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

PLAN SECTIONS AND ELEVATIONS OF VESSEL SAMPLING STATIONS "P", "Q", ...

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

PLAN SECTIONS AND ELEVATIONS OF VESSEL SAMPLING STATIONS "P", "Q", "S" CELLS MAIN PROCESSING BUILDING (CPP-601). INL DRAWING NUMBER 200-0601-00-291-053694. ALTERNATE ID NUMBER CPP-E-1394. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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

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

PLAN SECTIONS AND DETAILS OF CELL HATCHES MAIN PROCESSING BUILDING ...

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

PLAN SECTIONS AND DETAILS OF CELL HATCHES MAIN PROCESSING BUILDING (CPP-601). INL DRAWING NUMBER 200-0601-00-291-103256. ALTERNATE ID NUMBER 542-11-F-302. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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

BUILDING PLANS OF FUEL STORAGE BUILDING (CPP603). INL DRAWING NUMBER ...

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

BUILDING PLANS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103029. ALTERNATE ID NUMBER 542-31-B-21. - 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

AERIAL SHOWING COMPLETED REMOTE ANALYTICAL FACILITY (CPP627) ADJOINING FUEL PROCESSING ...

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

AERIAL SHOWING COMPLETED REMOTE ANALYTICAL FACILITY (CPP-627) ADJOINING FUEL PROCESSING BUILDING AND EXCAVATION FOR HOT PILOT PLANT TO RIGHT (CPP-640). INL PHOTO NUMBER NRTS-60-1221. J. Anderson, Photographer, 3/22/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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 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

MISCELLANEOUS SECTIONS AND DETAILS OF FUEL STORAGE BUILDING (CPP603). INL ...

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

MISCELLANEOUS SECTIONS AND DETAILS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103032. ALTERNATE ID NUMBER 542-31-B-24. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP603). PHOTO TAKEN LOOKING ...

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

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-20-1. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

WEST ELEVATIONS AND SECTIONS OF FUEL STORAGE BUILDING (CPP603). INL ...

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

WEST ELEVATIONS AND SECTIONS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-063-61-299-103031. ALTERNATE ID NUMBER 542-31-B-23. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SIDING AND ROOF DETAILS OF FUEL STORAGE BUILDING (CPP603). INL ...

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

SIDING AND ROOF DETAILS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103033. ALTERNATE ID NUMBER 542-31-B-25. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP603). PHOTO TAKEN LOOKING ...

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

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-20-3. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTHERN PORTION OF WEST ELEVATION OF FUEL STORAGE BUILDING (CPP603). ...

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

NORTHERN PORTION OF WEST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-20-4. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

OBLIQUE PHOTO OF NORTHWEST CORNER OF FUEL STORAGE BUILDING (CPP603). ...

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

OBLIQUE PHOTO OF NORTHWEST CORNER OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING SOUTHEAST. INL PHOTO NUMBER HD-54-14-4. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTHERN PORTION OF WEST ELEVATION OF FUEL STORAGE BUILDING (CPP603). ...

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

NORTHERN PORTION OF WEST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING SOUTHEAST. INL PHOTO NUMBER HD-54-20-2. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

VIEW OF FECF HOT CELL OF FUEL STORAGE BUILDING (CPP603). ...

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

VIEW OF FECF HOT CELL OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORHTWEST. INL PHOTO NUMBER HD-54-18-3. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

VIEW OF TRANSFER BASIN CORRIDOR OF FUEL STORAGE BUILDING (CPP603). ...

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

VIEW OF TRANSFER BASIN CORRIDOR OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTH. INL PHOTO NUMBER HD-54-17-2. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

OBLIQUE PHOTO OF NORTH ELEVATION OF FUEL STORAGE BUILDING (CPP603). ...

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

OBLIQUE PHOTO OF NORTH ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING SOUTH. INL PHOTO NUMBER HD-54-14-3. Mike Crane, Photographer, 8/2005 - 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

0BLIQUE PHOTO OF EAST ELEVATION OF FUEL STORAGE BUILDING (CPP603). ...

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

0BLIQUE PHOTO OF EAST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING WEST. INL PHOTO NUMBER HD-54-15-1. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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

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.

OBLIQUE PHOTO OF NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL ...

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

OBLIQUE PHOTO OF NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP-627) LOOKING SOUTHEAST. LABORATORY AND OFFICE BUILDING (CPP-602) APPEAR ON LEFT IN PHOTO. INL PHOTO NUMBER HD-22-2-2. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST ELEVATION OF HIGH BAY ADDITION OF FUEL STORAGE BUILDING ...

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

EAST ELEVATION OF HIGH BAY ADDITION OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-00-706-051286. - 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, EAST, NORTH ELEVATIONS AND SECTIONS OF FUEL STORAGE BUILDING ...

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

SOUTH, EAST, NORTH ELEVATIONS AND SECTIONS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103030. ALTERNATE ID NUMBER 542-31-B-22. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

INTERIOR OF SECOND FLOOR CONTROL ROOM OF FUEL STORAGE BUILDING ...

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

INTERIOR OF SECOND FLOOR CONTROL ROOM OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING SOUTHWEST. INL PHOTO NUMBER HD-54-19-2. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

10 CFR 434.601 - General.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 3 2014-01-01 2014-01-01 false General. 434.601 Section 434.601 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Building Energy Compliance Alternative § 434.601 General. 601.1 This subpart provides an...

10 CFR 434.601 - General.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false General. 434.601 Section 434.601 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Building Energy Compliance Alternative § 434.601 General. 601.1This subpart provides an...

10 CFR 434.601 - General.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 3 2012-01-01 2012-01-01 false General. 434.601 Section 434.601 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION ENERGY CODE FOR NEW FEDERAL COMMERCIAL AND MULTI-FAMILY HIGH RISE RESIDENTIAL BUILDINGS Building Energy Compliance Alternative § 434.601 General. 601.1This subpart provides an...

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

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.

VIEW OF CRANE LOADING AND UNLOADING AREA OF FUEL STORAGE ...

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

VIEW OF CRANE LOADING AND UNLOADING AREA OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTH. INL PHOTO NUMBER HD-54-17-4. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

VIEW OF CRANE LOADING AND UNLOADING AREA OF FUEL STORAGE ...

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

VIEW OF CRANE LOADING AND UNLOADING AREA OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING SOUTH. INL PHOTO NUMBER HD-54-17-1. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

VIEW OF SOUTH STORAGE BASIN NUMBER 1 OF FUEL STORAGE ...

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

VIEW OF SOUTH STORAGE BASIN NUMBER 1 OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-18-4. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

VIEW OF MIDDLE STORAGE BASIN NUMBER 2 OF FUEL STORAGE ...

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

VIEW OF MIDDLE STORAGE BASIN NUMBER 2 OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-17-3. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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

EAST/WEST TRUCK BAY AREA OF TRANSFER BASIN CORRIDOR OF FUEL ...

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

EAST/WEST TRUCK BAY AREA OF TRANSFER BASIN CORRIDOR OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHWEST. INL PHOTO NUMBER HD-54-19-1. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SPERTI Control Building (PER601) floor plan. Detail of cable inlet. ...

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

SPERT-I Control Building (PER-601) floor plan. Detail of cable inlet. Idaho Operations Office. Date: February 1955. INEEL index no. 760-0601-00-396-109139 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

SPERTI Control Building (PER601). Elevations. Note cable inlet on west ...

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

SPERT-I Control Building (PER-601). Elevations. Note cable inlet on west elevation. Idaho Operations Office. Date: February 1955. INEEL index no. 760-0601-00-396-109143 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

28 CFR 36.601 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.601... means a State law or local building code or similar ordinance, or part thereof, that establishes... designee. Certification of equivalency means a final certification that a code meets or exceeds the minimum...

28 CFR 36.601 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.601... means a State law or local building code or similar ordinance, or part thereof, that establishes... designee. Certification of equivalency means a final certification that a code meets or exceeds the minimum...

28 CFR 36.601 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ACCOMMODATIONS AND IN COMMERCIAL FACILITIES Certification of State Laws or Local Building Codes § 36.601... means a State law or local building code or similar ordinance, or part thereof, that establishes... designee. Certification of equivalency means a final certification that a code meets or exceeds the minimum...

SPERTI plot plan for control area. Includes Control Building (PER601), ...

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

SPERT-I plot plan for control area. Includes Control Building (PER-601), Gate House (PER-603), well sand settling tank, substation, and septic system. Date: February 1955. INEEL index no. 760-0101-00-396-109104 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

SPERTI Control Building (PER601) interior. Control panel with data readout ...

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

SPERT-I Control Building (PER-601) interior. Control panel with data readout equipment in control room. Panels and equipment were fabricated elsewhere at NRTS during SPERT-I construction. Photographer: R.G. Larsen. Date: November 21, 1955. INEEL negative no. 55-3208 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

A&M. Gate House (TAN601). Plan, elevations, sections, details. Shows expanded ...

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

A&M. Gate House (TAN-601). Plan, elevations, sections, details. Shows expanded building as attached to TAN-602. Ralph M. Parsons 902-2-ANP-601-A 22. Date: December 1952. INEEL index code no. 033-0602-00-693-106704 - Idaho National Engineering Laboratory, Test Area North, Scoville, Butte County, ID

19 CFR 10.601 - Retail packaging materials and containers.

Code of Federal Regulations, 2010 CFR

2010-04-01

...-Central America-United States Free Trade Agreement Rules of Origin § 10.601 Retail packaging materials and... Section 10.601 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... requirement. The United States importer of good C decides to use the build-down method, RVC = ((AV-VNM)/AV...

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.

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.

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

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.

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.

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

WEST ELEVATION OF REMOTE ANALYTICAL FACILITY (CPP627) AND HOT PILOT ...

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

WEST ELEVATION OF REMOTE ANALYTICAL FACILITY (CPP-627) AND HOT PILOT PLANT (CPP-640) LOOKING NORTHEAST. INL PHOTO NUMBER HD-22-2-1. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH ELEVATION OF HOT PILOT PLANT (CPP640) LOOKING SOUTH AFTER ...

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

NORTH ELEVATION OF HOT PILOT PLANT (CPP-640) LOOKING SOUTH AFTER REMOTE ANALYTICAL FACILITY (CPP-627) WAS REMOVED. PHOTO NUMBER HD-54-33-2. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP627) LOOKING ...

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

NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP-627) LOOKING SOUTHEAST. HEADEND PLANT (CPP-640) APPEARS IN THE BACKGROUND. INL PHOTO NUMBER HD-22-1-4. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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.

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

ARCHITECTURAL FLOOR PLAN OF PROCESS AND ACCESS AREAS HOT PILOT ...

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

ARCHITECTURAL FLOOR PLAN OF PROCESS AND ACCESS AREAS HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111679. ALTERNATE ID NUMBER 8952-CPP-640-A-2. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, 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.

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.

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

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.

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.

[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.

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627). INL PHOTO ...

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

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627). INL PHOTO NUMBER NRTS-54-12124. Unknown Photographer, 9/21/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

DETAILS OF REMOTE ANALYTICAL FACILITY (CPP627). INL DRAWING NUMBER 200062700098105071. ...

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

DETAILS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105071. ALTERNATE ID NUMBER 4272-14-108. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

MISCELLANEOUS ARCHITECTURAL DETAILS OF REMOTE ANALYTICAL FACILITY (CPP627). INL DRAWING ...

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

MISCELLANEOUS ARCHITECTURAL DETAILS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105631. ALTERNATE ID NUMBER 4272-814-134. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH ELEVATION OF HOT PILOT PLANT (CPP640) LOOKING NORTH. INL ...

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

SOUTH ELEVATION OF HOT PILOT PLANT (CPP-640) LOOKING NORTH. INL PHOTO NUMBER HD-22-3-1. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627). INL PHOTO ...

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

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627). INL PHOTO NUMBER NRTS-54-12573. R.G. Larsen, Photographer, 10/20/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627) SHOWING INITIAL ...

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

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING INITIAL EXCAVATION. INL PHOTO NUMBER NRTS-54-10703. Unknown Photographer, 5/21/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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.

MISCELLANEOUS ARCHITECTURAL DETAILS AND SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP627). ...

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

MISCELLANEOUS ARCHITECTURAL DETAILS AND SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105632. ALTERNATE ID NUMBER 4272-814-135. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH AND SOUTH SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP627). INL ...

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

NORTH AND SOUTH SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105068. ALTERNATE ID NUMBER 4272-14-105. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP627). INL ...

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

EAST AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105067. ALTERNATE ID NUMBER 4272-14-104. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627) SHOWING PLACEMENT ...

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

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING PLACEMENT OF PIERS. INL PHOTO NUMBER NRTS-54-11716. Unknown Photographer, 8/20/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

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.

16. Historic American Buildings Survey, Bill Engdahl for HedrichBlessing, Photographers, ...

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

16. Historic American Buildings Survey, Bill Engdahl for Hedrich-Blessing, Photographers, February, 1979 DRINKING FOUNTAIN WITH PEACOCK AND GRAPEVINE SPLASH PANEL. - Southern Pacific Railroad Passenger Station, 601 East Madison Street, Brownsville, Cameron County, TX

49 CFR 601.46 - Processing of petitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Processing of petitions. 601.46 Section 601.46 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ORGANIZATION, FUNCTIONS, AND PROCEDURES Emergency Procedures for Public...

CONSTRUCTION PROGRESS PHOTO REMOTE ANALYTICAL FACILITY (CPP627) SHOWING EMPLACEMENT OF ...

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

CONSTRUCTION PROGRESS PHOTO REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING EMPLACEMENT OF ROOF SLABS. INL PHOTO NUMBER NRTS-54-13463. R.G. Larsen, Photographer, 12/20/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

ARCHITECTURAL SECTIONS A, B, C, D, OF HOT PILOT PLANT ...

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

ARCHITECTURAL SECTIONS A, B, C, D, OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111681. ALTERNATE ID NUMBER 8952-CPP-640-A-5. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

15. Historic American Buildings Survey, Bill Engdahl for HedrichBlessing, Photographers, ...

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

15. Historic American Buildings Survey, Bill Engdahl for Hedrich-Blessing, Photographers, February, 1979 DRINKING FOUNTAIN WITH CHILDREN AND PAN PIPES IN SPLASH PANEL. - Southern Pacific Railroad Passenger Station, 601 East Madison Street, Brownsville, Cameron County, TX

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP640) OVERALL VIEW ...

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

CONSTRUCTION PROGRESS PHOTO OF HOT PILOT PLANT (CPP-640) OVERALL VIEW LOOKING SOUTHEAST; CONSTRUCTION 34 PERCENT COMPLETE. INL PHOTO NUMBER NRTS-60-3034. Holmes, Photographer, 6/23/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

ARCHITECTURAL ROOF PLAN AND WESTSOUTHEAST ELEVATIONS OF HOT PILOT PLANT ...

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

ARCHITECTURAL ROOF PLAN AND WEST-SOUTHEAST ELEVATIONS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111680. ALTERNATE ID NUMBER 8952-CPP-640-A-3. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

GFP-complementation assay to detect functional CPP and protein delivery into living cells

PubMed Central

Milech, Nadia; Longville, Brooke AC; Cunningham, Paula T; Scobie, Marie N; Bogdawa, Heique M; Winslow, Scott; Anastasas, Mark; Connor, Theresa; Ong, Ferrer; Stone, Shane R; Kerfoot, Maria; Heinrich, Tatjana; Kroeger, Karen M; Tan, Yew-Foon; Hoffmann, Katrin; Thomas, Wayne R; Watt, Paul M; Hopkins, Richard M

2015-01-01

Efficient cargo uptake is essential for cell-penetrating peptide (CPP) therapeutics, which deliver widely diverse cargoes by exploiting natural cell processes to penetrate the cell’s membranes. Yet most current CPP activity assays are hampered by limitations in assessing uptake, including confounding effects of conjugated fluorophores or ligands, indirect read-outs requiring secondary processing, and difficulty in discriminating internalization from endosomally trapped cargo. Split-complementation Endosomal Escape (SEE) provides the first direct assay visualizing true cytoplasmic-delivery of proteins at biologically relevant concentrations. The SEE assay has minimal background, is amenable to high-throughput processes, and adaptable to different transient and stable cell lines. This split-GFP-based platform can be useful to study transduction mechanisms, cellular imaging, and characterizing novel CPPs as pharmaceutical delivery agents in the treatment of disease. PMID:26671759

Changes of protein expression profiles in the amygdala during the process of morphine-induced conditioned place preference in rats.

PubMed

Lin, XiaoJing; Wang, QingSong; Cheng, Yong; Ji, JianGuo; Yu, Long-Chuan

2011-08-01

Repeated exposures to addictive drugs result in persistent or even permanent expression changes of proteins in addiction-related brain regions, such as nucleus accumbens, hippocampus and prefrontal cortex while the changes of protein content in amygdala were seldom studied. Here we aimed to find the proteins involved in the process of morphine-induced conditioned place preference (CPP). The model of morphine-induced CPP was established in rats and the rat amygdala tissues were obtained in different stages of morphine-induced CPP: establishment group, extinction group, reinstatement group and saline group as a control. Two-dimensional electrophoresis (2-DE) was performed to analyze and compare the changes of protein expression profiles in the amygdala of rats during the process of morphine-induced CPP. There were eighty proteins with 1.3-fold changes in amygdala relative to saline group, most of which were down-regulated. These differentially expressed proteins were mainly involved in metabolism, structure, cell signaling pathway and ubiquitin-proteasome pathway. And we further used methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting to confirm the results of proteomics. Mitosis activated protein kinase1 (MAPK1) was increased in the stages of extinction and reinstatement of morphine-induced CPP, while glial fibrillary acidic protein (GFAP) was decreased in the stage of extinction. Our results provide some proteins and cellular signaling pathways involved in the molecular mechanisms of opioid addiction in amygdala. Copyright © 2011 Elsevier B.V. All rights reserved.

FIRST FLOOR PLAN OF REMOTE ANALYTICAL FACILITY (CPP627) SHOWING REMOTE ...

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

FIRST FLOOR PLAN OF REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING REMOTE ANALYTICAL LABORATORY, DECONTAMINATION ROOM, AND MULTICURIE CELL ROOM. INL DRAWING NUMBER 200-0627-00-008-105065. ALTERNATE ID NUMBER 4272-14-102. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, 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

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.

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.

Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32.

PubMed Central

Slee, E A; Zhu, H; Chow, S C; MacFarlane, M; Nicholson, D W; Cohen, G M

1996-01-01

Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases. PMID:8670109

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.

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

SECOND FLOOR PLAN OF REMOTE ANALYTICAL FACILITY (CPP627) WARM LABORATORY ...

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

SECOND FLOOR PLAN OF REMOTE ANALYTICAL FACILITY (CPP-627) WARM LABORATORY ROOM, DECONTAMINATION ROOM, HOT CHEMISTRY LABORATORY, AND MULTICURIE CELL ROOM. INL DRAWING NUMBER 200-0627-00-098-105066. ALTERNATE ID NUMBER 4272-14-103. - 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

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.

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.

Implementation of quality by design principles in the development of microsponges as drug delivery carriers: Identification and optimization of critical factors using multivariate statistical analyses and design of experiments studies.

