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Sample records for 2-day fzp-withdrawn rats

  1. Mesospheric quasi-2-day wave structure and momentum fluxes observed by MF radars

    NASA Astrophysics Data System (ADS)

    Sridharan, S.; Gurubaran, S.; Rajaram, R.; Vincent, R.; Tsuda, T.; Nakamura, T.

    Equatorial mesospheric winds obtained simultaneously by MF radars located at Tirunelveli (8.7 N, 77.8 E), Pontianak (0N, 109 E) and Christmas Island (2 N, 157 W) for the years 1996-1997, are used to analyze the structure and momentum fluxes of quasi-2-day wave, a westward travelling global scale oscillation. From the phase delay experienced by quasi-2-day wave over the three equatorial sites, it is inferred that the wave is a westward propagating zonal wave number 3 to 5. Our preliminary results show that the quasi-2-day wave shows larger activity in meridional wind than in zonal wind. Amplitude of the quasi-2-day wave is observed to be larger in Pontianak, slightly less in Christmas Island and smaller in Tirunelveli. Mean period of the quasi-2-day wave also shows similar variability with larger period of around 2.1 days in Pontianak. In Christmas Island and Tirunelveli, it is around 2.05 and 2.03 days respectively. Meridional momentum flux divergence of quasi-2-day wave is estimated and seen to be anti-correlated with zonal wind accelerations. Intrinsic frequency provides an indication of the propagation characteristics of a given mode relative to the mean. The comparison of intrinsic frequency of quasi-2-day wave and zonal mean wind shows that critical regions present in some of the height regions, prohibit the wave propagation in the vertical direction. Extensive analysis will be carried out and the results from this analysis will be presented and discussed.

  2. Removal of T-Fasteners 2 Days After Gastrostomy is Feasible

    SciTech Connect

    Foster, A.; Given, M.; Thornton, E.; Geoghegan, T.; Keeling, F.; McGrath, F.; Lee, M. J.

    2009-03-15

    T-fastener gastropexy is widely performed as part of gastrostomy insertion. The current literature recommends removal of T-fasteners at 2 weeks. We present a series of patients in whom T-fasteners were removed at 2 days with no major complications. We removed T-fasteners in 109 patients (male-to-female ratio 59:50, age range 18 to 88 years, mean age 62 years) at 2 days after gastrostomy insertion. Indications for gastrostomy included amytrophic lateral sclerosis, cerebrovascular accidents, head and neck carcinoma, multiple sclerosis, and others, including brain tumours and chronic inflammatory demyelinating polyneuropathy. No peritubal leaks or other major complications were seen in the study population. In the study group, 15 minor complications were recorded (14%), including localised infection and pain, both of which resolved on removal of T-fasteners. We conclude that it is feasible and safe to remove T-fasteners at 2 days.

  3. Excitation and Evolution of the Quasi-2-Day Wave Observed in UARS/MLS Temperature Measurements.

    NASA Astrophysics Data System (ADS)

    Wu, D. L.; Fishbein, E. F.; Read, W. G.; Waters, J. W.

    1996-03-01

    The quasi-2-day wave is known as a strong and transient perturbation in the middle and upper atmosphere that often occurs shortly after solstice. The excitation mechanisms of this transient wave have been discussed for years, but no clear answer has yet been attained. In this paper, propagating characteristics of the 2-day wave are studied based on 8-mon temperature measurements from the Microwave Limb Sounder onboard the Upper Atmosphere Research Satellite. The studies are focused on the wave events that happened in January 1993 and in July-August 1993. The observations suggests that winter planetary waves could be responsible for triggering the summer 2-day wave through long penetration into the summer stratosphere. A connection is evident in the evolution of the wave amplitude between the summer 2-day wave generation and winter wave penetration. The data also suggest that the enhancement of the wave amplitude is a manifestation of both a local unstable wave and a global normal-mode Rossby wave.

  4. Preparing Corrections Staff for the Future: Results of a 2-Day Training About Aging Inmates.

    PubMed

    Masters, Julie L; Magnuson, Thomas M; Bayer, Barbara L; Potter, Jane F; Falkowski, Paul P

    2016-04-01

    The aging of the prison population presents corrections staff with unique challenges in knowing how to support inmates while maintaining security. This article describes a 2-day training program to introduce the aging process to select staff at all levels. While the results of a pre-posttest measure, using a modified version of Palmore's Facts on Aging Quiz, did not produce a statistically significant difference at the conclusion of the training, attendees did express satisfaction with the training and their newfound insight into the challenges faced by aging inmates. They also offered recommendations for future training to include more practical suggestions for the work environment.

  5. Observations of the quasi 2-day wave from the High Resolution Doppler Imager on UARS

    NASA Technical Reports Server (NTRS)

    Wu, D. L.; Hays, P. B.; Skinner, W. R.; Marshall, A. R.; Burrage, M. D.; Lieberman, R. S.; Ortland, D. A.

    1993-01-01

    A strong westward traveling oscillation, with a period of 2 days and zonal wave number 3, is observed in the mesospheric and lower thermospheric winds from the High Resolution Doppler Imager (HRDI) on the Upper Atmosphere Research Satellite (UARS). The important events happen in January, July, and September/October, of which the occurrence in January is the strongest with an amplitude over 60 m/s. Detailed analyses for the periods of January 1992 and January 1993 reveal a cause-and-effect relationship in the wave developing process at 95 km. The global structures of the wave amplitude and phase are also presented.

  6. Impact of a 2-Day Critical Care Ultrasound Course during Fellowship Training: A Pilot Study

    PubMed Central

    Dinh, Vi Am; Giri, Paresh C.; Rathinavel, Inimai; Nguyen, Emilie; Hecht, David; Dorotta, Ihab; Nguyen, H. Bryant; Chrissian, Ara A.

    2015-01-01

    Objectives. Despite the increasing utilization of point-of-care critical care ultrasonography (CCUS), standards establishing competency for its use are lacking. The purpose of this study was to evaluate the effectiveness of a 2-day CCUS course implementation on ultrasound-naïve critical care medicine (CCM) fellows. Methods. Prospective evaluation of the impact of a two-day CCUS course on eight CCM fellows' attitudes, proficiency, and use of CCUS. Ultrasound competency on multiple organ systems was assessed including abdominal, pulmonary, vascular, and cardiac systems. Subjects served as self-controls and were assessed just prior to, within 1 week after, and 3 months after the course. Results. There was a significant improvement in CCM fellows' written test scores, image acquisition ability, and pathologic image interpretation 1 week after the course and it was retained 3 months after the course. Fellows also had self-reported increased confidence and usage of CCUS applications after the course. Conclusions. Implementation of a 2-day critical care ultrasound course covering general CCUS and basic critical care echocardiography using a combination of didactics, live models, and ultrasound simulators is effective in improving critical care fellows' proficiency and confidence with ultrasound use in both the short- and long-term settings. PMID:26346694

  7. In vivo embryo production in cows superovulated 1 or 2 days after ovum pick-up.

    PubMed

    Surjus, Ricardo S; Prata, Alexandre B; Borsato, Marta; Mattos, Fernanda C S Z; Martins da Silveira, Mariana C; Mourão, Gerson B; Pires, Alexandre V; Wiltbank, Milo C; Sartori, Roberto

    2014-01-01

    The present study evaluated superovulatory responses and in vivo embryo production in cows treated with FSH starting 1 or 2 days after ovum pick-up (OPU). Thirty-three non-lactating Nelore cows were subjected to aspiration of all follicles ≥3mm for OPU. After OPU, cows were randomly divided into two groups in which the follicle superstimulatory treatments with FSH started 1 or 2 days after OPU (Groups D1 and D2, respectively). Data are presented as the least squares mean±s.e.m. The number of follicles ≥3mm before OPU was similar between groups (~34); however, cows in Group D2 had more follicles ≥3mm on the first day of FSH (15.2±2.3 vs 7.6±1.7; P=0.04) and a higher ratio of the number of follicles at first FSH/number of follicles before OPU (0.41±0.04 vs 0.24±0.02; P=0.01). In addition, Group D2 cows had a greater superovulatory response than did cows in Group D1 (18.9±2.8 vs 9.1±1.9 corpora lutea, respectively; P<0.03). However, there was no difference in the total number of recovered ova and embryos from cows in Groups D2 and D1 (5.1±1.4 vs 4.9±1.3, respectively; P>0.10). Nevertheless Group D2 cows had more freezable embryos than Group D1 cows (3.2±1.1 vs 1.3±0.5, respectively; P<0.05). Cows from Group D2 had a much higher proportion (P<0.001) of follicles ≥8mm compared with follicles ≥6mm and <8mm at the time of the last treatment with FSH. In conclusion, to obtain a greater production of viable embryos in superovulated cows after OPU, it is recommended to wait at least 2 days before starting FSH treatment.

  8. Phytotoxicity and Transport of Gallium (Ga) in Rice Seedlings for 2-Day of Exposure.

    PubMed

    Yu, Xiao-Zhang; Feng, Xing-Hui; Feng, Yu-Xi

    2015-07-01

    Hydroponic experiments were conducted with rice seedlings to investigate the accumulation and phytotoxicity of gallium nitrate. A linear decrease in relative growth rate, transpiration rate and water use efficiency was observed in rice seedlings with increasing Ga concentrations. However, inhibition of these selected parameters was noted different at different Ga treatments. Relative growth rate was more sensitive towards Ga treatments. Phyto-transport of Ga was apparent, but recovery of Ga in different parts of rice seedlings varied significantly: roots were dominant site for Ga accumulation. The total accumulation rates of Ga were positively correlated to Ga concentrations. Results indicated that the addition of Ga did not cause deleterious effects on plant physiological functions over a 2-day exposure period. Large amounts of Ga were removed from the hydroponic solution through rice seedlings. Accumulation of Ga in plant tissues resulted in growth inhibition of rice seedlings.

  9. Factors contributing to successful interorganizational collaboration: the case of CS2day.

    PubMed

    Olson, Curtis A; Balmer, Jann T; Mejicano, George C

    2011-01-01

    Continuing medical education's transition from an emphasis on dissemination to changing clinical practice has made it increasingly necessary for CME providers to develop effective interorganizational collaborations. Although interorganizational collaboration has become commonplace in most sectors of government, business, and academia, our review of the literature and experience as practitioners and researchers suggest that the practice is less widespread in the CME field. The absence of a rich scholarly literature on establishing and maintaining interorganizational collaborations to provide continuing education to health professionals means there is little information about how guidelines and principles for effective collaboration developed in other fields might apply to continuing professional development in health care and few models of successful collaboration. The purpose of this article is to address this gap by describing a successful interorganizational CME collaboration-Cease Smoking Today (CS2day)-and summarizing what was learned from the experience, extending our knowledge by exploring and illustrating points of connection between our experience and the existing literature on successful interorganizational collaboration. In this article, we describe the collaboration and the clinical need it was organized to address, and review the evidence that led us to conclude the collaboration was successful. We then discuss, in the context of the literature on effective interorganizational collaboration, several factors we believe were major contributors to success. The CS2day collaboration provides an example of how guidelines for collaboration developed in various contexts apply to continuing medical education and a case example providing insight into the pathways that lead to a collaboration's success. PMID:22190099

  10. Cerebral blood velocity and other cardiovascular responses to 2 days of head-down tilt

    NASA Technical Reports Server (NTRS)

    Frey, Mary A. B.; Mader, Thomas H.; Bagian, James P.; Charles, John B.; Meehan, Richard T.

    1993-01-01

    Spaceflight induces a cephalad redistribution of fluid volume and blood flow within the human body, and space motion sickness, which is a problem during the first few days of space flight, could be related to these changes in fluid status and in blood flow of the cerebrum and vestibular system. To evaluate possible changes in cerebral blood flow during simulated weightlessness, we measured blood velocity in the middle cerebral artery (MCA) along with retinal vascular diameters, intraocular pressure, impedance cardiography, and sphygmomanometry on nine men (26.2 +/- 6.6 yr) morning and evening for 2 days during continuous 10 deg head-down tilt (HDT). When subjects went from seated to head-down bed rest, their heart rate and retinal diameters decreased, and intraocular pressures increased. After 48 h of HDT, blood flow velocity in the MCA was decreased and thoracic impedance was increased, indicating less fluid in the thorax. Percent changes in blood flow velocities in the MCA after 48 h of HDT were inversely correlated with percent changes in retinal vascular diameters. Blood flow velocities in the MCA were inversely correlated (intersubject) with arterial pressures and retinal vascular diameters. Heart rate, stroke volume, cardiac output, systolic arterial pressure, and at times pulse pressure and blood flow velocities in the MCA were greater in the evening. Total peripheral resistance was higher in the morning. Although cerebral blood velocity is reduced after subjects are head down for 2 days, the inverse relationship with retinal vessel diameters, which have control analogous to that of cerebral vessels, indicates cerebral blood flow is not reduced.

  11. Simultaneous observations of the phase-locked 2 day wave at Adelaide, Cerro Pachon, and Darwin

    NASA Astrophysics Data System (ADS)

    Walterscheid, R. L.; Hecht, J. H.; Gelinas, L. J.; MacKinnon, A.; Vincent, R. A.; Reid, I. M.; Franke, S. J.; Zhao, Y.; Taylor, M. J.; Pautet, P. D.

    2015-03-01

    The Southern Hemisphere summer 2 day wave (TDW) is the most dramatic large-scale event of the upper mesosphere. The winds accelerate over ~1 week, may attain > 70 m/s, and are often accompanied by a near disappearance of the diurnal tide and stabilization of the period close to 48 h. We denote this as the phase-locked 2 day wave (PL/TDW). We have examined airglow and meteor radar (MR) wind data from the Andes Lidar Observatory (Cerro Pachon, Chile:30°S, 289.3°E), MR data from Darwin (12.5°S, 131°E) and airglow and medium frequency radar data from the University of Adelaide (34.7°S, 138.6°E) for the behavior of the TDW during the austral summers of 2010, 2012, and 2013. The Cerro Pachon and Adelaide sites are located at similar latitudes separated in longitude by about 120°. We find a remarkable coincidence between the TDW oscillations at Chile and Adelaide for the period January-February 2010. The oscillations are nearly in phase in terms of local time and the minima and maxima repeat at nearly the same local time from cycle to cycle consistent with a phase-locked wave number 3 TDW. Data for this and other years (including Darwin) show that the amplitude of the diurnal tide decreases when the TDW is largest and that this occurs when the period is close to 48 h. These observations support the proposal that the PL/TDW is a subharmonic parametric instability wherein the diurnal tide transfers energy to a TDW that is resonant at nearly 48 h.

  12. The Cease Smoking Today (CS2day) Initiative: A Guide to Pursue the 2010 IOM Report Vision for CPD

    ERIC Educational Resources Information Center

    Cervero, Ronald M.; Moore, Donald E., Jr.

    2011-01-01

    This article reviews the articles in this supplement that describe a smoking cessation project, Cease Smoking Today (CS2day) that demonstrated successful outcomes: physician adoption of a smoking cessation guideline and an increase in smoking quit rates. The authors examine how the activities of the CS2day project compared to the principles and…

  13. Ionospheric vertical plasma drift perturbations due to the quasi 2 day wave

    NASA Astrophysics Data System (ADS)

    Gu, Sheng-Yang; Liu, Han-Li; Li, Tao; Dou, Xiankang

    2015-05-01

    The thermosphere-ionosphere-mesosphere-electrodynamics-general circulation model is utilized to study the vertical E × B drift perturbations due to the westward quasi 2 day wave with zonal wave numbers 2 and 3 (W2 and W3). The simulations show that both wind components contribute directly and significantly to the vertical drift, which is not merely confined to low latitudes. The vertical drifts at the equator induced by the total wind perturbations of W2 are comparable with that at middle latitudes, while the vertical drifts from W3 are much stronger at middle latitudes than at the equator. The ion drift perturbations induced by the zonal and meridional wind perturbations of W2 are nearly in-phase with each other, whereas the phase discrepancies of the ion drift induced by the individual wind component of W3 are much larger. This is because the wind perturbations of W2 and W3 have different latitudinal structures and phases, which result in different ionospheric responses through wind dynamo.

  14. Influence of the sudden stratospheric warming on quasi-2-day waves

    NASA Astrophysics Data System (ADS)

    Gu, Sheng-Yang; Liu, Han-Li; Dou, Xiankang; Li, Tao

    2016-04-01

    The influence of the sudden stratospheric warming (SSW) on a quasi-2-day wave (QTDW) with westward zonal wave number 3 (W3) is investigated using the Thermosphere-Ionosphere-Mesosphere Electrodynamics General Circulation Model (TIME-GCM). The summer easterly jet below 90 km is strengthened during an SSW, which results in a larger refractive index and thus more favorable conditions for the propagation of W3. In the winter hemisphere, the Eliassen-Palm (EP) flux diagnostics indicate that the strong instabilities at middle and high latitudes in the mesopause region are important for the amplification of W3, which is weakened during SSW periods due to the deceleration or even reversal of the winter westerly winds. Nonlinear interactions between the W3 and the wave number 1 stationary planetary wave produce QTDW with westward zonal wave number 2 (W2). The meridional wind perturbations of the W2 peak in the equatorial region, while the zonal wind and temperature components maximize at middle latitudes. The EP flux diagnostics indicate that the W2 is capable of propagating upward in both winter and summer hemispheres, whereas the propagation of W3 is mostly confined to the summer hemisphere. This characteristic is likely due to the fact that the phase speed of W2 is larger, and therefore its waveguide has a broader latitudinal extension. The larger phase speed also makes W2 less vulnerable to dissipation and critical layer filtering by the background wind when propagating upward.

  15. Evidence of nonlinear interaction between quasi 2 day wave and quasi-stationary wave

    NASA Astrophysics Data System (ADS)

    Gu, Sheng-Yang; Liu, Han-Li; Li, Tao; Dou, Xiankang; Wu, Qian; Russell, James M.

    2015-02-01

    The nonlinear interaction between the westward quasi 2 day wave (QTDW) with zonal wave number s = 3 (W3) and stationary planetary wave with s = 1 (SPW1) is first investigated using both Thermosphere, Ionosphere, and Mesosphere Electric Dynamics (TIMED) satellite observations and the thermosphere-ionosphere-mesosphere electrodynamics general circulation model (TIME-GCM) simulations. A QTDW with westward s = 2 (W2) is identified in the mesosphere and lower thermosphere (MLT) region in TIMED/Sounding of the Atmosphere using Broadband Emission Radiometry (SABER) temperature and TIMED/TIMED Doppler Imager (TIDI) wind observations during 2011/2012 austral summer period, which coincides with a strong SPW1 episode at high latitude of the northern winter hemisphere. The temperature perturbation of W2 QTDW reaches a maximum amplitude of ~8 K at ~30°S and ~88 km in the Southern Hemisphere, with a smaller amplitude in the Northern Hemisphere at similar latitude and minimum amplitude at the equator. The maximum meridional wind amplitude of the W2 QTDW is observed to be ~40 m/s at 95 km in the equatorial region. The TIME-GCM is utilized to simulate the nonlinear interactions between W3 QTDW and SPW1 by specifying both W3 QTDW and SPW1 perturbations at the lower model boundary. The model results show a clear W2 QTDW signature in the MLT region, which agrees well with the TIMED/SABER temperature and TIMED/TIDI horizontal wind observations. We conclude that the W2 QTDW during the 2011/2012 austral summer period results from the nonlinear interaction between W3 QTDW and SPW1.

  16. Changes in blood biochemical markers before, during, and after a 2-day ultramarathon.

    PubMed

    Arakawa, Kazuyuki; Hosono, Akihiro; Shibata, Kiyoshi; Ghadimi, Reza; Fuku, Mizuho; Goto, Chiho; Imaeda, Nahomi; Tokudome, Yuko; Hoshino, Hideki; Marumoto, Mitsuhiro; Kobayashi, Masaaki; Suzuki, Sadao; Tokudome, Shinkan

    2016-01-01

    We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-α. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker - triglyceride - decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries. PMID:27186145

  17. Changes in blood biochemical markers before, during, and after a 2-day ultramarathon

    PubMed Central

    Arakawa, Kazuyuki; Hosono, Akihiro; Shibata, Kiyoshi; Ghadimi, Reza; Fuku, Mizuho; Goto, Chiho; Imaeda, Nahomi; Tokudome, Yuko; Hoshino, Hideki; Marumoto, Mitsuhiro; Kobayashi, Masaaki; Suzuki, Sadao; Tokudome, Shinkan

    2016-01-01

    We studied changes in blood markers of 18 nonprofessional, middle-aged runners of a 2-day, 130 km ultramarathon. Blood was sampled at baseline, after the goals on the first and second day, and at three time points (1, 3, and 5/6 days) after the race. Blood indices showed three patterns. First pattern indices showed essentially no changes after the two goals and after the race, including red blood cell indices, gamma-glutamyl transferase, and tumor necrosis factor-α. Second pattern markers, including the majority of indices, were elevated during the race (and also after the race for some parameters) and then returned to baseline afterward, including hemolysis/red blood cell destruction markers (indirect bilirubin) and an iron reservoir index (ferritin), muscle damage parameters (uric acid, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase), renal function markers (creatinine and blood urea nitrogen), liver injury index (alanine aminotransferase), lipid metabolism indices (free fatty acid), reactive oxygen species and inflammation parameters (white blood cells, interleukin-6, and C-reactive protein), and energy production and catecholamines (adrenaline, noradrenaline, and dopamine). Third pattern index of a lipid metabolism marker – triglyceride – decreased during the race periods and started returning to baseline from then onward. Some hormonal markers such as insulin, leptin, and adiponectin showed unique patterns. These findings appeared informative for nonprofessional athletes to know about an optimal physical activity level, duration, and total exercise for elevating physical performance and monitoring physical/mental conditioning as well as for prevention of overtraining and physical injuries. PMID:27186145

  18. Observations of Secondary Waves Generated from Interaction Between the 2-Day Wave and the Migrating Diurnal Tide.

    NASA Astrophysics Data System (ADS)

    Lieberman, R. S.; Riggin, D. M.; Siskind, D. E.; Nguyen, V.; Palo, S. E.; Mitchell, N. J.; Livesey, N. J.; Stober, G.; Wilhelm, S.; Jacobi, C.

    2015-12-01

    Nonlinear coupling between the migrating diurnal tide and the westward traveling quasi-2-day wave yields a westward-traveling "sum" wave with zonal wavenumber 4 and a period of 16 hours, and an eastward-traveling "difference" wave with a zonal wavenumber 2 and a period of 2 days. While the eastward 2-day wave has been reported in TIMED/SABER temperatures, the westward 16-hour wave lies outside SABER's Nyquist limits of resolution. To obtain simultaneous definitions of the parent and child waves, we examine hourly output from NOGAPS-ALPHA during January 2005, 2006 and 2008. The westward 16-hour wave maximizes in the winter hemisphere, and behaves like an inertia-gravity wave. The eastward 2-day wave maximizes at low latitudes, and exhibits a mixture of Kelvin and higher-order modes. The 16-hour and the eastward 2-day waves are of comparable magnitude, and alias to the same apparent frequency when viewed from the satellite perspective.

  19. Impact of the interaction between the quasi-2 day wave and tides on the ionosphere and thermosphere

    NASA Astrophysics Data System (ADS)

    Yue, Jia; Wang, Wenbin; Ruan, Haibing; Chang, Loren C.; Lei, Jiuhou

    2016-04-01

    The quasi-2 day wave (QTDW) can effectively interact with atmospheric tides in the mesosphere and lower thermosphere. We study the effect of this QTDW-tidal interaction on the ionosphere and thermosphere using the thermosphere-ionosphere-mesosphere electrodynamics general circulation model. This interaction reduces the amplitude of the migrating diurnal tide in the lower thermosphere by ~10 m/s in neutral winds and also generates sum and difference secondary waves in the lower thermosphere and E region ionosphere. As a result of the changed migrating diurnal tide and sum/difference secondary wave, vertical ion drift varies with local time at different longitudes by ~5 m/s. In addition, the changed migrating diurnal tide also modulates the thermospheric composition (O/N2). During a QTDW event, the ionosphere F2 region peak electron density (NmF2) is reduced due to the mixing effect of the QTDW dissipation; NmF2 also shows changes in local time variation due to the QTDW-tidal interaction. The sum and difference secondary waves can cause additional oscillations in vertical ion drift and ionospheric electron densities. The QTDW-tidal interaction is another mechanism by which the QTDW impacts the ionosphere and thermosphere, along with other mechanisms: QTDW modulation of the E region wind dynamo with a period of quasi-2 days and QTDW dissipation induced mixing in the thermosphere.

  20. Generation of secondary waves arising from nonlinear interaction between the quasi 2 day wave and the migrating diurnal tide

    NASA Astrophysics Data System (ADS)

    Nguyen, Vu A.; Palo, Scott E.; Lieberman, Ruth S.; Forbes, Jeffrey M.; Ortland, David A.; Siskind, David E.

    2016-07-01

    Theory and past observations have provided evidence that atmospheric tides and other global-scale waves interact nonlinearly to produce additional secondary waves throughout the space-atmosphere interaction region. However, few studies have investigated the generation region of nonlinearly generated secondary waves, and as a result, the manifestation and impacts of these waves are still poorly understood. This study focuses on the nonlinear interaction between the quasi 2 day wave (2dayW3) and the migrating diurnal tide (DW1), two of the largest global-scale waves in the atmosphere. The fundamental goals of this effort are to characterize the forcing region of the secondary waves and to understand how it relates to their manifestation on a global scale. First, the Fast Fourier Synoptic Mapping method is applied to Thermosphere Ionosphere Mesosphere Energetics and Dynamics-Sounding of the Atmosphere using Broadband Emission Radiometry satellite observations to provide new evidence of secondary waves. These results show that secondary waves are only significant above 80 km. The nonlinear forcing for each secondary wave is then computed by extracting short-term primary wave information from a reanalysis model. The estimated nonlinear forcing quantities are used to force a linearized tidal model in order to calculate numerical secondary wave responses. Model results show that the secondary waves are significant from the upper mesosphere to the middle thermosphere, highlighting the implications for the atmosphere-space weather coupling. The study also concludes that the secondary wave response is most sensitive to the nonlinear forcing occurring in the lower and middle mesosphere and not coincident with the regions of strongest nonlinear forcing.

  1. The quasi 2 day wave activities during 2007 austral summer period as revealed by Whole Atmosphere Community Climate Model

    NASA Astrophysics Data System (ADS)

    Gu, Sheng-Yang; Liu, Han-Li; Pedatella, N. M.; Dou, Xiankang; Li, Tao; Chen, Tingdi

    2016-03-01

    The quasi 2 day wave (QTDW) observed during 2007 austral summer period is well reproduced in an reanalysis produced by the data assimilation version of the Whole Atmosphere Community Climate Model (WACCM + Data Assimilation Research Testbed) developed at National Center for Atmospheric Research (NCAR). It is found that the QTDW peaked 3 times from January to February but with different zonal wave numbers. Diagnostic analysis shows that the mean flow instabilities, refractive index, and critical layers of QTDWs are fundamental for their propagation and amplification, and thus, the temporal variations of the background wind are responsible for the different wave number structures at different times. The westward propagating wave number 2 mode (W2) grew and maximized in the first half of January, when the mean flow instabilities related to the summer easterly jet were enclosed by the critical layers of the westward propagating wave number 3 (W3) and wave number 4 (W4) modes. This prevented W3 and W4 from approaching and extracting energy from the unstable region. The W2 decayed rapidly thereafter due to the recession of critical layer and thus the lack of additional amplification by the mean flow instability. The W3 peaked in late January, when the instabilities were still encircled by the critical layer of W4. The attenuation of W3 afterward was also due to the disappearance of critical layer and thus the lack of overreflection. Finally, the W4 peaked in late February when both the instability and critical layer were appropriate.

  2. Transient dehydration of lungs in tail-suspended rats

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Steskal, J.; Morey-Holton, E. R.

    1985-01-01

    The fluid balance in the lungs of rats exposed to head-down tilt is examined. Six Munich-Wister rats were suspended for 7 days and 10 Sprague-Dawley rats for 14 days using the technique of Morey (1979). The water contents of the lungs of the suspended and a control group are calculated and compared. The data reveal that the two-days suspended rats had dehydrated lungs; however, the lungs of the 14-day suspended and control group rats were similar. It is noted that the dehydration in the 2-day suspended rats is caused by general dehydration not the head-tilt position.

  3. Anhedonia in postpartum rats.

    PubMed

    Navarre, Brittany M; Laggart, Jillian D; Craft, Rebecca M

    2010-01-12

    Postpartum depression (PPD) is a debilitating illness, yet little is known about its causes. The purpose of this study was to examine a major symptom of depression during the postpartum period, anhedonia, by comparing sucrose preference in female rats that had undergone actual pregnancy or hormone-simulated pregnancy (HSP) to their respective controls. Whereas HSP rats showed significantly less preference than vehicle control rats for 1% sucrose solution during the first three weeks of the "postpartum" period, previously pregnant females showed only slightly depressed sucrose preference for the first 1-2 days postpartum, compared to non-pregnant controls. Habituation to 1% sucrose during the pregnancy period, which increased preference upon later testing in previously pregnant rats tested on postpartum day 2, did not significantly increase preference in HSP rats, suggesting that depressed preference in the latter group was not due to neophobia. Pre-treatment with desipramine did not prevent suppressed sucrose preference in HSP rats, and preference was even further suppressed following chronic sertraline treatment. These results suggest that estradiol withdrawal following HSP may cause anhedonia during the early "postpartum" period. In contrast, females that have undergone actual pregnancy are less likely to show this effect, suggesting that postpartum hormonal changes other than the dramatic decline in estradiol may buffer its negative mood effects.

  4. Juvenile hormone enhances aversive learning performance in 2-day old worker honey bees while reducing their attraction to queen mandibular pheromone.

    PubMed

    McQuillan, H James; Nakagawa, Shinichi; Mercer, Alison R

    2014-01-01

    Previous studies have shown that exposing young worker bees (Apis mellifera) to queen mandibular pheromone (QMP) reduces their aversive learning performance, while enhancing their attraction to QMP. As QMP has been found to reduce the rate of juvenile hormone (JH) synthesis in worker bees, we examined whether aversive learning in 2-day old workers exposed to QMP from the time of adult emergence could be improved by injecting JH (10 µg in a 2 µl volume) into the haemolymph. We examined in addition, the effects of JH treatment on worker attraction to QMP, and on the levels of expression of amine receptor genes in the antennae, as well as in the mushroom bodies of the brain. We found that memory acquisition and 1-hour memory recall were enhanced by JH. In contrast, JH treatment reduced the bees' attraction towards a synthetic strip impregnated with QMP (Bee Boost). Levels of expression of the dopamine receptor gene Amdop1 were significantly lower in the mushroom bodies of JH-treated bees than in bees treated with vehicle alone (acetone diluted with bee ringer). Expression of the octopamine receptor gene, Amoa1, in this brain region was also affected by JH treatment, and in the antennae, Amoa1 transcript levels were significantly lower in JH-treated bees compared to controls. The results of this study suggest that QMP's effects on JH synthesis may contribute to reducing aversive learning performance and enhancing attraction to QMP in young worker bees.

  5. Juvenile hormone enhances aversive learning performance in 2-day old worker honey bees while reducing their attraction to queen mandibular pheromone.

    PubMed

    McQuillan, H James; Nakagawa, Shinichi; Mercer, Alison R

    2014-01-01

    Previous studies have shown that exposing young worker bees (Apis mellifera) to queen mandibular pheromone (QMP) reduces their aversive learning performance, while enhancing their attraction to QMP. As QMP has been found to reduce the rate of juvenile hormone (JH) synthesis in worker bees, we examined whether aversive learning in 2-day old workers exposed to QMP from the time of adult emergence could be improved by injecting JH (10 µg in a 2 µl volume) into the haemolymph. We examined in addition, the effects of JH treatment on worker attraction to QMP, and on the levels of expression of amine receptor genes in the antennae, as well as in the mushroom bodies of the brain. We found that memory acquisition and 1-hour memory recall were enhanced by JH. In contrast, JH treatment reduced the bees' attraction towards a synthetic strip impregnated with QMP (Bee Boost). Levels of expression of the dopamine receptor gene Amdop1 were significantly lower in the mushroom bodies of JH-treated bees than in bees treated with vehicle alone (acetone diluted with bee ringer). Expression of the octopamine receptor gene, Amoa1, in this brain region was also affected by JH treatment, and in the antennae, Amoa1 transcript levels were significantly lower in JH-treated bees compared to controls. The results of this study suggest that QMP's effects on JH synthesis may contribute to reducing aversive learning performance and enhancing attraction to QMP in young worker bees. PMID:25390885

  6. Changes in the microflora and physiology of the anterior intestinal tract of pigs weaned at 2 days, with special reference to the pathogenesis of diarrhea.

    PubMed

    Barrow, P A; Fuller, R; Newport, M J

    1977-12-01

    The gastrointestinal microflora and gastric physiology of piglets weaned at 2 days was compared with that of piglets allowed to continue sucking the sow. Although there was a significantly higher count of Escherichia coli in the stomach, duodenum, and jejunum of the early-weaned compared with sow-reared pigs, these differences were not detectable in samples from the ileum. There were no quantitative differences in lactobacilli and in streptococci between the two treatments. Lactobacillus fermentum, L. acidophilus, Streptococcus salivarius, S. bovis, and related biotypes were isolated from both groups of pigs. L. fermentum and S. salivarius were isolated more frequently from sow-reared piglets. The weight of digesta in the stomach was greater in weaned than in sucking pigs and was even greater in scouring weaned pigs, suggesting that in scouring pigs there may be gastric stasis. The gastric pH was higher in the weaned pigs at 4 days of age, but gradually decreased up to 10 days, during which time the lactic acid concentration rose. In weaned pigs there was a highly significant negative correlation between pH and lactic acid concentration in the stomach digesta, and also a positive correlation between pH and number of E. coli. These correlations suggest that lactic acid, from bacterial fermentation, is the major component in the regulation of gastric pH in weaned pigs. Three of twenty sucking pigs, but none of the weaned pigs, were secreting HCl (chloride concentration > 3 mg/g, pH < 3.5). In sucking pigs there was an inverse relationship between the chloride and lactic acid concentrations in the digesta. In weaned scouring pigs there was a nonsignificant increase in pepsin concentration in the stomach tissue. There was a threefold increase in the total proteolytic activity of the stomach tissue.

  7. Prenatal Development of Interlimb Motor Learning in the Rat Fetus

    ERIC Educational Resources Information Center

    Robinson, Scott R.; Kleven, Gale A.; Brumley, Michele R.

    2008-01-01

    The role of sensory feedback in the early ontogeny of motor coordination remains a topic of speculation and debate. On E20 of gestation (the 20th day after conception, 2 days before birth), rat fetuses can alter interlimb coordination after a period of training with an interlimb yoke, which constrains limb movement and promotes synchronized,…

  8. Variability of the quasi-2-day wave and interaction with longer period planetary waves in the MLT at Cachoeira Paulista (22.7°S, 45°W)

    NASA Astrophysics Data System (ADS)

    Guharay, A.; Batista, P. P.; Clemesha, B. R.

    2015-08-01

    An exclusive study has been carried out with long term meteor wind data (2000-2014) to characterize the quasi-2-day wave (QTDW) in the mesosphere and lower thermosphere (MLT) and its interactions with the longer period planetary waves at Cachoeira Paulista (22.7°S, 45°W). The QTDW is observed to be dominant during late summer (January-February) all the years under consideration except 2013. All the wave parameters exhibit significant interannual variability. The maximum wave amplitude comes out to be 39 m/s, which is significantly higher than the reported northern hemispheric findings. The mean MLT period exhibits a wide range of variability (36-70 h) indicating the presence of multiple Rossby normal modes with varying zonal wave numbers. Modulations of the QTDW amplitude by the planetary waves with longer periodicities (>9 days) are evident, especially during summer. The nonlinear interactions between the 2-day wave and longer period waves are believed to give rise to a host of secondary waves with frequencies lying close to 2-day. The strong QTDW activity, as observed at this location, has potential to cause significant effect on the overlying ionosphere and hence the atmosphere-ionosphere dynamical coupling.

  9. Enhancement of proliferation in a rat hepatocyte co-culture model after mitogenic stimulation.

    EPA Science Inventory

    Primary mouse and rat hepatocyte cultures have long been the gold standard for assessment of cellular changes following chemical exposure. While helpful for assessing proliferative and responses in vitro, these cultures are limited to 1 or 2 days of incubation. Our motivation was...

  10. Vaginal thread formation in the healthy offspring of untreated Long-Evans rats

    EPA Science Inventory

    Vaginal threads are characterized as cords of mesenchymal tissue that cross the vaginal opening. They are sometimes apparent in rats after weaning, and typically disappear within 1-2 days as the female reaches puberty. If persistent, they can increase uncertainty in assessing rep...

  11. Lymphatic vessels in the developing diaphragm of the rat.

    PubMed

    Poggi, P; Marchetti, C; Calligaro, A; Casasco, A; Scelsi, R

    1991-01-01

    Diaphragms of fetal, neonatal and young albino rats have been observed both under light and electron microscopes to examine the presence and distribution of lymphatic vessels and their morphological features. In fetal diaphragms of between 18 and 22 days of gestation, no normal lymphatic vessels can be seen; only after birth, specifically in neonatal and 2-day-old rats, small lymphatic vessels appear; they are in close proximity to the blood vessels in the inner areas of the muscle. As the rats get older, lymphatic vessels are also observed in the subserosa where an abundant connective tissue is present. The fine structure of diaphragmatic lymphatic vessels is different at different ages. In neonatal rats of up to 2 days, the endothelial wall is very thin and often holed. The relationships between contiguous endothelial cells are characterized by simple end-to-end or overlapping structures. The basement membrane is virtually absent. Within the first week of life, the endothelial wall becomes more complex; along the wall, complex interdigitations between two contiguous endothelial cells often touch. A discontinuous basement membrane and collagen and elastic fibers surround the vessels. In the older rats (from 14 to 25 to 140 days), next to the complex interdigitations which characterize the junction between two contiguous endothelial cells, cellular flaps interdigitate forming a channel which opens out either to the exterior or the interior of the vessel. Dense bundles of elastic and collagen fibers are closely apposed to the endothelial wall.

  12. Estradiol promotes the rewarding effects of nicotine in female rats.

    PubMed

    Flores, Rodolfo J; Pipkin, Joseph A; Uribe, Kevin P; Perez, Adriana; O'Dell, Laura E

    2016-07-01

    It is presently unclear whether ovarian hormones, such as estradiol (E2), promote the rewarding effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day injection regimen involving 2 days of vehicle and 2 days of E2 administration. Two doses of E2 (25 or 250μg) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the rewarding effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06mg/kg/0.1mL). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the rewarding effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2.

  13. Nuclear criticality safety: 2-day training course

    SciTech Connect

    Schlesser, J.A.

    1997-02-01

    This compilation of notes is presented as a source reference for the criticality safety course. At the completion of this training course, the attendee will: be able to define terms commonly used in nuclear criticality safety; be able to appreciate the fundamentals of nuclear criticality safety; be able to identify factors which affect nuclear criticality safety; be able to identify examples of criticality controls as used as Los Alamos; be able to identify examples of circumstances present during criticality accidents; have participated in conducting two critical experiments; be asked to complete a critique of the nuclear criticality safety training course.

  14. Interaction of dimethylbenzanthracene and diethylstilbestrol on mammary adenocarcinoma formation in female ACI rats

    SciTech Connect

    Shellabarger, C.J.; McKnight, B.; Stone, J.P.; Holtzman, S.

    1980-06-01

    It has been reported that x-irradiation and diethylstilbestrol (DES) act synergistically on mammary adenocarcinoma formation in female ACI rats. The physical carcinogen, x-irradiation, was replaced by a chemical carcinogen, dimethylbenzanthracene (DMBA), and their interaction was studied in this system. Thirty-three female ACI rats were given 13.3 mg of DMBA per 100 grams of body weight. A total of 10 mammary adenocarcinomas were found, 8 in rats with a single mammary adenocarcinoma and 2 in a single rat, over a 266-day study period. Twenty-nine rats were implanted with a cholesterol pellet containing 5 mg of DES, and a total of 47 mammary adenocarcinomas were found, 5 in rats with a single mammary adenocarcinoma and 42 in 5 rats with 2 or more mammary adenocarcinomas. Twenty-four rats were given a combined treatment of both compounds, DES 2 days before DMBA, and a total of 126 mammary adenocarcinomas were found, 2 in rats with a single mammary adenocarcinoma and 124 in 18 rats with 2 or more mammary adenocarcinomas. The interaction between DMBA and DES was interpreted to be synergistic in regard to the proportion of rats with one or more mammary adenocarcinomas, and the median times of appearance of both first and second mammary adenocarcinomas. These interactions between DMBA and DES resemble the previously reported synergistic interactions between radiation and DES on mammary adenocarcinoma formation in female ACI rats.

  15. The rat choledochojejunostomy model for microsurgical training

    PubMed Central

    Lee, Jun Suh

    2016-01-01

    Purpose The feasibility of a rat choledochojejunostomy (CJ) training model was investigated, as an introductory model to microsurgery for general surgeons. Methods Roux-en-Y CJ was performed on 20 rats. Interrupted 10-0 prolene sutures were used to perform CJ. The animals were observed for 7 days and sacrificed and examined. Results The rats were divided into 2 groups of 10 based on surgical order. The CJ time showed a significant decrease from 36.2 ± 5.6 minutes in group 1 to 29.4 ± 5.7 minutes in group 2 (P = 0.015). The bile leakage rate was 40% in group 1 and 10% in group 2. The survival time was 5.4 ± 2.2 days in group 1 and 7 days in group 2 (P = 0.049). Conclusion The rat CJ training model is a feasible introductory model for general surgeons with no previous experience in microsurgery. PMID:27186568

  16. Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent diabetes mellitus rats.

    PubMed

    Anwer, Tarique; Sharma, Manju; Pillai, Krishna Kolappa; Iqbal, Muzaffar

    2008-06-01

    We investigated the effect of an aqueous extract of Withania somnifera (WS) on insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA(1)c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA(1)c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (K(ITT)) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.

  17. Phase I/II Study Evaluating Early Tolerance in Breast Cancer Patients Undergoing Accelerated Partial Breast Irradiation Treated With the MammoSite Balloon Breast Brachytherapy Catheter Using a 2-Day Dose Schedule

    SciTech Connect

    Wallace, Michelle; Martinez, Alvaro; Mitchell, Christina; Chen, Peter Y.; Ghilezan, Mihai; Benitez, Pamela; Brown, Eric; Vicini, Frank

    2010-06-01

    Purpose: Initial Phase I/II results using balloon brachytherapy to deliver accelerated partial breast irradiation (APBI) in 2 days in patients with early-stage breast cancer are presented. Materials and Methods: Between March 2004 and August 2007, 45 patients received adjuvant radiation therapy after lumpectomy with balloon brachytherapy in a Phase I/II trial delivering 2800 cGy in four fractions of 700 cGy. Toxicities were evaluated using the National Cancer Institute Common Toxicity Criteria for Adverse Events v3.0 scale and cosmesis was documented at >=6 months. Results: The median age was 66 years (range, 48-83) and median skin spacing was 12 mm (range, 8-24). The median follow-up was 11.4 months (5.4-48 months) with 21 patients (47%) followed >=1 year, 11 (24%) >=2 years, and 7 (16%) >=3 years. At <6 months (n = 45), Grade II toxicity rates were 9% radiation dermatitis, 13% breast pain, 2% edema, and 2% hyperpigmentation. Grade III breast pain was reported in 13% (n = 6). At >=6 months (n = 43), Grade II toxicity rates were: 2% radiation dermatitis, 2% induration, and 2% hypopigmentation. Grade III breast pain was reported in 2%. Infection was 13% (n = 6) at <6 months and 5% (n = 2) at >=6 months. Persistent seroma >=6 months was 30% (n = 13). Fat necrosis developed in 4 cases (2 symptomatic). Rib fractures were seen in 4% (n = 2). Cosmesis was good/excellent in 96% of cases. Conclusions: Treatment with balloon brachytherapy using a 2-day dose schedule resulted acceptable rates of Grade II/III chronic toxicity rates and similar cosmetic results observed with a standard 5-day accelerated partial breast irradiation schedule.

  18. Oh rats! Fever, rash and arthritis in a young woman.

    PubMed

    Brown, Carina M; Tsai, Gary; Sanchez-Flores, Xavi

    2015-01-01

    A 17-year-old girl presented with worsening right-sided hip and low back pain for 2 days. She had also experienced intermittent fevers and a recurring maculopapular rash over the past 2 weeks. Social history revealed the presence of three domestic rats living in the girl's home. Blood cultures returned positive for Streptobacillus moniliformis, the causative agent of rat-bite fever. Rat-bite fever often goes undiagnosed, as the clinical presentation is non-specific. Untreated, the infection can result in death due to sepsis or endocarditis. The bacterium is generally susceptible to penicillin antibiotics with full clinical recovery when treated in a timely and appropriate manner. After 4 weeks of intravenous antibiotics, our patient fully recovered without long-term sequelae. PMID:26701936

  19. Rats! Oh No, Not Rats!

    ERIC Educational Resources Information Center

    Strong, Gary E.

    1987-01-01

    Examples of problems encountered in a new library building--including rats and humidity--and a description of the library's collections provide a framework for this presentation of the California State Library's emergency management planning. Current preservation efforts are documented and the library's disaster and security plans are described.…

  20. Laboratory evaluation of WBA 8119 as a rodenticide for use against warfarin-resistant and non-resistant rats and mice.

    PubMed Central

    Redfern, R.; Gill, J. E.; Hadler, M. R.

    1976-01-01

    Feeding tests were carried out in the laboratory to evaluate WBA 8119 as a potential new rodenticide against wild common rats (Rattus norvegicus), ship rats (R. rattus) and house mice (Mus musculus). The results obtained are compared with data previously obtained for difenacoum, another member of the same series of 4-hydroxycoumarin anticoagulants. With warfarin-resistnat and non-resistant common rats, complete kills were obtained using a concentration of 0-0005% for 2 days, or 0-001% for 1 day: a 1-day test at 0-0005% killed 6 out of 10 and 17 out of 20 of the two types respectively. At 0-0005% complete kills of resistant ship rats were obtained after 2 days exposure and of resistant house mice after 1 day, but at 0-002% for 2 days there was some survival. Non-resistant ship rats and house mice were all killed after 2 days feeding on 0-002% bait. In 2-day palatability tests, R. norvegicus showed no significant aversion to the poison at 0-002% and 100% mortality was obtained. The poison was significantly unpalatable to R. rattus at 0-005% and to M. musculus at 0-005% and 0-002%, although with the last species these concentrations gave complete kills. It is concluded that WBA 8119 has greater activity than other known anticoagulants against the three commensal species examined. The laboratory results suggest that concentrations between 0-0005% and 0-002% would be suitable for field use against common rats, and between 0-002% and 0-005% for ship rats and house mice. PMID:1069820

  1. An intense traveling airglow front in the upper mesosphere-lower thermosphere with characteristics of a bore observed over Alice Springs, Australia, during a strong 2 day wave episode

    NASA Astrophysics Data System (ADS)

    Walterscheid, R. L.; Hecht, J. H.; Gelinas, L. J.; Hickey, M. P.; Reid, I. M.

    2012-11-01

    The Aerospace Corporation's Nightglow Imager observed a large step function change in airglow in the form of a traveling front in the OH Meinel (OHM) and O2atmospheric (O2A) airglow emissions over Alice Springs, Australia, on 2 February 2003. The front exhibited nearly a factor of 2 stepwise increase in the OHM brightness and a stepwise decrease in the O2A brightness. There was significant (˜25 K) cooling behind the airglow fronts. The OHM airglow brightness behind the front was among the brightest for Alice Springs that we have measured in 7 years of observations. The event was associated with a strong phase-locked 2 day wave (PL/TDW). We have analyzed the wave trapping conditions for the upper mesosphere and lower thermosphere using a combination of data and empirical models and found that the airglow layers were located in a region of ducting. The PL/TDW-disturbed wind profile was effective in supporting a high degree of ducting, whereas without the PL/TDW the ducting was minimal or nonexistent. The change in brightness in each layer was associated with a strong leading disturbance followed by a train of weak barely visible waves. In OHM the leading disturbance was an isolated disturbance resembling a solitary wave. The characteristics of the wave train suggest an undular bore with some turbulent dissipation at the leading edge.

  2. Consistent Pulmonary and Systemic Responses from Inhalation of Fine Concentrated Ambient Particles: Roles of Rat Strains Used and Physicochemical Properties

    PubMed Central

    Kodavanti, Urmila P.; Schladweiler, Mette C.; Ledbetter, Allen D.; McGee, John K.; Walsh, Leon; Gilmour, Peter S.; Highfill, Jerry W.; Davies, David; Pinkerton, Kent E.; Richards, Judy H.; Crissman, Kay; Andrews, Debora; Costa, Daniel L.

    2005-01-01

    Several studies have reported health effects of concentrated ambient particles (CAP) in rodents and humans; however, toxicity end points in rodents have provided inconsistent results. In 2000 we conducted six 1-day exposure studies where spontaneously hypertensive (SH) rats were exposed to filtered air or CAPs (≤ 2.5 μm, 1,138–1,765 μg/m3) for 4 hr (analyzed 1–3 hr afterward). In seven 2-day exposure studies in 2001, SH and Wistar Kyoto (WKY) rats were exposed to filtered air or CAP (≤ 2.5 μm, 144–2,758 μg/m3) for 4 hr/day × 2 days (analyzed 1 day afterward). Despite consistent and high CAP concentrations in the 1-day exposure studies, no biologic effects were noted. The exposure concentrations varied among the seven 2-day exposure studies. Except in the first study when CAP concentration was highest, lavageable total cells and macrophages decreased and neutrophils increased in WKY rats. SH rats demonstrated a consistent increase of lavage fluid γ -glutamyltransferase activity and plasma fibrinogen. Inspiratory and expiratory times increased in SH but not in WKY rats. Significant correlations were found between CAP mass (microgram per cubic meter) and sulfate, organic carbon, or zinc. No biologic effects correlated with CAP mass. Despite low chamber mass in the last six of seven 2-day exposure studies, the levels of zinc, copper, and aluminum were enriched severalfold, and organic carbon was increased to some extent when expressed per milligram of CAP. Biologic effects were evident in those six studies. These studies demonstrate a pattern of rat strain–specific pulmonary and systemic effects that are not linked to high mass but appear to be dependent on CAP chemical composition. PMID:16263512

  3. Estrogen-dependent visceral hypersensitivity following stress in rats

    PubMed Central

    Hubbard, Catherine S; Karpowicz, Jane M; Furman, Andrew J; da Silva, Joyce Teixeira; Traub, Richard J

    2016-01-01

    We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress. Stress was induced via a forced-swim paradigm. In a separate group of ovariectomized rats, E2 treatment induced visceral hypersensitivity at the 2 days post-stress time point, and this hypersensitivity returned to baseline at the 18 days post-stress time point. Vehicle-treated rats show no hypersensitivity following stress. During the MRI scans, rats were exposed to noxious colorectal distention. Across groups and time points, noxious visceral stimulation led to activations in the insula, anterior cingulate, and left amygdala, parabrachial nuclei, and cerebellum. A group-by-time interaction was seen in the right amygdala, ventral striatum-pallidum, cerebellum, hippocampus, mediodorsal thalamus, and pontine nuclei. Closer inspection of the data revealed that vehicle-treated rats showed consistent activations and deactivations across time, whereas estrogen-treated animals showed minimal deactivation with noxious visceral stimulation. This unexpected finding suggests that E2 may dramatically alter visceral nociceptive processing in the brain following an acute stressor. This study is the first to examine estrogen-stress dependent interactions in response to noxious visceral stimulation using functional MRI. Future studies that include other control

  4. Course of motor recovery following ventrolateral spinal cord injury in the rat.

    PubMed

    Webb, Aubrey A; Muir, Gillian D

    2004-11-01

    The purpose of this study was to determine the importance of the pathways running in the ventrolateral spinal funiculus for overground locomotion in adult, freely behaving rats. Left-sided ventrolateral cervical spinal cord injury was performed in adult female Long-Evans rats. The behavioural abilities of these animals were analyzed at 2 days, and weekly for up to 5.5 weeks following spinal cord injury. Behavioural testing consisted of Von Frey filament testing, ladder walking, a paw usage task, and the assessment of ground reaction forces during unrestrained trotting. Animals with injury to the left ventrolateral cervical spinal cord did not develop enhanced sensitivity to pedal mechanical stimulation. At 2 days following injury, animals had impaired skilled locomotion as indicated by increased number of footslips during ladder walking. At 2 days, these animals also used both limbs together more often for support while rearing, while using the forelimb ipsilateral to the injury less than did uninjured animals. Ground reaction force determination revealed that animals tend to bear less weight on the forelimb and hindlimb ipsilateral to the spinal cord injury 2 days after injury. All animals recovered normal or near normal sensorimotor abilities although subtle asymmetries in ground reaction forces were detectable at 5.5 weeks following spinal cord injury. These results suggest that axons in the ventrolateral spinal funiculi contribute to limb movements during exploration and locomotion but their roles can be served by other pathways after ventrolateral spinal injury. PMID:15325779

  5. Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.

    PubMed

    Gaspar, Renato Simões; Benevides, Renata Ohana Alves; Fontelles, João Lucas de Lima; Vale, Caroline Castro; França, Lucas Martins; Barros, Paulo de Tarso Silva; Paes, Antonio Marcus de Andrade

    2016-05-01

    Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis.

  6. Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.

    PubMed

    Gaspar, Renato Simões; Benevides, Renata Ohana Alves; Fontelles, João Lucas de Lima; Vale, Caroline Castro; França, Lucas Martins; Barros, Paulo de Tarso Silva; Paes, Antonio Marcus de Andrade

    2016-05-01

    Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis. PMID:26952035

  7. Transplantation of choroid plexus epithelial cells into contusion-injured spinal cord of rats

    PubMed Central

    Kanekiyo, Kenji; Nakano, Norihiko; Noda, Toru; Yamada, Yoshihiro; Suzuki, Yoshihisa; Ohta, Masayoshi; Yokota, Atsushi; Fukushima, Masanori; Ide, Chizuka

    2016-01-01

    Purpose: The effect of the transplantation of choroid plexus epithelial cells (CPECs) on locomotor improvement and tissue repair including axonal extension in spinal cord lesions was examined in rats with spinal cord injury (SCI). Methods: CPECs were cultured from the choroid plexus of green fluorescent protein (GFP)-transgenic rats, and transplanted directly into the contusion-injured spinal cord lesions of rats of the same strain. Locomotor behaviors were evaluated based on BBB scores every week after transplantation until 4 weeks after transplantation. Histological and immunohistochemical examinations were performed at 2 days, and every week until 5 weeks after transplantation. Results: Locomotor behaviors evaluated by the BBB score were significantly improved in cell-transplanted rats. Numerous axons grew, with occasional interactions with CPECs, through the astrocyte-devoid areas. These axons exhibited structural characteristics of peripheral nerves. GAP-43-positive axons were found at the border of the lesion 2 days after transplantation. Cavity formation was more reduced in cell-transplanted than control spinal cords. CPECs were found within the spinal cord lesion, and sometimes in association with astrocytes at the border of the lesion until 2 weeks after transplantation. Conclusion: The transplantation of CPECs enhanced locomotor improvement and tissue recovery, including axonal regeneration, in rats with SCI. PMID:26923614

  8. Genistein treatment reduces arterial contractions by inhibiting tyrosine kinases in ovariectomized hypertensive rats.

    PubMed

    Nevala, Riikka; Lassila, Markus; Finckenberg, Piet; Paukku, Kirsi; Korpela, Riitta; Vapaatalo, Heikki

    2002-09-27

    The aim of the present study was to evaluate the vascular effects of genistein in a short-term study. The ovariectomized spontaneously hypertensive rats (SHR) were divided into four groups (n = 8 in each), which received the following subcutaneous treatments either for 2 days or for 2 weeks: (1) solvent control (96% dimethylsulphoxide (DMSO) 1 ml/kg), (2) estradiol-17beta (25 microg/kg), (3) genistein (2.5 mg/kg; low-dose), and (4) genistein (25 mg/kg; high-dose). The renal arterial rings were studied using organ bath system. The renal artery contractions were attenuated by the 2-day low-dose genistein treatment as follows: angiotensin II (46%), noradrenaline (42%) KCl (36%), and endothelin-1 (34%). Only the angiotensin II-induced contractions were reduced by the 2-week treatment with estradiol-17beta (38%) and with the low-dose of genistein (31%). The 2-day genistein treatment reduced tyrosine phosphorylation, while the other treatments or treatment times had no effect. The 2-day low-dose genistein treatment had no estrogenic effect on the uterine morphology. The mechanism for attenuated contractility in the renal arteries after the 2-day low-dose genistein treatment is independent of the estrogenic effect of genistein, but is due to the tyrosine kinase inhibitory property of genistein.

  9. Choleretic activity of Gentiana lutea ssp. symphyandra in rats.

    PubMed

    Oztürk, N; Herekman-Demir, T; Oztürk, Y; Bozan, B; Başer, K H

    1998-08-01

    Effects of an ethanolic extract prepared from G. lutea ssp. symphyandra roots on the bile production and liver in rats were investigated. Bile flows of rats which were treated by a single i.p. dose of CCl(4) 24 h prior to experiments were measured after the cannulation of bile duct under urethane anaesthesia. After an equilibration period of 1 h, the lyophilized extract were administered intraduodenally (500 mg/kg i.p.), while control animals received physiological saline only. To monitor the effect of multiple dose therapy, rats received the same dose of G. lutea ssp. symphyandra extract for 3 days (2 days prior to CCl(4) administration) and their bile flows were measured after the cannulation. In all groups, bile samples were collected for 3 h with 15 min intervals. After the completion of bile flow experiment, rat livers were removed and put in neutral formaldehyde solution (10%) for the histological examination. According to results obtained, multiple dose treatment of rats with the plant extract normalized the decreased bile flow due CCl(4), whereas single dose therapy was ineffective on the impaired bile flow. These data indicate that the extract prepared from Gentiana lutea ssp. symphyandra roots has a hepatoprotective activity.

  10. Re-utilization of pyrimidine nucleotides during rat liver regeneration.

    PubMed Central

    Nikolov, E N; Dabeva, M D

    1985-01-01

    The changes in the specific radioactivities of the pool of total acid-soluble uridine nucleotides and of uridine and cytidine components of total cellular and nuclear RNA were monitored in regenerating rat liver for 12 days after partial hepatectomy. Evidence is presented for the re-utilization of pyrimidine nucleotides derived from cytoplasmic RNA degradation for the synthesis of new RNA. The extent of recycling was assessed and the true rate of rRNA turnover determined more accurately. The reutilization of the uridine components of RNA was 7.0%/day during the proliferative and 3.2%/day during the post-proliferative phase, whereas that of the cytidine nucleotides was more pronounced (9.6%/day and 18.1%/day respectively). The results reveal the existence of partial compartmentalization of pyrimidine ribonucleoside triphosphate pools in the nucleus and cytoplasm of rat liver cells. PMID:2408609

  11. Alterations in sulfur and nitrogen metabolism in rats with portacaval shunts

    SciTech Connect

    Benjamin, L.E.

    1985-01-01

    The effect of portacaval shunt (PCS) on methionine and cysteine metabolism was investigated. PCS rats excreted more urinary (/sup 35/S)sulfate and less (/sup 35/S)taurine than controls after injection of (/sup 35/S)methionine of (/sup 35/S)cysteine. Total urinary taurine excretion was unchanged. Under basal conditions PCS rats excreted more taurine than controls. Relative rates of transsulfuration in PCS and control rats were studied, and no difference in flux of /sup 35/S from methionine to cysteine was found. Total hepatic activities of three transsulfuration pathway enzymes were also unchanged after PCS. In contrast, hepatic activities of three cysteine-oxidizing enzymes were depressed after PCS, suggesting that changes in hepatic metabolism after PCS are selective. PCS rats fed a high (60%) casein diet ate less and took longer to recover their preoperative body weight than controls. All PCS rats had higher plasma ammonia and urinary orotic acid levels than controls. Increasing dietary protein elevated plasma ammonia and urinary orotic acid to a greater extent in PCS rats. After injection of (/sup 35/S)methionine or (/sup 35/S)cysteine, urinary /sup 35/S and (/sup 35/S)sulfate excretion increased and (/sup 35/S)taurine an total taurine excretion decreased in all rats fed 60% casein, but the effect was greater in PCS rats. Changes in cysteine sulfinate decarboxylase activity in rats fed a high protein diet was examined. Activity decreased 95% in rats fed diets containing between 18 and 75% casein. The effect was observed after feeding a 60% casein diet for 2 days and was reversed when rats were refed an 18% casein diet.

  12. Body core temperature of rats subjected to daily exercise limited to a fixed time

    NASA Astrophysics Data System (ADS)

    Shido, O.; Sugimoto, Naotoshi; Sakurada, Sotaro; Kaneko, Yoshiko; Nagasaka, Tetsuo

    Several timed daily environmental cues alter the pattern of nycthemeral variations in body core temperature in rodents. The present study investigated the effect of timed exercise on variations of daily body core temperature. Male rats were housed in cages with a running wheel at an ambient temperature of 24° C with a 12:12 h light/dark cycle. Timed daily exercise rats (TEX) were allowed access to the wheel for 6 h in the last half of the dark phase, freely exercising rats (FEX) could run at any time, and sedentary rats (NEX) were not allowed to run. After a 3-week exercise period, all animals were denied access to the wheel. The intraabdominal temperatures (Tab) and spontaneous activities of rats were measured for 6 days after the exercise period. The Tab values of the TEX rats were significantly higher than those of the other two groups only in the last half of the dark phase, while Tab in the FEX and NEX rats showed no significant difference. The specific Tab changes in the TEX rats lasted for 2 days after the exercise period. Spontaneous activity levels were higher in the TEX rats than the FEX and NEX rats in the last half of the dark phase for 1 day after the exercise period. The results suggest that daily exercise limited to a fixed time per day modifies nycthemeral variations of body core temperature in rats so that the temperature increases during the period when the animals had previously exercised. Such a rise in body core temperature is partly attributed to an increase in the spontaneous activity level.

  13. Rat Bite Fever

    MedlinePlus

    ... Issues Listen Español Text Size Email Print Share Rat Bite Fever Page Content Article Body Rat-bite fever is a disease that occurs in humans who have been bitten by an infected rat or, in some cases, squirrels, mice, cats, and ...

  14. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    SciTech Connect

    Bass, V.; Gordon, C.J.; Jarema, K.A.; MacPhail, R.C.; Cascio, W.E.; Phillips, P.M.; Ledbetter, A.D.; Schladweiler, M.C.; Andrews, D.; Miller, D.; Doerfler, D.L.; Kodavanti, U.P.

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  15. Hormone secretion by euthyroid and hypothyroid rat ovaries during the early stages of hCG-induced ovarian cyst development.

    PubMed

    Bruot, B C

    1987-02-01

    This study was undertaken to examine ovarian steroid production during the early stages of hCG-induced ovarian cyst formation in the hypothyroid rat. Rats were placed into two groups with one group made hypothyroid by adding thiouracil to their diet. After 10 days, each group was divided into two subgroups with one subgroup receiving daily injections of hCG for 2 days and the other subgroup receiving saline. On the morning of Day 13, ovaries were removed and incubated for 2 hr. No significant difference in progesterone secretion was observed. However, ovaries from hypothyroid, hCG-treated rats secreted significantly more testosterone and estradiol than ovaries from vehicle-treated, hypothyroid rats and euthyroid, hCG-treated rats. In a second experiment, ovaries from euthyroid and hypothyroid rats treated with hCG were incubated in medium supplemented with 100 nM androstenedione and 0 or 100 ng FSH/ml. FSH failed to affect progesterone, testosterone, and estradiol secretions by ovaries from euthyroid, hCG-treated rats. In contrast, FSH significantly enhanced testosterone and estradiol secretion by ovaries from hypothyroid, hCG-treated rats. These results support the hypothesis that increased levels of testosterone and estradiol secretion have a central role in the induction of polycystic ovaries by hCG in the hypothyroid rat. PMID:3101068

  16. /sup 20/neon ion- and x-ray-induced mammary carcinogenesis in female rats

    SciTech Connect

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to /sup 20/Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for /sup 20/Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that /sup 20/Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

  17. Effect of ovariectomy at birth on the regulation of sebaceous glands in rats.

    PubMed

    Toh, Y C

    1980-07-01

    Inbred Sprague-Dawley rats were ovariectomized within 24 h of birth. Sham-operated and untreated male and female rats were also included for comparison. At the age of 80 days, the secretion rate of sebum was assessed from the amount of skin-surface lipids that could be extracted by acetone and which had been produced during 2 days. There were no differences in sebum secretion, when expressed both in relationship to body weight and to surface area of the body, when rats ovariectomized at birth, sham-operated and intact female rats were compared. The removal of the ovaries within 24 h of birth increased the body weight, however. Although the weights of the pituitary, thyroid and adrenal glands, when corrected for body weight, were significantly smaller in rats ovariectomized at birth than in the sham-operated or intact female rats, there were no statistically significant differences in the absolute weights of these endocrine organs between neonatally spayed rats and sham-operated animals. The uterus became atrophic in the absence of ovaries. It has been concluded that the presence or absence of ovaries in the early stage of life had no effect on the activity of the sebaceous glands.

  18. Beyond knockout rats

    PubMed Central

    Huang, Guanyi; Tong, Chang; Kumbhani, Dhruv S; Ashton, Charles; Yan, Hexin

    2011-01-01

    The ability to “knockout” specific genes in mice via embryonic stem (ES) cell-based gene-targeting technology has significantly enriched our understanding of gene function in normal and disease phenotypes. Improvements on this original strategy have been developed to enable the manipulation of genomes in a more sophisticated fashion with unprecedented precision. The rat is the model of choice in many areas of scientific investigation despite the lack of rat genetic toolboxes. Most recent advances of zinc finger nucleases (ZFNs) and rat ES cells are diminishing the gap between rat and mouse with respect to reverse genetic approaches. Importantly, the establishment of rat ES cell-based gene targeting technology, in combination with the unique advantages of using rats, provides new, exciting opportunities to create animal models that mimic human diseases more faithfully. We hereby report our recent results concerning finer genetic modifications in the rat, and propose their potential applications in addressing biological questions. PMID:21383544

  19. Chronic administration of isocarbophos induces vascular cognitive impairment in rats.

    PubMed

    Li, Peng; Yin, Ya-Ling; Zhu, Mo-Li; Pan, Guo-Pin; Zhao, Fan-Rong; Lu, Jun-Xiu; Liu, Zhan; Wang, Shuang-Xi; Hu, Chang-Ping

    2016-04-01

    Vascular dementia, being the most severe form of vascular cognitive impairment (VCI), is caused by cerebrovascular disease. Whether organophosphorus causes VCI remains unknown. Isocarbophos (0.5 mg/kg per 2 days) was intragastrically administrated to rats for 16 weeks. The structure and function of cerebral arteries were assayed. The learning and memory were evaluated by serial tests of step-down, step-through and morris water maze. Long-term administration of isocarbophos reduced the hippocampal acetylcholinesterase (AChE) activity and acetylcholine (ACh) content but did not alter the plasma AChE activity, and significantly damaged the functions of learning and memory. Moreover, isocarbophos remarkably induced endothelial dysfunction in the middle cerebral artery and the expressions of ICAM-1 and VCAM-1 in the posterior cerebral artery. Morphological analysis by light microscopy and electron microscopy indicated disruptions of the hippocampus and vascular wall in the cerebral arteries from isocarbophos-treated rats. Treatment of isocarbophos injured primary neuronal and astroglial cells isolated from rats. Correlation analysis demonstrated that there was a high correlation between vascular function of cerebral artery and hippocampal AChE activity or ACh content in rats. In conclusion, chronic administration of isocarbophos induces impairments of memory and learning, which is possibly related to cerebral vascular dysfunction. PMID:26818681

  20. Sex Differences in Physiological Acclimatization after Transfer in Wistar Rats.

    PubMed

    Arts, Johanna W M; Kramer, Klaas; Arndt, Saskia S; Ohl, Frauke

    2014-10-30

    Most laboratory animals used in research are vendor-bred and transferred to research facilities. Transfer procedures might have considerable and unintended effects on research results. In the present study we compared physiological and behavioral parameters before and after external and internal transfer, as well as between transferred and non-transferred Wistar rats. The impact of both external and internal transfer on body weight, plasma corticosterone levels, heart rate, blood pressure, and locomotor activity was studied in both male and female Wistar rats, taking into account the sex differences in stress responsivity. External transfer was found to decrease body weight, increase plasma corticosterone, increase activity, increase heart rate in female rats, but decrease heart rate in male rats. Parameters showed differences between the sexes and light phases. This study shows that acclimatization after transfer is sex-specific and researchers should take the sex into consideration when determining the acclimatization period. It is recommended to allow for acclimatization of at least 8 days in males and two weeks in females after external transfer and timely (2 days before starting experiments) transfer the animals internally to the testing room.

  1. Changed sensitivity of adenylate cyclase signaling system to biogenic amines and peptide hormones in tissues of starving rats.

    PubMed

    Shpakov, A O; Kuznetsova, L A; Plesneva, S A; Pertseva, M N

    2007-07-01

    In the myocardium and skeletal muscles of rats deprived of food for 2 days, basal activity of adenylate cyclase decreased, while the sensitivity of adenylate cyclase signaling system to the stimulating effects of non-hormonal agents (guanine nucleotides and NaF) and beta-agonist isoproterinol modulating adenylate cyclase through stimulating G proteins increased. In starving organism, the regulatory effects of hormones realizing their effects through inhibitory G proteins (somatostatin in the myocardium and bromocryptin in the brain) weakened. Their inhibitory effects on forskolin-stimulated adenylate cyclase activity and stimulating effects on binding of guanosine triphosphate decreased. In the brain of starving rats, the differences in the sensitivity of the adenylate cyclase signaling system to hormones and nonhormonal agents were less pronounced than in the muscle tissues, which attested to tissue-specific changes in the functional state of this system under conditions of 2-day starvation.

  2. Female rats are more susceptible to central nervous system oxygen toxicity than male rats.

    PubMed

    Held, Heather E; Pilla, Raffaele; Ciarlone, Geoffrey E; Landon, Carol S; Dean, Jay B

    2014-01-01

    Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males. PMID:24771690

  3. Female rats are more susceptible to central nervous system oxygen toxicity than male rats.

    PubMed

    Held, Heather E; Pilla, Raffaele; Ciarlone, Geoffrey E; Landon, Carol S; Dean, Jay B

    2014-01-01

    Abstract Tonic-clonic seizures typify central nervous system oxygen toxicity (CNS-OT) in humans and animals exposed to high levels of oxygen, as are encountered during scuba diving. We previously demonstrated that high doses of pseudoephedrine (PSE) decrease the latency to seizure (LS) for CNS-OT in young male rats. This study investigated whether female rats respond similarly to PSE and hyperbaric oxygen (HBO). We implanted 60 virgin stock (VS) and 54 former breeder (FB) female rats with radio-telemetry devices that measured brain electrical activity. One week later, rats were gavaged with saline or PSE in saline (40, 80, 120, 160, or 320 mg/kg) before diving to five atmospheres absolute in 100% oxygen. The time between reaching maximum pressure and exhibiting seizure was LS. Vaginal smears identified estrus cycle phase. PSE did not decrease LS for VS or FB, primarily because they exhibited low LS for all conditions tested. VS had shorter LS than males at 0, 40, and 80 mg/kg (-42, -49, and -57%, respectively). FB also had shorter LS than males at 0, 40, and 80 mg/kg (-60, -86, and -73%, respectively). FB were older than VS (286 ± 10 days vs. 128 ± 5 days) and weighed more than VS (299 ± 2.7 g vs. 272 ± 2.1 g). Males tested were younger (88 ± 2 days), heavier (340 ± 4.5 g), and gained more weight postoperatively (7.2 ± 1.6 g) than either VS (-0.4 ± 1.5 g) or FB (-1.6 ± 1.5 g); however, LS correlated poorly with age, body mass, change in body mass, and estrus cycle phase. We hypothesize that differences in sex hormones underlie females' higher susceptibility to CNS-OT than males.

