcutaneous GnRH-A can be used as an alternative to confirm the diagnosis of CPP. Copyright 2009 S. Karger AG, Basel.

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

PubMed Central

Chen, Han-Ting

2015-01-01

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning. PMID:25691515

Environmental enrichment as a potential intervention for heroin seeking.

PubMed

Galaj, E; Manuszak, M; Ranaldi, R

2016-06-01

Heroin-related cues can trigger craving and relapse in addicts or heroin seeking in rats. In the present study we investigated whether environmental enrichment (EE) implemented after heroin exposure can reduce cue-induced reinstatement of heroin seeking and expression of heroin conditioned place preference. In Experiment 1, male Long Evans rats that already acquired a heroin self-administration habit, were housed in enriched or non-enriched environments, underwent extinction training and later were tested for cue-induced reinstatement of heroin seeking. In Experiment 2, rats were conditioned with heroin in one compartment of a CPP apparatus and saline in the other, exposed to 30days of enrichment or no enrichment and were later tested for heroin CPP. The results showed that exposure to EE significantly reduced responding during the reinstatement test (Experiment 1) and prevented the expression of heroin CPP (Experiment 2). Our findings suggest that EE can be an effective behavioral approach to diminish the effects of conditioned cues on heroin seeking. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Surface kinetic roughening caused by dental erosion: An atomic force microscopy study

NASA Astrophysics Data System (ADS)

Quartarone, Eliana; Mustarelli, Piercarlo; Poggio, Claudio; Lombardini, Marco

2008-05-01

Surface kinetic roughening takes place both in case of growth and erosion processes. Teeth surfaces are eroded by contact with acid drinks, such as those used to supplement mineral salts during sporting activities. Calcium-phosphate based (CPP-ACP) pastes are known to reduce the erosion process, and to favour the enamel remineralization. In this study we used atomic force microscopy (AFM) to investigate the surface roughening during dental erosion, and the mechanisms at the basis of the protection role exerted by a commercial CPP-ACP paste. We found a statistically significant difference (p<0.01) in the roughness of surfaces exposed and not exposed to the acid solutions. The treatment with the CPP-ACP paste determined a statistically significant reduction of the roughness values. By interpreting the AFM results in terms of fractal scaling concepts and continuum stochastic equations, we showed that the protection mechanism of the paste depends on the chemical properties of the acid solution.

Lethality of Rendang packaged in multilayer retortable pouch with sterilization process

NASA Astrophysics Data System (ADS)

Praharasti, A. S.; Kusumaningrum, A.; Frediansyah, A.; Nurhikmat, A.; Khasanah, Y.; Suprapedi

2017-01-01

Retort Pouch had become a choice to preserve foods nowadays, besides the used of the can. Both had their own advantages, and Retort Pouch became more popular for the reason of cheaper and easier to recycle. General Method usually used to estimate the lethality of commercial heat sterilization process. Lethality value wa s used for evaluating the efficacy of the thermal process. This study aimed to find whether different layers of pouch materials affect the lethality value and to find differences lethality in two types of multilayer retort pouch, PET/Aluminum Foil/Nylon/RCPP and PET/Nylon/Modified Aluminum/CPP. The result showed that the different layer arrangement was resulted different Sterilization Value (SV). PET/Nylon/Modified Aluminum/CPP had better heat penetration, implied by the higher value of lethality. PET/Nylon/Modified Aluminum/CPP had the lethality value of 6,24 minutes, whereas the lethality value of PET/Aluminum Foil/Nylon/RCPP was 3,54 minutes.

Caspase-Activated Cell-Penetrating Peptides Reveal Temporal Coupling Between Endosomal Release and Apoptosis in an RGC-5 Cell Model

PubMed Central

Johnson, James R.; Kocher, Brandon; Barnett, Edward M.; Marasa, Jayne; Piwnica-Worms, David

2012-01-01

Caspase-activatable cell-penetrating peptide (CPP) probes, designed for efficient cell uptake and specificity via cleavable intramolecular quenched-fluorophore strategies, show promise for identifying and imaging retinal ganglion cell apoptosis in vivo. However, initial cell uptake and trafficking events cannot be visualized because the probes are designed to be optically quenched in the intact state. To visualize subcellular activation events in real-time during apoptosis, a new series of matched quenched and non-quenched CPP probes were synthesized. In both native and staurosporine-differentiated RGC-5 cells, probe uptake was time- and concentration-dependent through clathrine-, caveolin- and pinocytosis-mediated endocytic mechanisms. During apoptosis, KcapTR488, a novel dual fluorophore CPP probe, revealed by multi-spectral imaging a temporal coupling of endosomal release and effector caspase activation in RGC-5 cells. The novel CPPs described herein provide new tools to study spatial and temporal regulation of endosomal permeability during apoptosis. PMID:22900707

Attention bias to threat indicates anxiety differences in sheep

PubMed Central

Lee, Caroline; Verbeek, Else; Doyle, Rebecca

2016-01-01

Humans and animals show increased attention towards threatening stimuli when they are in increased states of anxiety. The few animal studies that have examined this phenomenon, known as attention bias, have applied environmental manipulations to induce anxiety but the effects of drug-induced anxiety levels on attention bias have not been demonstrated. Here, we present an attention bias test to identify high and low anxiety states in sheep using pharmacological manipulation. Increased anxiety was induced using 1-methyl-chlorophenylpiperazine (m-CPP) and decreased anxiety with diazepam, and then we examined the behaviour of sheep in response to the presence of a dog as a threat. Increased attention towards the threat and increased vigilance were shown in sheep that received the m-CPP and reduced in sheep receiving the diazepam. The modulated attention towards a threat displayed by the m-CPP and diazepam animals suggests that attention bias can assess different levels of anxiety in sheep. Measuring attention bias has the potential to improve animal welfare assessment protocols. PMID:27277950

Corrosion Behavior of Cast Iron in Freely Aerated Stagnant Arabian Gulf Seawater

PubMed Central

Sherif, El-Sayed M.; Abdo, Hany S.; Almajid, Abdulhakim A.

2015-01-01

In this work, the results obtained from studying the corrosion of cast iron in freely aerated stagnant Arabian Gulf seawater (AGS) at room temperature were reported. The study was carried out using weight-loss (WL), cyclic potentiodynamic polarization (CPP), open-circuit potential (OCP), and electrochemical impedance spectroscopy (EIS) measurements and complemented by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) investigations. WL experiments between two and 10 days’ immersion in the test electrolyte indicated that the weight-loss the cast iron increases with increasing the time of immersion. CPP measurements after 1 h and 24 h exposure period showed that the increase of time decreases the corrosion via decreasing the anodic and cathodic currents, as well as decreasing the corrosion current and corrosion rate and increasing the polarization resistance of the cast iron. EIS data confirmed the ones obtained by WL and CPP that the increase of immersion time decreases the corrosion of cast iron by increasing its polarization resistance.

Cell Penetrating Peptides and Cationic Antibacterial Peptides

PubMed Central

Rodriguez Plaza, Jonathan G.; Morales-Nava, Rosmarbel; Diener, Christian; Schreiber, Gabriele; Gonzalez, Zyanya D.; Lara Ortiz, Maria Teresa; Ortega Blake, Ivan; Pantoja, Omar; Volkmer, Rudolf; Klipp, Edda; Herrmann, Andreas; Del Rio, Gabriel

2014-01-01

Cell penetrating peptides (CPP) and cationic antibacterial peptides (CAP) have similar physicochemical properties and yet it is not understood how such similar peptides display different activities. To address this question, we used Iztli peptide 1 (IP-1) because it has both CPP and CAP activities. Combining experimental and computational modeling of the internalization of IP-1, we show it is not internalized by receptor-mediated endocytosis, yet it permeates into many different cell types, including fungi and human cells. We also show that IP-1 makes pores in the presence of high electrical potential at the membrane, such as those found in bacteria and mitochondria. These results provide the basis to understand the functional redundancy of CPPs and CAPs. PMID:24706763

BIRD’S-EYE VIEW OF GnRH ANALOG USE IN A PEDIATRIC ENDOCRINOLOGY REFERRAL CENTER

PubMed Central

Watson, Sara E.; Greene, Ariana; Lewis, Katherine; Eugster, Erica A.

2017-01-01

Objective Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. Methods We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. Results A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). Conclusion Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP. PMID:25667370

Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.

PubMed

Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung

2016-04-01

Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.

Influence of Betaxolol on the Methamphetamine Dependence in Mice.

PubMed

Kim, Byoung-Jo; Park, Jong-Il; Eun, Hun-Jeong; Yang, Jong-Chul

2016-05-01

The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

2017-01-01

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

Studies of Current Induced Magnetization reversal and generation of GHz radiation in magnetic nanopillars

NASA Astrophysics Data System (ADS)

Alhajdarwish, Mustafa Yousef

This thesis describes studies of two phenomena: Current-Induced Magnetization Switching (CIMS), and Current-Induced Generation of GHz Radiation. The CIMS part contains results of measurements of current-perpendicular-to-plane (CPP) magnetoresistance (MR) and CIMS behavior on Ferromagnetic/Nonmetal/Ferromagnetic (F1/N/F2) nanopillars. Judicious combinations of F1 and F2 metals with different bulk scattering asymmetries, and with F1/N and N/F2 interfaces having different interfacial scattering asymmetries, are shown to be able to controllably, and independently, 'invert' both the CPP-MR and the CIMS. In 'normal' CPP-MR, R(AP) > R(P), where R(AP) and R(P) are the nanopillar resistances for the anti-parallel (AP) and parallel (P) orientations of the Fi and F2 magnetic moments. In 'inverse' CPP-MR, R(P) > R(AP). In 'normal' CIMS, positive current switches the nanopillar from the P to the AP state. In 'inverse' CIMS, positive current switches the nanopillar from AP to P. All four possible combinations of CPP-MR and CIMS---(a) 'normal'-'normal', (b) 'normal'- 'inverse', 'inverse'-'normal', and (d) 'inverse'-'inverse' are shown and explained. These results rule out the self-Oersted field as the switching source, since the direction of that field is independent of the bulk or interfacial scattering asymmetries. Successful use of impurities to reverse the bulk scattering asymmetry shows the importance of scattering off of impurities within the bulk F1 and F2 metals---i.e. that the transport must be treated as 'diffusive' rather than 'ballistic'. The GHz studies consist of five parts: (1) designing a sample geometry that allows reliable measurements; (2) making nanopillar samples with this geometry; (3) constructing a system for measuring frequencies up to 12 GHz and measuring current-driven GHz radiation data with it; (4) showing 'scaling' behavior of GHz data with the critical fields and currents for nominally identical (but actually slightly different) samples, and justifying such scaling; and (5) designing and constructing a system for frequency domain studies up to 40 GHz and for time domain studies.

The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned place preference and physical dependence.

PubMed

Alavi, Mohaddeseh Sadat; Hosseinzadeh, Hossein; Shamsizadeh, Ali; Roohbakhsh, Ali

2016-06-01

Previous studies show that some non-CB1/non-CB2 effects of cannabinoids are mediated through G protein coupled receptor 55 (GPR55). As this receptor is activated by some of cannabinoid receptor ligands and is involved in the modulation of pain, it was hypothesized that this receptor may also interact with opioids. This study examined the effect of atypical cannabinoid O-1602 as a GPR55 agonist on morphine-induced conditioned place preference (CPP) and physical dependence. We used a biased CPP model to evaluate the effect of O-1602 (0.2, 1 and 5mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP in male mice. The locomotor activities of mice were also recorded. Moreover, repeated administration of morphine (50, 50 and 75mg/kg/day) for three days, induced physical dependence. The withdrawal signs such as jumps and diarrhea were precipitated by administration of naloxone (5mg/kg, ip). The effect of O-1602 on the development of morphine physical dependence was assessed by injection of O-1602 (0.2, 1 and 5mg/kg) before morphine administrations. Morphine (40mg/kg, subcutaneous; sc), but not O-1602 (5mg/kg) elicited significant preference in the post-conditioning phase. O-1602 at the doses of 0.2 and 1mg/kg, but not 5mg/kg reduced acquisition of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 at the doses of 0.2, 1 and 5mg/kg also reduced expression of morphine CPP with an increase in locomotor activity at the dose of 5mg/kg. O-1602 had a significant inhibitory effect on development of morphine-induced physical dependence at the dose of 5mg/kg by decreasing jumps and diarrhea during withdrawal syndrome. The present results indicate that O-1602 decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Baroreflex dysfunction in sick newborns makes heart rate an unreliable surrogate for blood pressure changes.

PubMed

Govindan, Rathinaswamy B; Al-Shargabi, Tareq; Massaro, An N; Metzler, Marina; Andescavage, Nickie N; Joshi, Radhika; Dave, Rhiya; du Plessis, Adre

2016-06-01

Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns. Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis. We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres. In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants.

31P Solid-state NMR based monitoring of permeation of cell penetrating peptides into skin

PubMed Central

Desai, Pinaki R.; Cormier, Ashley R.; Shah, Punit P.; Patlolla, Ram R.; Paravastu, Anant K.; Singh, Mandip

2013-01-01

The main objective of the current study was to investigate penetration of cell penetrating peptides (CPPs: TAT, R8, R11 and YKA) through skin intercellular lipids using 31P magic angle spinning (MAS) solid-state NMR. In vitro skin permeation studies were performed on rat skin, sections (0–60, 61–120 and 121–180 µm) were collected and analyzed for 31P NMR signal. The concentration dependent shift of 0, 25, 50, 100 and 200 mg/ml of TAT on skin layers, diffusion of TAT, R8, R11 and YKA in the skin and time dependent permeation of R11 was measured on various skin sections using 31P solid-state NMR. Further, CPPs and CPP-tagged fluorescent dye encapsulate liposomes (FLip) in skin layers were tagged using confocal microscopy. The change in 31P NMR chemical shift was found to depend monotonically on the amount of CPP applied on skin, with saturation behavior above 100 mg/ml CPP concentration. R11 and TAT caused more shift in solid-state NMR peaks compared to other peptides. Furthermore, NMR spectra showed R11 penetration up to 180 µm within 30 min. The results of the solid-state NMR study were in agreement with confocal microscopy studies. Thus, 31P solid-state NMR can be used to track CPP penetration into different skin layers. PMID:23702274

Lesion of olfactory epithelium attenuates expression of morphine-induced behavioral sensitization and reinstatement of drug-primed conditioned place preference in mice.

PubMed

Niu, Haichen; Zheng, Yingwei; Huma, Tanzeel; Rizak, Joshua D; Li, Ling; Wang, Guimei; Ren, He; Xu, Liqi; Yang, Jianzhen; Ma, Yuanye; Lei, Hao

2013-01-01

Previous studies have shown that olfactory impairment by disrupting the olfactory epithelium prior to morphine administration attenuated the development addiction-related behaviors. However, it is unclear whether olfactory impairment will affect the expression of already established addiction-related behaviors. To address this issue, mice were conditioned with morphine to induce behavioral sensitization and condition placed preference (CPP). After an abstinence period, the animals were subjected to either an intranasal ZnSO(4) effusion (ZnE) or sham treatment with saline. Behavioral sensitization and CPP reinstatement were evaluated 24h later, as well as the expression of c-Fos protein, a marker of activated neural sites, in brain regions of interest. It was found that ZnE treatment attenuated morphine-induced behavioral sensitization and reinstatement of CPP. Compared to the saline-treated ones, the ZnE-treated animals showed reduced c-Fos expression in the nucleus accumbens (NAc) associated with behavioral sensitization, and in the NAc, cingulate cortex, dentate gyrus, amygdala, lateral hypothalamus and ventral tegmental area associated with CPP reinstatement. Together, these results demonstrated that acute olfactory impairment could attenuate already established addiction-related behaviors and expression of c-Fos in drug addiction related brain regions, perhaps by affecting the coordination between reward and motivational systems in the brain. Copyright © 2012 Elsevier Inc. All rights reserved.

Activity of Brazilian propolis against Aeromonas hydrophila and its effect on Nile tilapia growth, hematological and non-specific immune response under bacterial infection.

PubMed

Orsi, Ricardo O; Santos, Vivian G Dos; Pezzato, Luiz E; Carvalho, Pedro L P F DE; Teixeira, Caroline P; Freitas, Jakeline M A; Padovani, Carlos R; Sartori, Maria M P; Barros, Margarida M

2017-01-01

The effect of the ethanolic extract of propolis (EEP) on Aeromonas hydrophila was analyzed by determination of minimum inhibitory concentration (MIC). Then, the effects of crude propolis powder (CPP) on growth, hemato-immune parameters of the Nile tilapia, as well as its effects on resistance to A. hydrophila challenge were investigated. The CPP (0.5, 1.0, 1.5, 2.0, 2.5 and 3.0%) was added to the diet of 280 Nile tilapia (50.0 ± 5.7 g fish-1). Hemato-immune parameters were analyzed before and after the bacterial challenge. Red blood cell, hematocrit, hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), and hydrogen peroxide (H2O2) and nitric oxide (NO) were evaluated. The MIC of the EEP was 13% (v/v) with a bactericidal effect after 24 hours. Growth performance was significantly lower for those fish fed diets containing 2.5 and 3% of CPP compared to the control diet. Differences in CPP levels affected fish hemoglobin, neutrophils number and NO following the bacterial challenge. For others parameters no significant differences were observed. Our results show that although propolis has bactericidal properties in vitro, the addition of crude propolis powder to Nile tilapia extruded diets does not necessarily lead to an improvement of fish health.

The coalescent of a sample from a binary branching process.

PubMed

Lambert, Amaury

2018-04-25

At time 0, start a time-continuous binary branching process, where particles give birth to a single particle independently (at a possibly time-dependent rate) and die independently (at a possibly time-dependent and age-dependent rate). A particular case is the classical birth-death process. Stop this process at time T>0. It is known that the tree spanned by the N tips alive at time T of the tree thus obtained (called a reduced tree or coalescent tree) is a coalescent point process (CPP), which basically means that the depths of interior nodes are independent and identically distributed (iid). Now select each of the N tips independently with probability y (Bernoulli sample). It is known that the tree generated by the selected tips, which we will call the Bernoulli sampled CPP, is again a CPP. Now instead, select exactly k tips uniformly at random among the N tips (a k-sample). We show that the tree generated by the selected tips is a mixture of Bernoulli sampled CPPs with the same parent CPP, over some explicit distribution of the sampling probability y. An immediate consequence is that the genealogy of a k-sample can be obtained by the realization of k random variables, first the random sampling probability Y and then the k-1 node depths which are iid conditional on Y=y. Copyright © 2018. Published by Elsevier Inc.

Structural characterization and hypolipidemic effect of Cyclocarya paliurus polysaccharide in rat.

PubMed

Yang, Zhan-Wei; Ouyang, Ke-Hui; Zhao, Jing; Chen, Hui; Xiong, Lei; Wang, Wen-Jun

2016-10-01

Polysaccharide is one of the important active ingredients of Cyclocarya paliurus (Batal.) Iljinskaja leaves. The aims of this work were to analyze the structure of the polysaccharide of Cyclocarya paliurus (Batal.) Iljinskaja leaves (CPP), and to investigate the antihyperlipidemic effect of CPP on high-fat emulsion (HFE)-induced hyperlipidaemic rats. CPP, comprised of two polysaccharides with average molecular weight (Mw) of 1.35×10(5)Da and 9.34×10(3)Da, was consisted of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.00:2.23:0.64:0.49:0.63:4.16. Oral administration of CPP could significantly decrease levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), increase high density lipoprotein (HDL-C) in hyperlipidemic rats. CPP exerts therapeutic effects on hyperlipidaemic rats, by up-regulating expressions of adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor alpha (PPARα), via down-regulating fatty acid synthase (FAS) and hydroxy methylglutaryl coenzyme A reductase (HMG-CoA). This study demonstrates that CPP may be beneficial for the treatment of hyperlipidemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Re-evaluation of the reward comparison hypothesis for alcohol abuse.

PubMed

He, Alan Bo-Han; Chang, Yu-Chieh; Meng, Anna Wan Yun; Huang, Andrew Chih Wei

2017-08-14

This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further. Copyright © 2017 Elsevier B.V. All rights reserved.

Porous calcium polyphosphate bone substitutes: additive manufacturing versus conventional gravity sinter processing-effect on structure and mechanical properties.

PubMed

Hu, Youxin; Shanjani, Yaser; Toyserkani, Ehsan; Grynpas, Marc; Wang, Rizhi; Pilliar, Robert

2014-02-01

Porous calcium polyphosphate (CPP) structures proposed as bone-substitute implants and made by sintering CPP powders to form bending test samples of approximately 35 vol % porosity were machined from preformed blocks made either by additive manufacturing (AM) or conventional gravity sintering (CS) methods and the structure and mechanical characteristics of samples so made were compared. AM-made samples displayed higher bending strengths (≈1.2-1.4 times greater than CS-made samples), whereas elastic constant (i.e., effective elastic modulus of the porous structures) that is determined by material elastic modulus and structural geometry of the samples was ≈1.9-2.3 times greater for AM-made samples. X-ray diffraction analysis showed that samples made by either method displayed the same crystal structure forming β-CPP after sinter annealing. The material elastic modulus, E, determined using nanoindentation tests also showed the same value for both sample types (i.e., E ≈ 64 GPa). Examination of the porous structures indicated that significantly larger sinter necks resulted in the AM-made samples which presumably resulted in the higher mechanical properties. The development of mechanical properties was attributed to the different sinter anneal procedures required to make 35 vol % porous samples by the two methods. A primary objective of the present study, in addition to reporting on bending strength and sample stiffness (elastic constant) characteristics, was to determine why the two processes resulted in the observed mechanical property differences for samples of equivalent volume percentage of porosity. An understanding of the fundamental reason(s) for the observed effect is considered important for developing improved processes for preparation of porous CPP implants as bone substitutes for use in high load-bearing skeletal sites. Copyright © 2013 Wiley Periodicals, Inc.

Differences in bingeing behavior and cocaine reward following intermittent access to sucrose, glucose or fructose solutions

PubMed Central

Rorabaugh, Jacki M.; Stratford, Jennifer M.; Zahniser, Nancy R.

2015-01-01

Daily intermittent access to sugar solutions results in intense bouts of sugar intake (i.e. bingeing) in rats. Bingeing on sucrose, a disaccharide of glucose and fructose, has been associated with a “primed” mesolimbic dopamine (DA) pathway. Recent studies suggest glucose and fructose engage brain reward and energy sensing mechanisms in opposing ways and may drive sucrose intake through unique neuronal circuits. Here, we examined in male Sprague-Dawley rats whether or not (1) intermittent access to isocaloric solutions of sucrose, glucose or fructose results in distinctive sugar bingeing profiles and (2) previous sugar bingeing alters cocaine locomotor activation and/or reward, as determined by conditioned place preference (CPP). To encourage bingeing, rats were given 24-h access to water and 12 h-intermittent access to chow plus an intermittent bottle that contained water (control) or 8% solutions of sucrose, glucose or fructose for 9 days, followed by ad libitum chow diet and a 10 day cocaine (15 mg/kg; i.p.) CPP paradigm. By day 4 of the sugar bingeing diet, sugar bingeing in the fructose group surpassed the glucose group, with the sucrose group being intermediate. All three sugar groups had similar chow and water intake throughout the diet. In contrast, controls exhibited chow bingeing by day 5 without altering water intake. Similar magnitudes of cocaine CPP were observed in rats with a history of sucrose, fructose or chow (control) bingeing. Notably, the glucosebingeing rats did not demonstrate a significant cocaine CPP despite showing similar cocaine-induced locomotor activity as the other diet groups. Overall, these results show that fructose and glucose, the monosaccharide components of sucrose, produce divergent degrees of bingeing and cocaine reward. PMID:26079112

Surface bioengineering of diatomite based nanovectors for efficient intracellular uptake and drug delivery.