PubMed

Simonoska Crcarevska, Maja; Dimitrovska, Aneta; Sibinovska, Nadica; Mladenovska, Kristina; Slavevska Raicki, Renata; Glavas Dodov, Marija

2015-07-15

Microsponges drug delivery system (MDDC) was prepared by double emulsion-solvent-diffusion technique using rotor-stator homogenization. Quality by design (QbD) concept was implemented for the development of MDDC with potential to be incorporated into semisolid dosage form (gel). Quality target product profile (QTPP) and critical quality attributes (CQA) were defined and identified, accordingly. Critical material attributes (CMA) and Critical process parameters (CPP) were identified using quality risk management (QRM) tool, failure mode, effects and criticality analysis (FMECA). CMA and CPP were identified based on results obtained from principal component analysis (PCA-X&Y) and partial least squares (PLS) statistical analysis along with literature data, product and process knowledge and understanding. FMECA identified amount of ethylcellulose, chitosan, acetone, dichloromethane, span 80, tween 80 and water ratio in primary/multiple emulsions as CMA and rotation speed and stirrer type used for organic solvent removal as CPP. The relationship between identified CPP and particle size as CQA was described in the design space using design of experiments - one-factor response surface method. Obtained results from statistically designed experiments enabled establishment of mathematical models and equations that were used for detailed characterization of influence of identified CPP upon MDDC particle size and particle size distribution and their subsequent optimization. Copyright © 2015 Elsevier B.V. All rights reserved.

Mediodorsal nucleus of the thalamus is critical for the expression of memory of methamphetamine-produced conditioned place preference in rats.

PubMed

Kuo, C-S; Chai, S-C; Chen, H-H

2011-03-31

Methamphetamine (MA) is a powerful and highly addictive psychostimulant. However, the neural substrate mediating MA-induced conditioned effects, an essential part of addiction, remain unclear. The present study investigated the involvement of the anterior cingulate cortex (ACC), the lateral nucleus of amygdala (LNA), and the mediodorsal nucleus of the thalamus (MD) in MA-conditioned place preference (CPP). Rats underwent bilateral radio-frequency lesions of the ACC, LNA, or MD followed by MA CPP training. Lesions of the MD, but not the ACC or LNA, disrupted MA CPP learning. To clarify the role of the MD on the different stages of the MA CPP memory process, bilateral microinfusions of lidocaine into the MD were performed 5 min prior to each conditioning trial, immediately after the conditioning trial, or 5 min before the testing phase. Pretesting, but not pre- or post-conditioning, infusions of lidocaine into the MD impaired MA CPP. Furthermore, a clear preference for the previously conditioned MA paired cues was expressed when the rats were tested again 24 h after infusions of lidocaine. These results are interpreted as indicating that the MD is specifically involved in the memory retrieval process of MA associated memory which suggests the MD could have an important role in relapse in individuals suffering from MA addiction. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

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.

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

Relation of structural and vibratory kinematics of the vocal folds to two acoustic measures of breathy voice based on computational modeling

PubMed Central

Samlan, Robin A.; Story, Brad H.

2011-01-01

Purpose To relate vocal fold structure and kinematics to two acoustic measures: cepstral peak prominence (CPP) and the amplitude of the first harmonic relative to the second (H1-H2). Method A computational, kinematic model of the medial surfaces of the vocal folds was used to specify features of vocal fold structure and vibration in a manner consistent with breathy voice. Four model parameters were altered: degree of vocal fold adduction, surface bulging, vibratory nodal point, and supraglottal constriction. CPP and H1-H2 were measured from simulated glottal area, glottal flow and acoustic waveforms and related to the underlying vocal fold kinematics. Results CPP decreased with increased separation of the vocal processes, whereas the nodal point location had little effect. H1-H2 increased as a function of separation of the vocal processes in the range of 1–1.5 mm and decreased with separation > 1.5 mm. Conclusions CPP is generally a function of vocal process separation. H1*-H2* will increase or decrease with vocal process separation based on vocal fold shape, pivot point for the rotational mode, and supraglottal vocal tract shape, limiting its utility as an indicator of breathy voice. Future work will relate the perception of breathiness to vocal fold kinematics and acoustic measures. PMID:21498582

POST-RETRIEVAL PROPRANOLOL TREATMENT DOES NOT MODULATE RECONSOLIDATION OR EXTINCTION OF ETHANOL-INDUCED CONDITIONED PLACE PREFERENCE

PubMed Central

Font, Laura; Cunningham, Christopher L.

2012-01-01

The reconsolidation hypothesis posits that established emotional memories, when reactivated, become labile and susceptible to disruption. Post-retrieval injection of propranolol (PRO), a nonspecific β-adrenergic receptor antagonist, impairs subsequent retention performance of a cocaine- and a morphine-induced conditioned place preference (CPP), implicating the noradrenergic system in the reconsolidation processes of drug-seeking behavior. An important question is whether post-retrieval PRO disrupts memory for the drug-cue associations, or instead interferes with extinction. In the present study, we evaluated the role of the β-adrenergic system on the reconsolidation and extinction of ethanol-induced CPP. Male DBA/2J mice were trained using a weak or a strong conditioning procedure, achieved by varying the ethanol conditioning dose (1 or 2 g/kg) and the number of ethanol trials (2 or 4). After acquisition of ethanol CPP, animals were given a single post-retrieval injection of PRO (0, 10 or 30 mg/kg) and tested for memory reconsolidation 24 h later. Also, after the first reconsolidation test, mice received 18 additional 15-min choice extinction tests in which PRO was injected immediately after every test. Contrary to the prediction of the reconsolidation hypothesis, a single PRO injection after the retrieval test did not modify subsequent memory retention. In addition, repeated post-retrieval administration of PRO did not interfere with extinction of CPP in mice. Overall, our data suggest that the β-adrenergic receptor does not modulate the associative processes underlying ethanol CPP. PMID:22285323

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.

Relation of structural and vibratory kinematics of the vocal folds to two acoustic measures of breathy voice based on computational modeling.

PubMed

Samlan, Robin A; Story, Brad H

2011-10-01

To relate vocal fold structure and kinematics to 2 acoustic measures: cepstral peak prominence (CPP) and the amplitude of the first harmonic relative to the second (H1-H2). The authors used a computational, kinematic model of the medial surfaces of the vocal folds to specify features of vocal fold structure and vibration in a manner consistent with breathy voice. Four model parameters were altered: degree of vocal fold adduction, surface bulging, vibratory nodal point, and supraglottal constriction. CPP and H1-H2 were measured from simulated glottal area, glottal flow, and acoustic waveforms and were related to the underlying vocal fold kinematics. CPP decreased with increased separation of the vocal processes, whereas the nodal point location had little effect. H1-H2 increased as a function of separation of the vocal processes in the range of 1.0 mm to 1.5 mm and decreased with separation > 1.5 mm. CPP is generally a function of vocal process separation. H1*-H2* (see paragraph 6 of article text for an explanation of the asterisks) will increase or decrease with vocal process separation on the basis of vocal fold shape, pivot point for the rotational mode, and supraglottal vocal tract shape, limiting its utility as an indicator of breathy voice. Future work will relate the perception of breathiness to vocal fold kinematics and acoustic measures.

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

36 CFR 60.1 - Authorization and expansion of the National Register.

Code of Federal Regulations, 2010 CFR

2010-07-01

... districts, sites, buildings, structures, and objects significant in American history, architecture, archeology, engineering and culture. The regulations herein set forth the procedural requirements for listing...

75 FR 9434 - Civil Rights Division, Disability Rights Section; Agency Information Collection Activities Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-02

... Rights (or his or her designee) may certify that a State or local building code or similar ordinance that establishes accessibility requirements (Code) meets or exceeds the minimum requirements of the ADA for..., Policy and Planning Staff, Justice Management Division, Patrick Henry Building, Suite 1600, 601 D Street...

75 FR 27816 - Civil Rights Division, Disability Rights Section; Agency Information Collection Activities Under...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... certify that a State or local building code or similar ordinance that establishes accessibility requirements (Code) meets or exceeds the minimum requirements of the ADA for accessibility and usability of... Management Division, Patrick Henry Building, Suite 1600, 601 D Street, NW., Washington, DC 20530. Dated: May...

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.

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

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.

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.

PBF contextual view shows relationship between PBF Control Building (PER619, ...

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

PBF contextual view shows relationship between PBF Control Building (PER-619, in foreground at right) and SPERT-I Control Building (PER-601). Walkway with railing connects to waste reduction operations support building (PER-632), built in 1981. Note paneled stucco siding applied to PER-619 after 1980. Original concrete block is exposed at corner. Date: July 2004. INEEL negative no. HD-41-9-2 - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

21 CFR 601.14 - Regulatory submissions in electronic format.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Regulatory submissions in electronic format. 601... SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.14 Regulatory submissions in electronic format. (a) General. Electronic format submissions must be in a form that FDA can process, review, and...

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.

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.

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.

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.

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.

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.

Effectiveness of sodium bicarbonate combined with hydrogen peroxide and CPP-ACPF in whitening and microhardness of enamel.

PubMed

Ahrari, Farzaneh; Hasanzadeh, Nadia; Rajabi, Omid; Forouzannejad, Zakiyeh

2017-03-01

This study investigated the effects of sodium bicarbonate (NaHCO3) combined with 1.5% hydrogen peroxide (H2O2) and casein phosphopeptide amorphous calcium phosphate fluoride (CPP-ACPF) on color and microhardness of enamel. Seventy-five bovine incisors were immersed in a tea solution for 7.5 days. The specimens were randomly divided into five groups according to the whitening agent applied: 1) 94% NaHCO3, 2) a blend of 94% NaHCO3 and CPP-ACPF, 3) a blend of 94% NaHCO3 and 1.5% H2O2, 4) a blend of 94% NaHCO3, 1.5% H2O2 and CPP-ACPF, 5) control. The whitening procedure was performed for 10 times over 10 days. At each day, the buccal surfaces were covered with whitening agents for 5 minutes and then brushed for 30 seconds. After the 10 days, the teeth were again immersed in a tea solution for 10 minutes. Color assessment was performed at baseline (T1), after the first staining process (T2), after the whitening procedure (T3), and after the second staining process (T4). Finally, the specimens were subjected to microhardness test. There was a statistically significant difference in the color change between T2 and T3 stages among the study groups ( p <0.05), with the greatest improvement observed in group 4. Microhardness was significantly greater in groups 2 and 4, as compared to the other groups ( p <0.05). The combination of 94% NaHCO3, 1.5% H2O2 and CPP-ACPF was effective in improving color and microhardness of teeth with extrinsic stains and could be recommended in the clinical situation.

Effectiveness of sodium bicarbonate combined with hydrogen peroxide and CPP-ACPF in whitening and microhardness of enamel

PubMed Central

Hasanzadeh, Nadia; Rajabi, Omid; Forouzannejad, Zakiyeh

2017-01-01

Background This study investigated the effects of sodium bicarbonate (NaHCO3) combined with 1.5% hydrogen peroxide (H2O2) and casein phosphopeptide amorphous calcium phosphate fluoride (CPP-ACPF) on color and microhardness of enamel. Material and Methods Seventy-five bovine incisors were immersed in a tea solution for 7.5 days. The specimens were randomly divided into five groups according to the whitening agent applied: 1) 94% NaHCO3, 2) a blend of 94% NaHCO3 and CPP-ACPF, 3) a blend of 94% NaHCO3 and 1.5% H2O2, 4) a blend of 94% NaHCO3, 1.5% H2O2 and CPP-ACPF, 5) control. The whitening procedure was performed for 10 times over 10 days. At each day, the buccal surfaces were covered with whitening agents for 5 minutes and then brushed for 30 seconds. After the 10 days, the teeth were again immersed in a tea solution for 10 minutes. Color assessment was performed at baseline (T1), after the first staining process (T2), after the whitening procedure (T3), and after the second staining process (T4). Finally, the specimens were subjected to microhardness test. Results There was a statistically significant difference in the color change between T2 and T3 stages among the study groups (p<0.05), with the greatest improvement observed in group 4. Microhardness was significantly greater in groups 2 and 4, as compared to the other groups (p<0.05). Conclusions The combination of 94% NaHCO3, 1.5% H2O2 and CPP-ACPF was effective in improving color and microhardness of teeth with extrinsic stains and could be recommended in the clinical situation. PMID:28298972

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

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.

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.

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.

26 CFR 601.105 - Examination of returns and claims for refund, credit or abatement; determination of correct tax...

Code of Federal Regulations, 2010 CFR

2010-04-01

..., credit or abatement; determination of correct tax liability. 601.105 Section 601.105 Internal Revenue... abatement; determination of correct tax liability. (a) Processing of returns. When the returns are filed in... made for the payment of any additional tax so resulting, or refund is made of any overpayment. Returns...

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.

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.

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).

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.

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.

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.

7 CFR 1.601 - What is the purpose of this subpart, and to what license proceedings does it apply?

Code of Federal Regulations, 2010 CFR

2010-01-01

... license proceedings does it apply? 1.601 Section 1.601 Agriculture Office of the Secretary of Agriculture... of this subpart, and to what license proceedings does it apply? (a) Hearing process. (1) The... section 4(e). (c) Reservation of authority. Where the Forest Service notifies FERC that it is reserving...

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

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.

Relation of perceived breathiness to laryngeal kinematics and acoustic measures based on computational modeling

PubMed Central

Samlan, Robin A.; Story, Brad H.; Bunton, Kate

2014-01-01

Purpose To determine 1) how specific vocal fold structural and vibratory features relate to breathy voice quality and 2) the relation of perceived breathiness to four acoustic correlates of breathiness. Method A computational, kinematic model of the vocal fold medial surfaces was used to specify features of vocal fold structure and vibration in a manner consistent with breathy voice. Four model parameters were altered: vocal process separation, surface bulging, vibratory nodal point, and epilaryngeal constriction. Twelve naïve listeners rated breathiness of 364 samples relative to a reference. The degree of breathiness was then compared to 1) the underlying kinematic profile and 2) four acoustic measures: cepstral peak prominence (CPP), harmonics-to-noise ratio, and two measures of spectral slope. Results Vocal process separation alone accounted for 61.4% of the variance in perceptual rating. Adding nodal point ratio and bulging to the equation increased the explained variance to 88.7%. The acoustic measure CPP accounted for 86.7% of the variance in perceived breathiness, and explained variance increased to 92.6% with the addition of one spectral slope measure. Conclusions Breathiness ratings were best explained kinematically by the degree of vocal process separation and acoustically by CPP. PMID:23785184

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.

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

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.

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.

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.

[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.

Hypoxia facilitates neurogenic dural plasma protein extravasation in mice: a novel animal model for migraine pathophysiology

PubMed Central

Hunfeld, Anika; Segelcke, Daniel; Bäcker, Ingo; Mecheri, Badreddine; Hemmer, Kathrin; Dlugosch, Elisabeth; Andriske, Michael; Paris, Frank; Zhu, Xinran; Lübbert, Hermann

2015-01-01

Migraine animal models generally mimic the onset of attacks and acute treatment processes. A guinea pig model used the application of meta-chlorophenylpiperazine (mCPP) to trigger immediate dural plasma protein extravasation (PPE) mediated by 5-HT2B receptors. This model has predictive value for antimigraine drugs but cannot explain the delayed onset of efficacy of 5-HT2B receptor antagonists when clinically used for migraine prophylaxis. We found that mCPP failed to induce dural PPE in mice. Considering the role 5-HT2B receptors play in hypoxia-induced pulmonary vessel muscularization, we were encouraged to keep mice under hypoxic conditions and tested whether this treatment will render them susceptible to mCPP-induced dural PPE. Following four-week of hypoxia, PPE, associated with increased transendothelial transport, was induced by mCPP. The effect was blocked by sumatriptan. Chronic application of 5-HT2B receptor or nitric oxide synthase blockers during hypoxia prevented the development of susceptibility. Here we present a migraine model that distinguishes between a migraine-like state (hypoxic mice) and normal, normoxic mice and mimics processes that are related to chronic activation of 5-HT2B receptors under hypoxia. It seems striking, that chronic endogenous activation of 5-HT2B receptors is crucial for the sensitization since 5-HT2B receptor antagonists have strong, albeit delayed migraine prophylactic efficacy. PMID:26644235

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.

The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice.

PubMed

Martínez-Rivera, Freddyson J; Natal-Albelo, Eduardo J; Martínez, Namyr A; Orozco-Vega, Roberto A; Muñiz-Seda, Oscar A; Barreto-Estrada, Jennifer L

2015-04-01

Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking their anabolic effects, even though later on, many could develop neuropsychological dependence. Previously, we have shown that nandrolone induces conditioned place preference (CPP) in adult male mice. However, whether nandrolone induces CPP during adolescence remains unknown. In this study, the CPP test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for reward-related processes, the effect of nandrolone on the expression of D1DR in the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to our previous results, nandrolone induced CPP in adults. However, in adolescents, nandrolone failed to produce place preference. At the molecular level, nandrolone decreased D1DR expression in the NAc only in adult mice. Our data suggest that nandrolone may not be rewarding in adolescents at least during short-term use. The lack of nandrolone rewarding effects in adolescents may be due, in part to differences in D1DR expression during development. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of the anabolic steroid, nandrolone, in conditioned place preference and D1 dopamine receptor expression in adolescent and adult mice

PubMed Central

Martínez-Rivera, Freddyson J.; Natal-Albelo, Eduardo J.; Martínez, Namyr A.; Orozco-Vega, Roberto A.; Muñiz-Seda, Oscar A.; Barreto-Estrada, Jennifer L.

2015-01-01

Adolescents and adults engage in anabolic-androgenic steroid (AAS) misuse seeking their anabolic effects, even though later on, many could develop neuropsychological dependence. Previously, we have shown that nandrolone induces conditioned place preference (CPP) in adult male mice. However, whether nandrolone induces CPP during adolescence remains unknown. In this study, the CPP test was used to determine the rewarding properties of nandrolone (7.5 mg/kg) in adolescent mice. In addition, since D1 dopamine receptors (D1DR) are critical for reward-related processes, the effect of nandrolone on the expression of D1DR in the nucleus accumbens (NAc) was investigated by Western blot analysis. Similar to our previous results, nandrolone induced CPP in adults. However, in adolescents, nandrolone failed to produce place preference. At the molecular level, nandrolone decreased D1DR expression in the NAc only in adult mice. Our data suggest that nandrolone may not be rewarding in adolescents at least during short-term use. The lack of nandrolone rewarding effects in adolescents may be due, in part to differences in D1DR expression during development. PMID:25612844

Drug-seeking behavior in an invertebrate system: evidence of morphine-induced reward, extinction and reinstatement in crayfish

PubMed Central

Nathaniel, Thomas I.; Panksepp, Jules; Huber, Robert

2009-01-01

Several lines of evidence suggest that exploring the neurochemical basis of reward in invertebrate species may provide clues for the fundamental behavioral and neurobiology underpinnings of drug addiction. How the presence of drug-sensitive reward relates to a decrease in drug-seeking behavior and reinstatement of drug seeking behavior in invertebrate systems is not known. The present study of a conditioned place preference (CPP) paradigm in crayfish (Orconectes rusticus) explores morphine-induced reward, extinction and reinstatement. Repeated intra-circulatory infusions of 2.5μg/g, 5.0μg/g and 10.0μg/g doses of morphine over 5 days serve as a reward when paired with a distinct visual or tactile environment. Morphine-induced CPP was extinguished after repeated saline injections for 5 days in the previously morphine-paired compartment. After the previously established CPP had been eliminated during the extinction phase, morphine-experienced crayfish were challenged with 2.5 μg/g, 5.0 μg/g and 10.0 μg/g respectively. The priming injections of morphine reinstated CPP in all training doses, suggesting that morphine-induced CPP is unrelenting, and that with time, it can be reinstated by morphine following extinction in an invertebrate model just like in mammals. Together with other recent studies, this work demonstrates the advantage of using crayfish as an invertebrate animal model to investigate the basic biological processes that underline exposure to mammalian drugs of abuse. PMID:18822319

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.

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.

SPERT1. Contextual aerial view of SPERTI Reactor Pit Building (PER605) ...

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

SPERT-1. Contextual aerial view of SPERT-I Reactor Pit Building (PER-605) at top of view, and its accessories: the earth-shielded instrument cell (PER-606) immediately adjacent to it; the Guard House (PER-607) to its right; and the Terminal Building in lower center of view (PER-604). Camera faces west. Road and buried line leaving view at right lead to Control Building (PER-601) out of view. Sagebrush vegetation has been scraped from around buildings. Photographer: R.G. Larsen. Date: June 6, 1955. INEEL negative no. 55-1477. - Idaho National Engineering Laboratory, SPERT-I & Power Burst Facility Area, Scoville, Butte County, ID

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.