  4. Rhus coriaria ameliorates insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) rats.

    PubMed

    Anwer, Tarique; Sharma, Manju; Khan, Gyas; Iqbal, Muzaffar; Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Safhi, Mohammed Mohsen; Gupta, Nakul

    2013-01-01

    We have investigated the effect of methanolic extract of Rhus coriaria (RC) on hyperinsulinemia, glucose intolerance and insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (STZ, 100 mg/kg) to 2 days old rat pups. RC (200 mg/kg and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e, 90 days after STZ injection). A group of citrate control rats were also maintained which has received citrate buffer on the 2nd day of their birth. There was a significant increase in blood glucose, glycosylated hemoglobin (HbA1c) and serum insulin levels were observed in NIDDM control rats. Treatment with RC reduced the elevated levels of blood glucose, HbA1c and insulin in the NIDDM rats. An oral glucose tolerance test (OGTT) was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with RC. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. RC treatment significantly improved insulin sensitivity index (K(ITT)) which was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas RC treatment significantly prevented the rise in HOMA-R in NIDDM treated rats. Our data suggest that methanolic extract of RC significantly delayed the onset of hyperinsulinemia and glucose intolerance and improved insulin sensitivity in NIDDM rats.

  5. Behavioral thermoregulatory response to chlorpyrifos in the rat.

    PubMed

    Gordon, C J

    1997-12-31

    Chlorpyrifos (CHP) is a heavily used organophosphorous-based insecticide that elicits thermoregulatory dysfunction in the rat characterized by an initial period of hypothermia followed by a delayed hyperthermia lasting 24-72 h after exposure. The purpose of the present study was to determine (1) if the delayed hyperthermia is linked to CHP-induced hypothermia and (2) if the hypothermia and delayed hyperthermia are regulated by the CNS thermoregulatory centers. Core temperature (Tc) and motor activity (MA) of female Long-Evans rats were monitored via radiotelemetry. Rats housed in a temperature gradient were administered the control vehicle or CHP (25 mg/kg (p.o.)) while Tc, MA and ambient temperature (Ta) preferred by rats in the gradient (i.e. selected Ta) were recorded. There was an initial reduction in Tc concomitant with a decrease in selected Taa A gradual recovery in Tc occurred during the first night along with a preference for warmer Ta's and depressed MA. The day after CHP there was an elevation in Tc but no change in selected Ta, suggesting that the delayed rise in Tc was regulated. In another experiment, the hypothermic effects of CHP (25 mg/kg (p.o.)) were blocked by raising Ta from 22 to 31 degrees C immediately after CHP administration. Non-heated rats administered CHP underwent a marked period of hypothermia followed by an elevation in diurnal Tc for 2 days. Heated rats showed no hypothermic response but did undergo a hyperthermic response 48 h after CHP. MA was reduced during the first night after CHP in both non-heated and heated groups. Overall, the CHP-induced hyperthermia is not dependent on the development of hypothermia. Behavioral thermoregulatory observations suggest that both hypothermia and hyperthermia are regulated by CNS thermoregulatory centers. PMID:9482118

  6. Dynamics of locomotor activity and heat production in rats after acute stress.

    PubMed

    Pertsov, S S; Alekseeva, I V; Koplik, E V; Sharanova, N E; Kirbaeva, N V; Gapparov, M M G

    2014-05-01

    The dynamics of locomotor activity and heat production were studied in rats demonstrating passive and active behavior in the open field test at different time after exposure to acute emotional stress caused by 12-h immobilization during dark hours. The most pronounced changes in behavior and heat production followed by disturbances in circadian rhythms of these parameters were detected within the first 2 days after stress. In contrast to behaviorally active rats, the most significant decrease in locomotor activity and heat production of passive animals subjected to emotional stress was observed during dark hours. Circadian rhythms of behavior and heat production in rats tended to recover on day 3 after immobilization stress. These data illustrate the specificity of metabolic and behavioral changes reflecting the shift of endogenous biological rhythms in individuals with different prognostic resistance to stress at different terms after exposure to negative emotiogenic stimuli. PMID:24906959

  7. Effect of repeated oral administration on taurocholate on hepatic excretory function in the rat.

    PubMed

    Watkins, J B; Klaassen, C D

    1981-07-01

    The effect of repeated administration of taurocholate on bile acid pool size, biliary composition and biliary excretory capacity for bile acids and two xenobiotics was determined. The bile acid pool was increased 50 to 60% by oral administration of sodium taurocholate (300--900 mg/kg, 10 ml/kg) every 12 hr for 2 days to male Sprague-Dawley rats. Bile flow, biliary excretion of bile acids, cholesterol and phospholipid and the concentrations of phospholipid and bile acids in bile were increased in rats treated with 750 mg of taurocholate per kg. No effect was observed on Na+,K+ or Cl- levels. The biliary transport maximum for taurocholate was increased by 30% in rats treated with 750 mg/kg. In contrast, the plasma disappearance and biliary excretion of phenol-3,6-dibromphthalein and ouabain were not affected by taurocholate administration.

  8. Field trials of flocoumafen against warfarin-resistant infestations of the Norway rat (Rattus norvegicus Berk.).

    PubMed Central

    Buckle, A. P.

    1986-01-01

    The anticoagulant rodenticide flocoumafen was tested against warfarin-resistant Norway rats (Rattus norvegicus Berk.) infesting farm buildings. Complete control was obtained in 10-21 days (mean 14.2 days) in six treatments in which baits poisoned with 0.005% flocoumafen were maintained, in surplus, until rats ceased to feed from them. A further six treatments, in which the application of poisoned bait was restricted to periodic placements of 50 g, were also completely successful in 15-30 days (mean 21.0 days). Less poisoned bait was used in the restricted flocoumafen treatments than in the unrestricted treatments but the time taken to control the rat infestations was significantly longer. PMID:3755451

  9. Recovery from carotid artery catheterization performed under various anesthetics in male, Sprague-Dawley rats.

    PubMed

    Lawson, D M; Duke, J L; Zammit, T G; Collins, H L; DiCarlo, S E

    2001-07-01

    This study was designed to determine the time to recovery from carotid artery catheterization using multiple criteria and to compare recovery times between three common anesthetics. Male Sprague-Dawley rats, chronically instrumented with radio-telemetry transmitters, were anesthetized with sodium pentobarbital, halothane or a mixture of ketamine, xylazine and acepromazine before an indwelling catheter was placed in the carotid artery. The procedure was completed in less than 15 min. Changes in body weight, food and water consumption, blood pressure, heart rate and activity were used to determine recovery. As judged by recovery of body weight, animals anesthetized with each of the anesthetics recovered by the 4th day after catheterization. Food and water consumption normalized by 1-2 days after surgery. Heart rates and blood pressures during the light phase of the photoperiod were significantly increased for 2 days by all anesthetics. During the dark phase of the photoperiod, heart rates and blood pressures were not significantly affected by pentobarbital or halothane anesthesia, but were significantly decreased and increased respectively on the night immediately following surgery in the ketamine / xylazine / acepromazine-anesthetized rats. Delayed elevations of heart rate were observed in pentobarbital and halothane anesthetized rats on days and/or nights 5 and 6 post surgery. Animal activity patterns during the light phase of the photoperiod were not affected by pentobarbital or halothane, but were increased by ketamine 2 days after surgery. During the dark phase, halothane transiently reduced activity whereas ketamine-anesthetized rats showed reduced activity for 4 nights post surgery. These studies show that recovery depends on the criteria selected and the anesthetic used, but, in general, 2-4 days were required for recovery from this relatively simple procedure.

  10. Morin protects heart from beta-adrenergic-stimulated myocardial infarction: an electrocardiographic, biochemical, and histological study in rats.

    PubMed

    Pogula, Bharath Kumar; Maharajan, Mari Kannan; Oddepalli, Divya Rekha; Boini, Lavanya; Arella, Mounika; Sabarimuthu, Darlin Quine

    2012-09-01

    In recent years, polyphenols have attracted considerable attention as agents that protect cells or molecules from oxidative myocardial injury. The aim of the study was to prove the cardioprotective benefits of the flavonoid morin in isoproterenol-induced myocardial infarcted rats. Male Wistar rats are treated orally with morin (10 and 20 mg/kg) daily for a period of 21 days. After 21 days of pretreatment, isoproterenol (100 mg/kg) was injected subcutaneously to rats at an interval of 24 h for 2 days to induce myocardial infarction. Electrocardiographical abnormalities and biomarkers were measured in normal and experimental rats. Isoproterenol-induced myocardial infarcted rats showed significant (p<0.05) increase in the levels of cardiac markers. Pretreatment with morin regulated the abnormalities in electrocardiograph and biomarkers. The lipid peroxidation products were increased and indicated the increased lipid peroxidation in isoproterenol-induced myocardial infarcted rats. The rats pretreated with morin significantly reduced lipid peroxidation. The altered lipid metabolism was observed in isoproterenol-induced myocardial infarcted rats and in pretreatment with morin-regulated lipid metabolism. Histopathological study evidenced that the pretreatment with morin inhibited myocardial damage. The results of this study proved the protective effect of morin as pretreatment and are rational to understand the beneficial effects of morin on cardioprotection against myocardial injury. Based on the results, the cardioprotective ability of morin on human beings can be studied in the future.

  11. Early changes of type 2B fibers after denervation of rat EDL skeletal muscle.

    PubMed

    Germinario, Elena; Esposito, Alessandra; Megighian, Aram; Midrio, Menotti; Biral, Donatella; Betto, Romeo; Danieli-Betto, Daniela

    2002-05-01

    Skeletal muscle type 2B fibers normally receive a moderate level of motoneuron discharge. As a consequence, we hypothesize that type 2B fiber properties should be less sensitive to the absence of the nerve. Therefore, we have investigated the response of sarcoplasmic reticulum and myofibrillar proteins of type 2B fibers isolated from rat extensor digitorum longus muscle after denervation (2 and 7 days). Single fibers were identified by SDS-PAGE of myosin heavy chain isoforms. Electrophysiological and isometric contractile properties of the whole muscle were also analyzed. The pCa-tension relationship of type 2B single fibers was shifted to the left at 2 days and to right at 7 days after denervation, with significant differences in the Hill coefficients and pCa threshold values in 2- vs. 7-day-denervated fibers. The sarcoplasmic reticulum Ca2+ uptake capacity and rate significantly decreased after 2 days of denervation, whereas both increased at 7 days. Caffeine sensitivity of sarcoplasmic reticulum Ca2+ release was transitory and markedly increased in 2-day-denervated fibers. Our results indicate that type 2B fiber functional properties are highly sensitive to the interruption of nerve supply. Moreover, most of 2-day-denervated changes were reverted at 7 days. PMID:11960956

  12. Effect of fangchinoline on root resorption during rat orthodontic tooth movement

    PubMed Central

    Bao, Xingfu; Zhang, Yi; Machibya, Ferdinand; Zhang, Ying; Jiang, Huan; Yu, Dongsheng

    2012-01-01

    Objective To evaluate the short-term effect of fangchinoline, an antiinflammatory drug widely used in Asia, on root resorption that is associated with orthodontic tooth movement. Methods Twenty-four Wistar rats were randomly divided into 6 groups. Mesial forces of 0, 50, or 100 g were applied to the maxillary first molar of the rats in each group for 14 days by activating nickel-titanium closed-coil springs. One-half of the rats receiving each of these treatments also received injections of 200 µL fangchinoline every 2 days. Finally, movement of the maxillary first molars was measured using digitized radiographs. The molars were extracted and the surfaces of the root resorption craters were recorded using a scanning electron microscope. The distance the molars moved and resorptionarea ratio was measured, and results were analyzed using 2-way ANOVA tests. Results There were no statistical differences in the distances the first molars moved under 50 or 100 g force, regardless of treatment with fangchinoline. However, the resorption area ratios were significantly smaller in those rats that were treated with both tension and fangchinoline than in those rats treated by tension alone. Conclusions Fangchinoline reduced the resorption area ratio in rats and is therefore an important means of alleviating root resorption. PMID:23112944

  13. Skeletal response to corticosteroid deficiency and excess in growing male rats

    NASA Technical Reports Server (NTRS)

    Li, M.; Shen, Y.; Halloran, B. P.; Baumann, B. D.; Miller, K.; Wronski, T. J.

    1996-01-01

    The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not

  14. Differential regulation of hippocampal progenitor proliferation by opioid receptor antagonists in running and non-running spontaneously hypertensive rats.

    PubMed

    Persson, Anders I; Naylor, Andrew S; Jonsdottir, Ingibjörg H; Nyberg, Fred; Eriksson, Peter S; Thorlin, Thorleif

    2004-04-01

    Voluntary running in mice and forced treadmill running in rats have been shown to increase the amount of proliferating cells in the hippocampus. Little is known as yet about the mechanisms involved in these processes. It is well known that the endogenous opioid system is affected during running and other forms of physical exercise. In this study, we evaluated the involvement of the endogenous opioids in the regulation of hippocampal proliferation in non-running and voluntary running rats. Nine days of wheel running was compared with non-running in spontaneously hypertensive rats (SHR), a rat strain known to run voluntarily. On the last 2 days of the experimental period all rats received two daily injections of the opioid receptor antagonists naltrexone or naltrindole together with injections of bromodeoxyuridine to label dividing cells. Brain sections from the running rats showed approximately a five-fold increase in newly generated cells in the hippocampus, and this increase was partly reduced by naltrexone but not by naltrindole. By contrast, both naltrexone and naltrindole increased hippocampal proliferation in non-running rats. In non-running rats the administration of naltrexone decreased corticosterone levels and adrenal gland weights, whereas no significant effects on these parameters could be detected for naltrindole. However, adrenal gland weights were increased in naltrexone- but not in naltrindole-administered running rats. In addition, in voluntary running rats there was a three-fold increase in the hippocampal levels of Met-enkephalin-Arg-Phe compared with non-runners, indicating an increase in opioid activity in the hippocampus during running. These data suggest an involvement of endogenous opioids in the regulation of hippocampal proliferation in non-running rats, probably through hypothalamic-pituitary-adrenal axis modulation. During voluntary running in SHR naltrexone altered hippocampal proliferation via as yet unknown mechanisms. PMID:15078558

  15. A Blueberry-Enriched Diet Attenuates Nephropathy in a Rat Model of Hypertension via Reduction in Oxidative Stress

    PubMed Central

    Elks, Carrie M.; Reed, Scott D.; Mariappan, Nithya; Shukitt-Hale, Barbara; Joseph, James A.; Ingram, Donald K.; Francis, Joseph

    2011-01-01

    Objective and Background To assess renoprotective effects of a blueberry-enriched diet in a rat model of hypertension. Oxidative stress (OS) appears to be involved in the development of hypertension and related renal injury. Pharmacological antioxidants can attenuate hypertension and hypertension-induced renal injury; however, attention has shifted recently to the therapeutic potential of natural products as antioxidants. Blueberries (BB) have among the highest antioxidant capacities of fruits and vegetables. Methods and Results Male spontaneously hypertensive rats received a BB-enriched diet (2% w/w) or an isocaloric control diet for 6 or 12 weeks or 2 days. Compared to controls, rats fed BB-enriched diet for 6 or 12 weeks exhibited lower blood pressure, improved glomerular filtration rate, and decreased renovascular resistance. As measured by electron paramagnetic resonance spectroscopy, significant decreases in total reactive oxygen species (ROS), peroxynitrite, and superoxide production rates were observed in kidney tissues in rats on long-term dietary treatment, consistent with reduced pathology and improved function. Additionally, measures of antioxidant status improved; specifically, renal glutathione and catalase activities increased markedly. Contrasted to these observations indicating reduced OS in the BB group after long-term feeding, similar measurements made in rats fed the same diet for only 2 days yielded evidence of increased OS; specifically, significant increases in total ROS, peroxynitrite, and superoxide production rates in all tissues (kidney, brain, and liver) assayed in BB-fed rats. These results were evidence of “hormesis” during brief exposure, which dissipated with time as indicated by enhanced levels of catalase in heart and liver of BB group. Conclusion Long-term feeding of BB-enriched diet lowered blood pressure, preserved renal hemodynamics, and improved redox status in kidneys of hypertensive rats and concomitantly demonstrated

  16. Target cell toxicity of inhaled spermidine in rat lungs.

    PubMed Central

    Foster, J. R.; Smith, L. L.; Hext, P. M.; Brammer, A.; Soames, A. R.; Wyatt, I.

    1990-01-01

    Rats were exposed for a single 6-h period to varying concentrations of aerosols of the polyamine, spermidine trihydrochloride. They were subsequently killed at 6 h, 1, 2, 5, 9 and 14 days after the start of exposure. The lungs were examined for histopathological alterations at both light and electron microscopic level and assays of lung spermidine burdens performed. In rats killed at the 6-h termination period, lung spermidine levels had increased approximately 1.5-fold although concentrations in animals killed on days 1 and 2 showed only marginal increases. Concentrations peaked again on day 5 and henceforth decreased until control spermidine levels were again achieved on day 14. Exposure of rat lungs to spermidine resulted in a specific dose-dependent necrosis of Clara cells of the bronchiolar epithelium and alveolar Type II cells. At the lowest dose used (6 mg/m3) specific necrosis of the Clara cells was seen at the earliest time interval studied, i.e. 6 h, but these cells were rapidly lost and subsequently replaced without evidence of significant cell proliferation by the 2-day sacrifice period. At all higher dose levels additional necrosis of the alveolar Type II cells occurred which was not reversible but which progressed through alveolitis to a fully developed subchronic pneumonitis by 14 days. Images Fig. 4 p624-a Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:2206983

  17. Stimulation of lipid peroxidation by methyl mercury in rats

    SciTech Connect

    Yonaha, M.; Saito, M.; Sagai, M.

    1983-03-28

    As an index of lipid peroxidation, thiobarbituric acid (TBA)-reactive substances in the liver, kidney, and serum, and hydrocarbons (ethane and pentane) in the exhalation of rats injected subcutaneously with 10 mg/kg/day of methylmercuric chloride (MMC) were determined. Formation of TBA-reactive substances in the liver and kidney of rats was significantly increased 4 and 2 days after initial injection of MMC, respectively. The result for serum was similar to that for the kidney. The maximum ethane production in the exhaled gases was observed 4 days after initial injection of MMC, and thereafter decreased slowly. Pentane production was significantly increased 5 days after initial injection of MMC, and thereafter continued to increase. Glutathione peroxidase activity and amount of vitamin C in the liver were depleted 4 days after initial injection of MMC; vitamin E was not depleted. In the kidney, significant decreases of glutathione peroxidase activity and vitamin C content were also seen 4 days after initial injection of MMC, but vitamin E content was unaltered. Thus, a clear increase of lipid peroxidation as determined by measurement of TBA-reactive substances in tissues and of hydrocarbons in the exhaled gases of rats after MMC treatment was demonstrated, though there was a lag phase of several days before the increase of lipid peroxidation. It is suggested that the significant increase of lipid peroxide formation may be a result of depletion of defending factors against lipid peroxidation.

  18. Social deprivation enhances the vulnerability of male Wistar rats to stressor- and amphetamine-induced behavioral sensitization.

    PubMed

    Ahmed, S H; Stinus, L; Le Moal, M; Cador, M

    1995-01-01

    The aim of the present study was to assess the influence of experiential factors on the vulnerability of rats to develop amphetamine (AMPH)- and stressor-induced behavioral sensitization. Young male Wistar rats with previous social experience were isolated from their peers for 2 weeks. 1) The effect of this short-lasting social deprivation were: a) a reduced tendency to explore a fearful environment; b) a prolonged exploratory activity in response to a novel but little fearful environment; and c) a dose-dependent increase in the psychomotor stimulation induced by systemic AMPH injection. 2) After repeated AMPH injections (injection every other day for 10 days), isolated rats exhibited behavioral sensitization at lower doses (0.5 and 0.75 mg/kg) than those required for group-housed rats (1 mg/kg). 3) After being submitted to a repeated stressor (3, 7 or 14 footshock sessions, with 2 days between sessions), the isolated rats exhibited a greater increase in the behavioral responsivity to a subsequent AMPH challenge (1 mg/kg) than did the group-housed rats regardless of the number of stress sessions. In conclusion, these results suggest that experiential factors such as privation of contact with peers (social isolation) may make rats more vulnerable to the long-term repercussions of chronic environmental and pharmacological challenges. PMID:7724696

  19. Magnetic resonance imaging (MRI) and pathophysiology of the rat kidney in streptozotocin-induced diabetes.

    PubMed

    Lohr, J; Mazurchuk, R J; Acara, M A; Nickerson, P A; Fiel, R J

    1991-01-01

    Proton magnetic resonance imaging was performed on rats before induction of diabetes with streptozotocin (STZ) and at 2 and 12 days postinduction. Images revealed an increase in maximal longitudinal and axial dimensions of the kidneys at 2 days and a further increase at 12 days. Similarly, an increase in the size of the remaining kidney was seen in a rat which underwent uninephrectomy as a positive control. Two major differences were observed between the kidney undergoing compensatory hypertrophy and those developing diabetic nephropathy: (i) Expansion of the renal vasculature was seen only in images of the diabetic rat; (ii) A loss in conspicuity of the normal corticomedullary junction was seen in the T2-weighted images of the diabetic rat but not in the uninephrectomized rat. Histologic examination revealed that the medulla increased to a size greater than the cortex during diabetic nephropathy whereas the medullary volume was less than that of the cortex during compensatory hypertrophy. In vitro T1 relaxation times in cortex, outer medulla and inner medulla of kidneys from control rats were measured and compared with the same respective regions in diabetic rats. When these values were correlated with tissue water content, a linear increase in relaxation rate versus percent water content from cortex to inner medulla was found in the control kidneys, but this correlation was absent in diabetic nephropathy. These studies demonstrate that MRI is an effective noninvasive tool for studying the course of renal hypertrophy and hydration changes in the development of renal disease in STZ-induced diabetes in the rat.

  20. [The hemathological reactions in rats after partial screening from natural electromagnetic fields].

    PubMed

    Iamshanov, V A; Kovan'ko, E G; Koshelevskiĭ, V K; Iamshanov, Iu A; Ivanov, S D

    2005-01-01

    The influence of partial screening of EMF on the composition of white blood cells was studied in the experiments on rats. Two kinds of copper rings were used in these experiments: individual for each rat and common for the cage. It was shown that inside the ring the composition of blood cells was changed--in 3-5 hours the number of granulocytes increased and in 24 hours it restored to the initial level. The effect was more expressive in the experiments using individual rings. In control groups the experiment with plastic rings didn't reveal this effect. It was presumed that EMF prevented the decay of granulocytes. It leads to the increase of their guantity. It was revealed that there was a positive correlation between Ki-indexes of geomagnetic field (GMF) in 1-2 days before the experiments and the number of granulocytes in rats during 1995-2002. Ki-indexes reflect the degree of GMF disturbance. During magnetic storms the spreading of EMF in radio-frequency range changes. It was presumed that the effect of partial screening of EMF of rats and the activity of magnetic storms are similar in their influence on the composition of white blood cells of rats. PMID:16080624

  1. Effects of moderate-intensity light on vitamin A-deficient rat retinas

    SciTech Connect

    Carter-Dawson, L.; Kuwabara, T.; Bieri, J.G.

    1981-05-01

    The effects of moderate-intensity light (150 to 200 ft-cd) on retinal structure were compared between retinol-adequate and retinol-deficient rats after 1 to 6 days of light exposure during the 12 hr light phase of the cycle. Both damage to the outer segments and loss of photoreceptor cells were accelerated in retinol-adequate rats. Outer segments in retinas of retinol-adequate rats showed an abnormal staining pattern and disruption of disc structure in the distal portion about 2 days before those of retinol-deficient rats. After 4 days of exposure 24% of the photoreceptor cells had degenerated in the retinol-adequate retinas, but only 6% in the retinol-deficient retinas. By 6 days 65% and 41% of the photoreceptors had degenerated in the retinol-adequate and retinol-deficient retinas, respectively. Thus light exposure induced more rapid degeneration of photoreceptor cells in rats receiving adequate retinol than in those deficient in this vitamin.

  2. Sundarban Honey Confers Protection against Isoproterenol-Induced Myocardial Infarction in Wistar Rats

    PubMed Central

    Karim, Nurul; Hossain, Md. Sabir; Alam, Nadia

    2016-01-01

    The present study was designed to investigate the cardioprotective effects of Sundarban honey (SH) in rats with isoproterenol- (ISO-) induced myocardial infarction. Adult male Wistar Albino rats were pretreated with Sundarban honey (5 g/kg) daily for a period of 6 weeks. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at 24 h intervals for 2 days. ISO-induced myocardial damage was indicated by increased serum cardiac specific troponin I levels and cardiac marker enzyme activities including creatine kinase-MB, lactate dehydrogenase, aspartate transaminase, and alanine transaminase. Significant increases in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol levels were also observed, along with a reduction in the serum high-density lipoprotein-cholesterol level. In addition to these diagnostic markers, the levels of lipid peroxide products were significantly increased. The activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase were significantly decreased in the hearts after ISO-induced myocardial infarction. However, pretreatment of ischemic rats with Sundarban honey brought the biochemical parameters to near normalcy, indicating the protective effect of Sundarban honey against ISO-induced ischemia in rats. Histopathological findings of the heart tissues further confirmed the biochemical findings, indicating that Sundarban honey confers protection against ISO-induced oxidative stress in the myocardium. PMID:27294126

  3. Formation of fatty acid esterified vitamin D3 in rat skin by exposure to ultraviolet radiation

    SciTech Connect

    Takada, K.

    1983-04-01

    The formation of fatty acid esters of vitamin D3 was demonstrated in rat skin exposed to artificial ultraviolet rays by using multi-dimensional high-performance liquid chromatography, ultraviolet spectrophotometry, and gas-liquid chromatography-mass spectrometry. This result indicated that the fatty acid esters of 7-dehydrocholesterol in rat skin (at least 80% of 7-dehydrocholesterol in rat skin is esterified) is also isomerized into vitamin D3 ester in vivo. The initial percentage of the esterified form was 84.3% and this did not significantly change up to the time when about half of the skin total vitamin D3 disappeared (2 days). Consequently, it was speculated that the vitamin D3 ester was delivered into the blood circulation from skin without having been hydrolyzed. This was supported by the presence of vitamin D3 ester in rat plasma exposed to ultraviolet radiation. In addition, in connection with the study of the restriction of vitamin D3 synthesis, distribution of total vitamin D3 in rat skin exposed to ultraviolet irradiation in vivo was compared with that in isolated skin exposed to ultraviolet radiation. The dermal layer of the isolated skin contained about 4 times more total vitamin D3 than that of in vivo skin. This finding suggests not only that ultraviolet rays could not penetrate deeply into the in vivo skin, but that the restriction of cutaneous synthesis of vitamin D3 observed in vivo may arise from this reduced penetration of ultraviolet rays.

  4. Maternal behavior induced in male rats by bilateral lesions of the bed nucleus of the accessory olfactory tract.

    PubMed

    Izquierdo, M A; Collado, P; Segovia, S; Guillamón, A; del Cerro, M C

    1992-10-01

    In the present study, we investigate the effect of bilateral electrolytic lesions of the bed nucleus of the accessory olfactory tract (BAOT) in male Wistar rats that did not have care-pups experience, using a test of induced maternal behavior. Consistent with our previous findings in virgin female rats (10), there was a significantly shorter sensitization (3 days) and retrieval (2 days) latencies in the BAOT-lesioned group than in the sham-lesioned and intact-control male groups (12 days for both). Based on these findings, we propose that BAOT, a sexually dimorphic nucleus of the vomeronasal system, exerts an inhibitory modulation in the expression of parental behavior in male and female virgin rats. It may do so by maintaining an olfactory-based tonic inhibition of maternal behavior, thereby resulting in the adults' tonic avoidance of the pups until this inhibition is abolished by lesion, or reduced or overridden by appropriate hormonal and/or sensory influences.

  5. Preventive and therapeutic effects of low level laser irradiation on gentamicin vestibulotoxicity in rat utricle

    NASA Astrophysics Data System (ADS)

    Rhee, Chung-Ku; Oh, Yang Hee; Ahn, Jin-Chul; Jung, Min-Sang; Kim, Yeong-Sik; Suh, Myung-Whan

    2009-02-01

    Purpose: To investigate the effects of low level laser (LLL) irradiation for the prevention and treatment of aminoglycoside-induced vestibular ototoxicity. Materials and Methods: An organotypic culture of 2 to 4 days old rat utricular maculae hair cells was used. The cultured utricular hair cells were divided into 6 groups. Group C: the hair cells were cultured for 14 days. Group G: cultured hair cells were treated with 1 mM gentamicin (GM) for 48 hours. Group L: LLL irradiation with 670 nm diode laser 3 mW/cm2 for 60 min (10.8 J/cm2)/day for 14 days. Group LG: LLL irradiation 10.8 J/ cm2/day for 2 days followed by GM insult. Group GL: treated with GM and followed by LLL irradiation 10.8 J/ cm2/day for 12 days. LGL group: LLL irradiation 10.8 J/ cm2/day for 2 days, then GM insulted, followed by the LLLT 10.8 J/ cm2/day for 10 days. The hair cells in each group were examined and counted by confocal laser scanning electron microscope on 7th and 14th days after FM1-43 staining and observed by scanning electron microscope (SEM). Results: The number of vestibular hair cells of group G was significantly less than those in group C. Group L showed no difference compared to group C. Significantly higher numbers of cells were seen in Group LG and GL comparing to group G. The cells were more in LG than group GL. Group LGL showed the most vestibular hair cells compared to the G, LG, and GL groups. SEM showed damaged hair cells in group G while they were well preserved in groups C, L, LG, GL, and LGL. Conclusion: LLL irradiation before and after GM insult on utricular hair cells were most effective to prevent and treat GM ototoxicity. This study indicates that LLL irradiation may have clinical implications to treat various vestibular and cochlear inner ear diseases.

  6. What is Desert RATS?

    NASA Video Gallery

    The mission manager and test coordinators for the 2011 mission explain why Desert RATS was started 14 years ago, questions being studied in this year's activities, technologies being tested and the...

  7. Alcohol alters skeletal muscle heat shock protein gene expression in rats: these effects are moderated by sex, raised endogenous acetaldehyde, and starvation.

    PubMed

    Nakahara, Tatsuo; Hunter, Ross; Hirano, Makoto; Uchimura, Hideyuki; McArdle, Ann; Broome, Caroline S; Koll, Michael; Martin, Colin R; Preedy, Victor R

    2006-07-01

    Alcoholic myopathy is a common pathology characterized by wasting due to reduced protein synthesis, although the mechanisms involved remain unclear. Women are particularly sensitive and malnutrition exacerbates the myopathy. This study aimed to address (i) whether long-term alcohol feeding alters expression of heat shock proteins (HSPs) in male and female rats; (ii) the effect of immediate alcohol dosing with or without raised levels of endogenous acetaldehyde; and (iii) the effect of starvation. To address this, (i) male and female rats were fed alcohol in the long-term (6-7 weeks as 35% of energy in a liquid diet) and compared to controls fed the same diet with isoenergetic glucose; (ii) male rats given an immediate bolus (75 mmol ethanol per kilogram body weight intraperitoneally) 2.5 hours before sacrifice and compared to controls given a dose of saline (with or without pretreatment with cyanamide-an acetaldehyde dehydrogenase inhibitor which raises endogenous acetaldehyde); (iii) male rats starved for 1 or 2 days then immediately dosed with alcohol. Protein levels of HSP 27, HSP 60, and HSP 70 were measured in muscles of male rats fed alcohol and pair-fed control rats by SDS-PAGE and Western blotting in study I. Levels of HSP 27, HSP 60, HSP 70, and HSP 90 mRNA were analyzed in hind limb skeletal muscle by reverse transcription-polymerase chain reaction with an endogenous internal standard, glyceraldehyde-3-phosphate-dehydrogenase. (i) Long-term alcohol dosage reduced HSP 27 in male rats but not in females, whereas HSP 90 mRNA increased in long-term alcohol-fed female rats but not in male rats. These changes were reflected by a similar trend in HSP protein content, although statistical significance was not achieved. (ii) There was no effect on any of the HSP mRNAs in rats dosed immediately with alcohol or in combination with cyanamide. (iii) Starvation per se for 2 days was associated with an increase in HSP 27 mRNA. Alcohol administration after 2 days

  8. Low-level blast raises intracranial pressure and impairs cognitive function in rats: prophylaxis with processed cereal feed.

    PubMed

    Säljö, Annette; Bolouri, Hayde; Mayorga, Maria; Svensson, Berndt; Hamberger, Anders

    2010-02-01

    There is increasing evidence that even low levels of blast cause brain injury, but little is known about their thresholds and mechanisms. Exposure of rats to 10-60 kPa blasts elevate intracranial pressure (ICP) in a dose-dependent manner and impair cognitive function. We have evaluated a prophylactic measure against these brain injuries in a rat animal model, consisting of feeding them processed cereal. This type of feed is known to ameliorate disturbances in secretion of body fluids and to have anti-inflammatory effects. In humans, intake of processed cereals is effective against intestinal diarrhea and also reduces the symptoms of Ménière's disease. Rats were given either standard laboratory feed or processed cereal feed for 2 weeks before exposure to blast in a shock tube. The ICP was monitored at different time points up to 1 week after exposure to a 60-kPa blast, and for up to 24 h after exposure to a 30-kPa blast. Maximal ICP elevation was reached at 10 h in both groups. In the group of rats on standard feed exposed to 60 kPa, an ICP increase of 145% was noted at 10 h, and the corresponding increase in the rats fed processed cereal feed was only 50%. In rats exposed to a 30-kPa blast, those fed standard feed and processed cereal feed demonstrated increases of ICP of 80% and 40%, respectively. Cognitive function as measured by the Morris water maze was assessed in other groups of rats at 2 days after exposure to 10- or 30-kPa blasts. Their performance was significantly impaired at both exposure levels in rats on standard feed, but no functional impairment was seen in rats fed processed cereal feed.

  9. Serotonergic and noradrenergic lesions suppress the enhancing effect of maternal exercise during pregnancy on learning and memory in rat pups.

    PubMed

    Akhavan, M M; Emami-Abarghoie, M; Safari, M; Sadighi-Moghaddam, B; Vafaei, A A; Bandegi, A R; Rashidy-Pour, A

    2008-02-19

    The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase of the pups' learning. Maternal forced swimming by pregnant rats increased both acquisition and retention phases of the pups' learning. Also we found that the rat pups whose mother was submitted to forced-swimming during pregnancy had significantly higher brain, liver, heart and kidney weights compared with their sedentary counterparts. On the other hand we estimated the cell number of different regions of the hippocampus in the rat pups. We found that both exercise models during pregnancy increased the cell number in cornus ammonis subregion 1 (CA1) and dentate gyrus of the hippocampus in rat pups. To determine the role that noradrenergic and serotonergic neurotransmission and N-methyl-D-aspartate (NMDA) receptors hold in mediation of the maternal exercise in offspring, we used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), p-chloroamphetamine (PCA) and MK-801 to eliminate or block the above systems, respectively. Blocking the NMDA receptors, significantly abolished learning and memory in rat pups from all three experimental groups. Elimination of noradrenergic or serotonergic input did not significantly attenuate the learning and memory in rat pups whose mothers were sedentary, while it significantly reversed the positive effects of maternal exercise during pregnancy on rat pups' learning and memory. The presented results suggest that noradrenergic and serotonergic systems in offspring brain seem to have a crucial specific role in mediating the effects of maternal physical activity during pregnancy on rat pups' cognitive function in both models of voluntary and forced exercise.

  10. Evidence that FOXO3a is involved in oocyte apoptosis in the neonatal rat ovary.

    PubMed

    Sui, Xu-Xia; Luo, Li-Li; Xu, Jin-Jie; Fu, Yu-Cai

    2010-08-01

    Previous studies have proposed that the forkhead transcription factor FOXO3a is involved in cell cycle arrest and apoptosis and that it may also repress follicular development by inducing cell cycle arrest in ovaries. We have recently demonstrated that FOXO3a induces oocyte apoptosis of neonatal rat ovaries under in vitro conditions. In the present study, we evaluated the role of FOXO3a in oocyte apoptosis under in vivo conditions. Ovaries from rats were obtained from newborns on postnatal day (PD) 1, 2, 3, and 4. TUNEL assay results showed that oocyte apoptosis occurred mainly on PD 1 and 2. Immunohistochemical staining of FOXO3a, Bim, Fas ligand (FasL), p27KIP1, caspase-8, and caspase-3 showed that they were all expressed mainly in naked oocytes on PD 1 and 2. The percentage of positive FOXO3a staining of oocytes reached peak levels in the ovaries of 2-day-old rats, which was consistent with the rate of the apoptotic profiles determined by TUNEL. The percentage between TUNEL-positive and FOXO3a-positive oocytes in the nucleus showed no statistical differences within the 4-day-old rat ovaries. Furthermore, the positive oocyte percentage of the target factors of FOXO3a (Bim, p27KIP1, and FasL) and pro-apoptotic proteins (caspase-3 and caspase-8) also reached peak levels in the ovaries of 2-day-old rats, which was similar to the rate of FOXO3a-positive oocytes. These results suggest that FOXO3a in the oocyte nucleus is involved in oocyte apoptosis; that is, FOXO3a-positive oocytes may be the apoptotic cells. To verify this, rat oocytes were subjected to TUNEL and immunofluorescent double-labeling assays. We found that TUNEL-positive cells were also FOXO3a-, Bim-, or FasL-positive. To identify the downstream target of FOXO3a, double immunofluorescent staining with antibodies to Bim and FasL was performed. We found that FOXO3a-positive cells were also Bim- and FasL-positive. We conclude that the overexpression of FOXO3a in the oocyte nucleus of neonatal rat ovaries

  11. Diethylstilbestrol decreased adrenal cholesterol and corticosterone in rats.

    PubMed

    Haeno, Satoko; Maeda, Naoyuki; Yagi, Takeshi; Tahata, Sachi; Sato, Michiko; Sakaguchi, Kanako; Miyasho, Taku; Ueda, Hiromi; Yokota, Hiroshi

    2014-05-01

    The synthetic oestrogen diethylstilbestrol (DES), which is known to bind oestrogen receptors (ERs), has been reported to have adverse effects on endocrine homeostasis; however, the molecular mechanisms underlying these effects are poorly understood. In this study, we treated rats with DES and found high levels of this compound in the liver, adrenal glands and pituitary gland, as compared with other tissues. We have also detected early adverse effects of DES in the adrenal glands. The adrenal glands of rats treated with DES (340 μg/kg body weight every 2 days) for 2 weeks showed increased weight and size and a decreased fat droplet size. Following 1 week of treatment with DES, the blood and adrenal corticosterone levels were substantially decreased without any histological alterations. The levels of the precursors for corticosteroid biosynthesis in the adrenal glands were also decreased, as determined using mass spectroscopy. Cholesterol, the principal material of corticosteroid biosynthesis, decreased substantially in the adrenal glands after only 1 week of treatment with DES. In conclusion, cholesterol insufficiency results in a reduction in adrenal corticosterone biosynthesis, which may lead to endocrine dysfunction, such as reproductive toxicity.

  12. Electrical amygdala kindling in alcohol-withdrawal kindled rats.

    PubMed

    Ulrichsen, J; Woldbye, D P; Madsen, T M; Clemmesen, L; Haugbøl, S; Olsen, C H; Laursen, H; Bolwig, T G; Hemmingsen, R

    1998-01-01

    Repeated alcohol withdrawal has been shown to kindle seizure activity. The purpose of the present investigation was to study electrical amygdala kindling in rats previously exposed to alcohol-withdrawal kindling. In three independent experiments, male Wistar rats were subjected to multiple episodes each consisting of 2 days of severe alcohol intoxication and 5 days of alcohol withdrawal. In the first experiment, the alcohol-withdrawal kindled animals were divided into two groups depending on whether spontaneous alcohol-withdrawal seizures were observed in episodes 10-13. In the second and third experiments, the alcohol-withdrawal kindled animals were compared to a group in which alcohol-withdrawal kindling was prevented by diazepam treatment during the withdrawal reactions in order to discriminate between the effect of withdrawal and intoxication. Electrical kindling was initiated 28-35 days after the last alcohol dose by exposing the animals to daily electrical stimulations of the right amygdala. The results showed that amygdala kindling was facilitated in alcohol-withdrawal kindled animals which showed spontaneous withdrawal seizure activity, compared with animals exposed to multiple episodes of alcohol withdrawal which did not develop withdrawal seizures or with animals exposed to a single episode of alcohol intoxication. When compared to the control group, the alcohol-withdrawal kindled group with seizures also kindled at a faster rate, but the difference did not reach statistical significance and therefore the results must be regarded as preliminary at present.

  13. Effect of antioxidant treatment in global ischemia and ischemic postconditioning in the rat hippocampus.

    PubMed

    Domoráková, Iveta; Mechírová, Eva; Danková, Marianna; Danielisová, Viera; Burda, Jozef

    2009-09-01

    Ischemic postconditioning is a very effective way how to prevent delayed neuronal death. Effect of Ginkgo biloba extract (EGb 761; 40 mg/kg) posttreatment was studied on the rat model of transient forebrain ischemia and ischemia/postconditioning. Global ischemia was produced by four-vessel occlusion in Wistar male rats. Two experimental protocols were used: (a) 10 min of ischemia/7 days of reperfusion with or without EGb 761 treatment or (b) 10 min of ischemia/2 days of reperfusion/5 min of ischemia (postconditioning), following 5 days of reperfusion. EGb 761 was applied as follows: 30 min before 10 min of ischemia then 5 h, 1 and 2 days after 10 min of ischemia. Fluoro Jade B, marker for neuronal degeneration, was used for quantitative analysis of the most vulnerable hippocampal CA1 neurons. Cognitive and memory functions were tested by Morris water maze, as well. Administration of EGb 761 30 min before 10 min of ischemia or 5 h after ischemia has rather no protective effect on neuronal survival in CA1 region. Ten minutes of ischemia following ischemic postconditioning after 2 days of reperfusion trigger a significant neuroprotection of CA1 neurons, but it is abolished by EGb 761 posttreatment. Ischemia/postconditioning group showed a significant improvement of learning and memory on the seventh day of reperfusion. Protection of the most vulnerable CA1 neurons after ischemia/postconditioning is abolished by exogenous antioxidant treatment used in different time intervals after initial ischemia. Moreover, combination of EGb 761 administration with repeated stress (5 min ischemia used as postconditioning) causes cumulative injury of CA1 neurons.

  14. Extremely low-frequency magnetic field induces manganese accumulation in brain, kidney and liver of rats.

    PubMed

    Çelik, Mustafa Salih; Güven, Kemal; Akpolat, Veysi; Akdağ, Mehmet Zulkuf; Nazıroğlu, Mustafa; Gül-Güven, Reyhan; Çelik, M Yusuf; Erdoğan, Sait

    2015-06-01

    The aim of the present study was to determine the effects of extremely low-frequency magnetic field (ELF-MF) on accumulation of manganese (Mn) in the kidney, liver and brain of rats. A total of 40 rats were randomly divided into eight groups. Four control groups received 0, 3.75, 15 and 60 mg Mn per kg body weight orally every 2 days for 45 days, respectively. The remaining four groups received same concentrations of Mn and were also exposed to ELF-MF (1.5 mT; 50 Hz) for 4 h for 5 days a week during 45 days. Following the last exposure, kidney, liver and brain were taken from all rats and they were analyzed for Mn accumulation levels using an inductively coupled plasma-optical emission spectrometer. In result of the current study, we observed that Mn levels in brain, kidney and liver were higher in Mn groups than in control groups. Mn levels in brain, kidney and liver were also higher in Mn plus ELF-MF groups than in Mn groups. In conclusion, result of the current study showed that the ELF-MF induced manganese accumulation in kidney, liver and brain of rats.

  15. Neurochemical and neuroanatomic effects of 3,4-methylenedioxymethamphetamine (MDMA) in rats

    SciTech Connect

    Virus, R.; Commins, D.; Vosmer, G.; Woolverton, W.; Schuster, C.; Seiden, L.

    1986-03-05

    Rats injected s.c. twice daily for 4 consecutive days with 10,20, or 40 mg/kg MDMA or saline and sacrificed 2 weeks after the last injection showed dose-dependent reductions in serotonin (5-HT) concentrations in hypothalamus, hippocampus (HIP), striatum (STR), somatosensory cortex (SC) and other cortical areas (CTX). 5-HT depletion was maximal in HIP (11.5 +/- 1.7%) and SC (15.3 +/- 3.2%, p<0.001 in both cases) at the 40 mg/kg MDMA dose. Forty mg/kg MDMA also reduced the amounts of dopamine (DA) in STR (78.2 +/- 6.4%, p<0.001) and of norepinephrine (NE) in HIP (74.5 +/- 6.4%, P<0.025) and CTX (77.9 +/- 6.1%, p<0.05). In addition, 20 mg/kg MDMA markedly reduced the number of (/sup 3/H)5-HT uptake sites (V/sub max/ 35.2% of control) without affecting the affinity (K/sub m/) in HIP. Fink-Heimer staining showed that rats injected s.c. twice daily for 2 days with 80 mg/kg MDMA had greater degeneration of nerve terminals in STR (p<0.005) and pyramidal cells in Layer III of SC (p<0.01) than did control rats. These results clearly suggest that repeated exposure to MDMA selectively damages serotonergic neurons in the central nervous system of rats.

  16. Impaired up-regulation of type II corticosteroid receptors in hippocampus of aged rats.

    PubMed

    Eldridge, J C; Fleenor, D G; Kerr, D S; Landfield, P W

    1989-01-30

    Several recent investigations have reported a decline of rat hippocampal corticosteroid-binding receptors (CSRs) with aging. This decline has been proposed to be an initial cause (through disinhibition) of the elevated adrenal steroid secretion that apparently occurs with aging; however, it could instead be an effect of corticoid elevation (through down-regulation). In order to assess the effects of age on CSR biosynthetic capacity in the absence of down-regulatory influences of endogenous corticoids, as well as to study aging changes in CSR plasticity, we examined the up-regulation of hippocampal CSR that follows adrenalectomy (ADX). The rat hippocampus contains at least two types of CSR binding and differential analysis of types I and II CSR was accomplished by selective displacement of [3H]corticosterone with RU-28362, a specific type II agonist. In young (3 months old) Fischer-344 rat hippocampus, up-regulation of type II binding above 2-day ADX baseline was present by 3-7 days and increased still further by 8-10 days post-ADX; type I CSR density did not change significantly between 1 and 10 days post-ADX. However, in aged (24-26 months old) rats, type II CSR up-regulation did not occur over the 10 day post-ADX period. Thus, the age-related impairment of type II up-regulation may reflect an intrinsic deficit in CSR biosynthesis or lability that is independent of the acute endogenous adrenal steroid environment.

  17. Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats.

    PubMed

    Ni, Wei; Okauchi, Masanobu; Hatakeyama, Tetsuhiro; Gu, Yuxiang; Keep, Richard F; Xi, Guohua; Hua, Ya

    2015-10-01

    Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18months old) had either an intracaudate injection of 100μl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should be at more than 10mg/kg for a therapeutic duration more than 2days with a therapeutic time window of 12h to reduce ICH-induced white matter loss at 2months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage.

  18. Amnesia induced by morphine in spatial memory retrieval inhibited in morphine-sensitized rats.

    PubMed

    Farahmandfar, Maryam; Naghdi, Nasser; Karimian, Seyed Morteza; Kadivar, Mehdi; Zarrindast, Mohammad-Reza

    2012-05-15

    The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect.

  19. Estrogen replacement in ovariectomized rats affects strategy selection in the Morris water maze.

    PubMed

    Daniel, Jill M; Lee, Christopher D

    2004-09-01

    While estrogen enhances performance on some tasks of learning and memory, it has impairing or no effects on others. It has been proposed that estrogen differentially affects performance on various tasks of learning and memory by influencing the strategy used to solve a task. The goal of the present study was to determine if estrogen would influence strategy selection in the Morris water maze. Long-Evans rats were ovariectomized and implanted with Silastic capsules containing 25% estradiol diluted in cholesterol or 100% cholesterol. Rats were trained in a water maze task in which multiple strategies were available for use to locate a hidden escape platform that was moved to a new location for each set of four daily trials. During 10 days of acquisition trials, a visible floating landmark was always located in a static position relative to the hidden escape platform. Additionally, fixed extramaze cues visible to the animals surrounded the maze. Following acquisition, 2 days of probe trials were conducted in which the static landmark was removed. Estrogen replacement in ovariectomized rats resulted in impaired performance across 10 days of acquisition. Additionally, while removal of the visible landmark during the probe trials had no effect on the performance of the females receiving estrogen, it significantly disrupted performance of females receiving cholesterol treatment. These results indicate that estrogen replacement in ovariectomized rats biases an animal against using a landmark or static cue to aid in the location of a hidden escape platform in the water maze.

  20. Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

    PubMed Central

    Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further. PMID:25861636

  1. Natural antioxidant betanin protects rats from paraquat-induced acute lung injury interstitial pneumonia.

    PubMed

    Han, Junyan; Ma, Deshun; Zhang, Miao; Yang, Xuelian; Tan, Dehong

    2015-01-01

    The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-α levels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

  2. Inflammatory Biomarkers Associated with Lethal Rift Valley Fever Encephalitis in the Lewis Rat Model

    PubMed Central

    Caroline, Amy L.; Kujawa, Michael R.; Oury, Tim D.; Reed, Douglas S.; Hartman, Amy L.

    2016-01-01

    Rift Valley fever (RVF) is an emerging viral disease that causes significant human and veterinary illness in Africa and the Arabian Peninsula. Encephalitis is one of the severe complications arising from RVF virus (RVFV) infection of people, and the pathogenesis of this form of RVF is completely unknown. We use a novel reproducible encephalitic disease model in rats to identify biomarkers of lethal infection. Lewis rats were infected with RVFV strain ZH501 by aerosol exposure, then sacrificed daily to determine the course of infection and evaluation of clinical, virological, and immunological parameters. Weight loss, fever, and clinical signs occurred during the last 1–2 days prior to death. Prior to onset of clinical indications of disease, rats displayed marked granulocytosis and thrombocytopenia. In addition, high levels of inflammatory chemokines (MCP-1, MCS-F, Gro/KC, RANTES, and IL-1β) were detected first in serum (3–5 dpi) followed by brain (5–7 dpi). The results of this study are consistent with clinical data from human RVF patients and validate Lewis rats as an appropriate small animal model for RVF encephalitis. The biomarkers we identified here will be useful in future studies evaluating the efficacy of novel vaccines and therapeutics. PMID:26779164

  3. Evidence for time-of-day dependent effect of neurotoxic dorsomedial hypothalamic lesions on food anticipatory circadian rhythms in rats.

    PubMed

    Landry, Glenn J; Kent, Brianne A; Patton, Danica F; Jaholkowski, Mark; Marchant, Elliott G; Mistlberger, Ralph E

    2011-01-01

    The dorsomedial hypothalamus (DMH) is a site of circadian clock gene and immediate early gene expression inducible by daytime restricted feeding schedules that entrain food anticipatory circadian rhythms in rats and mice. The role of the DMH in the expression of anticipatory rhythms has been evaluated using different lesion methods. Partial lesions created with the neurotoxin ibotenic acid (IBO) have been reported to attenuate food anticipatory rhythms, while complete lesions made with radiofrequency current leave anticipatory rhythms largely intact. We tested a hypothesis that the DMH and fibers of passage spared by IBO lesions play a time-of-day dependent role in the expression of food anticipatory rhythms. Rats received intra-DMH microinjections of IBO and activity and body temperature (T(b)) rhythms were recorded by telemetry during ad-lib food access, total food deprivation and scheduled feeding, with food provided for 4-h/day for 20 days in the middle of the light period and then for 20 days late in the dark period. During ad-lib food access, rats with DMH lesions exhibited a lower amplitude and mean level of light-dark entrained activity and T(b) rhythms. During the daytime feeding schedule, all rats exhibited food anticipatory activity and T(b) rhythms that persisted during 2 days without food in constant dark. In some rats with partial or total DMH ablation, the magnitude of the anticipatory rhythm was weak relative to most intact rats. When mealtime was shifted to the late night, the magnitude of the food anticipatory activity rhythms in these cases was restored to levels characteristic of intact rats. These results confirm that rats can anticipate scheduled daytime or nighttime meals without the DMH. Improved anticipation at night suggests a modulatory role for the DMH in the expression of food anticipatory activity rhythms during the daily light period, when nocturnal rodents normally sleep.

  4. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    PubMed Central

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  5. Protective effect of morin on cardiac mitochondrial function during isoproterenol-induced myocardial infarction in male Wistar rats.

    PubMed

    Al Numair, Khalid S; Chandramohan, Govindasamy; Alsaif, Mohammed A; Baskar, Arul Albert

    2012-01-01

    Altered mitochondrial function and free radical-mediated tissue damage have been suggested as an important pathological event in isoproterenol (ISO)-induced cardiotoxicity. This study was undertaken to know the preventive effect of morin on mitochondrial damage in ISO-induced cardiotoxicity in male Wistar rats. Myocardial infarction (MI) in rats was induced by ISO (85 mg/kg) at an interval of 24 hours for 2 days. Morin was given to rats as pre-treatment for 30 days orally using an intragastric tube. ISO-treated rats showed a significant elevation of mitochondrial thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (HP) level and pre-treatment with morin significantly prevented the increase of TBARS and HP level to near normality. The level of enzymic and non-enzymic antioxidants was decreased significantly in ISO-treated rats and pre-treatment with morin significantly increased the levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, and reduced glutathione to normality. The activities of mitochondrial enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase were decreased significantly in ISO-treated myocardial ischemic rats and upon pre-treatment with morin restored these enzymes activity to normality. In addition, the decreased activities of cytochrome-C oxidase and NADH-dehydrogenases were observed in ISO-treated rats and pre-treatment with morin prevented the activities of cytochrome-C oxidase and NADH-dehydrogenase to normality. Pre-treatment with morin favorably restored the biochemical and functional parameters to near normal indicating morin to be a significant protective effect on cardiac mitochondrial function against ISO-induced MI in rats.

  6. Adrenarche in the rat.

    PubMed

    Pignatelli, Duarte; Xiao, Fang; Gouveia, Alexandra M; Ferreira, Jorge G; Vinson, Gavin P

    2006-10-01

    Normal pubertal development in humans involves two distinct processes: maturation of adrenal androgen secretion (adrenarche) and activation of the hypothalamic-pituitary-gonadal axis (gonadarche). One factor thought to contribute to the adrenarche in man is increased adrenal 17-hydroxylase (CYP17) activity. In the rat, there is evidence for adrenal involvement in the initiation of puberty, but the adrenal glands of this species are generally thought to express CYP17 only very poorly at best. To further examine the nature of postnatal adrenal development in rat, plasma samples and adrenal tissues were taken from animals aged 2-90 days, circulating adrenal steroids assayed, and adrenal zones assessed quantitatively. A relative increase in zona reticularis, and peaks of circulating cortisol, androstenedione, and 17-OH-progesterone were observed around postnatal days 16-20, clearly before the development of the gonads, which begins at 30-35 days. Quantitative reverse transcriptase PCR confirmed a peak in mRNA coding for CYP17 in adrenal tissue from rats of similar age. The results suggest that the rat adrenal has the capacity to secrete steroids arising from 17-hydroxylation, and that this may contribute to a process similar to human adrenarche.

  7. Rat on Mars

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This image taken on Mars by the panoramic camera on the Mars Exploration Rover Opportunity shows the rover's rock abrasion tool, also known as 'rat' (circular device in center), located on its instrument deployment device, or 'arm.' The image was acquired on the ninth martian day or sol of the rover's mission.

  8. Behavior modulation of rats to a robotic rat in multi-rat interaction.

    PubMed

    Shi, Qing; Ishii, Hiroyuki; Tanaka, Katsuaki; Sugahara, Yusuke; Takanishi, Atsuo; Okabayashi, Satoshi; Huang, Qiang; Fukuda, Toshio

    2015-10-01

    In this paper, we study the behavioral response of rats to a robotic rat during multi-rat interaction. Experiments are conducted in an open-field where a robotic rat called WR-5 is put together with three laboratory rats. WR-5 is following one rat (target), while avoiding the other two rats (outside observers) during interaction. The behavioral characteristics of each target rat is evaluated by scoring its locomotor activity and frequencies of performing rearing, body grooming and mounting actions. Additionally, the frequency of being mounted by other rats is also measured. Experimental results show that the target becomes more active after interaction. The rat species, with more active behavioral characteristics, is more susceptible to being adjusted by the robot. The increased time spent by the outside observers in the vicinity of the robot indicates that a biomimetic robot has the promise for modulating rat behavior even without direct interaction. Thus, this study provide a novel approach to shaping the sociality of animals living in groups. PMID:26414400

  9. Behavior modulation of rats to a robotic rat in multi-rat interaction.

    PubMed

    Shi, Qing; Ishii, Hiroyuki; Tanaka, Katsuaki; Sugahara, Yusuke; Takanishi, Atsuo; Okabayashi, Satoshi; Huang, Qiang; Fukuda, Toshio

    2015-10-01

    In this paper, we study the behavioral response of rats to a robotic rat during multi-rat interaction. Experiments are conducted in an open-field where a robotic rat called WR-5 is put together with three laboratory rats. WR-5 is following one rat (target), while avoiding the other two rats (outside observers) during interaction. The behavioral characteristics of each target rat is evaluated by scoring its locomotor activity and frequencies of performing rearing, body grooming and mounting actions. Additionally, the frequency of being mounted by other rats is also measured. Experimental results show that the target becomes more active after interaction. The rat species, with more active behavioral characteristics, is more susceptible to being adjusted by the robot. The increased time spent by the outside observers in the vicinity of the robot indicates that a biomimetic robot has the promise for modulating rat behavior even without direct interaction. Thus, this study provide a novel approach to shaping the sociality of animals living in groups.

  10. Evaluation of acute effects of melatonin on ethanol drinking in ethanol naïve rats

    PubMed Central

    Rather, Zahoor Ahmad; Chowta, Mukta N.; Bolumbu, Ganaraja; Rakesh, K. B.

    2015-01-01

    Objective: The objective was to evaluate the acute effect of melatonin on ethanol drinking in ethanol naïve rats and to determine the specificity of the effect of melatonin on ethanol intake as compared to an intake of plain tap water or sugar water. Materials and Methods: A total of three experiments (2 weeks duration each) using different drinking solutions (ethanol, plain tap water, sugar water) was conducted in individually housed male wistar rats of 5 weeks age. Each animal had access to bottles containing drinking solutions for 2 h a day. In each experiment, on day 1, day 2, day 4, day 5, day 8, day 9, day 11, day 12 rats received drinking solutions. Each individual rat received single doses of saline, melatonin (50 mg and 100 mg/kg), and naltrexone on day 2, 5, 9, and 12, 1-h before receiving drinking solution. The order of drug administration is permuted such a way that each animal received the drugs in a different order in different experiments. Results: Melatonin has significantly decreased ethanol consumption by the rats and effect is dose-dependent. Naltrexone also has caused a significant reduction in the ethanol consumption. The maximum reduction in ethanol consumption was seen with melatonin 100 mg/kg dose compared to melatonin 50 mg/kg and naltrexone. There was no statistically significant effect of melatonin on plain water and sugar solution intake. Conclusions: Melatonin decreases ethanol consumption in ethanol naïve rats. The effect of melatonin is similar to naltrexone affecting selectively ethanol consumption, but not plain water and sugar water consumption. PMID:26288469

  11. Flavor preferences conditioned by post-oral infusion of monosodium glutamate in rats.

    PubMed

    Ackroff, Karen; Sclafani, Anthony

    2011-09-01

    Monosodium glutamate (MSG), the prototypical umami source, can enhance preference for associated flavors in humans and rodents. Although MSG flavor preference has been attributed to its taste, vagally-mediated post-oral detection has also been demonstrated. Recent studies showed that water-restricted rats acquired a preference for a flavor paired with intragastric (IG) infusion of 60 mM MSG in rats. The present study extends this work by comparing MSG-based flavor conditioning in water- and food-restricted rats and testing the persistence of flavor preferences. Rats with IG catheters drank flavored solutions paired with volume-matched infusions of 60 mM MSG or water in daily 30-min sessions. Two training/test cycles were conducted, each with eight one-bottle training sessions followed by two two-bottle preference tests without infusions. Food- and water-restricted groups displayed similar preferences for the MSG-paired flavor. When non-reinforced testing was continued after the second cycle, the food-restricted group sustained its preference across three 2-day tests, but water-restricted rats lost their preference. Other food-restricted rats learned to prefer a flavor paired with intraduodenal infusion, indicating that gastric stimulation by MSG is not required. A third experiment showed that adding 2 mM of the nucleotide inosine monophosphate to the IG infusion of MSG did not significantly enhance flavor conditioning. Because MSG-based flavor preferences can be obtained with infusions that bypass the stomach, the site for detecting MSG reinforcement may be intestinal. PMID:21605576

  12. Evaluation of an experimental rat model for comparative studies of bleaching agents.

    PubMed

    Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Louzada; Rahal, Vanessa; Ervolino, Edilson; Jacinto, Rogério de Castilho; Gomes Filho, João Eduardo; Briso, André Luiz Fraga

    2016-04-01

    Dental materials in general are tested in different animal models prior to the clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents, by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats' vital teeth. Material and Methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals were untreated (control). The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated through histomorphometric analysis with inflammatory cell count in the coronal and radicular thirds of the pulp. Fibroblasts were also counted. Scores were attributed to odontoblastic layer and vascular changes. Tertiary dentin area and pulp chamber central area were measured histomorphometrically. Data were compared by analysis of variance and Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the coronal pulp occlusal third up to the 15-min application groups of each bleaching gel. In the groups exposed to each concentration for 30 and 45 min, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, reduction on the pulp chamber central area and enlargement of the tertiary dentin area were observed, without the detection of inflammation areas. Conclusion The rat model of extracoronal bleaching showed to be adequate for studies of bleaching protocols, as it was possible to observe alterations in the pulp tissues and tooth structure caused by different concentrations and application periods of bleaching agents. PMID:27119766

  13. Rat retinal transcriptome

    PubMed Central

    Kozhevnikova, Oyuna S.; Korbolina, Elena E.; Ershov, Nikita I.; Kolosova, Natalia G.

    2013-01-01

    Pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly, remains poorly understood due to the paucity of animal models that fully replicate the human disease. Recently, we showed that senescence-accelerated OXYS rats develop a retinopathy similar to human AMD. To identify alterations in response to normal aging and progression of AMD-like retinopathy, we compared gene expression profiles of retina from 3- and 18-mo-old OXYS and control Wistar rats by means of high-throughput RNA sequencing (RNA-Seq). We identified 160 and 146 age-regulated genes in Wistar and OXYS retinas, respectively. The majority of them are related to the immune system and extracellular matrix turnover. Only 24 age-regulated genes were common for the two strains, suggestive of different rates and mechanisms of aging. Over 600 genes showed significant differences in expression between the two strains. These genes are involved in disease-associated pathways such as immune response, inflammation, apoptosis, Ca2+ homeostasis and oxidative stress. The altered expression for selected genes was confirmed by qRT-PCR analysis. To our knowledge, this study represents the first analysis of retinal transcriptome from young and old rats with biologic replicates generated by RNA-Seq technology. We can conclude that the development of AMD-like retinopathy in OXYS rats is associated with an imbalance in immune and inflammatory responses. Aging alters the expression profile of numerous genes in the retina, and the genetic background of OXYS rats has a profound impact on the development of AMD-like retinopathy. PMID:23656783

  14. Glutathione S-transferase and gamma-glutamyl transpeptidase activities in cultured rat hepatocytes treated with tocotrienol and tocopherol.

    PubMed

    Ong, F B; Wan Ngah, W Z; Shamaan, N A; Md Top, A G; Marzuki, A; Khalid, A K

    1993-09-01

    1. The effect of tocotrienol and tocopherol on glutathione S-transferase (GST) and gamma-glutamyl transpeptidase (GGT) activities in cultured rat hepatocytes were investigated. 2. Tocotrienol and tocopherol significantly decreased GGT activities at 5 days in culture but tocotrienol also significantly decreased GGT activities at 1-2 days. 3. Tocotrienol and tocopherol treatment significantly decreased GST activities at 3 days compared to the control but tocotrienol also decreased GST activities at 1-3 days. 4. Tocotrienol showed a more pronounced effect at a dosage of greater than 50 microM tocotrienol at 1-3 days in culture compared to the control.

  15. Erythrocytosis in Spontaneously Hypertensive Rats

    PubMed Central

    Sen, Subha; Hoffman, George C.; Stowe, Nicholas T.; Smeby, Robert R.; Bumpus, F. Merlin

    1972-01-01

    During the study of an inbred strain of Wistar rats which spontaneously develop hypertension when they reach a weight of approximately 150 g, it was found that these animals also develop an erythrocytosis. A significant increase in red cell count was observed in spontaneously hypertensive (SH) rats (8-11 × 106 RBC/mm3) when compared with normotensive rats (6-7 × 106 RBC/mm3) of the same strain. This increase in red cell count paralleled the increase in body weight and the rise in blood pressure. Since the plasma volume, as measured with labeled albumin was normal, there was an absolute increase in red cells. The hematocrit and hemoglobin content of the blood measured in SH rats were only slightly greater than those found in normotensive rats. However, the mean cell volume (MCV) of the red cells in the SH rats was 45-47 μ3 as compared with 51-53 μ3 in normotensive rats. A fourfold increase in 24 hr 59Fe incorporation into the red cells was found in the SH rats when compared with normotensive controls. The bone marrow of the SH rats showed erythroid hyperplasia. When the SH rats were treated with α-methyldopa (Aldomet 200 mg/kg daily, i.p.) the red cell count fell in parallel with the drop in blood pressure. No change in red cell count or blood pressure was observed in normotensive rats treated in the same manner. The erythropoietin titer was high in SH rats, and was undetectable in normotensive rats. These observations suggest a direct relationship between the hypertension and the erythrocytosis mediated by erythropoietin; both are genetically controlled. PMID:5011107

  16. Analgesic Effect of Intra-Articular Injection of Temperature-Responsive Hydrogel Containing Bupivacaine on Osteoarthritic Pain in Rats

    PubMed Central

    Kim, Taemin; Seol, Dong Rim; Hahm, Suk-Chan; Ko, Cheolwoong; Kim, Eun-Hye; Chun, Keyoungjin; Kim, Junesun; Lim, Tae-Hong

    2015-01-01

    The present study examined the analgesic effects of slow-releasing bupivacaine from hydrogel on chronic arthritic pain in rats. Osteoarthritis (OA) was induced by monosodium iodoacetate (MIA) injection into the right knee joint. Hydrogel (HG: 20, 30, and 50 μL) and temperature-sensitive hydrogel containing bupivacaine (T-gel: 20, 30, and 50 μL) were injected intra-articularly 14 days after MIA injection. Behavioral tests were conducted. The rats showed a significant decrease in weight load and paw withdrawal threshold (PWT). Intra-articular 0.5% bupivacaine (10 and 20 μL) significantly reversed MIA-induced decreased PWT, with no effect on weight load. In normal rats, hydrogel did not produce significant changes in PWT but at 30 and 50 μL slightly decreased weight bearing; T-gel did not cause any changes in both the weight load and PWT. In OA rats, T-gel at 20 μL had a significant analgesic effect for 2 days, even though T-gel at 50 μL further reduced the weight load, demonstrating that intra-articular T-gel (20 μL) has long-lasting analgesic effects in OA rats. Thus, T-gel designed to deliver analgesics into the joint cavity could be an effective therapeutic tool in the clinical setting. PMID:26881207

  17. Glucose metabolic adaptations in the intrauterine growth-restricted adult female rat offspring.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Rogers, Lisa; Bassilian, Sara; Lee, W N Paul; Devaskar, Sherin U

    2006-06-01

    We studied glucose metabolic adaptations in the intrauterine growth-restricted (IUGR) rat offspring to decipher glucose homeostasis in metabolic programming. Glucose futile cycling (GFC), which is altered when there is imbalance between glucose production and utilization, was studied during a glucose tolerance test (GTT) in 2-day-old (n = 8), 2-mo-old (n = 22), and 15-mo-old (n = 22) female rat offspring. The IUGR rats exposed to either prenatal (CM/SP, n = 5 per age), postnatal (SM/CP, n = 6), or pre- and postnatal (SM/SP, n = 6) nutrient restriction were compared with age-matched controls (CM/CP, n = 5). At 2 days, IUGR pups (SP) were smaller and glucose intolerant and had increased hepatic glucose production and increased glucose disposal (P < 0.01) compared with controls (CP). At 2 mo, the GTT, glucose clearance, and GFC did not change. However, a decline in hepatic glucose-6-phosphatase (P < 0.05) and fructose-1,6-biphosphatase (P < 0.05) enzyme activities in the IUGR offspring was detected. At 15 mo, prenatal nutrient restriction (CM/SP) resulted in greater weight gain (P < 0.01) and hyperinsulinemia (P < 0.001) compared with postnatal nutrient restriction (SM/CP). A decline in GFC in the face of a normal GTT occurred in both the prenatal (CM/SP, P < 0.01) and postnatal calorie (SM/CP, P < 0.03) and growth-restricted offspring. The IUGR offspring with pre- and postnatal nutrient restriction (SM/SP) were smaller, hypoinsulinemic (P < 0.03), and hypoleptinemic (P < 0.03), with no change in GTT, hepatic glucose production, GFC, or glucose clearance. We conclude that there is pre- and postnatal programming that affects the postnatal compensatory adaptation of GFC and disposal initiated by changes in circulating insulin concentrations, thereby determining hepatic insulin sensitivity in a phenotype-specific manner. PMID:16449299

  18. Gravitational Biology: The Rat Model

    NASA Technical Reports Server (NTRS)

    1997-01-01

    In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

  19. URINARY CALCULI IN GERMFREE RATS

    PubMed Central

    Gustafsson, Bengt E.; Norman, Arne

    1962-01-01

    In a colony of germfree rats 50 per cent of the males had urinary calculi composed of calcium citrate and calcium oxalate. Genetically closely related conventional animals on the same sterilized diet did not present a single case of stone formation. The tendency to calculus formation disappeared when germfree animals were contaminated with the intestinal flora from conventional rats. The calculus formation can readily be explained by the high calcium, high citrate, and high pH of the urine. This pattern was changed to that of conventional rats when the germfree rats were infected with intestinal microorganisms. PMID:13903130

  20. Transient and reversible nephrotoxicity of sarin in rats.

    PubMed

    Bloch-Shilderman, Eugenia; Levy, Aharon

    2007-01-01

    Organophosphate (OP) poisoning, which inhibits cholinesterase activity, leads to severe cholinergic symptoms. Effective and quick management of these symptoms is considered critical to the clinical outcome. Acute renal damage following exposure to OP insecticides has been reported. Similar complications might occur following exposure to OP nerve agents, however, this subject has been studied only sporadically. In the present study, the effect of the nerve agent sarin on renal function was examined in rats. A single dose of sarin ( approximately 0.9 LD(50)) led to a significant reduction (of 45%) in renal function during the first 2 days post exposure, as exhibited by evaluation of the glomerular filtration rate, through measuring the clearance of ( 99m)Tc-DTPA. The urine volume was reduced by 50%, the urine specific gravity increased to 104% of the control value and massive hematuria and glucosuria were recorded 24-48 h post exposure. In addition, around 60% decrease in urine electrolytes was monitored during the first 2 days following exposure, with a recovery after 8 days. Post mortem gross inspection of the bladder, 24 h post exposure, revealed severe edema and hemorrhage. Treatment with the muscarinic antagonist atropine and the oxime TMB-4, at excessive doses administered 1 min post exposure, did not prevent most renal impairments. It has been concluded that sarin caused an acute renal dysfunction, possibly accompanied by bladder damage. These impairments were reversible, recovered spontaneously within 3-8 days, and were probably related to the state of shock and hypovolemia caused by the poisoning. However, if renal impairments are left unattended, they might contribute to the overall toxic manifestation and as a result aggravate the clinical state of intoxicated casualties.