PubMed

Terracciano, Monica; Shahbazi, Mohammad-Ali; Correia, Alexandra; Rea, Ilaria; Lamberti, Annalisa; De Stefano, Luca; Santos, Hélder A

2015-12-21

Diatomite is a natural porous silica material of sedimentary origin. Due to its peculiar properties, it can be considered as a valid surrogate of synthetic porous silica for nano-based drug delivery. In this work, we exploit the potential of diatomite nanoparticles (DNPs) for drug delivery with the aim of developing a successful dual-biofunctionalization method by polyethylene glycol (PEG) coverage and cell-penetrating peptide (CPP) bioconjugation, to improve the physicochemical and biological properties of the particles, to enhance the intracellular uptake in cancer cells, and to increase the biocompatibility of 3-aminopropyltriethoxysilane (APT) modified-DNPs. DNPs-APT-PEG-CPP showed hemocompatibility for up to 200 μg mL(-1) after 48 h of incubation with erythrocytes, with a hemolysis value of only 1.3%. The cytotoxicity of the modified-DNPs with a concentration up to 200 μg mL(-1) and incubation with MCF-7 and MDA-MB-231 breast cancer cells for 24 h, demonstrated that PEGylation and CPP-bioconjugation can strongly reduce the cytotoxicity of DNPs-APT. The cellular uptake of the modified-DNPs was also evaluated using the above mentioned cancer cell lines, showing that the CPP-bioconjugation can considerably increase the DNP cellular uptake. Moreover, the dual surface modification of DNPs improved both the loading of a poorly water-soluble anticancer drug, sorafenib, with a loading degree up to 22 wt%, and also enhanced the drug release profiles in aqueous solutions. Overall, this work demonstrates that the biofunctionalization of DNPs is a promising platform for drug delivery applications in cancer therapy as a result of its enhanced stability, biocompatibility, cellular uptake, and drug release profiles.

Monosodium glutamate-associated alterations in open field, anxiety-related and conditioned place preference behaviours in mice.

PubMed

Onaolapo, Olakunle James; Aremu, Olaleye Samuel; Onaolapo, Adejoke Yetunde

2017-07-01

The present study investigated changes in behaviour associated with oral monosodium glutamate (a flavouring agent), using the open field, elevated plus maze and conditioned place preference (CPP) paradigms, respectively. Mice were assigned to two groups for CPP [monosodium glutamate (MSG)-naïve (n = 40) and MSG-pretreated (n = 40)] and two groups for open field (OF) and elevated plus maze (EPM) tests [n = 40 each], respectively. Animals in respective groups were then divided into four subgroups (n = 10) (vehicle or MSG (80, 160 and 320 mg/kg)). MSG-naïve mice were observed in the CPP box in three phases (pre-conditioning, conditioning and post-conditioning). Mice were conditioned to MSG or an equivalent volume of saline. The MSG pretreatment group received vehicle or respective doses of MSG daily for 21 days, prior to conditioning. Mice in the OF or EPM groups received vehicle or doses of MSG (orally) for 21 days, at 10 ml/kg. Open field or EPM behaviours were assessed on days 1 and 21. At the end of the experiments, mice in the OF groups were sacrificed and brain homogenates used to assay glutamate and glutamine. Results showed that administration of MSG was associated with a decrease in rearing, dose-related mixed horizontal locomotor, grooming and anxiety-related response and an increase in brain glutamate/glutamine levels. Following exposure to the CPP paradigm, MSG-naïve and MSG-pretreated mice both showed 'drug-paired' chamber preference. The study concluded that MSG (at the administered doses) was associated with changes in open field activities, anxiety-related behaviours and brain glutamate/glutamine levels; its ingestion also probably leads to a stimulation of the brain reward system.

[Studying on purification technology of Resina Draconis phenol extracts based on design space method].

PubMed

Zhang, Jian; Zhang, Xin; Bi, Yu-An; Xu, Gui-Hong; Huang, Wen-Zhe; Wang, Zhen-Zhong; Xiao, Wei

2017-09-01

The "design space" method was used to optimize the purification process of Resina Draconis phenol extracts by using the concept of "quality derived from design" (QbD). The content and transfer rate of laurin B and 7,4'-dihydroxyflavone and yield of extract were selected as the critical quality attributes (CQA). Plackett-Burman design showed that the critical process parameters (CPP) were concentration of alkali, the amount of alkali and the temperature of alkali dissolution. Then the Box-Behnken design was used to establish the mathematical model between CQA and CPP. The variance analysis results showed that the P values of the five models were less than 0.05 and the mismatch values were all greater than 0.05, indicating that the model could well describe the relationship between CQA and CPP. Finally, the control limits of the above 5 indicators (content and transfer rate of laurine B and 7,4'-dihydroxyflavone, as well as the extract yield) were set, and then the probability-based design space was calculated by Monte Carlo simulation and verified. The results of the design space validation showed that the optimized purification method can ensure the stability of the Resina Draconis phenol extracts refining process, which would help to improve the quality uniformity between batches of phenol extracts and provide data support for production automation control. Copyright© by the Chinese Pharmaceutical Association.

Evaluation of a novel approach in the prevention of white spot lesions around orthodontic brackets.

PubMed

Yap, J; Walsh, L J; Naser-Ud Din, S; Ngo, H; Manton, D J

2014-03-01

The purpose of this study was to evaluate and compare the relative efficacy of a resin fissure sealant, nano-filled self-adhesive protective coating, resin infiltrant, glass ionomer cement (GIC), and GIC containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) in preventing the formation of subsurface lesions of enamel (SLE) adjacent to orthodontic brackets by acting as an enamel surface sealant (ESS). Eighty-five enamel specimens with molar tubes bonded at their centre were randomly divided into five groups, each treated with a different material at the bracket's periphery. Specimens were stored in an acetate demineralization solution at pH 4.5 for 7 days at 37 °C then imaged using quantitative light-induced fluorescence (QLF) to determine the difference in fluorescence (∆F) between sound- and acid-exposed enamel. Lesion cross-sections were then examined using backscattered scanning electron microscopy (SEM) to measure lesion depth. The use of GIC alone or incorporating CPP-ACP significantly reduced ∆F compared with other materials. Backscattered SEM images showed no measurable demineralization for enamel treated with either GIC material in contrast with other groups, which showed statistically significant demineralization levels. The fluoride-releasing effects and CPP-ACP benefits of the GIC materials show promise as an effective ESS in inhibiting enamel demineralization adjacent to orthodontic brackets. © 2014 Australian Dental Association.

48 CFR 627.304 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Procedures. 627.304 Section 627.304 Federal Acquisition Regulations System DEPARTMENT OF STATE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Patent Rights Under Government Contracts 627.304 Procedures. ...

CONSTRUCTION PROGRESS PHOTO SHOWING WEST STORAGE BASIN AT FUEL STORAGE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING WEST STORAGE BASIN AT FUEL STORAGE BUILDING (CPP-603). INL PHOTO NUMBER NRTS-51-689. Unknown Photographer, 1950 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Dexamethasone Attenuates the Enhanced Rewarding Effects of Cocaine Following Experimental Traumatic Brain Injury.

PubMed

Merkel, Steven F; Andrews, Allison M; Lutton, Evan M; Razmpour, Roshanak; Cannella, Lee Anne; Ramirez, Servio H

2017-07-01

Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent preclinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay. These studies were performed in order to determine whether proinflammatory activity in the nucleus accumbens (NAc), a key brain nucleus in the reward pathway, mediates enhanced cocaine-induced CPP in adolescent animals sustaining moderate CCI-TBI. Our data reveal robust glial activation in the NAc following CCI-TBI and a significant increase in the cocaine-induced CPP of untreated CCI-TBI mice. Furthermore, our results show that dexamethasone treatment following CCI-TBI can attenuate the cocaine place preference of injured animals without producing aversion in the CPP assay. Our studies also found that dexamethasone treatment significantly reduced the expression of select immune response genes including Monocyte chemoattractant protein-1 (MCP-1/CCL2) and intercellular adhesion molecule-1 ( ICAM-1), returning their expression to control levels, which prompted an investigation of peripheral blood monocytes in dexamethasone-treated animals. Experimental findings showed that no craniectomy/dexamethasone mice had a significant increase, while CCI-TBI/dexamethasone animals had a significant decrease in the percentage of circulating nonclassical patrolling monocytes. These results suggest that a portion of these monocytes may migrate to the brain in response to CCI-TBI, potentially sparing the development of chronic neuroinflammation in regions associated with the reward circuitry such as the NAc. Overall, our findings indicate that anti-inflammatory agents, such as dexamethasone, may be effective in normalizing the rewarding effects of cocaine following CCI-TBI.

Concentration of Calcium, Phosphate and Fluoride Ions in Microbial Plaque and Saliva after Using CPP-ACP Paste in 6-9 year-old Children

PubMed Central

HR, Poureslami; Ra, Hoseinifar; Re, Hoseinifar; H, Sharifi; P, Poureslami

2016-01-01

Statement of Problem: Dental caries is one of the most common chronic diseases in children. The balance between demineralization and remineralization of the decayed teeth depends on the calcium and phosphate content of the tooth surface. Therefore, if a product such as casein phospho peptides - amorphous calcium phosphate (CPP- ACP) which can significantly increase the availability of calcium and phosphate in the plaque and saliva should have an anti-caries protective effect. Objectives: The purpose of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children before and after applying the CPP-ACP paste. Materials and Methods: A total of 25 children aged between 6-9 years were selected for this clinical trial study. At first, 1 ml of unstimulated saliva was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. In the next step, CPP-ACP paste (GC Corp, Japan) was applied on the tooth surfaces and then the plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Ion meter instrument (Metrohm Co, Swiss) and the amounts of phosphate and fluoride ions were measured by Ion Chromatography instrument (Metrohm Co, Swiss). Data were analyzed using paired t-test at a p < 0.05 level of significance. Results: There were statistically significant differences in the calcium and phosphate concentration of the saliva and plaque before and after applying the CPP-ACP paste. There were also statistically significant differences in the fluoride levels of the plaque before and after applying the CPP-ACP paste. However, there were no statistically significant differences in the fluoride levels of the saliva before and after applying the CPP-ACP paste. Conclusions: In this study, the use of the CPP-ACP paste significantly increased the fluoride levels of the plaque and the calcium and phosphate levels of both saliva and plaque. Hence, CPP-ACP paste can facilitate the remineralization of tooth surfaces and is useful for protecting the primary teeth. PMID:28959745

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

PubMed

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

2013-08-01

The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on broilers with or without necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3 × 2 × 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were allowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10× dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis increased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin × virginiamycin × CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin × virginiamycin, P < 0.05). Aflatoxin increased lesion scores in unchallenged birds but not in challenged birds (aflatoxin × CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler performance and interact to decrease weight gain, virginiamycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of aflatoxin.

Nonpharmacologic and pharmacologic management of CPP crystal arthritis and BCP arthropathy and periarticular syndromes.

PubMed

Rosenthal, Ann K; Ryan, Lawrence M

2014-05-01

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies. Acute CPP arthritis is treated similarly to acute gouty arthritis, whereas chronic CPP and BCP arthropathy may respond to strategies used for osteoarthritis. Calcific tendonitis is treated with a variety of interventions designed to dissolve BCP crystals. A better understanding of the causes and larger well-planned trials of current therapies will lead to improved care. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of medial prefrontal cortex Narp in the extinction of morphine conditioned place preference.

PubMed

Blouin, Ashley M; Han, Sungho; Pearce, Anne M; Cheng, Kailun; Lee, Jongah J; Johnson, Alexander W; Wang, Chuansong; During, Matthew J; Holland, Peter C; Shaham, Yavin; Baraban, Jay M; Reti, Irving M

2013-01-15

Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus (AAV) expressing wild-type (WT) Narp into the mPFC of Narp KO mice rescued the extinction and the injection of AAV expressing a dominant negative form of Narp (NarpN) into the mPFC of WT mice impaired the extinction of morphine CPP. These findings suggest that Narp in the mPFC mediates the extinction of morphine CPP.

CPP-GMR films with a current-confined-path nano-oxide layer (CCP-NOL)

NASA Astrophysics Data System (ADS)

Fukuzawa, Hideaki; Yuasa, Hiromi; Iwasaki, Hitoshi

2007-03-01

We investigated the film performance and nanostructure of current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) spin-valve film with a current-confined-path nano-oxide layer (CCP-NOL). By applying ion-assisted oxidation (IAO) for the CCP-NOL formation, we enhanced the MR ratio to 5.4% at a small RA value of 500 mΩ µm2 for conventional Co90Fe10 layers. Furthermore, the use of bcc-Fe50Co50 also increased the MR ratio to 8.2% at a small RA value of 580 mΩ µm2. A modified Valet-Fert model for the CCP-NOL showed that the MR enhancement by the IAO is due to the improvement in resistivity of the CCP, and that by Fe50Co50 is due to a larger spin-dependent interface scattering effect. Analysis by cross-sectional TEM and three-dimensional atom probe confirmed the formation of the CCP-NOL structure. A reliability test for test element devices showed almost no change even under acceleration stress. The CPP-GMR spin-valve film with the CCP-NOL is extendable to future high-density recording heads due to its potential for a higher MR ratio at a small value of RA.

Dual peptide conjugation strategy for improved cellular uptake and mitochondria targeting.

PubMed

Lin, Ran; Zhang, Pengcheng; Cheetham, Andrew G; Walston, Jeremy; Abadir, Peter; Cui, Honggang

2015-01-21

Mitochondria are critical regulators of cellular function and survival. Delivery of therapeutic and diagnostic agents into mitochondria is a challenging task in modern pharmacology because the molecule to be delivered needs to first overcome the cell membrane barrier and then be able to actively target the intracellular organelle. Current strategy of conjugating either a cell penetrating peptide (CPP) or a subcellular targeting sequence to the molecule of interest only has limited success. We report here a dual peptide conjugation strategy to achieve effective delivery of a non-membrane-penetrating dye 5-carboxyfluorescein (5-FAM) into mitochondria through the incorporation of both a mitochondrial targeting sequence (MTS) and a CPP into one conjugated molecule. Notably, circular dichroism studies reveal that the combined use of α-helix and PPII-like secondary structures has an unexpected, synergistic contribution to the internalization of the conjugate. Our results suggest that although the use of positively charged MTS peptide allows for improved targeting of mitochondria, with MTS alone it showed poor cellular uptake. With further covalent linkage of the MTS-5-FAM conjugate to a CPP sequence (R8), the dually conjugated molecule was found to show both improved cellular uptake and effective mitochondria targeting. We believe these results offer important insight into the rational design of peptide conjugates for intracellular delivery.

The role of the laterodorsal tegmental nucleus in methamphetamine conditioned place preference and locomotor activity.

PubMed

Dobbs, Lauren K; Cunningham, Christopher L

2014-05-15

Methamphetamine (METH) indirectly stimulates the laterodorsal tegmental nucleus (LDT) acetylcholine (ACh) neurons to increase ACh within the ventral tegmental area (VTA). LDT ACh inhibition attenuates METH and saline locomotor activity. The aim of these experiments was to determine whether LDT ACh contributes to METH conditioned place preference (CPP). C57BL/6J mice received a bilateral electrolytic or sham lesion of the LDT. After recovery, mice received alternating pairings of METH (0.5 mg/kg) and saline with distinct tactile floor cues over 8 days. During preference tests, mice were given access to both floor types and time spent on each was recorded. Mice were tested again after exposure to both extinction and reconditioning trials. Brains were then processed for choline acetyltransferase immunohistochemistry to label LDT ACh neurons. Lesioned mice had significantly fewer LDT ACh neurons and showed increased saline and METH locomotor activity during the first conditioning trial compared to sham mice. Locomotor activity (saline and METH) was negatively correlated with the number of LDT ACh neurons. Lesioned and sham mice showed similar METH CPP following conditioning, extinction and reconditioning trials. LDT ACh neurons are not necessary for METH reward as indexed by CPP, but may be important for basal and METH-induced locomotor activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Exercise is associated with reduction in the anxiogenic effect of mCPP on acoustic startle.

PubMed

Fox, James H; Hammack, Sayamwong E; Falls, William A

2008-08-01

Voluntary exercise has been associated with reduced anxiety across several animal models. Manipulation of central 5-HT can alter anxiety-like behaviors and administration of the 5-HT agonist metachlorophenylpiperazine (mCPP) increases anxiety in rodents and humans. To examine whether the anxiolytic effect of exercise is associated with an alteration in 5-HT systems, we examined the anxiogenic effect of mCPP in exercising and nonexercising mice. C57BL/6J mice were given 2 weeks of free access to either a functioning or nonfunctioning running wheel. Mice were then tested for acoustic startle following systemic injection of either 0, 0.1, 0.3, or 1 mg/kg of mCPP. Consistent with its anxiogenic properties, mCPP produced a dose-dependent increase in acoustic startle in nonexercising mice. However, this anxiogenic effect was blunted in exercising mice. These findings suggest that exercise may help to reduce anxiety by altering 5-HT systems, perhaps by down-regulating postsynaptic 5HT 2B/2C receptors.

CONSTRUCTION PROGRESS PHOTO SHOWING EXCAVATION PIT FOR MAIN PROCESSING BUILDING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING EXCAVATION PIT FOR MAIN PROCESSING BUILDING (CPP-601) LOOKING SOUTH. INL PHOTO NUMBER NRTS-50-693. Unknown Photographer, 1950 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

12 CFR 627.2797 - Preservation of equity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Preservation of equity. 627.2797 Section 627.2797 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM TITLE IV CONSERVATORS, RECEIVERS, AND VOLUNTARY LIQUIDATIONS Voluntary Liquidation § 627.2797 Preservation of equity. (a) Immediately...

40 CFR 52.627-52.631 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false [Reserved] 52.627-52.631 Section 52.627-52.631 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Hawaii §§ 52.627-52.631 [Reserved] ...

Anti-Communist Vigilantes in the Philippines

DTIC Science & Technology

1988-06-03

including the founding chairman Jose Maria Sison and communist guerrilla leader Bernabe Buscayno, a.k.a. Kumander Dante. 2 Today, the CPP/NPA continues...arrest in 1976 of Jose Maria Sison, the CPP chairman. The new leadership modified the communist armed struggle by giving new impetus to urban guerilla...largest island In the Southern Philippines. The MNLF chairman Nur Misuari assisted CPP founder Jose Maria Sison in organizing the radical youth

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells

PubMed Central

Liu, Betty R.; Huang, Yue-Wern; Aronstam, Robert S.; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy. PMID:26942714

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

PubMed

Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

Antibronchospastic activity of MEN10,627, a novel tachykinin NK2 receptor antagonist, in guinea-pig airways.

PubMed

Perretti, F; Ballati, L; Manzini, S; Maggi, C A; Evangelista, S

1995-01-24

The antibronchospastic activity against acetylcholine, antigen, histamine plus platelet-activating factor (PAF) or the selective tachykinin neurokinin (NK)1 and NK2 receptor agonists of the novel tachykinin NK2 receptor antagonist, MEN10,627 (cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2 beta-5 beta)), was studied in anesthetized guinea-pigs. MEN10,627 (30-100 nmol/kg i.v.) reduced in a dose-dependent manner the bronchospasm induced by the tachykinin NK2 receptor agonist [beta Ala8]neurokinin A-(4-10) and the effect of the highest dose lasted up to 5 h from its administration. Conversely, airway constriction induced by the NK1 receptor agonist [Sar9]substance P sulfone or acetylcholine was unaffected by MEN10,627 up to a dose of 3 mumol/kg i.v. In animals sensitized with ovalbumin and pretreated with the endopeptidase inhibitor phosphoramidon, the aerosolized antigen produced a bronchospasm which was inhibited by MEN10,627 (30-100 nmol/kg i.v.) but not by the tachykinin NK1 receptor antagonist, (+/-)-CP96,345 ([2R,3R-cis- and [2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine]) (3 mumol/kg i.v.). Both MEN10,627 (30-100 nmol/kg i.v.) and (+/-)-CP96,345 (30-300 nmol/kg i.v.) reduced the PAF-induced hyperresponsiveness to histamine, without affecting the hypotension induced by PAF or the bronchospasm induced by histamine in guinea-pigs not exposed to PAF, showing the involvement of both tachykinin NK1 and NK2 receptors in this model. In summary, MEN10,627 behaves as a potent, selective and long-lasting tachykinin NK2 receptor antagonist in vivo. Further, tachykinin NK2 receptors could be activated during allergic responses and in the development of airway hyperresponsiveness.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery.

PubMed

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

PubMed Central

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. PMID:26491292

Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

2016-06-01

This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of GABAA receptors in dorsal raphe nucleus in stress-induced reinstatement of morphine-conditioned place preference in rats.

PubMed

Li, Chen; Staub, Daniel R; Kirby, Lynn G

2013-12-01

The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Our data indicate that stress inhibits the dorsal raphe nucleus (DRN)-5-HT system via stimulation of GABA synaptic activity by the stress neurohormone corticotropin-releasing factor and, more recently, that morphine history sensitizes DRN-5-HT neurons to GABAergic inhibitory effects of stress. We tested the hypothesis that DRN GABAA receptors contribute to stress-induced reinstatement of morphine-conditioned place preference (CPP). First, we tested if activation of GABAA receptors in the DRN would reinstate morphine CPP. Second, we tested if blockade of GABAA receptors in the DRN would attenuate swim stress-induced reinstatement of morphine CPP. CPP was induced by morphine (5 mg/kg) in a 4-day conditioning phase followed by a conditioning test. Upon acquiring conditioning criteria, subjects underwent 4 days of extinction training followed by an extinction test. Upon acquiring extinction criteria, animals underwent a reinstatement test. For the first experiment, the GABAA receptor agonist muscimol (50 ng) or vehicle was injected into the DRN prior to the reinstatement test. For the second experiment, the GABAA receptor antagonist bicuculline (75 ng) or vehicle was injected into the DRN prior to a forced swim stress, and then, animals were tested for reinstatement of CPP. Intraraphe injection of muscimol reinstated morphine CPP, while intraraphe injection of bicuculline attenuated swim stress-induced reinstatement. These data provide evidence that GABAA receptor-mediated inhibition of the serotonergic DRN contributes to stress-induced reinstatement of morphine CPP.

Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

PubMed

Kreiss, Deborah S; Coffman, Catherine F; Fiacco, Nicholas R; Granger, Jason C; Helton, Bernadette M; Jackson, Jennifer C; Kim, Leonid V; Mistry, Rishi S; Mizer, Tammie M; Palmer, Lolita V; Vacca, Jay A; Winkler, Stuart S; Zimmer, Benjamin A

2013-03-01

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD. Copyright © 2013. Published by Elsevier Inc.

Oxytocin and MDMA ('Ecstasy') enhance social reward in rats.

PubMed

Ramos, Linnet; Hicks, Callum; Caminer, Alex; Goodwin, Jack; McGregor, Iain S

2015-07-01

Oxytocin (OT), vasopressin (AVP) and 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') all increase social interaction in rats, perhaps by enhancing the rewarding value of social encounters. Here, we used the conditioned place preference (CPP) paradigm to assess the intrinsic rewarding effects of OT, AVP and MDMA, and whether these effects are enhanced by the presence of a conspecific, or a dynamic, tactile object (a tennis ball). Adult male rats received conditioning sessions in a CPP apparatus twice a day (vehicle at 10 a.m., drug at 3 p.m.). Experiment 1 involved conditioning with OT (0.5 mg/kg, intraperitoneal (i.p.)), AVP (0.005 mg/kg, i.p.) or MDMA (5 mg/kg, i.p.). Experiments 2 and 3 involved conditioning with the same treatments but in the presence of a conspecific receiving the same treatment (social-CPP) or in the presence of a tennis ball (object-CPP), respectively. Conditioned place preference was assessed 24 h, 2 weeks and 4 weeks later. OT, AVP and MDMA did not produce a conventional CPP. However, when the conditioning environment also contained a conspecific both OT and MDMA induced a significant CPP lasting for at least 4 weeks. Rats given OT and MDMA also developed a more modest yet significant CPP for the environment where they encountered a tennis ball. These results indicate that OT and MDMA can augment the rewarding effects of social interaction, but also interaction with a dynamic and tactile non-social object. AVP does not condition social- or object-CPPs and may promote social proximity by inducing generalized anxiety and defensive aggregation.

Acoustic analyses of thyroidectomy-related changes in vowel phonation.