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.

WADeG Cell Phone

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

2009-09-01

The on cell phone software captures the images from the CMOS camera periodically, stores the pictures, and periodically transmits those images over the cellular network to the server. The cell phone software consists of several modules: CamTest.cpp, CamStarter.cpp, StreamIOHandler .cpp, and covertSmartDevice.cpp. The camera application on the SmartPhone is CamStarter, which is "the" user interface for the camera system. The CamStarter user interface allows a user to start/stop the camera application and transfer files to the server. The CamStarter application interfaces to the CamTest application through registry settings. Both the CamStarter and CamTest applications must be separately deployed on themore » smartphone to run the camera system application. When a user selects the Start button in CamStarter, CamTest is created as a process. The smartphone begins taking small pictures (CAPTURE mode), analyzing those pictures for certain conditions, and saving those pictures on the smartphone. This process will terminate when the user selects the Stop button. The camtest code spins off an asynchronous thread, StreamIOHandler, to check for pictures taken by the camera. The received image is then tested by StreamIOHandler to see if it meets certain conditions. If those conditions are met, the CamTest program is notified through the setting of a registry key value and the image is saved in a designated directory in a custom BMP file which includes a header and the image data. When the user selects the Transfer button in the CamStarter user interface, the covertsmartdevice code is created as a process. Covertsmartdevice gets all of the files in a designated directory, opens a socket connection to the server, sends each file, and then terminates.« less

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.

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.

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.

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.

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.

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.

[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.

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.

25 CFR 115.601 - Under what circumstances may the BIA restrict your IIM account through supervision or an...

Code of Federal Regulations, 2013 CFR

2013-04-01

... property, including your financial affairs;” or (3) Determines through an administrative process that you..., DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES TRUST FUNDS FOR TRIBES AND INDIVIDUAL INDIANS IIM Accounts: Hearing Process for Restricting an IIM Account § 115.601 Under what circumstances may the BIA restrict...

25 CFR 115.601 - Under what circumstances may the BIA restrict your IIM account through supervision or an...

Code of Federal Regulations, 2012 CFR

2012-04-01

... property, including your financial affairs;” or (3) Determines through an administrative process that you..., DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES TRUST FUNDS FOR TRIBES AND INDIVIDUAL INDIANS IIM Accounts: Hearing Process for Restricting an IIM Account § 115.601 Under what circumstances may the BIA restrict...

25 CFR 115.601 - Under what circumstances may the BIA restrict your IIM account through supervision or an...

Code of Federal Regulations, 2014 CFR

2014-04-01

... property, including your financial affairs;” or (3) Determines through an administrative process that you..., DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES TRUST FUNDS FOR TRIBES AND INDIVIDUAL INDIANS IIM Accounts: Hearing Process for Restricting an IIM Account § 115.601 Under what circumstances may the BIA restrict...

25 CFR 115.601 - Under what circumstances may the BIA restrict your IIM account through supervision or an...

Code of Federal Regulations, 2011 CFR

2011-04-01

... property, including your financial affairs;” or (3) Determines through an administrative process that you..., DEPARTMENT OF THE INTERIOR FINANCIAL ACTIVITIES TRUST FUNDS FOR TRIBES AND INDIVIDUAL INDIANS IIM Accounts: Hearing Process for Restricting an IIM Account § 115.601 Under what circumstances may the BIA restrict...

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.

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.

28 CFR 42.601 - Purpose and application.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 42.601 Judicial Administration DEPARTMENT OF JUSTICE NONDISCRIMINATION; EQUAL EMPLOYMENT OPPORTUNITY; POLICIES AND PROCEDURES Procedures for Complaints of Employment Discrimination Filed Against Recipients of... procedures for processing and resolving complaints of employment discrimination filed against recipients of...

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.

Optimization of the Efficiency of a Neutron Detector to Measure (α, n) Reaction Cross-Section

NASA Astrophysics Data System (ADS)

Perello, Jesus; Montes, Fernando; Ahn, Tony; Meisel, Zach; Joint InstituteNuclear Astrophysics Team

2015-04-01

Nucleosynthesis, the origin of elements, is one of the greatest mysteries in physics. A recent particular nucleosynthesis process of interest is the charge-particle process (cpp). In the cpp, elements form by nuclear fusion reactions during supernovae. This process of nuclear fusion, (α,n), will be studied by colliding beam elements produced and accelerated at the National Superconducting Cyclotron Laboratory (NSCL) to a helium-filled cell target. The elements will fuse with α (helium nuclei) and emit neutrons during the reaction. The neutrons will be detected for a count of fused-elements, thus providing us the probability of such reactions. The neutrons will be detected using the Neutron Emission Ratio Observer (NERO). Currently, NERO's efficiency varies for neutrons at the expected energy range (0-12 MeV). To study (α,n), NERO's efficiency must be near-constant at these energies. Monte-Carlo N-Particle Transport Code (MCNP6), a software package that simulates nuclear processes, was used to optimize NERO configuration for the experiment. MCNP6 was used to simulate neutron interaction with different NERO configurations at the expected neutron energies. By adding additional 3He detectors and polyethylene, a near-constant efficiency at these energies was obtained in the simulations. With the new NERO configuration, study of the (α,n) reactions can begin, which may explain how elements are formed in the cpp. SROP MSU, NSF, JINA, McNair Society.

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.

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.

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

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

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

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

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.

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.

25 CFR 115.601 - Under what circumstances may the BIA restrict your IIM account through supervision or an...

Code of Federal Regulations, 2010 CFR

2010-04-01

...: Hearing Process for Restricting an IIM Account § 115.601 Under what circumstances may the BIA restrict... property, including your financial affairs;” or (3) Determines through an administrative process that you are an adult in need of assistance based on a finding by a licensed medical or mental health...

5. Photocopy of War Department drawing (original located at Fort ...

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

5. Photocopy of War Department drawing (original located at Fort McCoy, Wisconsin), GASOLINE STATION AND PUMP HOUSE, PLAN NUMBER 800-601 - Fort McCoy, Building No. T-1467, 1300' East of Intersection of South Ninth Avenue with South "J" Street, Sparta, Monroe County, WI

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

Extended Policies case

EIA Publications

2016-01-01

The Annual Energy Outlook 2016 (AEO2016) Extended Policies case includes selected policies that go beyond current laws and regulations. Existing tax credits that have scheduled reductions and sunset dates are assumed to remain unchanged through 2040. Other efficiency policies, including corporate average fuel economy standards, appliance standards, and building codes, are expanded beyond current provisions; and the U.S. Environmental Protection Agency (EPA) Clean Power Plan (CPP) regulations that reduce carbon dioxide emissions from electric power generation are tightened after 2030.

Covert Channels within IRC

DTIC Science & Technology

2011-03-24

in the secret file in bits. Therefore, CPP is a function of the size of the secret file and amount of covert information embedded per packet, while...CPS is dependent on the size of the secret file and the rate at which the covert packets are transmitted to the IRC server. • Build a covert...and decode a secret message. • Cover. The object being used to hide the secret information; this is often in the form of pictures [FPK07], audio

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.

20 CFR 422.601 - Scope and purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Employees' Benefits SOCIAL SECURITY ADMINISTRATION ORGANIZATION AND PROCEDURES Administrative Review Process Under the Coal Industry Retiree Health Benefit Act of 1992 § 422.601 Scope and purpose. The regulations in this subpart describe how the Social Security Administration (SSA) will conduct reviews of...

49 CFR 601.2 - Organization of the administration.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., and U.S. Virgin Islands FTA Regional Administrator, One Bowling Green, Room 429, New York, NY 10014... Administrator, Jackson Federal Building, 915 Second Avenue, Suite 3142, Seattle, WA 98174-1002 (206) 220-7954 Lower Manhattan Recovery Office FTA LMRO Director, One Bowling Green, Room 436, New York, NY 10004 (212...

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.

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.

[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.

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.

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

14 CFR 21.601 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PROCEDURES FOR PRODUCTS AND PARTS Technical Standard Order Authorizations § 21.601 Applicability. (a) This... requirements for the issuance of a letter of Technical Standard Order design approval. (b) For the purpose of..., articles means materials, parts, processes, or appliances) used on civil aircraft. (2) A TSO authorization...

[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.

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.

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.

Chloramphenicol decreases CB1 receptor expression in the nucleus accumbens and prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats.

PubMed

Amancio-Belmont, Octavio; Pérez-Vázquez, Diego; Ruiz-Contreras, Alejandra E; Pérez de la Mora, Miguel; Rueda-Orozco, Pavel E; Méndez-Díaz, Mónica; Prospero-Garcia, Oscar E

2017-08-01

Drug dependence seems to involve a learning and memory process. Since learning and memory depend on protein synthesis, drug dependence may depend on protein synthesis, too. Drug-induced reward is a crucial effect for the development of drug-dependence. We used chloramphenicol (CAP, a protein synthesis inhibitor), to evaluate its effects on amphetamine (amph)-seeking behavior, on CB1R expression and on protein synthesis in general, in specific areas of the brain. Two groups of Wistar adult male rats were subjected to amph-induced conditioned place preference (CPP). Rats in group 1 received amph and were kept in the chamber for 30min. Once this period elapsed, they received a subcutaneous injection of saline (veh) and were returned to their home-cage. Rats in group 2 were also treated with amph but received CAP (150mg/kgsc) instead of saline. Once CPP was evaluated rats were sacrificed and the prefrontal cortex (PFC), the nucleus accumbens (NAcc) and the hippocampus (Hipp) were isolated and prepared for CB1R Western blot analysis. A vivarium reared group of rats was added as a non-experimentally manipulated control group. Results indicate that group 1 developed CPP while increasing CB1R expression in the NAcc. Group 2 did not develop CPP, had lower CB1R expression in the PFC and lacked the CB1R increase in the NAcc observed in the amph+veh group. These results support the notion that among the underlying mechanisms for amph-seeking reward is an increase in CB1R, further supporting an interaction between dopamine/endocannabinoids in CPP learning. Copyright © 2017. Published by Elsevier Inc.

Involvement of ventral tegmental area ionotropic glutamate receptors in the expression of ethanol-induced conditioned place preference.

PubMed

Pina, Melanie M; Cunningham, Christopher L

2016-10-15

The ventral tegmental area (VTA) is a well-established neural substrate of reward-related processes. Activity within this structure is increased by the primary and conditioned rewarding effects of abused drugs and its engagement is heavily reliant on excitatory input from structures upstream. In the case of drug seeking, it is thought that exposure to drug-associated cues engages glutamatergic VTA afferents that signal directly to dopamine cells, thereby triggering this behavior. It is unclear, however, whether glutamate input to VTA is directly involved in ethanol-associated cue seeking. Here, the role of intra-VTA ionotropic glutamate receptor (iGluR) signaling in ethanol-cue seeking was evaluated in DBA/2J mice using an ethanol conditioned place preference (CPP) procedure. Intra-VTA iGluRs α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR)/kainate and N-methyl-d-aspartate (NMDAR) were blocked during ethanol CPP expression by co-infusion of antagonist drugs 6,7-dinitroquinoxaline-2,3-dione (DNQX; AMPA/kainate) and d-(-)-2-Amino-5-phosphonopentanoic acid (AP5; NMDA). Compared to aCSF, bilateral infusion of low (1 DNQX+100 AP5ng/side) and high (5 DNQX+500 AP5ng/side) doses of the AMPAR and NMDAR antagonist cocktail into VTA blocked ethanol CPP expression. This effect was site specific, as DNQX/AP5 infusion proximal to VTA did not significantly impact CPP expression. An increase in activity was found at the high but not low dose of DNQX/AP5. These findings demonstrate that activation of iGluRs within the VTA is necessary for ethanol-associated cue seeking, as measured by CPP. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of dorsal hippocampal orexin-2 receptor antagonism on the acquisition, expression, and extinction of morphine-induced place preference in rats.

PubMed

Sadeghi, Bahman; Ezzatpanah, Somayeh; Haghparast, Abbas

2016-06-01

Orexinergic system is involved in reward processing and drug addiction. Here, we investigated the effect of intrahippocampal CA1 administration of orexin-2 receptor (OX2r) antagonist on the acquisition, expression, and extinction of morphine-induced place preference in rats. Conditioned place preference (CPP) was induced by subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. Three experimental plots were designed; TCS OX2 29 as a selective antagonist of orexin-2 receptors (OX2rs) was dissolved in DMSO, prepared in solutions with different concentrations (1, 3, 10, and 30 nM), and was bilaterally microinjected into the CA1 and some neighboring regions (0.5 μl/side). Conditioning scores and locomotor activities were recorded during the test. Results demonstrate that intra-CA1 administration of the OX2r antagonist attenuates the induction of morphine CPP during the acquisition and expression phases. Effect of TCS OX2 29 on reduction of morphine CPP was dose-dependent and was more pronounced during the acquisition than the expression. Furthermore, higher concentrations of TCS OX2 29 facilitated the extinction of morphine-induced CPP and reduced extinction latency period. Nevertheless, administration of TCS OX2 29 solutions did not have any influence on locomotor activity of all phases. Our findings suggest that OX2rs in the CA1 region of hippocampus are involved in the development of the acquisition and expression of morphine CPP. Moreover, blockade of OX2rs could facilitate extinction and may abrogate or extinguish the ability of drug-related cues, implying that the antagonist might be considered as a propitious therapeutic agent in suppressing drug-seeking behavior.

27 CFR 19.601 - Finished products records.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Finished products records..., DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Processing Records § 19.601 Finished products records. (a) Bottling and packaging. A proprietor must maintain daily transaction records...

27 CFR 19.601 - Finished products records.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Finished products records..., DEPARTMENT OF THE TREASURY LIQUORS DISTILLED SPIRITS PLANTS Records and Reports Processing Records § 19.601 Finished products records. (a) Bottling and packaging. A proprietor must maintain daily transaction records...

27 CFR 19.601 - Finished products records.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Finished products records..., DEPARTMENT OF THE TREASURY ALCOHOL DISTILLED SPIRITS PLANTS Records and Reports Processing Records § 19.601 Finished products records. (a) Bottling and packaging. A proprietor must maintain daily transaction records...

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.

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.

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.

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.

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.

Cannabidiol Is a Potential Therapeutic for the Affective-Motivational Dimension of Incision Pain in Rats

PubMed Central

Genaro, Karina; Fabris, Débora; Arantes, Ana L. F.; Zuardi, Antônio W.; Crippa, José A. S.; Prado, Wiliam A.

2017-01-01

Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain. Additionally, we explored whether CBD underlies the reward of pain relief after systemic or rACC injection. Methods and Results: Male Wistar rats were submitted to a model of incision pain. All rats had mechanical allodynia, which was less intense after intraperitoneal CBD (3 and 10 mg/kg). Conditioned place preference (CPP) paradigm was used to assess negative reinforcement. Intraperitoneal CBD (1 and 3 mg/kg) inverted the CPP produced by peripheral nerve block even at doses that do not change mechanical allodynia. CBD (10 to 40 nmol/0.25 μL) injected into the rACC reduced mechanical allodynia in a dose-dependent manner. CBD (5 nmol/0.25 μL) did not change mechanical allodynia, but reduced peripheral nerve block-induced CPP, and the higher doses inverted the CPP. Additionally, CBD injected systemically or into the rACC at doses that did not change the incision pain evoked by mechanical stimulation significantly produced CPP by itself. Therefore, a non-rewarding dose of CBD in sham-incised rats becomes rewarding in incised rats, presumably because of pain relief or reduction of pain aversiveness. Conclusion: The study provides evidence that CBD influences different dimensions of the response of rats to a surgical incision, and the results establish the rACC as a brain area from which CBD evokes antinociceptive effects in a manner similar to the systemic administration of CBD. In addition, the study gives further support to the notion that the sensorial and affective dimensions of pain may be differentially modulated by CBD. PMID:28680401

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.

ADM. Aerial view of administration area. Camera facing westerly. From ...

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

ADM. Aerial view of administration area. Camera facing westerly. From left to right in foregound: Substation (TAN-605), Warehouse (TAN-628), Gate House (TAN-601), Administration Building (TAN-602). Left to right middle ground: Service Building (TAN-603), Warehouse (later known as Maintenance Shop or Craft Shop, TAN-604), Water Well Pump Houses, Fuel Tanks and Fuel Pump Houses, and Water Storage Tanks. Change House (TAN-606) on near side of berm. Large building beyond berm is A&M. Building, TAN-607. Railroad tracks beyond lead from (unseen) turntable to the IET. Date: June 6, 1955. INEEL negative no. 13201 - Idaho National Engineering Laboratory, Test Area North, 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.

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.

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

Preference conditioning in healthy individuals: correlates with hazardous drinking.

PubMed

Balodis, Iris M; Lockwood, Kathleen P; Magrys, Sylvia A; Olmstead, Mary C

2010-06-01

Conditioned reward is a classic measure of drug-induced brain changes in animal models of addiction. The process can be examined in humans using the Conditioned Pattern Preference (CPP) task, in which participants associate nonverbal cues with reward but demonstrate low awareness of this conditioning. Previously, we reported that alcohol intoxication does not affect CPP acquisition in humans, but our data indicated that prior drug use may impact conditioning scores. To test this possibility, the current study examined the relationship between self-reported alcohol use and preference conditioning in the CPP task. Working memory was assessed during conditioning by asking participants to count the cues that appeared at each location on a computer screen. Participants (69 female and 23 male undergraduate students) completed the Alcohol Use Disorders Identification Test (AUDIT) and the Rutgers Alcohol Problem Index (RAPI) as measures of hazardous drinking. Self-reported hazardous drinking was significantly correlated with preference conditioning in that individuals who scored higher on these scales exhibited an increased preference for the reward-paired cues. In contrast, hazardous drinking did not affect working memory errors on the CPP task. These findings support evidence that repeated drug use sensitizes neural pathways mediating conditioned reward and point to a neurocognitive disposition linking substance misuse and responses to reward-paired stimuli. The relationship between hazardous drinking and conditioned reward is independent of changes in cognitive function, such as working memory.

40 CFR 1042.601 - General compliance provisions for marine engines and vessels.

Code of Federal Regulations, 2010 CFR

2010-07-01

... aftertreatment components. For example, you must replace the catalyst if the catalyst assembly is stamped with a build date more than ten years ago and the manufacturer's instructions state that catalysts over ten years old must be replaced when the engine is rebuilt. (2) Measure pressure drop across the catalyst...

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.

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.

[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.

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

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.

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.

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.

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

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.

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.

Ways to Write a Milestone: Approaches to Operationalizing the Development of Competence in Graduate Medical Education.

PubMed

Leep Hunderfund, Andrea N; Reed, Darcy A; Starr, Stephanie R; Havyer, Rachel D; Lang, Tara R; Norby, Suzanne M

2017-09-01

To identify approaches to operationalizing the development of competence in Accreditation Council for Graduate Medical Education (ACGME) milestones. The authors reviewed all 25 "Milestone Project" documents available on the ACGME Web site on September 11, 2013, using an iterative process to identify approaches to operationalizing the development of competence in the milestones associated with each of 601 subcompetencies. Fifteen approaches were identified. Ten focused on attributes and activities of the learner, such as their ability to perform different, increasingly difficult tasks (304/601; 51%), perform a task better and faster (171/601; 45%), or perform a task more consistently (123/601; 20%). Two approaches focused on context, inferring competence from performing a task in increasingly difficult situations (236/601; 29%) or an expanding scope of engagement (169/601; 28%). Two used socially defined indicators of competence such as progression from "learning" to "teaching," "leading," or "role modeling" (271/601; 45%). One approach focused on the supervisor's role, inferring competence from a decreasing need for supervision or assistance (151/601; 25%). Multiple approaches were often combined within a single set of milestones (mean 3.9, SD 1.6). Initial ACGME milestones operationalize the development of competence in many ways. These findings offer insights into how physicians understand and assess the developmental progression of competence and an opportunity to consider how different approaches may affect the validity of milestone-based assessments. The results of this analysis can inform the work of educators developing or revising milestones, interpreting milestone data, or creating assessment tools to inform milestone-based performance measures.