  1. Laughing rats are optimistic.

    PubMed

    Rygula, Rafal; Pluta, Helena; Popik, Piotr

    2012-01-01

    Emotions can bias human decisions- for example depressed or anxious people tend to make pessimistic judgements while those in positive affective states are often more optimistic. Several studies have reported that affect contingent judgement biases can also be produced in animals. The animals, however, cannot self-report; therefore, the valence of their emotions, to date, could only be assumed. Here we present the results of an experiment where the affect-contingent judgement bias has been produced by objectively measured positive emotions. We trained rats in operant Skinner boxes to press one lever in response to one tone to receive a food reward and to press another lever in response to a different tone to avoid punishment by electric foot shock. After attaining a stable level of discrimination performance, the animals were subjected to either handling or playful, experimenter-administered manual stimulation - tickling. This procedure has been confirmed to induce a positive affective state in rats, and the 50-kHz ultrasonic vocalisations (rat laughter) emitted by animals in response to tickling have been postulated to index positive emotions akin to human joy. During the tickling and handling sessions, the numbers of emitted high-frequency 50-kHz calls were scored. Immediately after tickling or handling, the animals were tested for their responses to a tone of intermediate frequency, and the pattern of their responses to this ambiguous cue was taken as an indicator of the animals' optimism. Our findings indicate that tickling induced positive emotions which are directly indexed in rats by laughter, can make animals more optimistic. We demonstrate for the first time a link between the directly measured positive affective state and decision making under uncertainty in an animal model. We also introduce innovative tandem-approach for studying emotional-cognitive interplay in animals, which may be of great value for understanding the emotional-cognitive changes

  2. An experimental model for meningeal leukemia in rats (L5222). Effect of treatment with BCNU and cyclophosphamide.

    PubMed

    Fiebig, H H; Zeller, W H; Schmähl, D

    1976-11-15

    An experimental model of meningeal leukemia in rats is developed by intracerebral (IC) inoculation of leukemic cells from the transplantable acute leukemia L5222. The L5222 proliferates exponentially in the central nervous system (CNS) and the disease becomes systemic 2 days following IC inoculation. Chemotherapeutic studies with BCNU and cyclophosphamide yielded cures in a high percentage of cases when treatment began at an early stage of meningeal leukemia. When treatment was started at the advanced stage, only BCNU showed a large number of cures. However, cyclophosphamide resulted in a marked increase of life-span. The activity of cyclophosphamide against meningeal leukemia, which is in contrast to the results obtained by Skipper et. al. (1961) in the L1210 mouse leukemia, suggests that cyclophosphamide crosses in part the blood--brain barrier in a rat bearing meningeal leukemia. After subcutaneous inoculation, BCNU and cyclophosphamide showed the same rate of cures.

  3. Prospective cognition in rats

    PubMed Central

    Crystal, Jonathon D.

    2012-01-01

    Efforts to develop animal models of memory are critical for understanding the neural substrate of memory. Memory is essential for daily life and enables information to be stored and retrieved after seconds to years. The ability to remember episodes from the past is thought to be related to the ability to plan for the future. Here we focus on a particular aspect of prospective cognition, namely the ability to remember to take action when a future scenario occurs. This review focuses on a recently developed method to evaluate prospective memory in the rat. Available evidence suggests that rats remember to take action in the future, but little is known about the temporal specificity of such memories or about the flexibility and limitations of prospective memories. Recent studies that suggest that rats remember a specific past episode are reviewed to underscore potential approaches that may be used to explore the range and limits of prospective cognition. The review highlights some directions to explore, including the temporal specificity of prospective cognition, the range of flexibility or creativity within prospective cognition, and the constraints imposed by multiple motivational systems. PMID:23180886

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  7. Influence of enrichment on behavioral and neurogenic effects of antidepressants in Wistar rats submitted to repeated forced swim test.

    PubMed

    Possamai, Fernanda; dos Santos, Juliano; Walber, Thais; Marcon, Juliana C; dos Santos, Tiago Souza; Lino de Oliveira, Cilene

    2015-04-01

    Repeated forced swimming test (rFST) may detect gradual effects of antidepressants in adult rats. Antidepressants, as enrichment, affected behavior and neurogenesis in rats. However, the influence of enrichment on behavioral and neurogenic effects of antidepressants is unknown. Here, effects of antidepressants on rFST and hippocampal neurogenesis were investigated in rats under enriched conditions. Behaviors of male Wistar rats, housed from weaning in standard (SE) or enriched environment (EE), were registered during rFST. The rFST consisted of 15min of swimming (pretest) followed by 5min of swimming in the first (test), seventh (retest 1) and fourteenth (retest 2) days after pretest. One hour before the test, rats received an intraperitoneal injection of saline (1ml/kg), fluoxetine (2.5mg/kg) or imipramine (2.5 or 5mg/kg). These treatments were performed daily until the day of the retest 2. After retest 2, rats were euthanized for the identification of markers for neurogenesis in the hippocampus. Fluoxetine or imipramine decreased immobility in retests 1 and 2, as compared to saline. EE abolished these differences. In EE, fluoxetine or imipramine (5mg/kg) reduced immobility time in retest 2, as compared to the test. Independent of the housing conditions, fluoxetine and imipramine (5mg/kg) increased the ratio of immature neurons per progenitor cell in the hippocampus. In summary, antidepressants or enrichment counteracted the high immobility in rFST. Enrichment changed the effects of antidepressants in rFST depending on the type, and the dose of a substance but failed to change neurogenesis in control or antidepressant treated-rats. Effects of antidepressants and enrichment on rFST seemed neurogenesis-independent.

  8. Protection against adriamycin-induced skin necrosis in the rat by dimethyl sulfoxide and alpha-tocopherol.

    PubMed

    Svingen, B A; Powis, G; Appel, P L; Scott, M

    1981-09-01

    Extravasation of Adriamycin during i.v. infusion can cause serious local complications. We have used a rat skin model to study the protection afforded by dimethyl sulfoxide and alpha-tocopherol (vitamin E) against Adriamycin-induced skin necrosis. Topical daily application of 1 ml dimethyl sulfoxide for 2 days produced a small decrease in ulcer diameter of up to 11% at 2 weeks. Topical daily applications of 1 ml 10% alpha-tocopherol succinate in dimethyl sulfoxide for 2 days produced a marked decrease in ulcer diameter at 2 weeks of up to 68%. Daily topical application of 1 ml 10% alpha-tocopherol succinate in dimethyl sulfoxide for 7 days offered no greater protection than 2-day application. alpha-Tocopherol acetate appeared to have activity slightly less than that of alpha-tocopherol succinate in reducing ulcer size, and both compounds were considerably more active than was alpha-tocopherol alcohol. Administration of alpha-tocopherol succinate or alpha-tocopherol acetate i.p. had no significant effect upon ulcer diameter. Topically applied dimethyl sulfoxide and alpha-tocopherol may provide an effective way of treating accidentally extravasated Adriamycin in cancer patients.

  9. Evaluation of an experimental rat model for comparative studies of bleaching agents

    PubMed Central

    Cintra, Luciano Tavares Angelo; Benetti, Francine; Ferreira, Luciana Lousada; Rahal, Vanessa; Ervolino, Edilson; Jacinto, Rogério de Castilho; Gomes, João Eduardo; Briso, André Luiz Fraga

    2016-01-01

    ABSTRACT Dental materials, in general, are tested in different animal models prior to their clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats’ vital teeth. Material and methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals (control) were untreated. The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated by histomorphometric analysis with inflammatory cell counting in the coronal and radicular thirds of the pulp. The counting of fibroblasts was also performed. Scores were attributed to the odontoblastic layer and to vascular changes. The tertiary dentin area and the pulp chamber central area were histomorphometrically measured. Data were compared by the analysis of variance and the Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the occlusal third of the coronal pulp until the time of 15 min for both concentrations of bleaching gels. In 30 and 45 min groups of each concentration, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, a reduction in the pulp chamber central area and an enlargement of tertiary dentin area were observed without the detection of inflammation areas. Conclusion The rat model of extra coronal bleaching showed to be adequate for bleaching protocols studies, as it was possible to observe alterations in the pulp tissues and in the tooth structure caused by different concentrations and periods of application of bleaching agents. PMID:27008262

  10. Cell Injury and Repair Resulting from Sleep Loss and Sleep Recovery in Laboratory Rats

    PubMed Central

    Everson, Carol A.; Henchen, Christopher J.; Szabo, Aniko; Hogg, Neil

    2014-01-01

    Study Objectives: Increased cell injury would provide the type of change in constitution that would underlie sleep disruption as a risk factor for multiple diseases. The current study was undertaken to investigate cell injury and altered cell fate as consequences of sleep deprivation, which were predicted from systemic clues. Design: Partial (35% sleep reduction) and total sleep deprivation were produced in rats for 10 days, which was tolerated and without overtly deteriorated health. Recovery rats were similarly sleep deprived for 10 days, then allowed undisturbed sleep for 2 days. The plasma, liver, lung, intestine, heart, and spleen were analyzed and compared to control values for damage to DNA, proteins, and lipids; apoptotic cell signaling and death; cell proliferation; and concentrations of glutathione peroxidase and catalase. Measurements and Results: Oxidative DNA damage in totally sleep deprived rats was 139% of control values, with organ-specific effects in the liver (247%), lung (166%), and small intestine (145%). Overall and organ-specific DNA damage was also increased in partially sleep deprived rats. In the intestinal epithelium, total sleep deprivation resulted in 5.3-fold increases in dying cells and 1.5-fold increases in proliferating cells, compared with control. Two days of recovery sleep restored the balance between DNA damage and repair, and resulted in normal or below-normal metabolic burdens and oxidative damage. Conclusions: These findings provide physical evidence that sleep loss causes cell damage, and in a manner expected to predispose to replication errors and metabolic abnormalities; thereby providing linkage between sleep loss and disease risk observed in epidemiological findings. Properties of recovery sleep include biochemical and molecular events that restore balance and decrease cell injury. Citation: Everson CA, Henchen CJ, Szabo A, Hogg N. Cell injury and repair resulting from sleep loss and sleep recovery in laboratory rats

  11. Evaluation of an experimental rat model for comparative studies of bleaching agents

    PubMed Central

    CINTRA, Luciano Tavares Angelo; BENETTI, Francine; FERREIRA, Luciana Louzada; RAHAL, Vanessa; ERVOLINO, Edilson; JACINTO, Rogério de Castilho; GOMES, João Eduardo; BRISO, André Luiz Fraga

    2016-01-01

    ABSTRACT Dental materials in general are tested in different animal models prior to the clinical use in humans, except for bleaching agents. Objectives To evaluate an experimental rat model for comparative studies of bleaching agents, by investigating the influence of different concentrations and application times of H2O2 gel in the pulp tissue during in-office bleaching of rats’ vital teeth. Material and Methods The right and left maxillary molars of 50 Wistar rats were bleached with 20% and 35% H2O2 gels, respectively, for 5, 10, 15, 30, or 45 min (n=10 rats/group). Ten animals were untreated (control). The rats were killed after 2 or 30 days, and the maxillae were examined by light microscopy. Inflammation was evaluated through histomorphometric analysis with inflammatory cell count in the coronal and radicular thirds of the pulp. Fibroblasts were also counted. Scores were attributed to odontoblastic layer and vascular changes. Tertiary dentin area and pulp chamber central area were measured histomorphometrically. Data were compared by analysis of variance and Kruskal-Wallis test (p<0.05). Results After 2 days, the amount of inflammatory cells increased in the coronal pulp occlusal third up to the 15-min application groups of each bleaching gel. In the groups exposed to each concentration for 30 and 45 min, the number of inflammatory cells decreased along with the appearance of necrotic areas. After 30 days, reduction on the pulp chamber central area and enlargement of the tertiary dentin area were observed, without the detection of inflammation areas. Conclusion The rat model of extracoronal bleaching showed to be adequate for studies of bleaching protocols, as it was possible to observe alterations in the pulp tissues and tooth structure caused by different concentrations and application periods of bleaching agents. PMID:27119766

  12. [Cereal grain preference of rats].

    PubMed

    Wang, P Y

    1990-07-01

    Cereal grains are usually used as the main material for preparing rodenticide baits. However, the preferences for different grains varies according to species and habitats of rats, and locations. A formula accepted at one location may not be suitable in other places, where rats are accustomed to different types of food. It is therefore important to understand the feeding habits of local rat species before implementing a control program. Seven kinds of grains, including hulled rice, corn, barley, wheat, sorghum, pranuts, and sweet potatoes were tested to study the preferences of rats in the laboratory. The results revealed that Bandicota nemorivaga, Rattus losea and R. norvegicus prefer hulled rice; Apodemus agrarius and Mus musculus prefer peanuts, and R. rattus prefers corn. The influence of quality and nutrient contents of baits on the consumption of the rats is also discussed. PMID:2402029

  13. [Cereal grain preference of rats].

    PubMed

    Wang, P Y

    1990-07-01

    Cereal grains are usually used as the main material for preparing rodenticide baits. However, the preferences for different grains varies according to species and habitats of rats, and locations. A formula accepted at one location may not be suitable in other places, where rats are accustomed to different types of food. It is therefore important to understand the feeding habits of local rat species before implementing a control program. Seven kinds of grains, including hulled rice, corn, barley, wheat, sorghum, pranuts, and sweet potatoes were tested to study the preferences of rats in the laboratory. The results revealed that Bandicota nemorivaga, Rattus losea and R. norvegicus prefer hulled rice; Apodemus agrarius and Mus musculus prefer peanuts, and R. rattus prefers corn. The influence of quality and nutrient contents of baits on the consumption of the rats is also discussed.

  14. Nephrotoxicity of ifosfamide in rats.

    PubMed

    Springate, J E; Van Liew, J B

    1995-01-01

    Renal proximal tubule cell injury is an important side effect of the chemotherapeutic agent ifosfamide in humans. We investigated the effect of this medication on kidney function in rats. Animals received either 40 or 80 mg kg(-1) ifosfamide intraperitoneally daily for 3 days every 3 weeks for a total of four treatment courses. Ifosfamide-treated rats had significantly lower body weight and hematocrit than sterile water-treated control rats. Animals receiving 40 mg kg(-1) ifosfamide developed isolated phosphaturia after their fourth and final treatment course. Rats receiving 80 mg kg(-1) ifosfamide had low-grade glucosuria, phosphaturia and proteinuria throughout the study. Urine flow rate, creatinine clearance, urinary sodium and potassium excretion and kidney glutathione and malondialdehyde content were not affected by ifosfamide at either dose. These findings indicate that ifosfamide produces abnormalities in rat renal function resembling subclinical Fanconi syndrome.

  15. Adventitial Alterations Are the Main Features in Pulmonary Artery Remodeling due to Long-Term Chronic Intermittent Hypobaric Hypoxia in Rats

    PubMed Central

    Brito, Julio; Siques, Patricia; Arribas, Silvia M.; López de Pablo, Angel L.; González, M. Carmen; Naveas, Nelson; Flores, Karen; León-Velarde, Fabiola; Pulido, Ruth; Ordenes, Stefany; López, M. Rosario

    2015-01-01

    Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer. PMID:25738150

  16. Adventitial alterations are the main features in pulmonary artery remodeling due to long-term chronic intermittent hypobaric hypoxia in rats.

    PubMed

    Brito, Julio; Siques, Patricia; Arribas, Silvia M; López de Pablo, Angel L; González, M Carmen; Naveas, Nelson; Arriaza, Karem; Flores, Karen; León-Velarde, Fabiola; Pulido, Ruth; Ordenes, Stefany; López, M Rosario

    2015-01-01

    Long-term chronic intermittent exposure to altitude hypoxia is a labor phenomenon requiring further research. Using a rat model, we examined whether this type of exposure differed from chronic exposure in terms of pulmonary artery remodeling and other features. Rats were subjected to chronic hypoxia (CH, n = 9) and long-term intermittent hypoxia (CIH2x2; 2 days of hypoxia/2 days of normoxia, n = 10) in a chamber (428 Torr, 4,600 m of altitude) for 46 days and compared to rats under normoxia (NX, n = 10). Body weight, hematocrit, and right ventricle ratio were measured. Pulmonary artery remodeling was assessed using confocal microscopy of tissues stained with a nuclear dye (DAPI) and CD11b antibody. Both hypoxic conditions exhibited increased hematocrit and hypertrophy of the right ventricle, tunica adventitia, and tunica media, with no changes in lumen size. The medial hypertrophy area (larger in CH) depicted a significant increase in smooth muscle cell number. Additionally, CIH2x2 increased the adventitial hypertrophy area, with an increased cellularity and a larger prevalence of clustered inflammatory cells. In conclusion, CIH2x2 elicits milder effects on pulmonary artery medial layer muscularization and subsequent right ventricular hypertrophy than CH. However, CIH2x2 induces greater and characteristic alterations of the adventitial layer.

  17. War on Rats, 1972 Progress Report.

    ERIC Educational Resources Information Center

    District of Columbia Dept. of Environmental Services, Washington, DC.

    The City of Washington, D.C., with federal funding, declared war on one of the city's most pressing problems--rats. The War on Rats Program, in conjunction with Operation Clean Sweep, made a city-wide survey of rat infestations and recorded the areas of heavy rat infestation. After the problem areas had been identified, community organizations…

  18. Rat white matter injury model induced by endothelin-1 injection: technical modification and pathological evaluation.

    PubMed

    Ono, Hideaki; Imai, Hideaki; Miyawaki, Satoru; Nakatomi, Hirofumi; Saito, Nobuhito

    2016-01-01

    White matter injury is an important cause of functional disability of the brain. We comprehensively analyzed a modified endothelin-1 (ET‑1) injection-induced white matter injury model in the rat which is very valuable for investigating the underlying mechanisms of subcortical ischemic stroke. ET-1 was stereotactically injected into the internal capsule of the rat. To avoid complications with leakage of ET-1 into the lateral ventricle, the safest trajectory angle to the target was established. Rats with white matter injury were extensively evaluated for structural changes and functional sequelae, using motor function tests, magnetic resonance (MR) imaging, histopathology evolution, volume estimation of the lesion, and neuroanatomical identification of affected neurons using the retrograde tracer hydroxystilbamidine. Optimization of the trajectory of the ET-1 injection needle provided excellent survival rate. MR imaging visualized the white matter injury 2 days after surgery. Motor function deficit appeared temporarily after the operation. Histological studies confirmed damage of axons and myelin sheaths followed by inflammatory reaction and gliosis similar to lacunar infarction, with lesion volume of less than 1% of the whole brain. Hydroxystilbamidine injected into the lesion revealed wide spatial distribution of the affected neuronal population. Compared with prior ET-1 injection models, this method induced standardized amount of white matter damage and temporary motor function deficit in a reproducible and safe manner. The present model is valuable for studying the pathophysiology of not only ischemia, but a broader set of white matter damage conditions in the lissencephalic brain. PMID:27685774

  19. The purine nucleotide cycle. A pathway for ammonia production in the rat kidney.

    PubMed Central

    Bogusky, R T; Lowenstein, L M; Lowenstein, J M

    1976-01-01

    Particle-free extracts prepared from kidney cortex of rat catalyze the formation of ammonia via the purine nucleotide cycle. The cycle generates ammonia and fumarate from aspartate, using catalytic amounts of inosine monophosphate, adenylosuccinate, and adenosine monophosphate. The specific activities of the enzymes of the cycle are 1.27+/-0.27 nmol/mg protein per min (SE) for adenoylosuccinate synthetase, 1.38+/-0.16 for adenylosuccinase, and 44.0+/-3.3 for AMP deaminase. Compared with controls, extracts prepared from kidneys of rats fed ammonium chloride for 2 days show a 60% increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity, and a greater and more rapid synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate. Extracts prepared from kidneys of rats fed a potassium-deficient diet show a twofold increase in adenylosuccinate synthetase and a threefold increase in adenylosuccinase activity. In such extracts the rate of synthesis of ammonia and adenine nucleotide from aspartate and inosine monophosphate is also increased. These results show that the reactions of the purine nucleotide cycle are present and can operate in extracts of kidney cortex. The operational capacity of the cycle is accelerated by ammonium chloride feeding and potassium depletion, conditions known to increase renal ammonia excretion. Extracts of kidney cortex convert inosine monophosphate to uric acid. This is prevented by addition of allopurinol of 1-pyrophosphoryl ribose 5-phosphate to the reaction mixture. PMID:821968

  20. Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat.

    PubMed

    Colasanti, B; Khazan, N

    1975-09-17

    Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function.

  1. Effects of Three Different Fibrates on Intrahepatic Cholestasis Experimentally Induced in Rats

    PubMed Central

    El-Sisi, Alaa; Hegazy, Sahar

    2013-01-01

    Background. Activation of PPARα modulates cholesterol metabolism and suppresses bile acid synthesis. This study aims to evaluate the effect of PPARα agonists, fenofibrate, bezafibrate, and gemfibrozil, on acute cholestasis induced by ethinylestradiol (EE) plus chlorpromazine (CPZ) in rats. Method. 100 male albino rats (150–200 gm) were divided randomly into 10 equal groups. Control group received 1% methylcellulose vehicle; disease group received CPZ plus EE for 5 consecutive days; four groups received either ursodeoxycholic acid, fenofibrate, bezafibrate, or gemfibrozil for 7 days; 2 days before EE + CPZ, three other groups received one of the three fibrates after GW6471, a selective PPARα antagonist in addition to EE + CPZ. The final group received GW6471 alone. Results. The three fibrates showed marked reduction (P < 0.05) in serum levels of ALP, GGT, ALT, AST, total bile acids, bilirubin, TNFα, and IL-1β and in hepatic malondialdehyde level as well as a significant increase in bile flow rate (P < 0.05) in addition to improvements in histopathological parameters compared to diseased group. In groups which received GW6471, these effects were completely abolished with fenofibrate and partially blocked with bezafibrate and gemfibrozil. Conclusion. Short-term administration of fibrates to EE/CPZ-induced intrahepatic cholestatic rats exerted beneficial effects on hepatocellular damage and apoptosis. Fenofibrate anticholestatic effect was solely PPARα dependent while other mechanisms played part in bezafibrate and gemfibrozil actions. PMID:23997763

  2. Combination of hyperhomocysteinemia and ischemic tolerance in experimental model of global ischemia in rats.

    PubMed

    Kovalska, M; Kovalska, L; Tothova, B; Mahmood, S; Adamkov, M; Lehotsky, J

    2015-12-01

    Epidemiological studies show positive relationship between mild-to-moderate hyperhomocysteinemia (hHcy) and the risk of cerebrovascular diseases. The study determines whether hyperhomocysteinemia (risk factor of brain ischemia) alone or in combination with the ischemic preconditioning (IPC) affects the ischemia-induced neurodegenerative changes and imbalance in MAPK/p-ERK1/2 and MAPK/p-p38 expression in the rat brains. hHcy was induced by subcutaneous administration of homocysteine (0.45 μmol/g body weight) twice a day at 8 h intervals for 14 days. Rats were preconditioned by 5 min ischemia and 2 days later, 15 min of global forebrain ischemia was induced by four vessel occlusion. We observed that hHcy alone significantly increased neurodegeneration by Fluoro-Jade C and TUNEL possitive cells in hippocampus as well as in cortex. We found elevated level of MAPK/p-ERK and decreased level of MAPK/p-p38 after pre-ischemic challenge by Western blot and fluorescent immunohistochemistry. In conclusion, preconditioning even if combined with hHcy could preserve the neuronal tissue from lethal ischemic effect. This study provides evidence for the interplay and tight integration between ERK and p38 MAPKs signalling mechanisms in response to the hHcy and also if in association with brain ischemia/IPC challenge in the rat brain. PMID:26769838

  3. Effect of prenatal phenytoin administration on brain tryptophan metabolism of rat offspring during the preweaning period.

    PubMed

    Elmazar, M M; Sullivan, F M

    1980-10-01

    Serum 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) concentrations in control rat offspring increased progressively during the preweaning period reaching adult values by day 21. It has been shown the prenatal phenytoin administration (100 mg kg-1 orally, days 7-19 of pregnancy) increased serum tryptophan and brain tryptophan, 5-HT and 5-HIAA of rat offspring at 3 days of age but not at 4, 15 or 21 days of age. The effect of prenatal phenytoin administration on the offspring at 3 days of age was not observed when these pups were cross-fostered to control mothers at 2 days of age suggesting that the alteration in rain tryptophan metabolism during the development of tryptaminergic neurons in rat offspring, as a result of prenatal phenytoin administration is mediated through changes in lactation or nursing ability of the mothers. It is important that such non-specific factors are controlled when studying the effect of prenatally administered drugs on neonatal brain transmitter concentrations.

  4. State-dependent amygdala stimulation-induced cardiovascular effects in rats.

    PubMed

    Chiou, Ruei-Jen; Kuo, Chung-Chih; Liang, Keng-Chen; Yen, Chen-Tung

    2009-12-31

    Stimulation of the amygdala is known to produce pressor, depressor, or has no effects. The present study was performed to test whether amygdala cardiovascular effects are influenced by consciousness states and by different types of anesthetics. Adult rats were set up for stimulation amygdala and measurement of blood pressure in a chronic preparation. After recovery, same sites of the amygdala were stimulated electrically for several trials with the rat under conscious or anesthetic states induced by pentobarbital, urethane, ketamine, alpha-chloralose and urethane plus alpha-chloralose, respectively. The interval between any two stimulation trials was at least 2 days. The stimulation was an 80-Hz, 0.5-ms, 100-micro A square wave pulse train lasting for 15 s. Cardiovascular responsive sites were found in the central, medial, and basolateral nuclei of the amygdala. In stimulating these responsive sites, significantly different cardiovascular effects were induced under a conscious state and an anesthetized state of the animal, yet no significant differences were found among the various anesthetic agents. We conclude, that the cardiovascular influence of the amygdala is state-dependent in the rat.

  5. The protective role of zinc against acute toxicity of depleted uranium in rats.

    PubMed

    Hao, Yuhui; Ren, Jiong; Liu, Jing; Luo, Shenglin; Ma, Ting; Li, Rong; Su, Yongping

    2012-12-01

    Depleted uranium (DU) has been widely used in both civilian and military activities and contributes to health problems. This study was undertaken to evaluate the protective role of zinc against acute toxicity of DU. Sprague Dawley rats were injected with DU (10 mg/kg, i.p.) to create a toxicity model (DU group). Before and after the injection of DU, zinc sulphate (10 mg/kg, i.p.) was administered once a day for 2 days. The survival rates at 30 days post DU administration and the effects of zinc at 4 days post DU administration were evaluated. Our data indicate that zinc has obvious protective effects, especially pre-treatment with zinc. Rats pre-treated with zinc had significantly higher survival rates than rats in the DU group, with 60.03% more surviving. In addition, at 4 days post DU administration, the former had lower kidney uranium content, insignificant renal tubular epithelial cell necrosis and less transparent tubes. Meanwhile, blood urea nitrogen, creatinine and urine N-acethyl-β-d-glucosaminidase concentrations were significantly decreased; the gene expression levels of metallothionein (MT) in kidney tissues were significantly increased; and catalase levels were increased and malondialdehyde levels were decreased. In conclusion, pre-treatment with zinc significantly alleviated acute toxicity of DU, and the mechanism appeared to be related to the induction of MT synthesis and enhancement of the antioxidant function.

  6. Characteristic molecular and proteomic signatures of drug-induced liver injury in a rat model.

    PubMed

    Eun, Jung Woo; Bae, Hyun Jin; Shen, Qingyu; Park, Se Jin; Kim, Hyung Seok; Shin, Woo Chan; Yang, Hee Doo; Jin, Chan Young; You, Jueng Soo; Kang, Hyun Joo; Kim, Hoguen; Ahn, Young Min; Park, Won Sang; Lee, Jung Young; Nam, Suk Woo

    2015-02-01

    Drug-induced liver injury (DILI) is a major safety concern during drug development and remains one of the main reasons for withdrawal of drugs from the market. Although it is crucial to develop methods that will detect potential hepatotoxicity of drug candidates as early and as quickly as possible, there is still a lack of sensitive and specific biomarkers for DILI that consequently leads to a scarcity of reliable hepatotoxic data. Hence, in this study, we assessed characteristic molecular signatures in rat liver treated with drugs (pyrazinamide, ranitidine, enalapril, carbamazepine and chlorpromazine) that are known to cause DILI in humans. Unsupervised hierarchical clustering analysis of transcriptome changes induced by DILI-causing drugs resulted in three different subclusters on dendrogram, i.e., hepatocellular, cholestatic and mixed type of DILI at early time points (2 days), and multiclassification analysis suggested 31 genes as discernible markers for each DILI pattern. Further analysis for characteristic molecular signature of each DILI pattern provided a molecular basis for different modes of DILI action. A proteomics study of the same rat livers was used to confirm the results, and the two sets of data showed 60 matching classifiers. In conclusion, the data of different DILI-causing drug treatments from genomic analysis in a rat model suggest that DILI-specific molecular signatures can discriminate different patterns of DILI at an early exposure time point, and that they provide useful information for mechanistic studies that may lead to a better understanding of the molecular basis of DILI.

  7. Kupffer cell blockade prevents induction of portal venous tolerance in rat cardiac allograft transplantation

    SciTech Connect

    Kamei, T.; Callery, M.P.; Flye, M.W. )

    1990-05-01

    Pretransplant portal venous (pv) administration of donor antigen induces allospecific partial tolerance. Although the involved mechanism has not been defined, antigen presentation by Kupffer cells (KC) in the liver is considered to be critical. We evaluated the effect of KC blockade on this pv tolerance induction in Buffalo (RT1b) rats receiving Lewis (RT1(1)) cardiac heterotopic allografts. Control rats received no treatment, while experimental animals received 25 X 10(6) ultraviolet B-irradiated (12,000 J/m2) donor spleen cells via either the iv (systemic intravenous) or the pv routes 7 days before transplantation. Gadolinium chloride (GdCl3), a rare earth metal known to inhibit KC phagocytosis, was given (7 mg/kg) 1 and 2 days before pv preimmunization. Cardiac graft prolongation was obtained by pv (MST = 13.3 +/- 1.9 days, n = 6, vs control = 7.3 +/- 0.5 days, n = 6; P less than 0.001) but not by iv preimmunization (7.7 +/- 0.7 days, n = 6, NS vs control). KC blockade abolished the pv tolerance, as indicated by abrogation of graft prolongation (PV + GdCl3 = 8.0 +/- 0.8 days, n = 6, NS vs control). These findings suggest that effective alloantigen uptake by KC in the liver is essential for the induction of pv tolerance in rat cardiac transplantation.

  8. Reversal of impaired wound healing in irradiated rats by platelet-derived growth factor-BB

    SciTech Connect

    Mustoe, T.A.; Purdy, J.; Gramates, P.; Deuel, T.F.; Thomason, A.; Pierce, G.F. )

    1989-10-01

    This study examined the potential influence of platelet-derived growth factor-BB homodimers (PDGF-BB) on surgical incisions in irradiated animals with depressed wound healing. Rats were irradiated with either 800 rads total body or 2,500 rads surface irradiation. Parallel dorsal skin incisions were made 2 days later, and PDGF-BB was applied topically a single time to one of two incisions. In total body-irradiated rats, bone marrow-derived elements were severely depressed, wound macrophages were virtually eliminated, and PDGF-BB treatment was ineffective. However, in surface-irradiated rats, PDGF-BB treatment recruited macrophages into wounds and partially reversed impaired healing on day 7 (p less than 0.005) and day 12 (p less than 0.001). PDGF-BB-treated wounds were 50 percent stronger than the paired control wounds. The results suggest PDGF requires bone marrow-derived cells, likely wound macrophages, for activity and that it may be useful as a topical agent in postirradiation surgical incisions.

  9. Rapid Amygdala Kindling Causes Motor Seizure and Comorbidity of Anxiety- and Depression-Like Behaviors in Rats

    PubMed Central

    Chen, Shang-Der; Wang, Yu-Lin; Liang, Sheng-Fu; Shaw, Fu-Zen

    2016-01-01

    Amygdala kindling is a model of temporal lobe epilepsy (TLE) with convulsion. The rapid amygdala kindling has an advantage on quick development of motor seizures and for antiepileptic drugs screening. The rapid amygdala kindling causes epileptogenesis accompanied by an anxiolytic response in early isolation of rat pups or depressive behavior in immature rats. However, the effect of rapid amygdala kindling on comorbidity of anxiety- and depression-like behaviors is unexplored in adult rats with normal breeding. In the present study, 40 amygdala stimulations given within 2 days were applied in adult Wistar rats. Afterdischarge (AD) and seizure stage were recorded throughout the amygdala kindling. Anxiety-like behaviors were evaluated by the elevated plus maze (EPM) test and open field (OF) test, whereas depression-like behaviors were assessed by the forced swim (FS) and sucrose consumption (SC) tests. A tonic-clonic convulsion was provoked in the kindle group. Rapid amygdala kindling resulted in a significantly lower frequency entering an open area of either open arms of the EPM or the central zone of an OF, lower sucrose intake, and longer immobility of the FS test in the kindle group. Our results suggest that rapid amygdala kindling elicited severe motor seizures comorbid with anxiety- and depression-like behaviors. PMID:27445726

  10. Rapid Amygdala Kindling Causes Motor Seizure and Comorbidity of Anxiety- and Depression-Like Behaviors in Rats.

    PubMed

    Chen, Shang-Der; Wang, Yu-Lin; Liang, Sheng-Fu; Shaw, Fu-Zen

    2016-01-01

    Amygdala kindling is a model of temporal lobe epilepsy (TLE) with convulsion. The rapid amygdala kindling has an advantage on quick development of motor seizures and for antiepileptic drugs screening. The rapid amygdala kindling causes epileptogenesis accompanied by an anxiolytic response in early isolation of rat pups or depressive behavior in immature rats. However, the effect of rapid amygdala kindling on comorbidity of anxiety- and depression-like behaviors is unexplored in adult rats with normal breeding. In the present study, 40 amygdala stimulations given within 2 days were applied in adult Wistar rats. Afterdischarge (AD) and seizure stage were recorded throughout the amygdala kindling. Anxiety-like behaviors were evaluated by the elevated plus maze (EPM) test and open field (OF) test, whereas depression-like behaviors were assessed by the forced swim (FS) and sucrose consumption (SC) tests. A tonic-clonic convulsion was provoked in the kindle group. Rapid amygdala kindling resulted in a significantly lower frequency entering an open area of either open arms of the EPM or the central zone of an OF, lower sucrose intake, and longer immobility of the FS test in the kindle group. Our results suggest that rapid amygdala kindling elicited severe motor seizures comorbid with anxiety- and depression-like behaviors. PMID:27445726

  11. Voluntary exercise ameliorates cognitive deficits in morphine dependent rats: the role of hippocampal brain-derived neurotrophic factor.

    PubMed

    Miladi-Gorji, Hossein; Rashidy-Pour, Ali; Fathollahi, Yaghoub; Akhavan, Maziar M; Semnanian, Saeed; Safari, Manouchehr

    2011-10-01

    Chronic exposure to opiates impairs spatial learning and memory. Given the well-known beneficial effects of voluntary exercise on cognitive functions, we investigated whether voluntary exercise would ameliorate the cognitive deficits that are induced by morphine dependence. If an effect of exercise was observed, we aimed to investigate the possible role of hippocampal brain-derived neurotrophic factor (BDNF) in the exercise-induced enhancement of learning and memory in morphine-dependent rats. The rats were injected with bi-daily doses (10mg/kg, at 12h intervals) of morphine over a period of 10 days of voluntary exercise. Following these injections, a water maze task was performed twice a day for five consecutive days, followed by a probe trial 2 days later. A specific BDNF inhibitor (TrkB-IgG chimera) was used to block the hippocampal BDNF action during the 10 days of voluntary exercise. We found that voluntary exercise blocked the ability of chronic morphine to impair spatial memory retention. A blockade of the BDNF action blunted the exercise-induced improvement of spatial memory in the dependent rats. Moreover, the voluntary exercise diminished the severity of the rats' dependency on morphine. This study demonstrates that voluntary exercise ameliorates, via a TrkB-mediated mechanism, the cognitive deficits that are induced by chronic morphine. Thus, voluntary exercise might be a potential method to ameliorate some of the deleterious behavioral consequences of the abuse of morphine and other opiates.

  12. The effect of x rays, DTPA, and aspirin on the absorption of plutonium from the gastrointestinal tract of rats

    SciTech Connect

    Sullivan, M.F.; Gorham, L.S.; Miller, B.M.

    1983-04-01

    To measure the effect of radiation on plutonium transport, rats that were exposed to 250-kVp X rays were given /sup 238/Pu 3 days afterwards by either gavage or injection into a ligated segment of the duodenum. In a second group of experiments, rats were either injected intraduodenally with /sup 238/Pu-DTPA or administered the chelate intravenously and the /sup 238/Pu by gavage. In a third experiment, rats that had been gavaged with 200 or 400 mg/kg/day of aspirin for 2 days were injected intragastrically with /sup 238/Pu nitrate. Results of the first experiment showed a dose-dependent increase in /sup 238/Pu absorption between 800 and 1500 rad of lower-body X irradiation. Intravenous or intraduodenal injections of DTPA caused a marked increase in /sup 238/Pu absorption but resulted in decreased plutonium deposition in the skeleton and liver. Retention of /sup 238/Pu in the skeleton of rats given aspirin was double that of controls, but the effect on plutonium absorption was less marked than that of DTPA.

  13. Rapid Amygdala Kindling Causes Motor Seizure and Comorbidity of Anxiety- and Depression-Like Behaviors in Rats.

    PubMed

    Chen, Shang-Der; Wang, Yu-Lin; Liang, Sheng-Fu; Shaw, Fu-Zen

    2016-01-01

    Amygdala kindling is a model of temporal lobe epilepsy (TLE) with convulsion. The rapid amygdala kindling has an advantage on quick development of motor seizures and for antiepileptic drugs screening. The rapid amygdala kindling causes epileptogenesis accompanied by an anxiolytic response in early isolation of rat pups or depressive behavior in immature rats. However, the effect of rapid amygdala kindling on comorbidity of anxiety- and depression-like behaviors is unexplored in adult rats with normal breeding. In the present study, 40 amygdala stimulations given within 2 days were applied in adult Wistar rats. Afterdischarge (AD) and seizure stage were recorded throughout the amygdala kindling. Anxiety-like behaviors were evaluated by the elevated plus maze (EPM) test and open field (OF) test, whereas depression-like behaviors were assessed by the forced swim (FS) and sucrose consumption (SC) tests. A tonic-clonic convulsion was provoked in the kindle group. Rapid amygdala kindling resulted in a significantly lower frequency entering an open area of either open arms of the EPM or the central zone of an OF, lower sucrose intake, and longer immobility of the FS test in the kindle group. Our results suggest that rapid amygdala kindling elicited severe motor seizures comorbid with anxiety- and depression-like behaviors.

  14. Radiation induced heart disease in hypertensive rats

    SciTech Connect

    Lauk, S.; Trott, K.R.

    1988-01-01

    Spontaneously hypertensive Wistar rats were given single doses of X rays to their heart. Irradiation decreased the blood pressure before any myocardial radiation damage was apparent. Male rats, which were more hypertensive than female rats, had a shorter survival time after local heart irradiation than female rats. Antihypertensive treatment with hydralazine did not increase the survival time. It is considered that myocardial hypertrophy is the cause of the increased susceptibility of spontaneously hypertensive rats to local heart irradiation.

  15. Hydroxyl fasudil, an inhibitor of Rho signaling, improves erectile function in diabetic rats: a role for neuronal ROCK

    PubMed Central

    Sezen, Sena F.; Lagoda, Gwen; Musicki, Biljana; Burnett, Arthur L.

    2014-01-01

    Introduction The pathogenesis of diabetic erectile dysfunction (ED) includes neuropathy, but the molecular basis for neurogenic ED is incompletely understood. The RhoA/ROCK pathway has been implicated in diabetic neuropathy and in ED, but its role in diabetic neurogenic ED is not known. Aims The aim of this study was to determine whether hydroxyl fasudil, an ROCK inhibitor, affects diabetic neuropathy-related ED. Methods Type 1 diabetes mellitus was induced in male rats by streptozotocin (75 mg/kg, intraperitoneally). After 8 weeks, diabetic rats were administered hydroxyl fasudil, a selective ROCK inhibitor (10 mg/kg/day, intraperitoneally) or vehicle, for 4 weeks. Age-matched control, nondiabetic, rats were treated intraperitoneally for 4 weeks with saline. At week 12, after a 2 day wash-out, neuro-stimulated erectile function was evaluated. Major pelvic ganglia (MPG) were collected for western blot analysis of RhoA, ROCK-1, ROCK-2, phospho (P)-AKT (Ser473), and P-phosphatase and tensin homolog (P-PTEN) (Ser380/Thr382/383). Main outcome measures Effect of ROCK inhibitor hydroxyl fasudil on erectile function and ROCK/P-AKT/P-PTEN pathway in the MPG of diabetic rats. Results Erectile response was significantly (P<0.05) reduced in diabetic compared with nondiabetic rats, and was preserved (P<0.05) in diabetic rats treated with hydroxyl fasudil. In diabetic rats, RhoA and ROCK-2 protein expressions in MPG were increased (P<0.05) and remained increased in hydroxyl fasudil-treated rats. P-AKT (Ser473) expression was decreased (P<0.05), while P-PTEN (Ser380/Thr382/383) expression was increased (P<0.05) in MPG of diabetic compared to nondiabetic rats, and both were reversed (P<0.05) in diabetic rats treated with hydroxyl fasudil. Conclusion Improved erectile function and restored P-AKT and P-PTEN in the MPG with hydroxyl fasudil treatment suggest the role of Rho signaling via PTEN/AKT pathway in neurogenic diabetic ED. PMID:24919622

  16. Generation of Hprt-disrupted rat through mouse←rat ES chimeras

    PubMed Central

    Isotani, Ayako; Yamagata, Kazuo; Okabe, Masaru; Ikawa, Masahito

    2016-01-01

    We established rat embryonic stem (ES) cell lines from a double transgenic rat line which harbours CAG-GFP for ubiquitous expression of GFP in somatic cells and Acr3-EGFP for expression in sperm (green body and green sperm: GBGS rat). By injecting the GBGS rat ES cells into mouse blastocysts and transplanting them into pseudopregnant mice, rat spermatozoa were produced in mouse←rat ES chimeras. Rat spermatozoa from the chimeric testis were able to fertilize eggs by testicular sperm extraction combined with intracytoplasmic sperm injection (TESE-ICSI). In the present paper, we disrupted rat hypoxanthine-guanine phosphoribosyl transferase (Hprt) gene in ES cells and produced a Hprt-disrupted rat line using the mouse←rat ES chimera system. The mouse←rat ES chimera system demonstrated the dual advantages of space conservation and a clear indication of germ line transmission in knockout rat production. PMID:27062982

  17. Rat myocardial protein degradation.

    PubMed

    Steer, J H; Hopkins, B E

    1981-07-01

    1. Myocardial protein degradation rates were determined by following tyrosine release from rat isolated left hemi-atria in vitro. 2. After two 20 min preincubations the rate of tyrosine release from hemi-atria was constant for 4 h. 3. Skeletal muscle protein degradation was determined by following tyrosine release from rat isolated hemi-diaphragm (Fulks, Li & Goldberg, 1975). 4. Insulin (10(-7) M) inhibited tyrosine release from hemi-atria and hemi-diaphragm to a similar extent. A 48 h fast increased tyrosine release rate from hemi-diaphragm and decreased tyrosine release rate from hemi-atria. Hemi-diaphragm tyrosine release was inhibited by 15 mmol/l D-glucose but a variety of concentrations of D-glucose (0, 5, 15 mmol/l) had no effect on tyrosine release from hemi-atria. Five times the normal plasma levels of the branched-chain amino acids leucine, isoleucine and valine had no effect on tyrosine release from either hemi-atria or hemi-diaphragm.

  18. (/sup 3/H)AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin

    SciTech Connect

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

    1988-05-01

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

  19. Comparison of Burrowing and Stimuli-Evoked Pain Behaviors as End-Points in Rat Models of Inflammatory Pain and Peripheral Neuropathic Pain

    PubMed Central

    Muralidharan, Arjun; Kuo, Andy; Jacob, Meera; Lourdesamy, Jacintha S.; Carvalho, Lara Melo Soares Pinho De; Nicholson, Janet R.; Corradini, Laura; Smith, Maree T.

    2016-01-01

    Establishment and validation of ethologically-relevant, non-evoked behavioral end-points as surrogate measures of spontaneous pain in rodent pain models has been proposed as a means to improve preclinical to clinical research translation in the pain field. Here, we compared the utility of burrowing behavior with hypersensitivity to applied mechanical stimuli for pain assessment in rat models of chronic inflammatory and peripheral neuropathic pain. Briefly, groups of male Sprague-Dawley rats were habituated to the burrowing environment and trained over a 5-day period. Rats that burrowed ≤ 450 g of gravel on any 2 days of the individual training phase were excluded from the study. The remaining rats received either a unilateral intraplantar injection of Freund's complete adjuvant (FCA) or saline, or underwent unilateral chronic constriction injury (CCI) of the sciatic nerve- or sham-surgery. Baseline burrowing behavior and evoked pain behaviors were assessed prior to model induction, and twice-weekly until study completion on day 14. For FCA- and CCI-rats, but not the corresponding groups of sham-rats, evoked mechanical hypersensitivity developed in a temporal manner in the ipsilateral hindpaws. Although burrowing behavior also decreased in a temporal manner for both FCA-and CCI- rats, there was considerable inter-animal variability. By contrast, mechanical hyperalgesia and mechanical allodynia in the ipsilateral hindpaws of FCA- and CCI-rats respectively, exhibited minimal inter-animal variability. Our data collectively show that burrowing behavior is altered in rodent models of chronic inflammatory pain and peripheral neuropathic pain. However, large group sizes are needed to ensure studies are adequately powered due to considerable inter-animal variability. PMID:27242458

  20. Stress-reactive rats (high-avoidance female rats) have a shorter lifespan than stress-nonreactive rats (low-avoidance female rats)

    PubMed Central

    Ohta, Ryo; Kumagai, Fumiaki; Marumo, Hideki; Usumi, Kenji; Saito, Yoshiaki; Kuwagata, Makiko

    2015-01-01

    Although Hatano high-avoidance and low-avoidance rats (HAA and LAA, respectively) have been selectively bred for good versus poor avoidance learning, HAA rats are known to be more reactive to stress than LAA rats. In this study, HAA and LAA female rats were compared during reproductive aging by observing estrous cycles from 8 to 11 months of age. Furthermore, these rats were allowed to live out their natural lifespans, that is, until 24 months of age, in order to compare their survival and to clarify the relationship between reproductive aging and tumor development. At eight months of age, 2 of 35 HAA rats and 20 of 35 LAA rats had abnormal estrous cycles. The median lifespan of the HAA rats (673 days) was shorter than that of the LAA rats (733 days). The incidence of pituitary neoplasia was higher in the HAA rats than in the LAA rats. These results suggest that HAA female rats (i.e., stress-reactive rats) have a shorter lifespan than LAA female rats (i.e., stress-nonreactive rats) and develop pituitary neoplasia, which was one of the causal factors in their accelerated mortality. However, the onset of an age-matched abnormal cycle did not correspond with their lifespan. PMID:27182111

  1. Nonviral gene delivery to the rat kidney with polyethylenimine.

    PubMed

    Boletta, A; Benigni, A; Lutz, J; Remuzzi, G; Soria, M R; Monaco, L

    1997-07-01

    The aim of this study was to establish a nonviral method for gene delivery to the rat kidney. To this purpose, a panel of reagents was tested, including a monocationic lipid, DOTAP, a polycationic lipid, DOGS (or Transfectam), and three different forms of the cationic polymer polyethylenimine (PEI). A comparison among these compounds was performed in vivo, using luciferase as reporter gene. Complexes containing 10 microg of DNA were injected into the left renal artery of rats and allowed to remain in contact with the kidney for 10 min. Forty-eight hours later, luciferase expression levels in kidney extracts were measured. Kidneys injected with DNA complexed to the branched, 25-kD PEI polymer (PEI 25k) yielded activity levels significantly higher than control, sham-operated kidneys (2.7 x 10(4) vs. 5.2 x 10(3) RLU/kidney, respectively), whereas the other transfecting agents did not yield significant activity over controls. PEI 25k was therefore chosen for further optimization of transfection conditions. Dose-dependent luciferase expression was shown for 10, 50, and 100 microg of PEI-complexed DNA, reaching maximal levels of 2.4 x 10(5) RLU/kidney at 100 microg DNA. The optimal PEI nitrogen/DNA phosphate molar ratio was 10 equivalents. Luciferase activity peaked at 2 days, was still significantly higher than controls at 7 days, and was undetectable at 14 days post-injection. Using beta-galactosidase (beta-Gal) as a reporter, transgene expression was localized almost exclusively in proximal tubular cells.

  2. Assessing cognitive function after intracerebral hemorrhage in rats.

    PubMed

    MacLellan, Crystal L; Langdon, Kristopher D; Churchill, Kayla P; Granter-Button, Shirley; Corbett, Dale

    2009-03-17

    Preclinical studies must rigorously assess whether putative therapies improve motor and cognitive function following brain injury. Intracerebral hemorrhage (ICH) causes significant sensory-motor and cognitive deficits in humans. However, no study has evaluated cognition in rodent ICH models. Thus, we used a battery of tests to comprehensively examine whether a striatal ICH causes cognitive impairments in rats. Bacterial collagenase (or sterile saline for SHAM surgery) was injected into the striatum to create an ICH. Two days later, functional deficits were assessed using a neurological deficit scale (NDS), which is most sensitive to ICH injury. Sensory and/or motor deficits may confound cognitive testing; thus, we waited until these had resolved before testing learning and memory. Testing was conducted 1-7 months after ICH and included spontaneous alternation, elevated plus maze, open-field, Morris water maze, T-maze (win-shift and win-stay paradigms), and the radial arm maze (eight and four arms baited protocols). Significant motor deficits at 2 days completely resolved by 1 month, at which time cognitive testing began. In contrast to persistent cognitive deficits that occur after ICH in humans, we did not detect significant learning or memory deficits after ICH in rats. Our results suggest that these tests will not likely be useful for assessing outcome in experimental ICH studies. In conclusion, animal models that better mimic clinical ICH (both motor and cognitive deficits) must be developed. This may include increasing ICH severity or injuring other functional subdivisions within the striatum that may lead to more profound cognitive deficits.

  3. Spontaneous Changes in Taste Sensitivity of Single Units Recorded over Consecutive Days in the Brainstem of the Awake Rat

    PubMed Central

    Sammons, Joshua D.; Weiss, Michael S.; Escanilla, Olga D.; Fooden, Andrew F.; Victor, Jonathan D.

    2016-01-01

    A neuron’s sensitivity profile is fundamental to functional classification of cell types, and underlies theories of sensory coding. Here we show that gustatory neurons in the nucleus of the solitary tract (NTS) and parabrachial nucleus of the pons (PbN) of awake rats spontaneously change their tuning properties across days. Rats were surgically implanted with a chronic microwire assembly into the NTS or PbN. Following recovery, water-deprived rats had free access to a lick spout that delivered taste stimuli while cellular activity was recorded. In 12 rats for the NTS and 8 rats for the PbN, single units could be isolated at the same electrode on consecutive days (NTS, 14 units for 2–5 consecutive days, median = 2 days; PbN, 23 units for 2–7 days, median = 2.5 days). Waveforms were highly similar (waveform template correlation > 0.99) across days in 13 units in NTS and 13 units in PbN. This degree of similarity was rare (0.3% of pairs in NTS, 1.5% of pairs in PbN) when the waveforms were from presumed-different neurons (units recorded on nonconsecutive days with at least one intervening day in which there were no spikes, or from different wires or rats). Analyses of multi-day recordings that met this criterion for “same unit” showed that responses to taste stimuli appeared, disappeared, or shifted in magnitude across days, resulting in changes in tuning. These data imply, generally, that frameworks for cell classification and, specifically, that theories of taste coding, need to consider plasticity of response profiles. PMID:27479490

  4. Spontaneous Changes in Taste Sensitivity of Single Units Recorded over Consecutive Days in the Brainstem of the Awake Rat.

    PubMed

    Sammons, Joshua D; Weiss, Michael S; Escanilla, Olga D; Fooden, Andrew F; Victor, Jonathan D; Di Lorenzo, Patricia M

    2016-01-01

    A neuron's sensitivity profile is fundamental to functional classification of cell types, and underlies theories of sensory coding. Here we show that gustatory neurons in the nucleus of the solitary tract (NTS) and parabrachial nucleus of the pons (PbN) of awake rats spontaneously change their tuning properties across days. Rats were surgically implanted with a chronic microwire assembly into the NTS or PbN. Following recovery, water-deprived rats had free access to a lick spout that delivered taste stimuli while cellular activity was recorded. In 12 rats for the NTS and 8 rats for the PbN, single units could be isolated at the same electrode on consecutive days (NTS, 14 units for 2-5 consecutive days, median = 2 days; PbN, 23 units for 2-7 days, median = 2.5 days). Waveforms were highly similar (waveform template correlation > 0.99) across days in 13 units in NTS and 13 units in PbN. This degree of similarity was rare (0.3% of pairs in NTS, 1.5% of pairs in PbN) when the waveforms were from presumed-different neurons (units recorded on nonconsecutive days with at least one intervening day in which there were no spikes, or from different wires or rats). Analyses of multi-day recordings that met this criterion for "same unit" showed that responses to taste stimuli appeared, disappeared, or shifted in magnitude across days, resulting in changes in tuning. These data imply, generally, that frameworks for cell classification and, specifically, that theories of taste coding, need to consider plasticity of response profiles. PMID:27479490

  5. Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

    SciTech Connect

    Deman, Pierre; Vautrin, Mathias; Edouard, Magali; Stupar, Vasile; Bobyk, Laure; Farion, Regine; Elleaume, Helene; Remy, Chantal; Barbier, Emmanuel L.; Esteve, Francois; Adam, Jean-Francois

    2012-03-15

    Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

  6. Sodium Glucose Cotransporter 2 (SGLT2) Plays as a Physiological Glucose Sensor and Regulates Cellular Contractility in Rat Mesangial Cells

    PubMed Central

    Wakisaka, Masanori; Nagao, Tetsuhiko; Yoshinari, Mototaka

    2016-01-01

    Purpose Mesangial cells play an important role in regulating glomerular filtration by altering their cellular tone. We report the presence of a sodium glucose cotransporter (SGLT) in rat mesangial cells. This study in rat mesangial cells aimed to evaluate the expression and role of SGLT2. Methods The SGLT2 expression in rat mesangial cells was assessed by Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). Changes in the mesangial cell surface area at different glucose concentrations and the effects of extracellular Na+ and Ca2+ and of SGLT and Na+/Ca2+ exchanger (NCX) inhibitors on cellular size were determined. The cellular sizes and the contractile response were examined during a 6-day incubation with high glucose with or without phlorizin, an SGLT inhibitor. Results Western blotting revealed an SGLT2 band, and RT-PCR analysis of SGLT2 revealed the predicted 422-bp band in both rat mesangial and renal proximal tubular epithelial cells. The cell surface area changed according to the extracellular glucose concentration. The glucose-induced contraction was abolished by the absence of either extracellular Na+ or Ca2+ and by SGLT and NCX inhibitors. Under the high glucose condition, the cell size decreased for 2 days and increased afterwards; these cells did not contract in response to angiotensin II, and the SGLT inhibitor restored the abolished contraction. Conclusions These data suggest that SGLT2 is expressed in rat mesangial cells, acts as a normal physiological glucose sensor and regulates cellular contractility in rat mesangial cells. PMID:26999015

  7. Effects of treatment with estrogen and progesterone on the methamphetamine-induced cognitive impairment in ovariectomized rats.

    PubMed

    Ghazvini, Hamed; Khaksari, Mohammad; Esmaeilpour, Khadijeh; Shabani, Mohammad; Asadi-Shekaari, Majid; Khodamoradi, Mehdi; Sheibani, Vahid

    2016-04-21

    Methamphetamine (METH) is one of the most powerful psychostimulant that leads to long lasting cognitive impairment. Earlier researches demonstrated that ovarian hormones including estrogen and progesterone ameliorate cognitive function against various central nervous system disorders. Moreover, recent studies demonstrate a neuroprotective role against methamphetamine toxicity. In current study the effects of estrogen and progesterone alone or in combination, on spatial learning and memory in METH-exposed ovariectomized (OVX) rats are investigated. Three weeks after ovariectomy, the animals were treated by estrogen (1mg/kg, i.p.) and progesterone (8mg/kg, i.p.) alone and in combination or vehicle during 14 consecutive days. On the 28th day, rats were exposed to a single-day METH regimens (four injections of 6mg/kg, s.c, at 2h intervals) 30min after the hormones treatment. Finally, spatial learning and memory were examined using the Morris water maze 2days after the last treatment. The findings showed that estrogen and progesterone did not have significant effect on spatial learning and memory in non METH-exposed OVX rats. The treatment with estrogen and progesterone alone in METH-exposed rats, significantly improved spatial learning and memory impairment. On the other hand, the cognitive performance of animals that received combination of estrogen plus progesterone in METH-exposed rats did not significantly differ from that of METH-exposed animals that received vehicle injections. Taken together, the present findings suggest that treatment with ovarian hormones can partially improve spatial learning and memory deficits induced by methamphetamine in OVX rats. PMID:26944454

  8. Effects of treatment with estrogen and progesterone on the methamphetamine-induced cognitive impairment in ovariectomized rats.

    PubMed

    Ghazvini, Hamed; Khaksari, Mohammad; Esmaeilpour, Khadijeh; Shabani, Mohammad; Asadi-Shekaari, Majid; Khodamoradi, Mehdi; Sheibani, Vahid

    2016-04-21

    Methamphetamine (METH) is one of the most powerful psychostimulant that leads to long lasting cognitive impairment. Earlier researches demonstrated that ovarian hormones including estrogen and progesterone ameliorate cognitive function against various central nervous system disorders. Moreover, recent studies demonstrate a neuroprotective role against methamphetamine toxicity. In current study the effects of estrogen and progesterone alone or in combination, on spatial learning and memory in METH-exposed ovariectomized (OVX) rats are investigated. Three weeks after ovariectomy, the animals were treated by estrogen (1mg/kg, i.p.) and progesterone (8mg/kg, i.p.) alone and in combination or vehicle during 14 consecutive days. On the 28th day, rats were exposed to a single-day METH regimens (four injections of 6mg/kg, s.c, at 2h intervals) 30min after the hormones treatment. Finally, spatial learning and memory were examined using the Morris water maze 2days after the last treatment. The findings showed that estrogen and progesterone did not have significant effect on spatial learning and memory in non METH-exposed OVX rats. The treatment with estrogen and progesterone alone in METH-exposed rats, significantly improved spatial learning and memory impairment. On the other hand, the cognitive performance of animals that received combination of estrogen plus progesterone in METH-exposed rats did not significantly differ from that of METH-exposed animals that received vehicle injections. Taken together, the present findings suggest that treatment with ovarian hormones can partially improve spatial learning and memory deficits induced by methamphetamine in OVX rats.

  9. Regional brain glucose metabolism and blood flow in streptozocin-induced diabetic rats

    SciTech Connect

    Jakobsen, J.; Nedergaard, M.; Aarslew-Jensen, M.; Diemer, N.H. )

    1990-04-01

    Brain regional glucose metabolism and regional blood flow were measured from autoradiographs by the uptake of ({sup 3}H)-2-deoxy-D-glucose and ({sup 14}C)iodoantipyrine in streptozocin-induced diabetic (STZ-D) rats. After 2 days of diabetes, glucose metabolism in the neocortex, basal ganglia, and white matter increased by 34, 37, and 8%, respectively, whereas blood flow was unchanged. After 4 mo, glucose metabolism in the same three regions was decreased by 32, 43, and 60%. This reduction was paralleled by a statistically nonsignificant reduction in blood flow in neocortex and basal ganglia. It is suggested that the decrease of brain glucose metabolism in STZ-D reflects increased ketone body oxidation and reduction of electrochemical work.

  10. Pyrrolizidine alkaloids from Symphytum officinale L. and their percutaneous absorption in rats.

    PubMed

    Brauchli, J; Lüthy, J; Zweifel, U; Schlatter, C

    1982-09-15

    An analysis of a commercial sample of Symphyti radix originating from Poland with a total alkaloid content of 0.07% revealed the presence of 7 pyrrolizidine alkaloid-N-oxides: 7-acetyl intermedine, 7-acetyl lycopsamine as the main constituents and lycopsamine, intermedine, symphytine and traces of 2 further not yet identified alkaloids. The percutaneous absorption of these alkaloids was investigated in rats, using a crude alcoholic extract of the plant corresponding to a dose of 194 mg alkaloid-N-oxides/kg b.wt. The excretion of N-oxides in the urine during 2 days was in the range of 0.1-0.4% of the dose. The dermally absorbed N-oxides are not or only to a small extent converted to the free alkaloids in the organism. The oral application led to a 20-50 times higher excretion of N-oxides and free alkaloids in the urine. PMID:7128756

  11. Effect of consecutive cooling and immobilization on catecholamine metabolism in rat tissues

    NASA Technical Reports Server (NTRS)

    Matlina, E. S.; Waysman, S. M.; Zaydner, I. G.; Kogan, B. M.; Nozdracheva, L. V.

    1979-01-01

    The combined effect of two stressor stimuli--cooling and immobilization--acting successively on the sympathetic-adrenaline system was studied experimentally in rats that were cooled for 8 hours at 7 C on the first day and immobilized for 6 hours on the next day. The biochemical and histochemical methods used and the experimental technique involved are described in detail. The following conclusions were formulated: (1) the successive action of cooling and immobilization results in a stronger decrease in the adrenaline and noradrenaline content in the adrenal gland than that which could be due to a simple summation of the cooling and immobilization effects; (2) successive cooling and immobilization are followed by activation of catecholamine synthesis in the adrenal gland; and (3) 1-DOPA administration (45 mg/kg 3 times in 2 days) intraabdominally activated catecholamine synthesis in the adrenal glands in both the control and test animals.

  12. Nephrotoxic effects on offspring of rats chronically treated with mercuric chloride

    SciTech Connect

    Rusk, T.L.

    1983-08-01

    Repeated subcutaneous injections of HgCl/sub 2/ at a dose of either 4.0 or 2.0 mg/kg produced toxic effects in rats when administered during the last 9 days of gestation. Females exhibited diarrhea, anorexia and weight loss of varying severity. Maternal renal function was monitored by urinalysis and was shown to be impaired during the early days of treatment but returned to normal later. Histological evaluation of adult kidneys after 2 days of treatment demonstrated the nephrotoxic effects of HgCl/sub 2/. Evidence of the regenerative process was found in tubules lined with densely packed, flattened cuboidal epithelial cells. Pup birth weight among HgCl/sub 2/-exposed litters was significantly lower than that of control litters. Nephrotoxic effects were not identifiable in pups though the presence of mercury was confirmed in fetal kidneys. 93 refs., 7 figs., 3 tabs.

  13. Consequences of repeated ethanol exposure during early or late adolescence on conditioned taste aversions in rats.

    PubMed

    Saalfield, Jessica; Spear, Linda

    2015-12-01

    Alcohol use is prevalent during adolescence, yet little is known about possible long-lasting consequences. Recent evidence suggests that adolescents are less sensitive than adults to ethanol's aversive effects, an insensitivity that may be retained into adulthood after repeated adolescent ethanol exposure. This study assessed whether intermittent ethanol exposure during early or late adolescence (early-AIE or late-AIE, respectively) would affect ethanol conditioned taste aversions 2 days (CTA1) and >3 weeks (CTA2) post-exposure using supersaccharin and saline as conditioning stimuli (CS), respectively. Pair-housed male Sprague-Dawley rats received 4g/kg i.g. ethanol (25%) or water every 48 h from postnatal day (P) 25-45 (early AIE) or P45-65 (late AIE), or were left non-manipulated (NM). During conditioning, 30 min home cage access to the CS was followed by 0, 1, 1.5, 2 or 2.5g/kg ethanol i.p., with testing 2 days later. Attenuated CTA relative to controls was seen among early and late AIE animals at both CTA1 and CTA2, an effect particularly pronounced at CTA1 after late AIE. Thus, adolescent exposure to ethanol was found to induce an insensitivity to ethanol CTA seen soon after exposure and lasting into adulthood, and evident with ethanol exposures not only early but also later in adolescence.

  14. Male-specific suppression of hepatic microsomal UDP-glucuronosyl transferase activities toward sex hormones in the adult male rat administered bisphenol A.

    PubMed Central

    Shibata, Noriaki; Matsumoto, Junya; Nakada, Ken; Yuasa, Akira; Yokota, Hiroshi

    2002-01-01

    Various adverse effects of endocrine disruptors on the reproductive organs of male animals have been reported. We found that UDP-glucuronosyltransferase (UGT) activities towards bisphenol A, testosterone and oestradiol were significantly decreased in liver microsomes prepared from adult male Wistar rats administered with the endocrine disruptor bisphenol A (1 mg/2 days for 2 or 4 weeks). However, suppression of the transferase activities was not observed in female rats, even after bisphenol A treatment for 4 weeks. Diethylstilbestrol, which is well known as an endocrine disruptor, had the same effects, but p -cumylphenol had no effect on UGT activities towards sex hormones. Co-administration of an anti-oestrogen, tamoxifen, inhibited the suppression of the transferase activities by bisphenol A. Western blotting analysis showed that the amount of UGT2B1, an isoform of UGT which glucuronidates bisphenol A, was decreased in the rat liver microsomes by the treatment. Northern blotting analysis also indicated that UGT2B1 mRNA in the liver was decreased by bisphenol A treatment. The suppression of UGT activities, UGT2B1 protein and UGT2B1 mRNA expression did not occur in female rats. The results indicate that bisphenol A treatment reduces the mRNA expression of UGT2B1 and other UGT isoforms that mediate the glucuronidation of sex hormones in adult male rats, and this suggests that the endocrine balance may be disrupted by suppression of glucuronidation. PMID:12230427

  15. Beta-endorphin in genetically hypoprolactinemic rat: IPL nude rat

    SciTech Connect

    Cohen, H.; Sabbagh, I.; Abou-Samra, A.B.; Bertrand, J.

    1986-01-20

    Beta-endorphin has been reported to regulate not only stress- and suckling-induced but also basal prolactin secretion. In the aim to better evaluate the endogenous beta-endorphin-prolactin interrelation, the authors measured beta-endorphin levels in a new rat strain, genetically hypoprolactinemic and characterized by a total lack of lactation: IPL nude rat. Beta-endorphin was measured using a specific anti-h-..beta.. endorphin in plasma and extracts of anterior and neurointermediate lobes of the pituitary, hypothalamus and brain. Pituitary extracts were also chromatographed on Sephadex G50 column. Results obtained showed that in IPL nude females on diestrus and males, the beta-endorphin contents of the neurointermediate lobe was significantly lower than in normal rats, while the values found in the other organs and plasma were similar. However, elution pattern of the anterior pituitary extracts from male rats showed greater immunoactivity eluting as I/sup 125/ h-beta-endorphin than in normal rat; this was not the case for the female rat. These results are consistent with a differential regulation of beta-endorphin levels of anterior and neurointermediate lobe by catecholamines. Moreover they suggest that PRL secretion was more related to neurointermediate beta-endorphin. 40 references, 2 figures, 4 tables.

  16. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver

    PubMed Central

    Ballard, F. J.; Hanson, R. W.

    1967-01-01

    1. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase were measured in foetal, newborn and adult rat liver extracts by a radiochemical assay involving the fixation of [14C]bicarbonate. 2. Pyruvate-carboxylase activity in both foetal and adult liver occurs mainly in mitochondrial and nuclear fractions, with about 10% of the activity in the cytoplasm. 3. Similar studies of the intracellular distribution of phosphoenolpyruvate carboxykinase show that more than 90% of the activity is in the cytoplasm. However, in the 17-day foetal liver about 90% of the activity is in mitochondria and nuclei. 4. Pyruvate-carboxylase activity in both particulate and soluble fractions is very low in the 17-day foetal liver and increases to near adult levels before birth. 5. Phosphoenolpyruvate-carboxykinase activity in the soluble cell fraction increases 25-fold in the first 2 days after birth. This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. 6. Kinetic and other studies on the properties of phosphoenolpyruvate carboxykinase have shown no differences between the soluble and mitochondrial enzymes. 7. It is suggested that the appearance of the soluble phosphoenolpyruvate carboxykinase at birth initiates the rapid increase in overall gluconeogenesis at this stage. PMID:6049928

  17. Transcriptome profiling of the rat retina after optic nerve transection

    PubMed Central

    Yasuda, Masayuki; Tanaka, Yuji; Omodaka, Kazuko; Nishiguchi, Koji M.; Nakamura, Orie; Tsuda, Satoru; Nakazawa, Toru

    2016-01-01

    Glaucoma is a group of eye diseases characterized by alterations in the contour of the optic nerve head (ONH), with corresponding visual field defects and progressive loss of retinal ganglion cells (RGCs). This progressive RGC death is considered to originate in axonal injury caused by compression of the axon bundles in the ONH. However, the molecular pathomechanisms of axonal injury-induced RGC death are not yet well understood. Here, we used RNA sequencing (RNA-seq) to examine transcriptome changes in rat retinas 2 days after optic nerve transection (ONT), and then used computational techniques to predict the resulting alterations in the transcriptional regulatory network. RNA-seq revealed 267 differentially expressed genes after ONT, 218 of which were annotated and 49 unannotated. We also identified differentially expressed transcripts, including potentially novel isoforms. An in silico pathway analysis predicted that CREB1 was the most significant upstream regulator. Thus, this study identified genes and pathways that may be involved in the pathomechanisms of axonal injury. We believe that our data should serve as a valuable resource to understand the molecular processes that define axonal injury-driven RGC death and to discover novel therapeutic targets for glaucoma. PMID:27353354

  18. The effects of chronic alcohol consumption and exercise on the skeleton of adult male rats

    NASA Technical Reports Server (NTRS)

    Reed, Adam H.; McCarty, Heidi L.; Evans, Glenda L.; Turner, Russell T.; Westerlind, Kim C.

    2002-01-01

    BACKGROUND: Lifestyle factors are known to affect skeletal development and integrity. Specifically, running has been reported to increase risk of fatigue fractures, whereas chronic alcohol consumption has been shown to reduce bone formation and bone mass. The combined effect of exercise and alcohol on the skeleton has yet to be explored, although alcohol consumption is common among certain physically active populations (e.g., military recruits, college athletes). It was hypothesized that chronic alcohol consumption would accentuate the inherent risk associated with endurance running exercise. METHODS: Six-month-old male Sprague Dawley rats were assigned to one of five groups: baseline, exercise-alcohol diet, exercise-normal diet, sham-alcohol diet, and sham-normal diet. Alcohol-fed rats (35% caloric intake) received a liquid diet ad libitum. Normal animals were pair-fed the identical diet with a maltose dextrin caloric substitute. Exercise was conducted on a motorized treadmill 5 days/wk for 16 weeks. Sham rats were placed on a stationary treadmill for matching time periods. Fluorochrome labels were administered 3 days before baseline and at 10 and 2 days before animals were killed. Heart, soleus, and rectus femoris muscles were wet weighed to assess the effects of training. Tibiae were collected for static and dynamic histomorphometric measurements on cancellous and cortical bone. RESULTS: Muscle weights were larger in the exercised rats versus the sham rats. Alcohol had no significant effect on skeletal muscle weight but did result in larger heart weights in both alcohol-treated groups. Cancellous and periosteal bone formation rates were significantly decreased in the alcohol-fed rats versus rats on the normal diet and were associated with a significant reduction in trabecular thickness in the tibial metaphysis. Cortical and cross-sectional areas were also significantly lower in the alcohol-fed groups compared with the non-alcohol-fed groups. Exercise had no

  19. Hormonal changes in antiorthostatic rats

    NASA Technical Reports Server (NTRS)

    Popovic, V.; Popovic, P.; Honeycutt, C.

    1982-01-01

    Hypokinesia, especially hypokinesia with negative tilt ('antiorthostatic hypokinesia'), mimics some of the effects of weightlessness. It is shown that cardiac output is increased during early exposure of rats to antiorthostatic hypokinesia. The increase of the stroke volume and of the cardiac output observed in the antiorthostatic hypokinetic rats is probably the consequence of a blood volume shift toward the chest brought forth by head-down positioning of the animals. It is also possible that struggling of the animals to escape from the harness and an increased metabolism contribute to the elevation of cardiac output. In order to study this hypothesis 'stress hormones' were measured in the antiorthostatic rats. Plasma levels of ACTH, corticosterone and prolactin were measured in the arterial blood (0.3 ml) sampled before, during and after hypokinesia from chronic aortic cannulas of the rats.

  20. Autoshaping in micrencephalic rats

    SciTech Connect

    Goldstein, L.H.; Oakley, D.A.