PubMed

Solomon, Nancy Pearl; Awan, Shaheen N; Helou, Leah B; Stojadinovic, Alexander

2012-11-01

Changes in vocal function that can occur after thyroidectomy were tracked with acoustic analyses of sustained vowel productions. The purpose was to determine which time-based or spectral/cepstral-based measures of two vowels were able to detect voice changes over time in patients undergoing thyroidectomy. Prospective, longitudinal, and observational clinical trial. Voice samples of sustained /ɑ/ and /i/ recorded from 70 adults before and approximately 2 weeks, 3 months, and 6 months after thyroid surgery were analyzed for jitter, shimmer, harmonic-to-noise ratio (HNR), cepstral peak prominence (CPP), low-to-high ratio of spectral energy (L/H ratio), and the standard deviations of CPP and L/H ratio. Three trained listeners rated vowel and sentence productions for the four data collection sessions for each participant. For analysis purposes, participants were categorized post hoc according to voice outcome (VO) at their first postthyroidectomy assessment session. Shimmer, HNR, and CPP differed significantly across sessions; follow-up analyses revealed the strongest effect for CPP. CPP for /ɑ/ and /i/ differed significantly between groups of participants with normal versus negative (adverse) VO and between the pre- and 2-week postthyroidectomy sessions for the negative VO group. HNR, CPP, and L/H ratio differed across vowels, but both /ɑ/ and /i/ were similarly effective in tracking voice changes over time and differentiating VO groups. This study indicated that shimmer, HNR, and CPP determined from vowel productions can be used to track changes in voice over time as patients undergo and subsequently recover from thyroid surgery, with CPP being the strongest variable for this purpose. Evidence did not clearly reveal whether acoustic voice evaluations should include both /ɑ/ and /i/ vowels, but they should specify which vowel is used to allow for comparisons across studies and multiple clinical assessments. Copyright © 2012 The Voice Foundation. All rights reserved.

Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

PubMed Central

Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

2012-01-01

Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

Food deprivation facilitates reinstatement of morphine-induced conditioned place preference: Role of intra-accumbal dopamine D2-like receptors in associating reinstatement of morphine CPP with stress.

PubMed

Sadeghzadeh, Fatemeh; Babapour, Vahab; Haghparast, Abbas

2017-04-01

The high rate of relapse to drug use is one of the main problems in the treatment of addiction. Stress plays the essential role in drug abuse and relapse; nevertheless, little is known about the mechanisms underlying stress and relapse. Accordingly, the effects of intra-accumbal administration of Sulpiride, as a dopamine D2-like receptor antagonist, on an ineffective morphine dose + food deprivation(FD)- and morphine priming-induced reinstatement of conditioned place preference (CPP). About 104 adult male albino Wistar rats weighing 200-280 g were bilaterally implanted by cannula into the nucleus accumbens (NAc). Subcutaneous (sc) injection of morphine (5 mg kg -1 ) was used daily during a 3-day conditioning phase. After a 24-hr "off" period following achievement of extinction criterion, rats were tested for FD- and priming-induced reinstatement of morphine CPP by an ineffective (0.5 mg kg -1 , sc) and priming (1 mg kg -1 , sc) dose of morphine, respectively. In the next experiments, animals received different doses of intra-accumbal Sulpiride (0.25, 1, and 4 µg/0.5 µL saline) bilaterally and were subsequently tested for morphine reinstatement. Our findings indicated that the 24-hr FD facilitated reinstatement of morphine CPP. Furthermore, the D2-like receptor antagonist attenuated the ineffective morphine dose+ FD- and priming-induced reinstatement of morphine CPP dose-dependently. Also, contribution of D2-like receptors in mediation of the ineffective morphine dose+ FD-induced reinstatement of CPP was greater than morphine priming-induced reinstatement of CPP. The role of dopaminergic system in morphine reinstatement through a neural pathway in the NAc provides the evidence that D2-like receptor antagonist can be useful therapeutic targets for reinstatement of morphine CPP. © 2016 Wiley Periodicals, Inc.

High yield Cu-Co CPP GMR multilayer sensors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spallas, J.; Mao, M.; Law, B.

1997-01-15

We have fabricated and tested GMR magnetic flux sensors that operate in the CPP mode. This work is a continuation of the ultra-high density magnetic sensor research introduced at INTERMAG 96. We have made two significant modifications to the process sequence. First, contact to the sensor is made through a metal conduit deposited in situ with the multilayers. This deposition replaces electroplating. This configuration ensures a good electrical interface between the top of multilayer stack and the top contact, and a continuous, conductive current path to the sensor. The consequences of this modification are an increase in yield of operationalmore » devices to {ge}90% per wafer and a significant reduction of the device resistance to {le}560 milliohms and of the uniformity of the device resistance to {le}3%. Second, the as-deposited multilayer structure has been changed from [Cu 30 {angstrom}/Co 20 {angstrom}]{sub 18} (third peak) to [Cu 20.5 {angstrom}/Co 12 {angstrom}]{sub 30} (second peak) to increase the CPP and CIP responses. The sheet film second peak CIP GMR response is 18% and the sensitivity is 0.08 %/Oe. The sheet film third peak CIP GMR response is 8% and the sensitivity is 0. 05 %/Oe. The second peak CPP GMR response averaged over twenty devices on a four inch silicon substrate is 28% {+-} 6%. The response decreases radially from the substrate center. The average response at the center of the substrate is 33% {+-} 4%. The average second peak CPP sensitivity is 0.09 %/Oe {+-} 0.02 %/Oe. The best second peak CPP response from a single device is 39%. The sensitivity of that device is 0.13 %/Oe. The third peak CPP GMR response is approximately 14 %. The third peak CPP response sensitivity is 0.07 %/Oe. 6 refs., 3 figs.« less

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Casein phosphopeptides and CaCl2 increase penicillin production and cause an increment in microbody/peroxisome proteins in Penicillium chrysogenum.

PubMed

Domínguez-Santos, Rebeca; Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Ibáñez, Ana; Morales, Alejandro; Martín, Juan-Francisco

2017-03-06

Transport of penicillin intermediates and penicillin secretion are still poorly characterized in Penicillium chrysogenum (re-identified as Penicillium rubens). Calcium (Ca 2+ ) plays an important role in the metabolism of filamentous fungi, and casein phosphopeptides (CPP) are involved in Ca 2+ internalization. In this study we observe that the effect of CaCl 2 and CPP is additive and promotes an increase in penicillin production of up to 10-12 fold. Combination of CaCl 2 and CPP greatly promotes expression of the three penicillin biosynthetic genes. Comparative proteomic analysis by 2D-DIGE, identified 39 proteins differentially represented in P. chrysogenum Wisconsin 54-1255 after CPP/CaCl 2 addition. The most interesting group of overrepresented proteins were a peroxisomal catalase, three proteins of the methylcitrate cycle, two aminotransferases and cystationine β-synthase, which are directly or indirectly related to the formation of penicillin amino acid precursors. Importantly, two of the enzymes of the penicillin pathway (isopenicillin N synthase and isopenicillin N acyltransferase) are clearly induced after CPP/CaCl 2 addition. Most of these overrepresented proteins are either authentic peroxisomal proteins or microbody-associated proteins. This evidence suggests that addition of CPP/CaCl 2 promotes the formation of penicillin precursors and the penicillin biosynthetic enzymes in peroxisomes and vesicles, which may be involved in transport and secretion of penicillin. Penicillin biosynthesis in Penicillium chrysogenum is one of the best characterized secondary metabolism processes. However, the mechanism by which penicillin is secreted still remains to be elucidated. Taking into account the role played by Ca 2+ and CPP in the secretory pathway and considering the positive effect that Ca 2+ exerts on penicillin production, the analysis of global protein changes produced after CPP/CaCl 2 addition is very helpful to decipher the processes related to the biosynthesis and secretion of penicillin. Copyright © 2017 Elsevier B.V. All rights reserved.

12 CFR 627.2730 - Preservation of equity.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Preservation of equity. 627.2730 Section 627.2730 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM TITLE IV CONSERVATORS, RECEIVERS, AND VOLUNTARY LIQUIDATIONS Receivers and Receiverships § 627.2730 Preservation of equity. (a) Except...

23 CFR 627.5 - Applicable projects.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Applicable projects. 627.5 Section 627.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING § 627.5 Applicable projects. (a) A VE analysis shall be conducted prior to the completion of final...

23 CFR 627.5 - Applicable projects.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Applicable projects. 627.5 Section 627.5 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING § 627.5 Applicable projects. (a) A VE analysis shall be conducted prior to the completion of final...

46 CFR 169.627 - Compartments containing diesel fuel tanks.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Compartments containing diesel fuel tanks. 169.627 Section 169.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Ventilation § 169.627 Compartments containing diesel fuel tanks...

46 CFR 169.627 - Compartments containing diesel fuel tanks.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Compartments containing diesel fuel tanks. 169.627 Section 169.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) NAUTICAL SCHOOLS SAILING SCHOOL VESSELS Machinery and Electrical Ventilation § 169.627 Compartments containing diesel fuel tanks...

20 CFR 627.230 - Displacement.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Displacement. 627.230 Section 627.230... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.230 Displacement. (a) No currently employed worker shall be displaced by any participant (including partial displacement such as a...

20 CFR 627.230 - Displacement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Displacement. 627.230 Section 627.230... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.230 Displacement. (a) No currently employed worker shall be displaced by any participant (including partial displacement such as a...

20 CFR 627.230 - Displacement.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Displacement. 627.230 Section 627.230... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.230 Displacement. (a) No currently employed worker shall be displaced by any participant (including partial displacement such as a...

20 CFR 627.470 - Performance standards.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Performance standards. 627.470 Section 627... GOVERNING PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Administrative Standards § 627.470 Performance standards. (a) General. The Secretary shall prescribe performance standards for adult programs under title...

20 CFR 627.470 - Performance standards.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false Performance standards. 627.470 Section 627... GOVERNING PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Administrative Standards § 627.470 Performance standards. (a) General. The Secretary shall prescribe performance standards for adult programs under title...

48 CFR 627.203 - Patent indemnification of Government by contractor.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Patent indemnification of Government by contractor. 627.203 Section 627.203 Federal Acquisition Regulations System DEPARTMENT OF STATE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Patents 627.203 Patent indemnification of...

48 CFR 627.203 - Patent indemnification of Government by contractor.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Patent indemnification of Government by contractor. 627.203 Section 627.203 Federal Acquisition Regulations System DEPARTMENT OF STATE GENERAL CONTRACTING REQUIREMENTS PATENTS, DATA, AND COPYRIGHTS Patents 627.203 Patent indemnification of...

20 CFR 627.902 - Governor's actions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Governor's actions. 627.902 Section 627.902... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Transition Provisions § 627.902 Governor's actions. The...) Modify the Governor's coordination and special services plan in accordance with instructions issued by...

46 CFR 108.627 - Carbon dioxide alarm.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Carbon dioxide alarm. 108.627 Section 108.627 Shipping... EQUIPMENT Equipment Markings and Instructions § 108.627 Carbon dioxide alarm. Each carbon dioxide alarm must be identified by marking: “WHEN ALARM SOUNDS VACATE AT ONCE. CARBON DIOXIDE BEING RELEASED” next to...

20 CFR 627.450 - Program income.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Program income. 627.450 Section 627.450... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Administrative Standards § 627.450 Program income. (a) Definition of program income. (1) Program income means income received by the recipient or subrecipient that...

20 CFR 627.245 - Work experience.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Work experience. 627.245 Section 627.245... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.245 Work experience. (a) Definition. Work experience means a short-term or part-time training assignment with a public or private...

20 CFR 627.245 - Work experience.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Work experience. 627.245 Section 627.245... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.245 Work experience. (a) Definition. Work experience means a short-term or part-time training assignment with a public or private...

23 CFR 627.7 - VE programs.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false VE programs. 627.7 Section 627.7 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING § 627.7 VE programs. (a) The STA shall establish and sustain a VE program under which VE analyses are...

23 CFR 627.7 - VE programs.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false VE programs. 627.7 Section 627.7 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING § 627.7 VE programs. (a) The STA shall establish and sustain a VE program under which VE analyses are...

20 CFR 627.481 - Audit resolution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Audit resolution. 627.481 Section 627.481... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Administrative Standards § 627.481 Audit resolution. (a) Federal audit resolution. When the OIG issues an audit report to the Employment and Training...

20 CFR 627.420 - Procurement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Procurement. 627.420 Section 627.420... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Administrative Standards § 627.420 Procurement. (a) General. (1) For purposes of this section, the term procurement means the process which leads to any award of...

20 CFR 627.906 - Determinations on State and SDA implementation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... questioned costs related to the implementation of the provisions described in paragraph (b) of this section... implementation. 627.906 Section 627.906 Employees' Benefits EMPLOYMENT AND TRAINING ADMINISTRATION, DEPARTMENT OF... § 627.906 Determinations on State and SDA implementation. (a) The Department expects that the States and...

Investigation of spin-dependent transports and microstructure in NiMnSb-based magnetoresistive devices

NASA Astrophysics Data System (ADS)

Qu, Guanxiong; Cheng, P.-H.; Du, Ye; Sakuraba, Yuya; Kasai, Shinya; Hono, Kazuhiro

2017-11-01

We have fabricated fully epitaxial current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) devices using C1b-half Heusler compound NiMnSb, the first candidate of the half-metallic material, as the electrode with a Ag spacer. The device shows magnetoresistance ratios of 25% at 4.2 K and 9.6% at 290 K, which are one of the highest values for the CPP-GMR with half-Heusler compounds. However, these values are much lower compared to those reported for CPP-GMR devices with L21-full Heusler compounds. Careful analysis of the microstructure using scanning transmission electron microscopy and energy dispersive spectroscopy through the upper NiMnSb/Ag interface indicates the heterogeneous formation of Ag-rich solid solution or the island growth of Ag on top of NiMnSb, which clarified a difficulty in evaluating an intrinsic spin-polarization in NiMnSb from CPP-GMR devices. Thus, to evaluate a spin-polarization of a NiMnSb thin film, we fabricated non-local spin valve (NLSV) devices using NiMnSb with Cu channel wires, which is free from the diffusion of Cu to NiMnSb because of no annealing proccess after deposition of Cu. Finally, intrinsic spin polarization of the NiMnSb single layer was extrapolated to be around 50% from NLSV, suggesting a difficulty in obtaining half-metallic nature in the NiMnSb epitaxial thin film.

A comparative evaluation of APF gel, CPP/ACP paste alone and in combination with carbon dioxide laser on human enamel resistance to acid solubility using atomic absorption spectrometry: an in-vitro study.

PubMed

Nozari, Ali; Rafiee, Azade; Dehghan Khalili, Sara; Fekrazad, Reza

2018-04-01

The aim of this study was to compare the effects of acidulated phosphate fluoride (APF) gel, calcium phosphopeptide-amorphous calcium phosphate (CPP/ACP) paste alone and in combination with CO2 laser on the resistance of enamel to acid solubility. Ninety enamel sections were obtained from 15 extracted teeth and were randomly assigned to six groups: 1) control group; 2) APF group; 3) CPP-ACP group; 4) CO2 laser group; 5) APF + CO2 group; and 6) CPP-ACP + CO2 group. The specimens were individually demineralized in 0.1 M lactic acid solution with adjusted pH of 4.8 for 24h at 37 ºC. The acid solubility was determined using atomic absorption spectrometry. Statistical analysis was done using one-way ANOVA and Tukey-Kramer post hoc test (P<0.05). The average extent of calcium ion released (ppm) was estimated as follow: group 1: 6.974±1.757, group 2: 5.363±1.383, group 3: 6.962±1.489, group 4: 6.890±1.560, group 5: 4.803±1.080 and group 6: 6.789±1.218. Based on the between-group comparison results, group 2 and group 5 showed significant differences with the other groups. Under the studied conditions, only, the APF group alone and in combination with CO2 laser could decrease enamel acid solubility.

In vivo study of doxorubicin-loaded cell-penetrating peptide-modified pH-sensitive liposomes: biocompatibility, bio-distribution, and pharmacodynamics in BALB/c nude mice bearing human breast tumors

PubMed Central

Sun, Dan; Wang, Gui-Ling; Hei, Yu; Meng, Shuai; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2017-01-01

In vivo evaluation of drug delivery vectors is essential for clinical translation. In BALB/c nude mice bearing human breast cancer tumors, we investigated the biocompatibility, pharmacokinetics, and pharmacodynamics of doxorubicin (DOX)-loaded novel cell-penetrating peptide (CPP)-modified pH-sensitive liposomes (CPPL) (referred to as CPPL(DOX)) with an optimal CPP density of 4%. In CPPL, a polyethylene glycol (PEG) derivative formed by conjugating PEG with stearate via acid-degradable hydrazone bond (PEG2000-Hz-stearate) was inserted into the surface of liposomes, and CPP was directly attached to liposome surfaces via coupling with stearate to simultaneously achieve long circulation time in blood and improve the selectivity and efficacy of CPP for tumor targeting. Compared to PEGylated liposomes, CPPL enhanced DOX accumulation in tumors up to 1.9-fold (p<0.01) and resulted in more cell apoptosis as a result of DNA disruption as well as a relatively lower tumor growth ratio (T/C%). Histological examination did not show any signs of necrosis or inflammation in normal tissues, but large cell dissolving areas were found in tumors following the treatment of animals with CPPL(DOX). Our findings provide important and detailed information regarding the distribution of CPPL(DOX) in vivo and reveal their abilities of tumor penetration and potential for the treatment of breast cancer. PMID:29123382

Establishment of MicroRNA delivery system by PP7 bacteriophage-like particles carrying cell-penetrating peptide.

PubMed

Sun, Yanli; Sun, Yanhua; Zhao, Ronglan

2017-08-01

MicroRNAs have great therapeutic potential in cancer and other diseases. However, their instability and low in vivo delivery efficiency limits their application. Recombinant PP7 bacteriophage-based virus-like particles (VLPs) could protect microRNAs against rapid degradation by RNase by packaging specific exogenous pre-microRNAs using the pac site. Insertion of a cell-penetrating peptide (CPP) into the AB-loop of VLPs could significantly improve the delivery efficiency of microRNAs into mammalian cells. Unlike other microRNA delivery methods (viral or non-viral vectors), recombinant PP7 VLPs carrying a CPP and microRNA could be efficiently expressed in Escherichia coli using the one-plasmid double expression system. Here we showed that PP7 VLPs carrying a CPP penetrated hepatoma SK-HEP-1 cells and delivered the pre-microRNA-23b, which was processed into a mature product within 24 h; a concentration of 10 nM was sufficient for the inhibition of hepatoma cell migration via the downregulation of liver-intestine cadherin expression. Furthermore, PP7 VLPs carrying a CPP and a pre-microRNA were not infectious, replicative, or cytotoxic. Therefore, recombinant PP7 VLPs can be used for simultaneous and targeted delivery of both microRNAs and peptides because of their ability to package specific exogenous RNA using the pac site and to display peptides. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Virtual reality conditioned place preference using monetary reward

PubMed Central

Childs, Emma; Astur, Robert S.; de Wit, Harriet

2017-01-01

Computerized tasks based on conditioned place preference (CPP) methodology offer the opportunity to study learning mechanisms involved in conditioned reward in humans. In this study, we examined acquisition and extinction of a CPP for virtual environments associated with monetary reward ($). Healthy men and women (N=57) completed a computerized CPP task in which they controlled an avatar within a virtual environment. On day 1, subjects completed 6 conditioning trials in which one room was paired with high $ and another with low $. Acquisition of place conditioning was assessed by measuring the time spent in each room during an exploration test of the virtual environments and using self-reported ratings of room liking and preference. Twenty-four hours later, retention and extinction of CPP were assessed during 4 successive exploration tests of the virtual environments. Participants exhibited a place preference for (spent significantly more time in) the virtual room paired with high $ over the one paired with low $ (p=0.015). They also reported that they preferred the high $ room (p<0.001) and liked it significantly more than the low $ room (p<0.001). However, these preferences were short-lived: 24h later subjects did not exhibit a behavioral or subjective preference for the high $ room. These findings show that individuals exhibit transient behavioral and subjective preferences for a virtual environment paired with monetary reward. Variations on this task may be useful to study mechanisms and brain substrates involved in conditioned reward and to examine the influence of drugs upon appetitive conditioning. PMID:28108321

Cav1.2, but not Cav1.3, L-type calcium channel subtype mediates nicotine-induced conditioned place preference in miceo.

PubMed

Liu, Yudan; Harding, Meghan; Dore, Jules; Chen, Xihua

2017-04-03

Nicotine use is one of the most common forms of drug addiction. Although L-type calcium channels (LTCCs) are involved in nicotine addiction, the contribution of the two primary LTCC subtypes (Ca v 1.2 and 1.3) is unknown. This study aims to determine the contribution of these two LTCC subtypes to nicotine-induced conditioned place preference (CPP) responses by using transgenic mouse models that do not express Ca v 1.3 (Ca v 1.3 -/- ) or contain a mutation in the dihydropyridine (DHP) site of the Ca v 1.2 (Ca v 1.2DHP -/- ). We found a hyperbolic dose dependent nicotine (0.1-1mg/kg; 0.5mg/kg optimum) effect on place preference in wild type (WT) mice, that could be prevented by the DHP LTCC blocker nifedipine pretreatment. Similarly, Ca v 1.3 -/- mice showed nicotine-induced place preference which was antagonized by nifedipine. In contrast, nifedipine pretreatment of Ca v 1.2DHP -/- mice had no effect on nicotine-induced CPP responses, suggesting an involvement of Ca v 1.2 subtype in the nicotine-induced CPP response. Nifedipine alone failed to produce either conditioned place aversion or CPP in WT mice. These results collectively indicate Ca v 1.2, but not Ca v 1.3 LTCC subtype regulates, at least in part, the reinforcing effects of nicotine use. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of D-cycloserine on extinction and reinstatement of morphine-induced conditioned place preference.

PubMed

Lu, Guan-Yi; Wu, Ning; Zhang, Zhao-Long; Ai, Jing; Li, Jin

2011-10-10

d-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine recognition site on the N-methyl-d-aspartate (NMDA) receptor complex, has been shown to facilitate the extinction and prevent the relapse of cocaine-induced conditioned place preference (CPP) when administered before or after each extinction trail. However, some studies have suggested that DCS does not influence or even enhance relapse of seeking behavior on cocaine self-administration (SA) in rats or cocaine-dependent individuals undergoing clinical exposure treatment. Furthermore, there are no reports on the effects of DCS and the extinction of morphine-conditioned behaviors in mice. The present study investigated the effects of DCS on extinction by exposing mice to drug-paired cues and the subsequent reinstatement of morphine-primed CPP. Our results showed that DCS at doses of 7.5, 15, and 30mg/kg did not induce conditioned appetitive or aversive effects and DCS combined with morphine conditioning failed to affect the acquisition of morphine-induced CPP. Moreover, pretreatment with DCS (7.5, 15, and 30mg/kg, i.p.) prior to extinction training had no significant effects on the extinction and subsequent morphine-primed reinstatement of morphine-induced CPP. These results suggested that DCS may not be a powerful adjunct for cue exposure therapy of opioid addiction. In view of differing outcomes in both preclinical and clinical studies, the potential of DCS in exposure treatment of drug-seeking behaviors should be carefully evaluated. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Inferring Roles in Defense from Metabolic Allocation of Rice Diterpenoids.

PubMed

Lu, Xuan; Zhang, Juan; Brown, Benjamin; Li, Riqing; Rodríguez-Romero, Julio; Berasategui, Aileen; Liu, Bo; Xu, Meimei; Luo, Dangping; Pan, Zhiqiang; Baerson, Scott; Gershenzon, Jonathan; Li, Zhaohu; Sesma, Ane; Yang, Bing; Peters, Reuben J

2018-04-24

Among their responses to microbial infection, plants deploy an arsenal of natural antibiotic products. These historically have been identified on the basis of their antibiotic activity in vitro, which leaves open the question of their relevance to defense in planta. The vast majority of such natural products from the important crop plant rice (Oryza sativa) are diterpenoids whose biosynthesis proceeds via either ent- or syn- copalyl diphosphate (CPP) intermediates, and which were isolated on the basis of their antibiotic activity against the fungal blast pathogen Magnaporthe oryzae. However, rice plants in which the gene for the syn-CPP synthase Os-CPS4 is knocked-out do not exhibit increased susceptibility to M. oryzae. Here we show that knocking-out or knocking-down Os-CPS4 actually decreases susceptibility to the bacterial leaf blight pathogen Xanthomonas oryzae. By contrast, genetic manipulation of the gene for the ent-CPP synthase Os-CPS2 alters susceptibility to both M. oryzae and X. oryzae. Despite the secretion of diterpenoids dependent on Os-CPS2 or Os-CPS4 from roots, neither knock-out exhibited significant changes in the composition of their rhizosphere bacterial communities. Nevertheless, rice plants allocate substantial metabolic resources towards syn- and ent-CPP derived diterpenoids upon infection/induction. Further investigation revealed that Os-CPS4 plays a role in fungal non-host disease resistance. Thus, examination of metabolic allocation provides important clues into physiological function. © 2018 American Society of Plant Biologists. All rights reserved.