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.

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.

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

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

Spill Prevention Control and Countermeasure Plan, Headquarters, U.S. Army Garrison, Fort Ritchie, Maryland

DTIC Science & Technology

1993-04-01

additive (55 gal) - paint (180 gal total) - algicide (55 gal) - sodium bisulfite - lube oil (200 gal) - ethylene glycol (55 gal) - detergent (30 gal...I 2.6.1 Storage Hazardous materials stored in Building 601 include:I * 55 gal of fuel additive, • 180 gal total volume of paint, * 55 gal of algicide

World War II: A Chronology. December 1943

DTIC Science & Technology

1943-12-01

an: RAF aircraft ə t tack Sir,u harbor, probably damaging buildings on quayside. 2, Italy : Units of lOth Corps make gains on M . Ca1:.ino...by 4 B-25’:::> :,hich start fires dmong shore .buildings. 8 Italy : Units of 46th Div capture Cocuruzzo, on SVJ side of M . Cainino; 56th Div rnoves...conjunction with Itali <:ms, seizes positions on lv.i:. ;Lungo. ·Forty’:’"f~fth . Di’v moves tow~rd M . Cb.vallo; French attack M . Pc:.:ntq.no

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.

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

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.

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.

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.

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.

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

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.

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.

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.

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

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.

Neural correlates of admiration and compassion

PubMed Central

Immordino-Yang, Mary Helen; McColl, Andrea; Damasio, Hanna; Damasio, Antonio

2009-01-01

In an fMRI experiment, participants were exposed to narratives based on true stories designed to evoke admiration and compassion in 4 distinct categories: admiration for virtue (AV), admiration for skill (AS), compassion for social/psychological pain (CSP), and compassion for physical pain (CPP). The goal was to test hypotheses about recruitment of homeostatic, somatosensory, and consciousness-related neural systems during the processing of pain-related (compassion) and non-pain-related (admiration) social emotions along 2 dimensions: emotions about other peoples' social/psychological conditions (AV, CSP) and emotions about others' physical conditions (AS, CPP). Consistent with theoretical accounts, the experience of all 4 emotions engaged brain regions involved in interoceptive representation and homeostatic regulation, including anterior insula, anterior cingulate, hypothalamus, and mesencephalon. However, the study also revealed a previously undescribed pattern within the posteromedial cortices (the ensemble of precuneus, posterior cingulate cortex, and retrosplenial region), an intriguing territory currently known for its involvement in the default mode of brain operation and in self-related/consciousness processes: emotions pertaining to social/psychological and physical situations engaged different networks aligned, respectively, with interoceptive and exteroceptive neural systems. Finally, within the anterior insula, activity correlated with AV and CSP peaked later and was more sustained than that associated with CPP. Our findings contribute insights on the functions of the posteromedial cortices and on the recruitment of the anterior insula in social emotions concerned with physical versus psychological pain. PMID:19414310

Neural correlates of admiration and compassion.

PubMed

Immordino-Yang, Mary Helen; McColl, Andrea; Damasio, Hanna; Damasio, Antonio

2009-05-12

In an fMRI experiment, participants were exposed to narratives based on true stories designed to evoke admiration and compassion in 4 distinct categories: admiration for virtue (AV), admiration for skill (AS), compassion for social/psychological pain (CSP), and compassion for physical pain (CPP). The goal was to test hypotheses about recruitment of homeostatic, somatosensory, and consciousness-related neural systems during the processing of pain-related (compassion) and non-pain-related (admiration) social emotions along 2 dimensions: emotions about other peoples' social/psychological conditions (AV, CSP) and emotions about others' physical conditions (AS, CPP). Consistent with theoretical accounts, the experience of all 4 emotions engaged brain regions involved in interoceptive representation and homeostatic regulation, including anterior insula, anterior cingulate, hypothalamus, and mesencephalon. However, the study also revealed a previously undescribed pattern within the posteromedial cortices (the ensemble of precuneus, posterior cingulate cortex, and retrosplenial region), an intriguing territory currently known for its involvement in the default mode of brain operation and in self-related/consciousness processes: emotions pertaining to social/psychological and physical situations engaged different networks aligned, respectively, with interoceptive and exteroceptive neural systems. Finally, within the anterior insula, activity correlated with AV and CSP peaked later and was more sustained than that associated with CPP. Our findings contribute insights on the functions of the posteromedial cortices and on the recruitment of the anterior insula in social emotions concerned with physical versus psychological pain.

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.

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats

PubMed Central

Goenaga, Julianna; Hatch, Kayla N.; Henricks, Angela; Scott, Samantha; Hood, Lauren E.; Neisewander, Janet L.

2016-01-01

Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline + Isolated, (2) Nicotine + Isolated, (3) Saline + Social, or (4) Nicotine + Social. For Experiment 1, brain tissue was collected 90 min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90 min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. PMID:27435419

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.

Reconsolidation and update of morphine-associated contextual memory in mice.

PubMed

Escosteguy-Neto, Joao Carlos; Varela, Patricia; Correa-Neto, Nelson Francisco; Coelho, Laura Segismundo; Onaivi, Emmanuel S; Santos-Junior, Jair Guilherme

2016-04-01

Drug addiction can be viewed as a pathological memory that is constantly retrieved and reconsolidated. Since drug abuse takes place in different contexts, it could be considered that reconsolidation plays a role in memory updating. There is consistent evidence supporting the role of reconsolidation in the strength and maintenance of contextual memories induced by drugs of abuse. However, this role is not well established in memory update. The purpose of the current study was to assess the reconsolidation process over memory update. C57BL6 mice were subjected to a morphine-induced, conditioned place preference (CPP) paradigm. Based on CPP results, animals were divided into distinct experimental groups, according to the contextual characteristics of the re-exposure and a second CPP Test. Re-exposure in the original context was important for memory maintenance and re-exposure under discrete contextual changes resulted in memory updating, although original memory was maintained. Interestingly, cycloheximide, an inhibitor of protein synthesis, had different outcomes in our protocol. When the re-exposure was done under discrete contextual changes, cycloheximide treatment just after re-exposure blocked memory updating, without changes in memory maintenance. When re-exposure was done under the original context, only two subsequent cycloheximide injections (3 and 6h) disrupted later CPP expression. Considering the temporal window of protein synthesis in consolidation and reconsolidation, these findings suggest that re-exposure, according to the contextual characteristics in our protocol, could trigger both phenomena. Furthermore, when new information is present on retrieval, reconsolidation plays a pivotal role in memory updating. Copyright © 2016 Elsevier Inc. All rights reserved.

Social learning of an associative foraging task in zebrafish

NASA Astrophysics Data System (ADS)

Zala, Sarah M.; Määttänen, Ilmari

2013-05-01

The zebrafish ( Danio rerio) is increasingly becoming an important model species for studies on the genetic and neural mechanisms controlling behaviour and cognition. Here, we utilized a conditioned place preference (CPP) paradigm to study social learning in zebrafish. We tested whether social interactions with conditioned demonstrators enhance the ability of focal naïve individuals to learn an associative foraging task. We found that the presence of conditioned demonstrators improved focal fish foraging behaviour through the process of social transmission, whereas the presence of inexperienced demonstrators interfered with the learning of the control focal fish. Our results indicate that zebrafish use social learning for finding food and that this CPP paradigm is an efficient assay to study social learning and memory in zebrafish.

CREATING A "NEST" OF EMOTIONAL SAFETY: REFLECTIVE SUPERVISION IN A CHILD-PARENT PSYCHOTHERAPY CASE.

PubMed

Many, Michele M; Kronenberg, Mindy E; Dickson, Amy B

2016-11-01

Reflective supervision is considered a key practice component for any infant mental health provider to work effectively with young children and their families. This article will provide a brief history and discussion of reflective supervision followed by a case study demonstrating the importance of reflective supervision in the context of child-parent psychotherapy (CPP; A.F. Lieberman, C. Ghosh Ippen, & P. Van Horn, ; A.F. Lieberman & P. Van Horn, , 2008). Given that CPP leverages the caregiver-child relationship as the mechanism for change in young children who have been impacted by stressors and traumas, primary objectives of CPP include assisting caregivers as they understand the meaning of their child's distress and improving the caregiver-child relationship to make it a safe and supportive space in which the child can heal. As this case will demonstrate, when a clinician is emotionally triggered by a family's negative intergenerational patterns of relating, reflective supervision supports a parallel process in which the psychotherapist feels understood and contained by the supervisor so that she or he is able to support the caregiver's efforts to understand and contain the child. © 2016 Michigan Association for Infant Mental Health.

Impact of Surface Active Ionic Liquids on the Cloud Points of Nonionic Surfactants and the Formation of Aqueous Micellar Two-Phase Systems.

PubMed

Vicente, Filipa A; Cardoso, Inês S; Sintra, Tânia E; Lemus, Jesus; Marques, Eduardo F; Ventura, Sónia P M; Coutinho, João A P

2017-09-21

Aqueous micellar two-phase systems (AMTPS) hold a large potential for cloud point extraction of biomolecules but are yet poorly studied and characterized, with few phase diagrams reported for these systems, hence limiting their use in extraction processes. This work reports a systematic investigation of the effect of different surface-active ionic liquids (SAILs)-covering a wide range of molecular properties-upon the clouding behavior of three nonionic Tergitol surfactants. Two different effects of the SAILs on the cloud points and mixed micelle size have been observed: ILs with a more hydrophilic character and lower critical packing parameter (CPP < 1 / 2 ) lead to the formation of smaller micelles and concomitantly increase the cloud points; in contrast, ILs with a more hydrophobic character and higher CPP (CPP ≥ 1) induce significant micellar growth and a decrease in the cloud points. The latter effect is particularly interesting and unusual for it was accepted that cloud point reduction is only induced by inorganic salts. The effects of nonionic surfactant concentration, SAIL concentration, pH, and micelle ζ potential are also studied and rationalized.

The Canada Pension Plan's experience with investing its portfolio in equities.

PubMed

Sarney, M; Preneta, A M

For the past few years, the Canada Pension Plan (CPP) has been investing some of its assets in equities. Without changes, an imbalance between revenues and outlays would exhaust the CPP reserve fund by 2015. Creating an entity that was independent of government was one of several changes the federal and provincial governments enacted to achieve fuller funding. The governments created an independent Investment Board (the CPP Investment Board, or "CPPIB") to oversee the new investments. Because the plan already owned a large government bond portfolio, the CPPIB decided to invest new CPP funds in broad equity indices in March 1999. In 2000, the CPPIB began actively investing a portion of the CPP funds. Key features of that policy and some observations about its implementation include the following: In addition to investing CPP revenues in equities, reform also included contribution rate increases, benefit reductions, and a financing stabilizer. The new investment policy accounted for 25 percent of the total effect of all the reforms. It is premature to know if the investments will achieve their long-term performance objective. The new equity investments are projected by the Chief Actuary, in his most recent Actuarial Report, to earn a 4.5 percent real rate of return on Canadian equity and 5.0 percent real return on foreign equity for a blended real return of 4.65 percent based on an equity mix of 70 percent Canadian and 30 percent non-Canadian. However, it is too early to tell if the equity investments will achieve that goal over the long run. The Investment Board's mandate is to maximize returns. The Investment Board, which oversees the CPP's new investments, has broad discretion to pursue maximum returns on its assets without incurring undue risk of loss while keeping in mind the financial obligations and other assets of the CPP. Furthermore, it has developed into a professional investment organization staffed with private-sector experts in finance and investment. The board is designed to be independent of government. The federal and provincial governments designed the board to operate at arm's length from themselves. The process for selecting directors includes public- and private-sector participation, and the board is in compliance with several sets of governance guidelines for corporations. CPPIB management, with the support of its board of directors, has decided to implement a virtual corporation model involving a small team of senior executives setting strategies for implementation primarily by external professional firms. Consequently, as a virtual corporation, the board currently relies on external fund managers to make investments and vote proxies. Several measures are designed to ensure accountability to the public. The investment legislation subjects the board to overlapping layers of oversight to ensure accountability to the public. The features of this oversight include public meetings in each province as well as quarterly statements and annual reports to Parliament, the federal and provincial finance ministers, and the public. The 10 finance ministers review the CPPIB's mandate and regulations every 3 years, and the CPPIB is subject to a special examination every 6 years by an auditor appointed by the Federal Minister of Finance.

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.

Extinction of Contextual Cocaine Memories Requires Cav1.2 within D1R-Expressing Cells and Recruits Hippocampal Cav1.2-Dependent Signaling Mechanisms

PubMed Central

Lee, Anni S.; Fischer, Delaney K.; Van Kempen, Tracey A.; Mudragel, Vladimir; Glass, Michael J.

2017-01-01

Exposure to cocaine-associated contextual cues contributes significantly to relapse. Extinction of these contextual associations, which involves a new form of learning, reduces cocaine-seeking behavior; however, the molecular mechanisms underlying this process remain largely unknown. We report that extinction, but not acquisition, of cocaine conditioned place preference (CPP) in male mice increased Cav1.2 L-type Ca2+ channel mRNA and protein in postsynaptic density (PSD) fractions of the hippocampus, a brain region involved in drug–context associations. Moreover, viral-mediated deletion of Cav1.2 in the dorsal hippocampus attenuated extinction of cocaine CPP. Molecular studies examining downstream Cav1.2 targets revealed that extinction recruited calcium/calmodulin (Ca2+/CaMK)-dependent protein kinase II (CaMKII) to the hippocampal PSD. This occurred in parallel with an increase in phosphorylation of the AMPA GluA1 receptor subunit at serine 831 (S831), a CaMKII site, along with an increase in total PSD GluA1. The necessity of S831 GluA1 was further demonstrated by the lack of extinction in S831A GluA1 phosphomutant mice. Of note hippocampal GluA1 levels remained unaltered at the PSD, but were reduced near the PSD and at perisynaptic sites of dendritic spines in extinction-resistant S831A mutant mice. Finally, conditional knock-out of Cav1.2 in dopamine D1 receptor (D1R)-expressing cells resulted in attenuation of cocaine CPP extinction and lack of extinction-dependent changes in hippocampal PSD CaMKII expression and S831 GluA1 phosphorylation. In summary, we demonstrate an essential role for the hippocampal Cav1.2/CaMKII/S831 GluA1 pathway in cocaine CPP extinction, with data supporting contribution of hippocampal D1R-expressing cells in this process. These findings demonstrate a novel role for Cav1.2 channels in extinction of contextual cocaine-associated memories. SIGNIFICANCE STATEMENT Continued drug-seeking behavior, a defining characteristic of cocaine addiction, can be precipitated by contextual cues, yet the molecular mechanisms required for extinction of these context-specific memories remain poorly understood. Here, we have uncovered a novel and selective role of the Cav1.2 L-type Ca2+ channel and its downstream signaling pathway in the hippocampus that mediate extinction of cocaine conditioned place preference (CPP). We additionally provide evidence that supports a role of Cav1.2 within dopamine D1 receptor-expressing cells of the hippocampus for extinction of cocaine CPP. Therefore, these findings reveal a previously unknown role of Cav1.2 channels within the hippocampus and in D1 receptor-expressing cells in extinction of cocaine-associated memories, providing a framework for further exploration of mechanisms underlying extinction of cocaine-seeking behavior. PMID:29089442

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.

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.

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

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.

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.

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

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.

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.

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.

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

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.

76 FR 477 - Airworthiness Directives; Bombardier, Inc. Model CL-600-2A12 (CL-601) and CL-600-2B16 (CL-601-3A...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... to these aircraft if Bombardier Service Bulletin (SB) 601-0590 [Scheduled Maintenance Instructions... information: Challenger 601 Time Limits/Maintenance Checks, PSP 601-5, Revision 38, dated June 19, 2009. Challenger 601 Time Limits/Maintenance Checks, PSP 601A-5, Revision 34, dated June 19, 2009. Challenger 604...

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.

Adenovirus-mediated interleukin-18 mutant in vivo gene transfer inhibits tumor growth through the induction of T cell immunity and activation of natural killer cell cytotoxicity.

PubMed

Hwang, Kyung-Sun; Cho, Won-Kyung; Yoo, Jinsang; Seong, Young Rim; Kim, Bum-Kyeng; Kim, Samyong; Im, Dong-Soo

2004-06-01

We report here that gene transfer using recombinant adenoviruses encoding interleukin (IL)-18 mutants induces potent antitumor activity in vivo. The precursor form of IL-18 (ProIL-18) is processed by caspase-1 to produce bioactive IL-18, but its cleavage by caspase-3 (CPP32) produces an inactive form. To prepare IL-18 molecules with an effective antitumor activity, a murine IL-18 mutant with the signal sequence of murine granulocyte-macrophage (GM)- colony stimulating factor (CSF) at the 5'-end of mature IL-18 cDNA (GMmIL-18) and human IL-18 mutant with the prepro leader sequence of trypsin (PPT), which is not cleaved by caspase-3 (PPThIL-18CPP32-), respectively, were constructed. Adenovirus vectors carrying GMmIL-18 or PPThIL-18CPP32- produced bioactive IL-18. Ad.GMmIL-18 had a more potent antitumor effect than Ad.mProIL-18 encoding immature IL-18 in renal cell adenocarcinoma (Renca) tumor-bearing mice. Tumor-specific cytotoxic T lymphocytes, the induction of Th1 cytokines, and an augmented natural killer (NK) cell activity were detected in Renca tumor-bearing mice treated with Ad.GMmIL-18. An immunohistological analysis revealed that CD4+ and CD8+ T cells abundantly infiltrated into tumors of mice treated with Ad.GMmIL-18. Huh-7 human hepatoma tumor growth in nude mice with a defect of T cell function was significantly inhibited by Ad.PPThIL-18CPP32- compared with Ad.hProIL-18 encoding immature IL-18. Nude mice treated with Ad.PPThIL-18CPP32- contained NK cells with increased cytotoxicity. The results suggest that the release of mature IL-18 in tumors is required for achieving an antitumor effect including tumor-specific cellular immunity and augmented NK cell-mediated cytotoxicity. These optimally designed IL-18 mutants could be useful for improving the antitumor effectiveness of wild-type IL-18. Copyright 2004 Nature Publishing Group

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

17 CFR 230.601 - Definitions of terms used in §§ 230.601 to 230.610a.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Securities of Small Business Investment Companies § 230.601 Definitions of terms used in §§ 230.601 to 230... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Definitions of terms used in §§ 230.601 to 230.610a. 230.601 Section 230.601 Commodity and Securities Exchanges SECURITIES AND...

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

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.

Mechanisms of change: Testing how preventative interventions impact psychological and physiological stress functioning in mothers in neglectful families.

PubMed

Toth, Sheree L; Sturge-Apple, Melissa L; Rogosch, Fred A; Cicchetti, Dante

2015-11-01

The present study applies a multilevel approach to an examination of the effect of two randomized preventive interventions with mothers in neglectful families who are also contending with elevated levels of impoverishment and ecological risk. Specifically, we examined how participation in either child-parent psychotherapy (CPP) or psychoeducational parenting intervention (PPI) was associated with reductions in maternal psychological parenting stress and in turn physiological stress system functioning when compared to mothers involved in standard community services as well as a demographic comparison group of nonmaltreating mothers. The resulting group sizes in the current investigation were 44 for CPP, 34 for PPI, 27 for community services, and 52 for nonmaltreating mothers. Mothers and their 13-month-old infants were randomly assigned to intervention group at baseline. Mothers completed assessments on stress within the parenting role at baseline and postintervention. Basal cortisol was sampled at postintervention and 1-year follow-up. Latent difference score analyses examined change in these constructs over time. Results suggested that mothers within the CPP intervention experienced significant declines in child-related parenting stress, while mothers in the PPI intervention reported declines in parent-related parenting stress. In turn, significant decreases in stress within the CPP mothers were further associated with adaptive basal cortisol functioning at 1-year postintervention. The results highlight the value of delineating how participation in preventive interventions aimed at ameliorating child maltreatment in neglectful families within the context of poverty may operate through improvements in psychological and physiological stress functioning. Findings are discussed with respect to the importance of multilevel assessments of intervention process and outcome.