    1989-06-01

    An autoshaping procedure in which the illumination of a lever was predictive of food reinforcement was used to compare learning in rats with micrencephaly induced by irradiation on the 16th day of gestation and in sham-irradiated controls. Both groups showed equivalent levels of lever-directed activity, and the micrencephalic animals differentiated as well as the control animals between the predictive lever and a nonpredictive lever. The micrencephalic animals were able to redistribute their lever-directed activity when the significance of the levers was reversed and did so more readily than the control animals. Results support the claim that association learning survives either traumatic or developmental neocortical damage and have implications for remedial procedures following both head injury and developmental cerebral pathology in humans.

  1. Do infant rats cry?

    PubMed

    Blumberg, M S; Sokoloff, G

    2001-01-01

    In the current revival of interest in the emotional and mental lives of animals, many investigators have focused attention on mammalian infants that emit distress vocalizations when separated from the home environment. Perhaps the most intensively studied distress vocalization is the ultrasonic vocalization of infant rats. Since its discovery, this vocalization has been interpreted both as a communicatory signal for the elicitation of maternal retrieval and as the manifestation of emotional distress. In contrast, the authors examined the cardiovascular causes and consequences of the vocalization, and on the basis of this work, they hypothesized that the vocalization is the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that results in increased venous return to the heart. Therefore, the vocalization may be analogous to a sneeze, serving a physiological function while incidentally producing sound. PMID:11212634

  2. Signal detection in the rat.

    PubMed

    HACK, M H

    1963-02-22

    An auditory detection experiment was performed with rats as subjects, and the data were analyzed with a signal detection model. Rats were run at fixed sound pressure levels, and their responses were partitioned so that operating characteristics could be constructed. Measures of detectability, (d(e))((1/2)), were calculated from the operating characteristics, and show that (d(e))((1/2)) is a function of sound pressure levels, rising as these levels rise.

  3. Senescence-accelerated OXYS rats

    PubMed Central

    Stefanova, Natalia A; Kozhevnikova, Oyuna S; Vitovtov, Anton O; Maksimova, Kseniya Yi; Logvinov, Sergey V; Rudnitskaya, Ekaterina A; Korbolina, Elena E; Muraleva, Natalia A; Kolosova, Nataliya G

    2014-01-01

    Senescence-accelerated OXYS rats are an experimental model of accelerated aging that was established from Wistar stock via selection for susceptibility to cataractogenic effects of a galactose-rich diet and via subsequent inbreeding of highly susceptible rats. Currently, we have the 102nd generation of OXYS rats with spontaneously developing cataract and accelerated senescence syndrome, which means early development of a phenotype similar to human geriatric disorders, including accelerated brain aging. In recent years, our group found strong evidence that OXYS rats are a promising model for studies of the mechanisms of brain aging and neurodegenerative processes similar to those seen in Alzheimer disease (AD). The manifestation of behavioral alterations and learning and memory deficits develop since the fourth week of age, i.e., simultaneously with first signs of neurodegeneration detectable on magnetic resonance imaging and under a light microscope. In addition, impaired long-term potentiation has been demonstrated in OXYS rats by the age of 3 months. With age, neurodegenerative changes in the brain of OXYS rats become amplified. We have shown that this deterioration happens against the background of overproduction of amyloid precursor protein (AβPP), accumulation of β-amyloid (Aβ), and hyperphosphorylation of the tau protein in the hippocampus and cortex. The development of AMD-like retinopathy in OXYS rats is also accompanied by increased accumulation of Aβ in the retina. These published data suggest that the OXYS strain may serve as a spontaneous rat model of AD-like pathology and could help to decipher the pathogenesis of AD. PMID:24552807

  4. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS.

    PubMed

    Loth, Eduardo Alexandre; Cecatto, Vanessa; Biazim, Samia Khalil; Ferreira, José Henrique Fermino; Danielli, Caroline; Genske, Rodrigo Daniel; Gandra, Rinaldo Ferreira; Franco, Marcello Fabiano de

    2015-12-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring.

  5. EXPERIMENTAL PARACOCCIDIOIDOMYCOSIS IN PREGNANT RATS

    PubMed Central

    LOTH, Eduardo Alexandre; CECATTO, Vanessa; BIAZIM, Samia Khalil; FERREIRA, José Henrique Fermino; DANIELLI, Caroline; GENSKE, Rodrigo Daniel; GANDRA, Rinaldo Ferreira; de FRANCO, Marcello Fabiano

    2015-01-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb), is the most prevalent systemic mycosis in Latin America. There are few reports in the literature about the disease damages during pregnancy and the consequences to the fetuses and breeding. This study evaluated the implications of PCM during pregnancy on offspring and mothers in Wistar rats. Groups of rats were submitted to systemic Pb infection, by intraperitoneal infusion, and mated 30 days after the infection date. Immediately after birth, rats and neonates were sacrificed to obtain organs for standard histological examination, morphometric analysis, fungi recovery by plating (CFU) and dosing of anti-Pb antibodies by ELISA. There were no stillbirths or miscarriages, however, the fetuses from infected pregnant rats had lower body and organ weight but the fertility rate was 100%. The largest number of CFU was recovered from the organ of pregnant rats, the pathological examination revealed more severe infection in the same group, further on the largest number of granulomas and fungal field. It can be concluded that the PCM was more severe in the group of pregnant rats, with implications to the weight of offspring. PMID:27049707

  6. Alterations in structure of elastic laminae of rat pulmonary arteries in hypoxic hypertension.

    PubMed

    Liu, S Q

    1996-11-01

    The effect of hypoxic hypertension on the remodeling process of the elastic laminae of the rat hilar pulmonary arteries (PAs) was studied by electron microscopy. Rats were exposed to hypoxia (10% O2) for periods of 0.5, 2,6,12,48,96,144, and 240 h. Changes in the structure of the PA elastic laminae were examined and analyzed with respect to changes in the PA wall tensile stress. The PA blood pressure increased rapidly within the first several hours of hypoxia and reached a stable level within 2 days, whereas the PA wall tensile stress increased initially due to elevated blood pressure and then decreased after 48 h due to vessel wall thickening and returned to the control level after 4 days. In association with these changes, the elastic laminae, which appeared homogeneous in normal control rats, changed into structures composed of randomly oriented filaments and edematous contents with an increase in the volume during the early period of hypoxia and regained their homogeneous appearance and normal volume after 4 days. The changes in the elastic laminae were correlated with changes in the tensile stress. These changes were associated with a transient decrease in the stiffness of the PAs. In hypoxic rats given nifedipine, no change was found in the blood pressure, the tensile stress, or the structure of the elastic laminae of the PAs despite continuous exposure to hypoxia. These results suggested that altered tensile stress in the PA wall played a critical role in the initiation and regulation of structural changes in the elastic laminae and that these changes might contribute to alterations in the mechanical properties of the PA in hypoxic hypertension. PMID:8941540

  7. Gender differences in organ density in a rat simulated microgravity model

    NASA Astrophysics Data System (ADS)

    Pettis, Christopher Ryan; Witten, Mark Lee

    2004-01-01

    Research investigating the physiological effects of microgravity on the human body has demonstrated a shift of body fluids in actual spaceflight and in simulated Earth-based microgravity models in both males and females, possibly causing many deleterious physiological effects. Twenty-five anatomically normal female (NF) and 20 ovariectomized (OE) Fischer 344 rats were randomly selected to be in an experimental ( 1 h of 45° head-down tilt, 45HDT) or control ( 1 h of prone position) group. At the end of the hour experimental period, the density of the brain, lungs, heart, liver, and left and right kidneys were measured using spiral computed tomography (SCT) while the rats remained in their experimental positions. A sub-group of OE rats ( N=6) was administered estrogen replacement therapy on a daily basis ( 5 μg/kg body weight, s.c.) for 4 days and then underwent 1 h of 45HDT and SCT analysis at one day, 2 days, and 5 days to determine if estrogen replacement therapy would alter organ densities. Our data demonstrate that 1 h of 45HDT produced significant increases ( p<0.05) in the organ densities of the brain, liver, left kidney, and lung of the OE female group compared to their prone controls. However, only the brain density was significantly increased in the NF group. Estrogen replacement therapy caused a significant decrease in brain organ density at the 5 day time point compared to the 24 h time point. We conclude that estrogen plays a role in fluid distribution in a rat 45HDT model.

  8. REM sleep changes in rats induced by siRNA-mediated orexin knockdown.

    PubMed

    Chen, Lichao; Thakkar, Mahesh M; Winston, Stuart; Bolortuya, Yunren; Basheer, Radhika; McCarley, Robert W

    2006-10-01

    Short interfering RNAs (siRNA) targeting prepro-orexin mRNA were microinjected into the rat perifornical hypothalamus. Prepro-orexin siRNA-treated rats had a significant (59%) reduction in prepro-orexin mRNA compared to scrambled siRNA-treated rats 2 days postinjection, whereas prodynorphin mRNA was unaffected. The number of orexin-A-positive neurons on the siRNA-treated side decreased significantly (23%) as compared to the contralateral control (scrambled siRNA-treated) side. Neither the colocalized dynorphin nor the neighbouring melanin-concentrating hormone neurons were affected. The number of orexin-A-positive neurons on the siRNA-treated side did not differ from the number on the control side 4 or 6 days postinjection. Behaviourally, there was a persistent (approximately 60%) increase in the amount of time spent in rapid eye movement (REM) sleep during the dark (active) period for 4 nights postinjection, in rats treated with prepro-orexin siRNA bilaterally. This increase occurred mainly because of an increased number of REM episodes and decrease in REM-to-REM interval. Cataplexy-like episodes were also observed in some of these animals. Wakefulness and NREM sleep were unaffected. The siRNA-induced increase in REM sleep during the dark cycle reverted to control values on the 5th day postinjection. In contrast, the scrambled siRNA-treated animals only had a transient increase in REM sleep for the first postinjection night. Our results indicate that siRNA can be usefully employed in behavioural studies to complement other loss-of-function approaches. Moreover, these data suggest that the orexin system plays a role in the diurnal gating of REM sleep.

  9. Effect of global and regional sympathetic blockade on arterial pressure during water deprivation in conscious rats

    PubMed Central

    Veitenheimer, Britta J.; Engeland, William C.; Guzman, Pilar A.; Fink, Gregory D.

    2012-01-01

    Forty-eight hours of water deprivation (WD) in conscious rats results in a paradoxical increase in mean arterial pressure (MAP). Previous studies suggest this may be due to increased sympathetic nerve activity (SNA). However, this remains to be investigated in conscious, freely behaving animals. The purpose of this study was to determine, in conscious rats, the role of the sympathetic nervous system (SNS) in mediating WD-induced increases in MAP and to identify which vascular beds are targeted by increased SNA. Each rat was chronically instrumented with a radiotelemetry transmitter to measure MAP and heart rate (HR) and an indwelling venous catheter for plasma sampling and/or drug delivery. MAP and HR were continuously measured during a 2-day baseline period followed by 48 h of WD and then a recovery period. By the end of the WD period, MAP increased by ∼15 mmHg in control groups, whereas HR did not change significantly. Chronic blockade of α1/β1-adrenergic receptors significantly attenuated the WD-induced increase in MAP, suggesting a role for global activation of the SNS. However, the MAP response to WD was unaffected by selective denervations of the hindlimb, renal, or splanchnic vascular beds, or by adrenal demedullation. In contrast, complete adrenalectomy (with corticosterone and aldosterone replaced) significantly attenuated the MAP response to WD in the same time frame as α1/β1-adrenergic receptor blockade. These results suggest that, in conscious water-deprived rats, the SNS contributes to the MAP response and may be linked to release of adrenocortical hormones. Finally, this sympathetically mediated response is not dependent on increased SNA to one specific vascular bed. PMID:22904160

  10. Hippocampal angiotensin II receptors play an important role in mediating the effect of voluntary exercise on learning and memory in rat.

    PubMed

    Akhavan, Maziar M; Emami-Abarghoie, Mitra; Sadighi-Moghaddam, Bizhan; Safari, Manouchehr; Yousefi, Yasaman; Rashidy-Pour, Ali

    2008-09-26

    The beneficial effects of physical activity and exercise on brain functions such as improvement in learning and memory are well documented. The aim of this study was to examine the possible role of hippocampal angiotensin II receptors in voluntary exercise-induced enhancement of learning and memory in rat. In order to block the hippocampal angiotension II receptors, the animals received a single injection of latex microbeads for delivery of [Sar1 Thr8]-Angiotensin II into the hippocampus. The animals were exposed to five consecutive nights of exercise and then their learning and memory were tested on the Morris water maze (MWM) task using a two-trial-per-day for five consecutive days. A probe trial was performed 2 days after the last training day. Our results showed that hippocampal angiotensin II receptor blockade reversed the exercise-induced improvement in learning and memory in rat.

  11. ESTROGEN AND AGING AFFECT THE SYNAPTIC DISTRIBUTION OF ESTROGEN RECEPTOR BETA-IMMUNOREACTIVITY IN THE CA1 REGION OF FEMALE RAT HIPPOCAMPUS

    PubMed Central

    Waters, Elizabeth M.; Yildirim, Murat; Janssen, William G.M.; Lou, W.Y. Wendy; McEwen, Bruce S.; Morrison, John H.; Milner, Teresa A.

    2010-01-01

    Estradiol (E) mediates increased synaptogenesis in the hippocampal CA1 stratum radiatum (sr) and enhances memory in young and some aged female rats, depending on dose and age. Young females rats express more estrogen receptor α (ERα) immunolabeling in CA1sr spine synapse complexes than aged rats and ERα regulation is E sensitive in young but not aged rats. The current study examined whether estrogen receptor β (ERβ) expression in spine synapse complexes may be altered by age or E treatment. Young (3–4 months) and aged (22–23 months) female rats were ovariectomized 7 days prior to implantation of silastic capsules containing either vehicle (cholesterol) or E (10% in cholesterol) for 2 days. ERβ immunoreactivity (ir) in CA1sr was quantitatively analyzed using post-embedding electron microscopy. ERβ-ir was more prominent postsynaptically than presynaptically and both age and E treatment affected its synaptic distribution. While age decreased the spine synaptic complex localization of ERβ-ir (i.e., within 60 nm of the pre- and post-synaptic membranes), E treatment increased synaptic ERβ in both young and aged rats. In addition, the E treatment, but not age, increased dendritic shaft labeling. This data demonstrates that like ERα the levels of ERβ-ir decrease in CA1 axospinous synapses with age, however, unlike ERα the levels of ERβ-ir increase in these synapses in both young and aged rats in response to E. This suggests that synaptic ERβ may be a more responsive target to E, particularly in aged females. PMID:20875808

  12. Role of glutathione in lung retention of 99mTc-hexamethylpropyleneamine oxime in two unique rat models of hyperoxic lung injury.

    PubMed

    Audi, Said H; Roerig, David L; Haworth, Steven T; Clough, Anne V

    2012-08-15

    Rat exposure to 60% oxygen (O(2)) for 7 days (hyper-60) or to >95% O(2) for 2 days followed by 24 h in room air (hyper-95R) confers susceptibility or tolerance, respectively, of the otherwise lethal effects of subsequent exposure to 100% O(2). The objective of this study was to determine if lung retention of the radiopharmaceutical agent technetium-labeled-hexamethylpropyleneamine oxime (HMPAO) is differentially altered in hyper-60 and hyper-95R rats. Tissue retention of HMPAO is dependent on intracellular content of the antioxidant GSH and mitochondrial function. HMPAO was injected intravenously in anesthetized rats, and planar images were acquired. We investigated the role of GSH in the lung retention of HMPAO by pretreating rats with the GSH-depleting agent diethyl maleate (DEM) prior to imaging. We also measured GSH content and activities of mitochondrial complexes I and IV in lung homogenate. The lung retention of HMPAO increased by ≈ 50% and ≈ 250% in hyper-60 and hyper-95R rats, respectively, compared with retention in rats exposed to room air (normoxic). DEM decreased retention in normoxic (≈ 26%) and hyper-95R (≈ 56%) rats compared with retention in the absence of DEM. GSH content increased by 19% and 40% in hyper-60 and hyper-95R lung homogenate compared with normoxic lung homogenate. Complex I activity decreased by ≈ 50% in hyper-60 and hyper-95R lung homogenate compared with activity in normoxic lung homogenate. However, complex IV activity was increased by 32% in hyper-95R lung homogenate only. Furthermore, we identified correlations between the GSH content in lung homogenate and the DEM-sensitive fraction of HMPAO retention and between the complex IV/complex I activity ratio and the DEM-insensitive fraction of HMPAO retention. These results suggest that an increase in the GSH-dependent component of the lung retention of HMPAO may be a marker of tolerance to sustained exposure to hyperoxia.

  13. Effect of vasopressin on the expression of genes for key enzymes of hyaluronan turnover in Wistar Albino Glaxo and Brattleboro rat kidneys.

    PubMed

    Ivanova, Lyudmila N; Babina, Alina V; Baturina, Galina S; Katkova, Lyubov E

    2013-11-01

    Hyaluronan (HA), the major glycosaminoglycan of the interstitial matrix, is heterogeneously distributed within the kidney. Using real-time RT-PCR, we tested the assumption that renal HA may be involved in the long-term effect of vasopressin on water reabsorption. The expression of the genes encoding hyaluronan synthase-2 (Has2), hyaluronidase-1 and hyaluronidase-2 (Hyal1 and Hyal2) was studied in the kidneys of Wistar Albino Glaxo (WAG) and homozygous vasopressin-deficient Brattleboro rats treated with the V2 receptor-selective vasopressin analogue dDAVP (100 μg (kg body wt)(-1), i.p., twice a day for 2 days). The Has2 mRNA content was the highest in the kidney papilla of the hydrated WAG and control Brattleboro rats, devoid of vasopressin. In WAG rats, dDAVP induced a considerable decrease in Has2 mRNA content in the papilla, with less pronounced changes in the cortex. The changes elicited by dDAVP in Brattleboro rats tended to be the same as in WAG rats, but weaker. In contrast to Has2, dDAVP treatment caused a significant increase in the Hyal1 and Hyal2 mRNA content in the renal papilla of WAG and Brattleboro rats. In rats of both strains, there was a good fit between Hyal1 and Hyal2 transcriptional levels and changes in hyaluronidase activity in the renal tissue. It is suggested that vasopressin is able to inhibit the synthesis of HA and concomitantly promote its degradation in the interstitium of the renal papilla, thereby facilitating water flow between elements of the renal countercurrent system. The implications for this effect are discussed in the context of the data in the literature.

  14. The effects of prostaglandin F2alpha treatment on peripheral-type benzodiazepine receptors in the ovary and uterus during pseudopregnancy of rats.

    PubMed

    Bar-Ami, Shalom; Bendel, Nachum; Leschiner, Svetlana; Levin, Evgeny; Veenman, Leo; Gavish, Moshe

    2006-02-14

    A previous study by us indicated that peripheral-type benzodiazepine receptor (PBR) density may be increased in the ovaries and uterus of pregnant rats (Weizman R, Dagan E, Snyder SH, Gavish M. Impact of pregnancy and lactation on GABAA receptor and central-type and peripheral-type benzodiazepine receptors. Brain Res 1997;752:7-14). In the present study, the effects of prostaglandin F2alpha (PGF2alpha) on PBR density in the ovary and uterus of pseudopregnant rats were assayed. Pseudopregnancy was induced on day 29 post-partum (PP) by s.c. injection of 50IU pregnant mare serum gonadotropin (PMSG) and 3 days later by s.c. injection of 20IU human chorionic gonadotropin (hCG). PBR ligand binding density was assayed with the specific PBR ligand [3H]PK 11195. A two-fold increase in ovarian PBR density was observed 2 days after hCG administration compared with vehicle control rats and this effect was maintained for 3 weeks. In the uterus, a three-fold increase in PBR density was observed and this increase was maintained for 1 week after hCG administration. Pseudopregnancy did not appear to affect renal PBR density or affinity. Treatment with PGF2alpha, which causes luteolysis, resulted in an approximately 50% reduction of PBR density in the ovaries of pseudopregnant rats at day 53 PP compared to pseudopregnant control rats. Treatment with indomethacin, which prevents the formation of PGF2alpha, caused the PBR density in the uterus of pseudopregnant rats at day 53 PP to be twice as high as in pseudopregnant control rats. All the above treatments did not affect the affinity of [3H]PK 11195 to ovarian and uterine PBR. These data suggest that PBR density in corpora lutea and uterus during pseudopregnancy is regulated by PGF2alpha.

  15. Aging-related impairment of urine-concentrating mechanisms correlates with dysregulation of adrenocortical angiotensin type 1 receptors in male Fischer rats.

    PubMed

    Ji, Hong; Zheng, Wei; Wu, Xie; Speth, Robert C; Verbalis, Joseph G; Stein, Lauren M; Yosten, Gina L C; Samson, Willis K; Sandberg, Kathryn

    2016-03-15

    To investigate age-associated impairments in fluid homeostasis, 4-mo (young) and 32-mo (old) Fischer 344/BN male rats were studied before and after a dietary sodium load. Transferring young rats from a low-sodium (LS) to a high-sodium (HS) diet increased water intake and urine volume by 1.9- and 3.0-fold, respectively, while urine osmolality and plasma aldosterone decreased by 33 and 98%. Concomitantly, adrenocortical angiotensin type 1 receptor (AT1R) density decreased by 35%, and AT1bR mRNA decreased by 39%; no changes were observed in AT1aR mRNA. In contrast, the increase in water intake (1.4-fold) was lower in the old rats, and there was no effect of the HS diet on urine volume or urine osmolality. AT1R densities were 29% less in the old rats before transferring to the HS diet, and AT1R densities were not reduced as rapidly in response to a HS diet compared with the young animals. After 6 days on the HS diet, plasma potassium was lowered by 26% in the old rats, whereas no change was detected in the young rats. Furthermore, while plasma aldosterone was substantially decreased after 2 days on the HS diet in both young and old rats, plasma aldosterone was significantly lower in the old compared with the young animals after 2 wk on the LS diet. These findings suggest that aging attenuates the responsiveness of the adrenocortical AT1R to a sodium load through impaired regulation of AT1bR mRNA, and that this dysregulation contributes to the defects in water and electrolyte homeostasis observed in aging.

  16. False Context Fear Memory in Rats

    ERIC Educational Resources Information Center

    Bae, Sarah; Holmes, Nathan M.; Westbrook, R. Frederick

    2015-01-01

    Four experiments used rats to study false context fear memories. In Experiment 1, rats were pre-exposed to a distinctive chamber (context A) or to a control environment (context C), shocked after a delay in a second chamber (context B) and tested either in B or A. Rats pre-exposed to A froze just as much as control rats in B but more than control…

  17. Effect of indomethacin on capillary growth and microvasculature in chronically stimulated rat skeletal muscles

    PubMed Central

    Pearce, Steven C; Hudlická, Olga; Brown, Margaret D

    2000-01-01

    Capillary proliferation and microvessel diameters were studied in rat ankle flexors subjected to chronic electrical stimulation by implanted electrodes (10 Hz, 0.3 ms pulse width, up to 6 V, 8 h day−1) for 2 or 7 days with or without concurrent indomethacin treatment (≈2 mg day−1 in drinking water) to study the role of prostaglandins in the microcirculation in relation to capillary growth.Diameters of terminal arterioles, capillaries and confluent venules were measured in epi-illuminated muscles, together with capillary red cell velocity, to evaluate whether changes in capillary pressure and/or shear stress participate in capillary growth via release of prostaglandins.Cell proliferation was detected following bromodeoxyuridine (BrdU) incorporation and immuno-staining of frozen sections. Labelling was assessed as the percentage of all interstitial nuclei (Haematoxylin-stained) that were BrdU positive. By comparison with serial sections stained for alkaline phosphatase, from which the capillary-to-fibre ratio (C:F) was obtained, labelling was derived for nuclei colocalised either to capillaries or to other non-capillary interstitial cells.C:F increased to 1.89 ± 0.06 from 1.47 ± 0.04 in controls only after 7 days stimulation; indomethacin reduced this to 1.55 ± 0.07. Capillary labelling increased from 2.9 ± 0.5 % in controls to 11.3 ± 2.2 % after 2 days stimulation and 10.6 ± 0.8 % after 7 days. The increase was attenuated by indomethacin at both time points (to 5.8 ± 1.6 % and 4.2 ± 0.5 %, respectively).Non-capillary interstitial labelling (2.0 ± 0.4 % in controls) increased to 9.5 ± 2.7 % after 2 days stimulation and was back to normal after 7 days (3.2 ± 0.7 %). Indomethacin depressed the increase at 2 days to 4.0 ± 1.3 % and had no effect at 7 days (2.9 ± 0.13 %). Labelling in sham-operated rats with or without indomethacin or in vehicle-treated animals was no different from controls.Arteriolar and venular diameters were increased by 2 days of

  18. Does rat fetal DNA induce preeclampsia in pregnant rats?

    PubMed

    Konečná, B; Borbélyová, V; Celec, P; Vlková, B

    2015-02-01

    Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is unclear whether it is the cause or the consequence of the disease. The aim of this study was to prove whether injected rat fetal DNA induces preeclampsia-like symptoms in pregnant Wistar rats. They received daily i.p. injections of water or rat fetal DNA (400 μg) from gestation day 14 to 18. Blood pressure, proteinuria, placental and fetal weight were measured at gestation day 19. Plasma DNase activity, proteinuria and creatinine clearance were assessed. There was no significant difference in any of the measured parameters. The results of this study do not confirm the hypothesis that fetal DNA might induce preeclampsia. This is in contrast to others using human fetal DNA in mice. Further studies should be focused on the effects of fetal DNA from the same species protected from DNase activity.

  19. Prospective memory in the rat

    PubMed Central

    Wilson, A. George; Crystal, Jonathon D.

    2011-01-01

    The content of prospective memory is comprised of representations of an action to perform in the future. When people form prospective memories, they temporarily put the memory representation in an inactive state while engaging in other activities, and then activate the representation in the future. Ultimately, successful activation of the memory representation yields an action at an appropriate, but temporally distant, time. A hallmark of prospective memory is that activation of the memory representation has a deleterious effect on current ongoing activity. Recent evidence suggests that scrub jays and non-human primates, but not other species, are capable of future planning. We hypothesized that prospective memory produces a selective deficit in performance at the time when rats access a memory representation but not when the memory representation is inactive. Rats were trained in a temporal bisection task (90 min/day). Immediately after the bisection task, half of the rats received an 8-g meal (meal group) and the other rats received no additional food (no-meal group). Sensitivity to time in the bisection task was reduced as the 90-min interval elapsed for the meal group but not for the no-meal group. This time-based prospective-memory effect was not based on response competition, an attentional limit, anticipatory contrast, or fatigue. Our results suggest that rats form prospective memories, which produces a negative side effect on ongoing activity. PMID:21922257

  20. Source memory in the rat

    PubMed Central

    Crystal, Jonathon D.; Alford, Wesley T.; Zhou, Wenyi; Hohmann, Andrea G.

    2013-01-01

    Summary Source memory is a representation of the origin (source) of information. When source information is bound together, it makes a memory episodic, allowing us to differentiate one event from another [1, 2]. Here we asked if rats remember the source of encoded information. Rats foraged for distinctive flavors of food that replenished (or failed to replenish) at its recently encountered location according to a source-information rule. To predict replenishment, rats needed to remember where they had encountered a preferred food type (chocolate) with self-generated (walking along a runway encountering chocolate) or experimenter-generated (placement of the rat at the chocolate site by an experimenter) cues. Three lines of evidence implicate the presence of source memory. First, rats selectively adjusted revisits to the chocolate location based on source information, under conditions in which familiarity of events could not produce successful performance. Second, source memory was dissociated from location memory by different decay rates. Third, temporary inactivation of the CA3 region of the hippocampus with lidocaine selectively eliminated source memory, suggesting that source memory is dependent upon an intact hippocampus. Development of an animal model of source memory may be valuable to probe the biological underpinnings of memory disorders marked by impairments in source memory. PMID:23394830

  1. Tuberculosis Detection by Giant African Pouched Rats

    ERIC Educational Resources Information Center

    Poling, Alan; Weetjens, Bart; Cox, Christophe; Beyene, Negussie; Durgin, Amy; Mahoney, Amanda

    2011-01-01

    In recent years, operant discrimination training procedures have been used to teach giant African pouched rats to detect tuberculosis (TB) in human sputum samples. This article summarizes how the rats are trained and used operationally, as well as their performance in studies published to date. Available data suggest that pouched rats, which can…

  2. Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids

    PubMed Central

    Thiblin, Ingemar; Finn, Anja; Ross, Svante B; Stenfors, Carina

    1999-01-01

    The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. The DOPAC+HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone- and oxymetholone-treated rats, while the 5-HT synthesis rate was not affected by the AAS-treatments. The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were unaffected. The MAO-B activity was not changed. The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems. PMID:10217522

  3. Increased dopaminergic and 5-hydroxytryptaminergic activities in male rat brain following long-term treatment with anabolic androgenic steroids.

    PubMed

    Thiblin, I; Finn, A; Ross, S B; Stenfors, C

    1999-03-01

    1. The effects of treating groups of rats with four different anabolic androgenic steroids (AAS) (testosterone, nandrolone, methandrostenolone, and oxymetholone) on 5-hydroxytryptamine (5-HT) and dopamine (DA) neurones in different brain regions were examined. The AAS was injected six times with 1 week's interval and the rats were sacrificed 2 days after the final injection. 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), DA and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured. The effect on DA and 5-HT synthesis rate was analysed as the accumulation of 3,4-dihydroxyphenyl-alanine (DOPA) and 5-hydroxytryptophan (5-HTP), respectively, after inhibition of the amino acid decarboxylase with NSD-1015 (3-hydroxy-benzylhydrazine dihydrochloride). Additionally, the monoamine oxidase (MAO) activity was analysed in the hypothalamus. 2. The DOPAC + HVA/DA ratio was increased in the striatum in all treatment groups. However, the synthesis rate of DA was significantly increased only in the methandrostenolone treated group. 3. The 5-HIAA/5-HT ratio was increased in all treatment groups in the hippocampus, in the frontal cortex in the methandrostenolone-treated animals and in the hypothalamus in the testosterone- and oxymetholone-treated rats, while the 5-HT synthesis rate was not affected by the AAS-treatments. 4. The MAO-A activity was increased in the oxymetholone-treated rats while the other treatment groups were unaffected. The MAO-B activity was not changed. 5. The results indicate that relatively high doses of AAS increase dopaminergic and 5-hydroxytryptaminergic metabolism in male rat brain, probably due to enhanced turnover in these monaminergic systems. PMID:10217522

  4. Cocaine-induced locomotor sensitization in rats correlates with nucleus accumbens activity on manganese-enhanced MRI.

    PubMed

    Perrine, Shane A; Ghoddoussi, Farhad; Desai, Kirtan; Kohler, Robert J; Eapen, Ajay T; Lisieski, Michael J; Angoa-Perez, Mariana; Kuhn, Donald M; Bosse, Kelly E; Conti, Alana C; Bissig, David; Berkowitz, Bruce A

    2015-11-01

    A long-standing goal of substance abuse research has been to link drug-induced behavioral outcomes with the activity of specific brain regions to understand the neurobiology of addiction behaviors and to search for drug-able targets. Here, we tested the hypothesis that cocaine produces locomotor (behavioral) sensitization that correlates with increased calcium channel-mediated neuroactivity in brain regions linked with drug addiction, such as the nucleus accumbens (NAC), anterior striatum (AST) and hippocampus, as measured using manganese-enhanced MRI (MEMRI). Rats were treated with cocaine for 5 days, followed by a 2-day drug-free period. The following day, locomotor sensitization was quantified as a metric of cocaine-induced neuroplasticity in the presence of manganese. Immediately following behavioral testing, rats were examined for changes in calcium channel-mediated neuronal activity in the NAC, AST, hippocampus and temporalis muscle, which was associated with behavioral sensitization using MEMRI. Cocaine significantly increased locomotor activity and produced behavioral sensitization compared with saline treatment of control rats. A significant increase in MEMRI signal intensity was determined in the NAC, but not AST or hippocampus, of cocaine-treated rats compared with saline-treated control rats. Cocaine did not increase signal intensity in the temporalis muscle. Notably, in support of our hypothesis, behavior was significantly and positively correlated with MEMRI signal intensity in the NAC. As neuronal uptake of manganese is regulated by calcium channels, these results indicate that MEMRI is a powerful research tool to study neuronal activity in freely behaving animals and to guide new calcium channel-based therapies for the treatment of cocaine abuse and dependence.

  5. Hypolipidemic effect of SR‑BI gene delivery by combining cationic liposomal microbubbles and ultrasound in hypercholesterolemic rats.

    PubMed

    Liu, Fang; Zhu, Jiaan; Huang, Yunxia; Guo, Wei; Rui, Mengjie; Xu, Yuhong; Hu, Bing

    2013-06-01

    High-density lipoprotein (HDL) is a key mediator in reverse cholesterol transport and is involved in a mechanism known as 'selective lipid uptake', a process mediated by scavenger receptor B type I (SR‑BI), which is a HDL receptor. The aim of the present study was to investigate the therapeutic effect of the SR‑BI gene when delivered by combining cationic liposomal microbubbles (CLMs) and ultrasound (US) in hypercholesterolemic rats. Hypercholesterolemia was induced by administration of excessive doses of vitamin D3 and cholesterol in rats. The CLMs consisted of perfluoropropane gas encapsulated in a phospholipid shell using the sonication‑lyophilization method. The SR‑BI gene, mixed with the self‑made microbubbles, was transfected into hypercholesterolemic rat arteries using therapeutic US. SR‑BI protein expression was determined by western blot analysis 2 days post-transfection. Two weeks after transfection, total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and HDL serum concentrations were measured. Transfection efficiency of the SR‑BI gene in the SR‑BI + US/CLM group increased 6‑7‑fold compared with the SR‑BI group. Two weeks after transfection, plasma lipid levels in treated hypercholesterolemic rats were observed to be significantly reduced compared with rats that did not receive treatment. However, no significant change was observed in the SR‑BI group compared with that in the SR‑BI + US/CLM group. Results of the present study indicate that the combination of US and CLMs loaded with the SR‑BI gene may exert a protective role in hypercholesterolemia.

  6. Using rats for vision research.

    PubMed

    Reinagel, P

    2015-06-18

    A wide variety of species are used for the study of visual neuroscience. This is beneficial because fundamental mechanisms and theoretical principles of vision are likely to be highly conserved, while different species exhibit different visual capacities and present different technical advantages for experiments. Eight years ago my laboratory adopted the hooded rat as our primary preparation for vision research. To some this may be surprising, as nocturnal rodents have often been presumed to have poor vision and weak visual behavior. This commentary will provide my personal perspective on how I came to work with rats; discuss an example research project for which rats have been advantageous; and comment on the opportunities and challenges of the preparation.

  7. Rats are sensitive to ambiguity.

    PubMed

    Fast, Cynthia D; Blaisdell, Aaron P

    2011-12-01

    In the present study, we investigated response decisions made under conditions of incomplete information in rats. In Experiment 1, rats were trained on either a positive patterning (PP; A-, B-, AB+) or a negative patterning (NP; A+, B+, AB-) instrumental lever-press discrimination. Subjects that had learned an NP discrimination responded less to Cue A when Cue B was covered at test. The cover did not, however, affect test responses to Cue A in the PP condition. In Experiment 2, rats received concurrent training on both PP and NP discriminations. After concurrent training, responses to Cue A were different with B covered versus uncovered for both NP and PP discriminations. We discuss possible accounts for why exposure to a nonlinearly soluble discrimination (NP) may have affected sensitivity to cue ambiguity produced by the cover. These results have interesting implications for representational processes engaged in problem solving.

  8. Identification of Arabidopsis rat Mutants

    PubMed Central

    Zhu, Yanmin; Nam, Jaesung; Humara, Jaime M.; Mysore, Kirankumar S.; Lee, Lan-Ying; Cao, Hongbin; Valentine, Lisa; Li, Jingling; Kaiser, Anthony D.; Kopecky, Andrea L.; Hwang, Hau-Hsuan; Bhattacharjee, Saikat; Rao, Praveen K.; Tzfira, Tzvi; Rajagopal, Jyothi; Yi, HoChul; Veena; Yadav, Badam S.; Crane, Yan M.; Lin, Kui; Larcher, Yves; Gelvin, Matthew J.K.; Knue, Marnie; Ramos, Cynthia; Zhao, Xiaowen; Davis, Susan J.; Kim, Sang-Ic; Ranjith-Kumar, C.T.; Choi, Yoo-Jin; Hallan, Vipin K.; Chattopadhyay, Sudip; Sui, Xiangzhen; Ziemienowicz, Alicja; Matthysse, Ann G.; Citovsky, Vitaly; Hohn, Barbara; Gelvin, Stanton B.

    2003-01-01

    Limited knowledge currently exists regarding the roles of plant genes and proteins in the Agrobacterium tumefaciens-mediated transformation process. To understand the host contribution to transformation, we carried out root-based transformation assays to identify Arabidopsis mutants that are resistant to Agrobacterium transformation (rat mutants). To date, we have identified 126 rat mutants by screening libraries of T-DNA insertion mutants and by using various “reverse genetic” approaches. These mutants disrupt expression of genes of numerous categories, including chromatin structural and remodeling genes, and genes encoding proteins implicated in nuclear targeting, cell wall structure and metabolism, cytoskeleton structure and function, and signal transduction. Here, we present an update on the identification and characterization of these rat mutants. PMID:12805582

  9. Hematopoiesis in antiorthostatic, hypokinesic rats

    NASA Technical Reports Server (NTRS)

    Dunn, C. D. R.; Johnson, P. C.; Lange, R. D.

    1983-01-01

    Rats exposed to antiorthostatic, hypokinesia showed the following effects which are comparable to those seen in man during or after space flight: weight loss, reduced food and water consumption, transient increases in peripheral hematocrit and RBC count, decreasing MCV and reduced reticulocyte count. In addition, the hemoglobin P50 was shifted to the right. A significant shortening of RBC t1/2 was only seen after suspension. Changes in leukocyte and platelet numbers in suspended rats were also comparable to those in man during space flight, but leukocyte PHA sensitivity in rats showed no consistent alteration. The results demonstrate that this model reproduces many of the hematological effects of space flight and has potential as a tool in understanding the hematopoietic response to zero gravity.

  10. Teratology studies in the rat.

    PubMed

    Leroy, Mariline; Allais, Linda

    2013-01-01

    The rat is the rodent species of choice for the regulatory safety testing of xenobiotics, such as medicinal products, food additives, and other chemicals. Many decades of experience and extensive data have accumulated for both general and developmental toxicology investigations in this species. The high fertility and large litter size of the rat are advantages for teratogenicity testing. The study designs are well defined in the regulatory guidelines and are relatively standardized between testing laboratories across the world. Teratology studies address maternal- and embryo-toxicity following exposure during the period of organogenesis. This chapter describes the design and conduct of a teratology study in the rat in compliance with the regulatory guidelines. The procedures for the handling and housing of the pregnant animals, the caesarean examinations and the sampling of fetuses for morphological examinations are described. The utility and design of preliminary studies and the inclusion of satellite animals in the main study for toxicokinetic sampling are discussed.

  11. Potential nephrotoxic effects produced by steroidal saponins from hydro alcoholic extract of Tribulus terrestris in STZ-induced diabetic rats.

    PubMed

    Gandhi, Sonia; Srinivasan, B P; Akarte, Atul S

    2013-09-01

    Chronic hyperglycemia leads to the development of microvascular complications like diabetic nephropathy. The present study investigated the potential effects of the hydroalcoholic extract of Tribulus terrestris, a plant of Zygophyllaceae family, on the renal complications in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by administering STZ (90 mg/kg) to the 2-days old neonates. After 6 weeks of induction, diabetic rats were treated with 50 mg/kg hydroalcoholic extract of T. terrestris for 8 weeks. The anti-hyperglycaemic nature was confirmed by reduction in blood glucose and improvement in insulin levels. Diabetic renal injury associated with decrease in total proteins and albumin levels was observed to be improved by T. terrestris extract. Glomerular filtration rate along with inflammatory and growth factors, adiponectin and erythropoietin were also improved by the treatment, though the findings were not significant. However, the beneficial antidiabetic effects of T. terrestris extract in plasma were not observed in kidney histopathology. This was confirmed by the quantitative estimation of unhydrolyzed fraction of saponins (major component: protodioscin) in plasma and kidney samples of normal and diabetic rats. Hence, it can be concluded that 8 weeks treatment with T. terrestris extract produces potential toxic effects in kidney, which are independent of its anti-diabetic action.

  12. Nesfatin-1 increases intracellular calcium concentration by protein kinase C activation in cultured rat dorsal root ganglion neurons.

    PubMed

    Ozcan, Mete; Gok, Zeynep Betul; Kacar, Emine; Serhatlioglu, Ihsan; Kelestimur, Haluk

    2016-04-21

    Nesfatin-1 is a recently identified anorexigenic hypothalamic polypeptide derived from the posttranslational processing of nucleobindin 2 (NUCB2). Several studies have indicated that this neuropeptide may be participated in somatosensory and visceral transmission including pain signals in addition to energy metabolism. The aim of this study was to explore the possible role of nesfatin-1 in the transmission of peripheral neural signals by investigating the effects of nesfatin-1 on intracellular free calcium levels ([Ca(2+)]i) in cultured neonatal rat dorsal root ganglion (DRG) neurons. The effects of nesfatin-1 on [Ca(2+)]i in DRG neurons were investigated by using an in vitro calcium imaging system. DRG neurons were grown in primary culture following enzymatic and mechanical dissociation of ganglia from 1-or 2-day-old neonatal Wistar rats. Using the fura-2-based calcium imaging technique, the effects of nesfatin-1 on [Ca(2+)]i and role of the protein kinase C (PKC)-mediated pathway in nesfatin-1 effect were assessed. Nesfatin-1 elevated [Ca(2+)]i in cultured DRG neurons. The response was prevented by pretreating the cells with pertussis toxin. The protein kinase C inhibitor chelerythrine chloride suppressed nesfatin-1-induced rise in [Ca(2+)]i. The result shows that nesfatin-1 interacts with a G protein-coupled receptor, leading to an increase of [Ca(2+)]i, which is linked to protein kinase C activation in cultured rat DRG neurons.

  13. Dose-related neuropathic and anti-neuropathic effects of simvastatin in vincristine-induced neuropathic pain in rats.

    PubMed

    Bhalla, Shrutya; Singh, Nirmal; Jaggi, Amteshwar Singh

    2015-06-01

    The present study explores the role of simvastatin in vincristine-induced neuropathic pain, which was induced by administering vincristine (100 µg/kg i.p.) for 10 days (two 5 day cycles with 2 days pause). Pain was assessed by determining mechanical hyperalgesia, mechanical dynamic allodynia, heat hyperalgesia and cold allodynia. Biochemically, myeloperoxidase (MPO) activity was measured along with serum cholesterol levels. Simvastatin (7.5, 15 and 30 mg/kg) was administered for 14 days after administration of vincristine. Simvastatin (7.5 and 15 mg/kg) reversed vincristine-induced neuropathic pain and attenuated vincristine-induced increase in MPO, without altering cholesterol levels. Simvastatin at higher dose (30 mg/kg) did not alter neuropathic pain despite decreasing MPO levels. Furthermore, administration of simvastatin (30 mg/kg i.p.) in vincristine treated rats as well as it's per se administration in normal rats reduced cholesterol levels. Per se administration of simvastatin in normal rats produced neuropathic pain. It is concluded that simvastatin attenuates neuropathic pain only at lower doses with no reduction in cholesterol levels and anti-inflammatory effects may possibly reverse neuropathic pain. However, despite reducing inflammation, simvastatin did not confer beneficial effects at higher doses at which there is reduction in cholesterol levels, suggesting the critical role of cholesterol in neuropathic pain induction.

  14. A sulfated-polysaccharide fraction from seaweed Gracilaria birdiae prevents naproxen-induced gastrointestinal damage in rats.

    PubMed

    Silva, Renan O; Santana, Ana Paula M; Carvalho, Nathalia S; Bezerra, Talita S; Oliveira, Camila B; Damasceno, Samara R B; Chaves, Luciano S; Freitas, Ana Lúcia P; Soares, Pedro M G; Souza, Marcellus H L P; Barbosa, André Luiz R; Medeiros, Jand-Venes R

    2012-12-01

    Red seaweeds synthesize a great variety of sulfated galactans. Sulfated polysaccharides (PLSs) from seaweed are comprised of substances with pharmaceutical and biomedical potential. The aim of the present study was to evaluate the protective effect of the PLS fraction extracted from the seaweed Gracilaria birdiae in rats with naproxen-induced gastrointestinal damage. Male Wistar rats were pretreated with 0.5% carboxymethylcellulose (control group-vehicle) or PLS (10, 30, and 90 mg/kg, p.o.) twice daily (at 09:00 and 21:00) for 2 days. After 1 h, naproxen (80 mg/kg, p.o.) was administered. The rats were killed on day two, 4 h after naproxen treatment. The stomachs were promptly excised, opened along the greater curvature, and measured using digital calipers. Furthermore, the guts of the animals were removed, and a 5-cm portion of the small intestine (jejunum and ileum) was used for the evaluation of macroscopic scores. Samples of the stomach and the small intestine were used for histological evaluation, morphometric analysis and in assays for glutathione (GSH) levels, malonyldialdehyde (MDA) concentration, and myeloperoxidase (MPO) activity. PLS treatment reduced the macroscopic and microscopic naproxen-induced gastrointestinal damage in a dose-dependent manner. Our results suggest that the PLS fraction has a protective effect against gastrointestinal damage through mechanisms that involve the inhibition of inflammatory cell infiltration and lipid peroxidation.

  15. Suppression and augmentation of rat adjuvant arthritis with monoclonal anti-interferon-gamma antibody.

    PubMed Central

    Wiesenberg, I; Van der Meide, P H; Schellekens, H; Alkan, S

    1989-01-01

    The effects of a monoclonal antibody (MoAb DB-1), which neutralized rat interferon-gamma (IFN-gamma), on the induction and progression of adjuvant arthritis in Lewis rats induced by intraplantar injection of Freund's complete adjuvant was studied. The animals were treated intraperitoneally with MoAb DB-1 (0.3-5 mg) for various times. Prophylactic treatment with MoAb DB-1, starting 2 days prior to arthritis induction, inhibited oedema in both the injected and non-injected hind paws and delayed joint destruction as shown by radiography. However, despite continued MoAb treatment, the disease progressed. High doses of MoAb DB-1 exacerbated the disease. A control MoAb of the same isotype did not have significant effects on adjuvant arthritis. Therapeutic treatment with the MoAb DB-1 starting 8 days after arthritis induction caused only slight and short-lived inhibitory effects. IFN-gamma appears to be a critical lymphokine for the development of adjuvant arthritis. PMID:12412757

  16. Berberine chloride pretreatment exhibits neuroprotective effect against 6-hydroxydopamine-induced neuronal insult in rat

    PubMed Central

    Negahdar, Feraidoon; Mehdizadeh, Mehdi; Joghataei, Mohammad Taghi; Roghani, Mehrdad; Mehraeen, Fereshteh; Poorghayoomi, Ehsan

    2015-01-01

    Parkinson’s disease (PD) is a rather common movement disorder as a result of the degeneration of dopaminergic neurons within the substantianigra. Current treatments for PD afford symptomatic relief with no prevention of disease progression. Due to the neuroprotective and anti-apoptotic potential of the isoquinoline alkaloid berberine (BBR), this study was conducted to assess whether BBR pretreatment could attenuate behavioral and neuronal derangement in 6-hydroxydopamine (6-OHDA)-induced model of PD in the rat. Unilateral intrastriatal 6-OHDA-lesioned rats received BBR at doses of 25 and/or 50 mg/kg (i.p.) three times at an interval of 24 h, started 2 days before the surgery. After 1 week, apomorphine caused significant contralateral rotations and a significant reduction in the number of Nissl-stained and tyrosine-hydroxylase (TH)-positive neurons on the left side of the substantianigra. BBR pretreatment at a dose of 50 mg/kg significantly reduced rotations and prevented loss of TH-positive neurons. These results indicate pre-lesion administration of BBR could protect against 6-OHDA toxicity and this may be of benefit besides other available therapies in PD. PMID:26664381

  17. [Characteristics of brain tissue damage in kaolin-induced infantile rat hydrocephalus].

    PubMed

    Okuyama, T; Hashi, K; Okada, T; Sasaki, S

    1986-01-01

    Experimental hydrocephalus was induced by an intracisternal injection of 4% or 40% kaolin suspension in 2 days old Wistar rats. They were examined histologically and microangiographically 2 weeks after the injection of kaolin. Hydrocephalic rats were classified into 2 groups, severe hydrocephalic group A and mild hydrocephalic group B. In group A, a marked enlargement of the entire ventricular system with a thinning of the cerebral mantle was observed. On the other hand, the dilatation of the fourth ventricle was more pronounced compared with the other ventricles in group B. In group A, a spongy appearance of brain tissue was observed in the periventricular white matter accompanied with an intracerebral cavity. In these edematous areas, the lack of carbon black perfusion was apparent indicating an occurrence of microcirculatory disturbances. These microcirculatory disturbances and mechanical compression to the cerebral parenchyma may produce defective brain tissue (intracerebral cavity formation). The ependymal cell walls and subependymal glial cell layers were well preserved in spite of the damaged periventricular white matter. In group A, kaolin was present in the fourth ventricle and Sylvian aqueduct. Subependymal gliosis containing macrophages and newly produced blood vessels were observed in the region between the periventricular brain tissue and kaolin granules. These findings indicate that kaolin may produce changes in the ependymal cell and cerebral parenchyma as well as fibrosis and meningitis in the subarachnoid space. PMID:3964487

  18. Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats.

    PubMed

    Yang, Guang; Lobarinas, Edward; Zhang, Liyan; Turner, Jeremy; Stolzberg, Daniel; Salvi, Richard; Sun, Wei

    2007-04-01

    Neurophysiological studies of salicylate-induced tinnitus have generally been carried out under anesthesia, a condition that abolishes the perception of tinnitus and depresses neural activity. To overcome these limitations, measurement of salicylate induced tinnitus were obtained from rats using schedule induced polydipsia avoidance conditioning (SIPAC) and gap pre-pulse inhibition of acoustic startle (GPIAS). Both behavioral measures indicated that tinnitus was present after treatment with 150 and 250 mg/kg of salicylate; measurements with GPIAS indicated that the pitch of the tinnitus was near 16 kHz. Chronically implanted microwire electrode arrays were used to monitor the local field potentials and spontaneous discharge rate from multiunit clusters in the auditory cortex of awake rats before and after treatment with 150 mg/kg of salicylate. The amplitude of the local field potential elicited with 60 dB SPL tone bursts increased significantly 2h after salicylate treatment particularly at 16-20 kHz; frequencies associated with the tinnitus pitch. Field potential amplitudes had largely recovered 1-2 days post-salicylate when behavioral results showed that tinnitus was absent. The mean spontaneous spike recorded from the same multiunit cluster pre- and post-salicylate decreased from 22 spikes/s before treatment to 14 spikes/s 2h post-salicylate and recovered 1 day post-treatment. These preliminary physiology data suggest that salicylate induced tinnitus is associated with sound evoked hyperactivity in auditory cortex and spontaneous hypoactivity.

  19. Impacts of N-Butylphthalide on expression of growth factors in rats with focal cerebral ischemia

    PubMed Central

    Jiang, Yan; Sun, Leyu; Xuan, Xiaoyan; Wang, Jianping

    2016-01-01

    This study investigates the impacts of n-butylphthalide (NBP) on the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) in rats with focal cerebral ischemia. The thread embolization method was used to prepare the rat model of cerebral ischemia-reperfusion (CIR). The animals were divided into a sham operation group, a model control group and NBP treatment group. The NBP group was orally administered 25 mg/kg NBP twice a day after the surgery. The immunohistochemistry and reverse transcription-polymerase chain reaction were performed to observe the protein and mRNA expressions of VEGF and TGF-β 16 hours, 1 day and 2 days after inducing CIR. The mRNA and protein expressions of VEGF and TGF-β1 in the model control group and the NBP treatment group were all increased after CIR, and those of the NBP treatment group at each post-CIR time point were higher than the model control group (p < 0.01). After CIR, the expressions of VEGF and TGF-β1 increased, suggesting that VEGF and TGF-β1 exhibited protective effects towards the ischemic brain injuries, and that NBP could upregulate the expressions of VEGF and TGF-β1 in the peri-infarcted area, thus possibly protecting the ischemic brain tissues through this mechanism. PMID:26773175

  20. Nitric Oxide and Superoxide Anion Balance in Rats Exposed to Chronic and Long Term Intermittent Hypoxia

    PubMed Central

    Siques, Patricia; López de Pablo, Ángel Luis; Brito, Julio; Arribas, Silvia M.; Naveas, Nelson; González, M. Carmen; León-Velarde, Fabiola; López, M. Rosario

    2014-01-01

    Work at high altitude in shifts exposes humans to a new form of chronic intermittent hypoxia, with still unknown health consequences. We have established a rat model resembling this situation, which develops a milder form of right ventricular hypertrophy and pulmonary artery remodelling compared to continuous chronic exposure. We aimed to compare the alterations in pulmonary artery nitric oxide (NO) availability induced by these forms of hypoxia and the mechanisms implicated. Rats were exposed for 46 days to normoxia or hypobaric hypoxia, either continuous (CH) or intermittent (2 day shifts, CIH2x2), and assessed: NO and superoxide anion availability (fluorescent indicators and confocal microscopy); expression of phosphorylated endothelial NO synthase (eNOS), NADPH-oxidase (p22phox), and 3-nitrotyrosine (western blotting); and NADPH-oxidase location (immunohistochemistry). Compared to normoxia, (1) NO availability was reduced and superoxide anion was increased in both hypoxic groups, with a larger effect in CH, (2) eNOS expression was only reduced in CH, (3) NADPH-oxidase was similarly increased in both hypoxic groups, and (4) 3-nitrotyrosine was increased to a larger extent in CH. In conclusion, intermittent hypoxia reduces NO availability through superoxide anion destruction, without reducing its synthesis, while continuous hypoxia affects both, producing larger nitrosative damage which could be related to the more severe cardiovascular alterations. PMID:24719876

  1. Effects of cochlear ablation on amino acid levels in the rat cochlear nucleus and superior olive.

    PubMed

    Godfrey, Donald A; Jin, Yong-Ming; Liu, Xiaochen; Godfrey, Matthew A

    2014-03-01

    Amino acids have important roles in the chemistry of the auditory system, including communication among neurons. There is much evidence for glutamate as a neurotransmitter from auditory nerve fibers to cochlear nucleus neurons. Previous studies in rodents have examined effects of removal of auditory nerve input by cochlear ablation on levels, uptake and release of glutamate in cochlear nucleus subdivisions, as well as on glutamate receptors. Effects have also been reported on uptake and release of γ-aminobutyrate (GABA) and glycine, two other amino acids strongly implicated in cochlear nucleus synaptic transmission. We mapped the effects of cochlear ablation on the levels of amino acids, including glutamate, GABA, glycine, aspartate, glutamine, taurine, serine, threonine, and arginine, in microscopic subregions of the rat cochlear nucleus. Submicrogram-size samples microdissected from freeze-dried brainstem sections were assayed for amino acid levels by high performance liquid chromatography. After cochlear ablation, glutamate and aspartate levels decreased by 2 days in regions receiving relatively dense innervation from the auditory nerve, whereas the levels of most other amino acids increased. The results are consistent with a close association of glutamate and aspartate with auditory nerve fibers and of other amino acids with other neurons and glia in the cochlear nucleus. A consistent decrease of GABA level in the lateral superior olive could be consistent with a role in some lateral olivocochlear neurons. The results are compared with those obtained with the same methods for the rat vestibular nerve root and nuclei after vestibular ganglionectomy.

  2. Structural alterations in the rat brain and behavioral impairment after status epilepticus: An MRI study.

    PubMed

    Suleymanova, E M; Gulyaev, M V; Abbasova, K R

    2016-02-19

    Temporal lobe epilepsy (TLE) is one of the most common neurologic disorders often associated with behavioral impairments and cognitive deficit. Lithium-pilocarpine model of seizures in rodents reproduces many features of human convulsive status epilepticus (SE) and subsequent TLE. In this study, we have investigated changes in the rat brain after lithium-pilocarpine SE using a high-field MRI system for small animals in early and chronic periods after SE. We have studied the relationship between T2 relaxation time measured in these periods and the development of behavioral exploratory response to novelty and habituation in the open field test. A significant increase in T2 in the hippocampus and associated structures was found 2 days after SE and practically resolved by day seven, while an increase in T2 in the parietal and prefrontal cortex appeared 30 days after SE. High T2 values in the parietal cortex and thalamus on day two after SE were associated with an increased mortality risk. A substantial variability in T2 relaxation time was observed in the hippocampus and amygdala 30 days after SE. Rats survived after SE showed locomotor hyperactivity and disruption of long-term habituation in the open field test carried out 5 weeks after the seizures. Interestingly, T2 in the amygdala 30 days after SE had a strong correlation with hyperactivity in the novel open field. Therefore, the amygdala damage may be an important factor in the development of hyperactivity in the chronic period after SE. PMID:26674057

  3. Characterization of rat model of acute anterior uveitis using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

    2015-03-01

    Uveitis, or ocular inflammation, is a cause of severe visual impairment. Rodent models of uveitis are powerful tools used to investigate the pathological mechanisms of ocular inflammation and to study the efficacy of new therapies prior to human testing. In this paper, we report the utility of spectral-domain optical coherence tomography (SD-OCT) angiography in characterizing the inflammatory changes induced in the anterior segment of a rat model of uveitis. Acute anterior uveitis (AAU) was induced in two rats by intravitreal injection of a killed mycobacterial extract. One of them received a concurrent periocular injection of steroids to model a treatment effect. OCT imaging was performed prior to inflammation induction on day 0 (baseline), and 2 days post-injection (peak inflammation). Baseline and inflamed images were compared. OCT angiography identified swelling of the cornea, inflammatory cells in the anterior and posterior chambers, a fibrinous papillary membrane, and dilation of iris vessels in the inflamed eyes when compared to baseline images. Steroid treatment was shown to prevent the changes associated with inflammation. This is a novel application of anterior OCT imaging in animal models of uveitis, and provides a high resolution, in vivo assay for detecting and quantifying ocular inflammation and the response to new therapies.

  4. A histological study of the effect of growth hormone on odontogenesis in the Lewis dwarf rat.

    PubMed

    Symons, A L; Seymour, G J

    2000-02-01

    The effect of growth hormone (GH) on the dentition has been described in children with pituitary dwarfism where teeth fail to form; those that do form tend to be reduced in size and the eruption potential is diminished. The aim here was to examine the effect of GH on odontogenesis via molar development in Lewis (control), dwarf (Dw) and Dw GH-treated (Dw+GH) rats aged 3, 6, 9, 12 and 15 days. Dw+GH animals received a twice-daily dose (65 microg/kg) of GH which commenced at 2 days of age. Animals were killed, mandibles removed, processed to embedding in paraffin, sectioned and stained for histological examination of molar morphology during development. Variations in enamel mineralization and root development were observed. In 6-day-old animals, enamel mineralization was delayed in Dw and Dw+GH animals. Root initiation was evident at 6 days of age in controls but was not observed until 9 days of age in Dw and Dw+GH animals. At 12 days of age, maturation of enamel in Dw and Dw+GH animals remained delayed. By 15 days of age no variation in tooth development was evident. These data indicate that enamel mineralization is affected by the level of circulating GH in the rat. A specific deficiency of GH did not appear to delay bone resorption prior to tooth emergence. PMID:10716616

  5. Ovarian hormone replacement to aged ovariectomized female rats benefits acquisition of the morris water maze.

    PubMed

    Markham, J A; Pych, J C; Juraska, J M

    2002-11-01

    Ovarian steroids have been suggested to aid in preserving cognitive functioning during aging in both humans and other animals. Spatial memory relies heavily on the hippocampus, a structure that is sensitive to the influence of both ovarian hormones and aging. The present study investigated the outcome of ovarian hormone replacement during aging on performance in a spatial version of the Morris water maze. Female rats were ovariectomized at 14 months of age and received one of three types of replacement prior to testing at 16 months: acute estrogen replacement (2 days), chronic estrogen replacement (28 days), or chronic replacement of both estrogen and progesterone (28 days). Control animals, which did not receive replacement hormones, displayed significant overnight forgetting during acquisition of the task. Ovarian hormone replacement, both acute and chronic, prevented forgetting. Previous studies have demonstrated that high levels of ovarian hormones are detrimental to performance of young adult female rats on this task (Warren and Juraska, 1997; Chesler and Juraska, 2000). The current study found an opposite effect during aging: ovarian hormone replacement was beneficial. This suggests that animal models of menopause, aimed at exploring the protective effects of hormone replacement therapy on cognition during human female aging, require the use of aged female animals.

  6. Dehydroepiandrosterone reverses chronic hypoxia/reoxygenation-induced right ventricular dysfunction in rats.

    PubMed

    Dumas de La Roque, Eric; Bellance, Nadège; Rossignol, Rodrigue; Begueret, Hugues; Billaud, Marie; dos Santos, Pierre; Ducret, Thomas; Marthan, Roger; Dahan, Diana; Ramos-Barbón, David; Amor-Carro, Óscar; Savineau, Jean-Pierre; Fayon, Michael

    2012-12-01

    Dehydroepiandrosterone (DHEA) prevents chronic hypoxia-induced pulmonary hypertension and associated right ventricle dysfunction in rats. In this animal model, reoxygenation following hypoxia reverses pulmonary hypertension but not right ventricle dysfunction. We thus studied the effect of DHEA on the right ventricle after reoxygenation, i.e. after a normoxic recovery phase secondary to chronic hypoxia in rats. Right ventricle function was assessed in vivo by Doppler echocardiography and in vitro by the isolated perfused heart technique in three groups of animals: control, recovery (21 days of hypoxia followed by 21 days of normoxia) and recovery DHEA (30 mg · kg(-1) every 2 days during the recovery phase). Right ventricle tissue was assessed by optical and electron microscopy. DHEA abolished right ventricle diastolic dysfunction, as the echographic E wave remained close to that of controls (mean ± SD 76.5 ± 2.4 and 79.7 ± 1.7 cm · s(-1), respectively), whereas it was diminished to 40.3 ± 3.7 in the recovery group. DHEA also abolished right ventricle systolic dysfunction, as shown by the inhibition of the increase in the slope of the pressure-volume curve in isolated heart. The DHEA effect was related to cardiac myocytes proliferation. In conclusion, DHEA prevents right ventricle dysfunction in this animal model by preventing cardiomyocyte alteration.

  7. A histological study of the effect of growth hormone on odontogenesis in the Lewis dwarf rat.

    PubMed

    Symons, A L; Seymour, G J

    2000-02-01

    The effect of growth hormone (GH) on the dentition has been described in children with pituitary dwarfism where teeth fail to form; those that do form tend to be reduced in size and the eruption potential is diminished. The aim here was to examine the effect of GH on odontogenesis via molar development in Lewis (control), dwarf (Dw) and Dw GH-treated (Dw+GH) rats aged 3, 6, 9, 12 and 15 days. Dw+GH animals received a twice-daily dose (65 microg/kg) of GH which commenced at 2 days of age. Animals were killed, mandibles removed, processed to embedding in paraffin, sectioned and stained for histological examination of molar morphology during development. Variations in enamel mineralization and root development were observed. In 6-day-old animals, enamel mineralization was delayed in Dw and Dw+GH animals. Root initiation was evident at 6 days of age in controls but was not observed until 9 days of age in Dw and Dw+GH animals. At 12 days of age, maturation of enamel in Dw and Dw+GH animals remained delayed. By 15 days of age no variation in tooth development was evident. These data indicate that enamel mineralization is affected by the level of circulating GH in the rat. A specific deficiency of GH did not appear to delay bone resorption prior to tooth emergence.

  8. Threshold size for optimal passive pulmonary targeting and retention of rigid microparticles in rats

    PubMed Central

    Kutscher, Hilliard L.; Chao, Piyun; Deshmukh, Manjeet; Singh, Yashveer; Hu, Peidi; Joseph, Laurie B.; Reimer, David C.; Stein, Stanley; Laskin, Debra L.; Sinko, Patrick J.

    2010-01-01

    The relationship between microparticle (MP) size and lung targeting efficiency, intra-lung distribution and retention time was systematically studied after intravenous administration of rigid fluorescent polystyrene MPs of various sizes (2, 3, 6 and 10μm) to Sprague-Dawley rats. Total fluorescence was assessed and it was found that 2μm and 3μm MPs readily passed through the lung to the liver and spleen while 10μm MPs were completely entrapped in the lung for the one-week duration of the study. Approximately 84% of 6μm MPs that were initially entrapped in the lung were cleared over the next 2 days and 15% were cleared over the remaining 5 days. A Caliper IVIS® 100 small animal imaging system confirmed that 3μm MPs were not retained in the lung but that 6μm and 10μm MPs were widely distributed throughout the lung. Moreover, histologic examination showed MP entrapment in capillaries but not arterioles. These studies suggest that for rigid MPs the optimal size range required to achieve transient but highly efficiently targeting to pulmonary capillaries after IV injection is >6μm but <10μm in rats and that systemic administration of optimally sized MPs may be an efficient alternative to currently used inhalation-based delivery to the lung. PMID:20043961

  9. Swimming-based pica in rats.

    PubMed

    Nakajima, Sadahiko

    2016-09-01

    We have recently demonstrated that voluntary or forced running in activity wheels yields pica behavior (kaolin clay intake) in rats (Nakajima, 2016; Nakajima and Katayama, 2014). The present study provides experimental evidence that a single 40-min session of swimming in water also generates pica in rats, while showering rats with water does not produce such behavior. Because kaolin intake has been regarded as a measure of nausea in rats, this finding suggests that swimming activity, as well as voluntary or forced running, induces nausea in rats. PMID:27370361

  10. Susceptibility of laboratory rats against genotypes 1, 3, 4, and rat hepatitis E viruses.

    PubMed

    Li, Tian-Cheng; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Yasuda, Shumpei P; Yoshimatsu, Kumiko; Arikawa, Jiro; Takeda, Naokazu; Wakita, Takaji

    2013-04-12

    To determine whether or not rats are susceptible to hepatitis E virus (HEV) infection, each of group containing three laboratory rats (Wistar) were experimentally inoculated with genotypes 1, 3, 4 and rat HEV by intravenous injection. Serum and stool samples were collected and used to detect HEV RNA and anti-HEV antibodies by RT-PCR and ELISA, respectively. The virus infection was monitored up to 3 months after inoculation. None of the serum or stool samples collected from the rats inoculated with G1, G3, or G4 HEV indicated positive sign for virus replication. Although no alteration was observed in ALT level, rat HEV RNA was detected in stools from both of the rats inoculated with rat HEV, and both rats were positive for anti-rat HEV IgG and IgM from 3 weeks after inoculation. These results demonstrated that rats are susceptible to rat HEV but not to G1, G3, and G4 HEV. We also confirm that the nude rats were useful for obtaining a large amount of rat HEV and that the rat HEV was transmitted by the fecal-oral route.

  11. Slc:Wistar outbred rats show close genetic similarity with F344 inbred rats.

    PubMed

    Nakanishi, Satoshi; Serikawa, Tadao; Kuramoto, Takashi

    2015-01-01

    Although Slc:Wistar rats are used widely in biomedical research as outbred rats, close similarities in growth curves, survival rates, and immunological and biochemical phenotypes have been reported between Slc:Wistar and F344 inbred rats. We reported previously that nine genetic variations that were fixed in Slc:Wistar rats had identical genotypes in F344 rats. Here, we examined the genetic characteristics of Slc:Wistar rats using 27 simple-sequence length polymorphism (SSLP) markers and compared them with other Wistar stocks available in Japan and with some F344 strains. Among 27 SSLP loci, 23 (85%) were fixed in the Slc:Wistar rats, which was the highest among the other Wistar stocks. The 23 fixed loci shared identical genotypes with corresponding loci in F344 rats. Further, the predominant allele types in the unfixed loci had allele frequencies as high as 80%, and these alleles were identical in the F344 rats. When the nine genetic variations reported previously are added, a total of 32 (89%) out of the 36 loci examined were fixed and identical in the Slc:Wistar and F344 rat genomes. These findings indicate the low genetic variation in Slc:Wistar rats and the high genetic similarity between the Slc:Wistar and F344 inbred rats. This study demonstrates the importance of characterizing outbred rats and the need to pay ample attention to the genetic characteristics the Slc:Wistar rats for their proper use.

  12. Struvite Urolithiasis in Long-Evans Rats.

    PubMed

    Pang, Jassia; Borjeson, Tiffany M; Parry, Nicola M A; Fox, James G

    2015-12-01

    Struvite urinary calculi, which are composed of magnesium, ammonium, and phosphate, can cause complications including sepsis and renal failure. Struvite calculi were identified within the urinary bladder and renal pelvis of 2 Long-Evans rats that died within days after arrival from a commercial vendor. The remaining rats in the shipment were screened by physical examination, radiography, and ultrasonography, revealing an additional 2 animals that were clinically affected. These rats were euthanized, necropsied, and yielded similar findings to those from the first 2 rats. In addition, urine samples had an alkaline pH and contained numerous bacteria (predominantly Proteus mirabilis), leukocytes, and crystals. All calculi were composed completely of struvite. Another 7 rats in the shipment had alkaline urine with the presence of blood cells; 6 of these rats also had abundant struvite crystals, and P. mirabilis was cultured from the urine of 3 rats. Further investigation by the vendor identified 2 of 100 rats with struvite calculi from the same colony. Although no specific cause could be implicated, the fact that all the affected rats came from the same breeding area suggests a genetic or environmental triggering event; a contribution due to diet cannot be ruled out. Our findings suggest that the affected rats had metabolic disturbances coupled with bacterial infection that predisposed them to develop struvite calculi. During sudden increases of struvite urinary calculi cases in rats, urine cultures followed by appropriate surgical intervention and antibiotic therapy is warranted. Additional factors, including diet, merit attention as well. PMID:26678365

  13. Struvite Urolithiasis in Long–Evans Rats

    PubMed Central

    Pang, Jassia; Borjeson, Tiffany M; Parry, Nicola MA; Fox, James G

    2015-01-01

    Struvite urinary calculi, which are composed of magnesium, ammonium, and phosphate, can cause complications including sepsis and renal failure. Struvite calculi were identified within the urinary bladder and renal pelvis of 2 Long-Evans rats that died within days after arrival from a commercial vendor. The remaining rats in the shipment were screened by physical examination, radiography, and ultrasonography, revealing an additional 2 animals that were clinically affected. These rats were euthanized, necropsied, and yielded similar findings to those from the first 2 rats. In addition, urine samples had an alkaline pH and contained numerous bacteria (predominantly Proteus mirabilis), leukocytes, and crystals. All calculi were composed completely of struvite. Another 7 rats in the shipment had alkaline urine with the presence of blood cells; 6 of these rats also had abundant struvite crystals, and P. mirabilis was cultured from the urine of 3 rats. Further investigation by the vendor identified 2 of 100 rats with struvite calculi from the same colony. Although no specific cause could be implicated, the fact that all the affected rats came from the same breeding area suggests a genetic or environmental triggering event; a contribution due to diet cannot be ruled out. Our findings suggest that the affected rats had metabolic disturbances coupled with bacterial infection that predisposed them to develop struvite calculi. During sudden increases of struvite urinary calculi cases in rats, urine cultures followed by appropriate surgical intervention and antibiotic therapy is warranted. Additional factors, including diet, merit attention as well. PMID:26678365

  14. Correlation of cytotoxic activity in lungs to recovery of normal and gamma-irradiated cotton rats from respiratory syncytial virus infection

    SciTech Connect

    Sun, C.S.; Wyde, P.R.; Knight, V.

    1983-10-01

    Cotton rats (Sigmodon hispidus) that were exposed to 300, 600, or 900 rads of gamma irradiation and inoculated intranasally 2 days later with respiratory syncytial virus (RSV) exhibited prolonged virus shedding and delayed humoral and cytotoxic immune responses compared with comparably inoculated nonirradiated control rats. In nonirradiated animals and in animals exposed to 300 and 600 rads, levels of virus declined and then disappeared from the lungs during the period in which cytotoxic activity was maximal in the lungs of these animals. In contrast, in the group of cotton rats exposed to 900 rads of irradiation, local cytotoxic activity remained low throughout the 11-day observation period, and virus was not eliminated from the lungs. Although virus-neutralizing antibodies in serum and lavage fluids from these animals may have been involved, correlation of antibody concentrations with virus clearance from lungs was not as evident. These data suggest that cytotoxic effector cells have a positive role in eliminating RSV from the lungs of unprimed cotton rats.