The extinction of morphine-induced conditioned place preference by histone deacetylase inhibition.

PubMed

Wang, Ru; Zhang, Yan; Qing, Hua; Liu, Mei; Yang, Peng

2010-10-11

Recent evidence suggests that epigenetic mechanisms have an important role in the development of addictive behavior. However, little is known about the role of epigenetic mechanisms in the extinction of morphine-induced behavioral changes. In this study, we will examine the effect of histone deacetylase (HDAC) inhibitors on extinction of morphine-induced conditioned place preference (CPP). To facilitate extinction, rats will be administered an HDAC inhibitor (HDACi) following nonreinforced exposure to the conditioned context. To measure persistence, rats were subject to a reinstatement test using 3 mg/kg dose of morphine. To exclude the effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session, rats received injection of either NaBut or vehicle for 8 days. We found that HDAC inhibition during nonconfined extinction or confined extinction consolidation can facilitate extinction of morphine-induced CPP. We also showed that the extinction of drug seeking via HDAC inhibition modulates extinction learning such that reinstatement behavior is significantly attenuated. There is no effect of repeated NaBut injections themselves on morphine-CPP in the absence of extinction session. In conclusion, our results extend earlier reports on the ability of HDACi to modify the behavioral effects of drugs of abuse. Our increasing understanding of these epigenetic mechanisms will provide key answers to basic processes in drug addiction and hopefully provide insight into designing improved treatments for drug addiction. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

CONSTRUCTION PROGRESS PHOTO SHOWING EXCAVATION PIT FOR MAIN PROCESSING BUILDING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING EXCAVATION PIT FOR MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-50-885. Unknown Photographer, 10/30/1950 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING EMPLACEMENT STEEL BEAMS FUEL STORAGE BUILDING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING EMPLACEMENT STEEL BEAMS FUEL STORAGE BUILDING (CPP-603) LOOKING EAST. INL PHOTO NUMBER NRTS-51-1371. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

South Africa and the 21st Century Power Partnership: Paving the Way to a Clean, Reliable, and Resilient Power System

DOE Office of Scientific and Technical Information (OSTI.GOV)

2017-05-09

The 21st Century Power Partnership (21CPP) serves as an open, collaborative platform for sharing policy and regulatory best practices in the service of power system transformation. Established in 2012, the 21CPP South Africa Programme is a global initiative that connects South African stakeholders with an international community of expertise. This fact sheet details the 21CPP South Africa Programme.

Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation

PubMed Central

Pota, Vincenzo; Sansone, Pasquale; Aurilio, Caterina; Pace, Maria Caterina

2017-01-01

Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation. PMID:29359045

Pre-conditioned place preference treatment of chloral hydrate interrupts the rewarding effect of morphine.

PubMed

Sun, YongMei; Zong, Wei; Zhou, MuRu; Ma, YuanYe; Wang, JianHong

2015-08-01

The medical use of morphine as a pain killer is hindered by its side effects including dependence and further addiction. As the prototypical μ receptor agonist, morphine's rewarding effect can be measured by conditioned place preference (CPP) paradigms in animals. Chloral hydrate is a clinical sedative. Using a morphine CPP paradigm that mainly contains somatosensory cues, we found that pre-CPP treatment in rats using chloral hydrate for 6 consecutive days could disrupt the establishment of CPP in a U shape. Chloral hydrate had no effect on the body weight of rats. Our results indicate that prior treatment with chloral hydrate can interrupt the rewarding effect of morphine. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of fluoride dentifrice and casein phosphopeptide-amorphous calcium phosphate cream with and without fluoride in preventing enamel demineralization in a pH cyclic study.

PubMed

Sinfiteli, Priscila de Pinto; Coutinho, Thereza Christina Lopes; Oliveira, Patrícia Regina Almeida de; Vasques, Wesley Felisberto; Azevedo, Leandra Matos; Pereira, André Maues Brabo; Tostes, Monica Almeida

2017-01-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complexes are anticariogenic and capable of remineralizing the early stages of enamel lesions. The use of fluoride prevents dental decay and the association of CPP-ACP with fluoride can increase remineralization. To evaluate the effect of CPP-ACP and CPP-ACPF creams associated with a fluoride dentifrice to prevent enamel demineralization in a pH cyclic model. Previously selected by surface microhardness (SH) analysis, human enamel blocks (n = 56) were submitted to daily treatment with dentifrice in a pH-cycling model. The enamel blocks were divided into four groups; G1: Crest™ Cavity Protection - Procter & Gamble (1,100 ppmF of NaF); G2: Crest™ +MI Paste (MP) - Recaldent™ GC Corporation Tokyo, Japan); G3: Crest™ + MI Paste Plus (MPP) - Recaldent™ 900 ppm as NaF, GC Corporation Tokyo, Japan), and G4: control, saliva. Specimens were soaked alternatively in a demineralizing solution and in artificial saliva for 5 d. The fluoride dentifrice, with proportion of 1:3 (w/w), was applied three times for 60 s after the remineralization period. The undiluted MP and MPP creams were applied for 3 m/d. After cycling, SH was re-measured and cross section microhardness measurements were taken. The SH values observed for the groups G3 (257±70), G1 (205±70), and G2 (208±84) differed from the G4 group (98±110) (one-way ANOVA and Tukey's post hoc test). There were no differences between the groups G1xG2, G2xG3, and G1xG3 for demineralization inhibition. The percentage of volume mineral showed that, when applied with fluoride dentifrice, MPP was the most effective in preventing enamel demineralization at 50 µ from the outer enamel surface (Kruskal-Wallis and Mann Whitney p<0.05). Fluoride dentifrice associated with CPP-ACPF inhibited subsurface enamel demineralization.

Fluoride Varnishes against Dental Erosion Caused by Soft Drink Combined with Pediatric Liquid Medicine.

PubMed

Alexandria, Adílis Kalina; Valença, Ana Maria Gondim; Cabral, Lúcio Mendes; Maia, Lucianne Cople

2017-01-01

The present study evaluated the effect of NaF and CPP-ACP/NaF varnishes to reduce erosion produced by soft drink (SD) combined or not with pediatric liquid medicine. Enamel specimens were pre-treated with fluoride varnish, according to the following groups: NaF varnish (Duraphat®) or CPP-ACP/NaF varnish (MI varnishTM). Two types of erosive cycles were made: by soft drink erosion (SDE) or by pediatric liquid medicine plus soft drink erosion (PLM/SDE). Bovine enamel specimens were randomly assigned in six groups (n=10): G1=NaF + SDE; G2=CPP-ACP/NaF + SDE; G3=Distilled and deionized (DD) water + SDE; G4=NaF + PLM/SDE; G5=CPP-ACP/NaF + PLM/SDE and G6=DD water + PLM/SDE. Before treatments, the sample surface was divided in two areas (unexposed area-UA and exposed area-EA). The specimens were evaluated by 3D non-contact profilometry technique to determinate tooth structure loss (TSL) and surface roughness (Sa). Scanning electron microscopy (SEM) analysis was also performed. After SDE, G2 presented the lowest TSL values compared to G3 (p=0.008). G1 and G2 did not differ between them (p=0.203) and no groups differed among them despite Sa. Regarding TSL and Sa, G4 and G5 differed from G6 (p=0.0001), but not between them (p=1.00). Examining 3D and SEM images, the greatest differences between UA and EA were observed for G3 and G6. CPP-ACP/NaF varnish seems to be a promising treatment to reduce enamel loss from the erosion produced by a soft drink. Both varnishes also showed capacity to reduce TSL and Sa after erosion by soft drink combined to pediatric liquid medicine.

Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory.

PubMed

Alaghband, Yasaman; O'Dell, Steven J; Azarnia, Siavash; Khalaj, Anna J; Guzowski, John F; Marshall, John F

2014-12-01

The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal-associated (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine-context memory and suggest the involvement of an NMDA receptor-dependent Arc induction pathway in drug-cue memory interference. Copyright © 2014 Elsevier Inc. All rights reserved.

Morphine Modulates Adult Neurogenesis and Contextual Memory by Impeding the Maturation of Neural Progenitors.

PubMed

Zhang, Yue; Xu, Chi; Zheng, Hui; Loh, Horace H; Law, Ping-Yee

2016-01-01

The regulation of adult neurogenesis by opiates has been implicated in modulating different addiction cycles. At which neurogenesis stage opiates exert their action remains unresolved. We attempt to define the temporal window of morphine's inhibition effect on adult neurogenesis by using the POMC-EGFP mouse model, in which newborn granular cells (GCs) can be visualized between days 3-28 post-mitotic. The POMC-EGFP mice were trained under the 3-chambers conditioned place preference (CPP) paradigm with either saline or morphine. We observed after 4 days of CPP training with saline, the number of EGFP-labeled newborn GCs in sub-granular zone (SGZ) hippocampus significantly increased compared to mice injected with saline in their homecage. CPP training with morphine significantly decreased the number of EGFP-labeled GCs, whereas no significant difference in the number of EGFP-labeled GCs was observed with the homecage mice injected with the same dose of morphine. Using cell-type selective markers, we observed that morphine reduced the number of late stage progenitors and immature neurons such as Doublecortin (DCX) and βIII Tubulin (TuJ1) positive cells in the SGZ but did not reduce the number of early progenitors such as Nestin, SOX2, or neurogenic differentiation-1 (NeuroD1) positive cells. Analysis of co-localization between different cell markers shows that morphine reduced the number of adult-born GCs by interfering with differentiation of early progenitors, but not by inducing apoptosis. In addition, when NeuroD1 was over-expressed in DG by stereotaxic injection of lentivirus, it rescued the loss of immature neurons and prolonged the extinction of morphine-trained CPP. These results suggest that under the condition of CPP training paradigm, morphine affects the transition of neural progenitor/stem cells to immature neurons via a mechanism involving NeuroD1.

WHO systematic review of prevalence of chronic pelvic pain: a neglected reproductive health morbidity

PubMed Central

Latthe, Pallavi; Latthe, Manish; Say, Lale; Gülmezoglu, Metin; Khan, Khalid S

2006-01-01

Background Health care planning for chronic pelvic pain (CPP), an important cause of morbidity amongst women is hampered due to lack of clear collated summaries of its basic epidemiological data. We systematically reviewed worldwide literature on the prevalence of different types of CPP to assess the geographical distribution of data, and to explore sources of variation in its estimates. Methods We identified data available from Medline (1966 to 2004), Embase (1980 to 2004), PsycINFO (1887 to 2003), LILACS (1982 to 2004), Science Citation index, CINAHL (January 1980 to 2004) and hand searching of reference lists. Two reviewers extracted data independently, using a piloted form, on participants' characteristics, study quality and rates of CPP. We considered a study to be of high quality (valid) if had at least three of the following features: prospective design, validated measurement tool, adequate sampling method, sample size estimation and response rate >80%. We performed both univariate and multivariate meta-regression analysis to explore heterogeneity of results across studies. Results There were 178 studies (459975 participants) in 148 articles. Of these, 106 studies were (124259 participants) on dysmenorrhoea, 54 (35973 participants) on dyspareunia and 18 (301756 participants) on noncyclical pain. There were only 19/95 (20%) less developed and 1/45 (2.2%) least developed countries with relevant data in contrast to 22/43 (51.2%) developed countries. Meta-regression analysis showed that rates of pain varied according to study quality features. There were 40 (22.5%) high quality studies with representative samples. Amongst them, the rate of dysmenorrhoea was 16.8 to 81%, that of dyspareunia was 8 to 21.8%, and that for noncyclical pain was 2.1 to 24%. Conclusion There were few valid population based estimates of disease burden due to CPP from less developed countries. The variation in rates of CPP worldwide was due to variable study quality. Where valid data were available, a high disease burden of all types of pelvic pain was found. PMID:16824213

Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory

PubMed Central

Alaghband, Yasaman; O'Dell, Steven J.; Azarnia, Siavash; Khalaj, Anna J.; Guzowski, John F.; Marshall, John F.

2014-01-01

The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal associated gene (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine-context memory and suggest the involvement of an NMDA receptor-dependent Arc induction pathway in drug-cue memory interference. PMID:25225165

46 CFR 108.627 - Carbon dioxide alarm.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Carbon dioxide alarm. 108.627 Section 108.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Equipment Markings and Instructions § 108.627 Carbon dioxide alarm. Each carbon dioxide alarm must be identified by marking: “WHEN ALARM...

42 CFR 62.7 - What will an individual be awarded for participating in the scholarship program?

Code of Federal Regulations, 2011 CFR

2011-10-01

... participating in the scholarship program? 62.7 Section 62.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.7 What will an...

42 CFR 62.7 - What will an individual be awarded for participating in the scholarship program?

Code of Federal Regulations, 2013 CFR

2013-10-01

... participating in the scholarship program? 62.7 Section 62.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.7 What will an...

42 CFR 62.7 - What will an individual be awarded for participating in the scholarship program?

Code of Federal Regulations, 2010 CFR

2010-10-01

... participating in the scholarship program? 62.7 Section 62.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.7 What will an...

42 CFR 62.7 - What will an individual be awarded for participating in the scholarship program?

Code of Federal Regulations, 2012 CFR

2012-10-01

... participating in the scholarship program? 62.7 Section 62.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.7 What will an...

42 CFR 62.7 - What will an individual be awarded for participating in the scholarship program?

Code of Federal Regulations, 2014 CFR

2014-10-01

... participating in the scholarship program? 62.7 Section 62.7 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES FELLOWSHIPS, INTERNSHIPS, TRAINING NATIONAL HEALTH SERVICE CORPS SCHOLARSHIP AND LOAN REPAYMENT PROGRAMS National Health Service Corps Scholarship Program § 62.7 What will an...

7 CFR 58.627 - Milk and dairy products.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 3 2013-01-01 2013-01-01 false Milk and dairy products. 58.627 Section 58.627... Material § 58.627 Milk and dairy products. To produce ice cream and related products the raw milk and cream... commingled milk and cream meeting the bacteriological requirements of No. 1 shall be used. ...

7 CFR 58.627 - Milk and dairy products.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 3 2012-01-01 2012-01-01 false Milk and dairy products. 58.627 Section 58.627... Material § 58.627 Milk and dairy products. To produce ice cream and related products the raw milk and cream... commingled milk and cream meeting the bacteriological requirements of No. 1 shall be used. ...

7 CFR 58.627 - Milk and dairy products.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 3 2014-01-01 2014-01-01 false Milk and dairy products. 58.627 Section 58.627... Material § 58.627 Milk and dairy products. To produce ice cream and related products the raw milk and cream... commingled milk and cream meeting the bacteriological requirements of No. 1 shall be used. ...

27 CFR 6.27 - Proprietary interest.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Proprietary interest. 6.27 Section 6.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Interest in Retail License § 6.27 Proprietary interest. (a) Complete ownership....

7 CFR 58.627 - Milk and dairy products.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 3 2011-01-01 2011-01-01 false Milk and dairy products. 58.627 Section 58.627... Material § 58.627 Milk and dairy products. To produce ice cream and related products the raw milk and cream... commingled milk and cream meeting the bacteriological requirements of No. 1 shall be used. ...

7 CFR 58.627 - Milk and dairy products.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 3 2010-01-01 2010-01-01 false Milk and dairy products. 58.627 Section 58.627... Material § 58.627 Milk and dairy products. To produce ice cream and related products the raw milk and cream... commingled milk and cream meeting the bacteriological requirements of No. 1 shall be used. ...

27 CFR 6.27 - Proprietary interest.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Proprietary interest. 6.27 Section 6.27 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Unlawful Inducements Interest in Retail License § 6.27 Proprietary interest. (a) Complete ownership....

Facile and green synthesis of (La0.95Eu0.05)2O2S red phosphors with sulfate-ion pillared layered hydroxides as a new type of precursor: controlled hydrothermal processing, phase evolution and photoluminescence

PubMed Central

Wang, Xuejiao; Li, Ji-Guang; Zhu, Qi; Li, Xiaodong; Sun, Xudong; Sakka, Yoshio

2014-01-01

This study presents a facile and green route for the synthesis of (La0.95Eu0.05)2O2S red phosphors of controllable morphologies, with the sulfate-type layered hydroxides of Ln2(OH)4SO4·2H2O (Ln = La and Eu) as a new type of precursor. The technique takes advantage of the fact that the precursor has had the exact Ln:S molar ratio of the targeted phosphor, thus saving the hazardous sulfurization reagents indispensable to traditional synthesis. Controlled hydrothermal processing at 120 °C yielded phase-pure Ln2(OH)4SO4·2H2O crystallites in the form of either nanoplates or microprisms, which can both be converted into Ln2O2S phosphor via a Ln2O2SO4 intermediate upon annealing in flowing H2 at a minimum temperature of ∼ 700 °C. The nanoplates collapse into relatively rounded Ln2O2S particles while the microprisms retain well their initial morphologies at 1 200 °C, thus yielding two types of red phosphors. Photoluminescence excitation (PLE) studies found two distinct charge transfer (CT) excitation bands of O2− → Eu3+ at ∼ 270 nm and S2− → Eu3+ at ∼ 340 nm for the Ln2O2S phosphors, with the latter being stronger and both significantly stronger than the intrinsic intra-f transitions of Eu3+. The two types of phosphors share high similarities in the positions of PLE/PL (photoluminescence) bands and both show the strongest red emission at 627 nm (5D0 → 7F2 transition of Eu3+) under S2− → Eu3+ CT excitation at 340 nm. The PLE/PL intensities show clear dependence on particle morphology and calcination temperature, which were investigated in detail. Fluorescence decay analysis reveals that the 627 nm red emission has a lifetime of ∼ 0.5 ms for both types of the phosphors. PMID:27877631

MicroRNA-627 Mediates the Epigenetic Mechanisms of Vitamin D to Suppress Proliferation of Human Colorectal Cancer Cells and Growth of Xenograft Tumors in Mice

PubMed Central

Padi, Sathish K.R.; Zhang, Qunshu; Rustum, Youcef M; Morrison, Carl; Guo, Bin

2013-01-01

Background & Aims Vitamin D protects against colorectal cancer by unclear mechanisms. We investigated the effects of calcitriol (1α,25-dihydroxyvitamin D3, the active form of vitamin D) on levels of different microRNAs (miRs) in colorectal cancer (CRC) cells from humans and xenograft tumors in mice. Methods Expression of microRNAs in CRC cell lines was examined using the Ambion mirVana miRNA Bioarray. The effects of calcitriol on expression of miR-627 and cell proliferation were determined by real-time PCR and WST-1 assay, respectively; growth of colorectal xenograft tumors was examined in nude mice. Real-time PCR was used to analyze levels of miR-627 in human colon adenocarcinoma samples and non-tumor colon mucosa tissues (controls). Results In HT-29 cells, miR-627 was the only microRNA significantly upregulated by calcitriol. Jumonji domain containing 1A (JMJD1A), which encodes a histone demethylase, was found to be a target of miR-627. By downregulating JMJD1A, miR-627 increased methylation of histone H3K9 and suppressed expression of proliferative factors such as GDF15. Calcitriol induced expression of miR-627, which downregulated JMJD1A and suppressed growth of xenograft tumors from HCT-116 cells in nude mice. Overexpression of miR-627 prevented proliferation of CRC cell lines in culture and growth of xenograft tumors in mice. Conversely, blocking the activity of miR-627 inhibited the tumor suppressive effects of calcitriol in cultured CRC cells and in mice. Levels of miR-627 were decreased in human colon adenocarcinoma samples, compared with controls. Conclusions miR-627 mediates tumor-suppressive epigenetic activities of vitamin D on CRC cells and xenograft tumors in mice. The mRNA that encodes the histone demethylase JMJD1A is a direct target of miR-627. Reagents designed to target JMJD1A or its mRNA, or increase the function of miR-627, might have the same antitumor activities of vitamin D without the hypercalcemic side effects. PMID:23619147

Effect of Casein Phosphopeptide-amorphous Calcium Phosphate Treatment on Microtensile Bond Strength to Carious Affected Dentin Using Two Adhesive Strategies

PubMed Central

Bahari, Mahmoud; Savadi Oskoee, Siavash; Kimyai, Soodabeh; Pouralibaba, Firoz; Farhadi, Farrokh; Norouzi, Marouf

2014-01-01

Background and aims. The aim was to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on microtensile bond strength (μTBS) to carious affected dentin (CAD) using etch-and-rinse and self-etch adhesive systems. Materials and methods. The occlusal surface of 32 human molars with moderate occlusal caries was removed. Infected dentin was removed until reaching CAD and the teeth were randomly divided into two groups based on the Single Bond (SB) and Clearfil SE Bond (CSE) adhesive systems. Before composite resin bonding, each group was subdivided into three subgroups of ND, CAD and CPP-ACP-treated CAD (CAD-CPP) based on the dentin substrate. After dissecting samples to l-mm-thick cross-sections (each subgroup: n = 13), μTBS was measured at a strain rate of 0.5 mm/min. Data was analyzed using two-way ANOVA, independent samples t-test and post-hoc Tukey tests (α=0.05). Results. Bond strength of both adhesive systems to ND was significantly higher than that to CAD (P <0.001) and CAD/CPP (P < 0.001). There were no significant differences between the μTBS of SB to CAD and CAD-CPP (P > 0.05).μTBS of CSE to CAD-CPP was higher than that to CAD; however, the difference was not significant (P > 0.05). Significant differences were found between SB and CSE systems only with CAD substrate (P < 0.001). Conclusion. Regardless of the adhesive system used, surface treatment of CAD with CPP-ACP did not have a significant effect on bond strength. However, bond strength to CAD was higher with SB rather than with CSE. PMID:25346832

Evaluation of the Contralateral Inguinal Ring in Clinically Unilateral Inguinal Hernia: A Systematic Review and Meta-analysis

PubMed Central

Kokorowski, Paul J; Wang, Hsin-Hsiao Scott; Routh, Jonathan C; Hubert, Katherine C; Nelson, Caleb P

2013-01-01

Purpose The management of the contralateral inguinal canal in children with clinical unilateral inguinal hernia is controversial. Our objective was to systematically review the literature regarding management of the contralateral inguinal canal. Methods We searched MEDLINE, EMBASE, and Cochrane databases (1940–2011) using ‘hernia’ and ‘inguinal’ and either ‘pediatric,’ ‘infant,’ or ‘child,’ to identify studies of pediatric (age≤21 yrs) patients with inguinal hernia. Among clinical unilateral hernia patients, we assessed the number of cases with contralateral patent processus (CPP) and incidence of subsequent clinical metachronous contralateral hernia (MCH). We evaluated three strategies for contralateral management: expectant management, laparoscopic evaluation or pre-operative ultrasound. Pooled estimates of MCH or CPP were generated with random effects by study when heterogeneity was found (I2>50%, or Cochrane’s Q p≥0.10). Results We identified 2,477 non-duplicated studies, 129 of which met our inclusion criteria and had sufficient information for quantitative analysis. The pooled incidence of MCH after open unilateral repair was 7.3% (95% CI 6.5%–8.1%). Laparoscopic examination identified CPP in 30% (95% CI 26%–34%). Lower age was associated with higher incidence of CPP (p<0.01). The incidence of MCH after a negative laparoscopic evaluation was 0.9% (95% CI 0.5%–1.3%). Significant heterogeneity was found in studies and pooled estimates should be interpreted with caution. Conclusions The literature suggests that laparoscopically identified CPP is a poor indicator of future contralateral hernia. Almost a third of patients will have a CPP, while less than one in 10 will develop MCH when managed expectantly. Performing contralateral hernia repair in patients with CPP results in overtreatment in roughly 2 out of 3 patients. PMID:23963735

On the behavioural specificity of hypophagia induced in male rats by mCPP, naltrexone, and their combination.