Immediate early gene expression reveals interactions between social and nicotine rewards on brain activity in adolescent male rats.

PubMed

Bastle, Ryan M; Peartree, Natalie A; Goenaga, Julianna; Hatch, Kayla N; Henricks, Angela; Scott, Samantha; Hood, Lauren E; Neisewander, Janet L

2016-10-15

Smoking initiation predominantly occurs during adolescence, often in the presence of peers. Therefore, understanding the neural mechanisms underlying the rewarding effects of nicotine and social stimuli is vital. Using the conditioned place preference (CPP) procedure, we measured immediate early gene (IEG) expression in animals following exposure either to a reward-conditioned environment or to the unconditioned stimuli (US). Adolescent, male rats were assigned to the following CPP US conditions: (1) Saline+Isolated, (2) Nicotine+Isolated, (3) Saline+Social, or (4) Nicotine+Social. For Experiment 1, brain tissue was collected 90min following the CPP expression test and processed for Fos immunohistochemistry. We found that rats conditioned with nicotine with or without a social partner exhibited CPP; however, we found no group differences in Fos expression in any brain region analyzed, with the exception of the nucleus accumbens core that exhibited a social-induced attenuation in Fos expression. For Experiment 2, brain tissue was collected 90min following US exposure during the last conditioning session. We found social reward-induced increases in IEG expression in striatal and amydalar subregions. In contrast, nicotine reduced IEG expression in prefrontal and striatal subregions. Reward interactions were also found in the dorsolateral striatum, basolateral amygdala, and ventral tegmental area where nicotine alone attenuated IEG expression and social reward reversed this effect. These results suggest that in general social rewards enhance, whereas nicotine attenuates, activation of mesocorticolimbic regions; however, the rewards given together interact to enhance activation in some regions. The findings contribute to knowledge of how a social environment influences nicotine effects. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanisms of Change: Testing how Preventative Interventions Impact Psychological and Physiological Stress Functioning in Mothers in Neglectful Families

PubMed Central

Toth, Sheree L.; Sturge-Apple, Melissa L.; Rogosch, Fred A.; Cicchetti, Dante

2015-01-01

The present study applies a multilevel approach to an examination of the effect of two randomized preventative interventions with mothers in neglectful families who are also contending with elevated levels of impoverishment and ecological risk. Specifically, we examined how participation in either Child-Parent Psychotherapy (CPP) or Psychoeducational Parenting (PPI) interventions was associated with reductions in maternal psychological parenting stress and in turn physiological stress system functioning when compared to mothers involved in standard community services (CS) as well as a demographic comparison group of nonmaltreating mothers (NC). The resulting group sizes in the current investigation were: CPP (n = 44), PPI (n = 34), CS (n = 27), and NC (n = 52). Mothers and infants who were 13-months of age were randomly assigned to intervention group at baseline. Mothers completed assessments on stress within the parenting role at baseline and post-intervention. Basal cortisol was sampled at post-intervention and 1-year follow-up. Latent difference score analyses examined change in these constructs over time. Results suggested that mothers within the CPP intervention experienced significant declines in child-related parenting stress while mothers in the PPI intervention reported declines in parent-related parenting stress. In turn, significant decreases in stress within the CPP mothers were further associated with adaptive basal cortisol functioning at 1-year post-intervention. Results highlight the value of delineating how participation in preventtive interventions aimed at ameliorating child maltreatment in neglectful families within the context of poverty may operate through improvements in psychological and physiological stress functioning. Findings are discussed with respect to the importance of multi-level assessments of intervention process and outcome. PMID:26535951

Blockade of 5-HT2A/2C-type receptors impairs learning in female rats in the course of estrous cycle.

PubMed

Fedotova, Yu O; Ordyan, N E

2010-12-01

We studied the effects of chronic administration (14 days) of agonist of 5-HT2B/2C serotonin receptors m-CPP (0.5 mg/kg subcutaneously) and agonist of 5-HT2A/2C serotonin receptors ketanserin (0.1 mg/kg intraperitoneally) on conditioned reactions in female rats in different phases of the estrous cycle. Passive avoidance (PA) paradigm and Morris water maze were used as behavioral tests. Chronic administration of m-CPP did not affect PA retrieval during the proestrus and estrus phases, but improved the dynamics of spatial learning in Morris water maze in comparison with control rats. Chronic administration of ketanserin uniformly impaired processes of spatial and nonspatial learning in female rats irrespective to the phase of the estrous cycle. A modulating role of 5-HT2A/2C and 5-HT2B/2C serotonin receptors in process of learning in female rats during the key phases of the estrous cycle was demonstrated.

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.

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.

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.

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.

Using Android and Open Data Kit Technology in Data Management for Research in Resource-Limited Settings in the Niger Delta Region of Nigeria: Cross-Sectional Household Survey

PubMed Central

Maleghemi, Sylvester

2017-01-01

Background Data collection in Sub-Saharan Africa has traditionally been paper-based. However, the popularization of Android mobile devices and data capture software has brought paperless data management within reach. We used Open Data Kit (ODK) technology on Android mobile devices during a household survey in the Niger Delta region of Nigeria. Objective The aim of this study was to describe the pros and cons of deploying ODK for data management. Methods A descriptive cross-sectional household survey was carried out by 6 data collectors between April and May 2016. Data were obtained from 1706 persons in 601 households across 6 communities in 3 states in the Niger Delta. The use of Android mobile devices and ODK technology involved form building, testing, collection, aggregation, and download for data analysis. The median duration for data collection per household and per individual was 25.7 and 9.3 min, respectively. Results Data entries per device ranged from 33 (33/1706, 1.93%) to 482 (482/1706, 28.25%) individuals between 9 (9/601, 1.5%) and 122 (122/601, 20.3%) households. The most entries (470) were made by data collector 5. Only 2 respondents had data entry errors (2/1706, 0.12%). However, 73 (73/601, 12.1%) households had inaccurate date and time entries for when data collection started and ended. The cost of deploying ODK was estimated at US $206.7 in comparison with the estimated cost of US $466.7 for paper-based data management. Conclusions We found the use of mobile data capture technology to be efficient and cost-effective. As Internet services improve in Africa, we advocate their use as effective tools for health information management. PMID:29191798

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.

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.

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.

IMPLEMENTATION AND SUSTAINABILITY OF CHILD-PARENT PSYCHOTHERAPY: THE ROLE OF REFLECTIVE CONSULTATION IN THE LEARNING COLLABORATIVE MODEL.

PubMed

Noroña, Carmen Rosa; Acker, Michelle L

2016-11-01

Recent implementation science in mental health has focused on identifying the most effective strategies to disseminate and implement evidence-based treatments (EBTs) into real-world practice settings. The learning collaborative training methodology and its use of expert trainers/consultants have become increasingly popular as one of these approaches. Moreover, there is preliminary evidence that ongoing expert consultation may increase the adoption, learning, and sustainability of EBTs by an already practicing workforce and, consequently, help trainers, practitioners, and organizations address implementation barriers. This article describes the authors' experiences in facilitating Child-Parent Psychotherapy (CPP) training and explores the role of reflective clinical consultation as an active process that supports the implementation of a rich, but complex, model that requires sophisticated knowledge and skills from practitioners. It examines the intricate range of the CPP consultant's functions, which ultimately support clinicians' reflective practice as they learn and adopt this EBT. Reflective consultation is proposed as an essential component for the integration of knowledge, experience, and emotions in practitioners and as a catalyst for organizational change. Using their voices as trainers-consultants and those of their trainees, the authors discuss the implications of reflective consultation for the effective implementation and sustainability of CPP. Reflections are offered on lessons learned. © 2016 Michigan Association for Infant Mental Health.

Effect of glycerol concentrations on the mechanical properties of additive manufactured porous calcium polyphosphate structures for bone substitute applications.

PubMed

Sheydaeian, Esmat; Vlasea, Mihaela; Woo, Ami; Pilliar, Robert; Hu, Eugene; Toyserkani, Ehsan

2017-05-01

This article addresses the effects of glycerol (GLY) concentrations on the mechanical properties of calcium polyphosphate (CPP) bone substitute structures manufactured using binder jetting additive manufacturing. To achieve this goal, nine types of water-based binder solutions were prepared with 10, 12.5, and 15 wt % GLY liquid-binding agent, mixed, respectively, with 0, 0.75, and 1.5 wt % ethylene glycol diacetate (EGD) flow enhancer. The print quality of each of the solutions was established quantitatively using an image processing algorithm. The print quality analysis narrowed down the solutions to three batches containing 1.5 wt % EGD and variable amount of GLY. These solutions were used to manufacture porous CPP bone substitute samples, which were characterized physically to determine shrinkage, porosity, microstructure, and compression strength. The 12.5 wt % GLY, 1.5 wt % EGD solution resulted in the highest mechanical strength after sintering (34.6 ± 5.8 MPa), illustrating similar mechanical properties when compared to previous studies (33.9 ± 6.3 MPa) of additively manufactured CPP bone substitutes using a commercially available binder. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 828-835, 2017. © 2016 Wiley Periodicals, Inc.

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.

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.

Region-specific role of Rac in nucleus accumbens core and basolateral amygdala in consolidation and reconsolidation of cocaine-associated cue memory in rats.

PubMed

Ding, Zeng-Bo; Wu, Ping; Luo, Yi-Xiao; Shi, Hai-Shui; Shen, Hao-Wei; Wang, Shen-Jun; Lu, Lin

2013-08-01

Drug reinforcement and the reinstatement of drug seeking are associated with the pathological processing of drug-associated cue memories that can be disrupted by manipulating memory consolidation and reconsolidation. Ras-related C3 botulinum toxin substrate (Rac) is involved in memory processing by regulating actin dynamics and neural structure plasticity. The nucleus accumbens (NAc) and amygdala have been implicated in the consolidation and reconsolidation of emotional memories. Therefore, we hypothesized that Rac in the NAc and amygdala plays a role in the consolidation and reconsolidation of cocaine-associated cue memory. Conditioned place preference (CPP) and microinjection of Rac inhibitor NSC23766 were used to determine the role of Rac in the NAc and amygdala in the consolidation and reconsolidation of cocaine-associated cue memory in rats. Microinjections of NSC23766 into the NAc core but not shell, basolateral (BLA), or central amygdala (CeA) after each cocaine-conditioning session inhibited the consolidation of cocaine-induced CPP. A microinjection of NSC23766 into the BLA but not CeA, NAc core, or NAc shell immediately after memory reactivation induced by exposure to a previously cocaine-paired context disrupted the reconsolidation of cocaine-induced CPP. The effect of memory disruption on cocaine reconsolidation was specific to reactivated memory, persisted at least 2 weeks, and was not reinstated by a cocaine-priming injection. Our findings indicate that Rac in the NAc core and BLA are required for the consolidation and reconsolidation of cocaine-associated cue memory, respectively.

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.

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.

Extinction of Contextual Cocaine Memories Requires Cav1.2 within D1R-Expressing Cells and Recruits Hippocampal Cav1.2-Dependent Signaling Mechanisms.

PubMed

Burgdorf, Caitlin E; Schierberl, Kathryn C; Lee, Anni S; Fischer, Delaney K; Van Kempen, Tracey A; Mudragel, Vladimir; Huganir, Richard L; Milner, Teresa A; Glass, Michael J; Rajadhyaksha, Anjali M

2017-12-06

Exposure to cocaine-associated contextual cues contributes significantly to relapse. Extinction of these contextual associations, which involves a new form of learning, reduces cocaine-seeking behavior; however, the molecular mechanisms underlying this process remain largely unknown. We report that extinction, but not acquisition, of cocaine conditioned place preference (CPP) in male mice increased Ca v 1.2 L-type Ca 2+ channel mRNA and protein in postsynaptic density (PSD) fractions of the hippocampus, a brain region involved in drug-context associations. Moreover, viral-mediated deletion of Ca v 1.2 in the dorsal hippocampus attenuated extinction of cocaine CPP. Molecular studies examining downstream Ca v 1.2 targets revealed that extinction recruited calcium/calmodulin (Ca 2+ /CaMK)-dependent protein kinase II (CaMKII) to the hippocampal PSD. This occurred in parallel with an increase in phosphorylation of the AMPA GluA1 receptor subunit at serine 831 (S831), a CaMKII site, along with an increase in total PSD GluA1. The necessity of S831 GluA1 was further demonstrated by the lack of extinction in S831A GluA1 phosphomutant mice. Of note hippocampal GluA1 levels remained unaltered at the PSD, but were reduced near the PSD and at perisynaptic sites of dendritic spines in extinction-resistant S831A mutant mice. Finally, conditional knock-out of Ca v 1.2 in dopamine D1 receptor (D1R)-expressing cells resulted in attenuation of cocaine CPP extinction and lack of extinction-dependent changes in hippocampal PSD CaMKII expression and S831 GluA1 phosphorylation. In summary, we demonstrate an essential role for the hippocampal Ca v 1.2/CaMKII/S831 GluA1 pathway in cocaine CPP extinction, with data supporting contribution of hippocampal D1R-expressing cells in this process. These findings demonstrate a novel role for Ca v 1.2 channels in extinction of contextual cocaine-associated memories. SIGNIFICANCE STATEMENT Continued drug-seeking behavior, a defining characteristic of cocaine addiction, can be precipitated by contextual cues, yet the molecular mechanisms required for extinction of these context-specific memories remain poorly understood. Here, we have uncovered a novel and selective role of the Ca v 1.2 L-type Ca 2+ channel and its downstream signaling pathway in the hippocampus that mediate extinction of cocaine conditioned place preference (CPP). We additionally provide evidence that supports a role of Ca v 1.2 within dopamine D1 receptor-expressing cells of the hippocampus for extinction of cocaine CPP. Therefore, these findings reveal a previously unknown role of Ca v 1.2 channels within the hippocampus and in D1 receptor-expressing cells in extinction of cocaine-associated memories, providing a framework for further exploration of mechanisms underlying extinction of cocaine-seeking behavior. Copyright © 2017 the authors 0270-6474/17/3711895-18$15.00/0.

INTERIOR PHOTO OF HOT PILOT PLANT SECOND FLOOR DEPICTING DETAIL ...

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

INTERIOR PHOTO OF HOT PILOT PLANT SECOND FLOOR DEPICTING DETAIL OF SHIELDED CAVE (CPP-640) LOOKING SOUTHWEST. PHOTO TAKEN FROM NORTH. INL PHOTO NUMBER HD-54-40-2. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

INTERIOR PHOTO OF HOT PILOT PLANT SECOND FLOOR WITH SOUTH ...

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

INTERIOR PHOTO OF HOT PILOT PLANT SECOND FLOOR WITH SOUTH SECTION OF SHIELDED CAVE IN FOREGROUND (CPP-640) LOOKING NORTHWEST. INL PHOTO NUMBER HD-54-40-1. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

[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.

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.

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.

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.

Physical Therapy Treatment of Pelvic Pain.

PubMed

Bradley, Michelle H; Rawlins, Ashley; Brinker, C Anna

2017-08-01

Physical therapists offer a valuable service in the treatment of chronic pelvic pain (CPP). Physical therapists are trained in functional restoration of the whole body. The physical therapist is in the unique position to assess and treat CPP in restoration of transitional movement ease and tolerance for improved functional control with the ultimate goal of wellness. It is imperative that pelvic floor muscle overactivity, underactivity, or a combination there of is accurately assessed and treated to avoid exacerbation of symptoms. The physical therapist has treatment options to restore the function with education in independent management of CPP. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Not Available

The 21st Century Power Partnership's program in Mexico (21CPP Mexico) is one initiative of the Clean Energy Ministerial, carried out in cooperation with government and local stakeholders, drawing upon an international community of power system expertise. The overall goal of this program is to support Mexico's power system transformation by accelerating the transition to a reliable, financially robust, and low-carbon system. 21CPP Mexico activities focus on achieving positive outcomes for all participants, especially addressing critical questions and challenges facing policymakers, regulators, and system operators. In support of this goal, 21CPP Mexico taps into deep networks of expertise and professional connections.

A possible link between dysmenorrhoea and the development of chronic pelvic pain.

PubMed

Hardi, Gemma; Evans, Susan; Craigie, Meredith

2014-12-01

Anecdotally, severe dysmenorrhoea can pre-date the development of chronic pelvic pain (CPP). This study describes the timeline for the transition from dysmenorrhoea to CPP in a cohort of new patients attending a private gynaecology clinic. In 16.4% of cases, transition occurred within one year, and within 12 years in over 50%. Our study suggests clinicians need to observe women with severe dysmenorrhoea for signs of chronic pain. Further research is needed into the transition from dysmenorrhoea to CPP, and effective early interventions. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

CPP-115, a Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Cocaine Addiction

PubMed Central

Pan, Yue; Gerasimov, Madina R.; Kvist, Trine; Wellendorph, Petrine; Madsen, Karsten K.; Pera, Elena; Lee, Hyunbeom; Schousboe, Arne; Chebib, Mary; Bräuner-Osborne, Hans; Craft, Cheryl M.; Brodie, Jonathan D.; Schiffer, Wynne K.; Dewey, Stephen L.; Miller, Steven R.; Silverman, Richard B.

2011-01-01

Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. Using in vivo microdialysis techniques in freely moving rats and micro-PET imaging techniques, CPP-115 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at 1/300–1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20–40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects. PMID:22128851

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.

Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

PubMed

Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

2014-04-01

The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Remedial Investigation Report for Lake City Army Ammunition Plant. Volume 1

DTIC Science & Technology

1990-06-01

EXPLOSIVE COMPOUNDS 1 3-DNB ɘ 61 ɘ.61 ɘ.61 ɘ.61 ɘ.61 1 73 135-7N6 11 7 ɘ.56 ɘ.56 ɘ.56 ɘ.56 0.7 *J 3.24 ə 30 ə 30 ə,30 ə.30 ə.30 POX ɘ...COMPOUNDS * 5- TNB I37 ɘ.56 ɘ. 56 ɘ 56 ɘ. 56 ɘ,56 HMX 17 4 ə.,30 ə 30 < 1 340 ᝻,30 ə.30 POX IS0 1.67 ɘ.63 ɘ.63 ɘ.63 1 84 OTHERS (ALL NO OR...Torkelson and Rowe 1031 5-209 Evidence suggests that 1,1,2-TCA is embryo toxic to chicken eggs (Elovaara 1979). I,I,2-TCA was found to be weakly mutagenic

Comparison of Explosives Residues from the Blow-in-Place Detonation of 155-mm High-Explosive Projectiles

DTIC Science & Technology

2006-06-01

were M107 high-explosive deep-cavity 155-mm howitzer projectiles with a supplemental charge and an M739 point- detonating fuze mounted in the nose...M107, HE, w/o fuze IOP03E100-011 14 1390010809447 N340 Fuze, point-detonating, M739 MA-84B007-013 14 1375014151232 ML47 Cap, blasting, non-electric 30... M739 N340 0 21 0 ə Cap, blasting, M11 ML47 ə 27 ə ə Cap, blasting, M13 MN03 0 ə 0 ə Cap, blasting, M14 MN06 0 0 0 ə Cord, detonating M456 0

Effect of calcium pyrophosphate on microstructural evolution and in vitro biocompatibility of Ti-35Nb-7Zr composite by spark plasma sintering.