  15. Eating high fat chow, but not drinking sucrose or saccharin, enhances the development of sensitization to the locomotor effects of cocaine in adolescent female rats.

    PubMed

    Serafine, Katherine M; Bentley, Todd A; Koek, Wouter; France, Charles P

    2015-04-01

    Eating high fat chow accelerates the development of sensitization to cocaine-induced locomotion in female rats. It is not known whether consumption of sucrose or saccharin also increases sensitivity to the behavioral effects of cocaine or whether continuous (or intermittent) access to these feeding conditions is necessary to change sensitivity. Adolescent female Sprague-Dawley rats were assigned to one of seven feeding conditions from postnatal day 25 through to postnatal day 60. The rats either ate high fat (60% kcal from fat) chow and drank water or ate standard (17% kcal from fat) chow and drank either water, a 10% sucrose solution, or a 0.1% saccharin solution. The rats either had continuous access to high fat chow, sucrose, or saccharin, or had intermittent access (i.e. 2 days/week) to these substances, with access to water and standard chow on other days. As compared with standard chow, continuous (but not intermittent) access to high fat chow enhanced the development of sensitization to cocaine-induced (1-17.8 mg/kg) locomotion; drinking sucrose or saccharin (continuous or intermittent access) did not alter the development of sensitization to cocaine-induced locomotion. The impact of feeding condition on the behavioral effects of cocaine varies between sexes and across dietary composition.

  16. Response of BAX, Bcl-2 Proteins, and SIRT1/PGC-1α mRNA Expression to 8-Week Treadmill Running in the Aging Rat Skeletal Muscle.

    PubMed

    Li, Fang-Hui; Yu, Hai-Tao; Xiao, Lin; Liu, Yan-Ying

    2016-01-01

    The aim of this study was to analyze the effects of exercise training on Bax and Bcl-2 protein content and sirtuin1 (SIRT1) mRNA expression levels to prevent sarcopenia in aging rats. Eight 18 months old male Sprague-Dawley rats were trained 5 days weekly for 8 weeks on a treadmill, and eight sedentary rats served as controls. Gastrocnemius muscles were dissected 2 days after the last training session. The mRNA content of PGC-1α, caspase-3, NRF1, TFAM, SOD2, and SIRT1 was estimated by RT-PCR with GAPDH used as an internal control. The protein expression of BAX and Bcl-2 was assessed by Western immunoblot. After training, significant (p < 0.05) increases were noted for the gastrocnemius muscle weights, the gastrocnemius mass/body mass ratio, the bcl-2/BAX ratio, the Bcl-2 protein and the SIRT1, PGC-1α, NRF1, TFAM, SOD2 mRNA content in the trained gastrocnemius, relative to the control samples. No difference was found in the BAX protein between control and trained muscles, whereas the caspase-3 mRNA content decreased by 50 %, in the gastrocnemius muscle of trained animals. Exercise training may inhibit age-induced myonuclear apoptosis by stimulating SIRT1/PGC-1α mRNA expression, thereby preventing sarcopenia in aging rat. PMID:27526155

  17. Enhancement of therapeutic effects of recombinant interleukin 2 on a transplantable rat fibrosarcoma by the use of a sustained release vehicle, pluronic gel.

    PubMed

    Morikawa, K; Okada, F; Hosokawa, M; Kobayashi, H

    1987-01-01

    We have tested the feasibility of pluronic F-127 gel (PLF-127; a polyoxyethylene-polyoxypropylene surface active block copolymer) as a sustained release vehicle for topical administration of interleukin 2 (IL-2) in order to enhance the therapeutic effects of IL-2 against a rat fibrosarcoma, KMT-17. Injection of human DNA recombinant IL-2 (3 X 10(4) units s.c.) in 30% (w/w) PLF-127 into rats provided detectable serum IL-2 levels for up to 10 h, while injection of IL-2 alone provided detectable IL-2 levels for 3 h. When, following s.c. inoculation with 1 X 10(5) KMT-17 tumor cells into rats, IL-2 (6 X 10(4) units/day) in PLF-127 gels was injected s.c. around the growing tumor inoculum every 2 days for 10 days from Day 1 to Day 19, the survival days of rats were more prolonged [mean survival day, 32.3 +/- 5.4 (SD)] as compared with that of rats treated with saline [20.7 +/- 2.1] than mean survival days of rats treated with IL-2 alone [27.3 +/- 4.5] or PLF-127 alone [22.9 +/- 3.3]. Moreover, the span of mean survival days of rats treated with IL-2 in PLF-127 locally (31.7 +/- 5.9) was much longer than that of rats given IL-2 in PLF-127 systemically (22.8 +/- 3.4). By means of a Winn assay, stronger tumor neutralizing activities were observed in regional lymph node cells obtained from tumor bearing rats treated with IL-2 in PLF-127 than were observed in lymph node cells from rats treated with IL-2 alone or PLF-127 alone (percentage of inhibition, 90.3, 12.2, and -15.5%, respectively). The therapeutic effects of IL-2 were thus found to be consistent with the antitumor activity in regional lymph node cells. These results suggest that the enhanced therapeutic effects of IL-2 in PLF-127 are due to enhancement of antitumor immune responses induced by sustained IL-2 activity at the tumor sites. PMID:3491675

  18. Whiskers aid anemotaxis in rats.

    PubMed

    Yu, Yan S W; Graff, Matthew M; Bresee, Chris S; Man, Yan B; Hartmann, Mitra J Z

    2016-08-01

    Observation of terrestrial mammals suggests that they can follow the wind (anemotaxis), but the sensory cues underlying this ability have not been studied. We identify a significant contribution to anemotaxis mediated by whiskers (vibrissae), a modality previously studied only in the context of direct tactile contact. Five rats trained on a five-alternative forced-choice airflow localization task exhibited significant performance decrements after vibrissal removal. In contrast, vibrissal removal did not disrupt the performance of control animals trained to localize a light source. The performance decrement of individual rats was related to their airspeed threshold for successful localization: animals that found the task more challenging relied more on the vibrissae for localization cues. Following vibrissal removal, the rats deviated more from the straight-line path to the air source, choosing sources farther from the correct location. Our results indicate that rats can perform anemotaxis and that whiskers greatly facilitate this ability. Because air currents carry information about both odor content and location, these findings are discussed in terms of the adaptive significance of the interaction between sniffing and whisking in rodents. PMID:27574705

  19. Isolating Lysosomes from Rat Liver.

    PubMed

    Pryor, Paul R

    2016-04-01

    This protocol describes the generation of a fraction enriched in lysosomes from rat liver. The lysosomes are rapidly isolated using density-gradient centrifugation with gradient media that retain the osmolarity of the lysosomes such that they are functional and can be used in in vitro assays.

  20. Whiskers aid anemotaxis in rats

    PubMed Central

    Yu, Yan S. W.; Graff, Matthew M.; Bresee, Chris S.; Man, Yan B.; Hartmann, Mitra J. Z.

    2016-01-01

    Observation of terrestrial mammals suggests that they can follow the wind (anemotaxis), but the sensory cues underlying this ability have not been studied. We identify a significant contribution to anemotaxis mediated by whiskers (vibrissae), a modality previously studied only in the context of direct tactile contact. Five rats trained on a five-alternative forced-choice airflow localization task exhibited significant performance decrements after vibrissal removal. In contrast, vibrissal removal did not disrupt the performance of control animals trained to localize a light source. The performance decrement of individual rats was related to their airspeed threshold for successful localization: animals that found the task more challenging relied more on the vibrissae for localization cues. Following vibrissal removal, the rats deviated more from the straight-line path to the air source, choosing sources farther from the correct location. Our results indicate that rats can perform anemotaxis and that whiskers greatly facilitate this ability. Because air currents carry information about both odor content and location, these findings are discussed in terms of the adaptive significance of the interaction between sniffing and whisking in rodents. PMID:27574705

  1. Whiskers aid anemotaxis in rats.

    PubMed

    Yu, Yan S W; Graff, Matthew M; Bresee, Chris S; Man, Yan B; Hartmann, Mitra J Z

    2016-08-01

    Observation of terrestrial mammals suggests that they can follow the wind (anemotaxis), but the sensory cues underlying this ability have not been studied. We identify a significant contribution to anemotaxis mediated by whiskers (vibrissae), a modality previously studied only in the context of direct tactile contact. Five rats trained on a five-alternative forced-choice airflow localization task exhibited significant performance decrements after vibrissal removal. In contrast, vibrissal removal did not disrupt the performance of control animals trained to localize a light source. The performance decrement of individual rats was related to their airspeed threshold for successful localization: animals that found the task more challenging relied more on the vibrissae for localization cues. Following vibrissal removal, the rats deviated more from the straight-line path to the air source, choosing sources farther from the correct location. Our results indicate that rats can perform anemotaxis and that whiskers greatly facilitate this ability. Because air currents carry information about both odor content and location, these findings are discussed in terms of the adaptive significance of the interaction between sniffing and whisking in rodents.

  2. Transgenic hepatocarcinogenesis in the rat.

    PubMed Central

    Hully, J. R.; Su, Y.; Lohse, J. K.; Griep, A. E.; Sattler, C. A.; Haas, M. J.; Dragan, Y.; Peterson, J.; Neveu, M.; Pitot, H. C.

    1994-01-01

    Although transgenic hepatocarcinogenesis has been accomplished in the mouse with a number of genetic constructs targeting the oncogene to expression primarily in the liver, no example of this process has yet been developed in the rat. Because our understanding of the multistage nature of hepatocarcinogenesis is most advanced in the rat, we have developed a strain of transgenic rats carrying the promoter-enhancer sequences of the mouse albumin gene linked 5' to the simian virus-40 T antigen gene. A line of transgenic rats bearing this transgene has been developed from a single founder female. Five to six copies of the transgene, possibly in tandem, occur within the genome of the transgenic animals, which are maintained by heterozygous matings. Livers of transgenic animals are histologically normal after weaning; at 2 months of age, small foci of vacuolated cells appear in this organ. By 4 months of age, all animals exhibit focal lesions and nodules consisting primarily of small basophilic cells, many of which exhibit considerable cytoplasmic vacuolization. Mating of animals each bearing the transgene results in rats with a demyelinating condition that develops acutely in pregnant females and more chronically in males. Ultrastructural studies of these cells indicate that the vacuoles contain substantial amounts of glycogen, with the cells resembling hepatoblasts. Malignant neoplasms with both a glandular and a hepatoblastoma/hepatocellular carcinoma pattern arise from the nodules. Enzyme and immunohistochemical studies of all lesions reveal many similarities in gene expression to comparable lesions in rats subjected to chemically induced hepatocarcinogenesis, with certain exceptions. The placental form of glutathione-S-transferase is absent from all lesions in the transgenic animal, as is the expression of connexin 32. A significant number of lesions express serum albumin, and many, but not all, exhibit the T antigen. Lesions expressing the T antigen also contain

  3. Doxorubicine-congestive heart failure-increased big endothelin-1 plasma concentration: reversal by amlodipine, losartan, and gastric pentadecapeptide BPC157 in rat and mouse.

    PubMed

    Lovric-Bencic, Martina; Sikiric, Predrag; Hanzevacki, Jadranka S; Seiwerth, Sven; Rogic, Dunja; Kusec, Vesna; Aralica, Gorana; Konjevoda, Pasko; Batelja, Lovorka; Blagaic, Alenka B

    2004-05-01

    Overall, doxorubicine-congestive heart failure (CHF) (male Wistar rats and NMRI mice; 6 challenges with doxorubicine (2.5 mg/kg, i.p.) throughout 15 days and then a 4-week-rest period) is consistently deteriorating throughout next 14 days, if not reversed or ameliorated by therapy (/kg per day): a stable gastric pentadecapeptide BPC157 (GEPPPGKPADDAGLV, MW 1419, promisingly studied for inflammatory bowel disease (Pliva; PL 10, PLD-116, PL 14736)) (10 microg, 10 ng), losartan (0.7 mg), amlodipine (0.07 mg), given intragastrically (i.g.) (once daily, rats) or in drinking water (mice). Assessed were big endothelin-1 (BET-1) and plasma enzyme levels (CK, MBCK, LDH, AST, ALT) before and after 14 days of therapy and clinical status (hypotension, increased heart rate and respiratory rate, and ascites) every 2 days. Controls (distilled water (5 ml/kg, i.g., once daily) or drinking water (2 ml/mouse per day) given throughout 14 days) exhibited additionally increased BET-1 and aggravated clinical status, while enzyme values maintained their initial increase. BPC157 (10 microg/kg) and amlodipine treatment reversed the increased BET-1 (rats, mice), AST, ALT, CK (rats, mice), and LDH (mice) values. BPC157 (10 ng/kg) and losartan opposed further increase of BET-1 (rats, mice). Losartan reduces AST, ALT, CK, and LDH serum values. BPC157 (10 ng/kg) reduces AST and ALT serum values. Clinical status of CHF-rats and -mice is accordingly improved by the BPC157 regimens and amlodipine. PMID:15153646

  4. Repeated bouts of fast velocity eccentric contractions induce atrophy of gastrocnemius muscle in rats.

    PubMed

    Ochi, Eisuke; Nosaka, Kazunori; Tsutaki, Arata; Kouzaki, Karina; Nakazato, Koichi

    2015-10-01

    One bout of exercise consisting of fast velocity eccentric contractions has been shown to increase muscle protein degradation in rats. The present study tested the hypothesis that muscle atrophy would be induced after four bouts of fast velocity eccentric contractions, but not after four bouts of slow velocity eccentric contractions. Male Wistar rats were randomly placed into 3 groups; fast (180°/s) velocity (180EC, n = 7), slow (30°/s) velocity eccentric exercise (30EC, n = 7), or sham-treatment group (control, n = 7). The 180EC and 30EC groups received 4 sessions of 4 sets of 5 eccentric contractions of triceps surae muscles by extending the ankle joint during evoked electrical stimulation of the muscles, and the control group had torque measures, every 2 days, and all rats were sacrificed 1 day after the fourth session. Medial and lateral gastrocnemius wet mass were 4-6 % smaller, cross-sectional area of medial gastrocnemius was 6-7% smaller, and isometric tetanic torque of triceps surae muscles was 36 % smaller (p < 0.05) for 180EC than control at 1 day after the fourth session, but no such differences were evident between 30EC and control. The expressions of atrophy-related molecules such as FoxO1, FoxO3 and myostatin were upregulated (78-229 %) only for 180EC, but an increase in phosphorylated p70s6k (227%) was found only for 30EC at 1 day after the fourth session (p < 0.05). The level of Bax, a pro-apoptotic protein, was greater (p < 0.05) for 180EC than control. These results support the hypothesis that muscles are atrophied by repeated bouts of fast but not slow velocity eccentric contractions.

  5. Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning.

    PubMed

    Serafine, Katherine M; Bentley, Todd A; Kilborn, Dylan J; Koek, Wouter; France, Charles P

    2015-10-01

    Diet can impact sensitivity of rats to some of the behavioral effects of drugs acting on dopamine systems. The current study tested whether continuous access to sucrose is necessary to increase yawning induced by the dopamine receptor agonist quinpirole, or if intermittent access is sufficient. These studies also tested whether sensitivity to quinpirole-induced yawning increases in rats drinking the non-caloric sweetener saccharin. Dose-response curves (0.0032-0.32 mg/kg) for quinpirole-induced yawning were determined once weekly in rats with free access to standard chow and either continuous access to water, 10% sucrose solution, or 0.1% saccharin solution, or intermittent access to sucrose or saccharin (i.e., 2 days per week with access to water on other days). Cumulative doses of quinpirole increased then decreased yawning, resulting in an inverted U-shaped dose-response curve. Continuous or intermittent access to sucrose enhanced sensitivity to quinpirole-induced yawning. Continuous, but not intermittent, access to saccharin also enhanced sensitivity to quinpirole-induced yawning. In all groups, pretreatment with the selective D3 receptor antagonist PG01037 shifted the ascending limb of the quinpirole dose-response curve to the right, while pretreatment with the selective D2 receptor antagonist L-741,626 shifted the descending limb to the right. These results suggest that even intermittent consumption of diets containing highly palatable substances (e.g. sucrose) alters sensitivity to drugs acting on dopamine systems in a manner that could be important in vulnerability to abuse drugs.

  6. Effect of anti-interleukin 2 monoclonal antibody treatment on the survival of rat cardiac allograft

    SciTech Connect

    Sakagami, K.; Ohsaki, T.; Ohnishi, T.; Saito, S.; Matsuoka, J.; Orita, K.

    1989-03-01

    The effect of anti-interleukin 2 monoclonal antibody (anti-IL2 MoAb) and the accumulation of intravenously administered /sup 125/I-labeled anti-IL2 MoAb were examined in heterotopic rat cardiac allografts. Mouse anti-human recombinant IL2 MoAb was obtained by the hybridoma technique. The anti-IL2 MoAb, termed 8H-10, was an IgG2a which inhibited IL2-driven (/sup 3/H)TdR incorporation in cytolytic T lymphocyte line cells at a dilution of 2(6). 8H-10 was injected iv at a dose of 200 micrograms/day for 8 consecutive days, beginning on the day of transplantation. Hearts from F344 rats (RT11v1) were transplanted into ACI recipient rats (RT1av1). The mean survival time was 7.6 +/- 0.8 days in untreated controls, 9.0 +/- 1.2 days in additional controls treated with mouse anti-sheep red blood cell monoclonal antibody, and 25.3 +/- 18.4 days in the anti-IL2 MoAb (8H-10)-treated group (P less than 0.05). Furthermore, the accumulation of intravenously administered 125I-labeled anti-IL2 MoAb (8H-10) was specifically seen in the grafted heart. In conclusion, these results suggest that IL2 may play an important role in allograft rejection and that anti-IL2 MoAb may serve as a useful immunosuppressive agent in clinical transplantation.

  7. Effect of 2,450 MHz microwave radiation on the development of the rat brain

    SciTech Connect

    Inouye, M.; Galvin, M.J.; McRee, D.I.

    1983-12-01

    Male Sprague-Dawley rats were exposed to 2,450 MHz microwave radiation at an incident power density of 10 mW/cm2 daily for 3 hours from day 4 of pregnancy (in utero exposure) through day 40 postpartum, except for 2 days at the perinatal period. The animals were killed, and the brains removed, weighed, measured, and histologically examined at 15, 20, 30, and 40 days of age. The histologic parameters examined included the cortical architecture of the cerebral cortex, the decline of the germinal layer along the lateral ventricles, the myelination of the corpus callosum, and the decline of the external germinal layer of the cerebellar cortex. In 40-day-old rats, quantitative measurements of neurons were also made. The spine density of the pyramidal cells in layer III of the somatosensory cortex, and the density of basal dendritic trees of the pyramidal cells in layer V were measured in Golgi-Cox impregnated specimens. In addition, the density of Purkinje cells and the extent of the Purkinje cell layer in each lobule were measured in midsagittal sections of the cerebellum stained with thionin. There were no remarkable differences between microwave-exposed and control (sham-irradiated) groups for any of the histologic or quantitative parameters examined; however, the findings provide important information on quantitative measurements of the brain. The data from this study failed to demonstrate that there is a significant effect on rat brain development due to microwave exposure (10 mW/cm2) during the embryonic, fetal, and postnatal periods.

  8. Kangaroo rat bone compared to white rat bone after short-term disuse and exercise

    USGS Publications Warehouse

    Muths, E.; Reichman, O. J.

    1996-01-01

    Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly “stronger” bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.

  9. Kangaroo rat bone compared to white rat bone after short-term disuse and exercise.

    PubMed

    Muths, E; Reichman, O J

    1996-08-01

    Kangaroo rats (Dipodomys ordii) were used to study the effects of confinement on mechanical properties of bone with a long range objective of proposing an alternative to the white rat model for the study of disuse osteoporosis. Kangaroo rats exhibit bipedal locomotion, which subjects their limbs to substantial accelerative forces in addition to the normal stress of weight bearing. We subjected groups of kangaroo rats and white rats (Rattus norvegicus) to one of two confinement treatments or to an exercise regime; animals were exercised at a rate calculated to replicate their (respective) daily exercise patterns. White laboratory rats were used as the comparison because they are currently the accepted model used in the study of disuse osteoporosis. After 6 weeks of treatment, rats were killed and the long bones of their hind limbs were tested mechanically and examined for histomorphometric changes. We found that kangaroo rats held in confinement had less ash content in their hind limbs than exercised kangaroo rats. In general, treated kangaroo rats showed morphometric and mechanical bone deterioration compared to controls and exercised kangaroo rats appeared to have slightly "stronger" bones than confined animals. White rats exhibited no significant differences between treatments. These preliminary results suggest that kangaroo rats may be an effective model in the study of disuse osteoporosis.

  10. Generalized absence epilepsy and catalepsy in rats.

    PubMed

    Kuznetsova, G D; Petrova, E V; Coenen, A M; Van Luijtelaar, E L

    1996-10-01

    Adult WAG/Rij rats are considered adequate genetic models for human generalized absence epilepsy. Rats of this strain of 8, 12, and 18 weeks old and age-matched control Wistar rats were exposed to sound stimulation. After offset of stimulation, all WAG/Rij rats showed cataleptic or even cataplexic reactions, which could persist for up to 20 min. Age effects could be demonstrated. None of the Wistar rats showed cataleptic reactions. Electroencephalographic studies in WAG/Rij rats of 21 weeks showed that spike-wave discharges were abundantly present in the background electroencephalogram prior to sound stimulation. Age-matched Wistar rats had almost no spike-wave discharges. Spike-wave discharges in WAG/Rij rats disappeared during sound stimulation and were then increased compared to the prestimulation and stimulation periods. The electroencephalogram during the cataleptic state was also characterized by the presence of large amplitude 2 Hz waves, interspersed with spike-wave discharges. The data suggest that the cataleptic state can be elicited in genetically epilepsy-prone rats. The youngest WAG/Rij rats showed no spike-wave discharges during the cataleptic state. In all, the data suggest that epilepsy-prone animals are sensitive for catalepsy at an age at which the EEG signs of generalized absence epilepsy are not yet manifest. PMID:8884948

  11. Advances on genetic rat models of epilepsy.

    PubMed

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoro, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2015-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: 'phenotype to gene' and 'gene to phenotype'. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies.

  12. Advances on genetic rat models of epilepsy

    PubMed Central

    Serikawa, Tadao; Mashimo, Tomoji; Kuramoto, Takashi; Voigt, Birger; Ohno, Yukihiro; Sasa, Masashi

    2014-01-01

    Considering the suitability of laboratory rats in epilepsy research, we and other groups have been developing genetic models of epilepsy in this species. After epileptic rats or seizure-susceptible rats were sporadically found in outbred stocks, the epileptic traits were usually genetically-fixed by selective breeding. So far, the absence seizure models GAERS and WAG/Rij, audiogenic seizure models GEPR-3 and GEPR-9, generalized tonic-clonic seizure models IER, NER and WER, and Canavan-disease related epileptic models TRM and SER have been established. Dissection of the genetic bases including causative genes in these epileptic rat models would be a significant step toward understanding epileptogenesis. N-ethyl-N-nitrosourea (ENU) mutagenesis provides a systematic approach which allowed us to develop two novel epileptic rat models: heat-induced seizure susceptible (Hiss) rats with an Scn1a missense mutation and autosomal dominant lateral temporal epilepsy (ADLTE) model rats with an Lgi1 missense mutation. In addition, we have established episodic ataxia type 1 (EA1) model rats with a Kcna1 missense mutation derived from the ENU-induced rat mutant stock, and identified a Cacna1a missense mutation in a N-Methyl-N-nitrosourea (MNU)-induced mutant rat strain GRY, resulting in the discovery of episodic ataxia type 2 (EA2) model rats. Thus, epileptic rat models have been established on the two paths: ‘phenotype to gene’ and ‘gene to phenotype’. In the near future, development of novel epileptic rat models will be extensively promoted by the use of sophisticated genome editing technologies. PMID:25312505

  13. Inhibition of Intestinal Thiamin Transport in Rat Model of Sepsis

    PubMed Central

    Sassoon, Catherine S.; Zhu, Ercheng; Fang, Liwei; Subramanian, Veedamali S.; Said, Hamid M.

    2016-01-01

    Objective Thiamin deficiency is highly prevalent in patients with sepsis, but the mechanism by which sepsis induces thiamin deficiency is unknown. This study aimed to determine the influence of various severity of sepsis on carrier-mediated intestinal thiamin uptake, level of expressions of thiamin transporters (thiamin transporter-1 (THTR-1) and thiamin transporter-2 (THTR-2)), and mitochondrial thiamin pyrophosphate transporter (MTPPT). Design Randomized, controlled study Setting Research laboratory at a Veterans Affairs Medical Center Subjects Twenty-four Sprague-Dawley rats were randomized into controls, mild, moderate and severe sepsis with equal number of animals in each group. Measurements and Main Results Sepsis was induced by cecal ligation and puncture with the cecum ligated below the cecal valve at 25 %, 50 % and 75 % of cecal length, defined as severe, moderate and mild sepsis, respectively. Control animals underwent laparotomy only. After 2 days of induced sepsis, carrier-mediated intestinal thiamin uptake was measured using [3H]thiamin. Expressions of THTR-1, THTR-2, and MTPPT proteins and mRNA were measured. Proinflammatory cytokines (IL-1β and IL-6), and adenosine triphosphate (ATP) were also measured. Sepsis inhibited [3H]thiamin uptake and the inhibition was a function of sepsis severity. Both cell membranes thiamin transporters and MTPPT expression levels were suppressed; also levels of ATP in the intestine of animals with moderate and severe sepsis were significantly lower than that of sham operated controls. Conclusions For the first time we demonstrated that sepsis inhibited carrier-mediated intestinal thiamin uptake as a function of sepsis severity, suppressed thiamin transporters and MTPPT, leading to ATP depletion. PMID:27065466

  14. Interstitial photodynamic therapy in a rat liver metastasis model.

    PubMed Central

    van Hillegersberg, R.; Marijnissen, J. P.; Kort, W. J.; Zondervan, P. E.; Terpstra, O. T.; Star, W. M.

    1992-01-01

    Photodynamic therapy (PDT) of hepatic tumours has been restricted owing to the preferential retention of photosensitizers in liver tissue. We therefore investigated interstitial tumour illumination as a means of selective PDT. A piece of colon carcinoma CC531 was implanted in the liver of Wag/Rij rats. Photofrin was administered (5 mg kg-1 i.v.) 2 days before laser illumination. Tumours with a mean (+/- s.e.) diameter of 5.7 +/- 0.1 mm (n = 106, 20 days after implantation) were illuminated with 625 nm light, at 200 mW cm-1 from a 0.5 cm cylindrical diffuser and either 100, 200, 400, 800 or 1600 J cm-1. Control groups received either laser illumination only, Photofrin only or diffuser insertion only. Short-term effects were studied on the second day after illumination by light microscopy and computer-assisted integration of the circumference of damaged areas. Long-term effects were studied on day 36. To determine the biochemistry of liver damage and function, serum ASAT and ALAT levels were measured on day 1 and 2, and antipyrine clearance on day 1. Tumour and surrounding liver necrosis increased with light dose delivered (P < 0.001). Best long-term results were obtained at 800 J cm-1 with complete tumour remission in 4 out of 6 animals. No deterioration in liver function was found. The results of this study show the ability of interstitial PDT to cause major destruction of tumour tissue in the liver combined with minimal liver damage. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:1457339

  15. Effects of sustained (+/-)pindolol administration on serotonin neurotransmission in rats.

    PubMed Central

    Haddjeri, N; Blier, P

    2000-01-01

    OBJECTIVE: Given reports that (+/-)pindolol, a beta-adrenergic-5-HT1A/1B receptor antagonist, accelerates the onset of the therapeutic effect of certain antidepressant drugs in major depression, the aim of this study was to assess the effect of sustained (+/-)pindolol administration on the sensitivity of pre- and postsynaptic 5-HT1A receptors, terminal 5-HT1B autoreceptors and on overall 5-HT neurotransmission. DESIGN: Prospective animal study. ANIMALS: Sprague-Dawley rats. OUTCOME MEASURES: Modifications of the sensitivity of somatodendritic and postsynaptic 5-HT1A receptors using in vivo electrophysiological paradigms in animals treated with vehicle or (+/-)pindolol (20 mg/kg/day, subcutaneously) through osmotic minipumps for 2 weeks. RESULTS: (+/-)Pindolol attenuated the suppressant effect of the 5-HT autoreceptor agonist lysergic acid diethylamide (LSD) on the firing activity of 5-HT neurons, suggesting that (+/-)pindolol antagonized somatodendritic 5-HT1A autoreceptors in the dorsal raphe nucleus. However, following a 2-day washout period, the suppressant effect of LSD was still attenuated, indicating rather a desensitization of 5-HT1A autoreceptors had occurred. In the CA3 region of the dorsal hippocampus, (+/-)pindolol treatment did not modify the responsiveness of postsynaptic 5-HT1A receptors to microiontophoretic applications of 5-HT. Moreover, such a treatment modified neither the effectiveness of the electrical stimulation of 5-HT fibers nor the function of terminal 5-HT autoreceptors. Finally, the administration of the selective 5-HT1A receptor antagonist WAY 100635 (100 micrograms/kg, intravenously) did not increase the firing activity of dorsal hippocampus CA3 pyramidal neurons in rats treated with (+/-)pindolol, thus failing to reveal the enhanced tonic activation of postsynaptic 5-HT1A receptors associated with major classes of antidepressant treatments. CONCLUSION: Prolonged administration of (+/-)pindolol by itself is not sufficient to enhance

  16. 18F-DPA-714 PET Imaging for Detecting Neuroinflammation in Rats with Chronic Hepatic Encephalopathy

    PubMed Central

    Kong, Xiang; Luo, Song; Wu, Jin Rong; Wu, Shawn; De Cecco, Carlo N.; Schoepf, U. Joseph; Spandorfer, Adam J.; Wang, Chun Yan; Tian, Ying; Chen, Hui Juan; Lu, Guang Ming; Yang, Gui Fen; Zhang, Long Jiang

    2016-01-01

    Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. 11C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, 18F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE. This study was divided into two parts. The first part compared 18F-DPA-714 and 11C-PK11195 radiotracers in ten HE induced rats [bile duct ligation (BDL) and fed hyperammonemic diet (HD)] and 6 control rats. The animal subjects underwent dynamic positron emission tomography (PET) during 2-day intervals. The 11C-PK11195 PET study showed no differences in whole brain average percent injected dose per gram (%ID/g) values at all time points (all P>0.05), while the 18F-DPA-714 PET study showed higher whole brain average %ID/g values in HE rats compared to control group rats at 900 s to 3300 s after injecting radiotracer (all P<0.05). The second part of the study evaluated the effectiveness of ibuprofen (IBU) treatment to chronic HE. Forty rats were classified into six groups, including Sham+normal saline (NS), Sham+IBU, BDL+NS, BDL+HD+NS, BDL+IBU, and BDL+HD+IBU groups. 18F-DPA-714 PET was used to image neuroinflammation. Whole and regional brain average %ID/g values, neurological features, inflammatory factors and activated microglia showed better in the IBU groups than in the NS groups (all P<0.05) and no difference was seen in the Sham groups compared to IBU groups (all P>0.05). In conclusion, this study demonstrated that 18F-DPA-714 is an ideal TPSO radiotracer for imaging neuroinflammation and monitoring anti-neuroinflammation treatment efficacy of chronic HE. PMID:27279913

  17. Restoration of Normal Cerebral Oxygen Consumption with Rapamycin Treatment in a Rat Model of Autism-Tuberous Sclerosis.

    PubMed

    Chi, Oak Z; Wu, Chang-Chih; Liu, Xia; Rah, Kang H; Jacinto, Estela; Weiss, Harvey R

    2015-09-01

    Tuberous sclerosis (TSC) is associated with autism spectrum disorders and has been linked to metabolic dysfunction and unrestrained signaling of the mammalian target of rapamycin (mTOR). Inhibition of mTOR by rapamycin can mitigate some of the phenotypic abnormalities associated with TSC and autism, but whether this is due to the mTOR-related function in energy metabolism remains to be elucidated. In young Eker rats, an animal model of TSC and autism, which harbors a germ line heterozygous Tsc2 mutation, we previously reported that cerebral oxygen consumption was pronouncedly elevated. Young (4 weeks) male control Long-Evans and Eker rats were divided into control and rapamycin-treated (20 mg/kg once daily for 2 days) animals. Cerebral regional blood flow ((14)C-iodoantipyrine) and O2 consumption (cryomicrospectrophotometry) were determined in isoflurane-anesthetized rats. We found significantly increased basal O2 consumption in the cortex (8.7 ± 1.5 ml O2/min/100 g Eker vs. 2.7 ± 0.2 control), hippocampus, pons and cerebellum. Regional cerebral blood flow and cerebral O2 extractions were also elevated in all brain regions. Rapamycin had no significant effect on O2 consumption in any brain region of the control rats, but significantly reduced consumption in the cortex (4.1 ± 0.3) and all other examined regions of the Eker rats. Phosphorylation of mTOR and S6K1 was similar in the two groups and equally reduced by rapamycin. Thus, a rapamycin-sensitive, mTOR-dependent but S6K1-independent, signal led to enhanced oxidative metabolism in the Eker brain. We found decreased Akt phosphorylation in Eker but not Long-Evans rat brains, suggesting that this may be related to the increased cerebral O2 consumption in the Eker rat. Our findings suggest that rapamycin targeting of Akt to restore normal cerebral metabolism could have therapeutic potential in tuberous sclerosis and autism.

  18. Differential Susceptibility of SD and CD Rats to a Novel Rat Theilovirus

    PubMed Central

    Drake, Michael T; Riley, Lela K; Livingston, Robert S

    2008-01-01

    Antibodies to rat theilovirus (RTV) have been detected in rats for many years because of their serologic crossreactivity with strains of Theiler murine encephalomyelitis virus (TMEV) of mice. Little information exists regarding this pathogen, yet it is among the most common viruses detected in serologic surveys of rats used in research. In the study reported here, a novel isolate of RTV, designated RTV1, was cultured from the feces of infected rats. The RTV1 genome contained 8094 nucleotides and had approximately 95% identity with another rat theilovirus, NSG910, and 73% identity with TMEV strains. In addition, the genome size of RTV1 was similar to those of TMEV strains but larger than that reported for NSG910. Oral inoculation of Sprague–Dawley (SD) and CD male rats (n = 10 each group) with RTV1 revealed that SD rats were more susceptible than CD rats to RTV1 infection. At 14 d postinoculation, 100% of SD rats shed virus in the feces, and 70% were positive for RTV serum antibodies. By 56 d postinoculation 30% of SD rats continued to have detectable virus in the feces, and 90% had seroconverted. In contrast, in inoculated CD rats RTV was detected only in the feces at 14 d postinoculation, at which time 40% of CD rats were fecal positive. By 56 d postinoculation only 20% of CD rats had detectable RTV serum antibodies. Our data provide additional sequence information regarding a rat-specific Cardiovirus and indicate that SD rats are more susceptible than CD rats to RTV1 infection. PMID:19004372

  19. Genome Editing in Rats Using TALE Nucleases.

    PubMed

    Tesson, Laurent; Remy, Séverine; Ménoret, Séverine; Usal, Claire; Thinard, Reynald; Savignard, Chloé; De Cian, Anne; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio

    2016-01-01

    The rat is an important animal model to understand gene function and model human diseases. Since recent years, the development of gene-specific nucleases has become important for generating new rat models of human diseases, to analyze the role of genes and to generate human antibodies. Transcription activator-like (TALE) nucleases efficiently create gene-specific knockout rats and lead to the possibility of gene targeting by homology-directed recombination (HDR) and generating knock-in rats. We describe a detailed protocol for generating knockout and knock-in rats via microinjection of TALE nucleases into fertilized eggs. This technology is an efficient, cost- and time-effective method for creating new rat models.

  20. Histomorphometric analysis of rat skeleton following spaceflight

    NASA Technical Reports Server (NTRS)

    Wronski, T. J.; Morey-Holton, E. R.; Doty, S. B.; Maese, A. C.; Walsh, C. C.

    1987-01-01

    Male Sprague-Dawley rats were placed in orbit for 7 days aboard the space shuttle. Bone histomorphometry was performed in the long bones and lumbar vertebrae of flight rats and compared with data derived from ground-based control rats. Trabecular bone mass was not altered during the 1st wk of weightlessness. Strong trends were observed in flight rats for decreased periosteal bone formation in the tibial diaphysis, reduced osteoblast size in the proximal tibia, and decreased osteoblast surface and number in the lumbar vertebra. For the most part, histological indexes of bone resorption were normal in flight rats. The results indicate that 7 days of weightlessness are not of sufficient duration to induce histologically detectable loss of trabecular bone in rats. However, cortical and trabecular bone formation appear to be diminished during the 1st wk of spaceflight.

  1. Temporal precision in population—but not individual neuron—dynamics reveals rapid experience-dependent plasticity in the rat barrel cortex

    PubMed Central

    Eldawlatly, Seif; Oweiss, Karim G.

    2014-01-01

    Cortical reorganization following sensory deprivation is characterized by alterations in the connectivity between neurons encoding spared and deprived cortical inputs. The extent to which this alteration depends on Spike Timing Dependent Plasticity (STDP), however, is largely unknown. We quantified changes in the functional connectivity between layer V neurons in the vibrissal primary somatosensory cortex (vSI) (barrel cortex) of rats following sensory deprivation. One week after chronic implantation of a microelectrode array in vSI, sensory-evoked activity resulting from mechanical deflections of individual whiskers was recorded (control data) after which two whiskers on the contralateral side were paired by sparing them while trimming all other whiskers on the rat's mystacial pad. The rats' environment was then enriched by placing novel objects in the cages to encourage exploratory behavior with the spared whiskers. Sensory-evoked activity in response to individual stimulation of spared whiskers and adjacent re-grown whiskers was then recorded under anesthesia 1–2 days and 6–7 days post-trimming (plasticity data). We analyzed spike trains within 100 ms of stimulus onset and confirmed previously published reports documenting changes in receptive field sizes in the spared whisker barrels. We analyzed the same data using Dynamic Bayesian Networks (DBNs) to infer the functional connectivity between the recorded neurons. We found that DBNs inferred from population responses to stimulation of each of the spared whiskers exhibited graded increase in similarity that was proportional to the pairing duration. A significant early increase in network similarity in the spared-whisker barrels was detected 1–2 days post pairing, but not when single neuron responses were examined during the same period. These results suggest that rapid reorganization of cortical neurons following sensory deprivation may be mediated by an STDP mechanism. PMID:25505407

  2. Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats

    PubMed Central

    Bass, Virginia L.; Schladweiler, Mette C.; Nyska, Abraham; Thomas, Ronald F.; Miller, Desinia B.; Krantz, Todd; King, Charly; Gilmour, M. Ian; Ledbetter, Allen D.; Richards, Judy E.; Kodavanti, Urmila P.

    2016-01-01

    Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar–Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 μg/m3, 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0>B100>B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants. PMID:26514782

  3. Localization of vasopressin mRNA and immunoreactivity in pituicytes of pituitary stalk-transected rats after osmotic stimulation.

    PubMed Central

    Pu, L P; Van Leeuwen, F W; Tracer, H L; Sonnemans, M A; Loh, Y P

    1995-01-01

    The presence of [arginine] vasopressin (AVP) mRNA and AVP immunoreactivity in pituicytes of the neural lobe (NL) of intact and pituitary stalk-transected rats, with and without osmotic stimulation, was examined. AVP mRNA was analyzed by Northern blotting, as well as by in situ hybridization in combination with immunocytochemistry using anti-glial fibrillary acidic protein (GFAP) as a marker for pituicytes. In intact rats, a poly(A) tail-truncated 0.62-kb AVP mRNA was detected in the NL and was found to increase 10-fold with 7 days of continuous salt loading. Morphological analysis of the NL of 7-day salt-loaded rats revealed the presence of AVP mRNA in a significant number of GFAP-positive pituicytes in the NL and in areas most probably containing nerve fibers. Eight days after pituitary stalk transection the NL AVP mRNA diminished in animals given water to drink, whereas in those given 2% saline for 18 h followed by 6 h of water, a treatment repeated on 6 successive days beginning 2 days after surgery, the 0.62-kb AVP mRNA was present. The AVP mRNA in the pituitary stalk-transected, salt-loaded rats showed an exclusive cellular distribution in the NL, indicative of localization in pituicytes. Immunoelectron microscopy showed the presence of AVP immunoreactivity in a subpopulation of pituicytes 7 and 10 days after pituitary stalk transection in salt-loaded animals, when almost all AVP fibers had disappeared from the NL. These data show that a subset of pituicytes in the NL is activated to synthesize AVP mRNA and AVP in response to osmotic stimulation. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7479859

  4. Compound 49b Restores Retinal Thickness and Reduces Degenerate Capillaries in the Rat Retina following Ischemia/Reperfusion

    PubMed Central

    Liu, Li; Jiang, Youde

    2016-01-01

    We have recently reported that Compound 49b, a novel β-adrenergic receptor agonist, can significantly reduce VEGF levels in retinal endothelial cells (REC) grown in diabetic-like conditions. In this study, we investigated whether Compound 49b could protect the retina under hypoxic conditions using the ischemia-reperfusion (I/R)-induced model in rats, as well REC cultured in hypoxic conditions. Some rats received 1mM topical Compound 49b for the 2 (5 rats each group) or 10 (4 rats in each group) days post-I/R. Analyses for retinal thickness and cell loss in the ganglion cell layer was done at 2 days post-I/R, while numbers of degenerate capillaries and pericyte ghosts were measured at 10 days post-I/R. Additionally, REC were cultured in normal oxygen or hypoxia (5% O2) only or treated with 50 nM Compound 49b for 12 hours. Twelve hours after Compound 49b exposure, cells were collected and analyzed for protein levels of insulin-like growth factor binding protein 3 (IGFBP-3), vascular endothelial cell growth factor (VEGF) and its receptor (KDR), angiopoietin 1 and its receptor Tie2 for Western blotting. Data indicate that exposure to I/R significantly decreased retinal thickness, with increasing numbers of degenerate capillaries and pericyte ghosts. Compound 49b treatment inhibited these retinal changes. In REC cultured in hypoxia, levels of IGFBP-3 were reduced, which were significantly increased by Compound 49b. Hypoxia significantly increased protein levels of VEGF, KDR, Angiopoiein 1, and Tie2, which were reduced following Compound 49b treatment. These data strongly suggested that Compound 49b protected the retina against I/R-induced injury. This provides additional support for a role of β-adrenergic receptor actions in the retina. PMID:27439004

  5. Neuroprotective effect of remacemide hydrochloride in a perforant pathway stimulation model of status epilepticus in the rat.

    PubMed

    Halonen, T; Nissinen, J; Pitkänen, A

    1999-04-01

    Previous studies have demonstrated that remacemide and its desglycinyl metabolite, AR-R 2495AA, reduce neuronal damage in animal models of ischemia, subarachnoid hemorrhage, and traumatic brain injury. The aim of the present study was to investigate whether remacemide hydrochloride also alleviates seizure-induced neuronal damage in a model of status epilepticus induced by the stimulation of the perforant pathway (PP) in the rat. Chronic oral remacemide treatment (3 x 25 mg/kg/day) was started either 2 days before or 2 h after the beginning of PP stimulation (2 mA, 20 Hz, 0.1 ms pulse duration for 60 min). The effects of remacemide treatment on the severity of seizures, electroencephalogram (EEG) parameters, seizure-induced neuronal damage in the temporal lobe regions, and memory impairment were compared to unstimulated and stimulated vehicle-treated controls, and carbamazepine-pre-treated (3 x 40 mg/kg/day) rats. Both remacemide and carbamazepine pretreatments, but not remacemide posttreatment, decreased pyramidal cell damage in the CA3 and CA1 subregions of the hippocampus (P < 0.05). In addition, overall neuronal damage in the extrahippocampal temporal lobe regions (the piriform cortex, entorhinal cortex, and the amygdaloid complex) was milder in remacemide-pretreated rats compared to stimulated control rats (P < 0.01). The neuroprotective effect was most evident on the side contralateral to stimulation. Remacemide or carbamazepine pretreatment had no evident effect on the number or duration of behavioral seizures during PP stimulation. Neither drug altered the spectral parameters of the baseline EEG or prevented status epilepticus-induced EEG slowing observed 2 weeks after PP stimulation. Nor did remacemide or carbamazepine treatment alleviate spatial memory impairment determined in a Morris water-maze task 2 weeks after PP stimulation. Our data provide evidence that pretreatment with remacemide has a moderate neuroprotective effect against status epilepticus

  6. Human NgR-Fc Decoy Protein via Lumbar Intrathecal Bolus Administration Enhances Recovery from Rat Spinal Cord Contusion

    PubMed Central

    Wang, Xingxing; Yigitkanli, Kazim; Kim, Chang-Yeon; Sekine-Komo, Tomoko; Wirak, Dana; Frieden, Eric; Bhargava, Ajay; Maynard, George; Cafferty, William B.J.

    2014-01-01

    Abstract Axonal growth and neurological recovery after traumatic spinal cord injury (SCI) is limited by the presence of inhibitory proteins in myelin, several of which act via the NgR1 protein in neurons. A truncated soluble ligand-binding fragment of NgR1 serves as a decoy and promotes recovery in acute and chronic rodent SCI models. To develop the translational potential of these observations, we created a human sequence-derived NgR1(310)-Fc protein. This protein is active in vitro. When the human NgR1 decoy is administered by continuous intracerebroventricular infusion to rats with a spinal contusion injury at doses of 0.09–0.53 mg/kg/d, neurological recovery is improved. Effective doses double the percentage of rats able to bear weight on their hindlimbs. Next, we considered the half-life and distribution of NgR1(310)-Fc after bolus delivery to the lumbar intrathecal space. The protein is found throughout the neuraxis and has a tissue half-life of approximately 2 days in the rat, and 5 days in the nonhuman primate. At an intermittent, once every 4 day, lumbar bolus dosing schedule of 0.14 mg/kg/d, NgR1(310)-Fc promoted locomotor rat recovery from spinal cord contusion at least as effectively as continuous infusion in open field and grid walking tasks. Moreover, the intermittent lumbar NgR1(310)-Fc treatment increased the growth of raphespinal axons into the lumbar spinal cord after injury. Thus, human NgR1(310)-Fc provides effective treatment for recovery from traumatic SCI in this preclinical model with a simplified administration regimen that facilitates clinical testing. PMID:24964223

  7. Comparative cardiopulmonary toxicity of exhausts from soy-based biofuels and diesel in healthy and hypertensive rats.

    PubMed

    Bass, Virginia L; Schladweiler, Mette C; Nyska, Abraham; Thomas, Ronald F; Miller, Desinia B; Krantz, Todd; King, Charly; Ian Gilmour, M; Ledbetter, Allen D; Richards, Judy E; Kodavanti, Urmila P

    2015-01-01

    Increased use of renewable energy sources raise concerns about health effects of new emissions. We analyzed relative cardiopulmonary health effects of exhausts from (1) 100% soy biofuel (B100), (2) 20% soy biofuel + 80% low sulfur petroleum diesel (B20), and (3) 100% petroleum diesel (B0) in rats. Normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats were exposed to these three exhausts at 0, 50, 150 and 500 μg/m(3), 4 h/day for 2 days or 4 weeks (5 days/week). In addition, WKY rats were exposed for 1 day and responses were analyzed 0 h, 1 day or 4 days later for time-course assessment. Hematological parameters, in vitro platelet aggregation, bronchoalveolar lavage fluid (BALF) markers of pulmonary injury and inflammation, ex vivo aortic ring constriction, heart and aorta mRNA markers of vasoconstriction, thrombosis and atherogenesis were analyzed. The presence of pigmented macrophages in the lung alveoli was clearly evident with all three exhausts without apparent pathology. Overall, exposure to all three exhausts produced only modest effects in most endpoints analyzed in both strains. BALF γ-glutamyl transferase (GGT) activity was the most consistent marker and was increased in both strains, primarily with B0 (B0 > B100 > B20). This increase was associated with only modest increases in BALF neutrophils. Small and very acute increases occurred in aorta mRNA markers of vasoconstriction and thrombosis with B100 but not B0 in WKY rats. Our comparative evaluations show modest cardiovascular and pulmonary effects at low concentrations of all exhausts: B0 causing more pulmonary injury and B100 more acute vascular effects. BALF GGT activity could serve as a sensitive biomarker of inhaled pollutants.

  8. Isolation of rat adrenocortical mitochondria

    SciTech Connect

    Solinas, Paola; Fujioka, Hisashi; Tandler, Bernard; Hoppel, Charles L.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  9. Automatic Training of Rat Cyborgs for Navigation.

    PubMed

    Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

    2016-01-01

    A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs. PMID:27436999

  10. Toxicity and repellency to rats of actidione

    USGS Publications Warehouse

    Traub, R.; DeWitt, J.B.; Welch, J.F.; Newman, D.

    1950-01-01

    The antibiotic actidione was found to be highly repellent to laboratory rats and to significantly reduce gnawing attacks upon treated paperboards. Rats refused to accept food or water containing this material even under conditions of acute starvation and died of starvation and thirst,rather than accept water containing l.0 mg. of actidione per liter. The compound is highly toxic to .rats with the minimum .lethal dose by oral administration being approximately l.0 mg./Kg body weight. Paperboard treated with the compound resisted gnawing attacks by specially trained and motivated rats for periods of two hundred hours, although similar .untreated boards were pierced within thirty-to sixty minutes.

  11. Lead induced testicular hypersensitivity in stressed rats.

    PubMed

    Saxena, D K; Lal, B; Srivastava, R S; Chandra, S V

    1990-01-01

    Rats were immobilized for 2 h and treated i.p. with lead Pb2+ (8 mg/kg/day) for 45 d to investigate the testicular effects of lead on rats kept under immobilization stress. Marked alteration in SDH. G6PDH activity, cholesterol and ascorbic acid contents and reduced sperm counts associated with marked pathological changes in the testis of rats were observed after combined treatment with lead and immobilization stress in comparison to either alone. An increase in the disturbances of testicular androgen synthesis seems to be responsible for enhanced testicular injury in lead induced stressed rats. PMID:2401350

  12. Automatic Training of Rat Cyborgs for Navigation

    PubMed Central

    Yu, Yipeng; Wu, Zhaohui; Xu, Kedi; Gong, Yongyue; Zheng, Nenggan; Zheng, Xiaoxiang; Pan, Gang

    2016-01-01

    A rat cyborg system refers to a biological rat implanted with microelectrodes in its brain, via which the outer electrical stimuli can be delivered into the brain in vivo to control its behaviors. Rat cyborgs have various applications in emergency, such as search and rescue in disasters. Prior to a rat cyborg becoming controllable, a lot of effort is required to train it to adapt to the electrical stimuli. In this paper, we build a vision-based automatic training system for rat cyborgs to replace the time-consuming manual training procedure. A hierarchical framework is proposed to facilitate the colearning between rats and machines. In the framework, the behavioral states of a rat cyborg are visually sensed by a camera, a parameterized state machine is employed to model the training action transitions triggered by rat's behavioral states, and an adaptive adjustment policy is developed to adaptively adjust the stimulation intensity. The experimental results of three rat cyborgs prove the effectiveness of our system. To the best of our knowledge, this study is the first to tackle automatic training of animal cyborgs. PMID:27436999

  13. Lead induced testicular hypersensitivity in stressed rats.

    PubMed

    Saxena, D K; Lal, B; Srivastava, R S; Chandra, S V

    1990-01-01

    Rats were immobilized for 2 h and treated i.p. with lead Pb2+ (8 mg/kg/day) for 45 d to investigate the testicular effects of lead on rats kept under immobilization stress. Marked alteration in SDH. G6PDH activity, cholesterol and ascorbic acid contents and reduced sperm counts associated with marked pathological changes in the testis of rats were observed after combined treatment with lead and immobilization stress in comparison to either alone. An increase in the disturbances of testicular androgen synthesis seems to be responsible for enhanced testicular injury in lead induced stressed rats.

  14. Hyperammonemia in anorectic tumor-bearing rats

    SciTech Connect

    Chance, W.T.; Cao, L.; Nelson, J.L.; Foley-Nelson, T.; Fischer, J.E.

    1988-01-01

    Plasma ammonia concentrations were significantly elevated by 150% in anorectic rats bearing methylcholanthrene sarcomas. Assessment of ammonia levels in blood draining these sarcomas indicated nearly a 20-fold increase as compared with venous blood in control rats, suggesting the tumor mass as the source of this increase in ammonia. Infusing increasing concentrations of ammonium salts produced anorexia and alterations in brain amino acids in normal rats that were similar to those observed in anorectic tumor-bearing rats. Therefore, these results suggest that ammonia released by tumor tissue may be an important factor in the etiology of cancer anorexia.

  15. HIFU and Chemotherapy Synergistic Inhibitory Effect on Dunning AT2 Tumour-Bearing Rats

    NASA Astrophysics Data System (ADS)

    Curiel, Laura; Paparel, Philipe; Chesnais, Sabrina; Gelet, Albert; Chapelon, Jean-Yves

    2005-03-01

    Since there is no 100% satisfactory treatment for localized prostate cancer in patients presenting symptoms representing a poor prognosis (stage T3, high Gleason score, PSA level greater than 15 ng/ml, etc.), this study aimed to evaluate the therapeutic and synergistic inhibition effects of using High Intensity Focused Ultrasound (HIFU) in combination with chemotherapy (Taxane + Estramustine). Forty-one Dunning AT2 tumour-bearing Copenhagen rats receiving HIFU and/or chemotherapy were divided into four groups: control group; chemotherapy group; HIFU group; and HIFU-chemotherapy combined group. Increase in the tumour volume was observed over 3 weeks and the tumour volume doubling time was evaluated. Growth curves for each group were then plotted and statistically evaluated. HIFU treatment combined with Taxane + Estramusine was found to have a significant synergistic effect; on day 30, the distribution of tumour volume relative to the treatment group was significantly different (p = 0.0007). The control group volumes were significantly greater than those of the chemotherapy-only (p = 0.006) or HIFU-only group (p = 0.006). The greatest difference was observed between the chemotherapy plus HIFU combined group and the control group. Additionally, tumour-doubling times were 7.7 days for the control group, 13.2 days for the HIFU-only group, and 31.2 days for the chemotherapy plus HIFU group. The differences in tumour growth rates between the chemotherapy plus HIFU combined group and a chemotherapy-only + HIFU-only grouping was 3.8% (p = 0.0020). Thus, the combined chemotherapy plus HIFU treatment was clearly more effective in reducing the tumour size than HIFU only or chemotherapy only, which indicates a synergy between the two types of treatment. Our results suggest that this combined therapy could be useful for the treatment of high-risk prostate cancer.

  16. The influence of hormonal and neuronal factors on rat heart adrenoceptors

    PubMed Central

    Kunos, George; Mucci, Lucia; O'Regan, Seana

    1980-01-01

    1 The influence of hormonal and neuronal factors on adrenoceptors mediating increased cardiac force and rate of contraction were studied in rat isolated atria. The pharmacological properties of these receptors were deduced from the relative potencies of agonists and from the effects of selective α- and β-adrenoceptor antagonists. The numbers and affinities of α- and β-adrenoceptors were also determined by radioligand binding to ventricular membrane fragments. 2 Hypophysectomy reduced the inotropic potency of isoprenaline and increased the potency of phenylephrine and methoxamine in left atria. The effect of phenylephrine was inhibited by propranolol less effectively and by phentolamine or phenoxybenzamine more effectively in hypophysectomized than in control rats. The difference in block was smaller at low than at high antagonist concentrations. Similar but smaller changes were observed for chronotropic responses of right atria. 3 The decreased β- and increased α-receptor response after hypophysectomy was similar to that observed earlier in thyroidectomized rats (Kunos, 1977). These changes developed slowly after hypophysectomy (>2 weeks), they were both reversed within 2 days of thyroxine treatment (0.2 mg/kg daily), but were not affected by cortisone treatment (50 mg/kg every 12 h for 4 days). 4 Treatment of hypophysectomized rats for 2 days with thyroxine increased the density of [3H]-dihydroalprenolol ([3H]-DHA) binding sites from 27.5 ± 2.7 to 45.5 ± 5.7 fmol/mg protein and decreased the density of [3H]-WB-4101 binding sites from 38.7 ± 3.1 to 18.7 ± 2.5 fmol/mg protein. The affinity of either type of binding site for agonists or antagonist was not significantly altered by thyroxine treatment and the sum total of α1- and β-receptors remained the same. 5 Sympathetic denervation of thyroidectomized rats by 6-hydroxydopamine increased the inotropic potency of isoprenaline and noradrenaline and the blocking effect of propranolol, and decreased the

  17. Modulation of rat behaviour by using a rat-like robot.

    PubMed

    Shi, Qing; Ishii, Hiroyuki; Kinoshita, Shinichi; Takanishi, Atsuo; Okabayashi, Satoshi; Iida, Naritoshi; Kimura, Hiroshi; Shibata, Shigenobu

    2013-12-01

    In this paper, we study the response of a rat to a rat-like robot capable of generating different types of behaviour (stressful, friendly, neutral). Experiments are conducted in an open-field where a rat-like robot called WR-4 is put together with live rats. The activity level of each rat subject is evaluated by scoring its locomotor activity and frequencies of performing rearing (rising up on its hind limbs) and body grooming (body cuddling and head curling) actions, whereas the degree of preference of that is indicated by the robot-rat distance and the frequency of contacting WR-4. The moving speed and behaviour of WR-4 are controlled in real-time based on the feedback from rat motion. The activity level and degree of preference of rats for each experimental condition are analysed and compared to understand the influence of robot behaviour. The results of this study show that the activity level and degree of preference of the rat decrease when exposed to a stressful robot, and increase when the robot exhibit friendly behaviour, suggesting that a rat-like robot can modulate rat behaviour in a controllable, predictable way.

  18. Analysis of rat cytosolic 9-cis-retinol dehydrogenase activity and enzymatic characterization of rat ADHII.

    PubMed

    Popescu, G; Napoli, J L

    2000-01-01

    We report the characterization of two enzymes that catalyze NAD(+)-dependent 9-cis-retinol dehydrogenase activity in rat liver cystol. Alcohol dehydrogenase class I (ADHI) contributes > 80% of the NA D+-dependent 9-cis-retinol dehydrogenase activity recovered, whereas alcohol dehydrogenase class II (ADHII), not identified previously at the protein level, nor characterized enzymatically in rat, accounts for approximately 2% of the activity. Rat ADHII exhibits properties different from those described for human ADHII. Moreover, rat ADHII-catalyzed rates of ethanol dehydrogenation are markedly lower than octanol or retinoid dehydrogenation rates. Neither ethanol nor 4-methylpyrazole inhibits the 9-cis-retinol dehydrogenase activity of rat ADHII. We propose that ADHII represents the previously observed additional retinoid oxidation activity of rat liver cytosol which occurred in the presence of either ethanol or 4-methylpyrazole. We also show that human and rat ADHII differ considerably in enzymatic properties. PMID:10606766

  19. Interleukin-1 and tumor necrosis factor antagonists attenuate ethanol-induced inhibition of bone formation in a rat model of distraction osteogenesis.

    PubMed

    Perrien, Daniel S; Brown, Elizabeth C; Fletcher, Terry W; Irby, David J; Aronson, James; Gao, Guan G; Skinner, Robert A; Hogue, William R; Feige, Ulrich; Suva, Larry J; Ronis, Martin J J; Badger, Thomas M; Lumpkin, Charles K

    2002-12-01

    Chronic ethanol exposure inhibits rapid bone formation during distraction osteogenesis (DO; fracture and limb lengthening) and decreases volumetric bone mineral density (BMD) in a model of intragastric dietary infusion [total enteral nutrition (TEN)] in the rat. The hypothesis tested herein was that overexpression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha mediates these deleterious effects of ethanol on the rat skeleton. Two studies (study 1, female rats; study 2, male rats) were performed to test the potential protective effects of the IL-1 and TNF antagonists: IL-1 receptor antagonist (IL-1ra) and 30-kDa polyethylene glycol-conjugated soluble TNF receptor type 1 (sTNFR1). All rats were infused with a liquid diet +/- ethanol (EtOH) and underwent tibial fractures and DO. During distraction, the animals received a combination of IL-1ra (1.8-2.0 mg/kg/day) and sTNFR1 (2.0 mg/kg/2 days) or vehicle. A comparison of distracted tibial histological sections demonstrated 1) significant antagonist-related increases in bone column formation over the EtOH controls (studies 1 and 2), and 2) restoration of new bone equivalent to that of the TEN controls (study 2). In contrast, examination of intact proximal tibial metaphyses by peripheral quantitative computerized tomography revealed decreases in volumetric BMD of both EtOH control and EtOH antagonist groups (study 2). These results demonstrate that short-term systemic administration of IL-1 and TNF antagonists together protect rapid bone formation during DO from the deleterious effects of chronic ethanol but are ineffective in regard to intact bone homeostasis.

  20. Effect of Subchronic Intravenous Morphine Infusion and Naloxone-Precipitated Morphine Withdrawal on P-gp and Bcrp at the Rat Blood-Brain Barrier.

    PubMed

    Chaves, Catarina; Gómez-Zepeda, David; Auvity, Sylvain; Menet, Marie-Claude; Crété, Dominique; Labat, Laurence; Remião, Fernando; Cisternino, Salvatore; Declèves, Xavier

    2016-01-01

    Chronic morphine regimen increases P-glycoprotein (P-gp) and breast cancer-resistance protein (Bcrp) expressions at the rat blood–brain barrier (BBB) but what drives this effect is poorly understood. The objective of this study is to assess subchronic continuous morphine infusion and naloxone-precipitated morphine withdrawal effects on P-gp/Bcrp contents and activities at the rat BBB. Rats were treated either with (i) a continuous i.v. morphine for 120 h, (ii) escalating morphine dosing (10-40 mg/kg, i.p., 5 days), (iii) a chronic morphine regimen (10 mg/kg s.c., 5 days) followed by a withdrawal period (2 days) and treatment for 3 additional days. Animal behavior was assessed after naloxone-precipitated withdrawal (1 mg/kg, s.c.). P-gp/Bcrp expressions and activities were determined in brain microvessels by qRT-PCR, Western blot, UHPLC–MS/MS, and in situ brain perfusion of P-gp or Bcrp substrates. Results show continuous i.v. morphine did not change P-gp/Bcrp protein levels in rat brain microvessels, whereas naloxone-precipitated withdrawal after escalating or chronic morphine dose regimen increased Mdr1a and Bcrp mRNA levels by 1.4-fold and 2.4-fold, respectively. Conversely, P-gp/Bcrp protein expressions remained unchanged after naloxone administration, and brain uptake of [3H]-verapamil (P-gp) and [3H]-mitoxantrone (Bcrp) was not altered. The study concludes subchronic morphine infusion and naloxone-precipitated morphine withdrawal have poor effect on P-gp/Bcrp levels at the rat BBB.

  1. Angiogenesis and Improved Cerebral Blood Flow in the Ischemic Boundary Area Detected by MRI after Administration of Sildenafil to Rats with Embolic Stroke

    PubMed Central

    Li, Lian; Jiang, Quan; Zhang, Li; Ding, Guangliang; Zhang, Zheng Gang; Li, Qingjiang; Ewing, James R.; Lu, Mei; Panda, Swayamprava; Ledbetter, Karyn A.; Whitton, Polly A.; Chopp, Michael

    2007-01-01

    To dynamically investigate the long-term response of an ischemic lesion in rat brain to the administration of sildenafil, male Wistar rats subjected to embolic stroke were treated with sildenafil (n=11) or saline (n=10) at a dose of 10mg/Kg administered subcutaneously 24-hours after stroke and daily for an additional 6-days. Magnetic resonance images were acquired and functional performance was measured in all animals at 1-day, 2-days and weekly for 6-weeks post-stroke. All rats were sacrificed 6-weeks after stroke and endothelial barrier antigen immunostaining was employed for morphological analysis and quantification of cerebral vessels. Map-ISODATA was computed from T1, T2 and T1sat maps. ISODATA derived tissue signatures characterize the degree of ischemic injury. Based on the map-ISODATA calculated at 6-weeks, the ischemic lesion for each animal was divided into two specific regions, the ischemic boundary and ischemic core. The temporal profiles of cerebral blood flow (CBF) and tissue signature were retrospectively tracked in these two regions and were compared with histological evaluation and functional outcome. After 1-week of sildenafil treatment, the ischemic lesion exhibited two significantly different regions, with higher CBF level and correspondingly, lower tissue signature value in the boundary region than in the core region. Sildenafil treatment did not significantly reduce the lesion size, but did enhance angiogenesis. Functional performance was significantly increased after sildenafil treatment compared with the control group. Administration of sildenafil to rats with embolic stroke enhances angiogenesis and selectively increases the CBF level in the ischemic boundary, and improves neurological functional recovery compared to saline-treated rats. PMID:17188664

  2. Investigation of antioxidant, anti-inflammatory and DNA-protective properties of eugenol in thioacetamide-induced liver injury in rats.

    PubMed

    Yogalakshmi, Baskaran; Viswanathan, Periyasamy; Anuradha, Carani Venkatraman

    2010-02-01

    The present study investigated the preventive effect of eugenol, a naturally occurring food flavouring agent on thioacetamide (TA)-induced hepatic injury in rats. Adult male Wistar rats of body weight 150-180 g were used for the study. Eugenol (10.7 mg/kg b.w./day) was administered to rats by oral intubation for 15 days. TA was administered (300 mg/kg b.w., i.p.) for the last 2 days at 24h interval and the rats were sacrificed on the 16th day. Markers of liver injury (aspartate transaminase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase and bilirubin), inflammation (myeloperoxidase, tumor necrosis factor-alpha and interleukin-6), oxidative stress (lipid peroxidation indices, protein carbonyl and antioxidant status) and cytochrome P4502E1 activity were assessed. Expression of cyclooxygenase-2 (COX-2) and the extent of DNA damage were analyzed using immunoblotting and comet assay, respectively. Liver injury and collagen accumulation were assessed using histological studies by hematoxylin and eosin and Masson trichrome staining. Rats exposed to TA alone showed increased activities of hepatocellular enzymes in plasma, lipid peroxidation indices, inflammatory markers and pro-inflammatory cytokines and decreased antioxidant status in circulation and liver. Hepatic injury and necrosis were also evidenced by histology. Eugenol pretreatment prevented liver injury by decreasing CYP2E1 activity, lipid peroxidation indices, protein oxidation and inflammatory markers and by improving the antioxidant status. Single-cell gel electrophoresis revealed that eugenol pretreatment prevented DNA strand break induced by TA. Increased expression of COX-2 gene induced by TA was also abolished by eugenol. These findings suggest that eugenol curtails the toxic effects of TA in liver.

  3. Protective effects of vitamins (C and E) and melatonin co-administration on hematological and hepatic functions and oxidative stress in alloxan-induced diabetic rats.

    PubMed

    Allagui, Mohamed Salah; Feriani, Anouer; Bouoni, Zouhour; Alimi, Hichem; Murat, Jean Claud; El Feki, Abdelfattah

    2014-09-01

    The present study aimed to investigate the potential effects of vitamins (C and E)/melatonin co-administration on the hematologic and hepatic functions and oxidative stress in alloxan-induced diabetic rats. The intraperitoneal injection of alloxan (120 mg/kg b.w. for 2 days) induced a significant increase of blood glucose levels (hyperglycemia) associated with serious hematologic disorders (P < 0.01) evidenced by the decrease in the levels of red blood cell count (RBC) (-18%), hematocrit (Ht) (-18%), hemoglobin content (Hb) (-36%), mean corpuscular hemoglobin (MCH) (-17%), and mean corpuscular hemoglobin concentration (MCHC) (-16%). The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and the plasmatic levels of total cholesterol and triglyceride contents of diabetic rats were, however, noted to undergo significant increases by 42% (P < 0.01), 134% (P < 0.001), 27.5% (P < 0.01), 147% (P < 0.001), and 67% (P < 0.01), respectively, as compared to the control animals. Furthermore, a significant increase in malondialdehyde (MDA) content and a significant decrease in superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were observed in the plasma and hepatic tissues of diabetic rats when compared to the controls. Interestingly, the treatment with vitamins (C, E) in combination with melatonin was noted to reduce the plasma levels of glucose, lower the MDA levels, and restore the hematologic parameters and biochemical and antioxidant levels of diabetic rats back to normal values, alleviating diabetes metabolic disorders in rats. PMID:24919717

  4. Sexual Behavior Increases Cell Proliferation in the Rostral Migratory Stream and Promotes the Differentiation of the New Cells into Neurons in the Accessory Olfactory Bulb of Female Rats

    PubMed Central

    Corona, Rebeca; Retana-Márquez, Socorro; Portillo, Wendy; Paredes, Raúl G.

    2016-01-01

    We have previously demonstrated, that 15 days after female rats pace the sexual interaction, there is an increase in the number of new cells that reach the granular cell layer (GrL) of the accessory olfactory bulb (AOB). The aim of the present study was to evaluate, if the first sexual experience in the female rat increases cell proliferation in the subventricular zone (SVZ) and the rostral migratory stream (RMS). We also tested if this behavior promotes the survival of the new cells that integrate into the main olfactory bulb (MOB) and AOB 45 days after the behavioral test. Sexually, naive female rats were injected with the DNA synthesis marker 5′-bromo-2′-deoxyuridine (BrdU) on the day of the behavioral test. They were randomly divided into the following groups: Female rats placed alone in the mating cage (1); Females exposed to amyl acetate odor [banana scent, (2)]; Females that could see, hear, and smell the male but physical contact was not possible [exposed to male, (3)]; Female rats that could pace the sexual interaction (4); and females that mated without the possibility of pacing the sexual interaction (5). Animals were sacrificed 2 days after the behavioral test (proliferation) or 45 days later (survival). Our results show that 2 days after females were exposed to banana scent or to the male, they had a higher number of cells in the SVZ. Females, that mated in pace and no-paced conditions had more new cells in the RMS. At 45 days, no significant differences were found in the number of new cells that survived in the MOB or in the AOB. However, mating increased the percentage of new cells, that differentiated into neurons in the GrL of the AOB. These new cells expressed c-Fos after a second sexual encounter just before the females were sacrificed. No significant differences in plasma levels of estradiol and progesterone were observed between groups. Our results indicate that the first sexual experience increases cell proliferation in the RMS and mating

  5. PBPK MODELING OF DELTAMETHRIN IN RATS

    EPA Science Inventory

    The pyrethroid pesticide deltamethrin is cleared nearly twice as rapidly in human liver microsomes compared to rat liver microsomes. A species difference such as this could influence the toxic potency of deltamethrin between rats and humans. PBPK modeling is a tool that can be ut...

  6. Eating pattern of morphine dependent rats.

    PubMed

    Yanaura, S; Suzuki, T

    1979-10-01

    To analyze the drug ingestion patterns of rats in the course of dependence development while on the drug-admixed food (DAF) method, an automatic food intake measuring apparatus was developed. Rats were put on morphine-admixed food, and the food ingestion patterns were recorded with the apparatus in the course of dependence development, during drug withdrawal and at the time of challenge with levallorphan. The naive rats ate the regular diet intermittently at night, and the eating time of morphine-treated rats was longer than that of naive rats. The treated rats also exhibited a frequent eating behavior after 4--5 days on the morphine treatment. During morphine withdrawal, the animal gradually ate the regular diet at about 1-hour intervals, even after evolvement of abstinence signs. When the morphine-dependent rats were given levallorphan, they neither ate nor approached to the food for the first 2--3 hours, but after this time, showed abrupt increases in these activities. Thus, the drug intake pattern of rats in the course of morphine dependence development suggests a correlation between the stage of development of physical dependence and the stage when the animals frequently eat the drug-admixed food.

  7. Same-Different Categorization in Rats

    ERIC Educational Resources Information Center

    Wasserman, Edward A.; Castro, Leyre; Freeman, John H.