PubMed

Wright, F L; Rodgers, R J

2014-02-01

Serotonergic (5-hydroxytryptamine, 5-HT) and opioidergic mechanisms are intimately involved in appetite regulation. In view of recent evidence of positive anorectic interactions between opioid and various non-opioid substrates, our aim was to assess the behavioural specificity of anorectic responses to the opioid receptor antagonist naltrexone, the 5-HT2C/1B receptor agonist mCPP and their combination. Behavioural profiling techniques, including the behavioural satiety sequence (BSS), were used to examine acute drug effects in non-deprived male rats tested with palatable mash. Experiment 1 characterised the dose-response profile of mCPP (0.1-3.0 mg/kg), while experiment 2 assessed the effects of combined treatment with a sub-anorectic dose of mCPP (0.1 mg/kg) and one of two low doses of naltrexone (0.1 and 1.0 mg/kg). Experiment 1 confirmed the dose-dependent anorectic efficacy of mCPP, with robust effects on intake and feeding-related measures observed at 3.0 mg/kg. However, that dose was also associated with other behavioural alterations including increased grooming, reductions in locomotion and sniffing, and disruption of the BSS. In experiment 2, naltrexone dose-dependently reduced food intake and time spent feeding, effects accompanied by a behaviourally selective acceleration in the BSS. However, the addition of 0.1 mg/kg mCPP did not significantly alter the behavioural changes observed in response to either dose of naltrexone given alone. In contrast to recently reported positive anorectic interactions involving low-dose combinations of opioid receptor antagonists or mCPP with cannabinoid CB1 receptor antagonists, present results would not appear to provide any support for potentially clinically relevant anorectic interactions between opioid and 5-HT2C/1B receptor mechanisms.

Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats.

PubMed

Voigt, Robin M; Riddle, Jennifer L; Napier, T Celeste

2014-05-01

Fendiline is a GABAB receptor-positive allosteric modulator and L-type Ca²⁺ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans Following meth conditioning (1 mg/kg), fendiline (5 mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p < 0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p < 0.05) or those that received two injections that corresponded to the last 2 days of the 10-day treatment (p < 0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans.

In vitro evaluation of casein phosphopeptide-amorphous calcium phosphate effect on the shear bond strength of dental adhesives to enamel.

PubMed

Shadman, Niloofar; Ebrahimi, Shahram Farzin; Shoul, Maryam Azizi; Sattari, Hasti

2015-01-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is applied for remineralization of early caries lesions or tooth sensitivity conditions and may affect subsequent resin bonding. This in vitro study investigated the effect of CPP-ACP on the shear bond strength of dental adhesives to enamel. Sixty extracted human molar teeth were selected and randomly divided into three groups and six subgroups. Buccal or lingual surfaces of teeth were prepared to create a flat enamel surface. Adhesives used were Tetric N-Bond, AdheSE and AdheSE One F. In three subgroups, before applying adhesives, enamel surfaces were treated with Tooth Mousse CPP-ACP for one hour, rinsed and stored in 37°C temperature with 100% humidity. This procedure was repeated for 5 days and then adhesives were applied and Tetric N-Ceram composite was adhered to the enamel. This procedure was also fulfilled for the other three subgroups without CPP-ACP treatment. After 24 hour water storage, samples were tested for shear bond strength test in a universal testing machine. Failure modes were determined by stereomicroscope. Data were analyzed by t-test and one-way analysis of variance with P < 0.05 as the level of significance. In comparison between applied and non-applied CPP-ACP subgroups, there was no significant decrease in the shear bond strength to enamel only in Tetric N-Bond (P > 0.05). In non-applied CPP-ACP subgroups, there were statistically significant differences among all subgroups. Tetric N-Bond had the highest and AdheSE One F had the lowest shear bond strength. CPP-ACP application reduces the shear bond strength of AdheSE and AdheSE One F to enamel but not Tetric N-Bond.

In vitro evaluation of casein phosphopeptide-amorphous calcium phosphate effect on the shear bond strength of dental adhesives to enamel

PubMed Central

Shadman, Niloofar; Ebrahimi, Shahram Farzin; Shoul, Maryam Azizi; Sattari, Hasti

2015-01-01

Background: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is applied for remineralization of early caries lesions or tooth sensitivity conditions and may affect subsequent resin bonding. This in vitro study investigated the effect of CPP-ACP on the shear bond strength of dental adhesives to enamel. Materials and Methods: Sixty extracted human molar teeth were selected and randomly divided into three groups and six subgroups. Buccal or lingual surfaces of teeth were prepared to create a flat enamel surface. Adhesives used were Tetric N-Bond, AdheSE and AdheSE One F. In three subgroups, before applying adhesives, enamel surfaces were treated with Tooth Mousse CPP-ACP for one hour, rinsed and stored in 37°C temperature with 100% humidity. This procedure was repeated for 5 days and then adhesives were applied and Tetric N-Ceram composite was adhered to the enamel. This procedure was also fulfilled for the other three subgroups without CPP-ACP treatment. After 24 hour water storage, samples were tested for shear bond strength test in a universal testing machine. Failure modes were determined by stereomicroscope. Data were analyzed by t-test and one-way analysis of variance with P < 0.05 as the level of significance. Results: In comparison between applied and non-applied CPP-ACP subgroups, there was no significant decrease in the shear bond strength to enamel only in Tetric N-Bond (P > 0.05). In non-applied CPP-ACP subgroups, there were statistically significant differences among all subgroups. Tetric N-Bond had the highest and AdheSE One F had the lowest shear bond strength. Conclusion: CPP-ACP application reduces the shear bond strength of AdheSE and AdheSE One F to enamel but not Tetric N-Bond. PMID:25878683

Social housing conditions influence morphine dependence and the extinction of morphine place preference in adolescent mice.

PubMed

Bates, M L Shawn; Emery, Michael A; Wellman, Paul J; Eitan, Shoshana

2014-09-01

Adolescent opioid abuse is on the rise, and current treatments are not effective in reducing rates of relapse. Our previous studies demonstrated that social housing conditions alter the acquisition rate of morphine conditioned place preference (CPP) in adolescent mice. Specifically, the acquisition rate of morphine CPP is slower in morphine-treated animals housed with drug-naïve animals. Thus, here we tested the effect of social housing conditions on the development of morphine dependence and the extinction rate of an acquired morphine CPP. Adolescent male mice were group-housed in one of two housing conditions. They were injected for 6 days (PND 28-33) with 20 mg/kg morphine. Morphine only mice are animals where all four mice in the cage received morphine. Morphine cage-mate mice are morphine-injected animals housed with drug-naïve animals. Mice were individually tested for spontaneous withdrawal signs by quantifying jumping behavior 4, 8, 24, and 48 h after the final morphine injection. Then, mice were conditioned to acquire morphine CPP and were tested for the rate of extinction. Morphine cage-mates express less jumping behavior during morphine withdrawal as compared to morphine only mice. As expected, morphine cage-mate animals acquired morphine CPP more slowly than the morphine only animals. Additionally, morphine cage-mates extinguished morphine CPP more readily than morphine only mice. Social housing conditions modulate morphine dependence and the extinction rate of morphine CPP. Extinction testing is relevant to human addiction because rehabilitations like extinction therapy may be used to aid human addicts in maintaining abstinence from drug use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Stress and opioids: role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference.

PubMed

Bali, Anjana; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2015-04-01

Research studies have defined the important role of endogenous opioids in modulating stress-associated behavior. The release of β-endorphins in the amygdala in response to stress helps to cope with a stressor by inhibiting the over-activation of HPA axis. Administration of mu opioid agonists reduces the risk of developing post-traumatic stress disorder (PTSD) following a traumatic event by inhibiting fear-related memory consolidation. Similarly, the release of endogenous enkephalin and nociceptin in the basolateral amygdala and the nucleus accumbens tends to produce the anti-stress effects. An increase in dynorphin levels during prolonged exposure to stress may produce learned helplessness, dysphoria and depression. Stress also influences morphine-induced conditioned place preference (CPP) depending upon the intensity and duration of the stressor. Acute stress inhibits morphine CPP, while chronic stress potentiates CPP. The development of dysphoria due to increased dynorphin levels may contribute to chronic stress-induced potentiation of morphine CPP. The activation of ERK/cyclic AMP responsive element-binding (CREB) signaling in the mesocorticolimbic area, glucocorticoid receptors in the basolateral amygdala, and norepinephrine and galanin system in the nucleus accumbens may decrease the acute stress-induced inhibition of morphine CPP. The increase in dopamine levels in the nucleus accumbens and augmentation of GABAergic transmission in the median prefrontal cortex may contribute in potentiating morphine CPP. Stress exposure reinstates the extinct morphine CPP by activating the orexin receptors in the nucleus accumbens, decreasing the oxytocin levels in the lateral septum and amygdala, and altering the GABAergic transmission (activation of GABAA and inactivation of GABAB receptors). The present review describes these varied interactions between opioids and stress along with the possible mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats

PubMed Central

Voigt, Robin M.; Riddle, Jennifer L.; Napier, T. Celeste

2014-01-01

Rationale Fendiline is a GABAB receptor positive allosteric modulator and L-type Ca2+ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals. Objective The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans. Methods Following meth conditioning (1mg/kg), fendiline (5mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. Results Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p<0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p<0.05) or those that received two injections that corresponded to the last two days of the 10 day treatment (p<0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. Conclusion Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans. PMID:24264565

Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory.

PubMed

Kramar, Cecilia P; Barbano, M Flavia; Medina, Jorge H

2014-12-01

The role of the hippocampus in memory supporting associative learning between contexts and unconditioned stimuli is well documented. Hippocampal dopamine neurotransmission modulates synaptic plasticity and memory processing of fear-motivated and spatial learning tasks. Much less is known about the involvement of the hippocampus and its D1/D5 dopamine receptors in the acquisition, consolidation and expression of memories for drug-associated experiences, more particularly, in the processing of single pairing cocaine conditioned place preference (CPP) training. To determine the temporal dynamics of cocaine CPP memory formation, we trained rats in a one-pairing CPP paradigm and tested them at different time intervals after conditioning. The cocaine-associated memory lasted 24 h but not 72 h. Then, we bilaterally infused the dorsal hippocampus with the GABA A receptor agonist muscimol or the D1/D5 dopamine receptor antagonist SCH 23390 at different stages to evaluate the mechanisms involved in the acquisition, consolidation or expression of cocaine CPP memory. Blockade of D1/D5 dopamine receptors at the moment of training impaired the acquisition of cocaine CPP memories, without having any effect when administered immediately or 12 h after training. The expression of cocaine CPP memory was also affected by the administration of SCH 23390 at the moment of the test. Conversely, muscimol impaired the consolidation of cocaine CPP memory only when administered 12 h post conditioning. These findings suggests that dopaminergic inputs to the dorsal hippocampus are required for the acquisition and expression of one trial cocaine-associated memory while neural activity of this structure is required for the late consolidation of these types of memories. Copyright © 2014 Elsevier Inc. All rights reserved.

Perineal Massage Improves the Dyspareunia Caused by Tenderness of the Pelvic Floor Muscles.

PubMed

Silva, Ana Paula Moreira da; Montenegro, Mary Lourdes; Gurian, Maria Beatriz Ferreira; Mitidieri, Andreia Moreira de Souza; Lara, Lucia Alves da Silva; Poli-Neto, Omero Benedicto; Rosa E Silva, Julio Cesar

2017-01-01

Aim  To evaluate the long-term effectiveness of perineal Thiele massage in the treatment of women with dyspareunia caused by tenderness of the pelvic floor muscles. Methods  A total of 18 women with diagnoses of dyspareunia caused by tenderness of the pelvic floor muscles were included in the study. The women were divided in two groups: the dyspareunia (D) group - 8 women with dyspareunia caused by tenderness of the pelvic floor muscles; and the chronic pelvic pain group (CPP) group - 10 women with dyspareunia caused by tenderness of the pelvic floor muscles associated with CPP. Each patient filled out the Visual Analogue Scale (VAS), the McGill Pain Index, the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). After an evaluation, the women underwent transvaginal massage using the Thiele technique over a period of 5 minutes, once a week for 4 weeks. Results  All women had significant improvements in their dyspareunia according the VAS and the McGill Pain Index ( p  < 0,001), but the HADS scores did not show significant differences. Regarding sexual function, the D group showed improvements on all aspects of sexual function, while the CPP group showed differences only in the pain domain. Conclusion  Thiele massage is effective in the treatment of dyspareunia caused by tenderness of the pelvic floor muscles with a long-term pain relief. Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.

Dynamic Cerebrovascular and Intracranial Pressure Reactivity Assessment of Impaired Cerebrovascular Autoregulation in Intracranial Hypertension.

PubMed

Bragin, Denis E; Statom, Gloria; Nemoto, Edwin M

2016-01-01

We previously suggested that the discrepancy between a critical cerebral perfusion pressure (CPP) of 30 mmHg, obtained by increasing intracranial pressure (ICP), and 60 mmHg, obtained by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP [1], and that the determination of the critical CPP by the static cerebral blood flow (CBF) autoregulation curve is not valid with intracranial hypertension. Here, we demonstrated that induced dynamic ICP reactivity (iPRx), and cerebrovascular reactivity (CVRx) tests accurately identify the critical CPP in the hypertensive rat brain, which differs from that obtained by the static autoregulation curve. Step changes in CPP from 70 to 50 and 30 mmHg were made by increasing ICP using an artificial cerebrospinal fluid reservoir connected to the cisterna magna. At each CPP, a transient 10-mmHg increase in arterial pressure was induced by bolus intravenous dopamine. iPRx and iCVRx were calculated as ΔICP/Δ mean arterial pressure (MAP) and as ΔCBF/ΔMAP, respectively. The critical CPP at high ICP, obtained by iPRx and iCVRx, is 50 mmHg, where compromised capillary flow, transition of blood flow to nonnutritive microvascular shunts, tissue hypoxia, and brain-blood barrier leakage begin to occur, which is higher than the 30 mmHg determined by static autoregulation.

Lactosylated casein phosphopeptides as specific indicators of heated milks.

PubMed

Pinto, Gabriella; Caira, Simonetta; Cuollo, Marina; Fierro, Olga; Nicolai, Maria Adalgisa; Chianese, Lina; Addeo, Francesco

2012-02-01

Casein phosphopeptides (CPP) were identified in small amounts in milks heated at various intensities by using matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry. CPP selectively concentrated on hydroxyapatite (HA) were regenerated using phosphoric acid mixed in the matrix. Unphosphorylated peptides not retained by HA were removed by buffer washing. This procedure enhanced the MALDI signals of CPP that are ordinarily suppressed by the co-occurrence of unphosphorylated peptides. CPP, belonging to the β-casein (CN) family, i.e., (f1-29) 4P, (f1-28) 4P, and (f1-27) 4P, and the α(s2)-CN family, i.e., (f1-21) 4P and (f1-24) 4P, were observed in liquid and powder milk. The lactosylated counterparts were specific to intensely heated milks, but absent in raw and thermized/pasteurized milk. Most CPP with C-terminal lysines probably arose from the activity of plasmin; an enzyme most active in casein hydrolysis. A CPP analogue was used as the internal standard. The raw milk signature peptide β-CN (f1-28) 4P constituted ~4.3% of the total β-CN. Small amounts of lactosylated peptides, which varied with heat treatment intensity, were detected in the milk samples. The limit of detection of ultra-high-temperature milk adjunction in raw or pasteurized milk was ~10%.

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

PubMed

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

Blocking α4β2 and α7 nicotinic acetylcholine receptors inhibits the reinstatement of morphine-induced CPP by drug priming in mice.

PubMed

Feng, Bin; Xing, Jiang-hao; Jia, Dong; Liu, Shui-bing; Guo, Hong-ju; Li, Xiao-qiang; He, Xiao-sheng; Zhao, Ming-gao

2011-06-20

Investigating the interaction between nicotinic and opioid receptors is of great interest for both basic mechanistic and clinical reasons. Morphine and nicotine, two common drugs of abuse, share several behavioral and rewarding properties. However, little is known about the subtypes of nicotinic acetylcholine receptors (nAChR) in the reinstatement of morphine-induced conditioned place preference (CPP). In this study, we found that a non-specific nAChR agonist, nicotine (0.5mg/kg), had no effects on the reinstatement of morphine-induced CPP. However, we found that pretreatment with specific α(4)β(2) and α(7) nAChR subtype antagonists, dihydroxy-β-erithroidine (DHβE, 5mg/kg) and methyllycaconitine (MLA, 4 mg/kg), 20 min prior to administration of morphine, inhibited the reinstatement of morphine-induced CPP by drug priming in mice. Furthermore, depression of the reinstatement of morphine-induced CPP by a single DHβE or MLA treatment lasted at least three days later when the reinstatement was induced by morphine priming. The data suggest that specific nAChR subtypes, i.e., α(4)β(2) and α(7), may contribute to the reinstatement of morphine-induced CPP by drug priming in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Attachment Security Mediates the Longitudinal Association Between Child-Parent Psychotherapy and Peer Relations for Toddlers of Depressed Mothers

PubMed Central

Guild, Danielle J.; Toth, Sheree L.; Handley, Elizabeth D.; Rogosch, Fred A.; Cicchetti, Dante

2017-01-01

Numerous investigations have demonstrated that Child-Parent Psychotherapy (CPP) promotes secure attachment between mothers and offspring. However, the role of post-intervention attachment security as it relates to long-term child outcomes has never been evaluated. The present study therefore examined post-intervention attachment status as a mediator of the association between CPP for depressed mothers and their offspring and subsequent peer relations among offspring. Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or to a control group (DC; n = 55). A prior investigation with this sample indicated that offpring who received CPP attained significantly higher rates of secure attachment post-intervention, wheras insecure attachment continued to predominate for offspring in the DC group. The present study examined follow-up data of teachers’ reports on participants’ competence with classroom peers when they were approximately 9 years old. Findings indicated that children who received CPP were more likely to evidence secure attachments at post-intervention, which in turn was associated with more positive peer relationships at age 9. PMID:28401848

Attachment security mediates the longitudinal association between child-parent psychotherapy and peer relations for toddlers of depressed mothers.

PubMed

Guild, Danielle J; Toth, Sheree L; Handley, Elizabeth D; Rogosch, Fred A; Cicchetti, Dante

2017-05-01

Numerous investigations have demonstrated that child-parent psychotherapy (CPP) promotes secure attachment between mothers and offspring. However, the role of postintervention attachment security as it relates to long-term child outcomes has never been evaluated. The present study therefore examined postintervention attachment status as a mediator of the association between CPP for depressed mothers and their offspring and subsequent peer relations among offspring. Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or to a control group (n = 55). A prior investigation with this sample indicated that offspring who received CPP attained significantly higher rates of secure attachment postintervention, whereas insecure attachment continued to predominate for offspring in the control group. The present study examined follow-up data of teachers' reports on participants' competence with classroom peers when they were approximately 9 years old. Findings indicated that children who received CPP were more likely to evidence secure attachments at postintervention, which in turn was associated with more positive peer relationships at age 9.

CPP-TRS(C): On using visual cognitive symbols to enhance communication effectiveness

NASA Technical Reports Server (NTRS)

Tonfoni, Graziella

1994-01-01

Communicative Positioning Program/Text Representation Systems (CPP-TRS) is a visual language based on a system of 12 canvasses, 10 signals and 14 symbols. CPP-TRS is based on the fact that every communication action is the result of a set of cognitive processes and the whole system is based on the concept that you can enhance communication by visually perceiving text. With a simple syntax, CPP-TRS is capable of representing meaning and intention as well as communication functions visually. Those are precisely invisible aspects of natural language that are most relevant to getting the global meaning of a text. CPP-TRS reinforces natural language in human machine interaction systems. It complements natural language by adding certain important elements that are not represented by natural language by itself. These include communication intention and function of the text expressed by the sender, as well as the role the reader is supposed to play. The communication intention and function of a text and the reader's role are invisible in natural language because neither specific words nor punctuation conveys them sufficiently and unambiguously; they are therefore non-transparent.

Galnon Facilitates Extinction of Morphine-Conditioned Place Preference but Also Potentiates the Consolidation Process

PubMed Central

Zhao, Xiaojie; Yun, Keming; Seese, Ronald R.; Wang, Zhenyuan

2013-01-01

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process. PMID:24146862

Galnon facilitates extinction of morphine-conditioned place preference but also potentiates the consolidation process.

PubMed

Zhao, Xiaojie; Yun, Keming; Seese, Ronald R; Wang, Zhenyuan

2013-01-01

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process.

Synthesis of β-Calcium Pyrophosphate by sol-gel method

NASA Astrophysics Data System (ADS)

Windarti, T.; Taslimah; Haris, A.; Astuti, Y.; Darmawan, A.

2017-02-01

Beta calcium pyrophosphate [β-CPP, β-Ca2P2O7] can be used as bone graft extender in posterolateral lumbar fusion. In this research, β-CPP was synthesized by sol-gel method using phosphorus pentaoxide [P2O5] and calcium nitrate tetrahydrate [Ca(NO3)2.4H2O] as phosphorus and calcium precursors. The reaction was carried out in ethanol medium with Ca/P ratio of 1.67. After 21 hours of reaction and 20 hours of drying at 80°C, white powder of amorphous calcium phosphate (ACP) was produced. Transformation of ACP to β-CPP was undertaken by firring at 400-800°C for 8 hours. Transformations of amorphous to microcrystalline, semicrystalline and crystalline structures occur at 400, 600 and 800°C, respectively. The β-CPP with the crystallite size of 61.71 nm, Ca/P ratio of 0.89 and Ca/O ratio of 0.21 was achieved by firing at 800°C. Morphology changes due to firing in which irregular shape of β-CPP at 400° changed to regular cuboid at 600 °C and above.

Facilitation of Memory for Extinction of Drug-Induced Conditioned Reward: Role of Amygdala and Acetylcholine

PubMed Central

Schroeder, Jason P.; Packard, Mark G.

2004-01-01

These experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP. Rats were subsequently given limited extinction training, followed by immediate posttrial peripheral or intrabasolateral amygdala injections of oxotremorine. A second CPP test was then administered, and the amount of time spent in the previously amphetamine-paired and saline-paired apparatus compartments was recorded. Peripheral (0.07 or 0.01 mg/kg) or intra-amygdala (10 ηg/0.5μL) postextinction trial injections of oxotremorine facilitated CPP extinction. Oxotremorine injections that were delayed 2 h posttrial training did not enhance CPP extinction, indicating a time-dependent effect of the drug on memory consolidation processes. The findings indicate that memory consolidation for extinction of approach behavior to environmental stimuli previously paired with drug reward can be facilitated by posttrial peripheral or intrabasolateral amygdala administration of a cholinergic agonist. PMID:15466320

20 CFR 30.627 - Under what circumstances will OWCP waive the statutory requirement to coordinate these benefits?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Under what circumstances will OWCP waive the statutory requirement to coordinate these benefits? 30.627 Section 30.627 Employees' Benefits OFFICE OF...' Compensation Benefits § 30.627 Under what circumstances will OWCP waive the statutory requirement to coordinate...

20 CFR 627.240 - On-the-job training.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 20 Employees' Benefits 3 2012-04-01 2012-04-01 false On-the-job training. 627.240 Section 627.240... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.240 On-the-job training. (a) General—(1) On-the-job training (OJT) means training by an employer in the private or public sector given...

20 CFR 627.240 - On-the-job training.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false On-the-job training. 627.240 Section 627.240... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.240 On-the-job training. (a) General—(1) On-the-job training (OJT) means training by an employer in the private or public sector given...

46 CFR 108.627 - Carbon dioxide and clean agent alarms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Carbon dioxide and clean agent alarms. 108.627 Section 108.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Equipment Markings and Instructions § 108.627 Carbon dioxide and clean agent alarms. Each carbon dioxide alarm must be...

46 CFR 108.627 - Carbon dioxide and clean agent alarms.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Carbon dioxide and clean agent alarms. 108.627 Section 108.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Equipment Markings and Instructions § 108.627 Carbon dioxide and clean agent alarms. Each carbon dioxide alarm must be...

46 CFR 108.627 - Carbon dioxide and clean agent alarms.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Carbon dioxide and clean agent alarms. 108.627 Section 108.627 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Equipment Markings and Instructions § 108.627 Carbon dioxide and clean agent alarms. Each carbon dioxide alarm must be...

20 CFR 627.503 - Recipient-level review.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Recipient-level review. 627.503 Section 627... GOVERNING PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Grievances Procedures at the State and Local Level § 627.503 Recipient-level review. (a) If a complainant does not receive a decision at the SDA or the SSG...

20 CFR 627.480 - Audits.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Audits. 627.480 Section 627.480 Employees... UNDER TITLES I, II, AND III OF THE ACT Administrative Standards § 627.480 Audits. (a) Non-Federal Audits... Single Audit Act of 1984 (31 U.S.C. 7501-7) and 29 CFR part 96, the Department of Labor regulations which...

20 CFR 627.240 - On-the-job training.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false On-the-job training. 627.240 Section 627.240... PROGRAMS UNDER TITLES I, II, AND III OF THE ACT Program Requirements § 627.240 On-the-job training. (a) General—(1) On-the-job training (OJT) means training by an employer in the private or public sector given...