PubMed

Zhang, L; Tan, J; He, Z Y; Jiang, Y H

2018-09-01

β-type Ti-35Nb-7Zr alloy has attracted considerable attentions as a bone implant material. The alloy, however, has poor bioactivity, which difficult to form a strong osseointegration between the bone tissues. Combining Ti alloy with a bioactive and biodegradable ceramic has been of interest to researchers. But the large difference in physicochemical property of high-melting metal and ceramic elements would bring the manufacturing restriction. In this work, Ti-35Nb-7Zr-CPP composites were fabricated with mechanical alloy of Ti, Nb, Zr and Nano calcium pyrophosphate (CPP) powders mixture followed by spark plasma sintering (SPS) routes. The effect of CPP ceramic on microstructural evolution and in vitro biocompatibility were investigated. As the addition of CPP (10-30 wt%), ceramic elements spreading towards the matrix, the generated metal-ceramic bioactive phases CaTiO 3 are observed well consolidated with β-Ti matrix. With the CPP increasing, Ca and P atoms rapidly migrated to the β-Ti matrix to form granulated Ti 5 P 3 , which leads to the increasing porosity (10%-18%) in the composites. The results demonstrated that the favorable cell viability (the cell proliferation rates were higher than 100%) and growth inside the pores of the composites arise from the rough micro-porous surface and the release of bioactive metal-ceramic phase ions into the biological environment. The enhanced bioactivity and microstructural evolution behaviors of the Ti-35Nb-7Zr-CPP composites may provide a strategy for designing and fabricating multifunctional implants. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical evaluation of remineralization potential of casein phosphopeptide amorphous calcium phosphate nanocomplexes for enamel decalcification in orthodontics.

PubMed

Wang, Jun-xiang; Yan, Yan; Wang, Xiu-jing

2012-11-01

Enamel decalcification in orthodontics is a concern for dentists and methods to remineralize these lesions are the focus of intense research. The aim of this study was to evaluate the remineralizing effect of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) nanocomplexes on enamel decalcification in orthodontics. Twenty orthodontic patients with decalcified enamel lesions during fixed orthodontic therapy were recruited to this study as test group and twenty orthodontic patients with the similar condition as control group. GC Tooth Mousse, the main component of which is CPP-ACP, was used by each patient of test group every night after tooth-brushing for six months. For control group, each patient was asked to brush teeth with toothpaste containing 1100 parts per million (ppm) of fluoride twice a day. Standardized intraoral images were taken for all patients and the extent of enamel decalcification was evaluated before and after treatment over this study period. Measurements were statistically compared by t test. After using CPP-ACP for six months, the enamel decalcification index (EDI) of all patients had decreased; the mean EDI before using CPP-ACP was 0.191 ± 0.025 and that after using CPP-ACP was 0.183 ± 0.023, the difference was significant (t = 5.169, P < 0.01). For control group, the mean EDI before treatment was 0.188 ± 0.037 and that after treatment was 0.187 ± 0.046, the difference was not significant (t = 1.711, P > 0.05). CPP-ACP can effectively improve the demineralized enamel lesions during orthodontic treatment, so it has some remineralization potential for enamel decalcification in orthodontics.

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.

Effects of cocaine combined with a social cue on conditioned place preference and nucleus accumbens monoamines after isolation rearing in rats

PubMed Central

Grotewold, Susan K.; Wall, Vanessa L.; Goodell, Dayton J.; Hayter, Cassandra

2015-01-01

Rationale Social interaction during drug exposure can potentiate cocaine reward. Isolation rearing (ISO) during adolescence increases social interaction and may amplify this potentiation. Objectives The objectives of this study are to determine whether ISO alters conditioned place preference (CPP) for cocaine when combined with a social cue and to determine whether ISO alters the effects of cocaine when combined with social cue on nucleus accumbens shell (NAcS) dopamine (DA) and serotonin (5-HT). Methods Male and female rats were either ISO or group (GRP) reared for 4 weeks during adolescence. CPP was performed using a low dose of cocaine (2 mg/kg or saline) with or without exposure to a novel same-sex conspecific during conditioning. In vivo microdialysis was performed using the same parameters. Results ISO rats engaged in more social and aggressive behaviors during conditioning relative to GRP. Cocaine reduced social and aggressive behaviors in all rats. CPP was not influenced by rearing condition. Cocaine produced significant CPP, and a social cue produced CPP only in males. In contrast, the interaction of cocaine and a social cue on NAcS DA and 5-HT differed depending upon rearing condition. In isolates, cocaine-induced DA was attenuated, while cocaine plus a social cue produced potentiated DA and 5-HT. Conclusions Exposure to a low dose of cocaine in the presence of a social cue produced additive effects on CPP while producing synergistic effects on DA and 5-HT in the NAcS of ISO rats. The aversive effects of this compound stimulus may negate the rewarding effects in isolates. PMID:24553577

Intracranial pressure monitoring after primary decompressive craniectomy in traumatic brain injury: a clinical study.

PubMed

Picetti, Edoardo; Caspani, Maria Luisa; Iaccarino, Corrado; Pastorello, Giulia; Salsi, Pierpaolo; Viaroli, Edoardo; Servadei, Franco

2017-04-01

Intracranial pressure (ICP) monitoring represents an important tool in the management of traumatic brain injury (TBI). Although current information exists regarding ICP monitoring in secondary decompressive craniectomy (DC), little is known after primary DC following emergency hematoma evacuation. Retrospective analysis of prospectively collected data. Inclusion criteria were age ≥18 years and admission to the intensive care unit (ICU) for TBI and ICP monitoring after primary DC. Exclusion criteria were ICU length of stay (LOS) <1 day and pregnancy. Major objectives were: (1) to analyze changes in ICP/cerebral perfusion pressure (CPP) after primary DC, (2) to evaluate the relationship between ICP/CPP and neurological outcome and (3) to characterize and evaluate ICP-driven therapies after DC. A total of 34 patients were enrolled. Over 308 days of ICP/CPP monitoring, 130 days with at least one episode of intracranial hypertension (26 patients, 76.5%) and 57 days with at least one episode of CPP <60 mmHg (22 patients, 64.7%) were recorded. A statistically significant relationship was discovered between the Glasgow Outcome Scale (GOS) scores and mean post-decompression ICP (p < 0.04) and between GOS and CPP minimum (CPPmin) (p < 0.04). After DC, persisting intracranial hypertension was treated with: barbiturate coma (n = 7, 20.6%), external ventricular drain (EVD) (n = 4, 11.8%), DC diameter widening (n = 1, 2.9%) and removal of newly formed hematomas (n = 3, 8.8%). Intracranial hypertension and/or low CPP occurs frequently after primary DC; their occurence is associated with an unfavorable neurological outcome. ICP monitoring appears useful in guiding therapy after primary DC.

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.

Effects of Sodium Benzoate Treatment in Combination with An Extinction Training on the Maintenance of Cocaine-Supported Memory.

PubMed

Tsai, Yi-Ni; Tzeng, Wen-Yu; Cherng, Chianfang G; Liao, Tien You; Wu, Hsin-Hua; Lin, Jie-Kuan; Yu, Lung

2016-02-29

Activation of N-methyl-D-aspartate (NMDA) receptor can facilitate the extinction of various maladaptive memories. Sodium benzoate (NaB) has been known to enhance a naturally occurring full agonist on the glycine binding site of the NMDA receptor. This study aimed to test whether systemic NaB treatment can affect the extinction of a cocaine-supported memory, the cocaine-induced conditioned place preference (CPP). Following the establishment of the cocaine (10 mg/kg/conditioning × 3)-induced CPP, an extinction protocol, consisting of two consecutive extinction training bouts at an 8-h interval, was used. NaB (500 mg/kg) or an equivalent volume of saline was given immediately following each extinction training bout to test the modulating effect of NaB on the maintenance of cocaine-induced CPP. Moreover, NaB was bilaterally micro-infused into the medial prefrontal cortex (mPFC) to validate the involvement of this brain region in mediating systemic NaB treatment-produced effect on cocaine-induced CPP. Systemic (500 mg/kg) and intra-mPFC (10 μg/side) NaB treatment significantly decreased subsequent cocaine-induced CPP magnitude, although the NaB treatment or the extinction training alone did not affect such CPP magnitude. It was of importance to note that systemic or intra-mPFC NaB delivery did not affect mouse locomotor activity in the retests. These results, taken together, suggest that NaB treatment in combination with the extinction training may facilitate the extinction of the cocaine-supported memory. Moreover, systemic NaB treatment exerts such effects, at least in part, via its effect in the mPFC.

Influence of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference in rats.

PubMed

Gawel, Kinga; Labuz, Krzysztof; Jenda, Malgorzata; Silberring, Jerzy; Kotlinska, Jolanta H

2014-07-15

The influence of systemic administration of cholinesterase inhibitors, donepezil and rivastigmine on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (CPP) was examined in rats. Additionally, this study aimed to compare the effects of donepezil, which selectively inhibits acetylcholinesterase, and rivastigmine, which inhibits both acetylcholinesterase and butyrylcholinesterase on morphine reward. Morphine-induced CPP (unbiased method) was induced by four injections of morphine (5 mg/kg, i.p.). Donepezil (0.5, 1, and 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5, and 1 mg/kg, i.p.) were given 20 min before morphine during conditioning phase and 20 min before the expression or reinstatement of morphine-induced CPP. Our results indicated that both inhibitors of cholinesterase attenuated the acquisition and expression of morphine CPP. The results were more significant after rivastigmine due to a broader inhibitory spectrum of this drug. Moreover, donepezil (1 mg/kg) and rivastigmine (0.5 mg/kg) attenuated the morphine CPP reinstated by priming injection of 5mg/kg morphine. These properties of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist but not scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. All effects of cholinesterase inhibitors were observed at the doses that had no effects on locomotor activity of animals. Our results suggest beneficial role of cholinesterase inhibitors in reduction of morphine reward and morphine-induced seeking behavior. Finally, we found that the efficacy of cholinesterase inhibitors in attenuating reinstatement of morphine CPP provoked by priming injection may be due to stimulation of nicotinic acetylcholine receptors. Copyright © 2014 Elsevier B.V. All rights reserved.

Dopamine D1 receptor agonist treatment attenuates extinction of morphine conditioned place preference while increasing dendritic complexity in the nucleus accumbens core.

PubMed

Kobrin, Kendra L; Arena, Danielle T; Heinrichs, Stephen C; Nguyen, Olivia H; Kaplan, Gary B

2017-03-30

The dopamine D1 receptor (D1R) has a role in opioid reward and conditioned place preference (CPP), but its role in CPP extinction is undetermined. We examined the effect of D1R agonist SKF81297 on the extinction of opioid CPP and associated dendritic morphology in the nucleus accumbens (NAc), a region involved with reward integration and its extinction. During the acquisition of morphine CPP, mice received morphine and saline on alternate days; injections were given immediately before each of eight daily conditioning sessions. Mice subsequently underwent six days of extinction training designed to diminish the previously learned association. Mice were treated with either 0.5mg/kg SKF81297, 0.8mg/kg SKF81297, or saline immediately after each extinction session. There was a dose-dependent effect, with the highest dose of SKF81297 attenuating extinction, as mice treated with this dose had significantly higher CPP scores than controls. Analysis of medium spiny neuron morphology revealed that in the NAc core, but not in the shell, dendritic arbors were significantly more complex in the morphine conditioned, SKF81297-treated mice compared to controls. In separate experiments using mice conditioned with only saline, SKF81297 administration after extinction sessions had no effect on CPP and produced differing effects on dendritic morphology. At the doses used in our experiments, SKF81297 appears to maintain previously learned opioid conditioned behavior, even in the face of new information. The D1R agonist's differential, rather than unidirectional, effects on dendritic morphology in the NAc core suggests that it may be involved in encoding reward information depending on previously learned behavior. Published by Elsevier B.V.

Early-life experience decreases drug-induced reinstatement of morphine CPP in adulthood via microglial-specific epigenetic programming of anti-inflammatory IL-10 expression.

PubMed

Schwarz, Jaclyn M; Hutchinson, Mark R; Bilbo, Staci D

2011-12-07

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat nucleus accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene × early-life environment interaction on morphine-induced glial activation and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior.

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.

Early-Life Experience Decreases Drug-Induced Reinstatement of Morphine CPP in Adulthood via Microglial-Specific Epigenetic Programming of Anti-Inflammatory IL-10 Expression

PubMed Central

Schwarz, Jaclyn M.; Hutchinson, Mark R.; Bilbo, Staci D.

2012-01-01

A critical component of drug addiction research involves identifying novel biological mechanisms and environmental predictors of risk or resilience to drug addiction and associated relapse. Increasing evidence suggests microglia and astrocytes can profoundly affect the physiological and addictive properties of drugs of abuse, including morphine. We report that glia within the rat Nucleus Accumbens (NAcc) respond to morphine with an increase in cytokine/chemokine expression, which predicts future reinstatement of morphine conditioned place preference (CPP) following a priming dose of morphine. This glial response to morphine is influenced by early-life experience. A neonatal handling paradigm that increases the quantity and quality of maternal care significantly increases baseline expression of the anti-inflammatory cytokine IL-10 within the NAcc, attenuates morphine-induced glial activation, and prevents the subsequent reinstatement of morphine CPP in adulthood. IL-10 expression within the NAcc and reinstatement of CPP are negatively correlated, suggesting a protective role for this specific cytokine against morphine-induced glial reactivity and drug-induced reinstatement of morphine CPP. Neonatal handling programs the expression of IL-10 within the NAcc early in development, and this is maintained into adulthood via decreased methylation of the IL-10 gene specifically within microglia. The effect of neonatal handling is mimicked by pharmacological modulation of glia in adulthood with Ibudilast, which increases IL-10 expression, inhibits morphine-induced glial activation within the NAcc, and prevents reinstatement of morphine CPP. Taken together, we have identified a novel gene X early-life environment interaction on morphine-induced glial activation, and a specific role for glial activation in drug-induced reinstatement of drug-seeking behavior. PMID:22159099

Micro-CT and FE-SEM enamel analyses of calcium-based agent application after bleaching.

PubMed

Gomes, Mauricio Neves; Rodrigues, Flávia Pires; Silikas, Nick; Francci, Carlos Eduardo

2018-03-01

The objective of the present study is to evaluate the effects of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on bleached enamel. A bleaching agent (35% hydrogen peroxide) was applied, 4 × 8 min on premolar teeth (n = 8). A CPP-ACP paste was applied for 7 days. Prior and post-treatment, microtomography images were obtained and 3D regions of interest (ROIs) were selected, from outer enamel, extending to 110.2-μm depth. CT parameters of structure: thickness (St.Th), separation (St.Sp), and fragmentation index (Fr.I.) were calculated for each (ROI). Data was submitted to paired t tests at a 95% confidence level. The samples were evaluated at 3000 to 100,000 magnification. Quantitative analysis of enamel mineral content was also determined by SEM EDX. There was a significant increase in structure thickness and calcium content. The phosphorus content increased after bleaching. There was also a decreased separation and fragmentation index on the outer enamel to a depth of 56.2 μm (p < 0.05). There were no changes at 110.2-μm depth for the bleaching CPP-ACP association. A covering layer and decreased spaces between the hydroxyapatite crystals appeared around the enamel prisms, 7 days after the CPP-ACP application. The application of a CPP-ACP provides a compact structure on the enamel's outer surface, for 7 days, due to calcium deposition. CT parameters seem to be a useful tool for mineralizing and remineralizing future studies. CPP-ACP neutralizes any adverse effects on enamel surface when applied during a week after bleaching and minimizes any side effects of the bleaching treatment due to a more compact structure.

Parameters for abolishing conditioned place preference for cocaine from running and environmental enrichment in male C57BL/6J mice.

PubMed

Mustroph, M L; Pinardo, H; Merritt, J R; Rhodes, J S

2016-10-01

Evidence suggests that 4 weeks of voluntary wheel running abolishes conditioned place preference (CPP) for cocaine in male C57BL/6J mice. To determine the duration and timing of exposure to running wheels necessary to reduce CPP, and the extent to which the running per se influences CPP as compared to environmental enrichment without running. A total of 239 males were conditioned for 4days twice daily with cocaine (10mg/kg) and then split into 7 intervention groups prior to 4days of CPP testing. Experiment 1 consisted of two groups housed as follows: short sedentary group (SS; n=20) in normal cages for 1 week; the short running group (SR; n=20) with running wheels for 1 week. Experiment 2 consisted of five groups housed as follows; short 1 week of running followed by a 3 week sedentary period (SRS; n=20); a 3 week sedentary period followed by 1 week of running (SSR; n=20); long sedentary group (LS; n=66) in normal cages for 4 weeks; long running group (LR; n=66) with running wheels for 4 weeks; and long environmental enrichment group (EE; n=27) with toys for 4 weeks. Levels of running were similar in all running groups. Both running and environmental enrichment reduced CPP relative to sedentary groups. Results suggest that the abolishment of cocaine CPP from running is robust and occurs with as low as 1 week of intervention but may be related to enrichment component of running rather than physical activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Adolescent social defeat increases adult amphetamine conditioned place preference and alters D2 dopamine receptor expression

PubMed Central

Burke, Andrew R.; Watt, Michael J.; Forster, Gina L.

2011-01-01

Components of the brain’s dopaminergic system, such as dopamine receptors, undergo final maturation in adolescence. Exposure to social stress during human adolescence contributes to substance abuse behaviors. We utilized a rat model of adolescent social stress to investigate the neural mechanisms underlying this correlation. Rats exposed to repeated social defeat in adolescence (P35–P39) exhibited increased conditioned place preference (CPP) for amphetamine (1 mg/kg) in adulthood (P70). In contrast, rats experiencing foot-shock during the same developmental period exhibited amphetamine CPP levels similar to non-stressed controls. Our previous experiments suggested adolescent defeat alters dopamine activity in the mesocorticolimbic system. Furthermore, dopamine receptors have been implicated in the expression of amphetamine CPP. Therefore, we hypothesized that alteration to dopamine receptor expression in the mesocorticolimbic system may be associated with to heightened amphetamine CPP of adult rats exposed to adolescence defeat. We measured D1 and D2 dopamine receptor protein content in the medial prefrontal cortex, nucleus accumbens (NAc) and dorsal striatum following either adolescent social defeat or foot-shock stress and then adult amphetamine CPP. In controls, amphetamine CPP training reduced D2 receptor protein content in the NAc core. However, this down-regulation of NAc core D2 receptors was blocked by exposure to social defeat but not foot-shock stress in adolescence. These results suggest social defeat stress in adolescence alters the manner in which later amphetamine exposure down-regulates D2 receptors. Furthermore, persistent alterations to adult D2 receptor expression and amphetamine responses may depend on the type of stress experienced in adolescence. PMID:21933700

Inhibition of alpha7 nicotinic receptors in the ventral hippocampus selectively attenuates reinstatement of morphine-conditioned place preference and associated changes in AMPA receptor binding.

PubMed

Wright, Victoria L; Georgiou, Polymnia; Bailey, Alexis; Heal, David J; Bailey, Christopher P; Wonnacott, Susan

2018-04-17

Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine-conditioned place preference (morphine-CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence. The α7 nAChR antagonist methyllycaconitine (MLA; 4 mg/kg s.c.) had no effect on the acquisition, maintenance, reconsolidation or extinction of morphine-CPP but selectively attenuated morphine-primed reinstatement of CPP, in both mice and rats. Reinstatement of morphine-CPP in mice was accompanied by a selective increase in [ 3 H]-AMPA binding (but not in [ 3 H]-MK801 binding) in the ventral hippocampus that was prevented by prior treatment with MLA. Administration of MLA (6.7 μg) directly into the ventral hippocampus of rats prior to a systemic priming dose of morphine abolished reinstatement of morphine-CPP, whereas MLA delivered into the dorsal hippocampus or prefrontal cortex was without effect. These results suggest that α7 nAChRs in the ventral hippocampus play a specific role in the retrieval of associative drug memories following a period of extinction, making them potential targets for the prevention of relapse. © 2018 The Authors.Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

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

Central precocious puberty: treatment with triptorelin 11.25 mg.