    2012-01-01

    Same-different categorization is a fundamental feat of human cognition. Although birds and nonhuman primates readily learn same-different discriminations and successfully transfer them to novel stimuli, no such demonstration exists for rats. Using a spatial discrimination learning task, we show that rats can both learn to discriminate arrays of…

  8. Hypoglycaemic activity of Ocimum gratissimum in rats.

    PubMed

    Aguiyi, J C; Obi, C I; Gang, S S; Igweh, A C

    2000-08-01

    The hypoglycaemic effect of the methanolic extract of Ocimum gratissimum leaves was evaluated in normal and alloxan-induced diabetic rats. Intraperitoneal injection of the extract (400 mg/kg) significantly reduced plasma levels both in normal and diabetic rats by 56 and 68%, respectively. PMID:10925022

  9. Spatial Memory in Rats after 25 Hours

    ERIC Educational Resources Information Center

    Crystal, Jonathon D.; Babb, Stephanie J.

    2008-01-01

    We investigated the time course of spatial-memory decay in rats using an eight-arm radial maze. It is well established that performance remains high with retention intervals as long as 4 h, but declines to chance with a 24-h retention interval (Beatty, W. W., & Shavalia, D. A. (1980b). Spatial memory in rats: time course of working memory and…

  10. Stimulus Over-Selectivity in Rats

    ERIC Educational Resources Information Center

    Gibson, Evelyn; Reed, Phil

    2005-01-01

    The present study explored whether a similar phenomenon to stimulus over-selectivity occurred in rats, in the hope of establishing a non-human model for the autism. Rats were serially presented with two-15 seconds, two-element compound stimuli prior to the delivery of food, in an appetitive classical conditioning procedure. Each compound stimulus…

  11. Effect of Nd:YAG laser light on post-extractive socket healing in rats treated with zoledronic acid and dexamethasone

    NASA Astrophysics Data System (ADS)

    Mergoni, Giovanni; Merigo, Elisabetta; Passerini, Pietro; Corradi, Domenico; Maestri, Roberta; Bussolati, Ovidio; Bianchi, Massimiliano; Sala, Roberto; Govoni, Paolo; Namour, Samir; Vescovi, Paolo

    2016-03-01

    Introduction The effect of low level laser therapy (LLLT) on the healing process could be useful for the prevention of post-extractive Bisphosphonate-related Osteonecrosis of the Jaws (BRONJ). The aim of the study was to investigate the effect of LLLT on the post-extractive socket healing in rats treated with zoledronic acid and dexamethasone. Material and Methods Thirty male Sprague-Dawley rats were divided in 4 groups: control group (C, n = 5), laser group (L, n = 5), treatment group (T, n = 10) and treatment plus laser group (T+L, n = 10). Rats of group T and T+L received zoledronate 0,1 mg/Kg and dexamethasone 1 mg/Kg every 2 days for 10 weeks. Rats of group C and L were infused with vehicle. After 9 weeks the first maxillary molars were extracted in all rats. Rats of groups L and T+L received laser therapy (Nd:YAG, 1064 nm, 1.25W, 15Hz, 5 min, 14.37 J/cm2) in the socket area at days 0, 2, 4 and 6 after surgery. At 8 days from extraction, the sockets were clinically assessed with a grading score and the wound area was measured with a dedicate software. Histomorphometric evaluation and western blot analysis of osteopontin and osteocalcin expression were performed. Results Group T+L showed a trend toward a better clinical grading score compared to group T (grade I 22% Vs 28 % - grade II 56% Vs 28% - grade III 22% Vs 44%, respectively). The average wound area was similar among the groups. Inhibition of osteoclastic alveolar bone resorption was found in groups T and T+L (P<0.001). Rats of groups L and T+L showed a significant higher expression of osteocalcin compared to rats of groups C and T (C=0.3993; L=1.394; T=0.2922; T+L=1.156; P=0.0001). The expression of osteopontin did not show significant differences in the groups treated with Nd:YAG compared to the ones that did not receive laser irradiation. Conclusion Our findings suggest that laser irradiation after tooth extraction can promote osteoblast differentiation, as demonstrated by the higher expression of

  12. Ethinyl estradiol-induced cell proliferation in rat liver. Involvement of specific populations of hepatocytes.

    PubMed

    Mayol, X; Neal, G E; Davies, R; Romero, A; Domingo, J

    1992-12-01

    Hepatocyte proliferation was analyzed in vivo during the time course of continuous administration to rats of the liver tumor promoter ethinyl estradiol (EE) at 10 p.p.m. in the diet. EE-induced acute liver hyperplasia was detected in male and female Sprague-Dawley rats as an increased mitotic index of hepatocytes after 2 days of treatment. 5'-Bromodeoxyuridine (BrdU) labeling showed that proliferating hepatocytes were randomly distributed throughout the hepatic lobule. Subsequently, and still during the first few days of continuous EE treatment, hepatocyte proliferation decreased to control levels, and a transient increase in the incidence of apoptosis in the liver was detected. Although consistent with the concept of liver growth regression after mitogen-induced hyperplasia, these results differ from others reported to date in that, in our experiments, the cessation of cell proliferation and the subsequent growth regression occurred without withdrawal of EE in our experiments. After returning to control levels, hepatocellular proliferation again increased between 3 and 6 months of chronic treatment and remained activated during the following months of continuous treatment, as seen by accumulative BrdU labeling. Proliferating hepatocytes were predominantly located in zone 2 of the hepatic lobule at this time, surrounding a periportal zone of vacuolated hepatocytes, which were also induced by the treatment. Moreover, hyperplasia of basophilic hepatocytes was also seen around some portal spaces. In another set of experiments, chronic EE-induced activation was characterized by flow cytometry on hepatocytes isolated from male Fischer rats. Ploidy analysis of hepatocyte cell suspensions showed that the normal polyploid pattern of hepatocytes was altered by EE, the proportion of diploid hepatocytes rising considerably. The results also showed that these diploid cells were the most susceptible hepatocyte population to EE-induced proliferation, as shown by a combination of

  13. Is fructose sweeter than glucose for rats?

    PubMed

    Ramirez, I

    1996-11-01

    Because it is generally thought that the intensity of the taste of fructose is greater than that of glucose for rats, it seemed surprising when sham-fed rats drank substantially less of a mixture of 6% fructose plus saccharin than of a mixture of 6% glucose plus saccharin. At least 3 different factors contribute to this effect. First, the taste of fructose is less attractive to rats than is the taste of glucose; sham-fed rats strongly preferred glucose over fructose (no saccharin was used in this experiment). The second factor is experience. Rats having substantial previous experience with glucose, but not with fructose, consistently preferred glucose over fructose. Conversely, rats having substantial previous experience with fructose, but not with glucose, initially showed no consistent preference but subsequently tended to prefer glucose. The third factor is an interaction between saccharin and the type of sugar. Rats given only one solution at a time drink approximately as much fructose as glucose when the solutions contain no saccharin. The addition of 0.25% saccharin to 6% glucose stimulated intake, whereas the addition of the same amount of saccharin to 6% fructose did not stimulate intake. As a result, rats ingested substantially more of a mixture of 0.25% saccharin plus 6% glucose than they did of a comparable mixture of saccharin and fructose, even though rats ingest similar amounts of fructose and glucose without saccharin in single-bottle tests. Because the differential effect of saccharin on intake appeared within 2 h in naive rats, and did not greatly change over a 3-day period, it is probably not attributable to conditioning. These results suggest that these sugars have qualitatively different tastes. PMID:8916185

  14. Mitochondrial DNA Phylogeography of the Norway Rat

    PubMed Central

    Song, Ying; Lan, Zhenjiang; Kohn, Michael H.

    2014-01-01

    Central Eastern Asia, foremost the area bordering northern China and Mongolia, has been thought to be the geographic region where Norway rats (Rattus norvegicus) have originated. However recent fossil analyses pointed to their origin in southern China. Moreover, whereas analyses of fossils dated the species' origin as ∼1.2–1.6 million years ago (Mya), molecular analyses yielded ∼0.5–2.9 Mya. Here, to study the geographic origin of the Norway rat and its spread across the globe we analyzed new and all published mitochondrial DNA cytochrome-b (cyt-b; N = 156) and D-loop (N = 212) sequences representing wild rats from four continents and select inbred strains. Our results are consistent with an origin of the Norway rat in southern China ∼1.3 Mya, subsequent prehistoric differentiation and spread in China and Asia from an initially weakly structured ancestral population, followed by further spread and differentiation across the globe during historic times. The recent spreading occurred mostly from derived European populations rather than from archaic Asian populations. We trace laboratory strains to wild lineages from Europe and North America and these represent a subset of the diversity of the rat; leaving Asian lineages largely untapped as a resource for biomedical models. By studying rats from Europe we made the observation that mtDNA diversity cannot be interpreted without consideration of pest control and, possibly, the evolution of rodenticide resistance. However, demographic models explored by forward-time simulations cannot fully explain the low mtDNA diversity of European rats and lack of haplotype sharing with their source from Asia. Comprehensive nuclear marker analyses of a larger sample of Norway rats representing the world are needed to better resolve the evolutionary history of wild rats and of laboratory rats, as well as to better understand the evolution of anticoagulant resistance. PMID:24586325

  15. Social exclusion intensifies anxiety-like behavior in adolescent rats.

    PubMed

    Lee, Hyunchan; Noh, Jihyun

    2015-05-01

    Social connection reduces the physiological reactivity to stressors, while social exclusion causes emotional distress. Stressful experiences in rats result in the facilitation of aversive memory and induction of anxiety. To determine the effect of social interaction, such as social connection, social exclusion and equality or inequality, on emotional change in adolescent distressed rats, the emotional alteration induced by restraint stress in individual rats following exposure to various social interaction circumstances was examined. Rats were assigned to one of the following groups: all freely moving rats, all rats restrained, rats restrained in the presence of freely moving rats and freely moving rats with a restrained rat. No significant difference in fear-memory and sucrose consumption between all groups was found. Change in body weight significantly increased in freely moving rats with a restrained rat, suggesting that those rats seems to share the stressful experience of the restrained rat. Interestingly, examination of the anxiety-like behavior revealed only rats restrained in the presence of freely moving rats to have a significant increase, suggesting that emotional distress intensifies in positions of social exclusion. These results demonstrate that unequally excluded social interaction circumstances could cause the amplification of distressed status and anxiety-related emotional alteration.

  16. Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction.

    PubMed

    Garg, Monika; Khanna, Deepa; Kalra, Sanjeev; Balakumar, Pitchai

    2016-10-01

    Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses. PMID:27148865

  17. Changes in levels of 8-hydroxyguanine in DNA, its repair and OGG1 mRNA in rat lungs after intratracheal administration of diesel exhaust particles.

    PubMed

    Tsurudome, Y; Hirano, T; Yamato, H; Tanaka, I; Sagai, M; Hirano, H; Nagata, N; Itoh, H; Kasai, H

    1999-08-01

    Diesel exhaust particles (DEP), an environmental pollutant, are known to induce lung cancer in experimental animals. To clarify whether reactive oxygen species (ROS) are involved in its carcinogenic mechanism, we examined the levels of 8-hydroxyguanine (8-OH-Gua), its total repair and the repair enzyme OGG1 mRNA in female Fischer 344 rat lungs, as markers of the response to ROS, after DEP was intratracheally instilled. The 8-OH-Gua levels in both DEP-treated groups (2 and 4 mg) were increased during the 2-8 h following exposure to DEP. The 8-OH-Gua repair activities in the DEP-treated groups decreased during the period from 2 h to 2 days following DEP exposure and then recovered to the level of the control group at 5 days after exposure. OGG1 mRNA was induced in rats treated with 4 mg DEP for 5-7 days after administration. In conclusion, the 8-OH-Gua level in rat lung DNA increases markedly at an early phase after DEP exposure, by the generation of ROS and the inhibition of 8-OH-Gua repair activity, and induction of OGG1 mRNA is also a good marker of cellular oxidative stress during carcinogenesis. PMID:10426809

  18. Salmonella choleraesuis and Salmonella typhimurium associated with liver cells after intravenous inoculation of rats are localized mainly in Kupffer cells and multiply intracellularly.

    PubMed

    Nnalue, N A; Shnyra, A; Hultenby, K; Lindberg, A A

    1992-07-01

    Male Sprague-Dawley rats were inoculated intravenously with Salmonella choleraesuis or Salmonella typhimurium and used over 3 consecutive days to produce highly enriched (greater than 95% homogenous) preparations of Kupffer and mononuclear cells (KC), liver endothelial cells (LEC), and hepatocytes. The methods involved collagenase perfusion of the liver in situ, differential centrifugation of liver cells over a Percoll gradient, and selective attachment of the cells to plastic or to culture dishes coated with collagen. The different cell preparations were then assayed for the number and location, intracellular or extracellular, of associated viable bacteria. Most of the viable bacteria recovered were associated with KC and were mainly intracellular. The intracellular bacteria in KC from rats infected with either bacterial strain increased about 20- to 50-fold over 2 days. Some of the bacteria associated with LEC and in some experiments with hepatocytes also survived treatment with gentamicin and increased in number with time. Intracellular bacteria were readily visualized in KC by light microscopy and transmission electron microscopy. On rare occasions, bacteria were seen within LEC from rats infected with S. choleraesuis but not from those infected with S. typhimurium. Microcolonies of S. typhimurium but not of S. choleraesuis were occasionally found on the surface of some LEC. Bacteria were not seen within or on the surface of hepatocytes by transmission or scanning electron microscopy. The integration of microscopic and viability data suggested that most intracellular S. choleraesuis organisms in KC had been killed whereas most intracellular S. typhimurium organisms were viable.

  19. Correlation between the cumulative analgesic effect of electroacupuncture intervention and synaptic plasticity of hypothalamic paraventricular nucleus neurons in rats with sciatica☆

    PubMed Central

    Xu, Qiuling; Liu, Tao; Chen, Shuping; Gao, Yonghui; Wang, Junying; Qiao, Lina; Liu, Junling

    2013-01-01

    In the present study, a rat model of chronic neuropathic pain was established by ligation of the sciatic nerve and a model of learning and memory impairment was established by ovariectomy to investigate the analgesic effect of repeated electroacupuncture stimulation at bilateral Zusanli (ST36) and Yanglingquan (GB34). In addition, associated synaptic changes in neurons in the paraventricular nucleus of the hypothalamus were examined. Results indicate that the thermal pain threshold (paw withdrawal latency) was significantly increased in rats subjected to 2-week electroacupuncture intervention compared with 2-day electroacupuncture, but the analgesic effect was weakened remarkably in ovariectomized rats with chronic constrictive injury. 2-week electroacupuncture intervention substantially reversed the chronic constrictive injury-induced increase in the synaptic cleft width and thinning of the postsynaptic density. These findings indicate that repeated electroacupuncture at bilateral Zusanli and Yanglingquan has a cumulative analgesic effect and can effectively relieve chronic neuropathic pain by remodeling the synaptic structure of the hypothalamic paraventricular nucleus. PMID:25206591

  20. Peripheral gene expression profile of mechanical hyperalgesia induced by repeated cold stress in SHRSP5/Dmcr rats.

    PubMed

    Kozaki, Yasuko; Umetsu, Rena; Mizukami, Yukako; Yamamura, Aya; Kitamori, Kazuya; Tsuchikura, Satoru; Ikeda, Katsumi; Yamori, Yukio

    2015-09-01

    Repeated cold stress (RCS) is known to transiently induce functional disorders associated with hypotension and hyperalgesia. In this study, we investigated the effects of RCS (24 and 4 °C alternately at 30-min intervals during the day and 4 °C at night for 2 days, followed by 4 °C on the next 2 consecutive nights) on the thresholds for cutaneous mechanical pain responses and on peripheral expression of "pain-related genes" in SHRSP5/Dmcr rats, which are derived from stroke-prone spontaneously hypertensive rats. To define genes peripherally regulated by RCS, we detected changes in the expression of pain-related genes in dorsal root ganglion cells by PCR-based cDNA subtraction analysis or DNA microarray analysis, and confirmed the changes by RT-PCR. We found significantly changed expression in eight pain-related genes (upregulated: Fyn, St8sia1, and Tac 1; downregulated: Ctsb, Fstl1, Itpr1, Npy, S100a10). At least some of these genes may play key roles in hyperalgesia induced by RCS.

  1. Cytochrome P450 induction in mallard duck (MD), black-crowned night heron (BCNH) and Fisher-344 rat

    USGS Publications Warehouse

    Melancon, M.J.; Rattner, B.A.; Stegeman, John J.

    1991-01-01

    P450 induction was studied in adult and pipping MDs, pipping BCNHs, and rats. Adult MDs and rats received i.p. injection of corn oil, 3-methylcholanthrene (MC) in corn oil (20 mg/kg), saline or phenobarbital (PB) in saline (80 mg/kg) for 3 days. MD and BCNH embryos received MC and PB by injection into the aircell approximately 2 days before pipping and were sacrificed at pipping. Hepatic microsomes were assayed for protein, arylhydrocarbon hydroxylase (AHH), benzphetamine-N-demethylase (BEND), ethoxy-resorufin-O-dealkylase (EROD), pentoxyresorufin-O-dealkylase (PROD), benzyloxyresorufin-O-dealkylase (BROD), ethoxycoumarin-O-dealkylase (ECOD), and by SDS-PAGE with western blot using a polyclonal anti-P4S0IIB antibody and a monoclonal anti-P450IA antibody (MAb 1-12-3). Although species and age caused substantial differences in responses, all treated groups showed an increase in one or more monooxygenase assays. All animals treated with MC showed a strong induction of a protein recognized by anti-P450IA, and all those treated with PB showed strong induction of a band recognized by anti-P450IIB.

  2. Peripheral gene expression profile of mechanical hyperalgesia induced by repeated cold stress in SHRSP5/Dmcr rats.

    PubMed

    Kozaki, Yasuko; Umetsu, Rena; Mizukami, Yukako; Yamamura, Aya; Kitamori, Kazuya; Tsuchikura, Satoru; Ikeda, Katsumi; Yamori, Yukio

    2015-09-01

    Repeated cold stress (RCS) is known to transiently induce functional disorders associated with hypotension and hyperalgesia. In this study, we investigated the effects of RCS (24 and 4 °C alternately at 30-min intervals during the day and 4 °C at night for 2 days, followed by 4 °C on the next 2 consecutive nights) on the thresholds for cutaneous mechanical pain responses and on peripheral expression of "pain-related genes" in SHRSP5/Dmcr rats, which are derived from stroke-prone spontaneously hypertensive rats. To define genes peripherally regulated by RCS, we detected changes in the expression of pain-related genes in dorsal root ganglion cells by PCR-based cDNA subtraction analysis or DNA microarray analysis, and confirmed the changes by RT-PCR. We found significantly changed expression in eight pain-related genes (upregulated: Fyn, St8sia1, and Tac 1; downregulated: Ctsb, Fstl1, Itpr1, Npy, S100a10). At least some of these genes may play key roles in hyperalgesia induced by RCS. PMID:25972297

  3. Experiment K-6-17. Structural changes and cell turnover in the rats small intestine induced by spaceflight

    NASA Technical Reports Server (NTRS)

    Phillips, R. W.; Sawyer, H. R.; Smirnov, K. V.

    1990-01-01

    The purpose of this project was to test the hypothesis that the generalized, whole body decrease in synthetic activity associated with microgravity conditions of space flight as evidenced by negative nitrogen balance and muscle atrophy (Nicogossian and Parker, 1982; Oganov, 1981), as well as inhibited lymphocyte proliferation (Bechler and Cogoli, 1986), would be evident in cells characterized by a rapid rate of turnover. As a model, researchers chose to study the turnover of mucosal cells lining the jejunum of the small intestine, since these cells are among the most rapidly proliferating in the body. Under normal conditions, epithelial cells that line the small intestine are continually produced in the crypts of Lieberkuhn. These cells migrate out of the crypts onto intestinal villi, are progressively pushed up the villus as new crypt cells are formed, and ultimately reach the tip of villi where they are then descquamated. In rats, the entire process, from initial proliferation in crypts to desquamation, takes approximately 2 days (Cairnie et al., 1965; Lipkin, 1973). In this study, researchers determined the mitotic index for mucosal cells lining the proximal, middle, and distal regions of the jejunum in rats from three treatment groups (synchronous control, vivarium control and flight), and measured the depth of the crypts of Lieberkuhn and the length of villi present in each of the three jejunal regions sampled.

  4. Analgesic effect of simultaneous exposure to infrared laser radiation and μT magnetic field in rats

    NASA Astrophysics Data System (ADS)

    Cieslar, Grzegorz; Mrowiec, Janina; Kasperczyk, Slawomir; Sieron-Stoltny, Karolina; Sieron, Aleksander

    2008-03-01

    The aim of the experiment was to estimate the effect of repeated simultaneous exposures to infrared laser radiation and μT variable magnetic field used in magnetostimulation on pain perception in rats, as well as the involvement of endogenous opioid system in the mechanism of this effect. In experimental group clean-shaven scull of male Wistar rats placed individually in a specially designed plastic chamber were simultaneously exposed to infrared laser radiation (wavelength - 855 nm, mean power - 4,1 mW, energy density - 30 J/cm2) and variable magnetic field of saw-like shape of impulse, at a frequency of basic impulse 180-195 Hz and mean induction value of 120 μT generated by magneto-laser applicator of device for magnetostimulation Viofor JPS (Med & Life, Poland) 12 minutes daily for 2 periods of 5 consecutive days, with 2 days-lasting break between them, while control animals were sham-exposed. The pain perception was determined by means of "hot plate" test on the basis of calculated analgesic index. As a result of repeated exposures a significant increase in analgesic index persisting also till 14 th day after the end of a cycle of exposures was observed. This analgesic effect was inhibited by prior i.p. injection of opioid antagonist - Naloxone.

  5. Leptin ameliorates ischemic necrosis of the femoral head in rats with obesity induced by a high-fat diet

    PubMed Central

    Zhou, Lu; Jang, Kyu Yun; Moon, Young Jae; Wagle, Sajeev; Kim, Kyoung Min; Lee, Kwang Bok; Park, Byung-Hyun; Kim, Jung Ryul

    2015-01-01

    Obesity is a risk factor for ischemic necrosis of the femoral head (INFH). The purpose of this study was to determine if leptin treatment of INFH stimulates new bone formation to preserve femoral head shape in rats with diet-induced obesity. Rats were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks to induce progressive development of obesity. Avascular necrosis of the femoral head (AVN) was surgically induced. Adenovirus-mediated introduction of the leptin gene was by intravenous injection 2 days before surgery-induced AVN. At 6 weeks post-surgery, radiologic and histomorphometric assessments were performed. Leptin signaling in tissues was examined by Western blot. Osteogenic markers were analyzed by real-time RT-PCR. Radiographs showed better preservation of femoral head architecture in the HFD-AVN-Leptin group than the HFD-AVN and HFD-AVN-LacZ groups. Histology and immunohistochemistry revealed the HFD-AVN-Leptin group had significantly increased osteoblastic proliferation and vascularity in infarcted femoral heads compared with the HFD-AVN and HFD-AVN-LacZ groups. Intravenous injection of leptin enhanced serum VEGF levels and activated HIF-1α pathways. Runx 2 and its target genes were significantly upregulated in the HFD-AVN-Leptin group. These results indicate that leptin resistance is important in INFH pathogenesis. Leptin therapy could be a new strategy for INFH. PMID:25797953

  6. Acute myocardial infarction in rats.

    PubMed

    Wu, Yewen; Yin, Xing; Wijaya, Cori; Huang, Ming-He; McConnell, Bradley K

    2011-01-01

    With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial

  7. [Nosema sp. in white rats].

    PubMed

    Grobov, O F; Karakuiumchiani, M K; Orlova-Sokol'skaia, I A

    1975-01-01

    In 14 days after the intraperitoneal infection of mice with 30% brain emulsion of white mice or of newly-born rats in the peritoneal liquid there were found spores of Nosema sp. 5.37 plus or minus 0.88 x 3.04 plus or minus 0.07 in size. The subsequent attempts to passage this organism on the mice by adminestering into them the suspension from the brain and internal organs of infected animals yielded ho results. The material for diagnosing on microsporidians of mammals is being discussed.

  8. Anxiolytic Treatment Impairs Helping Behavior in Rats.

    PubMed

    Ben-Ami Bartal, Inbal; Shan, Haozhe; Molasky, Nora M R; Murray, Teresa M; Williams, Jasper Z; Decety, Jean; Mason, Peggy

    2016-01-01

    Despite decades of research with humans, the biological mechanisms that motivate an individual to help others remain poorly understood. In order to investigate the roots of pro-sociality in mammals, we established the helping behavior test, a paradigm in which rats are faced with a conspecific trapped in a restrainer that can only be opened from the outside. Over the course of repeated test sessions, rats exposed to a trapped cagemate learn to open the door to the restrainer, thereby helping the trapped rat to escape (Ben-Ami Bartal et al., 2011). The discovery of this natural behavior provides a unique opportunity to probe the motivation of rodent helping behavior, leading to a deeper understanding of biological influences on human pro-sociality. To determine if an affective response motivates door-opening, rats receiving midazolam, a benzodiazepine anxiolytic, were tested in the helping behavior test. Midazolam-treated rats showed less helping behavior than saline-treated rats or rats receiving no injection. Yet, midazolam-treated rats opened a restrainer containing chocolate, highlighting the socially specific effects of the anxiolytic. To determine if midazolam interferes with helping through a sympatholytic effect, the peripherally restricted beta-adrenergic receptor antagonist nadolol was administered; nadolol did not interfere with helping. The corticosterone response of rats exposed to a trapped cagemate was measured and compared to the rats' subsequent helping behavior. Rats with the greatest corticosterone responses showed the least helping behavior and those with the smallest responses showed the most consistent helping at the shortest latency. These results are discussed in terms of their implications for the interaction between stress and pro-social behavior. Finally, we observed that door-opening appeared to be reinforcing. A novel analytical tool was designed to interrogate the pattern of door-opening for signs that a rat's behavior on one session

  9. A critical point of male gonad development: neuroendocrine correlates of accelerated testicular growth in rats during early life.

    PubMed

    Dygalo, Nikolay N; Shemenkova, Tatjana V; Kalinina, Tatjana S; Shishkina, Galina T

    2014-01-01

    Testis growth during early life is important for future male fertility and shows acceleration during the first months of life in humans. This acceleration coincides with the peak in gonadotropic hormones in the blood, while the role of hypothalamic factors remains vague. Using neonatal rats to assess this issue, we found that day 9 of life is likely critical for testis development in rats. Before this day, testicular growth was proportional to body weight gain, but after that the testes showed accelerated growth. Hypothalamic kisspeptin and its receptor mRNA levels begin to elevate 2 days later, at day 11. A significant increase in the mRNA levels for gonadotropin-releasing hormone (GnRH) receptors in the hypothalamus between days 5 and 7 was followed by a 3-fold decrease in GnRH mRNA levels in this brain region during the next 2 days. Starting from day 9, hypothalamic GnRH mRNA levels increased significantly and positively correlated with accelerated testicular growth. Triptorelin, an agonist of GnRH, at a dose that had no effect on testicular growth during "proportional" period, increased testis weights during the period of accelerated growth. The insensitivity of testicular growth to GnRH during "proportional" period was supported by inability of a 2.5-fold siRNA knockdown of GnRH expression in the hypothalamus of the 7-day-old animals to produce any effect on their testis weights. GnRH receptor blockade with cetrorelix was also without effect on testis weights during "proportional" period but the same doses of this GnRH antagonist significantly inhibited "accelerated" testicular growth. GnRH receptor mRNA levels in the pituitary as well as plasma LH concentrations were higher during "accelerated" period of testicular growth than during "proportional" period. In general, our data defined two distinct periods in rat testicular development that are primarily characterized by different responses to GnRH signaling.

  10. Electroencephalographic changes in albino rats subjected to stress

    NASA Technical Reports Server (NTRS)

    Mercier, J.; Assouline, G.; Fondarai, J.

    1980-01-01

    Twenty one albino Wistar rats were subjected to stress for 7 hours. There was a significant difference in the slopes of regression lines for 7 nonulcerous rats and those for 14 ulcerous rats. Nonulcerous rats subjected to stress showed greater EEG curve synchronization than did ulcerous rats. If curve synchronization can be equated to a relaxed state, it may therefore be possible to explain the protective action of hypnotics, tranquilizers and analgesics on ulcers.

  11. Persistent Seoul virus infection in Lewis rats.

    PubMed

    Compton, S R; Jacoby, R O; Paturzo, F X; Smith, A L

    2004-07-01

    Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80-39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.

  12. Total parenteral nutrition in diabetic rats

    SciTech Connect

    Norcross, E.D.; Stein, T.P.

    1986-03-01

    Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using /sup 15/N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats.

  13. Altered proportions of RCS-rat eyes.

    PubMed

    Schreckenberger, M; Eichhorn, M; Gottanka, J; Döbig, C; Lütjen-Drecoll, E

    1994-10-01

    The growth pattern of RCS-rat eyes with hereditary retinal degeneration was analysed morphometrically, evaluating midsagittal sections of the entire globe and sections of the chamber angle region. No changes of the axial diameter of RCS-rat eyes were found if compared with eyes of age-matched controls. There were, however, characteristic proportional changes in the anterior eye segment of RCS rats. The distance between the peripheral end of Descemet's membrane (DM) and both the posterior end of Schlemm's canal and the ora serrata were significantly elongated indicating that this region might be most susceptible to growth factors. The length of the posterior globe up to the level of the ora serrata was shorter in RCS rats than in control rats. In addition, in RCS-rat eyes the pars plana was significantly elongated and the pars plicata shortened. Ultrastructural changes of ciliary epithelium were not seen before 7 months of age in RCS rats. They were only present in those parts of the circumference in which the stromal capillaries also revealed structural changes. The ciliary epithelial alterations were therefore considered secondary to narrowing or rarefication in the adjacent blood vessels.

  14. Embryolethality of butyl benzyl phthalate in rats

    SciTech Connect

    Ema, N.; Itami, T.; Kawasaki, H. )

    1991-03-15

    The developmental toxicity of butyl benzyl phthalate (BBP) was studied in Wistar rats. Pregnant rats were given BBP at a dosage of 0, 0.25, 0.5, 1.0 or 2.0% in the diet from day 0 to day 20 of pregnancy. Morphological examinations of the fetuses revealed no evidence of teratogenesis. In the 2.0% group, all dams exhibited complete resorption of all the implanted embryos, and their food consumption, body weight gain and adjusted weight gain during pregnancy were markedly lowered. To determine whether the embryolethality was the result of reduced food consumption during pregnancy, a pair-feeding study was performed in which the pregnant rats received the same amount of diet consumed by the 2.0% BBP-treated pregnant rats. The pair-fed and 2.0 % BBP-treated pregnant rats showed significant and comparable reductions in the adjusted weight gain. The number of live fetuses was lowered in the pair-fed group. However, the complete resorption of all the implanted embryos was not found in any of the pair-fed pregnant rats. The data suggest that the embryolethality observed in the 2.0 % BBP-treated pregnant rats is attributable to the effects o dietary BBP.

  15. Wood rats and kangaroo rats: potential reservoirs of the Lyme disease spirochete in California.

    PubMed

    Lane, R S; Brown, R N

    1991-05-01

    The etiologic agent of Lyme disease, Borrelia burgdorferi Johnson, Schmid, Hyde, Steigerwalt & Brenner, was isolated repeatedly from dusky-footed wood rats, Neotoma fuscipes Baird, and California kangaroo rats, Dipodomys californicus Merriam, in northern California. All animals were collected in a region endemic for Lyme disease but for which the natural reservoir of B. burgdorferi was unknown. Similar attempts to isolate spirochetes from lizards, other species of rodents, jack rabbits, and deer between 1987 and 1991 were unsuccessful. Spirochetes isolated from wood rats and kangaroo rats were antigenically similar to strains of B. burgdorferi that had been isolated previously from the western black-legged tick, Ixodes pacificus Cooley & Kohls, in California. Similar enzootic cycles involving wood rats or kangaroo rats should be sought in other regions of the United States where the reservoirs of this spirochete are unknown.

  16. Isomer-specific biotransformation of perfluorooctane sulfonamide in Sprague-Dawley rats.

    PubMed

    Ross, Matthew S; Wong, Charles S; Martin, Jonathan W

    2012-03-20

    Great variability exists in perfluorooctane sulfonate (PFOS) isomer patterns in human and wildlife samples, including unexpectedly high percentages (e.g., >40%) of branched isomers in human sera. Previous in vitro tests showed that branched PFOS-precursors were biotransformed faster than the corresponding linear isomer. Thus, high percentages of branched PFOS may be a biomarker of PFOS-precursor exposure in humans. We evaluated this hypothesis by examining the isomer-specific fate of perfluorooctane sulfonamide (PFOSA), a known PFOS-precursor, in male Sprague-Dawley rats exposed to commercial PFOSA via food for 77 days (83.0 ± 20.4 ng kg(-1) day(-1)), followed by 27 days of depuration. Elimination half-lives of the two major branched PFOSA isomers (2.5 ± 1.0 days and 3.7 ± 1.2 days) were quicker than for linear PFOSA (5.9 ± 4.6 days), resulting in a depletion of branched PFOSA isomers in blood and tissues relative to the dose. A corresponding increase in the total branched isomer content of PFOS, the ultimate metabolite, in rat serum was not observed. However, a significant enrichment of 5m-PFOS and a significant depletion of 1m-PFOS were observed, relative to authentic electrochemical PFOS. The data cannot be directly extrapolated to humans, due to known differences in the toxicokinetics of PFOS in rodents and humans. However, the results confirm that in vivo exposure to commercially relevant PFOS-precursors can result in a distinct PFOS isomer profile that may be useful as a biomarker of exposure source.

  17. Failure of delayed and prolonged hypothermia to favorably affect hemorrhagic stroke in rats.

    PubMed

    MacLellan, Crystal; Shuaib, Ashfaq; Colbourne, Frederick

    2002-12-20

    Prolonged hypothermia reduces global and focal cerebral ischemic injury in rodents even when delayed for hours. However, it is not known whether hypothermia can reduce injury following intracerebral hemorrhage (ICH). Accordingly, we studied striatal injury and concomitant motor deficits after 2 days of hypothermia, induced 1 h after creation of an ICH by infusion of bacterial collagenase. Rats were first trained to retrieve food pellets in the Montoya staircase task. They were then implanted with core temperature telemetry probes and later subjected to normothermic ICH or sham operation (vehicle injection). Half self-regulated temperature after surgery; others were cooled to 33 degrees C (24 h) and then 35 degrees C (24 h). Hypothermia did not affect behavioral scores of sham animals (89.8% of baseline in staircase test) or histology. Untreated (normothermic) ICH rats lost 23.1 mm(3) of tissue at a 1-month survival, which significantly impaired food pellet retrieval (66.0% retrieval) with the contralateral limb (tested on days 21-25). Contrary to our hypothesis, hypothermia failed to lessen either the reaching impairment (62.8%) or the lesion (22.2 mm(3)). While other hemorrhagic insults or complications may be improved with hypothermia, our data suggest that it will not salvage tissue that is quickly lost after ICH. We also assessed walking across a horizontal ladder and spontaneous paw usage in a cylinder test at 1-4 weeks after ICH, but neither test was sufficiently sensitive to this mild insult. This indicates that skilled reaching is more severely disrupted than spontaneous paw usage or walking after a striatal hemorrhage. PMID:12468045

  18. Glutathione depletion induces heme oxygenase-1 (HSP32) mRNA and protein in rat brain.

    PubMed

    Ewing, J F; Maines, M D

    1993-04-01

    In mammalian systems, the heme oxygenase (HO) isozymes HO-1 (HSP32) and HO-2 oxidatively cleave the heme molecule to produce bile pigments and carbon monoxide. Although HO-1 is inducible by various chemicals in systemic organs and cell culture systems, this communication reports for the first time the induction of this stress protein and its transcript by a chemical in the brain. In addition, this study demonstrates expression of HO-1 in select populations of cells in the brain in response to GSH depletion. Specifically, treatment of adult rats with diethyl maleate (DEM; 4.7 mmol/kg) caused a pronounced decrease in brain GSH content within 1 h. GSH levels remained significantly depressed for at least 24 h postinjection. Northern blot analysis of brain poly(A)+ mRNA following DEM treatment revealed on the average a sixfold increase in the 1.8-kb HO-1 mRNA level compared with that of controls; concomitant with this change was a decrease in GSH levels. Total brain HO activity was not significantly altered along with the increase in HO-1 mRNA level. The increase in transcription of HO-1 was a direct response to GSH depletion, as judged by the observation that treatment of neonatal rats with L-buthionine-(S,R)-sulfoximine (BSO) (3 mmol/kg, twice daily, for 2 days), a selective inhibitor of GSH synthesis, caused a marked depression in total brain GSH level and a concomitant increase in brain 1.8-kb HO-1 mRNA content. The magnitude of the increase was up to approximately 11.5-fold that of the control level, as evidenced by northern blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Primed Mycobacterial Uveitis (PMU): Histologic and Cytokine Characterization of a Model of Uveitis in Rats

    PubMed Central

    Pepple, Kathryn L.; Rotkis, Lauren; Van Grol, Jennifer; Wilson, Leslie; Sandt, Angela; Lam, Deborah L.; Carlson, Eric; Van Gelder, Russell N.

    2015-01-01

    Purpose The purpose of this study was to compare the histologic features and cytokine profiles of experimental autoimmune uveitis (EAU) and a primed mycobacterial uveitis (PMU) model in rats. Methods In Lewis rats, EAU was induced by immunization with interphotoreceptor binding protein peptide, and PMU was induced by immunization with a killed mycobacterial extract followed by intravitreal injection of the same extract. Clinical course, histology, and the cytokine profiles of the aqueous and vitreous were compared using multiplex bead fluorescence immunoassays. Results Primed mycobacterial uveitis generates inflammation 2 days after intravitreal injection and resolves spontaneously 14 days later. CD68+ lymphocytes are the predominant infiltrating cells and are found in the anterior chamber, surrounding the ciliary body and in the vitreous. In contrast to EAU, no choroidal infiltration or retinal destruction is noted. At the day of peak inflammation, C-X-C motif ligand 10 (CXCL10), IL-1β, IL-18, and leptin were induced in the aqueous of both models. Interleukin-6 was induced 2-fold in the aqueous of PMU but not EAU. Cytokines elevated in the aqueous of EAU exclusively include regulated on activation, normal T cell expressed and secreted (RANTES), lipopolysaccharide-induced CXC chemokine (LIX), growth-related oncogene/keratinocyte chemokine (GRO/KC), VEGF, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), and IL-17A. In the vitreous, CXCL10, GRO/KC, RANTES, and MIP-1α were elevated in both models. Interleukin-17A and IL-18 were elevated exclusively in EAU. Conclusions Primed mycobacterial uveitis generates an acute anterior and intermediate uveitis without retinal involvement. Primed mycobacterial uveitis has a distinct proinflammatory cytokine profile compared with EAU, suggesting PMU is a good complementary model for study of immune-mediated uveitis. CXCL10, a proinflammatory cytokine, was increased in the aqueous and

  20. Methaqualone metabolism by rat liver microsomes.

    PubMed

    Manowitz, P; Shull, C M

    1976-01-01

    A rat hepatic microsomal system has been established which metabolizes methaqualone. The microsomes are obtained from livers of rats treated with phenobarbital. The methaqualone is dissolved in polyethylene glycol-200 prior to addition to the incubation mixture. A comparison is made between the metabolites obtained in this in vitro system and metabolites obtained from urines of phenobarbital treated rats injected with methaqualone. The same two and sometimes three metabolites, as determined by thin layer and gas liquid chromatography, were found in both the complete microsomal incubation system and the urines.

  1. Skeletal muscle metabolism in hypokinetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, M. E.

    1984-01-01

    Muscle growth, protein metabolism, and amino acid metabolism were studied in various groups of rats. Certain groups were adrenaliectomized; some rats were suspended while others (the controls) were weight bearing. Results show that: (1) metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating glucocorticoids; (2) metabolic changes in the soleus muscle due to higher steroid levels are probably potentiated by greater numbers of steroid receptors; and (3) not all metabolic responses of the soleus muscle to unloading are due to the elevated levels of glucocorticoids or the increased sensitivity of this muscle to these hormones.

  2. Regional heterogeneity of expression of renal NPRs, TonEBP, and AQP-2 mRNAs in rats with acute kidney injury.

    PubMed

    Cha, Seung Ah; Park, Byung Mun; Jung, Yu Jin; Kim, Soo Mi; Kang, Kyung Pyo; Kim, Won; Kim, Suhn Hee

    2015-07-01

    To understand the pathophysiology of ischemia/reperfusion (I/R) - induced acute kidney injury (AKI), the present study defined changes in renal function, plasma renotropic hormones and its receptors in the kidney 2, 5, or 7 days after 45 min-renal ischemia in rats. Blood urea nitrogen, plasma creatinine, and osmolarity increased 2 days after I/R injury and tended to return to control level 7 days after I/R injury. Decreased renal function tended to return to control level 5 days after I/R injury. However, plasma concentrations of atrial natriuretic peptide and renin did not change. In control kidney, natriuretic peptide receptor (NPR)-A, -B and -C mRNAs were highly expressed in medulla (ME), inner cortex (IC), and outer cortex (OC), respectively, and tonicity-responsive enhancer binding protein (TonEBP), auqaporin-2 (AQP-2) and eNOS mRNAs were highly expressed in ME. NPR-A and -B mRNA expressions were markedly decreased 2 days after I/R injury. On 5 days after I/R injury, NPR-A mRNA expression increased in OC and recovered to control level in IC but not in ME. NPR-B mRNA expression was increased in OC, and recovered to control level in IC and ME. NPR-C mRNA expression was markedly decreased in OC 2 and 5 days after I/R injury. TonEBP, APQ-2 and eNOS mRNA expressions were markedly decreased 2 days after I/R injury and did not recover in ME 7 days after I/R injury. Therefore, we suggest that there is a regional heterogeneity of regulation of renal NPRs, TonEBP, and APQ-2 mRNA in AKI. PMID:25858778

  3. Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats.

    PubMed

    Tanaka, Masami; Watanabe, Minoru; Yokomi, Izuru; Matsumoto, Naoki; Sudo, Katsuko; Satoh, Hitoshi; Igarashi, Tsuneo; Seki, Azusa; Amano, Hitoshi; Ohura, Kiyoshi; Ryu, Kakei; Shibata, Shunichi; Nagayama, Motohiko; Tanuma, Jun-ichi

    2015-01-01

    Rats with dwarfism accompanied by skeletal abnormalities, such as shortness of the limbs, tail, and body (dwarf rats), emerged in a Jcl-derived Sprague-Dawley rat colony maintained at the Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine. Since the dwarfism was assumed to be due to a genetic mutation based on its frequency, we bred the dwarf rats and investigated their characteristics in order to identify the causative factors of their phenotypes and whether they could be used as a human disease model. One male and female that produced dwarf progeny were selected, and reproduction was initiated by mating the pair. The incidence of dwarfism was 25.8% among the resultant litter, and dwarfism occurred in both genders, suggesting that it was inherited in an autosomal recessive manner. At 12 weeks of age, the body weights of the male and female dwarf rats were 40% and 57% of those of the normal rats, respectively. In soft X-ray radiographic and histological examinations, shortening and hypoplasia of the long bones, such as the tibia and femur, were observed, which were suggestive of endochondral ossification abnormalities. An immunohistochemical examination detected an aggrecan synthesis disorder, which might have led to delayed calcification and increased growth plate thickening in the dwarf rats. We hypothesized that the principal characteristics of the dwarf rats were systemically induced by insufficient cartilage calcification in their long bones; thus, we named them cartilage calcification insufficient (CCI) rats.

  4. Rats are the smart choice: Rationale for a renewed focus on rats in behavioral genetics.

    PubMed

    Parker, Clarissa C; Chen, Hao; Flagel, Shelly B; Geurts, Aron M; Richards, Jerry B; Robinson, Terry E; Solberg Woods, Leah C; Palmer, Abraham A

    2014-01-01

    Due in part to their rich behavioral repertoire rats have been widely used in behavioral studies of drug abuse-related traits for decades. However, the mouse became the model of choice for researchers exploring the genetic underpinnings of addiction after the first mouse study was published demonstrating the capability of engineering the mouse genome through embryonic stem cell technology. The sequencing of the mouse genome and more recent re-sequencing of numerous inbred mouse strains have further cemented the status of mice as the premier mammalian organism for genetic studies. As a result, many of the behavioral paradigms initially developed and optimized for rats have been adapted to mice. However, numerous complex and interesting drug abuse-related behaviors that can be studied in rats are very difficult or impossible to adapt for use in mice, impeding the genetic dissection of those traits. Now, technological advances have removed many of the historical limitations of genetic studies in rats. For instance, the rat genome has been sequenced and many inbred rat strains are now being re-sequenced and outbred rat stocks are being used to fine-map QTLs. In addition, it is now possible to create "knockout" rats using zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and related techniques. Thus, rats can now be used to perform quantitative genetic studies of sophisticated behaviors that have been difficult or impossible to study in mice. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

  5. Vasopressin V2 receptor mRNA expression and cAMP accumulation in aging rat kidney.

    PubMed

    Klingler, C; Preisser, L; Barrault, M B; Lluel, P; Horgen, L; Teillet, L; Ancellin, N; Corman, B

    1997-06-01

    The ability of the kidney to regulate water balance is impaired with age, although the secretion of vasopressin is maintained in senescent animals. This suggests that the cellular response to antidiuretic hormone is reduced in aging kidney. To test this hypothesis, the relationship between the expression of the vasopressin. V2 receptor mRNA and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- and 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old animals (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12, respectively). The concentration of vasopressin corresponding to half-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comparable sensitivity of the renal cells with age. The age-related impaired response to vasopressin of the V2 receptor was specific for females and was not observed in males. Direct stimulation of adenylyl cyclase by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V2 receptor mRNA level in the MTAL was constant between 10 and 30 mo whether the animals were normally hydrated or dehydrated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V2 mRNA or in posttranslational processing mechanisms or in the coupling between the V2 receptor and adenylyl cyclase. PMID:9227590

  6. Time-of-day modulation of homeostatic and allostatic sleep responses to chronic sleep restriction in rats.

    PubMed

    Deurveilher, S; Rusak, B; Semba, K

    2012-06-15

    To study sleep responses to chronic sleep restriction (CSR) and time-of-day influences on these responses, we developed a rat model of CSR that takes into account the polyphasic sleep patterns in rats. Adult male rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 4 days, beginning at the onset of the 12-h light phase ("3/1" protocol). Electroencephalogram (EEG) and electromyogram (EMG) recordings were made before, during, and after CSR. During CSR, total sleep time was reduced by ∼60% from baseline levels. Both rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) during SO periods increased initially relative to baseline and remained elevated for the rest of the CSR period. In contrast, NREMS EEG delta power (a measure of sleep intensity) increased initially, but then declined gradually, in parallel with increases in high-frequency power in the NREMS EEG. The amplitude of daily rhythms in NREMS and REMS amounts was maintained during SO periods, whereas that of NREMS delta power was reduced. Compensatory responses during the 2-day post-CSR recovery period were either modest or negative and gated by time of day. NREMS, REMS, and EEG delta power lost during CSR were not recovered by the end of the second recovery day. Thus the "3/1" CSR protocol triggered both homeostatic responses (increased sleep amounts and intensity during SOs) and allostatic responses (gradual decline in sleep intensity during SOs and muted or negative post-CSR sleep recovery), and both responses were modulated by time of day.

  7. Effects of short-term acetaminophen and celecoxib treatment on orthodontic tooth movement and neuronal activation in rat.

    PubMed

    Stabile, A C; Stuani, M B S; Leite-Panissi, C R A; Rocha, M J A

    2009-08-14

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for pain relief in orthodontics, but clinical studies reported that they may reduce tooth movement (TM). By other side, TM seems to activate brain structures related to nociception, but the effects of NSAIDs in this activation have not been studied yet. We analyzed the effect of short-term treatment with acetaminophen or celecoxib in the separation of rat upper incisors, as well as in neuronal activation of the spinal trigeminal nucleus, following tooth movement. Thirty rats (400-420 g) were pretreated through oral gavage (1 ml/dose) with acetaminophen (200mg/kg), celecoxib (50mg/kg) or vehicle (carboxymethylcellulose 0.4%). After 30 min, they received an activated (30 g) orthodontic appliance for TM. In controls, this appliance was immediately removed after its introduction. Rats received ground food, and every 12h, one of the drugs or vehicle. After 48 h, they were anesthetized, maxilla was radiographed, and were perfused with 4% paraformaldehyde. Brains were further processed for Fos immunohistochemistry. TM induced incisor distalization (p<0.05) and neuronal activation of the spinal trigeminal nucleus. Treatment with both drugs did not affect tooth movement, but reduced c-fos expression in the caudalis subnucleus. No changes in c-fos expression were seen in the oralis and interpolaris subnuclei. We conclude that neither celecoxib nor acetaminophen seems to affect tooth movement, when used for 2 days, but both drugs are able to reduce the activation of brain structures related to nociception. Short-term treatment with celecoxib, thus, may be a therapeutic alternative to acetaminophen when the latter is contraindicated.

  8. Time-of-day modulation of homeostatic and allostatic sleep responses to chronic sleep restriction in rats.

    PubMed

    Deurveilher, S; Rusak, B; Semba, K

    2012-06-15

    To study sleep responses to chronic sleep restriction (CSR) and time-of-day influences on these responses, we developed a rat model of CSR that takes into account the polyphasic sleep patterns in rats. Adult male rats underwent cycles of 3 h of sleep deprivation (SD) and 1 h of sleep opportunity (SO) continuously for 4 days, beginning at the onset of the 12-h light phase ("3/1" protocol). Electroencephalogram (EEG) and electromyogram (EMG) recordings were made before, during, and after CSR. During CSR, total sleep time was reduced by ∼60% from baseline levels. Both rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS) during SO periods increased initially relative to baseline and remained elevated for the rest of the CSR period. In contrast, NREMS EEG delta power (a measure of sleep intensity) increased initially, but then declined gradually, in parallel with increases in high-frequency power in the NREMS EEG. The amplitude of daily rhythms in NREMS and REMS amounts was maintained during SO periods, whereas that of NREMS delta power was reduced. Compensatory responses during the 2-day post-CSR recovery period were either modest or negative and gated by time of day. NREMS, REMS, and EEG delta power lost during CSR were not recovered by the end of the second recovery day. Thus the "3/1" CSR protocol triggered both homeostatic responses (increased sleep amounts and intensity during SOs) and allostatic responses (gradual decline in sleep intensity during SOs and muted or negative post-CSR sleep recovery), and both responses were modulated by time of day. PMID:22492816

  9. Neuroprotective effect of L-carnitine in the 3-nitropropionic acid (3-NPA)-evoked neurotoxicity in rats.

    PubMed

    Binienda, Zbigniew; Virmani, Ashraf; Przybyla-Zawislak, Beata; Schmued, Larry

    2004-09-01

    A plant and fungal toxin, 3-NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, succinate dehydrogenase (SDH). Inhibition of SDH disturbs electron transport and leads to cellular energy deficits and neuronal injury. We have shown that pretreatment with l-carnitine, while not significantly attenuating SDH inhibition, prevented hypothermia and oxidative stress-associated increased activity of free radical-scavenging enzymes. Here, a neurohistological method was applied to examine the effect of carnitine pretreatment against 3-NPA-induced neurotoxicity. Twenty adult male Sprague-Dawley rats were randomly divided into two groups (n = 10/group). Rats in the first group were injected twice with 3-NPA at 30 mg/kg s.c., 2 days apart, and the second group of animals received l-carnitine pretreatment at 100 mg/kg 30-40 min before 3-NPA administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro-Jade B. In the three animals that survived 3-NPA dosing, one exhibited no pathology, one exhibited moderate unilateral damage to the striatum, and the third exhibited extensive bilateral neuronal degeneration in multiple forebrain regions. In the seven surviving animals that received l-carnitine prior to 3-NPA insult, six exhibited no lesions, while one exhibited a modest unilateral lesion in the striatum. It appears that l-carnitine is protective against 3-NPA-induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration.

  10. Effect of Roux-en-Y Gastric Bypass Surgery on Bile Acid Metabolism in Normal and Obese Diabetic Rats

    PubMed Central

    Bhutta, Hina Y; Rajpal, Neetu; White, Wendy; Freudenberg, Johannes M.; Liu, Yaping; Way, James; Rajpal, Deepak; Cooper, David C.; Young, Andrew; Tavakkoli, Ali; Chen, Lihong

    2015-01-01

    In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans. PMID:25798945

  11. One-year study of spatial memory performance, brain morphology, and cholinergic markers after moderate controlled cortical impact in rats.

    PubMed

    Dixon, C E; Kochanek, P M; Yan, H Q; Schiding, J K; Griffith, R G; Baum, E; Marion, D W; DeKosky, S T

    1999-02-01

    Persistent cognitive deficits are one of the most important sequelae of head injury in humans. In an effort to model some of the structural and neuropharmacological changes that occur in chronic postinjury brains, we examined the longitudinal effects of moderate vertical controlled cortical impact (CCI) on place learning and memory using the Morris water maze (MWM) test, morphology, and vesicular acetylcholine (ACh) transporter (VAChT) and muscarinic receptor subtype 2 (M2) immunohistochemistry. Vertical CCI (left parietal cortex, 4 m/sec, 2.5 mm; n = 10) or craniotomy (sham) was produced in male Sprague-Dawley rats (n = 10). Place learning was tested at 2 weeks, 4 weeks, 3 months, 6 months, and 12 months postinjury with the escape platform in a different maze quadrant for each time point. At each interval, rats received 5 days of water maze acquisition (latency to find hidden platform), a probe trial to measure place memory, and 2 days of visible platform trials to control for nonspecific deficits. At 3 weeks, half the animals were sacrificed for histology. At these injury parameters, CCI produced no significant differences in place learning between injured and sham rats at 2 weeks, 4 weeks, or 6 months after injury. However, at 3 and 12 months, the injured rats took significantly longer to find the hidden platform than the sham rats. Probe trial performance differed only at 12 months postinjury between injured (25.73+/-2.1%, standard error of the mean) and sham rats (44.09+/-7.0%, p < 0.05). The maze deficits at 1 year were not due to a worsening of performance, but may have resulted from a reduced ability of injured rats to benefit from previous water maze experience. Hemispheric loss of 30.4+/-5.5 mm3 was seen at 3 weeks after injury (versus respective sham). However, hemispheric loss almost doubled by 1 year after injury (51.5+/-8.5 mm3, p < 0.05 versus all other groups). Progressive tissue loss was also reflected by a three- to fourfold increase in

  12. Influence of icing on muscle regeneration after crush injury to skeletal muscles in rats.

    PubMed

    Takagi, Ryo; Fujita, Naoto; Arakawa, Takamitsu; Kawada, Shigeo; Ishii, Naokata; Miki, Akinori

    2011-02-01

    The influence of icing on muscle regeneration after crush injury was examined in the rat extensor digitorum longus. After the injury, animals were randomly divided into nonicing and icing groups. In the latter, ice packs were applied for 20 min. Due to the icing, degeneration of the necrotic muscle fibers and differentiation of satellite cells at early stages of regeneration were retarded by ∼1 day. In the icing group, the ratio of regenerating fibers showing central nucleus at 14 days after the injury was higher, and cross-sectional area of the muscle fibers at 28 days was evidently smaller than in the nonicing group. Besides, the ratio of collagen fibers area at 14 and 28 days after the injury in the icing group was higher than in the nonicing group. These findings suggest that icing applied soon after the injury not only considerably retarded muscle regeneration but also induced impairment of muscle regeneration along with excessive collagen deposition. Macrophages were immunohistochemically demonstrated at the injury site during degeneration and early stages of regeneration. Due to icing, chronological changes in the number of macrophages and immunohistochemical expression of transforming growth factor (TGF)-β1 and IGF-I were also retarded by 1 to 2 days. Since it has been said that macrophages play important roles not only for degeneration, but also for muscle regeneration, the influence of icing on macrophage activities might be closely related to a delay in muscle regeneration, impairment of muscle regeneration, and redundant collagen synthesis. PMID:21164157

  13. Gallic acid improved behavior, brain electrophysiology, and inflammation in a rat model of traumatic brain injury.

    PubMed

    Sarkaki, Alireza; Farbood, Yaghoub; Gharib-Naseri, Mohammad Kazem; Badavi, Mohammad; Mansouri, Mohammad Taghi; Haghparast, Abbas; Mirshekar, Mohammad Ali

    2015-08-01

    Traumatic brain injury (TBI) is one of the main causes of intellectual and cognitive disabilities. In the clinic it is essential to limit the development of cognitive impairment after TBI. In this study, the effects of gallic acid (GA; 100 mg/kg, per oral, from 7 days before to 2 days after TBI induction) on neurological score, passive avoidance memory, long-term potentiation (LTP) deficits, and levels of proinflammatory cytokines including interleukin-1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) in the brain have been evaluated. Brain injury was induced following Marmarou's method. Data were analyzed by one-way and repeated measures ANOVA followed by Tukey's post-hoc test. The results indicated that memory was significantly impaired (p < 0.001) in the group treated with TBI + vehicle, together with deterioration of the hippocampal LTP and increased brain tissue levels of IL-1β, IL-6, and TNF-α. GA treatment significantly improved memory and LTP in the TBI rats. The brain tissue levels of IL-1β, IL-6, and TNF-α were significantly reduced (p < 0.001) in the group treated with GA. The results suggest that GA has neuroprotective properties against TBI-induced behavioral, electrophysiological, and inflammatory disorders, probably via the decrease of cerebral proinflammatory cytokines.

  14. Assessment of physical traits of rat offspring derived from mothers exposed to dioxin.

    PubMed

    Rosińczuk, Joanna; Całkosiński, Ireneusz

    2015-09-01

    Negative effects of dioxin action are associated with limited abilities of their bio-degradation along with continuously increasing production and long-term bio-accumulation of those toxins in living organisms. Dioxins penetrate through placenta to fetus indicating indirect toxic effects on offspring of mothers exposed to the action of these toxins. During lactation a significant part of dioxins is excreted from organism with milk, which contributes to further accumulation of those compounds and multiple exceeding of maximal permissible dose of dioxins in newborns feeding with mother's milk. The aim of the study was to determine how a single dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administered to females 3 weeks before getting pregnant affects the parturition duration, labour delay, number and weight of offspring. The studies were performed on rat offspring deriving from primigravida females from the Buffalo strain, which 3 weeks before getting pregnant were administered with a single dose of TCDD. The obtained results revealed that labours in females exposed to dioxin effects were characterized by significant temporal range and their end occurred 3 weeks later compared to females from the control group, which gave birth within a very narrow temporal range ending within 2 days. Offspring obtained from females exposed to the TCDD action was smaller in number and was characterized by smaller rearing and smaller birth weight even after the first month of life; however weight gain in both groups was similar and it was twelve-fold increase.

  15. The effects of Danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats.

    PubMed

    Chan, K; Lo, A C; Yeung, J H; Woo, K S

    1995-05-01

    The effects of Danshen (Salvia miltiorrhiza), a popular traditional Chinese medicinal herb on the pharmacokinetics and pharmacodynamics of R- and S-warfarin stereoisomers were studied in rats. After a single oral dose of racemic warfarin (2 mg kg-1), treatment with oral Danshen extract (5 g kg-1, twice daily) for 3 days significantly altered the overall pharmacokinetics of both R- and S-warfarin and increased the plasma concentrations of both enantiomers over a period of 24 h and the prothrombin time over 2 days. At steady-state levels of racemic warfarin (0.2 mg kg-1 day-1 for 5 days) the 3-day treatment of Danshen extract (5 g kg-1, twice daily) not only prolonged the prothrombin time but also increased the steady-state plasma concentrations of R- and S-warfarin. The results indicate that Danshen extracts can increase the absorption rate constant, area under plasma concentration-time curves, maximum concentrations and elimination half-lives, but decreases the clearances and apparent volume of distribution of both R- and S-warfarin. The pharmacokinetic and pharmacodynamic interactions of warfarin during co-treatment with Danshen extract observed in this study indicate an explanation for the clinically observed incidents of exaggerated warfarin adverse effects when traditional Chinese medicinal herbs or herbal products such as Danshen and Danggui (observed in a previous study) were co-administered. PMID:7494191

  16. Therapeutic potential of cannabidiol against ischemia/reperfusion liver injury in rats.

    PubMed

    Fouad, Amr A; Jresat, Iyad

    2011-11-16

    The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5mg/kg, i.v.) was given 1h following the procedure and every 24h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia-reoxygenation injury.

  17. A comparative study of lung toxicity in rats induced by three types of nanomaterials

    NASA Astrophysics Data System (ADS)

    Lin, Zhiqing; Ma, Li; X, Zhu-ge; Zhang, Huashan; Lin, Bencheng

    2013-12-01

    The public is increasingly exposed to various engineered nanomaterials because of their mass production and wide application. Even when the biological effects of nanomaterials have been assessed, the underlying mechanisms of action in vivo are poorly understood. The present study was designed to seek a simple, effective, and oxidative stress-based biomarker system used for screening toxicity of nanomaterials. Nano-ferroso-ferric oxide (nano-Fe3O4), nano-silicon dioxide (nano-SiO2), and single-walled carbon nanotubes (SWCNTs) were dispersed in corn oil and characterized using transmission electron microscopy (TEM). Rats were exposed to the three nanomaterials by intratracheal instillation once every 2 days for 5 weeks. We investigated their lung oxidative and inflammatory damage by bronchoalveolar lavage fluid (BALF) detection and comparative proteomics by lung tissue. Two-dimensional electrophoresis (2-DE) of proteins isolated from the lung tissue, followed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, was performed. In the present study, we chose to detect lactate dehydrogenase, total antioxidant capacity, superoxide dismutase, and malondialdehyde as the biomarker system for screening the oxidative stress of nanomaterials and IL-6 as the inflammatory biomarker in BALF. Proteomics analysis revealed 17 differentially expressed proteins compared with the control group: nine were upregulated and eight were downregulated. Our results indicated that exposure by intratracheal instillation to any of the three typical nanomaterials may cause lung damage through oxidative damage and/or an inflammatory reaction.

  18. Survival of fetal rat pancreases frozen to -78 and -196 degrees.

    PubMed Central

    Mazur, P; Kemp, J A; Miller, R H

    1976-01-01

    Transplantation of pancreases may have clinical utility in the treatment of diabetes, for it has been shown that chemically induced diabetes in rats can be reversed by the transplantation of greater than or equal to four syngeneic fetal pancreases. Allogeneic transplants produce serious immunological problems, but the problems could be ameliorated if tissue-typed organs could be stored in the frozen state. Unfortunately, nearly all attempts to freeze organs have failed. Nevertheless, recent developments in the physical-chemical analysis of freezing injury and its successful application to the freezing of mammalian embryos encouraged us to attempt the freezing of 16 1/2- to 17 1/2-day intact fetal pancreases. The analysis indicated that to achieve success pancreases would have to be cooled less than 1 degree/min and diluted extremely slowly after thawing. Experiments with embryos and red cells indicated that high survivals might require high concentrations of protective solutes and slow warming. These predictions were accurate. After freezing to -78 or -196 degrees and thawing under optimal conditions, the fetal pancreases synthesized 80-100% as much protein as unfrozen controls and they yielded viable allografts. Optimal conditions included suspension in 2 M dimethylsulfoxide, freezing at 0.3 degrees/min, and slow dilution to preclude osmotic shock. PMID:1069298

  19. Skeletal muscle fiber, nerve, and blood vessel breakdown in space-flown rats

    NASA Technical Reports Server (NTRS)

    Riley, D. A.; Ilyina-Kakueva, E. I.; Ellis, S.; Bain, J. L.; Slocum, G. R.; Sedlak, F. R.

    1990-01-01

    Histochemical and ultrastructural analyses were performed postflight on hind limb skeletal muscles of rats orbited for 12.5 days aboard the unmanned Cosmos 1887 biosatellite and returned to Earth 2 days before sacrifice. The antigravity adductor longus (AL), soleus, and plantaris muscles atrophied more than the non-weight-bearing extensor digitorum longus, and slow muscle fibers were more atrophic than fast fibers. Muscle fiber segmental necrosis occurred selectively in the AL and soleus muscles; primarily, macrophages and neutrophils infiltrated and phagocytosed cellular debris. Granule-rich mast cells were diminished in flight AL muscles compared with controls, indicating the mast cell secretion contributed to interstitial tissue edema. Increased ubiquitination of disrupted myofibrils implicated ubiquitin in myofilament degradation. Mitochondrial content and succinic dehydrogenase activity were normal, except for subsarcolemmal decreases. Myofibrillar ATPase activity of flight AL muscle fibers shifted toward the fast type. Absence of capillaries and extravasation of red blood cells indicated failed microcirculation. Muscle fiber regeneration from activated satellite cells was detected. About 17% of the flight AL end plates exhibited total or partial denervation. Thus, skeletal muscle weakness associated with spaceflight can result from muscle fiber atrophy and segmental necrosis, partial motor denervation, and disruption of the microcirculation.

  20. Critical assessment of lifelong phenotype correction in hyperbilirubinemic Gunn rats after retroviral mediated gene transfer.

    PubMed

    Nguyen, T H; Aubert, D; Bellodi-Privato, M; Flageul, M; Pichard, V; Jaidane-Abdelghani, Z; Myara, A; Ferry, N

    2007-09-01

    Among inherited diseases of the liver, Crigler-Najjar type 1 disease (CN-1), which results from complete deficiency in bilirubin UDP-glucuronosyltransferase activity (B-UGT1), is an attractive target for gene therapy studies. Hyperbilirubinemic Gunn rats, a model of CN-1, were injected at 2 days of age with lentiviral or oncoretroviral vectors encoding the human B-UGT1. After injection, bilirubinemia was normalized for up to 95 weeks. Bilirubin conjugates were present in the bile, demonstrating liver transduction. PCR and enzyme activity analysis confirmed gene and phenotype correction in liver. We observed that when using a strong viral promoter, a complete correction was achieved with less than 5% of B-UGT1 copy per haploid genome and after a reconstitution of 12% B-UGT1 normal activity. Liver histology remained normal throughout the experiment and tissue distribution analysis revealed preferential hepatocyte transduction after systemic delivery. Finally, no adverse immune response occurred even after induction of nonspecific liver inflammation, suggesting immune ignorance to the therapeutic protein. Our present results document the lifelong safety of gene therapy for CN-1 with retroviral vectors. They offer a better delineation of liver gene correction level required to achieve complete correction of bilirubinemia and pave the way for future clinical application of gene therapy for inherited liver disorders.

  1. The Toxic Effect of Manganese on the Acetylcholinesterase Activity in Rat Brains

    PubMed Central

    Yousefi Babadi, Vahid; Sadeghi, Leila; Shirani, Kobra; Malekirad, Ali Akbar; Rezaei, Mohammad

    2014-01-01

    Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson's disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat's brain by MnCl2 injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days. PMID:25246936

  2. Both acute and chronic buspirone treatments have different effects on regional 5-HT synthesis in Flinders Sensitive Line rats (a rat model of depression) than in control rats

    PubMed Central

    Nishi, Kyoko; Kanemaru, Kazuya; Hasegawa, Shu; Watanabe, Arata; Diksic, Mirko

    2009-01-01

    The main objective of this investigation was to evaluate the effects of buspirone, a 5-HT1A agonist with some partial agonist properties and also an antidepressant, on regional 5-HT synthesis in Flinders Sensitive Line (FSL) rats (“depressed”), and to compare the effects to the Flinders Resistant Line (FRL) control rats (not “depressed”). In addition results were compared to those previously reported in normal Sprague-Dawley (SPD) rats (normal control). Serotonin synthesis in both FSL and FRL rats was measured following acute and chronic treatments with buspirone. Both of these strains were derived from the SPD rats. No direct comparison was done between the FSL saline and FRL saline groups, or the FSL buspirone and FRL buspirone groups, because the objective of the studies was to evaluate effects of buspirone in these two strains. The results show that acute treatment with buspirone elevates 5-HT synthesis throughout the brain in the FRL rats. In the FSL rats, there were reductions in some brain regions (e.g., dorsal and median raphe, amygdala, anterior olfactory nucleus, substantia nigra reticulate), while in other regions, there were increases in the synthesis observed (e.g., frontal, parietal, visual and somatosensory cortices, ventral hippocampus). In twenty out of the thirty brain regions investigated in the FSL rats, there was no significant change in the synthesis following acute buspirone treatment. During the chronic treatment, buspirone produced a significant reduction of 5-HT synthesis in fifteen out of thirty brain regions in the FRL rats. In the FSL rats, buspirone produced a significant elevation of the synthesis in ten out of thirty brain regions. In both the FSL and FRL rats, buspirone produced rather different effects than those reported previously for SPD (normal) rats. The acute effect in the FSL rats was somewhat similar to the effect reported previously for the SPD rats, while in the FRL rats, the acute buspirone treatment produced an

  3. Urinary excretion values in 2-day food-deprived, unrestrained chimpanzees.

    NASA Technical Reports Server (NTRS)

    Mcnew, J. J.; Sabbot, I. M.; Hoshizaki, T.; Mandell, A. J.; Spooner, C. E.; Marcus, I.; Adey, W. R.

    1972-01-01

    A study was conducted to determine the baseline 24-hr urinary excretion values in the young, unrestrained chimpanzee, and also changes in urinary values, if any, induced by the two-day food deprivation stress. Urine was analyzed for volume, osmolarity, creatinine, creatine, urea nitrogen, 17-hydroxycorticosteroids (17-OHCS), 3-methoxy-4-hydroxymandelic acid (VMA), calcium, and inorganic phosphorus. Significant increases due to food deprivation stress were observed for volume, creatine, urea nitrogen, 17-OHCS, VMA, and phosphorus values, with significant decreases in osmolarity and calcium. All values approached normal levels by the second poststress day. No significant changes were observed in creatinine. A comparison is drawn between human and chimpanzee adaptation to stress.

  4. Factors Contributing to Successful Interorganizational Collaboration: The Case of CS2day

    ERIC Educational Resources Information Center

    Olson, Curtis A.; Balmer, Jann T.; Mejicano, George C.

    2011-01-01

    Continuing medical education's transition from an emphasis on dissemination to changing clinical practice has made it increasingly necessary for CME providers to develop effective interorganizational collaborations. Although interorganizational collaboration has become commonplace in most sectors of government, business, and academia, our review…

  5. Developing and Implementing an Effective Framework for Collaboration: The Experience of the CS2day Collaborative

    ERIC Educational Resources Information Center

    Ales, Mary W.; Rodrigues, Shelly B.; Snyder, Robyn; Conklin, Mary

    2011-01-01

    Organizations from varied sectors have pursued collaboration to better fulfill their missions, facilitate decision making, solve more complex problems, and respond more rapidly to a changing environment. While these benefits are evident through the products and services provided, few organizations evaluate the factors that contribute to the…

  6. Rat Bite Fever Resembling Rheumatoid Arthritis.

    PubMed

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  7. Rat Bite Fever Resembling Rheumatoid Arthritis

    PubMed Central

    Akter, Ripa; Boland, Paul; Daley, Peter; Rahman, Proton; Al Ghanim, Nayef

    2016-01-01

    Rat bite fever is rare in Western countries. It can be very difficult to diagnose as blood cultures are typically negative and a history of rodent exposure is often missed. Unless a high index of suspicion is maintained, the associated polyarthritis can be mistaken for rheumatoid arthritis. We report a case of culture-positive rat bite fever in a 46-year-old female presenting with fever and polyarthritis. The clinical presentation mimicked rheumatoid arthritis. Infection was complicated by discitis, a rare manifestation. We discuss the diagnosis and management of this rare zoonotic infection. We also review nine reported cases of rat bite fever, all of which had an initial presumptive diagnosis of a rheumatological disorder. Rat bite fever is a potentially curable infection but can have a lethal course if left untreated. PMID:27366177

  8. 2011 Desert RATS Sights and Sounds

    NASA Video Gallery

    Watch scenes from the 2011 Desert Research and Technology Studies (RATS) analog field test, as NASA scientists and engineers drive the Space Exploration Vehicle, assemble equipment in the Habitat D...

  9. Hypergravity induced prolactin surge in female rats

    NASA Technical Reports Server (NTRS)

    Megory, E.; Oyama, J.

    1985-01-01

    Acute initial exposure to hypergravity (HG) was previously found to induce prolonged diestrous in rats, which was followed by return to normal estrous cycling upon more prolonged exposure to continuous HG. Bromergocryptine was found to prevent this prolonged diestrous. In this study it is found that in female rats 20 h of 3.14 G exposure (D-1 1200 h until D-2 0800 h) can induce prolactin surge at D-2 1600 h. Shorter exposure time (8 h), or exposure during a different part of the estrous cycle (19 h: from D-1 0700 h until D-2 0200 h) could not elicit this prolactin surge. Similar exposure of male rats of HG did not alter significantly their prolactin levels. It is possible that the hypothalamus of male and female rats responds differently to stimulation by HG.