Noncovalent interaction-assisted drug delivery system with highly efficient uptake and release of paclitaxel for anticancer therapy.

PubMed

Wei, Yuping; Ma, Liang; Zhang, Liang; Xu, Xia

2017-01-01

An effective drug delivery system requires efficient drug uptake and release inside cancer cells. Here, we report a novel drug delivery system, in which paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through noncovalent interaction designed based on molecular simulations. This CPP/PTX complex confers high efficiency in delivering PTX into cancer cells not by endocytosis but by an energy-independent pathway. Once inside cells, the noncovalent interaction between PTX and the CPP may allow fast release of PTX within cells due to the direct translocation of CPP/PTX. This drug delivery system exhibits strong capacity for inhibition of tumor growth and offers a new avenue for the development of advanced drug delivery systems for anticancer therapy.

Studies of proteoglycan involvement in CPP-mediated delivery.

PubMed

Wittrup, Anders; Zhang, Si-He; Belting, Mattias

2011-01-01

Cell-penetrating peptides (CPPs) are widely used to deliver macromolecular cargoes to intracellular sites of action. Many CPPs have been demonstrated to rely on cell surface heparan sulfate proteoglycans (HSPGs) for efficient cellular entry and delivery. In this chapter, we describe methods for the study of PG involvement in CPP uptake. We provide descriptions of how to determine whether uptake of a CPP of interest is dependent on PGs. We also provide detailed protocols for the purification of PGs by anion-exchange chromatography as well as the characterization of the HSPG core protein composition of a cell line of interest. Finally, we present methods for modulating the expression level of specific HSPG core proteins as a means to determine the core protein specificity in the uptake of a particular CPP.

Global Demographic Change and Its Implications for Military Power

DTIC Science & Technology

2011-01-01

cent (rather than 9 percent). 11 James W. Vaupel, James R. Carey , and Kaare Christensen, “Aging: It’s Never Too Late,” Science, Vol. 301, No. 5640...3, June 2004, pp. 627–642. 14 Expenses include facility services (hospitalization and nursing home stays), professional services, drugs, dental ...www.census.gov/ipc/www/idb/ Vaupel, James W., James R. Carey , and Kaare Christensen, “Aging: It’s Never Too Late,” Science, Vol. 301, No. 5640, September 19

Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora.

PubMed

Patel, Ravi R; Sundin, George W; Yang, Ching-Hong; Wang, Jie; Huntley, Regan B; Yuan, Xiaochen; Zeng, Quan

2017-01-01

Erwinia amylovora is a Gram-negative bacterial plant pathogen in the family Enterobacteriaceae and is the causal agent of fire blight, a devastating disease of apple and pear. Fire blight is traditionally managed by the application of the antibiotic streptomycin during bloom, but this strategy has been challenged by the development and spread of streptomycin resistance. Thus, there is an urgent need for effective, specific, and sustainable control alternatives for fire blight. Antisense antimicrobials are oligomers of nucleic acid homologs with antisense sequence of essential genes in bacteria. The binding of these molecules to the mRNA of essential genes can result in translational repression and antimicrobial effect. Here, we explored the possibility of developing antisense antimicrobials against E. amylovora and using these compounds in fire blight control. We determined that a 10-nucleotide oligomer of peptide nucleic acid (PNA) targeting the start codon region of an essential gene acpP is able to cause complete growth inhibition of E. amylovora . We found that conjugation of cell penetrating peptide (CPP) to PNA is essential for the antimicrobial effect, with CPP1 [(KFF)3K] being the most effective against E. amylovora . The minimal inhibitory concentration (MIC) of anti- acpP -CPP1 (2.5 μM) is comparable to the MIC of streptomycin (2 μM). Examination of the antimicrobial mechanisms demonstrated that anti- acpP -CPP1 caused dose-dependent reduction of acpP mRNA in E. amylovora upon treatment and resulted in cell death (bactericidal effect). Anti- acpP -CPP1 (100 μM) is able to effectively limit the pathogen growth on stigmas of apple flowers, although less effective than streptomycin. Finally, unlike streptomycin that does not display any specificity in inhibiting pathogen growth, anti- acpP -CPP1 has more specific antimicrobial effect against E. amylovora . In summary, we demonstrated that PNA-CPP can cause an effective, specific antimicrobial effect against E. amylovora and may provide the basis for a novel approach for fire blight control.

Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora

PubMed Central

Patel, Ravi R.; Sundin, George W.; Yang, Ching-Hong; Wang, Jie; Huntley, Regan B.; Yuan, Xiaochen; Zeng, Quan

2017-01-01

Erwinia amylovora is a Gram-negative bacterial plant pathogen in the family Enterobacteriaceae and is the causal agent of fire blight, a devastating disease of apple and pear. Fire blight is traditionally managed by the application of the antibiotic streptomycin during bloom, but this strategy has been challenged by the development and spread of streptomycin resistance. Thus, there is an urgent need for effective, specific, and sustainable control alternatives for fire blight. Antisense antimicrobials are oligomers of nucleic acid homologs with antisense sequence of essential genes in bacteria. The binding of these molecules to the mRNA of essential genes can result in translational repression and antimicrobial effect. Here, we explored the possibility of developing antisense antimicrobials against E. amylovora and using these compounds in fire blight control. We determined that a 10-nucleotide oligomer of peptide nucleic acid (PNA) targeting the start codon region of an essential gene acpP is able to cause complete growth inhibition of E. amylovora. We found that conjugation of cell penetrating peptide (CPP) to PNA is essential for the antimicrobial effect, with CPP1 [(KFF)3K] being the most effective against E. amylovora. The minimal inhibitory concentration (MIC) of anti-acpP-CPP1 (2.5 μM) is comparable to the MIC of streptomycin (2 μM). Examination of the antimicrobial mechanisms demonstrated that anti-acpP-CPP1 caused dose-dependent reduction of acpP mRNA in E. amylovora upon treatment and resulted in cell death (bactericidal effect). Anti-acpP-CPP1 (100 μM) is able to effectively limit the pathogen growth on stigmas of apple flowers, although less effective than streptomycin. Finally, unlike streptomycin that does not display any specificity in inhibiting pathogen growth, anti-acpP-CPP1 has more specific antimicrobial effect against E. amylovora. In summary, we demonstrated that PNA–CPP can cause an effective, specific antimicrobial effect against E. amylovora and may provide the basis for a novel approach for fire blight control. PMID:28469617

Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets.

PubMed

Luk, Geraldine S M; Leung, Connie Y H; Sia, Sin Fun; Choy, Ka-Tim; Zhou, Jie; Ho, Candy C K; Cheung, Peter P H; Lee, Elaine F; Wai, Chris K L; Li, Pamela C H; Ip, Sin-Ming; Poon, Leo L M; Lindsley, William G; Peiris, Malik; Yen, Hui-Ling

2015-10-01

Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for which the mode of transmission remains unclear. We studied the transmission of genetically related poultry and human H7N9 influenza viruses differing by four amino acids, including the host determinant PB2 residue 627. A/Silkie chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Interspecies transmission via the airborne route was observed for ferrets exposed to the SCk1772- or HK3263-infected chickens, while low numbers of copies of influenza viral genome were detected in the air, predominantly at particle sizes larger than 4 μm. In ferrets, the human isolate HK3263 replicated to higher titers and transmitted more efficiently via direct contact than SCk1772. We monitored "intrahost" and "interhost" adaptive changes at PB2 residue 627 during infection and transmission of the Sck1772 that carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%, respectively. For SCk1772, positive selection for K627 over E627 was observed in ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263 that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted among chickens while either V627 or K627 was transmitted to ferrets with a narrow transmission bottleneck. Overall, our results suggest direct contact as the main mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised fitness and transmissibility in both avian and mammalian species. We studied the modes of H7N9 transmission, as this information is crucial for developing effective control measures for prevention. Using chicken (SCk1772) and human (HK3263) H7N9 isolates that differed by four amino acids, including the host determinant PB2 residue 627, we observed that both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Chicken-to-ferret transmission via the airborne route was observed, along with the detection of viral genome in the air at low copy numbers. In ferrets, HK3263 transmitted more efficiently than SCk1772 via direct contact. During the transmission of SCk1772 that contained E and HK3263 that contained V/K/E polymorphism at PB2 residue 627, positive selections of E627 and K627 were observed in chickens and ferrets, respectively. In addition, PB2-V627 was transmitted and stably maintained in both avian and mammalian species. Our results support applying intervention strategies that minimize direct and indirect contact at the poultry markets during epidemics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Transmission of H7N9 Influenza Viruses with a Polymorphism at PB2 Residue 627 in Chickens and Ferrets

PubMed Central

Luk, Geraldine S. M.; Leung, Connie Y. H.; Sia, Sin Fun; Choy, Ka-Tim; Zhou, Jie; Ho, Candy C. K.; Cheung, Peter P. H.; Lee, Elaine F.; Wai, Chris K. L.; Li, Pamela C. H.; Ip, Sin-Ming; Poon, Leo L. M.; Lindsley, William G.

2015-01-01

ABSTRACT Poultry exposure is a major risk factor for human H7N9 zoonotic infections, for which the mode of transmission remains unclear. We studied the transmission of genetically related poultry and human H7N9 influenza viruses differing by four amino acids, including the host determinant PB2 residue 627. A/Silkie chicken/HK/1772/2014 (SCk1772) and A/HK/3263/14 (HK3263) replicated to comparable titers in chickens, with superior oropharyngeal over cloacal shedding; both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Interspecies transmission via the airborne route was observed for ferrets exposed to the SCk1772- or HK3263-infected chickens, while low numbers of copies of influenza viral genome were detected in the air, predominantly at particle sizes larger than 4 μm. In ferrets, the human isolate HK3263 replicated to higher titers and transmitted more efficiently via direct contact than SCk1772. We monitored “intrahost” and “interhost” adaptive changes at PB2 residue 627 during infection and transmission of the Sck1772 that carried E627 and HK3263 that carried V/K/E polymorphism at 60%, 20%, and 20%, respectively. For SCk1772, positive selection for K627 over E627 was observed in ferrets during the chicken-to-ferret or ferret-to-ferret transmission. For HK3263 that contained V/K/E polymorphism, mixed V627 and E627 genotypes were transmitted among chickens while either V627 or K627 was transmitted to ferrets with a narrow transmission bottleneck. Overall, our results suggest direct contact as the main mode for H7N9 transmission and identify the PB2-V627 genotype with uncompromised fitness and transmissibility in both avian and mammalian species. IMPORTANCE We studied the modes of H7N9 transmission, as this information is crucial for developing effective control measures for prevention. Using chicken (SCk1772) and human (HK3263) H7N9 isolates that differed by four amino acids, including the host determinant PB2 residue 627, we observed that both viruses transmitted efficiently among chickens via direct contact but inefficiently via the airborne route. Chicken-to-ferret transmission via the airborne route was observed, along with the detection of viral genome in the air at low copy numbers. In ferrets, HK3263 transmitted more efficiently than SCk1772 via direct contact. During the transmission of SCk1772 that contained E and HK3263 that contained V/K/E polymorphism at PB2 residue 627, positive selections of E627 and K627 were observed in chickens and ferrets, respectively. In addition, PB2-V627 was transmitted and stably maintained in both avian and mammalian species. Our results support applying intervention strategies that minimize direct and indirect contact at the poultry markets during epidemics. PMID:26202239

Inhibition of Avian Influenza A Virus Replication in Human Cells by Host Restriction Factor TUFM Is Correlated with Autophagy.

PubMed

Kuo, Shu-Ming; Chen, Chi-Jene; Chang, Shih-Cheng; Liu, Tzu-Jou; Chen, Yi-Hsiang; Huang, Sheng-Yu; Shih, Shin-Ru

2017-06-13

Avian influenza A viruses generally do not replicate efficiently in human cells, but substitution of glutamic acid (Glu, E) for lysine (Lys, K) at residue 627 of avian influenza virus polymerase basic protein 2 (PB2) can serve to overcome host restriction and facilitate human infectivity. Although PB2 residue 627 is regarded as a species-specific signature of influenza A viruses, host restriction factors associated with PB2 627 E have yet to be fully investigated. We conducted immunoprecipitation, followed by differential proteomic analysis, to identify proteins associating with PB2 627 K (human signature) and PB2 627 E (avian signature) of influenza A/WSN/1933(H1N1) virus, and the results indicated that Tu elongation factor, mitochondrial (TUFM), had a higher binding affinity for PB2 627 E than PB2 627 K in transfected human cells. Stronger binding of TUFM to avian-signature PB2 590 G/ 591 Q and PB2 627 E in the 2009 swine-origin pandemic H1N1 and 2013 avian-origin H7N9 influenza A viruses was similarly observed. Viruses carrying avian-signature PB2 627 E demonstrated increased replication in TUFM-deficient cells, but viral replication decreased in cells overexpressing TUFM. Interestingly, the presence of TUFM specifically inhibited the replication of PB2 627 E viruses, but not PB2 627 K viruses. In addition, enhanced levels of interaction between TUFM and PB2 627 E were noted in the mitochondrial fraction of infected cells. Furthermore, TUFM-dependent autophagy was reduced in TUFM-deficient cells infected with PB2 627 E virus; however, autophagy remained consistent in PB2 627 K virus-infected cells. The results suggest that TUFM acts as a host restriction factor that impedes avian-signature influenza A virus replication in human cells in a manner that correlates with autophagy. IMPORTANCE An understanding of the mechanisms that influenza A viruses utilize to shift host tropism and the identification of host restriction factors that can limit infection are both critical to the prevention and control of emerging viruses that cross species barriers to target new hosts. Using a proteomic approach, we revealed a novel role for TUFM as a host restriction factor that exerts an inhibitory effect on avian-signature PB2 627 E influenza virus propagation in human cells. We further found that increased TUFM-dependent autophagy correlates with the inhibitory effect on avian-signature influenza virus replication and may serve as a key intrinsic mechanism to restrict avian influenza virus infection in humans. These findings provide new insight regarding the TUFM mitochondrial protein and may have important implications for the development of novel antiviral strategies. Copyright © 2017 Kuo et al.

Behavioral and Molecular Analysis of Nicotine-Conditioned Place Preference in Zebrafish

PubMed Central

Kedikian, Ximena; Faillace, Maria Paula; Bernabeu, Ramón

2013-01-01

Studies using mice and rats have demonstrated that nicotine induces a conditioned place preference (CPP), with more effective results obtained by using biased procedures. Zebrafish have also been used as a model system to identify factors influencing nicotine-associated reward by using an unbiased design. Here, we report that zebrafish exhibited putative nicotine biased CPP to an initially aversive compartment (nicotine-paired group). A counterbalanced nicotine-exposed control group did not show a significant preference shift, providing evidence that the preference shift in the nicotine-paired group was not due to a reduction of aversion for this compartment. Zebrafish preference was corroborated by behavioral analysis of several indicators of drug preference, such as time spent in the drug-paired side, number of entries to the drug-paired side, and distance traveled. These results provided strong evidence that zebrafish may actually develop a preference for nicotine, although the drug was administrated in an aversive place for the fish, which was further supported by molecular studies. Reverse transcription-quantitative real-time PCR analysis depicted a significant increase in the expression of α7 and α6 but not α4 and β2 subunits of the nicotinic receptor in nicotine-paired zebrafish brains. In contrast, zebrafish brains from the counterbalanced nicotine group showed no significant changes. Moreover, CREB phosphorylation, an indicator of neural activity, accompanied the acquisition of nicotine-CPP. Our studies offered an incremental value to the drug addiction field, because they further describe behavioral features of CPP to nicotine in zebrafish. The results suggested that zebrafish exposed to nicotine in an unfriendly environment can develop a preference for that initially aversive place, which is likely due to the rewarding effect of nicotine. Therefore, this model can be used to screen exogenous and endogenous molecules involved in nicotine-associated reward in vertebrates. PMID:23894483

Single Prazosin Infusion in Prelimbic Cortex Fosters Extinction of Amphetamine-Induced Conditioned Place Preference.

PubMed

Latagliata, Emanuele C; Lo Iacono, Luisa; Chiacchierini, Giulia; Sancandi, Marco; Rava, Alessandro; Oliva, Valeria; Puglisi-Allegra, Stefano

2017-01-01

Exposure to drug-associated cues to induce extinction is a useful strategy to contrast cue-induced drug seeking. Norepinephrine (NE) transmission in medial prefrontal cortex has a role in the acquisition and extinction of conditioned place preference induced by amphetamine. We have reported recently that NE in prelimbic cortex delays extinction of amphetamine-induced conditioned place preference (CPP). A potential involvement of α1-adrenergic receptors in the extinction of appetitive conditioned response has been also suggested, although their role in prelimbic cortex has not been yet fully investigated. Here, we investigated the effects of the α1-adrenergic receptor antagonist prazosin infusion in the prelimbic cortex of C57BL/6J mice on expression and extinction of amphetamine-induced CPP. Acute prelimbic prazosin did not affect expression of amphetamine-induced CPP on the day of infusion, while in subsequent days it produced a clear-cut advance of extinction of preference for the compartment previously paired with amphetamine (Conditioned stimulus, CS). Moreover, prazosin-treated mice that had extinguished CS preference showed increased mRNA expression of brain-derived neurotrophic factor ( BDNF ) and post-synaptic density 95 ( PSD-95 ) in the nucleus accumbens shell or core, respectively, thus suggesting that prelimbic α1-adrenergic receptor blockade triggers neural adaptations in subcortical areas that could contribute to the extinction of cue-induced drug-seeking behavior. These results show that the pharmacological blockade of α1-adrenergic receptors in prelimbic cortex by a single infusion is able to induce extinction of amphetamine-induced CPP long before control (vehicle) animals, an effect depending on contingent exposure to retrieval, since if infused far from or after reactivation it did not affect preference. Moreover, they suggest strongly that the behavioral effects depend on post-treatment neuroplasticity changes in corticolimbic network, triggered by a possible "priming" effect of prazosin, and point to a potential therapeutic power of the antagonist for maladaptive memories.

Ultrastructural Investigation of Pelvic Peritoneum in Patients With Chronic Pelvic Pain and Subtle Endometriosis in Association With Chromoendoscopy.

PubMed

Mehdizadehkashi, Abolfazl; Tahermanesh, Kobra; Fazel Anvari-Yazdi, Abbas; Chaichian, Shahla; Azarpira, Negar; Nobakht, Maliheh; Abed, Seyedeh Mehr; Hashemi, Neda

2017-01-01

To evaluate the pelvic peritoneum under chromoendoscopy by scanning electron microscopy (SEM) as well as light microscopy with hematoxylin and eosin staining and immunohistochemistry (IHC) assays in patients with chronic pelvic pain (CPP) associated with subtle endometriosis. Case series study (Canadian Task Force classification II). A referral academic community tertiary medical center. Three women aged 29 to 37 years were referred to the obstetrics and gynecology clinic of the tertiary university hospital with CPP. They were suspicious for endometriosis, were not responding to medical treatments, and had undergone previous pelvic laparoscopy to determine the stage of endometriosis and preparation of peritoneal samples under the guidance of staining with methylene blue in 0.25% dilution. Comparison of stained and unstained pelvic peritoneal samples after the instillation of 0.25% methylene blue into the pelvic cavity. In 3 patients, laparoscopic examination showed minimal endometriosis. A total of 18 samples (9 stained and 9 unstained) from the 3 patients were prepared for SEM. Ten of the samples (55.6%) showed microstructural peritoneal destruction (7 of 9 stained [77.7%] and 3 of 9 [33.4%] unstained). Eighteen samples (9 stained and 9 unstained) from the 3 patients were also prepared for IHC. Six of these samples (33.3%) were S-100-positive, including 4 of 9 (44.4%) stained samples and 2 of 9 (22.2%) unstained samples. In general, in the context of CPP and endometriosis, there is no established relationship between the severity of pain and stage of endometriosis. In the pathophysiology of CPP associated with endometriosis, ultrastructural changes can play a significant role. Under methylene blue staining, some destroyed areas were detected, but the stained areas do not necessarily correlate with increased microstructural peritoneal destruction. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Palmitoylethanolamide attenuates cocaine-induced behavioral sensitization and conditioned place preference in mice.

PubMed

Zambrana-Infantes, Emma; Rosell Del Valle, Cristina; Ladrón de Guevara-Miranda, David; Galeano, Pablo; Castilla-Ortega, Estela; Rodríguez De Fonseca, Fernando; Blanco, Eduardo; Santín, Luis Javier

2018-03-01

Cocaine addiction is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors. Previous studies have demonstrated that cocaine, as well as other drugs of abuse, alters the levels of lipid-based signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels of NAEs have shown sensitivity to cocaine self-administration and extinction training in rodents. Given this background, the aim of this study was to investigate the effects of repeated or acute administration of palmitoylethanolamide (PEA), an endogenous NAE, on psychomotor sensitization and cocaine-induced contextual conditioning. To this end, the potential ability of repeated PEA administration (1 or 10 mg/kg, i.p.) to modulate the acquisition of cocaine-induced behavioral sensitization (BS) and conditioned place preference (CPP) was assessed in male C57BL/6J mice. In addition, the expression of cocaine-induced BS and CPP following acute PEA administration were also studied. Results showed that repeated administration of both doses of PEA were able to block the acquisition of cocaine-induced BS. Furthermore, acute administration of both doses of PEA was able to abolish the expression of BS, while the highest dose also abolished the expression of cocaine-induced CPP. Taken together, these results indicate that exogenous administration of PEA attenuated psychomotor sensitization, while the effect of PEA in cocaine-induced CPP depended on whether PEA was administered repeatedly or acutely. These findings could be relevant to understand the role that NAEs play in processes underlying the development and maintenance of cocaine addiction. Copyright © 2018 Elsevier Inc. All rights reserved.

Birth-death models and coalescent point processes: the shape and probability of reconstructed phylogenies.

PubMed

Lambert, Amaury; Stadler, Tanja

2013-12-01

Forward-in-time models of diversification (i.e., speciation and extinction) produce phylogenetic trees that grow "vertically" as time goes by. Pruning the extinct lineages out of such trees leads to natural models for reconstructed trees (i.e., phylogenies of extant species). Alternatively, reconstructed trees can be modelled by coalescent point processes (CPPs), where trees grow "horizontally" by the sequential addition of vertical edges. Each new edge starts at some random speciation time and ends at the present time; speciation times are drawn from the same distribution independently. CPPs lead to extremely fast computation of tree likelihoods and simulation of reconstructed trees. Their topology always follows the uniform distribution on ranked tree shapes (URT). We characterize which forward-in-time models lead to URT reconstructed trees and among these, which lead to CPP reconstructed trees. We show that for any "asymmetric" diversification model in which speciation rates only depend on time and extinction rates only depend on time and on a non-heritable trait (e.g., age), the reconstructed tree is CPP, even if extant species are incompletely sampled. If rates additionally depend on the number of species, the reconstructed tree is (only) URT (but not CPP). We characterize the common distribution of speciation times in the CPP description, and discuss incomplete species sampling as well as three special model cases in detail: (1) the extinction rate does not depend on a trait; (2) rates do not depend on time; (3) mass extinctions may happen additionally at certain points in the past. Copyright © 2013 Elsevier Inc. All rights reserved.

Virtual reality conditioned place preference using monetary reward.

PubMed

Childs, Emma; Astur, Robert S; de Wit, Harriet

2017-03-30

Computerized tasks based on conditioned place preference (CPP) methodology offer the opportunity to study learning mechanisms involved in conditioned reward in humans. In this study, we examined acquisition and extinction of a CPP for virtual environments associated with monetary reward ($). Healthy men and women (N=57) completed a computerized CPP task in which they controlled an avatar within a virtual environment. On day 1, subjects completed 6 conditioning trials in which one room was paired with high $ and another with low $. Acquisition of place conditioning was assessed by measuring the time spent in each room during an exploration test of the virtual environments and using self-reported ratings of room liking and preference. Twenty-four hours later, retention and extinction of CPP were assessed during 4 successive exploration tests of the virtual environments. Participants exhibited a place preference for (spent significantly more time in) the virtual room paired with high $ over the one paired with low $ (p=0.015). They also reported that they preferred the high $ room (p<0.001) and liked it significantly more than the low $ room (p<0.001). However, these preferences were short-lived: 24h later subjects did not exhibit a behavioral or subjective preference for the high $ room. These findings show that individuals exhibit transient behavioral and subjective preferences for a virtual environment paired with monetary reward. Variations on this task may be useful to study mechanisms and brain substrates involved in conditioned reward and to examine the influence of drugs upon appetitive conditioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Amphetamine reward in food restricted mice lacking the melanin-concentrating hormone receptor-1.