PubMed

Chiocca, Elena; Dati, Eleonora; Baroncelli, Giampiero I; Cassio, Alessandra; Wasniewska, Malgorzata; Galluzzi, Fiorella; Einaudi, Silvia; Cappa, Marco; Russo, Gianni; Bertelloni, Silvano

2012-01-01

Few data are available on quarterly 11.25 mg GnRH analog treatment in central precocious puberty (CPP). To assess the efficacy of triptorelin 11.25 mg in children with CPP. 17 patients (16 females) with CPP (7.9 ± 0.9 years) were treated with triptorelin 11.25 mg/90 days. Gonadotropins, basal-, and GnRH-stimulated peak, gonadal steroids, and pubertal signs were assessed at preinclusion and at inclusion visit, 3 months, 6 months, and 12 months of treatment. Results. At 3, 6, and 12 months, all patients had suppressed LH peak (<3 IU/L after GnRH stimulation), as well as prepubertal oestradiol levels. Mean LH peak values after GnRH test significantly decreased from 25.7 ± 16.5 IU/L at baseline to 0.9 ± 0.5 IU/L at M3 (P < 0.0001); they did not significantly changed at M6 and M12. Triptorelin 11.25 mg/90 days efficiently suppressed the pituitary-gonadal axis in children with CPP from first administration.

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.

Brain Circuits of Methamphetamine Place Reinforcement Learning: The Role of the Hippocampus-VTA Loop.

PubMed

Keleta, Yonas B; Martinez, Joe L

2012-03-01

The reinforcing effects of addictive drugs including methamphetamine (METH) involve the midbrain ventral tegmental area (VTA). VTA is primary source of dopamine (DA) to the nucleus accumbens (NAc) and the ventral hippocampus (VHC). These three brain regions are functionally connected through the hippocampal-VTA loop that includes two main neural pathways: the bottom-up pathway and the top-down pathway. In this paper, we take the view that addiction is a learning process. Therefore, we tested the involvement of the hippocampus in reinforcement learning by studying conditioned place preference (CPP) learning by sequentially conditioning each of the three nuclei in either the bottom-up order of conditioning; VTA, then VHC, finally NAc, or the top-down order; VHC, then VTA, finally NAc. Following habituation, the rats underwent experimental modules consisting of two conditioning trials each followed by immediate testing (test 1 and test 2) and two additional tests 24 h (test 3) and/or 1 week following conditioning (test 4). The module was repeated three times for each nucleus. The results showed that METH, but not Ringer's, produced positive CPP following conditioning each brain area in the bottom-up order. In the top-down order, METH, but not Ringer's, produced either an aversive CPP or no learning effect following conditioning each nucleus of interest. In addition, METH place aversion was antagonized by coadministration of the N-methyl-d-aspartate (NMDA) receptor antagonist MK801, suggesting that the aversion learning was an NMDA receptor activation-dependent process. We conclude that the hippocampus is a critical structure in the reward circuit and hence suggest that the development of target-specific therapeutics for the control of addiction emphasizes on the hippocampus-VTA top-down connection.

Brain-derived neurotrophic factor (BDNF) in the rostral anterior cingulate cortex (rACC) contributes to neuropathic spontaneous pain-related aversion via NR2B receptors.

PubMed

Zhang, Le; Wang, Gongming; Ma, Jinben; Liu, Chengxiao; Liu, Xijiang; Zhan, Yufeng; Zhang, Mengyuan

2016-10-01

The rostral anterior cingulate cortex (rACC) plays an important role in pain affect. Previous investigations have reported that the rACC mediates the negative affective component of inflammatory pain and contributed to the aversive state of nerve injury-induced neuropathic pain. Brain-derived neurotrophic factor (BDNF), an activity-dependent neuromodulator in the adult brain, is believed to play a role in the development and maintenance of inflammatory and neuropathic pain in the spinal cord. However, whether and how BDNF in the rACC regulates pain-related aversion due to peripheral nerve injury is largely unknown. Behaviorally, using conditioned place preference (CPP) training in rats, which is thought to reveal spontaneous pain-related aversion, we found that CPP was acquired following spinal clonidine in rats with partial sciatic nerve transection. Importantly, BDNF was upregulated within the rACC in of rats with nerve injury and enhanced the CPP acquisition, while a local injection of a BDNF-tropomyosin receptor kinase B (TrkB) antagonist into the rACC completely blocked this process. Finally, we demonstrated that the BDNF/TrkB pathway exerted its function by activating the NR2B receptor, which is widely accepted to be a crucial factor contributing to pain affect. In conclusion, our results demonstrate that the BDNF/TrkB-mediated signaling pathway in the rACC is involved in the development of neuropathic spontaneous pain-related aversion and that this process is dependent upon activation of NR2B receptors. These findings suggest that suppression of the BDNF-related signaling pathway in the rACC may provide a novel strategy to overcome pain-related aversion. Copyright © 2016 Elsevier Inc. All rights reserved.

NAc Shell Arc/Arg3.1 Protein Mediates Reconsolidation of Morphine CPP by Increased GluR1 Cell Surface Expression: Activation of ERK-Coupled CREB is Required

PubMed Central

Lv, Xiu-Fang; Sun, Lin-Lin; Han, Ji-Sheng

2015-01-01

Background: Relapse into drug abuse evoked by reexposure to the drug-associated context has been a primary problem in the treatment of drug addiction. Disrupting the reconsolidation of drug-related context memory would therefore limit the relapse susceptibility. Methods: Morphine conditioned place preference (CPP) was used to assess activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and correlative molecule expression in the Nucleus accumbens (NAc) shell during the reconsolidation of morphine CPP. U0126 and Arc/Arg3.1 antisense oligodeoxynucleotide were adapted to evaluate the role and the underlying mechanism of Arc/Arg3.1 during the reconsolidation. Results: The retrieval of morphine CPP in rats specifically increased the Arc/Arg3.1 protein level in the NAc shell, accompanied simultaneously by increases in the phosphorylation of extracellular signal-regulated kinase1/2 (pERK1/2), the phosphorylation of Cyclic Adenosine monophosphate (cAMP) response element-binding (pCREB), and the up-regulation of the membrane α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors GluR1 subunit level. Intra-NAc shell infusion U0126, an inhibitor of the Mitogen-activated protein kinase kinase (MEK), prevented the retrieval-induced up-regulation of pERK1/2, pCREB, Arc/Arg3.1, and membrane GluR1 immediately after retrieval of morphine CPP. The effect of disrupting the reconsolidation of morphine CPP by U0126 could last for at least 14 days, and could not be evoked by a priming injection of morphine. Furthermore, the specific knockdown of Arc/Arg3.1 in the NAc shell decreased the membrane GluR1 level, and impaired both the reconsolidation and the reinstatement of morphine CPP. Conclusions: Arc/Arg3.1 in the NAc shell mediates the reconsolidation of morphine-associated context memory via up-regulating the level of membrane of GluR1, for which the local activation of the ERK-CREB signal pathway, as an upstream mechanism of Arc/Arg3.1, is required. PMID:25746394

Disequilibrium dihedral angles in layered intrusions: the microstructural record of fractionation

NASA Astrophysics Data System (ADS)

Holness, Marian; Namur, Olivier; Cawthorn, Grant

2013-04-01

The dihedral angle formed at junctions between two plagioclase grains and a grain of augite is only rarely in textural equilibrium in gabbros from km-scale crustal layered intrusions. The median of a population of these disequilibrium angles, Θcpp, varies systematically within individual layered intrusions, remaining constant over large stretches of stratigraphy with significant increases or decreases associated with the addition or reduction respectively of the number of phases on the liquidus of the bulk magma. The step-wise changes in Θcpp are present in Upper Zone of the Bushveld Complex, the Megacyclic Unit I of the Sept Iles Intrusion, and the Layered Series of the Skaergaard Intrusion. The plagioclase-bearing cumulates of Rum have a bimodal distribution of Θcpp, dependent on whether the cumulus assemblage includes clinopyroxene. The presence of the step-wise changes is independent of the order of arrival of cumulus phases and of the composition of either the cumulus phases or the interstitial liquid inferred to be present in the crystal mush. Step-wise changes in the rate of change in enthalpy with temperature (ΔH) of the cooling and crystallizing magma correspond to the observed variation of Θcpp, with increases of both ΔH and Θcpp associated with the addition of another liquidus phase, and decreases of both associated with the removal of a liquidus phase. The replacement of one phase by another (e.g. olivine ⇔ orthpyroxene) has little effect on ΔH and no discernible effect on Θcpp. An increase of ΔH is manifest by an increase in the fraction of the total enthalpy budget that is the latent heat of crystallization (the fractional latent heat). It also results in an increase in the amount crystallized in each incremental temperature drop (the crystal productivity). An increased fractional latent heat and crystal productivity result in an increased rate of plagioclase growth compared to that of augite during the final stages of solidification, causing a step-wise increase in Θcpp. Step-wise changes in the geometry of three-grain junctions in fully solidified gabbros thus provide a clear microstructural marker for the progress of fractionation.

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

Mutations of the KISS1 Gene in Disorders of Puberty

PubMed Central

Silveira, L. G.; Noel, S. D.; Silveira-Neto, A. P.; Abreu, A. P.; Brito, V. N.; Santos, M. G.; Bianco, S. D. C.; Kuohung, W.; Xu, S.; Gryngarten, M.; Escobar, M. E.; Arnhold, I. J. P.; Mendonca, B. B.; Kaiser, U. B.; Latronico, A. C.

2010-01-01

Context: Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Objective: Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Patients: Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. Methods: The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Results: Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild type. After preincubation of wild-type and mutant kp54 in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared with the wild type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Conclusion: Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison with the wild type, suggesting a role for this mutation in the precocious puberty phenotype. PMID:20237166

Mutations of the KISS1 gene in disorders of puberty.

PubMed

Silveira, L G; Noel, S D; Silveira-Neto, A P; Abreu, A P; Brito, V N; Santos, M G; Bianco, S D C; Kuohung, W; Xu, S; Gryngarten, M; Escobar, M E; Arnhold, I J P; Mendonca, B B; Kaiser, U B; Latronico, A C

2010-05-01

Kisspeptin, encoded by the KISS1 gene, is a key stimulatory factor of GnRH secretion and puberty onset. Inactivating mutations of its receptor (KISS1R) cause isolated hypogonadotropic hypogonadism (IHH). A unique KISS1R-activating mutation was described in central precocious puberty (CPP). Our objective was to investigate KISS1 mutations in patients with idiopathic CPP and normosmic IHH. Eighty-three children with CPP (77 girls) and 61 patients with IHH (40 men) were studied. The control group consisted of 200 individuals with normal pubertal development. The promoter region and the three exons of KISS1 were amplified and sequenced. Cells expressing KISS1R were stimulated with synthetic human wild-type or mutant kisspeptin-54 (kp54), and inositol phosphate accumulation was measured. In a second set of experiments, kp54 was preincubated in human serum before stimulation of the cells. Two novel KISS1 missense mutations, p.P74S and p.H90D, were identified in three unrelated children with idiopathic CPP. Both mutations were absent in 400 control alleles. The p.P74S mutation was identified in the heterozygous state in a boy who developed CPP at 1 yr of age. The p.H90D mutation was identified in the homozygous state in two unrelated girls with CPP. In vitro studies revealed that the capacity of the P74S and H90D mutants to stimulate IP production was similar to the wild type. After preincubation of wild-type and mutant kp54 in human serum, the capacity to stimulate signal transduction was significantly greater for P74S compared with the wild type, suggesting that the p.P74S variant is more stable. Only polymorphisms were found in the IHH group. Two KISS1 mutations were identified in unrelated patients with idiopathic CPP. The p.P74S variant was associated with higher kisspeptin resistance to degradation in comparison with the wild type, suggesting a role for this mutation in the precocious puberty phenotype.

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.

South Africa and the 21st Century Power Partnership (Fact Sheet). 21st Century Power Partnership; 21st Century Power Partnership

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

None

Established in 2012, the 21CPP South Africa Programme is a global initiative that connects South African stakeholders with an international community of expertise. The overall goal of this program is to support South Africa’s power system transformation by accelerating the transition to a reliable, financially robust, and low-carbon power system. 21CPP activities focus on achieving positive outcomes for all participants, especially addressing critical questions and challenges facing system planners, regulators, and operators. In support of this goal, 21CPP taps into deep networks of expertise among leading industry practitioners.

Annual Energy Outlook 2016 With Projections to 2040

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

None, None

The Annual Energy Outlook 2016 (AEO2016), prepared by the U.S. Energy Information Administration (EIA), presents long-term projections of energy supply, demand, and prices through 2040. The projections, focused on U.S. energy markets, are based on results from EIA’s National Energy Modeling System (NEMS). NEMS enables EIA to make projections under alternative, internallyconsistent sets of assumptions. The analysis in AEO2016 focuses on the Reference case and 17 alternative cases. EIA published an Early Release version of the AEO2016 Reference case (including U.S. Environmental Protection Agency’s (EPA) Clean Power Plan (CPP)) and a No CPP case (excluding the CPP) in May 2016.

Channel plasmon-polariton guiding by subwavelength metal grooves.

PubMed

Bozhevolnyi, Sergey I; Volkov, Valentyn S; Devaux, Eloïse; Ebbesen, Thomas W

2005-07-22

We report on realization of channel plasmon-polariton (CPP) propagation along a subwavelength metal groove. Using imaging with a near-field microscope and end-fire coupling with a tapered fiber connected to a tunable laser at telecommunication wavelengths (1425-1620 nm), we demonstrate low-loss (propagation length approximately 100 microm) and well-confined (mode width approximately 1.1 microm) CPP guiding along a triangular 0.6 microm-wide and 1 microm-deep groove in gold. We develop a simple model based on the effective-index method that accounts for the main features of CPP guiding and provides a clear physical picture of this phenomenon.

Diet-induced obesity causes ghrelin resistance in reward processing tasks.

PubMed

Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

2015-12-01

Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

48 CFR 3401.601 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false General. 3401.601 Section 3401.601 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION GENERAL ED ACQUISITION REGULATION SYSTEM Contracting Authority and Responsibilities 3401.601 General...

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.

Correlation between cerebral hemodynamic and perfusion pressure changes in non-human primates

NASA Astrophysics Data System (ADS)

Ruesch, A.; Smith, M. A.; Wollstein, G.; Sigal, I. A.; Nelson, S.; Kainerstorfer, J. M.

2017-02-01

The mechanism that maintains a stable blood flow in the brain despite changes in cerebral perfusion pressure (CPP), and therefore guaranties a constant supply of oxygen and nutrients to the neurons, is known as cerebral auto-regulation (CA). In a certain range of CPP, blood flow is mediated by a vasomotor adjustment in vascular resistance through dilation of blood vessels. CA is known to be impaired in diseases like traumatic brain injury, Parkinson's disease, stroke, hydrocephalus and others. If CA is impaired, blood flow and pressure changes are coupled and thee oxygen supply might be unstable. Lassen's blood flow auto-regulation curve describes this mechanism, where a plateau of stable blood flow in a specific range of CPP corresponds to intact auto-regulation. Knowing the limits of this plateau and maintaining CPP within these limits can improve patient outcome. Since CPP is influenced by both intracranial pressure and arterial blood pressure, long term changes in either can lead to auto-regulation impairment. Non-invasive methods for monitoring blood flow auto-regulation are therefore needed. We propose too use Near infrared spectroscopy (NIRS) too fill this need. NIRS is an optical technique, which measures microvascular changes in cerebral hemoglobin concentration. We performed experiments on non-human primates during exsanguination to demonstrate that thee limits of blood flow auto-regulation can be accessed with NIRS.

Inhibition of Hippocampal β-Adrenergic Receptors Impairs Retrieval But Not Reconsolidation of Cocaine-Associated Memory and Prevents Subsequent Reinstatement

PubMed Central

Otis, James M; Fitzgerald, Michael K; Mueller, Devin

2014-01-01

Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment. PMID:23907403

Cell-Penetrating Peptide-Mediated Delivery of Cas9 Protein and Guide RNA for Genome Editing.

PubMed

Suresh, Bharathi; Ramakrishna, Suresh; Kim, Hyongbum

2017-01-01

The clustered, regularly interspaced, short palindromic repeat (CRISPR)-associated (Cas) system represents an efficient tool for genome editing. It consists of two components: the Cas9 protein and a guide RNA. To date, delivery of these two components has been achieved using either plasmid or viral vectors or direct delivery of protein and RNA. Plasmid- and virus-free direct delivery of Cas9 protein and guide RNA has several advantages over the conventional plasmid-mediated approach. Direct delivery results in shorter exposure time at the cellular level, which in turn leads to lower toxicity and fewer off-target mutations with reduced host immune responses, whereas plasmid- or viral vector-mediated delivery can result in uncontrolled integration of the vector sequence into the host genome and unwanted immune responses. Cell-penetrating peptide (CPP), a peptide that has an intrinsic ability to translocate across cell membranes, has been adopted as a means of achieving efficient Cas9 protein and guide RNA delivery. We developed a method for treating human cell lines with CPP-conjugated recombinant Cas9 protein and CPP-complexed guide RNAs that leads to endogenous gene disruption. Here we describe a protocol for preparing an efficient CPP-conjugated recombinant Cas9 protein and CPP-complexed guide RNAs, as well as treatment methods to achieve safe genome editing in human cell lines.

The interplay between ventro striatal BDNF levels and the effects of valproic acid on the acquisition of ethanol-induced conditioned place preference in mice.

PubMed

Dos Santos, Manuel Alves; Escudeiro, Sarah Sousa; Vasconcelos, Germana Silva; Matos, Natália Castelo Branco; de Souza, Marcos Romário Matos; Patrocínio, Manoel Cláudio Azevedo; Dantas, Leonardo Pimentel; Macêdo, Danielle; Vasconcelos, Silvânia Maria Mendes

2017-11-01

Alcohol addiction is a chronic, relapsing and progressive brain disease with serious consequences for health. Compulsive use of alcohol is associated with the capacity to change brain structures involved with the reward pathway, such as ventral striatum. Recent evidence suggests a role of chromatin remodeling in the pathophysiology of alcohol dependence and addictive-like behaviors. In addition, neuroadaptive changes mediated by the brain-derived neurotrophic factor (BDNF) seems to be an interesting pharmacological target for alcoholism treatment. In the present study, we evaluated the effects of the deacetylase inhibitor valproic acid (VPA) (300mg/kg) on the conditioned rewarding effects of ethanol using conditioned place preference (CPP) (15% v/v; 2g/kg). Ethanol rewarding effect was investigated using a biased protocol of CPP. BDNF levels were measured in the ventral striatum. Ethanol administration induced CPP. VPA pretreatment did not reduce ethanol-CPP acquisition. VPA pretreatment increased BDNF levels when compared to ethanol induced-CPP. VPA pretreatment increased BDNF levels even in saline conditioned mice. Taken together, our results indicate a modulatory effect of VPA on the BDNF levels in the ventral striatum. Overall, this study brings initial insights into the involvement of neurotrophic mechanisms in the ventral striatum in ethanol-induced addictive-like behavior. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of hippocampal β-adrenergic receptors impairs retrieval but not reconsolidation of cocaine-associated memory and prevents subsequent reinstatement.

PubMed

Otis, James M; Fitzgerald, Michael K; Mueller, Devin

2014-01-01

Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment.

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.

Evaluation of quality of life and sexual satisfaction in women suffering from chronic pelvic pain with or without endometriosis.