  10. Corona Discharge Influences Ozone Concentrations Near Rats

    SciTech Connect

    Goheen, Steven C.; Gaither, Kari A.; Anantatmula, Shantha M.; Mong, Gary M.; Sasser, Lyle B.; Lessor, Delbert L.

    2004-02-26

    Ozone is produced by corona discharge in air. Its production is enhanced near grounded water. Whether grounded animals behave like grounded water, producing more ozone was investigated. Rats were exposed to corona discharge in a plastic cage. The concentration of ozone in the gas phase was monitored. The ozone concentration exceeded ambient levels only in the presence of corona discharge and either rats or water. When water or rats were exposed to corona discharge, ozone levels were more than 10 times higher than controls. Ozone levels increased rapidly with applied voltage. There was also a correlation between the distance of the corona needle to the rats and the amount of ozone produced. As the distance increased, ozone production decreased. These results are discussed in relation to the potential exposure of mammals to ozone in the vicinity of corona discharge and electric fields.

  11. Phylogenetics of the laboratory rat Rattus norvegicus.

    PubMed

    Canzian, F

    1997-03-01

    A genealogic tree was constructed for inbred strains of the laboratory rat, including 63 strains and 214 of their substrains. Information on genetic and biochemical marker typings of these lines was collected from the literature and from the World Wide Web. Data on 995 polymorphisms were processed into a phylogenetic distance matrix, and a tree was obtained by the Fitch-Margoliash distance matrix method. The inbred strains of the laboratory rat showed an average polymorphism for pairwise comparison of 53%. Strain BN showed the highest genetic divergence from all the other ones. Comparison with the mouse phylogenetic tree indicated that laboratory rats possess a higher diversity than inbred strains of mice not derived from wild species. These results provide a phylogenetic basis in the choice of rat strains for genetic linkage experiments.

  12. Rat sperm motility analysis: methodologic considerations

    EPA Science Inventory

    The objective of these studies was to optimize conditions for computer-assisted sperm analysis (CASA) of rat epididymal spermatozoa. Methodologic issues addressed include sample collection technique, sampling region within the epididymis, type of diluent medium used, and sample c...

  13. Eating behavior reveals rats' preference for morphine.

    PubMed

    Yanaura, S; Suzuki, T; Kawai, T

    1980-04-01

    Using an automatic food intake measuring apparatus ("food intakometer"), we recorded the approach behavior to food, eating behavior and food intake of morphine dependent rats and examined the relationship among these factors and morphine dependence. Morphine dependent rats were produced by the drug-admixed food (DAF) method. In the choice trial of free feeding group, morphine dependent rats showed only the approach behavior both to drug-free diet and to morphine-admixed food, then ate the morphine-admixed food and approached the drug-free diet at the same period. Eating behavior in the case of morphine-admixed food was observed not only at night but also during thee feeding group, morphine dependent rats showed only the approach behavior both to drug-free diet and to morphine-admixed food, then ate the morphine-admixed food and approached the drug-free diet at the same period. Eating behavior in the case of morphine-admixed food was observed not only at night but also during the day time in the morphine dependent rats. In the choice trial of the limited feeding group, preference for morphine rapidly increased in every choice trial of each session and the preference rate became stable at about 60%. Eating patterns of these rats were similar to these in the free feeding group. When these rats were given morphine prior to the choice trial, eating behavior of those on the morphine-admixed food was inhibited dose-dependently, while eating behavior of these on the drug-free diet was enhanced dose-dependently. When these rats were allowed free access to drug-free diet for 1 hour previously to the choice trial, eating behavior of the rats on the morphine-admixed food in the choice trial was markedly enhanced. Thus, the rats clearly showed drug-seeking behavior and seemed to be able to distinguish between the need for morphine and satisfaction without it. Morphine dependent rats apparently can control their required maintenance dose.

  14. Methamphetamine enhances sexual behavior in female rats.

    PubMed

    Winland, Carissa; Haycox, Charles; Bolton, Jessica L; Jampana, Sumith; Oakley, Benjamin J; Ford, Brittany; Ornelas, Laura; Burbey, Alexandra; Marquette, Amber; Frohardt, Russell J; Guarraci, Fay A

    2011-06-01

    The present study evaluated the effects of methamphetamine (MA) on sexual behavior in female rats. In Experiment 1, ovariectomized, hormone-primed rats were injected with MA (1.0mg/kg, i.p.) or saline prior to a test for mate choice wherein females could mate with two males simultaneously. Female rats treated with saline returned to their preferred mate faster after receiving intromissions and visited their preferred mate at a higher rate than their non-preferred mate. In contrast, MA-treated female rats spent a similar amount of time with their preferred and non-preferred mate and failed to return to their preferred mate faster than to their non-preferred mate following intromissions. Two weeks later, the females received the same drug treatment but were tested for partner preference wherein females could spend time near a male or female stimulus rat. All subjects spent more time near the male stimulus than the female stimulus. However, the MA-treated rats visited the male stimulus more frequently and spent less time near the female stimulus than the saline-treated rats. Similar to Experiment 1, female rats in Experiment 2 were tested for mate choice and then two weeks later tested for partner preference; however, females received three daily injections of MA (1.0mg/kg, i.p.) or saline. Females treated chronically with MA returned to both males faster following intromissions than females treated with saline, independent of preference (i.e., preferred mate and non-preferred mate). Furthermore, MA-treated rats were more likely to leave either male (i.e., preferred or non-preferred mate) than saline-treated rats after receiving sexual stimulation. Although MA-treated subjects spent more time near the male stimulus than the female stimulus, they spent less time near either when compared to saline-treated subjects. The present results demonstrate that MA affects sexual behavior in female rats partly by increasing locomotion and partly by directly affecting sexual

  15. Anxiolytic Treatment Impairs Helping Behavior in Rats

    PubMed Central

    Ben-Ami Bartal, Inbal; Shan, Haozhe; Molasky, Nora M. R.; Murray, Teresa M.; Williams, Jasper Z.; Decety, Jean; Mason, Peggy

    2016-01-01

    Despite decades of research with humans, the biological mechanisms that motivate an individual to help others remain poorly understood. In order to investigate the roots of pro-sociality in mammals, we established the helping behavior test, a paradigm in which rats are faced with a conspecific trapped in a restrainer that can only be opened from the outside. Over the course of repeated test sessions, rats exposed to a trapped cagemate learn to open the door to the restrainer, thereby helping the trapped rat to escape (Ben-Ami Bartal et al., 2011). The discovery of this natural behavior provides a unique opportunity to probe the motivation of rodent helping behavior, leading to a deeper understanding of biological influences on human pro-sociality. To determine if an affective response motivates door-opening, rats receiving midazolam, a benzodiazepine anxiolytic, were tested in the helping behavior test. Midazolam-treated rats showed less helping behavior than saline-treated rats or rats receiving no injection. Yet, midazolam-treated rats opened a restrainer containing chocolate, highlighting the socially specific effects of the anxiolytic. To determine if midazolam interferes with helping through a sympatholytic effect, the peripherally restricted beta-adrenergic receptor antagonist nadolol was administered; nadolol did not interfere with helping. The corticosterone response of rats exposed to a trapped cagemate was measured and compared to the rats’ subsequent helping behavior. Rats with the greatest corticosterone responses showed the least helping behavior and those with the smallest responses showed the most consistent helping at the shortest latency. These results are discussed in terms of their implications for the interaction between stress and pro-social behavior. Finally, we observed that door-opening appeared to be reinforcing. A novel analytical tool was designed to interrogate the pattern of door-opening for signs that a rat’s behavior on one

  16. The effect of GABA stimulation on GABAA receptor subunit protein and mRNA expression in rat cultured cerebellar granule cells.

    PubMed Central

    Platt, K. P.; Zwartjes, R. E.; Bristow, D. R.

    1996-01-01

    1. After 8 days in vitro, rat cerebellar granule cells were exposed to 1 mM gamma-aminobutyric acid (GABA) for periods of 1, 2, 4, 6, 8 and 10 days. The effect of the GABA exposure on GABAA receptor alpha 1, alpha 6 and beta 2,3 subunit protein expression and alpha 1 and alpha 6 subunit steady-state mRNA levels, was examined using Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. 2. GABA exposure for 2 days decreased alpha 1 (35 +/- 10%, mean +/- s.e.mean), beta 2,3 (21 +/- 9%) and alpha 6 (28 +/- 10%) subunit protein expression compared to control levels. The GABA-mediated reduction in alpha 1 subunit expression after 2 days treatment was abolished in the presence of the GABAA receptor antagonist, Ru 5135 (10 microM). 3. GABA exposure for 8 days increased alpha 1 (26 +/- 10%, mean +/- s.e.mean) and beta 2,3 (56 +/- 23%) subunit protein expression over control levels, whereas alpha 6 subunit protein expression remained below control levels (by 38 +/- 10%). However, after 10 days GABA exposure, alpha 6 subunit protein expression was also increased over control levels by 65 +/- 29% (mean +/- s.e.mean). 4. GABA exposure did not change the alpha 1 or alpha 6 subunit steady-state mRNA levels over and 8 day period, nor did it alter the expression of cyclophilin mRNA over 1-8 days. 5. These results suggest that chronic GABA exposure of rat cerebellar granule cells has a bi-phasic effect on GABAA receptor subunit expression that is independent of changes to mRNA levels. Therefore, the regulation of the GABAA receptor expression by chronic agonist treatment appears to involve post-transcriptional and/or post-translational processes. Images Figure 1 Figure 3 Figure 4 PMID:8968548

  17. How rats combine temporal cues.

    PubMed

    Guilhardi, Paulo; Keen, Richard; MacInnis, Mika L M; Church, Russell M

    2005-05-31

    The procedures for classical and operant conditioning, and for many timing procedures, involve the delivery of reinforcers that may be related to the time of previous reinforcers and responses, and to the time of onsets and terminations of stimuli. The behavior resulting from such procedures can be described as bouts of responding that occur in some pattern at some rate. A packet theory of timing and conditioning is described that accounts for such behavior under a wide range of procedures. Applications include the food searching by rats in Skinner boxes under conditions of fixed and random reinforcement, brief and sustained stimuli, and several response-food contingencies. The approach is used to describe how multiple cues from reinforcers and stimuli combine to determine the rate and pattern of response bouts.

  18. Percutaneous nitroglycerin absorption in rats.

    PubMed

    Horhota, S T; Fung, H L

    1979-05-01

    Percutaneous nitroglycerin absorption was studied in shaved rats by monitoring unchanged plasma drug concentrations for up to 4 hr. Drug absorption from the neat liquid state or from an alcoholic solution was considerably poorer than that from a commercial ointment. This observation was unanticipated since the driving force for percutaneous drug absorption was assumed to be drug thermodynamics. Potential artifacts such as drug volatilization from the skin, reduction of surface area through droplet formation, and vehicle occlusion were investigated, but they did not appear to be responsible for the observed results. Two experimental aqueous nitroglycerin gels were prepared with polyethylene glycol 400. One gel contained just sufficient polyethylene glycol to solubilize the nitroglycerin; the other had excess polyethylene glycol to solubilize nitroglycerin far below saturation. Both gels gave extremely low plasma nitroglycerin levels. The composite data suggested that percutaneous nitroglycerin absorption is highly vehicle dependent and that this dependency cannot be explained by simple consideration of drug thermodynamic activity.

  19. Sleep Homeostasis in Infant Rats

    PubMed Central

    Blumberg, Mark S.; Middlemis-Brown, Jessica E.; Johnson, Eric D.

    2008-01-01

    Homeostatic regulation is a defining characteristic of sleep but has rarely been examined in infants. This study presents an automated method of sleep deprivation in which 5-day-old rats were shocked whenever the nuchal muscle became atonic. The intensity of shock was always set at the minimal level required to maintain arousal. Deprived pups exhibited rapid increases in sleep pressure, as evidenced by increased attempts to enter sleep and subsequent increases in sensory threshold; this increased sensory threshold was not due to sensory adaptation of peripheral receptors. In addition, myoclonic twitching was suppressed during the 30-min deprivation period, leading to rebound twitching during recovery sleep. These results provide the earliest demonstration of the homeostatic regulation of sleep in an altricial mammal. PMID:15598134

  20. Rat growth during chronic centrifugation

    NASA Technical Reports Server (NTRS)

    Pitts, G. C.; Oyama, J.

    1978-01-01

    Female weanling rats were chronically centrifuged at 4.15 G with controls at terrestrial gravity. Samples were sacrificed for body composition studies at 0, 28, 63, 105 and 308 days of centrifugation. The centrifuged group approached a significantly lower mature body mass than the controls (251 and 318g) but the rate of approach was the same in both groups. Retirement to 1G on the 60th day resulted in complete recovery. Among individual components muscle, bone, skin, CNS, heart, kidneys, body water and body fat were changed in the centrifuged group. However, an analysis of the growth of individual components relative to growth of the total fat-free compartment revealed that only skin (which increased in mass) was responding to centrifugation per se.

  1. Thyroid function in hemidecorticate rats.

    PubMed

    Munhoz, C O; Tosello, D O; Fernandez, G A; Merzel, J

    1988-01-01

    1. Thyroid function was evaluated in hemidecorticate (HD) and control (C) rats by determining serum T3 and T4 levels and the development of incisors and mandibles and through analysis of various histological features of the thyroid such as follicle size, colloid droplet content and [3H]-glycine uptake by follicular cells. 2. HD animals presented normal levels of circulating T3 but significantly lower T4 levels. 3. There was slight atrophy of the gland in HD animals and fewer colloid droplets were present in the cytoplasm of the follicular cells in this group, indicating a reduction in the breakdown of thyroglobulin. [3H]-glycine uptake by HD indicated that the rate of thyroglobulin biosynthesis was not altered in the experimental animals. 4. The growth of mandibles (weight) and incisors (weight and length) was reduced in HD compared to the control animals. 5. These results suggest that hemidecortication causes mild hypothyroidism (trophoprivic type) probably by affecting hypothalamic function.

  2. Quantity Discrimination in Domestic Rats, Rattus norvegicus

    PubMed Central

    Cox, Laura; Montrose, V. Tamara

    2016-01-01

    Simple Summary Quantity discrimination involves distinguishing which of two quantities is greater. This discrimination between larger and smaller quantities has only been demonstrated in rats post extensive training. We tested whether domestic rats could perform quantity discrimination without explicit training. We found that rats could distinguish the greater amount in comparisons of 1 vs. 2, 2 vs. 3, 3 vs. 5, 3 vs. 8, 4 vs. 6, and 4 vs. 8. Rats could not distinguish between 3 vs. 4, 4 vs. 5 and 5 vs. 6. We also found that as the ratio between quantities became finer the choice of the larger quantity decreased. We conclude that rats can perform quantity discrimination without extensive training and that their quantity discrimination ability is influenced by the ratio between quantities. Abstract Quantity discrimination is a basic form of numerical competence where an animal distinguishes which of two amounts is greater in size. Whilst quantity discrimination in rats has been investigated via training paradigms, rats’ natural quantity discrimination abilities without explicit training for a desired response have not been explored. This study investigated domestic rats’ ability to perform quantity discrimination. Domestic rats (n = 12) were examined for their ability to distinguish the larger amount under nine quantity comparisons. One-sample t-tests identified a significant preference for the larger quantity in comparisons of 1 vs. 2, 2 vs. 3, 3 vs. 5, 3 vs. 8, 4 vs. 6, and 4 vs. 8. No preference between quantities was found for comparisons of 3 vs. 4, 4 vs. 5 and 5 vs. 6. Overall, this study drew two key conclusions. Firstly, that domestic rats are capable of performing quantity discrimination without extensive training. Secondly, as subjects adhered to Weber’s law, it was concluded that the approximate number system underpins domestic rats’ ability to perform spontaneous quantity discrimination. PMID:27527223

  3. Can You Find the Rat Holes?

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Using its rock abrasion tool, otherwise known as 'Rat,' NASA's Mars Exploration Rover Opportunity dotted the slope of 'Endurance Crater' with dimples that give scientists a glimpse into its layered geologic history. This image from the rover's navigation camera, taken on sol 169 (July 15, 2004), highlights the prolific work of the robotic 'rodent.' How many Rat holes can you identify? You will be able to check your answer against an image to be posted soon with all the holes identified.

  4. Collagenous skeleton of the rat mystacial pad.

    PubMed

    Haidarliu, Sebastian; Simony, Erez; Golomb, David; Ahissar, Ehud

    2011-05-01

    Anatomical and functional integrity of the rat mystacial pad (MP) is dependent on the intrinsic organization of its extracellular matrix. By using collagen autofluorescence, in the rat MP, we revealed a collagenous skeleton that interconnects whisker follicles, corium, and deep collagen layers. We suggest that this skeleton supports MP tissues, mediates force transmission from muscles to whiskers, facilitates whisker retraction after protraction, and limits MP extensibility.

  5. A digital rat atlas of sectional anatomy

    NASA Astrophysics Data System (ADS)

    Yu, Li; Liu, Qian; Bai, Xueling; Liao, Yinping; Luo, Qingming; Gong, Hui

    2006-09-01

    This paper describes a digital rat alias of sectional anatomy made by milling. Two healthy Sprague-Dawley (SD) rat weighing 160-180 g were used for the generation of this atlas. The rats were depilated completely, then euthanized by Co II. One was via vascular perfusion, the other was directly frozen at -85 °C over 24 hour. After that, the frozen specimens were transferred into iron molds for embedding. A 3% gelatin solution colored blue was used to fill the molds and then frozen at -85 °C for one or two days. The frozen specimen-blocks were subsequently sectioned on the cryosection-milling machine in a plane oriented approximately transverse to the long axis of the body. The surface of specimen-blocks were imaged by a scanner and digitalized into 4,600 x2,580 x 24 bit array through a computer. Finally 9,475 sectional images (arterial vessel were not perfused) and 1,646 sectional images (arterial vessel were perfused) were captured, which made the volume of the digital atlas up to 369.35 Gbyte. This digital rat atlas is aimed at the whole rat and the rat arterial vessels are also presented. We have reconstructed this atlas. The information from the two-dimensional (2-D) images of serial sections and three-dimensional (3-D) surface model all shows that the digital rat atlas we constructed is high quality. This work lays the foundation for a deeper study of digital rat.

  6. Thermoregulation in hypergravity-acclimated rats

    NASA Technical Reports Server (NTRS)

    Monson, Conrad B.; Patterson, Susan L.; Horowitz, John M.; Oyama, Jiro

    1989-01-01

    The effect of acclimation to hypergravity on thermoregulatory responses of rats was determined by comparing data on core temperature, T(c), tail temperature, and O2 consumption in rats raised at 1 G (C) and at 2.1 G. It was found that, when C rats were exposed to an ambient temperature of 9 C concurrently with exposure to 2.1 G, the T(c) fell by about 6 C, while in rats acclimated to 2.1 G, the T(c) fell only by 1 C. Results of O2 consumption measurements showed that C rats exposed simultaneously to cold and hypergravity were not activating their thermogenic mechanism sufficiently to prevent a fall in T(c). In other experiments, rats acclimated to either 1 or 2.1 G were found to lack the ability to maintain their T(c) when exposed to a 5.8-G field or when cold-stressed at 1 G for extended times.

  7. Hematological Characteristics of the BB Wistar Rat.

    PubMed

    Wright, J R; Yates, A J; Shah, N T; Neff, J C; Covey, D W; Thibert, P

    1983-01-01

    Complete blood counts, differential white blood cell and platelet counts were performed on male and female BB Wistar diabetic rats (BBWd), their nondiabetic siblings (BBWnd) and outbred Wistar rats of the line from which the BB Wistar rats were derived. Most of the observed changes were strain-related (those present in both BBWd and BBWnd but not in control rats) rather than diabetes-related (those in BBWd but neither BBWnd nor control rats) and therefore probably due to the inbreeding process. The BBW strain had significantly lower numbers of white cells and platelets, as well as markedly changed differential white cell counts. Differential counts showed a pattern of lymphopenia, neutrophilia, monocytosis and eosinophilia. It is possible that these white blood cell changes contribute to the increased susceptibility to infection reported for the BBW strain. No significant difference in serum immunoglobulin concentrations was found in any of these three groups of rats. There- fore, hypogammaglobutinemia cannot account for the increased susceptibility to infections, but it is not possible to rule out an abnormality in the distribution of immunoglobulin fractions as an etiological factor. PMID:15311399

  8. Sham intake of ethanol in "P" rats.

    PubMed

    Rowland, N E; Morian, K R

    1994-01-01

    Alcohol-preferring (P) rats were surgically fitted with gastric fistulas, and intakes of 10% ethanol solution were measured in 1-h sessions either with the fistula closed (normal drinking) or open (sham drinking). In water-replete P rats in which ethanol access was limited to 1 h/day, no increase in intake was noted in the sham compared with normal drinking tests in the day. A small increase was seen when the sham drinking test was conducted at night. In water-deprived P rats, sham intake of ethanol was elevated over intakes in closed fistula trials. However, in comparison with water intake on separate test days, sham intake of ethanol by P rats was lower and satiated after 15-30 min. The absence of robust sham alcohol drinking in P rats is similar to what we have previously reported in normal Sprague-Dawley rats, suggesting that preabsorptive factors alone do not account for the strain differences in ethanol preference.

  9. Hypergravity suppresses bone resorption in ovariectomized rats

    NASA Astrophysics Data System (ADS)

    Ikawa, Tesshu; Kawaguchi, Amu; Okabe, Takahiro; Ninomiya, Tadashi; Nakamichi, Yuko; Nakamura, Midori; Uehara, Shunsuke; Nakamura, Hiroaki; Udagawa, Nobuyuki; Takahashi, Naoyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2011-04-01

    The effects of gravity on bone metabolism are unclear, and little has been reported about the effects of hypergravity on the mature skeleton. Since low gravity has been shown to decrease bone volume, we hypothesized that hypergravity increases bone volume. To clarify this hypothesis, adult female rats were ovariectomized and exposed to hypergravity (2.9G) using a centrifugation system. The rats were killed 28 days after the start of loading, and the distal femoral metaphysis of the rats was studied. Bone architecture was assessed by micro-computed tomography (micro-CT) and bone mineral density was measured using peripheral quantitative CT (pQCT). Hypergravity increased the trabecular bone volume of ovariectomized rats. Histomorphometric analyses revealed that hypergravity suppressed both bone formation and resorption and increased bone volume in ovariectomized rats. Further, the cell morphology, activity, proliferation, and differentiation of osteoclasts and osteoblasts exposed to hypergravity were evaluated in vitro. Hypergravity inhibited actin ring formation in mature osteoclasts, which suggested that the osteoclast activity was suppressed. However, hypergravity had no effect on osteoblasts. These results suggest that hypergravity can stimulate an increase in bone volume by suppressing bone resorption in ovariectomized rats.

  10. Colonic Fermentation Promotes Decompression sickness in Rats

    PubMed Central

    de Maistre, Sébastien; Vallée, Nicolas; Gempp, Emmanuel; Lambrechts, Kate; Louge, Pierre; Duchamp, Claude; Blatteau, Jean-Eric

    2016-01-01

    Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body’s H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production. PMID:26853722

  11. Chronic inhalation exposure of rats to nitromethane.

    PubMed

    Griffin, T B; Coulston, F; Stein, A A

    1996-07-01

    Male and female Long-Evans rats were housed in inhalation chambers and exposed to vapors of nitromethane (NM) at either 100 or 200 ppm. The animals were exposed 7 hr per day, 5 days per week for 2 years. Control groups of rats were also housed in a similar inhalation chamber, but NM was not introduced into the chamber. The animals were observed daily for signs of pharmacologic or toxicologic effect and body weights were recorded periodically. At the 2-year termination of the exposure period, clinical laboratory examinations (serum chemistry and hematology) were performed on selected animals and all surviving animals were sacrificed. All animals were necropsied and subjected to a thorough histopathologic examination. During the study there were no pharmacologic effects from exposure to NM at either 100 or 200 ppm. There was no effect on mortality on either sex at either exposure level. Body weights of male rats exposed to NM were not significantly different from those of control rats, but the body weights of female rats of both exposure groups were slightly less than their controls. There was no effect of exposure of rats of either sex to either level of NM on hematology. There were no clinically significant effects on serum chemistry. There were no effects of exposure to NM on organ weights. There were no significant differences in the nonneoplastic or neoplastic pathology related to exposure to NM. PMID:8812175

  12. Antiosteoporotic activity of icariin in ovariectomized rats.

    PubMed

    Nian, H; Ma, M-H; Nian, S-S; Xu, L-L

    2009-04-01

    Icariin was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were divided into sham and OVX groups. The OVX rats were then subdivided into five groups treated with water, nylestriol (1 mg/kg body weight, weekly, orally) or icariin (ICA) (5, 25, and 125 mg/kg body weight, daily, orally) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by ICA treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with ICA. In addition, ICA (125 mg/kg body weight) completely corrected the decreased serum concentration of Calcium, Phosphorus, and E(2) observed in OVX rats. ICA (125 mg/kg body weight) increased biomechanical strength significantly in comparison to the sham group. Histological results also showed its protective action through promotion of bone formation. The findings, assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters, showed that ICA has a definite antiosteoporotic effect, similar to estrogen, especially effective for prevention bone fracture induced by estrogen deficiency. PMID:19269147

  13. Quantity Discrimination in Domestic Rats, Rattus norvegicus.

    PubMed

    Cox, Laura; Montrose, V Tamara

    2016-01-01

    Quantity discrimination is a basic form of numerical competence where an animal distinguishes which of two amounts is greater in size. Whilst quantity discrimination in rats has been investigated via training paradigms, rats' natural quantity discrimination abilities without explicit training for a desired response have not been explored. This study investigated domestic rats' ability to perform quantity discrimination. Domestic rats ( n = 12) were examined for their ability to distinguish the larger amount under nine quantity comparisons. One-sample t -tests identified a significant preference for the larger quantity in comparisons of 1 vs. 2, 2 vs. 3, 3 vs. 5, 3 vs. 8, 4 vs. 6, and 4 vs. 8. No preference between quantities was found for comparisons of 3 vs. 4, 4 vs. 5 and 5 vs. 6. Overall, this study drew two key conclusions. Firstly, that domestic rats are capable of performing quantity discrimination without extensive training. Secondly, as subjects adhered to Weber's law, it was concluded that the approximate number system underpins domestic rats' ability to perform spontaneous quantity discrimination. PMID:27527223

  14. Ontogeny of rat thymic dendritic cells.

    PubMed Central

    Vicente, A; Varas, A; Alonso, L; Gómez de Moral, M; Zapata, A G

    1994-01-01

    In the present study we have combined various in vivo and in vitro approaches to analyse the appearance and development throughout ontogeny and postnatal life of the dendritic cell (DC) populations of rat thymus. The in situ ultrastructural study demonstrated immature interdigitating cells (IDC)/DC in the thymus of 17-day-old embryonic rats, but thymic stromal cell cultures from 16-day-old fetal rats seemed to contain DC precursors which, after several days in culture, produced strongly class II major histocompatibility complex (MHC)-positive, mature DC. According to morphology and class II MHC expression we also defined three different DC populations in the late embryonic rat thymus; two of them, which remained in the adult rat thymus, could represent distinct developmental stages within the IDC/DC lineage. The third cell subset might be involved in a massive process of negative selection, presumably occurring at the end of fetal life in the rat thymus. In supporting the existence of thymic DC subpopulations, we also demonstrated a differential expression of various cell markers, including CD4, CD8, CD25, adhesion molecules and the antigen recognized by OX44 monoclonal antibody (mAb), on thymic DC during both embryonic and adult life. Their possible significance for the attributed functions to thymic DC are discussed extensively. Images Figure 1 Figures 3-5 Figures 6-9 PMID:7913915

  15. Hematological Characteristics of the BB Wistar Rat.

    PubMed

    Wright, J R; Yates, A J; Shah, N T; Neff, J C; Covey, D W; Thibert, P

    1983-01-01

    Complete blood counts, differential white blood cell and platelet counts were performed on male and female BB Wistar diabetic rats (BBWd), their nondiabetic siblings (BBWnd) and outbred Wistar rats of the line from which the BB Wistar rats were derived. Most of the observed changes were strain-related (those present in both BBWd and BBWnd but not in control rats) rather than diabetes-related (those in BBWd but neither BBWnd nor control rats) and therefore probably due to the inbreeding process. The BBW strain had significantly lower numbers of white cells and platelets, as well as markedly changed differential white cell counts. Differential counts showed a pattern of lymphopenia, neutrophilia, monocytosis and eosinophilia. It is possible that these white blood cell changes contribute to the increased susceptibility to infection reported for the BBW strain. No significant difference in serum immunoglobulin concentrations was found in any of these three groups of rats. There- fore, hypogammaglobutinemia cannot account for the increased susceptibility to infections, but it is not possible to rule out an abnormality in the distribution of immunoglobulin fractions as an etiological factor.

  16. Hypergravity modulates behavioral nociceptive responses in rats

    NASA Astrophysics Data System (ADS)

    Kumei, Y.; Shimokawa, R.; Toda, K.; Kawauchi, Y.; Makita, K.; Terasawa, M.; Ohya, K.; Shimokawa, H.

    Hypergravity (2G) exposure elevated the nociceptive threshold (pain suppression) concomitantly with evoked neuronal activity in the hypothalamus. Young Wistar male rats were exposed to 2G by centrifugal rotation for 10 min. Before and after 2G exposure, the nociceptive threshold was measured as the withdrawal reflex by using the von Frey type needle at a total of 8 sites of each rat (nose, four quarters, upper and lower back, tail), and then rats were sacrificed. Fos expression was examined immunohistochemically in the hypothalamic slices of the 2G-treated rats. When rats were exposed to 2G hypergravity, the nociceptive threshold was significantly elevated to approximately 150 to 250% of the 1G baseline control levels in all the examination sites. The 2G hypergravity remarkably induced Fos expression in the paraventricular and arcuate nuclei of the hypothalamus. The analgesic effects of 2G hypergravity were attenuated by naloxone pretreatment. Data indicate that hypergravity induces analgesic effects in rats, mediated through hypothalamic neuronal activity in the endogenous opioid system and hypothalamo-pituitary-adrenal axis.

  17. Colonic Fermentation Promotes Decompression sickness in Rats.

    PubMed

    de Maistre, Sébastien; Vallée, Nicolas; Gempp, Emmanuel; Lambrechts, Kate; Louge, Pierre; Duchamp, Claude; Blatteau, Jean-Eric

    2016-01-01

    Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body's H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force-feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force-fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 ± 35 ppm versus 118 ± 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production.

  18. Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

    SciTech Connect

    Iwai, J; Friedman, R; Tassinari, L

    1980-01-01

    Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.

  19. Effects of carnosine on prooxidant-antioxidant status in heart tissue, plasma and erythrocytes of rats with isoproterenol-induced myocardial infarction.

    PubMed

    Evran, Betül; Karpuzoğlu, Hande; Develi, Seval; Kalaz, Esra Betül; Soluk-Tekkeşin, Merva; Olgaç, Vakur; Doğru-Abbasoğlu, Semra; Uysal, Müjdat

    2014-02-01

    Rats were injected with isoproterenol (ISO; 110 mg/kg, ip, 2 doses, 24 h interval) to induce acute myocardial infarction (AMI) and were sacrificed 6 and 24 h after the last ISO injection. The heart tissue, plasma and erythrocytes of these rats were evaluated for cardiac markers and oxidative stress parameters. Levels of cardiac troponin T (cTnT) and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST) in plasma were increased 6 and 24 h after ISO treatment. The levels of malondialdehyde (MDA), diene conjugate (DC), and protein carbonyl (PC) were increased in heart tissue and plasma, while levels of erythrocyte MDA and glutathione (GSH) and plasma ferric reducing antioxidant power (FRAP) were also increased. However, GSH levels and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased in heart tissue of rats with AMI. We also investigated the effects of carnosine (CAR) treatment on these parameters 24 h after the last ISO injection. CAR (250 mg/kg/day; ip) treatments were carried out either 10 days before ISO injection or 2 days concomitant with ISO. Pretreatment with CAR decreased plasma LDH and AST activities and ameliorated cardiac histopathological changes in ISO-treated rats. Cardiac MDA, DC and PC levels decreased, but GSH levels and SOD and GSH-Px activities increased. However, the increases in plasma MDA and PC levels as well as erythrocyte H(2)O(2)-induced MDA and GSH levels did not change due to CAR pretreatment. In conclusion, our findings indicate that CAR pretreatment may have protective effects on ISO-induced cardiac toxicity by decreasing oxidative stress.

  20. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    PubMed

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR.

  1. Bioluminescent Imaging Reveals Novel Patterns of Colonization and Invasion in Systemic Escherichia coli K1 Experimental Infection in the Neonatal Rat

    PubMed Central

    Witcomb, Luci A.; Collins, James W.; McCarthy, Alex J.; Frankel, Gadi

    2015-01-01

    Key features of Escherichia coli K1-mediated neonatal sepsis and meningitis, such as a strong age dependency and development along the gut-mesentery-blood-brain course of infection, can be replicated in the newborn rat. We examined temporal and spatial aspects of E. coli K1 infection following initiation of gastrointestinal colonization in 2-day-old (P2) rats after oral administration of E. coli K1 strain A192PP and a virulent bioluminescent derivative, E. coli A192PP-lux2. A combination of bacterial enumeration in the major organs, two-dimensional bioluminescence imaging, and three-dimensional diffuse light imaging tomography with integrated micro-computed tomography indicated multiple sites of colonization within the alimentary canal; these included the tongue, esophagus, and stomach in addition to the small intestine and colon. After invasion of the blood compartment, the bacteria entered the central nervous system, with restricted colonization of the brain, and also invaded the major organs, in line with increases in the severity of symptoms of infection. Both keratinized and nonkeratinized surfaces of esophagi were colonized to a considerably greater extent in susceptible P2 neonates than in corresponding tissues from infection-resistant 9-day-old rat pups; the bacteria appeared to damage and penetrate the nonkeratinized esophageal epithelium of infection-susceptible P2 animals, suggesting the esophagus represents a portal of entry for E. coli K1 into the systemic circulation. Thus, multimodality imaging of experimental systemic infections in real time indicates complex dynamic patterns of colonization and dissemination that provide new insights into the E. coli K1 infection of the neonatal rat. PMID:26351276

  2. The Multi-Target Drug M30 Shows Pro-Cognitive and Anti-Inflammatory Effects in a Rat Model of Alzheimer's Disease.

    PubMed

    Pimentel, Luisa S; Allard, Simon; Do Carmo, Sonia; Weinreb, Orly; Danik, Marc; Hanzel, Cecilia E; Youdim, Moussa B; Cuello, A Claudio

    2015-01-01

    Current therapies for Alzheimer's disease (AD) offer partial symptomatic relief and do not modify disease progression. There is substantial evidence indicating a disease onset years before clinical diagnosis, at which point no effective therapy has been found. In this study, we investigated the efficacy of a new multi-target drug, M30, at relatively early stages of the AD-like amyloid pathology in a robust rat transgenic model. McGill-R-Thy1-APP transgenic rats develop the full AD-like amyloid pathology in a progressive fashion, and have a minimal genetic burden. McGill rats were given 5 mg/kg M30 or vehicle per os, every 2 days for 4 months, starting at a stage where the transgenic animals suffer detectable cognitive impairments. At the completion of the treatment, cognitive functions were assessed with Novel Object Location and Novel Object Recognition tests. The brains were then analyzed to assess amyloid-β (Aβ) burden and the levels of key inflammatory markers. Long-term treatment with M30 was associated with both the prevention and the reversal of transgene-related cognitive decline. The effects on cognition were accompanied by a shift of the Aβ-immunoreactive material toward an amyloid plaque aggregated molecular form, diminished molecular signs of CNS inflammation and a change in microglia morphology toward a surveying phenotype. This study is the first to demonstrate the therapeutic potential of M30 in a rat model of the AD amyloid pathology. It provides a rationale for further investigations with M30 and with potential multi-target approaches to delay, prevent or reverse the progression the AD pathology at early disease-stages. PMID:26401560

  3. Sertraline behavioral response associates closer and dose-dependently with cortical rather than hippocampal serotonergic activity in the rat forced swim stress.

    PubMed

    Mikail, Hudu G; Dalla, Christina; Kokras, Nikolaos; Kafetzopoulos, Vasilios; Papadopoulou-Daifoti, Z

    2012-09-10

    The rat Forced Swim Test (FST) is widely used to investigate the response to antidepressant treatment. Selective serotonin reuptake inhibitors (SSRIs) elongate swimming duration during the FST, while climbing duration is unaffected. In the present study, we aimed to correlate behavioral effects of the SSRI sertraline in the FST with respective changes in the serotonergic activity of the hippocampus and the prefrontal cortex. Male rats were subjected to the standard FST (two swim sessions in two consecutive days) and between the two sessions they received three i.p. injections of sertraline (10 mg/kg or 40 mg/kg) or vehicle. All rats were killed immediately after the second FST session. Unstressed animals received the same administration schemes and were killed in equivalent time-points. Serotonin and its metabolite 5-HIAA were assayed in the hippocampus and the prefrontal cortex with the use of high-performance liquid chromatography (HPLC-ED) and their ratio 5-HIAA/5-HT was calculated. Sertraline enhanced swimming and decreased immobility duration at both doses. Serotonergic activity was not altered by the 2-day swim stress in either brain region, while subchronic sertraline treatment enhanced 5-HT levels and decreased 5-HIAA/5-HT in the hippocampus and the prefrontal cortex. The serotonin turnover rate (5-HIAA/5-HT ratio) decrease is probably indicative of reduced 5-HT metabolism, as a result of 5-HT reuptake inhibition. This effect was significant in the prefrontal cortex of unstressed rats only after a higher dose of sertraline. In the prefrontal cortex, but not in the hippocampus, immobility duration was negatively correlated with 5-HT tissue levels, whereas swimming duration was positively correlated with 5-HT. These results indicate that after antidepressant treatment, behavior during the FST can be predictive of respective serotonergic changes, especially in the prefrontal cortex.

  4. Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats

    PubMed Central

    Wang, Zi; Huang, Haizhen; Yang, Shaozhong; Huang, Shanshan; Guo, Jingxuan; Tang, Qi; Qi, Feng

    2016-01-01

    Purpose The analgesic effect of ropivacaine (Rop) for nerve block lasts only ~3–6 hours for single use. The aim of this study was to develop long-acting regional anesthetic Rop nanoparticles and investigate the effects of sciatic nerve block on postoperative pain in rats. Materials and methods Rop nanoparticles were developed using polyethylene glycol-co-polylactic acid (PELA). One hundred and twenty adult male Wistar rats were randomly divided into four groups (n=30, each): Con (control group; 0.9% saline, 200 µL), PELA (PELA group; 10 mg), Rop (Rop group; 0.5%, 200 µL), and Rop-PELA (Rop-PELA group; 10%, 10 mg). Another 12 rats were used for the detection of Rop concentration in plasma. The mechanical withdrawal threshold and thermal withdrawal latency were measured at 2 hours, 4 hours, 8 hours, 1 day, 2 days, 3 days, 5 days, and 7 days after incision. The expression of c-FOS was determined by immunohistochemistry at 2 hours, 8 hours, 48 hours, and 7 days. Nerve and organ toxicities were also evaluated at 7 days. Results The duration of Rop absorption in the plasma of the Rop-PELA group was longer (>8 hours) than that of the Rop group (4 hours). Mechanical withdrawal threshold and thermal withdrawal latency in the Rop-PELA group were higher than that in other groups (4 hours–3 days). c-FOS expression in the Rop-PELA group was lower than that in the control group at 2 hours, 8 hours, and 48 hours and lower than that in the Rop group at 8 hours and 48 hours after paw incision. Slight foreign body reactions were observed surrounding the sciatic nerve at 7 days. No obvious pathophysiological change was found in the major organs after Rop-PELA administration at 7 days. Conclusion Rop-PELA provides an effective analgesia for nerve block over 3 days after single administration, and the analgesic mechanism might be mediated by the regulation of spinal c-FOS expression. However, its potential long-term tissue toxicity needs to be further investigated. PMID:27274236

  5. Rat hepatocyte culture model of macrosteatosis: Effect of macrosteatosis induction and reversal on viability and liver-specific function

    PubMed Central

    Nativ, Nir I.; Yarmush, Gabriel; Chen, Alvin; Dong, David; Henry, Scot D.; Guarrera, James V.; Klein, Kenneth M.; Maguire, Tim; Schloss, Rene; Berthiaume, Francois; Yarmush, Martin L.

    2013-01-01

    Background & Aims A common cause of liver donor ineligibility is macrosteatosis. Recovery of such livers could enhance donor availability. Living donor studies have shown diet-induced reduction of macrosteatosis enables transplantation. However, cadaveric liver macrosteatotic reduction must be performed ex vivo within hours. Towards this goal, we investigated the effect of accelerated macrosteatosis reduction on hepatocyte viability and function using a novel system of macrosteatotic hepatocytes. Methods Hepatocytes isolated from lean Zucker rats were cultured in a collagen sandwich, incubated for 6 days in fatty acid-supplemented medium to induce steatosis, and then switched for 2 days to medium supplemented with lipid metabolism promoting agents. Intracellular lipid droplet size distribution and triglyceride, viability, albumin and urea secretion, and bile canalicular function were measured. Results Fatty acid-supplemented medium induced microsteatosis in 3 days and macrosteatosis in 6 days, the latter evidenced by large lipid droplets dislocating the nucleus to the cell periphery. Macrosteatosis significantly impaired all functions tested. Macrosteatosis decreased upon returning hepatocytes to standard medium, and the rate of decrease was 4-fold faster with supplemented agents, yielding 80% reduction in 2 days. Viability of macrosteatosis reduced hepatocytes was similar to control lean cells. Accelerated macrosteatotic reduction led to faster recovery of urea secretion and bile canalicular function, but not of albumin secretion. Conclusions Macrosteatosis reversibly decreases hepatocyte function and supplementary agents accelerate macrosteatosis reduction and some functional restoration with no effect on viability. This in vitro model may be useful to screen agents for macrosteatotic reduction in livers before transplantation. PMID:23872604

  6. Intermittent heat exposure and thirst in rats.

    PubMed

    Barney, Christopher C; Kuhrt, David M

    2016-04-01

    Adequate water intake, supporting both cardiovascular function and evaporative cooling, is a critical factor in mitigating the effects of heat waves, which are expected to increase with global warming. However, the regulation of water intake during periods of intermittent heat exposure is not well understood. In this study, the effects of access to water or no access during intermittent heat exposure were assessed using male Sprague-Dawley rats exposed to 37.5°C for 4 h/day. After 7 days of intermittent heat exposure, reductions in evaporative water loss were observed in all animals and reductions in water intake following heat exposure occurred as the days of heat exposure increased. Rats that were not allowed water during the 7 days of exposure had decreased rehydration levels, however, rats allowed access to water increased water intake during exposure and exhibited higher overall rehydration levels over the same time period. Peripheral administration of angiotensinII, mimicking activation of volemic thirst, or hypertonic saline solution, activating intracellular thirst, did not result in alteration of water intake in rats exposed to heat with access to water compared to control rats. In contrast, rats exposed to heat without access to water had reduced water intake after administration of hypertonic saline and increased water intake after administration of angiotensinIIcompared to control rats. These experiments demonstrate that thirst responses to intermittent heat exposure are altered by providing water during heat exposure and that intermittent heat exposure without access to water alters drinking responses to both intracellular and extracellular thirst challenges.

  7. Renal function in single-kidney rats.

    PubMed

    Provoost, A P; De Keijzer, M H; Wessel, J N; Molenaar, J C

    1989-01-01

    Can a single kidney survive for a normal life span? This is the type of question frequently asked by patients and especially by parents of children who lose one kidney in early childhood. Based on our wide experience with single-kidney rats, we will try to give an answer to this question. After the removal of its counterpart, the single remaining kidney will rapidly adapt to the new situation by a compensatory increase in the glomerular filtration rate (GFR) and renal mass. This is true not only for intact kidneys but also for damaged ones. The GFR level obtained by damaged kidneys will be less than that of intact single kidneys, however, depending on the degree of initial damage. The GFR is stable for a certain period of time, which is longer for intact single kidneys than for damaged kidneys and also depends on the daily protein intake; after that renal function will deteriorate. This decline in GFR is preceded by a marked increase in urinary protein excretion. Although the follow-up period is not completed yet, the survival time of single intact kidneys in rats on a normal diet is expected to be 15%-20% less than the normal rat life span. In rats on a lifelong high protein intake the kidney survival time drops to 40% below the normal rat life span. In rats on a moderately reduced protein intake, however, single intact kidneys may survive for a normal life span. The situation is worse for single damaged kidneys. Depending on the severity of the initial damage, kidney survival time will be much less than a normal life span. We studied rats with an initial recovery to 75% of renal function. Despite this initial recovery, the animals died of renal failure within 50% of the expected life span. A low-protein diet prolonged the renal survival by about 12%, a high-protein diet shortened it by the same percentage.

  8. Calcium-deprived rats avoid sweet compounds.

    PubMed

    Tordoff, M G; Rabusa, S H

    1998-07-01

    To characterize the link between calcium status and sweet solution intake, rats fed a diet containing 25 mmol Ca2+/kg (Ca-25, low calcium) or 150 mmol Ca2+/kg (Ca-150, control) were given 48-h two-bottle tests with a choice between water and various concentrations of a nutrient (sucrose, Polycose, ethanol and/or corn oil). Rats fed the Ca-25 diet had significantly lower sucrose intakes and preferences over the entire range tested (10-320 g/L) even though the same (Experiment 1), or identically treated (Experiment 2a) rats had normal Polycose and ethanol intakes and normal (Experiment 1, 2b) or significantly greater (Experiment 2a) corn oil intakes. In additional tests, rats fed the Ca-25 diet had significantly lower intakes relative to rats fed the Ca-150 diet of other sweeteners (30 mmol/L D-phenylalanine, 1 mmol/L saccharin and 0.3 mmol/L aspartame), significantly higher intakes of 0.5 mg/L capsaicin and 300 mmol/L monosodium glutamate, and normal intakes of 10 g/L or 80 g/L safflower oil and 10 g/L peanut oil. In a three-cup macronutrient selection experiment (Experiment 3), calcium-deprived rats ate significantly less of a high sucrose carbohydrate source and significantly more of a protein source than did controls. These results suggest that calcium deficiency reduces the rat's liking for sweetness, irrespective of the type or form of sweetener, and that this is not due to a general reduction in energy intake.

  9. [Pituitary function of dysgenesic femal rats. Studies with grafting method].

    PubMed

    Vanhems, E; Busquet, J

    1975-01-01

    Misulban administered to pregnant rats on the 15th day of gestation provoked gonadal dysgenesia in the offspring. Study of the pituitary function of dysgenesic female rats, realized by grafting method, showed gonadotrophic hypersecretion.

  10. Effect of simulated weightlessness on energy metabolism in the rat

    NASA Technical Reports Server (NTRS)

    Jordan, J. P.; Sykes, H. A.; Crownover, J. C.; Schatte, C. L.; Simmons, J. B., II; Jordan, D. P.

    1982-01-01

    Results of measurements of food uptake and body weight changes occurring in rats suspended from a harness so that the antigravity muscles were not used for locomotion are presented. The rats were tested in pairs, with both in a harness but only one suspended off its hind legs; this section lasted 7 days. A second phase of the experiment involved feeding the nonsuspended rat the same amount of food the experimental rat had consumed the previous day. All rats experienced decreased in body weight and food intake in the first stage, while in the second stage the suspended rat lost more weight. The total oxygen uptake, CO2 output, and rate of C-14O2 production were depressed in the suspended rats, then returned to normal levels once the rats were back on the ground. It is concluded that the gross metabolic processes are unaffected by simulated weightlessness.

  11. High prevalence of rat hepatitis E virus in wild rats in China.

    PubMed

    Li, Wei; Guan, Dawei; Su, Juan; Takeda, Naokazu; Wakita, Takaji; Li, Tian-Cheng; Ke, Chang Wen

    2013-08-30

    Serum samples from a total of 713 wild rats captured in Zhanjiang city in China from December 2011 to September 2012 were investigated for the prevalence of rat hepatitis E virus (HEV) by exploring rat HEV-specific antibodies and RNA. By an ELISA based on recombinant rat HEV-like particles (HEV-LPs), 23.3% (166/713) of the rats were positive for anti-HEV IgG, and 8.3% (59/713) were positive for anti-HEV IgM. The IgG-positive rates in Rattus norvegicus, Bandicota indica, Rattus flavipectus, Rattus rattoides losea, and Rattus rattus hainanus, were 27.8% (64/230), 23.0% (40/174), 19.9% (34/171), 21.5% (26/121), and 11.8% (2/17), while the IgM-positive rates were 8.3% (19/230), 6.9% (12/174), 8.2% (14/171), 10.7% (13/121), and 5.9% (1/17), respectively. The IgG-positive rate of the rats captured in rural areas, 24.1% (84/348), was higher than that in the central area of Zhanjiang city, 15.1% (32/212). The highest IgG-positive rates, as high as 45.3% (39/86), were detected in wild rats trapped in the garbage dump. Twelve of the 59 IgM-positive serum samples were positive for HEV RNA, which was detected in all of the wild rat species except R. rattus hainanus. A phylogenetic analysis of the partial genome of rat HEV ORF1 indicated that all of the 12 HEV strains belong to rat HEV, and no other genotype HEV were detected. The rat HEV from Zhangjiang city could be classified into three separated clusters, suggesting that the infection due to rat HEV with a variety of genome entities occurs extensively among wild rats in China.

  12. Urea synthesis in rats fed diet containing kidney beans.

    PubMed

    Scislowski, P W; Grant, G; Harris, I; Pickard, K; Pusztai, A

    1992-10-01

    When rats were fed a diet containing kidney bean (Phaesolus vulgaris) urea excretion was increased 3-5 fold. Isolated liver mitochondria from rats fed the kidney bean diet produced 40% more citrulline in the presence of arginine than mitochondria isolated from control rats. Mitochondrial activities of urea cycle enzymes and N-acetylglutamate synthetase were similar in animals fed diets containing kidney bean or lactalbumin. The possible mechanisms causing acute urea production in rats fed with kidney bean are discussed.

  13. Urea synthesis in rats fed diet containing kidney beans.

    PubMed

    Scislowski, P W; Grant, G; Harris, I; Pickard, K; Pusztai, A

    1992-10-01

    When rats were fed a diet containing kidney bean (Phaesolus vulgaris) urea excretion was increased 3-5 fold. Isolated liver mitochondria from rats fed the kidney bean diet produced 40% more citrulline in the presence of arginine than mitochondria isolated from control rats. Mitochondrial activities of urea cycle enzymes and N-acetylglutamate synthetase were similar in animals fed diets containing kidney bean or lactalbumin. The possible mechanisms causing acute urea production in rats fed with kidney bean are discussed. PMID:1445392

  14. An experimental task to examine the mirror system in rats

    PubMed Central

    Takano, Yuji; Ukezono, Masatoshi

    2014-01-01

    The mirror system in the brain is considered to be a neural basis of sociality, but previous studies have been limited to primates. Here we report an experimental task to examine the mirror system in rats. We show that a rat could reach to a pellet and grasp and eat it in front of another rat that was observing the reaching, which indicates that the task will enable us to start exploring the rat mirror system. PMID:25323637

  15. Social influences on morphine sensitization in adolescent rats.

    PubMed

    Hofford, Rebecca S; Schul, Destri L; Wellman, Paul J; Eitan, Shoshana

    2012-05-01

    Given that social influences are among the strongest predictors of adolescents' drug use, this study examines the effects of social interactions on morphine sensitization in both adolescent and adult rats. Rats treated with morphine (twice daily, 6 days, 2.5-10 mg/kg, subcutaneously, s.c.) or saline were group-housed in two different conditions. Thus, four experimental groups were examined for each age group: (1) morphine-treated rats housed physically and visually separate from saline-injected rats ('morphine only'); (2) morphine-treated rats housed together with saline-injected rats ('morphine cage-mates'); (3) saline-injected rats housed together with morphine-treated rats ('saline cage-mates'); and (4) saline-injected rats housed physically and visually separate from morphine-treated rats ('saline only'). Starting 9 days following the last morphine injection, rats were individually examined once daily for 5 consecutive days for their locomotor response to 2.5 mg/kg of morphine. For both age groups, there were no significant differences in morphine-induced hyper-locomotion between saline cage-mates and saline only rats. Morphine only rats exhibited morphine locomotor sensitization as compared to both the saline only and saline cage-mates rats. Notably, a significant difference was observed between the adolescent morphine cage-mates and morphine only rats. The adolescent morphine cage-mates did not exhibit the enhanced locomotor response as compared to the saline only and saline cage-mate rats. A trend of reduced morphine locomotor sensitization was observed in the adult morphine cage-mates as compared to morphine only but it did not reach statistical significance. Thus, this study demonstrates social influences on morphine sensitization which are more prevalent in adolescents as compared to adults.

  16. An experimental task to examine the mirror system in rats.

    PubMed

    Takano, Yuji; Ukezono, Masatoshi

    2014-01-01

    The mirror system in the brain is considered to be a neural basis of sociality, but previous studies have been limited to primates. Here we report an experimental task to examine the mirror system in rats. We show that a rat could reach to a pellet and grasp and eat it in front of another rat that was observing the reaching, which indicates that the task will enable us to start exploring the rat mirror system. PMID:25323637

  17. Nigella Sativa reverses osteoporosis in ovariectomized rats

    PubMed Central

    2014-01-01

    Background Osteoporosis poses a significant public health issue. It is a skeletal disorder characterized by compromised bone strength that predisposes to increased risk of fracture. There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis. About 33% of women over 50 will experience bone fractures as a result of osteoporosis. Nigella Sativa (NS) has been shown to have beneficial effects on bone and joint diseases. The present study was conducted to elucidate the protective effect of Nigella Sativa on osteoporosis produced by ovariectomy in rats. Methods Female Wistar rats aged 12–14 months were divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized supplemented with nigella sativa (OVX-NS) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. After 12 weeks, plasma levels of calcium (Ca+2), phosphorous (Pi), alkaline phosphatase (ALP), amino terminal collagen type 1 telopeptide, malondialdehyde (MDA), nitrates, nitric oxide surrogate, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Histological examination of the liver and the tibia was conducted. Histomorphometric analysis of the tibia was also performed. Results OVX rats showed significant decrease in plasma Ca+2, accompanied by a significant increase in plasma ALP, amino terminal collagen type 1 telopeptide, MDA, nitrates, TNF-α and IL-6. These changes were reversed by NS supplementation in OVX-NS group to be near SHAM levels. Histological examination of the tibias revealed discontinuous eroded bone trabeculae with widened bone marrow spaces in OVX rats accompanied by a significant decrease in both cortical and trabecular bone thickness compared to Sham rats. These parameters were markedly reversed in OVX-NS rats. Histological examination of the liver showed mononuclear cellular infiltration and congestion of blood vessels at the portal area in OVX rats which were not found

  18. Pharmacokinetics of memantine in rats and mice.

    PubMed

    Beconi, Maria G; Howland, David; Park, Larry; Lyons, Kathryn; Giuliano, Joseph; Dominguez, Celia; Munoz-Sanjuan, Ignacio; Pacifici, Robert

    2011-12-15

    To evaluate the potential of memantine as a therapeutic agent for Huntington's disease (HD) we have undertaken a series of in vitro, ex vivo and whole animal studies to characterize its pharmacokinetics (PK) and pharmacodynamics (PD) in rats and mice. Results from these studies will enable determination of memantine exposures needed to engage the related functional PD marker and help predict the dose regimen for clinical trials to test its proposed mechanism of action; the selective blockade of extrasynaptic, but not synaptic, NMDA receptors. The studies reported here describe the PK of memantine in rats and mice at low (1 mg/kg) and high (10 mg/kg) doses. Our studies indicate that the clearance mechanisms of memantine in rats and mice are different from those in human, and that clearance needs to be taken into account when extrapolating to the human. In rats only, there is a significant metabolic contribution to memantine clearance at lower dose levels. While memantine is primarily cleared renally in all three species, the proportion of total systemic clearance above the glomerular filtration rate (GFR) is much higher in rats and mice (~13, 4.5, and 1.4 times higher than GFR in rats, mice, and humans, respectively), suggesting that the contribution of active transport to memantine elimination in rats and mice is more significant than in the human. In rats and mice, memantine had a short half-life (<4 h) and steep Cmax/Cmin ratios (>100). In the human, the half-life of memantine was reported to be very long (60-80 h) with a Cmax/Cmin ratio at steady state concentrations of ~1.5. A small change in the clearance of memantine - for example due to renal impairment or competition for the elimination pathway with a co-administered drug - will likely affect exposure and, therefore, the selectivity of memantine on NMDA receptors . The PK differences observed between these species demonstrate that the PK in mice and rats cannot be directly extrapolated to the human. Further

  19. Relaxin and drinking in pregnant rats.

    PubMed

    Hornsby, D J; Wilson, B C; Summerlee, A J

    2001-01-01

    Work reported in this chapter describes the potential role of relaxin in resetting cardiovascular thresholds in pregnant rats. Relaxin, a polypeptide produced primarily by the ovary in pregnant animals in many species, is also produced in the brain. Exogenous administration of relaxin into the brain causes a profound drinking response which is negated by pretreatment with a specific monoclonal antibody to rat relaxin when the antibody is injected into the brain. Neutralizing the action of endogenous brain relaxin in pregnant rats also blocks the normal increase in drinking that is observed in rats at night during the second half of pregnancy. Relaxin acts through the forebrain angiotensin system at the level of the subfornical organ (an important interface between the blood, the brain and the cerebrospinal fluid) as blockade of the angiotensin II receptor action negates several central actions of relaxin. Expression of angiotensin II AT1 receptors in the subfornical organ increases in parallel with the increase in circulating relaxin seen in the second half of pregnancy. Neutralizing the effects of endogenous brain relaxin, using central injections of the monoclonal antibody, blocks this increase in the expression of angiotensin II AT1 receptors in subfornical organ. These data imply that relaxin in the brain may act to affect central cardiovascular thresholds in rats and this may be important for the normal physiology of pregnancy.

  20. A rat model for hepatitis E virus

    PubMed Central

    Mishra, Niraj; Verbeken, Erik; Ramaekers, Kaat; Dallmeier, Kai

    2016-01-01

    ABSTRACT Hepatitis E virus (HEV) is one of the prime causes of acute viral hepatitis, and chronic hepatitis E is increasingly recognized as an important problem in the transplant setting. Nevertheless, the fundamental understanding of the biology of HEV replication is limited and there are few therapeutic options. The development of such therapies is partially hindered by the lack of a robust and convenient animal model. We propose the infection of athymic nude rats with the rat HEV strain LA-B350 as such a model. A cDNA clone, pLA-B350, was constructed and the infectivity of its capped RNA transcripts was confirmed in vitro and in vivo. Furthermore, a subgenomic replicon, pLA-B350/luc, was constructed and validated for in vitro antiviral studies. Interestingly, rat HEV proved to be less sensitive to the antiviral activity of α-interferon, ribavirin and mycophenolic acid than genotype 3 HEV (a strain that infects humans). As a proof-of-concept, part of the C-terminal polymerase sequence of pLA-B350/luc was swapped with its genotype 3 HEV counterpart: the resulting chimeric replicon replicated with comparable efficiency as the wild-type construct, confirming that LA-B350 strain is amenable to humanization (replacement of certain sequences or motifs by their counterparts from human HEV strains). Finally, ribavirin effectively inhibited LA-B350 replication in athymic nude rats, confirming the suitability of the rat model for antiviral studies. PMID:27483350

  1. Cardiopulmonary Changes with Moderate Decompression in Rats

    NASA Technical Reports Server (NTRS)

    Robinson, R.; Little, T.; Doursout, M.-F.; Butler, B. D.; Chelly, J. E.

    1996-01-01

    Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

  2. Radioimmunoimaging of pneumocystis carinii infection in rats

    SciTech Connect

    Vallabhajosula, S.; Shane, L.B.; Goldsmith, S.J.; Lipszyc, H.; Walzer, P.

    1984-01-01

    Pneumocystis carinil pneumonia (PCP) is seen in patients with impaired immunity due to chemotherapeutic suppression or to a primary disorder, congenital or AIDS. Although radiogallium imaging has been helpful in the workup of PCP, it is non-specific. Since there is no early specific non-invasive method to diagnose PCP, the authors are developing an imaging technique using radiolabeled antibodies. Fulminant PCP was induced in rats by injecting cortisone, 20mg 2-3 times/wk for 8 wks. PC cells isolated from rat lung were injected into rabbits. The antiserum thus derived was separated and purified using Protein-A bound sepharose column with identification of IgG by polyacrylamide gel electrophoresis. Both rabbit antipneumocystis antibodies and purified IgG(Sigma) were iodinated with I-131 to a high specific activity (3-5..mu..Ci/ug) using a lactoperoxidase method. /sup 131/I-labeled specific and non-specific IgG were injected into rats with PC infection and imaged with an Anger camera. After sacrifice, I-131 activity/gram tissue (lung, liver, heart) was determined and expressed as organ ratios. An increased uptake of specific antibody in lungs of rats with PCP was demonstrated by organ counting and imaging. This increase was not seen in normal controls or rats injected with non-specific IgG. These data provide a basis for radioimmunoimaging of infectious diseases.

  3. Glutathione system in young spontaneously hypertensive rats.

    PubMed

    Lee, S K; Arunkumar, Sundaram; Sirajudeen, K N S; Singh, H J

    2010-12-01

    Glutathione (GSH) forms a part of the antioxidant system that plays a vital role in preventing oxidative stress, and an imbalance in the oxidant/antioxidant system has been linked to the pathogenesis of hypertension. The aim of this study was to investigate the status of the GSH system in the kidney of spontaneously hypertensive rats (SHR). Components of the GSH system, including glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), and total GSH content, were measured in the kidneys of 4, 6, 8, 12, and 16 weeks old SHR and Wistar-Kyoto (WKY) rats. Systolic blood pressure of SHR was significantly higher from the age of 6 weeks onwards compared with age-matched WKY rats. GPx activity in the SHR was significantly lower from the age of 8 weeks onwards when compared to that in age-matched WKY rats. No significant differences were evident in the GPx-1 protein abundance, and its relative mRNA levels, GR, GST activity, and total GSH content between SHR and age-matched WKY rats. The lower GPx activity suggests of an impairment of the GSH system in the SHR, which might be due to an abnormality in its protein rather than non-availability of a cofactor. Its role in the development of hypertension in SHR however remains unclear.

  4. Ultrasonic evoked responses in rat cochlear nucleus

    PubMed Central

    Du, Yi; Ping, Junli; Li, Nanxin; Wu, Xihong; Li, Liang; Galbraith, Gary

    2009-01-01

    Numerous studies have reported auditory brainstem responses evoked by stimuli within the “normal” hearing range of rats, with maximum sensitivity peaking around 16 kHz. Yet rats also emit and respond to sounds in the ultrasonic (US) frequency range (30-100 kHz). However very few electrophysiological studies have recorded auditory brainstem responses using US stimuli, and none have exceeded 70 kHz. We report here short-latency (1-3 ms) evoked potentials recorded in rat cochlear nucleus (CN) to US stimuli ranging from 40-90 kHz. Robust responses were recorded in 33 of 36 CN recording sites to stimuli ranging from 40-60 kHz; and twenty-eight of these sites continued to yield well defined responses out to 90 kHz. Latencies systematically increased and overall amplitudes decreased with increasing US frequency. Amplitudes differed significantly in the three CN subnuclei, being largest in posterior-ventral (PVCN) and smallest in anterior-ventral (AVCN). The fact that well defined responses can be recorded to stimuli as high as 90 kHz significantly extends the recorded upper frequency range of neural activity in the brainstem auditory pathway of the rat. These evoked potential results agree with the well documented behavioral repertoire of rats in the US frequency range. PMID:17803975

  5. Purification and sequence of rat oxyntomodulin.

    PubMed Central

    Collie, N L; Walsh, J H; Wong, H C; Shively, J E; Davis, M T; Lee, T D; Reeve, J R

    1994-01-01

    Structural information about rat enteroglucagon, intestinal peptides containing the pancreatic glucagon sequence, has been based previously on cDNA, immunologic, and chromatographic data. Our interests in testing the physiological actions of synthetic enteroglucagon peptides in rats required that we identify precisely the forms present in vivo. From knowledge of the proglucagon gene sequence, we synthesized an enteroglucagon C-terminal octapeptide common to both proposed enteroglucagon forms, glicentin and oxyntomodulin, but sharing no sequence overlap with glucagon. We then developed a radioimmunoassay using antibodies raised against the octapeptide that was specific for enteroglucagon peptides without cross-reacting with glucagon. Rat intestine was extracted, and one presumptive enteroglucagon form was purified by following the enteroglucagon C-terminal octapeptide-like immunoreactivity through several HPLC purification steps. Structural characterization of the material by amino acid composition, microsequence, and mass spectral analyses identified the peptide as rat oxyntomodulin. The 37-residue peptide consists of pancreatic glucagon plus the C-terminal extension, Lys-Arg-Asn-Arg-Asn-Asn-Ile-Ala. This now permits synthesis of an unambiguous duplicate of endogenous rat oxyntomodulin for physiological studies. Images PMID:7937770

  6. Opiates and cerebral functional activity in rats

    SciTech Connect

    Trusk, T.C.

    1986-01-01

    Cerebral activity was measured using the free-fatty acid (1-/sup 14/C) octanoate as a fast functional tracer in conscious, unrestrained rats 5 minutes after intravenous injection of heroin, cocaine or saline vehicle. Regional changes of octanoate labeling density in the autoradiograms relative to saline-injected animals were used to determine the functional activity effects of each drug. Heroin and cocaine each produced a distinctive pattern of activity increases and suppression throughout the rat brain. Similar regional changes induced by both drugs were found in limbic brain regions implicated in drug reinforcement. Labeled octanoate autoradiography was used to measure the cerebral functional response to a tone that had previously been paired to heroin injections. Rats were trained in groups of three consisting of one heroin self-administration animal, and two animals receiving yoked infusion of heroin or saline. A tone was paired with each infusion during training. Behavioral experiments in similarly trained rats demonstrated that these training conditions impart secondary reinforcing properties to the tone in animals previously self-administering heroin, while the tone remains behaviorally neutral in yoked-infusion rats. Cerebral functional activity was measured during presentation of the tone without drug infusion. Octanoate labeling density changed in fifteen brain areas in response to the tone previously paired to heroin without response contingency. Labeling density was significantly modified in sixteen regions as a result of previously pairing the tone to response-contingent heroin infusions.

  7. Beacon immunoreactivity in the rat hypothalamus.

    PubMed

    Ng, Y K; Brailoiu, G C; Dun, S L; Ling, E A; Yang, J; Chang, J K; Dun, N J

    2006-05-01

    Beacon (BC) is a peptide of 73 amino acids, whose gene expression was first reported in the hypothalamus of Psammomys obesus (or Israeli sand rat). To appreciate better the functional role of BC in normal rats and sand rats, the distribution of BC immunoreactivity (irBC) and its subcellular localization were studied in the brain of Sprague-Dawley rats. In the hypothalamus, intense staining was present in neurons of the supraoptic (SO), paraventricular (PVH), and accessory neurosecretory nuclei and in cell processes of median eminence. Double labeling of the hypothalamic sections with mouse monoclonal oxytocin (OT) antibody and rabbit polyclonal BC antiserum revealed that nearly all OT-immunoreactive cells from SO, PVH, and accessory neurosecretory nuclei were irBC. Double labeling of the sections with guinea pig vasopressin (VP) antiserum and BC antiserum showed that a population of VP-immunoreactive neurons was irBC. By immunoelectron microscopy, immunoreactive product was associated with mitochondrial membranes or appeared as electron-dense bodies in many PVH and SO neurons. Most of the neurosecretory granules were unstained for BC. Taken together, our results indicate the presence of beacon in the OT-containing neurons and a population of VP-containing neurons, mostly associated with mitochondrial membrane. Insofar as the amino acids sequence of beacon is identical to that of ubiquitin-like 5, it is possible that the distribution of BC immunoreactivity noted in our study is that of ubiquitin-like 5 peptide in the rat hypothalamus.

  8. Immunopathological features of rat Staphylococcus aureus arthritis.

    PubMed Central

    Bremell, T; Lange, S; Holmdahl, R; Rydén, C; Hansson, G K; Tarkowski, A

    1994-01-01

    Staphylococcus aureus is the most common bacterial species found in nongonococcal bacterial arthritis in humans. We present the first description, to our knowledge, of an outbreak of spontaneous staphylococcal arthritis in a rat colony. In a group of 10 rats, 9 displayed arthritis. Clinically, the most obvious findings were arthritis of one or both hindpaws and malaise. Bacteriophage typing showed the common phage type 85 in isolates recovered from the joints, blood, and bedding of rats and from the nose and cheeks of one person from the staff of the animal facility. The S. aureus strain proved to produce staphylococcal enterotoxin A and exhibited strong binding to collagen types I and II and bone sialoprotein, which are potentially important virulence factors. When the recovered S. aureus strain was injected intravenously into healthy rats, severe septic arthritis was induced in almost all of the animals. The arthritic lesions were characterized by infiltration of phagocytic cells and T lymphocytes into the synovium. Many of the synovial cells strongly expressed major histocompatibility complex class II molecules. Increased levels of interleukin 6 in serum as well as a prominent polyclonal B-cell activation were noted throughout the disease course. Pretreatment of S. aureus-injected rats in vivo with an antibody to the alpha beta T-cell receptor significantly decreased the severity of the arthritis. Our results indicate that alpha beta + T lymphocytes contribute to an erosive and persistent course of S. aureus arthritis. Images PMID:8188356

  9. Plasma cholesterol transport in anhepatic rats.

    PubMed Central

    Quarfordt, S H; Landis, B; Cucchiaro, G; Yamaguchi, Y; Oswald, B

    1992-01-01

    The plasma appearance of newly synthesized cholesterol in anhepatic laboratory diet-fed rats was 10% of the intact rat. In intact rats this cholesterol was mainly ester in lower density lipoproteins, but for anhepatic rats it was virtually only free in high density lipoprotein. Chylomicron cholesterol ester was removed much more slowly from anhepatic than control plasma and returned primarily as free in high density lipoproteins, with the control return 10 times the anhepatic return. Lower density lipoprotein cholesterol ester transfer to an extravascular pool in anhepatic rats was less than 10% of controls. The liver was responsible for 95% of the extravascular lower density lipoprotein ester pool and only 50% of the for high density lipoprotein ester. Despite decreased anhepatic lipoprotein catabolism, the mass of both plasma low and high density lipoproteins progressively decreased indicating an even greater decrease in influx. The anhepatic fractional catabolic rate of apo A1 was similar to controls, but that of apo E was considerably less. Despite the unchanged catabolism of apo A1 and the reduced catabolism of apo E, plasma apo A1 decreased less than apo E after hepatectomy. The anhepatic data confirm the pivotal role of the liver in maintaining plasma low and high density lipoprotein cholesterol concentrations. They suggest that, in addition to its anabolic and catabolic functions, the liver also acts as a reservoir buffering changes in plasma concentration. Images PMID:1569195

  10. Neurotransmitters in rats fed fumonisin B1.

    PubMed

    Porter, J K; Voss, K A; Chamberlain, W J; Bacon, C W; Norred, W P

    1993-03-01

    Fumonisin B1, a toxin produced by Fusarium moniliforme, has been associated with a neurotoxic syndrome in horses known as equine leukoencephlomalacia. Previous investigations showed that F. moniliforme cultured on corn and incorporated into rat chow increased brain 5-hydroxyindoleacetic acid (5HIAA) and 5HIAA: serotonin (5HT) ratios in these animals. Therefore, this study was undertaken to determine whether fumonisin B1 would produce related neurochemical effects in the brain and pineal gland of male and female rats. Rats were fed fumonisin B1 at 15, 50, and 150 ppm for 4 weeks. No differences occurred in brain concentrations of norepinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, 3-methoxytyramine, homovanillic acid, 5HT, 5HIAA, and the 5HIAA to 5HT ratios in either male or female rats, nor where there differences between the sexes. When compared across sexes, the norepinephrine to dopamine ratios were decreased (P < 0.05) in the 150-ppm-treated animals. This may suggest a fumonisin B1-induced imbalance in brain norepinephrine and/or dopamine. No differences were observed in pineal norepinephrine, 5HT, 5HIAA, and the 5HIAA to 5HT ratios. Since fumonisin B1 failed to duplicate the effects of the F. moniliforme-induced imbalances in 5HT and 5HIAA metabolism in the brains of rats, other mycotoxins from F. moniliforme may be responsible for these effects.