PubMed

Geuzaine, Annabelle; Tyhon, Amélie; Grisar, Thierry; Brabant, Christian; Lakaye, Bernard; Tirelli, Ezio

2014-04-01

Chronic food restriction (FR) and maintenance of low body weight have long been known to increase the rewarding and motor-activating effects of addictive drugs. However, the neurobiological mechanisms through which FR potentiates drug reward remain largely unknown. Melanin-concentrating hormone (MCH) signaling could be one of these mechanisms since this peptide is involved in energy homeostasis and modulates mesolimbic dopaminergic transmission. The purpose of the present study was to test this hypothesis by investigating the impact of FR on amphetamine reward in wild-type (WT) and knockout mice lacking the melanin-concentrating hormone receptor-1 (MCHR1-KO). The rewarding effects of amphetamine (0.75-2.25 mg/kg, i.p.) were measured with the conditioned place preference (CPP) technique. The food of the mice was restricted to maintain their body weight at 80-85% of their free-feeding (FF) weight throughout the entire CPP experiment. Locomotor activity of the animals was recorded during the conditioning sessions. Our results show that locomotion of all the food-restricted mice treated with saline or amphetamine increased over the sessions whatever the genotype. On the place preference test, the amplitude of CPP induced by 0.75 mg/kg amphetamine was higher in food restricted WT mice than in free-fed WT mice and food restricted MCHR1-KO mice. However, FR did not affect amphetamine reward in MCHR1-KO mice. The present results indicate that MCH signaling could be involved in the ability of FR to increase amphetamine-induced CPP. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of Acute Withdrawal on Ethanol-Induced Conditioned Place Preference in DBA/2J mice

PubMed Central

Dreumont, Sarah E.; Cunningham, Christopher L.

2013-01-01

Rationale Re-exposure to ethanol during acute withdrawal might facilitate the transition to alcoholism by enhancing the rewarding effect of ethanol. Objective The conditioned place preference (CPP) procedure was used to test whether ethanol reward is enhanced during acute withdrawal. Methods DBA/2J mice were exposed to an unbiased one-compartment CPP procedure. Ethanol (0.75, 1.0 or 1.5 g/kg IP) was paired with a distinctive floor cue (CS+), whereas saline was paired with a different floor cue (CS−). The Withdrawal (W) group received CS+ trials during acute withdrawal produced by a large dose of ethanol (4 g/kg) given 8 h before each trial. The No Withdrawal (NW) group did not experience acute withdrawal during conditioning trials, but was matched for acute withdrawal experience. Floor preference was tested in the absence of ethanol or acute withdrawal. Results All groups eventually showed a dose-dependent preference for the ethanol-paired cue, but development of CPP was generally more rapid and stable in the W groups than in the NW groups. Acute withdrawal suppressed the normal activating effect of ethanol during CS+ trials, but there were no group differences in test activity. Conclusions Acute withdrawal enhanced ethanol’s rewarding effect as indexed by CPP. Since this effect depended on ethanol exposure during acute withdrawal, the enhancement of ethanol reward was likely mediated by the alleviation of acute withdrawal, i.e., negative reinforcement. Enhancement of ethanol reward during acute withdrawal may be a key component in the shift from episodic to chronic ethanol consumption that characterizes alcoholism. PMID:24096534

Basal forebrain projections to the lateral habenula modulate aggression reward.

PubMed

Golden, Sam A; Heshmati, Mitra; Flanigan, Meghan; Christoffel, Daniel J; Guise, Kevin; Pfau, Madeline L; Aleyasin, Hossein; Menard, Caroline; Zhang, Hongxing; Hodes, Georgia E; Bregman, Dana; Khibnik, Lena; Tai, Jonathan; Rebusi, Nicole; Krawitz, Brian; Chaudhury, Dipesh; Walsh, Jessica J; Han, Ming-Hu; Shapiro, Matt L; Russo, Scott J

2016-06-30

Maladaptive aggressive behaviour is associated with a number of neuropsychiatric disorders and is thought to result partly from the inappropriate activation of brain reward systems in response to aggressive or violent social stimuli. Nuclei within the ventromedial hypothalamus, extended amygdala and limbic circuits are known to encode initiation of aggression; however, little is known about the neural mechanisms that directly modulate the motivational component of aggressive behaviour. Here we established a mouse model to measure the valence of aggressive inter-male social interaction with a smaller subordinate intruder as reinforcement for the development of conditioned place preference (CPP). Aggressors develop a CPP, whereas non-aggressors develop a conditioned place aversion to the intruder-paired context. Furthermore, we identify a functional GABAergic projection from the basal forebrain (BF) to the lateral habenula (lHb) that bi-directionally controls the valence of aggressive interactions. Circuit-specific silencing of GABAergic BF-lHb terminals of aggressors with halorhodopsin (NpHR3.0) increases lHb neuronal firing and abolishes CPP to the intruder-paired context. Activation of GABAergic BF-lHb terminals of non-aggressors with channelrhodopsin (ChR2) decreases lHb neuronal firing and promotes CPP to the intruder-paired context. Finally, we show that altering inhibitory transmission at BF-lHb terminals does not control the initiation of aggressive behaviour. These results demonstrate that the BF-lHb circuit has a critical role in regulating the valence of inter-male aggressive behaviour and provide novel mechanistic insight into the neural circuits modulating aggression reward processing.

Transcriptome Sequencing of Codonopsis pilosula and Identification of Candidate Genes Involved in Polysaccharide Biosynthesis

PubMed Central

Gao, Jian Ping; Wang, Dong; Cao, Ling Ya; Sun, Hai Feng

2015-01-01

Background Codonopsis pilosula (Franch.) Nannf. is one of the most widely used medicinal plants. Although chemical and pharmacological studies have shown that codonopsis polysaccharides (CPPs) are bioactive compounds and that their composition is variable, their biosynthetic pathways remain largely unknown. Next-generation sequencing is an efficient and high-throughput technique that allows the identification of candidate genes involved in secondary metabolism. Principal Findings To identify the components involved in CPP biosynthesis, a transcriptome library, prepared using root and other tissues, was assembled with the help of Illumina sequencing. A total of 9.2 Gb of clean nucleotides was obtained comprising 91,175,044 clean reads, 102,125 contigs, and 45,511 unigenes. After aligning the sequences to the public protein databases, 76.1% of the unigenes were annotated. Among these annotated unigenes, 26,189 were assigned to Gene Ontology categories, 11,415 to Clusters of Orthologous Groups, and 18,848 to Kyoto Encyclopedia of Genes and Genomes pathways. Analysis of abundance of transcripts in the library showed that genes, including those encoding metallothionein, aquaporin, and cysteine protease that are related to stress responses, were in the top list. Among genes involved in the biosynthesis of CPP, those responsible for the synthesis of UDP-L-arabinose and UDP-xylose were highly expressed. Significance To our knowledge, this is the first study to provide a public transcriptome dataset prepared from C. pilosula and an outline of the biosynthetic pathway of polysaccharides in a medicinal plant. Identified candidate genes involved in CPP biosynthesis provide understanding of the biosynthesis and regulation of CPP at the molecular level. PMID:25719364

Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

PubMed

Nemoto, E M; Snyder, J V; Carroll, R G; Morita, H

1975-01-01

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.

SAXS characterization of the interactions among digested food compounds and the anti-oxidant and anti-inflammatory activities of the formed nanocomplexes.

PubMed

Yang, Yingkang; Wang, Xiaoqi; Chen, Guijie; Zhou, Wenhua; Zeng, Xiaoxiong; Hu, Bing; Li, Yunqi; Huang, Qingrong

2018-06-06

In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale. The Df value generally increases with an increase in the CS/CPP mass ratio. As a representative of polyphenols, (-)-epigallocatechin gallate (EGCG) associates with CS and CPP, forming nanocomplexes with a spherical shape and average particle size of around 208 nm. The formed CS-EGCG-CPP nanocomplexes do not affect the antioxidant activity of EGCG in the in vitro assays. Moreover, in the cellular assay, the nanocomplexes protect the RAW264.7 cells against H2O2-induced oxidative injury. In addition, the nanocomplexes significantly inhibit the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), TNF-α, IL-1β and IL-6. Furthermore, they inhibit the expression of iNOS, phosphorylation and degradation of IκB, as well as the translocation of NF-κB p65; this indicates that the mechanism for their anti-inflammatory activity is via the mediation of the NF-κB signaling pathway.

Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference, and delays morphine extinction in rats.

PubMed

Fan, Yaodong; Niu, Haichen; Rizak, Joshua D; Li, Ling; Wang, Guimei; Xu, Liqi; Ren, He; Lei, Hao; Yu, Hualin

2012-10-01

It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor (NMDAR), play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 (GLT-1) (ceftriaxone) are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP) than either compound alone. A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory (acquisition, extinction, and reinstatement of morphine preference) in rats. A low dose of neither MK-801 (0.05 mg/kg, i.p.) nor ceftriaxone (25 mg/kg, i.p.) alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. The combined action of a low dose of an NMDAR antagonist (MK-801) and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.

Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

PubMed

Moulton, H M; Fletcher, S; Neuman, B W; McClorey, G; Stein, D A; Abes, S; Wilton, S D; Buchmeier, M J; Lebleu, B; Iversen, P L

2007-08-01

The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.

Molecular evolution of the CPP-like gene family in plants: insights from comparative genomics of Arabidopsis and rice.

PubMed

Yang, Zefeng; Gu, Shiliang; Wang, Xuefeng; Li, Wenjuan; Tang, Zaixiang; Xu, Chenwu

2008-09-01

CPP-like genes are members of a small family which features the existence of two similar Cys-rich domains termed CXC domains in their protein products and are distributed widely in plants and animals but do not exist in yeast. The members of this family in plants play an important role in development of reproductive tissue and control of cell division. To gain insights into how CPP-like genes evolved in plants, we conducted a comparative phylogenetic and molecular evolutionary analysis of the CPP-like gene family in Arabidopsis and rice. The results of phylogeny revealed that both gene loss and species-specific expansion contributed to the evolution of this family in Arabidopsis and rice. Both intron gain and intron loss were observed through intron/exon structure analysis for duplicated genes. Our results also suggested that positive selection was a major force during the evolution of CPP-like genes in plants, and most amino acid residues under positive selection were disproportionately located in the region outside the CXC domains. Further analysis revealed that two CXC domains and sequences connecting them might have coevolved during the long evolutionary period.

Comparing of the Effects of Hypericin and Synthetic Antidepressants on the Expression of Morphine-Induced Conditioned Place Preference

PubMed Central

Assadi, Assad; Zarrindast, Mohammad Reza; Jouyban, Abolghasem; Samini, Morteza

2011-01-01

The effect of hypericin on the expression of morphine-induced conditioned place preference (CPP) was investigated and compared with the effect of the synthetic antidepressants. The CPP paradigms took place over six days using an unbiased procedure. The results demonstrate that intra-peritoneal (IP) injection of morphine sulfate (2.5, 5 and 10 mg/Kg) significantly induce the CPP in rat. Intra-peritoneal and intracerebroventricular (ICV) injection of hypericin and/or synthetic antidepressants augmented morphine-induced CPP. It has been suggested that the adrenergic, serotonergic and dopaminergic neurotransmissions play an important role in mediating the antidepressant effect of hypericin and this effect may be due to its inhibitory effect on the reuptake of neurotransmitters. Morphine produces a reinforcement (reward) effect by activating. The μ-receptors that facilitate dopaminergic transmission. Serotonin is also a potent stimulator of dopamine release in such a way that an increase in brain serotonin could possibly stimulate the dopaminergic system. In conclusion, it may suggest that the augmentation of morphine-induced CPP by hypericin and synthetic antidepressants may be related to the increasing dopamine and serotonin concentrations in synaptic clefts. PMID:24250400

Effects of scopolamine on morphine-induced conditioned place preference in mice.

PubMed

Tan, Hua; Liu, Ning; Wilson, Fraser A W; Ma, Yuanye

2007-09-01

It is well known that the cholinergic system plays a crucial role in learning and memory. Psychopharmacological studies in humans and animals have shown that a systemic cholinergic blockade may induce deficits in learning and memory. Accumulated studies have indicated that learning and memory play an important role in drug addition. In the present study, in order to get a further understanding about the functions of the cholinergic system in drug-related learning and memory, we examined the effects of scopolamine (0.5, 1.0 and 2.0 mg/kg) on morphine-induced conditioned place preference (CPP). Two kinds of morphine exposure durations (4 days and 12 days) were used. The main finding was that all doses of scopolamine enhanced the extinction of morphine-induced CPP in mice treated with morphine for 12 days. However, in mice treated with morphine for 4 days, all doses of scopolamine did not inhibit morphine-induced CPP. The highest dose (2.0 mg/kg) of scopolamine even significantly delayed the extinction of morphine-induced CPP. Our results suggest that the effects of a systemic cholinergic blockade on morphine-induced CPP depend on the morphine exposure time.

GluR2-3Y Inhibits the Acquisition and Reinstatement of Morphine-Induced Conditioned Place Preference in Rats.

PubMed

Lin, Xiao-Jing; Zhang, Jian-Jun; Yu, Long-Chuan

2016-04-01

Accumulating evidence indicates that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) are involved in the relapse to abused drugs. However, the role of AMPARs containing the GluR2 subunit in opiate addiction is still unclear. GluR2-3Y, an interfering peptide, prevents the endocytosis of AMPARs containing the GluR2 subunit. In this study, we explored the effect of intravenous injection of GluR2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (mCPP) in rats. We found that infusion of GluR2-3Y (1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of mCPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of mCPP. Injection of GluR2-3Y (1.5 nmol/g) after mCPP extinction blocked the morphine-induced reinstatement of mCPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.

Effects of CCK-8 on the reinstatement of morphine-induced CPP and expression of behavioral sensitization in rats.

PubMed

Wen, D; Zang, G; Sun, D; Yang, S; Yu, F; Li, S; Ma, C; Cong, B

2013-05-15

Cholecystokinin octapeptide (CCK-8), a neuropeptide, plays an important role in morphine dependence and several addictive behaviors. We have previously reported that CCK-8 attenuates the acquisition of morphine-induced conditioned place preference (CPP), but the possible functions of CCK-8 on drug relapse remain unclear. Here we evaluated the effects of CCK-8 on the reinstatement of extinguished morphine-induced CPP and behavioral sensitization. A single injection of 0.1 and 1μg CCK-8 (i.c.v.) significantly attenuated both drug- (morphine) and stress- (foot shock) primed reinstatement of CPP and reduced the escalated locomotor activity in reinstatement tests. Additionally, CCK-8 blocked the expression of morphine-induced behavioral sensitization. However, administration of CCK-8 (0.01, 0.1 and 1μg) alone to morphine-pretreated rats could not trigger reinstatement of CPP and had no significant effect on threshold sensitivity to foot shock. In conclusion, our study identifies a distinct inhibitory effect of CCK-8 on the reinstatement of drug-seeking behavior and provides a potential application to the medication of drug relapse. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

A novel cell penetrating peptide carrier for the delivery of nematocidal proteins drug

NASA Astrophysics Data System (ADS)

Kim, Jea Hyun

Nematodes have recently become a primary source of harmful diseases to the environment that inflict harsh damages to pine trees and marine species. However, nematodes cannot be killed by normal pesticides or chemicals due to their thick outer protective layer mainly composed of collagen and cuticles. Thus, a novel approach to trigger intracellular delivery of chemicals through the layers of nematodes is required. In this study, the selection of the novel CPP was carefully progressed through protein database and serial digested fragmentation, internalization of each amino sequence was analyzed through flow cytometry and confocal microscope. As one of the most effective CPP material, JH 1.6 was compared with other major CPPs and its cellular toxicity was investigated. Furthermore, JH 1.6 was attached to various RNA, DNA, and proteins and internalization efficiency was evaluated for mammalian cells. To examine its effects on nematodes in vivo, JH 1.6 was conjugated with nematocidal protein - botulinum neurotoxin (BnT) and treated in C.elegans as a model animal. The results showed that JH 1.6 had high relative internalization rate and low cellular toxicity compared to other major CPP such as TAT and GV1001 peptides.

Serotonin systems upregulate the expression of hypothalamic NUCB2 via 5-HT2C receptors and induce anorexia via a leptin-independent pathway in mice.

PubMed

Nonogaki, Katsunori; Ohba, Yukie; Sumii, Makiko; Oka, Yoshitomo

2008-07-18

NEFA/nucleobindin2 (NUCB2), a novel satiety molecule, is associated with leptin-independent melanocortin signaling in the central nervous system. Here, we show that systemic administration of m-chlorophenylpiperazine (mCPP), a serotonin 5-HT1B/2C receptor agonist, significantly increased the expression of hypothalamic NUCB2 in wild-type mice. The increases in hypothalamic NUCB2 expression induced by mCPP were attenuated in 5-HT2C receptor mutant mice. Systemic administration of mCPP suppressed food intake in db/db mice with leptin receptor mutation as well as lean control mice. On the other hand, the expression of hypothalamic NUCB2 and proopiomelanocortin (POMC) was significantly decreased in hyperphagic and non-obese 5-HT2C receptor mutants compared with age-matched wild-type mice. Interestingly, despite increased expression of hypothalamic POMC, hypothalamic NUCB2 expression was decreased in 5-HT2C receptor mutant mice with heterozygous mutation of beta-endorphin gene. These findings suggest that 5-HT systems upregulate the expression of hypothalamic NUCB2 via 5-HT2C receptors, and induce anorexia via a leptin-independent pathway in mice.

Differences in cocaine-induced place preference persistence, locomotion and social behaviors between C57BL/6J and BALB/cJ mice

PubMed Central

WANG, Jian-Li; WANG, Bei; CHEN, Wen

2014-01-01

C57BL/6J and BALB/cJ mice display significant differences in sociability and response to drugs, but the phenotypic variability of their susceptibility to cocaine is still not well known. In this study, the differences between these two mice strains in the persistence of cocaine-induced conditioned place preference (CPP), as well as the locomotion and social behaviors after the 24-hour withdrawal from a four-day cocaine (20 mg/kg/day) administration were investigated. The results showed that the cocaine-induced CPP persisted over two weeks in C57BL/6J mice, while it diminished within one week among BALB/cJ mice. After 24-hours of cocaine withdrawal, high levels of locomotion as well as low levels of social interaction and aggressive behavior were found in C57BL/6J mice, but no significant changes were found in BALB/cJ mice, indicating that cocaine-induced CPP persistence, locomotion and social behavior are not consistent between these two strains, and that overall C57BL/6J mice are more susceptible to cocaine than BALB/cJ mice at the tested doses. PMID:25297083

Differences in cocaine-induced place preference persistence, locomotion and social behaviors between C57BL/6J and BALB/cJ mice.

PubMed

Wang, Jian-Li; Wang, Bei; Chen, Wen

2014-09-01

C57BL/6J and BALB/cJ mice display significant differences in sociability and response to drugs, but the phenotypic variability of their susceptibility to cocaine is still not well known. In this study, the differences between these two mice strains in the persistence of cocaine-induced conditioned place preference (CPP), as well as the locomotion and social behaviors after the 24-hour withdrawal from a four-day cocaine (20 mg/kg/day) administration were investigated. The results showed that the cocaine-induced CPP persisted over two weeks in C57BL/6J mice, while it diminished within one week among BALB/cJ mice. After 24-hours of cocaine withdrawal, high levels of locomotion as well as low levels of social interaction and aggressive behavior were found in C57BL/6J mice, but no significant changes were found in BALB/cJ mice, indicating that cocaine-induced CPP persistence, locomotion and social behavior are not consistent between these two strains, and that overall C57BL/6J mice are more susceptible to cocaine than BALB/cJ mice at the tested doses.

New Potent Membrane-Targeting Antibacterial Peptides from Viral Capsid Proteins

PubMed Central

Dias, Susana A.; Freire, João M.; Pérez-Peinado, Clara; Domingues, Marco M.; Gaspar, Diana; Vale, Nuno; Gomes, Paula; Andreu, David; Henriques, Sónia T.; Castanho, Miguel A. R. B.; Veiga, Ana S.

2017-01-01

The increasing prevalence of multidrug-resistant bacteria urges the development of new antibacterial agents. With a broad spectrum activity, antimicrobial peptides have been considered potential antibacterial drug leads. Using bioinformatic tools we have previously shown that viral structural proteins are a rich source for new bioactive peptide sequences, namely antimicrobial and cell-penetrating peptides. Here, we test the efficacy and mechanism of action of the most promising peptides among those previously identified against both Gram-positive and Gram-negative bacteria. Two cell-penetrating peptides, vCPP 0769 and vCPP 2319, have high antibacterial activity against Staphylococcus aureus, MRSA, Escherichia coli, and Pseudomonas aeruginosa, being thus multifunctional. The antibacterial mechanism of action of the two most active viral protein-derived peptides, vAMP 059 and vCPP 2319, was studied in detail. Both peptides act on both Gram-positive S. aureus and Gram-negative P. aeruginosa, with bacterial cell death occurring within minutes. Also, these peptides cause bacterial membrane permeabilization and damage of the bacterial envelope of P. aeruginosa cells. Overall, the results show that structural viral proteins are an abundant source for membrane-active peptides sequences with strong antibacterial properties. PMID:28522994

De novo biosynthesis of cytokinins in the biotrophic fungus Claviceps purpurea.

PubMed

Hinsch, Janine; Vrabka, Josef; Oeser, Birgitt; Novák, Ondřej; Galuszka, Petr; Tudzynski, Paul

2015-08-01

Disease symptoms of some phytopathogenic fungi are associated with changes in cytokinin (CK) levels. Here, we show that the CK profile of ergot-infected rye plants is also altered, although no pronounced changes occur in the expression of the host plant's CK biosynthesis genes. Instead, we demonstrate a clearly different mechanism: we report on the first fungal de novo CK biosynthesis genes, prove their functions and constitute a biosynthetic pathway. The ergot fungus Claviceps purpurea produces substantial quantities of CKs in culture and, like plants, expresses enzymes containing the isopentenyltransferase and lonely guy domains necessary for de novo isopentenyladenine production. Uniquely, two of these domains are combined in one bifunctional enzyme, CpIPT-LOG, depicting a novel and potent mechanism for CK production. The fungus also forms trans-zeatin, a reaction catalysed by a CK-specific cytochrome P450 monooxygenase, which is encoded by cpp450 forming a small cluster with cpipt-log. Deletion of cpipt-log and cpp450 did not affect virulence of the fungus, but Δcpp450 mutants exhibit a hyper-sporulating phenotype, implying that CKs are environmental factors influencing fungal development. © 2015 Society for Applied Microbiology and John Wiley & Sons Ltd.

Maintenance of the Hanford cone penetrometer platform during fiscal year 1999

DOE Office of Scientific and Technical Information (OSTI.GOV)

IWATATE, D.F.

This SOW describes services requested of Applied Research and Associates, Inc. (ARA), as a commercial provider of cone penetrometer equipment and services, to provide routine inspection and minimum preventive maintenance on the Hanford CP Platform (CPP) during Fiscal Year 1999. This SOW specifically pertains to the maintenance of the CPP and associated support equipment and is limited in scope to routine preventive maintenance and identification of any deficiencies. ARA is the original manufacturer of the CPP and will conduct this work following the vendor-prepared maintenance schedule.

Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery.

PubMed

Goswami, Dibakar; Vitorino, Hector Aguilar; Machini, M Teresa; Espósito, Breno P

2015-11-01

There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model. Transmission Electron Microscope images of the curcumin-loaded micelles confirmed the formation of nanofibers. These results indicate the potential of CPP-drug conjugates for use as nanocarriers. © 2015 Wiley Periodicals, Inc.

Salivary pH level and bacterial plaque evaluation in orthodontic patients treated with Recaldent products.