PubMed

Tripoli, Tatiana M; Sato, Hélio; Sartori, Marair G; de Araujo, Fábio Fernando; Girão, Manoel J B C; Schor, Eduardo

2011-02-01

Chronic pelvic pain (CPP) is one of the most frequent symptoms in women of reproductive age. This is an enigmatic clinical condition that results from the complex interactions of physiological and psychological factors with direct impact on the social, marital, and professional lives of women. To evaluate the quality of life and sexual satisfaction of women who suffer from CPP with or without endometriosis. Forty-nine patients who had been diagnosed with endometriosis and 35 patients with CPP diagnosed with another gynecological condition, all 84 of whom were treated at the Chronic Pelvic Pain and Endometriosis Clinic at Universidade Federal de São Paulo (UNIFESP) from January to July of 2008. The controls were 50 healthy women from the Family Planning Clinic at UNIFESP. World Health Organization Quality of Life Assessment-Bref (WHOQOL-BREF) quality of life questionnaire and the Golombok-Rust Inventory of Sexual Satisfaction (GRISS). No statistically significant differences were observed between the groups with CPP symptoms, in either the results from the WHOQOL-BREF or in the GRISS questionnaire. In both questionnaires, differences were observed when the two groups of symptomatic women were compared with the group of healthy women. CPP caused by endometriosis or other gynecological conditions leads to a significant reduction of quality of life and sexual satisfaction. © 2010 International Society for Sexual Medicine.

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.

Does systemic administration of casein phosphopeptides affect orthodontic movement and root resorption in rats?

PubMed

Crowther, Lachlan; Shen, Gang; Almuzian, Mohammed; Jones, Allan; Walsh, William; Oliver, Rema; Petocz, Peter; Tarraf, Nour E; Darendeliler, M Ali

2017-10-01

To assess the potential effects of casein phosphopeptides (CPPs) on orthodontically induced iatrogenic root resorption (OIIRR) and orthodontic teeth movement. Forty Wistar rats (aged 11 weeks) were randomly divided into experimental group (EG; n = 20) that received a diet supplemented with CPP and control group (CG; n = 20) devoid of diet supplement. A 150 g force was applied using nickel titanium (NiTi) coil that was bonded on maxillary incisors and extended unilaterally to a maxillary first molar. At Day 28, animals in both groups were euthanized. Volumetric assessment of root resorption craters and linear measurement of maxillary first molars movement were blindly examined using a micro-computed tomography scan. Nine rats were excluded from the experiment due to loss during general anesthesia or appliances' failure. Intra-operator reproducibility was high in both volumetric and linear measurements, 92.8 per cent and 98.5-97.6 per cent, respectively. The results reveal that dietary CPP has statistically insignificant effect on the overall OIIRR and orthodontic movement. CPP seems to have statistically insignificant effect on the volume of OIIRR and orthodontic movement in rats. A long-term study with larger sample size using a different concentration of CPP is required to clarify the dentoalveolar effect of CPP. © The Author 2017. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com

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

Childhood physical punishment and the onset of drinking problems: evidence from metropolitan China

PubMed Central

Cheng, Hui G.; Anthony, James C.; Huang, Yuequin; Lee, Sing; Liu, Zhaorui; He, Yanling

2011-01-01

Background Evidence in support of a suspected causal association linking childhood physical punishment (CPP) and later alcoholic beverage-related disturbances has been found in metropolitan China. Here, the focus shifts to the CPP association with the estimated risk of starting to drink, having the first drinking problem, and transitioning from first drink to the first drinking problem. Methods Data are from the World Mental Health Surveys-metropolitan China study, with representative samples of adult household residents living in two metropolitan cities, Beijing and Shanghai. Recalled information was available for early life experiences (including CPP, other childhood adversities, and parental alcohol and drug problems), as well as the onset age of drinking and drinking problems. Survival analyses were used to estimate the hazard ratio. A structural equation modeling approach was used to control for other inter-correlated childhood adversities. Results Cox proportional hazards modeling discloses statistically robust associations linking CPP with drinking and drinking problems, as well as more rapid transitions from first drink to first drinking problem, even after accounting for other childhood adversities and parental drinking problems. These associations cannot be attributed to a more general noxious family environment. Conclusions These results lay a foundation for future experimental studies on the possible causal relationship linking CPP with the onset of drinking problems and the transition from drinking to drinking problems. PMID:21474254

Proteolytic cleavage and activation of PAK2 during UV irradiation-induced apoptosis in A431 cells.

PubMed

Tang, T K; Chang, W C; Chan, W H; Yang, S D; Ni, M H; Yu, J S

1998-09-15

Exposure of mammalian cells to ultraviolet (UV) light elicits a cellular response and can also lead to apoptotic cell death. In this report, we show that a 36-kDa myelin basic protein (MBP) kinase detected by an in-gel kinase assay can be dramatically activated during the early stages of UV irradiation-triggered apoptosis of A431 cells. Immunoblot analysis revealed that this 36-kDa MBP kinase could be recognized by an antibody against the C-terminal regions of a family of p21Cdc42/Rac-activated kinases (PAKs). By using this antibody and a PAK2-specific antibody against the N-terminal region of PAK2 as studying tools, we further demonstrated that UV irradiation caused cleavage of PAK2 to generate a 36-kDa C-terminal catalytic fragment and a 30-kDa N-terminal fragment in A431 cells. The appearance of the 36-kDa C-terminal catalytic fragment of PAK2 matched exactly with the activation of the 36-kDa MBP kinase in A431 cells upon UV irradiation. In addition, UV irradiation also led to activation of CPP32/caspase-3, but not ICH-1L/caspase-2 and ICE/caspase-1, in A431 cells and the kinetics of activation of CPP32/caspase-3 appeared to correlate well with that of DNA fragmentation and of cleavage/activation of PAK2, respectively. Moreover, blockage of activation of CPP32/caspase-3 by pretreating the cells with two specific tetrapeptidic inhibitors for caspases (Ac-DEVD-cho and Ac-YVAD-cmk) could significantly attenuate the extent of cleavage/activation of PAK2 induced by UV irradiation. Collectively, the results demonstrate that cleavage and activation of PAK2 can be induced during the early stages of UV irradiation-triggered apoptosis and indicate the involvement of CPP32/caspase-3 in this process.

48 CFR 9.601 - Definition.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Definition. 9.601 Section 9.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Contractor Team Arrangements 9.601 Definition. Contractor team arrangement, as used...

48 CFR 9.601 - Definition.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Definition. 9.601 Section 9.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Contractor Team Arrangements 9.601 Definition. Contractor team arrangement, as used...

48 CFR 9.601 - Definition.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Definition. 9.601 Section 9.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Contractor Team Arrangements 9.601 Definition. Contractor team arrangement, as used...

48 CFR 9.601 - Definition.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Definition. 9.601 Section 9.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Contractor Team Arrangements 9.601 Definition. Contractor team arrangement, as used...

48 CFR 9.601 - Definition.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Definition. 9.601 Section 9.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING CONTRACTOR QUALIFICATIONS Contractor Team Arrangements 9.601 Definition. Contractor team arrangement, as used...

Microwave Photonic Architecture for Direction Finding of LPI Emitters: Post-Processing for Angle of Arrival Estimation

DTIC Science & Technology

2016-09-01

mean- square (RMS) error of 0.29° at ə° resolution. For a P4 coded signal, the RMS error in estimating the AOA is 0.32° at 1° resolution. 14...FMCW signal, it was demonstrated that the system is capable of estimating the AOA with a root-mean- square (RMS) error of 0.29° at ə° resolution. For a...Modulator PCB printed circuit board PD photodetector RF radio frequency RMS root-mean- square xvi THIS PAGE INTENTIONALLY LEFT BLANK xvii

78 FR 59757 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-27

... continues to be available to consumers and businesses. As an essential part of restoring confidence, the... particularly interested in knowing how banks have used the money that Treasury has invested through the CPP... participants in the CPP are utilizing TARP capital. Affected public: Private Sector: Businesses or other for...

75 FR 34213 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-16

... participants in the CPP are utilizing TARP capital. Respondents: Private Sector: Businesses or other for-profit... continues to be available to consumers and businesses. As an essential part of restoring confidence, the... particularly interested in knowing how banks have used the money that Treasury has invested through the CPP...

78 FR 34160 - Proposed Collection; Comment Request; Office of Financial Stability

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-06

... Purchase Program (CPP) under which the Department has purchased qualifying capital in U.S. banking... Treasury has invested through the CPP. Consequently, the Treasury is seeking responses from banking..., maintenance, and purchase of services to provide information. Dated: June 3, 2013. Dawn D. Wolfgang, Treasury...

Replication of Child-Parent Psychotherapy in Community Settings: Models for Training

ERIC Educational Resources Information Center

Van Horn, Patricia; Osofsky, Joy D.; Henderson, Dorothy; Korfmacher, Jon; Thomas, Kandace; Lieberman, Alicia F.

2012-01-01

Child-parent psychotherapy (CPP), an evidence-based dyadic therapeutic intervention for very young children exposed to trauma, is becoming the go-to therapeutic intervention for infant mental health practitioners. Although CPP has been shown to be effective for rebuilding the parent-child relationship, reducing trauma symptoms, and reducing…

CPP magnetoresistance of magnetic multilayers: A critical review

NASA Astrophysics Data System (ADS)

Bass, Jack

2016-06-01

We present a comprehensive, critical review of data and analysis of Giant (G) Magnetoresistance (MR) with Current-flow Perpendicular-to-the-layer-Planes (CPP-MR) of magnetic multilayers [F/N]n (n=number of repeats) composed of alternating nanoscale layers of ferromagnetic (F) and non-magnetic (N) metals, or of spin-valves that allow control of anti-parallel (AP) and parallel (P) orientations of the magnetic moments of adjacent F-layers. GMR, a large change in resistance when an applied magnetic field changes the moment ordering of adjacent F-layers from AP to P, was discovered in 1988 in the geometry with Current flow in the layer-Planes (CIP). The CPP-MR has two advantages over the CIP-MR: (1) relatively simple two-current series-resistor (2CSR) and more general Valet-Fert (VF) models allow more direct access to the underlying physics; and (2) it is usually larger, which should be advantageous for devices. When the first CPP-MR data were published in 1991, it was not clear whether electronic transport in GMR multilayers is completely diffusive or at least partly ballistic. It was not known whether the properties of layers and interfaces would vary with layer thickness or number. It was not known whether the CPP-MR would be dominated by scattering within the F-metals or at the F/N interfaces. Nothing was known about: (1) spin-flipping within F-metals, characterized by a spin-diffusion length, lsfF; (2) interface specific resistances (AR=area A times resistance R) for N1/N2 interfaces; (3) interface specific resistances and interface spin-dependent scattering asymmetry at F/N and F1/F2 interfaces; and (4) spin-flipping at F/N, F1/F2 and N1/N2 interfaces. Knowledge of spin-dependent scattering asymmetries in F-metals and F-alloys, and of spin-flipping in N-metals and N-alloys, was limited. Since 1991, CPP-MR measurements have quantified the scattering and spin-flipping parameters that determine GMR for a wide range of F- and N-metals and alloys and of F/N pairs. This review is designed to provide a history of how knowledge of CPP-MR parameters grew, to give credit for discoveries, to explain how combining theory and experiment has enabled extraction of quantitative information about these parameters, but also to make clear that progress was not always direct and to point out where disagreements still exist. To limit its length, the review considers only collinear orientations of the moments of adjacent F-layers. To aid readers looking for specific information, we have provided an extensive table of contents and a detailed summary. Together, these should help locate over 100 figures plus 17 tables that collect values of individual parameters. In 1997, CIP-MR replaced anisotropic MR (AMR) as the sensor in read heads of computer hard drives. In principle, the usually larger CPP-MR was a contender for the next generation read head sensor. But in 2003, CIP-MR was replaced by the even larger Tunneling MR (TMR), which has remained the read-head sensor ever since. However, as memory bits shrink to where the relatively large specific resistance AR of TMR gives too much noise and too large an R to impedance match as a read-head sensor, the door is again opened for CPP-MR. We will review progress in finding techniques and F-alloys and F/N pairs to enhance the CPP-MR, and will describe its present capabilities.

Enhancing Price Response Programs through Auto-DR: California's 2007 Implementation Experience

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

Kiliccote, Sila; Wikler, Greg; Chiu, Albert

2007-12-18

This paper describes automated demand response (Auto-DR) activities, an innovative effort in California to ensure that DR programs produce effective and sustainable impacts. Through the application of automation and communication technologies coupled with well-designed incentives and DR programs such as Critical Peak Pricing (CPP) and Demand Bidding (DBP), Auto-DR is opening up the opportunity for many different types of buildings to effectively participate in DR programs. We present the results of Auto-DR implementation efforts by the three California investor-owned utilities for the Summer of 2007. The presentation emphasizes Pacific Gas and Electric Company's (PG&E) Auto-DR efforts, which represents the largestmore » in the state. PG&E's goal was to recruit, install, test and operate 15 megawatts of Auto-DR system capability. We describe the unique delivery approaches, including optimizing the utility incentive structures designed to foster an Auto-DR service provider community. We also show how PG&E's Critical Peak Pricing (CPP) and Demand Bidding (DBP) options were called and executed under the automation platform. Finally, we show the results of the Auto-DR systems installed and operational during 2007, which surpassed PG&E's Auto-DR goals. Auto-DR is being implemented by a multi-disciplinary team including the California Investor Owned Utilities (IOUs), energy consultants, energy management control system vendors, the Lawrence Berkeley National Laboratory (LBNL), and the California Energy Commission (CEC).« less

Porphyrin framework solids. Synthesis and structure of hybrid coordination polymers of tetra(carboxyphenyl)porphyrins and lanthanide-bridging ions.

PubMed

Muniappan, Sankar; Lipstman, Sophia; George, Sumod; Goldberg, Israel

2007-07-09

New types of porphyrin-based framework solids were constructed by reacting meso-tetra(3-carboxyphenyl)porphyrin and meso-tetra(4-carboxyphenyl)metalloporphyrins with common salts of lanthanide metal ions. The large size, high coordination numbers and strong affinity for oxo ligands of the latter, combined with favorable hydrothermal reaction conditions, allowed the formation of open three-dimensional single-framework architectures by coordination polymerization, in which the tetradentate porphyrin units are intercoordinated by multinuclear assemblies of the bridging metal ions. The latter serve as construction pillars of the supramolecular arrays, affording stable structures. Several modes of coordination polymerization were revealed by single-crystal X-ray diffraction. They differ by the spatial functionality of the porphyrin building blocks, the coordination patterns of the lanthanide-carboxylate assemblies, and the topology of the resulting frameworks. The seven new reported structures exhibit periodically spaced 0.4-0.6 nm wide channel voids that perforate the respective crystalline polymeric architectures and are accessible to solvent components. Materials based on the m-carboxyphenyl derivative reveal smaller channels than those based on the p-carboxyphenyl analogues. An additional complex of the former with a smaller third-row transition metal (Co) is characterized by coordination connectivity in two dimensions only. Thermal and powder-diffraction analyses confirm the stability of the lanthanide-TmCPP (TmCPP=tetra(m-carboxyphenyl)porphyrin) frameworks.

48 CFR 22.601 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false [Reserved] 22.601 Section 22.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS APPLICATION OF LABOR LAWS TO GOVERNMENT ACQUISITIONS Walsh-Healey Public Contracts Act 22.601 [Reserved] ...

49 CFR 601.45 - Required information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 7 2012-10-01 2012-10-01 false Required information. 601.45 Section 601.45 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL TRANSIT ADMINISTRATION... Transportation Systems § 601.45 Required information. A petition for relief under this section shall: (a...

48 CFR 46.601 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false General. 46.601 Section 46.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT QUALITY ASSURANCE Material Inspection and Receiving Reports 46.601 General. Agencies shall prescribe procedures and...

48 CFR 1346.601 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false General. 1346.601 Section 1346.601 Federal Acquisition Regulations System DEPARTMENT OF COMMERCE CONTRACT MANAGEMENT QUALITY ASSURANCE Material Inspection and Receiving Reports 1346.601 General. Each DOC operating unit shall develop...

48 CFR 2846.601 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true General. 2846.601 Section 2846.601 Federal Acquisition Regulations System DEPARTMENT OF JUSTICE Contract Management QUALITY ASSURANCE Material Inspection and Receiving Reports 2846.601 General. Bureaus shall prescribe procedures and...

20 CFR 416.601 - Introduction.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Introduction. 416.601 Section 416.601 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Representative Payment § 416.601 Introduction. (a) Explanation of representative payment. This...

20 CFR 416.601 - Introduction.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 20 Employees' Benefits 2 2013-04-01 2013-04-01 false Introduction. 416.601 Section 416.601 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Representative Payment § 416.601 Introduction. (a) Explanation of representative payment. This...

5 CFR 950.601 - Release of contributor information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.601 Release of contributor information. (a....601 Section 950.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... charitable organization or organizations designated. A PCFO's failure to honor a contributor's wish may...

5 CFR 950.601 - Release of contributor information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.601 Release of contributor information. (a....601 Section 950.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... charitable organization or organizations designated. A PCFO's failure to honor a contributor's wish may...

5 CFR 950.601 - Release of contributor information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.601 Release of contributor information. (a....601 Section 950.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... charitable organization or organizations designated. A PCFO's failure to honor a contributor's wish may...

5 CFR 950.601 - Release of contributor information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.601 Release of contributor information. (a....601 Section 950.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... charitable organization or organizations designated. A PCFO's failure to honor a contributor's wish may...

5 CFR 950.601 - Release of contributor information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... PRIVATE VOLUNTARY ORGANIZATIONS Miscellaneous Provisions § 950.601 Release of contributor information. (a....601 Section 950.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE... charitable organization or organizations designated. A PCFO's failure to honor a contributor's wish may...

48 CFR 601.403 - Individual deviations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Individual deviations. 601.403 Section 601.403 Federal Acquisition Regulations System DEPARTMENT OF STATE GENERAL DEPARTMENT OF STATE ACQUISITION REGULATIONS SYSTEM Deviations from the FAR 601.403 Individual deviations. The...

5 CFR 731.601 - Savings provision.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Savings provision. 731.601 Section 731.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) SUITABILITY Savings Provision § 731.601 Savings provision. No provision of the regulations in...

5 CFR 731.601 - Savings provision.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Savings provision. 731.601 Section 731.601 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT (CONTINUED) CIVIL SERVICE REGULATIONS (CONTINUED) SUITABILITY Savings Provision § 731.601 Savings provision. No provision of the regulations in...

40 CFR 91.601 - Applicability.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Applicability. 91.601 Section 91.601 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONTROL OF EMISSIONS FROM MARINE SPARK-IGNITION ENGINES Selective Enforcement Auditing Regulations § 91.601...

7 CFR 1580.601 - Implementation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 10 2010-01-01 2010-01-01 false Implementation. 1580.601 Section 1580.601 Agriculture Regulations of the Department of Agriculture (Continued) FOREIGN AGRICULTURAL SERVICE, DEPARTMENT OF AGRICULTURE TRADE ADJUSTMENT ASSISTANCE FOR FARMERS § 1580.601 Implementation. Trade adjustment assistance is...

48 CFR 23.601 - Requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Requirements. 23.601 Section 23.601 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC... DRUG-FREE WORKPLACE Notice of Radioactive Material 23.601 Requirements. (a) The clause at 52.223-7...

47 CFR 101.601 - Eligibility.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Eligibility. 101.601 Section 101.601 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Private Operational Fixed Point-to-Point Microwave Service § 101.601 Eligibility. Any person, or...

47 CFR 101.601 - Eligibility.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Eligibility. 101.601 Section 101.601 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Private Operational Fixed Point-to-Point Microwave Service § 101.601 Eligibility. Any person, or...

47 CFR 101.601 - Eligibility.

Code of Federal Regulations, 2014 CFR

2014-10-01

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47 CFR 101.601 - Eligibility.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Eligibility. 101.601 Section 101.601 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Private Operational Fixed Point-to-Point Microwave Service § 101.601 Eligibility. Any person, or...