  11. Impaired pancreatic duct-cell growth in focal areas of regeneration after partial pancreatectomy in the adult Goto-Kakizaki rat, a spontaneous model of non-insulin dependent diabetes mellitus.

    PubMed

    Plachot, C; Portha, B

    2001-03-01

    The Paris colony of adult Goto-Kakizaki (GK/Par) rat, a genetic model of non-insulin dependent diabetes mellitus, is characterized by a restriction of the beta-cell mass and reduced beta-cell regeneration capacity. In order to have a better understanding of the impaired mechanism(s) leading to reduced beta-cell plasticity in the GK/Par rat, we have investigated duct-cell growth capacity following 90% pancreatectomy, a well-defined procedure leading in non-diabetic rats, to sequential duct proliferation and subsequent differentiation. To this aim, we have performed pancreatectomy in 8-10-week-old male normoglycaemic Wistar and diabetic GK rats. Duct-cell proliferation and apoptosis were evaluated at different time points: day 0 (D0), day 2 (D2), day 7 (D7) and day 14 (D14) after pancreatectomy. A transient wave of duct-cell proliferation was observed on D2 in both small and main ducts in the pancreatectomized Wistar rats. A similar increase occurred in the similarly treated GK rats, but to a higher extent as compared to the Wistar rats. Thereafter, duct-cell proliferation from main or small ducts returned to non-pancreatectomized values on D7 and remained at this level on D14 in both the Wistar and GK pancreatectomized groups. In the common pancreatic duct, the number of proliferative duct-cells was higher in GK rats compared to Wistar on D0. In both the operated Wistar and GK rats, duct-cell proliferation from the common pancreatic duct similarly decreased on D2. On D7 and D14, the same parameter returned to non-pancreatectomized values in the Wistar rats, while it was maintained lower in the GK rats as compared to the GK values on D0. In focal areas of regeneration, duct-cell proliferation was significantly lower in the pancreatectomized GK group compared to the age-related Wistar group on D7 (Wistar: 5.85+/-0.98%, GK: 3.02+/-0.69%; p < 0.01) and D14 (Wistar: 3.82+/-0.29%, GK: 2.62+/-0.27%; ns). Only a few apoptotic duct-cells were observed, with no difference

  12. Aspartate carbamoyltransferase from rat liver

    PubMed Central

    Bresnick, E.; Mossé, Helena

    1966-01-01

    1. Aspartate-carbamoyltransferase activity was concentrated from rat-liver preparations. Only l-aspartate, β-benzyl-l-aspartate and β-erythro-hydroxy-dl-aspartate were carbamoylated enzymically. The Km for l-aspartate and carbamoyl phosphate have been determined by three methods: colorimetric procedure, radioactive assay with [14C]aspartate and an assay with [14C]carbamoyl phosphate. 2. The Km for aspartate has been determined as a function of the pH; the pK of the functional group at the active site of the enzyme, pKe, was at pH9·0. Enzymic activity was diminished in the presence of N-ethylmaleimide, p-hydroxymercuribenzoate and the heavy metals Ag+, Hg2+, or Zn2+. The inhibitions could be prevented by mercaptoethanol. These findings suggested the association of a thiol group with the enzymic activity. 3. Enzymic activity was also decreased by sodium lauryl sulphate, urea and dioxan. Competitive inhibition (with l-aspartate) was manifested by maleate, succinate, oxaloacetate, β-erythro-hydroxy-dl-aspartate and β-benzyl-l-aspartate. The Ki for most of these inhibitions has been determined. 4. The properties of the liver enzyme are compared with those of Escherichia coli aspartate carbamoyltransferase and the implications of the findings are discussed. PMID:5339547

  13. The rat oocyte synthesises melatonin.

    PubMed

    Sakaguchi, Kenichiro; Itoh, Masanori T; Takahashi, Noriyuki; Tarumi, Wataru; Ishizuka, Bunpei

    2013-01-01

    Melatonin (N-acetyl-5-methoxytryptamine) is an indoleamine originally identified in the pineal gland, where it is synthesised enzymatically from serotonin (5-hydroxytryptamine) by the sequential action of arylalkylamine N-acetyltransferase (AANAT) and acetylserotonin O-methyltransferase (ASMT; also known as hydroxyindole O-methyltransferase). Melatonin directly affects ovarian functions and previous studies have suggested that melatonin is synthesised in the ovary. In the present study, we examined whether AANAT and ASMT are expressed in the adult rat ovary. Reverse transcription-polymerase chain reaction analyses demonstrated that both AANAT and ASMT mRNAs are expressed in the ovary. Western blotting for AANAT protein showed that the ovary, like the pineal gland, contains this enzymatic protein with a molecular mass of 24kDa. Immunohistochemistry revealed that the AANAT protein is localised to the oocyte, corpus luteum and medulla, including mast cells. AANAT protein was found in oocytes at all stages of follicular development, and its levels in oocytes increased progressively throughout follicular development. Furthermore, isolated oocytes metabolised exogenous serotonin to melatonin. These findings demonstrate that melatonin is synthesised from serotonin in oocytes. Melatonin synthesised in the oocyte may be implicated in its own growth or maturation, for example, by acting as a calmodulin antagonist or an antioxidant.

  14. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  15. Deficits in reproductive behaviour in septally lesioned female rats.

    PubMed

    Gogate, M G; Brid, S V; Wingkar, K C

    1991-12-01

    Estrous cycle and sexual behaviour were studied in septally lesioned female albino Wistar rats. In lesioned rats the vaginal smears showed continuous diestrus and the females failed to exhibit sexual receptivity during the postoperative period. Ovarian and uterine weights in lesioned rats were also significantly decreased. The results suggest that the septal nuclei exert a modulatory influence on female sexual behaviour. PMID:1816101

  16. EVALUATION OF PERFLUOROOCTANE SULFONATE (PFOS) IN THE RAT BRAIN

    EPA Science Inventory

    This study examined whether there is a differential distribution of PFOS within the brain, and compares adult rats with neonatal rats at an age when formation of the blood-brain barrier is not yet complete (postnatal day 7). Male and female Sprague-Dawley rats (60-70 day old, 4/...

  17. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation.

    PubMed

    Yderstraede, K B; Starklint, H; Steinbruchel, D; Jørgensen, T W; Gotfredsen, C F

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding. PMID:8401812

  18. Fetal rat pancreas transplantation in BB rats: immunohistochemical and functional evaluation.

    PubMed

    Yderstraede, K B; Starklint, H; Steinbruchel, D; Jørgensen, T W; Gotfredsen, C F

    1993-01-01

    Spontaneously diabetic BB/Wor rats received either a syngeneic fetal pancreas transplant or adult islets. In the former, 4-8 fetal pancreases were transplanted, and in the latter, 3-5000 islets. Transplantation was performed by transferring a blood clot containing the pancreases or islets to the renal subcapsular space. Insulin therapy was undertaken postoperatively, except in one experiment with adult islets. Of the fetal pancreas transplanted BB rats, 52% became normoglycaemic, and 21% remained so throughout an observation period of 10 months. Nephrectomy caused a prompt return of diabetes. The histological appearance of the grafts transplanted to the diabetic animals closely resembled that of grafts transplanted to normal rats in a parallel series. For comparison a group of BB rats received a syngeneic transplant of isolated adult islets from WF rats or BBW rats. Following adult islet transplantation, 5 out of 6 animals became hyperglycaemic after a median of 20.5 days when no insulin was given post-transplantation. Four out of 5 animals became hyperglycaemic after a median of 23 days when supportive insulin therapy was administered after the transplantation. The results indicate that recurrent diabetes is not inevitable following syngeneic fetal pancreas transplantation to spontaneously diabetic BB rats. Recurrent diabetes was only occasionally associated with mononuclear cell infiltration. Transplanted tissue was well-preserved and vascularized; mega-islets were a constant finding.

  19. Neighborhood Sanitation: Rat Complaints and Rat Control on the Near West Side, Newark, New Jersey and North Hill, Akron, Ohio

    ERIC Educational Resources Information Center

    Margulis, Harry L.

    1978-01-01

    Analyses suggest that monthly rate of change in rat complaints is best explained by procedures which increase agency visibility, time-dependent cycles dictated by agency operation and intervention, and dynamics of a rat population. Effective rat control occurs when blocks are environmentally improved and annual cycle links weakened. (Author/MA)

  20. The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats.

    PubMed

    Chang, Heng-Chih; Yang, Yea-Ru; Wang, Paulus S; Kuo, Chia-Hua; Wang, Ray-Yau

    2013-01-01

    Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I) injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and these effects could

  1. Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats.

    PubMed

    Liu, X; Yu, M; Chen, Y; Zhang, J

    2016-08-01

    Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg-1·day-1 for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines. PMID:27509307

  2. Alterations in stress-associated behaviors and neurochemical markers in adult rats after neonatal short-lasting local inflammatory insult.

    PubMed

    Anseloni, V C Z; He, F; Novikova, S I; Turnbach Robbins, M; Lidow, I A; Ennis, M; Lidow, M S

    2005-01-01

    Recently, there has been a growing interest in long-term consequences of neonatal pain because modern neonatal intensive care units routinely employ procedures that cause considerable pain and may be followed by local inflammation and hyperalgesia lasting for several hours or even days. To address this question, we developed a rat model of short lasting (<2 days) early local inflammatory insult produced by a single injection of 0.25% carrageenan (CAR) into the plantar surface of a hindpaw. Previously, we demonstrated that rats receiving this treatment within the first week after birth grow into adults with a global reduction in responsiveness to acute pain. Here, we report that these animals also manifest a low anxiety trait associated with reduced emotional responsiveness to stress. This conclusion is based in the following observations: (a) rats in our model display reduced anxiety on an elevated plus-maze; (b) in the forced swim test, these rats exhibit behavioral characteristics associated with stronger ability for stress coping; and (c) these animals have reduced basal and stress-induced plasma levels of such stress-related neuroendocrine markers as corticotropin-releasing factor, vasopressin, and adrenocorticotrophic hormone. In addition, we used DNA microarray and real-time reverse-transcriptase polymerase chain reaction to profile long-term changes in gene expression in the midbrain periaqueductal gray (PAG; a region involved in both stress and pain modulation) in our animal model. Among the affected genes, serotonergic receptors were particularly well represented. Specifically, we detected increase in the expression of 5-HT1A, 5-HT1D, 5-HT2A, 5-HT2C and 5-HT4 receptors. Several of these receptors are known to be involved in the anxiolytic and analgesic activity of the PAG. Finally, to determine whether neonatal inflammatory insult induces elevation in maternal care, which may play a role in generating long-term behavioral alterations seen in our model, we

  3. Galunisertib (LY2157299), a transforming growth factor-β receptor I kinase inhibitor, attenuates acute pancreatitis in rats

    PubMed Central

    Liu, X.; Yu, M.; Chen, Y.; Zhang, J.

    2016-01-01

    Galunisertib (LY2157299), a selective ATP-mimetic inhibitor of TGF-β receptor I (TGF-βRI), is the only known TGF-β pathway inhibitor. In the present study, we investigated the effect of galunisertib on taurocholate (TAC)-induced acute pancreatitis (AP) in rats, and the role of TGF-β and NF-κB signaling pathways. AP was induced by infusion of TAC into the pancreatic duct of Sprague-Dawley male rats (n=30). The rats (220±50 g) were administered galunisertib intragastrically [75 mg·kg-1·day-1 for 2 days (0 and 24 h)]. Serum IL-1β, IL-6, TNF-α, amylase (AMY), lipase (LIP), and myeloperoxidase (MPO) levels were measured by ELISA. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); NF-κBp65 and TGF-β1 proteins, as well as TGF-βRI and p-Smad2/3 proteins, were detected by western blot assay. Cell apoptosis was detected by TUNEL assay. H&E staining was used to evaluate the histopathological alterations of the pancreas. Galunisertib treatment attenuated the severity of AP and decreased the pancreatic histological score. In addition, number of apoptotic cells were significantly increased in the galunisertib-treated group (16.38±2.26) than in the AP group (8.14±1.27) and sham-operated group (1.82±0.73; P<0.05 and P<0.01, respectively). Galunisertib decreased the expression levels of TGF-βRI and p-Smad2/3 and inhibited NF-κB activation and p65 translocation compared with the sham-operated group. Furthermore, serum IL-1β, IL-6, TNF-α, AMY and LIP levels and tissue MPO activity were significantly decreased in the galunisertib-treated group. Our data demonstrate that galunisertib attenuates the severity of TAC-induced experimental AP in rats by inducing apoptosis in the pancreas, inhibiting the activation of TGF-β signals and NF-κB as well as the secretion of pro-inflammatory cytokines. PMID:27509307

  4. A two-generation oral gavage reproduction study with potassium perfluorobutanesulfonate (K+PFBS) in Sprague Dawley rats.

    PubMed

    Lieder, Paul H; York, Raymond G; Hakes, Daniel C; Chang, Shu-Ching; Butenhoff, John L

    2009-05-01

    (approximately 2 days) at this dose, a finding consistent with the body weight reduction. Essentially no effects were observed in the F1 females. F2 pups had normal body weights. The reproductive NOAEL was >1000mg/kg/day in both generations.

  5. Daily rhythm of nociception in rats.

    PubMed

    Christina, AJM; Merlin, NJ; Vijaya, C; Jayaprakash, S; Murugesh, N

    2004-03-25

    BACKGROUND: Many behavioral and physiological variables exhibit daily rhythmicity. Few investigations of the daily rhythmicity in nociception have been conducted, and conflicting results have been obtained. The present study evaluated the daily rhythmicity in nociception in Wistar rats. METHODS: Nociception was investigated by Eddy's hot plate method, tail immersion method, and tail clip method. The latency between the noxious stimulus and the animal's response was recorded as reaction time. Separate groups of rats were tested in 4-hour intervals for 24 hours. RESULTS: There was clear daily variation in response latency. Reaction time was shortest a few hours before lights-on and longest at the light-dark transition. CONCLUSION: Nociception exhibits robust daily rhythmicity in rats. Sensitivity to pain is highest late in the dark phase of the light-dark cycle and lowest at the light-dark transition.

  6. Daily rhythm of nociception in rats

    PubMed Central

    Christina, AJM; Merlin, NJ; Vijaya, C; Jayaprakash, S; Murugesh, N

    2004-01-01

    Background Many behavioral and physiological variables exhibit daily rhythmicity. Few investigations of the daily rhythmicity in nociception have been conducted, and conflicting results have been obtained. The present study evaluated the daily rhythmicity in nociception in Wistar rats. Methods Nociception was investigated by Eddy's hot plate method, tail immersion method, and tail clip method. The latency between the noxious stimulus and the animal's response was recorded as reaction time. Separate groups of rats were tested in 4-hour intervals for 24 hours. Results There was clear daily variation in response latency. Reaction time was shortest a few hours before lights-on and longest at the light-dark transition. Conclusion Nociception exhibits robust daily rhythmicity in rats. Sensitivity to pain is highest late in the dark phase of the light-dark cycle and lowest at the light-dark transition. PMID:15043763

  7. Weight control and restraint of laboratory rats

    NASA Technical Reports Server (NTRS)

    Hilado, C. J.; Van Breda Kolff, K.

    1979-01-01

    The use of restrained and confined rats in some procedures used in combustion toxicology introduces the problems of obtaining rats of the appropriate size for the apparatus, and of identifying any artifacts resulting from the use of restraint alone. Feeding studies indicate that controlled feeding of fast-growing strains such as the Sprague-Dawley can hold rat size essentially constant for significant periods of time. The undesirable aspects are the need to cage the animals individually, with resultant psychological as well as metabolic effects. Restraint studies of slow-growing strains such as the Fischer 344 indicate that denying access to food and water for periods of several hours at a time interrupts normal gain only temporarily.

  8. Placentophagia in Weanling Female Laboratory Rats

    PubMed Central

    Harding, Kaitlyn M.; Lonstein, Joseph S.

    2014-01-01

    Placentophagia is common in parturient mammals and offers physiological and behavioral advantages for mothers. In natural environments, weanlings are often present during the birth of younger siblings, but it is unknown if weanling rats are placentophagic or prefer placenta over other substances. To examine this, primiparous rats were remated during the postpartum estrus and weanling females remained in the nest during their mother’s next parturition. Continuous observation revealed that 58% of weanlings were placentophagic. To determine if this placentophagia occurs away from parturient mothers, weanling females still living in their natal nest were offered placenta, liver, or cake frosting in a novel chamber. They ingested more placenta and liver than frosting. Thus, many weanling female laboratory rats are placentophagic during birth of younger siblings but do not selectively prefer placenta when tested outside their natal nest. Consequences of placentophagia by weanlings are unknown, but it may promote their alloparenting or postpartum mothering. PMID:24604548

  9. Body temperature regulation and thermoneutrality in rats.

    PubMed

    Poole, S; Stephenson, J D

    1977-04-01

    Various concepts of thermoneutrality were considered for a proposed study of the role of hypothalamic amines in temperature regulation of rats. The classic definition, the ambient temperature over which metabolic rate is minimum and constant, gave a range of approximately 28 to 32 degrees C. However, within this temperature range rats were inactive, the inactivity apparently representing a behavioural response to heat stress and itself responsible for the reduced metabolic rate; certain thermoregulatory effectors were also activated to increase heat loss. Therefore an alternative range, 18.0 +/- 1.9 (mean +/- S.D.) to 28.1 +/- 1.0 degrees C, was defined in which rats displayed normal activity, behavioural thermoregulations being absent.

  10. Opportunity Leaves a Trail of 'Rat' Holes

    NASA Technical Reports Server (NTRS)

    2004-01-01

    NASA's Mars Exploration Rover Opportunity's rock abrasion tool, known informally as the 'Rat,' has nibbled seven holes into the slope of 'Endurance Crater.' This image from the rover's navigation camera was released previously (PIA06716) without the Rat holes labeled so that viewers could try to find the holes themselves. Here, the holes have been identified. Starting from the uppermost pictured (closest to the crater rim) to the lowest, the Rat hole targets are: 'Tennessee,' 'Cobblehill,' 'Virginia,' 'London,' 'Grindstone,' 'Kettlestone,' and 'Drammensfjorden.' These holes were drilled on sols 138 (June 13, 2004), 143 (June 18), 145 (June 20), 148 (June 23), 151 (June 26), 153 (June 28) and 161 (July 7), respectively. Each hole is 4.5 centimeters (1.8 inches) in diameter.

  11. Body temperature regulation and thermoneutrality in rats.

    PubMed

    Poole, S; Stephenson, J D

    1977-04-01

    Various concepts of thermoneutrality were considered for a proposed study of the role of hypothalamic amines in temperature regulation of rats. The classic definition, the ambient temperature over which metabolic rate is minimum and constant, gave a range of approximately 28 to 32 degrees C. However, within this temperature range rats were inactive, the inactivity apparently representing a behavioural response to heat stress and itself responsible for the reduced metabolic rate; certain thermoregulatory effectors were also activated to increase heat loss. Therefore an alternative range, 18.0 +/- 1.9 (mean +/- S.D.) to 28.1 +/- 1.0 degrees C, was defined in which rats displayed normal activity, behavioural thermoregulations being absent. PMID:585477

  12. Renin responses to hemorrhage in conscious rats

    SciTech Connect

    Roarty, T.P.; Chadwick. K.J.; Raff, H.

    1986-03-01

    The authors investigated the role of beta adrenergic inhibition on the renin response to graded hemorrhage (hem) in conscious rats. Chronic femoral arterial (for measurement of mean arterial pressure - MAP) and venous (for drug infusion) catheters were implanted at least 5 days before experimentation. Hem was administered in < 2 min. 10 rats (CTL) were exposed to a total of 21 episodes of hemorrhage. 13 rats (B-block) were given 1 mg/kg propranolol hydrochloride iv 20 min prior to hem (24 episodes total). Plasma renin activity (PRA) was measured by radioimmunoassay. Pre-hem PRA levels were measured in the first 1 ml of hem blood. Hem resulted in hem volume-dependent decreases in blood pressure and increase-response to hemorrhage.

  13. Renin responses to hemorrhage to conscious rats

    SciTech Connect

    Roarty, T.P.; Chadwick, K.J.; Raff, H.

    1986-03-01

    The authors investigated the role of beta adrenergic inhibition on the renin response to graded hemorrhage (hem) in conscious rats. Chronic femoral arterial (for measurement of mean arterial pressure - MAP) and venous (for drug infusion) catheters were implanted at least 5 days before experimentation. Hem was administered in < 2 min. 10 rats (CTL) were exposed to a total of 21 episodes of hemorrhage. 13 rats (B-block) were given 1 mg/kg propranolol hydrochloride iv 20 min prior to hem (24 episodes total). Plasma renin activity (PRA) was measured by radioimmunoassay. Pre-hem PRA levels were measured in the first 1 ml of hem blood. Hem resulted in hem volume-dependent decreases in blood pressure and increases in PRA. B-block did not significantly alter the mean renin response to hemorrhage.

  14. Activation of Akt/FoxO and inactivation of MEK/ERK pathways contribute to induction of neuroprotection against transient global cerebral ischemia by delayed hypoxic postconditioning in adult rats.

    PubMed

    Zhan, Lixuan; Li, Danfang; Liang, Donghai; Wu, Baoxing; Zhu, Pingping; Wang, Yanmei; Sun, Weiwen; Xu, En

    2012-10-01

    Ischemic postconditioning, a series of mechanical interruptions of blood flow immediately after reperfusion, has been described in brain studies. However, hypoxic postconditioning (HPC) has never been reported in transient global cerebral ischemia (tGCI) adult rat model. The purpose of this study is to explore the effects of neuroprotection by delayed HPC against tGCI in adult rats and investigate underlying mechanisms involving the Akt/Forkhead transcription factor, class O (FoxO) and mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathways. Postconditioning with 60-120 min hypoxia significantly reduced cell death in hippocampal CA1 subregion after 10 min of tGCI. Postconditioning was effective only when applied 1-2 days after tGCI. Nevertheless, the combination of hypoxic preconditioning and postconditioning provided no additive protection. Additionally, postconditioning increased phosphorylation of Akt and FoxOs after tGCI. Inhibiting phosphorylation of Akt and FoxOs with LY294002 suppressed the postconditioning-induced neuroprotection. In addition, postconditioning blocked the increase of MEK and ERK phosphorylation after tGCI. Inhibiting phosphorylation of MEK and ERK with U0126 attenuated neuronal damage after tGCI. These results suggest that delayed HPC exerts neuroprotection against tGCI-induced injury in adult rats. The activation of Akt/FoxO and inactivation of MEK/ERK pathways by postconditioning contributed to the induction of neuroprotection against tGCI.

  15. Interpretation of male rat renal tubule tumors

    SciTech Connect

    Rodgers, I.S.; Baetcke, K.P.

    1993-12-01

    Based on an analysis of recent scientific studies, a Technical Panel of the U.S. Environmental Protection Agency`s (EPA) Risk Assessment Forum recently advised EPA risk assessors against using information on certain male rat renal tubule tumors to assess human risk under conditions specified in a new Forum report. Risk assessment approaches generally assume that chemicals producing tumors in laboratory animals are a potential cancer hazard to humans. For most chemicals, including classical rodent kidney carcinogens such as N-ethyl-N-hydroxyethylnitrosamine, this extrapolation remains appropriate. Some chemicals, however, induce accumulation of {alpha}{sub 2u}-globulin ({alpha}{sub 2u}-g), a low molecular weight protein, in the male rat kidney. The {alpha}{sub 2u}-g accumulation initiates a sequence of events that appears to lead to renal tubule tumor formation. Female rats and other laboratory mammals administered the same chemicals do not accumulate low molecular weight protein in the kidney, and they do not develop renal tubule tumors. Because humans appear to be more like other laboratory animals than like the male rat, in this special situation, the male rat is not a good model for assessing human risk. The Forum report stresses the need for full scrutiny of a substantial set of data to determine when it is reasonable to presume that renal tumors in male rats are linked to a process involving {alpha}{sub 2u}-g accumulation and to select appropriate procedures for estimating human risks under such circumstances. 92 refs.

  16. Rats exhibit reference-dependent choice behavior.

    PubMed

    Bhatti, Mehwish; Jang, Hyeran; Kralik, Jerald D; Jeong, Jaeseung

    2014-07-01

    Human preferences depend on whether a chosen outcome appears to be a loss or a gain compared with what had been expected, i.e., in comparison to a reference point. Because reference dependence has such a strong influence on human decision-making, it is important to uncover its origins, which will in turn help delineate the underlying mechanisms. It remains unknown whether rats use reference points in decision-making, and yet, the study of rats could help address the question of whether reference dependence is evolutionarily conserved among mammals and could provide a nonhuman animal model to investigate the neural mechanisms underlying this important cognitive process. The aim of the current study was to determine whether rats show reference-dependent choice behavior. We developed a novel paradigm by modifying the "T" maze by installing "pockets" to the left and right of the "T" stem that held reward pellets so rats would potentially develop reference values for each option prior to choice. We found that the rats were indeed sensitive to the way alternatives were presented. That is, they exhibited reference-dependent choice behavior by avoiding the choice option framed as a loss (e.g., having four reward pellets in the pocket, but receiving only one), at least under conditions with certain outcomes and clear differences between the reference and outcome quantities. Despite the small number of rats in this study, this species-level capacity suggests that reference dependence in general and loss aversion in particular may be conserved traits that evolved at or before the emergence of mammals.

  17. Comparative analysis of global gene expression profiles between diabetic rat wounds treated with vacuum-assisted closure therapy, moist wound healing or gauze under suction.

    PubMed

    Derrick, Kathleen L; Norbury, Kenneth; Kieswetter, Kris; Skaf, Jihad; McNulty, Amy K

    2008-12-01

    How differential gene expression affects wound healing is not well understood. In this study, Zucker diabetic fatty (fa/fa) male inbred rats were used to investigate gene expression during wound healing in an impaired wound-healing model. Whole genome microarray surveys were used to gain insight into the biological pathways and healing processes in acute excisional wounds treated with vacuum-assisted closure (V.A.C.). Therapy, moist wound healing (MWH) or gauze under suction (GUS). Global gene expression analyses after 2 days of healing indicated major differences with respect to both number of genes showing fold changes and pathway regulation between the three different wound treatments. Statistical analysis of expression profiles indicated that 5072 genes showed a >1.6-fold change with V.A.C. Therapy compared with 3601 genes with MWH and 3952 genes with GUS. Pathways and related genes associated with the early phases of wound healing diverged between treatment groups. For example, pathways involving angiogenesis, cytoskeletal regulation and inflammation were associated with elevated gene expression following V.A.C. Therapy. This study is the first to assess wound healing by whole genome interrogation in a diabetic rat model treated with different healing modalities.

  18. Reduced expression of the liver/beta-cell glucose transporter isoform in glucose-insensitive pancreatic beta cells of diabetic rats.

    PubMed Central

    Thorens, B; Weir, G C; Leahy, J L; Lodish, H F; Bonner-Weir, S

    1990-01-01

    Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor. Images PMID:2204056

  19. Reduced Expression of the Liver/Beta-Cell Glucose Transporter Isoform in Glucose-Insensitive Pancreatic Beta Cells of Diabetic Rats

    NASA Astrophysics Data System (ADS)

    Thorens, Bernard; Weir, Gordon C.; Leahy, John L.; Lodish, Harvey F.; Bonner-Weir, Susan

    1990-09-01

    Rats injected with a single dose of streptozocin at 2 days of age develop non-insulin-dependent diabetes 6 weeks later. The pancreatic beta islet cells of these diabetic rats display a loss of glucose-induced insulin secretion while maintaining sensitivity to other secretagogues such as arginine. We analyzed the level of expression of the liver/beta-cell glucose transporter isoform in diabetic islets by immunofluorescence staining of pancreas sections and by Western blotting of islet lysates. Islets from diabetic animals have a reduced expression of this beta-cell-specific glucose transporter isoform and the extent of reduction is correlated with the severity of hyperglycemia. In contrast, expression of this transporter isoform in liver is minimally modified by the diabetes. Thus a decreased expression of the liver/beta-cell glucose transporter isoform in beta cells is associated with the impaired glucose sensing characteristic of diabetic islets; our data suggest that this glucose transporter may be part of the beta-cell glucose sensor.

  20. Central beta-adrenergic receptors play an important role in the enhancing effect of voluntary exercise on learning and memory in rat.

    PubMed

    Ebrahimi, Shima; Rashidy-Pour, Ali; Vafaei, Abbas A; Akhavan, Maziar M

    2010-03-17

    The beneficial effects of physical activity and exercise on brain functions such as improvement in learning and memory are well documented. The aim of this study was to examine the role of the beta-adrenergic system in voluntary exercise-induced enhancement of learning and memory in rat. In order to block the beta-adrenergic receptors, the animals were received propranolol (a beta-blocker), or nadolol (a peripherally acting beta-blocker) before each night of five consecutive nights of exercise. Then their learning and memory were tested on the water maze task using a two-trials-per-day for 5 consecutive days. A probe trial was performed 2 days after the last training day. Our results showed that propranolol, but not nadolol reversed the exercise-induced improvement in learning and memory in rat. Our findings indicate that central beta-adrenergic receptors play an important role in mediating the beneficial effects of voluntary exercise on learning and memory.

  1. Detection of procathepsin D in rat milk.

    PubMed

    Benes, P; Koelsch, G; Dvorak, B; Fusek, M; Vetvicka, V

    2002-09-01

    The presence of procathepsin D, a zymogen of the soluble lysosomal aspartic proteinase cathepsin D, was detected in rat milk using Western blot analysis and assay of proteolytic activity in acidic buffers. No other forms of cathepsin D were found. Two different polyclonal anti-procathepsin D antibodies were used for immunochemical detection of procathepsin D. Both antibodies we found to recognize rat procathepsin D. Proteolytic activity in acidic buffers was detected using a fluorogenic substrate specific for cathepsin D and was abolished by pepstatin A, a specific inhibitor of aspartic proteinases. This study represents third demonstration of presence of procathepsin D in mammal breast milk. Potential sources and physiological functions are discussed.

  2. [Electromagnetic Shielding Alters Behaviour of Rats].

    PubMed

    Temuryants, N A; Kostyuk, A S; Tumanyants, K N

    2015-01-01

    It has been found that long-term electromagnetic shielding (19 hours per day for 10 days) leads to an increase in the duration of passive swimming time in male rats, decrease the duration of active swimming in the "forced swim" test as well as decrease of libido. On the other hand animals kept under the "open field" conditions do not show significant deviations from their normal behavior. Therefore, one could conclude that moderate electromagnetic shielding causes a depression-like state in rats. PMID:26080600

  3. Fenbendazole treatment and litter size in rats.

    PubMed

    Johnston, Nancy A; Bieszczak, Jeremiah R; Verhulst, Steven; Disney, Kimberly E; Montgomery, Kyle E; Toth, Linda A

    2006-11-01

    Fenbendazole is commonly used in laboratory animal medicine as an anthelmintic for elimination of pinworms. It is generally regarded as a safe drug with minimal side effects. In our facility, 2 breeding colonies of rats were treated with fenbendazole to eliminate pinworms. Analysis of the breeding records revealed that feeding Sprague-Dawley rats a diet containing fenbendazole on a continuous basis for 7 consecutive weeks was associated with a significant reduction in litter size. Although the mechanism underlying this effect is unknown, the finding prompts caution when using fenbendazole to treat valuable breeding colonies or strains that are poor breeders.

  4. Aspartame and the rat brain monoaminergic system.

    PubMed

    Perego, C; De Simoni, M G; Fodritto, F; Raimondi, L; Diomede, L; Salmona, M; Algeri, S; Garattini, S

    1988-12-01

    A high dose of aspartame (APM) was administered to rats to study possible effects on brain monoaminergic systems. APM and its metabolite phenylalanine (Phe) were given orally at doses of 1000 and 500 mg/kg, respectively. Significant increases were seen in brain Phe and tyrosine (Tyr) levels. Two different approaches were used to study monoaminergic systems: whole tissue measurements by HPLC-ED and in vivo voltammetry in freely moving rats. Dopamine, serotonin and their metabolites were taken as indexes of neuronal activity. In spite of the high dose used, no modification was found in monoamines or their metabolites in striatum, hippocampus and nucleus accumbens.

  5. The oncogenic action of ionizing radiation on rat skin

    SciTech Connect

    Burns, F.J.

    1991-01-01

    Progress has occurred in several areas corresponding to the specific aims of the proposal: (1) Progression and multiple events in radiation carcinogenesis of rat skin as a function of LET; (2) cell cycle kinetics of irradiated rat epidermis as determined by double labeling and double emulsion autoradiography; (3) oncogene activation detected by in situ hybridization in radiation-induced rat skin tumors; (4) amplification of the c-myc oncogene in radiation-induced rat skin tumors as a function of LET; and (5) transformation of rat skin keratinocytes by ionizing radiation in combination with c-Ki-ras and c-myc oncogenes. 111 refs., 13 figs., 12 tabs.

  6. Metabolism of pyridalyl in rats.

    PubMed

    Nagahori, Hirohisa; Saito, Koichi; Tomigahara, Yoshitaka; Isobe, Naohiko; Kaneko, Hideo

    2009-12-01

    Metabolism of pyridalyl [2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether] was examined in male and female Sprague-Dawley rats. After a single oral administration of [dichlorophenyl-(14)C]pyridalyl at 5 or 500 mg/kg, the (14)C concentration in blood reached maxima at 2 to 10 h and then decreased rapidly with a biological half-life of approximately 11 to 12 h. (14)C concentrations in liver, fat, adrenal gland, and spleen were relatively high at a low dose, reaching 2.3 to 2.7, 1.9 to 2.3, 1.1 to 1.9, and 1.4 ppm, respectively, in these tissues at 2 to 24 h after administration. Although (14)C elimination from fat and hair and skin was relatively slow compared with that from other tissues, the total residue on the 7th day was low, in the range of 1.3 to 2.3% of the dose. The (14)C distribution in tissues with a high dose, as examined by whole-body autoradiography, was similar to that observed for the low dose. Results revealed that more than 88% of the dosed radiocarbon was excreted within 1 day after administration, with cumulative (14)C excretion into urine and feces 7 days after administration of 1.7 to 2.6 and 98.7 to 101.7%, respectively. One urinary and fecal major metabolite (resulting from O-dealkylation) and two minor metabolites were identified by NMR and mass spectrometry. Residual (14)C in fat was extracted, and analysis by thin-layer chromatography showed it to be due to pyridalyl itself. No marked sex-related differences were observed in (14)C elimination, (14)C distribution, and metabolites. PMID:19773539

  7. Differential hippocampal protein expression between normal aged rats and aged rats with postoperative cognitive dysfunction: A proteomic analysis.

    PubMed

    Li, Yang; Wang, Saiying; Ran, Ke; Hu, Zhonghua; Liu, Zhaoqian; Duan, Kaiming

    2015-08-01

    The aim of the present study was to investigate the differences in the expression of hippocampal proteins between normal control aged rats and aged rats with postoperative cognitive dysfunction (POCD). A total of 24 aged rats were randomly divided into a surgery group (n=12) and a control group (n=12). The rats in the surgery group were treated with 2 h isoflurane anesthesia and splenectomy, while the rats in the control group received 40% oxygen for 2 h without surgery. The cognitive functions of the two groups were examined using a Y-maze test. The protein expression profiles of the hippocampus of six aged rats (three rats with POCD and three from the normal control group) were assessed using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. A total of three differential proteins were further confirmed between the POCD rats and normal rats using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The expression levels of 21 proteins in the rats with POCD were significantly different compared with the normal control rats. These proteins were functionally clustered to synaptic plasticity (three proteins), oxidative stress (four proteins), energy production (six proteins), neuroinflammation (three proteins) and glutamate metabolism (two proteins). In addition, three proteins (fatty acid binding protein 7, brain, glutamate dehydrogenase 1 and glutamine synthetase), associated with astrocytic function, were significantly different in the rats with POCD compared with those in the normal control (P<0.05). Similar changes in the mRNA expression levels of the three proteins in the hippocampi of POCD rats were also detected using RT-qPCR. Neuroinflammation, glutamate toxicity and oxidative stress were possibly involved in the pathological mechanism underlying POCD in aged rats. In addition, astrocytes may also be important in POCD in aged rats. PMID:25936412

  8. Rescue from dwarfism by thyroid function compensation in rdw rats.

    PubMed

    Furudate, Sen-ichi; Ono, Masao; Shibayama, Keiko; Ohyama, Yoshihide; Kuwada, Masahiro; Kimura, Toshimi; Kameya, Toru

    2005-10-01

    The rdw rat was initially reported as having hereditary dwarfism caused by pituitary dysfunction. Subsequent studies on the rdw rat, however, have demonstrated that the primary cause of rdw dwarfism is present in the thyroid gland but not in the pituitary gland. The primary cause of rdw rat disorders is a missense mutation of the thyroglobulin (Tg) gene by a one-point mutation. In the present study, we attempted to rescue the dwarfism of the rdw rats using a diet supplemented with thyroid powder (T-powder) and a thyroid graft (T-graft). The infants of the rdw rat were successfully raised to a mature stage body weight, accompanied by elevation of serum growth hormone (GH) and prolactin (PRL), by the T-powder. Furthermore, the T-graft successfully increased the body weight with fertility. The serum GH and PRL levels in the T-graft rdw rat significantly increased. The serum thyroid-stimulating hormone (TSH) levels in the T-graft rdw rat were significantly decreased but were significantly higher than those in the control rat. The GH and PRL mRNA expression in the rdw rat with the T-graft was virtually the same as that of the control, but the TSH beta mRNA differed from that of the control rats. Thus, the dwarfism in the rdw rat is rescued by thyroid function compensation, such as that afforded by T-powder and T-graft.

  9. [Foci of the rat mite Ornithonyssus bacoti (Mesostigmata, Macronyssidae) and rat-mite dermatitis in Moscow].

    PubMed

    Lopatina, Iu V; Sokolova, T V; Niiazova, M V

    1992-01-01

    High density of the rat population in Moscow in 1990-1991 resulted in the appearance of Ornithonyssus bacoti foci and of cases of the rat-mite dermatitis in humans. A total of 36 foci of the disease were examined and eradicated. A method for the detection of such foci has been developed. Two types of foci are distinguished, communal and industrial, and their specific features as regards the rodent and mite populations and clinical features of dermatitis in humans are described. A system of measures for liquidation of foci of rat mites is suggested, including rat and mite eradication and treatment of the patients. Specific features of these measures for various types of foci and in case of a focus reappearance are enumerated. PMID:1299760

  10. Hepatitis E Virus Genotype 3 in Wild Rats, United States

    PubMed Central

    Volk, Kylie; Van Den Bussche, Ronald A.

    2012-01-01

    The role of rodents in the epidemiology of zoonotic hepatitis E virus (HEV) infection has been a subject of considerable debate. Seroprevalence studies suggest widespread HEV infection in commensal Rattus spp. rats, but experimental transmission has been largely unsuccessful and recovery of zoonotic genotype 3 HEV RNA from wild Rattus spp. rats has never been confirmed. We surveyed R. rattus and R. norvegicus rats from across the United States and several international populations by using a hemi-nested reverse transcription PCR approach. We isolated HEV RNA in liver tissues from 35 of 446 rats examined. All but 1 of these isolates was relegated to the zoonotic HEV genotype 3, and the remaining sequence represented the recently discovered rat genotype from the United States and Germany. HEV-positive rats were detected in urban and remote localities. Genetic analyses suggest all HEV genotype 3 isolates obtained from wild Rattus spp. rats were closely related. PMID:22840202

  11. Core temperature of tailless rats exposed to centrifugation

    NASA Technical Reports Server (NTRS)

    Monson, C. B.; Oyama, J.

    1984-01-01

    The role of the tail in the altered thermoregulation of rats during acute exposure to hypergravity was investigated, using groups of rats of two ages: 55 days (young) and 138 days (old). Rectal and foot temperature changes were measured in intact and tailless rats subjected to 1 h centrifugation of 2.8 G, with preceding (1 h) and following (1-3 h) 1 G periods. At 22 C, the loss of body heat from the tail per se does not measurably contribute to the hypothermia induced by hypergravity. However, the heat loss from the feet was greater in the tailless rats than in the intact rats from the young group of animals, although there was no significant difference between the tailless and intact rats in the old animal group. It is concluded that the inhibition of heat production is a significant factor in the hypothermia of centrifuged tailless rats, as it has been previously shown to be in the intact animals.

  12. Aging effects on oxidative phosphorylation in rat adrenocortical mitochondria.

    PubMed

    Solinas, Paola; Fujioka, Hisashi; Radivoyevitch, Tomas; Tandler, Bernard; Hoppel, Charles L

    2014-06-01

    Does aging in itself lead to alteration in adrenocortical mitochondrial oxidative phosphorylation? Mitochondria from Fischer 344 (F344) rats (6 and 24 months old), Brown Norway rats (6 and 32 months old) and F344-Brown Norway hybrid rats (6 and 30 months old) were compared. Mitochondria were isolated from extirpated adrenal cortex. The yields of mitochondria were quantitatively similar in all rat strains irrespective of age. In order to assess the activity of each mitochondrial complex, several different substrates were tested and the rate of oxidative phosphorylation measured. Aging does not affect mitochondrial activity except in the F344 rat adrenal cortex where the maximal ADP-stimulated oxidative phosphorylation decreased with age. We hypothesize that impaired synthesis of steroid hormones by the adrenal cortex with age in F344 rats might be due to decreased adrenocortical mitochondrial oxidative phosphorylation. We conclude that aging results in adrenocortical mitochondria effects that are non-uniform across different rat strains.

  13. Hepatitis E virus genotype 3 in wild rats, United States.

    PubMed

    Lack, Justin B; Volk, Kylie; Van Den Bussche, Ronald A

    2012-08-01

    The role of rodents in the epidemiology of zoonotic hepatitis E virus (HEV) infection has been a subject of considerable debate. Seroprevalence studies suggest widespread HEV infection in commensal Rattus spp. rats, but experimental transmission has been largely unsuccessful and recovery of zoonotic genotype 3 HEV RNA from wild Rattus spp. rats has never been confirmed. We surveyed R. rattus and R. norvegicus rats from across the United States and several international populations by using a hemi-nested reverse transcription PCR approach. We isolated HEV RNA in liver tissues from 35 of 446 rats examined. All but 1 of these isolates was relegated to the zoonotic HEV genotype 3, and the remaining sequence represented the recently discovered rat genotype from the United States and Germany. HEV-positive rats were detected in urban and remote localities. Genetic analyses suggest all HEV genotype 3 isolates obtained from wild Rattus spp. rats were closely related. PMID:22840202

  14. Witnessing traumatic events causes severe behavioral impairments in rats.

    PubMed

    Patki, Gaurav; Solanki, Naimesh; Salim, Samina

    2014-12-01

    Witnessing a traumatic event but not directly experiencing it can be psychologically quite damaging. In North America alone, ∼30% of individuals who witness a traumatic event develop post-traumatic stress disorder (PTSD). While effects of direct trauma are evident, consequences of indirect or secondary trauma are often ignored. Also unclear is the role of social support in the consequences of these experiences. The social defeat paradigm, which involves aggressive encounters by a large Long-Evans male rat (resident) towards a smaller Sprague-Dawley male rat (intruder), is considered a rodent model of PTSD. We have modified this model to create a trauma witness model (TWM) and have used our TWM model to also evaluate social support effects. Basically, when an intruder rat is placed into the home cage of a resident rat, it encounters an agonistic behavior resulting in intruder subordination. The socially defeated intruder is designated the SD rat. A second rat, the cage mate of the SD, is positioned to witness the event and is the trauma witnessing (TW) rat. Experiments were performed in two different experimental conditions. In one, the SD and TW rats were cagemates and acclimatized together. Then, one SD rat was subjected to three sessions of social defeat for 7 d. TW rat witnessed these events. After each social defeat exposure, the TW and SD rats were housed together. In the second, the TW and SD rats were housed separately starting after the first defeat. At the end of each protocol, depression-anxiety-like behavior and memory tests were conducted on the SD and TW rats, blood withdrawn and specific organs collected. Witnessing traumatic events led to depression- and anxiety-like behavior and produced memory deficits in TW rats associated with elevated corticosterone levels.

  15. Persistent Rat Virus Infection in Smooth Muscle of Euthymic and Athymic Rats

    PubMed Central

    Jacoby, Robert O.; Johnson, Elizabeth A.; Paturzo, Frank X.; Ball-Goodrich, Lisa

    2000-01-01

    Rat virus (RV) infection can cause disease or disrupt responses that rely on cell proliferation. Therefore, persistent infection has the potential to amplify RV interference with research. As a step toward determining underlying mechanisms of persistence, we compared acute and persistent RV infections in infant euthymic and athymic rats inoculated oronasally with the University of Massachusetts strain of RV. Rats were assessed by virus isolation, in situ hybridization, and serology. Selected tissues also were analyzed by Southern blotting or immunohistochemistry. Virus was widely disseminated during acute infection in rats of both phenotypes, whereas vascular smooth muscle cells (SMC) were the primary targets during persistent infection. The prevalence of virus-positive cells remained moderate to high in athymic rats through 8 weeks but decreased in euthymic rats by 2 weeks, coincident with seroconversion and perivascular infiltration of mononuclear cells. Virus-positive pneumocytes and renal tubular epithelial cells also were detected through 8 weeks, implying that kidney and lung excrete virus during persistent infection. Viral mRNA was detected in SMC of both phenotypes through 8 weeks, indicating that persistent infection includes virus replication. However, only half of the SMC containing viral mRNA at 4 weeks stained for proliferating cell nuclear antigen, a protein expressed in cycling cells. The results demonstrate that vasculotropism is a significant feature of persistent infection, that virus replication continues during persistent infection, and that host immunity reduces, but does not eliminate, infection. PMID:11090184

  16. Apoptosis-inducing factor and calpain upregulation in glutamate-induced injury of rat spiral ganglion neurons.

    PubMed

    Ding, Zhong-Jia; Chen, Xin; Tang, Xiao-Xu; Wang, Xi; Song, Yong-Li; Chen, Xiao-Dong; Wang, Jian; Wang, Ren-Feng; Mi, Wen-Juan; Chen, Fu-Quan; Qiu, Jian-Hua

    2015-08-01

    Spiral ganglion neuron (SGN) damage and apoptosis can lead to noise-induced hearing loss, age-associated hearing loss and, in certain cases, auditory neuropathy. The apoptosis-inducing factor (AIF)-associated pathway may be important in this process. The present study aimed to investigate the expression levels of AIF and calpain in damaged SGNs. Glutamate (Glu) perfusion and cell culture in different concentrations of Glu were performed to damage the SGNs of Sprague-Dawley (SD) rats, with saline water used as a control Different concentrations (5, 10, 20 and 40 mM) of Glu were injected into the cochlear tympanic canal of 18 SD rats, and 10, 20 and 40 mM Glu were added to SGN cultures. Auditory brainstem responses (ABR) were measured prior to and 2 days following the injection of Glu. Immunofluorescent staining was used to detect the SGN damage and the expression levels of AIF and calpain in vivo and in in vitro. Transmission electron microscopy (TEM) was used to measure cell apoptosis and reverse transcription-quantitative polymerase chain reaction was used to analyse the gene expression levels of AIF and calpain in the damaged SGNs. The TEM identified mitochondrial vacuolisation, swelling of the SGN and heterochromatin formation. Injection of Glu reduced the number of SGNs and induced apoptosis. AIF was observed to translocate into the nuclei of the SGNs in the 20 and 40 mM Glu groups, and the expression levels of AIF and calpain were markedly upregulated in the modiolus of the Glu-damaged SGNs. The upregulation of AIF and calpain may be important in the process of SGN damage and apoptosis. PMID:25891494

  17. 24-h Langendorff-perfused neonatal rat heart used to study the impact of adenoviral gene transfer.

    PubMed

    Wiechert, S; El-Armouche, A; Rau, T; Zimmermann, W-H; Eschenhagen, T

    2003-08-01

    The human genome project has increased the demand for simple experimental systems that allow the impact of gene manipulations to be studied under controlled ex vivo conditions. We hypothesized that, in contrast to adult hearts, neonatal hearts allow long-term perfusion and efficient gene transfer ex vivo. A Langendorff perfusion system was modified to allow perfusion for >24 h with particular emphasis on uncompromised contractile activity, sterility, online measurement of force of contraction, inotropic response to beta-adrenergic stimulation, and efficient gene transfer. The hearts were perfused with serum-free medium (DMEM + medium 199, 4 + 1) supplemented with hydrocortisone, triiodothyronine, ascorbic acid, insulin, pyruvate, l-carnitine, creatine, taurine, l-glutamine, mannitol, and antibiotics recirculating (500 ml/2 hearts) at 1 ml/min. Hearts from 2 day-old rats beat constantly at 135-155 beats/min and developed active force of 1-2 mN. During 24 h of perfusion, twitch tension increased to approximately 165% of initial values (P < 0.05), whereas the inotropic response to isoprenaline remained constant. A decrease in total protein content of 10% and histological examination indicated moderate edema, but actin and calsequestrin concentration remained unchanged and perfusion pressure remained constant at 7-11 mmHg. Perfusion with a LacZ-encoding adenovirus at 3 x 108 active virus particles yielded homogeneous transfection of approximately 80% throughout the heart and did not affect heart rate, force of contraction, or response to isoprenaline compared with uninfected controls (n = 7 each). Taken together, the 24-h Langendorff-perfused neonatal rat heart is a relatively simple, inexpensive, and robust new heart model that appears feasible as a test bed for functional genomics.

  18. Effects of Org 7797 on early, late and inducible arrhythmias following coronary artery occlusion in rats and dogs.

    PubMed Central

    Winslow, E.; Campbell, J. K.; Barron, E.; Marshall, R. J.; Muir, A. W.

    1991-01-01

    1. The class Ic steroidal antiarrhythmic agent, Org 7797, was compared with two other Ic agents, flecainide and propafenone for intravenous activity against ischaemia-related cardiac arrhythmias and for electrophysiological actions in vivo. In addition the haemodynamic effects of Org 7797 were assessed in greyhounds. 2. Org 7797 (0.5 mg kg-1) significantly reduced the expected incidence of early ischaemia-induced ventricular fibrillation (VF) in rats and greyhound dogs and at doses of 0.5-1.0 mg kg-1 antagonized reperfusion-induced arrhythmias. Comparative studies in rats showed Org 7797 to be 2-4 times more potent than flecainide or propafenone. 3. Org 7797 (0.5 mg kg-1) slowed intracardiac conduction in anaesthetized beagles and again was at least 2-4 times more potent than flecainide or propafenone. 4. Org 7797 (0.5 and 2.0 mg kg-1), flecainide (1.0 and 2.0 mg kg-1) or propafenone (0.5 and 2.0 mg kg-1), did not significantly prevent induction of tachyarrhythmias (VT) in dogs with 5-6 day old myocardial infarcts although all 3 drugs appeared to prevent induced VF. All 3 drugs (notably flecainide) did however reduce the VT rate. 5. All 3 drugs (1-2 mg kg-1) suppressed spontaneous tachyarrhythmias in conscious beagle dogs with 1-2 day old infarcts. Propafenone was the least effective. 6. In an antifibrillatory dose (0.5 mg kg-1), the major haemodynamic effect of Org 7797 was a 10% increase in peripheral vascular resistance. Stroke volume, cardiac output and coronary blood flow were unchanged. In therapeutic doses, Org 7797 was also less negatively chronotropic than flecainide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1810599

  19. Lysine and Arginine Reduce the Effects of Cerebral Ischemic Insults and Inhibit Glutamate-Induced Neuronal Activity in Rats

    PubMed Central

    Kondoh, Takashi; Kameishi, Makiko; Mallick, Hruda Nanda; Ono, Taketoshi; Torii, Kunio

    2010-01-01

    Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg), arginine (0.6 g/kg), or their combined administration (0.6 g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects. PMID:20589237

  20. Relation between microPET imaging and rotational behavior in a parkinsonian rat model induced by medial forebrain bundle axotomy.

    PubMed

    Liu, Limin; Zhang, Wenzhong; Gong, Xiaoli; Liang, Xibin; Wang, Xiaomin

    2014-05-15

    The purpose of the current study was to examine the relation between apomorphine (APO) induced rotational behavior and the pre- and post-synaptic dopaminergic function in a parkinsonian rat model induced by medial forebrain bundle (MFB) axotomy. The brains of these rats were unilaterally lesioned by mechanical transection of the nigrostriatal dopamine pathway at the MFB. Behavioral studies were carried out by APO challenge prior to and 1, 3, and 5 weeks after MFB axotomy. MicroPET scans with [(11)C]CFT and [(11)C]raclopride were performed 2 days after the behavioral test. The two PET scans were separated by an interval of 24-48 h. Immunohistochemistry was conducted 4 days after the last PET scan. Our data showed that [(11)C]CFT binding decreased progressively 1, 3, and 5 weeks postlesion, and there was a significant nonlinear correlation between [(11)C]CFT uptake ratio (right/left) and APO induced rotations. In contrast, [(11)C]raclopride binding only increased significantly 3 weeks postlesion, and there was a positive linear correlation between [(11)C]raclopride uptake ratio (right/left) and APO induced rotations. Postmortem immunohistochemical studies confirmed the loss of both striatal dopamine fibers and nigral neurons on the lesioned side. These findings not only demonstrate the relation between APO induced rotational behavior and the pre- and post-synaptic dopamine function but also indicate the utility and validity of in vivo PET imaging in understanding disease mechanisms and progression, which should in turn lead to development of new therapies. PMID:24548854

  1. Characterization of acute biliary hyperplasia in Fisher 344 Rats administered the Indole-3-Carbinol Analog, NSC-743380

    SciTech Connect

    Eldridge, Sandy R.; Covey, Joseph; Morris, Joel; Fang, Bingliang; Horn, Thomas L.; Elsass, Karen E.; Hamre, John R.; McCormick, David L.; Davis, Myrtle A.

    2014-12-15

    NSC-743380 (1-[(3-chlorophenyl)-methyl]-1H-indole-3-carbinol) is in early stages of development as an anticancer agent. Two metabolites reflect sequential conversion of the carbinol functionality to a carboxaldehyde and the major metabolite, 1-[(3-chlorophenyl)-methyl]-1H-indole-3-carboxylic acid. In an exploratory toxicity study in rats, NSC-743380 induced elevations in liver-associated serum enzymes and biliary hyperplasia. Biliary hyperplasia was observed 2 days after dosing orally for 2 consecutive days at 100 mg/kg/day. Notably, hepatotoxicity and biliary hyperplasia were observed after oral administration of the parent compound, but not when major metabolites were administered. The toxicities of a structurally similar but pharmacologically inactive molecule and a structurally diverse molecule with a similar efficacy profile in killing cancer cells in vitro were compared to NSC-743380 to explore scaffold versus target-mediated toxicity. Following two oral doses of 100 mg/kg/day given once daily on two consecutive days, the structurally unrelated active compound produced hepatic toxicity similar to NSC-743380. The structurally similar inactive compound did not, but, lower exposures were achieved. The weight of evidence implies that the hepatotoxicity associated with NSC-743380 is related to the anticancer activity of the parent molecule. Furthermore, because biliary hyperplasia represents an unmanageable and non-monitorable adverse effect in clinical settings, this model may provide an opportunity for investigators to use a short-duration study design to explore biomarkers of biliary hyperplasia. - Highlights: • NSC-743380 induced biliary hyperplasia in rats. • Toxicity of NSC-743380 appears to be related to its anticancer activity. • The model provides an opportunity to explore biomarkers of biliary hyperplasia.

  2. Regression of retinal capillaries following N-methyl-D-aspartate-induced neurotoxicity in the neonatal rat retina.

    PubMed

    Asano, Daiki; Nakahara, Tsutomu; Mori, Asami; Sakamoto, Kenji; Ishii, Kunio

    2015-02-01

    Degeneration of retinal capillaries occurs following N-methyl-D-aspartate (NMDA)-induced retinal neurotoxicity, and the degree of capillary degeneration decreases in an age-dependent manner. To determine the role of vascular endothelial growth factor (VEGF) in the high susceptibility of capillaries to neuronal damage during the early postnatal stage, this study compares the vascular regression patterns between NMDA-treated retinas and retinas treated with N-[2-chloro-4-{(6,7-dimethoxy-4-quinazolinyl)oxy}phenyl]-N'-propylurea (KRN633), a VEGF receptor tyrosine kinase inhibitor, in neonatal rats. Two days after a single intravitreal injection of NMDA (200 nmol/eye) on postnatal day (P) 7, substantial retinal neuron loss and delayed expansion of the retinal vascular bed were observed. The reduction in the capillary density in the central retina reached statistical significance 4 days after NMDA treatment. In retinas of rats injected subcutaneously with KRN633 (10 mg/kg) on P7 and P8, simplified vasculature attributable to capillary regression and prevention of endothelial cell growth were seen on P9, whereas no visible changes in the morphology of the retinal layers were observed. The degree of capillary degeneration in NMDA-treated retinas was less than that in KRN633-treated retinas. No apparent changes in immunoreactivities for VEGF were found 2 days after NMDA treatment. These results indicate that neuronal cell loss in the retina precedes retinal capillary degeneration following NMDA treatment, and VEGF-dependent immature capillaries might be more susceptible to NMDA-induced neuronal damage. PMID:25284371

  3. Construction and characterization of an infectious cDNA clone of rat hepatitis E virus.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Haga, Kei; Nakamura, Tomofumi; Ochiai, Susumu; Takaji, Wakita; Johne, Reimar

    2015-06-01

    Rat hepatitis E virus (HEV) is related to human HEV and has been detected in wild rats worldwide. Here, the complete genome of rat HEV strain R63/DEU/2009 was cloned downstream of the T7 RNA polymerase promoter and capped genomic RNA generated by in vitro transcription was injected into nude rats. Rat HEV RNA could be detected in serum and faeces of rats injected intrahepatically, but not in those injected intravenously. Rat HEV RNA-positive faecal suspension was intravenously inoculated into nude rats and Wistar rats leading to rat HEV RNA detection in serum and faeces of nude rats, and to seroconversion in Wistar rats. In addition, rat HEV was isolated in PLC/PRF/5 cells from the rat HEV RNA-positive faecal suspension of nude rats and then passaged. The cell culture supernatant was infectious for nude rats. Genome analysis identified nine point mutations of the cell-culture-passaged virus in comparison with the originally cloned rat HEV genome. The results indicated that infectious rat HEV could be generated from the cDNA clone. As rats are widely used and well-characterized laboratory animals, studies on genetically engineered rat HEV may provide novel insights into organ tropism, replication and excretion kinetics as well as immunological changes induced by hepeviruses.

  4. Construction and characterization of an infectious cDNA clone of rat hepatitis E virus.

    PubMed

    Li, Tian-Cheng; Yang, Tingting; Yoshizaki, Sayaka; Ami, Yasushi; Suzaki, Yuriko; Ishii, Koji; Haga, Kei; Nakamura, Tomofumi; Ochiai, Susumu; Takaji, Wakita; Johne, Reimar

    2015-06-01

    Rat hepatitis E virus (HEV) is related to human HEV and has been detected in wild rats worldwide. Here, the complete genome of rat HEV strain R63/DEU/2009 was cloned downstream of the T7 RNA polymerase promoter and capped genomic RNA generated by in vitro transcription was injected into nude rats. Rat HEV RNA could be detected in serum and faeces of rats injected intrahepatically, but not in those injected intravenously. Rat HEV RNA-positive faecal suspension was intravenously inoculated into nude rats and Wistar rats leading to rat HEV RNA detection in serum and faeces of nude rats, and to seroconversion in Wistar rats. In addition, rat HEV was isolated in PLC/PRF/5 cells from the rat HEV RNA-positive faecal suspension of nude rats and then passaged. The cell culture supernatant was infectious for nude rats. Genome analysis identified nine point mutations of the cell-culture-passaged virus in comparison with the originally cloned rat HEV genome. The results indicated that infectious rat HEV could be generated from the cDNA clone. As rats are widely used and well-characterized laboratory animals, studies on genetically engineered rat HEV may provide novel insights into organ tropism, replication and excretion kinetics as well as immunological changes induced by hepeviruses. PMID:25634930

  5. Okara ameliorates glucose tolerance in GK rats.

    PubMed

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-05-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  6. Liver uptake of biguanides in rats.

    PubMed

    Sogame, Yoshihisa; Kitamura, Atsushi; Yabuki, Masashi; Komuro, Setsuko

    2011-09-01

    Metformin is an oral antihyperglycaemic agent widely used in the management of non-insulin-dependent diabetes mellitus. The liver is the primary target, metformin being taken up into human and rat hepatocytes via an active transport mechanism. The present study was designed to compare hepatic uptake of two biguanides, metformin and phenformin, in vitro and in vivo. In in vitro experiments, performed using rat cryopreserved hepatocytes, phenformin exhibited a much higher affinity and transport than metformin, with marked differences in kinetics. The K(m) values for metformin and phenformin were 404 and 5.17μM, respectively, with CLint (V(max)/K(m)) values 1.58μl/min per 10(6) cells and 34.7μl/min per 10(6) cells. In in vivo experiments, when (14)C-metformin and (14)C-phenformin were given orally to male rats at a dose of 50mg/kg, the liver concentrations of radioactivity at 0.5 hour after dosing were 21.5μg eq./g with metformin but 147.1μg eq./g for phenformin, ratios of liver to plasma concentrations being 4.2 and 61.3, respectively. In conclusion, the results suggest that uptake of biguanides by rat hepatocytes is in line with the liver distribution found in vivo, phenformin being more efficiently taken up by liver than metformin after oral administration.

  7. Lobeline produces conditioned taste avoidance in rats.

    PubMed

    Harrod, S B; Dwoskin, L P; Bardo, M T

    2004-05-01

    Previous results indicate that pretreatment with lobeline attenuates methamphetamine (METH) self-administration in rats, but not by acting as a substitute reinforcer. Given these findings, it has been suggested that lobeline may serve as a useful pharmacotherapy for psychostimulant abuse. However, because lobeline produces emesis and nausea in humans, the present study examined whether lobeline has direct effects on taste avoidance behavior in rats within the same dose range shown previously to decrease METH self-administration. Two experiments utilized a Pavlovian conditioning procedure to determine if lobeline produces conditioned taste avoidance (CTA) in rats. In Experiments 1 and 2, rats consumed either novel milk or salt solutions, respectively, and within 10 min, were injected with lobeline (0.3-3.0 mg/kg) or METH (0.3-3.0 mg/kg). A single-bottle test conducted 48 h after flavor-drug pairings indicated that the dose of lobeline that reduced METH self-administration in a previous study (i.e., 3.0 mg/kg) also produced reliable CTA for milk and salt solution. These findings suggest a need to develop lobeline analogs that reduce METH self-administration, but do not produce CTA following the consumption of a novel solution.

  8. Baroreflex Function in Rats after Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Hasser, Eileen M.

    1997-01-01

    Prolonged exposure of humans to decreased gravitational forces during spaceflight results in a number of adverse cardiovascular consequences, often referred to as cardiovascular deconditioning. Prominent among these negative cardiovascular effects are orthostatic intolerance and decreased exercise capacity. Rat hindlimb unweighting is an animal model which simulates weightlessness, and results in similar cardiovascular consequences. Cardiovascular reflexes, including arterial and cardiopulmonary baroreflexes, are required for normal adjustment to both orthostatic challenges and exercise. Therefore, the orthostatic intolerance and decreased exercise capacity associated with exposure to microgravity may be due to cardiovascular reflex dysfunction. The proposed studies will test the general hypothesis that hindlimb unweighting in rats results in impaired autonomic reflex control of the sympathetic nervous system. Specifically, we hypothesize that the ability to reflexly increase sympathetic nerve activity in response to decreases in arterial pressure or blood volume will be blunted due to hindlimb unweighting. There are 3 specific aims: (1) To evaluate arterial and cardiopulmonary baroreflex control of renal and lumbar sympathetic nerve activity in conscious rats subjected to 14 days of hindlimb unweighting; (2) To examine the interaction between arterial and cardiopulmonary baroreflex control of sympathetic nerve activity in conscious hindlimb unweighted rats; (3) to evaluate changes in afferent and/or central nervous system mechanisms in baroreflex regulation of the sympathetic nervous system. These experiments will provide information related to potential mechanisms for orthostatic and exercise intolerance due to microgravity.

  9. Shifts in the psychophysical function in rats.

    PubMed

    Guilhardi, Paulo; Macinnis, Mika L M; Church, Russell M; Machado, Armando

    2007-06-01

    The primary goal was to compare results from a free-operant procedure with pigeons [Machado, A., Guilhardi, P., 2000. Shifts in the psychometric function and their implications for models of timing. J. Exp. Anal. Behav. 74, 25-54, Experiment 2] with new results obtained with rats. The secondary goal was to compare the results of both experiments with dependent variables that were not used in the original publication. As in the original study with pigeons, rats were trained on a two-alternative free-operant psychophysical procedure in which left lever press responses were reinforced during the first and second quarters of a 60-s trial, and right lever press responses were reinforced during the third and fourth quarters of the trial. The quarters were reinforced according to four independent variable interval (VI) schedules of reinforcement. The VI duration was manipulated in each quarter, and shifts in the psychophysical functions that relate response rate with time since trial onset were measured. The results obtained with rats were consistent with those previously obtained with pigeons. In addition, results not originally reported were also consistent between rats and pigeons, and provided insights into the perception, memory, and decision processes in Scalar Expectancy Theory and Learning-to-Time Theory.

  10. Pack rats (Neotoma spp.): Keystone ecological engineers?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The potential role of two species of pack rats (Neotoma albigula and Neotoma micropus) as keystone ecological engineers was examined by estimating the species diversity of invertebrates living in the nest middens, and nitrogen mineralization rates in soils associated with the middens. Although pack-...

  11. Central action of phenylethylamine in rats.

    PubMed

    Jagiełło-Wójtowicz, E

    1981-01-01

    Phenylethylamine (PEA), 10, 50 and 100 microgram/rat ivc depressed the spontaneous and explorative motor activities, did not affect the body temperature and potentiated the action of hypnotics. The PEA-induced depression of motor activity was antagonized by spiperone, phenoxybenzamine, propranolol and, slightly, by alpha-MT. In rats with total chemical destruction of catecholamine neurons and in rats with selective lesion of dopamine neurons, PEA increased motor activity. Similar effect was observed after administration of reserpine, reserpine together with 6-hydroxydopamine and yohimbine. PEA potentiated the amphetamine and apomorphine stereotypy but inhibited amphetamine hypermotility: in the latter experiment slight periodical stereotyped head movements were observed. PEA did not affect haloperidol and fluphenazine induced catalepsy. It did not change the immobility period in the behavioral despair test. In doses of 0 . 1, 1 and 10 mg/kg iv it potentiated flexor reflex of the hind paw of the spinal rat. Phentolamine (10 mg/kg iv) and propranolol (5 mg/kg iv) slightly potentiated the stimulatory effect of PEA. In doses of 50 and 100 microgram ivc PEA did not affect the level and utilization of noradrenaline, and did not change the level of dopamine but depressed its utilization in the cerebral cortex, striatum and hippocampus. PMID:7196039

  12. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  13. The Helsinki Rat Microsurgical Sidewall Aneurysm Model

    PubMed Central

    Marbacher, Serge; Marjamaa, Johan; Abdelhameed, Essam; Hernesniemi, Juha; Niemelä, Mika; Frösen, Juhana

    2014-01-01

    Experimental saccular aneurysm models are necessary for testing novel surgical and endovascular treatment options and devices before they are introduced into clinical practice. Furthermore, experimental models are needed to elucidate the complex aneurysm biology leading to rupture of saccular aneurysms. Several different kinds of experimental models for saccular aneurysms have been established in different species. Many of them, however, require special skills, expensive equipment, or special environments, which limits their widespread use. A simple, robust, and inexpensive experimental model is needed as a standardized tool that can be used in a standardized manner in various institutions. The microsurgical rat abdominal aortic sidewall aneurysm model combines the possibility to study both novel endovascular treatment strategies and the molecular basis of aneurysm biology in a standardized and inexpensive manner. Standardized grafts by means of shape, size, and geometry are harvested from a donor rat's descending thoracic aorta and then transplanted to a syngenic recipient rat. The aneurysms are sutured end-to-side with continuous or interrupted 9-0 nylon sutures to the infrarenal abdominal aorta. We present step-by-step procedural instructions, information on necessary equipment, and discuss important anatomical and surgical details for successful microsurgical creation of an abdominal aortic sidewall aneurysm in the rat. PMID:25350840

  14. Voluntary Oral Administration of Losartan in Rats.

    PubMed

    Diogo, Lucília N; Faustino, Inês V; Afonso, Ricardo A; Pereira, Sofia A; Monteiro, Emília C; Santos, Ana I

    2015-09-01

    Gavage is a widely performed technique for daily dosing in laboratory rodents. Although effective, gavage comprises a sequence of potentially stressful procedures for laboratory animals that may introduce bias into experimental results, especially when the drugs to be tested interfere with stress-dependent parameters. We aimed to test vehicles suitable for drug delivery by voluntary ingestion in rats. Specifically, Male Wistar rats (age, 2 to 3 mo) were used to test nut paste (NUT), peanut butter (PB), and sugar paste (SUG) as vehicles for long-term voluntary oral administration of losartan, an angiotensin II receptor blocker. Vehicles were administered for 28 d without drug to assess effects on the glucose level and serum lipid profile. Losartan was mixed with vehicles and either offered to the rats or administered by gavage (14 d) for subsequent quantification of losartan plasma levels by HPLC. After a 2-d acclimation period, all rats voluntarily ate the vehicles, either alone or mixed with losartan. NUT administration reduced blood glucose levels. The SUG group had higher concentrations of losartan than did the gavage group, without changes in lipid and glucose profiles. Our results showed that NUT, PB, and SUG all are viable for daily single-dose voluntary ingestion of losartan and that SUG was the best alternative overall. Drug bioavailability was not reduced after voluntary ingestion, suggesting that this method is highly effective for chronic oral administration of losartan to laboratory rodents. PMID:26424254

  15. Dermal absorption of inorganic germanium in rats.

    PubMed

    Yokoi, Katsuhiko; Kawaai, Takae; Konomi, Aki; Uchida, Yuka

    2008-11-01

    So-called germanium 'health' products including dietary supplements, cosmetics, accessories, and warm bath service containing germanium compounds and metalloid are popular in Japan. Subchronic and chronic oral exposure of germanium dioxide (GeO(2)), popular chemical form of inorganic germanium causes severe germanium toxicosis including death and kidney dysfunction in humans and experimental animals. Intestinal absorption of neutralized GeO(2) or germanate is almost complete in humans and animals. However, it is not known whether germanium is cutaneously absorbed. We tested dermal absorption of neutralized GeO(2) or germanate using male F344/N rats. Three groups of rats were treated with a 3-h topical application of hydrophilic ointment containing graded level of neutralized GeO(2) (pH 7.4): 0, 0.21 and 0.42 mg GeO(2)/g. Germanium concentration in blood and tissues sampled from rats after topical application of inorganic germanium was measured by inductively coupled plasma-mass spectrometry. Animals topically applied 0.42 mg GeO(2)/g ointment had significantly higher germanium concentrations in plasma, liver, and kidney than those of rats that received no topical germanium. The results indicate that skin is permeable to inorganic germanium ion or germanate and recurrent exposure of germanium compounds may pose a potential health hazard.

  16. Cardiac Muscle Studies with Rat Ventricular Strips

    ERIC Educational Resources Information Center

    Whitten, Bert K.; Faleschini, Richard J.

    1977-01-01

    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  17. On the absorption of alendronate in rats.

    PubMed

    Lin, J H; Chen, I W; deLuna, F A

    1994-12-01

    Alendronate is an antiosteolytic agent under investigation for the treatment of a number of bone disorders. Since the compound is a zwitterion with five pKa values and is completely ionized in the intestine at the physiological pH, absorption is poor; less than 1% of an oral dose is available systemically in rats. In the present studies, absorption was found to be predominantly in the upper part of the small intestine. Administration of buffered solutions of alendronate (pH 2-11) did not improve absorption. Whereas food markedly impaired the absorptio