PubMed

Marchisio, O; Esposito, M R; Genovesi, A

2010-08-01

Dental caries and resulting tooth decay can produce a multifactorial destructive process with a very high incidence. Cariogenic bacteria attack enamel with acids that produce subsurface lesions, thereby weakening the enamel and allowing bacterial progression into the dentin. The formation of dental decay, because of demineralization of the tooth structure, can be prevented or delayed by increasing the rate of the tooth's remineralization and replacement relative to the tooth's rate of demineralization. This rebuilding of enamel may be accelerated by the addition of amorphous calcium phosphate (ACP) with the aid of casein phosphopeptide (CPP) (Recaldent molecule). In this study, the role of CPP in stabilizing and releasing ACP on the tooth surface has been investigated to better understand its efficacy in the prevention of tooth demineralization in orthodontic patients. Twenty-five patients who wore fixed orthodontic appliances were enrolled in this clinical trial. It was explained to the patients that CPP-ACP would be used for 3 weeks and then suspended for an additional 3 weeks. Salivary pH evaluation, plaque pH evaluation and oral hygiene index (OHI) were performed at T0, T1 and T2. Results showed an increase in OHI level and an increase of the salivary pH (76% of the patients). Instead of plaque pH level that showed trivial results, only 48% of the patients showed a bacterial plaque pH increase. In conclusion, this study has not provided unequivocal evidence for the protective properties of Recaldent molecule. Long-term studies are necessary to better understand the role of this molecule.

Current advancements in the diagnosis and treatment of chronic pelvic pain.

PubMed

Morrissey, Darlene; Ginzburg, Natasha; Whitmore, Kristene

2014-07-01

The diagnosis and treatment of chronic pelvic pain (CPP) have moved away from targeting a specific organ to multifactorial and multidisciplinary individualized approach to treatment strategies. The purpose of this article is to review the current advancements in diagnosis and treatment of CPP. Recognition that response to current treatment approach to CPP syndrome is variable; organizations such as the European Association of Urology, American Urologic Association, International Continence Society, International Association for the Study of Pain, and others have integrated the most current evidence and management strategies from multiple specialties (urology, gynecology, pain medicine, gastroenterology, colorectal surgery, neurology, physiotherapy, and psychology). The 1 World Congress on Pelvic Pain met in 2013 to further collaborate on diagnosis and management of CPP. A multimodal clinical phenotype system has also been implemented to help understand cause and guide therapy. New classification systems allow for overlap of mechanisms between conditions and a multidisciplinary treatment approach.

Conceptual design report for the project to install leak detection in FAST-FT-534/548/549

DOE Office of Scientific and Technical Information (OSTI.GOV)

Galloway, K.J.

1992-07-01

This report provides conceptual designs and design recommendations for installing secondary containment and leak detection systems for three sumps at the Fluorinel and Storage Facility (FAST), CPP-666. The FAST facility is located at the Idaho Chemical Processing Plant (ICPP) at the Idaho National Engineering Laboratory (INEL). The three sumps receive various materials from the FAST water treatment process. This project involves sump upgrades to meet appropriate environmental requirements. The steps include: providing sump modifications or designs for the installation of leak chases and/or leakage accumulation, coating the sump concrete with a chemical resistant sealant (except for sump VES-FT-534 which ismore » already lined with stainless steel) to act as secondary containment, lining the sumps with a primary containment system, and providing a means to detect and remove primary containment leakage that may occur.« less

Emergence of the virulence-associated PB2 E627K substitution in a fatal human case of highly pathogenic avian influenza virus A(H7N7) infection as determined by Illumina ultra-deep sequencing.

PubMed

Jonges, Marcel; Welkers, Matthijs R A; Jeeninga, Rienk E; Meijer, Adam; Schneeberger, Peter; Fouchier, Ron A M; de Jong, Menno D; Koopmans, Marion

2014-02-01

Avian influenza viruses are capable of crossing the species barrier and infecting humans. Although evidence of human-to-human transmission of avian influenza viruses to date is limited, evolution of variants toward more-efficient human-to-human transmission could result in a new influenza virus pandemic. In both the avian influenza A(H5N1) and the recently emerging avian influenza A(H7N9) viruses, the polymerase basic 2 protein (PB2) E627K mutation appears to be of key importance for human adaptation. During a large influenza A(H7N7) virus outbreak in the Netherlands in 2003, the A(H7N7) virus isolated from a fatal human case contained the PB2 E627K mutation as well as a hemagglutinin (HA) K416R mutation. In this study, we aimed to investigate whether these mutations occurred in the avian or the human host by Illumina Ultra-Deep sequencing of three previously uninvestigated clinical samples obtained from the fatal case. In addition, we investigated three chicken samples, two of which were obtained from the source farm. Results showed that the PB2 E627K mutation was not present in any of the chicken samples tested. Surprisingly, the avian samples were characterized by the presence of influenza virus defective RNA segments, suggestive for the synthesis of defective interfering viruses during infection in poultry. In the human samples, the PB2 E627K mutation was identified with increasing frequency during infection. Our results strongly suggest that human adaptation marker PB2 E627K has emerged during virus infection of a single human host, emphasizing the importance of reducing human exposure to avian influenza viruses to reduce the likelihood of viral adaptation to humans.

The effect of CPP-ACP on enamel wear under severe erosive conditions.

PubMed

Ranjitkar, Sarbin; Kaidonis, John A; Richards, Lindsay C; Townsend, Grant C

2009-06-01

In addition to its role as a remineralizing agent in preventing dental caries, recent evidence has shown that casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) can protect teeth against erosion. The aim of this study was to determine whether CPP-ACP could reduce enamel wear rates under severe erosive conditions simulating heavy attrition and gastric regurgitation. Enamel specimens were subjected to 10,000 wear cycles at a load of 100 N and pH 1.2 in a tooth wear machine. The machine was stopped every 2 min (160 cycles), and CPP-ACP in the form of a paste was applied for 5 min in experimental group 1. A paste with the same formulation but without CPP-ACP was applied in experimental group 2. No paste was applied in the control group. A linear mixed model analysis indicated that the mean wear rates in experimental group 1 (0.44+/-0.05 mm(3) per 1000 cycles) and in experimental group 2 (0.63+/-0.06 mm(3) per 1000 cycles) were significantly lower than that in the control group (0.92+/-0.11 mm(3) per 1000 cycles) (p<0.05). The mean wear rate in experimental group 1 was also lower than that in experimental group 2 (p<0.05). Wear facets in experimental groups 1 and 2 were noted to be smoother and more polished than those in the control group. Both remineralizing and lubricating properties of the paste containing CPP-ACP appear to contribute to wear reduction in enamel. These findings may lead to new strategies for the clinical management of tooth wear.

Musculoskeletal Dysfunctions in Patients With Chronic Pelvic Pain: A Preliminary Descriptive Survey.

PubMed

Mieritz, Rune Mygind; Thorhauge, Kirsten; Forman, Axel; Mieritz, Hanne Beck; Hartvigsen, Jan; Christensen, Henrik Wulff

The purpose of this study was to determine the prevalence of musculoskeletal dysfunctions based on a standardized clinical examination of patients with chronic pelvic pain (CPP) who were referred to a specialized tertiary care center for laparoscopic examination. In addition, we stratified levels of self-reported pelvic pain, self-rated health, education, and work status based on musculoskeletal dysfunction status. This study used a cross-sectional design to determine the prevalence of musculoskeletal dysfunctions in women with CPP who were referred to a tertiary care center specializing in care of women with CPP. The women completed a questionnaire and underwent a blinded systematic objective clinical examination of the musculoskeletal system by a doctor of chiropractic who then categorized the patients as having or not having musculoskeletal dysfunction. Ninety-four patients returned the questionnaire, completed the clinical examination, and fulfilled the inclusion criteria. More than half of the referred patients with CPP (48 out of 94) had musculoskeletal dysfunctions in the lumbar/pelvic region. No statistically significant differences were found between the groups with respect to self-rated health, education, work status, and pain level. Pain location was significantly different after Bonferroni correction in 1 out of the 36 aspects. In this sample of CPP patients, 51% were categorized as having a musculoskeletal dysfunction. Overall, CPP patients were similar with respect to certain characteristics, such as age, body mass index, and pain level, regardless of their classification; however, patients with musculoskeletal dysfunction tended to report more pain in the front and back of the lower limbs. Copyright © 2016. Published by Elsevier Inc.

Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats.

PubMed

Lin, Jue; Liu, Lingqi; Wen, Quan; Zheng, Chunming; Gao, Yang; Peng, Shuxian; Tan, Yalun; Li, Yanqin

2014-01-01

The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTHWEST. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-51-1390. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) LOOKING EAST. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. INL PHOTO NUMBER NRTS-51-1547. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

PubMed

Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

2017-10-15

Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this organization using isolated deep zone cartilage cells and a sol-gel hydroxyapatite coated bone substitute material composed of calcium polyphosphate (CPP). Developing a layer of calcified cartilage at the interface should contribute to enhancing the success of this "osteochondral-like" construct following implantation to repair cartilage defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Tracking voice change after thyroidectomy: application of spectral/cepstral analyses.

PubMed

Awan, Shaheen N; Helou, Leah B; Stojadinovic, Alexander; Solomon, Nancy Pearl

2011-04-01

This study evaluates the utility of perioperative spectral and cepstral acoustic analyses to monitor voice change after thyroidectomy. Perceptual and acoustic analyses were conducted on speech samples (sustained vowel /α/ and CAPE-V sentences) provided by 70 participants (36 women and 34 men) at four study time points: prior to thyroid surgery and 2 weeks, 3 months and 6 months after thyroidectomy. Repeated measures analyses of variance focused on the relative amplitude of the dominant harmonic in the voice signal (cepstral peak prominence, CPP), the ratio of low-to-high spectral energy, and their respective standard deviations (SD). Data were also examined for relationships between acoustic measures and perceptual ratings of overall severity of voice quality. Results showed that perceived overall severity and the acoustic measures of the CPP and its SD (CPPsd) computed from sentence productions were significantly reduced at 2-week post-thyroidectomy for 20 patients (29% of the sample) who had self-reported post-operative voice change. For this same group of patients, the CPP and CPPsd computed from sentence productions improved significantly from 2-weeks post-thyroidectomy to 6-months post-surgery. CPP and CPPsd also correlated well with perceived overall severity (r = -0.68 and -0.79, respectively). Measures of CPP from sustained vowel productions were not as effective as those from sentence productions in reflecting voice deterioration in the post-thyroidectomy patients at the 2-week post-surgery time period, were weaker correlates with perceived overall severity, and were not as effective in discriminating negative voice outcome (NegVO) from normal voice outcome (NormVO) patients as compared to the results from the sentence-level stimuli. Results indicate that spectral/cepstral analysis methods can be used with continuous speech samples to provide important objective data to document the effects of dysphonia in a post-thyroidectomy patient sample. When used in conjunction with patient's self-report and other general measures of vocal dysfunction, the acoustic measures employed in this study contribute to a complete profile of the patient's vocal condition.

Effect of fluoride dentifrice and casein phosphopeptide-amorphous calcium phosphate cream with and without fluoride in preventing enamel demineralization in a pH cyclic study

PubMed Central

Sinfiteli, Priscila de Pinto; Coutinho, Thereza Christina Lopes; de Oliveira, Patrícia Regina Almeida; Vasques, Wesley Felisberto; Azevedo, Leandra Matos; Pereira, André Maues Brabo; Tostes, Monica Almeida

2017-01-01

Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) complexes are anticariogenic and capable of remineralizing the early stages of enamel lesions. The use of fluoride prevents dental decay and the association of CPP-ACP with fluoride can increase remineralization. Objective: To evaluate the effect of CPP-ACP and CPP-ACPF creams associated with a fluoride dentifrice to prevent enamel demineralization in a pH cyclic model. Material and Methods: Previously selected by surface microhardness (SH) analysis, human enamel blocks (n = 56) were submitted to daily treatment with dentifrice in a pH-cycling model. The enamel blocks were divided into four groups; G1: Crest™ Cavity Protection - Procter & Gamble (1,100 ppmF of NaF); G2: Crest™ +MI Paste (MP) - Recaldent™ GC Corporation Tokyo, Japan); G3: Crest™ + MI Paste Plus (MPP) - Recaldent™ 900 ppm as NaF, GC Corporation Tokyo, Japan), and G4: control, saliva. Specimens were soaked alternatively in a demineralizing solution and in artificial saliva for 5 d. The fluoride dentifrice, with proportion of 1:3 (w/w), was applied three times for 60 s after the remineralization period. The undiluted MP and MPP creams were applied for 3 m/d. After cycling, SH was re-measured and cross section microhardness measurements were taken. Results: The SH values observed for the groups G3 (257±70), G1 (205±70), and G2 (208±84) differed from the G4 group (98±110) (one-way ANOVA and Tukey's post hoc test). There were no differences between the groups G1xG2, G2xG3, and G1xG3 for demineralization inhibition. The percentage of volume mineral showed that, when applied with fluoride dentifrice, MPP was the most effective in preventing enamel demineralization at 50 µ from the outer enamel surface (Kruskal-Wallis and Mann Whitney p<0.05). Conclusion: Fluoride dentifrice associated with CPP-ACPF inhibited subsurface enamel demineralization. PMID:29211281

[Study on effects of Corydalis yanhusuo and L-THP on dopamine of reward circuitry in conditioned place preference rats and comparison].

PubMed

Yu, Shou-Yang; Yang, Pei-Run; Qian, Gang; Wu, Ming-Song; Bai, Wei-Feng; Tu, Ping; Luo, Su-Yuan

2013-11-01

To study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects. The CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors. Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P < 0.01 or P < 0.05), and revealed a remarkably lower dopamine content in VTA, NAc and PFC and the significant increase in the expression of D2 receptor (P < 0.01 or P < 0.05). The down-regulation of the increased dopamine content in reward nervous circuitry and the up-regulation of the expression of D2 receptor may be one of mechanisms of C. yanhusuo and L-THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

42 CFR 485.627 - Condition of participation: Organizational structure.

Code of Federal Regulations, 2013 CFR

2013-10-01

... participation: Organizational structure. (a) Standard: Governing body or responsible individual. The CAH has a... structure. 485.627 Section 485.627 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION...

42 CFR 485.627 - Condition of participation: Organizational structure.

Code of Federal Regulations, 2014 CFR

2014-10-01

... participation: Organizational structure. (a) Standard: Governing body or responsible individual. The CAH has a... structure. 485.627 Section 485.627 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION...

42 CFR 485.627 - Condition of participation: Organizational structure.

Code of Federal Regulations, 2012 CFR

2012-10-01

... participation: Organizational structure. (a) Standard: Governing body or responsible individual. The CAH has a... structure. 485.627 Section 485.627 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) STANDARDS AND CERTIFICATION CONDITIONS OF PARTICIPATION...

23 CFR 627.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Definitions. 627.3 Section 627.3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING... consist of several contracts or phases over several years. Value engineering. The systematic application...

23 CFR 627.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Definitions. 627.3 Section 627.3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING... consist of several contracts or phases over several years. Value engineering. The systematic application...

23 CFR 627.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Definitions. 627.3 Section 627.3 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS VALUE ENGINEERING... consist of several contracts or phases over several years. Value engineering. The systematic application...

Amino Acid Substitutions in Polymerase Basic Protein 2 Gene Contribute to the Pathogenicity of the Novel A/H7N9 Influenza Virus in Mammalian Hosts

PubMed Central

Mok, Chris Ka Pun; Lee, Horace Hok Yeung; Lestra, Maxime; Nicholls, John Malcolm; Chan, Michael Chi Wai; Sia, Sin Fun; Zhu, Huachen; Poon, Leo Lit Man; Guan, Yi

2014-01-01

ABSTRACT A novel avian-origin influenza A/H7N9 virus emerged in 2013 to cause more than 130 cases of zoonotic human disease, with an overall case fatality rate of around 30% in cases detected. It has been shown that an E-to-K amino acid change at residue 627 of polymerase basic protein 2 (PB2) occurred frequently in the H7N9 isolates obtained from humans but not in viruses isolated from poultry. Although this mutation has been reported to confer increased mammalian pathogenicity in other avian influenza subtypes, it has not been experimentally investigated in the H7N9 virus. In this study, we determined the contribution of PB2-E627K in H7N9 virus to its pathogenicity in mammalian hosts. In addition, the compensatory role of the PB2 mutations T271A, Q591K, and D701N in H7N9 virus was investigated. We characterized the activity of polymerase complexes with these PB2 mutations and found that they enhance the polymerase activity in human 293T cells. The rescued mutants enhanced growth in mammalian cells in vitro. Mice infected with the H7N9 mutant containing the avian signature protein PB2-627E showed a marked decrease in disease severity (weight loss) and pathology compared to mice infected with the wild-type strain (PB2-627K) or other PB2 mutants. Also, mutants with PB2-627E showed lower virus replication and proinflammatory cytokine responses in the lungs of the virus-infected mice, which may contribute to pathogenicity. Our results suggest that these amino acid substitutions contribute to mouse pathogenicity and mammalian adaptation. IMPORTANCE A novel avian H7N9 influenza A virus emerged in east China in 2013 to cause zoonotic human disease associated with significant mortality. It is important to understand the viral genetic markers of mammalian adaptation and disease severity in this H7N9 virus. Since many human (but not avian) H7N9 virus isolates have an amino acid substitution at position E627K in the polymerase basic protein 2 (PB2) gene, we investigated the role of this and other functionally related mutations for polymerase activity in vitro, virus replication competence, and pathogenicity in the mouse model. We found that E627K and functionally related mutations are associated with increased polymerase activity, increased viral replication competence, and increased disease severity in mice. PMID:24403592

Compositional Characteristics and In Vitro Evaluations of Antioxidant and Neuroprotective Properties of Crude Extracts of Fucoidan Prepared from Compressional Puffing-Pretreated Sargassum crassifolium

PubMed Central

Yang, Wen-Ning; Chen, Po-Wei; Huang, Chun-Yung

2017-01-01

Fucoidan, a fucose-containing sulfated polysaccharide with diverse biological functions, is mainly recovered from brown algae. In this study, we utilized a compressional-puffing process (CPP) to pretreat Sargassum crassifolium (SC) and extracted fucoidans from SC by warm water. Three fucoidan extracts (SC1: puffing at 0 kg/cm2; SC2: puffing at 1.7 kg/cm2; and SC3: puffing at 6.3 kg/cm2) were obtained, and their composition, and antioxidant and neuroprotective activities were examined. The results suggest that CPP decreased the bulk density of algal samples, expanded the algal cellular structures, and eliminated the unpleasant algal odor. The extraction yields of fucoidans were increased and impurities of fucoidans were decreased by increasing the pressures used in CPP. The SC1–SC3 extracts displayed various characteristics of fucoidan as illustrated by the analyses of composition, Fourier transform infrared (FTIR) spectroscopy, and molecular weight. All three extracts SC1–SC3 showed antioxidant activity dose-dependently. Although both SC1 and SC2 possessed high and similar neuronal protective properties, SC2 showed a higher extraction yield, higher efficacy in the reversion of H2O2-induced cytotoxicity in rat pheochromocytoma PC-12 cells, and lower impurities compared with SC1, and thus SC2 is suggested as a good candidate for a therapeutic agent in the preventive treatment of neurodegenerative diseases. PMID:28629153

Association of contextual cues with morphine reward increases neural and synaptic plasticity in the ventral hippocampus of rats.

PubMed

Alvandi, Mina Sadighi; Bourmpoula, Maria; Homberg, Judith R; Fathollahi, Yaghoub

2017-11-01

Drug addiction is associated with aberrant memory and permanent functional changes in neural circuits. It is known that exposure to drugs like morphine is associated with positive emotional states and reward-related memory. However, the underlying mechanisms in terms of neural plasticity in the ventral hippocampus, a region involved in associative memory and emotional behaviors, are not fully understood. Therefore, we measured adult neurogenesis, dendritic spine density and brain-derived neurotrophic factor (BDNF) and TrkB mRNA expression as parameters for synaptic plasticity in the ventral hippocampus. Male Sprague Dawley rats were subjected to the CPP (conditioned place preference) paradigm and received 10 mg/kg morphine. Half of the rats were used to evaluate neurogenesis by immunohistochemical markers Ki67 and doublecortin (DCX). The other half was used for Golgi staining to measure spine density and real-time quantitative reverse transcription-polymerase chain reaction to assess BDNF/TrkB expression levels. We found that morphine-treated rats exhibited more place conditioning as compared with saline-treated rats and animals that were exposed to the CPP without any injections. Locomotor activity did not change significantly. Morphine-induced CPP significantly increased the number of Ki67 and DCX-labeled cells in the ventral dentate gyrus. Additionally, we found increased dendritic spine density in both CA1 and dentate gyrus and an enhancement of BDNF/TrkB mRNA levels in the whole ventral hippocampus. Ki67, DCX and spine density were significantly correlated with CPP scores. In conclusion, we show that morphine-induced reward-related memory is associated with neural and synaptic plasticity changes in the ventral hippocampus. Such neural changes could underlie context-induced drug relapse. © 2017 Society for the Study of Addiction.

Integrated Proteomic Pipeline Using Multiple Search Engines for a Proteogenomic Study with a Controlled Protein False Discovery Rate.

PubMed

Park, Gun Wook; Hwang, Heeyoun; Kim, Kwang Hoe; Lee, Ju Yeon; Lee, Hyun Kyoung; Park, Ji Yeong; Ji, Eun Sun; Park, Sung-Kyu Robin; Yates, John R; Kwon, Kyung-Hoon; Park, Young Mok; Lee, Hyoung-Joo; Paik, Young-Ki; Kim, Jin Young; Yoo, Jong Shin

2016-11-04

In the Chromosome-Centric Human Proteome Project (C-HPP), false-positive identification by peptide spectrum matches (PSMs) after database searches is a major issue for proteogenomic studies using liquid-chromatography and mass-spectrometry-based large proteomic profiling. Here we developed a simple strategy for protein identification, with a controlled false discovery rate (FDR) at the protein level, using an integrated proteomic pipeline (IPP) that consists of four engrailed steps as follows. First, using three different search engines, SEQUEST, MASCOT, and MS-GF+, individual proteomic searches were performed against the neXtProt database. Second, the search results from the PSMs were combined using statistical evaluation tools including DTASelect and Percolator. Third, the peptide search scores were converted into E-scores normalized using an in-house program. Last, ProteinInferencer was used to filter the proteins containing two or more peptides with a controlled FDR of 1.0% at the protein level. Finally, we compared the performance of the IPP to a conventional proteomic pipeline (CPP) for protein identification using a controlled FDR of <1% at the protein level. Using the IPP, a total of 5756 proteins (vs 4453 using the CPP) including 477 alternative splicing variants (vs 182 using the CPP) were identified from human hippocampal tissue. In addition, a total of 10 missing proteins (vs 7 using the CPP) were identified with two or more unique peptides, and their tryptic peptides were validated using MS/MS spectral pattern from a repository database or their corresponding synthetic peptides. This study shows that the IPP effectively improved the identification of proteins, including alternative splicing variants and missing proteins, in human hippocampal tissues for the C-HPP. All RAW files used in this study were deposited in ProteomeXchange (PXD000395).

Efficacy of calcium- and fluoride-containing materials for the remineralization of primary teeth with early enamel lesion.

PubMed

Memarpour, Mahtab; Soltanimehr, Elham; Sattarahmady, Naghmeh

2015-09-01

The aim of the study was to determine the efficacy of different products containing fluoride, calcium and phosphate for enamel remineralization in eroded primary teeth. A total of 90 sound primary canine teeth were randomly divided into 5 groups of 18 teeth each: 1) control (polished enamel), 2) 5% DuraShield sodium fluoride varnish, 3) 500 ppm fluoridated toothpaste, 4) casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) cream, and 5) Clinpro White varnish containing functionalized tri-calcium phosphate (fTCP). Enamel microhardness (EMH) was measured in all samples before and after demineralization and after 28 days of remineralization. Also 8 samples in groups 2 to 5 and four samples of sound and demineralized enamel were examined with atomic force microscopy (AFM). All data were analyzed with one-way ANOVA (p<0.05). Mean microhardness of demineralized enamel was significantly lower than in enamel at baseline (p<0.001). Remineralization significantly increased microharness in groups 2 to 5 compared to the control group (p<0.001). Percent EMH after remineralization with CPP-ACP was significantly higher than after fTCP (p=0.029), toothpaste (p< 0.001) or fluoride varnish (p<0.001); however, there was no significant difference between toothpaste and fluoride varnish (p=0.062). Microhardness increased more after fTCP treatment than after treatment with sodium fluoride varnish (p<0.001) or fluoridated toothpaste (p=0.045). AFM images showed that enamel roughness decreased most after treatment with fTCP, followed by CPP-ACP, toothpaste and fluoride varnish. The efficacy of CPP-ACP cream for remineralizing eroded enamel was greater than fluoride toothpaste, fluoride varnish or fTCP varnish. © 2015 Wiley Periodicals, Inc.